The energy landscape of folding in n-C14H30 described by a machine-learned potential.

Folding and unfolding in molecules as simple as short hydrocarbons and as complicated as large proteins continue to be an active research field. Here, we investigate folding in n-C14H30 using both density functional theory (DFT)/B3LYP calculations of 27 772 local minima and a kinetic transition network calculated for a previously reported potential energy surface (PES) obtained by fitting roughly 250 000 B3LYP energies. In addition to generating a database of minima and the transition states that connect them, these calculations and the PES based on them have been used to develop a simple and accurate model for the energy landscape.

AppRaise: Software for Quantifying Evidence Uncertainty in Systematic Reviews Using a Posterior Mixture Model.

Rationale: Systematic reviews are essential for evidence-based healthcare decision-making. While it is relatively straightforward to quantitatively assess random errors in systematic reviews, as these are typically reported in primary studies, the assessment of biases often remains narrative. Primary studies seldom provide quantitative estimates of biases and their uncertainties, resulting in systematic reviews rarely including such measurements.

Routine Doppler Ultrasonography Does Not Differentiate Acute Tubular Necrosis and Rejection in Early Pediatric Kidney Transplantation.

Introduction: Differentiating acute tubular necrosis (ATN) from rejection in pediatric kidney transplant (KT) recipients remains challenging and necessitates invasive biopsy. Doppler ultrasound-derived resistive index (RI) is a noninvasive modality to assess graft status, but its diagnostic utility in children is unclear. This study evaluates RI's ability to distinguish ATN and rejection in KT.

Qualitative insights from an online community-based exercise intervention for persons living with HIV.

Introduction: Online community-based exercise (CBE) is a rehabilitation strategy that can promote health outcomes among people living with HIV. We aimed to describe experiences implementing a community-based exercise (CBE) intervention with adults living with HIV.

Methods: We conducted a longitudinal qualitative descriptive study involving interviews with adults living with HIV and persons implementing an online tele-coaching CBE intervention.

Vitamin C Does Not Affect Platelet Counts in Patients With Sepsis: A Post hoc Analysis of the Lessening Organ Dysfunction With Vitamin C Randomized Trial.

Objective: Vitamin C has been linked to alterations in platelet count and aggregation behavior. Given recent findings suggesting an association between vitamin C and adverse outcomes in patients with septic shock, we aimed to investigate whether vitamin C influences mortality in septic patients through its impact on platelets.

Design: Post hoc analysis of the Lessening Organ Dysfunction With Vitamin C (LOVIT) randomized trial (clinicaltrials.

Discovery of an exquisitely selective WDR5 chemical probe accelerated by a high-quality DEL-ML Hit.

Herein we present the rapid development of LH168, a potent and highly selective chemical probe for WDR5, streamlined by utilizing a DEL-ML (DNA encoded library-machine learning) hit as the chemical starting point. LH168 was comprehensively characterized in bioassays and demonstrated potent target engagement at the WIN-site pocket of WDR5, with an EC of approximately 10 nM, a long residence time, and exceptional proteome-wide selectivity for WDR5. In addition, we present the X-ray co-crystal structure and provide insights into the structure-activity relationships (SAR).

Neighborhood clustering analysis to define epithelial-stromal interface for tumor infiltrating lymphocyte evaluation.

Evaluation of tumor infiltrating lymphocytes as recommended by current guidelines is largely based on stromal regions within the tumor. In the context of epithelial malignancies, the epithelial region and the epithelial-stromal interface are not assessed, because of technical difficulties in manually discerning lymphocytes when admixed with epithelial tumor cells. The inability to quantify immune cells in epithelial-associated areas may negatively impact evaluation of patient response to immune checkpoint therapies.

Development and preliminary inter-rater reliability of the new PROOF tool to measure fidelity of problem-solving therapy for depression delivered by non-specialists in a low-resource African setting.

Problem-solving therapy (PST) is a brief psychological intervention often implemented for depression. Currently, there are no tools with well-evidenced reliability to measure PST fidelity. This pilot study aimed to measure the inter-rater reliability and agreement of the blem-Slving Therapy idelity (PROOF) scale, comprising binary 14-item adherence and an 8-item competence subscales.

Hippocampal subfield and amygdala volumes are associated with difficulties in emotion regulation of depressed patients with a history of childhood maltreatment.

Background: Previous studies indicate that hippocampal (subfield) and amygdala volumes may correlate with specific cognitive functions, coping strategies and emotion regulation. Here, we investigated associations between emotional processing and volumes of hippocampal subfields and amygdala. We focused on depressed patients since emotional dysregulation and hippocampal volume shrinkage are characteristic of them.

Physical morbidities in survivors of testicular germ cell tumors during childhood, adolescence, and young adulthood: a population-based retrospective matched cohort study.

