Stem-cell biology: a move in the right direction.

Heart failure and renal insufficiency as well as pulmonary hypertension are pathophysiologically closely associated as a cardio-renal or cardio-pulmonary-renal syndrome. Due to the frequent hospitalization of patients affected by this syndrome, it is of high medical and also health economic relevance. Besides the inhibition of the renin-angiotensin-aldosterone system (RAAS), multimodal treatment options are available with mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors and sodium-glucose transporter 2 (SGLT-2) inhibitors. Profound knowledge of the pathophysiology and the therapeutic options is as necessary for an optimized medical care as patient-oriented, transdisciplinary and cross-sectoral care.
© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
Klinik für Nieren‑, Hochdruck- und Autoimmunerkrankungen, Klinikum der Landeshauptstadt Stuttgart gKAöR, Katharinenhospital, Kriegsbergstr. 60, 70174, Stuttgart, Deutschland. sekretariat.schwenger@klinikum-stuttgart.de.
Klinik für Innere Medizin III - Klinik für Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg, Deutschland.
Klinik für Nieren‑, Hochdruck- und Autoimmunerkrankungen, Klinikum der Landeshauptstadt Stuttgart gKAöR, Katharinenhospital, Kriegsbergstr. 60, 70174, Stuttgart, Deutschland.
Klinik für Kardiologie, Herz- und Gefäßzentrum Bad Bevensen, Bad Bevensen, Deutschland.
Herzinsuffizienz und Niereninsuffizienz sowie pulmonale Hypertonie sind als kardiorenales oder kardiopulmorenales Syndrom pathophysiologisch eng miteinander verzahnt. Aufgrund der häufigen Hospitalisierung der hiervon betroffenen Patienten kommt diesem Syndrom eine hohe medizinische, aber auch gesundheitsökonomische Relevanz zu. Neben der Blockade des Renin-Angiotensin-Aldosteron-Systems stehen mit den Mineralokortikoidrezeptorantagonisten, Angiotensinrezeptor-Neprilysin-Inhibitoren sowie Natrium-Glukose-Kotransporter-2(SGLT-2)-Inhibitoren multimodale Therapiemöglichkeiten zur Verfügung. Die Kenntnis der pathophysiologischen Grundlagen und der therapeutischen Optionen ist für eine optimierte medizinische Betreuung genauso notwendig wie eine patientenorientierte, transdisziplinäre und sektorenübergreifende Versorgung.
[Renal insufficiency in the context of cardio-pulmonary-renal pathophysiology].

Water and energy are closely interlinked during their production and consumption processes. The limited and temporary distribution of energy and water resources poses a significant environmental challenge. Industrial wastewater treatment plants are essential elements of water production and also significant energy consumers. This study proposes a methodology for energy management of a wastewater treatment plant. Specifically, it examines the impact of optimum operating conditions on energy costs for a dairy wastewater treatment plant using a dissolved air flotation process. Monte Carlo simulation was used to optimize the parameters and to determine the reuse potential of dairy effluent. Firstly, the optimum operating conditions were determined. The results revealed a maximum fat, oil, and grease removal efficiency of 97% and a chemical oxygen demand removal efficiency of 70%. The optimum conditions were pH of 8, a saturation pressure of 5 bars, and a recirculation ratio of 33%. The optimum concentrations of coagulant and flocculant that contain polyaluminum chloride and cationic polymer were 20 mg/L and 25 mg/L, respectively. The results of the simulation study gave a recirculation ratio of 26.31%, a polyaluminum chloride concentration of 42.5 mg/L, a cationic polymer concentration of 36.31 mg/L, and a saturation pressure of 4.61 bars. Finally, energy cost assessment was performed using a newly developed model which showed that the energy cost indicator of the existing process was lower than optimum operating conditions. The reuse potential of dairy effluent as cooling water was found to be 52%.
Environmental Engineering Department, Engineering Faculty, Harran University, Sanliurfa, Turkey.
Environmental Engineering Department, Engineering Faculty, Harran University, Sanliurfa, Turkey. iyesilnacar@gmail.com.
Energy cost assessment of a dairy industry wastewater treatment plant.

Department of Pediatrics and Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Department of Chemistry, University of Illinois At Chicago, Chicago, IL, USA.
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Department of Communication Sciences and Disorders, Northwestern University, Chicago, IL, USA.
Department of Chemistry, University of Illinois At Chicago, Chicago, IL, USA. cologna@uic.edu.Laboratory of Integrated Neuroscience, University of Illinois At Chicago, 845 W Taylor Street, Room 4500, Chicago, IL, 60607, USA. cologna@uic.edu.
Correction to: Characterization of the Cerebrospinal Fluid Proteome in Patients with Fragile X-Associated Tremor/Ataxia Syndrome.

Imaging plays a leading role in detection and diagnosis of fetal head and neck lesions. These lesions comprise a heterogeneous group of congenital tumors and malformations. Complementary imaging modalities that can be used in prenatal medicine are ultrasound and MRI. The authors discuss imaging characteristics of fetal lesions, assessment of potential complications and pregnancy management options for the most common pathology of the fetal head and neck.
Department of Neuroradiology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, USA. feygin@email.chop.edu.
Department of Neuroradiology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, USA.

Photobiomodulation (PBM) has been shown to improve cell proliferation and cell migration. Many cell types have been investigated, with most studies using deep penetrating red light irradiation. Considering the interest of surface biostimulation of oral mesenchymal cells after surgical wound, the present study aimed to assess green light irradiation effects on Dental Pulp Stem Cells' (DPSC) proliferation and migration. To understand the mechanisms underlying these effects, we investigated cytoskeleton organization and subsequent cell shape and stiffness. A 532-nm wavelength Nd:YAG laser (30 mW) was applied between 30 and 600 s on DPSC in vitro. Cell proliferation was analyzed at 24, 48, and 72 h after irradiation, by cell counting and enzymatic activity quantification (paranitrophenylphosphate phosphatase (pNPP) test). A wound healing assay was used to study cell migration after irradiation. Effects of PBM on cytoskeleton organization and cell shape were assessed by actin filaments staining. Elasticity changes after irradiation were quantified in terms of Young's modulus measured using Atomic Force Microscopy (AFM) force spectroscopy. Green light significantly improved DPSC proliferation with a maximal effect obtained after 300-s irradiation (energy fluence 5 J/cm2). This irradiation had a significant impact on cell migration, improving wound healing after 24 h. These results were concomitant with a decrease of cells' Young's modulus after irradiation. This cell softening was explained by actin cytoskeleton reorganization, with diminution of cell circularity and more abundant pseudopodia. This study highlights the interest of green laser PMB for the proliferation and migration of mesenchymal stem cells, with encouraging results for clinical application, especially for surgical wound healing procedures.
LBN, University Montpellier, 545 Av Pr JL Viala, 34193 CEDEX 4, Montpellier, France.
LBN, University Montpellier, 545 Av Pr JL Viala, 34193 CEDEX 4, Montpellier, France.Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.
L2C, CNRS, University Montpellier, Montpellier, France.
LBN, University Montpellier, 545 Av Pr JL Viala, 34193 CEDEX 4, Montpellier, France. pierre-yves.collart-dutilleul@umontpellier.fr.
Effects of green light photobiomodulation on Dental Pulp Stem Cells: enhanced proliferation and improved wound healing by cytoskeleton reorganization and cell softening.

Based on current guidelines, surgical and nonsurgical therapies are viable frontline treatment for patients with locoregional oropharyngeal carcinoma (OPC). We sought to compare financial parameters between chemoradiation and transoral robotic surgery (TORS) in this patient population.Case-control study.In this study we identified patients with selected American Joint Committee on Cancer 7th Edition stage II to IVa OPC treated with TORS between January 2013 and December 2014. Fifteen patients who underwent TORS were stage matched with 15 patients treated with chemoradiation. Total charges and cost data for each patient were analyzed at 4-month and 1-year time points; functional and oncologic outcomes were assessed.There were no significant differences in functional and oncologic outcomes. Patients undergoing TORS had a longer inpatient hospital stay, and most required a nasogastric tube for an average of 3.5 days. There were no local or regional recurrences. Across all time points, the TORS group had lower charges and costs compared to the chemoradiation group, with 14% lower costs at 1 year. In the chemoradiation group, nearly two-thirds of costs came from radiation therapy and pharmacy expenses. Chemotherapy accounted for most pharmacy costs. The costs of operating the surgical robot accounted for a about half of surgical costs.Selected patients with stage II to IVa oropharyngeal carcinoma treated with TORS may incur lower costs than those treated nonsurgically. With rising healthcare spending, the financial impact of treatment might be considered for those patients eligible for treatment regimens with comparable functional and oncologic outcomes.3b Laryngoscope, 129:1604-1609, 2019.
© 2018 The American Laryngological, Rhinological and Otological Society, Inc.
Department of Otolaryngology, Division of Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, California, U.S.A.
Department of Medicine, Division of Oncology, Stanford University School of Medicine, Palo Alto, California, U.S.A.
Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, U.S.A.
Cost comparison of treatment for oropharyngeal carcinoma.

Venous thromboembolism (VTE) is a common complication of colon cancer. In the present study, we aimed to explore the association of the oncogene COX7C to VTE in colon cancer patients. Samples from 580 patients were examined histologically for VTE and pathological characteristic of cancer. Gene mutation and expression analysis were performed using polymerase chain reaction-based assays to evaluate genes related to VTE, including COX7C. Univariate analysis between clinical pathological factors and VTE was conducted. Logistic regression analysis was performed for the prediction of VTE by pathological factors and gene expressions. Among patients investigated, a total of 56 patients had VTE. COX7C had a significant correlation with VTE (p < 0.001). Despite a correlation between tumor size, invasion depth of tumor, lymph node metastasis, lymph node metastasis, distant metastasis, lymphovascular invasion, histologic type and pathology type, Ki-67, and some other genes, to VTE (p > 0.05), only COX7C expression demonstrated significance in its ability to predict VTE. Here, we show that COX7C upregulation strongly correlates with VTE in colon cancer, which implicates its role as a biomarker and therapeutic target of VTE in colon cancer.
Department of Nursing, Quanzhou First Hospital Affiliated To Fujian Medical University, No.250 East Street, Licheng District, Quanzhou, 362000, Fujian, China.
Department of Geriatric, Quanzhou First Hospital Affiliated To Fujian Medical University, No.250 East Street, Licheng District, Quanzhou, 362000, Fujian, China.
Second Department of Gastrointestinal Surgery, Quanzhou First Hospital Affiliated To Fujian Medical University, No.250 East Street, Licheng District, Quanzhou, 362000, Fujian, China.
Department of Anesthesiology, Quanzhou First Hospital Affiliated To Fujian Medical University, No.250 East Street, Licheng District, Quanzhou, 362000, Fujian, China. zengjingyang138168@163.com.
The expression level of COX7C associates with venous thromboembolism in colon cancer patients.

The oncofetal alpha-fetoprotein (AFP) is reexpressed in the majority of hepatocellular carcinomas and may be used as a target molecule for an immunotherapy or prophylaxis against this tumor. We investigated the potential of DNA vaccination with AFP-expressing plasmid DNA to induce an immune response against AFP-expressing tumor cells in DBA/2 mice. 62.5% of mice vaccinated with AFP-expressing plasmid DNA, rejected subcutaneous syngeneic AFP-expressing P815 tumors, whereas only 16.7% of mice vaccinated with control plasmid rejected these tumor cells (P=.03). Mean survival of mice after challenge with subcutaneous AFP-expressing tumor cells was prolonged for 8 days in mice vaccinated with AFP-expressing DNA (35 days) compared to mice vaccinated with control plasmid (27 days). To rule out possible autoimmune reactions against regenerating liver, which also reexpresses AFP, we evaluated the influence of AFP-specific DNA vaccination on liver regeneration in DBA/2 mice. Histologic quantification of proliferating hepatocytes and of the amount of necrotic liver tissue in carbon tetrachloride-damaged liver did not reveal statistically significant differences in mice vaccinated with AFP-expressing plasmid compared to control mice. These data suggest that AFP-specific DNA vaccination represents a useful tool to inhibit growth of AFP-expressing tumors in mice that does not affect liver regeneration.
Department of Medicine I, University of Bonn, Bonn, Germany.
DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice.

Rock bream iridovirus (RBIV) is one of the most dangerous pathogens that causes the highest mortality in the aquaculture of rock bream (Oplegnathus fasciatus). Even though RBIV infection leads to huge economic loss, proteome studies on RBIV-infected rock bream have not been conducted to provide information about the differential protein expression pattern by the host protection system.The purpose of this study was to investigate the protein expression patterns in spleens of rock bream olive after infection by RBIV or mixed infection by RBIV and bacteria.Depending on the infection intensity and sampling time point, fish were divided into five groups: uninfected healthy fish at week 0 as the control (0C), heavily infected fish at week 0 (0H), heavily mixed RBIV and bacterial infected fish at week 0 (0MH), uninfected healthy fish at week 3 (3C), and lightly infected fish at week 3 (3L). Proteins were extracted from the spleens of infected rock bream. We used 2-DE analysis with LC-MS/MS to investigate proteome changes in infected rock bream.The results of the LC-MS/MS analyses showed different protein expression profiles after infection. Proteins related to oxygen transport and energy generation, such as hemoglobin, beta-globin, and ATP synthase, were mostly expressed in the infected spleen. Whereas proteins involved in structure and cell movement, such as tubulin, myosin, actin binding proteins, and intermediate filament proteins, were down-regulated in the infected spleens. The protein expression profiles between infection by RBIV and mixed infection by RBIV and bacteria showed similar patterns.Our results indicated that infection by RBIV or mixed infection by RBIV and bacteria triggered energy generation and oxygen-transport, but cell migration and constructional changes in the spleen were extremely decreased.
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
Pathology Research Division, National Institute of Fisheries Science, Busan, Republic of Korea.
Department of Aquatic Life Medicine, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea.
Department of Marine Biology and Aquaculture, College of Marine Science, Gyeongsang National University, Tongyeong, Republic of Korea.
Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea.
Department of Chemistry, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea. hcha@kosin.ac.kr.
Proteome profile of spleen in rock bream (Oplegnathus fasciatus) naturally infected with rock bream iridovirus (RBIV).

The association of arterial stiffness and arterial calcification: the Rotterdam study.

We have previously described hTDE1, the human homologue of the recently described TDE1/TMS family of proteins whose members have been identified in several species. Although a defined biochemical activity has yet to be assigned to TDE1/TMS family members, previous results point to the overexpression of family members in tumor cell lines or tissues. To define whether hTDE1 may directly impact on neoplastic transformation, we derived and characterized stable Rat-1 transfectants that constitutively express hTDE1 at the plasma membrane. Expression of hTDE1 in Rat-1 transfectants had a significant effect on cell contact inhibition in vitro as judged by a focus formation assay. In addition, by monitoring caspase-3 activity and Hoechst staining, we determined that hTDE1 overexpression partially protects cells from serum starvation- and etoposide-induced apoptosis. Finally, hTDE1 Rat-1-expressing clones accelerated the formation of tumors in a nude mouse assay. Our results suggest that hTDE1 contributes directly to oncogenesis in vivo that may in part be explained by its effect on apoptosis in vitro.
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montreal, Quebec, Canada.
Human TDE1, a TDE1/TMS family member, inhibits apoptosis in vitro and stimulates in vivo tumorigenesis.

The aim of this study is to investigate the results of fluorescein angiography (FA)-guided reduced-fluence photodynamic therapy (PDT) in the treatment of chronic central serous chorioretinopathy (CSCR), with the hypothesis that indocyanine green angiography (ICGA) guidance is avoidable in some cases.This retrospective study includes a consecutive nonrandomized series of chronic CSCR cases. All eyes were examined with FA and the ones that had discrete active leakage areas or points had undergone reduced-fluence PDT.The study included 45 eyes of 41 patients with a mean age of 48.8 ± 10.7. The main duration of last chronic CSCR episode was 13.0 ± 11.9 months. Thirty-nine (86.7%) out of 45 consecutive eyes had active leakage area(s) on FA, which enabled them to be treated with PDT. Remaining six eyes had undergone ICGA examination and had received an ICGA-guided PDT. In FA-guided eyes, the mean BCVA improved from 0.44 ± 0.25 Snellen lines to 0.63 ± 0.32 lines in the last control visit (p < 0.001). Both central macular thickness and subfoveal choroidal thickness decreased significantly in treated eyes. Thirty-eight eyes (97.4%) in FA-guided group and six eyes (100.0%) in ICGA-guided group had total resorption of subretinal fluid.This study provides basis to support the hypothesis that FA-guided half-fluence PDT may be justified as an alternative method of treatment in appropriate cases of chronic CSCR without compromising the therapeutic success.
Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey. akoytak@yahoo.com.
Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey.
Fluorescein angiography as a primary guide for reduced-fluence photodynamic therapy for the treatment of chronic central serous chorioretinopathy.

Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.Modern Diet and PhysiologyResearch Center, YaleUniversity, New Haven, CT, USA.Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. dana.small@yale.edu.Modern Diet and PhysiologyResearch Center, YaleUniversity, New Haven, CT, USA. dana.small@yale.edu.Department of Psychology, Yale University, New Haven, CT, USA. dana.small@yale.edu.

We aimed to assess the prevalence and outcomes of esophageal perforation in very low birth weight infants. This retrospective cohort study utilized the US National Inpatient Sample dataset for the years 2000 to 2017. A total of 1,755,418 very low birth weight infants were included; of them, 861 (0.05%) were diagnosed with esophageal perforation. The majority (77.9%) of infants were in the birth weight category < 1000 g and 77.7% in infants ≤ 28 weeks of gestation. The majority (73%) of infants were tracheally intubated and received mechanical ventilation; of them, 24 infants (2.8%) had tracheostomy. Mortality associated with esophageal perforation was 25.8%. Regression analysis did not show an association between esophageal perforation and increased mortality in preterm infants (aOR = 1.0, CI: 0.83-1.20, p = 0.991). Procedures encountered in these infants include thoracentesis (10.8%), laparotomy (4.1%), percutaneous abdominal drainage (4.1%), and gastrostomy tube insertion (6.2%), whereas the rest of the infants were managed conservatively. There was a significant trend for increasing prevalence of esophageal perforation over the years.Conclusion: Esophageal perforation does not independently increase the risk for mortality in very low birth weight infants. The increasing prevalence is possibly related to increased care offered to infants at limits of viability in recent years. What is Known: • Knowledge about esophageal perforation is derived from anecdotal single-center case reports. • Esophageal perforation in neonates is mostly iatrogenic. • It is considered a critical complication that is associated with high mortality. What is New: • This is the first and largest national study on prevalence of esophageal perforation in preterm infants. • Esophageal perforation does not independently increase the risk for mortality. • Septicemia and pneumothorax are frequent complications to esophageal perforation.
Department of Neonatology, Cleveland Clinic Children's, 900 Euclid Avenue, M31-37, Cleveland, OH, 44195, USA. elgendm@ccf.org.
Department of Pediatrics, Michigan State University/Sparrow Health System, Lansing, MI, USA.
Department of Neonatology, Cleveland Clinic Children's, 900 Euclid Avenue, M31-37, Cleveland, OH, 44195, USA.
Esophageal perforation in very low birth weight infants.

High data quality is of crucial importance to the integrity of research projects. In the conduct of multi-center observational cohort studies with increasing types and quantities of data, maintaining data quality is challenging, with few published guidelines.The Cure Glomerulonephropathy (CureGN) Network has established numerous quality control procedures to manage the 70 participating sites in the United States, Canada, and Europe. This effort is supported and guided by the activities of several committees, including Data Quality, Recruitment and Retention, and Central Review, that work in tandem with the Data Coordinating Center to monitor the study. We have implemented coordinator training and feedback channels, data queries of questionable or missing data, and developed performance metrics for recruitment, retention, visit completion, data entry, recording of patient-reported outcomes, collection, shipping and accessing of biological samples and pathology materials, and processing, cataloging and accessing genetic data and materials.We describe the development of data queries and site Report Cards, and their use in monitoring and encouraging excellence in site performance. We demonstrate improvements in data quality and completeness over 4 years after implementing these activities. We describe quality initiatives addressing specific challenges in collecting and cataloging whole slide images and other kidney pathology data, and novel methods of data quality assessment.This paper reports the CureGN experience in optimizing data quality and underscores the importance of general and study-specific data quality initiatives to maintain excellence in the research measures of a multi-center observational study.
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Division of Nephrology, Maisonneuve-Rosemont Hospital, Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
Arbor Research Collaborative for Health, Ann Arbor, MI, 48104, USA.
Stanford University Medical Center, Stanford, CA, 94305, USA.
Department of Medicine, Division of Nephrology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Pediatrics-Renal, Baylor College of Medicine, Houston, TX, USA.
NYU Langone Health, Department of Pediatrics, Division of Nephrology, New York, NY, USA.
Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Pathology, Division of AI and Computational Pathology, Department of Medicine, Division of Nephrology, Duke University, Durham, NC, USA.
Laboratory of Molecular Nephrology, Istituto Giannina Gaslini, IRCCS, Genoa, Italy.
Emory University, Department of Pediatrics, Division of Nephrology, Atlanta, GA, USA.
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
University of Michigan, Division of Nephrology, Ann Arbor, MI, USA.
Center for Clinical and Translational Research, the Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
University of Michigan, Division of Nephrology, Department of Pediatrics, Ann Arbor, MI, USA.
Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
Center for Translational Research, Children's National Hospital, Washington, DC, USA.
Contemporary clinical trials communications
Contemp Clin Trials Commun. 2021-06;22():100749.
Improving data quality in observational research studies: Report of the Cure Glomerulonephropathy (CureGN) network.

Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases, including cancer. The inositol-requiring kinase 1α (IRE1α)-X-box binding protein 1 (XBP1) pathway is the most evolutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1α-XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which luciferase was fused in-frame with the spliced (active) form of XBP1. Using cells expressing this reporter construct, we identified 162 genes for which siRNA inhibition resulted in alteration in XBP1 splicing. These genes express diverse types of proteins modulating a wide range of cellular processes. Pathway analysis identified a set of genes implicated in the pathogenesis of breast cancer. Several genes, including BCL10, GCLM, and IGF1R, correlated with worse relapse-free survival (RFS) in an analysis of patients with triple-negative breast cancer (TNBC). However, in this cohort of 1,908 patients, only high GCLM expression correlated with worse RFS in both TNBC and non-TNBC patients. Altogether, our study revealed unidentified roles of novel pathways regulating the UPR, and these findings may serve as a paradigm for exploring novel therapeutic opportunities based on modulating the UPR.Implications: Genome-wide RNAi screen identifies novel genes/pathways that modulate IRE1α-XBP1 signaling in human tumor cells and leads to the development of improved therapeutic approaches targeting the UPR.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/5/745/F1.large.jpg Mol Cancer Res; 16(5); 745-53. ©2018 AACR.
©2018 American Association for Cancer Research.
Department of Radiation Oncology, Stanford University, Stanford, California.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Institute for Immunity, Transplantation and Infection, and Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California.
High-Throughput Bioscience Center, Department of Chemical and Systems Biology, Stanford University, Stanford, California.
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Department of Radiation Oncology, The Ohio State University, Columbus, Ohio.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. akoong@mdanderson.org.
A Human Genome-Wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1α-XBP1 Activation.

Distrust in scientific expertise1-14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2-4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice9-11. There is a lack of understanding about how this distrust evolves at the system level13,14. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change11, and highlight the key role of network cluster dynamics in multi-species ecologies15.
Physics Department, George Washington University, Washington, DC, USA. neiljohnson@gwu.edu.Institute for Data, Democracy and Politics, George Washington University, Washington, DC, USA. neiljohnson@gwu.edu.
Institute for Data, Democracy and Politics, George Washington University, Washington, DC, USA.
Physics Department, George Washington University, Washington, DC, USA.
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
Department of Computer Science, University of Miami, Coral Gables, FL, USA.
Department of Political Science, George Washington University, Washington, DC, USA.
The online competition between pro- and anti-vaccination views.

Nanoparticles have been used to deliver siRNA to tissues and cells to silence specific genes in diverse organisms. Research and clinical application of nanoparticles like liposomes for drug delivery requires targeting them to specific anatomic regions or cell types, while avoiding off-target effects or clearance by the liver, kidney, or the immune system. Delivery to the central nervous system (CNS) presents additional challenges to cross the blood-brain barrier (BBB) to specific cell types like neurons, astrocytes, or glia. Here, we describe the generation of three different liposomal siRNA delivery vehicles to the CNS using the thin film hydration method. Utilizing cationic or anionic liposomes protects the siRNA from serum nucleases and proteases en route. To deliver the siRNA specifically to the CNS, the liposomes are complexed to a peptide that acts as a neuronal address by binding to nicotinic acetylcholine receptors (nAchRs). When injected intravenously or instilled intranasally, these liposome-siRNA-peptide complexes (LSPCs) or peptide addressed liposome-encapsulated therapeutic siRNA (PALETS) resist serum degradation, effectively cross the BBB, and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.
Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. mzabel@colostate.edu.
Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Methods in molecular biology (Clifton, N.J.)
siRNA Therapeutics for Protein Misfolding Diseases of the Central Nervous System.

The meaningful engagement of male partners in antenatal care (ANC) can positively impact maternal and newborn health outcomes. The Tanzania National Plan for the Elimination of Mother to Child Transmission of HIV recommends male partners attend the first ANC appointment as a strategy for HIV prevention and treatment. This recommendation seeks to increase uptake of HIV and reproductive healthcare services, but unintended consequences of these guidelines may negatively impact women's ANC experiences. This study qualitatively examined the impact of policy promoting male engagement on women's ANC experiences.The study was conducted in two urban clinics in Kilimanjaro Region, Tanzania. In-depth interviews were conducted with 19 participants (13 women and 6 male partners) attending a first ANC appointment. A semi-structured guide was developed, applying Kabeer's Social Relations Approach. Data were analyzed using applied thematic analysis, combining memo writing, coding, synthesis, and comparison of themes.Male attendance impacted the timing of women's presentation to ANC and experience during the first ANC visit. Women whose partners could not attend delayed their presentation to first ANC due to fears of being interrogated or denied care because of their partner absence. Women presenting with partners were given preferential treatment by clinic staff, and women without partners felt discriminated against. Women perceived that the clinic prioritized men's HIV testing over involvement in pregnancy care.Study findings indicate the need to better assess and understand the unintended impact of policies promoting male partner attendance at ANC. Although male engagement can benefit the health outcomes of mothers and newborn children, our findings demonstrate the need for improved methods of engaging men in ANC. ANC clinics should identify ways to make clinic settings more male friendly, utilize male attendance as an opportunity to educate and engage men in pregnancy and newborn care. At the same time, clinic policies should be cognizant to not discriminate against women presenting without a partner.
Kilimanjaro Clinical Research Institute, Moshi, Tanzania. h.osaki@kcri.ac.tz.
Duke Global Health Institute, Duke University, Durham, NC, USA.
Kilimanjaro Clinical Research Institute, Moshi, Tanzania.Duke Global Health Institute, Duke University, Durham, NC, USA.
Duke Global Health Institute, Duke University, Durham, NC, USA.Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Department of Epidemiology and Biostatistics, Kilimanjaro Christian Medical University College, Moshi, Tanzania.Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Kilimanjaro Clinical Research Institute, Moshi, Tanzania.Department of Epidemiology and Biostatistics, Kilimanjaro Christian Medical University College, Moshi, Tanzania.
Duke Global Health Institute, Duke University, Durham, NC, USA.Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
BMC Pregnancy Childbirth. 2021-10-26;21(1):720.
Male engagement guidelines in antenatal care: unintended consequences for pregnant women in Tanzania.

Healthy ageing has been associated with a bias toward positive information and greater psychological well-being. However, to what extent this positivity bias also applies to prioritizing positive information under emotional competition is unclear. Old and young adults performed a word-face interference task, in which they responded to the valence of positive and negative target-words while ignoring happy or angry distractor-faces that could be affectively congruent or incongruent. A control condition with scrambled neutral distractor-faces was also used. Findings showed small facilitation effects with faster responses when targets and distractors were affectively congruent and large interference effects with slower responses when targets and distractors were affectively incongruent compared to the control condition. Importantly, whereas for younger adults there was a similar pattern of interference from happy and angry distractor-faces, for older adults there was greater interference from angry distractor-faces. The present findings are discussed in the context of emotional bias literature.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Department of Psychology, Sapienza University of Rome, Rome, Italy.
Department of Psychology, Bournemouth University, Poole, UK.
Department of Psychology, Sapienza University of Rome, Rome, Italy. anna.pecchinenda@uniroma1.it.
It is not always positive: emotional bias in young and older adults.

Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Renal Medicine, University College Cork, Cork, Ireland.
Division of Nephrology, Columbia University, New York, New York, USA.
Division of Pediatric Nephrology, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Division of Nephrology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Validation of Diagnosis Codes to Identify Infection-Related Acute Care Events in Patients With Glomerular Disease.

Connexin proteins form gap junctions controlling exchange of ions and small molecules between cells and play an important role in movement of lymph within lymphatic vessels. Connexin47 (CX47) is highly expressed in lymphatic endothelial cells and CX47 missense mutations, i.e., R260C, cosegregate with primary lymphedema in humans. However, studies utilizing CX47 knockout mice have failed to demonstrate any lymphatic anomalies. To unravel the lymphatic consequences of expressing a mutant CX47 protein, we used CRISPR technology to create a mouse carrying a Cx47 missense mutation (Cx47R259C) equivalent to the human CX47R260C missense mutation associated with human primary lymphedema. Intradermal Evans Blue dye injection identified a 2-fold increase in regional lymph nodes in homozygous Cx47R259C mice compared to wildtype, particularly in the jugular region (4.8 ± 0.4 and 2.0 ± 0.0, respectively, p<0.01). Associated lymphatic channels were increased in Cx47R259C mice and mesenteric lymph reflux occurred in homozygous Cx47R259C mice but not in wildtype. Contractility of superficial cervical lymphatics, assessed by pressure myography, was reduced in homozygous Cx47R259C mice compared to wildtype. In conclusion, our data are the first to demonstrate a role for the Cx47 protein in lymphatic anatomy and function. This phenotype is similar to that found with other valve deficient mouse mutants, e.g., in Foxc2. Of significance, this study is the first to use CRISPR technology to develop a pre-clinical model of primary lymphedema and demonstrates the importance of distinguishing between lack of and presence of mutant protein when developing clinically relevant animal models for translation of pre-clinical findings.
Copyright by International Society of Lymphology.
Department of Surgery, University of Arizona, Tucson, Arizona, USA.
Department of Pediatrics, University of Arizona, Tucson, Arizona, USA.
Department of Surgery, University of Arizona, Tucson, Arizona, USA.Department of Medical Education, TCU and UNTHSC School of Medicine, Fort Worth, TX, USA.
Department of Physiology, University of Arizona, Tucson, Arizona, USA.
GEMM Core, Bio5 Institute, University of Arizona, Tucson, Arizona, USA.
Abnormal lymphatic phenotype in a CRISPR mouse model of the human lymphedema-causing Connexin47 R260C point mutation.

Soybean is largely grown and considered among the top oilseed crops. Three Pakistani cultivars, NARC-II (N), Swat-84 (S), and Rawal-I (R) were employed for RNA-Seq based transcriptome analysis to explore their genetic potential and performance in our local environment.We grew the plants in glass house at same conditions and sampled leaves for RNA-Seq analysis in triplicate for each variety. We retrieved 2225 differentially expressed genes (DEGs) between S vs R, 2591 DEGs between S vs N, and 1221 DEGs between R vs N cultvars. These genes consist of transcription factors representing Basic Helix-loop Helix, myeloblastosis, ethylene response factors, and WRKY amino acid motif (WRKY) type major families that were up-regulated. KEGG pathway analysis revealed that MAPK, plant hormone signal transduction, and Phenylpropanoid biosynthesis pathways were the most dominant pathways involved in plant defense and growth. Comparative analysis showed that Swat-84 (S) cultivar had better gene expression among these varieties having higher number of DEGs, where mostly genes related to important phenotypic traits were up regulated.This is a pilot study to investigate and functionally characterise the DEG involved in the stress response in the cultivars studied.
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan. waseem_haider@comsats.edu.pk.
Exploring the genetic potential of Pakistani soybean cultivars through RNA-seq based transcriptome analysis.

In response to the COVID-19 pandemic, the US DEA allowed controlled substance prescriptions to be issued following a telemedicine encounter. This study evaluated changes in opioid prescribing in Kentucky counties with low and high rates of broadband subscription before, during, and after a series of statewide emergency declarations that may have affected health care access.The study used the prescription drug monitoring program to analyze records of opioid analgesic prescriptions dispensed to opioid-naïve individuals in high (N = 26) and low (N = 94) broadband access counties during 3 periods: before a state of emergency (SOE) and executive order (EO) limiting nonemergent health care services (January 2019-February 2020), while the EO was active (March-April 2020), and after health care services began reopening (May-December 2020). Marginal generalized estimating equations-type negative binomial models were fit to compare prescription counts by broadband access over the 3 periods.Rates of opioid dispensing to opioid-naïve individuals decreased significantly during the EO, but increased nearly to pre-SOE levels after health care services began reopening. Dispensing rates in low broadband counties were higher than those in high broadband counties during all time periods, although these differences were negligible after adjusting for potential confounders. During the EO, prescriptions were written for longer days' supply in both county types.The overall dramatic reduction in opioid prescribing rates should be considered when evaluating annual opioid prescribing trends. However, broadband subscription rate did not appear to influence opioid prescriptions dispensed in Kentucky during the EO.
© 2022 National Rural Health Association.
Department of Pharmacy Practice and Science, University of Kentucky, Lexington, Kentucky, USA.
Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.Kentucky Injury Prevention and Research Center, University of Kentucky, Lexington, Kentucky, USA.
Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky, USA.
Department of Biomedical Informatics, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Department of Behavioral Science, University of Kentucky, Lexington, Kentucky, USA.Center on Drug and Alcohol Research, University of Kentucky, Lexington, Kentucky, USA.
The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association
Broadband internet subscription rates and opioid prescribing via telemedicine during the COVID-19 pandemic.

Exome and genome sequencing have drastically accelerated novel disease gene discoveries. However, discovery is still hindered by myriad variants of uncertain significance found in genes of undetermined biological function. This necessitates intensive functional experiments on genes of equal predicted causality, leading to a major bottleneck.We apply the loss-of-function observed/expected upper-bound fraction metric of intolerance to gene inactivation to curate a list of predicted haploinsufficient disease genes. Using data from the 100,000 Genomes Project, we adopt a gene-to-patient approach that matches de novo loss-of-function variants in constrained genes to patients with rare disease. Through large-scale aggregation of data, we reduce excess analytical noise currently hindering novel discoveries.Results from 13,949 trios revealed 643 rare, de novo predicted loss-of-function events filtered from 1044 loss-of-function observed/expected upper-bound fraction-constrained genes. A total of 168 variants occurred within 126 genes without a known disease-gene relationship. Of these, 27 genes had >1 kindred affected, and for 18 of these genes, multiple kindreds had overlapping phenotypes. Two years after initial analysis, 11 of 18 (61%) of these genes have been independently published as novel disease gene discoveries.Using large cohorts and adopting gene-based approaches can rapidly and objectively accelerate dominantly inherited novel gene discovery by targeting the most appropriate genes for functional validation.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Program in Medical and Population Genetics, Broad institute of MIT and Harvard, Boston, MA; Center for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA. Electronic address: E.Seaby@soton.ac.uk.
Genomics England, Dawson Hall, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Program in Medical and Population Genetics, Broad institute of MIT and Harvard, Boston, MA; Center for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA.
Program in Medical and Population Genetics, Broad institute of MIT and Harvard, Boston, MA; Center for Genomic Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA.
Genetics in medicine : official journal of the American College of Medical Genetics
A gene-to-patient approach uplifts novel disease gene discovery and identifies 18 putative novel disease genes.

Spinal cord injury (SCI) is a common disease of the nervous system, including primary and secondary injuries. Neuronal inflammation after SCI is the most important pathological process of SCI and a chemical barrier to nerve function recovery after injury. Ski, an evolutionarily conserved functional transcriptional regulator protein, is upregulated in reactive astrocytes after SCI and regulates the biological characteristics of astrocytes. However, its role in the glial inflammatory response triggered by reactive astrocytes after spinal cord ischemia and its exact mechanism remains unclear. This study investigated the role and mechanism of Ski in the inflammatory response triggered by reactive astrocytes induced by oxygen and sugar deprivation/reoxygenation (OGD/R) model in vitro. In the ODG/R model, Ski expression was upregulated. In contrast, Ski upregulation was accompanied by increased levels of iNOS, IL-1β, IL-6, TNF-α, and other inflammation-related factors. These results indicated that the inflammatory response triggered by astrocytes was significantly enhanced in OGD/R-stimulated astrocytes. Astrocytes were transfected with Ski specific siRNA to knock out Ski and subsequently attenuate OGD-induced astrocyte-triggered inflammation. Our results also suggest that Ski downregulation downregulates the expression of iNOS, IL-1β, IL-6, and TNF-α in OGD/R-induced reactive astrocytes by inhibiting the activity of the NF-κB signaling pathway. In conclusion, downregulation of Ski can effectively inhibit glial inflammation in SCI by inhibiting the activity of the NF-κB pathway. These findings suggest that Ski is a promising therapeutic target for inflammatory responses after SCI.In conclusion, Ski downregulation can effectively inhibit glial inflammation in SCI by inhibiting the activity of the NF-κB pathway. These findings suggest that Ski might serve as a promising target for the treatment of inflammatory responses after SCI.
Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
The Second Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou 730000, PR China.
The Second Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou 730000, PR China; Gansu Provincial Maternal and Child Health Hospital, 143 Qilihe North Street, Lanzhou 730050, PR China.
The Second Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou 730000, PR China. Electronic address: 840620161@qq.com.
Ski Regulates the Inflammatory Response of Reactive Astrocytes Induced by Oxygen Glucose Deprivation/Reoxygenation (OGD/R) Through the NF-κB Pathway.

To improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measurement uncertainty U Meas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that U Meas decreased 59.3-80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of U Meas could be explained by improved measurement procedures as well as a higher standardization. The vast majority (89.6%) of the individual responses pc i exceeded the 95% confidence interval defined by U Meas , indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the epiphyseal measurement sites. Non-significant to small positive inter-site correlations between bone sites, but very large positive inter-site correlation between muscle sites suggests that substantial WSV exists in the tibia bone, but much less so in the calf musculature. Furthermore, endocortical circumference, an indicator of the individual's bone geometry could partly explain WSV and BSV. These results demonstrate the existence of substantial BSV bone, and that it is partly driven by WSV, and likely also by physical activity and dietary habits prior to bed rest. In addition, genetic and epigenetic variation could potentially explain BSV, but not WSV. As to the latter, differences of bone characteristics and the bone resorption process could offer an explanation for its existence. The study has also demonstrated the importance of duplicate baseline measurements. Finally, we provide here a rationale for worst case scenarios with partly effective countermeasures in long-term space missions.
Copyright © 2022 Böcker, Schmitz, Mittag, Jordan and Rittweger.
Department of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, Germany.
Department of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, Germany.Institute of Medical Biometry, Informatics and Epidemiology (IMBIE), University Hospital Bonn, Bonn, Germany.
Chair of Aerospace Medicine, University of Cologne, Cologne, Germany.German Aerospace Center, Head of Institute of Aerospace Medicine, Cologne, Germany.
Department of Muscle and Bone Metabolism, German Aerospace Center, Institute of Aerospace Medicine, Cologne, Germany.Department of Pediatrics and Adolescent Medicine, University Hospital of Cologne, Cologne, Germany.
Between-Subject and Within-Subject Variaton of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons leading to skeletal muscle denervation. Earlier studies have shown that motor neuron degeneration begins in motor cortex and descends to the neuromuscular junction (NMJ) in a dying forward fashion. However, accumulating evidences support that ALS is a distal axonopathy where early pathological changes occur at the NMJ, prior to onset of clinical symptoms and propagates towards the motor neuron cell body supporting dying back hypothesis. Despite several evidences, series of events triggering NMJ disassembly in ALS are still obscure. Neuromuscular junction is a specialized tripartite chemical synapse which involves a well-coordinated communication among the presynaptic motor neuron, postsynaptic skeletal muscle, and terminal Schwann cells. This review provides comprehensive insight into the role of NMJ in ALS pathogenesis. We have emphasized the molecular alterations in cellular components of NMJ leading to loss of effective neuromuscular transmission in ALS. Further, we provide a preview into research involved in exploring NMJ as potential target for designing effective therapies for ALS.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Department of Research, Sir Ganga Ram Hospital, Delhi, India.Department of Biotechnology, Jamia Hamdard, Delhi, India.
Department of Research, Sir Ganga Ram Hospital, Delhi, India.Department of Biomedical Science, Bhaskaracharya College of Applied Sciences, University of Delhi, Delhi, India.
Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Research, Sir Ganga Ram Hospital, Delhi, India.
Department of Biotechnology, Jamia Hamdard, Delhi, India.
Department of Neurophysiology, Sir Ganga Ram Hospital, Delhi, India.
Department of Research, Sir Ganga Ram Hospital, Delhi, India. vibha.taneja@sgrh.com.
Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.

Coronavirus disease 2019 (COVID-19) is now the third leading cause of death in the United States. Malnutrition in hospitalized patients increases risk of complications. However, the effect of malnutrition on outcomes in patients infected is unclear. This study aims to identify the impact of malnutrition on mortality and adverse hospital events in patients hospitalized with COVID-19.This study used data from the National COVID Cohort Collaborative (N3C), a COVID-19 repository containing harmonized, longitudinal electronic health record data from US health systems. Malnutrition was categorized into three groups based on condition diagnosis: (1) none documented, (2) history of malnutrition, and (3) hospital-acquired malnutrition. Multivariable logistic regression was performed to determine whether malnutrition was associated with mortality and adverse events, including mechanical ventilation, acute respiratory distress syndrome, extracorporeal membrane oxygenation, and hospital-acquired pressure injury, in hospitalized patients with COVID-19.Of 343,188 patients hospitalized with COVID-19, 11,206 had a history of malnutrition and 15,711 had hospital-acquired malnutrition. After adjustment for potential confounders, odds of mortality were significantly higher in patients with a history of malnutrition (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.63-1.79; P < 0.001) and hospital-acquired malnutrition (OR, 2.5; 95% CI, 2.4-2.6; P < 0.001). Adjusted odds of adverse hospital events were also significantly elevated in both malnutrition groups.Results indicate the risk of mortality and adverse inpatient events in adults with COVID-19 is significantly higher in patients with malnutrition. Prevention, diagnosis, and treatment of malnutrition could be a key component in improving outcomes in these patients.
© 2022 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.
University of Nebraska Medical Center, College of Allied Health Professions, Omaha, Nebraska, USA.Department of Pharmaceutical and Nutrition Care, Nebraska Medicine, Omaha, Nebraska, USA.
Department of Neurological Sciences, University of Nebraska Medical Center, College of Medicine, Omaha, Nebraska, USA.Great Plains IDeA-CTR, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Department of Internal Medicine, University of Nebraska Medical Center, College of Medicine, Omaha, Nebraska, USA.Veterans Administration Nebraska-Iowa Health Systems, Omaha, Nebraska, USA.
Department of Biostatistics, University of Nebraska Medical Center, College of Public Health, Omaha, Nebraska, USA.
University of Nebraska Medical Center, College of Allied Health Professions, Omaha, Nebraska, USA.
Department of Emergency Medicine, University of Nebraska Medical Center, College of Medicine, Omaha, Nebraska, USA.
National COVID Cohort Collaborative (N3C) Consortium
JPEN. Journal of parenteral and enteral nutrition
Impact of malnutrition on clinical outcomes in patients diagnosed with COVID-19.

To compare the effects of different thyroid screening scenarios, using the universal and targeted high-risk case-finding approaches with different diagnostic tests on the prevalence of subclinical hypothyroidism (SCH), thyroid autoimmunity, and pregnancy outcomes after adjustments for the intervention.During a secondary analysis of data collected in Tehran Thyroid and Pregnancy Study, a total of 2277 women from the total population, including 1303 high-risk individuals for thyroid dysfunction. The Cochran-Mantel-Haenszel method, adjusted for the intervention, was also used to evaluate the relationships between different screening scenarios [i.e., universal approach using thyroid-stimulating hormone (TSH) and/or thyroid peroxidase antibody (TPOAb) tests and targeted high-risk case-finding approach using TSH and/or TPOAb tests] and pregnancy outcomes (i.e., preterm delivery and NICU admission). The universal approach using both TSH and TPOAb measurements was considered as the reference scenario. We analyzed outcomes of different screening methods in individuals treated with LT4, compared to those individuals who were not treated.Compared to the universal screening approach with both TSH and TPOAb measurements, the targeted high-risk case-finding approach overlooked approximately 42%, 62%, and 74% of women with elevated TSH (> 4 µlU/mL) when using both TSH and TPOAb tests, TSH alone, and TPO alone, respectively. After adjusting for the missed cases, 2.86% of women with preterm delivery and 2.76% of women with NICU admission were missed when they were screened using the targeted high-risk case-finding approach by measuring both TSH and TPOAb. The percentage of missed cases increased when applying the targeted approach with the TSH test alone, without measuring TPOAb. Overall, 4.16% and 4.02% of women with preterm delivery and NICU admission were overlooked in this scenario, respectively. After adjustments for the intervention, the probability of NICU admission in neonates of mothers, who were screened using the targeted high-risk case-finding approach with TPOAb measurement, was 2.31 folds higher than those screened by the reference scenario.This study suggests that although the targeted high-risk case-finding approach including both TSH and TPOAb tests, may overlook some women with SCH, it is a reasonable option since it is not associated with a higher risk of adverse pregnancy outcomes.
© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).
Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.
Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.Department of Midwifery, Varamin-Pishva Branch, Islamic Azad University, Tehran, Iran.
Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran. fah.tehrani@gmail.com.
Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Journal of endocrinological investigation
The targeted high-risk case-finding approach versus universal screening for thyroid dysfunction during pregnancy: thyroid-stimulating hormone (TSH) and/or thyroid peroxidase antibody (TPOAb) test?

In early 2020, the California National Primate Research Center implemented surveillance to address the threat of SARS-CoV-2 infection in its nonhuman primate colony.To detect antiviral antibodies, multi-antigen assays were developed and validated on enzyme immunoassay and multiplex microbead immunofluorescent assay (MMIA) platforms. To detect viral RNA, RT-PCR was also performed.Using a 4plex, antibody was identified in 16/16 experimentally infected animals; and specificity for spike, nucleocapsid, receptor binding domain, and whole virus antigens was 95.2%, 93.8%, 94.3%, and 97.1%, respectively on surveillance samples. Six laboratories compared this MMIA favorably with nine additional laboratory-developed or commercially available assays. Using a screen and confirm algorithm, 141 of the last 2441 surveillance samples were screen-reactive requiring confirmatory testing. Although 35 samples were reactive to either nucleocapsid or spike; none were reactive to both. Over 20 000 animals have been tested and no spontaneous infections have so far been confirmed across the NIH sponsored National Primate Research Centers.
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Primate Assay Laboratory, California National Primate Research Center, University of California, Davis, Davis, California, USA.
Primate Assay Laboratory, California National Primate Research Center, University of California, Davis, Davis, California, USA.Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Primate Assay Laboratory, California National Primate Research Center, University of California, Davis, Davis, California, USA.Department Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Developing and validating SARS-CoV-2 assays for nonhuman primate surveillance.

The extensive use of the insecticide chlorpyrifos (CPF) throughout the world has brought increased scrutiny on its environmental and health impact. CPF is a cholinergic neurotoxicant; however, exposure to low noncholinergic doses is associated with numerous neurodevelopmental effects in animal models. In this study, we aimed to assess CPF for its potential to disrupt thyroid hormone signalling and investigate the short- and long-term effects on neurodevelopment by using Xenopus laevis.The thyroid hormone (TH) disrupting potential of CPF was assessed using TH-sensitive transgenic Tg(thibz:eGFP) tadpoles. The consequences of early embryonic exposure were examined by exposing fertilized eggs for 72 h to environmentally relevant CPF concentrations (10-10 M and 10-8 M). Three endpoints were evaluated: (1) gene expression in whole embryonic brains immediately after exposure, (2) mobility and brain morphology 1 week after exposure, and (3) brain morphology and axon diameters at the end of metamorphosis (2 months after the exposure).CPF disrupted TH signalling in Tg(thibz:eGFP) tadpoles. The expression of genes klf9, cntn4, oatp1c1, and tubb2b was downregulated in response to CPF. Tadpoles exposed to CPF exhibited increased mobility and altered brain morphology compared to control tadpoles. Early embryonic exposure of CPF affected myelinated axon diameter, with exposed animals exhibiting shifted frequency distributions of myelinated axons diameters towards smaller diameters in the hindbrain of froglets.This study provides more evidence of the endocrine and neurodevelopment disrupting activity of CPF. Further experimental and epidemiological studies are warranted to determine the long-term consequences of early CPF exposure on brain development.
Unité PhyMA Laboratory, Adaptation du Vivant, Muséum National d'Histoire Naturelle, Paris, France.Unité Eco-Anthropologie, Hommes et Environnements, Muséum National d'Histoire Naturelle, Musée de l'Homme, Paris, France.Laboratoire de Métrologie et d'Essais, Paris, France.
Unité PhyMA Laboratory, Adaptation du Vivant, Muséum National d'Histoire Naturelle, Paris, France.
Unité Eco-Anthropologie, Hommes et Environnements, Muséum National d'Histoire Naturelle, Musée de l'Homme, Paris, France.
Short- and Long-Term Effects of Chlorpyrifos on Thyroid Hormone Axis and Brain Development in Xenopus laevis.

Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Division of Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Department of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
The nasopharyngeal and salivary microbiomes in COVID-19 patients with and without asthma.

As the number of cancer survivors continues to increase and given the shortage of oncology clinicians in safety net health care settings, primary care providers (PCPs) in these settings will increasingly provide cancer survivorship care. In order to ensure equitable care for low-income and underserved breast and colon cancer survivors, it is essential to understand the safety-net PCPs' perspective. We conducted semi-structured, in-depth qualitative interviews with 11 PCPs working in a safety-net health care system to identify their needs in caring for cancer survivors. Interviews were audio-recorded and professionally transcribed. Two coders independently coded the interviews and conducted regular meetings until we reached consensus on the results. Analysis was based in grounded theory and performed using the constant comparative method. Thematic analysis identified six themes as follows: (1) Cancer survivorship care can be integrated with the whole person and chronic disease care management that occurs in primary care; (2) PCPs' perceptions regarding patients' survivorship care needs and their confidence in meeting those needs; (3) preference for a shared care model; (4) coordination of care; (5) PCPs' need for survivorship care education and training; and (6) unique issues involved in the care of older cancer survivors. PCPs in the safety-net believe that providing comprehensive survivorship care requires coordination of care through the cancer continuum. Tools like checklists, electronic health records-based communication, and convenient electronic consultations with cancer specialists would enhance the quality of survivorship care. Respondents advocate the inclusion of survivorship care education in medical education. The continuity of care with PCPs means that they play a particularly important role in the care of older cancer survivors.
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Niharika.dixit@ucsf.edu.
Hematology/Oncology, Stanford School of Medicine, Palo Alto, CA, USA.
Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.Center for Vulnerable Populations, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
School of Social Sciences, Humanities, and Arts, University of California Merced, Merced, CA, USA.
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Intramural Research, National Institute On Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
Journal of cancer education : the official journal of the American Association for Cancer Education
Identifying the Needs of Primary Care Providers Caring for Breast and Colon Cancer Survivors in the Safety-Net: a Qualitative Study.

Adolescents' daily lives have been disrupted during the Coronavirus disease 2019 (COVID-19) pandemic. It remains unclear how changes in adolescents' daily physical and social behaviours affect their sleep. The present study examined the daily and average effects of physical activity and social media use (i.e., video chatting, texting, and social networking sites) on adolescent girls' sleep during the COVID-19 pandemic. Adolescent girls aged 12-17 years (N = 93; 69% White) from a larger longitudinal study completed a 10-day daily diary protocol during state-mandated stay-at-home orders. Girls reported on daily sleep (duration, timing, quality), physical activity, and social media use during COVID-19. Multilevel modelling was used to examine the within- and between-person effects of physical activity and social media on sleep duration, timing, and quality during the 10-day period. Between-person associations indicate that youth with greater social media use (texting, video chatting, and social networking) and less physical activity had later sleep timing across the 10-day study period. Only video chatting was associated with shorter sleep duration. There were no within-person effects of physical activity or social media activities on sleep outcomes. Findings indicate that physical activity and social media use may impact later adolescent sleep timing during the COVID-19 pandemic. It will be critical for research to examine the potential long-term costs of delayed sleep timing, and whether targeting specific youth behaviours associated with sleep and circadian disruption improve mental and physical health during the COVID-19 pandemic and beyond.
© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.
Department of Psychology, Rutgers University, New Brunswick, New Jersey, USA.
Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Daily and average associations of physical activity, social media use, and sleep among adolescent girls during the COVID-19 pandemic.

Maternal behavior depends on a multitude of factors, including environmental ones, such as Endocrine Disrupting Chemicals (EDCs), which are increasingly attracting attention. Bisphenol A (BPA), an EDC present in plastic, is known to exert negative effects on maternal behavior. Bisphenol S (BPS), a BPA substitute, seems to share some endocrine disrupting properties. In this study, we focused on the analysis of the effects of low-dose (i.e., 4 µg/kg body weight/day, EFSA TDI for BPA) BPA or BPS exposure throughout pregnancy and lactation in mice.We administered adult C57BL/6 J females orally BPA, BPS, or vehicle from mating to offspring weaning. We assessed the number of pups at birth, the sex ratio, and the percentage of dead pups in each litter, and during the first postnatal week, we observed spontaneous maternal behavior. At the weaning of the pups, we sacrificed the dams and analyzed the oxytocin system, known to be involved in the control of maternal care, in the hypothalamic magnocellular nuclei.At birth, pups from BPA-treated dams tended to have a lower male-to-female ratio compared to controls, while the opposite was observed among BPS-treated dams' litters. During the first postnatal week, offspring mortality impacted differentially in the BPA and BPS litters, with more female dead pups among the BPA litters, while more male dead pups in the BPS litters, sharpening the difference in the sex ratio. BPA- and BPS-treated dams spent significantly less time in pup-related behaviors than controls. Oxytocin immunoreactivity in the paraventricular and supraoptic nuclei was increased only in the BPA-treated dams.Alterations in maternal care, along with the treatment itself, may affect, later in life, the offspring's physiology and behavior. Exposure to BPs during sensitive developmental periods represents a risk for both dams and offspring, even at low environmentally relevant doses, through the functional alteration of neural circuits controlling fundamental behaviors for pup survival, such as maternal behaviors.
Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, Turin, Italy.Department of Neuroscience Rita Levi-Montalcini, University of Turin, Turin, Italy.
Unit of Neuroscience, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Exposure to either Bisphenol A or S Represents a Risk for Crucial Behaviors for Pup Survival, Such as Spontaneous Maternal Behavior in Mice.

Female survivors of endometrial and rectal cancers have increased risk of urinary incontinence. Survivors with prior radiation therapy are counseled against mesh incontinence surgery. We hypothesize that urethral radiation dose varies based on modality which may influence surgical risks. We aimed to demonstrate urethral radiation dose differences between vaginal brachytherapy (VBT) and external beam radiation therapy (EBRT).This is a retrospective cohort study of women exposed to VBT for endometrial cancer and EBRT for rectal cancer. The urethra was contoured on CT imaging to calculate radiation doses in centigray (cGy). The primary outcome was the percent of treatment radiation dose estimated to be received by the urethra based on the volume dose to 0.2 cc of urethra. Secondary outcomes were point doses to the bladder neck, mid-urethra, and total mean urethral dose. Descriptive statistics described demographic characteristics. Bivariate analyses compared urethral radiation dose based on radiation modality.Between 2014-2017, 32 women treated were included: 18 with VBT and 14 with EBRT. Mean ± SD urethral volume doses were lower in VBT (1266 cGy ± 533, 42.2% of prescribed treatment dose) compared to EBRT (5051 cGy ± 192, 100.2% of prescribed treatment dose), p < 0.0001. VBT also had significantly lower mean total urethral dose and point doses to bladder neck and mid- urethra compared to EBRT (p < 0.0001).The female urethra is exposed to significantly less radiation in VBT compared to EBRT. These data highlight that modality of pelvic radiation should be considered in treatment counseling on urinary incontinence in women.
© 2022. The International Urogynecological Association.
Wake Forest Department of Urology, Division of Female Pelvic Health, Winston-Salem, NC, USA.
Wake Forest Department of Radiation Oncology, Winston-Salem, NC, USA.
Wake Forest School of Medicine, Winston-Salem, NC, USA.
Wake Forest Department of Urology, Division of Female Pelvic Health, Winston-Salem, NC, USA. cparkera@wakehealth.edu.
An assessment of urethral radiation exposure in the treatment of endometrial and rectal cancers.

Coronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with six million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID-19-caused death, effective medication to relieve COVID-19-associated symptoms and alleviate disease progression is still in high demand. In particular, one in three COVID-19 patients have signs of long COVID syndrome and are termed, long haulers. At present, there are no effective ways to treat long haulers. In this study, we determine the effectiveness of inhibiting mitogen-activated protein kinase (MEK) signaling in preventing SARS-CoV-2-induced lung damage in mice. We showed that phosphorylation of extracellular signal-regulated kinase, a marker for MEK activation, is high in SARS-CoV-2-infected lung tissues of mice and humans. We also showed that selumetinib, a specific inhibitor of the upstream MEK kinases, reduces cell proliferation, reduces lung damage following SARS-CoV-2 infection, and prolongs the survival of the infected mice. Selumetinib has been approved by the US Food and Drug Administration to treat cancer. Further analysis indicates that amphiregulin, an essential upstream molecule, was upregulated following SARS-CoV-2 infection. Our data suggest that MEK signaling activation represents a target for therapeutic intervention strategies against SARS-CoV-2-induced lung damage and that selumetinib may be repurposed to treat COVID-19.
© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
Department of Pediatrics, The Wells Center for Pediatrics Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Inhibition of MEK signaling prevents SARS-CoV2-induced lung damage and improves the survival of infected mice.

Division of Pediatric Pulmonology, Allergy & Immunology, Weill Cornell Medicine, New York, New York, USA.
Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA.
Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA.
Department of Pediatrics, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, New York, USA.
Division of Pediatric Pulmonology, Allergy & Immunology, Weill Cornell Medicine, New York, New York, USA.Drukier Institute for Children's Health, Weill Cornell Medicine, New York, New York, USA.Department of Genetic Medicine, Weill Cornell Medicine, New York, New York, USA.
Division of Pediatric Pulmonology, Allergy & Immunology, Weill Cornell Medicine, New York, New York, USA.Drukier Institute for Children's Health, Weill Cornell Medicine, New York, New York, USA.
Asthma 17q21 polymorphism associates with decreased risk of COVID-19 in children.

Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.Division of Otolaryngology, Department of Surgery, Veterans Affairs, Birmingham, Alabama, USA.
International forum of allergy & rhinology
Gabapentin improves parosmia after COVID-19 infection.

Hippocampal newborn neurons integrate into functional circuits where they play an important role in learning and memory. We previously showed that perinatal exposure to Aroclor 1254, a commercial mixture of polychlorinated biphenyls (PCBs) associated with alterations of cognitive function in children, disrupted the normal maturation of excitatory synapses in the dentate gyrus. We hypothesized that hippocampal immature neurons underlie some of the cognitive effects of PCBs.We used newly generated neurons to examine the effects of PCBs in mice following maternal exposure. Newborn dentate granule cells were tagged with enhanced green fluorescent protein using a transgenic mouse line. The transcriptome of the newly generated granule cells was assessed using RNA sequencing.Gestational and lactational exposure to 6 mg/kg/day of Aroclor 1254 disrupted the mRNA expression of 1,308 genes in newborn granule cells. Genes involved in mitochondrial functions were highly enriched with 154 genes significantly increased in exposed compared to control mice. The upregulation of genes involved in oxidative phosphorylation was accompanied by signs of endoplasmic reticulum stress and an increase in lipid peroxidation, a marker of oxidative stress, in the subgranular zone of the dentate gyrus but not in mature granule cells in the granular zone. Aroclor 1254 exposure also disrupted the expression of synaptic genes. Using laser-captured subgranular and granular zones, this effect was restricted to the subgranular zone, where newborn neurons are located.Our data suggest that gene expression in newborn granule cells is disrupted by Aroclor 1254 and provide clues to the effects of endocrine-disrupting chemicals on the brain.
Neuroendocrinology Unit, GIGA-Neurosciences, University of Liège, Liège, Belgium.
Vollum Institute, Oregon Health and Science University, Portland, Oregon, USA.
Cellular and Tissular Biology, GIGA-Neurosciences, University of Liège, Liège, Belgium.
Induction of Oxidative Stress and Alteration of Synaptic Gene Expression in Newborn Hippocampal Granule Cells after Developmental Exposure to Aroclor 1254.

Flame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported that developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown.To further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses.The neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs being more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to a higher risk of autism spectrum disorders and neurodegenerative disorders. Impacted lipid classes included ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest a heightened risk of brain metabolic disease.This study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern.
Department of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Department of Chemistry, NC State University, Raleigh, North Carolina, USA.
Department of Biological Sciences, NC State University, Raleigh, North Carolina, USA.Center for Human Health and the Environment, NC State University, Raleigh, North Carolina, USA.
Center for Human Health and the Environment, NC State University, Raleigh, North Carolina, USA.
Impacts of Gestational FireMaster 550 Exposure on the Neonatal Cortex Are Sex Specific and Largely Attributable to the Organophosphate Esters.

Implementation of new skilled nursing facility (SNF) Medicare payment policy, the Patient Driven Payment Model (PDPM), resulted in immediate declines in physical and occupational therapy staffing. This study characterizes continuing impacts of PDPM in conjunction with COVID-19 on SNF therapy staffing and examines variability in staffing changes based on SNF organizational characteristics.We analyzed Medicare administrative data from a national cohort of SNFs between January 2019 and March 2022. Interrupted time series mixed effects regression examined changes in level and trend of total therapy staffing minutes/patient-day during PDPM and COVID-19 and by type of staff (therapists, assistants, contractors, and in-house staff). Secondary analyses examined the variability in staffing by organizational characteristics.PDPM resulted in a -6.54% level change in total therapy staffing, with larger declines for assistants and contractors. Per-patient staffing fluctuated during COVID-19 as the census changed. PDPM-related staffing declines were larger in SNFs that were: Rural, for-profit, chain-affiliated, provided more intensive therapy, employed more therapy assistants, and admitted more Medicare patients before PDPM. COVID-19 resulted in larger staffing declines in rural SNFs but smaller early declines in SNFs that were hospital-based, for-profit, or received more relief funding.SNFs that historically engaged in profit-maximizing behaviors (e.g., providing more therapy via lower-paid assistants) had larger staffing declines during PDPM compared to other SNFs. Therapy staffing fluctuated during COVID-19, but PDPM-related reductions persisted 2 years into the pandemic, especially in rural SNFs. Results suggest specific organizational characteristics that should be targeted for staffing and quality improvement initiatives.
Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA.
Department of Occupational Therapy, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Center for Health Workforce Studies, Department of Family Medicine, University of Washington, Seattle, Washington, USA.
UCLA Borun Center, University of California Los Angeles, Los Angeles, California, USA.Geriatric Research Education & Clinical Center, VA Geriatric Research Education and Clinical Center, Los Angeles, California, USA.RAND Corporation, Santa Monica, California, USA.
Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA.Center for Health Workforce Studies, Department of Family Medicine, University of Washington, Seattle, Washington, USA.
Journal of the American Geriatrics Society
Dual impacts of Medicare payment reform and the COVID-19 pandemic on therapy staffing in skilled nursing facilities.

Adapting drug treatments for patients on hemodialysis with multiple chronic pathologies is a complex affair. When prescribing a medication, the risk-benefit analysis usually focuses primarily on the indication of the drug class prescribed. However, the pharmacokinetics of the chosen drug should also be taken into account. The purpose of our review was to identify the drugs to be favored in each therapeutic class, according to their safety and pharmacokinetic profiles, for the most common chronic diseases in patients on chronic hemodialysis.We conducted a narrative review of the literature using Medline and Web of Science databases, targeting studies on the most commonly-prescribed drugs for non-communicable diseases in patients on chronic hemodialysis.The search identified 1224 articles, 95 of which were further analyzed. The main classes of drugs included concern the cardiovascular system (anti-hypertensives, anti-arrhythmics, anti-thrombotics, hypocholesterolemics), the endocrine and metabolic pathways (anti-diabetics, gastric anti-secretory, anticoagulant, thyroid hormones, anti-gout) and psychiatric and neurological disorders (antidepressants, anxiolytics, antipsychotics and anti-epileptics).We report on the most often prescribed drugs for chronic pathologies in patients on chronic hemodialysis. Most of them require adaptation, and in some cases one better alternative stands out among the drug class. More pharmacokinetic data are needed to define the pharmacokinetics in the various dialysis techniques.
© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.
Service Pharmacie, Hopital Universitaire de Nimes, CHU Carémeau, Nîmes, France. Clarisse.roux@chu-nimes.fr.Institut Desbrest d'Epidemiologie et Santé publique (IDESP), INSERM, Montpellier, France. Clarisse.roux@chu-nimes.fr.
Service Pharmacie, Hopital Universitaire de Nimes, CHU Carémeau, Nîmes, France.
Institut Desbrest d'Epidemiologie et Santé publique (IDESP), INSERM, Montpellier, France.Service Néphrologie Dialyse Apherese, Hopital Universitaire de Nimes, CHU Carémeau, Nîmes, France.
Service Néphrologie Dialyse Apherese, Hopital Universitaire de Nimes, CHU Carémeau, Nîmes, France.
Institut Desbrest d'Epidemiologie et Santé publique (IDESP), INSERM, Montpellier, France. olivier.moranne@chu-nimes.fr.Service Néphrologie Dialyse Apherese, Hopital Universitaire de Nimes, CHU Carémeau, Nîmes, France. olivier.moranne@chu-nimes.fr.
Choosing the right chronic medication for hemodialysis patients. A short ABC for the dialysis nephrologist.

The continuing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with decreased susceptibility to neutralizing antibodies is of clinical importance. Several spike mutations associated with immune escape have evolved independently in association with different variants of concern (VOCs). How and when these mutations arise is still unclear. We hypothesized that such mutations might arise in the context of persistent viral replication in immunosuppressed hosts.Nasopharyngeal specimens were collected longitudinally from two immunosuppressed patients with persistent SARS-CoV-2 infection. Plasma was collected from these same patients late in disease course. SARS-CoV-2 whole genome sequencing was performed to assess the emergence and frequency of mutations over time. Select Spike mutations were assessed for their impact on viral entry and antibody neutralization in vitro.Our sequencing results revealed the intrahost emergence of spike mutations that are associated with circulating VOCs in both immunosuppressed patients (del241-243 and E484Q in one patient, and E484K in the other). These mutations decreased antibody-mediated neutralization of pseudotyped virus particles in cell culture, but also decreased efficiency of spike-mediated cell entry.These observations demonstrate the de novo emergence of SARS-CoV-2 spike mutations with enhanced immune evasion in immunosuppressed patients with persistent infection. These data suggest one potential mechanism for the evolution of VOCs and emphasize the importance of continued efforts to develop antiviral drugs for suppression of viral replication in hospitalized settings.
© 2022 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.
Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, Illinois, USA.
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA.
Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Transplant infectious disease : an official journal of the Transplantation Society
De novo emergence of SARS-CoV-2 spike mutations in immunosuppressed patients.

An increasing number of international studies demonstrate serious negative effects of the COVID-19 pandemic on the timely diagnosis of cancer and on cancer treatment. Our study aimed to quantitatively and qualitatively evaluate the capacities of German Comprehensive Cancer Centers (CCCs) in different areas of complex oncology care during the first 2 years of the COVID-19 pandemic.Prospective panel survey over 23 rounds among 18 CCCs in Germany between March 2020 and June 2022.The COVID-19 pandemic substantially affected the oncological care system in Germany during the first 2 years. Persistent limitations of care in CCCs primarily affected follow-up (- 21%) and psycho-oncologic care (- 12%), but also tumor surgery (- 9%). Substantial limitations were also reported for all other areas of multidisciplinary oncological care.This study documents the limitations of oncological care during the COVID-19 pandemic and highlights the need to develop strategies to avoid similar limitations in the future.
Division of Clinical Epidemiology and Aging Research (C070), Unit of Cancer Survivorship (C071), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. v.arndt@dkfz-heidelberg.de.
Division of Clinical Epidemiology and Aging Research (C070), Unit of Cancer Survivorship (C071), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Urology, Comprehensive Cancer Center/Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Comprehensive Cancer Center München, Institute for Tumor Metabolism, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany.
Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
Medical Clinic and Polyclinic II, Center for Oncology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Medical Clinic I, National Center for Tumor Diseases (NCT/UCC), University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
University Cancer Center (UCT) Frankfurt-Marburg, Frankfurt University Hospital, Frankfurt, Germany.
Medical Clinic III and Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), University Hospital Bonn, Bonn, Germany.
Comprehensive Cancer Center Tübingen-Stuttgart and Department of Women's Health, University Hospital Tübingen, Tübingen, Germany.
Medical Clinic IV and Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), University Hospital of RWTH Aachen, Aachen, Germany.
Comprehensive Cancer Center Ulm (CCCU) and Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
Department of Hematology, Oncology and Clinical Immunology, Comprehensive Cancer Center/Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Clinic I for Internal Medicine and Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), University Hospital Cologne, Cologne, Germany.
Medical Clinic and Polyclinic III, LMU Hospital, Munich, Germany.
Charité Comprehensive Cancer Center (CCCC), Berlin, Germany.
University Cancer Center (UCT), University Medical Center Mainz, Mainz, Germany.
University Cancer Center Leipzig and Department of Medicine II, University of Leipzig Medical Center, Leipzig, Germany.
Department of Visceral and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany.
Tumor Center Freiburg, Institute of Molecular Medicine and Cell Research, Freiburg, Germany.
West German Tumor Center (WTZ) Essen and Clinic for Dermatology, Essen University Hospital, Essen, Germany.
Comprehensive Cancer Center Tübingen-Stuttgart and Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Society, Berlin, Germany.Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.
Journal of cancer research and clinical oncology
Cancer care in German centers of excellence during the first 2 years of the COVID-19 pandemic.

Polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs) having numerous toxicological properties, including thyroid endocrine disruption. Our aim was to assess the impact of POPs on thyroid hormones among 12-year-old children, while taking puberty into consideration.Exposure to 7 PCBs, 4 OCPs, and 6 PFASs (in µg/L), and free tri-iodothyronine (fT3, pg/mL), free thyroxine (fT4, ng/dL), and thyroid-stimulating hormones (TSH, mIU/L) were assessed through blood-serum measurements at age 12 years in 249 boys and 227 girls of the PELAGIE mother-child cohort (France). Pubertal status was clinically rated using the Tanner stages. For each POP, associations were estimated using linear regression, adjusted for potential confounders.Among boys, hexachlorobenzene and perfluorodecanoic acid were associated with decreased fT3 (log-scale; β [95% confidence interval] = -0.07 [-0.12,-0.02] and β = -0.03 [-0.06,-0.00], respectively). Intermediate levels of perfluorohexanesulfonic acid (PFHxS) and PCB180 were associated, respectively, with increased and decreased fT4. After stratification on pubertal status, PCBs and OCPs were associated with decreased TSH only in the more advanced Tanner stages (3-5) and with decreased fT3 among early Tanner stages (1-2). Among girls, PFHxS was associated with decreased TSH (log-scale; β = -0.15 [-0.29,-0.00]), and perfluorooctanoic acid was associated with decreased fT3 (β2nd_tercile = -0.06 [-0.10,-0.03] and β3rd_tercile = -0.04 [-0.08,-0.00], versus. 1st tercile).This cross-sectional study highlights associations between some POPs and thyroid function disruption, which appears consistent with the literature. Considering that the associations were sex-specific and moderated by pubertal status in boys, complex endocrine interactions are likely involved.
© 2022 The Author(s). Published by S. Karger AG, Basel.
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France.
AP-HP, Pôle Biologie-Pathologie Henri Mondor, Créteil, France.Inserm IMRB, Faculté de Santé, Créteil, France.
Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France.
CHU Rennes, Inserm CIC1414, Rennes, France.
Centre de Toxicologie du Québec (CTQ), Institut national de santé publique du Québec (INSPQ), Quebec, Québec, Canada.
Inserm IMRB, Faculté de Santé, Créteil, France.
Département de Psychologie, Université du Québec à Montréal, Montréal, Québec, Canada.Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada.
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France, cecile.chevrier@univ-rennes1.fr.
Persistent Organic Pollutant Exposure and Thyroid Function among 12-Year-Old Children.

This study was carried out to investigate the effects of abdominal subcutaneous adiposity and visceral adiposity on osteoporotic compression fractures.The study group consisted of a total of 152 individuals aged 50-80 years; 76 were included in the vertebral fracture group and 76 in the healthy control group, whose bone mineral density was calculated. In order to determine the distribution of abdominal fat in both groups, four different measurements, i.e., sagittal abdominal diameter (SAD), abdominal diameter (AD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST), were made using lumbar magnetic resonance imaging (MRI). The visceral fat ratio (VFR) was also calculated based on these measurements.There was a significant difference between the patient and control groups in VST and DST values, both when gender distribution was and was not taken into account (p < 0.006 for all cases). There was no significant difference between the patient and control groups in SAD and AS values, both when only female patients were considered, and gender distribution was not taken into account (p > 0.25 for all cases). On the other hand, in the analysis, when only male patients were considered, the SAD and AD values of the patient group were found to be significantly lower than those of the control group (p = 0.046 and p = 0.048, respectively).In conclusion, the study findings indicated that high SAD values in the male gender and high VST and DST values in both genders were associated with low lumbar vertebral fracture risk.
© 2022. The Author(s), under exclusive licence to International Skeletal Society (ISS).
Department of Radiology, Ermenek State Hospital, 70400, Karaman, Turkey.
Department of Radiology, Akdeniz University School of Medicine, Dumlupınar bulvarıArapsuyu, 07059, Antalya, Turkey. aysekeven@gmail.com.
Department of Biostatistics, Faculty of Medicine, Yüzüncü Yıl University, Van, Turkey.
Department of Radiology, Akdeniz University School of Medicine, Dumlupınar bulvarıArapsuyu, 07059, Antalya, Turkey.
Evaluation of the relationship between abdominal fat distribution and osteoporotic vertebral compression fracture with MRI.

