K2 channel positive modulation reduces alcohol drinking in female C57BL/6J mice.

Although men have historically exhibited higher levels of alcohol use disorder (AUD) diagnosis, the gap between men and women has been diminishing quickly. Preclinical screening for pharmacological treatments for AUD has typically focused solely on males, ignoring the possibility that males and females may differ mechanistically for the same behavioral phenotype. To ensure the efficacy of treatment targets across the sexes, it is crucial to study the pharmacological effects of AUD treatments in males and females.

Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3-I148M Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults.

PNPLA3-I148M genotype is the strongest predictive single-nucleotide polymorphism for liver fat. We examine whether PNPLA3-I148M modifies associations between oxidative gaseous air pollutant exposure (O) with i) liver fat and ii) multi-omics profiles of miRNAs and metabolites linked to liver fat. Participants were 69 young adults (17-22 years) from the Meta-AIR cohort.

Quantifying structural changes in organised biomineralized surfaces using synchrotron Polarisation-induced Contrast X-ray Fluorescence.

The quantitative characterization of the structure of biomineral surfaces is needed for guiding regenerative strategies. Current techniques are compromised by a requirement for extensive sample preparation, limited length-scales, or the inability to repeatedly measure the same surface over time and monitor structural changes. We aim to address these deficiencies by developing Calcium (Ca) K-edge Polarisation Induced Contrast X-ray Fluorescence (PIC-XRF) to quantify hydroxyapatite (HAp) crystallite structural arrangements in high and low textured surfaces.

A collagen-based laboratory model to mimic sex-specific features of calcific aortic valve disease.

Calcific aortic valve disease (CAVD) shows in the deposition of calcium phosphates in the collagen-rich layer of the valve leaflets. This stiffens the leaflets and eventually leads to heart failure. Recent research suggests that CAVD follows sex-specific pathways: at the same severity of the disease, women tend to have fewer and less crystalline calcifications, and the phases of their calcifications are decidedly different than those of men; namely, dicalcium phosphate dihydrate (DCPD) - one of the mineral phases in CAVD - occurs almost exclusively in females.

Perspective: Challenges for Personalized Nutrition in the Current U.S. Regulatory Framework and Future Opportunities.

Personalized Nutrition (PN) aims to provide tailored dietary recommendations to improve a person's health outcomes by integrating a multitude of individual-level information and support desired behavior changes. The field is rapidly evolving with technological advances. As new biomarkers are discovered, wearables and other devices can now provide up-to-the-minute insights, and artificial intelligence (AI) and machine learning (ML) models support recommendations and lifestyle behavior change.

Lung cancer screening program quality indicators - review & recommendations - An International Association for the Study of Lung Cancer Delphi process study.

Introduction: Lung cancer screening (LCS) using low-dose-computed tomography reduces lung cancer mortality in high-risk individuals. Evaluating and monitoring LCS programs are important to ensure and improve quality, efficiency and participant outcomes. There is no agreement on LCS quality indicators (QIs).

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Novel tertiary diarylethylamines as functionally selective agonists of the kappa opioid receptor.

Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC = 14 nM, 83 % E) that did not elicit a β-arrestin-2 recruitment functional response (E < 10 %).

The acute management of penetrating carotid artery injuries-A systematic review.

Background: Penetrating carotid artery injuries (CAI) are rare with high morbidity and mortality. We aimed to perform a systematic review of the published literature to evaluate the workup and management of penetrating CAI.

Methods: Studies of acute management of adult trauma patients with penetrating common or internal carotid artery injuries on MEDLINE or EMBASE from 1946 through July 2024 were included following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement methodology.

Mobilize the Troops! Military Involvement in the History of Testicular Cancer.

This review examines the historical evolution of testicular cancer (TCa) treatment, emphasizing the transformative impact of World War II. Prior to the war, cases of more than 50 testicular tumors were exceedingly rare. The mobilization of American troops, especially after the German Blitz, resulted in widespread military health screenings, leading to a surge in incidental TCa diagnoses during the 1940s.

Floating BiOBr/TiC aerogel spheres for efficient degradation of quinolone antibiotics: Rapid oxygen transfer via triphase interface and effective charges separation by internal electric field.