Background: While testicular germ cell tumors (TGCT) survival exceeds 90%, many survivors of adult TGCT are at risk for treatment toxicities. Less is known about physical morbidities in children, adolescents, and young adults (CAYA) with TGCT.

Methods: We used the Pediatric Oncology Group of Ontario Networked Information System, the Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy, and the Ontario Cancer Registry to identify all CAYA males diagnosed with TGCT from 1992 to 2021 at age 11-21 years in Ontario, Canada.

Kin-Directed Altruism and Male Androphilia in Thailand: Investigating the Roles of Femininity and Neuroticism.

The kin selection hypothesis (KSH) proposes that same-sex attracted individuals offset their lowered direct reproduction via kin-directed altruism that increases close genetic relatives' reproduction, thereby enhancing inclusive fitness. Retrospective research found that childhood concerns for kin's well-being are elevated among birth-assigned males who are androphilic (i.e.

Drugs linked to blepharitis, meibomian gland dysfunction, and chalazion: a real-world, population-based pharmacovigilance analysis.

Background: Blepharitis, meibomian gland dysfunction (MGD), and chalazia are common disorders impacting quality of life. This population-based, pharmacovigilance study aims to identify systemic drugs disproportionately linked to these disorders.

Methods: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) were analysed (Q4 2003 to Q2 2024).

The feasibility and effect of a peer-facilitated, remote handcycling sport program for aging adults with spinal cord injury or disease: a mixed methods case series.

Study Design: Concurrent mixed methods case series.

Objectives: To examine the feasibility and effect of a peer-facilitated, remote handcycling sport program on physical, psychological, and social health of individuals with spinal cord injury or disease (SCI/D) aged ≥50 years.

Setting: Participants' homes.

Cannabis impacts female fertility as evidenced by an in vitro investigation and a case-control study.

Cannabis consumption and legalization is increasing globally, raising concerns about its impact on fertility. In humans, we previously demonstrated that tetrahydrocannabinol (THC) and its metabolites reach the ovarian follicle. An extensive body of literature describes THC's impact on sperm, however no such studies have determined its effects on the oocyte.

Distinct Neural Mechanisms of Visual and Sound Adaptation in the Cat Visual Cortex.

Sensory areas exhibit modular selectivity to stimuli, but they can also respond to features outside of their basic modality. Several studies have shown cross-modal plastic modifications between visual and auditory cortices; however, the exact mechanisms of these modifications are yet not completely known. To this aim, we investigated the effect of 12 min of visual versus sound adaptation (referring to forceful application of an optimal/nonoptimal stimulus to a neuron[s] under observation) on the infragranular and supragranular primary visual neurons (V1) of the cat (Felis catus).

Analyzing Reddit Social Media Content in the United States Related to H5N1: Sentiment and Topic Modeling Study.

Background: The H5N1 avian influenza A virus represents a serious threat to both animal and human health, with the potential to escalate into a global pandemic. Effective monitoring of social media during H5N1 avian influenza outbreaks could potentially offer critical insights to guide public health strategies. Social media platforms like Reddit, with their diverse and region-specific communities, provide a rich source of data that can reveal collective attitudes, concerns, and behavioral trends in real time.

Delineation of the post-operative primary tumour and nodal clinical target volumes in oral cavity squamous cell carcinoma: European Society for Radiotherapy and Oncology (ESTRO) clinical guidelines.

Background And Purpose: To date, no consensus guidelines have been published that systematically guide delineation of primary and nodal Clinical Target Volumes (CTVs) in patients who require post-operative radiotherapy (PORT) for mucosal Head and Neck squamous cell carcinoma (HNSCC). As a result, significant individual, institutional and national variation exists in the way that CTVs are delineated in the post-operative setting, leading to considerable heterogeneity in radiotherapy treatment.

Methods: A multi-disciplinary group of experts convened by the European Society for Radiotherapy and Oncology (ESTRO) set-out principles for the multi-disciplinary management of oral cavity squamous cell carcinoma (OCSCC).

Modulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade.

The success of immune checkpoint inhibitors is limited by multiple factors, including poor T cell infiltration and function within tumors, partly due to a dense extracellular matrix (ECM). Here, we investigate modulating the ECM by targeting integrin α5β1, a major fibronectin-binding and organizing integrin, to improve immunotherapy outcomes. Use of a function-blocking murinized α5β1 antibody reduces fibronectin fibril formation, enhances CD8 T cell transendothelial migration, increases vascular permeability, and decreases vessel-associated collagen.

Repurposing glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of depression: A systematic review of preclinical, observational and clinical investigations.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently used for metabolic conditions, have demonstrated potential antidepressant effects via neuromodulatory pathways. This systematic review aims to provide evidence on the antidepressant effects of GLP-1 RAs and elucidate their underlying mechanism of action.

Methods: We examined studies that investigated the effect of GLP-1 RAs on depressive symptoms.