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, USA.Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.
Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, USA.Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.
University of Connecticut School of Nursing, Storrs, Connecticut, USA.
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.

We present the case of a patient with germline CHEK2-mutated metastatic castration-resistant prostate cancer (mCRPC) who responded to bipolar androgen therapy (BAT) combined with pembrolizumab after progressing through multiple lines of therapy. The patient was diagnosed in his 40s following an elevated screening prostate-specific antigen and biopsy. Over the course of 20 years, he progressed through nearly all standard therapies including androgen deprivation, combined androgen blockade, traditional chemotherapy, targeted therapies and experimental agents. He was ultimately treated with BAT, whereby the patient's cycle was between low (castrate) and high (supraphysiological) testosterone levels. This counterintuitive approach resulted in a marked response to BAT plus pembrolizumab consolidation lasting 13 months. His underlying germline mutation in CHEK2, an important mediator of DNA repair, may have sensitised the cancer cells to the DNA damage caused by BAT. Single case report outcomes should not be used as evidence of efficacy for treatment regimes. Our case supports further investigation into BAT plus immunotherapy for patients with DNA repair-deficient mCRPC.
© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA benjamin.t.berger@duke.edu andrew.armstrong@duke.edu.
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina, USA.
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota Academic Health Center, Minneapolis, Minnesota, USA.
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA benjamin.t.berger@duke.edu andrew.armstrong@duke.edu.Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina, USA.
Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation.

Large bowel obstruction (LBO) after colorectal surgery draws wide differentials. To our knowledge, LBO due to blind colonic limb mucocele of a side-to-end colorectal anastomosis has not yet been described. We report a man in his late 50s presenting with pain, abdominal distension and constipation. He had extensive surgical history; notably, a side-to-end colorectal anastomosis was fashioned following Hartmann-type colostomy reversal. CT and MRI suggested a mucus-filled short blind colonic segment compressing the anastomotic site and causing LBO. Flexible sigmoidoscopy under general anaesthesia showed external rectal compression and lumen narrowing. Transrectal needle aspiration of the blind segment yielded 145 mL of mucoid fluid. The patient's symptoms improved and he was discharged with outpatient Gastrografin enema and flexible sigmoidoscopy which confirmed successful blind segment emptying. This case highlights that blind colonic loop mucoceles in colorectal anastomosis can rarely cause obstruction, and endoscopic management is feasible when accurate diagnosis is confirmed on imaging.
St George's, University of London, London, UK luke.peacock@nhs.net.General Surgery, William Harvey Hospital, Ashford, UK.
General Surgery, William Harvey Hospital, Ashford, UK.
Blind loop mucocele of a side-to-end colorectal anastomosis as a rare cause of large bowel obstruction.

Emergency Medicine, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA.
Emergency Medicine, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA b.sutarjono@saba.edu.
Type A aortic dissection identified by point-of-care ultrasound but missed by CT angiogram.

The release of inflammatory cytokines, namely tumor necrosis factor-α (TNF-α), plays an important role in the pathogenesis of cardiomyopathy. TNF-α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF-α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg-1 , i.p) twice weekly for 3 weeks (21 mg. kg-1 cumulative dose). DCM rats were treated with RPL (1 mg. kg-1 orally, daily), IFX (5 mg. kg-1 ; i.p. once) or their combination for 4 weeks starting next day of last DOX dose. Echocardiography was conducted followed by a collection of blood and left ventricle (LV) for biochemical and histological investigations. DCM rats revealed deteriorated cardiac function (increased CK-MB activity, LVIDs, LVIDd, ESV, and EDV, while decreased EF% and FS%), hypertrophy (increased HW/TL, β-MHC, and α-actin), inflammation (increased IL-1β, IL-6, and TNF-α). The activation of Wnt/β-catenin along with increased gene expression of RAS components (RENIN, ACE, and AT1) were evident. LV architecture also revealed abnormalities and some degree of fibrosis. Treatment with RPL and/or IFX suppressed TNF-α and consequently improved most of these parameters suppressing Wnt/β-catenin/RAS axis. Combined RPL and IFX treatment was the best among all treatments. In conclusion, Wnt/β-catenin/RAS axis is implicated in DOX-induced cardiomyopathy. The upstream TNF-α was proved for the first time in-vivo to stimulate this axis where its inhibition by RPL or IFX prevented DCM. Targeting this axis at two points using RPL and IFX showed better therapeutic efficacy.
Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Department of Histology and Cell Biology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.
Department of Cardiology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.
Journal of biochemical and molecular toxicology
Infliximab substantially re-silenced Wnt/β-catenin signaling and ameliorated doxorubicin-induced cardiomyopathy in rats.

Curcumin is a safe, non-toxic, readily available and naturally occurring compound, an active constituent of Curcuma longa (turmeric). Curcumin could potentially treat diseases, but faces poor physicochemical and pharmacological characteristics. To overcome these limitations, we developed a stable, water-soluble formulation of curcumin called cyclodextrin-complexed curcumin (CDC). We have previously shown that direct delivery of CDC to the lung following lipopolysaccharides exposure reduces acute lung injury (ALI) and effectively reduces lung injury, inflammation and mortality in mice following Klebsiella pneumoniae. Recently, we found that administration of CDC led to a significant reduction in angiotensin-converting enzyme 2 and signal transducer and activator of transcription 3 expression in gene and protein levels following pneumonia, indicating its potential in treating coronavirus disease 2019 (COVID-19). In this review, we consider the clinical features of ALI and acute respiratory distress syndrome (ARDS) and the role of curcumin in modulating the pathogenesis of bacterial/viral-induced ARDS and COVID-19.
© 2022 John Wiley & Sons Australia, Ltd.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Clinical and experimental pharmacology & physiology
Clin Exp Pharmacol Physiol. 2023-04;50(4):267-276.
Therapeutic potential of curcumin in ARDS and COVID-19.

Although rare and unusual occurrences, a ruptured ectopic molar pregnancy (MP) and a ruptured uterine fibroid can lead to significant maternal morbidity and mortality. We present a unique case of these complications developing concurrently-resulting in the haemodynamic compromise of an otherwise healthy young female patient. The patient underwent a diagnostic laparoscopy which converted into a laparotomy, salpingectomy and myomectomy. Comprehensive histopathology confirmed the diagnosis of a ruptured ectopic complete MP and ruptured uterine fibroid. The patient recovered quickly within days. Prompt definitive management, conclusive histopathology and adequate follow-up were the hallmarks of this singular case. These key factors lead to the rare diagnosis of ruptured ectopic MP and uterine fibroid, prevention of adverse outcomes and provision of comprehensive patient care.
Obstetrics and Gynaecology, Royal Prince Alfred Hospital Women and Babies Ambulatory Care, Camperdown, New South Wales, Australia marietta.tanudisastro@health.nsw.gov.au.Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
Obstetrics and Gynaecology, Royal Prince Alfred Hospital Women and Babies Ambulatory Care, Camperdown, New South Wales, Australia.
Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Ruptured ectopic molar pregnancy and ruptured uterine fibroid: a challenging rare diagnosis.

Rubinstein-Taybi syndrome, also known as broad thumb-hallux syndrome, is a rare autosomal dominant genetic disorder. This multiorgan syndrome is linked to a pathogenic mutation in the CREBBP or EBP300 genes.We present a patient with a hitherto unreported constellation of anterior segment abnormalities, including congenital glaucoma, congenital corneal keloid, cataract, and distinct facial and systemic features including a high-arched palate, low-set posteriorly rotated ears, Café-au-lait spots on the back, broad terminal phalanges of hands and feet, and bilateral cryptorchidism. The characteristic dysgenetic angle features and ultrasound biomicroscopic findings described in this case report show the occurrence of concomitant congenital keloid with glaucoma.Genetic testing revealed a heterozygous one-base pair duplication in exon 3 of the CREBBP gene (c.886dupC), a novel frameshift pathogenic mutation in the CREBBP gene that has not been previously reported in a clinical setting.
Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India sushmita_kaushik@yahoo.com.
Congenital glaucoma as a presenting feature of Rubinstein-Taybi syndrome in an infant with a novel pathogenic variant in the CREBBP gene.

Fistula formation between the kidney, colon and the skin is an extremely rare complication arising from renal infections secondary to renal stone formation. During the 1980s, reports of nephrocolic fistulas, with or without involvement of the skin, were commonly caused by genitourinary tuberculosis. Due to improvements in diagnosis and specifically the development of anti-Koch's therapy, the incidence of nephrocolic or nephrocolocutaneous fistulas has become uncommon especially in developed countries.We report a case of a patient residing in a developing country, presenting with a 20-year history of a left flank lesion extruding minimal purulent output daily. He was seen at the emergency department due to weakness and was managed as a case of urosepsis. Contrast-enhanced CT scan and fistulogram showed a staghorn calculus in the left kidney with connections to the descending colon and skin. The patient eventually underwent a left hemicolectomy with en bloc excision of the kidney and fistula tract.
Department of Surgery, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines rocky_awp@yahoo.com.
Department of Surgery, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.
Nephrocolocutaneous fistula from a staghorn calculus.

University of California San Francisco School of Medicine, San Francisco, California, USA.
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA.
Clinical Research Unit, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA.
Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Dermatology Service, Veterans Affairs Health Care System, San Francisco, California, USA.
Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA; Department of Neurology, University of California San Francisco, San Francisco, California, USA; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA.
Department of Dermatology, University of California San Francisco, San Francisco, California, USA. Electronic address: Katrina.abuabara@ucsf.edu.
The Journal of investigative dermatology
Skin Barrier Function and Cognition among Older Adults.

Herpes simplex virus (HSV) infection in newborn infants is a potentially devastating disease leading to death and disability. Skin, eye and mouth (SEM) infections account for approximately half of the cases in the USA. The appearance of skin findings often guides clinicians towards early diagnosis of HSV infection, prompt interventions and life-saving management; however, less than half of neonates with proven disease present with characteristic vesicular lesions. Furthermore, if SEM infections are not treated promptly, there is significant risk of progression to central nervous system and disseminated disease. We present a case of HSV-2 infection in a neonate with an atypical zosteriform eruption on day 3 of life. This case demonstrates that neonatal HSV can unusually present in a zosteriform rash. By elucidating this unique presentation, we highlight atypical HSV skin presentation and emphasise on the importance of earlier diagnosis and antiviral treatment to prevent the associated morbidity and mortality.
Internal Medicine, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Department of Pediatrics and Department of Dermatology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.Department of Pediatrics, Springfield Clinic, Springfield, Illinois, USA.
Pediatrics-Infectious Diseases, Southern Illinois University School of Medicine, Springfield, Illinois, USA esaleh84@siumed.edu.
Neonatal herpes simplex presenting as a zosteriform eruption.

The Triple-Code Model stipulates that numerical information from different formats and modalities converges on a common magnitude representation in the Intraparietal Sulcus (IPS). To what extent the representations of all numerosity forms overlap remains unsolved. It has been postulated that the representation of symbolic numerosities (for example, Arabic digits) is sparser and grounded in an existing representation that codes for non-symbolic numerosity information (i.e., sets of objects). Other theories argue that numerical symbols represent a separate number category that emerges only during education. Here, we tested a unique group of sighted tactile Braille readers with numerosities 2, 4, 6 and 8 in three number notations: Arabic digits, sets of dots, tactile Braille numbers. Using univariate methods, we showed a consistent overlap in activations evoked by these three number notations. This result shows that all three used notations are represented in the IPS, which may suggest at least a partial overlap between the representations of the three notations used in this experiment. Using MVPA, we found that only non-automatized number information (Braille and sets of dots) allowed successful number classification. However, the numerosity of one notation could not be predicted above chance from the brain activation patterns evoked by another notation (no cross-classification). These results show that the IPS may host independent number codes in overlapping cortical circuits. In addition, they suggest that the level of training in encoding a given type of number information is an important factor that determines the amount of exploitable information and needs to be controlled for in order to identify the neural code underlying numerical information per se.
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Institute of Psychology, Jagiellonian University, Krakow, Poland. Electronic address: mhczarnecka@gmail.com.
Institute of Psychology, Jagiellonian University, Krakow, Poland; Biological Psychology and Neuropsychology, University of Hamburg, Hamburg, Germany.
Institute of Psychology, Jagiellonian University, Krakow, Poland; Department of Psychology, University of Illinois, Urbana Champaign.
The Maria Grzegorzewska University, Warsaw, Poland.
Laboratory of Language Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Department of General and Biological Psychology, Psychologische Hochschule Berlin, Berlin, Germany.
UMR CNRS 8240, Laboratory for the Psychology of Child Development and Education, University of Paris, Paris, France.
Institute of Psychology, Jagiellonian University, Krakow, Poland. Electronic address: m.szwed@uj.edu.pl.
Cortex; a journal devoted to the study of the nervous system and behavior
Overlapping but separate number representations in the intraparietal sulcus-Probing format- and modality-independence in sighted Braille readers.

Acute ischemic stroke (AIS) is a leading cause of mortality that occurs when an embolus becomes lodged in the cerebral vasculature and obstructs blood flow in the brain. The severity of AIS is determined by the location and how extensively emboli become lodged, which are dictated in large part by the cerebral flow and the dynamics of embolus migration which are difficult to measure in vivo in AIS patients. Computational fluid dynamics (CFD) can be used to predict the patient-specific hemodynamics and embolus migration and lodging in the cerebral vasculature to better understand the underlying mechanics of AIS. To be relied upon, however, the computational simulations must be verified and validated. In this study, a realistic in vitro experimental model and a corresponding computational model of the cerebral vasculature are established that can be used to investigate flow and embolus migration and lodging in the brain. First, the in vitro anatomical model is described, including how the flow distribution in the model is tuned to match physiological measurements from the literature. Measurements of pressure and flow rate for both normal and stroke conditions were acquired and corresponding CFD simulations were performed and compared with the experiments to validate the flow predictions. Overall, the CFD simulations were in relatively close agreement with the experiments, to within ±7% of the mean experimental data with many of the CFD predictions within the uncertainty of the experimental measurement. This work provides an in vitro benchmark data set for flow in a realistic cerebrovascular model and is a first step towards validating a computational model of AIS.
© 2023 Bhardwaj, Craven, Sever, Costanzo, Simon and Manning.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, United States.
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, United States.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, United States.Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, United States.
Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, United States.Department of Surgery, Penn State Hershey Medical Center, Hershey, PA, United States.
Modeling flow in an in vitro anatomical cerebrovascular model with experimental validation.

This systematic review is part of a broader evidence synthesis which aims to produce two systematic reviews to address a significant gap in the evidence base identified by Luchenski et al. (2018) and by (White, 2018). The first review (which is the subject of this protocol) will use meta-analysis to examine the effectiveness of different psychosocial interventions in (1) reducing problematic substance use; (2) improving mental health; and (3) improving housing stability for adults experiencing homelessness. The second review (which is covered by a separate title registration and protocol) will be of the experiences of adults experiencing homelessness when accessing or using psychosocial interventions, and will be a qualitative evidence synthesis using thematic synthesis (Thomas & Harden, 2008).
© 2022 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.
Policy Evaluation and Research Unit Manchester Metropolitan University Manchester UK.
Centre for Homelessness Impact London UK.
Canterbury Christchurch University Canterbury UK.
PROTOCOL: The effectiveness of psychosocial interventions for reducing problematic substance use, improving mental health, and improving housing stability for adults experiencing homelessness: A systematic review and meta-analysis.

Strong light fields have created opportunities to tailor novel functionalities of solids1-5. Floquet-Bloch states can form under periodic driving of electrons and enable exotic quantum phases6-15. On subcycle timescales, lightwaves can simultaneously drive intraband currents16-29 and interband transitions18,19,30,31, which enable high-harmonic generation16,18,19,21,22,25,28-30 and pave the way towards ultrafast electronics. Yet, the interplay of intraband and interband excitations and their relation to Floquet physics have been key open questions as dynamical aspects of Floquet states have remained elusive. Here we provide this link by visualizing the ultrafast build-up of Floquet-Bloch bands with time-resolved and angle-resolved photoemission spectroscopy. We drive surface states on a topological insulator32,33 with mid-infrared fields-strong enough for high-harmonic generation-and directly monitor the transient band structure with subcycle time resolution. Starting with strong intraband currents, we observe how Floquet sidebands emerge within a single optical cycle; intraband acceleration simultaneously proceeds in multiple sidebands until high-energy electrons scatter into bulk states and dissipation destroys the Floquet bands. Quantum non-equilibrium calculations explain the simultaneous occurrence of Floquet states with intraband and interband dynamics. Our joint experiment and theory study provides a direct time-domain view of Floquet physics and explores the fundamental frontiers of ultrafast band-structure engineering.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Department of Physics, Philipps-University of Marburg, Marburg, Germany.
Laboratory for Materials Simulations, Paul Scherrer Institute, Villigen PSI, Switzerland.Department of Physics, University of Fribourg, Fribourg, Switzerland.
Department of Physics, University of Regensburg, Regensburg, Germany.
A.V. Rzhanov Institute of Semiconductor Physics and V.S. Sobolev Institute of Geology and Mineralogy SB RAS, Novosibirsk, Russian Federation.
Max Planck Institute for the Structure and Dynamics of Matter, Hamburg, Germany. michael.sentef@mpsd.mpg.de.
Department of Physics, Philipps-University of Marburg, Marburg, Germany. hoefer@physik.uni-marburg.de.Department of Physics, University of Regensburg, Regensburg, Germany. hoefer@physik.uni-marburg.de.
Department of Physics, University of Regensburg, Regensburg, Germany. rupert.huber@physik.uni-regensburg.de.
Build-up and dephasing of Floquet-Bloch bands on subcycle timescales.

Hepatic dysfunction (HD) is frequently associated with chronic tricuspid regurgitation (TR), and is a risk factor for TR surgery. Late referral of patients with TR is associated with the progression of TR and HD, as well as an increase in surgical morbidity and mortality. Many patients with severe TR suffer from HD; however, their clinical impact is not well documented.This retrospective review was conducted between October 2008 and July 2017. In total, 159 consecutive patients underwent surgery for TR; 101 with moderate to severe TR were included. We divided patients into N (normal liver function; n=56) and HD (HD; n=45) groups. HD was defined as clinically or radiologically diagnosed liver cirrhosis, or a preoperative Model for End-Stage Liver Disease (MELD)-XI score ≥13. Perioperative data were compared between groups, and changes in the MELD score following TR surgery were estimated in the HD group. Long-term survival rates were analyzed, and analyses were performed to obtain the assessment tool and cutoff value to determine the degree of HD affecting late mortality.The preoperative demographics of both groups were similar, excluding the presence of HD. The EuroSCORE II, MELD score, and prothrombin time international normalization ratio were significantly higher in the HD group, and although early mortality was comparable between groups [N group: 0%, HD group: 2.2% (n=1); P=0.446], intensive care unit and hospital stays were significantly longer in the HD group. The MELD score in the HD group temporarily increased immediately after surgery, and then decreased. The long-term survival rates were significantly lower in the HD group. The most suitable tool for predicting late mortality was the MELD-XI score, with a cutoff value of 13 points.Surgery for patients with severe TR can be performed with relatively low morbidity and operative mortality, regardless of associated HD. MELD scores significantly improved after TR surgery in patients with HD. Even with favorable early outcomes, compromised long-term survival with HD suggests the need to develop an assessment tool that can evaluate the appropriate timing for TR surgery.
2023 Journal of Thoracic Disease. All rights reserved.
Cardiovascular Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan-si, Korea.
Influence of hepatic dysfunction in patients who underwent tricuspid valve surgery.

During the past decades, the advent of different microneedle patch (MNPs) systems paves the way for the targeted and efficient delivery of several growth factors into the injured sites. MNPs consist of several micro-sized (25-1500 μm) needle rows for painless delivery of incorporated therapeutics and increase of regenerative outcomes. Recent data have indicated the multifunctional potential of varied MNP types for clinical applications. Advances in the application of materials and fabrication processes enable researchers and clinicians to apply several MNP types for different purposes such as inflammatory conditions, ischemic disease, metabolic disorders, vaccination, etc. Exosomes (Exos) are one of the most interesting biological bioshuttles that participate in cell-to-cell paracrine interaction with the transfer of signaling biomolecules. These nano-sized particles, ranging from 50 to 150 nm, can exploit several mechanisms to enter the target cells and deliver their cargo into the cytosol. In recent years, both intact and engineered Exos have been increasingly used to accelerate the healing process and restore the function of injured organs. Considering the numerous benefits provided by MNPs, it is logical to hypothesize that the development of MNPs loaded with Exos provides an efficient therapeutic platform for the alleviation of several pathologies. In this review article, the authors collected recent advances in the application of MNP-loaded Exos for therapeutic purposes.
Copyright © 2023 Elsevier B.V. All rights reserved.
Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Koç University Research Centre for Translational Medicine (KUTTAM), Koç University School of Medicine, Istanbul, Turkey.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of General and Vascular Surgery, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: rahbarghazir@tbzmed.ac.ir.
Chemical Engineering Faculty, Sahand University of Technology, Tabriz 51335-1996, Iran. Electronic address: khoshfetrat@sut.ac.ir.
International journal of biological macromolecules
Exosome-loaded microneedle patches: Promising factor delivery route.

Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina. Electronic address: elstond@musc.edu.
Journal of the American Academy of Dermatology
Letter from the Editor: Antibody screening in patients with inflammatory myopathies.

Adipose tissue is composed of a collection of cells with valuable structural and regenerative function. Taken as an autologous graft, these cells can be used to address soft tissue defects and irregularities, while also providing a reparative effect on the surrounding tissues. Adipose-derived stem or stromal cells are primarily responsible for this regenerative effect through direct differentiation into native cells and via secretion of numerous growth factors and cytokines that stimulate angiogenesis and disrupt pro-inflammatory pathways. Separating adipose tissue into its component parts, i.e., cells, scaffolds and proteins, has provided new regenerative therapies for skin and soft tissue pathology, including that resulting from radiation. Recent studies in both animal models and clinical trials have demonstrated the ability of autologous fat grafting to reverse radiation induced skin fibrosis. An improved understanding of the complex pathologic mechanism of RIF has allowed researchers to harness the specific function of the ASCs to engineer enriched fat graft constructs to improve the therapeutic effect of AFG.
Section of Plastic & Reconstructive Surgery, University of Chicago Medical Center, Chicago, IL 60615, USA.
Deconstructing Fat to Reverse Radiation Induced Soft Tissue Fibrosis.

While laparoscopic gastrectomy is a prominent therapeutic approach for distal gastric cancer, the clinical benefits of 3D laparoscopy over 2D laparoscopy remain unclear. We aimed to compare the clinical outcomes of 3D laparoscopy and 2D laparoscopy for distal gastric cancer resection through a systematic review and meta-analysis.We searched PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published from inception through January 2023, according to the PRISMA guidelines. The MD or RR was used to compare 3D and 2D distal gastrectomy. Random-effects meta-analysis was estimated using the inverse variance and Mantel-Haenszel method for binary outcomes and the DerSimonian-Laird estimator for continuous outcomes.After reviewing 559 studies, 6 manuscripts met the inclusion criteria. The analysis included 689 patients, with 348 (50.5%) in the 3D group and 341 (49.5%) in the 2D group. 3D laparoscopic gastrectomy reduces the operative time (WMD - 28.57 min, 95% CI - 50.70 to - 6.44, p = 0.011), intraoperative blood loss (WMD - 6.69 mL, 95% CI - 8.09 to - 5.29, p < 0.001), and postoperative hospital stay (WMD - 0.92 days, 95% CI - 1.43 to - 0.42, p < 0.001). There were no significant differences in time to first postoperative flatus (WMD - 0.22 days, 95% CI - 0.50 to 0.05, p = 0.110), postoperative complications (Relative Risk 0.56, 95% CI 0.22 to 1.41, p = 0.217), and the number of retrieved lymph nodes (WMD 1.25, 95% CI - 0.54 to 3.03, p = 0.172) between 3 and 2D laparoscopic distal gastrectomy.Our study highlights the potential advantages of 3D laparoscopy in distal gastrectomy, including shorter operative time, postoperative hospital stay, and decreased intraoperative blood loss.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Department of Medicine, Positivo University, Curitiba, Brazil.Department of Statistics and Biostatistics, Anhembi Morumbi University, Curitiba, Brazil.
Department of Surgery, The Johns Hopkins University, 600 N. Wolfe St, Blalock 618, Baltimore, MD, 21093, USA.
Department of Surgery, Northwest Hospital, Randallstown, MD, USA.Universidad Científica del Sur, Lima, Peru.
Department of Surgery, The Johns Hopkins University, 600 N. Wolfe St, Blalock 618, Baltimore, MD, 21093, USA. gadrale1@jhmi.edu.
3D versus 2D laparoscopic distal gastrectomy in patients with gastric cancer: a systematic review and meta-analysis.

To assess the effect of aromatherapy with lavender oil alone, and in combination with music, on pain and anxiety during extracorporeal shockwave lithotripsy for kidney stones.This was a single-centre prospective, randomised controlled trial. The subjects were block randomised into 3 study groups, Group 1: Control; Group 2: Aromatherapy only; Group 3: Aromatherapy and music. All subjects were given patient-controlled intravenous alfentanil as standard analgesia. The primary outcome measures were pain and anxiety scores using visual analogue scale (VAS) and State-Trait Anxiety Inventory.Ninety patients were recruited and randomised prospectively into Group 1 (n = 30), Group 2 (n = 30), and Group 3 (n = 30). For pain outcome, both Group 2 and Group 3 showed a trend towards lower mean VAS pain scores of 2.73 in both groups compared to the control with a mean VAS score of 3.50, but it was not statistically significant (p = 0.272). There was no significant difference in anxiety scores between groups post-treatment.Our study was unable to show a significant improvement in pain relief and anxiety when aromatherapy with lavender oil was added to standard analgesia alone during shockwave lithotripsy. There was also no difference when aromatherapy was combined with music.
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Department of Urology, National University Hospital, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore, 119228, Singapore. terencelaw83@gmail.com.
Department of Urology, National University Hospital, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore, 119228, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Does addition of aromatherapy and music help to reduce pain and anxiety during shockwave lithotripsy compared to standard analgesia alone? A randomised controlled trial.

University of Rochester School of Medicine and Dentistry, Rochester, New York.
Department of Dermatology, University of Rochester Medical Center, Rochester, New York. Electronic address: crichardson@urmc.rochester.edu.
Serologic differences between dermatomyositis and antisynthetase syndrome using a commercially available autoantibody panel: A retrospective cohort study.

Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts.We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence.Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates.Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%.An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined.
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA toker@jhu.edu.Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.Department of Patient Safety, The Risk Management Foundation of the Harvard Medical Institutions Inc, Boston, Massachusetts, USA.
Department of Patient Safety, The Risk Management Foundation of the Harvard Medical Institutions Inc, Boston, Massachusetts, USA.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Candello, The Risk Management Foundation of the Harvard Medical Institutions Inc, Boston, Massachusetts, USA.Department of Risk Management & Analytics, Coverys, Boston, Massachusetts, USA.
Burden of serious harms from diagnostic error in the USA.

Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing´ syndrome and neurodegenerative disorders of humans and models of human diseases. . The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNFα, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1β and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1β, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders.
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina.
Dept. of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
Corcept Therapeutics, Menlo Park, Ca, USA.
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina.Dept. of Physiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina. alejandrodenicola@gmail.com.Dept. of Human Biochemiistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. alejandrodenicola@gmail.com.
Stress-induced Neuroinflammation of the Spinal Cord is Restrained by Cort113176 (Dazucorilant), A Specific Glucocorticoid Receptor Modulator.

Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the auditory system are unknown.Molecular docking and molecular dynamics (MD) simulation were used for predicting effective drugs. The CCK-8 assay was conducted for assessing cell viability in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. MitoSox Red staining revealed reactive oxygen species (ROS) amounts. TMRM staining was used to assess the mitochondrial membrane potential (ΔΨm). Immunofluorescence staining of myosin 7a was used to examine hair cells (HCs) in cisplatin-treated neonatal mouse cochlear explants, while TUJ-1 immunostaining was used for the detection of spiral ganglion neurons (SGNs). Cleaved caspase-3 and TUNEL immunostaining were utilized for apoptosis assessment. Immunoblot was carried out to detect PI3K-AKT signaling effectors.Pretreatment with CN or CD significantly increased cell viability and reduced mitochondrial dysfunction and ROS accumulation in cisplatin-treated HEI-OC1 cells. Immunofluorescent staining of cochlear explants showed that CN and CD attenuated cisplatin-induced damage to SGNs and HCs. Immunoblot revealed that CN and CD downregulated the expression of cleaved caspase-3 and activated PI3K-AKT signaling in cisplatin-injured HEI-OC1 cells.CD and CN can reduce ototoxicity caused by cisplatin and might help treat cisplatin-associated hearing loss.
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, China.
Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Cinchonine and cinchonidine alleviate cisplatin-induced ototoxicity by regulating PI3K-AKT signaling.

Exposure to pathogen-associated molecular patterns (PAMPs) induces an augmented, broad-spectrum antimicrobial response to subsequent infection, a phenomenon termed innate immune memory. This study examined the effects of treatment with β-glucan, a fungus-derived dectin-1 ligand, or monophosphoryl lipid A (MPLA), a bacteria-derived Toll-like receptor 4 ligand, on innate immune memory with a focus on identifying common cellular and molecular pathways activated by these diverse PAMPs. Treatment with either PAMP prepared the innate immune system to respond more robustly to Pseudomonas aeruginosa infection in vivo by facilitating mobilization of innate leukocytes into blood, recruitment of leukocytes to the site of infection, augmentation of microbial clearance, and attenuation of cytokine production. Examination of macrophages ex vivo showed amplification of metabolism, phagocytosis, and respiratory burst after treatment with either agent, although MPLA more robustly augmented these activities and more effectively facilitated killing of bacteria. Both agents activated gene expression pathways in macrophages that control inflammation, antimicrobial functions, and protein synthesis and suppressed pathways regulating cell division. β-glucan treatment minimally altered macrophage differential gene expression in response to lipopolysaccharide (LPS) challenge, whereas MPLA attenuated the magnitude of the LPS-induced transcriptional response, especially cytokine gene expression. These results show that β-glucan and MPLA similarly augment the innate response to infection in vivo. Yet, MPLA more potently induces alterations in macrophage metabolism, antimicrobial functions, gene transcription and the response to LPS.
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.
Department of Anesthesiology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.Department of Anesthesiology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.
Department of Chemical and Biomolecular Engineering, Vanderbilt University, 2301 Vanderbilt Place, Nashville 37235, Tennessee.
Department of Chemical and Biomolecular Engineering, Vanderbilt University, 2301 Vanderbilt Place, Nashville 37235, Tennessee.Department of Molecular Physiology and Biophysics, Vanderbilt University, 2215 Garland Avenue, Nashville 37232, Tennessee.
Department of Surgery, Quillen College of Medicine, East Tennessee State University, 325 North State of Franklin Road, Johnson City 37604, Tennessee.Center for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, 325 North State of Franklin Road, Johnson City 37604, Tennessee.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.Department of Anesthesiology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville 37232, Tennessee.Department of Surgery, Quillen College of Medicine, East Tennessee State University, 325 North State of Franklin Road, Johnson City 37604, Tennessee.Center for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, 325 North State of Franklin Road, Johnson City 37604, Tennessee.
Bacteria- and fungus-derived PAMPs induce innate immune memory via similar functional, metabolic, and transcriptional adaptations.

Synthetic antisense oligonucleotides (ASOs) and duplex RNAs (dsRNAs) are an increasingly successful strategy for drug development. After a slow start, the pace of success has accelerated since the approval of Spinraza (nusinersen) in 2016 with several drug approvals. These accomplishments have been achieved even though oligonucleotides are large, negatively charged, and have little resemblance to traditional small-molecule drugs-a remarkable achievement of basic and applied science. The goal of this review is to summarize the foundation underlying recent progress and describe ongoing research programs that may increase the scope and impact of oligonucleotide therapeutics.
Copyright © 2023 Elsevier Ltd. All rights reserved.
The Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
The Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA. Electronic address: david.corey@utsouthwestern.edu.
Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.

A major problem with mRNA therapeutics is that mRNA is usually degraded within a few hours after entering the cytosol. New approaches for in vitro synthesis of circular mRNA have allowed increased levels and duration of protein synthesis from mRNA therapeutics due to the long half-life of circular mRNA. However, it remains difficult to genetically encode circular mRNAs in mammalian cells. Here, we describe the adaptation of the Tornado (Twister-optimized RNA for durable overexpression) system to achieve in-cell synthesis of circular mRNAs. We screen different promoters and internal ribosomal entry sites (IRESs) and identify combinations that result in high levels of circular mRNA and protein expression. We show that these circular mRNAs can be packaged into virus-like particles (VLPs), thus enabling prolonged protein expression. Overall, these data describe a platform for synthesis of circular mRNAs and how these circular mRNAs can improve VLP therapeutics.
Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA. Electronic address: srj2003@med.cornell.edu.
Highly efficient cellular expression of circular mRNA enables prolonged protein expression.

A novel class of benzoxaboroles was reported to induce cancer cell death but the mechanism was unknown. Using a forward genetics platform, we discovered mutations in cleavage and polyadenylation specific factor 3 (CPSF3) that reduce benzoxaborole binding and confer resistance. CPSF3 is the endonuclease responsible for pre-mRNA 3'-end processing, which is also important for RNA polymerase II transcription termination. Benzoxaboroles inhibit this endonuclease activity of CPSF3 in vitro and also curb transcriptional termination in cells, which results in the downregulation of numerous constitutively expressed genes. Furthermore, we used X-ray crystallography to demonstrate that benzoxaboroles bind to the active site of CPSF3 in a manner distinct from the other known inhibitors of CPSF3. The benzoxaborole compound impeded the growth of cancer cell lines derived from different lineages. Our results suggest benzoxaboroles may represent a promising lead as CPSF3 inhibitors for clinical development.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Medical Scientist Training Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, Program in Molecular Medicine and Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Biochemistry and Biophysics and Integrative Program in Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: ltong@columbia.edu.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jef.debrabander@utsouthwestern.edu.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, Program in Molecular Medicine and Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: deepak.nijhawan@utsouthwestern.edu.
Anticancer benzoxaboroles block pre-mRNA processing by directly inhibiting CPSF3.

Biomass aerogels are a promising kind of environment-friendly thermal insulation material. However, the flammability, poor water resistance, and thermal instability of biomass aerogels limit their applications. Herein, freeze-drying and thermal imidization were used to create konjac glucomannan (KGM), boron nitride (BN), and polyimide (PI)-based aerogels with a semi-interpenetrating network structure. The introduction of BN was beneficial to improve the mechanical properties and thermal stability of aerogels. The imidization process of PI improved the hydrophobicity, mechanical property, and flame retardancy of the aerogels. The synergistic effect of PI and BN reduced the peak heat release rate and total heat release rate of KGM-based aerogel by 55.8 % and 35 %, respectively, and endowed aerogel with good self-extinguishing performance. Moreover, the results of thermal conductivity and infrared thermal imaging demonstrated that the aerogels had excellent thermal insulation properties, and could effectively manage thermal energy over a wide range of temperatures. This study provides a simple method for the preparation of heat-insulating aerogel with high fire safety, which has broad application prospects in the field of energy saving and emission reduction.
Hubei Key Laboratory of Industry Microbiology, National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China.
Hunan Provincial Key Laboratory of Cytochemistry, Changsha University of Science and Technology, Changsha 410114, China.
Hubei Key Laboratory of Industry Microbiology, National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China; Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK. Electronic address: JIANGFT@mail.hbut.edu.cn.
Konjac glucomannan-based aerogels with excellent thermal stability and flame retardancy for thermal insulation application.

Bacterial resistance to various drugs is a major problem concerning the field of antibacterial agents. Fortunately, peptides with antibacterial activity can alleviate this problem. In this study, a short peptide (AVGAV) with excellent antibacterial activity was successfully screened from a peptide library by a self-made membrane chromatographic packing. The AVGAV peptide exhibits good biocompatibility and is non-toxic and non-irritating, which ensures that it presents safe antibacterial effects. AVGAV promoted wound healing in a mouse wound bacterial infection model. Most importantly, as a synthetic antimicrobial peptide, AVGAV can alleviate the problem of bacterial resistance, thus improving its application potential. This study provides a solution to the existing and potential problem of bacterial resistance.
College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao, 266071, China. conghailin@sdut.edu.cn.
College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao, 266071, China. conghailin@sdut.edu.cn.State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China.School of Materials Science and Engineering, Shandong University of Technology, Zibo 255000, China.
College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao, 266071, China. conghailin@sdut.edu.cn.State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao 266071, China.
College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Institute of Biomedical Materials and Engineering, Qingdao University, Qingdao, 266071, China. conghailin@sdut.edu.cn.Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Screening and investigation of a short antimicrobial peptide: AVGAV.

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; Department of Dermatology, University of Florida, Gainesville, Florida. Electronic address: grant@uchc.edu.
Balancing patient benefits and environmental impacts of emollient ingredients: An ethical argument.

Telomere maintenance and elongation allows cells to gain replicative immortality and evade cellular senescence during cancer development. While most cancers use telomerase to maintain telomere lengths, a subset of cancers engage the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is present in 5%-10% of all cancers, although the prevalence is dramatically higher in certain cancer types, including complex karyotype sarcomas, isocitrate dehydrogenase-mutant astrocytoma (WHO grade II-IV), pancreatic neuroendocrine tumours, neuroblastoma and chromophobe hepatocellular carcinomas. ALT is maintained through a homology-directed DNA repair mechanism. Resembling break-induced replication, this aberrant process results in dramatic cell-to-cell telomere length heterogeneity, widespread chromosomal instability and chronic replication stress. Additionally, ALT-positive cancers frequently harbour inactivating mutations in either chromatin remodelling proteins (ATRX, DAXX and H3F3A) or DNA damage repair factors (SMARCAL1 and SLX4IP). ALT can readily be detected in tissue by assessing the presence of unique molecular characteristics, such as large ultrabright nuclear telomeric foci or partially single-stranded telomeric DNA circles (C-circles). Importantly, ALT has been validated as a robust diagnostic and prognostic biomarker for certain cancer types and may even be exploited as a therapeutic target via small molecular inhibitors and/or synthetic lethality approaches.
Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Pharmacology, Physiology & Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.Pharmacology, Physiology & Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA heaphyc@bu.edu.Pathology and Laboratory Medicine, Boston Medical Center, Boston, Massachusetts, USA.
Alternative lengthening of telomeres: mechanism and the pathogenesis of cancer.

Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: christinahuang1000@gmail.com.
Renaissance School of Medicine, Stony Brook University, Stony Brook, New York.
Department of Dermatology, Emory University School of Medicine, Emory Center for Ethics, Emory University School of Medicine, Atlanta, Georgia.
Addressing patient requests for treatment of noninflamed seborrheic keratoses.

RNA plays pivotal roles in most cellular processes, serving as both the traditional carrier of genetic information and as a key regulator of cellular functions. The advent of chemical technologies has contributed critically to the analysis of cellular RNA structures, functions, and interactions. Many of these methods and molecules involve the utilization of chemically reactive handles in RNAs, either introduced externally or inherent within the polymer itself. Among these handles, the 2'-hydroxyl (2'-OH) group has emerged as an exceptionally well-suited and general chemical moiety for the modification and profiling of RNAs in intracellular studies. In this review, we provide an overview of the recent advancements in intracellular applications of acylation at the 2'-OH group of RNA. We outline progress made in probing RNA structure and interactomes, controlling RNA function, RNA imaging, and analyzing RNA-small molecule interactions, all achieved in living cells through this simple chemical handle on the biopolymer.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA. Electronic address: kool@stanford.edu.
2'-OH as a universal handle for studying intracellular RNAs.

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.
Department of Education, Hsin-Chu Branch, National Taiwan University Hospital, Hsinchu, Taiwan.PhD Program in Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
Division of Neurology, China Medical University Hospital, Taichung, Taiwan.
Department of Education, National Taiwan University Hospital, Taipei, Taiwan.
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Graduate Institutes of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.

Obesity poses significant health risks and can negatively impact an individual's quality of life. The human obesity phenotype results from the differentiation of pre-adipocytes into adipocytes, which leads to hypertrophy and hyperplasia in adipose tissue. The molecular mechanisms by which long non-coding RNAs (lncRNAs) modulate adipocyte differentiation, a process implicated in obesity development, remain poorly characterized. A lncRNA which suppressed the hepatic gluconeogenesis and lipogenesis (lncSHGL) was newly identified. Our research aims to elucidate the functional role and mechanistic underpinnings of suppressor of lncSHGL in adipocyte differentiation. We observed that lncSHGL expression progressively diminished during 3T3-L1 differentiation and was downregulated in the liver and perirenal adipose tissue of ob/ob mice. lncSHGL acts as a molecular sponge for miR-149, with Mospd3 identified as a target of miR-149.Overexpression of lncSHGL and inhibition of miR-149 led to suppressed 3T3-L1 proliferation, decreased lipid droplet accumulation, and attenuated promoter activity of PPARγ2 and C/EBPα. These changes consequently resulted in reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα, as well as inhibited the PI3K/AKT/mTOR signaling pathway. In contrast, lncSHGL suppression yielded opposing outcomes. Moreover, the effects of lncSHGL overexpression and miR-149 inhibition on reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα were reversible upon miR-149 overexpression and Mospd3 suppression. These findings were further validated in vivo. We also discovered a significant increase in methylation levels during 3T3-L1 differentiation, with lncSHGL highly expressed in the presence of a methylation inhibitor. In conclusion. lncSHGL methylation facilitates adipocyte differentiation by modulating the miR-149/Mospd3 axis. Targeting lncSHGL expression may represent a promising therapeutic strategy for obesity-associated adipogenesis, particularly in the context of fatty liver disease.
Emergency Department, The First Affiliated Hospital of Xiamen University, Xiamen, China.Emergency Department, Xiamen Key Laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine, Xiamen, China.
Methylation of lncSHGL promotes adipocyte differentiation by regulating miR-149/Mospd3 axis.

In eukaryotic genomes, transcriptional machinery and nucleosomes compete for binding to DNA sequences; thus, a crucial aspect of gene regulatory element function is to modulate chromatin accessibility for transcription factor (TF) and RNA polymerase binding. Recent structural studies have revealed multiple modes of TF engagement with nucleosomes, but how initial pioneering results in steady-state DNA accessibility for further TF binding and RNA polymerase II (RNAPII) engagement has been unclear. Even less well understood is how distant sites of open chromatin interact with one another, such as when developmental enhancers activate promoters to release RNAPII for productive elongation. Here, we review evidence for the centrality of the conserved SWI/SNF family of nucleosome remodeling complexes, both in pioneering and in mediating enhancer-promoter contacts. Consideration of the nucleosome unwrapping and ATP hydrolysis activities of SWI/SNF complexes, together with their architectural features, may reconcile steady-state TF occupancy with rapid TF dynamics observed by live imaging.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
University of Nebraska Medical Center, Department of Genetics, Cell Biology & Anatomy, Omaha, NE, USA.
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: steveh@fredhutch.org.
Epigenetic pioneering by SWI/SNF family remodelers.

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA tjdoyle@bwh.harvard.edu.
Université Paris Cité, INSERM UMR 1152, F-75018, Paris, France.Service de Rhumatologie, Hôpital Bichat-Claude Bernard, AP-HP, F-75018, Paris, France.
Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, California, USA.
Department of Medicine, National Jewish Health, Denver, Colorado, USA.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Medicine, Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Medicine, Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Hôpital Pitié Salpétrière, Public Health Department, F75013, Paris, France.
Université Paris Cité, INSERM UMR 1152, F-75018, Paris, France.Department of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Hopital Bichat-Claude Bernard, APHP, Paris, France.
Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Denver, Colorado, USA.
Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, folic acid (FA), and 5-methyltetrahydrofolate (5mTHF), at concentrations of 5 μM, 500 nM, 50 nM, and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages, and cell proliferation and F-actin were monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and F-actin formation. We also found that FOLR1 protein level was positively regulated by folate concentration and the non-canonical Wnt/planar cell polarity (PCP) pathway signaling was significantly enriched among different folate conditions in RNA-sequencing analyses. We demonstrated for the first time that FOLR1 could promote the transcription of Vangl2, one of PCP core genes. The transcription of Vangl2 was down-regulated under folate-deficient condition, which resulted in a decrease in PCP activity and F-actin formation. In summary, we identified a distinct advantage of FA in cell proliferation and F-actin formation over 5mTHF, as well as demonstrating that FOLR1 could promote transcription of Vangl2 and provide a new mechanism by which folate deficiency can contribute to the etiology of NTDs.
© 2023 Federation of American Societies for Experimental Biology.
Department of Reproductive Medicine Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Department of Reproductive Medicine Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.Departments of Molecular and Human Genetics and Medicine, Baylor College of Medicine, Houston, Texas, USA.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Folate regulation of planar cell polarity pathway and F-actin through folate receptor alpha.

Transcutaneous spinal stimulation (TSS) has become a valuable tool for facilitating rehabilitation in individuals with neurological deficits. A significant constraint arises from the need for precise knowledge of stimulation locations to effectively apply TSS for targeted functional enhancement.In this study, we investigate whether single-site or simultaneous multi-site stimulation over the lumbar spinal cord is advantageous for recruitment of specific motor pools projecting to lower limb muscles and generates higher leg extensor forces in neurologically intact individuals. Tests were performed in a supine position. TSS was delivered at T10-T11, T11-T12, T12-L1, and L1-L2 intervertebral spaces individually, then through all four locations simultaneously. The peak-to-peak amplitude of spinally evoked motor potentials and the forces generated by lower limb muscles were compared at the common motor threshold intensity level across all stimulation conditions.Recruitment of motor pools projecting to proximal and distal lower limb muscles followed their topographical rostro-caudal arrangement along the lumbosacral enlargement. Single-site stimulation, apart from the T10-T11 location, resulted in larger responses in both proximal and distal muscles while also generating higher knee-extension and plantarflexion forces when compared to multi-site stimulation.Both motor response and force generation were reduced when using multi-site TSS when compared to single-site stimulation. This demonstrates that the segmental effects of TSS are important to consider when performing multi-site TSS.
School of Engineering Medicine, Texas A&M University, Houston, TX, USA.
Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX, USA.
Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX, USA. Electronic address: dgsayenko@houstonmethodist.org.
Multi-site lumbar transcutaneous spinal cord stimulation: When less is more.

Nasopharyngeal carcinoma is a major public health problem in several countries, particularly in Southeast Asia and North Africa. However, the mechanism underlying the malignant biological behaviors of nasopharyngeal carcinoma is not fully clear. Our study intended to investigate the functional importance and molecular mechanism of proteasome 26 S subunit ATPase 2 (PSMC2) in the progression of nasopharyngeal carcinoma. We examined the expression of PSMC2 in both nasopharyngeal carcinoma tissues and normal healthy tissues using immunohistochemistry (IHC). Additionally, we conducted a series of cell experiments to verify the functional roles of PSMC2 and to explore the underlying pathway involved. The results revealed that PSMC2 was significantly upregulated in nasopharyngeal carcinoma tissues compared to normal tissues. Moreover, high PSMC2 was shown to closely correlate with the pathological stage and tumor infiltrate in nasopharyngeal carcinoma patients. Functionally, we observed a suppression of nasopharyngeal carcinoma progression upon knocking down PSMC2. This was evidenced by inhibited cell proliferation and migration in vitro, as well as impaired cell growth in vivo, along with increased apoptosis. Mechanistically, the inhibitory effects of PSMC2 silence on nasopharyngeal carcinoma could be reversed by the addition of AKT activator. Overall, our study sheds light on a novel mechanism underlying the development and progression of nasopharyngeal carcinoma, with PSMC2 exerting a positive regulatory role through the modulation of the AKT signaling pathway. A deeper understanding of PSMC2 may contribute to the development of improved treatment strategies for nasopharyngeal carcinoma.
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, Henan, China.
Department of Throat Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, ZhengZhou, Henan, China.
Medical Service, Zhengzhou hospital of Traditional Chinese medicine, Zhengzhou, Henan, China.
PSMC2 knockdown exerts an anti-tumor role in nasopharyngeal carcinoma through regulating AKT signaling pathway.

Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, and cell biology reveal this exquisitely specific E3-E2 pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 Å away, mediated by E2 multisite phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data show that phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, rigidifies the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, NV 89154, USA.
Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Technical University of Munich, School of Natural Sciences, Munich 85748, Germany.
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Technical University of Munich, School of Natural Sciences, Munich 85748, Germany. Electronic address: schulman@biochem.mpg.de.
Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies.

Lactylation is a lactate-induced post-translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient-derived xenograft and organoid models. A cell-penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.
Copyright © 2023 Elsevier Inc. All rights reserved.
State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai 200120, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Shaoyang University, Shaoyang 422001, China.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Medical Scientist Training Program, Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.
State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Shanghai 200072, China.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: yuanjian229@hotmail.com.
Metabolic regulation of homologous recombination repair by MRE11 lactylation.

Warren Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address: sara_ragi@brown.edu.
Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Dermatology Department, University of Connecticut School of Medicine, Farmington, Connecticut; Dermatology Department, University of Florida College of Medicine, Gainesville, Florida.
Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Ethical issues of patient images freely accessible on the internet.

Homologous repair deficiency (HRD) impedes double-strand break repair, which is a common driver of carcinogenesis. Positive HRD status can be used as theranostic markers of response to platinum- and PARP inhibitor-based chemotherapies. Here, we aimed to fully investigate the therapeutic and prognostic potential of HRD in pancreatic adenocarcinoma (PAAD) and identify effective biomarkers related to HRD using comprehensive bioinformatics analysis. The HRD score was defined as the unweighted sum of the LOH, TAI, and LST scores, and it was obtained based on the previous literature. To characterize PAAD immune infiltration subtypes, the ConsensusClusterPlus package in R was used to conduct unsupervised clustering. A WGCNA was conducted to elucidate the gene coexpression modules and hub genes in the HRD-related gene module of PAAD. The functional enrichment study was performed using Metascape. LASSO analysis was performed using the glmnet package in R, while the random forest algorithm was realized using the randomForest package in R. The prognostic variables were evaluated using univariate Cox analysis. The prognostic risk model was built using the LASSO approach. ROC curve and KM survival analyses were performed to assess the prognostic potential of the risk model. The half-maximal inhibitory concentration (IC50) of the PARP inhibitors was estimated using the pRRophetic package in R and the Genomics of Drug Sensitivity in Cancer database. The rms package in R was used to create the nomogram. A high HRD score indicated a poor prognosis and an advanced clinical process in PAAD patients. PAAD tumors with high HRD levels revealed significant T helper lymphocyte depletion, upregulated levels of cancer stem cells, and increased sensitivity to rucaparib, Olaparib, and veliparib. Using WGCNA, 11 coexpression modules were obtained. The red module and 122 hub genes were identified as the most correlated with HRD in PAAD. Functional enrichment analysis revealed that the 122 hub genes were mainly concentrated in cell cycle pathways. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were screened via LASSO analysis and a random forest algorithm, and they were validated using independent validation sets. No direct association between HRD and CKS1B, HJURP, or TPX2 has not been reported in the literature so far. Thus, these findings indicated that CKS1B, HJURP, and TPX2 have potential as diagnostic and prognostic biomarkers for PAAD. We constructed a novel HRD-related prognostic model that provides new insights into PAAD prognosis and immunotherapy. Based on bioinformatics analysis, we comprehensively explored the therapeutic and prognostic potential of HRD in PAAD. One novel HRD-related gene signature consisting of CKS1B, HJURP, and TPX2 were identified through the combination of WGCNA, LASSO analysis and a random forest algorithm. A novel HRD-related risk model that can predict clinical prognosis and immunotherapeutic response in PAAD patients was constructed.
Department of General surgery, The People's Hospital of Chizhou, Chizhou, Anhui Province, China.
Department of Nursing, The People's Hospital of Chizhou, Chizhou, Anhui Province, China.
Department of General surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Department of general surgery, Anqing First People's Hospital, Anqing, Anhui Province, China.
Identification of novel potential homologous repair deficiency-associated genes in pancreatic adenocarcinoma via WGCNA coexpression network analysis and machine learning.

Compounds binding to the bromodomains of bromodomain and extra-terminal (BET) family proteins, particularly BRD4, are promising anticancer agents. Nevertheless, side effects and drug resistance pose significant obstacles in BET-based therapeutics development. Using high-throughput screening of a 200,000-compound library, we identified small molecules targeting a phosphorylated intrinsically disordered region (IDR) of BRD4 that inhibit phospho-BRD4 (pBRD4)-dependent human papillomavirus (HPV) genome replication in HPV-containing keratinocytes. Proteomic profiling identified two DNA damage response factors-53BP1 and BARD1-crucial for differentiation-associated HPV genome amplification. pBRD4-mediated recruitment of 53BP1 and BARD1 to the HPV origin of replication occurs in a spatiotemporal and BRD4 long (BRD4-L) and short (BRD4-S) isoform-specific manner. This recruitment is disrupted by phospho-IDR-targeting compounds with little perturbation of the global transcriptome and BRD4 chromatin landscape. The discovery of these protein-protein interaction inhibitors (PPIi) not only demonstrates the feasibility of developing PPIi against phospho-IDRs but also uncovers antiviral agents targeting an epigenetic regulator essential for virus-host interaction and cancer development.
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
Department of Biochemistry and Molecular Biology, The University of Iowa, Iowa City, IA 52242, USA.
State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009, P.R. China.
Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA. Electronic address: jizhou@utmb.edu.
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: cheng-ming.chiang@utsouthwestern.edu.
IDR-targeting compounds suppress HPV genome replication via disruption of phospho-BRD4 association with DNA damage response factors.

Magnetic resonance imaging plays an important role in characterizing microstructural changes and reorganization after traumatic injuries to the nervous system. In this study, we tested the feasibility of ex-vivo spinal cord diffusion tensor imaging (DTI) in combination with in vivo brain functional MRI to characterize spinal reorganization and its supraspinal association after a hemicontusion cervical spinal cord injury (SCI). DTI parameters (fractional anisotropy [FA], mean diffusion [MD]) and fiber orientation changes related to reorganization in the contused cervical spinal cord were compared to sham specimens. Altered fiber density and fiber directions occurred across the ipsilateral and contralateral hemicords but with only ipsilateral FA and MD changes. The hemicontusion SCI resulted in ipsilateral fiber breaks, voids and vivid fiber reorientations along the injury epicenter. Fiber directional changes below the injury level were primarily inter-hemispheric, indicating prominent below-level cross-hemispheric reorganization. In vivo resting state functional connectivity of the brain from the respective rats before obtaining the spinal cord samples indicated spatial expansion and increased connectivity strength across both the sensory and motor networks after SCI. The consistency of the neuroplastic changes along the neuraxis (both brain and spinal cord) at the single-subject level, indicates that distinctive reorganizational relationships exist between the spinal cord and the brain post-SCI.
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 300 Cedar St, New Haven, CT 06520, United States. Electronic address: jelena.mihailovic@yale.edu.
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 300 Cedar St, New Haven, CT 06520, United States. Electronic address: basavaraju.ganganna@yale.edu.
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 300 Cedar St, New Haven, CT 06520, United States. Electronic address: fahmeed.hyder@yale.edu.
Department of Radiology, Rutgers Biomedical and Health Sciences-New Jersey Medical School, 30 Bergen Street, Newark, NJ 07103, United States.
Department of Neurosurgery, Rutgers Biomedical and Health Sciences-New Jersey Medical School. 205 South Orange Avenue, Newark, NJ 07103, United States. Electronic address: elkabest@njms.rutgers.edu.
Division of Neurosurgery, Hackensack Meridian School of Medicine, Mountainside Medical Center, Montclair, NJ, United States. Electronic address: robert.heary@mountainsidehosp.com.
Department of Radiology, Rutgers Biomedical and Health Sciences-New Jersey Medical School, 30 Bergen Street, Newark, NJ 07103, United States. Electronic address: kannursr@njms.rutgers.edu.
Cross-hemicord spinal fiber reorganization associates with cortical sensory and motor network expansion in the rat model of hemicontusion cervical spinal cord injury.

Bacteria use a diverse range of carbohydrates to generate a profusion of glycans, with amino sugars, such as N-acetylglucosamine (GlcNAc), being prevalent in the cell wall and in many exopolysaccharides. The primary substrate for GlcNAc-containing glycans, UDP-GlcNAc, is the product of the bacterial hexosamine pathway and a key target for bacterial metabolic glycan engineering. Using the strategy of expressing NahK, to circumvent the hexosamine pathway, it is possible to directly feed the analogue of GlcNAc, N-azidoacetylglucosamine (GlcNAz), for metabolic labeling in Escherichia coli. The cytosolic production of UDP-GlcNAz was confirmed by using fluorescence-assisted polyacrylamide gel electrophoresis. The key question of where GlcNAz is incorporated was interrogated by analyzing potential sites including peptidoglycan (PGN), the biofilm-related exopolysaccharide poly-β-1,6-N-acetylglucosamine (PNAG), lipopolysaccharide (LPS), and the enterobacterial common antigen (ECA). The highest levels of incorporation were observed in PGN with lower levels in PNAG and no observable incorporation in LPS or ECA. The promiscuity of the PNAG synthase (PgaCD) toward UDP-GlcNAz in vitro and the lack of undecaprenyl-pyrophosphoryl-GlcNAz intermediates generated in vivo confirmed the incorporation preferences. The results of this work will guide the future development of carbohydrate-based probes and metabolic engineering strategies.
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Department of Chemistry, University of North Carolina at Charlotte, Charlotte, North Carolina 28223-0001, United States.
Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 0A4, Canada.
Metabolic Usage and Glycan Destinations of GlcNAz in E. coli.

Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that SMAD7 gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of SMAD7 variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in SMAD7 were genotyped among 696 CRC patients and 696 healthy participants using the MassARRAY iPLEX platform. SNPs were evaluated for their associations with CRC using logistic regression analysis under multiple genetic models. The false-positive report probability (FPRP) analysis was used to validate the positive findings. Our study indicated that rs11874392 showed an increased association with CRC risk (odds ratio, 1.31; 95% confidence interval, 1.04-1.67; p = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, p = 0.028), individuals with smoking (OR = 1.87, p = 0.026), and drinking (OR = 1.38, p = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, p = 0.003), but not with colon cancer. FPRP analysis demonstrated that all of these associations were statistically significant (FPRP <0.2). Additionally, rs11874392 was the strongest predictive model for CRC. This study provides evidence that the SMAD7 rs11874392 is related to an increased susceptibility to CRC.
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.The Second Ward of Oncology and Hematology Department, The People's Hospital of XiangXiang, Xiangxiang, China.
Department of Intrarenal Rheumatology and Immunology, The People's Hospital of XiangXiang, Xiangxiang, China.
The Second Ward of Oncology and Hematology Department, The People's Hospital of XiangXiang, Xiangxiang, China.
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
SMAD7 gene polymorphisms and their influence on patients with colorectal cancer.

Neonatal respiratory distress syndrome (NRDS) is a common complication of gestational diabetes mellitus (GDM) and late preterm births. Research suggests that SIRT1 was involved in LPS-induced acute respiratory distress syndrome, but its mechanism remains to be further explored. Here, pregnant rats were intraperitoneally injected with 45 mg/Kg streptozotocin at day 0 of gestation to induce GDM and injected with LPS at day 17 of gestation to induce late preterm birth. Pioglitazone (a PPARγ agonist) was administered from day 17 to parturition in GDM group, and it was administered for 3 days before LPS injection in late preterm birth group. SRT1720 (a SIRT1 activator) was administered by oral gavage from day 0 to day 17 in both groups. Our data showed that activation of SIRT1 or PPARγ alleviated the abnormal blood glucose metabolism and lung tissue injury, downregulated expression of surfactant proteins (SP-B and SP-C), and decreased activation of the PI3K/AKT pathway induced by GDM and late preterm birth in neonatal rats. Moreover, an insulin resistance model was established by treating primary AT-II cells with insulin. Activation of SIRT1 reversed insulin-induced reduction in cell proliferation, glucose consumption, SP-B and SP-C expression, and the activity of the PI3K/AKT pathway and increase in cellular inflammation and apoptosis. Mechanistically, SIRT1 upregulated PPARγ expression via deacetylation of QKI5, an RNA binding protein that can stabilize its target mRNA molecules, and then activated the PI3K/AKT pathway. In conclusion, SIRT1 promotes the expression of PPARγ via upregulation of QKI5 and activates the PI3K/AKT pathway, thus mitigating NRDS caused by GDM and late preterm birth.
Department of Pediatrics, The First Affiliated Hospital of Air Force Military Medical University, Xi'an, China.
SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway.

Chronic kidney disease (CKD) patients have a high risk of cardiovascular disease. Indoxyl sulfate (IS) is a uremic toxin that has been shown to inhibit nitric oxide production and cause cell senescence by inducing oxidative stress. High-density lipoprotein (HDL) has a protective effect on the cardiovascular system; however, its impacts on IS-damaged endothelial cells are still unknown. This study aimed to explore the effects of exogenous supplement of HDL on vascular endothelial cells in a uremia-mimic environment. Tube formation, migration, adhesion, and senescence assays were used to evaluate the cell function of human aortic endothelial cells (HAECs). Reactive oxygen species generation was measured by using Amplex red assay. L-NAME and MCI186 were used as a nitric oxide synthase inhibitor and a free radical scavenger, respectively. HDL exerted anti-inflammatory and antioxidant effects via HIF-1α/HO-1 activation and IL-1β/TNF-α/IL-6 inhibition in IS-stimulated HAECs. HDL improved angiogenesis ability through upregulating Akt/eNOS/VEGF/SDF-1 in IS-stimulated HAECs. HDL decreased endothelial adhesiveness via downregulating VCAM-1 and ICAM-1 in IS-stimulated HAECs. Furthermore, HDL reduced cellular senescence via upregulating SIRT1 and downregulating p53 in IS-stimulated HAECs. Importantly, the above beneficial effects of HDL were mainly due to its antioxidant ability. In conclusion, HDL exerted a comprehensive protective effect on vascular endothelial cells against damage from IS through its antioxidant ability. The results of this study might provide a theoretical basis for potential HDL supplementation in CKD patients with endothelial damage.
Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Departments of Internal Medicine, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Departments of Internal Medicine, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
Departments of Internal Medicine, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.Departments of Internal Medicine, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.Department of Research, Taipei Medical University Hospital, Taipei, Taiwan.Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
High-density lipoprotein protects vascular endothelial cells from indoxyl sulfate insults through its antioxidant ability.

Endometriosis is a benign high prevalent disease exhibiting malignant features. However, the underlying pathogenesis and key molecules of endometriosis remain unclear. By integrating and analysis of existing expression profile datasets, we identified coxsackie and adenovirus receptor (CXADR), as a novel key gene in endometriosis. Based on the results of immunohistochemistry (IHC), we confirmed significant down-regulation of CXADR in ectopic endometrial tissues obtained from women with endometriosis compared with healthy controls. Further in vitro investigation indicated that CXADR regulated the stability and function of the phosphatases and AKT inhibitors PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2) and PTEN (phosphatase and tensin homolog). Loss of CXADR led to phosphorylation of AKT and glycogen synthase kinase-3β (GSK-3β), which resulted in stabilization of an epithelial-mesenchymal transition (EMT) factor, SNAIL1 (snail family transcriptional repressor 1). Therefore, EMT processs was induced, and the proliferation, migration and invasion of Ishikawa cells were enhanced. Over-expression of CXADR showed opposite effects. These findings suggest a previously undefined role of AKT/GSK-3β signaling axis in regulating EMT and reveal the involvement of a CXADR-induced EMT, in pathogenic progression of endometriosis.
Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.Center for Reproductive Health, and System Biology, Data Sciences, School of Basic Medical Science, Central South University, Changsha, China.
Department of Gynaecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, China.
Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
CXADR promote epithelial-mesenchymal transition in endometriosis by modulating AKT/GSK-3β signaling.

Single-nucleotide polymorphisms linked with the rs1474868 T allele (MFN2 [mitofusin-2] T/T) in the human mitochondrial fusion protein MFN2 gene are associated with reduced platelet MFN2 RNA expression and platelet counts. This study investigates the impact of MFN2 on megakaryocyte and platelet biology.Mice with megakaryocyte/platelet deletion of Mfn2 (Mfn2-/- [Mfn2 conditional knockout]) were generated using Pf4-Cre crossed with floxed Mfn2 mice. Human megakaryocytes were generated from cord blood and platelets isolated from healthy subjects genotyped for rs1474868. Ex vivo approaches assessed mitochondrial morphology, function, and platelet activation responses. In vivo measurements included endogenous/transfused platelet life span, tail bleed time, transient middle cerebral artery occlusion, and pulmonary vascular permeability/hemorrhage following lipopolysaccharide-induced acute lung injury.Mitochondria was more fragmented in megakaryocytes derived from Mfn2-/- mice and from human cord blood with MFN2 T/T genotype compared with control megakaryocytes. Human resting platelets of MFN2 T/T genotype had reduced MFN2 protein, diminished mitochondrial membrane potential, and an increased rate of phosphatidylserine exposure during ex vivo culture. Platelet counts and platelet life span were reduced in Mfn2-/- mice accompanied by an increased rate of phosphatidylserine exposure in resting platelets, especially aged platelets, during ex vivo culture. Mfn2-/- also decreased platelet mitochondrial membrane potential (basal) and activated mitochondrial oxygen consumption rate, reactive oxygen species generation, calcium flux, platelet-neutrophil aggregate formation, and phosphatidylserine exposure following dual agonist activation. Ultimately, Mfn2-/- mice showed prolonged tail bleed times, decreased ischemic stroke infarct size after cerebral ischemia-reperfusion, and exacerbated pulmonary inflammatory hemorrhage following lipopolysaccharide-induced acute lung injury. Analysis of MFN2 SNPs in the iSPAAR study (Identification of SNPs Predisposing to Altered ALI Risk) identified a significant association between MFN2 and 28-day mortality in patients with acute respiratory distress syndrome.Mfn2 preserves mitochondrial phenotypes in megakaryocytes and platelets and influences platelet life span, function, and outcomes of stroke and lung injury.
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.
Division of Hematology and Oncology, Bloodworks Northwest Research Institute, Seattle, WA (L.G.).
David Geffen School of Medicine and UCLA Health (R.S., E.D.A.), Los Angeles, CA.
University of Iowa (A.S.E.), Iowa City, IA.
Department of Nutrition and Integrative Physiology (A.N.F., S. Boudina), University of Utah, Salt Lake City, UT.
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Department of Nutrition and Integrative Physiology (A.N.F., S. Boudina), University of Utah, Salt Lake City, UT.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (D.C.C.).Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA (D.C.C.).
Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China (Y.W.).Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China (Y.W.).
Department of Biostatistics, School of Public Health, Nanjing Medical University, Jiangsu, China (C.J.).
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Division of Hematology and Hematologic Malignancies (R.A.C., M.T.R., P.F.B), University of Utah, Salt Lake City, UT.Department of Internal Medicine (P.F.B., J.W.R, M.T.R., R.A.C.), University of Utah, Salt Lake City, UT.Department of Pathology (R.A.C., M.T.R.), University of Utah, Salt Lake City, UT.
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Division of Hematology and Hematologic Malignancies (R.A.C., M.T.R., P.F.B), University of Utah, Salt Lake City, UT.Department of Internal Medicine (P.F.B., J.W.R, M.T.R., R.A.C.), University of Utah, Salt Lake City, UT.Department of Pathology (R.A.C., M.T.R.), University of Utah, Salt Lake City, UT.The Geriatric Research Education and Clinical Center (GRECC), George E. Wahlen Department of Veterans Affairs Medical Center (VAMC), Salt Lake City, UT (M.T.R.).
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Division of Hematology and Hematologic Malignancies (R.A.C., M.T.R., P.F.B), University of Utah, Salt Lake City, UT.Department of Internal Medicine (P.F.B., J.W.R, M.T.R., R.A.C.), University of Utah, Salt Lake City, UT.
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Oklahoma Medical Research Foundation (A.S.W.), Oklahoma City, OK.
Molecular Medicine Program, (S.J., Y.K., S. Bhatlekar, F.D., H.B., A.M., V.M., E.T., G.H., N.K., B.K.M., B.J.S., K.H., N.D.T., S. Boudina, R.A.C., M.T.R., P.F.B., A.S.W., J.W.R.), University of Utah, Salt Lake City, UT.Department of Internal Medicine (P.F.B., J.W.R, M.T.R., R.A.C.), University of Utah, Salt Lake City, UT.
Mitofusin-2 Regulates Platelet Mitochondria and Function.

Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project.We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES).Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups.Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
Departments of Neurology, NYU Grossman School of Medicine, New York, New York, USA.Department of Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, New York, USA.
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada, USA.Department of Neurology, University of Washington, Seattle, Washington, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.Framingham Heart Study, Framingham, Massachusetts, USA.Slone Epidemiology Center; Departments of Anatomy & Neurobiology, Neurology, and Medicine, Department of Epidemiology, Boston University Chobanian & Avedisian School of Medicine; Boston University School of Public Health, Boston, Massachusetts, USA.
Departments of Neuroscience and Psychiatry, University of California, San Diego, California, USA.
Departments of Neurology, NYU Grossman School of Medicine, New York, New York, USA.
Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.Encompass Health Braintree Rehabilitation Hospital, Braintree, Massachusetts, USA.
Institute for Neurodegenerative Disorders, Invicro, LLC, New Haven, Connecticut, USA.
Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.VA Boston Healthcare System, Boston, Massachusetts, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.Framingham Heart Study, Framingham, Massachusetts, USA.
Department of Physical Medicine & Rehabilitation, Massachusetts General Hospital, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, Massachusetts, USA.
Department of Psychiatry and Behavioral Sciences, VA Northwest Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System; University of Washington School of Medicine, Seattle, Washington, USA.
Department of Clinical Research & Leadership, The George Washington University School of Medicine & Health Sciences, Washington, District of Columbia, USA.
Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Gordon Center for Medical Imaging, Mass General Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, USA.
Banner Alzheimer's Institute and Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.University of Arizona, Arizona State University, Translational Genomics Research Institute, Phoenix, Arizona, USA.
DIAGNOSE CTE Research Project Investigators
Alzheimer's & dementia : the journal of the Alzheimer's Association
Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-11C-Pittsburgh compound B (PiB) Aβ-PET to predict cognitive decline. A cohort of 153 participants who previously underwent PiB-PET scans and comprehensive clinical assessments were used in this study. Our analyses revealed that baseline Aβ is significantly associated with the rate of change in cognitive composite scores, with cognition declining more rapidly when baseline PiB Aβ levels were higher. In contrast, no signification association was identified between the rate of change in PiB-PET Aβ and cognitive decline. Additionally, the ability of the rate of change in the PiB-PET measures to predict cognitive decline was significantly influenced by APOE ε4 carrier status. These results suggest that a single PiB-PET scan is sufficient to predict cognitive decline and that longitudinal measures of Aβ accumulation do not improve the prediction of cognitive decline once someone is amyloid positive.
Departments of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Departments of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Knight Alzheimer's Disease Research Center, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Banner Alzheimer's Institute, Phoenix, AZ, USA.
Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Divison of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Departments of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. Electronic address: benzingert@wustl.edu.
Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?

S-Nitrosation is a cysteine post-translational modification fundamental to cellular signaling. This modification regulates protein function in numerous biological processes in the nervous, cardiovascular, and immune systems. Small molecule or protein nitrosothiols act as mediators of NO signaling by transferring the NO group (formally NO+) to a free thiol on a target protein through a transnitrosation reaction. The protein targets of specific transnitrosating agents and the extent and functional effects of S-nitrosation on these target proteins have been poorly characterized. S-nitroso-coenzyme A (CoA-SNO) was recently identified as a mediator of endogenous S-nitrosation. Here, we identified direct protein targets of CoA-SNO-mediated transnitrosation using a competitive chemical-proteomic approach that quantified the extent of modification on 789 cysteine residues in response to CoA-SNO. A subset of cysteines displayed high susceptibility to modification by CoA-SNO, including previously uncharacterized sites of S-nitrosation. We further validated and functionally characterized the functional effects of S-nitrosation on the protein targets phosphofructokinase (platelet type), ATP citrate synthase, and ornithine aminotransferase.
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States.
Department of Biochemistry, Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Identification of Protein Targets of S-Nitroso-Coenzyme A-Mediated S-Nitrosation Using Chemoproteomics.

A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames (ORFs). To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a stepwise approach using multiple CRISPR-Cas9 screens to elucidate non-canonical ORFs and putative microproteins implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream ORFs (uORFs) exhibited selective functionality independent of main coding sequences. A microprotein encoded by one of these ORFs, ASNSD1-uORF or ASDURF, was upregulated, associated with MYC-family oncogenes, and promoted medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future studies seeking to define new cancer targets.
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands.
Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA; Department of Pathology, Boston Children's Hospital, Boston MA 02115, USA.
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45229, USA.
Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany; German Centre for Cardiovascular Research, Partner Site Berlin, 13347 Berlin, Germany.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands. Electronic address: s.vanheesch@prinsesmaximacentrum.nl.
Department of Pediatrics, Division of Pediatric Hematology/Oncology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: prensner@umich.edu.
Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma.

The very-low-density lipoprotein receptor (VLDLR) comprises eight LDLR type A (LA) domains and supports entry of distantly related alphaviruses, including Eastern equine encephalitis virus (EEEV) and Semliki Forest virus (SFV). Here, by resolving multiple cryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesis and functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2 A domain) to engage more than one LA domain simultaneously. However, no single LA domain is necessary or sufficient to support efficient EEEV infection. Whereas all EEEV strains show conservation of two VLDLR-binding sites, the EEEV PE-6 strain and a few other EEE complex members feature a single amino acid substitution that enables binding of LA domains to an additional site on the E2 B domain. These structural and functional analyses informed the design of a minimal VLDLR decoy receptor that neutralizes EEEV infection and protects mice from lethal challenge.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
The Center for Vaccine Research and Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: fremont@wustl.edu.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mdiamond@wustl.edu.
Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus.

Objective.Current radiotherapy guidelines for glioma target volume definition recommend a uniform margin expansion from the gross tumor volume (GTV) to the clinical target volume (CTV), assuming uniform infiltration in the invaded brain tissue. However, glioma cells migrate preferentially along white matter tracts, suggesting that white matter directionality should be considered in an anisotropic CTV expansion. We investigate two models of anisotropic CTV expansion and evaluate their clinical feasibility.Approach.To incorporate white matter directionality into the CTV, a diffusion tensor imaging (DTI) atlas is used. The DTI atlas consists of water diffusion tensors that are first spatially transformed into local tumor resistance tensors, also known as metric tensors, and secondly fed to a CTV expansion algorithm to generate anisotropic CTVs. Two models of spatial transformation are considered in the first step. The first model assumes that tumor cells experience reduced resistance parallel to the white matter fibers. The second model assumes that the anisotropy of tumor cell resistance is proportional to the anisotropy observed in DTI, with an 'anisotropy weighting parameter' controlling the proportionality. The models are evaluated in a cohort of ten brain tumor patients.Main results.To evaluate the sensitivity of the model, a library of model-generated CTVs was computed by varying the resistance and anisotropy parameters. Our results indicate that the resistance coefficient had the most significant effect on the global shape of the CTV expansion by redistributing the target volume from potentially less involved gray matter to white matter tissue. In addition, the anisotropy weighting parameter proved useful in locally increasing CTV expansion in regions characterized by strong tissue directionality, such as near the corpus callosum.Significance.By incorporating anisotropy into the CTV expansion, this study is a step toward an interactive CTV definition that can assist physicians in incorporating neuroanatomy into a clinically optimized CTV.
© 2024 Institute of Physics and Engineering in Medicine.
Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Division of Radiation Biophysics, 100 Blossom St, Boston, MA 02114, United States of America.
Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Division of Radiation Biophysics, 100 Blossom St, Boston, MA 02114, United States of America.Aarhus University Hospital, Danish Centre for Particle Therapy, Palle Juul-Jensens Blvd. 99, DK-8200 Aarhus, Denmark.Aarhus University, Department of Clinical Medicine, Palle Juul-Jensens Blvd. 82, DK-8200 Aarhus, Denmark.
Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, 100 Blossom St, Boston, MA 02114, United States of America.
Massachusetts General Hospital and Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, 149 Thirteenth St, Charlestown, MA 02129, United States of America.
The influence of anisotropy on the clinical target volume of brain tumor patients.

The rapid synthesis of a range of enantioenriched allylic esters is enabled by a new 3-component catalytic enantioselective 1,2-carboesterification of readily available dienes with carboxylic acids and potassium alkyltrifluoroborates. The chiral copper catalyst, formed in situ from Cu(OTf)2 and (4S,4'S)-2,2'-(cyclopentane-1,1-diyl)bis(4-phenyl-4,5-dihydrooxazole), is implicated in both the generation of alkyl radicals from the alkyltrifluoroborates as well as the enantioselective formation of C-O bonds. Potassium salts of primary and secondary alkyltrifluoroborates as well as several benzylic trifluoroborates, tert-butyltrifluoroborate, and phenyltrifluoroborate participate in the reaction. The regioselectivity and enantioselectivity are strongly impacted by variations in all of the reaction components, which in turn are thought to impact the C-O bond-forming reductive elimination from a [Cu(III)] intermediate.
Chemistry Department, Natural Science Complex, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Enantioenriched Allylesters via a Copper-Catalyzed Diene Carboesterification with Alkyltrifluoroborates and Carboxylic Acids.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cellular Imaging Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Center for Advanced Genome Engineering, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Center for Pediatric Neurological Disease Research, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Center for In Vivo Imaging and Therapy, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: stacey.ogden@stjude.org.
Cytoneme signaling provides essential contributions to mammalian tissue patterning.

The TAM family of receptor tyrosine kinases is implicated in multiple distinct oncogenic signaling pathways. However, to date, there are no FDA-approved small molecule inhibitors for the TAM kinases. Inhibitor design and screening rely on tools to study the kinase activity. Our goal was to address this gap by designing a set of synthetic peptide substrates for each of the TAM family members: Tyro3, Axl, and Mer. We used an in vitro phosphoproteomics workflow to determine the substrate profile of each TAM kinase and input the identified substrates into our data processing pipeline, KINATEST-ID, producing a position-specific scoring matrix for each target kinase and generating a list of candidate synthetic peptide substrates. We synthesized and characterized a set of those substrate candidates, systematically measuring their initial phosphorylation rate with each TAM kinase by LC-MS. We also used the multimer modeling function of AlphaFold2 (AF2) to predict peptide-kinase interactions at the active site for each of the novel candidate peptide sequences against each of the TAM family kinases and observed that, remarkably, every sequence for which it predicted a putative catalytically competent interaction was also demonstrated biochemically to be a substrate for one or more of the TAM kinases. This work shows that kinase substrate design can be achieved using a combination of preference motifs and structural modeling, and it provides the first demonstration of peptide-protein interaction modeling with AF2 for predicting the likelihood of constructive catalytic interactions.
Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, United States.
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, United States.
Novel Substrate Prediction for the TAM Family of RTKs Using Phosphoproteomics and Structure-Based Modeling.

Cells self-organize molecules in space and time to generate complex behaviors, but we lack synthetic strategies for engineering spatiotemporal signaling. We present a programmable reaction-diffusion platform for designing protein oscillations, patterns, and circuits in mammalian cells using two bacterial proteins, MinD and MinE (MinDE). MinDE circuits act like single-cell radios, emitting frequency-barcoded fluorescence signals that can be spectrally isolated and analyzed using digital signal processing tools. We define how to genetically program these signals and connect their spatiotemporal dynamics to cell biology using engineerable protein-protein interactions. This enabled us to construct sensitive reporter circuits that broadcast endogenous cell signaling dynamics on a frequency-barcoded imaging channel and to build control signal circuits that synthetically pattern activities in the cell, such as protein condensate assembly and actin filamentation. Our work establishes a paradigm for visualizing, probing, and engineering cellular activities at length and timescales critical for biological function.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Biophysics Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: smcoyle@wisc.edu.
A programmable reaction-diffusion system for spatiotemporal cell signaling circuit design.

The tolerance of the translation apparatus toward noncanonical amino acids (ncAAs) has enabled the creation of diverse natural-product-like peptide libraries using mRNA display for use in drug discovery. Typical experiments testing for ribosomal ncAA incorporation involve radioactive end point assays to measure yield alongside mass spectrometry experiments to validate incorporation. These end point assays require significant postexperimental manipulation for analysis and prevent higher throughput analysis and optimization experiments. Continuous assays for in vitro translation involve the synthesis of fluorescent proteins which require the full complement of canonical AAs for function and are therefore of limited utility for testing of ncAAs. Here, we describe a new, continuous fluorescence assay for in vitro translation based on detection of a short peptide tag using an affinity clamp protein, which exhibits changes in its fluorescent properties upon binding. Using this assay in a 384-well format, we were able to validate the incorporation of a variety of ncAAs and also quickly test for the codon reading specificities of a variety of Escherichia coli tRNAs. This assay enables rapid assessment of ncAAs and optimization of translation components and is therefore expected to advance the engineering of the translation apparatus for drug discovery and synthetic biology.
Chemistry, Virginia Commonwealth University, 1001 W Main Street, Richmond, 23220 Virginia, United States.Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Richmond, 23298-0037 Virginia, United States.
Continuous Fluorescence Assay for In Vitro Translation Compatible with Noncanonical Amino Acids.

Viral infection and the antiviral innate immune response are regulated by the RNA modification m6A. m6A directs nearly all aspects of RNA metabolism by recruiting RNA-binding proteins that mediate the fate of m6A-containing RNA. m6A controls the antiviral innate immune response in diverse ways, including shielding viral RNA from detection by antiviral sensors and influencing the expression of cellular mRNAs encoding antiviral signaling proteins, cytokines, and effector proteins. While m6A and the m6A machinery are important for the antiviral response, the precise mechanisms that determine how the m6A machinery selects specific viral or cellular RNA molecules for modification during infection are not fully understood. In this review, we highlight recent findings that shed light on how viral infection redirects the m6A machinery during the antiviral response. A better understanding of m6A targeting during viral infection could lead to new immunomodulatory and therapeutic strategies against viral infection.
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: stacy.horner@duke.edu.
Modifying the antiviral innate immune response by selective writing, erasing, and reading of m6A on viral and cellular RNA.

Cellular form and function emerge from complex mechanochemical systems within the cytoplasm. Currently, no systematic strategy exists to infer large-scale physical properties of a cell from its molecular components. This is an obstacle to understanding processes such as cell adhesion and migration. Here, we develop a data-driven modeling pipeline to learn the mechanical behavior of adherent cells. We first train neural networks to predict cellular forces from images of cytoskeletal proteins. Strikingly, experimental images of a single focal adhesion (FA) protein, such as zyxin, are sufficient to predict forces and can generalize to unseen biological regimes. Using this observation, we develop two approaches-one constrained by physics and the other agnostic-to construct data-driven continuum models of cellular forces. Both reveal how cellular forces are encoded by two distinct length scales. Beyond adherent cell mechanics, our work serves as a case study for integrating neural networks into predictive models for cell biology.
James Franck Institute, University of Chicago, Chicago, IL 60637, USA; Department of Physics, University of Chicago, Chicago, IL 60637, USA; Kadanoff Center for Theoretical Physics, University of Chicago, Chicago, IL 60637, USA.
Department of Cell & Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
James Franck Institute, University of Chicago, Chicago, IL 60637, USA; Department of Physics, University of Chicago, Chicago, IL 60637, USA.
James Franck Institute, University of Chicago, Chicago, IL 60637, USA; Department of Physics, University of Chicago, Chicago, IL 60637, USA. Electronic address: gardel@uchicago.edu.
Department of Cell & Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA. Electronic address: poakes@luc.edu.
James Franck Institute, University of Chicago, Chicago, IL 60637, USA; Department of Physics, University of Chicago, Chicago, IL 60637, USA; Kadanoff Center for Theoretical Physics, University of Chicago, Chicago, IL 60637, USA. Electronic address: vitelli@uchicago.edu.
Machine learning interpretable models of cell mechanics from protein images.

Energy metabolism supports neuronal function. While it is well established that changes in energy metabolism underpin brain plasticity and function, less is known about how individual neurons modulate their metabolic states to meet varying energy demands. This is because most approaches used to examine metabolism in living organisms lack the resolution to visualize energy metabolism within individual circuits, cells, or subcellular regions. Here, we adapted a biosensor for glycolysis, HYlight, for use in Caenorhabditis elegans to image dynamic changes in glycolysis within individual neurons and in vivo. We determined that neurons cell-autonomously perform glycolysis and modulate glycolytic states upon energy stress. By examining glycolysis in specific neurons, we documented a neuronal energy landscape comprising three general observations: 1) glycolytic states in neurons are diverse across individual cell types; 2) for a given condition, glycolytic states within individual neurons are reproducible across animals; and 3) for varying conditions of energy stress, glycolytic states are plastic and adapt to energy demands. Through genetic analyses, we uncovered roles for regulatory enzymes and mitochondrial localization in the cellular and subcellular dynamic regulation of glycolysis. Our study demonstrates the use of a single-cell glycolytic biosensor to examine how energy metabolism is distributed across cells and coupled to dynamic states of neuronal function and uncovers unique relationships between neuronal identities and metabolic landscapes in vivo.
Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06536.Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536.
Vollum Institute, Oregon Health & Science University, Portland, OR 97239.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden 01307, Germany.
Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06536.Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536.Vollum Institute, Oregon Health & Science University, Portland, OR 97239.
Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06536.Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536.Wu Tsai Institute, Yale University, New Haven, CT 06510.
Proceedings of the National Academy of Sciences of the United States of America
Local and dynamic regulation of neuronal glycolysis in vivo.

Pain, when treated inadequately, puts preterm infants at a greater risk of developing clinical and behavioural sequelae because of their immature pain system. Preterm infants in need of intensive care are repeatedly and persistently exposed to noxious stimuli, and this happens during a critical window of their brain development with peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations. Nearly two-thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period. These neonates are endotracheally intubated and require repeated endotracheal suctioning. Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants, causing moderate to severe pain. Even with improved nursing performance and standard procedures based on neonatal needs, endotracheal suctioning remains associated with mild pain.To evaluate the benefits and harms of non-pharmacological interventions for the prevention of pain during endotracheal suctioning in mechanically ventilated neonates. Non-pharmacological interventions were compared to no intervention, standard care or another non-pharmacological intervention.We conducted searches in June 2023 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Embase, CINAHL and three trial registries. We searched the reference lists of related systematic reviews, and of studies selected for inclusion.We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that included term and preterm neonates who were mechanically ventilated via endotracheal tube or via tracheostomy tube and required endotracheal suctioning performed by doctors, nurses, physiotherapists or other healthcare professionals.Our main outcome measures were validated composite pain scores (including a combination of behavioural, physiological and contextual indicators). Secondary outcomes included separate physiological and behavioural pain indicators. We used standard methodological procedures expected by Cochrane. For continuous outcome measures, we used a fixed-effect model and reported mean differences (MDs) with 95% confidence intervals (CIs). For categorical outcomes, we reported the typical risk ratio (RR) and risk difference (RD) and 95% CIs. We assessed risk of bias using the Cochrane RoB 1 tool, and assessed the certainty of the evidence using GRADE.We included eight RCTs (nine reports), which enroled 386 infants, in our review. Five of the eight studies were included in a meta-analysis. All studies enrolled preterm neonates. Facilitated tucking versus standard care (four studies) Facilitated tucking probably reduces Premature Infant Pain Profile (PIPP) score during endotracheal suctioning (MD -2.76, 95% CI 3.57 to 1.96; I² = 82%; 4 studies, 148 infants; moderate-certainty evidence). Facilitated tucking probably has little or no effect during endotracheal suctioning on: heart rate (MD -3.06 beats per minute (bpm), 95% CI -9.33 to 3.21; I² = 0%; 2 studies, 80 infants; low-certainty evidence); oxygen saturation (MD 0.87, 95% CI -1.33 to 3.08; I² = 0%; 2 studies, 80 infants; low-certainty evidence); or stress and defensive behaviours (SDB) (MD -1.20, 95% CI -3.47 to 1.07; 1 study, 20 infants; low-certainty evidence). Facilitated tucking may result in a slight increase in self-regulatory behaviours (SRB) during endotracheal suctioning (MD 0.90, 95% CI 0.20 to 1.60; 1 study, 20 infants; low-certainty evidence). No studies reported intraventricular haemorrhage (IVH). Familiar odour versus standard care (one study) Familiar odour during endotracheal suctioning probably has little or no effect on: PIPP score (MD -0.30, 95% CI -2.15 to 1.55; 1 study, 40 infants; low-certainty evidence); heart rate (MD -6.30 bpm, 95% CI -16.04 to 3.44; 1 study, 40 infants; low-certainty evidence); or oxygen saturation during endotracheal suctioning (MD -0.80, 95% CI -4.82 to 3.22; 1 study, 40 infants; low-certainty evidence). No studies reported SRB, SDB or IVH. White noise (one study) White noise during endotracheal suctioning probably has little or no effect on PIPP (MD -0.65, 95% CI -2.51 to 1.21; 1 study, 40 infants; low-certainty evidence); heart rate (MD -1.85 bpm, 95% CI -11.46 to 7.76; 1 study, 40 infants; low-certainty evidence); or oxygen saturation (MD 2.25, 95% CI -2.03 to 6.53; 1 study, 40 infants; low-certainty evidence). No studies reported SRB, SDB or IVH.Facilitated tucking / four-handed care / gentle human touch probably reduces PIPP score. The evidence of a single study suggests that facilitated tucking / four-handed care / gentle human touch slightly increases self-regulatory and approach behaviours during endotracheal suctioning. Based on a single study, familiar odour and white noise have little or no effect on any of the outcomes compared to no intervention. The use of expressed breast milk or oral sucrose suggests that there is no discernible advantage of one method over the other for reducing pain during endotracheal suctioning. None of the studies reported on any of the prespecified secondary outcomes of adverse events.
Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Neonatology, UZ Brussel, Jette, Belgium.
Midwifery Research, Education and Policymaking, Universiteit Antwerpen, Brussel, Belgium.
Physiotherapy and Neonatology, UZ Brussel, Jette, Belgium.
Neonatology, UZ Brussel, Jette, Belgium.CEBAM, Belgian Centre for Evidence-Based Medicine, Leuven, Belgium.Vrije Universiteit Brussel, Brussels, Belgium.
The Cochrane database of systematic reviews
Cochrane Database Syst Rev. 2024-01-18;1():CD013353.
Non-pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.

Cardiopulmonary arrest (CA) is a major cause of death/disability in the U.S. with poor prognosis and survival rates. Current therapeutic challenges are physiologically complex because they involve hypoperfusion (decreased cerebral blood flow), neuroinflammation, and mitochondrial dysfunction. We previously discovered novel serum/glucocorticoid-regulated kinase 1 (SGK1) is highly expressed in brain of neurons that are susceptible to ischemia (hippocampus and cortex). We inhibited SGK1 and utilized pharmacological (specific inhibitor, GSK650394) and neuron-specific genetic approaches (shRNA) in rodent models of CA to determine if SGK1 is responsible for hypoperfusion, neuroinflammation, mitochondrial dysfunctional, and neurological deficits after CA. Inhibition of SGK1 alleviated cortical hypoperfusion and neuroinflammation (via Iba1, GFAP, and cytokine array). Treatment with GSK650394 enhanced mitochondrial function (via Seahorse respirometry) in the hippocampus 3 and 7 days after CA. Neuronal injury (via MAP2, dMBP, and Golgi staining) in the hippocampus and cortex was observed 7 days after CA but ameliorated with SGK1-shRNA. Moreover, SGK1 mediated neuronal injury by regulating the Ndrg1-SOX10 axis. Finally, animals subjected to CA exhibited learning/memory, motor, and anxiety deficits after CA, whereas SGK1 inhibition via SGK1-shRNA improved neurocognitive function. The present study suggests the fundamental roles of SGK1 in brain circulation and neuronal survival/death in cerebral ischemia-related diseases.
Stroke Center for Research, Louisiana State University Health, Shreveport, LA, USA.Department of Neurology, Louisiana State University Health, Shreveport, LA, USA.
Department of Cellular Biology and Anatomy, Louisiana State University Health, Shreveport, LA, USA.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia.

RNA secondary structure plays essential roles in encoding RNA regulatory fate and function. Most RNAs populate ensembles of alternatively paired states and are continually unfolded and refolded by cellular processes. Measuring these structural ensembles and their contributions to cellular function has traditionally posed major challenges, but new methods and conceptual frameworks are beginning to fill this void. In this review, we provide a mechanism- and function-centric compendium of the roles of RNA secondary structural ensembles and minority states in regulating the RNA life cycle, from transcription to degradation. We further explore how dysregulation of RNA structural ensembles contributes to human disease and discuss the potential of drugging alternative RNA states to therapeutically modulate RNA activity. The emerging paradigm of RNA structural ensembles as central to RNA function provides a foundation for a deeper understanding of RNA biology and new therapeutic possibilities.
Therapeutic Innovation Center (THINC), Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Therapeutic Innovation Center (THINC), Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: anthony.mustoe@bcm.edu.
Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states.

Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome.To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments.We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023.We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies.We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation. We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence.We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years). We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I2 = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I2 = 78%; very low-certainty evidence). The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I2 = 0%; low-certainty evidence). We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I2 = 0%; very low-certainty evidence) or on the length of hospitalisation (MD -20.0 days, 95% CI -39.92 to -0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence). No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement. Funding No trials reported sources of commercial funding or conflicts of interest between researchers. Ongoing studies We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found.TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.
Research Methodology Department, Instituto Nacional de Pediatría, Mexico City, Mexico.
Clinical Nutrition Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Pediatric Oncology Department, Instituto Nacional de Pediatría, Mexico City, Mexico.
Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Medical Library, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Cochrane Database Syst Rev. 2024-01-18;1():CD011039.
Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

Disparities in youth homelessness by racial/ethnic, sexual, and gender identities are well documented, though this literature lacks specificity regarding intersectional social identities of youth who are most likely to experience homelessness. Population-based cross-sectional data on youth from the 2019 Minnesota Student Survey (N = 80,456) were used to examine the relationship between parent caring and intersections of minoritized identities that experience the highest prevalence of two distinct types of unaccompanied unstable housing with expanded categories of sexual and gender identities. Exhaustive chi-square automatic interaction detection models revealed that low parent caring was the most common predictor of unaccompanied homelessness and running away, but there was important variation among youth of color at the intersection of sexual and gender identities. The findings reveal a more complex story of disparities in unaccompanied unstable housing among youth with multiple marginalized social identities and highlight the need to create culturally informed prevention and intervention strategies for parents of LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and questioning) youth of color. The implications for prevention and intervention among subgroups with the highest prevalence are discussed in the context of interlocking systems of power and oppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota Twin Cities.
Department of Family Social Science, College of Education and Human Development, University of Minnesota Twin Cities.
Division of General Pediatrics and Adolescent Health, Department of Pediatrics, University of Minnesota Twin Cities.
Department of Human Development and Family Sciences, University of Texas at Austin.
Department of Family Medicine and Community Health, Institute for Sexual and Gender Health, University of Minnesota Medical School.
Unaccompanied unstable housing among racially, ethnically, sexually, and gender diverse youth: Intersecting identities bearing the greatest burden.

Decreased mobility is a hallmark of aging. Olfactory dysfunction is common in older adults and may be associated with declines in mobility.To determine whether poor olfaction was associated with faster declines in mobility in older adults.This cohort study included 2500 participants from the Health, Aging, and Body Composition Study. Participants completed the Brief Smell Identification Test during the year 3 clinical visit (1999-2000) and were followed for up to 7 years. A data analysis was conducted between January and July 2023.Olfaction was defined as good (test score, 11-12), moderate (9-10), hyposmia (7-8), or anosmia (0-6).Mobility was measured using the 20-m usual and fast walking tests in clinical visit years 3 to 6, 8, and 10 and the 400-m fast walking test in years 4, 6, 8, and 10.The primary analyses included 2500 participants (1292 women [51.7%]; 1208 men [48.3%]; 960 Black [38.4%] and 1540 White [61.6%] individuals; mean [SD] age, 75.6 [2.8] years). Multivariate-adjusted analyses showed that poor olfaction was associated with slower walking speed at baseline and a faster decline over time. Taking the 20-m usual walking test as an example, compared with participants with good olfaction, the speed at baseline was 0.027 (95% CI, 0-0.053) m/s slower for those with hyposmia and 0.034 (95% CI, 0.005-0.062) m/s slower for those with anosmia. Longitudinally, the annual decline was 0.004 (95% CI, 0.002-0.007) m/s/year faster for those with hyposmia and 0.01 (95% CI, 0.007-0.013) m/s/year faster for those with anosmia. Similar results were obtained for the 20-m and 400-m fast walking tests. Further, compared with participants with good olfaction, the odds of being unable to do the 400-m test were 2.02 (95% CI, 1.17-3.48) times higher for those with anosmia at the year 8 visit and 2.73 (95% CI, 1.40-5.35) times higher at year 10. Multiple sensitivity and subgroup analyses supported the robustness and generalizability of the findings.The results of this cohort study suggest that poor olfaction is associated with a faster decline in mobility in older adults. Future studies should investigate underlying mechanisms and potential health implications.
Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing.
Laboratory of Epidemiology and Population Science, Intramural Research Program of the National Institutes of Health, National Institute on Aging, Bethesda, Maryland.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill.
JAMA otolaryngology-- head & neck surgery
JAMA Otolaryngol Head Neck Surg. 2024-03-01;150(3):201-208.

Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS.To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC).This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up.The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 μm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 μm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 μm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance.This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 μm and light-room ARA at 750 μm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou, China.
Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston.
NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.Experimental Ophthalmology, The Hong Kong Polytechnic University, Hong Kong, China.
Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect.

Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for CTCL are still poorly understood though recent studies suggest chemical exposures may play a role in its development. To further characterize patient-centered risk factors for CTCL, especially compared with matched controls, we performed one of the largest prospective cohort survey studies to date to examine patient-reported exposures and health-related quality of life (HRQoL) in association with concurrent clinical disease characteristics. Patient demographics, lifestyle factors, and chemical exposures were collected via clinical data and surveys. Descriptive statistics, ANOVA, Chi-square tests and t tests were utilized to compare patient-reported exposures and HRQoL in patients with CTCL versus matched healthy controls (HC). Statistically significant differences were identified between patients and HC in terms of race (non-white race 22.4% in CTCL patients vs. 18.8% in HC, P = 0.01), and education level (high school or less 41.6% in CTCL patients vs. 14.3% in HC, P = 0.001), but not with Fitzpatrick skin type (P = 0.11) or smoking status (P = 0.28). Notably, 36.0% of the CTCL patients reported exposures to chemicals, a near threefold increased percentage when compared to HC (12.9%). Among various chemical exposures, 27.0% of the CTCL patients specifically reported industrial chemical exposure, a more than two-fold increased percentage when compared to HC (12.9%). Itch and pain were significantly associated with skin disease severity (as evaluated by CTCL-specific mSWAT score) in advanced stage disease (stages IIB-IVB) (r = 0.48 and 0.57, P < 0.05). Itch and body mass index (BMI) were weakly associated with skin disease severity in early-stage disease (stages IA-IIA) (r = 0.27 and 0.20, P < 0.05).
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. alan.zhou@northwestern.edu.
Chemical exposures and demographic associations in cutaneous T-cell lymphoma: a large single institution physician validated cohort study.

High-deductible health plans (HDHPs) have grown rapidly and may adversely affect access to comprehensive cancer care.To evaluate the association of HDHPs with out-of-pocket medical costs and outpatient physician visits among patients with cancer.Using 2003 to 2017 data from the deidentified Optum Clinformatics Data Mart database from individuals with employer-sponsored health coverage, adults aged 18 to 64 years with cancer who were enrolled in low-deductible (≤$500 annually) health plans during a baseline year were identified. Patients whose employers then mandated a switch to an HDHP (≥$1000 annual deductible) were assigned to the HDHP group, while contemporaneous individuals with cancer at baseline who had no option but to continue enrollment in low-deductible plans were assigned to the control group. The 2 groups were matched on demographic variables (age, sex, race and ethnicity, US Census region, rural vs urban, and neighborhood poverty level), cancer type, morbidity score, number of baseline physician visits by specialty type, baseline out-of-pocket costs, and employer characteristics. These cohorts were followed up for up to 3 years after the baseline year. Data were analyzed from July 2021 to December 2022.Employer-mandated HDHP enrollment.Out-of-pocket medical expenditures and outpatient visits to primary care physicians, cancer specialists, and noncancer specialists.After matching, the sample included 45 708 patients with cancer (2703 patients in the HDHP group and 43 005 matched individuals in the control group); mean (SD) age in the HDHP and control groups was 52.9 (9.3) years and 52.9 (2.3) years, respectively, with 58.5% females in both groups. The matching procedure yielded variable weights for each individual in the control group, resulting in a weighted control group sample of 2703 patients. Patients with cancer who were switched to HDHPs experienced an increase in annual out-of-pocket medical expenditures of 68.1% (95% CI, 51.0%-85.3%; absolute increase, $1349.80 [95% CI, $1060.30-$1639.20]) after the switch compared with those who remained in traditional health plans. At follow-up, the number of oncology visits did not differ between the 2 groups (relative difference, 0.1%; 95% CI, -8.4% to 9.4%); however, the HDHP group had 10.8% (95% CI, -15.5% to -5.9%) fewer visits to primary care physicians and 5.9% (95% CI, -11.2% to -0.3%) fewer visits to noncancer specialists.Results of this cohort study suggest that after enrollment in HDHPs, patients with cancer experienced substantial increases in out-of-pocket medical costs. The number of visits to oncologists was unchanged during follow-up, but the number of visits to noncancer physicians was lower. These findings suggest that HDHPs are unlikely to unfavorably affect key oncology services but might lead to less comprehensive care of cancer survivors.
Department of Medicine, Massachusetts General Hospital, Boston.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Department of Medicine, Duke University, Durham, North Carolina.Duke-Margolis Center for Health Policy, Durham, North Carolina.
Out-of-Pocket Costs and Outpatient Visits Among Patients With Cancer in High-Deductible Health Plans.

Anti-vascular endothelial growth factor (VEGF) treatment through intravitreal or subretinal administrations has been proven effective for VEGF-driven pediatric vitreoretinal diseases but are not feasible for advanced cases, such as shallow traction retinal detachments or peripheral circumferential retinal detachments which adhere to the lens. Intra-anterior chamber injection (IAcI) of anti-VEGF may be a viable alternative in such cases but needs evaluation.To investigate the effects and safety of IAcI of anti-VEGF to treat VEGF-driven pediatric vitreoretinal diseases.This was a retrospective observational case series study conducted at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine in China. The study included 14 eyes of 13 children diagnosed with vitreoretinal disease exhibiting elevated vascular activity between January and August 2023.IAcI with ranibizumab.Retinal vascular abnormalities, vitreous hemorrhage resolution, and complications 1 month and 3 months after injection.Of 13 patients included in this study, 12 were male. The mean age was 4.6 years (range, 1 month to 9 years). Six patients were diagnosed with familial exudative vitreoretinopathy, 4 with morning glory syndrome, 1 with retinopathy of prematurity, and 2 with chronic retinal detachments of unknown causes. At 1-month postoperative follow-up, vascular activity had decreased in 14 of 14 eyes. At 3-month follow-up, vascular activity had resolved in 7 of 14 eyes, persisted in 6 of 14 eyes, and reactivated in 1 of 14 eyes. On final observation, no complications were reported.These findings support the possibility of treatment using IAcI with ranibizumab to decrease retinal vascular abnormalities in familial exudative vitreoretinopathy or retinopathy of prematurity or related conditions, but further studies are needed to understand more precise benefits and risks. This approach might be considered in cases where intravitreal or subretinal injection are not feasible, recognizing the limitations of these findings and that longer-term outcomes still need to be monitored.
Department of Ophthalmology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Intra-Anterior Chamber Injection of Ranibizumab in Advanced Pediatric Vitreoretinal Diseases.

Single sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known.To investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults.This retrospective analysis of a longitudinal cohort study, the Health, Aging, and Body Composition (Health ABC) study, incorporated data from April 1997 to July 2013, featuring a 16-year follow-up with annual examinations and questionnaires. The cohort comprised 3075 men and women, aged 70 to 79 years at baseline, residing in Memphis, Tennessee, and Pittsburgh, Pennsylvania. All participants with complete sensory testing and covariate data at analytical baseline (year 5, 2002) were included. The data were analyzed September 1, 2022.Visual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002.The main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB).A total of 1825 individuals (mean [SD] age, 77.4 [3.2] years; 957 [52%] female) were included in this study. Multivariable analysis of HABCPPB decline indicated that having 1 sensory impairment (β estimate, -0.01 [95% CI, -0.02 to -0.001]); 2 sensory impairments (β estimate, -0.01 [95% CI, -0.02 to -0.01]); 3 sensory impairments (β estimate, -0.03 [95% CI, -0.04 to -0.02]); or 4 sensory impairments (β estimate, -0.04 [95% CI, -0.05,-0.03]) was significantly associated with a steeper HABCPPB score decline in a dose-dependent manner. Adjusted Cox proportional hazards models indicated that having 1 sensory impairment (hazard ratio [HR], 1.35 [95% CI, 1.01-1.81]), 2 sensory impairments (HR, 1.58 [95% CI, 1.19-2.11]), 3 sensory impairments (HR, 1.79 [95% CI, 1.33-2.42]), or 4 sensory impairments (HR, 1.97 [95% CI, 1.39-2.79]) was significantly associated with increased mortality risk in a similarly dose-dependent manner.In this retrospective cohort study, the degree and number of multiple sensory impairments were associated with worse physical functioning and increased mortality risk. These findings represent an opportunity for further investigation into the value of screening, prevention, and treatment of sensory impairments to reduce morbidity and mortality in older adults.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland.
National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, Maryland.
Department of Psychiatry and Behavior Sciences, Johns Hopkins University, Baltimore, Maryland.
Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland.Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland.
JAMA Otolaryngol Head Neck Surg. 2024-03-01;150(3):217-225.
Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment.

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.
Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.Canadian Medication Appropriateness and Deprescribing Network, Montreal, Quebec, Canada.
Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada.
Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Right to Care, NPC, Centurion, South Africa.London School of Hygiene and Tropical Medicine, London, United Kingdom.
Canadian Medication Appropriateness and Deprescribing Network, Montreal, Quebec, Canada.
Sinai Health System-University Health Network Antimicrobial Stewardship Program, University of Toronto, Toronto, Canada.Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
Pneumocystis jirovecii pneumonia in people living with HIV: a review.

Aggregation prone molecules, such as tau, form both historically well characterized fibrillar deposits (neurofibrillary tangles) and recently identified phosphate-buffered saline (PBS) extract species called proteopathic seeds. Both can cause normal endogenous tau to undergo templated misfolding. The relationship of these seeds to the fibrils that define tau-related diseases is unknown. We characterized the aqueous extractable and sarkosyl insoluble fibrillar tau species derived from human Alzheimer brain using mass spectrometry and in vitro bioassays. Post-translational modifications (PTMs) including phosphorylation, acetylation and ubiquitination are identified in both preparations. PBS extract seed competent tau can be distinguished from sarkosyl insoluble tau by the presence of overlapping, but less abundant, PTMs and an absence of some PTMs unique to the latter. The presence of ubiquitin and other PTMs on the PBS-extracted tau species correlates with the amount of tau in the seed competent size exclusion fractions, with the bioactivity and with the aggressiveness of clinical disease. These results demonstrate that the PTMs present on bioactive, seed competent PBS extract tau species are closely related to, but distinct from, the PTMs of mature paired helical filaments, consistent with the idea that they are a forme fruste of tau species that ultimately form fibrils.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA.
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA.
Alzheimer proteopathic tau seeds are biochemically a forme fruste of mature paired helical filaments.

Center for Excellence in Vascular Biology (P.K.J., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.
Center for Excellence in Vascular Biology (P.K.J., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.Center for Interdisciplinary Cardiovascular Sciences (M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.Channing Division of Network Medicine (M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.
Center for Excellence in Vascular Biology (P.K.J., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.Center for Interdisciplinary Cardiovascular Sciences (M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston.
Macrophage Heterogeneity and Efferocytosis: Beyond the M1/M2 Dichotomy.

Recurrence after curative-intent treatment occurs in 20%-50% of patients with stage II-IV colorectal cancer (CRC), underscoring the need for early detection of minimal residual disease (MRD) using circulating tumor DNA (ctDNA). Here, we examined the pattern of use of a tumor-informed ctDNA assay in CRC MRD monitoring in routine clinical practice at Mayo Clinic, Rochester.We conducted a retrospective analysis of health records of patients with CRC who had at least one tumor-informed ctDNA assay from May 2019 through July 1, 2022. Recurrence was defined as radiographic evidence of disease. Descriptive characteristics of the cohort, ctDNA results, and subsequent interventions were recorded.Of the 120 patients included, the median age at diagnosis was 67 years, 46% were female, and 94% were White. At diagnosis, 10 patients had stage I, 23 stage II, 60 stage III, and 25 stage IV disease. Of 476 ctDNA assays performed, 70% were performed in patients who had recurrent disease most commonly to monitor the effectiveness of therapeutic interventions and 16% resulted in a change in clinical decision making. There were 110 recurrences identified in 62 patients, as some patients experienced more than one recurrence over time. Compared with serum carcinoembryonic antigen levels, ctDNA results correlated better with radiologic imaging.Routine ctDNA monitoring for MRD detection has been adopted in clinical practice; however, 84% of ctDNA assays performed did not result in a change in clinical management. This suggests the need for further clinical research data to guide routine clinical use of ctDNA MRD testing in CRC.
Division of Oncology, Mayo Clinic, Rochester, MN.
Department of Medicine, Mayo Clinic, Rochester, MN.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.
Department of Radiation Oncology, Mayo Clinic, Rochester, MN.
Department of Hematology and Oncology, University Hospitals, Cleveland, OH.
Department of Surgery, Mayo Clinic, Rochester, MN.
Division of Oncology, Mayo Clinic, Rochester, MN.Department of Medicine, Mayo Clinic, Rochester, MN.
Tumor-Informed Circulating Tumor DNA for Minimal Residual Disease Detection in the Management of Colorectal Cancer.

Glioblastomas (GBMs) are central nervous system tumors that resist standard-of-care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable antitumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation.Our reverse translational investigations leveraged single-cell RNA sequencing and cytometry of human gliomas to characterize TREM2 expression across myeloid subpopulations. Using 2 distinct murine glioma models, we examined the role of Trem2 on tumor progression and immune modulation of myeloid cells. Furthermore, we designed a method of tracking phagocytosis of glioma cells in vivo and employed in vitro assays to mechanistically understand the influence of TREM2 signaling on tumor uptake.We discovered that TREM2 expression does not correlate with immunosuppressive pathways, but rather showed strong a positive association with the canonical phagocytosis markers lysozyme (LYZ) and macrophage scavenger receptor (CD163) in gliomas. While Trem2 deficiency was found to be dispensable for gliomagenesis, Trem2+ myeloid cells display enhanced tumor uptake compared to Trem2- cells. Mechanistically, we demonstrate that TREM2 mediates phagocytosis via Syk signaling.These results indicate that TREM2 is not associated with immunosuppression in gliomas. Instead, TREM2 is an important regulator of phagocytosis that may be exploited as a potential therapeutic strategy for brain tumors.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Department of Translational Molecular Pathology, Neurosurgery at the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.Department of Translational Molecular Pathology, The University of Texas, MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
Department of Translational Molecular Pathology, Neurosurgery at the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Genomic Medicine, Neurosurgery at the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Neurological Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA.
Department of Electrical and Computer Engineering, University of Houston, Houston, Texas, USA.
Departments of Translational Molecular Pathology, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.
Department of Hematopoietic Biology & Malignancy, Neurosurgery at the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Triggering receptor expressed on myeloid cells 2 (TREM2) regulates phagocytosis in glioblastoma.

Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (T.T., T.O.Y., J.H.), Yale University School of Medicine, New Haven, CT.
Section of Critical Care, Department of Pediatrics (E.V.S.F.), Yale University School of Medicine, New Haven, CT.
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine (T.T., T.O.Y., J.H.), Yale University School of Medicine, New Haven, CT.Yale Cooperative Center of Excellence in Hematology (J.H.), Yale University School of Medicine, New Haven, CT.
Platelet Mitochondrial Fusion and Function in Vascular Integrity.

Division of Pulmonary and Critical Care Medicine, Columbia University, New York, NY, USA.
Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL, USA.
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA chad.newton@utsouthwestern.edu.
Reply: Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.

The production and secretion of VLDLs (very-low-density lipoproteins) by hepatocytes has a direct impact on liver fat content, as well as the concentrations of cholesterol and triglycerides in the circulation and thus affects both liver and cardiovascular health, respectively. Importantly, insulin resistance, excess caloric intake, and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased plasma levels of atherogenic lipoproteins. Cholesterol and triglycerides in remnant particles generated by VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease and have garnered increasing attention over the last few decades. Presently, however, increased risk of atherosclerosis is not the only concern when considering today's cardiometabolic patients, as they often also experience hepatic steatosis, a prevalent disorder that can progress to steatohepatitis and cirrhosis. This duality of metabolic risk highlights the importance of understanding the molecular regulation of the biogenesis of VLDL, the lipoprotein that transports triglycerides and cholesterol out of the liver. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, which has led to many exciting new molecular insights that are the topic of this review. Increasing our understanding of the biology of this pathway will aid to the identification of novel therapeutic targets to improve both the cardiovascular and the hepatic health of cardiometabolic patients. This review focuses, for the first time, on this duality.
Department of Paediatrics, University Medical Center Groningen, University of Groningen, the Netherlands (W.v.Z., B.v.d.S., J.A.K.).
Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (H.N.G.).
VLDL Biogenesis and Secretion: It Takes a Village.

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes.In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses.We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort.We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine.The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.Mathematical Informatics Laboratory, Division of Information Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara, 630-0192, Japan.
Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.
Breast and Endocrine Surgery, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.Department of Next-generation Clinical Genomic Medicine, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Department of Breast Surgery, Shimane University Hospital, Enyacho 89-1, Izumo, Shimane, 693-0021, Japan.
Department of Breast Surgery and Oncology, Kanagawa Cancer Center, 2-3-2 Nakano, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
Department of Breast Surgery, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.
Department of Breast and Endocrine Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Mathematical Informatics Laboratory, Division of Information Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara, 630-0192, Japan.
Department of Breast Surgery, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi Chuo-ku, Kobe-shi, Hyogo, 650-0047, Japan.
Breast Surgical Oncology, The Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.Department of Pathology and Tumor Biology, Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.
Breast Oncology Center, The Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan. kkosuke@kuhp.kyoto-u.ac.jp.
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, 54 Kawahara-cho, Shogoin Sakyo-ku, Kyoto, 606-8507, Japan. toi@kuhp.kyoto-u.ac.jp.Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. toi@kuhp.kyoto-u.ac.jp.
Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.
Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, Arizona, USA.Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA.
Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA.
Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, Arizona, USA.Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA.
Vitamin D deficiency promotes intracranial aneurysm rupture.

Hahn School of Nursing and Health Science, University of San Diego, San Diego, CA 92110, United States.
School of Nursing, Columbia University, New York, NY 10032, United States.
Department of Biomedical Informatics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, United States.
Journal of the American Medical Informatics Association : JAMIA
Advancing the science of visualization of health data for lay audiences.

The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic.This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated.The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy.The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.
Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.The Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China.
MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Thyroid Surgery, West China Tianfu Hospital, Chengdu, China.
Thyroid and Breast Surgery, West China Fourth Hospital, Chengdu, China.
Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospital, Chengdu, China.
Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China. leijianyong@scu.edu.cn.The Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. leijianyong@scu.edu.cn.
Circulating small extracellular vesicle-based miRNA classifier for follicular thyroid carcinoma: a diagnostic study.

Paracoccidioidomycosis is an infection with the potential for environmental dissemination, especially in regions of hot and humid climate, where human cases have been recorded in the Southwestern Amazon of Brazil, specifically in the state of Acre. Despite studies providing information about the presence of these fungi in soil and animal samples, such as armadillos, further investigations are still needed to determine the epidemiological distribution of the genus Paracoccidioides. The aim of this study was to detect the occurrence of Paracoccidioides fungi in the Southwestern Amazon. To achieve this, 60 soil samples were collected from armadillo burrows on rural properties in the in the municipalities of Acrelândia, Bujari, Plácido de Castro, Rio Branco, Sena Madureira, and Senador Guiomard, located in the state of Acre, Brazil. Fungal DNA was extracted from these samples using the DNEASY® PowerSoil kit-Quiagen, followed by Nested PCR technique with ITS4 and ITS5 as external primers, and PBITS-E and PBITS-R as internal primers. DNA amplification products of about 380 bp compatible with Paracoccidioides spp. were detected in six samples (10%), being sequenced and identified as P. brasiliensis. These findings indicate that the soils of the Acre state could be considered a potential source for Paracoccidioides spp., suggesting that local infections are likely.
© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.
Graduate Program in Biodiversity and Biotechnology, Federal University of Acre, Rio Branco, AC, 69920-900, Brazil. Iasminysf@gmail.com.
Tropical Medicine Center, Faculty of Medicine, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil.
Graduate Program in Biodiversity and Biotechnology, Federal University of Acre, Rio Branco, AC, 69920-900, Brazil.
Department of Chemical and Biological Sciences, São Paulo State University Júlio de Mesquita Filho , Botucatu, SP, 18618-687, Brazil.
Center for Biological and Natural Sciences, Federal University of Acre, Rio Branco, AC, 69920-900, Brazil.
Graduate Program in Biodiversity and Biotechnology, Federal University of Acre, Rio Branco, AC, 69920-900, Brazil.Center for Biological and Natural Sciences, Federal University of Acre, Rio Branco, AC, 69920-900, Brazil.
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
Molecular detection of Paracoccidioides spp. in environmental samples from the Southwestern Amazon.

Above a concentration threshold, the viscosity of solutions of proteins increases abruptly, which hampers the injectability of therapeutic formulations. Concentrations above 200 g/L are an ideal goal for subcutaneous application of antibodies. Molecular additives, such as amino acids (e.g., arginine) help decrease the viscosity, but they are used at concentrations as high as about 200 mmol/L. We addressed the question of whether poly(amino acids) could be more efficient than small molecular additives. We observed marked fluidification of a model therapeutic monoclonal antibody (mAb) solution by poly(d,l-glutamic acid) and poly(l-glutamic acid) derivatives added at concentrations of <6.5 g/L (i.e., a mAb/polymer chain molar ratio between 4:1 and 1:1 mol/mol). The bare poly(glutamate) parent chains were compared with polyethylene glycol-grafted chains as PEGylation is a common way to enhance stability. Viscosity could be decreased to ∼20 mPa s as compared to values of ∼100 mPa s in the absence of polymers at 200 g/L mAb. Formation of complexes between the mAb and the polyglutamates was characterized by capillary electrophoresis analysis in dilute solutions (1 g/L mAb) and by observation of phase separation at higher concentrations, suggesting tight association at about 2:1 mol/mol mAb/polymer. Altogether, these results show that polyglutamate derivatives hold an untapped potential as an excipient for fluidification of concentrated protein solutions.
Département de Chimie, PASTEUR, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris 75005, France.
Biologics Formulation & Process Development, Biologics Drug Product Development Department, SANOFI R&D, 13 quai Jules Guesde- BP 14, Vitry-sur-Seine 94403, France.
Poly(glutamic acid)-Based Viscosity Reducers for Concentrated Formulations of a Monoclonal IgG Antibody.

There is a growing need for solid organ transplantation (SOT) for people living with human immunodeficiency virus (HIV). With the advent of antiretroviral therapy, people living with HIV are experiencing increased life expectancies and are, therefore, developing more comorbidities, including end-stage organ disease. In cases of advanced organ failure, SOT is often the best therapeutic option to improve quality of life and overall survival. As organ shortages persist, transplantation of organs from donors with HIV to recipients with HIV has become a potential therapeutic option. This article first reviews the current state of organ transplantation from donors without HIV to recipients with HIV (HIV D-/R+) by organ and discusses key lessons learned from these transplant trials, including those about drug-drug interactions, rejection, and opportunistic infections. It then explores transplantation from donors with HIV to recipients with HIV (HIV D+/R+), a new frontier. Finally, it investigates challenges of implementation, including public awareness and regulatory requirements, and explores future directions for SOT in people living with HIV.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Overcoming barriers and stigma: new frontiers in solid organ transplantation for people with HIV.

Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms.Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on the modified Rankin Scale) at discharge and during follow-up. Multivariate regression analyses were performed adjusting for all described patient characteristics.Among a total of 2192 patients with anterior circulation aneurysm, complete occlusion of the treated aneurysm was achieved in 2089 (95.3%) patients at discharge. The occlusion rate remained stable (94.7%) during follow-up. Regression analysis identified hypertension (P < .02), aneurysm diameter (P < .001), neck diameter (P < .05), calcification (P < .01), and morphology (P = .002) as preexisting risk factors for postsurgical complications and neurological deterioration at discharge. Furthermore, intraoperative aneurysm rupture (odds ratio 2.863 [CI 1.606-5.104]; P < .01) and simultaneous clipping of more than 1 aneurysm (odds ratio 1.738 [CI 1.186-2.545]; P < .01) were shown to be associated with an increased risk of postsurgical complications. Yet, none of the surgical-related parameters had an impact on neurological deterioration. Analyzing volume-outcome relationship revealed comparable complication rates (P = .61) among all 15 participating centers.Our international, multicenter analysis presents current microsurgical treatment practices in patients with anterior circulation aneurysms and identifies preexisting and surgery-related risk factors for postoperative complications and neurological deterioration. These findings may assist in decision-making for the optimal therapeutic regimen of unruptured anterior circulation aneurysms.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
Department of Neurosurgery, Hospital of the University of Pennsylvania, Penn Medicine, Philadelphia, Pennsylvania, USA.
Department of Neurosurgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich (TUM), Munich, Germany.
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Neurosurgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich (TUM), Munich, Germany.
Department of Neurosurgery, University of Texas Health and Science Center at San Antonio, San Antonio, Texas, USA.
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Department of Neurosurgery, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
Division of Neurological Surgery, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Federal Center of Neurosurgery, Novosibirsk, Russia.
Department of Neurosurgery, University Medical Center Mainz, Mainz, Germany.
Department of Neurosurgery, Pohang Stroke and Spine Hospital, Pohang, Korea.
Department of Neurosurgery, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Microsurgical Clipping of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation of Perioperative Outcomes.

Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.
Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia.Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.School of Life Sciences, University of Technology Sydney, Ultimo, New South Wales 2007, Australia.
School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia.
Hfe Permease and Haemophilus influenzae Manganese Homeostasis.

We develop county-level measures of structural and institutional barriers to care, and test associations between these barriers and birth outcomes for US-born Black and White mothers using national birth records for 2014-2017. Results indicate elevated odds of greater preterm birth severity for Black mothers in counties with higher uninsurance rates among Black adults, fewer Black physicians per Black residents, and fewer publicly-funded contraceptive services. Most structural barriers were not associated with small-for-gestational-age birth, and barriers defined for Black residents were not associated with birth outcomes for White mothers, with the exception of Black uninsurance rate. Structural determinants of care may influence preterm birth risk for Black Americans.
Copyright © 2024 Elsevier Ltd. All rights reserved.
Department of Family and Consumer Studies, University of Utah, Salt Lake City, UT, 84112, USA. Electronic address: david.curtis@fcs.utah.edu.
Department of Economics, University of Utah, Salt Lake City, UT, 84112, USA.
Department of Epidemiology, Emory University, Atlanta, GA, 30322, USA.
Department of Pediatrics, University of Utah, Salt Lake City, UT, 84112, USA.
Structural barriers to health care as risk factors for preterm and small-for-gestational-age birth among US-born Black and White mothers.

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.
Copyright © 2023. Published by Elsevier Inc.
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB.
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Human Genetics, University of California, Los Angeles, Los Angees, CA, USA.
Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: yue@northwestern.edu.
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. Electronic address: joseph.costello@ucsf.edu.
Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.

Laminin, a major component of the basal lamina in the CNS, is also expressed in oligodendrocytes (OLs). However, the function of OL-derived laminin remains largely unknown. Here, we performed loss-of-function studies using two OL-specific laminin-α5 conditional knockout mouse lines. Both mutants were grossly normal and displayed intact blood-brain barrier (BBB) integrity. In a mouse model of intracerebral hemorrhage (ICH), control mice and both mutants exhibited comparable hematoma size and neurological dysfunction. In addition, similar levels of hemoglobin and IgG leakage were detected in the mutant brains compared to the controls, indicating comparable BBB damage. Consistent with this finding, subsequent studies revealed no differences in tight junction protein (TJP) and caveolin-1 expression among control and knockout mice, suggesting that neither paracellular nor transcellular mechanism was affected in the mutants. Furthermore, compared to the controls, both mutant lines showed comparable oligodendrocyte number, oligodendrocyte proliferation rate, MBP/MAG levels, and SMI-32 expression, highlighting a minimal role of OL-derived laminin-α5 in OL biology. Together, these findings highlight a dispensable role of OL-derived laminin-α5 in both brain homeostasis and ICH pathogenesis.
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.Current Address: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
A dispensable role of oligodendrocyte-derived laminin-α5 in brain homeostasis and intracerebral hemorrhage.

Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored.To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use.The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower.Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.
© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.Department of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center,New Orleans, Louisiana, USA.
Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka, Zambia.
Office of the State Forensic Pathologist, Ministry of Home Affairs, Lusaka, Zambia.
Department of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center,New Orleans, Louisiana, USA.
Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy.

The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic antivirals and continue to provide new drugs through synthesis, medicinal chemistry, and optimization decades after discovery. Here, we demonstrate an approach using computational analysis typically used for rational drug design to identify and develop natural product-inspired antivirals. This was done with the goal of identifying natural product prototypes to aid the effort of progressing toward safe, effective, and affordable broad-spectrum inhibitors of Betacoronavirus replication by targeting the highly conserved RNA 2'-O-methyltransferase (2'-O-MTase). Machaeriols RS-1 (7) and RS-2 (8) were identified using a previously outlined informatics approach to first screen for natural product prototypes, followed by in silico-guided synthesis. Both molecules are based on a rare natural product group. The machaeriols (3-6), isolated from the genus Machaerium, endemic to Amazonia, inhibited the SARS-CoV-2 2'-O-MTase more potently than the positive control, Sinefungin (2), and in silico modeling suggests distinct molecular interactions. This report highlights the potential of computationally driven screening to leverage natural product libraries and improve the efficiency of isolation or synthetic analog development.
Department of Drug Discovery, Biomedical Sciences and Public Health, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, NE Atlanta, Georgia 30322, United States.
Department of Chemistry & Biochemistry, Utah State University, Logan, Utah 84322, United States.
Informatics and Computational Approaches for the Discovery and Optimization of Natural Product-Inspired Inhibitors of the SARS-CoV-2 2'-O-Methyltransferase.

Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA).This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility.The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88-0.95) for ADNEX with CA125, 0.90 (0.84-0.94) for ADNEX without CA125, and 0.85 (0.80-0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%.ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA.clinicaltrials.gov NCT01698632 and NCT02847832.
Department of Oncology, Laboratory of Tumour Immunology and Immunotherapy, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.Department of Development and Regeneration, KU Leuven, Leuven, Belgium.Queen Charlotte's and Chelsea Hospital, Imperial College, London, UK.Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
Department of Oncology, Laboratory of Tumour Immunology and Immunotherapy, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden.Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Department of Development and Regeneration, KU Leuven, Leuven, Belgium.Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.Department of Oncology, Gynaecological Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
Department of Oncology, Laboratory of Tumour Immunology and Immunotherapy, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.Oncoinvent AS, Oslo, Norway.
Department of Oncology, Laboratory of Tumour Immunology and Immunotherapy, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
Department of Pathology, UZ Leuven, Leuven, Belgium.
Department of Laboratory Medicine, UZ Leuven, Leuven, Belgium.
Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University, Prague, Czech Republic.General University Hospital, Prague, Czech Republic.
Department of Obstetrics and Gynecology, Ziekenhuis Oost-Limburg, Genk, Belgium.
Department of Gynecologic Oncology, National Cancer Institute of Milan, Milan, Italy.
Department of Development and Regeneration, KU Leuven, Leuven, Belgium.Queen Charlotte's and Chelsea Hospital, Imperial College, London, UK.
Department of Development and Regeneration, KU Leuven, Leuven, Belgium. ben.vancalster@kuleuven.be.Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands. ben.vancalster@kuleuven.be.Leuven Unit for Health Technology Assessment Research (LUHTAR), KU Leuven, Leuven, Belgium. ben.vancalster@kuleuven.be.
Comparison of the ADNEX and ROMA risk prediction models for the diagnosis of ovarian cancer: a multicentre external validation in patients who underwent surgery.

Low temperature is a major environmental factor limiting plant growth and crop production. Epigenetic regulation of gene expression is important for plant adaptation to environmental changes, whereas the epigenetic mechanism of cold signaling in rice (Oryza sativa) remains largely elusive. Here, we report that the histone deacetylase (HDAC) OsHDA716 represses rice cold tolerance by interacting with and deacetylating the transcription factor OsbZIP46. The loss-of-function mutants of OsHDA716 exhibit enhanced chilling tolerance, compared with the wild-type plants, while OsHDA716 overexpression plants show chilling hypersensitivity. On the contrary, OsbZIP46 confers chilling tolerance in rice through transcriptionally activating OsDREB1A and COLD1 to regulate cold-induced calcium influx and cytoplasmic calcium elevation. Mechanistic investigation showed that OsHDA716-mediated OsbZIP46 deacetylation in the DNA-binding domain reduces the DNA-binding ability and transcriptional activity as well as decreasing OsbZIP46 protein stability. Genetic evidence indicated that OsbZIP46 deacetylation mediated by OsHDA716 reduces rice chilling tolerance. Collectively, these findings reveal that the functional interplay between the chromatin regulator and transcription factor fine-tunes the cold response in plant and uncover a mechanism by which HDACs repress gene transcription through deacetylating nonhistone proteins and regulating their biochemical functions.
© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Key Laboratory of Biorheological Science and Technology of Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.
Histone deacetylase OsHDA716 represses rice chilling tolerance by deacetylating OsbZIP46 to reduce its transactivation function and protein stability.

Plants need to acclimate to different stresses to optimize growth under unfavorable conditions. In Arabidopsis (Arabidopsis thaliana), the abundance of the chloroplast envelope protein FATTY ACID EXPORT PROTEIN1 (FAX1) decreases after the onset of low temperatures. However, how FAX1 degradation occurs and whether altered FAX1 abundance contributes to cold tolerance in plants remains unclear. The rapid cold-induced increase in RHOMBOID-LIKE PROTEASE11 (RBL11) transcript levels, the physical interaction of RBL11 with FAX1, the specific FAX1 degradation after RBL11 expression, and the absence of cold-induced FAX1 degradation in rbl11 loss-of-function mutants suggest that this enzyme is responsible for FAX1 degradation. Proteomic analyses showed that rbl11 mutants have higher levels of FAX1 and other proteins involved in membrane lipid homeostasis, suggesting that RBL11 is a key element in the remodeling of membrane properties during cold conditions. Consequently, in the cold, rbl11 mutants show a shift in lipid biosynthesis toward the eukaryotic pathway, which coincides with impaired cold tolerance. To test whether cold sensitivity is due to increased FAX1 levels, we analyzed FAX1 overexpressors. The rbl11 mutants and FAX1 overexpressor lines show superimposable phenotypic defects upon exposure to cold temperatures. Our re-sults show that the cold-induced degradation of FAX1 by RBL11 is critical for Arabidop-sis to survive cold and freezing periods.
Plant Physiology, University of Kaiserslautern, Kaiserslautern D-67653, Germany.
Plant Biochemistry, Faculty of Biology, Ludwig-Maximilians-Universität Munich, Planegg-Martinsried 82152, Germany.
Max Planck Institut for Molecular Plant Physiology, Central Metabolism, Potsdam D-14476, Germany.
Molecular Biotechnology and Systems Biology, University of Kaiserslautern, Kaiserslautern D-67653, Germany.
Computational Systems Biology, University of Kaiserslautern, Kaiserslautern D-67653, Germany.
Institute for Molecular Physiology and Biotechnology of Plants, IMBIO, University of Bonn, Bonn D-53115, Germany.
Plant Biology, Center for Human and Molecular Biology (ZHMB), Saarland University, Saarbrücken D-66123, Germany.
Degradation of FATTY ACID EXPORT PROTEIN1 by RHOMBOID-LIKE PROTEASE11 contributes to cold tolerance in Arabidopsis.

Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, the Netherlands.
Infectious Diseases Research Collaboration, Kampala, Uganda.
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, the Netherlands.Department of Infection Biology, London School of Hygiene and Tropical Medicine, United Kingdom.
Plasmodium malariae and Plasmodium ovale-Prevalent and Relevant.

SUPPRESSOR OF MAX2 (SMAX)1-LIKE (SMXL) proteins are a plant-specific clade of type I HSP100/Clp-ATPases. SMXL genes are present in virtually all land plant genomes. However, they have mainly been studied in angiosperms. In Arabidopsis (Arabidopsis thaliana), 3 functional SMXL subclades have been identified: SMAX1/SMXL2, SMXL345, and SMXL678. Of these, 2 subclades ensure endogenous phytohormone signal transduction. SMAX1/SMXL2 proteins are involved in KAI2 ligand (KL) signaling, while SMXL678 proteins are involved in strigolactone (SL) signaling. Many questions remain regarding the mode of action of these proteins, as well as their ancestral roles. We addressed these questions by investigating the functions of the 4 SMXL genes in the moss Physcomitrium patens. We demonstrate that PpSMXL proteins are involved in the conserved ancestral MAX2-dependent KL signaling pathway and negatively regulate growth. However, PpSMXL proteins expressed in Arabidopsis cannot replace SMAX1 or SMXL2 function in KL signaling, whereas they can functionally replace SMXL4 and SMXL5 and restore root growth. Therefore, the molecular functions of SMXL proteins are conserved, but their interaction networks are not. Moreover, the PpSMXLC/D clade positively regulates SL signal transduction in P. patens. Overall, our data reveal that SMXL proteins in moss mediate crosstalk between the SL and KL signaling pathways.
Université Paris-Saclay, INRAE, AgroParisTech, Institut Jean-Pierre Bourgin (IJPB), 78000 Versailles, France.LIPME, Université de Toulouse, INRAE, CNRS, Castanet-Tolosan 31326, France.
Université Paris-Saclay, INRAE, AgroParisTech, Institut Jean-Pierre Bourgin (IJPB), 78000 Versailles, France.Institut de biologie moléculaire des plantes (IBMP), CNRS, University of Strasbourg, 12 rue du Général Zimmer, 67000 Strasbourg, France.
Université Paris-Saclay, INRAE, AgroParisTech, Institut Jean-Pierre Bourgin (IJPB), 78000 Versailles, France.
CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
SUPPRESSOR OF MAX2 1-LIKE (SMXL) homologs are MAX2-dependent repressors of Physcomitrium patens growth.

RECIST criteria for progressive disease, partial response, and complete response, reflecting +20%, -30%, and -100% tumor size changes, respectively, are critical outcome variables in oncology clinical trials. Herein, we evaluated post-immunotherapy tumor size change correlation with outcomes.We used a unique clinical trial data resource, a multicenter basket trial in patients with rare solid tumors treated with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) between 2017 and 2023 (National Cancer Institute/Southwest Oncology Group-sponsored DART trial [NCT02834013]) (open at 1083 sites at its peak). Outcome associations were evaluated by survival analysis techniques including Martingale residuals.In 638 evaluable patients, we found strong linear relationships between percent change in tumor measurement up to a 40%-50% increase and progression-free (PFS) and overall survival (OS) (both Cox regression P < .001; landmark analyses based on day 65). Pearson R correlation between survival estimates and tumor change category were -0.94, -0.89, and -0.89 (PFS) and -0.84, -0.90, and -0.90 (OS) for median, 6-month (PFS), and 1-year (OS) and for 1-year (PFS) and 2-year (OS) estimates.Percent change in tumor measurement per RECISTv1.1 (the sum of longest dimensions of target lesions) has a linear association with PFS and OS up to a 40% to 50% increase in tumor measurement in this cohort of patients with rare cancers who received combination immune checkpoint blockade. Quantitative first scan tumor measurement changes include important information to evaluate the potential efficacy of a therapy beyond the proportion of patients who achieve an objective response.
© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
SWOG Cancer Research Network Statistical Center, Seattle, WA, USA.Division of Public Health, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Department of Medical Oncology, University of California at San Diego Moores Cancer Center, La Jolla, CA, USA.
Department of Medicine, Northwestern University, Chicago, IL, USA.
Division of Public Health, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Cancer Therapy Evaluation Program, Division of Cancer Treatment & Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (during conduct of trial for E Sharon).
Cancer Therapy Evaluation Program, Division of Cancer Treatment & Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (during conduct of trial for E Sharon).Department of Medicine, Dana-Farber/Harvard Cancer Center, Boston, MA, USA (current).
Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA.
Journal of the National Cancer Institute
Correlation between tumor size change and outcome in a rare cancer immunotherapy basket trial.

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce. Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12). We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold's bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl's gyrus. Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
UMR 1253, iBrain, Université de Tours, Inserm, 37000 Tours, France.Department of Neurosurgery, CHRU de Tours, 37000 Tours, France.
Sherbrooke Connectivity Imaging Laboratory, Department of Computer Science, Faculty of Sciences, Université de Sherbrooke, J1K 2X9 Sherbrooke, Quebec, Canada.Imeka Solutions, J1H 4A7 Sherbrooke, Quebec, Canada.
Imeka Solutions, J1H 4A7 Sherbrooke, Quebec, Canada.
CNRS, Integrative Neuroscience and Cognition Center (UMR 8002), Université de Paris Cité, 75006 Paris, France.Wellcome Centre for Integrative Neuroimaging, University of Oxford, OX1 3QD Oxford, UK.
CNRS, Integrative Neuroscience and Cognition Center (UMR 8002), Université de Paris Cité, 75006 Paris, France.
Sherbrooke Connectivity Imaging Laboratory, Department of Computer Science, Faculty of Sciences, Université de Sherbrooke, J1K 2X9 Sherbrooke, Quebec, Canada.
Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, 34090 Montpellier, France.Team 'Plasticity of Central Nervous System, Stem Cells and Glial Tumors', U1191 Laboratory, Institute of Functional Genomics, National Institute for Health and Medical Research (INSERM), University of Montpellier, 34000, Montpellier, France.
Department of Neurosurgery, Lariboisière Hospital, AP-HP, 75010 Paris, France.Frontlab, CNRS UMR 7225, INSERM U1127, Paris Brain Institute (ICM), 75013 Paris, France.UFR Médecine, Université de Paris Cité, 75006 Paris, France.
Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks.

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
Nuclear translocation matters: Role of FABP7 in driving glioblastoma stemness and invasion: Reply to Mu et al.

Energy-based surgical instruments produce surgical smoke, which contains harmful byproducts, such as polycyclic aromatic hydrocarbons, volatile organic compounds, particulate matter, and viable microorganisms. The research setting has shifted from the laboratory to the operating room. However, significant heterogeneity in the methods of detection and placement of samplers, diversity in the tissue operated on, and types of surgeries tested has resulted in variability in detected levels and composition of surgical smoke. State regulation limiting surgical smoke exposure through local evacuators is expanding but has yet to reach the national regulatory level. However, most studies have not shown levels above standard established limits but relatively short bursts of high concentrations of these harmful by-products. This review highlights the limitations of the current research and unsupported conclusions while also suggesting further areas of interest that need more focus to improve Occupational Safety and Health Administration guidelines.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.Curriculum in Toxicology & Environmental Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Toxicological sciences : an official journal of the Society of Toxicology
Surgical smoke and its components, effects, and mitigation: a contemporary review.

This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples.A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ( baseline ) and 12 months after ( follow-up ) the first opioid prescription ( index date ). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type.A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone.Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Division of Pharmaceutical Evaluation and Policy, Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.Center for Mental Healthcare and Outcomes Research, Central Arkansas Veterans Healthcare Systems, North Little Rock, AR 72211, United States.
Division of Pharmaceutical Evaluation and Policy, Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.Center for Mental Healthcare and Outcomes Research, Central Arkansas Veterans Healthcare Systems, North Little Rock, AR 72211, United States.
College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

During public health emergencies, health communication materials to contain the outbreak are needed promptly, which prevents the use of standard approaches for getting feedback from the intended audience. We propose a strategy for rapidly obtaining community feedback on new health communication materials during the public health emergencies. We illustrate this with COVID-19 testing campaign in a Vietnamese-American enclave in the USA. The project included community-based COVID-19 testing and communication activities to increase the awareness of the testing centers and encourage frequent testing. Our strategy involves two main components: (i) use of a research team with an existing trust relationship with the community and that includes researchers from that community and (ii) co-design of communication materials using community-based gatekeepers and a cultural broker. We developed brochures and posters to increase the awareness of the COVID-19 testing services. The cultural broker and community-based partners identified salient message concepts and worked with the researchers to define the objectives and content of the materials, which were then reviewed by the entire team. In lieu of standard pretesting, we relied on feedback on mockups of the materials and subsequent revisions from the community-based gatekeepers and cultural broker. Our strategy strikes a balance between the need to urgently disseminate new materials and the need for community input. One key takeaway is that effective planning for public health emergencies must start long before the crisis occurs.
Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Rapidly developing communications materials during public health emergencies: the Âu Cơ campaign in the USA.

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia.Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia.
Children's Cancer Centre, Royal Children's Hospital, Parkville, Victoria, Australia.Murdoch Children's Research Institute, Parkville, Victoria, Australia.Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
A paradigm shift in how we treat pediatric low-grade glioma-Targeting the molecular drivers.

To measure pediatrician adherence to evidence-based guidelines in the treatment of young children with attention-deficit/hyperactivity disorder (ADHD) in a diverse healthcare system using natural language processing (NLP) techniques.We extracted structured and free-text data from electronic health records (EHRs) of all office visits (2015-2019) of children aged 4-6 years in a community-based primary healthcare network in California, who had ≥1 visits with an ICD-10 diagnosis of ADHD. Two pediatricians annotated clinical notes of the first ADHD visit for 423 patients. Inter-annotator agreement (IAA) was assessed for the recommendation for the first-line behavioral treatment (F-measure = 0.89). Four pre-trained language models, including BioClinical Bidirectional Encoder Representations from Transformers (BioClinicalBERT), were used to identify behavioral treatment recommendations using a 70/30 train/test split. For temporal validation, we deployed BioClinicalBERT on 1,020 unannotated notes from other ADHD visits and well-care visits; all positively classified notes (n = 53) and 5% of negatively classified notes (n = 50) were manually reviewed.Of 423 patients, 313 (74%) were male; 298 (70%) were privately insured; 138 (33%) were White; 61 (14%) were Hispanic. The BioClinicalBERT model trained on the first ADHD visits achieved F1 = 0.76, precision = 0.81, recall = 0.72, and AUC = 0.81 [0.72-0.89]. Temporal validation achieved F1 = 0.77, precision = 0.68, and recall = 0.88. Fairness analysis revealed low model performance in publicly insured patients (F1 = 0.53).Deploying pre-trained language models on a variable set of clinical notes accurately captured pediatrician adherence to guidelines in the treatment of children with ADHD. Validating this approach in other patient populations is needed to achieve equitable measurement of quality of care at scale and improve clinical care for mental health conditions.
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, United States.
Computer Science Department, University of the North, Barranquilla 080020, Colombia.
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, United States.
Division of Developmental-Behavioral Pediatrics, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, United States.
Measuring quality-of-care in treatment of young children with attention-deficit/hyperactivity disorder using pre-trained language models.

Domestication can be considered a specialized mutualism in which a domesticator exerts control over the reproduction or propagation (fitness) of a domesticated species to gain resources or services. The evolution of crops by human-associated selection provides a powerful set of models to study recent evolutionary adaptations and their genetic bases. Moreover, the domestication and dispersal of crops such as rice, maize, and wheat during the Holocene transformed human social and political organization by serving as the key mechanism by which human societies fed themselves. Here we review major themes and identify emerging questions in three fundamental areas of crop domestication research: domestication phenotypes and syndromes, genetic architecture underlying crop evolution, and the ecology of domestication. Current insights on the domestication syndrome in crops largely come from research on cereal crops such as rice and maize, and recent work indicates distinct domestication phenotypes can arise from different domestication histories. While early studies on the genetics of domestication often identified single large-effect loci underlying major domestication traits, emerging evidence supports polygenic bases for many canonical traits such as shattering and plant architecture. Adaptation in human-constructed environments also influenced ecological traits in domesticates such as resource acquisition rates and interactions with other organisms such as root mycorrhizal fungi and pollinators. Understanding the ecological context of domestication will be key to developing resource-efficient crops and implementing more sustainable land management and cultivation practices.
Center for Genomics and Systems Biology, New York University, New York, NY 10003, USA.
Center for Genomics and Systems Biology, New York University, New York, NY 10003, USA.Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.Institute for the Study of the Ancient World, New York University, New York, NY, 10028, USA.
Domestication and the evolution of crops: variable syndromes, complex genetic architectures, and ecological entanglements.

Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma.We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts.There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534).The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.
Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
Department of Neurology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
Department of Biostatistics, NYU School of Global Public Health, New York, New York, USA.
Department of Radiology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
Department of Neurosurgery, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
Department of Neuro-oncology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.
Department of Neuropathology, Ruprecht-Karls-University, Heidelberg, Germany.CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Department of Radiation Oncology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.Brain and Spine Tumor Center, Laura and Isaac Perlmutter Cancer Center, New York, New York, USA.
Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA.Brain and Spine Tumor Center, Laura and Isaac Perlmutter Cancer Center, New York, New York, USA.
Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas.

To evaluate breast imaging fellowship program directors' perspectives on the virtual interview process.A 20-question survey constructed by members of the Fellowship Match Committee of the Society of Breast Imaging was distributed to all 99 breast imaging program directors registered with the Society. An initial e-mail with a link to the survey was distributed on September 9, 2022, and the survey was closed on October 1, 2022. Results were compiled and a descriptive statistical analysis was performed utilizing Microsoft Excel.There were 63 total responses (63/99, 64% response rate). There was a wide distribution in both the number of applications received and the number of interviews each program offered. Just under a fifth (12/63, 19%) of programs received 1 to 5 applications, whereas a quarter (16/63, 25%) received over 40 applications. In contrast, over a quarter (17/63, 27%) of programs interviewed 1 to 5 applicants, and only a small number (3/63, 5%) interviewed over 40 applicants. When reporting what worked best with the virtual interview process, the responses fell into the following 4 categories: efficiency, flexibility, virtual format, or other. When reporting what did not work well, the most common response (14/37, 38%) was conveying the atmosphere of the program in the virtual setting.This study provides an assessment of the virtual interview experience from the perspective of breast imaging fellowship programs, which may be useful in optimizing future interview experiences for programs and applicants.
© Society of Breast Imaging 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Department of Radiology, University of Virginia, Charlottesville, VA, USA.
Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Radiology, Northwestern Medicine, Chicago, IL, USA.
Anderson Cancer Center, The University of Texas, Houston, MD, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Breast Imaging Fellowship Virtual Interviews: The Program Director's Perspective.

RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases.RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank.In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [-0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (-0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60).PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.Department of Surgery, Faculty of Medicine, Université Laval, Québec, Canada.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, Canada.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, Canada.
School of Nutrition, Université Laval, Québec, Canada.Centre Nutrition, santé et société, Institut sur la nutrition et les aliments fonctionnels, Université Laval, Québec, Canada.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.School of Nutrition, Université Laval, Québec, Canada.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, 2725 chemin Ste-Foy, Québec, QC G1V 4G5, Canada.Department of Medicine, Faculty of Medicine, Université Laval, 2325 Rue de l'Université, Québec, QC G1V 0A6, Canada.
Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk.

Cyclocarya paliurus leaf is a medicinal and edible homologous plant, which possess various bioactive components with significant health benefits. However, the quality and safety of the aqueous extract from Cyclocarya paliurus leaves (CPLAE) vary greatly due to the raw materials and preparation technology. At present, chromatographic fingerprinting has been widely used for qualitative and quantitative analysis of traditional Chinese medicine (TCM). In this study, a method combining high performance liquid chromatography (HPLC) fingerprint with quantitative analysis was established and successfully applied to the characterization and quality evaluation of the CPLAE. In addition, the genetic safety of the CPLAE was evaluated by genotoxicity tests, including Ames test, chromosomal aberration test of Chinese hamster lung (CHL) cell in vitro, and bone marrow micronucleus test in mice. The results showed that 10 batches of CPLAE samples were analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), and the similarity of chromatographic fingerprint of each batch was above 0.961, indicating good similarity. At the same time, the 6 compounds with high absorption strength in the chromatogram were quantitatively analyzed. The results showed that all 6 compounds had good regression (R2=1.000) in the test range, and the recoveries ranged from 96.25% to 102.46%. The results of the 3 genotoxicity tests showed that the highest dose of CPLAE had no genotoxicity. In conclusion, the newly established chromatographic fingerprint and multi-component quantitative analysis method is stable and accurate, and can be used for the identification and quality evaluation of the CPLAE. Moreover, the CPLAE has the characteristics of safety and high quality as functional materials in food.
Scientific Research Center, Infinitus (China) Company Ltd., 6th Floor, Tower A, Infinitus Plaza, 2nd Yuncheng South Road, Baiyun District, Guangzhou 510000, P.R. China.
Ethnopharmacology Level 3 Laboratory, National Administration of Traditional Chinese Medicine, South-Central Minzu University, 182 Minyuan Road, Hongshan District, Wuhan 430074, P.R. China.
The chromatographic fingerprinting study and genotoxicity evaluation of aqueous extract from Cyclocarya paliurus leaves.

Fibroblast growth factor-21 (FGF21) is an intercellular signaling molecule secreted by metabolic organs, including skeletal muscle, in response to intracellular stress. FGF21 crosses the blood-brain barrier and acts via the nervous system to coordinate aspects of the adaptive starvation response, including increased lipolysis, gluconeogenesis, fatty acid oxidation, and activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Given its beneficial effects for hepatic lipid metabolism, pharmaceutical FGF21 analogues are used in clinical trials treatment of fatty liver disease. We predicted pharmacologic treatment with FGF21 increases HPA axis activity and skeletal muscle glucocorticoid signaling and induces skeletal muscle atrophy in mice. Here we found a short course of systemic FGF21 treatment decreased muscle protein synthesis and reduced tibialis anterior weight; this was driven primarily by its effect in female mice. Similarly, intracerebroventricular FGF21 reduced tibialis anterior muscle fiber cross-sectional area; this was more apparent among female mice than male littermates. In agreement with the reduced muscle mass, the topmost enriched metabolic pathways in plasma collected from FGF21-treated females were related to amino acid metabolism, and the relative abundance of plasma proteinogenic amino acids was increased up to 3-fold. FGF21 treatment increased hypothalamic Crh mRNA, plasma corticosterone, and adrenal weight, and increased expression of glucocorticoid receptor target genes known to reduce muscle protein synthesis and/or promote degradation. Given the proposed use of FGF21 analogues for the treatment of metabolic disease, the study is both physiologically relevant and may have important clinical implications.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA 95616, USA.
Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA 95616, USA.Department of Biological Sciences, California State University Sacramento, Sacramento, CA 95819, USA.
Aging & Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA.
FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.

Heart failure (HF) poses a significant economic burden in the US, with costs projected to reach $70 billion by 2030. Cost-effectiveness analyses play a pivotal role in assessing the economic value of HF therapies. In this review, we overview the cost-effectiveness of HF therapies and discuss ways to improve patient access. Based on current costs, guideline directed medical therapies for HF with reduced ejection fraction provide high economic value except for sodium-glucose cotransporter-2 inhibitors, which provide intermediate economic value. Combining therapy with the four pillars of medical therapy also has intermediate economic value, with incremental cost-effectiveness ratios ranging from $73,000 to $98,500/ quality adjusted life-years. High economic value procedures include cardiac resynchronization devices, implantable cardioverter-defibrillators, and coronary artery bypass surgery. In contrast, advanced HF therapies have previously demonstrated intermediate to low economic value, but newer data appear more favorable. Given the affordability challenges of HF therapies, additional efforts are needed to ensure optimal care for patients. The recent Inflation Reduction Act contains provisions to reform policy pertaining to drug price negotiation and out-of-pocket spending, as well as measures to increase access to existing programs, including the Medicare low-income subsidy. On a patient level, it is also important to encourage patient and physician awareness and discussions surrounding medical costs. Overall, a broad approach to improving available therapies and access to care is needed to reduce the growing clinical and economic morbidity of HF.
Copyright © 2024 Elsevier Inc. All rights reserved.
Department of Medicine, Stanford University School of Medicine, United States of America.
Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, United States of America; Palo Alto Veterans Affairs Healthcare System, Palo Alto, CA, United States of America.
Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, United States of America; Palo Alto Veterans Affairs Healthcare System, Palo Alto, CA, United States of America. Electronic address: ats114@stanford.edu.

To assess performance of an artificial intelligence (AI) decision support software in assessing and recommending biopsy of triple-negative breast cancers (TNBCs) on US.Retrospective institutional review board-approved review identified patients diagnosed with TNBC after US-guided biopsy between 2009 and 2019. Artificial intelligence output for TNBCs on diagnostic US included lesion features (shape, orientation) and likelihood of malignancy category (benign, probably benign, suspicious, and probably malignant). Artificial intelligence true positive was defined as suspicious or probably malignant and AI false negative (FN) as benign or probably benign. Artificial intelligence and radiologist lesion feature agreement, AI and radiologist sensitivity and FN rate (FNR), and features associated with AI FNs were determined using Wilcoxon rank-sum test, Fisher's exact test, chi-square test of independence, and kappa statistics.The study included 332 patients with 345 TNBCs. Artificial intelligence and radiologists demonstrated moderate agreement for lesion shape and orientation (k = 0.48 and k = 0.47, each P <.001). On the set of examinations using 6 earlier diagnostic US, radiologists recommended biopsy of 339/345 lesions (sensitivity 98.3%, FNR 1.7%), and AI recommended biopsy of 333/345 lesions (sensitivity 96.5%, FNR 3.5%), including 6/6 radiologist FNs. On the set of examinations using immediate prebiopsy diagnostic US, AI recommended biopsy of 331/345 lesions (sensitivity 95.9%, FNR 4.1%). Artificial intelligence FNs were more frequently oval (q < 0.001), parallel (q < 0.001), circumscribed (q = 0.04), and complex cystic and solid (q = 0.006).Artificial intelligence accurately recommended biopsies for 96% to 97% of TNBCs on US and may assist radiologists in classifying these lesions, which often demonstrate benign sonographic features.
Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Artificial Intelligence Decision Support for Triple-Negative Breast Cancers on Ultrasound.

This narrative review examines the complex connection between infectious diseases and their neurological effects. It provides a detailed analysis of recent instances and insights derived from various pathogens. As we explore the realm of infectious agents, including viruses, bacteria, parasites, and fungi, a thorough and diverse analysis reveals the intricacies of neurological problems. The review begins by examining viral infections, specifically focusing on how viruses invade the neurological system and its subsequent effects. Significant instances from recent widespread disease outbreaks function as instructive benchmarks, highlighting the progressing comprehension of these ever-changing interconnections. The article examines the complex pathophysiology of neurological problems caused by bacterial infections. It presents current cases that illustrate the various ways these complications might manifest and the difficulties faced in their therapeutic management. Parasitic and fungal infections, which are typically overlooked, are being carefully examined to emphasize their distinct role in causing neurological complications. The mentioned cases highlight the importance of being thoroughly aware of these less-explored areas ranging from protozoan parasites to opportunistic fungal infections. In addition to the immediate effects caused by infectious agents, the review investigates autoimmune responses activated by infections. It provides a detailed examination of specific instances that shed light on the complex relationship between viral triggers and future neurological problems. This text elaborates on the intricacy of autoimmune-related neurological issues, highlighting the necessity for a comprehensive approach to diagnosing and treating them. The narrative next redirects its attention to the diagnostic difficulties that arise when interpreting the neurological symptoms of viral disorders. This article provides a thorough examination of existing diagnostic tools, along with an investigation into new technologies that have the potential to improve our capacity to identify and comprehend complex presentations. This debate connects to the following examination of treatment methods, where current cases that showcase successful interventions are carefully examined to extract valuable insights into good clinical management. The discussion focuses on the public health implications of preventive efforts against infectious infections, including their neurological consequences. The story emphasizes the link between infectious diseases and overall societal health, advocating for a proactive strategy to reduce the impact of neurological complications. The abstract concludes by providing a prospective viewpoint, highlighting areas of research that still need to be addressed, and suggesting potential future avenues. This narrative review seeks to provide a comprehensive resource for physicians, researchers, and public health professionals dealing with the complex field of neurological manifestations in infectious diseases. It combines recent examples, synthesizes current information, and offers a holistic perspective.
Medicine, Sri Balaji Action Medical Institute, Delhi, IND.
Pure and Applied Biology, Ladoke Akintola University of Technology, Ogbomoso, NGA.General Medicine, Stavropol State Medical University, Stavropol, RUS.
Medicine, Bahria University Medical and Dental College, Karachi, PAK.
Medicine, Sir Syed College of Medical Sciences, Karachi, PAK.
Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, PAK.
Internal Medicine, Burjeel Hospital, Abu Dhabi, ARE.
Medicine, NMC Royal Family Medical Centre, Abu Dhabi, ARE.
Medicine, Shaheed Mohtarma Benazir Bhutto Medical College, Karachi, PAK.
Medicine, Ziauddin University, Karachi, PAK.
Medicine, Menoufia University, Shibin El Kom, EGY.
Pain Medicine, Paolo Procacci Foundation, Rome, ITA.
Internal Medicine/Cardiology, Dow University of Health Sciences, Karachi, PAK.
Internal Medicine, Dow University of Health Sciences, Karachi, PAK.
Medicine, Sanjay Gandhi Memorial Hospital, Delhi, IND.
Internal Medicine, Khyber Teaching Hospital, Peshawar, PAK.
Neurological Manifestations of Infectious Diseases: Insights From Recent Cases.

Clostridium difficile infection (CDI) is a debilitating nosocomial infection. C. difficile produces toxins A and B, which cause inflammation. Existing therapies have issues with recurrence, cost, and safety. We aim to discover a safe, effective, and economical nonmicrobiological therapeutic approach against CDI.We included human primary peripheral blood mononuclear cells (PBMCs), fresh human colonic explants, and humanized HuCD34-NCG mice. Toxin A+B+ VPI 10463 and A-B+ ribotype 017 C. difficile strains were used. We used single-cell RNA profiling and high-throughput screening to find actionable toxin B-dependent pathways in PBMCs.Histamine 1 receptor-related drugs were found among the hit compounds that reversed toxin-mediated macrophage inflammatory protein (MIP) 1α expression in PBMCs. We identified loratadine as the safest representative antihistamine for therapeutic development. Loratadine inhibited toxin B-induced MIP-1α secretion in fresh human colonic tissues. Oral loratadine (10 mg/kg/d) maintained survival, inhibited intestinal CCl3 messenger RNA expression, and prevented vancomycin-associated recurrence in the VPI 10463-infected mice and ribotype 017-infected hamsters. Splenocytes from loratadine-treated mice conferred anti-inflammatory effects to the VPI 10463-infected T/B-cell--deficient Rag-/- mice. Oral loratadine suppressed human MIP-1α expression in monocytes/macrophages in toxin B-expressing ribotype 017-infected humanized HuCD34-NCG mice.Loratadine may be repurposed to optimize existing therapies against CDI.
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.Department of Gastroenterology, The First Hospital of China Medical University, Shenyang City, China.
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USA.
Department of Gastroenterology, The First Hospital of China Medical University, Shenyang City, China.
Loratadine, a Food and Drug Administration–approved antihistamine, inhibits toxin B–mediated proinflammatory macrophage inflammatory protein 1α secretion from immune cells. Its anti-inflammatory effect ameliorates intestinal inflammation in Clostridium difficile–infected animals. Loratadine may be repurposed to optimize existing therapies.
Loratadine as an Anti-inflammatory Agent Against Clostridium difficile Toxin B.

In this work, we developed a high-fidelity beating heart simulator that provides accurate mitral valve pathophysiology. The benchtop platform is based on a biorobotic hybrid heart that combines preserved intracardiac tissue with soft robotic cardiac muscle providing dynamic left ventricular motion and precise anatomical features designed for testing intracardiac devices, particularly for mitral valve repair. The heart model is integrated into a mock circulatory loop, and the active myocardium drives fluid circulation producing physiological hemodynamics without an external pulsatile pump. Using biomimetic soft robotic technology, the heart can replicate both ventricular and septal wall motion, as well as intraventricular pressure-volume relationships. This enables the system to recreate the natural motion and function of the mitral valve, which allows us to demonstrate various surgical and interventional techniques. The biorobotic cardiovascular simulator allows for real-time hemodynamic data collection, direct visualization of the intracardiac procedure, and compatibility with clinical imaging modalities.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology; Cambridge, MA, USA 02139.Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA 02139.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology; Cambridge, MA, USA 02139.
Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA 02115.
Cardiovascular Research Center, Massachusetts General Hospital; Charlestown, MA, USA 02114.Cardiovascular Innovation Research Center, Heart Vascular Thoracic Institute, Cleveland Clinic; Cleveland, OH, USA 44195.Imaging Sciences, Imaging Institute, Cleveland Clinic; Cleveland, OH, USA 44195.Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic; Cleveland, OH, USA 44196.
Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator.

Anterior Cruciate Ligament (ACL) reconstruction is one of the most common surgeries being currently done. As we usher into the era of Individualized Anatomic Reconstruction, it is very important to understand the native anatomy of ACL. We aimed to assess the ACL footprint dimensions in our patients and correlate it with anthropometric variables, which can help in preoperative decision making.A total of 143 eligible patients with suspected ACL injury presented during the study period. Out of which 92 were included in the study. Data on patient's age, sex, height, weight and body mass index (BMI) was recorded. The length and area of both the tibial and femoral footprints were measured on MRI. The footprint dimensions were correlated with the recorded anthropometric data.The ACL tibial footprint length and area, and femoral footprint length and area were found to be 13.3 ± 2.23 mm, 142.6 ± 26.16 mm2, 11.2 ± 1.97 mm, 125.8 ± 28.75 mm2 respectively. Footprint in males was significantly larger than females. A weak (ρ- 0.21 to 0.4) correlation with weight and moderate (ρ- 0.41 to 0.6) correlation with height was observed. Multivariate linear regression analysis yielded height to be the only significant predictor of footprint dimension from which predictive equations were drawn.Height was found to be the most significant predictor of footprint dimensions in our patients. The predictive equations and graphs can aid in preoperative surgical decision making resulting in a more anatomical ACL reconstruction and improve the post-operative results.
Department of Orthopaedics, All India Institute of Medical Sciences, Veerbhadra Road, Rishikesh, Uttarakhand, 249203, India.
Department of Trauma Surgery, All India Institute of Medical Sciences, Veerbhadra Road, Rishikesh, Uttarakhand, 249203, India.
Journal of clinical orthopaedics and trauma
Can patient anthropometry predict the anterior cruciate ligament footprint dimensions? - An MRI-based observational study on north Indian population.

The objective of this study was to systematically review the standardized neurodevelopmental assessments used to study preschool-aged children's cognitive development in Spanish-speaking Latin America.The authors systematically searched PubMed, PsycINFO, and ERIC databases for peer-reviewed articles from Spanish-speaking Latin American countries. Articles were included if they measured cognitive development among children aged 2-6 years using at least one standardized assessment tool; 97 articles were included and reviewed in accordance with PRISMA guidelines to assess their use of these tools.Ninety-seven studies across 13 countries used a total of 41 assessments to measure cognitive development; most widely used were the Wechsler intelligence scales (n = 46/97), particularly the Wechsler Preschool and Primary Scale of Intelligence and Wechsler Intelligence Scale for Children (n = 23 and 29, respectively). Other common assessments included the McCarthy Scales of Children's Abilities (n = 9), Raven's Progressive Matrices (n = 9), Child Neuropsychological Assessment (n = 8), and Peabody Picture Vocabulary Test (n = 7). In regions where normative data for a given assessment were unpublished, authors commonly used norms from the United States, Mexico, or Spain or did not report standard scores in their analyses.The wide range of tools used in these studies presents a challenge for generalizing results when measuring the neurodevelopment of Latin American preschool-aged children. The low availability of normative data for specific regions reveals concerns if some tools are culturally and linguistically appropriate even when Spanish is a common language, particularly in low-resource settings. Future work to forge greater consistency in the use of validated measures, clarity in reporting research methods, and publication of regional normative data would benefit the field.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, United States.
Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, United States.Department of Emergency Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, United States.Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, United States.Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Neurodevelopmental assessments used to measure preschoolers' cognitive development in Latin America: a systematic review.

Cathepsins (Cats) are proteases that mediate the successful entry of SARS-CoV-2 into host cells. We designed and synthesized a tailored series of 21 peptidomimetics and evaluated their inhibitory activity against human cathepsins L, B, and S. Structural diversity was realized by combinations of different C-terminal warhead functions and N-terminal capping groups, while a central Leu-Phe fragment was maintained. Several compounds were identified as promising cathepsin L and S inhibitors with Ki values in the low nanomolar to subnanomolar range, for example, the peptide aldehydes 9a and 9b (9a, 2.67 nM, CatL; 0.455 nM, CatS; 9b, 1.76 nM, CatL; 0.512 nM, CatS). The compounds' inhibitory activity against the main protease of SARS-CoV-2 (Mpro) was additionally investigated. Based on the results at CatL, CatS, and Mpro, selected inhibitors were subjected to investigations of their antiviral activity in cell-based assays. In particular, the peptide nitrile 11e exhibited promising antiviral activity with an EC50 value of 38.4 nM in Calu-3 cells without showing cytotoxicity. High metabolic stability and favorable pharmacokinetic properties make 11e suitable for further preclinical development.
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, An der Immenburg 4, Bonn 53121, Germany.
Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research Göttingen, Kellnerweg 4, Göttingen 37077, Germany.
Faculty of Biology and Psychology, University Göttingen, Göttingen 37073, Germany.
Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research Göttingen, Kellnerweg 4, Göttingen 37077, Germany.Faculty of Biology and Psychology, University Göttingen, Göttingen 37073, Germany.
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland.Excellence Cluster Controlling Microbes to Fight Infections (CMFI), Tübingen 72076, Germany.
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland.
Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Braunschweig 38124, Germany.Partner Site Hannover-Braunschweig, German Center for Infection Research (DZIF), Braunschweig 38124, Germany.
ACS pharmacology & translational science
Cathepsin-Targeting SARS-CoV-2 Inhibitors: Design, Synthesis, and Biological Activity.

Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90089, USA.Department of Otolaryngology Head and Neck, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA, 90033, USA.
Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical Center, 127S. San Vicente Blvd, Los Angeles, CA, 90048, USA.
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90089, USA.
Department of Otolaryngology Head and Neck, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA, 90033, USA. sinha@med.usc.edu.
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90089, USA. dechenli@usc.edu.Department of Otolaryngology Head and Neck, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA, 90033, USA. dechenli@usc.edu.
Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma.

Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition.Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures.We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials.Mutation position influences Aβ burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aβ burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.Meharry School of Medicine, Meharry College, Nashville, Tennessee, USA.
Institute for Neurological Research FLENI, Montañeses, Buenos Aires, Argentina.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Neuroscience Research Australia, Sydney, NSW, Australia.University of New South Wales, Sydney, NSW, Australia.
UK Dementia Research Institute and Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mayo Clinic, Jacksonville, Florida, USA.
Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Indiana University School of Medicine, Indianapolis, Indiana, USA.
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.University hospital Tübingen, Tübingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.Ludwig Maximilian University of Munich, Munich, Germany.Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
The University of Tokyo, Bunkyo City, Tokyo, Japan.
Brown University, Providence, Rhode Island, USA.
Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Banner Alzheimer Institute, Banner Health, Phoenix, Arizona, USA.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.Ludwig Maximilian University of Munich, Munich, Germany.
Department of Nuclear Medicine, Technical University of Munich, Munich, Germany.
Columbia University Medical Center, New York, New York, USA.
Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

This paper presents a machine learning-based prediction for dementia, leveraging transfer learning to reuse the knowledge learned from prediction of mild cognitive impairment, a precursor of dementia. We also examine the impacts of temporal aspects of longitudinal data and sex differences. The methodology encompasses key components such as setting the duration window, comparing different modeling strategies, conducting comprehensive evaluations, and examining the sex-specific impacts of simulated scenarios. The findings reveal that cognitive deficits in females, once detected at the mild cognitive impairment stage, tend to deteriorate over time, while males exhibit more diverse decline across various characteristics without highlighting specific ones. However, the underlying reasons for these sex differences remain unknown and warrant further investigation.
Mechanical, Aerospace and Biomedical Engineering, University of Tennessee, Knoxville, USA.
Department of Artificial Intelligence and Informatics, Mayo Clinic, Rochester, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, USA.
Department of Neurology, Mayo Clinic, Rochester, USA.
Proceedings (IEEE Int Conf Bioinformatics Biomed)
Proceedings. IEEE International Conference on Bioinformatics and Biomedicine
Proceedings (IEEE Int Conf Bioinformatics Biomed). 2023-12;2023():2097-2100.
Harnessing Transfer Learning for Dementia Prediction: Leveraging Sex-Different Mild Cognitive Impairment Prognosis.

The Citarum watershed is West Java Province's most important water resource; hence, harmful compounds should be monitored regularly. This study assessed pollution levels along with ecological and health risks from Cd, Pb, Mn, Fe, Cu, Cr, and Hg contamination in river water, sediment, groundwater, and soil in Citarum's upper watershed. In river water, the average amounts of Cd, Pb, Mn, Fe, Cu, Cr, and Hg were 0.002, 0.05, 0.092, 0.649, 0.022, 0.001, and 0.421 mg/L. In sediment, they were 7.4, 1175.1, 32,289.9, 37.3, 3.9, and 0.015 mg/kg. The mean concentrations of Cd, Pb, Mn, Fe, Cu, Cr, and Hg in groundwater were 0.004, 0.046, 0.567, 0.366, 0.019, 0.001, and 0.177 mg/L, and in soil, BDL, 10.2, 744.6, 50,094.1, 45.6, 5.9, and 0.015 mg/kg. The river water and groundwater were highly polluted by PTEs, with HPI values of 14,733 and 933, respectively. While PTEs pollution levels and risk in sediment and soil were low based on I-geo, CF, PLI, and M-ERM-Q values, PTEs contamination in river water may cause adverse impacts on aquatic living organisms (HQ > 1). The population doing recreational activities in river ecosystems was still safe from non-carcinogenic and carcinogenic impacts due to PTEs exposure from river water and sediment (THI < 1 and TCR value < 1E-04), while the population in the upper Citarum River was not safe from the carcinogenic risk due to PTE exposure from groundwater and soil (TCR > 1E-04). The sensitivity analysis showed that Cd concentration in groundwater is the most influential factor in cancer risk, with a total contribution of 99.9%. Therefore, a reduction in Cd concentration in groundwater is important to reduce cancer risk in the population.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Research Center for Geological Resources, National Research and Innovation Agency, Bandung, 40135, Indonesia. ratna.dwi@fkm.unair.ac.id.Faculty of Public Health, Universitas Airlangga, Surabaya, 60155, Indonesia. ratna.dwi@fkm.unair.ac.id.
Research Center for Geological Resources, National Research and Innovation Agency, Bandung, 40135, Indonesia. rizk002@brin.go.id.
Research Center for Geological Resources, National Research and Innovation Agency, Bandung, 40135, Indonesia.
Research Center for Limnology and Water Resources, National Research and Innovation Agency, Cibinong, 16911, Indonesia.
Research Center for Environmental and Clean Technology, National Research and Innovation Agency, Bandung, 40135, Indonesia.
Polytechnic of Energy and Mining, Ministry of Energy and Mineral Resources, Bandung, 40211, Indonesia.
Potentially toxic elements contamination in the water resources: an integrated risk assessment approach in the upper Citarum watershed area.

Dementia is among the leading causes of cognitive and functional loss and disability in older adults. Past studies suggested sex differences in health conditions and progression of cognitive decline. Existing studies on the temporal trajectory of health conditions for patient characterization after dementia diagnosis are scarce and ambiguous. Thus, there's limited and unclear research on how health conditions change over time after a dementia diagnosis. To this end, we aim to analyze the shift in medical conditions and examine sex-specific changes in patterns of chronic health conditions after dementia diagnosis. We centered our analysis on a 15-year window around the point of dementia diagnosis, encompassing the 5 years leading up to the diagnosis and the 10 years following it. We introduce (i) MedMet, a network metric to quantify the contribution of each medical condition, and (ii) growth and decay function for temporal trajectory analysis of medical conditions. Our experiments demonstrate that certain health conditions are more prevalent among females than males. Thus, our findings underscore the pressing need to examine differences between men and women, which could be important for healthcare utilization after a dementia diagnosis.
Artificial Intelligence & Informatics, Mayo Clinic, Rochester, MN, USA.
Quantitative Health Science Research, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Proceedings (IEEE Int Conf Bioinformatics Biomed). 2023-12;2023():4065-4072.
Navigating Sex-Specific Disease Dynamics in Incident Dementia.

Describing the characteristics and sources of health state utility values and reporting practice in the literature of cost-utility analyses facilitates an understanding of the level of the transparency, validity, and generalizability of cost-utility analyses. Improving the quality of reporting will support investigators in describing the incremental value of emerging glaucoma interventions.To describe the state of practice among published glaucoma cost-utility analysis studies, focusing on valuation of health and the quality of reporting.We searched several databases including Medline, CINHAL, Embase, Web of Science, Scopus, Biosis previews, the Health Economic Evaluations Database, and the NHS Economic Evaluation Database (NHS EED). We included full-text, English, published cost-utility analyses of glaucoma interventions with quality-adjusted life years (QALYs) as the primary outcome measure to calculate incremental cost-utility ratios. Excluded studies were non-English language, reviews, editorials, protocols, or other types of economic studies (cost-benefit, cost-minimization, cost-effectiveness). Study characteristics, operational definitions of glaucoma health states and health state utilities were extracted. The original source of the health utility was reviewed to determine the scale of measurement and the source of preference weighting. Items from the Systematic Review of Utilities for Cost-Effectiveness (SpRUCE checklist) were used to assess the reporting and quality of health utilities in glaucoma CUA.43 CUAs were included, with 11 unique sources of health utilities. A wide range of health utilities for the same Hodapp-Parrish-Anderson glaucoma health states were reported; ocular hypertension (0.84-0.95), mild (0.68-0.94), moderate (0.57-0.92), advanced (0.58-0.88), severe/blind (0.46-0.76), and bilateral blindness (0.26-0.5). Most studies reported the basis for using health utilities (34, 79%) and any assumptions or adjustments applied to the health utilities (22, 51%). Few studies reported a framework for assessing the relevance of health utilities to a decision context (8, 19%). Even fewer (3, 7%) applied a systematic search strategy to identify health utilities and used a structured assessment of quality for inclusion. Overall, reporting has not improved over time.This review describes that few CUAs describe important rationale for using health state utility values. Including additional details on the search, appraisal, selection, and inclusion process of health utility values improves transparency, generalizability and supports the assessment of the validity of study conclusions. Future investigations should aim to use health utilities on the same scale of measurement across health states and consider the source and relevance to the decision context/purpose of conducting that cost-utility study.
School of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, BC, V6T1Z3, Canada. kevin.kennedy@ubc.ca.
Department of Ophthalmology and Visual Sciences, University of Alberta, 400, 10924, 107 Avenue, Edmonton, AB, T5H 0X5, Canada.
Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
College of Pharmacy-Pharmacy Systems Outcomes and Policy, University of Illinois Chicago, Chicago, USA.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
The European journal of health economics : HEPAC : health economics in prevention and care
Systematic methodological review of health state values in glaucoma cost-utility analyses.

Pseudomonas aeruginosa is an important cause of lower respiratory tract infections, such as ventilator-associated bacterial pneumonia (VABP). Using inhaled antibiotics to treat VABP can achieve high drug concentrations at the infection site while minimizing systemic toxicities. Despite the theoretical advantages, clinical trials have failed to show a benefit for inhaled antibiotic therapy in treating VABP. A potential reason for this discordance is the presence of biofilm-embedded bacteria in lower respiratory tract infections. Drug selection and dosing are often based on data from bacteria grown planktonically. In the present study, an in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model was optimized to evaluate the activity of simulated epithelial lining fluid exposures of inhaled and intravenous doses of polymyxin B and tobramycin against two P. aeruginosa strains. Antibiotic activity was also determined against the P. aeruginosa strains grown planktonically. Our study revealed that inhaled antibiotic exposures were more active than their intravenous counterparts across biofilm and planktonic populations. Inhaled exposures of polymyxin B and tobramycin exhibited comparable activity against planktonic P. aeruginosa. Although inhaled polymyxin B exposures were initially more active against P. aeruginosa biofilms (through 6 h), tobramycin was more active by the end of the experiment (48 h). Together, these data slightly favor the use of inhaled tobramycin for VABP caused by biofilm-forming P. aeruginosa that are not resistant to either antibiotic. The optimized in vitro air-liquid interface pharmacokinetic/pharmacodynamic biofilm model may be beneficial for the development of novel anti-biofilm agents or to optimize antibiotic dosing for infections such as VABP.
Department of Pharmacy Practice, University of Illinois Chicago College of Pharmacy, Chicago, IL, USA.
Mass Spectrometry Core, Research Resources Center, University of Illinois Chicago, Chicago, IL, USA.
Fluorescence Imaging Core, Research Resources Center, University of Illinois Chicago, Chicago, IL, USA.
Department of Pharmacy Practice, University of Illinois Chicago College of Pharmacy, Chicago, IL, USA. bulman@uic.edu.
NPJ Biofilms Microbiomes. 2024-03-01;10(1):16.
Optimization of an in vitro Pseudomonas aeruginosa Biofilm Model to Examine Antibiotic Pharmacodynamics at the Air-Liquid Interface.

Purpose: To evaluate the visual, intraocular pressure (IOP), and anatomic outcomes of eyes with loss to follow-up (LTFU) after intravitreal or periocular steroid injections. Methods: Patients receiving intraocular or periocular steroid injections and with LTFU for at least 180 days were included in this retrospective cohort study. Charts were reviewed for the visual acuity (VA), IOP, and central foveal thickness at the visit before LTFU, the first return visit, and 3, 6, and 12 months after return. Results: Fifty-three eyes of 47 patients were identified. The mean (±SD) age was 62.3 ± 14.9 years, the mean LTFU time was 295 ± 181.2 days (range, 182-1101), and the mean follow-up after return was 354 ± 339.3 days (range, 32-1141). The overall mean number of steroid injections was 5.2 ± 3.9 (range, 1-18). Compared with the mean logMAR VA at the visit before LTFU (0.59 [Snellen 20/77]), the mean VA remained stable at all timepoints after return as follows: return visit (0.62 [20/83]; P = .6), month 3 (0.55 [20/70]; P = .6), month 6 (0.55 [20/70]; P = .5), month 12 (0.64 [20/87]; P = .6), and final visit (0.69 [20/97]; P = .2). At the first return visit, 8 (15%) of 53 patients had an IOP of 21 mm Hg or higher (range, 21-31); 2 required treatment with a new antihypertensive medication (latanoprost and timolol, respectively). Conclusions: Patients with LTFU after receiving steroid injections maintained their VA. No patient required incisional glaucoma surgery. Compared with other etiologies, eyes with diabetic macular edema had a greater increase in IOP.
Mid Atlantic Retina, Retina Service of Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Hamilton Regional Eye Institute, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.Department of Surgery, McMaster University, Hamilton, ON, Canada.
Outcomes of Eyes Lost to Follow-up After Treatment With Intraocular or Periocular Steroid Injections.

Quantifying pain in patients admitted to intensive care units (ICUs) is challenging due to the increased prevalence of communication barriers in this patient population. Previous research has posited a positive correlation between pain and physical activity in critically ill patients. In this study, we advance this hypothesis by building machine learning classifiers to examine the ability of accelerometer data collected from daily wearables to predict self-reported pain levels experienced by patients in the ICU. We trained multiple Machine Learning (ML) models, including Logistic Regression, CatBoost, and XG-Boost, on statistical features extracted from the accelerometer data combined with previous pain measurements and patient demographics. Following previous studies that showed a change in pain sensitivity in ICU patients at night, we performed the task of pain classification separately for daytime and nighttime pain reports. In the pain versus no-pain classification setting, logistic regression gave the best classifier in daytime (AUC: 0.72, F1-score: 0.72), and CatBoost gave the best classifier at nighttime (AUC: 0.82, F1-score: 0.82). Performance of logistic regression dropped to 0.61 AUC, 0.62 F1-score (mild vs. moderate pain, nighttime), and CatBoost's performance was similarly affected with 0.61 AUC, 0.60 F1-score (moderate vs. severe pain, daytime). The inclusion of analgesic information benefited the classification between moderate and severe pain. SHAP analysis was conducted to find the most significant features in each setting. It assigned the highest importance to accelerometer-related features on all evaluated settings but also showed the contribution of the other features such as age and medications in specific contexts. In conclusion, accelerometer data combined with patient demographics and previous pain measurements can be used to screen painful from painless episodes in the ICU and can be combined with analgesic information to provide moderate classification between painful episodes of different severities.
Federal University of Minas Gerais/Department of Computer Science, Belo Horizonte, Brazil.
University of Florida/J. Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, USA.University of Florida/Intelligent Critical Care Center, Gainesville, Florida, USA.
University of Florida/J. Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, USA.
University of Florida/Intelligent Critical Care Center, Gainesville, Florida, USA.University of Florida/Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, Gainesville, Florida, USA.
University of Florida/Department of Anesthesiology, College of Medicine, Gainesville, Florida.
IEEE Int Conf Bioinform Biomed Workshops
IEEE International Conference on Bioinformatics and Biomedicine workshops. IEEE International Conference on Bioinformatics and Biomedicine
IEEE Int Conf Bioinform Biomed Workshops. 2023-12;2023():2207-2212.
Diurnal Pain Classification in Critically Ill Patients using Machine Learning on Accelerometry and Analgesic Data.

Diabetic wound healing is a substantial clinical challenge, characterized by delayed angiogenesis and unresolved inflammation. Lentinan, a polysaccharide extracted from shiitake mushrooms, has the potential to regulate both macrophage polarization and angiogenesis, though this aspect remains inadequately explored. To facilitate lentinan's clinical utility, we have developed a GelMA hydrogel encapsulated with lentinan (10 μM), offering a controlled release mechanism for sustained lentinan delivery at the wound site. Application of the lentinan-encapsulated delivery system topically significantly expedites wound closure compared to control groups. Furthermore, histological examination demonstrates enhanced neovascularization and reduced inflammation in lentinan-treated wounds, as evidenced by increased M2 macrophage infiltration. Moreover, our results indicated that lentinan-induced AMPK activation promotes DAF16 expression, enhancing the resistance of macrophages and HUVECs to oxidative stress in high-glucose environments, thereby promoting M2 macrophage polarization and angiogenesis. All these findings underscore lentinan's capacity to modulate macrophage polarization and angiogenesis via the AMPK/DAF16 pathway, ultimately facilitating the healing of diabetic wounds.
Copyright © 2024 Elsevier B.V. All rights reserved.
Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 101100, China. Electronic address: jiazhiweivip@163.com.
Department of Sports Medicine, Fourth Medical Center of PLA General Hospital, Beijing 100048, China.
Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 101100, China.
Department of Sports Medicine, Fourth Medical Center of PLA General Hospital, Beijing 100048, China. Electronic address: weilichn@126.com.
Lentinan-loaded GelMA hydrogel accelerates diabetic wound healing through enhanced angiogenesis and immune microenvironment modulation.

Neuropathic pain affects a large percentage of the U.S. population and leads to tremendous morbidity. Numerous nonsurgical and surgical treatments have been utilized to try and manage neuropathic pain with varying degrees of success. Recent research investigating ways to improve prosthetic control have identified new mechanisms for preventing neuromas in both motor and sensory nerves with free muscle and dermal grafts, respectively. These procedures have been used to treat chronic neuropathic pain in nonamputees, as well, in order to reduce failure rates found with traditional neurectomy procedures. Herein, we focus our attention on Dermal Sensory-Regenerative Peripheral Nerve Interfaces (DS-RPNI, free dermal grafts) which can be used to physiologically cap sensory nerves following neurectomy and have been shown to significantly decrease neuropathic pain.
Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Management of Neuropathic Pain with Neurectomy Combined with Dermal Sensory Regenerative Peripheral Nerve Interface (DS-RPNI).

Chronic pain resulting from peripheral nerve injury remains a common issue in the United States and affects 7 to 10% of the population. Regenerative Peripheral Nerve Interface (RPNI) surgery is an innovative surgical procedure designed to treat posttraumatic neuropathic pain, particularly when a symptomatic neuroma is present on clinical exam. RPNI surgery involves implantation of a transected peripheral nerve into an autologous free muscle graft to provide denervated targets to regenerating axons. RPNI surgery has been found in animal and human studies to be highly effective in addressing postamputation pain. While most studies have reported its uses in the amputation patient population for the treatment of neuroma and phantom limb pain, RPNI surgery has recently been used to address refractory headache, postmastectomy pain, and painful donor sites from the harvest of neurotized flaps. This review summarizes the current understanding of RPNI surgery for the treatment of chronic neuropathic pain.
Section of Plastic Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan.
Regenerative Peripheral Nerve Interface Surgery for the Management of Chronic Posttraumatic Neuropathic Pain.

Healthcare practitioners face significant risks of workplace violence due to various reasons such as hospital congestion, miscommunication, and aggressive behaviours of patients and relatives. Exposure to workplace violence may disrupt the workflow process and compromise patient care in healthcare facilities, ultimately affecting job performance, reducing job satisfaction, and negatively affecting the physical and mental health of healthcare practitioners. This study aimed to review all the published studies conducted on the experiences of workplace violence among healthcare practitioners. This study is a systematic review of qualitative studies. Data were collected through online databases including ScienceDirect, PubMed, MEDLINE and JSTOR were searched from the year 2015-2021. The inclusion criteria were: qualitative methods and mixed methods of data collection and analysis; studies that were carried out among healthcare practitioners who have been experience on workplace violence; scope of the primary studies included experience of workplace violence; and published in English/Malay in academic journal between 2015 and 2021. A total of 15 papers were included in the final analysis. The overall quality of the included papers was high. Of the 15 papers, 12 studies fully met the CASP criteria. The results of the 15 included studies were organised into the thematic groups of: i) verbal violence as the common workplace violence; ii) perceived causes of workplace violence and iii) seeking help. Across different countries, verbal violence was the most common type of workplace violence reported by healthcare practitioners. This review also identified that a lack of information, failure to meet patient expectations, and delayed treatment were the main contributing factors to workplace violence.
© Penerbit Universiti Sains Malaysia, 2024.
Emergency Department, Hospital Sultan Idris Shah Serdang, Selangor, Malaysia.
Department of Special Care Nursing, Kulliyah of Nursing, International Islamic University Malaysia, Pahang, Malaysia.
Department of Community Medicine, Kulliyah of Medicine, International Islamic University Malaysia, Pahang, Malaysia.
The Malaysian journal of medical sciences : MJMS
A Qualitative Systematic Review of Healthcare Practitioners' Experience of Workplace Violence.

The financial burden of breast cancer treatment and reconstruction is a significant concern for patients. Patient desire for preoperative cost-of-care counseling while navigating the reconstructive process remains unknown. A cross-sectional survey of women from the Love Research Army was conducted. An electronic survey was distributed to women over 18 years of age and at least 1 year after postmastectomy breast reconstruction. Descriptive statistics and multivariable modeling were used to determine desire for and occurrence of cost-of-care discussions, and factors associated with preference for such discussions. Secondary outcomes included the association of financial toxicity with desire for cost discussions. Among 839 women who responded, 620 women (74.1%) did not speak to their plastic surgeon and 480 (57.4%) did not speak to a staff member regarding costs of breast reconstruction. Of the 550 women who reported it would have been helpful to discuss costs, 315 (57.3%) were not engaged in a financial conversation initiated by a health care provider. A greater proportion of women who reported financial toxicity, compared to those who did not, would have preferred to discuss costs with their plastic surgeon (65.2% vs. 43.5%, p < 0.001) or a staff member (75.5% vs. 59.3%, p < 0.001). Among women with financial toxicity, those who had some form of insurance (private, Medicaid, Medicare, other ) were significantly more likely to prefer a cost-of-care discussion ( p < 0.001, p = 0.02, p = 0.05, p = 0.01). Financial discussions about the potential costs of breast reconstruction seldom occurred in this national cohort. Given the reported preference and unmet need for financial discussions by a majority of women, better cost transparency and communication is needed.
Section of Plastic and Reconstructive Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.Department of Health Behavior and Health Education, University of Michigan, Ann Arbor, Michigan.Ann Arbor VA Center for Clinical Management Research, Ann Arbor, Michigan.
Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia.
Financial Toxicity in Breast Reconstruction: The Role of the Surgeon-Patient Cost-of-Care Discussion.

Purpose: To examine the outcomes of chandelier endoillumination-assisted scleral buckling (chandelier scleral buckling) for rhegmatogenous retinal detachments (RRDs) and compare them with those of standard scleral buckling using indirect ophthalmoscopy. Methods: A literature search was performed on April 15, 2023. Outcomes analyzed included the primary anatomic success rates, surgical duration, and complication rates. A meta-analysis of proportions estimated the pooled success rate of chandelier scleral buckling. In addition, meta-analyses compared the success rates between pseudophakic eyes and phakic eyes having chandelier scleral buckling and compared success rates and surgical duration between standard scleral buckling and chandelier scleral buckling. Results: Thirty studies with 1133 eyes were included. The pooled primary anatomic success rate of chandelier scleral buckling was 91.7% (95% CI, 89.6%-93.6%). In studies comparing success rates between the 2 techniques, there was no significant difference (risk ratio, 1.01; 95% CI, 0.94-1.08; P = .80). The surgical times were significantly shorter with chandelier scleral buckling than with standard scleral buckling (mean difference, -18.83; 95% CI, -30.88 to -6.79; P = .002). There was no significant difference in the success rate between pseudophakic eyes and phakic eyes (risk ratio, 0.99; 95% CI, 0.91-1.08; P = .89). No cases of endophthalmitis were reported. Conclusions: Chandelier endoillumination-assisted scleral buckling may be a promising technique given its high rate of primary anatomic success for RRDs and success rates similar to those of standard scleral buckling. There was no significant difference in the efficacy of chandelier scleral buckling between pseudophakic eyes and phakic eyes.
Department of Ophthalmology, Northwell Health Eye Institute, Great Neck, NY, USA.
Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA.
Department of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York, University at Buffalo, Buffalo, NY USA.
Institute of Ophthalmology & Visual Science, Rutgers New Jersey Medical School, Newark, NJ, USA.
Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Otolaryngology-Head and Neck Surgery, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Department of Ophthalmology, Icahn School of Medicine, Mount Sinai Medical Center, and New York City Health and Hospitals, New York, NY, USA.
Outcomes of Chandelier-Assisted Scleral Buckling in Rhegmatogenous Retinal Detachments: Systematic Review and Meta-analysis.

In this article, we examine the 60-year history of diversity efforts within the Section of Plastic Surgery at the University of Michigan (UofM) in the context of national trends. We describe the experiences of pioneering Underrepresented in Medicine (URiM) and female graduates of the program. James Norris, MD, and Christine Sullivan, MD, were the first URiM and female graduates from UofM in 1974 and 1989, respectively. Currently, women constitute over one-half the plastic surgery trainees at UofM, but URiM trainee representation remains limited. Dr. Adeyiza Momoh and Dr. Amy Alderman were the first URiM and female faculty members hired in 2011 and 2004, respectively. At present, there are four URiM and seven female faculty members in the Section. With a shared vision, supportive leadership, and motivation to change, faculty diversity has increased substantially. Additional strategies, including ongoing pipeline programs in medicine and science for URiM and women, are needed to further increase workforce diversity in plastic surgery.
Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
Section of Plastic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
A Historical Review of Racial, Ethnic, and Gender Diversity in Plastic Surgery at the University of Michigan.

The University of Michigan has played an important role in advancing gender-affirming surgery programs in the United States. The University of Michigan was home to a little-known gender identity clinic shortly after the opening of the first such clinic at Johns Hopkins. Since 1995, the University of Michigan Comprehensive Services Program (UMCGSP) has been continually offering surgical services to transgender and gender diverse patients. Here, we present the history of both programs, drawn from program documents and oral history, and explore their implications for the future sustainability of gender-affirming surgery programs. The original gender identity clinic opened in 1968, and operated in a multidisciplinary fashion, similar to other clinics at the time. Eventually, the clinic was closed due to disinvestment and lack of sufficient providers to maintain the program, problems which are being increasingly recognized as barriers for similar programs. The modern program, UMCGSP is perhaps the longest continually running gender-affirming surgical program at an academic center. In spite of challenges, key investments in education, statewide community engagement, and the development of a comprehensive care model have helped UMCGSP avoid the pitfalls of the earlier clinic and remain relevant throughout its nearly 30-year history. In the face of rising challenges to gender-affirming care in the United States, much can be learned from the sustainability of the UMCGSP. Institutions seeking to maintain gender-affirming surgery programs should ensure the availability of comprehensive care and promote the education of the health care workforce.
Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois.
Department of Human Centered Design and Engineering, University of Washington, Seattle, Washington.
University of Michigan Medical School, Medical School, Ann Arbor, Michigan.
A History of Gender-Affirming Surgery at the University of Michigan: Lessons for Today.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.
New York City Health + Hospital/Bellevue, New York, NY, USA.The Brooklyn Hospital Center, Brooklyn, NY, USA.
The Brooklyn Hospital Center, Brooklyn, NY, USA.Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY, USA.
Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY, USA.Texas Children's Hospital, Houston, TX, USA.
The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians
Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Purpose: To evaluate the effect of mean ocular perfusion pressure on the foveal avascular zone (FAZ) area in eyes with successful retinal detachment (RD) surgery. Methods: This prospective pilot fellow eye-controlled study measured the intraoperative mean ocular perfusion pressure in eyes having surgery for rhegmatogenous RD (RRD). Postoperatively, the FAZ area was measured; the change was calculated as the difference in the FAZ area between the operated eye and the contralateral control eye. Results: The study comprised 8 patients with a mean age (±SD) of 53.38 ± 13.92 years. The mean superficial FAZ area was not different between operated eyes and control eyes, while the deep FAZ area was significantly larger in operated eyes. There was a strong negative correlation between the mean ocular perfusion pressure and the change in the deep FAZ area (Spearman ρ, -0.73; P = .04); the correlation between the mean ocular perfusion pressure and the change in the superficial FAZ area was not significant (Spearman ρ, -0.24; P = .57). A significant linear regression was found between the mean ocular perfusion pressure and the change in the deep FAZ area (R2 = 0.388). The predicted enlargement of the deep FAZ area was 0.03 mm with every 1 mm Hg decrease in the mean ocular perfusion pressure. Conclusions: Lower intraoperative mean ocular perfusion pressure is associated with enlargement of the deep FAZ area in eyes having successful RRD surgery.
Ophthalmology Department, Shifa International Hospital, Islamabad, Pakistan.Ophthalmology Department, Alshifa Trust Eye Hospital, Islamabad, Pakistan.
Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia.
Ophthalmology Department, Shifa International Hospital, Islamabad, Pakistan.
Mean Ocular Perfusion Pressure Effect During Pars Plana Vitrectomy on the Foveal Avascular Zone: A Pilot Study.

Kienbock disease, or avascular necrosis of the lunate, is an uncommon cause of a painful and stiff wrist. Management options range from conservative treatment in the form of immobilization and corticosteroid injections to a wide variety of surgical treatments that depend on the structural integrity of the lunate, intercarpal relationships, and the condition of the articular cartilage of the wrist. A particularly difficult problem lies in the management of young patient in whom vascularized bone grafting of the lunate has failed but in whom arthritis has not yet developed. Pyrocarbon lunate implant arthroplasty is a newer treatment option for such a patient, and allows the preservation of the remainder of the proximal carpal row while directly addressing the degenerative lunate. This article describes the evidence and surgical technique for lunate implant arthroplasty and presents an illustrative case example.
Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
Pyrocarbon Lunate Arthroplasty: An Option for the Young Patient with Advanced Kienbock Disease.

In the setting of bone defects, the injured vasculature and loss of hemodynamic inflow leads to hematoma formation and low oxygen tension which stimulates vascular expansion through the HIf-1α pathway. Most importantly, this pathway upregulates sprouting of type H vessels (CD31hiEmcnhi vessels). H vessels engage in direct interaction with perivascular osteoprogenitor cells (OPCs), osteoblasts, and preosteoclasts of bone formation and remodeling. This angiogenic-osteogenic coupling leads to synchronous propagation of vascular and bony tissue for regenerative healing. A growing body of literature demonstrates that H vessels constitute a large portion of bone's innate capacity for osteogenic healing. We believe that CD31hiEmcnhi vessels play a role in bone healing during distraction osteogenesis (DO). DO is a procedure that utilizes traction forces to facilitate induction of endogenous bone formation and regeneration of surrounding soft tissues such as skin, muscle, tendon, and neurovascular structures. While the H vessel response to mechanical injury is adequate to facilitate healing in normal healthy tissue, it remains inadequate to overcome the devastation of radiation. We posit that the destruction of CD31hiEmcnhi vessels plays a role in precluding DO's effectiveness in irradiated bone defect healing. We aim, therefore, to recapitulate the normal pathway of bony healing by utilizing the regenerative capacity of H vessels. We hypothesize that using localized application of deferoxamine (DFO) will enhance the H vessel-mediated vasculogenic response to radiation damage and ultimately enable osteogenic healing during DO. This discovery could potentially be exploited by developing translational therapeutics to hopefully accelerate bone formation and shorten the DO consolidation period, thereby potentially expanding DO's utilization in irradiated bone healing. Sprague-Dawley rats were divided into three groups: DO, radiation with DO (xDO), and radiation with DO and DFO implantation (xDODFO). Experimental groups received 35 Gy of radiation. All groups underwent DO. The treatment group received injections into the osteotomy site, every other day, beginning on postoperative day (POD) 4 of DFO. Animals were sacrificed on POD 40. For immunohistochemical analysis, mandibles were dissected and fixed in 4% paraformaldehyde for 48 hours, decalcified in Cal-Ex II for 2 days, dehydrated through graded ethanol of increasing concentration, and then embedded in paraffin. Samples were cut into 7-μm thick longitudinally oriented sections including the metaphysis and diaphysis. CD31 and Emcn double immunofluorescent staining were performed to evaluate the extent of CD31hiEmcnhi vessel formation. Bone sections were then stained with conjugated antibodies overnight at 4°C. Nuclei were stained with Hoechst. Slides were also double stained with Osterix and CD31 to study the quantity of H vessel-mediated recruitment of OPCs to accelerate bone healing. Images were acquired with a Nikon Ti2 widefield microscope and analyzed in NIS- Elements Advanced Research 5.41.02 software. The abundance of type H vessels is represented by the area fraction of CD31 + Emcn+ vessel area inside the regenerate sample. OPC concomitant proliferation into the distraction gap is represented by the area fraction of Osterix+ cell area inside of the regenerate sample. There were 6× more type H vessels in DO groups than in xDO groups. Localized DFO significantly increased the abundance of type H vessels of irradiated DO animals compared to xDO by 15× ( p = 0.00133531). Moreover, the DO and xDODFO groups with higher abundance of type H vessels also demonstrated better angiogenesis and osteogenesis outcomes. Interestingly, xDODFO groups doubled the quantity of H vessel formation compared to DO, indicating a supraphysiologic response ( p = 0.044655055). Furthermore, H vessel-mediated recruitment of OPCs mimicked the described H vessel formation trend in our study groups. Irradiated DO groups contained 3× less OPCs compared to DO controls. DFO treatment to xDO animals remediated irradiation damage by containing 12× Osterix+ cells. Finally, DFO treatment of irradiated animals quadrupled osteoprogenitor recruitment into the distraction gap compared to DO controls. In this study, we developed a novel approach to visualize CD31hiEmcnhi in paraffin sections to study DO regeneration. Normal DO demonstrated a significant upregulation of H vessel formation and associated angiogenic-osteogenic coupling. Radiation severely decreased H vessel formation along with an associated significant diminution of new bone formation and nonunion. DFO administration, however, resulted in vascular replenishment and the restoration of high quantities of CD31hiEmcnhi and OPCs, recapitulating the normal process of bony regeneration and repair. DFO treatment remediated new bone formation and bony union in irradiated fields associated with increased H vessel angiogenic-osteogenic coupling. While further studies are required to optimize this approach, the results of this study are incredibly promising for the long-awaited translation of localized DFO into the clinical arena.
H Vessel Formation as a Marker for Enhanced Bone Healing in Irradiated Distraction Osteogenesis.

Background: Type 2 diabetes (T2D) requires close collaboration between patients and their care management team, often including endocrinology. Primary care pharmacist impact on diabetes management in collaboration with endocrinology is not well established. Objective: To assess if pharmacy and endocrinology collaboration results in a greater A1c reduction in patients with T2D vs endocrinology alone. Methods: This retrospective, observational cohort study was conducted in adult outpatients with T2D and baseline A1c >9% who saw endocrinology within 1 year preceding the study period (January 1, 2021 to January 1, 2022). Patients were included if they had a follow-up A1c 6 months (±90 days) from index date and completed at least 1 endocrinology visit during the study period. Patients managed by endocrinology/primary care pharmacist collaboration (Endo/PharmD) were compared with those who received endocrinology care alone (Endo). Primary outcome was change in A1c from baseline to 6 months. Secondary outcomes included total number of completed visits and percentage of patients achieving A1c <6.5%, <7%, <8%, and <9% between groups at 6 months. Results: A total of 418 patients were included (22 Endo/PharmD, 396 Endo). The change in follow-up A1c was not significantly different between groups, -0.481% (standard error [SE] = 0.396); P = 0.6179. Endo/PharmD patients had significantly more provider visits during the study period (5.3 ± 2.3 vs 2.3 ± 1.2; P < 0.001). No significant difference was observed in odds of A1c goal attainment between groups at 6 months. Conclusion and Relevance: Endocrinology/primary care pharmacist collaboration occurred infrequently but was associated with a trend toward greater A1c reduction in patients with T2D and A1c >9%.
Department of Pharmacy, Cleveland Clinic Foundation, Cleveland, OH, USA.
Department of Endocrinology, Cleveland Clinic Foundation, Cleveland, OH, USA.
Quantitative Health Sciences Department, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Endocrinology/Primary Care Pharmacy Collaboration vs Endocrinology Care Alone in Patients With Type 2 Diabetes and A1c >9.

Chimeric antigen receptor (CAR) T cell therapy has markedly improved the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). The relative positioning of tumor lesions in lymphoma varies among patients, manifesting as either aggregation (clumped together) or dissemination (spread throughout the body). Prognostic significance of factors indicating the relative positioning of tumor lesions in CAR T cell therapy remains underexplored. For aggregation, prior research proposed the tumor volume surface ratio (TVSR), linking it to prognosis in chemotherapy. Regarding dissemination, indicators such as disease stage or extranodal involvement, commonly used in clinical practice, have not demonstrated prognostic significance in CAR T cell therapy. This study aims to analyze current indicators of tumor aggregation or dissemination and introduce a novel indicator to assess the prognostic value of tumor lesions' relative positioning in DLBCL patients undergoing CAR T cell therapy.This retrospective study included 42 patients receiving CAR T cell therapy. Lesion image information was obtained from the last PET/CT scan prior to CAR T cell infusion, including total metabolic tumor volume, total tumor surface, diameter of lymphoma masses, and the sites of tumor lesions. We evaluated TVSR and bulky disease as descriptors of tumor aggregation. We refined existing indicators, stage III&IV and >1 site extranodal involvement, to distill a new indicator, termed 'extra stage', to better represent tumor dissemination. The study examined the prognostic significance of tumor aggregation and dissemination.Our findings indicate that TVSR, while prognostically valuable in chemotherapy, lacks practical prognostic value in CAR T cell therapy. Conversely, bulky disease emerged as an optimal prognostic indicator of tumor aggregation. Both bulky disease and extra stage were associated with poor prognosis and exhibiting synergistic prognostic impact in CAR T cell therapy.Overall, the relative positioning of tumor lesions significantly influences the prognosis of patients with DLBCL receiving CAR T cell therapy. The ideal scenario involves tumors with minimal dissemination and no aggregation.
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Medical Imaging, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Indicators describing the tumor lesion aggregation and dissemination and their impact on the prognosis of patients with diffuse large B cell lymphoma receiving chimeric antigen receptor T cell therapy.

Citrus leprosis is the most important viral disease affecting citrus. The disease is caused predominantly by CiLV-C and is transmitted by Brevipalpus yothersi Baker mites. This study brings some insight into the colonization of B. yothersi in citrus [(Citrus × sinensis (L.) Osbeck (Rutaceae)] previously infested by viruliferous or non-viruliferous B. yothersi. It also assesses the putative role of shelters on the behavior of B. yothersi. Expression of PR1 and PR4 genes, markers of plant defense mechanisms, were evaluated by RT-qPCR to correlate the role of the plant hormonal changes during the tri-trophic virus-mite-plant interplay. A previous infestation with either non-viruliferous and viruliferous mites positively influenced oviposition and the number of adult individuals in the resulting populations. Mite populations were higher on branches that had received a previous mite infestation than branches that did not. There was an increase in the expression of PR4, a marker gene in the jasmonic acid (JA) pathway, in the treatment with non-viruliferous mites, indicating a response from the plant to their feeding. Conversely, an induced expression of PR1, a marker gene in the salicylic acid (SA) pathway, was observed mainly in the treatment with viruliferous mites, which suggests the activation of a plant response against the pathogen. The earlier mite infestation, as well as the presence of leprosis lesions and a gypsum mixture as artificial shelters, all fostered the growth of the B. yothersi populations after the second infestation, regardless of the presence or absence of CiLV-C. Furthermore, it is suggested that B. yothersi feeding actually induces the JA pathway in plants. At the same time, the CiLV-C represses the JA pathway and induces the SA pathway, which benefits the mite vector.
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Laboratório de Acarologia (AcaroLab), Faculdade de Ciências Agrárias e Veterinárias (FCAV-Unesp), Universidade Estadual Paulista, Via de Acesso Prof. Paulo Donato Castellane s/nº, Jaboticabal, São Paulo, CEP 14884-900, Brazil.
Instituto Biológico/IB, São Paulo, São Paulo, 04014-002, Brazil.Centro de Citricultura Sylvio Moreira/IAC, Cordeirópolis, São Paulo, 13490-970, Brazil.
Fundo de Defesa da Citricultura/Fundecitrus, Araraquara, São Paulo, 14807-040, Brazil.
Instituto Biológico/IB, São Paulo, São Paulo, 04014-002, Brazil.
Instituto Biológico/IB, São Paulo, São Paulo, 04014-002, Brazil.Embrapa Mandioca e Fruticultura, Cruz das Almas, Bahia, 44380-000, Brazil.
Laboratório de Acarologia (AcaroLab), Faculdade de Ciências Agrárias e Veterinárias (FCAV-Unesp), Universidade Estadual Paulista, Via de Acesso Prof. Paulo Donato Castellane s/nº, Jaboticabal, São Paulo, CEP 14884-900, Brazil. daniel.andrade@unesp.br.
Brevipalpus yothersi Baker (Tenuipalpidae) development in sweet orange plants is influenced by previous mite infestation and the presence of shelters.

Diabetes, a disease marked by consistent high blood glucose levels, is associated with various complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Notably, skeletal fragility has emerged as a significant complication in both type 1 (T1D) and type 2 (T2D) diabetic patients. This review examines noninvasive imaging studies that evaluate skeletal outcomes in adults with T1D and T2D, emphasizing distinct skeletal phenotypes linked with each condition and pinpointing gaps in understanding bone health in diabetes. Although traditional DXA-BMD does not fully capture the increased fracture risk in diabetes, recent techniques such as quantitative computed tomography, peripheral quantitative computed tomography, high-resolution quantitative computed tomography, and MRI provide insights into 3D bone density, microstructure, and strength. Notably, existing studies present heterogeneous results possibly due to variations in design, outcome measures, and potential misclassification between T1D and T2D. Thus, the true nature of diabetic skeletal fragility is yet to be fully understood. As T1D and T2D are diverse conditions with heterogeneous subtypes, future research should delve deeper into skeletal fragility by diabetic phenotypes and focus on longitudinal studies in larger, diverse cohorts to elucidate the complex influence of T1D and T2D on bone health and fracture outcomes.
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, United States.
Department of Medicine, Endocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, United States.Department of Medicine, Endocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
Use of noninvasive imaging to identify causes of skeletal fragility in adults with diabetes: a review.

Using two decades of data from 12 low-income countries in West Africa, we show that dust carried by harmattan trade winds increases infant and child mortality. Health investments respond to dust exposure, consistent with compensating behaviours. Despite these efforts, surviving children still exhibit negative health impacts. Our data allow us to investigate differential impacts over time and across countries. We find declining impacts over time, suggesting adaptation. Using national-level measures of macroeconomic conditions and health resources, we find suggestive evidence that both economic development and public health improvements have contributed to this adaptation, with health improvements playing a larger role.
© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Economic Society.
University of California San Diego, USA.
Dust and Death: Evidence from the West African Harmattan.

Inhibition of the Hsp90 C-terminal domain offers a promising opportunity to treat numerous diseases/indications. Furthermore, the development of Hsp90 C-terminal inhibitors (CTIs) is advantageous over N-terminal inhibitors because it avoids the detriments associated with induction of the heat shock response (HSR). However, the lack of co-crystal structures of small molecules bound to the C-terminus have hindered their development. Therefore, structure-activity relationship (SAR) studies have been pursued to optimize such inhibitors. Noviose sugar surrogates, also known as noviomimetics have been prepared to investigate the size and nature of the C-terminal domain binding pocket. Herein, we report the synthesis and anti-proliferative activity manifested by this new series of Hsp90 C-terminal inhibitors.
This journal is © The Royal Society of Chemistry.
Department of Chemistry and Biochemistry, Warren Center for Drug Discovery, University of Notre Dame Notre Dame Indiana 46556 USA bblagg@nd.edu.
Cancer Center at Illinois, University of Illinois Urbana-Champaign Urbana Illinois 61801 USA.
Development of Hsp90 C-terminal inhibitors with noviomimetics that manifest anti-proliferative activities.

Prior work on Muslims' mental health help-seeking factors has emphasized their rejection attitudes, religious and cultural beliefs, and familiarity with mental health (Aloud & Rathur, 2009; Ali et al., 2021). However, no research has examined differences in these factors across different Muslim ethnic groups, and particularly among Muslim women. 1214 Muslim women living in the USA completed online questionnaires. Data was stratified based on history of mental health visits to control for previous service utilization. MANOVAs assessed ethnic group differences in beliefs, familiarity, and rejection attitudes toward professional mental healthcare. Results revealed significant differences between ethnic groups in all three factors; these differences depended on the women's history of service utilization. Findings suggest that barriers to accessing professional mental healthcare differ among Muslim ethnic groups. Results are discussed in light of clinical implications and other contributing factors to the underutilization of professional mental healthcare among ethnically diverse American Muslim women.
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, USA.
Department of Family Relations and Applied Nutrition, University of Guelph, Canada.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, USA.
Ethnic Differences in Muslim Women's Mental Health Beliefs, Rejection Attitudes, and Familiarity with Professional Mental Healthcare.

Neuropsychological and Cognitive Rehabilitation Service, Rehabilitation Unit & Clinical Psychology Unit, ASST Valle Olona, Varese, Italy. Electronic address: nicoletta.beschin@gmail.com.
Department of Psychology, Bangor University, Bangor, Wales, UK.

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina (UNC) School of Medicine, Chapel Hill, North Carolina, USA.Department of Genetics, Neuroscience Center and.UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, UNC, Chapel Hill, North Carolina, USA.
Department of Molecular Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Biochemistry, Department of Biophysics, Simmons Comprehensive Cancer Center and.
Department of Pathology, Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.Kidney Cancer Program, Simmons Comprehensive Cancer Center, Department of Urology.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis.

Priapism is defined as penile erection lasting more than four hours that is unrelated to sexual arousal. Priapism is classified based on the oxygenation of the penile tissue into ischemic and non-ischemic subtypes. As the most common form, ischemic priapism is usually associated with pain and carries a significant risk of permanent loss of erectile function; thus, rapid intervention is necessary. Initial therapy consists of corporal aspiration and injection of sympathomimetic agents. If detumescence is not achieved, a cavernosal shunt is necessary. Non-ischemic priapism is less common than the ischemic type and is usually the result of perineal trauma. In this subtype, there is usually no pain and treatment is initially conservative. Recurrent (stuttering) priapism is a variant of the ischemic subtype, but is self-limiting and usually occurs during sleep with a duration of less than three to four hours. In the case of prolonged erection, therapy is analogous to that of the ischemic subtype.
© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität, Rudolf-Buchheim-Straße 8, 35392, Gießen, Deutschland. jens.rosellen@uk-gm.de.
Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität, Rudolf-Buchheim-Straße 8, 35392, Gießen, Deutschland.
Der Priapismus ist definiert als eine penile Erektion über mehr als 4 h Dauer unabhängig von einer sexuellen Erregung. Hierbei erfolgt abhängig von der Oxygenierung des penilen Gewebes eine Klassifizierung in einen ischämischen und nicht-ischämischen Subtyp. Der ischämische Priapismus ist als häufigste Form meist mit Schmerzen assoziiert und birgt bei verzögertem Therapiebeginn ein erhebliches Risiko für einen permanenten Verlust der Erektionsfähigkeit. Die initiale Therapie besteht in der korporalen Aspiration und Injektion von Sympathomimetika. Bei Nichterreichen einer Detumeszenz ist ein kavernosaler Shunt notwendig. Ein nicht-ischämischer Priapismus ist seltener als der ischämische Typ und meist Folge eines perinealen Traumas. Bei diesem Subtyp liegen meist keine Schmerzen vor und die Therapie erfolgt zunächst konservativ. Ein rekurrenter („stuttering“) Priapismus ist eine Variante des ischämischen Subtyps, aber selbstlimitierend und meist im Schlaf auftretend mit einer Dauer unter 3 bis 4 h. Bei einer prolongierten Erektion erfolgt hier eine Therapie analog zu der des ischämischen Subtyps.

Department of Emergency and Critical Care Medicine, West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.Health Emergency Management Research Center, China-PUMC C.C. Chen Institute of Health, Sichuan University.
Journal of chemotherapy (Florence, Italy)
Comparison of bamlanivimab with or without etesevimab and casirivimab-imdevimab in clinical outcomes in patients with COVID-19: a systematic review and meta-analysis.

Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT).A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses.Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12).This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Department of Radiation Oncology, CNS/Pediatrics Section, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hypofractionated radiotherapy for glioblastoma: A large institutional retrospective assessment of 2 approaches.

The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI.Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial-spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI- fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls.MTR was decreased across multiple white matter tracts in patients when compared to healthy children, P < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, P < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, Ps < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, Ps < .01, but not healthy control children.Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.
Program in Neurosciences and Mental Health, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Program in Neurosciences and Mental Health, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada.Medical Imaging, University of Toronto, Toronto, Ontario, Canada.
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Multimodal imaging with magnetization transfer and diffusion tensor imaging reveals evidence of myelin damage in children and youth treated for a brain tumor.

In the present study, proper manual for powdered infant formula with probiotics (PIF-P) to prevent the contamination of Cronobacter sakazakii was investigated. First, the population of C. sakazakii and LAB in three different PIF-P samples were quantitatively analyzed after reconstituted with hydrothermal treatments. When C. sakazakii was inoculated into reconstituted infant formula with probiotics (RIF-P), it was immediately reduced below the detection limit by 60-65 °C hydrothermal treatment whereas reduction levels of LAB was 1-2 log CFU/g. When heat resistance of C. sakazakii inoculated to PIF-P with 4 h drying was compared with that inoculated to RIF-P samples, the heat resistance of C. sakazakii increased significantly after the inoculation in PIF-P with drying. Metagenomic analysis revealed that Lactobacillus and Bifidobacterium were dominant genus in all three groups and there was no significant difference in the microbial community of untreated PIF sample and hydrothermal treated samples.The online version contains supplementary material available at 10.1007/s10068-023-01503-x.
© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Department of Food Engineering, Dankook University, Cheonan, Chungnam 31116 Republic of Korea.
Inactivation of Cronobacter sakazakii in powdered infant formula with probiotics and metagenomic analysis.

ARID1B haploinsufficiency in humans causes Coffin-Siris syndrome, associated with developmental delay, facial dysmorphism, and intellectual disability. The role of ARID1B has been widely studied in neuronal development, but whether it also regulates stem cells remains unknown. Here, we employ scRNA-seq and scATAC-seq to dissect the regulatory functions and mechanisms of ARID1B within mesenchymal stem cells (MSCs) using the mouse incisor model. We reveal that loss of Arid1b in the GLI1+ MSC lineage disturbs MSCs' quiescence and leads to their proliferation due to the ectopic activation of non-canonical Activin signaling via p-ERK. Furthermore, loss of Arid1b upregulates Bcl11b, which encodes a BAF complex subunit that modulates non-canonical Activin signaling by directly regulating the expression of activin A subunit, Inhba. Reduction of Bcl11b or non-canonical Activin signaling restores the MSC population in Arid1b mutant mice. Notably, we have identified that ARID1B suppresses Bcl11b expression via specific binding to its third intron, unveiling the direct inter-regulatory interactions among BAF subunits in MSCs. Our results demonstrate the vital role of ARID1B as an epigenetic modifier in maintaining MSC homeostasis and reveal its intricate mechanistic regulatory network in vivo, providing novel insights into the linkage between chromatin remodeling and stem cell fate determination.
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA.
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA. ychai@usc.edu.
ARID1B maintains mesenchymal stem cell quiescence via inhibition of BCL11B-mediated non-canonical Activin signaling.

The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep-GBM)-like tumors. Co-transfection of TRIM24 with HRasV12 also induces Ep-GBM-like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep-GBM specimens. Using single-cell RNA-sequencing (scRNA-Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku-dependent DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA-PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep-GBM-like transformation. Targeting DNA-PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep-GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep-GBM-like transformation and suggest a potential therapeutic strategy for patients with Ep-GBM.
© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.
State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Pediatric Translational Medicine Institute, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, 200127, China.
CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Department of Neurology, Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
TRIM24 Cooperates with Ras Mutation to Drive Glioma Progression through snoRNA Recruitment of PHAX and DNA-PKcs.

Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro, and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization.
Copyright © 2024. Published by Elsevier B.V.
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St., CSA 148, Los Angeles, CA 90033, USA.
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St., CSA 148, Los Angeles, CA 90033, USA. Electronic address: joldak@usc.edu.
Matrix biology : journal of the International Society for Matrix Biology
Ameloblastin and its multifunctionality in amelogenesis: A review.