The limited transport of oxygen at the solid-liquid interface and the poor charge separation efficiency of single catalyst significantly impedes the generation of reactive oxygen species (ROS), thereby weakening the application potential of photocatalytic technology in water pollution control. Herein, a hollow porous photocatalytic aerogel sphere (calcium alginate/cellulose nanofibers (CA/CNF)) loaded BiOBr/TiC, combining a favourable mass transfer structure with effective catalytic centers was firstly presented. The floatability and hollow pore structure facilitated rapid O transfer via a triphase interface, thereby promoting the generation of ROS.

The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy.

The severity of spinal muscular atrophy (SMA) is inversely correlated with the number of survival of motor neuron 2 (SMN2) copies an individual has. This observational, retrospective analysis of natural history data included untreated individuals with a genetic diagnosis of types 1-3 SMA and stratified disease-related characteristics by SMN2 copy number. The outcomes investigated were time to: death, permanent ventilation, respiratory support, feeding support, scoliosis surgery, and achievement and loss of motor milestones.

Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial.

Background: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.

Patients And Methods: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk.

CA-SQBG: Cross-attention guided Siamese quantum BiGRU for drug-drug interaction extraction.

Accurate and efficient drug-drug interaction extraction (DDIE) from the medical corpus is essential for pharmacovigilance, drug therapy and drug development. To solve the problems of unbalance dataset and lack of accurate manual annotations in DDIE, a cross-attention guided Siamese quantum BiGRU (CA-SQBG) is constructed to improve feature representation learning ability for DDIE. It mainly consists of two quantum BiGRUs (QBiGRUs) and a cross-attention, where two QBiGRUs are Siamese implemented in a variational quantum environment to learn the contextual semantic feature representation of drug pairs, cross-attention is employed to learn mutual information from the Siamese QBiGRUs, which in turn allows the two modules to extract DDI more collaboratively.

A retrospective evaluation of patient characteristics and recommendations of a novel multidisciplinary clinic for persons with advanced disability from multiple sclerosis.

Context: Persons with advanced multiple sclerosis (MS) require care beyond the disease modifying treatments offered in conventional MS clinics to address their complex physical and psychosocial needs. In the novel MS Comprehensive and Palliative Care (MSCPC) Program, an MS neurologist, palliative care specialist, and physiatrist collaborate to identify these needs and improve symptom control.

Objectives: To characterize the medical, physical, and psychosocial concerns of persons with advanced disability from MS and describe the recommended interventions of the MSCPC Program.

Mitigating dithiothreitol interference to gold/thiol interface in electrochemical detection of cathepsin B activity toward multiplex protease analysis.

Proteases are overexpressed at various stages of conditions such as cancers and thus can serve as biomarkers for disease diagnosis. Electrochemical techniques to detect the activity of extracellular proteases have gained attraction due to their multiplexing capability. Here we employ an electrochemical approach based on a 3 × 3 gold (Au) microelectrode array (MEA) functionalized with (2-aminoethyl)ferrocene (AEF) tagged specific peptide substrates to monitor cathepsin B (CB) protease activity.

Emotional intelligence as a predictor of functional outcomes in psychotic disorders.

Psychotic disorders are associated with significant impairment in psychosocial functioning, yet mechanisms associated with this impairment remain poorly understood. Emotional intelligence, a component of social cognition, is associated with psychosocial functioning in this population. However, prior work has used relatively small samples, reported inconsistent relations between functioning domains and emotional intelligence, and inconsistently considered negative symptoms.

24-Epibrassinolide treatment alleviates frost damage of apple flower via regulating proline, ROS, and energy metabolism.

Frost damage to apple flowers significantly affects both the quality and yield of apples, potentially leading to substantial economic losses. This study investigates the application of the environmentally friendly plant hormone 24-epibrassinolide (EBR) on apple flowers to assess its effects under frost stress conditions. The findings indicate that exogenous EBR treatment maintained favorable flower morphology, mitigated pistil browning, and reduced ion leakage.

AhASRK1, a peanut dual-specificity kinase that activates the Ca-ROS-MAPK signalling cascade to mediate programmed cell death induced by aluminium toxicity via ABA.

Aluminium (Al)-induced programmed cell death (PCD) is thought to be a main cause of Al phytotoxicity. However, the underlying mechanism by which Al induces PCD in plants is unclear. In this study, we characterized the function of AhASRK1 (Aluminum Sensitive Receptor-like protein Kinase1), an Al-induced LRR-type receptor-like kinase gene.