How SNARE proteins generate force to fuse membranes.

Membrane fusion is central to fundamental cellular processes such as exocytosis, when an intracellular machinery fuses membrane-enclosed vesicles to the plasma membrane for contents release. The core machinery components are the SNARE proteins. SNARE complexation pulls the membranes together, but the fusion mechanism remains unclear.

Fluoride-induced testicular and ovarian toxicity: evidence from animal studies.

Fluoride (F), as a natural element found in a wide range of sources such as water and certain foods, has been proven to be beneficial in preventing dental caries, but concerns have been raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form of F, has the ability to accumulate in reproductive organs and interfere with hormonal regulation and oxidative stress pathways, contributing to reproductive toxicity. While the exact mechanisms of F-induced reproductive toxicity are not fully understood, this review aims to elucidate the mechanisms involved in testicular and ovarian injury.

sVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration.

Recent studies have suggested that sVEGFR3 is involved in cardiac diseases by regulating lymphangiogenesis; however, results are inconsistent. The aim of this study was to investigate the function and mechanism of sVEGFR3 in myocardial ischemia/reperfusion injury (MI/RI). sVEGFR3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to oxygen-glucose deprivation/reperfusion.

GRAiCE: reconstructing terrestrial water storage anomalies with recurrent neural networks.

The Gravity Recovery and Climate Experiment (GRACE) and its follow-on (GRACE-FO) missions have provided estimates of Terrestrial Water Storage Anomalies (TWSA) since 2002, enabling the monitoring of global hydrological changes. However, temporal gaps within these datasets and the lack of TWSA observations prior to 2002 limit our understanding of long-term freshwater variability. In this study, we develop GRAiCE, a set of four global monthly TWSA reconstructions from 1984 to 2021 at 0.

Predictors, patterns, and correlates of moderate-severe psychological distress among New York City College Students during Waves 2-4 of COVID-19.

The COVID-19 pandemic may have exacerbated mental health conditions by introducing and/or modifying stressors, particularly in university populations. We examined longitudinal patterns, time-varying predictors, and contemporaneous correlates of moderate-severe psychological distress (MS-PD) among college students. During 2020-2021, participants completed self-administered questionnaires quarterly (T1 = 562, T2 = 334, T3 = 221, and T4 = 169).

Poor fixation stability does not account for motion perception deficits in amblyopia.

People with amblyopia show deficits in global motion perception, especially at slow speeds. These observers are also known to have unstable fixation when viewing stationary fixation targets, relative to healthy controls. It is possible that poor fixation stability during motion viewing interferes with the fidelity of the input to motion-sensitive neurons in visual cortex.

Adherence to tuberculosis (TB) treatment in high compared to low TB burden countries: study protocol for a systematic review and meta-analysis with a qualitative meta-synthesis of themes.

Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries.

Imaging Approach to Pulmonary Hypertension.

Pulmonary hypertension is a rare but important clinical problem that presents a sometimes challenging diagnostic dilemma. The diagnosis of pulmonary hypertension relies on a combination of clinical testing and radiologic imaging, with chest computed tomography (CT) often serving as the primary imaging modality for comprehensive evaluation of the chest. Chest CT can be used to evaluate for causes of pulmonary hypertension including chronic lung disease, pulmonary artery obstruction, and congenital heart disease.

Digital Profiling of Immune Biomarkers in Breast Cancer: Relation to Anthracycline Benefit.

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial.

An umbrella review and meta-analysis of 87 meta-analyses examining healthcare workers' mental health during the COVID-19 pandemic.

During the COVID-19 pandemic, healthcare workers (HCWs) experienced several changes in their work (e.g., longer hours, new policies) that affected their mental health.

Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.

Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial.

Background: People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits.

Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability.

Methods: We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20-40 years) from the RESIST Senior Individuals (SI) cohort.

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.

Racial and ethnic disparities in post-acute care service utilization after stroke.

Evidence examining disparities in post-acute care (PAC) utilization among various racial and ethnic groups after stroke and the influence of social determinants of health (SDOH) in these decisions is lacking. Thus, we searched the literature from January 2000 to November 2023 regarding PAC among individuals after stroke through: 1) Pubmed, 2) Scopus, 3) Web of Science, 4) Embase, and 5) CINAHL. We found 14 studies.

Systematic review and meta-analysis of pathogenic GJB2 variants in the Asian population.

Objectives: Define the extent to which pathogenic GJB2 (gap junction beta-2) variants are responsible for non-syndromic hearing loss (NSHL) in the Asian population.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. CINAHL, Embase, and PubMed's MEDLINE were accessed from 1997 to 2023 using permutations of the MeSH terms: "Asian," ''Southeast Asian,'' "South Asian," "East Asian," "Southeastern Asian," and "GJB2.

Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.

Neurons are equipped with microtubules of different stability with stable and dynamic domains often coexisting on the same microtubule. While dynamic microtubules undergo random transitions between disassembly and assembly, stable ones persist long enough to serve as platforms for tubulin-modifying enzymes (known as writers) that attach molecular components to the α- or β-tubulin subunits. The combination of these posttranslational modifications (PTMs) results in a "tubulin code," dictating the behavior of selected proteins (known as readers), some of which were shown to be crucial for neuronal function.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Identification of GBN5 as a molecular biomarker of pan-cancer species by integrated multi-omics analysis.

Introduction: We conducted a panoramic analysis of GBN5 expression and prognosis in 33 cancers, aiming to deepen the systematic understanding of GBN5 in cancer.

Materials And Methods: We employed a multi-omics approach, including transcriptomic, genomic, proteomic, single-cell cytomic, spatial transcriptomic, and genomic data, to explore the prognostic value and potential oncogenic mechanisms of GBN5 across pan-cancers from multiple perspectives.

Results: We found that GBN5 was differentially expressed in multiple tumors and showed early diagnostic value.

Interest in digital health tools for miscarriage support: A qualitative assessment of Canadian women facing early pregnancy loss.

Background: Early pregnancy loss (EPL) occurs in 10%-15% of all pregnancies but remains an underrecognized and undertreated condition. In Canada, resources to support individuals and their partners facing EPL remain scarce despite a high burden of psychosocial sequelae. Digital health tools hold the potential to fill important gaps in reproductive healthcare.