Molecular basis for shifted receptor recognition by an encephalitic arbovirus.

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.

Tibiofemoral cartilage strain and recovery following a 3-mile run measured using deep learning segmentation of bone and cartilage.

Objective: We sought to measure the deformation of tibiofemoral cartilage immediately following a 3-mile treadmill run, as well as the recovery of cartilage thickness the following day. To enable these measurements, we developed and validated deep learning models to automate tibiofemoral cartilage and bone segmentation from double-echo steady-state magnetic resonance imaging (MRI) scans.

Design: Eight asymptomatic male participants arrived at 7 a.

IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4 T cell proliferation.

Interleukin (IL)-7 promotes T cell expansion during lymphopenia. We studied the metabolic basis in CD4 T cells, observing increased glucose usage for nucleotide synthesis and oxidation in the tricarboxylic acid (TCA) cycle. Unlike other TCA metabolites, glucose-derived citrate does not accumulate upon IL-7 exposure, indicating diversion into other processes.

Long-Term Impact of an Online Physician Group-Coaching Program to Improve Burnout and Self-Compassion in Trainees.

Goal: To evaluate long-term outcomes of Better Together Physician Coaching, a digital life-coaching program to improve resident well-being.

Methods: We performed a secondary analysis of survey data from the pilot program implementation between January 2021 and June 2022. An intention-to-treat analysis was completed for baseline versus post-6 months and baseline versus post-12 months for all outcome measures.

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

Hemorrhagic Shock Presenting as the First Manifestation of Inflammatory Stricturing Crohn's Disease.

While hematochezia is common in Crohn's disease (CD), severe gastrointestinal hemorrhage causing hemodynamic instability is rare. Strictures, another frequent complication, usually cause obstructive symptoms. We report the first case of hemorrhagic shock from ulcerated ileal strictures as the initial presentation of CD.

Differential encoding of mammalian proprioception by voltage-gated sodium channels.

Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the essential nature of proprioceptive signaling in daily life, the mechanisms governing proprioceptor activity are poorly understood. Here, we identified nonredundant roles for two voltage-gated sodium channels (Nas), Na1.

Strategic Switching from Conventional Urea to Nano-Urea for Sustaining the Rice-Wheat Cropping System.

In the face of declining crop yields, inefficient fertilizer usage, nutrient depletion, and limited water availability, the efficiency of conventional NPK fertilizers is a critical issue in India. The hypothesis of this study posits that nano-nitrogen could enhance growth and photosynthetic efficiency in crop plants compared to conventional fertilizers. For this, a randomized block design (RBD) field experiment was conducted with six treatments: no nitrogen (T1), 100% N through urea (T2), and varying levels of N replacement with nano-nitrogen (33%: T3; 50%: T4; 66%: T5; and 100%: T6).

Nano-Delivery Revolution: Harnessing Mesenchymal Stem Cell-Derived Exosomes' Potential for Wound Healing.

Stem cell transplantation has proven effective in treating acute and chronic wounds, but its limitations, such as low cellular viability and the need for specialized transportation, highlight the necessity for alternative approaches. This review explores the potential of engineered exosomes, containing identified miRNAs/peptides, as a more stable and efficient cell-free therapy for regenerative medicine, particularly in wound healing. The discussion emphasizes the benefits of exosomes, including their stability, reduced damage, and consistent biological activity, paving the way for innovative applications like lyophilized exosomes, mist spray delivery, and exosome-based scaffolds.

The Impact of Role Models on Sexual Minority Women: A Qualitative Interview Study.

Sexual minority women (e.g., lesbian, bisexual, pansexual) have increased risk of experiencing various mental health problems compared to sexual minority men and heterosexual individuals.

Mammographic Vascular Microcalcifications as a Surrogate Parameter for Coronary Heart Disease: Correlation to Cardiac Computer Tomography and Proposal of a Classification Score.

Objective: This study develops a BI-RADS-like scoring system for vascular microcalcifications in mammographies, correlating breast arterial calcification (BAC) in a mammography with coronary artery calcification (CAC), and specifying differences between microcalcifications caused by BAC and microcalcifications potentially associated with malignant disease.

