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.

Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.

One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.

Lay views in Southern France of the acceptability of refusing to provide treatment because of alleged futility.

Aim: To carry out a detailed study of existing positions in the French public of the acceptability of refusing treatment because of alleged futility, and to try to link these to people's age, gender, and religious practice.

Method: 248 lay participants living in southern France were presented with 16 brief vignettes depicting a cancer patient at the end of life who asks his doctor to administer a new cancer treatment he has heard about. Considering that this treatment is futile in the patient's case, the doctor refuses to prescribe it.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Oocytes with impaired meiotic maturation contain increased mtDNA deletions.

Purpose: Induction of meiotic competence is a major goal of the controlled ovarian stimulation used in ART. Do factors intrinsic to the oocyte contribute to oocyte maturation? Deletions in mtDNA accumulate in long-lived post mitotic tissues and are found in human oocytes. If oogenesis cleanses the germline of deleterious deletions in mtDNA, meiotically competent oocytes should contain lower levels of mtDNA deletions vs.

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.

Versatility of Caenorhabditis elegans as a Model Organism for Evaluating Foodborne Neurotoxins and Food Bioactive Compounds in Nutritional Neuroscience.

Epidemiological evidence has shown that the regular ingestion of vegetables and fruits is associated with reduced risk of developing chronic diseases. The introduction of the 3Rs (replacement, reduction, and refinement) principle into animal experiments has led to the use of valid, cost-effective, and efficient alternative and complementary invertebrate animal models which are simpler and lower in the phylogenetic hierarchy. Caenorhabditis elegans (C.

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.

Association of LR treatment response category with outcome of patients with hepatocellular carcinoma on explant pathology.

Objectives: Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient's eligibility for LT. Imaging has a modest sensitivity of approximately 40-77% for detecting pathologically viable HCC in post-LRT patients.

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).

Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Kinetics of recovery and normalization of running biomechanics following aerobic-based exercise-induced muscle damage in recreational male runners.

Objectives: The study aimed to examine the effects of exercise-induced muscle damage on running kinetics.

Design: Twenty-six adult recreational male runners performed 60 min of downhill running (-10 %) at 65 % of maximal heart rate. Running gait changes, systemic and localized muscle damage markers were assessed pre - and post-exercise induced muscle damage protocol.

Ethnicity predicts long-term depressive symptom patterns in older adults with type 2 diabetes.

Objectives: Depression is a chronic disorder that significantly affects functional decline in older adults, especially those with type 2 diabetes (T2D). Ethnic groups may experience different depression risks and severities, yet the effect of ethnicity on depression trajectories and specific dimensions in older adults with T2D remains largely unexamined. We examined the longitudinal associations of ethnicity with depression and its specific dimensions over time in older Ashkenazi and non-Ashkenazi Jews with T2D.

Revumenib: a new era in acute leukemia treatment.

The AUGMENT-101 clinical trial reported that the use of revumenib led to improved overall survival (OS) and complete remission (CR)/CR with partial hematologic recovery (CRh) in patients with acute leukemias and has released updated data with longer follow-up of Phase 2 results. Additionally, revumenib has received FDA approval for its use in relapsed or refractory (r/r) lysine methyltransferase 2A rearranged (KMT2A-r) acute leukemias.

Stereotactic injection of murine brain tumor cells for neuro-oncology studies.

Glioblastomas (GBMs) are the most common and aggressive brain tumors, with a poor prognosis. Effective preclinical models are crucial to investigate GBM biology and develop novel treatments. Syngeneic models, which consist in injecting murine GBM cells into mice with a similar genetic background, offer reproducibility, cost-effectiveness, and an intact immune system, making them ideal for immunotherapy research.

Congenital Pulmonary Vascular Anomalies and Disease.

Congenital pulmonary vascular disease is a daunting and diverse topic spanning both pulmonary arterial and venous anomalies. Given advancements in treatment, patients with congenital anomalies have longer life expectancies into adulthood and practicing radiologists are bound to come across these patients during their daily practice. Additionally, many anomalies are discovered incidentally on imaging, yet may still have implications for patient care.

Osteonecrosis of the Humerus: Trends in Surgical Management of a Nationwide Sample From 2010 to 2021.

Introduction: The humeral head is the second most common site for osteonecrosis but its epidemiology is poorly described. This study aimed to better understand its treatment in the United States by 1) evaluating total operative procedures with rates normalized to the annual surgical volume; 2) determining trends of non-joint preserving (shoulder arthroplasty) vs. joint preserving procedures; and 3) quantifying rates of operative techniques in different aged cohorts (<50 vs.