For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited.To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant.Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled.Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed.The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported.Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group.Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer.ClinicalTrials.gov Identifier: NCT05184712.
Sun Yat-sen University Cancer Center, Guangzhou, China.
Fujian Provincial Tumor Hospital, Fuzhou, China.
The Second Hospital of Anhui Medical University, Hefei, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
Renmin Hospital of Wuhan University, Wuhan, China.
Mianyang Central Hospital, Mianyang, China.
Shandong Cancer Prevention and Treatment Institute, Jinan, China.
The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
The First Affiliated Hospital of Nanchang University, Nanchang, China.
The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Weifang No. 2 People's Hospital, Weifang, China.
Zhejiang Cancer Hospital, Hangzhou, China.
Harbin Medical University Cancer Hospital, Harbin, China.
Beijing Chest Hospital, Capital Medical University, Beijing, China.
Yuncheng Central Hospital of Shanxi Province, Yuncheng, China.
Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, China.
Xiangyang Central Hospital, Xiangyang, China.
Taizhou Municipal Hospital, Taizhou, China.
Sichuan Provincial People's Hospital, Chengdu, China.
Army Medical Center of Chinese People's Liberation Army, Chongqing, China.
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
West China Hospital of Sichuan University, Chengdu, China.
The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.
Yibin Second People's Hospital, Yibin, China.
Tongji Hospital of Tongji Medical College of Hust, Wuhan, China.
Jiangsu Cancer Hospital, Nanjing, China.
Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Affiliated Cancer Hospital and Institution of Guangzhou Medical University, Guangzhou, China.
The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
The Second Xiangya Hospital of Central South University, Changsha, China.
Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China.
Affiliated Hospital of Guangdong Medical University, Guangzhou, China.
Tangdu Hospital of the Fourth Military Medical University, Xi'an, China.
Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, China.
Anhui Provincial Cancer Hospital, Hefei, China.
Gansu Provincial Cancer Hospital, Lanzhou, China.
Jilin Cancer Hospital, Changchun, China.
Xingtai People's Hospital, Xingtai, China.
Huaihe Hospital of Henan University, Kaifeng, China.
Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University), Shenzhen, China.
The First People's Hospital of Foshan, Foshan, China.
The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
The First Affiliated Hospital of Soochow University, Suzhou, China.
General Hospital of Ningxia Medical University, Yinchuan, China.
Zhongshan City People's Hospital, Zhongshan, China.
Nanfang Hospital Nanfang Medical University, Guangzhou, China.
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats.T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies.Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk.BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.
Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, China.Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.Department of Endocrinology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China.
National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, China.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission, Shandong University, Jinan, China.Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Department of Biology, University College London, London, UK.
Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, China.Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.National Key Laboratory for Innovation and Transformation of Luobing Theory, Shandong University, Jinan, China.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission, Shandong University, Jinan, China.Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Department of Endocrinology & Geriatrics, Shandong Provincial Hospital, Shandong University, Jinan, China.Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes.

Clarifying the formation mechanism of single-atom sites guides the design of emerging single-atom catalysts (SACs) and facilitates the identification of the active sites at atomic scale. Herein, a molten-salt atomization strategy is developed for synthesizing zinc (Zn) SACs with temperature universality from 400 to 1000/1100 °C and an evolved coordination from Zn-N2Cl2 to Zn-N4. The electrochemical tests and in situ attenuated total reflectance-surface-enhanced infrared absorption spectroscopy confirm that the Zn-N4 atomic sites are active for electrochemical carbon dioxide (CO2) conversion to carbon monoxide (CO). In a strongly acidic medium (0.2 m K2SO4, pH = 1), the Zn SAC formed at 1000 °C (Zn1NC) containing Zn-N4 sites enables highly selective CO2 electroreduction to CO, with nearly 100% selectivity toward CO product in a wide current density range of 100-600 mA cm-2. During a 50 h continuous electrolysis at the industrial current density of 200 mA cm-2, Zn1NC achieves Faradaic efficiencies greater than 95% for CO product. The work presents a temperature-universal formation of single-atom sites, which provides a novel platform for unraveling the active sites in Zn SACs for CO2 electroreduction and extends the synthesis of SACs with controllable coordination sites.
School of Materials Science & Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.School of Engineering, Westlake University, Hangzhou, Zhejiang, 310030, China.
Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo, Zhejiang, 315200, China.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Key Laboratory of Precision and Intelligent Chemistry, National Synchrotron Radiation Laboratory, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), University of Science and Technology of China, Hefei, Anhui, 230026, China.
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.
School of Engineering, Westlake University, Hangzhou, Zhejiang, 310030, China.
Key Laboratory of Automobile Materials Ministry of Education and College of Materials Science and Engineering, Jilin University, Changchun, Jilin, 130022, China.
Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo, Zhejiang, 315200, China.
Department of Environmental Science and Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA, 91125, USA.
Merging Contaminants Research Center, Beijing Normal University, Zhuhai, Guangdong, 519087, China.
Advanced materials (Deerfield Beach, Fla.)
Universal Formation of Single Atoms from Molten Salt for Facilitating Selective CO2 Reduction.

Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable.To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC.This prospective nonrandomized controlled trial was conducted at a single center from June 3, 2020, to July 19, 2022, and included 60 patients with advanced NSCLC with driver variations without radiologically detectable disease after TKI and LCT. The median (range) follow-up time was 19.2 (3.8-29.7) months. Data analysis was conducted from December 15, 2022, to May 10, 2023.Cessation of TKI treatment and follow-up every 3 months. Treatment was restarted in patients with progressive disease (defined by the Response Evaluation Criteria in Solid Tumors 1.1 criteria), detectable ctDNA, or elevated carcinoembryonic antigen (CEA) levels, whichever manifested first, and treatment ceased if all indicators were negative during follow-up surveillance.Progression-free survival (PFS). Secondary end points were objective response rate, time to next treatment, and overall survival.Among the total study sample of 60 participants (median [range] age, 55 [21-75] years; 33 [55%] were female), the median PFS was 18.4 (95% CI, 12.6-24.2) months and the median (range) total treatment break duration was 9.1 (1.5-28.1) months. Fourteen patients (group A) remained in TKI cessation with a median (range) treatment break duration of 20.3 (6.8-28.1) months; 31 patients (group B) received retreatment owing to detectable ctDNA and/or CEA and had a median PFS of 20.2 (95% CI, 12.9-27.4) months with a median (range) total treatment break duration of 8.8 (1.5-20.6) months; and 15 patients (group C) who underwent retreatment with TKIs due to progressive disease had a median PFS of 5.5 (95% CI, 1.5-7.2) months. For all participants, the TKI retreatment response rate was 96%, the median time to next treatment was 29.3 (95% CI, 25.3-35.2) months, and the data for overall survival were immature.The findings of this nonrandomized controlled trial suggest that this adaptive de-escalation TKI strategy for patients with NSCLC is feasible in those with no lesions after LCT and a negative ctDNA test result. This might provide a de-escalation treatment strategy guided by ctDNA for the subset of patients with advanced NSCLC.ClinicalTrials.gov Identifier: NCT03046316.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Geneplus-Beijing Institute, Beijing, China.
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.Chinese Thoracic Oncology Group, Guangzhou, Guangdong, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.Chinese Thoracic Oncology Group, Guangzhou, Guangdong, China.
Circulating Tumor DNA-Guided De-Escalation Targeted Therapy for Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial.

Key Laboratory of Biology and Germplasm Innovation of Perennial Rice from Ministry of Agriculture and Rural Affairs, School of Agriculture, Yunnan University, Kunming 650091, China.
Cereal Crops Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China.
Wenshan Academy of Agricultural Sciences, Wenshan 663000, China.
State Key Laboratory of Crop Gene Resources and Breeding, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100081, China. Electronic address: zhangfan03@caas.cn.
Key Laboratory of Biology and Germplasm Innovation of Perennial Rice from Ministry of Agriculture and Rural Affairs, School of Agriculture, Yunnan University, Kunming 650091, China. Electronic address: hfengyi@ynu.edu.cn.
Key Laboratory of Biology and Germplasm Innovation of Perennial Rice from Ministry of Agriculture and Rural Affairs, School of Agriculture, Yunnan University, Kunming 650091, China. Electronic address: lyhuang@ynu.edu.cn.
Alternative splicing drives the functional diversification of a bHLH transcription factor in the control of growth and drought tolerance in rice.

The present study evaluated the performance of multiwalled carbon nanotube (MWCNT)@MgAl-layered double hydroxide (LDH) nanoparticles loaded on poly-2 aminothiazole (PAT)/chitosan (CS) matrix (CPML) to remove Cd2+ ions from aqueous solution. The removal efficiency of modified CS/PAT with MWCNT@MgAl-LDHs was increased significantly compared to pure CS/PAT. The influence of heavy metal ion concentration, pH, temperature, adsorbent dosage, and contact time on the adsorption was examined. The optimum conditions for the adsorption of Cd2+ ions were 25 0C with the adsorbent dosage of 0.06 g and initial concentration for adsorption of the Cd2+ 100 mg/L at pH = 8. The maximum adsorption capacity was measured to be 1106.19 mg/g. The values of thermodynamic parameters namely Gibbs free energy (ΔG°), entropy change (ΔS°), and enthalpy change (ΔH°) indicated the feasibility, spontaneity and the endothermic nature of the adsorption process, respectively. The pseudo-second-order kinetics and the Langmuir model were selected as the best models for the adsorption process. Also, CPML nanocomposite (NC) was successfully tested for p-nitrophenol (p-NP) reduction in the presence of NaBH4. The reaction was nearly completed in 6 min. The fabricated CPML-NC could be reused for three consecutive cycles.
© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Department of Organic Chemistry, Razi University, Kermanshah, 67149-67346 Iran.
Department of Organic Chemistry, Razi University, Kermanshah, 67149-67346 Iran.Nanoscience and Nanotechnology Research Center, Razi University, Kermanshah, 67149-67346 Iran.
Journal of environmental health science & engineering
Preparation and characterization of CS/PAT/ MWCNT@MgAl-LDHs nanocomposite for Cd2+ removal and 4-nitrophenol reduction.

Carbohydrate recognition is imperative for the induction of sperm acrosomal exocytosis (AE), an essential phenomenon in mammalian fertilization. In mouse sperm, polynorbornene 100-mers displaying fucose or mannose moieties were effective at inducing AE. In contrast, glycopolymers exhibiting glucose sugars resulted in no AE activation. To further elucidate the role of ligand density on the activation of AE in mouse sperm, a triple-stain flow cytometry assay was employed to determine the efficacy of polynorbornene block copolymers with barbell-like sequences as initiators of AE. Triblock (ABA or ABC) copolymers were synthesized by ring-opening metathesis polymerization (ROMP) with one or two activating sugars, mannose or fucose, and one nonactivating sugar, glucose. The active ligand fractions in the polymers varied from 10, 20, or 40%. Simultaneously, random copolymers comprising 20% activating ligands were prepared to confirm the importance of ligand positionality in AE activation in mouse sperm. Polynorbornene 100-mers possessing two 10-mer blocks of activating sugars were the most effective copolymers at inducing AE with levels of AE comparable to their homopolymer counterparts and more effective than their random analogues. Small-angle X-ray scattering (SAXS) was then performed to verify that there were no differences in the conformations of the glycopolymers contributing to their varying AE activity. SAXS data analysis confirmed that all of the glycopolymers assumed semiflexible cylindrical structures with similar radii and Kuhn lengths. These findings suggest that the overall ligand density of the sugar moieties in the polymer is less important than the positionality of short blocks of high-density ligands for AE activation in mouse sperm.
© 2024 The Authors. Published by American Chemical Society.
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States.
Triblock Glycopolymers with Two 10-mer Blocks of Activating Sugars Enhance the Activation of Acrosomal Exocytosis in Mouse Sperm.

College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Department of Anatomy, Histology and Embryology, Health Science Center, Peking University, Beijing 100191, China.
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address: wangjf@cau.edu.cn.
College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China. Electronic address: chenfangch@sina.com.
Acrylamide drives amidase-mediated gut dysbiosis to aggravate colitis.

Health Economist and Research Director, Studio di Economia Sanitaria, Via Stefanardo da Vimercate, 19, Milan, 20128, Italy. carlo.lazzaro@tiscalinet.it.Biology and Biotechnologies Department Lazzaro Spallanzani , University of Pavia, Pavia, 27100, Italy. carlo.lazzaro@tiscalinet.it.
Letter to the Editor: Lazzaro responds to Kennedy et al.

Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1+ progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-CreER;Fgfr1fl/fl mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA, 90033, USA.State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA, 90033, USA.
Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA, 90033, USA. ychai@usc.edu.
FGF signaling modulates mechanotransduction/WNT signaling in progenitors during tooth root development.

To document the 10-year results of transoral mandibular preservation surgery for patients with T1-2 squamous cell carcinoma (SCC) arising from the lateral oropharynx.This was a retrospective 30-year review using STROBE guidelines at an academic, tertiary referral center. A total of 294 patients with T1-2 SCC of the lateral oropharynx were reviewed. Only 19% of patients were never-smokers, suggesting a predominantly HPV-negative population. All patients had transoral mandibular preservation surgery. Follow-up therapy included neck dissection (76.5%), induction chemotherapy (57.8%), and postoperative radiation therapy (31.6%) Local control, survival, and functional endpoints, as well as the consequences of local recurrence, were analyzed.The 10-year local disease control was 88.3%. Local recurrence was salvaged in 50% of cases, resulting in an overall 94.5% local control rate. The overall 10-year survival was 50%. Mortality was related to metachronous second primary cancer (MSPC) (29.2%), medical comorbidities (25.7%), uncontrolled local recurrence (10%), and complications following transoral resection (4.2%). In multivariate analysis, the development of an MSPC significantly increased (p < 0.005) the risk of death. Overall, 95.2% of patients achieved mandibular preservation. However, gastrostomy and tracheostomy dependence occurred in 1% and 0.3% of cases, respectively.For a patient population with a significant percentage of tobacco-associated oropharyngeal cancer (OPC), transoral surgery was associated with long-term minimal postoperative complications and a high rate of local control. MSPC was the main cause of death during the first 10 postoperative years. Such long-term figures support transoral surgery as an effective first-line treatment for early-stage predominantly tobacco-related OPC.4 Laryngoscope, 134:4564-4572, 2024.
© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.
Université Paris Cité, Service d'Otorhinolaryngologie et de Chirurgie Cervico-Faciale, HEGP, AP-HP, Paris, France.
Division of Head & Neck Surgery, Department of Otolaryngology, Stanford University, Palo Alto, California, U.S.A.
Ten-Year Efficacy of Transoral Surgery for Squamous Carcinoma of the Lateral Oropharynx.

Antibody is specific reagent that be utilized in various field of biomedical research. Monoclonal antibodies are mostly produced using two common techniques namely hybridoma and antibody engineering, which suffer from some limitations such as boring screening procedures, long production time, low efficacy and a degree of automation. To address these limitations, various microfluidics techniques have been developed for the antibody isolation and screening.This study specifically investigates nearly recent reports published in peer-reviewed journals indexed in various databases including Web of Science, Scopus, PubMed, Google Scholar, and Science Direct.In this study, we identified a total of seventy papers from a pool of 130 articles. These papers focus on the application of three major groups of microfluidic platforms, namely valves, microwells, and droplets, in the development of antibodies using hybridoma method and phage display technology. We provide a summary of these applications and also discuss the key findings in this field. Additionally, we illustrate our discussion with several examples to enhance understanding.Microfluidics has the potential to serve as a valuable tool in streamlining complex laboratory procedures involved in antibody discovery. However, it is important to note that microfluidics is limited to laboratory settings. Further enhancements are needed to address existing challenges and to make microfluidics a reliable, accurate, and cost-effective tool for antibody discovery.
Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, P.O. Box 14395/1179, Tehran, IR Iran.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Faculty of Chemistry, Razi University, Kermanshah, 6714414971 Iran.Nanobiotechnology Department, Faculty of Innovative Science and Technology, Razi University, Kermanshah, 6714414971 Iran.
Journal of diabetes and metabolic disorders
A mini review on recent progress of microfluidic systems for antibody development.

Speed of processing (SOP) cognitive training may improve indicators of the quality of life (QoL) in people living with HIV. In this 2-year, longitudinal, randomized, controlled trial, 216 participants ages 40 years and older with HIV-associated neurocognitive disorder or borderline HIV-associated neurocognitive disorder were assigned to one of three groups: (a) 10 hr of SOP training (n = 70); (b) 20 hr of SOP training (n = 73), or (c) 10 hr of internet navigation control training (a contact control group; n = 73). Participants completed several QoL measures at baseline, posttest, and Year 1 and Year 2 follow-ups. Using linear mixed-effect models, no strong pattern of training effects across QoL outcomes was apparent, with small-magnitude, nonsignificant, between-group differences in depression, locus of control, and Medical Outcomes Study-HIV scales. In conclusion, despite prior work showing some transfer of SOP cognitive training improving QoL, that was not observed. Implications for research and practice are posited.
Copyright © 2024 Association of Nurses in AIDS Care.
David E. Vance is a Professor, School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA.Pariya L. Fazeli is an Associate Professor, School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA.Andres Azuero is a Professor, School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA.Jennifer S. Frank is an Instructor, School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama, USA.Virginia G. Wadley is an Associate Professor (retired), School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.James L. Raper is a Professor and Director of the 1917 (HIV/AIDS) Clinic (retired), School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.Caitlin N. Pope is an Assistant Professor, Department of Health, Behavior & Society, University of Kentucky, Lexington, Kentucky, USA.Alexandra Jacob is a Medical Clinical Psychology Doctoral Student, Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA.Karlene K. Ball is a Professor, Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
The Journal of the Association of Nurses in AIDS Care : JANAC
J Assoc Nurses AIDS Care. ;35(2):104-121.
A 2-Year, Randomized, Clinical Trial Examining the Effects of Speed of Processing Cognitive Training on Quality-of-Life Indicators in Adults With HIV-Associated Neurocognitive Disorder in Birmingham, Alabama: Results of the Think Fast Study.

Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, United States.Harvard Medical School, Boston, MA, United States.
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.Malaya Translational and Clinical Pharmacometrics Group, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia.Department of Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia.Certara Drug Development Solutions, Certara, Radnor, PA, United States.
Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
Editorial: Commercialization and industrialization of pharmacology of infectious diseases: 2022.

Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: renfazheng@cau.edu.cn.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: an-peng@cau.edu.cn.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: luo.yongting@cau.edu.cn.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: luojj@cau.edu.cn.
Temporal-specific single-cell atlas of human type A aortic dissection reveals immune cell dynamics and therapeutic targets.

Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Chongqing Key Laboratory on Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.
Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: ghshui@genetics.ac.cn.
Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address: huchrong@tmmu.edu.cn.
CSF multi-omics of intracerebral hemorrhage from onset to reperfusion underscores lipid metabolism in functional outcome.

Vivian L. Smith Department of Neurosurgery, McGovern Medical School, the University of Texas Health Science Center at Houston, Houston , Texas , USA.
Vivian L. Smith Department of Neurosurgery, McGovern Medical School, the University of Texas Health Science Center at Houston, Houston , Texas , USA.Memorial Hermann Hospital-TMC, Houston , Texas , USA.
Commentary: Clinical Predictors of Overall Survival in Very Elderly Patients With Glioblastoma: A National Cancer Database Multivariable Analysis.

Virus-encoded microRNAs (miRNAs) exert diverse regulatory roles in the biological processes of both viruses and hosts. This study delves into the functions of AcMNPV-miR-2, an early miRNA encoded by Autographa californica multiple nucleopolyhedrovirus (AcMNPV). AcMNPV-miR-2 targets viral early genes ac28 (lef-6), ac37 (lef-11), ac49, and ac63. Overexpression of AcMNPV-miR-2 leads to reduced production of infectious budded virions (BVs) and diminished viral DNA replication. Delayed polyhedron formation was observed through light and transmission electron microscopy, and the larval lifespan extended in oral infection assays. Moreover, the mRNA expression levels of two Lepidoptera-specific immune-related proteins, Gloverin and Spod-11-tox, significantly decreased. These findings indicate that AcMNPV-miR-2 restrains viral load, reducing host immune sensitivity. This beneficial effect enables the virus to combat host defense mechanisms and reside within the host for an extended duration.Virus-encoded miRNAs have been extensively studied for their pivotal roles in finetuning viral infections. Baculoviruses, highly pathogenic in insects, remain underexplored concerning their encoded miRNAs. Previous reports outlined three AcMNPV-encoded miRNAs, AcMNPV-miR-1, -miR-3, and -miR-4. This study delves into the functions of another AcMNPV-encoded miRNA, AcMNPV-miR-2 (Ac-miR-2). Through a comprehensive analysis of target gene expression, the impact on larvae, and variations in host immune-related gene expression, we elucidate a functional pathway for Ac-miR-2. This miRNA suppresses viral load and infectivity and prolongs lifespans of infected larva by downregulating specific viral early genes and host immune-related genes. These mechanisms ultimately serve the virus's primary goal of enhanced propagation. Our study significantly contributes to understanding of the intricate regulatory mechanisms of virus-encoded miRNAs in baculovirus infections.
School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
AcMNPV-miR-2 affects Autographa californica nucleopolyhedrovirus infection by regulating the expression of ac28 and several other viral early genes.

Soft and biological matter come in a variety of shapes and geometries. When soft surfaces that do not fit into each other due to a mismatch in Gaussian curvatures form an interface, beautiful geometry-induced patterns are known to emerge. In this paper, we study the effect of geometry on the dynamical response of soft surfaces moving relative to each other. Using a simple experimental scheme, we measure friction between a highly bendable thin polymer sheet and a hydrogel substrate. At this soft and low-friction interface, we find a strong dependence of friction on the relative geometry of the two surfaces-a flat sheet experiences significantly larger friction on a spherical substrate than on flat or cylindrical substrate. We show that the stress developed in the sheet due to its geometrically incompatible confinement is responsible for the enhanced friction. This mechanism also leads to a transition in the nature of friction as the sheet radius is increased beyond a critical value. Our finding reveals a hitherto unnoticed mechanism based on an interplay between geometry and elasticity that may influence friction significantly in soft, biological, and nanoscale systems. In particular, it provokes us to reexamine our understanding of phenomena such as the curvature dependence of biological cell mobility.
Department of Physics, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
Geometry-induced friction at a soft interface.

Cognition and Brain Science, School of Psychology, Georgia Institute of Technology, Atlanta, GA 30332.Center of Excellence in Computational Cognition, Georgia Institute of Technology, Atlanta, GA 30332.
School of Mathematics, Georgia Institute of Technology, Atlanta, GA 30332.
Linking faces to social cognition: The temporal pole as a potential social switch.

People living with HIV (PLWH) experience high rates of childhood trauma exposure, which is a significant risk factor for the development of posttraumatic stress disorder (PTSD). Because Black Americans living in urban environments are exposed to high levels of trauma, suffer from chronic PTSD, and are at increased risk for HIV infection, it is important to understand how HIV status interacts with childhood maltreatment to influence PTSD symptom severity and underlying psychophysiology.The current cross-sectional study assessed whether HIV status interacts with childhood maltreatment to influence PTSD symptom severity and heart rate variability during a dark-enhanced startle (DES) task in 88 Black women with (n=30) and without HIV (n=58).HIV was associated with greater PTSD symptom severity only in women with low levels of childhood maltreatment (p=.024). Startle potentiation during DES was highest in women living without HIV and with high childhood maltreatment (p=.018). In women who had experienced low levels of childhood maltreatment, respiratory sinus arrhythmia (RSA) was lower during the dark phase of DES in women living without HIV than women living with HIV (WLWH), (p=.046). RSA during the light phase of DES was lower in WLWH than in women living without HIV (p=.042).In the current sample of Black women, HIV status was associated with PTSD symptom severity in a manner dependent on level of childhood maltreatment, suggesting that HIV status may be an important factor to consider for behavioral and pharmacological treatment strategies for PTSD. Additionally, HIV status is associated with lower percent potentiation to darkness and lower RSA during the light phase of DES, suggesting physiological mechanisms by which HIV may contribute to PTSD symptoms in individuals exposed to low levels of childhood maltreatment.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.Emory National Primate Research Center, Atlanta, Georgia.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA.
Emory National Primate Research Center, Atlanta, Georgia.
University of Louisville, Department of Psychological and Brain Sciences, Louisville, Kentucky.
Department of Psychology, Georgia State University, Atlanta, Georgia.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA.Grady Health System, Atlanta, GA.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.
HIV status affects PTSD symptom severity, psychophysiology, and heart rate variability in women with low but not high exposure to childhood maltreatment.

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.New Cornerstone Science Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.Department of Ophthalmology and Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Engineering Research Center of Medical Information Technology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.Division of Nephrology and Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.Frontier Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan 610212, China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.New Cornerstone Science Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.Frontier Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan 610212, China.
Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.

Recent progress in out-of-equilibrium closed quantum systems has significantly advanced the understanding of mechanisms behind their evolution toward thermalization. Notably, the concept of nonthermal fixed points (NTFPs)-responsible for the emergence of spatiotemporal universal scaling in far-from-equilibrium systems-has played a crucial role in both theoretical and experimental investigations. In this work, we introduce a differential equation that has the universal scaling associated with NTFPs as a solution. The advantage of working with a differential equation, rather than only with its solution, is that we can extract several insightful properties not necessarily present in the solution alone. How the differential equation is derived allows physical interpretation of the universal exponents in terms of the time dependence of the amplitude of the distributions and their momentum scaling. Employing two limiting cases of the equation, we determined the universal exponents related to the scaling using the distributions near just two momentum values. We established a solid agreement with previous investigations by validating this approach with three distinct physical systems. This consistency highlights the universal nature of scaling due to NTFPs and emphasizes the predictive capabilities of the proposed differential equation. Moreover, under specific conditions, the equation predicts a power-law related to the ratio of the two universal exponents, leading to implications concerning particle and energy transport. This suggests that the observed power-laws in far-from-equilibrium turbulent fluids could be related to the universal scaling due to NTFPs, potentially offering insights into the study of turbulence.
Física e Ciência dos Materiais, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13560-970, Brazil.
Física e Ciência dos Materiais, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13560-970, Brazil.Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843.Department of Physics & Astronomy, Texas A&M University, College Station, TX 77843.
Universal scaling in far-from-equilibrium quantum systems: An equivalent differential approach.

Regulated cell cycle progression ensures homeostasis and prevents cancer. In proliferating cells, premature S phase entry is avoided by the E3 ubiquitin ligase anaphasepromoting complex/cyclosome (APC/C), although the APC/C substrates whose degradation restrains G1-S progression are not fully known. The APC/C is also active in arrested cells that exited the cell cycle, but it is not clear whether APC/C maintains all types of arrest. Here, by expressing the APC/C inhibitor, EMI1, we show that APC/C activity is essential to prevent S phase entry in cells arrested by pharmacological cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition (Palbociclib). Thus, active protein degradation is required for arrest alongside repressed cell cycle gene expression. The mechanism of rapid and robust arrest bypass from inhibiting APC/C involves CDKs acting in an atypical order to inactivate retinoblastoma-mediated E2F repression. Inactivating APC/C first causes mitotic cyclin B accumulation which then promotes cyclin A expression. We propose that cyclin A is the key substrate for maintaining arrest because APC/C-resistant cyclin A, but not cyclin B, is sufficient to induce S phase entry. Cells bypassing arrest from CDK4/6 inhibition initiate DNA replication with severely reduced origin licensing. The simultaneous accumulation of S phase licensing inhibitors, such as cyclin A and geminin, with G1 licensing activators disrupts the normal order of G1-S progression. As a result, DNA synthesis and cell proliferation are profoundly impaired. Our findings predict that cancers with elevated EMI1 expression will tend to escape CDK4/6 inhibition into a premature, underlicensed S phase and suffer enhanced genome instability.
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Immuno-Oncology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Computational Medicine Program, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
University of North Carolina Proteomics Core Facility, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
University of North Carolina Proteomics Core Facility, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.

Rechargeable zinc-air batteries (ZABs) are regarded as a remarkably promising alternative to current lithium-ion batteries, addressing the requirements for large-scale high-energy storage. Nevertheless, the sluggish kinetics involving oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) hamper the widespread application of ZABs, necessitating the development of high-efficiency and durable bifunctional electrocatalysts. Here, we report oxygen atom-bridged Fe, Co dual-metal dimers (FeOCo-SAD), in which the active site Fe-O-Co-N6 moiety boosts exceptional reversible activity toward ORR and OER in alkaline electrolytes. Specifically, FeOCo-SAD achieves a half-wave potential (E1/2) of 0.87 V for ORR and an overpotential of 310 mV at a current density of 10 mA cm-2 for OER, with a potential gap (ΔE) of only 0.67 V. Meanwhile, FeOCo-SAD manifests high performance with a peak power density of 241.24 mW cm-2 in realistic rechargeable ZABs. Theoretical calculations demonstrate that the introduction of an oxygen bridge in the Fe, Co dimer induced charge spatial redistribution around Fe and Co atoms. This enhances the activation of oxygen and optimizes the adsorption/desorption dynamics of reaction intermediates. Consequently, energy barriers are effectively reduced, leading to a strong promotion of intrinsic activity toward ORR and OER. This work suggests that oxygen-bridging dual-metal dimers offer promising prospects for significantly enhancing the performance of reversible oxygen electrocatalysis and for creating innovative catalysts that exhibit synergistic effects and electronic states.
Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education), Carbon Neutrality Interdisciplinary Science Centre/College of Environmental Science and Engineering, Nankai University, Tianjin 300350, People's Republic of China.
State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan 430200, People's Republic of China.
State of Key Laboratory of Natural Medicines School of Engineering, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
College of Environment, Hohai University, Nanjing 210098, People's Republic of China.
Oxygen-bridging Fe, Co dual-metal dimers boost reversible oxygen electrocatalysis for rechargeable Zn-air batteries.

Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.IMPORTANCEPhloroglucinol is an important intermediate in the bacterial degradation of polyphenols, a highly abundant class of plant natural products. Recent research has identified key enzymes of the phloroglucinol degradation pathway in butyrate-producing anaerobic bacteria, which involves cleavage of a linear triketide intermediate by a beta ketoacid cleavage enzyme, requiring acetyl-CoA as a co-substrate. This paper reports a variant of the pathway in the lactic acid bacterium Collinsella sp. zg1085, which involves cleavage of the triketide intermediate by a homolog of deoxyribose-5-phosphate aldolase, highlighting the variety of mechanisms for phloroglucinol degradation by different anaerobic bacterial taxa.
Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China.Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, China.Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China.
Department of Pharmacy, Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, Yangzhou, Jiangsu, China.
Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
An aldolase-dependent phloroglucinol degradation pathway in Collinsella sp. zg1085.

Gliding motility proceeds with little changes in cell shape and often results from actively driven surface flows of adhesins binding to the extracellular environment. It allows for fast movement over surfaces or through tissue, especially for the eukaryotic parasites from the phylum apicomplexa, which includes the causative agents of the widespread diseases malaria and toxoplasmosis. We have developed a fully three-dimensional active particle theory which connects the self-organized, actively driven surface flow over a fixed cell shape to the resulting global motility patterns. Our analytical solutions and numerical simulations show that straight motion without rotation is unstable for simple shapes and that straight cell shapes tend to lead to pure rotations. This suggests that the curved shapes of Plasmodium sporozoites and Toxoplasma tachyzoites are evolutionary adaptations to avoid rotations without translation. Gliding motility is also used by certain myxo- or flavobacteria, which predominantly move on flat external surfaces and with higher control of cell surface flow through internal tracks. We extend our theory for these cases. We again find a competition between rotation and translation and predict the effect of internal track geometry on overall forward speed. While specific mechanisms might vary across species, in general, our geometrical theory predicts and explains the rotational, circular, and helical trajectories which are commonly observed for microgliders. Our theory could also be used to design synthetic microgliders.
Institute for Theoretical Physics, Heidelberg University, Heidelberg 69120, Germany.Bioquant-Center, Heidelberg University, Heidelberg 69120, Germany.
A geometrical theory of gliding motility based on cell shape and surface flow.

The variation in the soil microbial community along the altitude gradient has been widely documented. However, the structure and function of the microbial communities distributed along the altitude gradient in the crater still need to be determined. We gathered soil specimens from different elevations within the Nushan volcano crater to bridge this knowledge gap. We investigated the microbial communities of bacteria and fungi in the soil. It is noteworthy that the microbial alpha diversity peaks in the middle of the crater. However, network analysis shows that bacterial (nodes 760 vs 613 vs 601) and fungal (nodes 328 vs 224 vs 400) communities are most stable at the bottom and top of the crater, respectively. Furthermore, the soil microbial network exhibited a decline, followed by an increase across varying altitudes. The core microorganisms displayed the highest correlation with pH and alkaline phosphatase (AP, as determined through redundancy analysis (RDA) and Mantel tests for correlation analysis. The fungal community has a higher number of core microorganisms, while the bacterial core microorganisms demonstrate greater susceptibility to environmental factors. In conclusion, we utilized Illumina sequencing techniques to assess the disparities in the structure and function of bacteria and fungi in the soil.IMPORTANCEThese findings serve as a foundation for future investigations on microbial communities present in volcanic soil.
School of Life Sciences, Anhui Agricultural University, Hefei, China.National Engineering Laboratory of Crop Stress Resistance Breeding, Anhui Agricultural University, Hefei, China.Key Laboratory of Crop Stress Resistance and High-Quality Biology of Anhui Province, Anhui Agricultural University, Hefei, China.
Difference in microbial community structure along a gradient of crater altitude: insights from the Nushan volcano.

We provide the mathematical and empirical foundations of the friendship paradox in networks, often stated as Your friends have more friends than you. We prove a set of network properties on friends of friends and characterize the concepts of ego-based and alter-based means. We propose a network property called inversity that quantifies the imbalance in degrees across edges and prove that the sign of inversity determines the ordering between ego-based or alter-based means for any network, with implications for interventions. Network intervention problems like immunization benefit from using highly connected nodes. We characterize two intervention strategies based on the friendship paradox to obtain such nodes, with the alter-based and ego-based strategy. Both strategies provide provably guaranteed improvements for any network structure with variation in node degrees. We demonstrate that the proposed strategies obtain several-fold improvement (100-fold in some networks) in node degree relative to a random benchmark, for both generated and real networks. We evaluate how inversity informs which strategy works better based on network topology and show how network aggregation can alter inversity. We illustrate how the strategies can be used to control contagion of an epidemic spreading across a set of village networks, finding that these strategies require far fewer nodes to be immunized (less than 50%, relative to random). The interventions do not require knowledge of network structure, are privacy-sensitive, are flexible for time-sensitive action, and only require selected nodes to nominate network neighbors.
Yale School of Management, Yale University, New Haven, CT 06511.
John Heinz III College of Public Policy and Management, Carnegie Mellon University, Pittsburgh, PA 15213.
Department of Sociology, College of Liberal Arts, Purdue University, West Lafayette, IN 47907.
On the friendship paradox and inversity: A network property with applications to privacy-sensitive network interventions.

An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells. Furthermore, patients exhibited high serum levels of inflammatory cytokines, mimicking the profile observed in individuals with gain-of-function mutations in STAT factors. Flow cytometry analysis of patients' blood cells revealed typical alterations associated with autoimmunity and all patients presented with autoantibodies. These findings further supported the notion that a loss of function in negative regulators of cytokine pathways can lead to a broad spectrum of autoimmune manifestations and that PTPN2 along with SOCS1 haploinsufficiency constitute a new group of monogenic autoimmune diseases that can benefit from targeted therapy.
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, Université Paris Cité, INSERM UMR 1163 , Paris, France, IHU-Imagine, Université de Paris, Paris, France.
Centre International de Recherche en Infectiologie, Inserm, U1111, CNRS, UMR5308, École Normale Supérieure de Lyon , Lyon, France.
Centre International de Recherche en Infectiologie, Inserm, U1111, CNRS, UMR5308, École Normale Supérieure de Lyon , Lyon, France.Department of Medical Genetics, Hospices Civils de Lyon, Bron, France.
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative , Paris, France.
Université Paris Cité, CNRS, Epigenetics and Cell Fate , Paris, France.
National Referee Centre for Pediatric-Onset Rheumatism and Autoimmune Diseases, Hospices Civils de Lyon, Pediatric Nephrology, Rheumatology, Dermatology Unit, Mother and Children University Hospital ; Lyon, France.
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, Université Paris Cité, INSERM UMR 1163 , Paris, France, IHU-Imagine, Université de Paris, Paris, France.Service de Médecine Interne, Centre National de Référence des Cytopénies Auto-immunes de L'adulte, Hôpital Henri Mondor, Fédération Hospitalo-Universitaire TRUE InnovaTive TheRapy for ImmUne disordErs, Assistance Publique Hôpitaux de Paris, Université Paris Est Créteil , Créteil, France.
Department of Adult Hematology, Necker-Enfants Malades University Hospital and Centre de Référence des déficits Immunitaires Héréditaires, Assistance Publique Hôpitaux de Paris, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France.
Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, UMR_S938, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Sorbonne Université, Hôpital Armand Trousseau , Paris, France.
Centre de Référence National des Cytopénies Auto-immunes de l'Enfant , Bordeaux, France.Pediatric Oncology Hemato-Immunology Unit, University Hospital, Plurithématique Centre d'Investigation Clinique, 1401, INSERM , Bordeaux, France.
Institute of Pathology, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Université Claude Bernard Lyon 1 , Lyon, France.Société Française de Foetopathologie Paris , Paris, France.
Centre Hospitalier Universitaire de Reims, Service de Pédiatrie Spécialisée et Généralisée, Université Reims Champagne Ardenne , Reims, France.
Service d'Immunopathologie Clinique, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris , Paris, France.
Service Médecine Interne, Hôpital Intercommunal de Créteil , Créteil, France.
Genomic Platform, INSERM UMR 1163, Imagine Institute, University Paris Cité , Paris, France.
Bioinformatic Platform, INSERM UMR 1163, Imagine Institute, University Paris Cité , Paris, France.
Centre International de Recherche en Infectiologie, Inserm, U1111, CNRS, UMR5308, École Normale Supérieure de Lyon , Lyon, France.National Referee Centre for Pediatric-Onset Rheumatism and Autoimmune Diseases, Hospices Civils de Lyon, Pediatric Nephrology, Rheumatology, Dermatology Unit, Mother and Children University Hospital ; Lyon, France.
Haploinsufficiency in PTPN2 leads to early-onset systemic autoimmunity from Evans syndrome to lupus.

The recurrent spillovers of coronaviruses (CoVs) have posed severe threats to public health and the global economy. Bat severe acute respiratory syndrome (SARS)-like CoVs RsSHC014 and WIV1, currently circulating in bat populations, are poised for human emergence. The trimeric spike (S) glycoprotein, responsible for receptor recognition and membrane fusion, plays a critical role in cross-species transmission and infection. Here, we determined the cryo-electron microscopy (EM) structures of the RsSHC014 S protein in the closed state at 2.9 Å, the WIV1 S protein in the closed state at 2.8 Å, and the intermediate state at 4.0 Å. In the intermediate state, one receptor-binding domain (RBD) is in the down position, while the other two RBDs exhibit poor density. We also resolved the complex structure of the WIV1 S protein bound to human ACE2 (hACE2) at 4.5 Å, which provides structural basis for the future emergence of WIV1 in humans. Through biochemical experiments, we found that despite strong binding affinities between the RBDs and both human and civet ACE2, the pseudoviruses of RsSHC014, but not WIV1, failed to infect 293T cells overexpressing either human or civet ACE2. Mutagenesis analysis revealed that the Y623H substitution, located in the SD2 region, significantly improved the cell entry efficiency of RsSHC014 pseudoviruses, which is likely accomplished by promoting the open conformation of spike glycoproteins. Our findings emphasize the necessity of both efficient RBD lifting and tight RBD-hACE2 binding for viral infection and underscore the significance of the 623 site of the spike glycoprotein for the infectivity of bat SARS-like CoVs.The bat SARS-like CoVs RsSHC014 and WIV1 can use hACE2 for cell entry without further adaptation, indicating their potential risk of emergence in human populations. The S glycoprotein, responsible for receptor recognition and membrane fusion, plays a crucial role in cross-species transmission and infection. In this study, we determined the cryo-EM structures of the S glycoproteins of RsSHC014 and WIV1. Detailed comparisons revealed dynamic structural variations within spike proteins. We also elucidated the complex structure of WIV1 S-hACE2, providing structural evidence for the potential emergence of WIV1 in humans. Although RsSHC014 and WIV1 had similar hACE2-binding affinities, they exhibited distinct pseudovirus cell entry behavior. Through mutagenesis and cryo-EM analysis, we revealed that besides the structural variations, the 623 site in the SD2 region is another important structural determinant of spike infectivity.
The Ministry of Education Key Laboratory of Protein Science, Beijing, China.Beijing Frontier Research Center for Biological Structure, Beijing, China.School of Life Sciences, Tsinghua University, Beijing, China.
Structural determinants of spike infectivity in bat SARS-like coronaviruses RsSHC014 and WIV1.

Identification of monogenic causes of immune dysregulation provides insight into human immune response and signaling pathways associated with autoimmunity. Here, Jeanpierre et al. (https://doi.org/10.1084/jem.20232337) identify new germline variants in the gene encoding PTPN2 associated with loss of regulatory function, enhanced JAK/STAT signaling, and early-onset autoimmunity.
Division of Rheumatology/Immunology, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA.

JAAD Game Changers: Epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia: A systematic review.

JAAD Game Changer: Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients.

JAAD Game Changers: Guidelines for phototherapy of mycosis fungoides and Sézary syndrome: A consensus statement of the US Cutaneous Lymphoma Consortium.

JAAD Game Changers: The use of oral antibiotics before isotretinoin therapy in patients with acne.

Author Affiliation: Duquesne University, Pittsburgh, Pennsylvania.
Practical Strategies for Nurse Leaders to De-Implement Low-Value Nursing Practices.

What's in a Gas-Brief Guidance for Nursing Educators on the Purpose of Arterial Blood Gas Testing.

Unit of Urology, Department of Emergency and Organ Transplantation, Aldo Moro University, Bari, Italy - minafra.p@gmail.com.Unit of Urology, Mater Dei Hospital, Bari, Italy - minafra.p@gmail.com.
Unit of Urology, Department of Emergency and Organ Transplantation, Aldo Moro University, Bari, Italy.
What conclusions can (and cannot) be drawn three years after transperineal laser ablation of prostate?

We examined the possibility of a cross-modal effect in naïve Cotesia vestalis, a parasitoid wasp of diamondback moth larvae, by using artificial flower models of four colours (blue, green, yellow, and red) in the absence or presence of floral scent collected from Brassica rapa inflorescences. In a four-choice test, regardless of the floral scent, non-starved female wasps visited green and yellow models significantly more often than blue and red ones, although no significant difference was observed between visits to the green and yellow models. They seldom visited blue and red models. When starved, the wasps became even more particular, visiting yellow significantly more frequently than green models, irrespective of the presence of the floral scent, indicating that they preferred to use yellow visual cues in their food search. Furthermore, a factorial analysis of variance revealed a significant effect of the interaction between model colour and floral scent on the wasps' visits to flower models. The floral scent induced starved and non-starved wasps to visit yellow and green models about twice as often as without the scent. A cross-modal effect of olfactory perception on the use of chromatic information by wasps may allow them to search efficiently for food sources.
Institute for Plant Protection, National Agriculture and Food Research Organization (NARO), Kannondai 3-1-3, Tsukuba, Ibaraki, 305-8604, Japan. kugimiya@affrc.go.jp.
Institute for Plant Protection, National Agriculture and Food Research Organization (NARO), Kannondai 3-1-3, Tsukuba, Ibaraki, 305-8604, Japan.Tohoku Agricultural Research Center, NARO, Akahira 4, Shimo-kuriyagawa, Morioka, Iwate, 020-0198, Japan.
Center for Ecological Research, Kyoto University, Hirano 2-509-3, Otsu, Shiga, 520-2113, Japan.
Reinforced colour preference of parasitoid wasps in the presence of floral scent: a case study of a cross-modal effect.

Rare earth (RE)-doped CaS phosphors have been widely used as light-emitting components in various fields. Nevertheless, the application of nanosized CaS particles is still significantly limited by their poor water resistance and weak luminescence. Herein, a lattice-matching strategy is developed by growing an inert shell of cubic NaYF4 phase on the CaS luminescent core. Due to their similarity in crystal structure, a uniform core-shell heterostructure (CaS:Ce3+@NaYF4) can be obtained, which effectively protects the CaS:Ce3+ core from degradation in aqueous environment and enhances its luminescence intensity. As a proof of concept, a label-free aptasensor is further constructed by combining core-shell CaS:Ce3+@NaYF4 and Au nanoparticles (AuNPs) for the ultrasensitive detection of kanamycin antibiotics. Based on the efficient FRET process, the detection linear range of kanamycin spans from 100 to 1000 nM with a detection limit of 7.8 nM. Besides, the aptasensor shows excellent selectivity towards kanamycin antibiotics, and has been successfully applied to the detection of kanamycin spiked in tap water and milk samples, demonstrating its high potential for sensing applications.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China.
Department of Biomedical Engineering, City University of Hong Kong, Hong Kong SAR, 999077, China. yozhang@cityu.edu.hk.
School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China. xhzhu@shu.edu.cn.
Lattice matching enables construction of CaS@NaYF4 heterostructure with synergistically enhanced water resistance and luminescence for antibiotic detection.

An investigation by the publisher found a number of articles, including this one, published in Journal of Pediatric Genetics in Volume 12, Number 02, 95-96, in June 2023 (DOI: 10.1055/s-0042-1759781), with a number of concerns, including but not limited to undeclared conflicts of interest and manipulated peer review procedures. As a result, the publisher has retracted and removed this article.
Divisions of Pediatric Neurology and Genetics and Behavioral-Developmental Pediatrics, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, Meram, Konya, Türkiye.
Retraction Note: Importance of Religious Coping in Bereaved Parents after the Death of a Child with Genetic Disorder.

An investigation by the publisher found a number of articles, including this one, published in Journal of Pediatric Genetics in Volume 12, Number 03, 185-186, in September 2023 (DOI: 10.1055/s-0043-1764300), with a number of concerns, including but not limited to undeclared conflicts of interest and manipulated peer review procedures. As a result, the publisher has retracted and removed this article.
Retraction Note: A Brief View of The Prophet Ayyub's (Alayhi As-Salam) Disease: Was It Job's Syndrome?

Ribosomopathies arise from the disruptions in ribosome biogenesis within the nucleolus, which is organized via liquid-liquid phase separation (LLPS). The roles of LLPS in ribosomopathies remain poorly understood. Here, we generated human induced pluripotent stem cell (hiPSC) models of ribosomopathy caused by mutations in small nucleolar RNA (snoRNA) gene SNORD118. Mutant hiPSC-derived neural progenitor cells (NPCs) or neural crest cells (NCCs) exhibited ribosomopathy hallmark cellular defects resulting in reduced organoid growth, recapitulating developmental delay in patients. SNORD118 mutations in NPCs disrupted nucleolar morphology and LLPS properties coupled with impaired ribosome biogenesis and a translational downregulation of fibrillarin (FBL), the key LLPS effector acting via the intrinsically disordered region (IDR) motif. IDR-depleted FBL failed to rescue NPC defects, whereas a chimeric FBL with swapped IDR motif from an unrelated protein mitigated ribosomopathy and organoid growth defects. Thus, SNORD118 human iPSC models revealed aberrant phase separation and nucleolar functions as potential pathogenic mechanisms in ribosomopathies.
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Impaired phase separation and nucleolar functions in hiPSC models of SNORD118-related ribosomopathies.

Most nonconventional luminogens enjoy good water solubility and biocompatibility, showing unique application prospects in fields like biological imaging. Although clustering-triggered emission (CTE) mechanisms have been proposed to explain such emissions, the have not been thoroughly elucidated, which limits their development and application. Here, the photoluminescence properties of carboxymethyl β-cyclodextrin (CM-β-CD) aqueous solution are utilized to further investigate the effects of changes in concentration, in order to elucidate the emission mechanism through cryo-transmission electron microscopy (cryo-TEM), small-angle X-ray scattering (SAXS), molecular interaction analysis, and theoretical calculation. The results showed that the size distribution, morphology, and distance between water aggregates were successfully correlated with the cluster emission centers. The emission mechanism of nonconventional luminogen solutions was more clearly and intuitively elucidated, which has a promoting effect on the emission and application of this field. It is interesting that temperature-dependent emission spectra show the blue-shift phenomenon of PL with increasing excitation wavelengths. Moreover, due to its strong static quenching effect for Fe3+, CM-β-CD can efficiently detect Fe3+ in mixed-ion aqueous solutions. It provides a strategy to clarify the CTE mechanism of nonconventional luminogen solutions more clearly and its application of mixed-ion detection.
Engineering Research Center for Eco-Dyeing and Finishing of Textiles, Key Laboratory of Advanced Textile Materials and Manufacturing Technology, Ministry of Education, College of Textile Science and Engineering (International Institute of Silk), Zhejiang Sci-Tech University, Hangzhou, China.
Zhejiang Sci-Tech University Shaoxing-Keqiao Research Institute, Zhejiang Provincial Innovation Center of Advanced Textile Technology, Building 7, Cross border E-commerce Park, Huashe Street, Keqiao District, Shaoxing City, Zhejiang, China.
Engineering Research Center for Eco-Dyeing and Finishing of Textiles, Key Laboratory of Advanced Textile Materials and Manufacturing Technology, Ministry of Education, College of Textile Science and Engineering (International Institute of Silk), Zhejiang Sci-Tech University, Hangzhou, China.Zhejiang Sci-Tech University Shaoxing-Keqiao Research Institute, Zhejiang Provincial Innovation Center of Advanced Textile Technology, Building 7, Cross border E-commerce Park, Huashe Street, Keqiao District, Shaoxing City, Zhejiang, China.MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.
Luminescence : the journal of biological and chemical luminescence
Clustering-triggered emission mechanism of carboxymethyl β-cyclodextrin aqueous solution and efficient recognition of Fe3+ in mixed ions.

Department of Psychobiology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Sleep Institute, Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil.
Department of Psychobiology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.Sleep Institute, Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil.
The effects of the space environment on circadian rhythm and sleep in astronauts: An emphasis on the telomere length dynamics associated with sleep.

This study aimed to elucidate the risk factors associated with alcohol use disorders (AUDs) among inpatients with schizophrenia at a specialized mental hospital in Baoding city, China.This cross-sectional survey comprised 301 comorbid patients. Three binary logistic regression models were used to investigate the factors linked to AUDs in patients with schizophrenia. Propensity score matching analysis was conducted to validate inconsistent variables identified by the regression models.Significant differences were observed between the comorbid and non-comorbid groups concerning sex (P < .001), disposition (P = .049), smoking habits (P < .001), place of residence (P = .010), family relationships (P = .002), family history of mental disorders (P = .008), history of alcoholism (P = .003), onset latency (P = .005), impulsivity (P < .001), suicide or self-injury history (P < .001), and obvious aggressive behavior (P < .001) in univariate analyses. The area under the curve values for the three regression models were 0.83 (P < .001), 0.80 (P < .001), and 0.81 (P < .001), respectively. Binary logistic regression and propensity score matching analyses indicated that introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independent risk factors associated with AUDs in inpatients with schizophrenia with an odds ratio of > 1.Introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independently associated with the AUDs in inpatients with schizophrenia. Future studies should prioritize longitudinal studies to discern the evolving dynamics of potential confounding risk factors.
Hebei Provincial Mental Health Center, Baoding, China.Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, China.The Sixth Clinical Medical College of Hebei University, Baoding, China.
Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Risk Factors of Alcohol Use Disorders Among Inpatients with Schizophrenia: An Institutional-Based Cross-sectional Survey.

Immune-surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a novel function for intracellular C3d, we discovered that C3d engaged T cell responses against malignant plasma cells in the bone marrow of mice that had developed multiple myeloma spontaneously. Our results show that C3d internalized by cells augments immune surveillance by several mechanisms. In one, C3d induces a master transcription regulator, E2f1, to increase the expression of long non-coding (lnc) RNAs, to generate peptides for MHC-I presentation and increase MHC-I expression. In another, C3d increases expression of RNAs encoding ribosomal proteins linked to processing of defective ribosomal products (DRiPs) that arise from non-canonical translation and known to promote immunosurveillance. Cancer cells are uniquely susceptible to increased expression and presentation of mutant peptides given the extent of protein misfolding and accumulation of somatic mutations. Accordingly, although C3d can be internalized by any cell, C3d preferentially targets malignant clones by evoking specific T cell mediated immunity (CMI) and sparing most non-transformed polyclonal B cells and plasma cells with lower mutation loads. Malignant plasma cell deletion was blocked by cyclosporin or by CD8 depletion confirming that endogenous T cells mediated malignant clone clearance. Besides the potential for therapeutic application our results highlight how intracellular C3d modifies cellular metabolism to augment immune surveillance.We show that intracellular soluble fragment 3d of complement (C3d) induces regression of spontaneous multiple myeloma in mice reducing tumor burden by 10 fold, after 8 weeks. C3d enables cell-mediated immunity to target multiple myeloma clones sparing non-transformed polyclonal B cells and plasma cells with lower mutation loads. We show that C3d increases the expression of ribosomal subunits associated with the translation of defective ribosomal products (DRiPs). C3d also decreases expression of protein arginine methyl transferase (PRMT) 5 which in turn relieves E2f1 repression increasing the expression of Lnc RNAs and derived peptides that evoke anti-tumor cellular immunity. The approach increases MHC-I expression by tumor cells and generates a CMI response that overcomes tumor immune-evasion strategies.Tumors are immunogenic in part because of somatic mutations that originate novel peptides that once presented on MHC engage cell-mediated immunity (CMI). However, in spite of the higher mutation load most tumors evade immunity. We discovered that a component of the complement system (C3d) overcomes tumor immune evasion by augmenting expression of ribosomal proteins and lncRNAs linked to the presentation of novel peptides by tumor cells. C3d induced CMI targets cancer cells sparing non transformed cells uncovering a novel function for complement in immune surveillance.
bioRxiv : the preprint server for biology
Complement C3d enables protective immunity capable of distinguishing spontaneously transformed from non-transformed cells.

Université de Lorraine, Nancy, France. Electronic address: jean-paul.fischer@univ-lorraine.fr.
University of Edinburgh, Human Cognitive Neuroscience, Psychology, UK. Electronic address: r.d.mcintosh@ed.ac.uk.

Institute for Biosciences, Sensory and Cognitive Ecology, University of Rostock, Albert-Einstein-Str. 3, Rostock, 18059, Germany.
Faculty of Science and Engineering, Biological and Marine Science, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, UK.
Geospatial Ecology of Marine Megafauna Lab, Marine Mammal Institute, and Department of Fisheries, Wildlife and Conservation Sciences, Oregon State University, Newport, OR, 97365, USA.
Institute for Biosciences, Sensory and Cognitive Ecology, University of Rostock, Albert-Einstein-Str. 3, Rostock, 18059, Germany. frederike.hanke@uni-rostock.de.
Correction to: Welldeveloped spatial reversal learning abilities in harbor seals (Phoca vitulina) : Issue : 25_5_Issue.

Centre for Clinical Brain Sciences, University of Edinburgh, UK; Health & Community Sciences, University of Exeter, UK. Electronic address: a.zeman@exeter.ac.uk.
Department of Psychology, University of Bonn, Germany.
School of Psychology, University of New South Wales, Sydney, Australia.
Institute of Philosophy II, Ruhr-Universität Bochum, Germany.
School of Psychology, University of Sussex, UK.

Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Department of Psychiatry, University of Arizona, Tucson, Arizona, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Department of Psychiatry and Psychotherapy, University of Freiburg, Freiburg, Germany.

Sleep diaries and other subjective measures are essential for the assessment of insomnia.

Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo , Egypt.
Commentary: Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model.
The objective of this systematic review is to understand the experiences of care partner engagement in patient safety at the direct care level from the perspective of care partners, patients, and health care professionals.Care partner engagement is a strategy for promoting patient safety in hospitals at the direct care level (ie, at the point where patient care is delivered). When present, care partners can increase safety by watching, listening, and taking action to protect admitted patients. To improve care partner presence policies and safety engagement strategies within hospitals, a comprehensive understanding of the current qualitative evidence about the breadth of experiences of care partner engagement in patient safety is required.This review will include qualitative studies that consider the experiences of care partners, adult patients, and health care professionals. The engagement of care partners in patient safety within pediatric hospital settings will not be considered.This review will follow the JBI methodology for systematic reviews of qualitative evidence. A preliminary literature search was conducted in MEDLINE and a full search strategy was developed for MEDLINE, Embase, CINAHL, and PsycINFO (all via Ovid), as well as the Cochrane Database of Systematic Reviews and JBI Evidence Synthesis . The JBI approach to study selection, critical appraisal, data extraction, data synthesis, and assessment of confidence will be followed. Two reviewers will test the screening criteria and data extraction protocol.PROSPERO CRD42023476286.
Health Quality Programs, School of Nursing, Queen's University, Kingston, ON, Canada.
Health Quality Programs, School of Nursing, Queen's University, Kingston, ON, Canada.Queen's Collaboration for Health Care Quality, Queen's University, Kingston, ON, Canada.
THIS Institute, University of Cambridge, Cambridge, England.
Queen's Collaboration for Health Care Quality, Queen's University, Kingston, ON, Canada.Bracken Health Science Library, Queen's University, Kingston, ON, Canada.
Care partner engagement in patient safety at the direct care level in hospital: a qualitative systematic review protocol.
The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities.This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens.Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients.Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
School of Medicine, Nankai University, Tianjin, 300071, China; Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China.
Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China.
School of Medicine, Nankai University, Tianjin, 300071, China; Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China. Electronic address: Julianna_hu@163.com.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
Prognosis and treatment regimens for patients with different lymph node statuses in locally advanced cervical cancer.
Soft pneumatic actuators (SPAs) produce motions for soft robots with simple pressure input, however, they require to be appropriately designed to fit the target application. Available design methods employ kinematic models and optimization to estimate the actuator response and the optimal design parameters to achieve a target actuator's shape. Within SPAs, bellow SPAs excel in rapid prototyping and large deformation, yet their kinematic models often lack accuracy due to the geometry complexity and the material nonlinearity. Furthermore, existing shape-matching algorithms are not providing an end-to-end solution from the desired shape to the actuator. In addition, despite the availability of computational design pipelines, an accessible and user-friendly toolbox for direct application remains elusive. This article addresses these challenges, offering an end-to-end shape-matching design framework for bellow SPAs to streamline the design process, and the open-source toolbox SPADA (Soft Pneumatic Actuator Design frAmework) implementing the framework with a graphic user interface for easy access. It provides a kinematic model grounded on a modular design to improve accuracy, finite element method (FEM) simulations, and piecewise constant curvature (PCC) approximation. An artificial neural network-trained surrogate model, based on FEM simulation data, is trained for fast computation in optimization. A shape-matching algorithm, merging three-dimensional (3D) PCC segmentation and a surrogate model-based genetic algorithm, identifies optimal actuator design parameters for desired shapes. The toolbox, implementing the proposed design framework, has proven its end-to-end capability in designing actuators to precisely match two-dimensional shapes with root-mean-squared-errors of 4.16, 2.70, and 2.51 mm, and demonstrating its potential by designing a 3D deformable actuator.
© Yao Yao et al. 2024; Published by Mary Ann Liebert, Inc.
Oxford Robotics Institute, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Oxford Robotics Institute, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.Department of Mechanical, Energy, Management and Transport Engineering-DIME, University of Genoa, Genoa, Italy.
SPADA: A Toolbox of Designing Soft Pneumatic Actuators for Shape Matching Based on Surrogate Modeling.
This systematic review examines the evidence on the incidence and prevalence of inborn errors of metabolism (IEMs) in low- and middle-income countries (LMICs).IEMs are a set of conditions that can either be inherited or result from spontaneous mutations. Although each condition is rare in isolation, various specific disorders within the IEM group have an estimated global prevalence of 50.9 per 100,000 live births. A precise estimate of the prevalence and incidence of IEMs in LMICs can help determine the necessity for extensive newborn screening programs.This review will cover studies conducted in LMICs, reporting on IEMs in infants and children under the age of 5 years. Studies that calculate birth prevalence and incidence of IEMs will be included. Studies that provide information on the causes, clinical characteristics, treatment, case fatality rates, mortality rates, and other outcomes will also be considered.The databases to be searched include PubMed, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Scopus, and gray literature sources. No date or language restrictions will be applied. Our search will encompass analytical and descriptive observational studies, which will be critically appraised by 2 independent reviewers. Data will be extracted using JBI data extraction tools. If sufficient data are available, a meta-analysis will be performed. Alternatively, if data are limited, we will present our findings in narrative format using tables and figures.PROSPERO CRD42023457421.
Kalam Institute of Health Technology: A JBI Affiliated Group, Visakhapatnam, Andhra Pradesh, India.
The Northeast Institute for Evidence Synthesis and Translation, Rutgers School of Nursing, A JBI Center of Excellence, Newark, NJ, USA.
Epidemiological burden of inborn errors of metabolism in low- and middle-income countries: a systematic review protocol.
The objective of this review is to synthesize the experiences of informal caregivers' feeding practices for children with cancer.Changes in eating among children with cancer impact their nutritional status, leading to several negative outcomes. In addition to interventions given by health care providers, informal caregivers' experiences in feeding these children are worth exploring.This review will include qualitative studies or the qualitative component of mixed method studies examining informal caregivers' experiences of feeding children with cancer who are under 18 years of age. Children may be in any phase of the cancer journey, and may be at a health care facility or at home. Studies from any country, published in English or Thai in any year up to the present, will be considered for inclusion.This review will follow the JBI approach for qualitative systematic reviews. A full search strategy for PubMed was developed from an initial limited search of PubMed and CINAHL (EBSCOhost) to identify articles on the topic. The search strategy will be adapted for each database, including Embase (Ovid), PubMed, CINAHL (EBSCOhost), Cochrane Library (CENTRAL), LILACS (BVS), PsycINFO (Ovid), Web of Science Core Collection, Scopus, and ThaiJO (TCI). The reference lists of studies included in the review will be hand-searched for additional studies. Sources of unpublished studies and gray literature will also be searched. Two reviewers will separately screen for eligible studies, perform the critical appraisal, and extract data. They will then synthesize via meta-aggregation and summarize the data. The final synthesized findings will be graded using the ConQual approach to establish confidence in the qualitative research synthesis.PROSPERO CRD42024501382.
Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on Behalf of JBI.
Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Mahidol University Ramathibodi School of Nursing: A JBI Affiliated Group, Bangkok, Thailand.
Informal caregivers' feeding experiences for children with cancer: a qualitative systematic review protocol.
Although mucosal melanomas are rare and constitute approximately 1.4% of all melanomas, the prognosis of patients with mucosal melanoma is poorer in comparison to cutaneous melanomas. Despite their poor prognosis, limited treatment options are currently available for patients with advanced disease. These noncutaneous subtypes of melanomas are not responding to treatment used for cutaneous melanomas. We performed RNA sequencing on four mucosal melanoma samples comprising of two primary tumors and two corresponding metastases. A TRIM33 :: CSDE1 fusion was detected in both the primary tumor and metastasis of a vulvar melanoma, supporting the fusion to be a driver in oncogenesis. Vulvar melanoma is the third tumor to have been reported to harbor TRIM33 :: CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Department of Molecular Diagnostics, Holy Cross Cancer Center.Division of Medical Biology, Institute of Biology, Jan Kochanowski University, Kielce, Poland.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
High-resolution RNA-sequencing reveals TRIM33 :: CSDE1 gene fusion in metastasizing vulvar melanoma.
Hidradenitis Suppurativa Unit, Department of Dermatology, Hospital Universitario Virgen de las Nieves Granada, Granada, Spain.
Hidradenitis Suppurativa Unit, Department of Dermatology, Hospital Universitario Virgen de las Nieves Granada, Granada, Spain; TECe19-Dermatología Clínica y Traslacional, Granada Institute for Biosanitary Research, Granada, Spain. Electronic address: alejandromolinaleyva@gmail.com.
Use of cryoanesthesia and a punch biopsy tool in the drainage of hidradenitis suppurativa abscesses.
Department of Dermatology and Venereology, Istanbul Medeniyet University, Istanbul, Turkey. Electronic address: derm.ozanerdem@gmail.com.
Department of Dermatology and Venereology, Istanbul Medeniyet University, Istanbul, Turkey.
A practical and affordable surgical light-integrated camera system for dermatologic surgery video recordings.
The membrane lipid damage caused by reactive oxygen species(ROS) and various peroxides, namely lipid peroxidation, plays an important role in the progression of diabetic nephropathy (DN).We previously reported that vitamin D receptor(VDR) plays an active role in DN mice by modulating autophagy disorders. However, it is unclear whether the ATP-citrate lyase (ACLY)/NF-E2-related factor-2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway is associated with the reduction of lipid peroxidation by VDR in the DN model. We found that in the DN mouse model, VDR knockout significantly aggravated mitochondrial morphological damage caused by DN, increased the expression of ACLY, promoted the accumulation of ROS, lipid peroxidation products Malondialdehyde(MDA) and 4-hydroxy-2-nonenal (4-HNE),consumed the Nrf2/Keap1 system, thus increasing lipid peroxidation. However, the overexpression of VDR and intervention with the VDR agonist paricalcitol (Pari) can reduce the above damage. On the other hand, cellular experiments have shown that Pari can significantly reduce the elevated expression of ACLY and ROS induced by advanced glycation end products (AGE). However, ACLY overexpression partially eliminated the positive effects of the VDR agonist. Next, we verified the transcriptional regulation of ACLY by VDR through chromatin immunoprecipitation (ChIP)-qPCR and dual luciferase experiments. Moreover, in AGE models, knockdown of ACLY decreased lipid peroxidation and ROS production, while intervention with Nrf2 inhibitor ML385 partially weakened the protective effect of ACLY downregulation. In summary, VDR negatively regulates the expression of ACLY through transcription, thereby affecting the state of Nrf2/Keap1 system and regulating lipid peroxidation, thereby inhibiting kidney injury induced by DN.
© 2024 Federation of American Societies for Experimental Biology.
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China.
Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Vitamin D receptor alleviates lipid peroxidation in diabetic nephropathy by regulating ACLY/Nrf2/Keap1 pathway.
Department Guidance and Counseling, Universitas PGRI Palembang, Jln. Jend. A. Yani, Lr Gotong royong 9/10 Ulu, Palembang, Indonesia. Electronic address: erfankonselor@gmail.com.
Department Guidance and Counseling, Universitas PGRI Palembang, Jln. Jend. A. Yani, Lr Gotong royong 9/10 Ulu, Palembang, Indonesia.
Universitas Mathlaul Anwar, Jl. Labuan KM 23 Cikaliung, Sindanghayu, Kec. Saketi, Kab, Pandeglang Banten, Indonesia.
Universitas PGRI Palembang, Jln. Jend. A. Yani, Lr Gotong royong 9/10 Ulu, Palembang, Indonesia. Electronic address: mtaheriakhbar@univpgri-palembang.ac.id.
Universitas PGRI Palembang, Jln. Jend. A. Yani, Lr Gotong royong 9/10 Ulu, Palembang, Indonesia.
AI in substance use recovery: Innovation or risk? A call for caution.
Department of Dermatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Dermatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: werth@pennmedicine.upenn.edu.
Overlapping clinical features in anti-synthetase syndrome and dermatomyositis: A case series.
Department of Dermatology, Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
Department of Dermatology, Peking University First Hospital, Beijing, PR China. Electronic address: drlihang@126.com.
Utilizing magnetic discs combined with thin silicone gel sheets for pressure therapy in earlobe keloid postexcision.
This corrects the article on p. 1 in vol. 30, PMID: 38714490.
Copyright © 2024 by The Korean Society of Menopause.
Center for Gynecologic Cancer, National Cancer Center, Goyang, Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea.
Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Inje University Haeundae Paik Hospital, Busan, Korea.
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Obstetrics and Gynecology, Chungbuk National University Hospital, Cheongju, Korea.
Department of Obstetrics and Gynecology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea. jylee@kuh.ac.kr.
Corrigendum: 2023 Korean Society of Menopause - Osteoporosis Guidelines Part I.
Radiation stability of food packaging materials is the key to ensuring food quality. In this study, 60Co γ-ray was selected to investigate the radiation resistance of food packaging polystyrene (PS) resin material, although the FTIR analysis showed that the intensity of several peaks decreased slightly. The gel permeation chromatography (GPC) results displayed that the value of peak molecular weight (Mp) of PS went from 2.68 × 105 g/mol down to 2.22 × 105 g/mol. Moreover, the residual mass (Res) of PS increased from 7.208 to 30.23%, indicating that the tendency of coking of PS was stronger after irradiation. In addition, the peak intensities of the three main pyrolysis products -CH2-, CH4, and CH2=CH2 increased by more than 30% compared to unirradiated PS, and a large number of them were detected in the whole pyrolysis process. Moreover, mechanical property analysis finds that both breaking strength and elongation data increased before irradiation dose of 50 kGy, then, decreased sharply with further increase of irradiation dose. The theoretical bond order analysis confirmed that the tertiary carbon bond attaching the benzene ring had the lowest bond energy. This study can give helpful guidance when using PS for food packing materials.
State Key Laboratory of Environment-Friendly Energy Materials, Southwest University of Science and Technology, Mianyang 621010, P. R. China.National Co-innovation Center for Nuclear Waste Disposal and Environmental Safety, Southwest University of Science and Technology, Mianyang 621010, P. R. China.
State Key Laboratory of Environment-Friendly Energy Materials, Southwest University of Science and Technology, Mianyang 621010, P. R. China.National Co-innovation Center for Nuclear Waste Disposal and Environmental Safety, Southwest University of Science and Technology, Mianyang 621010, P. R. China.Tianfu Institute of Research and Innovation, Southwest University of Science and Technology, Chengdu 610299, P. R. China.
Nuclear Medicine Laboratory of Mianyang Central Hospital, Mianyang 621010, P. R. China.
Research on the Stability and Response of Food Packaging Polystyrene Resin Materials to γ-ray Irradiation.
Department of Dermatology, Penn State Health Medical Center, Hershey, Pennsylvania. Electronic address: mhelm2@pennstatehealth.psu.edu.
Department of Dermatology, Penn State Health Medical Center, Hershey, Pennsylvania.
Department of Emergency Medicine, Brooke Army Medical Center, San Antonio, TX, USA. brit.long@yahoo.com.
Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, ON, Canada.
Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
Just the facts: evaluation and management of hemophilia.
Department of General Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan, ROC.
Department of Addiction Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan, ROC.
Integrating youth-specific services in substance use disorder treatment: Insights from Taiwan.
Author Affiliations: Cardiothoracic Intensive Care Unit, Duke University Hospital, Durham, North Carolina (Bolick, Rieger, Ridley, Daniel, Dykes); and Strategic Services Associate Patient Safety & Quality Improvement, Heart Services, Duke University Hospital, Durham, North Carolina (Pena).
Breathing Exercises Prior to Ambulation after Heart Surgeries Impact on Patient Ambulation Goals, Anxiety, and Pain.
Regeneron Pharmaceuticals Inc., Tarrytown, New York. Electronic address: tien.nguyen2@regeneron.com.
Regeneron Pharmaceuticals Inc., Tarrytown, New York.
Regeneron Pharmaceuticals Inc., Dublin, Ireland.
Commentary: Response to Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study .
Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. Electronic address: dr_kridin@hotmail.com.
Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; Department of Dermatology, University of Lübeck, Lübeck, Germany.
Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel.
Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University of Lübeck, Lübeck, Germany.
Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany.
The risk of different subtypes of psoriasis following an episode of guttate psoriasis.
The incidence of heart transplants in the USA has increased by 85.8% since 2011, resulting in a growing population of recipients requiring long-term immunosuppressive therapy. While essential for preventing organ rejection, this therapy significantly increases melanoma risk. This meta-analysis investigates the incidence and risk factors of melanoma in heart transplant recipients. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting melanoma incidence in heart transplant recipients. Relative risk (RR) was synthesized from standardized incidence ratios, hazard ratios, incidence rate ratios, and standardized mortality ratios. The meta-analysis incorporated 10 studies, including 22 415 heart transplant recipients. The pooled RR was 2.21 (95% confidence interval: 1.32-3.71; P = 0.003), indicating a significantly elevated melanoma risk. This study highlights the critical need for preventive dermatological strategies in heart transplant recipients and calls for further research into the impact of different immunosuppressive regimens on melanoma risk. Despite limitations, these findings offer valuable insights for optimizing long-term patient care.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Department of Internal Medicine, Lakeland Regional Health Medical Center, Lakeland, Florida, USA.
International incidence of melanoma in heart transplant recipients: a meta-analysis.
College of Life Sciences, Qingdao Agricultural University, Qingdao 266109, China.
Key Laboratory of National Forestry and Grassland Administration on Grassland Resources and Ecology in the Yellow River Delta, College of Grassland Science, Qingdao Agricultural University, Qingdao 266109, China.
Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA. Electronic address: sluan@berkeley.edu.
Key Laboratory of National Forestry and Grassland Administration on Grassland Resources and Ecology in the Yellow River Delta, College of Grassland Science, Qingdao Agricultural University, Qingdao 266109, China. Electronic address: yanggf@qau.edu.cn.
Advancing insights into calcium homeostasis and signaling in plant growth and resilience.
Translating Evidence to Practice in Clinical Communication Safety.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. hakan.westerblad@ki.se.
The Nutraceutical Alliance Inc., Guelph, ON, Canada.
High-quality experimental records and physiology-based assessments outperform automated procedures and complex statistics. Introducing Methods in Applied Physiology , a new topical collection.
First Department of Pediatrics, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 49th Konstantinoupoleos Street, Thessaloniki, Greece. yan_dot@yahoo.com.
Centre of Genetics for Rare Diseases, Papageorgiou Hospital, Thessaloniki, Greece.
First Department of Pediatrics, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 49th Konstantinoupoleos Street, Thessaloniki, Greece.
Type IV collagen-related nephropathy as a diagnosis in nephrotic syndrome.
Groningen Institute for Evolutionary Life Sciences, University of Groningen, 9747 AG, Groningen, The Netherlands. flavia.berlinghieri93@gmail.com.Department of Biological Sciences, Macquarie University, North Ryde, NSW, Australia. flavia.berlinghieri93@gmail.com.
CoNISMa, Consorzio Nazionale Interuniversitario per le Scienze del Mare, Rome, Italy.
Groningen Institute for Evolutionary Life Sciences, University of Groningen, 9747 AG, Groningen, The Netherlands.
Department of Biological Sciences, Macquarie University, North Ryde, NSW, Australia.
Correction to: Are lateralized and bold fish optimistic or pessimistic?
This review will analyze the effectiveness of early childhood education interventions to improve complementary feeding practices in children aged 4 to 36 months.Healthy eating habits, which start with food introduction, can influence children's growth and development. Educational actions carried out at school for children who are beginning to eat, involving families and school staff who attend daycare centers, can serve as strategies to improve complementary feeding practices.The review will consider randomized clinical trials, cluster-randomized clinical trials, and controlled clinical trials that evaluate the effectiveness of early childhood education interventions involving children aged 4 to 36 months, their families, or school staff to improve complementary feeding. In their absence, observational cohort, case-control, and cross-sectional studies may be considered.This review will be conducted in line with the JBI methodology for systematic reviews of effectiveness. The search for relevant studies will be conducted in PubMed, Embase (Ovid), BIREME, Scopus, the Cochrane Library (Cochrane Central Register of Controlled Trials CENTRAL and Cochrane Database of Systematic Reviews), CINAHL (EBSCOhost), and the ProQuest Databases (ProQuest Central). No date or language limitations will be applied. Two independent reviewers will select studies by screening titles, abstracts, and keywords against the inclusion criteria. This will be followed by full-text screening. Two independent reviewers will then evaluate the quality of the sources and perform data extraction. GRADEpro will be used to assess the certainty in the findings, which will be reported in the systematic review and, if possible, grouped in a meta-analysis.PROSPERO CRD42022384704.
Postgraduate Master's Program in Health Sciences, Federal University of Amazonas, Manaus, AM, Brazil.
Institute of Health and Biotechnology, Federal University of Amazonas, Manaus, AM, Brazil.
Department of Collective Health, Faculty of Medicine, Federal University of Amazonas, Manaus, AM, Brazil.
Department of Health Sciences, Macquarie University, Sydney, NSW, Australia.
Effectiveness of early childhood education interventions to improve complementary feeding practices in children 4 to 36 months of age: a systematic review protocol.
T7 RNA polymerase has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using Saccharomyces cerevisiae. We isolated highly active variants of this fusion enzyme, which exhibited roughly two orders of magnitude higher protein expression compared to the wild-type enzyme. We demonstrate the programmable control of gene expression using T7 RNAP-based genetic circuits in yeast and validate enhanced performance of these engineered variants in mammalian cells. This study presents a robust, orthogonal gene regulatory system applicable across diverse eukaryotic hosts, enhancing the versatility and efficiency of synthetic biology applications.
Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.Authors contributed equally.
Department of Bioengineering, Rice University, Houston, TX, USA.Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.Authors contributed equally.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.
Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.
Dermatology Unit, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Dermatology Unit, Hospital Mater Dei, Belo Horizonte, Brazil; Department of Dermatology, Oregon Health and Science University, Portland, Oregon.
Department of Dermatology, Oregon Health and Science University, Portland, Oregon.
Department of Dermatology, Oregon Health and Science University, Portland, Oregon; Providence Portland Medical Center, Portland, Oregon.
Dermatology Unit, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Department of Dermatology, Oregon Health and Science University, Portland, Oregon. Electronic address: leachmas@ohsu.edu.
Thin and in situ melanomas of unfavorable prognosis: A retrospective observational analysis of local recurrence, metastasis, and death in early-stage disease.
Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York; Rutgers New Jersey Medical School, Newark, New Jersey.
Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York.
Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York. Electronic address: Prince.Adotama@nyulangone.org.
Assessing the inclusion of postinflammatory hyperpigmentation outcomes in acne vulgaris clinical trials.
Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
John Sealy School of Medicine, University of Texas Medical Branch, Galveston, Texas.
Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: nicholas.gulati@mssm.edu.
Associations Between Cutaneous and Noncutaneous Adverse Events Among Patients on Immune Checkpoint Inhibitors.
Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina. Electronic address: kennedyka20@students.ecu.edu.
Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Social Sciences & Health Policy, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Response to deucravacitinib in psoriasis patients with prior biologic therapy failures: A retrospective study.
Dermatology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Sorbonne University, Medicine Faculty of Sorbonne Université, Paris, France.
Sorbonne University, Medicine Faculty of Sorbonne Université, Paris, France; Dermatology Department, Tenon University Hospital, and CIMI, U11-35 Assistance Publique-Hôpitaux de Paris, Paris, France.
Pathology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Paris Cité University, Medicine Faculty of Paris Cité, Paris, France.
Dermatology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Pathology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Dermatology Department, Cochin Hospital, ApHp and Paris Cité University, Paris, France.
Dermatology Department, René Dubos Hospital, Pontoise, France.
Dermatology Department, Montpellier University Hospital, Montpellier, France.
Dermatology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Paris Cité University, Medicine Faculty of Paris Cité, Paris, France.
Immunology and Internal Medicine Department, Saint Antoine University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Immunology and Internal Medicine Department, Bicêtre University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Dermatology Department, Tenon University Hospital, and CIMI, U11-35 Assistance Publique-Hôpitaux de Paris, Paris, France.
Dermatology Department, Nîmes University Hospital, Nîmes, France.
Dermatology Department, Brest University Hospital, Brest, France.
Dermatology Department, Lyon Sud University Hospital, Lyon, France.
Pneumology Department, Avicenne Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Nord University, INSERM UMR1272, Groupe Sarcoïdose Francophone, GSF, Bobigny, France.
Paris Cité University, Medicine Faculty of Paris Cité, Paris, France; Pneumology Department, Saint-Louis University Hospital, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Paris, France.
Pneumology Department, Avicenne Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Nord University, INSERM UMR1272, Groupe Sarcoïdose Francophone, GSF, Bobigny, France; Groupe Sarcoïdose Francophone (Group GFS), Paris, France.
Dermatology Department, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address: thibault.mahevas@aphp.fr.
Groupe d’étude des maladies systémiques en dermatologie (EMSED)
Favorable prognosis of subcutaneous sarcoidosis: French cohort of 80 patients compared with dermal sarcoidosis.
Department of Dermatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China.
Guangdong Mental Health Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Guangdong Mental Health Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: houcl1975@163.com.
Department of Dermatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: zhushencq@hotmail.com.
Exploring suicidal and self-injurious behaviors signal strength of biologics in treating psoriasis or psoriatic arthritis: A 10-year real-world pharmacovigilance analysis using the FDA Adverse Event Reporting System database.
INSERM UMR1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; University Paris Cité, Paris, France.
University Paris Cité, Paris, France; Institut Pasteur, Centre Médical de l'Institut Pasteur, Paris, France.
University Paris Cité, Paris, France; Institut Pasteur, Icareb, Paris, France.
CHR d'Orléans, Service de Dermatologie, Orléans, France.
Clinique du Val d'ouest, Service de Chirurgie, Ecully, France.
CHU de Caen, Laboratoire de Microbiologie, Caen, France; Normandy University, Rouen, France.
University Paris Cité, Paris, France; Institut Pasteur, Centre Médical de l'Institut Pasteur, Paris, France. Electronic address: aude.nassif@pasteur.fr.
INSERM UMR1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; University Paris Cité, Paris, France; Department of Genomic Medicine of Rare Diseases, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
Clinical characteristics and genetic analysis of 14 patients affected with acne (A) fulminans and hidradenitis suppurativa (SH): ASH syndrome, a new phenotypic entity.
Obstructive sleep apnoea (OSA) is associated with hypertension, and OSA treatment can reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but with a modest mean effect size and vast heterogeneity among studies. The aim of this individual patient data (IPD) meta-analysis was to understand which OSA phenotypes could benefit the most in terms of BP reduction.A systematic review of randomised controlled trials that compared continuous positive airway pressure (CPAP) with either passive or active treatment was conducted. Studies were eligible if they included adult patients with OSA diagnosed by full polysomnography or cardiorespiratory polygraphy (defined as apnoea-hypopnoea index >5 events·h-1) and if BP was measured both before and after CPAP treatment.In total, 36 parallel studies (n=9434 patients) were included. CPAP treatment was associated with BP reduction in patients with uncontrolled office SBP only, while BP was not reduced by CPAP in patients with controlled BP (SBP -2.6 versus 0 mmHg; p<0.0001; DBP -1.7 versus -1 mmHg; p=0.091). Differences were seen also when BP changes were compared between patients aged ≤60 versus >60 years after multiple imputation only (p=0.0127 for SBP and p=0.017 for DBP). No differences were seen in terms of BP reduction when comparing patients with/without severe nocturnal hypoxia.This IPD meta-analysis of the BP effects of OSA treatment with CPAP shows that OSA patients with uncontrolled BP at baseline benefit the most from CPAP therapy in terms of BP reduction. These results have important implications for the decision on how to best manage arterial hypertension associated with OSA.
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Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano IRCCS, Milan, Italy m.pengo@auxologico.it.Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Department of Pulmonology and Sleep Disorders Centre, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Respiratory Department, Hospital Universitari Arnau de Vilanova - IRBLleida, Lleida, Spain.Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Charles Perkins Centre, University of Sydney, Sydney, Australia.Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, St Leonards, Australia.
Unidades de Hipertensão, Instituto do Coração (InCor) e Disciplina de Nefrologia, Universidade de São Paulo, São Paulo, Brazil.
Department of Medicine, University of Verona, Verona, Italy.
Division of Cardiology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Division of Respiratory Medicine, Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China.
Adelaide Institute for Sleep Health (AISH) and Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.Pneumology Department, Hospital Universitario Politécnico La Fe, Valencia, Spain.
Koc University School of Medicine, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Faculty of Medicine, Health and Human Sciences and Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Sydney, Australia.
Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
Biostatistic Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Faculty of Life Sciences and Medicine, King's College London, London, UK.
NIHR Biomedical Research Centre Oxford, University of Oxford, Oxford, UK.
Biostatistic Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy.Laboratory of Quantitative Methods for Life, Health and Society, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano IRCCS, Milan, Italy.Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Effect of CPAP therapy on blood pressure in patients with obstructive sleep apnoea: a worldwide individual patient data meta-analysis.
Division of Urology, San Luigi Gonzaga Hospital, Department of Oncology, University of Turin, Orbassano, Turin, Italy.
Division of Urology, San Luigi Gonzaga Hospital, Department of Oncology, University of Turin, Orbassano, Turin, Italy - sabrinatitti.decillis@gmail.com.
Department of Surgery, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.
Early prostatic artery control (EPAC) during robot-assisted radical prostatectomy: a new surgical technique aiming to improve early potency recovery.
University of Virginia School of Medicine, Charlottesville, Virginia. Electronic address: nef2gp@virginia.edu.
University of Virginia School of Medicine, Charlottesville, Virginia.
Department of Dermatology, University of Virginia, Charlottesville, Virginia.
Department of Plastic Surgery, University of Virginia, Charlottesville, Virginia.
Hidradenitis suppurativa diagnosis does not predispose patients to greater complication risk for body contouring surgery.
Department of Dermatology, Eastern Virginia Medical School, Macon & Joan Brock Virginia Health Sciences at Old Dominium University, Norfolk, Virginia.
Department of Trial Design & Optimization, TriNetX, LLC, Cambridge, Massachusetts.
Department of Dermatology, Eastern Virginia Medical School, Macon & Joan Brock Virginia Health Sciences at Old Dominium University, Norfolk, Virginia. Electronic address: enoscw@odu.edu.
Interleukin 23 inhibition associates with lower incidence of cardiovascular risk factor type diseases compared with biologic-naïve patients with psoriasis: A retrospective cohort study.
Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. aaron.johnston2@ucalgary.ca.
Department of Family Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Discipline of Emergency Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Letter to the Editor: The current state of emergency medicine is a long-term threat to EM residency training.
Yale School of Medicine, New Haven, Connecticut.
Department of Dermatology, Yale School of Medicine, New Haven, Connecticut.
Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Electronic address: sarika.ramachandran@yale.edu.
Enduring gaps in representation: A comprehensive reanalysis of skin of color in popular medical education materials.
Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, Massachusetts.
Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Department of Dermatology, Lahey Hospital & Medical Center, Burlington, Massachusetts; Department of Dermatology, Harvard Medical School, Boston, Massachusetts. Electronic address: Maryanne.M.Senna@lahey.org.
5α-reductase inhibitor exposure for dermatologic conditions does not increase the risk of female breast or gynecologic cancers: A population-based propensity score-matched cohort study.
Rutgers New Jersey Medical School, Newark, New Jersey.
Division of Nephrology, Maimonides Medical Center, Brooklyn, New York.
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Department of Dermatology, Weill Cornell Medicine, New York, New York. Electronic address: shl9032@med.cornell.edu.
Higher sodium excretion is not associated with increased odds of developing atopic dermatitis in a large retrospective cohort study.
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: scheinkman@med.miami.edu.
Department of Dermatology, CES University, Medellín, Colombia.
Department of Dermatology, Panamerican University, Mexico City, Mexico.
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida.
Determining the medical Spanish translation capabilities of three artificial intelligence translation models for Mohs micrographic surgical instructions.
Drexel University College of Medicine, Philadelphia, Pennsylvania. Electronic address: ana334@drexel.edu.
Drexel University College of Medicine, Philadelphia, Pennsylvania.
Department of Dermatology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
Incidence of rosacea associated with hormonal intrauterine devices: A comparative study with nonhormonal intrauterine devices.
Department of Dermatology, Stanford University School of Medicine, Stanford, California.
Department of Dermatology, Stanford University School of Medicine, Stanford, California. Electronic address: jljia@stanford.edu.
Department of Dermatology, University of California San Francisco, San Francisco, California.
From clinic to Capitol Hill: Dermatologists driving policy change.
Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: sheenyishuan@gmail.com.
Pretreatment neutrophil-to-lymphocyte ratio predicts survival in primary mucosal melanoma.
Department of Paediatrics, RCSI University of Medicine & Health Sciences, 123 St. Stephen's Green, Dublin, Ireland. Dermotwildes@rcsi.com.Department of Paediatric Nephrology, Children's Health Ireland, Dublin, Ireland. Dermotwildes@rcsi.com.
Department of Paediatrics, RCSI University of Medicine & Health Sciences, 123 St. Stephen's Green, Dublin, Ireland.Department of Paediatric Nephrology, Children's Health Ireland, Dublin, Ireland.
Department of Paediatric Nephrology, Children's Health Ireland, Dublin, Ireland.
Type IV-Collagen associated nephropathy-a form of nephrotic syndrome.
Department of Emergency Medicine, Queen's University, Kingston, ON, Canada. abhangu@qmed.ca.
Department of Medicine, Queen's University, Kingston, ON, Canada.
Department of Emergency Medicine, Queen's University, Kingston, ON, Canada.
Modern day scurvy in a patient with agoraphobia: A case report.
The objectives of this review were to comprehensively identify the best available qualitative evidence on parents' and guardians' experiences of barriers and facilitators in accessing autism spectrum disorder (ASD) diagnostic services for their children, and to develop recommendations based on the review for addressing barriers to timely diagnosis and early intervention.Early identification of ASD is a priority because the best chance for improving symptoms occurs through early and intensive intervention. A definitive ASD diagnosis is often a prerequisite for children to access publicly funded services, yet obtaining a diagnosis in itself can be stressful, frustrating, and time-consuming for many families. It is essential to understand the barriers and facilitators parents and guardians face in accessing ASD diagnostic services for their children.This qualitative systematic review considered studies conducted worldwide that included parents and guardians of children up to 18 years of age who had accessed or who were attempting to access ASD diagnostic services for their children.This review was conducted in accordance with the JBI methodology for systematic reviews of qualitative evidence. A literature search included CINAHL (EBSCOhost), CINAHL Plus (EBSCOhost), MEDLINE (EBSCOhost), APA PsycINFO (EBSCOhost), Social Services Abstracts (ProQuest), ERIC (EBSCOhost), and Embase. Gray literature sources included ProQuest Dissertations and Theses, Google Scholar, Google, OpenGrey, other online resources (government and organizational websites), and reference lists of retrieved records. No language, date, or country limits were applied to the searches. Retrieved records from the academic databases, gray literature, and reference lists of retrieved records were screened, with potentially relevant records examined in full against the inclusion criteria. Eligible studies were critically appraised for methodological quality, and those included in this review were subjected to data extraction of descriptive details and study findings relevant to the review question. Study findings were synthesized and assigned confidence scores. All reviewers agreed upon the categories and finalized synthesized findings.The 36 included studies varied in qualitative research designs and were assessed as having high methodological quality. There were 661 eligible participants, and 55 credible and unequivocal research findings were extracted. The research findings yielded 6 categories and 3 synthesized findings with moderate confidence scores. Parents' and guardians' ability to access ASD diagnostic services for their children is affected by i) encountering health care providers who actively listened to and addressed parents' and guardians' concerns instead of dismissing them, providing a sense of support and validation; ii) facing extended waiting times and associated financial burdens, resulting in frustration and associated financial impact when delays occurred; and iii) encountering health care providers lacking specialized knowledge about ASD, contributing to parents' and guardians' confusion due to inaccurate or conflicting diagnoses related to ASD comorbidities.Many parents described their journey in accessing ASD assessment and diagnostic services for their children as cumbersome. Parents' and guardians' experiences were affected by the level of perceived support by and knowledge of health care providers; confusion surrounding inaccurate/mixed diagnoses related to ASD, lengthy delays, and systemic and contextual barriers in navigating the pathway to ASD assessment and diagnosis that included socioeconomic and cultural disparities.PROSPERO CRD42018100127.
Faculty of Nursing, Memorial University, St. John's, NL, Canada.Memorial University Nursing Collaboration for Evidence-based Health Care: A JBI Affiliated Group, St. John's, NL, Canada.
Memorial University Nursing Collaboration for Evidence-based Health Care: A JBI Affiliated Group, St. John's, NL, Canada.Health Sciences Library, Memorial University, St. John's, NL, Canada.
Division of Pediatrics, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
Parents' and guardians' experiences of barriers and facilitators in accessing autism spectrum disorder diagnostic services for their children: a qualitative systematic review.
MD Program, Weill Cornell Medical College, New York, New York.
Gonadocorticoid exposure is associated with increased odds of lichen planopilaris and frontal fibrosing alopecia: A large retrospective cohort study.
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013 Paris, France; Neurocenter, Lucerne Cantonal Hospital, Unversity Teaching and Research Hospital, Lucerne, Switzerland. Electronic address: brigitte.kaufmann@luks.ch.
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013 Paris, France. Electronic address: paolo.bartolomeo@icm-institute.org.
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié-Salpêtrière, F-75013 Paris, France; Laboratory of Functional Neurosciences (UR UPJV 4559), University Hospital of Amiens and University of Picardie Jules Verne, Amiens, France.
Unveiling spatial and non-spatial aspects of neglect in everyday behavior.
Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 ( ccr5Δ32 ), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.
Division of Pathobiology and Immunology, Oregon National Primate Research Center.
Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York City, New York.
Division of Pathobiology and Immunology, Oregon National Primate Research Center.Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?
Enzyme replacement therapy (ERT) is the only approved disease-modifying treatment modality for Pompe disease, a rare, inherited metabolic disorder caused by a deficiency in the acid α-glucosidase (GAA) enzyme that catabolizes lysosomal glycogen. First-generation recombinant human GAA (rhGAA) ERT (alglucosidase alfa) can slow the progressive muscle degeneration characteristic of the disease. Still, most patients experience diminished efficacy over time, possibly because of poor uptake into target tissues. Next-generation ERTs aim to address this problem by increasing bis-phosphorylated high mannose (bis-M6P) N-glycans on rhGAA as these moieties have sufficiently high receptor binding affinity at the resultant low interstitial enzyme concentrations after dosing to drive uptake by the cation-independent mannose 6-phosphate receptor on target cells. However, some approaches introduce bis-M6P onto rhGAA via non-natural linkages that cannot be hydrolyzed by natural human enzymes and thus inhibit the endolysosomal glycan trimming necessary for complete enzyme activation after cell uptake. Furthermore, all rhGAA ERTs face potential inactivation during intravenous delivery (and subsequent non-productive clearance) as GAA is an acid hydrolase that is rapidly denatured in the near-neutral pH of the blood. One new therapy, cipaglucosidase alfa plus miglustat, is hypothesized to address these challenges by combining an enzyme enriched with naturally occurring bis-M6P N-glycans with a small-molecule stabilizer. Here, we investigate this hypothesis by analyzing published and new data related to the mechanism of action of the enzyme and stabilizer molecule. Based on an extensive collection of in vitro, preclinical, and clinical data, we conclude that cipaglucosidase alfa plus miglustat successfully addresses each of these challenges to offer meaningful advantages in terms of pharmacokinetic exposure, target-cell uptake, endolysosomal processing, and clinical benefit.
Copyright © 2024 Byrne, Parenti, Schoser, van der Ploeg, Do, Fox, Goldman, Johnson, Kang, Mehta, Mondick, Sheikh, Sitaraman Das, Tuske, Brudvig, Weimer and Mozaffar.
Department of Pediatrics in the College of Medicine, University of Florida, Gainesville, FL, United States.
Metabolic Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Friedrich-Baur-Institute, Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Erasmus MC University Medical Center, Rotterdam, Netherlands.
M6P-Therapeutics, St Louis, MO, United States.
Amicus Therapeutics, Inc., Princeton, NJ, United States.
Metrum Research Group, Tariffville, CT, United States.
Incyte Corporation, Wilmington, DE, United States.
Department of Neurology, University of California, Irvine, Irvine, CA, United States.
Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease.
Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs' safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20-30 minutes was deemed feasible; specific sequences are suggested.The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.
Department of radiology and nuclear medicine, Université Laval, Québec, QC, Canada.Quebec Heart and Lung Institute, Québec, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
Department of Medical Biophysics, Robarts Research Institute, University of Western Ontario, London, ON, Canada.
Division of Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada.Canadian Consortium on Neurodegeneration in Aging, Toronto, ON, Canada.
Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada.Canadian Consortium on Neurodegeneration in Aging, Toronto, ON, Canada.Baycrest Academy for Research and Education, Baycrest Health Sciences, Toronto, ON, Canada.
Department of Psychiatry, McGill University, Montreal, QC, Canada.Douglas Mental Health University Institute, Montreal, QC, Canada.
Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.Department of Psychiatry, McGill University, Montreal, QC, Canada.Douglas Mental Health University Institute, Montreal, QC, Canada.
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Recommendations on Imaging in the Context of Alzheimer's Disease-Modifying Therapies from the CCNA Imaging Workgroup.
Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina. Electronic address: pelin.sagut@gmail.com.
College of Medicine, California Northstate University College of Medicine, Elk Grove, California.
Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
Private Academic Consultant, Phonhong, Lao People's Democratic Republic.
University Centre for Research & Development Department of Pharmaceutical Sciences, Chandigarh University, Mohali, Punjab, India.
European journal of clinical investigation
Lung damage in SARS-CoV-2 patients: Correspondence.
Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia , Pennsylvania , USA.
Letter: The Rising Shift to Open Access Journals in Neurosurgery With Exuberant Fees: Challenges and Limitations.
Immunotherapy treatments that target programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) have revolutionized the treatment of metastatic melanoma and currently represent the standard first-line treatment for this type of cancer. However, it is still not entirely clear which biomarkers are cost-effective, simple, and highly reliable. This systematic review and meta-analysis aims to analyze the predictive value of the baseline neutrophil-lymphocyte ratio (NLR) regarding disease progression and overall survival of patients with metastatic melanoma undergoing treatment with PD-1/PD-L1 blockade. PubMed, Scopus, and Web of Science were searched for studies comparing high versus low NLR. We performed the meta-analysis using RStudio v4.4.2 software. A total of 20 studies and 2691 patients were included, all with diagnoses of melanoma. The majority of the individuals were male 2278 (84, 65%). The median overall survival (OS) and progression-free survival (PFS) ranged from 5.0 to 44.4 and from 1.8 to 15.0 months, respectively. Compared with the high NLR ratio, the low exposure group achieved better rates of OS [hazard ratio (HR), 2.07; 95% CI, 1.73-2.48; P < 0.00001; I ² = 47%]. Regarding PFS, there was a statistically significant difference between groups with tendencies toward the low NLR exposure group (HR, 1.59; 95% CI, 1.39-1.81; P < 0.00001; I²=31%]. This systematic review and meta-analysis revealed significant lower OS in melanoma patients treated with PD-1/PD-L1 blockade who had elevated baseline NLR values. Furthermore, an increased PFS was observed in patients with a lower baseline NLR value. This study highlights NLR as an important prognostic biomarker for patients with metastatic melanoma who are candidates for treatment with PD-1 and PD-L1.
Lutheran University of Brazil, Canoas, Rio Grande do Sul, Brazil.
Federal University of Pará, Belém, Brazil.
Federal University of Acre, Rio Branco, Acre, Brazil.
Federal University of Amazonas, Manaus, Amazonas, Brazil.
Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
Dante Pazzanese Institute of Cardiology, São Paulo, Brazil.
Association of baseline neutrophil-to-lymphocyte ratio and prognosis in melanoma patients treated with PD-1/PD-L1 blockade: a systematic review and meta-analysis.
The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group ( P < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression.
Dermatologie, Hôpital Saint-Louis AP-HP, Paris.
Dermatologie, CHU Dijon Bourgogne, Dijon.
Dermatologie, CHU de Montpellier, Montpellier.
Dermatologie, Hôpital Saint-André, Bordeaux.
Dermatologie, CHU de Grenoble Hôpital Sud Services des urgences, Échirolles.
Dermatologie, Centre hospitalier régional universitaire de Besançon, Besançon.
Dermatologie, Hôpital AP-HM Timone, Université Aix Marseille, Marseille.
Dermatologie, Hôpital Ambroise-Paré AP-HP, Boulogne-Billancourt.
Dermatologie, C.H. Annecy Genevois, Epagny Metz-Tessy.
Dermatologie, Hôpital Avicenne AP-HP, Bobigny.
Oncologie Médicale, Centre Eugène Marquis, Rennes.
Dermatologie, CHRU de Nancy - Hôpitaux de Brabois, Vandœuvre-lès-Nancy.
Soins palliatifs, CHU de Lille, Lille, France.
Real-life effectiveness on overall survival of continued immune checkpoint inhibition following progression in advanced melanoma: estimation from the Melbase cohort.
This systematic review aims to evaluate the prevalence of reductions in psychosocial wellbeing among patient with melanoma in situ (MIS). It also aims to identify factors associated with psychosocial reactions, the instruments used to measure psychosocial outcomes, and to evaluate existing intervention programs for supporting this population. Search strategies for different databases including PubMed, Embase, Scopus, PsycINFO, and Web of Science were designed and implemented. A total of 2378 records were identified, resulting in 22 included papers. Various aspects of psychosocial wellbeing were evaluated in the reviewed articles, with fear of cancer recurrence being the most frequently investigated among patients diagnosed with melanoma. Only 2 of the 22 studies reported data for MIS patients, indicating no significant difference in psychosocial welling between patients with MIS and those at higher stages. Regarding interventional support, there is a notable lack of interventions specifically addressing the psychosocial needs of MIS patients. Our findings highlight a significant research gap on psychosocial wellbeing following a MIS diagnosis and suggest a shortage of targeted psychosocial interventions for this growing patient population. The observed variability in measuring psychosocial aspects presents challenges in identifying the essential components of effective interventions. Future research should prioritize employing mixed methodologies and addressing the unique needs of MIS patients.
Dermatology Research Centre, Frazer Institute.
Centre for Health Services Research.Centre for Online Health, The University of Queensland, Brisbane, Queensland, Australia.
Psychosocial wellbeing in people with melanoma in-situ: a systematic review.
Nursing Department, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan City, Taiwan.
Department of Addiction Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan City, Taiwan.
Reducing mechanical restraint in emergency departments: International perspectives and Taiwan's experience.
Department of Biology, Blinn College, Bryan, Texas, USA.
Department of Medicine, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.School of Arts and Sciences, Rutgers University, New Brunswick, New Jersey, USA.
RE: The use and impact of pathology tests in emergency department patients with mental health-related complaints: A cross sectional study.
A major challenge is retention of complex clinical skills. Spacing training and testing have been demonstrated to increase knowledge and skill retention but the combination has not been previously investigated in complex clinical skills. The aim of our study was to compare the effectiveness of combined spacing and testing for Basic Life Support (BLS) and Advance Life Support (ALS) simulation training in one group (intervention group), with combined spacing and testing, and another group (control) that received simulation training in a single-session simulation training without testing.A quasi-experimental study.Thirteen nursing students were in the intervention group and 18 in the control group. After three months, there was no significant reduction in retention of BLS knowledge (p > 0.05) or BLS skills (p < 0.05) in the intervention group, but there was a significant reduction in both (p < 0.05) in the control group. We found no significant reduction in retention of ALS knowledge in the control group (p > 0.05), but there was a significant reduction in the intervention group (p < 0.05). There was no significant decay of ALS skills in both groups (p < 0.05).This is the first study to demonstrate that combined spacing and testing could be highly effective for complex skills simulation training to increase retention after three months.
School of Medical Sciences, University of Campinas, Campinas, Brazil.
School of Nursing, University of Campinas, Campinas, Brazil.
Health Research Institute, Edge Hill University, Ormskirk, UK.
School of Medical Sciences, University of Campinas, Campinas, Brazil.Institute of Medical Education Research Rotterdam, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands.
The importance of combined use of spacing and testing effects for complex skills training: A quasi-experimental study.
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are the first therapy shown to improve clinical outcomes for patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) greater than 40%. Nationwide adoption of SGLT2is in the US since publication of the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) in August 2021 is unknown.To examine trends and hospital-level variation in SGLT2i adoption.This cohort study included patients with LVEF greater than 40% who were hospitalized for decompensated HF at 1 of 557 sites in the US between July 1, 2021, and September 30, 2023, from the Get With The Guidelines-Heart Failure registry.Patient-level trends and site-level variation in prescription rates of SGLT2i at hospital discharge. Site-level variation was quantified using the median odds ratio, which describes the average odds that a patient being treated at one vs another randomly selected hospital would receive SGLT2i therapy at discharge.Of 158 849 patients (median [IQR] age, 76 [66-85] years; 89 816 females [56.5%]), 22 126 eligible patients (13.9%) with HF and an LVEF greater than 40% were prescribed an SGLT2i at hospital discharge. Quarterly prescription rates increased from 4.2% in July to September 2021 to 23.5% in July to September 2023 (P for trend < .001). SGLT2i prescription was more likely among patients with HF with mildly reduced LVEF (41%-49%) than in those with preserved LVEF (≥50%; 5127 of 27 712 patients [18.5%] vs 16 999 of 131 137 patients [13.0%]; absolute standardized difference, 16.7%). After adjustment for patient characteristics, there was a high variance between hospitals in the rate of SGLT2i prescription (median odds ratio, 2.12; 95% CI, 2.02-2.25). Among 518 hospitals with 10 or more eligible discharges, 11 hospitals (2.1%) discharged 50% or more of their patients with an SGLT2i prescription, while 232 (44.8%) discharged fewer than 10% of eligible patients with an SGLT2i prescription.For patients with HF and an LVEF greater than 40%, discharge prescription of SGLT2is increased from 4.2% to 23.5% during the first 2 years after the EMPEROR-Preserved trial demonstrating treatment benefits; however, these rates varied across US hospitals.
University of Missouri Kansas City's Healthcare Institute for Innovations in Quality, Kansas City.Saint Luke's Mid America Heart Institute, Kansas City, Missouri.
Duke Clinical Research Institute, Durham, North Carolina.
Duke Clinical Research Institute, Durham, North Carolina.Division of Cardiology, Duke University School of Medicine, Durham, North Carolina.
Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles, Los Angeles.Associate Section Editor, JAMA Cardiology.
Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor in Patients Hospitalized With Heart Failure With Mildly Reduced or Preserved Ejection Fraction.
Department of Neurosurgery, The People's Hospital of Jianyang City, Jianyang , China.
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing , China.
Letter: Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model.
PGY5 Emergency Medicine, University of Toronto, Pre-Hospital and Critical Care Transport Resident, Ornge, Toronto, ON, Canada. sparsh.shah@mail.utoronto.ca.
St Michael's Hospital, Ornge, Toronto, ON, Canada.
The role of partial resuscitative endovascular balloon occlusion of the aorta in pre-hospital trauma.
The aim of this review was to describe future options for long-acting HIV treatment and preexposure prophylaxis (PrEP) regimens featuring both innovations with currently approved antiretrovirals and a profile of investigational agents in the pipeline.Newer formulations and modes of delivery for existing antiretroviral drugs and a number of investigational agents are under study for long-acting HIV treatment and PrEP. Regimens with weekly oral dosing for HIV treatment, monthly oral dosing for HIV PrEP, and injectable agents with longer dosing intervals (every 3 months or longer) for treatment and PrEP are in clinical development. Newer agents with novel mechanisms of action and newer modes of administration including vaginal rings, implants, patches, and rectal douches also are under investigation.Despite the success of current antiretroviral therapy and PrEP with one-pill, once-daily regimens, there is a continuing need for new formulations, investigational agents, and novel modes of delivery to overcome barriers to implementation and ensure real-world effectiveness. Newer long-acting antiretroviral regimens for HIV treatment and PrEP using novel preparations and strategies will offer choice, enhance adherence, decrease toxicity, and improve patient and provider satisfaction.
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
Future options for long-acting HIV treatment and prevention.
Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT and discuss how our peer-mentoring cohort is removing hurdles for new faculty and advancing nuclear receptor biology.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.
Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Department of Population Sciences, Division of Health Equities, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
A Stronger IMPACT on Career Development for Early- and Mid-career Faculty.
Recent research on efficacy and safety of long-acting preexposure prophylaxis (PrEP) holds the promise to transform HIV prevention in high HIV burden settings. We review emerging findings regarding early end-user acceptability of long-acting PrEP modalities, feasibility of integrating long-acting PrEP into health systems, and considerations regarding drug resistance and cost.Long-acting PrEP, particularly injectables, was found to be highly acceptable among individuals across key populations in high HIV burden settings. Concerns around use of long-acting PrEP highlight the importance of choice and ability to switch methods. Existing provider-level barriers to oral PrEP implementation (e.g., overburdened staff, training gaps) may impact long-acting PrEP rollout - however, utilization of PrEP implementation strategies such as task-shifting, timely PrEP training for all providers, differentiated service delivery, and integration with sexual health services, may mitigate barriers. Studies modeling injectable PrEP scale-up demonstrate substantial benefits in HIV mortality reduction, outweighing risks of increased integrase inhibitor resistance, but also highlight the urgency of pricing long-acting PrEP to ensure access and affordability.Long-acting PrEP could be a game changer in HIV prevention in high burden settings. There is an urgent need for rapid scale production and price reductions to ensure access in high HIV burden settings. Implementation strategies are needed to address individual and provider-level barriers.
Division of Infectious Diseases, Geffen School of Medicine.Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, USA.Division of Epidemiology and Biostatistics, School of Public Health, University of Cape Town, South Africa.
Division of Epidemiology and Biostatistics, School of Public Health, University of Cape Town, South Africa.
Division of Infectious Diseases, Geffen School of Medicine.
Transforming HIV prevention: the promise of long-acting preexposure prophylaxis in high HIV burden settings.
Department of Paediatric Nephrology, Royal Manchester Children's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK. demetria.theodorou@mft.nhs.uk.
Department of Paediatric Nephrology, Royal Manchester Children's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK.
Weight of evidence: reevaluating BMI criteria as a barrier for kidney transplantation in children.
Division of Dermatology, Cooper Medical School of Rowan University, Camden, New Jersey. Electronic address: wrheymann@gmail.com.
Turning our attention to melanoma risk in turner syndrome.
Department of Dermatology, Center for Global Health, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, and Florida Center for Dermatology, St Augustine, Florida. Electronic address: jonkantor@gmail.com.
This Month in JAAD International: February 2025: Melanoma biopsy approaches in Australia and guidelines adherence.
Department of Dermatology and Dermatologic Surgery Medical University of South Carolina, Charleston, South Carolina. Electronic address: elstond@musc.edu.
Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01).Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.5 h followed by a 1-week washout and an oral dose of omadacycline 300 mg. The data were analyzed using noncompartmental PK.The maximum plasma concentration (Cmax) and area under the curve extrapolated to infinity (AUC0-∞) after intravenous administration of omadacycline were similar between healthy volunteers and people with CF. The absorption kinetics of oral omadacycline, encompassing both the rate (Cmax and time to Cmax [tmax]) and the extent (AUC0-∞), also showed consistency between healthy volunteers and people with CF. The absolute bioavailability of the oral tablet formulation of omadacycline in people with CF (31.2%) was also consistent with that observed in healthy volunteers (34.5%). In comparing the two routes of administration, intravenous omadacycline 100 mg provided plasma exposures equivalent to those with oral omadacycline 300 mg in people with CF, as evidenced by geometric mean ratios for both AUC0-∞ (0.9381; 90% confidence intervals [CI] 0.6783-1.2975) and Cmax (0.7746; 90% CI 0.5478-1.0951).Overall, the similarity in plasma PK observed in this study when comparing healthy volunteers and infected patients indicates that no dosing alterations are necessary when using omadacycline in people with CF.
Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
College of Pharmacy, CHA University, Seongnam-si, South Korea.
Division of Pulmonary and Clinical Care Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.Anton Yelchin CF Clinic, University of Southern California, Los Angeles, CA, USA.
Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA. beringer@usc.edu.Anton Yelchin CF Clinic, University of Southern California, Los Angeles, CA, USA. beringer@usc.edu.
Pharmacokinetics of Omadacycline in Adults with Cystic Fibrosis.
Division of Pediatric Nephrology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA, 94304, USA. shinam@stanford.edu.
Optimizing kidney health following pediatric liver transplantation: current challenges and future directions.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310003, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310003, China. Electronic address: huangxing66@zju.edu.cn.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310003, China. Electronic address: liangtingbo@zju.edu.cn.
mRNA vaccines for gastrointestinal malignancies: cutting-edge advances and future perspectives.
Cutaneous malignant melanoma (CMM) is one of the most aggressive and lethal types of skin cancer. Cytoskeletal remodeling is a key factor in the progression of CMM. Previous research has shown that activating transcription factor 3 (ATF3) inhibits metastasis in bladder cancer by regulating actin cytoskeleton remodeling through gelsolin. However, whether ATF3 plays a similar role in cytoskeletal remodeling in CMM cells remains unknown. Various gene and protein expression analyses were performed using techniques such as reverse transcription quantitative PCR, western blot, immunofluorescent staining, and immunohistochemical staining. CMM viability, migration, and invasion were examined through cell counting kit-8 and transwell assays. The interactions between cell division cycle 42 (CDC42) and ATF3 were investigated using chromatin immunoprecipitation and dual-luciferase reporter assays. CDC42 was upregulated in CMM tissues and cells. Cytoskeletal remodeling of CMM cells, as well as CMM cell proliferation, migration, and invasion, were inhibited by CDC42 or ATF3. ATF3 targeted the CDC42 promoter region to regulate its transcriptional activity. ATF3 suppresses cytoskeletal remodeling in CMM cells, thereby inhibiting CMM progression and metastasis through CDC42. This research may provide a foundation for using ATF3 as a therapeutic target for CMM.
Department of Dermatology, Affiliated Hospital of Hebei Engineering University.
Department of Stomatology, Handan First Hospital.
Medical Cosmetic Center, Affiliated Hospital of Hebei Engineering University, Handan City, Hebei Province, China.
ATF3 regulates CDC42 transcription and influences cytoskeleton remodeling, thus inhibiting the proliferation, migration and invasion of malignant skin melanoma cells.
National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: weiwq@cicams.ac.cn.
Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: lining@cicams.ac.cn.
Rare tumor list provide vast opportunities for novel drug development in China.
Département de phytologie, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, Québec City, QC, Canada.Centre de recherche et d'innovation sur les végétaux, Université Laval, Québec City, QC, Canada.Institute de Biologie Intégrative et des Systèmes, Université Laval, Québec City, QC, Canada.L'Institute EDS, Université Laval, Québec City, QC, Canada.
Biochemistry and cell biology = Biochimie et biologie cellulaire
Artificial intelligence in academia: opportunities, challenges, and ethical considerations.
One of the challenges of evidence-based medicine is balancing population-level findings with individualized care. Average treatment effect studies, including cohort studies and randomized controlled trials, offer insights into factors affecting disease likelihood at group level or subgroup level (precision medicine), but are limited in predicting individual outcomes. This limitation arises because average treatment effect studies operate within a probabilistic causal framework, indicating how likely a disease is when a certain individual or contextual factor is present: if X, then probably Y.
Copyright © 2025. Published by Elsevier Inc.
Rotterdam School of Management, Erasmus University Rotterdam, Rotterdam, the Netherlands. Electronic address: jdul@rsm.nl.
Journal of the American Academy of Child and Adolescent Psychiatry
J Am Acad Child Adolesc Psychiatry. 2024-11-29;():.
Editorial: Identifying the Perfect Predictor of Absence of Disease: A Shift Toward Necessary Condition Analysis in Evidence-Based Medicine?
College of Life Sciences, Capital Normal University, Beijing 100048, China.
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China.
College of Life Sciences, Capital Normal University, Beijing 100048, China; Department of Paleobiology, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013, USA; Department of Entomology, University of Maryland, College Park, MD 20742, USA.
College of Life Sciences, Capital Normal University, Beijing 100048, China; Department of Paleobiology, National Museum of Natural History, Smithsonian Institution, Washington, DC 20013, USA.
School of Earth Sciences and Engineering, Guangdong Provincial Key Lab of Geological Processes and Mineral Resources, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: shichf5@mail.sysu.edu.cn.
College of Life Sciences, Capital Normal University, Beijing 100048, China. Electronic address: rendong@mail.cnu.edu.cn.
Reconstructing fossil insect communities and palaeoclimates for the Middle Jurassic Yanliao Biota in the Daohugou area of China.
To evaluate the midterm survival, clinical, and hemodynamic outcomes of the On-X mechanical mitral valve, based on the 5-year results of the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT).PROACT Mitral was a multicenter study evaluating 401 patients who underwent mitral valve replacement (MVR) with either Standard or Conform-X On-X mitral valves, comparing low-dose and standard-dose warfarin. Here we report prespecified secondary outcomes of survival, New York Heart Association (NYHA) functional classification, and valve hemodynamics as assessed by core lab-adjudicated echocardiography at 1, 3, and 5 years in the pooled population.Actuarial survival was 99.7% at 1 year, 95.1% at 3 years, and 92.4% at 5 years, with no significant difference between the Standard and Conform-X cuffs. Hemodynamic analysis revealed a mean transvalvular pressure gradient (MG) of 4.6 ± 2.0 mm Hg at 1 year, with no interaction between valve size and patient body surface area. MG values were consistent over time. Quality of life improved with 96.6% of patients in NYHA class I or II at the latest available follow-up of 3 or 5 years. There were no significant differences in survival, clinical, or hemodynamic outcomes between valve sizes.The On-X mechanical mitral valve demonstrated favorable survival, stable hemodynamics, and enhanced quality of life up to 5 years postimplantation. Derived from high-quality, rigorous randomized trial data, these findings can guide decision making in young patients requiring MVR.
Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: mruel@ottawaheart.ca.
Division of Cardiac Surgery, London Health Sciences Centre, Western University, London, Ontario, Canada.
Cardiothoracic Division, MultiCare Health System, Tacoma, Wash.
Department of Cardiovascular and Thoracic Surgery, Franciscan St Francis Health, Indianapolis, Ind.
Department of Surgery, Washington University SL, St. Louis, Mo.
Robotic Cardiac Surgery, The Heart Hospital Baylor Plano, Plano, Tex.
Division of Cardiothoracic Surgery, Emory University Hospital Midtown, Atlanta, Ga.
Department of Cardiovascular and Thoracic Surgery, UT Southwestern Medical Center, Dallas, Tex.
Department of Cardiac Surgery, Hartford Hospital, Hartford, Conn.
Department of Cardiac Services, Maine Medical Center, Portland, Maine.
Division of Cardiothoracic Surgery, University of Arizona, Tucson Heart Center, Tucson, Ariz.
Department of Cardiovascular and Thoracic Surgery, Loma Linda University Medical Center, Loma Linda, Calif.
Sentara Health Research Center, Sentara Norfolk General Hospital, Norfolk, Va.
Cardiovascular and Thoracic Surgery, St Joseph Mercy Hospital, Ann Arbor, Mich.
Cardiovascular Surgery, Florida Hospital, Orlando, Fla.
Department of Cardiac Surgery, Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada.
Heart & Vascular Institute, University Hospitals-Cleveland, Cleveland, Ohio.
Division of Cardiovascular Surgery, St Paul's and Vancouver General Hospital, Vancouver, British Columbia, Canada.
Division of Cardiothoracic Surgery, University of Kentucky, Lexington, Ky.
Department of Cardiology, Southern Arizona VA Medical Center, Tucson, Ariz.
Cardiovascular and Thoracic Surgery, Novant Clinical Research Institute, Winston-Salem, NC.
Department of Cardiac Surgery, NYU Langone Hospitals, New York, NY.
Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Okla.
Division of Cardiothoracic Surgery, Montefiore Medical Center, Bronx, NY.
Cardiac Surgery, Swedish Medical Center, Seattle, Wash.
Division of Cardiology, Duke Clinical Research Institute, Duke University, Durham, NC.
Division of Cardiothoracic Surgery, Mount Sinai Saint Luke's, New York, NY.
The Journal of thoracic and cardiovascular surgery
J Thorac Cardiovasc Surg. 2024-11-29;():.
Midterm survival, clinical, and hemodynamic outcomes of a novel mechanical mitral valve prosthesis.
Background Salmonella Typhi (S. Typhi) is increasingly resistant to multiple antibiotics, posing a challenge in treatment, particularly in multidrug-resistant (MDR) cases. Carbapenems, including doripenem, ertapenem, and meropenem, have been considered last-resort options. This study evaluates the effectiveness of these carbapenems against S. Typhi isolates in a clinical setting in Peshawar, Pakistan. Objective To assess the effectiveness of the carbapenem antibiotics, doripenem, ertapenem, and meropenem, against S. Typhi. Methods This study collected data from blood cultures of patients diagnosed with S. Typhi infections at the Hayatabad Medical Complex in Peshawar, Pakistan for two years: from January 1, 2022, to December 31, 2023. Sensitivity testing was performed using the disk diffusion method in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. The analysis examined the sensitivity rates of the three antibiotics and compared their effectiveness. Results A total of 626 S. Typhi isolates were tested. Only 11.98% of the isolates were sensitive to doripenem, while 88.02% were resistant to it. In contrast, 35.5% of the isolates responded to ertapenem, with 64.5% being resistant. Meropenem showed the highest efficacy, with 42.7% of the isolates demonstrating sensitivity. These findings highlight the growing challenge of managing multidrug-resistant (MDR) S. Typhi infections, especially in regions where resistance to carbapenems is becoming prevalent. Conclusion Meropenem proved to be more effective against S. Typhi compared to doripenem and ertapenem. The study emphasizes the need for ongoing monitoring of resistance patterns and the exploration of alternative or combination treatment options. These findings have immediate clinical implications for empiric therapy choices and highlight the urgent need for antibiotic stewardship programs in endemic regions.
Department of Medicine, Medical Teaching Institution (MTI) Hayatabad Medical Complex, Peshawar, PAK.
Department of Internal Medicine, Hayatabad Medical Complex, Peshawar, PAK.
Department of Medicine, Hayatabad Medical Complex, Peshawar, PAK.
Department of Pathology, Khyber Girls Medical College, Peshawar, PAK.Department of Microbiology, Hayatabad Medical Complex, Peshawar, PAK.
Department of Pharmacy, Hayatabad Medical Complex, Peshawar, PAK.
Doripenem, Ertapenem, and Meropenem Sensitivity in Salmonella Typhi: A Cross-Sectional Study From Pakistan.
The immunonutritional status of cancer patients has a profound impact on lifespan. Prognostic Nutritional Index (PNI) evaluates prognosis in operated patients with both neoplastic and non-neoplastic conditions. This study estimates the overall survival (OS) of Mexican patients operated on gastrointestinal stromal tumors (GIST) based on PNI.Immune-nutritional status was retrospectively analyzed in a cohort of 104 patients operated on GIST. Receiver operating characteristic (ROC) curves and X-tile software were used to estimate the optimal cutoff point and predict OS stratifying patients by PNI. Survival curves were obtained through Kaplan-Meier and log-rank methods. Multivariate analysis of survival was performed by Cox regression.PNI (≥ 36.5) (p = 0.024) and mitotic index (≥ 5) (p = 0.013) were the only independent prognostic scores; the PNI-high group had better survival with 81.5% less risk of death (HR = 0.185). High PNI was correlated with favorable characteristics, i.e., low/intermediate risk (p = 0.046), reduced mitotic index (< 5) (p = 0.001), and younger age (< 55 years, p = 0.047).PNI ≥ 36.5 entails a better prognosis for Mexican patients with surgically resected GIST. PNI represents a simple, reliable, and cost-effective prognostic tool, besides the pathological approach.
Department of Pathology, Instituto Nacional de Cancerología, Av. San Fernando 22, Col. Sección XVI, Tlalpan, 14080, Ciudad de México, Mexico. rhgoepfert@gmail.com.
Oncological Diseases Research Unit (UIEO), Hospital Infantil de México Federico Gómez (HIMFG), Mexico City, Mexico.
Clinical Research Division, Instituto Nacional de Cancerología, Mexico City, Mexico.
Basic Research Division, Instituto Nacional de Cancerología, Mexico City, Mexico.
Laboratory of Translational Cardiology, Research Unit UNAM-INC, Instituto Nacional de Cardiología, Mexico City, Mexico.
Emergency Department, Instituto Nacional de Neurología y Neurocirugía Dr. Manuel Velasco Suárez , Mexico City, Mexico.Internal Medicine Division, Hospital General Dr. Manuel Gea González, Mexico City, Mexico.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Prognostic Nutritional Index is a valuable preoperative prognostic biomarker in Mexican patients surgically intervened on gastrointestinal stromal tumors: a retrospective cohort study.
This randomized controlled study was conducted to analyze the effect of hand massage on the fatigue level of the women receiving brachytherapy.It was determined that 12 patients were included in each group (control and hand massage group), so 24 women with gynecologic cancer were included in the study. The application was performed on each hand for 5 min, a total of 10 min in hand massage group. Hand massage was applied before each brachytherapy (at the first, second, and third sessions, a total of three times) every other day for 1 week in the hand massage group. No intervention was performed to the control group during the study. The data were collected using the Patient Information Form and Brief Fatigue Inventory (BFI).At the end of the brachytherapy, the fatigue severity score and impact of fatigue on activities of daily living scores of the group that applied hand massage were determined to be lower than the control group (p < 0.05).It was determined that hand massage effectively controlled fatigue and the impact of fatigue on activities of daily living. Hand massage is a safe and economical method that can be performed by certified nurses.This clinical trial is registered at ClinicalTrials.gov (NCT06056713-09/21/2023).
Halil Bayraktar Health Services Vocational College, Erciyes University, Kayseri, Turkey. dilekea@erciyes.edu.tr.
Faculty of Health Sciences, University of Bakırçay, İzmir, Turkey.
Department of Radiation Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
The effect of hand massage on fatigue in women with cancer receiving brachytherapy: randomized clinical trial.
Drug-resistant tuberculosis infections are a major threat to global public health. The essential mycobacterial ClpC1P1P2 protease has received attention as a prospective target for novel antibacterial therapeutics. However, efforts to probe its function in cells are constrained by our limited knowledge of its physiological proteolytic repertoire. Here, we interrogate the role of mycobacterial ClpS in directing N-degron pathway proteolysis by ClpC1P1P2 in Mycolicibacterium smegmatis. Binding assays demonstrate that mycobacterial ClpS binds canonical primary destabilizing residues (Leu, Phe, Tyr, Trp) with moderate affinity. N-degron binding restricts the conformational flexibility of a loop adjacent to the ClpS N-degron binding pocket and strengthens ClpS•ClpC1 binding affinity ~30-fold, providing a mechanism for cells to prioritize N-degron proteolysis when substrates are abundant. Proteolytic reporter assays in M. smegmatis confirm degradation of substrates bearing primary N-degrons, but suggest that secondary N-degrons are absent in mycobacteria. This work expands our understanding of the mycobacterial N-degron pathway and identifies ClpS as a critical component for substrate specificity, providing insights that may support the development of improved Clp protease inhibitors.
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware, USA.
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware, USA.
ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis.
Cyanobacteria developed oxygenic photosynthesis and represent the phylogenetic ancestors of chloroplasts. The model strain Anabaena sp. strain PCC 7120 grows as filaments of communicating cells and can form heterocysts, cells specialized for N2 fixation. In the Anabaena genome, ORF all2390 is annotated as encoding a SulA homolog, but sequence similarity to SulA of model bacteria is insignificant. We generated strains that lacked or overexpressed all2390, both of which showed instances of increased cell size, and observed that purified All2390 protein interfered with the in vitro polymerization of FtsZ. Heterocyst frequency diminished by all2390 inactivation and increased by all2390 overexpression. Overexpression retarded the dismantlement of Z-ring structures that determines commitment in the differentiating cells. Thus, All2390 can influence cell division affecting heterocyst differentiation. An All2390-GFP fusion protein localized to the thylakoid membranes including the honeycomb membranes, which harbor photosynthetic complexes, in the heterocyst polar regions. Notably, all2390 expression strongly increased under high light, conditions under which growth of the null mutant is compromised. Thus, All2390 appears essential for adaptation to high light conditions. We named All2390 ThyD to reflect its thylakoidal localization and its dual role in cell division dynamics and acclimation of thylakoid membranes to increased light intensity.
© 2024 The Author(s). Molecular Microbiology published by John Wiley & Sons Ltd.
Instituto de Bioquímica Vegetal y Fotosíntesis, CSIC and Universidad de Sevilla, Seville, Spain.
ThyD Is a Thylakoid Membrane Protein Influencing Cell Division and Acclimation to High Light in the Multicellular Cyanobacterium Anabaena sp. Strain PCC 7120.
The benefit of patient-reported outcomes (PRO) in routine oncology practice is increasingly recognized. This study aimed to develop a team-based monitoring and intervention system using electronic PRO (ePRO) and to evaluate its impact at an outpatient oncology clinic.Patients receiving chemotherapy at our department were eligible for this study. Those who had access to a smartphone or tablet (Bring Your Own Device [BYOD]) and consented participated, and reported 28 symptoms weekly via 3H P-guardian downloaded on their BYOD. E-mail alerts were sent to attending healthcare providers when participants reported at least grade 3 severity for any of nine symptoms (decreased appetite, nausea, vomiting, diarrhea, shortness of breath, pain, insomnia, fatigue, and sadness), which prompted interventions. Comparisons of overall survival (OS), emergency room visits, and hospitalizations were conducted using propensity scores.Among 203 patients who received chemotherapy from September 2021 to August 2023, 77 participated in ePRO monitoring. The overall response rate was 55% (1991 valid responses out of a total of 3597 expected time points), and the median individual response rate was 66% (range, 0-100%). Of 1991 valid responses, 250 (13%) prompted alerts, and most interventions were initiated by making telephone calls. OS and other clinical outcomes were better in ePRO participants compared with non-participants, but these outcomes did not differ significantly between the ePRO and pre-ePRO eras.It was feasible to develop a multi-professional team-based monitoring and intervention system using ePRO at a single-center outpatient oncology clinic. Our results indicate that weekly monitoring of ePRO, along with corresponding interventions, may benefit patients receiving chemotherapy.
Department of Oncology, Ina Central Hospital, 1313-1 Koshiro-Kubo, Ina, Nagano, 396-8555, Japan. skurosaw@inahp.jp.
Nursing Division, Ina Central Hospital, Ina, Japan.
Pharmaceutical Division, Ina Central Hospital, Ina, Japan.
Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Oncology, Ina Central Hospital, 1313-1 Koshiro-Kubo, Ina, Nagano, 396-8555, Japan.
Feasibility and usefulness of symptom monitoring with electronic patient-reported outcomes: an experience at single-center outpatient oncology clinic.
Vulvar and vaginal melanomas (VVMs) are rare malignancies, but they are relatively more common among Asian women. This makes the collection of data on VVMs in this population crucial. Moreover, no cohort studies have examined and compared the effects of immune checkpoint inhibitors (ICIs) on VVM in Asian women. Therefore, we aimed to investigate the clinical characteristics of VVMs in Japanese women and the effects of ICI treatment. This single-center, retrospective cohort study included patients who were histologically diagnosed with VVM at our hospital between March 2005 and December 2023. The Kaplan-Meier analysis was used to compare the prognosis of vulvar melanoma (VuM) and vaginal melanoma (VaM) throughout entire treatments and compare the efficacies of ICIs and conventional chemotherapies in VVM. In total, 28 women with VuM ( n = 14) and VaM ( n = 14) were included. There were no significant differences in overall survival (OS) [median OS: not reached (95% confidence interval (CI), 13.2-NA) vs. 30.2 months (95% CI, 23.2-NA), log-rank test, P = 0.456] between the VuM and VaM groups. The progression-free survival (median progression-free survival: 14.7 vs. 5.2 months, P = 0.002) and OS (median OS: 33.8 vs. 7.2 months, P < 0.001) were significantly better for the ICI-treated group than for the conventional chemotherapy-treated group in VVM. The prognosis of patients with VVM improved significantly with the advent of ICI, demonstrating the importance of ICI in the treatment of VVM.
Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
Clinical features of vulvar and vaginal malignant melanomas and the effects of immune checkpoint inhibitors in Japanese patients: a single-center, retrospective cohort study.
Center for AIDS Research, University of California, San Francisco (UCSF), San Francisco, California, USA.
Long-acting ART and preexposure prophylaxis: profound promise but stunted access.
This qualitative study aims to deeply understand the emotional experiences of mutuality relationships between lung cancer patients undergoing chemotherapy and their caregivers, providing insights for developing cancer-related mutuality interventions.Using a qualitative research method with semi-structured interviews, 15 pairs of patients and their caregivers from the Department of Respiratory Medicine at the Affiliated People's Hospital of Xuzhou Medical University were selected as subjects. Data were qualitatively and inductively analyzed using Braun and Clarke's thematic analysis method.Five themes and fourteen sub-themes were extracted from the experiences and interactions between patients and caregivers: reciprocity and mutual support (support provided by patients to caregivers, support provided by caregivers to patients), challenges (lack of communication, difficulty in adaptation, role changes, economic burdens), change and adaptation (living with the disease, social support), negative outcomes (increased burden on caregivers, disruption of social activities and family relationships), and intervention needs (need for disease knowledge, humanistic care, communication skills).The findings of this study provide healthcare professionals with information on the mutual support and challenges faced by chemotherapy patients and their caregivers in coping with cancer. This information aims to facilitate culturally-based psychological interventions, enhance mutuality, improve quality of life, and promote the entire family's adaptation to the disease.
Xuzhou Medical University, Xuzhou, China.
Xuzhou Medical University, Xuzhou, China. 13372225241@163.com.
Experiences of mutuality between Chinese lung cancer patients and family caregivers during chemotherapy: a qualitative study.
Decoding the HIV-1 immune response, including its humoral arm, in post-treatment controllers (PTCs) is paramount to unveil immune correlates of viral control, which could help developing novel strategies towards HIV-1 remission. Here, we review novel findings on the humoral response to HIV-1 in PTCs.New data reveal the heterogeneity of humoral immune profiles in PTCs, principally influenced by viral exposure and dynamics. Stably aviremic PTCs, akin early ART-treated individuals, show minimal antibody B-cell response. Conversely, virally exposed PTCs develop functionally coordinated and effective humoral responses to HIV-1. They can produce antibodies cross-neutralizing heterologous HIV-1 viruses, including broadly neutralizing antibodies (bNAbs) exerting selective immune pressure. PTCs also elicit neutralizing antibodies against contemporaneous autologous viruses presumed to play a major role in sustaining viral suppression.The immune mechanisms underlying virologic control in PTCs likely involve various immune effectors. Notably, functional HIV-1 humoral responses can generate bNAbs and autologous neutralizing antibodies; however, their exact contribution to maintaining long-term control of plasma viremia and the precise mechanisms driving their induction require further investigation.
Institut Pasteur, Université Paris Cité, Humoral Immunology Unit, Paris, France.
Humoral immunity in HIV-1 post-treatment controllers.
Several new intervention strategies have shown significant improvements over antiretroviral therapy (ART) in eliciting lasting posttreatment control (PTC) of HIV-1. Advances in mathematical modelling have offered mechanistic insights into PTC and the workings of these interventions. We review these advances.Broadly neutralizing antibody (bNAb)-based therapies have shown large increases over ART in the frequency and the duration of PTC elicited. Early viral dynamics models of PTC with ART have been advanced to elucidate the underlying mechanisms, including the role of CD8+ T cells. These models characterize PTC as an alternative set-point, with low viral load, and predict routes to achieving it. Large-scale omic datasets have offered new insights into viral and host factors associated with PTC. Correspondingly, new classes of models, including those using learning techniques, have helped exploit these datasets and deduce causal links underlying the associations. Models have also offered insights into therapies that either target the proviral reservoir, modulate immune responses, or both, assessing their translatability.Advances in mathematical modeling have helped better characterize PTC, elucidated and quantified mechanisms with which interventions elicit it, and informed translational efforts.
Department of Chemical Engineering, Indian Institute of Science, Bengaluru, India.
Université Paris Cité, Inserm, IAME, Paris, France.
Department of Chemical Engineering, Indian Institute of Science, Bengaluru, India.Department of Bioengineering, Indian Institute of Science, Bengaluru, India.
Advances in the mathematical modeling of posttreatment control of HIV-1.
Human Movement Science, Faculty of Sport Science, Ruhr University Bochum, Bochum, Germany; School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Australia. Electronic address: daniel.hahn@rub.de.
Department of Rehabilitation & Prevention Engineering, Institute of Applied Medical Engineering, RWTH Aachen University, Aachen, Germany.
Centre of Precision Rehabilitation for Spinal Pain, School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
Department of Bioengineering, Imperial College London, London, UK.
Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology
J Electromyogr Kinesiol. 2025-02;80():102963.
The unprecedented progresses in neuromechanics over the past 50 years - In celebration of the 50th anniversary of the international society of biomechanics.
High-temperature carbonization typically used in the preparation of advanced electrocatalysts poses significant challenges in preserving abundant functional groups essential for reactant adsorption and component stabilization. To address this, a solvothermal synthesis followed by non-carbonization annealing approach is proposed to fabricate a series of cobalt-based organic-inorganic hybrids derived from cobalt-based glycerate nanospheres (GNs). Notably, annealing in phosphorous and inert atmospheres preserves the solid nanospherical structure, whereas treatment in sulfur-rich environments results in the formation of hollowed nanospheres. Among these hybrids, phosphorized solid cobalt GNs (Co-P-GNs) exhibit the highest catalytic activity for hydrogen evolution reaction (HER), achieving a low overpotential of 152 mV at 10 mA cm-2. Meanwhile, sulfurized hollow cobalt-iron GNs (Co-Fe-S-HGNs) demonstrate good performance in catalyzing oxygen evolution reaction (OER), with a low overpotential of 273 mV at 10 mA cm-2. Both catalysts exhibit robust stability and maintain 100 % Faradaic efficiency during operation in electrolyzers for water splitting. The high performance not only stems from the well-dispersed phosphide and sulfide crystallites, offering ample catalytic active sites; but also benefits from the partially thermolyzed organic matrix enriched with heteroatoms and functional groups, which facilitates ion adsorption to initiate the reactions and tightly clenches loaded components to stabilize the active species.