Materials And Methods: This retrospective single-center cohort study evaluated 124 consecutive female patients (with a median age of 57 years). The presence of CAC was evaluated based on the Agatston score obtained from non-enhanced coronary computed tomography, and the calcifications detected in the mammography were graded on a four-point Likert scale, with the following criteria: (1) no visible or sporadically scattered microcalcifications, (2) suspicious microcalcification not distinguishable from breast arterial calcification, (3) minor breast artery calcifications, and (4) major breast artery calcifications.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Filsuvez (Birch Triterpenes) Topical Gel.

Filsuvez (birch triterpenes) topical gel received approval in 2023 for the treatment of epidermolysis bullosa (EB) in pediatric patients (aged ≥6 months) and adults. It promotes wound healing by modulating inflammation, encouraging new tissue formation, and maintaining the skin barrier. In a randomized, double-blind, controlled, parallel-group, phase III trial (EASE, NCT03068780), 223 patients were randomly assigned to two groups: the first group received treatment with birch triterpenes topical gel (study gel, n = 109), and the second group received treatment with vehicle gel (n = 114).

Zelsuvmi (Berdazimer) Topical Gel.

Zelsuvmi (berdazimer) topical gel has been approved recently for the treatment of molluscum contagiosum (MC) in patients aged ≥1 year. In three phase 3, randomized, double-blind, vehicle-controlled trials of similar design, berdazimer was investigated for the treatment of MC. Berdazimer or vehicle was applied once daily on MC lesions until complete lesion clearance was observed or for up to 12 weeks.

Lysozyme-coated nanoparticles for active uptake and delivery of synthetic RNA and plasmid-encoded genes in plants.

Nanoparticle-mediated delivery of nucleic acids and proteins into intact plants has the potential to modify metabolic pathways and confer desirable traits in crops. Here we show that layered double hydroxide (LDH) nanosheets coated with lysozyme are actively taken up into the root tip, root hairs and lateral root junctions by endocytosis, and translocate via an active membrane trafficking pathway in plants. Lysozyme coating enhanced nanosheet uptake by (1) loosening the plant cell wall and (2) stimulating the expression of endocytosis and other membrane trafficking genes.

Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

How People With Vision Impairment Use Their Gaze to Hit a Ball.

Purpose: Understanding the impact of vision impairment on dynamic tasks requiring visual processing is crucial for developing effective adaptive strategies that support individuals with vision impairment in optimizing their performance in natural tasks. This study aimed to establish the gaze patterns used by individuals with vision impairment when hitting a moving target.

Methods: Nineteen tennis players with vision impairment were recruited and their eye and head movements were tracked while they returned tennis serves.

Loss of Mfn1 but not Mfn2 enhances adipogenesis.

Objective: A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.

Methods: We characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.

AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer.

Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10-15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.

Mechanisms of recalcitrant fucoidan breakdown in marine Planctomycetota.

Marine brown algae produce the highly recalcitrant polysaccharide fucoidan, contributing to long-term oceanic carbon storage and climate regulation. Fucoidan is degraded by specialized heterotrophic bacteria, which promote ecosystem function and global carbon turnover using largely uncharacterized mechanisms. Here, we isolate and study two Planctomycetota strains from the microbiome associated with the alga Fucus spiralis, which grow efficiently on chemically diverse fucoidans.

FISPGHAN statement on the global public health impact of metabolic dysfunction-associated steatotic liver disease.

As rates of obesity rise worldwide, incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, is increasing, worsening the burden of healthcare systems. The council of the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) identified the topic of MASLD epidemiology, treatment, and prevention as a global priority issue to be addressed by an expert team, with the goal to describe feasible and evidence-based actions that may contribute to reducing MASLD risk. The FISPGHAN member societies nominated experts in the field.

Impact of an Online Group-Coaching Program on Ambulatory Faculty Physician Well-Being: A Randomized Trial.

Background: Physician burnout contributes to distress, turnover, and poor patient outcomes. Evidence suggests individual professional coaching may mitigate burnout but is costly and time intensive. Group coaching evidence is lacking.

'You want to shield your kids': Patients' and their adult-children's serious illness conversations.

Context: Timely and transparent serious illness conversations (SIC) between family caregivers and patients facilitate high-quality end-of-life care and patients' and family caregivers' mental wellbeing, but frequently do not occur, happen too late, or are incomplete. While social relations and roles shape communication, few studies explore their influence on patient-caregiver SICs.

Objectives: Investigate how the parent-child relation and roles shape SICs between cancer patients and their adult-child caregivers (ACC), the largest caregiver population.