IL-21 shapes the B cell response in a context-dependent manner.

The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 B cells.

Long-Term Safety and Efficacy with Roflumilast Cream 0.15% in Patients Aged ≥6 Years with Atopic Dermatitis: A Phase 3 Open-Label Extension Trial.

Safety and efficacy of roflumilast cream 0.15% for atopic dermatitis (AD) were demonstrated in two 4-week phase 3 trials. Evaluate long-term safety, tolerability, and efficacy of roflumilast cream 0.

Lectin Microarray Analysis of Salivary Gland Glycoproteins from the Arboviral Vector Aedes aegypti and the Malaria Vector Anopheles stephensi.

Background And Objectives: Salivary glands proteins but not glycoconjugates have been previously studied in mosquito vectors of human diseases. Glycoconjugates from salivary gland-derived proteins from human-feeding tick vectors can elicit hypersensitivity reactions which may also occur with mosquito bites. Protein glycoconjugate in salivary glands of the principal arboviral vector Aedes aegypti and the rapidly spreading malaria vector Anopheles stephensi were therefore investigated.

Global Use, Adaptation, and Sharing of Massive Open Online Courses for Emergency Health on the OpenWHO Platform: Survey Study.

Background: The COVID-19 pandemic demonstrated the global need for accessible content to rapidly train health care workers during health emergencies. The massive open access online course (MOOC) format is a broadly embraced strategy for widespread dissemination of trainings. Yet, barriers associated with technology access, language, and cultural context limit the use of MOOCs, particularly in lower-resource communities.

Surprising features of nuclear receptor interaction networks revealed by live-cell single-molecule imaging.

Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells.

Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory diffuse large B-cell lymphoma: A phase III bridging study in Chinese patients.

Background: Patients with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options and poor outcomes.

Methods: This phase III study (NCT04236141) evaluated the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab (Pola+BR) versus BR in Chinese patients with transplant-ineligible R/R DLBCL to support regulatory submission in China. Patients were randomized 2:1 to receive Pola+BR or placebo+BR.

Elevated CA19-9 within the normal range suggests poorer prognosis in stage II CRC: A retrospective analysis of a large sample in a single center.

Objective: Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range.

Medical Student Confidence in Meeting Disability Competencies: Results of a national survey-based study.

People with disabilities have recently been declared a population at increased risk of health disparities, and research has cited a lack of physician training as a cause of that increased risk. Prior studies demonstrate that physicians lack confidence in caring for people with disabilities, but there is little research on disability competency among medical students. This study assessed medical students' confidence in six disability-related competencies and tested for associations between perceived confidence and students' personal demographics and institutional characteristics.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Metformin Alleviates Doxorubicin-Induced Cardiotoxicity via Preserving Mitochondrial Dynamics Balance and Calcium Homeostasis.

Doxorubicin (DOX) is a commonly used chemotherapeutic medication for treating malignancies, although its cardiotoxicity limits its use. There is growing evidence that alteration of the mitochondrial fission/fusion dynamic processes accompanied by excessive reactive oxygen species (ROS) production and alteration of calcium Ca homeostasis are potential underlying mechanisms of DOX-induced cardiotoxicity (DIC). Metformin (Met) is an AMP-activated protein kinase (AMPK) activator that has antioxidant properties and cardioprotective effects.

Transforming Non-Digital, Clinical Workflows to Detect and Track Vision-Threatening Diabetic Retinopathy via a Digital Platform Integrating Artificial Intelligence: Implementation Research.

Introduction: Screening diabetic retinopathy (DR) for timely management can reduce global blindness. Many existing DR screening programs worldwide are non-digital, standalone, and deployed with grading retinal photographs by trained personnel. To integrate the screening programs, with or without artificial intelligence (AI), into hospital information systems to improve their effectiveness, the non-digital workflow must be transformed into digital.

Geochemical partitioning and leaching behaviour of geogenic contaminants from the partially weathered rocks in chronic kidney disease of unknown etiology (CKDu) endemic regions in Sri Lanka.

Studies regarding geochemical partitioning and leaching behavior of Hofmeister ions, which is considered as a risk/causative factor for chronic kidney disease of unknown etiology (CKDu), are scarce. Therefore, Hofmeister ions' leaching behavior of partially weathered rocks from CKDu endemic (Girandurukotte) and non-endemic (Sewanagala) areas, Sri Lanka were compared. Rock mineralogy was analyzed using X-ray Diffraction, and total ion contents were determined using alkaline and acid digestions.

Strong adsorption of guanidinium cations to the air-water interface.