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China.
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China. Electronic address: guoxm@just.edu.cn.
Key Laboratory of Advanced Electrode Materials for Novel Solar Cells for Petroleum and Chemical Industry of China, School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou, Jiangsu 215009, China. Electronic address: lichsheng@163.com.
School of the Environmental and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China. Electronic address: jhzhang6@just.edu.cn.
Journal of colloid and interface science
Non-carbonization annealing toward regulation of cobalt-based organic-inorganic hybrids as advanced electrocatalysts for water splitting.
Department of Neurosurgery, Central Medical College and Hospital, Cumilla , Bangladesh.
Department of Neurosurgery, Holy Family Red Crescent Medical College, Dhaka , Bangladesh.
Letter: Angiographic Features of Meningiomas Predicting Extent of Preoperative Embolization.
Parents' supportive care needs directly affect their quality of life and the quality of care for their children diagnosed with leukemia.To identify supportive care needs of Chinese parents in the unobserved subgroups who care for children with leukemia and to examine the associations of the latent class membership with individual characteristics.A multicenter cross-sectional survey study was conducted. A total of 221 parents who had children with leukemia were surveyed in China with the Chinese version of the Supportive Care Needs Survey for Caregivers of Children with Pediatric Cancer (SCNS-C-Ped-C). Latent profile analysis (LPA) was applied to identify latent classes of parents according to supportive care needs. Binary logistic regression model was used to identify the association between individual characteristics and the latent class membership.LPA results suggested a 2-class solution: class 1- high supportive care needs class (n = 126, 57.0%) and class 2- low supportive care needs class (n = 95, 43.0%). The class membership was significantly associated with children's treatment duration, family income, distance to the hospital, parents' caregiving ability, and coping strategy.There existed two distinct classes of parents caring for children with leukemia on the basis of supportive care needs. Children's treatment duration, parents' socio-demographic characteristics, caregiving ability, and coping strategy significantly influenced class membership.This study highlights the need for tailored interventions to address the specific needs of parents, especially those in the high supportive care needs class. Healthcare providers should consider factors related to the class membership when developing the supportive care interventions. Addressing these supportive care needs could improve both parental well-being and the quality of care provided to their children.
School of Nursing, Naval Medical University, Shanghai, China.
School of Nursing, Fudan University, 305 Fenglin Road, Shanghai, 200032, China.
Department of Nursing, Children's Hospital of Fudan University, Shanghai, China.
Department of Hematology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Hematology, Children's Hospital of Chongqing Medical University, Chongqing, China.
School of Nursing, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong District, Shanghai, 201203, China. gengzh200890@163.com.
School of Nursing, Fudan University, 305 Fenglin Road, Shanghai, 200032, China. yuancr@fudan.edu.cn.
Supportive care needs of parents caring for children with leukemia: a latent profile analysis.
The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both in vivo and in vitro. In bovine pulmonary artery endothelial cells, UPR suppression counteracted the protective effects of GHRHAnt in lipopolysaccharide (LPS)-induced endothelial hyperpermeability. In mouse lungs, UPR activation enhanced the beneficial effects of GHRHAnt against LPS-induced acute lung injury. Our observations - which are focused on lung endothelial cells and tissues - enhance our knowledge on the mechanisms mediating the barrier function and contribute to the development of novel therapies toward sepsis, direct and indirect lung injury. The effects of UPR modulation on the effects of GHRHAnt in other tissues are unknown, and they are the subject of future investigations.
School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana, USA.
Department of Clinical Endocrinology, Medical University of Lodz, Lodz, Poland.
Unfolded protein response modulates the effects of GHRH antagonists in experimental models of in vivo and in vitro lung injury.
Radiation therapy can cause acute and long-term side effects despite advances in treatment delivery techniques. While significant research has been conducted to prevent the occurrence of toxicity, there is a need for evidence-based supportive care measures to manage radiation side effects. This analysis aims to examine the current state of supportive care trials in radiation oncology and identify areas that require further study.A Clinicaltrials.gov search was conducted using the term radiation toxicity to identify registered trials with a primary endpoint of toxicity management. These studies were further classified as supportive care interventions or toxicity prevention. Study details were evaluated for all supportive care trials.Of the thirty-eight supportive care trials identified, most were observational/uncategorized (50%), in phase III (28.9%), or phase II (13.2%). Head and neck (42.1%), genitourinary (18.4%), and breast (13.2%) were the most studied disease sites. Xerostomia (23.7%), mucositis (18.4%), and dermatitis (18.4%) were the most evaluated toxicities. Medication-based (28.9%), procedures (28.9%), and topical agents (21.1%) were the most common interventions. Thirty-two studies included patient-reported outcomes (PROs; 84.2%), of which seventeen trials (53.1%) had PROs as a primary endpoint.Only a small portion of supportive care trials generate high-level evidence to evaluate interventions with patient-reported endpoints. More supportive care trials are needed to effectively manage radiation toxicities and promote compliance and long-term quality of life during and after radiation therapy. Increased funding from government and industry sponsors is required to support this research.
Albany Medical College, 50 New Scotland Avenue, MC-41, Albany, NY, 12208, USA. wint2@amc.edu.
Department of Radiation Oncology, University of Cincinnati, 3151 Bellevue Ave., ML 0757, Cincinnati, OH, 45267, USA.
Department of Radiation Oncology, University of Cincinnati, 3151 Bellevue Ave., ML 0757, Cincinnati, OH, 45267, USA. frankaaj@ucmail.uc.edu.
Evaluation of clinical trials addressing supportive care measures for management of acute and chronic radiation toxicities.
Department of Medicine, Federal University of Mato Grosso, Sinop , Mato Grosso , Brazil.
Department of Medicine, Universidade do Extremo Sul Catarinense, Criciúma , Santa Catarina , Brazil.
School of Medicine, Federal University of Ceará, Sobral , Ceará , Brazil.
Department of Internal Medicine, Mandaqui Medical Complex, São Paulo , São Paulo , Brazil.
Department of Medicine, Sciences Medical School of Santos, Santos , São Paulo , Brazil.
Department of Neurosurgery, São Lucas Hospital, Juína , Mato Grosso , Brazil.
Department of Occupational Medicine, Kaiser Permanente, Los Angeles , California , USA.
In Reply: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.
Department of Anesthesiology, Hospital Fundación Santa Fe de Bogotá, Bogotá , Colombia.
Letter: Hypertonic Saline Solution Versus Mannitol for Brain Relaxation During Craniotomies: A Systematic Review and Updated Meta-Analysis.
Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100 mg/m2 given once every 3 weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer. The treatment dramatically influenced every clinical and laboratory parameter, especially regarding nutritional status despite a high protein intake. In terms of medium eGFR decay, chemoradiotherapy reduced the renal function of about 8 ml/min/1.73m2 in 6 weeks, harboring some cases of mild acute kidney injury and acute kidney disease. Furthermore, patients with eGFR < 60 mL/min/1.73m2 pre-treatment were just 3 (5%), becoming 5 (8.3%) at the end despite the high-protein diet implemented following ESPEN guidelines. The drop in eGFR did not correlate with weight loss during treatment or with anthropometric parameters pre and post. Nutritional counselling pre-, during, post-treatments plays a crucial role in preventing malnutrition and sarcopenia, leading to better oncological and nephrological outcomes too.
Clinical Nutrition, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Translational Oncology ARCO Foundation, Cuneo, Italy.
Nephrology and Dialysis, Università Degli Studi Di Cagliari, G. Brotzu Hospital, Cagliari, Italy.
Department of Otorhinolaryngology, IRCCS San Raffaele Scientific Institute, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy.
Clinical Nutrition, IRCCS San Raffaele Scientific Institute, Milan, Italy.Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Department of Otorhinolaryngology, IRCCS San Raffaele Scientific Institute, Milan, Italy. mirabile.aurora@hsr.it.Vita-Salute San Raffaele University, Milan, Italy. mirabile.aurora@hsr.it.
Nephrotoxicity in locally advanced head and neck cancer: when the end justifies the means to preserve nutritional status during chemoradiation.
This study aimed to investigate the subtypes of spiritual well-being among patients with early-stage lung cancer, examine the characteristics of each subtype, and determine the relationship between spiritual well-being and perceived social support as well as hope within these subtypes.A sample of 418 patients with early-stage lung cancer from three hospitals in Hubei Province completed the general sociodemographic questionnaire, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being, the Perceived Social Support Scale, and the Herth Hope Index. Latent profile analysis (LPA) was used to identify the patterns of spiritual well-being in patients with early-stage lung cancer, and influencing factors of different patterns were identified by univariate analysis and multinomial logistic regression analysis.Three latent classes were identified: the low spiritual well-being (C1, 33.97%), the moderate spiritual well-being (C2, 38.28%), and the high spiritual well-being (C3, 27.75%). Factors such as nationality, religion, annual household disposable income, perceived social support scores, and hope scores influenced the potential categories of spiritual well-being in patients with early-stage lung cancer.The spiritual well-being of patients with early-stage lung cancer varies, necessitating customized spiritual care to meet the diverse needs of patients. Additionally, providing comprehensive social support and helping patients achieve positive states of spiritual well-being can promote better cancer treatment outcomes.
Zhongnan Hospital of Wuhan University, Wuhan, 430062, Hubei, China.
The Central Hospital of Wuhan, Wuhan, 430014, Hubei, China.
Hubei University of Arts and Science, Xiangyang, 441053, Hubei, China. 3137945771@qq.com.
A latent profile analysis of spiritual well-being and their relation to perceived social support and hope in patients with early-stage lung cancer.
Cancer survivors experience an array of physical, psychological, and social problems after treatment has ended. Perceived social isolation may exacerbate the effects of physical problems on mental health. We examined the association between physical health (cancer-related fatigue and physical function) and mental health (depression and anxiety symptoms) in cancer survivors in the first year of survivorship (i.e., up to one year after the end of treatment with curative intent), as well as the moderating role of perceived social isolation.Survey data were collected from 118 cancer survivors who completed treatment with curative intent in the last year. We assessed mental and physical health symptoms, as well as perceived social isolation.In multivariable analyses, fatigue was significantly associated with both depression (β = 0.279, 95% CI: 0.193,0.362) and anxiety symptoms (β = 0.189, 95% CI: 0.106,0.272). Social isolation moderated the effect of fatigue on depression and anxiety such that higher social isolation exacerbated the association of fatigue with mental health.Cancer survivors who continue to experience fatigue after curative treatment are at risk for mental health problems, including depression and anxiety symptoms. For cancer survivors who feel socially isolated, the association between fatigue and mental health may be stronger. The current standard of care for survivorship does not sufficiently address psychosocial needs. Future research should evaluate the inclusion of social support interventions in early-term survivorship care.
Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, CU 420644, Rochester, NY, 14642, USA. julie.kittel-moseley@va.gov.
Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, CU 420644, Rochester, NY, 14642, USA.Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.
Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, CU 420644, Rochester, NY, 14642, USA.
Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.
Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Fatigue, impaired physical function and mental health in cancer survivors: the role of social isolation.
To explore the mechanism by which coping styles of bladder cancer patients influence the relationship between family functioning and delay in seeking medical care. This knowledge could provide a basis for developing interventions to address delayed medical care for patients with bladder cancer.A total of 312 patients with bladder cancer were investigated using the General Information Questionnaire, Questionnaire on the patient's medical condition, the Medical Coping Style Scale, and the Family Functioning Rating Scale.The median delay time for bladder cancer patients was 44.5 days, and the family functioning score at (124.50 ± 24.86), with the face dimension score at (1.66 ± 0.53), the recuse dimension score at (2.48 ± 0.66), and the yield dimension score at (1.34 ± 0.57). The total score of family functioning and each dimension were positively correlated with the delay time of medical care, the coping styles (face) were negatively correlated with the delay time of medical care, and the coping styles (recuse and yield) were positively correlated with it. The mediating effect model showed that family function had an indirect effect through coping styles (face, recuse, and yield), with a total effect of 0.369, and coping styles (face, recuse, and yield) had a mediating effect on the delay time of medical care (indirect effect sizes were 0.123, 0.096, and 0.114, respectively).The coping styles of patients with bladder cancer play a mediating role between family functioning and the delay in seeking medical care. Medical staff should encourage bladder cancer patients to adopt a proactive coping approach and improve the support capacity of bladder cancer patients' families to effectively shorten the delay time.
School of Nursing, Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia Autonomous Region, China.
School of Nursing, Inner Mongolia Medical University, Hohhot, 010059, Inner Mongolia Autonomous Region, China. nyhllch@163.com.
Association between family functioning and delay in seeking medical care of Chinese bladder cancer patients: the mediating effect of coping styles.
Exploring the experiences and perceptions of head and neck cancer (HNC) patients undergoing proton heavy ion therapy who develop taste dysfunction during treatment to improve taste dysfunction management for these patients.A qualitative study design using a descriptive phenomenological approach.Conducted individual face-to-face semi-structured interviews in the Head and Neck Tumor Department of the Shanghai Proton and Heavy Ion Center from February to April 2024.The experiences of patients with HNC undergoing proton and heavy ion radiotherapy revealed four key themes: the diversity of taste dysfunction (including reduced or lost perception of sweet, sour, bitter, and other tastes, as well as altered and distorted taste of certain foods); the impact of taste dysfunction on quality of life (changes in dietary habits, malnutrition and weight fluctuations, mental health, and social impacts); strategies for coping with taste dysfunction (altering dietary habits and increasing the use of seasonings to compensate for taste reduction, seeking social support, and engaging in mental health activities to manage emotional distress); and expectations from the healthcare team (need for information and support, psychological support services, and monitoring and evaluation).Patients with HNC undergoing proton and heavy ion therapy experience significant taste dysfunction. Therefore, during proton and heavy ion therapy for HNC, it is crucial to closely monitor and effectively manage taste dysfunction to enhance patients' quality of life and treatment outcomes. Future research should further explore the mechanisms of taste dysfunction and develop interventions to better meet patients' needs and improve the individualization of treatment.
Department of Nursing, Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China.Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China.Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China.
Department of Nursing, Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China. hong_whw@aliyun.com.Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, China. hong_whw@aliyun.com.Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, China. hong_whw@aliyun.com.
Taste dysfunction symptoms experience in head and neck cancer patients undergoing proton and heavy ion therapy: a qualitative study.
Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
Loma Linda University School of Medicine, Loma Linda, CA, USA.
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom.
The Evidence Is Clear, Exercise Is Not Better Than Antidepressants or Therapy: It Is Crucial to Communicate Science Honestly.
Mobile health applications have been widely adopted among breast cancer survivors for disease management; however, their use specifically for the prevention of breast cancer-related lymphedema (BCRL) remains sparse. This study is aimed at developing a WeChat-based intervention program for the prevention of BCRL based on the common-sense model (CSM).This study was designed based on intervention mapping. First, a longitudinal investigation was conducted to determine the predictive effect of illness perception on BCRL prevention behaviors among breast cancer survivors. An intervention program was then constructed based on the CSM and longitudinal results. Finally, a WeChat mini-program was developed, and 15 patients were recruited to test its usability and user satisfaction through usability tests based on typical tasks and the Post-Study System Usability Questionnaire (PSSUQ), respectively.The longitudinal study revealed that identity, personal control, illness coherence, and behavioral and physical factors in the causes dimension could positively predict prevention behaviors, whereas treatment control and uncontrollable factors exhibited negative predictive effects. This study then developed an individualized intervention program and a WeChat mini-program (named Nantian e-Care ) consisting of five modules: resources, questionnaires, homepage, consultation, and personal center. Patients could read BCRL-related educational content, watch functional exercise videos, self-measure arm circumference, and consult questions. The five-task completion rates were 80.00 ~ 100.00%, the average completion time was 9.47 ~ 33.31 s, and the scores of PSSUQ were greater than 5 points (full score 7 points).This study proposed a feasible intervention program for the prevention of BCRL and developed a customized WeChat mini-program with high usability and user satisfaction.Chinese Clinical Trial Registry, URL: https://www.chictr.org.cn/ , ChiCTR2100048798.
School of Nursing, Chongqing Medical University, No. 1 Medical College Road, Yuzhong District, Chongqing, 400016, China.
The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, Guangdong Province, China.
School of Nursing, Sun Yat-Sen University, No. 74 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, Guangdong Province, China.
School of Nursing, Sun Yat-Sen University, No. 74 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, Guangdong Province, China. yanjun@mail.sysu.edu.cn.
Development and evaluation of a WeChat-based intervention program for prevention of breast cancer-related lymphedema.
Patients with triple-negative breast cancer (TNBC) are at high risk for breast cancer recurrence and metastatic disease, yet the scholarly literature on the distress and uncertainty of this vulnerable population is limited. This study aimed to characterize the experiences of patients with TNBC and obtain feedback about the development of a supportive care intervention targeted to this population's psychosocial needs.From 9/2021 to 2/2023, we purposefully recruited 23 patients with stage I-III TNBC who recently completed curative therapy and conducted a parallel mixed qualitative and quantitative study. We conducted in-depth semi-structured interviews regarding the transition from curative therapy to surveillance. Patients also completed self-report measures of fear of cancer recurrence (FCR) (Fear of Cancer Recurrence Inventory Severity) and psychological distress (Hospital Anxiety and Depression Scale; PROMIS Anxiety).Patients were, on average, 51 years old (SD = 13.56). Most patients (87.0%) reported elevated FCR (cutoff = 16; M = 18.91; SD = 6.22). Major themes identified in the qualitative interviews included feelings of dissimilarity among other breast cancer survivors, quality of life interference persisting in the surveillance phase, shifting the focus away from cancer as a coping strategy, and FCR as a primary concern. Patients also shared preferences for a TNBC-specific supportive care intervention.Patients with TNBC experience significant challenges during the transition from curative therapy to surveillance and desire psychosocial support during this critical period. These findings illustrate potential intervention targets for a future supportive care intervention tailored to patients with TNBC.
Massachusetts General Hospital, Yawkey Center, Suite 9A, 55 Fruit St, Boston, MA, 02114, USA. kepost@mgh.harvard.edu.Harvard Medical School, Boston, MA, USA. kepost@mgh.harvard.edu.
Georgetown University School of Medicine, Washington, D.C, USA.
Massachusetts General Hospital, Yawkey Center, Suite 9A, 55 Fruit St, Boston, MA, 02114, USA.Harvard Medical School, Boston, MA, USA.
Not out of the woods: perspectives from patients with triple-negative breast cancer.
Palliative whole-brain radiotherapy (WBRT) is a useful treatment modality for patients diagnosed with brain metastasis. Our study aimed to document parotid doses using a short course of 20 Gy in five fractions (SC-WBRT) and compare them with the known xerostomia parameters.We retrieved dosimetric parameters for 59 patients who received SC-WBRT. The contouring of parotids was done retrospectively. The data was stratified depending on the lower edge of the planning target volume (PTV) border, up to either the first cervical vertebra (C1) or the second cervical vertebra (C2). The biologically effective dose (BED) of the parotid dose constraints from the literature was calculated and corrected to obtain the dose for a five-fraction treatment. These were used as a reference for assessing the parotid doses of our cohort.With SC-WBRT, the mean doses of either gland (11.46 Gy) and of total parotids (11.48 Gy) were statistically significantly less than the BED corrected constraints of 12.82 Gy (p < 0.01) and 15.31 Gy (p < 0.01). Patients with PTV to C1, compared to those with a PTV to C2, had significantly lower mean doses of either gland (9.44 Gy vs 12.76 Gy, p < 0.01) and total parotid dose (9.44 Gy vs 12.78 Gy, p < 0.01). Patients with PTV to C1 had doses significantly lower than all the reference dose parameters.Routine delineation and documentation of parotid dosimetry would enable parotid sparing, irrespective of the dose regimen used. SC-WBRT provides better parotid sparing dosimetrically which may reduce the related toxicities even in palliative settings. Limiting the lower border of the PTV to C1 will further decrease the parotid doses.
Department of Radiation Oncology, National Cancer Institute, Nagpur, India.
Department of Medical Physics, National Cancer Institute, Nagpur, India.
Organs in plain sight-parotid gland doses in short-course palliative whole-brain radiotherapy.
The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored. To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin-eosin (H&E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings. We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4. Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.Institute of Urology, Anhui Medical University, Hefei, China.Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 526545298@qq.com.Institute of Urology, Anhui Medical University, Hefei, China. 526545298@qq.com.Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. 526545298@qq.com.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. wangweimiwai@126.com.Institute of Urology, Anhui Medical University, Hefei, China. wangweimiwai@126.com.Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. wangweimiwai@126.com.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. haozongyao@ahmu.edu.cn.Institute of Urology, Anhui Medical University, Hefei, China. haozongyao@ahmu.edu.cn.Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. haozongyao@ahmu.edu.cn.
Based on network pharmacology, the mechanism of Dioscin in alleviating renal tubular epithelial cell injury induced by calcium oxalate crystals was explored.
Our study aims to assess the association between chemotherapy-induced oral ulcerative mucositis (CT-UM) or radiotherapy-induced oral ulcerative mucositis (RT-UM) and the burden of illness (BOI), dysphagia, and disparities among patients with cancers of the oral cavity, lip, and pharynx (CLOP) and hematopoietic stem cell transplant patients (HSCT).The study used US national data to investigate the association between UM and the BOI-length of stay (LOS) and dysphagia. The BOI was measured by length of stay (LOS), dysphagia, and associated disparities in these outcomes. This investigation was conducted using generalized linear models (glm).An analysis was conducted on a sample of 820 patients with CT-UM and 1010 patients with RT-UM, out of a total of 59,710 hospitalized CLOP patients, and 1380 patients with CT-UM from 10,885 total hospitalized HSCT patients. Among, CLOP patients, CT-UM status was associated with increased LOS (Coeff,1.54; 95% CI 1.36 to 1.74) and also associated with a greater likelihood of dysphagia (aOR, 2.11; 95% CI 1.52-2.95). However, among CLOP, RT-UM status was also associated with increased LOS (Coeff, 1.33; 95% CI 1.14-1.55), but there was no association of d RT-UM status and dysphagia (aOR = 1.21; 95% CI 0.84-1.77). Among HSCT patients, CT-UM status was associated with increased LOS and greater likelihood of dysphagia (Coeff, 1.09; 95% CI 1.02-1.16 and aOR = 2.08; 95% CI 1.11-3.9, respectively). Further, UM outcomes disproportionately affect females, Blacks, Hispanics, Medicaid recipients, and those with lower incomes.The findings highlight the need for more effective methods of screening for and preventing UM in order to decrease BOI, especially in the context of systemic treatments. Additionally, new computational methods including artificial intelligence for mucositis prediction should be the center of future studies.
Boston Medical Center, Boston University School of Medicine, Boston, MA, 02118, USA.
Department of Medicine, Division of Hematology and Oncology, University at Buffalo, Buffalo, NY, 14203, USA.
City of Hope Comprehensive Cancer Center, Duarte CA and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical System, Los Angeles, CA, USA.
Department of Medicine, University at Buffalo, Buffalo, NY, 14203, USA.
Department of Medicine, Division of Hematology and Oncology, University at Buffalo, Buffalo, NY, 14203, USA. spoolakk@buffalo.edu.
Cancer treatment-induced ulcerative mucositis serves as a significant predictor of burden of illness including dysphagia, and associated disparities among hospitalized cancer patients.
Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, Hofu, Yamaguchi, Japan. Electronic address: tnagamine@outlook.com.
Perioperative administration of esketamine during cesarean section is a double-edged sword.
Division of Hematology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Oncology & Palliative Care1101. E. Marshall Street, Suite 6030, Box 980230, Richmond, VA, 23298-0230, USA. Brian.Cassel@vcuhealth.org.
To the editor, in response to Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States .
Background and objectives: Self-management of chronic conditions can help individuals take control of their health, both improving well-being and reducing the burden on health and social care resources. This study explored the potential of our co-produced self-management tool, My Life Today (MLT), to help people with dementia identify, plan and monitor aspects of their lives that are important to them and that help to maintain or improve well-being.Research design and methods: We asked people with dementia to try using MLT. We conducted semi-structured interviews after one month and further interviews one month later. We also interviewed people who had supported the person with dementia to use MLT ('supporters'). We adopted a realist approach to thematic analysis to explore what works, for whom, under what circumstances.Results: Sixteen people with dementia and four supporters took part. All but one had mild to moderate cognitive impairment, and one had severe cognitive impairment. People with dementia used MLT according to their perceptions of its usefulness, their capabilities, and whether they had support. Using MLT helped most to think more positively about their activities and achievements and feel reassured by identifying the activities they were doing. Supporters and some people with dementia also derived benefits from planning and problem-solving to include more pleasurable activities.Discussion and implications: People with dementia and supporters found MLT a helpful tool. Mechanisms of engagement with MLT resonate with theories of behaviour change concerning the evaluation of capabilities and feelings of confidence in the ability to complete MLT and plan activities. Offering simple self-management tools such as MLT could form part of a post-diagnostic support package for people with dementia. Providing flexibility in when tools are offered and how they are used can allow for differences in attitudes and capabilities and increase the likelihood of engagement.
University of Exeter Medical School, University of Exeter, UK.
Centre for Applied Dementia Studies, University of Bradford, Bradford, UK.Wolfson Centre for Applied Health Research, UK.
Department of Psychology, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
University of Exeter Medical School, University of Exeter, UK.NIHR Applied Research Collaboration South-West Peninsula, UK.
Qualitative evaluation of My Life Today - A co-produced personal tool from the IDEAL programme to help people with dementia monitor valued aspects of their lives.
This study aimed to explore the thoughts and experiences of young men with cancer regarding the risk of infertility and the oncofertility counseling they received at diagnosis and during their cancer trajectory.This qualitative study was conducted from October 2023 to February 2024 at the Copenhagen University Hospital-Rigshospitalet. Inclusion criteria were male adolescents and young adults with cancer aged 15-29 years. We conducted fourteen individual, semi-structured, qualitative interviews with male adolescents and young adults with either leukemia, lymphoma, or testicular cancer. Data were analyzed using thematic analysis.Three themes were identified: (1) Young men with cancer have existential thoughts about future children; (2) young men call for information and communication about the risk of reduced fertility chances after cancer; (3) young men experience challenges related to cryopreservation of semen.Young men desire children after cancer and fertility preservation offers reassurance. Psychological and physical fertility issues often impact body image and masculinity during cancer. Oncofertility counseling is limited, usually brief at diagnosis; however, discussions on treatment-related fertility challenges remain sparse during follow-up. Young men often experience stress related to fertility preservation at diagnosis, which they feel is not recognized by healthcare professionals. This underscores the need for better oncofertility education for healthcare professionals and closer collaboration between oncologists, hematologists, and fertility specialists.
Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. line.bentsen.01@regionh.dk.
Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.Occupational Science, Department of Public Health, User Perspectives and Community-based Interventions, University of Southern Denmark, Odense, Denmark.
Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Navigating an uncertain future: a qualitative study exploring thoughts about fertility and oncofertility counseling among young men with cancer.
Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.
© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.
Laboratory of Neuro Imaging (LONI), USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, USC Keck School of Medicine, Los Angeles, California, USA.
Department of Occupational Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.
Otology/Neurotology, Pacific Neuroscience Institute, Los Angeles, California, USA.
The Spatial Organization of Ascending Auditory Pathway Microstructural Maturation From Infancy Through Adolescence Using a Novel Fiber Tracking Approach.
This retrospective study included 311 patients who had increased nuchal translucency (NT ≥3 mm) or nuchal septations (NSs) during the first trimester from January 2018 to December 2020. These patients were divided into 3 groups: (1) patients with NT thickness between 3 and 5 mm and without NS (NT 3-5 mm group, n = 131), (2) patients with NT thickness >5 mm and without NS (NT >5 mm group, n = 105), and (3) patients with NS (NS group, n = 75). The incidence of abnormal pregnancy outcomes was 92.0% in the NS group, which was significantly higher (both P's < 0.01) compared with that in the NT 3-5 mm group (57.3%) and NT >5 mm group (75.2%). Multivariate logistic regression analysis illustrated that the sonographic evidence of NS was associated with a higher risk of abnormal pregnancy outcomes compared with NT 3-5 mm (odds ratio [OR] = 8.552; 95% confidence interval [CI]: 3.411-21.441; P < 0.01) and NT >5 mm (odds ratio [OR] = 3.636; 95% CI: 1.391-9.524; P < 0.01). After NT measurement entered the multivariate logistic regression as a continuous confounder, patients with NS were still associated with a higher risk of composite abnormal outcomes compared with those without NS (odds ratio [OR] = 4.820; 95% CI: 1.877-12.380; P < 0.01). In conclusion, the presence of NS during the first trimester was significantly associated with a high risk of abnormal pregnancy outcomes.
Department of Ultrasonography, Mianyang Central Hospital, Mianyang, Sichuan, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Association of First Trimester Nuchal Septations With Abnormal Pregnancy Outcomes.
The purpose of this study is to investigate the relationship between preoperative cystatin C levels and the risk of serious postoperative complications in esophageal cancer (EC) patients, utilizing advanced machine learning (ML) methodologies.We conducted an observational cohort study, involving 524 EC patients from December 2014 to July 2022. ML models, including logistic regression (LR) and multilayer perceptron (MLP), were applied to investigate the relationship between cystatin C and the serious postoperative complications. The predictive value of cystatin C was evaluated using receiver operating characteristic (ROC) analysis. Based on a restricted cubic spline (RCS) method, the potential nonlinear association was scrutinized.The morbidity of serious postoperative complications was 8.78%. Bleeding volume, operating time, NRS2002 score, PONS score, and cystatin C were significantly associated with serious postoperative complications. The MLP model demonstrated superior predictive accuracy (AUC = 0.775, 95% CI: 0.701-0.849) compared to the LR model (AUC = 0.714, 95% CI: 0.630-0.798) and cystatin C alone (AUC = 0.612, 95% CI: 0.526-0.699). High cystatin C level independently predicted serious postoperative complications in EC patients. A positive and linear association was found between cystatin C and serious complications.This research uncovers a notable correlation between cystatin C and the severe complications in EC patients after esophagectomy. Employing ML techniques offers a robust method for forecasting patient outcomes and emphasizes the potential of cystatin C as a predictive biomarker in medical practice.
Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China.Chongqing Municipal Health Commission Key Laboratory of Intelligent Clinical Nutrition and Transformation, Chongqing, 400042, China.
Department of Clinical Nutrition, The Thirteenth People's Hospital of Chongqing, Chongqing, 400053, China.
Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China. hx_xu2015@163.com.Chongqing Municipal Health Commission Key Laboratory of Intelligent Clinical Nutrition and Transformation, Chongqing, 400042, China. hx_xu2015@163.com.
Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China. lina_1124@126.com.Chongqing Municipal Health Commission Key Laboratory of Intelligent Clinical Nutrition and Transformation, Chongqing, 400042, China. lina_1124@126.com.
Utilizing machine learning approaches to investigate the relationship between cystatin C and serious complications in esophageal cancer patients after esophagectomy.
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, 201600, PR China.
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, 201600, PR China. Electronic address: wangyusun@hotmail.com.
COVID-19's silent scars: The urgent link between SARS-CoV-2 infection and long-term mental health consequences.
Making CAR T-cell therapies more affordable.
The Caries Impacts and Experiences Questionnaire for Children (CARIES-QC) is a disease-specific questionnaire that assesses the impact of caries on the oral health-related quality of life of children. This study aimed to establish a baseline for caries-specific impact on schoolchildren in Saudi Arabia and to examine its association with dental care utilization.This cross-sectional study used random stratified cluster sampling among 4th-6th graders in Jeddah. Two surveys were administered: (1) a general parental survey and (2) CARIES-QC, a self-reported survey for children. Clinical examinations were conducted using the decayed, missing due to caries, and filled teeth (DMFT/dmft) index. Descriptive statistics provided CARIES-QC baseline estimates, and multilevel linear regression was performed to examine the relationships between CARIES-QC scores, DMFT/dmft index, and care utilization.A total of 805 children aged 8-13 years participated. The overall median CARIES-QC score was six (interquartile range, 3-11). A higher DMFT/dmft index was associated with a higher CARIES-QC score (p < 0.05). Children who had never visited a dentist had lower CARIES-QC scores (β = -1.18, 95% confidence interval: -2.33; -0.02, p = 0.045) than those who had visited a dentist in the past 12 months. After adjusting for reasons for dental visits, the CARIES-QC scores were not associated with prior dental visits (p = 0.086).A higher DMFT/dmft index was associated with higher CARIES-QC scores, but prior dental care utilization was not significantly associated with improved CARIES-QC scores. Future research should explore other factors that influence the relationship between care utilization and caries-specific quality of life.
Department of Preventive Dentistry, Faculty of Dentistry, Umm Al-Qura University, Makkah, Saudi Arabia.
Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pediatric Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
JED2 Academic and Training Affairs, Ministry of Health, Jeddah, Saudi Arabia.
Caries Impacts and Experiences and Dental Care Utilization for Saudi Schoolchildren: Caries Impacts and Experiences Questionnaire for Children - A Disease-Specific Measure.
This study investigated how imagery-based suggestions were embodied in perception and behaviour. In Experiment 1, participants listened to several suggestion scripts while stretching the left arm (they were required not to move). During 30 s, the script invited participants to imagine the experimenter facing them. During the following 30 s, they imagined him placing either a heavy dictionary or a light paper sheet on their hand (implicit suggestions). During the last 30 s, suggestions explicitly described how the object pushed its support down. In two other conditions, participants really performed these actions with real objects. Results showed that after implicit and explicit suggestions, the arm lowered more in the dictionary condition than in the paper sheet one. Similar patterns were observed in conditions with real objects. In Experiment 2, we used the same imagery-based suggestions but added a condition where participants imagined the dictionary placed on a table. Moreover, we measured the participants' centre of pressure (CP). Results showed that after implicit and explicit suggestions, the participants' arm lowered more in the dictionary on the arm condition than in other conditions. After implicit suggestions, CP moved more rightward in the dictionary on the arm condition than the paper sheet one. Finally, perceived difficulty was lower in the paper sheet condition than in other conditions. Regarding embodied cognition theories, results suggest that participants behaved as if the sensorimotor processes activated by mental images became integrated to the processes related to the actual situation. Further studies are needed to test whether other processes might be complementary involved.
Université Paris Nanterre, LICAE (Laboratoire des Interactions Cognition Action Emotion), Nanterre Cedex, France.
Université de Lorraine, 2LPN-CEMA Group (Cognition-Emotion-Action), Nancy Cedex, France.Université de Toulon, Impact de l'Activité Physique sur la Santé (UR IAPS n°201723207F), Toulon, France.
Quarterly journal of experimental psychology (2006)
A new experimental paradigm to investigate how imagery-based suggestions are embodied.
The posterior cerebellum and anterior basal ganglia are critical subcortical structures for learning and identifying dynamic action sequences, in concert with the neocortex. The present analysis investigates the role of action sequences during social mentalizing, termed here dynamic or sequential social mentalizing. Although the role of the cerebellum in dynamic social mentalizing was extensively investigated during the last decade, the basal ganglia were long ignored. We conducted an activation likelihood estimation coordinate-based meta-analysis of sequential social mentalizing tasks (with 485 participants in 17 studies). These tasks required participants to make social mentalizing inferences ranging from low-level goals to high-level beliefs and traits, while either memorizing, generating or predicting temporal sequences of the social actions involved (i.e., social sequencing condition), or not (i.e., social non-sequencing control condition), or did so for nonsocial objects (i.e., nonsocial sequencing control condition). The tasks also occasionally included inconsistencies in social behavior. Results revealed that the cerebellum exhibited a preference for social, sequencing, and inconsistent information, while the basal ganglia showed a preference for sequencing and inconsistency, without a general preference for social input. Meta-analytic connectivity analysis further showed evidence of coactivation between mentalizing areas of the cerebellum, basal ganglia and cerebral neocortex. The present work underscores the role of subcortical structures in social mentalizing about dynamic action sequences.
Vrije Universiteit Brussel and Center for Neuroscience, Brussel, Belgium.
Mentalizing About Dynamic Social Action Sequences Is Supported by the Cerebellum, Basal Ganglia, and Neocortex: A Meta-Analysis of Activation and Connectivity.
Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique used to modulates cortical brain activity. However, its effects on brain metabolites within the dorsolateral prefrontal cortex (DLPFC), a crucial area targeted for brain stimulation in mental disorders, remain unclear. This study aimed to investigate whether prefrontal tDCS over the left and right DLPFC modulates levels of key metabolites, including gamma-aminobutyric acid (GABA), glutamate (Glu), glutamine/glutamate (Glx), N-acetylaspartate (NAA), near to the target region and to explore potential sex-specific effects on these metabolite concentrations. A total of 41 healthy individuals (19 female, M_age = 25 years, SD = 3.15) underwent either bifrontal active (2 mA for 20 min) or sham tDCS targeting the left (anode: F3) and right (cathode: F4) DLPFC within a 3 Tesla MRI scanner. Magnetic resonance spectroscopy (MRS) was used to monitor neurometabolic changes before, during, and after 40 min of tDCS, with measurements of two 10-min intervals during stimulation. A single voxel beneath F3 was used for metabolic quantification. Results showed a statistically significant increase in Glx levels under active tDCS compared to the sham condition, particularly during the second 10-min window and persisting into the post-stimulation phase. No significant changes were observed in other metabolites, but consistent sex differences were detected. Specifically, females showed lower levels of NAA and GABA under active tDCS compared to the sham condition, while no significant changes were observed in males. E-field modeling showed no significant differences in field magnitudes between sexes, and the magnitude of the e-fields did not correlate with changes in Glx levels between active and sham stimulation during the second interval or post-stimulation. This study demonstrates that a single session of prefrontal tDCS significantly elevates Glx levels in the left DLPFC, with effects persisting post-stimulation. However, the observed sex differences in the neurochemical response to tDCS were not linked to specific stimulation intervals or variations in e-field magnitudes, highlighting the complexity of tDCS effects and the need for personalized neuromodulation strategies.
Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany.NeuroImaging Core Unit Munich (NICUM), University Hospital LMU, Munich, Germany.Department of Psychology, Ludwig Maximilian University, Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany.International Max Planck Research School for Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany.
NeuroImaging Core Unit Munich (NICUM), University Hospital LMU, Munich, Germany.
Department of Psychology, Ludwig Maximilian University, Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany.Department of Psychology, Charlotte Fresenius Hochschule, Munich, Germany.
Department of Radiology, University Hospital LMU, Munich, Germany.
Harvard Medical School, Boston, Massachusetts, USA.A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Psychiatry and Psychotherapy, University Hospital LMU, Munich, Germany.NeuroImaging Core Unit Munich (NICUM), University Hospital LMU, Munich, Germany.Munich Center for Neurosciences (MCN), Ludwig Maximilian University LMU, Munich, Germany.
Exploring the Effects of Prefrontal Transcranial Direct Current Stimulation on Brain Metabolites: A Concurrent tDCS-MRS Study.
Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of General Surgery, Chi-Mei Foundation Medical Center, Tainan, Taiwan.
Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Psychology, Chung Shan Medical University, and Clinical Psychological Room, Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan. suying@ncku.edu.tw.Department of Nursing, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. suying@ncku.edu.tw.
Correction to: Relationship between dyadic communication and body image among women with breast cancer.
Cancer treatment often results in adverse financial consequences-also termed financial toxicity. To build upon limited research in pediatric oncology, we conducted a qualitative study exploring families' lived experiences with financial toxicity and their perspectives on potential mitigation strategies.We conducted in-depth semi-structured interviews with a purposive sample of English- and Spanish-speaking family caregivers, 3-24 months following diagnosis. We performed a thematic analysis focused on elucidating relationships between components/domains of financial toxicity, identifying mitigating and exacerbating factors, eliciting latent constructs for measurement, and querying caregivers' perspectives on interventions. We organized relationships between themes into a framework to compare with prior theoretically derived models.We interviewed 21 caregivers, diverse with respect to income, age, race and ethnicity, family structure/composition, and patient characteristics. We identified four themes relating to financial toxicity: increased spending on providing care to patients/siblings, reduced income due to challenges in maintaining employment, new or worsened material hardship, and heightened psychological distress regarding finances. We also identified an additional theme pertaining to response behaviors directed at managing financial toxicity, with helpful or harmful downstream effects. Factors that exacerbated or lessened financial toxicity included awareness of resources, geography, and community. Caregivers suggested potential mitigation strategies, including proactive education and resource provision.Pediatric patients and families can experience substantial financial impacts, which may differ from experiences of adults with cancer. These findings suggest a need for careful screening and measurement, as well as family-centered interventions and policies to reduce long-term consequences.
Cancer and Blood Disorders Center, Seattle Children's Hospital, University of Washington, M/S MB.8.501, 4800 Sand Point Way NE, Seattle, WA, 98105, USA. tim.ohlsen@seattlechildrens.org.Seattle Children's Research Institute, Seattle, WA, USA. tim.ohlsen@seattlechildrens.org.
University of Washington School of Medicine, Seattle, WA, USA.
Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Cancer and Blood Disorders Center, Seattle Children's Hospital, University of Washington, M/S MB.8.501, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.
Cancer and Blood Disorders Center, Seattle Children's Hospital, University of Washington, M/S MB.8.501, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
Seattle Children's Research Institute, Seattle, WA, USA.Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Financial toxicity among pediatric oncology families during therapy and early survivorship: a qualitative analysis.
Incidental findings in diagnostic imaging are common, but follow-up recommendations often lack consistency. The Society of Radiologists in Ultrasound (SRU) issued guidelines in 2021 for managing incidentally detected gallbladder polyps, aiming to balance follow-up with avoiding overtreatment. There is variable adherence to these guidelines in radiology reports, however, which makes it difficult for the clinician to pursue appropriate follow-up for the patient. The purpose of this project is to test the feasibility of a Large Language Model (LLM)-based tool to incorporate SRU guidelines into radiology reports. Additionally, we propose a framework for closely integrating societal follow-up recommendations into radiology reports, using this tool as an example.Following institutional review board approval, we retrospectively reviewed gallbladder ultrasound examinations performed on adult ED patients in 2022. Data on patient demographics and radiology report content were collected. Using the 2021 SRU guidelines, we developed an interactive tool employing a retriever-augmented generator (RAG) and prompt engineering. A board-certified radiologist tested the accuracy, whereas a board-certified emergency medicine physician assessed the clarity and consistency of the recommendations.The interactive tool, GB-PRL, outperformed leading closed-source and open-source LLMs, achieving 100% accuracy in risk categorization and follow-up recommendations on hypothetical user queries (P < 0.001). The tool also showed superior accuracy compared to radiology reports on retrospective data (P = 0.04). Although GB-PRL demonstrated greater clarity and consistency, the improvement from the radiology reports was not statistically significant (P = 0.22). Further work is needed for prospective testing of GB-PRL before integrating it into clinical practice.
Department of Emergency Medicine, Mayo Clinic, Rochester, MN.
Increasing Adherence to Societal Recommendations in Radiology Reporting: A Feasibility Study Using Society of Radiologists in Ultrasound Guidelines for Incidentally Detected Gallbladder Polyps.
The human brain is organized as a hierarchical global network. Functional connectivity research reveals that sensory cortices are connected to corresponding association cortices via a series of intermediate nodes linked by synchronous neural activity. These sensory pathways and relay stations converge onto central cortical hubs such as the default-mode network (DMN). The DMN regions are believed to be critical for representing concepts and, hence, language acquisition and use. Although prior research has established that major senses are placed at a similar distance from the DMN-five to six connective steps-it is still unknown how the olfactory system functionally connects to the large-scale cortical hubs of the human brain. In this study, we investigated the connective distance from olfactory seed areas to the DMN. The connective distance involves a series of three to four intermediate steps. Furthermore, we parcellated the olfactory cortical subregions and found evidence of two distinct olfactory pathways. One emerges from the anterior olfactory nucleus and olfactory tubercle; it involves early access to the orbitofrontal cortex, known for processing reward and multisensory signals. The other emerges from the frontal and temporal regions of the piriform cortex, involving the anterior insula, intermediate frontal sulcus, and parietal operculum. The results were confirmed in a replication cohort. Our results provide evidence that olfaction has unique early access to the central cortical networks via dual pathways.
Department of Psychology, Stockholm University, Stockholm, Sweden.Karolinska Institute, Stockholm, Sweden.
Department of Radiology, Gordon Center for Medical Imaging, Boston, Massachusetts, USA.Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Karolinska Institute, Stockholm, Sweden.Center for Lifespan Developmental Research (LEADER), School of Behavioral, Social and Legal Sciences, Örebro University, Örebro, Sweden.
Department of Psychology, Stockholm University, Stockholm, Sweden.
Stepwise pathways from the olfactory cortex to central hub regions in the human brain.
In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.
Department of Neurosurgery, University of Texas Health Science Center, Houston, Texas, USA.Department of Neuroscience, High Resolution Brain Imaging Lab, Baylor College of Medicine, Houston, Texas, USA.
Department of Neuroscience, High Resolution Brain Imaging Lab, Baylor College of Medicine, Houston, Texas, USA.
Department of Neurosurgery, University of Texas Health Science Center, Houston, Texas, USA.
Global Impact of Aging on the Hemodynamic Response Function in the Gray Matter of Human Cerebral Cortex.
Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.
Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.Department of Critical Care Medicine, Nanjing Chest Hospital, Nanjing, China.
Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China. xgh4290@163.com.Department of Nursing, Nanjing Chest Hospital, Nanjing, China. xgh4290@163.com.
Correction to: Risk factors for cancer‑related cognitive impairment among individuals with lung cancer: a systematic review and meta‑analysis.
Weighted MRI images are widely used in clinical as well as open-source neuroimaging databases. Weighted images such as T1-weighted, T2-weighted, and proton density-weighted (T1w, T2w, and PDw, respectively) are used for evaluating the brain's macrostructure; however, their values cannot be used for microstructural analysis, as they lack physical meaning. Quantitative MRI (qMRI) relaxation rate parameters (e.g., R1 and R2) do contain microstructural physical meaning. Nevertheless, qMRI is rarely done in large-scale clinical databases. Currently, the weighted images ratio T1w/T2w is used as a quantifier to approximate the brain's microstructure. In this paper, we test three additional quantifiers that approximate quantitative maps, which can help bring quantitative MRI to the clinic for easy use. Following the signal equations and using simple mathematical operations, we combine the T1w, T2w, and PDw images to estimate the R1 and R2 maps. We find that two of these quantifiers (T1w/PDw and T1w/ln(T2w)) can approximate R1, and that (ln(T2w/PDw)) can approximate R2, in 3 datasets that were tested. We find that this approach also can be applied to T2w scans taken from widely available DTI (Diffusion Tensor Imaging) datasets. We tested these quantifiers on both in vitro phantom and in vivo human datasets. We found that the quantifiers accurately represent the quantitative parameters across datasets. Finally, we tested the quantifiers within a clinical context, and found that they are robust across datasets. Our work provides a simple pipeline to enhance the usability and quantitative accuracy of MRI weighted images.
The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Approximating R1 and R2: A Quantitative Approach to Clinical Weighted MRI.
We aimed to identify metastatic breast cancer (MBC) patients' preferences for exercise programs and identify patients' characteristics associated with these preferences, to facilitate implementation of exercise programs for MBC patients.We used data from a multinational cross-sectional survey conducted among MBC patients. Patients reported their preferred exercise frequency, intensity, type, session duration, and supervision mode. We used latent class analysis to identify subgroups with similar preferences and descriptive statistics to compare demographic and clinical characteristics of patients within subgroups.Four distinct classes were identified based on data from 409 participants. Class 1 (47% of participants) is characterized by a preference for moderate exercise with supervision within the health care setting. Most participants in this class had bone metastases. Class 2 (30%) is characterized by a preference for vigorous exercise with supervision. This class included participants who were, on average, younger, and had a higher education level. Class 3 (13%) is characterized by a preference for active walking. These participants were less likely to have bone metastases or comorbidities. Class 4 (10%) is characterized by a preference for recreational walking and included participants who were, on average, older, and less likely to be employed.We identified four classes of patients with different preferences for exercise programs. Many patients with MBC express exercise preferences that meet the current guideline recommendations. Some patients with MBC may benefit from targeted education to align their preferences and behavior with the amount of exercise that is necessary to gain health benefits.
Center for Quality of Life, Netherlands Cancer Institute/Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands. m.sweegers@nki.nl.Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. m.sweegers@nki.nl.
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Division of Nursing, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, and Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
Department for Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany.
Gipuzkoa Cancer Unit, OSID-Onkologikoa, BioGipuzkoa, Osakidetza, San Sebastian, Spain.
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Center for Quality of Life, Netherlands Cancer Institute/Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Metastatic breast cancer patients' preferences for exercise programs: a latent class analysis using data from a survey in five European countries.
Dipartimento di Scienze Giuridiche Cesare Beccaria - Università degli Studi di Milano, Via festa del Perdono, 7, 20122 Milano, Italy.
Laboratorio di Istopatologia Forense e Microbiologia Medico Legale - Sezione di Medicina Legale e delle Assicurazioni - Dipartimento di Scienze Biomediche per la Salute - Università degli Studi di Milano, Via Luigi Mangiagalli, 37, 20133 Milano, Italy.
Laboratorio di Istopatologia Forense e Microbiologia Medico Legale - Sezione di Medicina Legale e delle Assicurazioni - Dipartimento di Scienze Biomediche per la Salute - Università degli Studi di Milano, Via Luigi Mangiagalli, 37, 20133 Milano, Italy. Electronic address: guendalina.gentile@unimi.it.
Letter to the Editor regarding the Article Complex suicides involving the use of firearms and hanging: A retrospective study and review of the literature .
People affected by breast cancer experience a multitude of toxicities and unmet needs across physical, cognitive, psychosocial, and economic domains that adversely impact their quality of life. High-quality and diverse supportive care is required to improve outcomes and rehabilitation for people affected by breast cancer. However, the availability and access to high-quality supportive care services is limited due to factors including cost and demand. As such, many people affected by breast cancer do not receive optimal supportive care. The Think Pink Foundation facilitates free-of-charge supportive care services to breast cancer survivors, their families, and caregivers through 'The Living Centre'. Think Pink seeks to provide a high-quality survivorship care model that overcomes barriers associated with the economic burden of cancer. Within its suite of services, The Living Centre offers ongoing exercise classes, creative therapy, support groups, specialist breast cancer nurse consultations, wellness services, and education support through face-to-face and online service provision. This paper outlines the development, model of care, service provision, and planning for future outcomes and economic evaluation of The Living Centre as a supportive care model for others to consider establishing in their local context. This paper may therefore directly inform the development of cancer survivorship care services globally to increase equitable access to optimal supportive care.
Human Performance Research Centre, INSIGHT Research Institute, Faculty of Health, University of Technology Sydney (UTS), Sydney, NSW, Australia. darren.haywood@uts.edu.au.Department of Mental Health, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia. darren.haywood@uts.edu.au.Department of Psychiatry, Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia. darren.haywood@uts.edu.au.School of Population Health, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia. darren.haywood@uts.edu.au.Think Pink Foundation, Docklands, VIC, Australia. darren.haywood@uts.edu.au.
Think Pink Foundation, Docklands, VIC, Australia.
Human Performance Research Centre, INSIGHT Research Institute, Faculty of Health, University of Technology Sydney (UTS), Sydney, NSW, Australia.
Human Performance Research Centre, INSIGHT Research Institute, Faculty of Health, University of Technology Sydney (UTS), Sydney, NSW, Australia.Department of Mental Health, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
School of Population Health, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.
Human Performance Research Centre, INSIGHT Research Institute, Faculty of Health, University of Technology Sydney (UTS), Sydney, NSW, Australia.Think Pink Foundation, Docklands, VIC, Australia.Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia.Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.Cancer and Palliative Care Outcomes Centre, Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD, Australia.Institute for Health Research, University of Notre Dame Australia, Perth, WA, Australia.
The living centre: an innovative open-access model of breast cancer survivorship care.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect in patients with breast cancer undergoing chemotherapy. This study aimed to assess the effects of three different intermittent hypothermia temperatures applied to the hands and feet on CIPN symptoms in patients with breast cancer undergoing chemotherapy.In total, 108 patients were randomly divided into three experimental groups (n = 36). Patients wore cold gloves and foot covers (groups 1-3, three 10 °C intervals from 0 to - 30 °C) for 15 min before and after each infusion. CIPN symptoms and their interference with activities of daily living (ADL) were assessed before the intervention and after the third and sixth cycles. Hypothermia tolerability and safety were also evaluated.Baseline characteristics were similar across groups. After three intervention cycles, the scores were lower in group 3 than in group 1 for finger/hand numbness, toe/foot numbness, finger/hand/toe/foot discomfort, muscle/joint pain, and arm/leg weakness. After six intervention cycles, group 3 showed lower scores than group 1 for finger/hand tingling, toe/foot tingling, and difficulty maintaining balance. After six cycles of intervention, the influence of CIPN on ADL in all dimensions (except getting along with others) and the total score was lower in group 3 than in group 1. Additionally, CIPN symptoms and effects on activities of daily living were significant across time, groups, and interactions.Intermittent hand-foot therapy (- 20 to - 30 °C) was the most effective for improving symptoms and ability to perform day-to-day activities. All temperatures tested were well-tolerated and safe.
Tianjin First Central Hospital, Tianjin, 300190, China.
North China University of Science and Technology, Tangshan, 063210, China.
Tangshan People's Hospital, Tangshan, 063000, China. 1398693979@qq.com.
Tangshan People's Hospital, Tangshan, 063000, China.
Tangshan Second Hospital, Tangshan, 063000, China.
Tangshan People's Hospital, Tangshan, 063000, China. zhoulizhi72@126.com.
Effects of intermittent hand-foot hypothermia therapy on chemotherapy-induced peripheral neurotoxicity.
Patients receiving immunotherapy need to have a good understanding of how immunology works and which toxicities they can expect. This study aimed to assess patients' knowledge on their immunotherapies and their quality of life before and after receiving immunotherapy for the first time in a cancer centre.From July 2018 to September 2020, all patients treated at the cancer centre receiving first-time immunotherapy were invited to participate in a cross-sectional descriptive study. Non-probabilistic sampling was used to recruit 138 patients, who answered a basal ad hoc questionnaire with ten items assessing their previous knowledge on immunotherapy. Clinical variables were collected from records and by advanced clinical specialist nurses' interviews, and quality of life was evaluated at 2 points (basal and 8 weeks of treatment), using the European Organisation for Research and Treatment of Cancer-Quality of Life C30 scale.Our descriptive analysis of 138 participants with solid tumours showed that 98.5% knew they were receiving immunotherapy. Regarding complications, 89.8% reported that skin reactions were a major problem. The pre-post comparison of overall health status/health-related quality of life did not show significant changes with treatment.Our participants were comprised primarily of men with lung cancer, receiving care at a multidisciplinary outpatient unit where they got information from their oncologist and were later assessed by clinical nurse specialists. Almost all considered themselves to be well informed, despite receiving the immunotherapy for the first time. Specific expertise, skills and abilities of the health team, oncologist and nurses providing the care that patients receiving immunotherapy needs are essential.
Teaching and Training Department, Catalan Institute of Oncology (ICO), Avenida Gran Vía de L'Hospitalet 199-203, L'Hospitalet-Barcelona, 08908, Barcelona, Spain.Nursing Research Group (GRIN-IDIBELL), Barcelona, Spain.
E-Oncologia Unit, Catalan Institute of Oncology (ICO), Avenida Gran Vía de L'Hospitalet 199, L'Hospitalet-Barcelona, 08908, Barcelona, Spain.
Oncology Unit, Catalan Institute of Oncology (ICO), Avenida Gran Vía de L'Hospitalet 199, L'Hospitalet-Barcelona, 08908, Barcelona, Spain.
Cancer Care Oncology Unit, Catalan Institute of Oncology (ICO), Avenida Gran Vía de L'Hospitalet 199, L'Hospitalet-Barcelona, 08908, Barcelona, Spain.
Teaching and Training Department, Catalan Institute of Oncology (ICO), Avenida Gran Vía de L'Hospitalet 199-203, L'Hospitalet-Barcelona, 08908, Barcelona, Spain. mfo@iconcologia.net.Nursing Research Group (GRIN-IDIBELL), Barcelona, Spain. mfo@iconcologia.net.GRIN IDIBELL Research Group, IDIBELL/Universitat de Barcelona, Barcelona, Spain. mfo@iconcologia.net.
Knowledge and quality of life in cancer patients receiving immunotherapy for the first time. A cross-sectional study about being informed.
Correction to Estimating the Viscoelastic Properties of the Human Brain at 7 T MRI Using Intrinsic MRE and Nonlinear Inversion .
The prediction of subject traits using brain data is an important goal in neuroscience, with relevant applications in clinical research, as well as in the study of differential psychology and cognition. While previous prediction work has predominantly been done on neuroimaging data, our focus is on electroencephalography (EEG), a relatively inexpensive, widely available and non-invasive data modality. However, EEG data is complex and needs some form of feature extraction for subsequent prediction. This process is sometimes done manually, risking biases and suboptimal decisions. Here we investigate the use of data-driven Kernel methods for prediction from single channels using the EEG spectrogram, which reflects macro-scale neural oscillations in the brain. Specifically, we introduce the idea of reinterpreting the spectrogram of each channel as a probability distribution, so that we can leverage advanced machine learning techniques that can handle probability distributions with mathematical rigour and without the need for manual feature extraction. We explore how the resulting technique, Kernel mean embedding regression, compares to a standard application of Kernel ridge regression as well as to a non-Kernelised approach. Overall, we found that the Kernel methods exhibit improved performance thanks to their capacity to handle nonlinearities in the relation between the EEG spectrogram and the trait of interest. We leveraged this method to predict biological age in a multinational EEG data set, HarMNqEEG, showing the method's capacity to generalise across experiments and acquisition setups.
Departamento de Ciencia y Tecnología de la Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.CONICET, Buenos Aires, Argentina.Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Wellcome Centre for Integrative Neuroimaging, Oxford University, Oxford, UK.
Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.Wellcome Centre for Integrative Neuroimaging, Oxford University, Oxford, UK.Oxford Centre for Human Brain Activity, Department of Psychiatry, Oxford University, Oxford, UK.
Predicting Subject Traits From Brain Spectral Signatures: An Application to Brain Ageing.
Data aggregation across multiple research centers is gaining importance in the context of MRI research, driving diverse high-dimensional datasets to form large-scale heterogeneous sample, increasing statistical power and relevance of machine learning and deep learning algorithm. Site-related effects have been demonstrated to introduce bias in MRI features and confound subsequent analyses. Although Combating Batch (ComBat) technique has been recently reported to successfully harmonize multi-scale neuroimaging features, its performance assessments are still limited and largely based on qualitative visualizations and statistical analyses. In this study, we stand out by using a robust cross-validation approach to assess ComBat performances applied on volume- and surface-based measures acquired across three sites. A machine learning approach based on Multi-Class Gaussian Process Classifier was applied to predict imaging site based on raw and harmonized brain features, providing quantitative insights into ComBat effectiveness, and verifying the association between biological covariates and harmonized brain features. Our findings showed differences in terms of ComBat performances across measures of regional brain morphology, demonstrating tissue specific site effect modeling. ComBat adjustment of site effects also varied across regional level of each specific volume-based and surface-based measures. ComBat effectively eliminates unwanted data site-related variability, by maintaining or even enhancing data association with biological factors. Of note, ComBat has demonstrated flexibility and robustness of application on unseen independent gray matter volume data from the same sites.
Department of Neurosciences and Mental Health, Fondazione IRCS Cà Granda Ospedale Policlinico, Milano, Italy.Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.
Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.
Unit of Psychiatry and Clinical Psychobiology, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.University Vita-Salute San Raffaele, Milano, Italy.
Section of Psychiatry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Department of Psychiatry and Psychotherapy, Philipps-University Marburg/Marburg University Hospital, Marburg, Germany.
Department of Neurosciences and Mental Health, Fondazione IRCS Cà Granda Ospedale Policlinico, Milano, Italy.Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy.
Assessment of ComBat Harmonization Performance on Structural Magnetic Resonance Imaging Measurements.
Department of Health Policy, Institute for Pharmacological Research Mario Negri IRCCS, Milan, Italy. livio.garattini@marionegri.it.
Department of Health Policy, Institute for Pharmacological Research Mario Negri IRCCS, Milan, Italy.Department of Social and Political Sciences, CERGAS-SDA and F. Dondena, Bocconi University, Milan, Italy.
Obesity epidemic in European countries: from an unaddressed risk factor to a medicalized disease?
Analyze hematopoietic ADR signals of PARP inhibitors (Olaparib, Niraparib, Rucaparib, Talazoparib) using FAERS data to inform clinical practice.Extracted ASCII data for these drugs from Q1 2019 to Q2 2024. Employed SMQ and PT for standardization. Screened ADR signals via ROR, PRR, and MHRA method, comparing SMQ ratios.Hematopoietic ADRs peaked within 30 days post-treatment, with cytopenia and leukopenia most prevalent. Niraparib showed the highest adverse event count and signal intensity. Olaparib and Talazoparib also indicated strong hematotoxicity.PARP inhibitors vary in ADR incidence and duration, necessitating personalized treatment plans for optimized safety and rational use.
Pharmacy, China Pharmaceutical University, Nanjing, China.
School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Department of Pharmacy, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, China.
Department of Pharmacy, Chengdu Jinniu District People's Hospital, Chengdu, China.Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University.
Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University.Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China.Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain.
Hematopoietic adverse events associated with PARP inhibitors: A FAERS database study.
The human hippocampus is a key region in cognitive and emotional processing, but also a vulnerable and plastic region. Accordingly, there is a great interest in understanding how variability in the hippocampus' structure relates to variability in behavior in healthy and clinical populations. In this study, we aimed to link interindividual variability in subregional hippocampal networks (i.e., the brain grey matter networks of hippocampal subregions) to variability in behavioral phenotype. To do so, we used a multiblock multivariate approach mapping the association between grey matter volume in hippocampal subregions, grey matter volume in the whole brain regions, and behavioral variables in healthy adults. To ensure the robustness and generalizability of the findings, we implemented a cross-cohort discovery and validation framework. This framework utilized two independent cohorts: the Human Connectome Project Young Adult (HCP-YA) cohort and the Human Connectome Project Aging (HCP-A) cohort, enabling us to assess the replicability and generalizability of hippocampal-brain-behavior phenotypes across different age groups in the population. Our results highlighted a left anterior hippocampal morphological network including the left amygdala and the posterior midline structures whose expression relates to higher self-regulation, life satisfaction, and better performance at standard neuropsychological tests. The cross-cohort generalizability of the hippocampus-brain-behavior mapping demonstrates its relevance beyond a specific population sample. Our previous work in developmental populations showed that the hippocampus' head co-maturates with most of the brain during childhood. The current data-driven study further suggests that grey matter volume in the left hippocampal head network would be particularly relevant for self-regulation abilities in adults that influence a range of life outcomes. Future studies should thus investigate the factors influencing the development of this morphological network across childhood, as well as its relationship to neurocognitive phenotypes in various brain diseases.
Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Centre Jülich, Jülich, Germany.
Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Centre Jülich, Jülich, Germany.Key Laboratory of Cognition and Personality, Ministry of Education, Faculty of Psychology, Southwest University, Chongqing, China.
Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Discovery, Replicability, and Generalizability of a Left Anterior Hippocampus' Morphological Network Linked to Self-Regulation.
Daptomycin-Induced Eosinophilic Pneumonitis.
Necrotizing Soft Tissue Infection Due to Vibrio vulnificus After Bathing in the Baltic Sea.
Department of Surgery, Lankenau Medical Center, Wynnewood, PA. Electronic address: foxt@mlhs.org.
Department of Surgery, Lankenau Medical Center, Wynnewood, PA.
Department of Interventional Radiology, Lankenau Medical Center, Wynnewood, PA.
Department of Vascular Surgery, Lankenau Medical Center, Wynnewood PA.
Persistent primitive hypoglossal artery presenting as a pulsatile neck mass.
The research aimed to collect experience and viewpoints related to the nutrition management of patients with digestive tract cancers from medical care staff, patients, and family caregivers and provide reasonable and effective references for the mode of nutrition management of these patients.Using a phenomenological qualitative research method, six physicians, six nurses, three nutritionists, six patients, and six family caregivers from a tertiary A cancer hospital in Jiangsu Province were chosen by purposive sampling methods from February to June 2023. Data was collected through semi-structured in-depth interviews and analyzed by the content analysis method.Data analysis revealed two major themes, each with four subcategories: current status of clinical nutrition management tract cancers which consisted of lack of whole-process nutrition management model, inadequate role of nutrition management professionals, lack of a mechanism for continuous improvement of nutrition management quality, and lack of nutrition science popularization and training system and influencing factors of clinical nutrition management that contained patient-related factors, family-related factors, medical staff-related factors, and hospital environment and policy-related factors. Nutritional management of digestive cancer patients is currently inadequate and should be viewed through an integrated perspective. Improvements should be made at four angles: patient, family, healthcare provider, and hospital environment by establishing a multidisciplinary nutritional management team.
The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital &, Jiangsu Institute of Cancer Research, Nanjing, 210009, China.
Department of Nursing, Fudan University Shanghai Cancer Center, No. 270, Dong'an Road, Shanghai, 200032, China.Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong'an Road, Shanghai, 200032, China.
Department of Colorectal Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research &, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
School of Nursing, Nanjing Medical University, Nanjing, 211166, China.
School of Nursing, Nanjing Medical University, Nanjing, 211166, China. qinxu@njmu.edu.cn.
School of Health Policy and Management, Nanjing Medical University, Nanjing, China. yaojun@njmu.edu.cn.Institute of Healthy Jiangsu Development, Nanjing Medical University, Nanjing, China. yaojun@njmu.edu.cn.
Current status and influencing factors of nutrition management in patients with digestive tract cancer from the integrated perspective of medical care staff, patients, and family caregivers: a qualitative study.
Chemotherapy dose-limiting toxicities (DLT) pose a significant challenge in successful colon cancer treatment. Body composition analysis may enable tailored interventions thereby supporting the mitigation of chemotherapy toxic effects. This study aimed to evaluate and compare the effectiveness of using three-dimensional (3D) CT body composition measures from the entire lumbar spine levels (L1-L5) versus a single vertebral level (L3), the current gold standard, in predicting chemotherapy DLT in colon cancer patients.Retrospective analysis of 184 non-metastatic colon cancer patients receiving adjuvant chemotherapy was performed. DLT was defined as any occurrence of dose reduction or discontinuation due to chemotherapy toxicity. Using artificial intelligence (AI) auto-segmentation, 3D body composition measurements were obtained from patients' L1-L5 levels on CT imaging. The effectiveness of patients' 3D L3 body composition measurement and incorporating data from the entire L1-L5 (including L3) region in predicting DLT was examined.Of the 184 patients, 112 (60.9%) experienced DLT. Neuropathy was the most common toxicity (49/112, 43.8%) followed by diarrhea (35.7%) and nausea/vomiting (33%). Patients with DLT had lower muscle volume at all lumbar levels compared to those without. The machine learning model incorporating L1-L5 data and patient clinical data achieved high predictive performance (AUC = 0.75, accuracy = 0.75), outperforming the prediction using single L3 level (AUC = 0.65, accuracy = 0.65).Evaluating a patient's body composition allowed prediction of chemotherapy toxicities for colon cancer. Incorporating fully automated body composition analysis of CT slices from the entire lumbar region offers promising performance in early identification of high-risk individuals, with the ultimate aim of improving patient's quality of life.
Department of Surgery, Western Precinct, University of Melbourne, Melbourne, Australia.
Department of Surgery, Western Precinct, University of Melbourne, Melbourne, Australia.Department of Colorectal Surgery, Western Health, Melbourne, Australia.
Department of Oncology, Western Health, Melbourne, Australia.
Department of Surgery, Western Precinct, University of Melbourne, Melbourne, Australia.Department of Radiology, Western Health, Melbourne, Australia.
Department of Surgery, University of Melbourne, Melbourne, Australia.
Department of Surgery, Western Precinct, University of Melbourne, Melbourne, Australia. justin.yeung@unimelb.edu.au.Department of Colorectal Surgery, Western Health, Melbourne, Australia. justin.yeung@unimelb.edu.au.
Improving the prediction of chemotherapy dose-limiting toxicity in colon cancer patients using an AI-CT-based 3D body composition of the entire L1-L5 lumbar spine.
Delivering care that is responsive to who or what is most important to patients and family caregivers is a key aspect of quality care, yet it remains unclear how clinicians can best support individuals in expressing their personal values. We aimed to describe patient- and family caregiver-identified facilitators and barriers to engaging in values discussions with clinicians following implantation of a left ventricular assist device (LVAD).Using a qualitative descriptive approach, patients with an LVAD and their caregivers participated in 1-on-1 semistructured interviews and self-reported sociodemographics (January 2023-July 2023). Qualitative data were analyzed using thematic analysis and descriptive statistics were computed for quantitative data.Patients (n = 27; ages 30-76 years) were predominantly male (59%) and non-Hispanic Black (67%). Caregivers (n = 21; ages 27-76) were female (76%), non-Hispanic Black (67%), and a spouse/partner (62%). Facilitators (5 shared across patient/caregiver groups; 8 unique across patient/caregiver groups) included a perceived close relationship (patient/caregiver), values alignment (patient/caregiver), clinician discussion initiation (patient/caregiver), facing an impending decision (patient/caregiver), 1-on-1 dyadic interactions (patient/caregiver), being assertive (patient), positive dyadic communication (caregiver), and involvement of a third party (caregiver). Barriers (2 shared; 7 unique) included belief that their values are already known (patient/caregiver), sensitivity about values (patient/caregiver), uncertainty about timing (patient), poor clinical communication (patient), patient hopelessness (patient), perceived lack of clinician time (caregiver), and having a reserved personality (caregiver).Findings offer insight into actionable facilitators and barriers to discussions promoting incorporation of patient and family values into LVAD maintenance and chronic disease management.
School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: abechth@uab.edu.
School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama.
Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Division of Geriatric Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado; VA Eastern Colorado Geriatric Research Education and Clinical Center, Denver, Colorado.
Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Cardiology Clinic, UAB Hospital, Birmingham, Alabama.
Facilitators and Barriers to Values Discussions Following LVAD Implantation: Perspectives from Diverse Patients and Family Caregivers.
Graduate School, College of Medicine, Yonsei University, Seoul 03722, South Korea. Electronic address: subaek@yuhs.ac.
Declaration of martial law in South Korea: a threat to democracy.
Dilated cardiomyopathy (DCM) is a leading cause of heart failure (HF) characterized by left ventricular dilatation and systolic dysfunction not explained by abnormal loading conditions. Despite its prevalence, DCM's epidemiology and prognosis remain poorly studied in our country.A retrospective observational study encompassed patients discharged from all Spanish public hospitals between 2016 and 2021 diagnosed with DCM. Data were extracted from the Minimum Basic Data Set. The study focused on hospital admissions, comorbidities, in-hospital mortality, and readmission rates for circulatory system diseases at 30 and 365 days.Among 27,402 index episodes, DCM was the primary diagnosis in 12.4%, predominantly affecting men (72.5%). In-hospital mortality was 8.7%, with significant predictors including cardiogenic shock (OR: 12.4, 95% CI: 9.6-15.9), advanced or metastatic cancer (OR: 4.3, 95% CI: 3.8-5.0), renal failure (OR: 2.4, 95% CI: 2.2-2.7), and chronic liver disease (OR: 2.4, 95% CI: 2.1-2.8). Readmission rates were 7.9% at 30 days and 25.5% at 365 days, predominantly due to HF. Multivariate analysis identified age (IRR: 1.02, 95% CI: 1.01-1.02), female sex (IRR: 0.87, 95% CI: 0.79-0.96), severe hematological diseases (IRR: 2.12, 95% CI: 1.45-3.10), and metastatic cancer (IRR: 1.65, 95% CI: 1.31-2.07) as predictors of 30-day readmissions. At 365 days, predictors included age (IRR: 1.02, 95% CI: 1.01-1.02), female sex (IRR: 0.80, 95% CI: 0.74-0.86), severe hematological diseases (IRR: 2.43, 95% CI: 1.66-3.56), and renal failure (IRR: 1.42, 95% CI: 1.31-1.55).This study highlights the substantial hospitalization burden and mortality risk among DCM patients, emphasizing the necessity for advanced management strategies and specialized cardiac care.
Copyright © 2024 Hellenic Society of Cardiology. Publishing services by Elsevier Inc. All rights reserved.
Cardiology Department, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain; Faculty of Health Sciences, Universidad Alfonso X el Sabio (UAX), Villanueva de la Cañada, Madrid, Spain. Electronic address: athalbertus@gmail.com.
Cardiology Department, Hospital Universitario Reina Sofía, Córdoba, Spain; The Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba University, Córdoba, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
Institute for the Improvement of Health Care (IMAS Foundation), Madrid, Spain; Preventive Medicine Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
Institute for the Improvement of Health Care (IMAS Foundation), Madrid, Spain.
Institute for the Improvement of Health Care (IMAS Foundation), Madrid, Spain; Preventive Medicine Department, Área Sanitaria de Santiago y Barbanza, Instituto de Investigaciones Sanitarias de Santiago, Santiago de Compostela (A Coruña), Spain.
Cardiology Department, Hospital General Universitario de Toledo, Toledo, Spain.
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese
Comprehensive analysis of clinical characteristics, management, and prognosis in patients with dilated cardiomyopathy discharged from Spanish hospitals.
The present study investigated the clinical feasibility of replacing a part of conventional physiotherapy (PT) with Nintendo Wii® for the recovery of motor function and activities of daily living (ADL) in patients with glioma.This study included 10 patients with first-episode gliomas who were admitted to the neurosurgery department of a tertiary hospital. According to the patients' preferences, they were allocated to conventional PT or Wii® rehabilitation groups in which a part of the conventional PT sessions were replaced with Wii® training. The Fugl-Meyer Assessment (FMA), Short Physical Performance Battery (SPPB), Functional Independence Measure (FIM), and Hospital Anxiety and Depression Scale (HAD) measures were compared between the treatment groups using the Mann-Whitney U test.The Wii® rehabilitation and conventional PT groups included four (age 39 [26-53] years, n = 2 each WHO grade III and IV) and six patients (age 72 [59-80] years; all WHO grade IV), respectively. No patient dropouts were observed. The beneficial changes did not differ significantly between the conventional PT and Wii® groups (FMA: 1.0 vs. 1.5, SPPB: - 1.0 vs. - 0.5, FIM: - 2.5 vs. 2.5, HAD: 6 vs. 0). No adverse events such as falls were observed in either treatment group.Wii® rehabilitation had comparable effects with conventional PT for the inpatient rehabilitation of patients with glioma, with no adverse effects. Wii® rehabilitation showed potential as a home-based training modality because no physical assistance was required. Further investigation will be required because of the selection bias as a non-randomized trial.Exergame Wii® could be an effective rehabilitation tool for brain tumor patients.
Department of Rehabilitation Medicine, Kyorin University Hospital, Tokyo, Japan.
Department of Rehabilitation Medicine, Faculty of Medicine, Kyorin University, Tokyo, Japan. s-tashiro@ks.kyorin-u.ac.jp.Department of Rehabilitation Medicine, Keio University School of Medicine, Tokyo, Japan. s-tashiro@ks.kyorin-u.ac.jp.
Department of Rehabilitation Medicine, Faculty of Medicine, Kyorin University, Tokyo, Japan.
Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan.
Fuji Brain Institute and Hospital, Shizuoka, Japan.
Department of Rehabilitation Medicine, Faculty of Medicine, Kyorin University, Tokyo, Japan. yamada-shin@ks.kyorin-u.ac.jp.
Could video game-based physical rehabilitation substitute for conventional physiotherapy in patients with glioma? A proof-of-concept study.
Lung cancer remains one of the most diagnosed cancers in Canada and continues to be the leading cause of cancer deaths in Canada, responsible for 25% of all cancer deaths. Prior studies consistently report poor experiences of people with lung cancers. The study purpose was to explore the reasons for consistently poorer reported experience of people with lung cancer compared to people with gastrointestinal cancers, who previously have reported positive cancer care experiences within the same context, and to better understand key differences that influence patient experience.This qualitative study used semi-structured interviews of people living with lung cancer (LC) and gastrointestinal cancers (GIC) undergoing radiotherapy at a tertiary cancer centre. Thematic content analysis was conducted to analyse interview transcripts. A person-centred care framework was used to guide the development of the interview guide and data analysis.We interviewed 16 participants (10 LC and 6 GIC). Participants with LC reported poor experience leading to and at the time of their cancer diagnosis, including delays in their diagnosis and anxiety related to their diagnosis. Most participants in both groups reported severe symptoms prior to their radiotherapy. However, the symptoms of people living with LC further worsened during the radiation therapy with the addition of treatment side effects, while the symptoms of people living with GIC were better controlled during treatment. Participants living with LC noted poor communication, gaps in coordination and uncertainty. They acknowledged awareness of support services and other resources, but they reported no interest in accessing them.This study identified gaps in patient experience of people living with LC compared to GIC and proposed ideas for quality improvement projects, including expediting the diagnosis process, enhancing communication with patients around their lung cancer diagnosis, improved symptom management, and timing of supportive care services.
Department of Oncology, University of Calgary, Calgary, Canada. petra.grendarova@bccancer.bc.ca.BC Cancer, Victoria, Canada. petra.grendarova@bccancer.bc.ca.Division of Radiation Oncology, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada. petra.grendarova@bccancer.bc.ca.
Department of Oncology, University of Calgary, Calgary, Canada.
Department of Community Health Sciences, University of Calgary, Calgary, Canada.Alberta Strategy for Patient-Oriented Research (AbSPORU) Patient Engagement Team, Calgary, AB, Canada.
Department of Oncology, University of Calgary, Calgary, Canada.Tom Baker Cancer Centre, Calgary, Canada.Division of Radiation Oncology, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada.
Experience of individuals with lung and gastrointestinal cancers undergoing radiation therapy: a qualitative study.
The traditional analytical framework taken by neuroimaging studies in general, and lesion-behavior studies in particular, has been inferential in nature and has focused on identifying and interpreting statistically significant effects within the sample under study. While this framework is well-suited for hypothesis testing approaches, achieving the modern goal of precision medicine requires a different framework that is predictive in nature and that focuses on maximizing the predictive power of models and evaluating their ability to generalize beyond the data that were used to train them. However, few tools exist to support the development and evaluation of predictive models in the context of neuroimaging or lesion-behavior research, creating an obstacle to the widespread adoption of predictive modeling approaches in the field. Further, existing tools for lesion-behavior analysis are often unable to accommodate categorical outcome variables and often impose restrictions on the predictor data. Researchers therefore often must use different software packages and analytical approaches depending on (a) whether they are addressing a classification versus regression problem and (b) whether their predictor data correspond to binary lesion images, continuous lesion-network images, connectivity matrices, or other data modalities. To address these limitations, we have developed a MATLAB software toolkit that supports both inferential and predictive modeling frameworks, accommodates both classification and regression problems, and does not impose restrictions on the modality of the predictor data. The toolkit features both a graphical user interface and scripting interface, includes implementations of multiple mass-univariate, multivariate, and machine learning models, features built-in and customizable routines for hyper-parameter optimization, cross-validation, model stacking, and significance testing, and automatically generates text-based descriptions of key methodological details and modeling results to improve reproducibility and minimize errors in the reporting of methods and results. Here, we provide an overview and discussion of the toolkit's features and demonstrate its functionality by applying it to the question of how expressive and receptive language impairments relate to lesion location, structural disconnection, and functional network disruption in a large sample of patients with left hemispheric brain lesions. We find that impairments in expressive versus receptive language are most strongly associated with left lateral prefrontal and left posterior temporal/parietal damage, respectively. We also find that impairments in expressive vs. receptive language are associated with partially overlapping patterns of fronto-temporal structural disconnection and with similar functional networks. Importantly, we find that lesion location and lesion-derived network measures are highly predictive of both types of impairment, with predictions from models trained on these measures explaining ~30%-40% of the variance on average when applied to data from patients not used to train the models. We have made the toolkit publicly available, and we have included a comprehensive set of tutorial notebooks to support new users in applying the toolkit in their studies.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa, USA.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA.
Iowa Brain-Behavior Modeling Toolkit: An Open-Source MATLAB Tool for Inferential and Predictive Modeling of Imaging-Behavior and Lesion-Deficit Relationships.
The present study aimed to examine the efficacy of Mindfulness-Based Cancer Recovery (MBCR) training on fatigue and sleep quality of Iranian female patients with cancer.Thirty female patients with cancer were randomized to one of the MBCR and control groups. Subjects of the MBCR group received 8 sessions of MBCR training, while subjects of the control group received a 1-day didactic stress management seminar (SMS). All participants responded to the Cancer Fatigue Scale (CFT) and the Pittsburgh Sleep Quality Scale (PSQL) as pre- and post-test measures.Using MANCOVA for analyzing data revealed a significant improvement in the level of fatigue among subjects of the MBCR group compared to the controls; however, MBCR had no significant effect on the level of sleep quality.The Mindfulness-Based Cancer Recovery program can be considered an effective approach to reducing fatigue for Iranian female patients with cancer. The clinical implications of this finding require further investigation.The study was registered with the Iranian Registry of Clinical Trials (IRCT) on 24 June 2024; see [IRCT20240315061296N1].
Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran. basharpoor_sajjad@uma.ac.ir.
University of Mohaghegh Ardabili, Ardabil, Iran.
Department of Radiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Research Center for Psychiatry and Behavior Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. somayedaneshvar@sums.ac.ir.
School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia.
Mindfulness-Based Cancer Recovery (MBCR) training: the efficacy on fatigue and sleep quality of Iranian female patients with cancer.
The purpose of this study is to investigate the diagnostic accuracy of a new noninvasive imaging technique, ultrasound-guided attenuation parameter (UGAP), in diagnosing hepatic steatosis. This single-center retrospective study included 81 UGAP studies performed to guide therapy between July 2022 and June 2023 at a large academic medical center. Patients with either liver biopsy or Magnetic resonance-based proton-density fat fraction (MRI-PDFF) within 12 months of US-UGAP imaging, irrespective of order, were included. Patient demographics, body mass index, liver function tests, UGAP values, MRI-PDFF values, and liver biopsy results were obtained from a review of the medical records. Presence of steatosis was defined as PDFF >5.2% or >5% of hepatocytes with steatosis at pathology. Area under the ROC curve (AUROC) was used to measure UGAP accuracy for the detection of hepatic steatosis with statistical significance P < 0.05. There was a significant positive correlation between UGAP and MRI-PDFF (r = 0.463; P < 0.001; confidence interval [CI]: 0.220;0.651). The AUROC to differentiate absence of steatosis (n = 21) from presence of steatosis (n = 32) for UGAP with MRI as the gold standard was 0.760 (P < 0.001; CI: 0.623;0.867). A UGAP value >0.66 had 78% sensitivity and 67% specificity to identify steatosis presence on MRI-PDFF. The AUROC to differentiate absence of steatosis (n = 11) from presence of steatosis (n = 21) for UGAP with pathology as the gold standard was 0.894 (P < 0.001; CI: 0.734;0.974). A UGAP value >0.57 had 100% sensitivity and 64% specificity to identify steatosis presence at pathology. UGAP is an accurate measure for detecting the presence of hepatic steatosis and may be a noninvasive method for metabolic dysfunction-associated steatotic liver disease diagnosis and follow-up.
University of Pittsburgh School of Medicine, Pittsburgh, PA.
UPMC Department of Radiology, Pittsburgh, PA.
UPMC Department of Pathology, Pittsburgh, PA.
UPMC Department of Hepatology, Pittsburgh, PA.
Accuracy of Ultrasound-Guided Attenuation Parameter for Diagnosing Hepatic Steatosis.
Not harming others is widely regarded as a fundamental tenet of human morality. Harm aversion based on the consequences of an action is called utilitarianism while focusing on the action itself is associated with deontology. This study investigated how interoceptive processing affects the neural processing of utilitarian and deontological moral decision-making. The study utilized the heartbeat-evoked potential (HEP), an averaged electrophysiological component from electroencephalogram (EEG) to gauge cardiac interoceptive processing. Twenty-seven participants were asked to make utilitarian and deontological decisions for personal and impersonal moral dilemmas (18 for each) with direct and indirect harm actions, respectively, while their EEG and electrocardiogram were being recorded. We found no difference in HEPs between personal and impersonal moral dilemmas. In contrast, differential HEPs were observed between utilitarian and deontological moral decision-making, regardless of type of dilemmas. Significant differences were observed over centro-posterior electrodes between 110 and 172 milliseconds after R-peaks during the Scenario Phase, and over right fronto-temporal electrodes between 314 and 404 milliseconds after R-peaks in the Decision Phase. We confirmed that these differences in HEP amplitude between deontological and utilitarian decisions did not stem from cardiac artifacts. These findings reveal that the brain utilizes interoceptive information to make subsequent moral decisions.
Graduate School of Medicine, Osaka University, Osaka, Japan.
Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.Center for Information and Neural Networks (CiNet), National Institute of Information and Communication Technology, Osaka, Japan.
Interoceptive Brain Processing Influences Moral Decision Making.
Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is a circuit-based treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI (23 fMRI runs) to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Based upon these findings, we hypothesize that the suppression of the DMN by ALIC DBS is mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Department of Psychiatry and Behavioral Sciences, Keck School of Medicine of USC, Los Angeles, California, USA.
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.Department of Neurology and Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
Department of Neurosurgery, University of Arizona, Tucson, Arizona, USA.
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.Department of Neurological Surgery, University of California, San Francisco, California, USA.
Therapeutic DBS for OCD Suppresses the Default Mode Network.
Queuosine (Q) is a modification of the wobble base in tRNAs that decode NA(C/U) codons. It is ubiquitous in bacteria, including many pathogens. Streptococcus mutans is an early colonizer of dental plaque biofilm and a key player in dental caries. Using a combination of genetic and physiological approaches, the predicted Q synthesis and salvage pathways were validated in this organism. These experiments confirmed that S. mutans can synthesize Q de novo through similar pathways found in Bacillus subtilis and Escherichia coli. However, S. mutans has a distinct salvage pathway compared to these model organisms, as it uses a transporter belonging to the energy coupling factor (ECF) family controlled by a preQ1-dependent riboswitch. Furthermore, Q levels in this oral pathogen depended heavily on the media composition, suggesting that micronutrients can affect Q-mediated translation efficiency.
Department of Microbiology and Cell Science, IFAS, University of Florida, Gainesville, Florida, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.
Department of Microbiology and Cell Science, IFAS, University of Florida, Gainesville, Florida, USA.Genetics Institute, University of Florida, Gainesville, Florida, USA.
Environmental Control of Queuosine Levels in Streptococcus mutans tRNAs.
It is now understood that brain metastases do not occur randomly but have distinct spatial patterns depending on the origin of the cancer. According to the seed and soil hypothesis, the final colonization of metastatic cells is the result of their adaptation to the altered environment. To investigate the most favorable microenvironment for brain metastasis, we analyzed neuroimaging data from 177 patients with breast cancer brain metastasis and 548 patients with lung cancer brain metastasis to create a replicable probabilistic map of metastatic locations. Additionally, we used population-based data from open repositories to generate brain atlases of diverse microenvironment features, including gene expression, functional connectivity, glucose metabolism, and neurotransmitter transporters/receptors. We then compared the spatial correlation between brain metastasis frequency and these features, after which we constructed a general linear model to identify the most significant variables that contributed to tumor location predilection. Our findings revealed that brain metastases from breast cancer and lung cancer had distinct radiographic characteristics and distribution patterns. Breast cancer tended to metastasize in brain regions with decreased expression of genes associated with immunity and metabolism and reduced levels of connectomic hubness and glucose metabolism. In contrast, lung cancer had a higher probability of metastasizing in regions with active metabolism. Moreover, neurotransmitter systems play various roles in determining tumor location. These results provide new insights into the adaptation of metastatic cells to the brain microenvironment and illustrate how factors on diverse biological scales can affect the colonization of brain metastases.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.
Laboratory for Space Environment and Physical Science, Harbin Institute of Technology, Harbin, China.Institute of Science and Technology for Brain-Inspired Intelligence and Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Research Center for Social Computing and Information Retrieval, Harbin Institute of Technology, Harbin, China.Frontiers Science Center for Matter Behave in Space Environment, Harbin Institute of Technology, Harbin, China.
Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.
Laboratory for Space Environment and Physical Science, Harbin Institute of Technology, Harbin, China.
Department of Radiology, Tsukuba University Hospital, University of Tsukuba, Ibaraki, Japan.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Graduate School of Systems and Information Engineering, University of Tsukuba, Ibaraki, Japan.
The Spatial Distribution of Brain Metastasis Is Determined by the Heterogeneity of the Brain Microenvironment.
Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface (BCI) to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other BCI studies to ensure the successful placement of stimulation electrodes.
Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Department of Neurological Surgery, University of Chicago, Chicago, Illinois, USA.
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Neurosurgery, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois, USA.Committee on Computational Neuroscience, University of Chicago, Chicago, Illinois, USA.Neuroscience Institute, University of Chicago, Chicago, Illinois, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
A Roadmap for Implanting Electrode Arrays to Evoke Tactile Sensations Through Intracortical Stimulation.
Learning new categories is fundamental to cognition, occurring in daily life through various sensory modalities. However, it is not well known how acquiring new categories can modulate the brain networks. Resting-state functional connectivity is an effective method for detecting short-term brain alterations induced by various modality-based learning experiences. Using fMRI, our study investigated the intricate link between novel category learning and brain network reorganization. Eighty-four adults participated in an object categorization experiment utilizing visual (n = 41, with 20 females and a mean age of 23.91 ± 3.11 years) or tactile (n = 43, with 21 females and a mean age of 24.57 ± 2.58 years) modalities. Resting-state networks (RSNs) were identified using independent component analysis across the group of participants, and their correlation with individual differences in object category learning across modalities was examined using dual regression. Our results reveal an increased functional connectivity of the frontoparietal network with the left superior frontal gyrus in visual category learning task and with the right superior occipital gyrus and the left middle temporal gyrus after tactile category learning. Moreover, the somatomotor network demonstrated an increased functional connectivity with the left parahippocampus exclusively after tactile category learning. These findings illuminate the neural mechanisms of novel category learning, emphasizing distinct brain networks' roles in diverse modalities. The dynamic nature of RSNs emphasizes the ongoing adaptability of the brain, which is essential for efficient novel object category learning. This research provides valuable insights into the dynamic interplay between sensory learning, brain plasticity, and network reorganization, advancing our understanding of cognitive processes across different modalities.
Department of Neurology, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
Institute of Cognitive Neuroscience, Department of Biopsychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
Resting-State Network Plasticity Following Category Learning Depends on Sensory Modality.
Age-related atrophy of the human hippocampus and the enthorinal cortex starts accelerating at around age 60. Due to the contributions of these regions to many cognitive functions seamlessly used in everyday life, this can heavily impact the lives of elderly people. The hippocampus is not a unitary structure, and mechanisms of its age-related decline appear to differentially affect its subfields. Human and animal studies have suggested that altered sleep is associated with hippocampal atrophy. Yet, we know little about subfield specific effects of altered sleep in healthy aging and their effect on cognition. Here, in a sample of 118 older middle-aged and older adults (Mage = 63.25 y, range: 50-80 y), we examined the association between highly reliable hippocampal subfield and entorhinal cortex volumetry (n = 112), sleep measures derived from multi-night recordings of portable electroencephalography (n = 61) and episodic memory (n = 117). Objective sleep efficiency-but not self-report measures of sleep-was associated with entorhinal cortex volume when controlling for age. Age-related differences in subfield volumes were associated with objective sleep efficiency, but not with self-report measures of sleep. Moreover, participants characterized by a common multivariate pattern of subfield volumes that contributed to positive sleep-subfield volume associations, showed lower rates of forgetting. Our results showcase the benefit of objective sleep measures in identifying potential contributors of age-related differences in brain-behavior couplings.
Brain Imaging Centre, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
Brain Imaging Centre, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Brain Imaging Centre, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary.
Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
Brain Imaging Centre, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.Doctoral School of Biology and Sportbiology, Institute of Biology, Faculty of Sciences, University of Pécs, Pécs, Hungary.
Brain Imaging Centre, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
Momentum Laboratory of Neuroimmunology, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary.
Multi-Night Electroencephalography Reveals Positive Association Between Sleep Efficiency and Hippocampal Subfield and Entorhinal Cortex Volumes in Healthy Aging.
White matter hyperintensities (WMH) of presumed vascular origin are a magnetic resonance imaging (MRI)-based biomarker of cerebral small vessel disease (CSVD). WMH are associated with cognitive decline and increased risk of stroke and dementia, and are commonly observed in aging, vascular cognitive impairment, and neurodegenerative diseases. The reliable and rapid measurement of WMH in large-scale multisite clinical studies with heterogeneous patient populations remains challenging, where the diversity of imaging characteristics across studies adds additional complexity to this task. We present segcsvdWMH, a convolutional neural network-based tool developed to provide reliable and accurate WMH quantification across diverse clinical datasets. segcsvdWMH was developed using a large dataset consisting of over 700 fluid-attenuated inversion recovery MRI scans from seven multisite studies, spanning a wide range of clinical populations, WMH burdens, and imaging protocols. Model training incorporated anatomical information through a novel hierarchical segmentation approach, together with extensive data augmentation techniques to improve performance across varied imaging conditions. Benchmarked against three widely available segmentation tools, segcsvdWMH demonstrated superior accuracy, achieving mean Dice score improvements of 7.8% ± 9.7% over HyperMapp3r, 21.8% ± 8.6% over SAMSEG, and 43.5% ± 7.1% over WMH-SynthSeg across four diverse test datasets. segcsvdWMH also maintained consistently high Dice scores across these test datasets (mean DSC = 0.86 ± 0.08), and exhibited strong, stable correlations with periventricular, deep, and total WMH ground truth volumes (mean r = 0.99 ± 0.01). Additionally, segcsvdWMH was robust to low and moderate levels of simulated MRI spike noise artifacts and maintained strong performance across a range of binary segmentation thresholds and WMH burden levels. These findings suggest that segcsvdWMH may provide more accurate and robust WMH segmentation performance for heterogeneous clinical datasets characterized by varying degrees of CSVD severity.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.Centre for Clinical Brain Sciences, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
Centre for Clinical Brain Sciences, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
University Health Network's Krembil Brain Institute, Edmond J Safra Program in Parkinson's Disease and the Rossy PSP Centre, Toronto Western Hospital, Toronto, Ontario, Canada.Division of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Canada.
Department of Psychiatry, Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, Canada.
Rotman Research Institute, Baycrest Health Sciences, Toronto, Canada.Division of Biostatistics, Dalla Lana School of Public Health, Toronto, Canada.
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Department of Medical Imaging, University of Toronto, Toronto, Canada.Physical Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Toronto, Canada.
Department of Medical Imaging, University of Toronto, Toronto, Canada.
Department of Medical Imaging, University of Toronto, Toronto, Canada.Physical Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.Physical Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.Computational Radiology and Artificial Intelligence Unit, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.Physical Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Toronto, Canada.
SEB Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.Physical Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada.
ONDRI Investigators, ADNI, CAIN Investigators, colleagues from the Foundation Leducq Transatlantic Network of Excellence
segcsvdWMH: A Convolutional Neural Network-Based Tool for Quantifying White Matter Hyperintensities in Heterogeneous Patient Cohorts.
The thalamus is a collection of gray matter nuclei that play a crucial role in sensorimotor processing and modulation of cortical activity. Characterizing thalamic nuclei non-invasively with structural MRI is particularly relevant for patient populations with Parkinson's disease, epilepsy, dementia, and schizophrenia. However, severe head motion in these populations poses a significant challenge for in vivo mapping of thalamic nuclei. Recent advancements have leveraged the compressed sensing (CS) framework to accelerate structural MRI acquisition times in MPRAGE sequence variants, while fast segmentation tools like FastSurfer have reduced processing times in neuroimaging research. In this study, we evaluated thalamic nuclei segmentations derived from six different MPRAGE variants with varying degrees of CS acceleration (from about 9 to about 1-min acquisitions). Thalamic segmentations were initialized from either FastSurfer or FreeSurfer, and the robustness of the thalamic nuclei segmentation tool to different initialization inputs was evaluated. Our findings show minimal sequence effects with no systematic bias, and low volume variability across sequences for the whole thalamus and major thalamic nuclei. Notably, CS-accelerated sequences produced less variable volumes compared to non-CS sequences. Additionally, segmentations of thalamic nuclei initialized from FastSurfer and FreeSurfer were highly comparable. We provide the first evidence supporting that a good segmentation quality of thalamic nuclei with CS T1-weighted image acceleration in a clinical 3T MRI system is possible. Our findings encourage future applications of fast T1-weighted MRI to study deep gray matter. CS-accelerated sequences and rapid segmentation methods are promising tools for future studies aiming to characterize thalamic nuclei in vivo at 3T in both healthy individuals and clinical populations.
Center for Mind/Brain Sciences-CIMeC, University of Trento, Rovereto, Italy.
Center for Mind/Brain Sciences-CIMeC, University of Trento, Rovereto, Italy.Data Science for Health, Fondazione Bruno Kessler, Trento, Italy.
Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland.Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.Signal Processing Laboratory 5 (LTS5), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Advancing Thalamic Nuclei Segmentation: The Impact of Compressed Sensing on MRI Processing.
The ability to integrate semantic information into the context of a sentence is essential for human communication. Several studies have shown that the predictability of a final keyword based on the sentence context influences semantic integration on the behavioral, neurophysiological, and neural level. However, the architecture of the underlying network interactions for semantic integration across the lifespan remains unclear. In this study, 32 healthy participants (30-75 years) performed an auditory cloze probability task during functional magnetic resonance imaging (fMRI), requiring lexical decisions on the sentence's final words. Semantic integration demands were implicitly modulated by presenting sentences with expected, unexpected, anomalous, or pseudoword endings. To elucidate network interactions supporting semantic integration, we combined univariate task-based fMRI analyses with seed-based connectivity and between-network connectivity analyses. Behavioral data revealed typical semantic integration effects, with increased integration demands being associated with longer response latencies and reduced accuracy. Univariate results demonstrated increased left frontal and temporal brain activity for sentences with higher integration demands. Between-network interactions highlighted the role of task-positive and default mode networks for sentence processing with increased semantic integration demands. Furthermore, increasing integration demands led to a higher number of behaviorally relevant network interactions, suggesting that the increased between-network coupling becomes more relevant for successful task performance as integration demands increase. Our findings elucidate the complex network interactions underlying semantic integration across the aging continuum. Stronger interactions between various task-positive and default mode networks correlated with more efficient processing of sentences with increased semantic integration demands. These results may inform future studies with healthy old and clinical populations.
Research Group Cognition and Plasticity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.Wilhelm Wundt Institute for Psychology, Leipzig University, Leipzig, Germany.Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Research Group Cognition and Plasticity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Research Group Cognition and Plasticity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.Wilhelm Wundt Institute for Psychology, Leipzig University, Leipzig, Germany.
University Clinic and Outpatient Clinic for Radiology, University Hospital Halle (Saale), Halle, Germany.Halle MR Imaging Core Facility (HMRICF), Halle (Saale), Germany.
Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.Department of Neurosurgery, University Hospital Halle (Saale), Halle, Germany.
Department of Neurosurgery, University Hospital Halle (Saale), Halle, Germany.
Department of Neurosurgery, University Hospital Halle (Saale), Halle, Germany.Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany.
Semantic Integration Demands Modulate Large-Scale Network Interactions in the Brain.
Effective presentations are crucial for disseminating knowledge and cultivating skilled learners. Cognitive load theory (CLT) offers a framework for optimizing instructional design by managing the mental effort required for learning. This article explores principles from CLT with practical suggestions to create brain-friendly presentations, focusing on intrinsic, extraneous, and germane cognitive loads. Intrinsic load can be managed through pretraining, organizing topics from simple to complex, and segmenting topics. Extraneous load should be minimized through coherence, signaling, redundancy, and spatial/temporal contiguity principles to eliminate unnecessary cognitive burden. Germane load can be enhanced by incorporating personalization, contextualization, relevance, interactive elements, and variability to promote deeper engagement and schema construction. This article emphasizes applying CLT principles to aid the reader in translating theory into practice.
Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY.
Department of Neuroscience, University of Kentucky College of Medicine, Lexington, KY.
Department of Radiology, University of Kentucky College of Medicine, Lexington, KY.
Designing Brain-Friendly Ultrasound Presentations: Applying Cognitive Load Theory for Enhanced Learning.
Department of Dentistry, Radboud University Medical Center, Nijmegen, The Netherlands. Lucky.vanGennip@radboudumc.nl.
Department of Dentistry, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Correction to: Oral foci of infection and their relationship with hospital stay after haematopoietic cell transplantation.
The aim of this study was to investigate the effect of a 6-month Guolin Qigong on quality of life and serum cortisol among patients with cancer.This study was a two-arm and non-randomized controlled trial. Forty-nine patients with cancer who were over 18 years of age and diagnosed with cancer were enrolled in this study and assigned to either the Guolin Qigong intervention group (IG, n = 26) or the usual care group (UC, n = 23) for 6 months. During the Guolin Qigong exercise, the participants completed a training program consisting of five sessions per week and 40-60 min per session. The UC group maintained their usual lifestyle. The main outcomes included self-reported quality of life (European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30) and well-being (General Well-Being Schedule, GWB). The second outcome was stress-related hormone serum cortisol measured by enzyme-linked immunosorbent assay. All measurements were assessed at baseline and 6 months.Forty-nine participants (57.4% females, 26 in IG vs 23 in UC) were enrolled in the study, and forty-five participants completed all tests after the 6-month intervention (48.9% females, 25 in IG vs 20 in UC). Compared to the UC group, quality of life, physical function, and pain significantly improved in the IG (P < 0.05). Similarly, some sub-scales of GWB improved in the IG group compared to the UC group, especially for cheerful distracted and overall score (P < 0.05). However, there was no significant difference in serum cortisol between the two groups either at baseline or after intervention (P > 0.05).Six-month Guolin Qigong could improve quality of life, physical function, and pain, and have a beneficial effect on the well-being of cancer patients. Further studies are warranted to confirm these results.
Physical Education Department, Hainan Tropical Ocean University, Sanya, 572022, Hainan, China.
Institute for Health and Sport, Victoria University, Melbourne, Australia.
School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China. renwwang@163.com.
School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China.
Department of Kinesiology, Boise State University, Boise, 83725, USA.
Yunnan Plateau Thermal Health Industry Innovation Research Institute, Tengchong, 679100, China.Department of Health and Kinesiology, University of Illinois at Urban-Champaign, Champaign, 61801, USA.
Effect of Qigong exercise on quality of life and cortisol in patients with cancer: a non-randomized controlled trial.
Servicio de Farmacia, Hospital Universitario de Getafe, Madrid, España. Electronic address: eva.negro@salud.madrid.org.
Servicio de Farmacia, Hospital Universitario Ramón y Cajal, Madrid, España.
Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria
Emergency County Hospital Dr. Constantin Opriș , Baia Mare, Department of Forensic Medicine, Street George Coșbuc 31, Baia Mare, Maramureș, 430031, Romania. Electronic address: drmoldovanradu@yahoo.com.
Iuliu Haţieganu University of Medicine and Pharmacy, Department of Internal Medicine, Street Victor Babeș 8, Cluj-Napoca, Cluj, 400347, Romania.
University of Medicine and Pharmacy Carol Davila Bucharest Departament of Foresic Medicine, Street Bulevardul Eroii Sanitari 8, Bucharest, 050474, Romania.
Immunohistochemical study of ATP1A3 and plakophilin 2 as new potential markers in the diagnosis of myocardial ischemia.
This study aims to enhance compliance with lower limb lymphedema (LLL) prevention care measures post-gynecologic oncology surgery (GOS) through quality control circle (QCC) activity, aiming to improve patient recovery outcomes and reduce postoperative complications.A 6-month QCC activity was conducted within the hospital, employing the ten-step plan-do-check-act model for QCC activity. The root causes of inadequate implementation of LLL prevention care measures were analyzed, leading to the development of relevant strategies and protocols. Compliance rates of preventive care measures pre- and post-QCC activity were compared.The focus of this improvement initiative was on inadequate postoperative preventive measures and lack of standardized discharge preventive measures. Strategies included ensuring nurses proficiently assess LLL following gynecologic malignancy surgeries, enhancing standardized preventive measures for LLL post-GOS, and establishing personalized and diversified education models. Following the implementation of QCC activity, there was a significant improvement in the compliance rate of LLL prevention care measures. The compliance rate increased from 74.00% before the activity to 92.80%, surpassing the target rate by 119.00%, with an improvement rate of 25.40%. Comprehensive evaluations of circle members' abilities showed significant improvement, with notable increases in problem-solving abilities, initiative, and confidence.Implementation of QCC activity resulted in a substantial improvement in compliance with LLL prevention care measures following GOS, ensuring safer and more effective patient care services.
Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China.
Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China. 916856527@qq.com.
A quality control circle to improve preventive care for lower limb lymphedema in gynecologic oncology surgery.
CLEC12B is a C-type lectin receptor involved in the inhibition of NKs-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes and inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown. Upon phosphorylation of its immunoreceptor tyrosine-based inhibitory motif, we demonstrate that CLEC12B increases the production of innate chemokines from human melanocytes through the activation of the signal transducer and activator of transcription 1/IFN regulatory factor 1-mediated IFNγ pathway, resulting in chemoattraction of immune cells. We have demonstrated CLEC12B to potentiate the effect of IFNγ in primed melanocytes. Furthermore, CLEC12B recognizes cutaneous (Staphylococcus aureus and E coli) but not gut (Listeria monocytogenes) bacteria and is capable of modulating their chemokine responses. Finally, we have shown that CLEC12B senses motifs present on human melanocytes and fibroblasts but not keratinocytes. Together, these results demonstrate that CLEC12B plays an important function in the human skin, bridging innate and adaptative immunity. This mechanism is of great interest because IFNγ and cellular recruitment are key initial steps involved in inflammation of many skin pathologies, making this receptor an interesting therapeutic target.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), University of Côte d'Azur, Nice, France.
TheUniversity of Queensland, Brisbane, Australia.
CNRS, UPS, Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, Toulouse, France.
UMR3347 CNRS, INSERM U1021, Institut Curie, Orsay, France.
Institute for Immunology & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), University of Côte d'Azur, Nice, France; Department of Dermatology, University of Côte d'Azur, Centre Hospitalier Universitaire de Nice (CHU), Nice, France.
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), University of Côte d'Azur, Nice, France. Electronic address: Meri.TULIC@univ-cotedazur.fr.
CLEC12B Regulates Melanocyte Immunity and Homeostasis in the Skin through the Signal Transducer and Activator of Transcription 1/IRF1 Axis.
To investigate the effects of dynamic-static combined relaxation therapy on fatigue and sleep disorders in breast cancer patients undergoing chemotherapy.A total of 114 patients receiving chemotherapy at Tangshan People's Hospital (September 2023-June 2024) were randomly divided into three groups: control (routine nursing), experiment group 1 (static Benson relaxation), and experiment group 2 (dynamic yoga + static Benson relaxation). The intervention lasted 8 weeks. Cancer-related fatigue and sleep disorders were assessed before and after intervention using the Revised Piper Fatigue Scale and the Pittsburgh Sleep Quality Index (PSQI).Prior to intervention, there were no significant differences in fatigue and sleep quality across groups (P > 0.05). Post-intervention, both experiment groups showed significant improvements in fatigue and sleep quality compared to the control (P < 0.001). Experiment group 2 showed greater reductions in behavior, body, and total fatigue scores compared to experiment group 1 (P < 0.001). Sleep quality also improved significantly in both experiment groups, with experiment group 2 demonstrating superior outcomes in sleep quality, duration, daytime dysfunction, and total PSQI score (P < 0.05).The Benson relaxation technique and dynamic-static combined relaxation therapy are effective in reducing fatigue and improving sleep quality in breast cancer chemotherapy patients, with the dynamic-static combined relaxation therapy offering greater benefits.RMYY-LLKS-2024068.
Tangshan People's Hospital, Tangshan, 063001, China. zhoulizhi72@126.com.
Tangshan People's Hospital, Tangshan, 063001, China.
Second Hospital of Tangshan, Tangshan, 063000, China.
Effects of dynamic and static relaxation therapy on cancer-induced fatigue and sleep disorders in patients with breast cancer undergoing chemotherapy: a randomized control trial.
To identify risk factors for dysphagia in individuals who sustained traumatic cervical SCI. The pathophysiologic mechanisms of dysphagia in individuals with traumatic cervical spinal cord injury (SCI) are not well understood yet. Several risk factors for developing dysphagia after SCI were postulated including mechanical ventilation, tracheostomy, age, female sex, anterior surgical approach, SCI severity, and multilevel spinal fusion.Retrospective analysis: Candidate explanatory variables, including injury severity, age, neurological level of injury, surgical approach, number of fused spinal segments, and tracheostomy including its type, were analyzed using univariate and multivariable statistical analyses.We included patients, who were treated at the BG Trauma Center Murnau between 2013 and 2022.Datasets of a total of 407 patients with traumatic cervical SCI were included.Dysphagia prevalence and identification of associated risk factors.Our analysis included 407 individuals, of whom 22.6% had dysphagia. Tracheostomy and age were identified as the main risk factors for dysphagia after traumatic cervical SCI. Contrary to previous literature, injury severity, an anterior surgical approach, the type of tracheostomy, a higher neurological level of SCI, and multilevel spinal fusion did not show an increased risk after accounting for other factors.Our study identifies age and tracheostomy as primary risk factors for dysphagia after SCI, allowing to identify patients at risk and inform early-stage clinical management.
Copyright © 2025 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Spinal Cord Injury Center, BG Trauma Center Murnau, Murnau, Germany; ParaMove, SCI Research Unit, BG Trauma Center Murnau, Murnau, Germany.
Spinal Cord Injury Center, BG Trauma Center Murnau, Murnau, Germany.
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria; Department of Artificial Intelligence and Human Interfaces, Paris Lodron University of Salzburg, Salzburg, Austria.
Swiss Paraplegic Centre, Nottwil, Switzerland.
ParaMove, SCI Research Unit, BG Trauma Center Murnau, Murnau, Germany; Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria.
Spinal Cord Injury Center, BG Trauma Center Murnau, Murnau, Germany; ParaMove, SCI Research Unit, BG Trauma Center Murnau, Murnau, Germany; Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria. Electronic address: iris.leister@bgu-murnau.de.
Archives of physical medicine and rehabilitation
Risk Factors for Dysphagia After Traumatic Cervical Spinal Cord Injury: A Retrospective Study.
Early and accurate identification of the risk of psychological distress allows for timely intervention and improved prognosis. Current methods for predicting psychological distress among lung cancer patients using readily available data are limited. This study aimed to develop a robust machine learning (ML) model for determining the risk of psychological distress among lung cancer patients.A cross-sectional study was designed to collect data from 342 lung cancer patients. Least Absolute Shrinkage and Selection Operator (LASSO) was used for feature selection. Model training and validation were conducted with bootstrap resampling method. Fivefold cross-validation evaluated and optimized the model with parameter tuning. Feature importance was assessed using SHapley additive exPlanations (SHAP) method.The model identified seven independent risk factors of psychological distress: residence (β = 0.141), diagnosis duration (β = 0.055), TNM stage (β = 0.098), pain severity (β = 0.067), perceived stigma (β = 0.052), illness perception (β = 0.100), and coping style (β = 0.097). Among the eight ML algorithms evaluated, the extreme gradient boosting (XGBoost) algorithm demonstrated the highest performance with AUROC values of 0.988, 0.945, and 0.922 for the training, validation, and test sets, respectively. The model's results were further explained using SHAP, which revealed the importance and contribution of each risk factor to the overall distress risk. A web-based tool was developed based on this model to facilitate clinical use.The XGBoost classifier demonstrated exceptional performance, and clinical implementation of the web-based risk calculator can serve as an easy-to-use tool for health practitioners to formulate early prevention and intervention strategies.
Division of Science & Technology and Foreign Affairs, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, China.
School of Data Science, The Chinese University of Hong Kong, Shenzhen, 518172, China.
Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, China.
Nursing Department, Universitat Rovira I Virgili, 43002, Tarragona, Spain.
Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Jiangbei District, No. 6 of the 7Th Branch of Panxi Road, Chongqing, 400020, China. cqszyyrenyi@163.com.
Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 101402, China. shanghongcai@126.com.
Development and validation of a web-based calculator for determining the risk of psychological distress based on machine learning algorithms: A cross-sectional study of 342 lung cancer patients.
This multi-institutional observational study aimed to assess the incidence, severity, and impact of radiotherapy-related late toxicities of the cervical skin and soft tissue in head and neck cancer patients. We also explored patient interest in fat grafting as a potential treatment for skin and soft tissue sequelae.This study was conducted across 19 institutions in Japan. The study involved head and neck cancer patients who received ≥ 60 Gy of cervical radiotherapy concomitant with a history of neck dissection and were free of cancer recurrence ≥ 3 years after the final treatment. Consenting outpatients completed a self-administered questionnaire to collect data on symptom severity and the attending outpatient physicians reported data on demographics and treatments in a case report form.A total of 222 patients were enrolled. The incidence proportion of late cervical skin and soft tissue toxicities was 96%, with 32% of patients reporting their symptoms as severe, and 69% of patients reporting an impact on quality of life (QOL). An interest in or consideration of fat grafting was reported by 34% of patients, with a greater desire among those with severe symptoms.This study elucidated the incidence, severity, and life impact of late toxicities affecting the cervical skin and soft tissue after radiotherapy for head and neck cancer. These late toxicities were highly prevalent and significantly impacted QOL. There is a substantial demand for new treatments, such as fat grafting, to address these complications and enhance the QOL for survivors of head and neck cancer.
Department of Plastic and Reconstructive Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. takhigas@east.ncc.go.jp.
Biostatistics Division, Center for Research Administration and Support, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Division of Plastic and Reconstructive Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Department of Head and Neck Surgery, Mishima Central Hospital, Shizuoka, Japan.
Department of Plastic Reconstructive Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Department of Plastic and Reconstructive Surgery, Saitama Cancer Center, Saitama, Japan.
Department of Plastic and Reconstructive Surgery, Kyorin University, Tokyo, Japan.
Department of Plastic and Reconstructive Surgery, National Cancer Center Hospital, Tokyo, Japan.
Department of Plastic and Reconstructive Surgery, Aichi Cancer Center Hospital, Aichi, Japan.
Department of Plastic and Reconstructive Surgery, Kyushu University Hospital, Fukuoka, Japan.
Department of Plastic and Reconstructive Surgery, Shinshu University, Matsumoto, Japan.
Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Plastic and Reconstructive Surgery, Okayama University, Okayama, Japan.
Department of Plastic and Reconstructive Surgery, The University of Tokyo, Tokyo, Japan.
Department of Plastic and Reconstructive Surgery, Iwate Medical University, Morioka, Japan.
Department of Plastic Surgery, Hyogo Medical University, Hyogo, Japan.
Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Department of Plastic and Reconstructive Surgery, University of Occupational and Environmental Health, Fukuoka, Japan.
Department of Plastic and Reconstructive Surgery, Jikei University School of Medicine, Tokyo, Japan.
Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan.
Impact of radiotherapy-related late toxicities of skin and soft tissue in the neck on quality of life in head and neck cancer patients: a multi-institutional observational study in Japan.
School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK. Electronic address: b.g.frenguelli@warwick.ac.uk.
A term as Editor-in-Chief of Neuropharmacology: Ups and downs and highs and lows.
To assess whether the Life's Essential 8 (LE8) score mediates the association of socioeconomic status (SES) with atrial fibrillation (AF) and heart failure (HF).A total of 236,754 participants from the UK Biobank were included. SES was determined based on household income, education attainment, and employment status using latent class analysis. Cox regression was utilized to explore the association of SES with AF and HF after adjusting for age, sex, ethnicity, and alcohol status. Counterfactual mediation analysis was employed to calculate the mediation proportion of the LE8 score. Stratified analysis was conducted based on age and sex.With a median of 13.61 years of follow-up, 14,635 cases of AF and 6878 cases of HF were documented. The HR (95% CI) of the total effect of SES on AF was 1.43 (1.36, 1.48). The indirect effect mediated by the LE8 score was 1.14 (1.13, 1.15), with the mediation proportion being 40.84 (36.97, 47.01)%. The total effect of SES on HF was 2.44 (2.26, 2.59). The indirect effect was 1.28 (1.25, 1.29), with the mediation proportion being 36.77 (34.59, 39.06)%. The mediation proportion was greater for AF in age < 60 years compared to age ≥ 60 years, and it was also higher in males than females for both AF and HF.Approximately one-third of the socioeconomic inequalities in AF and HF could be explained by the LE8 score. These findings highlighted the importance of integrating cardiovascular health promotion into public health policies aimed at mitigating socioeconomic health inequalities.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China.
Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People's Hospital, Yichang, Hubei 443003, China.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: ylyang377@zzu.edu.cn.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address: xzshi@zzu.edu.cn.
Role of Life's Essential 8 score in mediating socioeconomic status in the incidence of atrial fibrillation and heart failure: a population-based cohort study.
Repetitive transcranial magnetic stimulation (rTMS) is a promising approach in improving swallowing function after stroke. However, comparative efficacy of different rTMS protocols for poststroke dysphagia (PSD) remains unclear.PubMed, Embase, and Cochrane database were systematically searched for eligible random controlled trials (RCTs) from inception to August 30, 2024.RCTs comparing rTMS with control or head-to-head comparisons of 2 rTMS protocols in patients with PSD.Data were extracted by 2 independent reviewers. A network meta-analysis combining direct and indirect evidence was conducted to assess the pooled findings of RCTs with standard mean difference (SMD) with 95% credible interval (CrI).Eighteen RCTs involving 760 participants (mean age of 62.4 [range 49.7-74.7] years; 45.7% women) were included. Pooled data showed that high frequency (HF)/ipsilesional hemisphere (ipsi-hemi) (SMD, -0.94; 95% CrI, -1.51 to -0.44), HF/bilateral hemisphere (bi-hemi) (SMD, -2.59; 95% CrI, -3.50 to -1.72), HF/ipsilesional cerebellar (ipsi-CRB) (SMD, -0.79; 95% CrI, -1.55 to -0.10), HF/bilateral cerebellar (bi-CRB) (SMD, -1.02; 95% CrI, -1.83 to -0.29), and HF/ipsi-hemi + low frequency (LF)/contralesional hemisphere (contra-hemi) (SMD, -2.72; 95% CrI, -4.12 to -1.41) rTMS all significantly improved swallowing function compared with control. For patients with acute stroke, HF/ipsi-hemi rTMS had a positive effect (SMD, -1.36; 95% CrI, -2.86 to -0.02); in subacute stage, HF/ipsi-hemi + LF/contra-hemi rTMS showed the best efficacy (SMD, -2.68; 95% CrI, -4.26 to -1.26). However, rTMS failed to improve swallowing function in chronic stage.This network meta-analysis showed that most of the rTMS protocols (HF/ipsi-hemi, HF/bi-hemi, HF/ipsi-CRB, HF/bi-CRB, and HF/ipsi-hemi + LF/contra-hemi) may improve swallowing function in patients with PSD. The HF/ipsi-hemi rTMS had a positive effect in acute stage and the HF/ipsi-hemi + LF/contra-hemi protocol seemed to have the best efficacy when applied in subacute stroke.
Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China; Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China; Clinical Research Center for Precision Diagnosis and Treatment of Neurological Diseases of Fujian Province, Fuzhou, China.
Department of Rehabilitation Medicine, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China.
Department of Statistical Science, University College London, London, United Kingdom.
Department of Rehabilitation Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China; Department of Rehabilitation Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Stroke Research Center, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China; Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China; Clinical Research Center for Precision Diagnosis and Treatment of Neurological Diseases of Fujian Province, Fuzhou, China. Electronic address: houweidu@fjmu.edu.cn.
Repetitive Transcranial Magnetic Stimulation Strategies for Poststroke Dysphagia: A Systematic Review and Network Meta-analysis.
Tumor-associated macrophages (TAMs), which differentiate from tissue-resident macrophages, are recognized for their ability to influence cancer progression and metastasis. However, the specific role of Kupffer cells (KCs), the intrinsic macrophages of the liver, in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we describe a novel mechanism by which exosomes derived from HCC cells induce KCs to transition into TAMs, thereby facilitating the metastasis of HCC in an IL6-JAK1-ACAP4 axis-dependent manner. Mechanistically, the exosome-mediated domestication of KCs by hepatoma cells constitutes one of the primary sources of IL6 production in the HCC microenvironment. IL6 then activates JAK1 to phosphorylate its downstream effector ACAP4 at Tyr843, a novel phosphorylation site identified in this context, which in turn promotes ARF6-GTPase activity and hepatoma cell migration. Furthermore, we found that the levels of IL6, as well as the phosphorylation of JAK1 and ACAP4 at Tyr843, were significantly greater in tumor tissues from HCC patients than in adjacent tissues. These findings suggest that the IL6-JAK1-ACAP4 axis may be a promising therapeutic target for HCC. Importantly, we screened bufalin, an active ingredient derived from Venenum Bufonis, and discovered that it inhibits JAK1 and disrupts the IL6-induced phosphorylation of ACAP4. This inhibition not only impairs hepatoma cell migration but also prevents the metastasis of HCC. These findings demonstrate the interplay between hepatoma cells and KCs through the IL6-JAK1-ACAP4 axis, thereby promoting HCC metastasis, and reveal the therapeutic potential of bufalin for the treatment of HCC through JAK1 inhibition.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230027, China.
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.National Institute of Traditional Chinese Medicine Constitution and Preventive Treatment of Diseases, Beijing University of Chinese Medicine, Beijing, 100029, China.
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.Department of Hepatobiliary, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
Department of Neurology, Northwestern Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
International journal of biological sciences
Kupffer Cell-derived IL6 Promotes Hepatocellular Carcinoma Metastasis Via the JAK1-ACAP4 Pathway.
Department of Biology, McMaster University, Hamilton, ON, Canada.
Macaulay Library, Cornell Lab of Ornithology, Cornell University, Ithaca, NY, USA.
Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada.Department of Statistics, University of Manitoba, Winnipeg, MB, Canada.
Exercising during cancer treatment reduces fatigue, improves quality of life, and increases survival, yet 60-70% of Australians undergoing cancer treatment do not meet current physical activity (PA) recommendations. This study aimed to explore barriers and enablers to PA amongst people undergoing cancer treatment and develop a video resource targeting these barriers.The study was guided by the capability, opportunity, motivation, behaviour (COM-B) and behaviour change wheel (BCW) frameworks. Focus groups were conducted with people undergoing cancer treatment. Thematic analysis of qualitative data generated themes representing barriers and enablers to PA which were mapped to behaviour change techniques (BCTs) and incorporated into a video.Four focus groups were conducted with 15 participants (mean age 57, range 21-75). Eighteen themes were generated and mapped to six domains of the COM-B. The main barriers to exercise were physical (cancer-related fatigue), psychological (fear of overexertion), and inconsistent messaging. Enabling factors included accessible information about PA and incorporating PA into the care plan. Six BCTs were identified: information about health consequences; information about emotional consequences; demonstration of the behaviour; social comparison; information about others' approval; and credible source. These were incorporated into the production of an 11-minute video.This research facilitated development of a novel, theory-informed video aimed at improving uptake of PA amongst people undergoing cancer treatment. Evaluating the acceptability and effectiveness of the video is needed to support implementation of this intervention into standard care.Incorporating BCTs into a video promoting PA may enhance PA uptake and health outcomes for people undergoing cancer treatment.
Department of Physiotherapy, Melbourne School of Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. nburgess1@student.unimelb.edu.au.Department of Physiotherapy, Austin Health, Heidelberg, Australia. nburgess1@student.unimelb.edu.au.
Department of Physiotherapy, Austin Health, Heidelberg, Australia.
Department of Physiotherapy, Melbourne School of Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.Department of Health Services Research, The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Physiotherapy, Melbourne School of Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.Department of Physiotherapy, Austin Health, Heidelberg, Australia.Institute for Breathing and Sleep, Heidelberg, Victoria, Australia.
Department of Physiotherapy, Melbourne School of Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.Institute for Breathing and Sleep, Heidelberg, Victoria, Australia.
Integrating behaviour change techniques into a video intervention to promote physical activity during cancer treatment (VidEx): a qualitative, theory-informed study.
Department of Emergency Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. henry9@ualberta.ca.Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. henry9@ualberta.ca.
Department of Emergency Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
ED discharge instructions: moving beyond English and French.
The effect of Meaning-Centered Interventions (MCI) in advanced cancer patients requires further comprehensive research.Two researchers independently searched the PubMed, EMBASE, SCOPUS, Cochrane, and PsycINFO databases to investigate the impact of MCI on anxiety and depressive symptoms, sense of meaning, and quality of life (QoL) in patients with advanced cancer from inception to April 2024. Statistical analyses were conducted using standardized mean difference (SMD) as the effect size with Stata 17.0 software for analysis, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was employed to assess the certainty of evidence.Data from 12 eligible studies, involving a total of 1,459 participants, were included in the review. The analysis found that 3 studies with 321 participants reported an improvement in the quality of life (QoL) of patients with advanced cancer within one month after the intervention, compared to the control group (SMD, 0.27; 95% CI, 0.03 to 0.52; I2 = 0%; p = 0.03). However, this effect did not persist during the 2-6 months following the intervention. In addition, 4 studies with 434 participants indicated that MCI was associated with an enhanced sense of meaning (SMD, 0.22; 95% CI, 0.09 to 0.36; I2 = 0%; p = 0.002). Furthermore, 8 studies with 1,192 participants and 7 studies with 1,156 participants found that MCI was associated with a reduction in depressive symptoms (SMD, -0.15; 95% CI, -0.24 to -0.05; I2 = 44.8%; p = 0.002) and anxiety symptoms (SMD, -0.16; 95% CI, -0.26 to -0.07; I2 = 46.3%; p = 0.001), respectively.Moderate-quality evidence indicates that MCI enhances the sense of meaning among patients with advanced cancer and reduces depressive and anxiety symptoms, but it does not improve their QoL.
Nursing Department, Shaoxing People's Hospital, No. 568, Zhongxing North Road, Yuecheng District, Shaoxing City, 312000, Zhejiang Province, China.
Department of Radiotherapy, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
Nursing Department, Shaoxing People's Hospital, No. 568, Zhongxing North Road, Yuecheng District, Shaoxing City, 312000, Zhejiang Province, China. zhuhaiyan6789@163.com.
Effectiveness of meaning-centered interventions on anxiety and depressive symptoms, sense of meaning, and quality of life in patients with advanced cancer: a meta-analysis of randomized controlled trials.
The growing number of athletes diagnosed with cancer requires a better understanding of their background, experiences, and specific goals to provide personalized care. Therefore, the purpose of this study was to explore the lived experiences of collegiate athletes in the United States diagnosed with cancer, reflecting on various barriers and challenges because of their cancer diagnosis, as they relate to their athletic participation and educational experiences.This qualitative study used a phenomenological approach to study the nature and states of lived experiences in collegiate athlete cancer survivors diagnosed with cancer between the ages of 10 and 39 years old. Eighteen collegiate athlete cancer survivors (14 females and 4 males) participated in semi-structured interviews.The mean age at the time of the interviews was 22.3 ± 1.6 years. Seventeen participants (94%) identified as white/Caucasian. Five themes related to challenges emerged from the interviews: (1) academic challenges, (2) athletic challenges, (3) gaps in support, (4) side effects, and (5) mental health challenges. The mental health needs of collegiate athlete cancer survivors have been notably reported.As research on young cancer survivors increases, there is an opportunity for a deeper understanding of their lived experiences. The themes that emerged from this study are important and meaningful to increase the educational and athletic support as well as the mental and physical health of these survivors.
Health Sciences, Rocky Mountain University of Health Professions, Provo, UT, USA. kelly.franks@rm.edu.Health and Life Sciences, Providence Christian College, Pasadena, CA, USA. kelly.franks@rm.edu.
Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State Health Children's Hospital, Hershey, PA, USA.Department of Public Health Sciences, Penn State University College of Medicine, Hershey, PA, USA.
Brooks College of Health Professions, Trine University, Fort Wayne, IN, USA.
Health Sciences, Rocky Mountain University of Health Professions, Provo, UT, USA.
The challenges experienced by collegiate athlete cancer survivors.
Department of Pediatrics, Cumming School of Medicine, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada. jennifer.thull-freedman@albertahealthservices.ca.Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada. jennifer.thull-freedman@albertahealthservices.ca.
Department of Pediatrics, Cumming School of Medicine, University of Calgary, 2500 University Dr NW, Calgary, AB, T2N 1N4, Canada.
Author response to ED discharge instructions: moving beyond English and French .
Department of Family Practice, University of British Columbia, Vancouver, BC, Canada. david.jerome@ubc.ca.Division of Clinical Sciences, Northern Ontario School of Medicine, Thunder Bay, ON, Canada. david.jerome@ubc.ca.Department of Family Medicine, University of Alberta, Edmonton, AB, Canada. david.jerome@ubc.ca.
Queen's University School of Medicine, Kingston, ON, Canada.
Just the facts: exercise-associated hyponatremia.
To compare the treatment of osteoradionecrosis (ORN) using a protocol that incorporates antimicrobial photodynamic therapy with a conventional treatment protocol.This retrospective study analyzed 55 patients diagnosed with ORN at a reference hospital between 2002 and 2021. Patients were treated using two different clinical protocols. Clinical treatment success was defined as the epithelialization of the ORN lesion, along with the absence of pain and local infection.A total of 53 ORN lesions were included, with a median development time of 30 months. The patient cohort was predominantly male (83.02%), with a median age of 58 years. The main causes of ORN were prosthetic trauma (28.30%) and dental extractions due to infection (32.07%). Good oral hygiene and hygiene of the lesion were identified as protective factors for achieving clinical success, with a significant correlation to lesion epithelialization (p ≤ 0.0001). ORN developed more rapidly in tumors of the oral cavity, with a median time of 8 months, compared to oropharyngeal tumors, which had a median time of 39 months (p = 0.01).The proposed treatment protocol, which includes antimicrobial photodynamic therapy, demonstrated greater effectiveness compared to the conventional protocol, achieving clinical success in 75% of the lesions analyzed in a shorter timeframe (p ≤ 0.0001). Additionally, maintaining proper oral and lesion hygiene is crucial for successful outcomes, and ORN develops more rapidly in patients with oral cavity tumors.
© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Researcher at the Molecular Oncology Research Center, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela Street - Dr. Paulo Prata, Barretos, São Paulo, 14784-400, Brazil.
Dentistry Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Radiotherapy Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Epidemiology and Biostatistics Unit, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Researcher at the Molecular Oncology Research Center, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela Street - Dr. Paulo Prata, Barretos, São Paulo, 14784-400, Brazil. fabilivazquez@gmail.com.
Effectiveness of a protocol with antimicrobial photodynamic therapy for treating osteoradionecrosis: a retrospective study.
In 2023, 35,000 new cases of breast cancer were diagnosed, becoming the first type of tumour diagnosed in Spain. This tumour and its treatments generate important changes in the patient's quality of life. Alterations in the range of motion, pain and both physical and psychological disability are some of the effects that breast cancer generates in patients. Physical prehabilitation could be an opportunity to prevent some of these adverse effects.The objective of this review was to analyse the changes in objective and subjective variables in patients with breast cancer who undergo prehabilitation compared to those who perform other interventions.Eight databases were used for the bibliographic search of the present review. Following the selected inclusion and exclusion criteria, seven studies were analysed. The quality of these studies was assessed with the PEDro scale. The structural characteristics of the various articles were examined, as well as the objective (ROM and biomarker) and subjective study variables (pain, physical and mental recovery, quality of life and psychological aspects.A total of 1054 patients were analysed in the present review. All objective variables improved in the group that underwent physical prehabilitation. Subjective variables also improved in said group, although the improvement achieved in psychological aspects was not maintained over time.Physical prehabilitation is an interesting strategy to generate changes in breast cancer patients.
Department of Physiotherapy, Institute of Biomedicine of Málaga (IBIMA), Chair of Physiotherapy and Disability, Faculty of Health Sciences, Andalucía Tech, University of Málaga, 29071, Málaga, Spain.
Department of Physiotherapy, Institute of Biomedicine of Málaga (IBIMA), Chair of Physiotherapy and Disability, Faculty of Health Sciences, Andalucía Tech, University of Málaga, 29071, Málaga, Spain. mgsa23@uma.es.
Department of Physiotherapy, Institute of Biomedicine of Málaga (IBIMA), Chair of Physiotherapy and Disability, Faculty of Health Sciences, Andalucía Tech, University of Málaga, 29071, Málaga, Spain.School of Clinical Sciences of the Faculty of Health, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
Physical prehabilitation in patients with breast cancer: a systematic review.
MKA Breast Cancer Clinic, Tepe Prime, Cankaya, 06800, Ankara, Turkey. altundag66@yahoo.com.
Use of scalp cooling therapy in patients with breast or gynecological cancers undergoing chemotherapy may be associated with a higher risk of systemic recurrence.
First Department of Obstetrics and Gynecology, Papageorgiou General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Department of Midwifery, School of Health and Care Sciences, University of West Attica, Athens, Greece.
What midwives should know about fertility awareness and its impact on reproductive behavior.
High-risk pregnancies require special attention in maternal and child health services, given the high potential for complications that can affect maternal and fetal health. The continuity of care (COC) approach is expected to increase family independence and prevent pregnancy complications. This study aims to analyze the effectiveness of COC in improving the family independence of high-risk pregnant women in preventing pregnancy complications.This study used a quasi-experimental design with a pretest-posttest approach without a control group, involving 134 high-risk pregnant women, in the target area at the Wonoayu Community Health Centre, Sidoarjo, Indonesia from February to May 2024, who were selected through purposive sampling. Data were collected through structured questionnaires before and after the COC intervention, which included assessing knowledge and family roles in supporting pregnant women's health. The COC mentoring program was implemented for three months, with a focus on family education and involvement in maternal healthcare. A validated questionnaire measured family self-reliance before and after the intervention.The study showed a significant increase in family self-reliance, with a p<0.001 in all aspects measured, including fulfilment of physiological and psychological needs, preparation for labor, the postpartum period, and preparation after the baby is born. This increase suggests that the COC intervention is effective in empowering families to support high-risk pregnant women. Before the intervention, the mean score for physiological and psychological needs fulfilment was 17.45, which increased to 36.42 after the intervention (p<0.001). In addition, labor preparation also showed a significant increase from 11.40 to 24.38, as well as postpartum preparation from 13.00 to 28.79, and preparation after the baby is born from 13.25 to 28.75 (all p<0.001).The consistent improvement in all measured aspects, indicated that the COC intervention not only improved families' knowledge and skills, but also contributed to their preparedness in supporting pregnant women during and after pregnancy.
Department of Midwifery, Poltekkes Kemenkes Surabaya, Surabaya, Indonesia.
Department of Environmental Health, Poltekkes Kemenkes Surabaya, Surabaya, Indonesia.
Department of Blood Bank Technology, Poltekkes Kemenkes Semarang, Semarang, Indonesia.
The role of continuity of care in high-risk pregnant women in Indonesia.
Nanomedicine enables precision-targeted therapies through a non-invasive approach, and nanoparticles may be biologically affected during their colonization in vivo. Ensuring the efficient expression of their ex vivo performance in vivo, while ensuring biosafety, is of great significance. Previous studies have employed genetically engineered E. coli following in vivo entry as a genetically engineered targeting synergist, to enhance the effect of focused ultrasound ablation by exploiting its targeted colonization of tumor tissue. However, the proliferation process of the actual potentiating nanomaterials, i.e., the aerosol proteins produced by genetically engineered E. coli, in vivo has not been precisely observed. The authors of this paper demonstrate this spatiotemporal change in the expression of gas vesicle proteins while genetically engineered E. coli reproduces following tumor colonization. Based on their targeting and proliferative properties, the authors chose to intervene in the treatment at the maximal gas vesicle protein count to enhance the monitoring and utilization of the potentiator. By examining the therapeutic potential of the novel combination of genetic engineering and focused ultrasound, we present a robust strategy that improves the efficiency of non-invasive treatments.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University Chongqing 400016 China zoujzh@cqmu.edu.cn +86-13708302390.Department of Ultrasound Medicine, Chongqing Shapingba Hospital, School of Medicine, Chongqing University Chongqing 400033 China.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University Chongqing 400016 China zoujzh@cqmu.edu.cn +86-13708302390.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University Chongqing 400016 China zoujzh@cqmu.edu.cn +86-13708302390.Department of Ultrasound, The People's Hospital of Chongqing Liang Jiang New Area Chongqing 400010 China.
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University Chongqing 400016 China zoujzh@cqmu.edu.cn +86-13708302390.Department of Ultrasound, Chongqing General Hospital, Chongqing University 401147 China.
Genetically engineered gas vesicle proteins with proliferative potential for synergistic targeted tumor therapy.
Groningen Centre for Health Law and Aletta Jacobs School of Public Health, University of Groningen, Groningen 9700 AS, Netherlands. Electronic address: m.m.e.hesselman@rug.nl.
Groningen Centre for Health Law and Aletta Jacobs School of Public Health, University of Groningen, Groningen 9700 AS, Netherlands.
Johns Hopkins Center for Health Security and Johns Hopkins Institute for Planetary Health, Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Department of Public Policy and Department of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
UK Faculty of Public Health, London, UK.
O'Neill Institute for National and Global Health Law, Georgetown University Law Center, Washington, DC, USA.
Ensuring health at the heart of climate change Advisory Opinion.
To develop an appropriate intervention utilizing acceptance and commitment therapy (ACT) tailored specifically for cancer patients undergoing radiotherapy, and to investigate its impact on hope, psychological resilience, psychological flexibility, and psychological distress among cancer patients receiving proton and heavy ion therapy.Eighty participants were allocated into an intervention group (n = 40) or a control group (n = 40) based on their admission time. The control and intervention groups underwent a 3-week health education program, with the intervention group additionally participating in a 3-week, 6-session acceptance and commitment therapy (ACT) group psychological intervention. Discrepancies in hope levels, psychological resilience, psychological flexibility, and psychological distress between the two groups were assessed at baseline, post-intervention, and a 3-month follow-up using linear mixed-effects analysis (LMM).LMM analyses revealed that at the end of the intervention, scores for hope and psychological resilience were higher in the intervention group compared to the control group (P = 0.025, P = 0.003), and scores for psychological flexibility were lower in the intervention group (P = 0.001). Furthermore, at the 3-month follow-up, HHI scores remained higher in the intervention group compared to the control group (P = 0.015). In contrast, scores for psychological flexibility and psychological distress were lower in the intervention group (P = 0.001, P = 0.001). These differences persisted even after adjusting for baseline values.A psychological intervention program based on the ACT model of treatment helps to promote psychological recovery in cancer patients with radiotherapy. Evidence is provided for the effectiveness of positive clinical psychological interventions.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300068349) on 15th February, 2023.
Department of Nursing, Shanghai Proton and Heavy Ion Center, Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Fudan University Cancer Hospital, Shanghai, China.
Department of Nursing, Shanghai Proton and Heavy Ion Center, Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Fudan University Cancer Hospital, Shanghai, China. hong_whw@aliyun.com.
Efficacy of acceptance and commitment therapy on psychological rehabilitation in cancer patients treated with proton and heavy ion therapy: a non-randomized controlled trial.
University of California, San Diego, Department of Psychiatry, School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0804, USA. Electronic address: jaredyoung@ucsd.edu.
Leveling up: Strategies for taking Neuropharmacology and us all to new heights.
The distance between the ribosome and the RNA polymerase active centers, known as the mRNA loop length, is crucial for transcription-translation coupling. Despite the existence of multiple expressomes with varying mRNA loop lengths, their in vivo roles remain largely unexplored. This study examines the mechanisms governing transcription termination in the Escherichia coli galactose operon, revealing a crucial role in the transcription and translation coupling state. The operon utilizes both Rho-independent and Rho-dependent terminators. Our findings demonstrate that long-loop coupled transcription-translation complexes preferentially terminate at the upstream Rho-independent terminator, while short-loop complexes bypass it, terminating at the downstream Rho-dependent terminator. The efficiency of the Rho-independent terminator is enhanced by an extended U-track, suggesting a novel mechanism to overcome ribosome inhibition. These results uncover a new regulatory layer in transcription termination, challenging the traditional view of this process as random and highlighting a predetermined mechanism based on the coupling state. We propose that tandem terminators may function as regulatory checkpoints under fluctuating ribosome-RNAP coupling conditions, which can occur due to specific cellular states or factors affecting ribosome or RNAP binding efficiency. This suggests a previously overlooked mechanism that could refine transcription termination choices and expand our understanding of transcription regulation.
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Cancer Research Institute, Chungnam National University, Daejeon, Republic of Korea.
Department of Biological Sciences, College of Biological Sciences and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
Deciphering the Coupling State-Dependent Transcription Termination in the Escherichia coli Galactose Operon.
Department of Dermatology, Tallaght University Hospital, Dublin, Ireland.
Expect the unexpected: a saying to bear in mind.
Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: morsaban1@tauex.tau.ac.il.
Division of Pulmonary Medicine, Barzilai University Medical Center, Ashkelon, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel.
A case series on trauma care in Gaza: reflections.
Department of Surgery, Nasser Hospital, Gaza Strip, occupied Palestinian territory.
Clinic of Emergency Medicine, The Arctic University of Norway, Tromsø, Norway.
Faculty of Medicine, Islamic University of Gaza, Gaza Strip, occupied Palestinian territory. Electronic address: osaidalserr@hotmail.com.
A case series on trauma care in Gaza: reflections - Authors' reply.
Critical Care Unit, Bnei Zion Medical Center, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Critical Care Division, Rambam Health Care Campus, Haifa 3109601, Israel. Electronic address: danyep@technion.ac.il.
Department of Paediatrics, University of Melbourne, Melbourne 3052, VIC, Australia. Electronic address: ntkatz@student.unimelb.edu.au.
University of Toronto, Toronto, ON, Canada.
University of Cape Town, Rondebosch, South Africa; Case Western Reserve University, Cleveland, OH, USA.
University of Bedfordshire, Luton, Bedfordshire, UK.
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Cognitive decline is intricately linked to various factors such as obesity, stress, poor sleep, and circadian rhythm misalignment, which are interrelated in their impact on cognitive health. Irregular food-intake timing further compounds these issues. The practice of prolonged nightly fasting (PNF) may help synchronize food intake with circadian rhythms, potentially mitigating adverse effects of cognitive decline and associated factors.A pilot nationwide, remotely delivered, 2-arm randomized controlled trial was conducted to assess the 8-week outcomes of cognition, stress, and sleep, after a PNF intervention (14-hr nightly fast, 6 nights/week, no calories after 8 pm) compared to a health education (HED) control condition. Participants were living with memory decline, stress, and obesity and had weekly check-in calls to report fasting times (PNF) or content feedback (HED).Participants were enrolled from 37 states in the US; N = 58, 86% women, 71% white, 93% non-Latinx, mean (SD) age 50.1 (5.1) years and BMI 35.6 (3.6) kg/m2. No group differences existed at baseline. Linear mixed-effects models were used to compare outcome change differences between groups. Compared to the HED control, the PNF intervention was associated with improved sleep quality (B = -2.52; SE = 0.90; 95% CI -4.30--0.74; p = 0.006). Perceived stress and everyday cognition significantly changed over time (p < 0.02), without significant difference by group.Changing food intake timing to exclude nighttime eating and promote a fasting period may help individuals living with obesity, memory decline, and stress to improve their sleep. Improved sleep quality may lead to additional health benefits.
Edson College of Nursing and Health Innovation, Phoenix, AZ, USA.
Edson College of Nursing and Health Innovation, Phoenix, AZ, USA.Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
Department of Psychology, College of Arts and Sciences, University of South Alabama, College of Liberal Arts and Sciences, Mobile, AL, USA.
Barrett Honors College, Arizona State University, Tempe, AZ, USA.
School of Nursing, University of Alabama Birmingham, Mobile, AL, USA.
Journal of clinical and translational science
Health impacts of a remotely delivered prolonged nightly fasting intervention in stressed adults with memory decline and obesity: A nationwide randomized controlled pilot trial.
Preclinical and clinical pharmacologic evidence indicates that orexin systems are relevant to sleep-wake cycle regulation and dimensions of reward and cognition, providing the basis for hypothesizing that they may be effective as therapeutics in mental disorders. Due to the limited efficacy and tolerability profiles of existing treatments for Major Depressive Disorder (MDD), investigational compounds in novel treatment classes are needed; seltorexant, an orexin receptor antagonist, is a potential new treatment currently under investigation.Mechanisms implicated in MDD, including reward and sleep, are first overviewed. Then, the safety, tolerability, and efficacy profiles of seltorexant and the wider context of orexin receptor antagonism for depression are discussed in focus. Preclinical and clinical data are also discussed. PubMed, Medline, Cochrane Library, Embase, Scopus, and Web of Science were systematically searched from inception to 10 October 2024, in accordance with PRISMA guidelines.Early clinical evidence suggests that seltorexant is effective in treating MDD, both in individuals diagnosed with insomnia and those not, although greater antidepressant effects are observed in individuals with severe sleep disturbance. Results from large phase III clinical trials are needed to confirm efficacy and safety.
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.Department of Psychiatry, Veteran Health Service Medical Center, Seoul, Republic of Korea.
Expert Opin Emerg Drugs. 2025-01-19;():1-11.
Seltorexant for major depressive disorder.
1) To determine the efficacy of Cognitive Behavioral Therapy for Insomnia (CBT-I) for improving insomnia, alcohol-related outcomes, and daytime functioning at post-treatment and at 3- and 6-month follow-up, in a largely African American Veteran sample; 2) Evaluate whether improvement in insomnia is associated with a reduction in alcohol-related outcomes post-treatment.An RCT of CBT-I (n = 31) compared to Quasi-Desensitization therapy (QDT, n = 32), eight weekly in-person sessions, with assessments at baseline, end of treatment (8 weeks), and 3- and 6-months post-treatment. Primary outcomes were the Insomnia Severity Index (ISI) total score, and Percent Days Abstinent (PDA). Secondary outcomes were sleep diary variables, drinks per day, percentage non-heavy drinking days, Penn Alcohol Craving Scale, PCS and MCS scale (from the SF-12), BDI and STAI-Trait subscale total scores.Post-treatment data were obtained from 88.9% of participants. Although CBT-I improved insomnia with effect sizes (E.S.) larger than the meta-analytic estimates, QDT was equally efficacious in improving insomnia (E.S. = -1.63 vs. -1.50), improving abstinence (E.S. = 1.54 vs. 1.91) and next-day functioning (E.S. = 0.26 vs. -0.17). Across treatment groups, remission from insomnia was associated with a lower post-treatment alcohol craving score (2.79, 95% CI 1.14, 4.44 vs. 9.51, 95% CI 6.06, 12.95 in non-responders), an effect that persisted for 6 months after treatment.CBT-I and QDT are equally effective for treating insomnia during early recovery from AUD. Reduced alcohol craving may be a mechanism by which a remission from insomnia improves drinking outcomes.
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104.Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA 19104.
Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA 19104.
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104.
University of Hawaii Psychiatry Residency Program, Hawaii, HI 96813.
Michigan Medicine, University of Michigan, Ann Arbor, MI 48109.
medRxiv : the preprint server for health sciences
A Randomized Controlled Trial of Cognitive Behavioral Therapy for Insomnia During Early Recovery from Alcohol Use Disorder Among Veterans.
We seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of the response of pancreatic cancer to the NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, and cisplatin), stromal-targeting drugs (calcipotriol and losartan), and an immune checkpoint inhibitor (anti-PD-L1). We developed a set of ordinary differential equations describing changes in tumor size (growth and regression) under the influence of five cocktails of treatments. Model calibration relies on three tumor volume measurements obtained over a 14-day period in a genetically engineered pancreatic cancer model (KrasLSLG12D-Trp53LSLR172H-Pdx1-Cre). Our model reproduces tumor growth in the control and treatment scenarios with an average concordance correlation coefficient (CCC) of 0.99±0.01. We conduct leave-one-out predictions (average CCC=0.74±0.06), mouse-specific predictions (average CCC=0.75±0.02), and hybrid, group-informed, mouse-specific predictions (average CCC=0.85±0.04). The developed mathematical model demonstrates high accuracy in fitting the experimental tumor data and a robust ability to predict tumor response to treatment. This approach has important implications for optimizing combination NGC treatment strategies.
Department of Aerospace Engineering and Engineering Mechanics, The University of Texas at Austin, Austin, Texas, 78712.Department of Mathematics, The University of Texas at Austin, Austin, Texas, 78712.
Department of Radiology, Institute of Regenerative Medicine, Institute of Translational Medicine and Therapeutics, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
Department of Radiology, Department of Biomedical Engineering The University of Alabama, Birmingham, Birmingham, Alabama, 35223.
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, 78712.Department of Diagnostic Medicine, The University of Texas at Austin, Austin, Texas, 78712.Department of Oncology, The University of Texas at Austin, Austin, Texas, 78712.Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, Texas, 78712.Livestrong Cancer Institutes The University of Texas at Austin, Austin, Texas, 78712.Department of Imaging Physics The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030.
Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, Texas, 78712.Texas Advanced Computing Center Austin, Texas, 78758.
Modeling tumor dynamics and predicting response to chemo-, targeted-, and immune-therapies in a murine model of pancreatic cancer.
Division of Nephrology, Dialysis, Transplantation, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
Roxadustat: More Than an Erythropoietic Agent?
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.
Response to Avoid Preclinical Errors When Using Urine Biomarkers of Exposure.
A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022. The primary outcome was the proportion of patient-quarter observations with ODT use stratified by age, sex, fragility fracture, and documented osteoporosis. Cuzick tests were performed to assess trends ODT use.Analysis of 166 673 420 patient-quarter observations revealed that over 70% of patients with fragility fractures did not have documented osteoporosis. Among women aged ≥65 years with documented osteoporosis, ODT fill rates increased between 2011 and 2022 from 36.3% to 50.1% for women without fragility fractures (P < .001) and from 30.8% to 43.7% for women with fragility fractures (P < .001). However, ODT fill rates declined (9.2% to 7.4% between 2011 and 2022) for women with fragility fractures and no documented osteoporosis (P = .015). Similar trends were observed among women aged 50-64 years and men.ODT use for patients with documented osteoporosis has increased but remains low. Low rates of ODT use for patients with fragility fractures in the absence of documented osteoporosis suggests that underdiagnosis of osteoporosis contributes to underuse of ODTs.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.
Division of General Medicine and Geriatrics, John T. Milliken Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.Center for Advancing Health Services, Policy & Economics Research, Washington University in St. Louis, St. Louis, MO 63110, USA.Optum Labs, Eden Prairie, MN 55344, USA.
Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Finance, Carlson School of Management, University of Minnesota, Minneapolis, MN 55455, USA.
Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Division of Endocrinology, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Center for Clinical and Translational Research, Maine Health Institute for Research, Scarborough, ME 04074, USA.
Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.Institute for Health Computing, University of Maryland, North Bethesda, MD 20852, USA.Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
The Journal of clinical endocrinology and metabolism
J Clin Endocrinol Metab. 2025-01-15;():.
Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.
Cognos Therapeutics, Inc., Inglewood , California , USA.Department of Neurological Surgery, Keck School of Medicine, University of Southern California (USC), Los Angeles , California , USA.USC/Norris Comprehensive Cancer Center, Los Angeles , California , USA.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, USC, Los Angeles , California , USA.
In Reply: Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model.
Mycotoxin, a secondary metabolite of fungus, found worldwide and concerning in crops and food, causes multiple acute and chronic toxicities. Its toxic profile includes hepatotoxicity, carcinogenicity, teratogenicity, estrogenicity, immunotoxicity, and neurotoxicity, leading to deleterious impact on human and animal health. Emerging evidence suggests that it adversely affects perinatal health and progeny by its ability to cross placental barriers.Due to its wide occurrence and potential toxicity on reproductive health, it is essential to understand the mechanisms of mycotoxin-related reproductive toxicity. This review summarizes the toxicities and mechanisms of mycotoxin on maternal and offspring reproduction among mammalian species. Approaches for effective mycotoxin alleviation are also discussed, providing strategies against mycotoxin contamination.The profound mycotoxin toxicities in female mammalian reproduction affect follicle assembly, embryo development, and fetus growth, thereby decreasing offspring fertility. Factors from endocrine system such as hypothalamic-pituitary-gonadal axis and gut-ovarian axis, placenta ABC transporters, organelle and cytoskeleton dynamics, cell cycle control, genomic stability, and redox homeostasis are found to be closely related to mycotoxin toxicities. Approaches from physical, chemical, biological, and supplementation of natural antioxidants are discussed for the mycotoxin elimination, while their applications are not widespread. Available ways for mycotoxin and its toxicities alleviation need further study. Since a species-, time-, and dose-specific response might exist in mycotoxin toxicities, more consideration should be given to the protocols for mycotoxin toxicity studies, such as experimental animal models, exposure duration, and dosage. Specific mechanism for mycotoxin, especially form a molecular biology perspective, could be investigated with multi-omics technologies and advanced imaging techniques. Mass spectrometry with algorithms may provide more accurate exposure assessments, and it may be further helpful to identify the high-risk individuals in the future.
Copyright © 2025. Published by Elsevier B.V.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China; Key Laboratory of Research On Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Reproductive Medicine of Guangxi Medical and Health Key Discipline Construction Project, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China. Electronic address: sunsc@njau.edu.cn.
Mycotoxin toxicity and its alleviation strategy on female mammalian reproduction and fertility.
Hebrew University Faculty of Medicine, Jerusalem, Israel.
Department of Counseling Psychology, Santa Clara University, Santa Clara, California, USA.
Cancer statistics, 2025: A hinge moment for optimism to morph into hope?
Complex craniofacial trauma is defined as those traumatic injuries that are not responding to initial treatment and may involve chronic infection, tissue exposure, and soft tissue contusions. Typical reconstruction using a Y-shaped microvascular venous anastomotic free flap is labor intensive. Although free flap grafts have been used in many applications, their use for combined microvascular anastomotic therapy remains an unexplored but attractive possibility.Correcting facial contour trauma is challenging because it requires careful planning of flap design, composition, and ancillary procedures METHODS: This study analyzed a retrospective cohort of 28 craniofacial trauma patients (18 males; 10 females) who underwent Y-shaped microvascular venous anastomosis free flap grafting for treatment of the defects between January 2020 and January 2022, and were followed up for more than 6 months after the procedure.The causes of defects were high-voltage electrical injuries (n = 12), after excision of scalp malignant tumors (n = 8), grade III burns (n = 6), and trauma (n = 2). By adjusting the height of the tissue and the different tissue components, the flaps were designed in three dimensions by contour mapping so that they had different thicknesses depending on the defect. Custom-sized flaps with a reliable envelope were taken while minimizing the loss of overlying skin. 6 flaps were based on two perforators, and another 19 were based on one perforator. Nine flaps were harvested in an inlay fashion. All flaps were fully viable and no donor lesions were present in any case. Contour and symmetry were improved in all patients, and all grafted patients were evaluated for pre- and postoperative aesthetic restoration.Our findings suggest that the Y-shaped microvascular venous anastomosis free flap approach may be a reliable alternative for aesthetic reconstruction of facial contour trauma.
Copyright © 2024. Published by Elsevier Masson SAS.
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, 563000 China; The Collaborative Innovation Center of Tissue, Damage Repair and Regeneration Medicine of Zunyi Medical University, 563000 China.
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, 563000 China; The Collaborative Innovation Center of Tissue, Damage Repair and Regeneration Medicine of Zunyi Medical University, 563000 China. Electronic address: zairongdoc04@163.com.
Journal of stomatology, oral and maxillofacial surgery
J Stomatol Oral Maxillofac Surg. 2025-01-14;():102203.
Y-shaped venous anastomosis combined with free flap for the treatment of complex craniofacial trauma.
Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran. Langarizadeh.m@iums.ac.ir.
Iran University of Medical Sciences, Tehran, Iran.
Correction: Key performance indicators of hospital supply chain: a systematic review.
In the United States, zoning and land use policies have been linked to high housing costs and residential segregation. Yet almost all zoning and land use data come from a handful of cross-sectional surveys, which are costly, time intensive, subject to low response rates and measurement error and are quickly dated. As an alternative, we construct the National Zoning and Land Use Database using natural language processing techniques on publicly available administrative data. We show this new database and our parsimonious measure of exclusionary zoning, the Zoning Restrictiveness Index, to be consistent with the Wharton Residential Land Use Regulatory Index (2018) and the National Longitudinal Land Use Survey (2019). Additionally, we overcome other limitations of these survey approaches, both by capturing previously omitted and important elements of land use policy and by revealing the land use regulations for a near-universe of municipalities in the San Francisco and Houston metropolitan statistical areas. We make all code and data publicly available, allowing the National Zoning and Land Use Database to be replicated in future years to ensure accurate, up-to-date and longitudinal nationwide zoning and land use data.
Office of Population Research and School of Public and International Affairs; Princeton University, Princeton, NJ, USA.
Department of Sociology, Princeton University, Princeton, NJ, USA.
Using Natural Language Processing to Construct a National Zoning and Land Use Database.
Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.Imperial College, London, UK.
Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
The Newcastle-upon-Tyne Hospitals NHS Foundation Trust, UK.
The Newcastle-upon-Tyne Hospitals NHS Foundation Trust, UK.Newcastle University Medicine Malaysia, Johor, Malaysia.
Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.London School of Hygiene and Tropical Medicine, UK.
Manchester University NHS Foundation Trust, UK.
British HIV Association guidelines on the management of opportunistic infection in people living with HIV: The clinical management of non-tuberculous mycobacteria 2024.
Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Kao Autoimmunity Institute and Department of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Macrophages Contribute to Cardiac Fibrosis and Diastolic Dysfunction in Systemic Sclerosis.
Every Story Matters: public voices in the COVID-19 Inquiry.
JNCQ0125-Implementing a Care-Based Nursing Workforce Model: Implications for Missed Care, Teamwork, and Satisfaction.
NanoHealth and Optical Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
NanoHealth and Optical Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
NanoHealth and Optical Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. bella.manshian@kuleuven.be.Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. bella.manshian@kuleuven.be.Leuven Cancer Institute, KU Leuven, Leuven, Belgium. bella.manshian@kuleuven.be.
Correction: Silver nanoparticle induced immunogenic cell death can improve immunotherapy.