Combining Deep-UV second harmonic generation spectroscopy with molecular simulations, we confirm and quantify the specific adsorption of guanidinium cations to the air-water interface. Using a Langmuir analysis of measurements at multiple concentrations, we extract the Gibbs free energy of adsorption, finding it larger than typical thermal energies. Molecular simulations clarify the role of polarizability in tuning the thermodynamics of adsorption, and establish the preferential parallel alignment of guanidinium at the air-water interface.

Modeling DNA methyltransferase function to predict epigenetic correlation patterns in healthy and cancer cells.

DNA methylation is a crucial epigenetic modification that orchestrates chromatin remodelers that suppress transcription, and aberrations in DNA methylation result in a variety of conditions such as cancers and developmental disorders. While it is understood that methylation occurs at CpG-rich DNA regions, it is less understood how distinct methylation profiles are established within various cell types. In this work, we develop a molecular-transport model that depicts the genomic exploration of DNA methyltransferase within a multiscale DNA environment, incorporating biologically relevant factors like methylation rate and CpG density to predict how patterns are established.

The ecdysone-induced bZIP transcription factor MafB establishes a positive feedback loop to enhance vitellogenesis and reproduction in the mosquito.

Female mosquitoes require a vertebrate blood meal to activate reproduction, transmitting numerous devastating human diseases. Vitellogenesis is a central event of female reproduction that involves the massive production of vitellogenin (Vg) in the fat body and the maturation of ovaries. This process is controlled by the steroid hormone 20-hydroxyecdysone (20E); however, its molecular regulatory basis remains not completely understood.

Infectious keratitis following photorefractive keratectomy: a 13-year study at a tertiary center.

Introduction: Infectious keratitis is a rare but devastating complication following photorefractive keratectomy (PRK) that may lead to visual impairment. This study assessed the clinical features, treatment strategies, and outcomes of post-PRK infectious keratitis.

Methods: This retrospective study was conducted on patients with post-PRK infectious keratitis presenting to Khalili Hospital, Shiraz, Iran, from June 2011 to March 2024.

Characterization of mint virus C, a new member of the genus Carlavirus.

Here, we report the complete genome sequence of a new carlavirus causing mosaic on mint plants in Italy, which we have tentatively named "mint virus C" (MVC). Flexuous particles of around 600 nm were observed using transmission electron microscopy, and next-generation sequencing was performed to determine the nucleotide sequence of the MVC genome, which was found to be 8558 nt long, excluding the poly(A) tail, and shows the typical organization of a carlavirus. The putative proteins encoded by MVC are 44-56% identical to the closest matches in the NCBI database, suggesting that MVC should be considered a member of a new species in the genus Carlavirus.

Patient- and clinician-based evaluation of large language models for patient education in prostate cancer radiotherapy.

Background: This study aims to evaluate the capabilities and limitations of large language models (LLMs) for providing patient education for men undergoing radiotherapy for localized prostate cancer, incorporating assessments from both clinicians and patients.

Methods: Six questions about definitive radiotherapy for prostate cancer were designed based on common patient inquiries. These questions were presented to different LLMs [ChatGPT‑4, ChatGPT-4o (both OpenAI Inc.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Ribotyping Staphylococcus epidermidis Using Probabilistic Sequence Analysis and Levenshtein Distance Algorithm.

Staphylococcus epidermidis (S. epidermidis) live in different human locations and natural environments. For ribotyping S.

A Consistent Lack of Consistency: Definitions, Evidentiary Expectations and Potential Use of Meaningful Change Data in Clinical Outcome Assessments Across Stakeholders. Results from a DIA Working Group Literature Review and Survey.

Background: Clinical outcome assessments (COAs) measure how patients feel or function and can be used to understand which patients experience benefits of treatment and which do not. Interpretation of COA data is influenced by how meaningful change is defined. We aimed to compare how different stakeholders define, assess, and use meaningful change for decisions that impact patients.

Fluoroscopy-guided aspiration of the acutely dislocated total hip arthroplasty: a feasible, high-yield, and safe procedure.

Objective: To determine the feasibility, yield, and safety of fluoroscopic-guided aspiration of the acutely dislocated total hip arthroplasty (AD-THA).

Materials And Methods: IRB-approved, retrospective review of fluoroscopic-guided aspirations of AD-THA (January 2005-December 2023) was performed. Data from electronic charts and fluoroscopy images/reports were obtained.

Brief Report: Stated Preferences for Long-Acting Injectable ART Among Mobile Men Living With HIV in Malawi: A Qualitative Study.

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV).

Methods: We conducted a qualitative substudy within two parent trials in 24 health facilities in Malawi that enrolled MLHIV ≥15 years not on ART.

Brief Report: Genital Microbiome, Inflammation, and Tenofovir Levels in Transgender Men and Cisgender Women Taking Oral PrEP.

Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP.

Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP.

Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.

Purpose: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects.