A Functional Response in Resource Selection Links Multiscale Responses of a Large Carnivore to Human Mortality Risk.

Theory suggests that animals make hierarchical, multiscale resource selection decisions to address the hierarchy of factors limiting their fitness. Ecologists have developed tools to link population-level resource selection across scales; yet, theoretical expectations about the relationship between coarse- and fine-scale selection decisions at the individual level remain elusive despite their importance to fitness. With GPS-telemetry data collected across California, USA, we evaluated resource selection of mountain lions (Puma concolor; n = 244) relative to spatial variation in human-caused mortality risk.

Examining social attention as a predictor of problem drinking behavior: A longitudinal study using eye-tracking.

Background: Researchers have long been interested in identifying objective markers for problem drinking susceptibility informed by the environments in which individuals drink. However, little is known of objective cognitive-behavioral indices relevant to the social contexts in which alcohol is typically consumed. Combining group-based alcohol administration, eye-tracking technology, and longitudinal follow-up over a 2-year span, the current study examined the role of social attention in predicting patterns of problem drinking over time.

Induced Chirality in QDs Using Thermoresponsive Elastin-like Polypeptides.

Circular dichroism (CD) spectroscopy has emerged as a potent tool for probing chiral small-molecule ligand exchange on natively achiral quantum dots (QDs). In this study, we report a novel approach to identifying QD-biomolecule interactions by inducing chirality in CdS QDs using thermoresponsive elastin-like polypeptides (ELPs) engineered with C-terminal cysteine residues. Our method is based on a versatile two-step ligand exchange process starting from monodisperse oleate-capped QDs in nonpolar media and proceeding through an easily accessed achiral glycine-capped QD intermediate.

Detection of elevated succinate in brain during circulatory arrest in a piglet model: A 3T H MR spectroscopy study.

Purpose: To measure and validate elevated succinate in brain during circulatory arrest in a piglet model of cardiopulmonary bypass.

Methods: Using data from an archive of 3T H MR spectra acquired in previous in-magnet studies, dynamic plots of succinate, spectral simulations and difference spectra were generated for analysis and validation.

Results: Elevation of succinate during circulatory arrest was observed and validated.

Estimation of Ligand Binding Free Energy Using Multi-eGO.

The computational study of ligand binding to a target protein provides mechanistic insight into the molecular determinants of this process and can improve the success rate of drug design. All-atom molecular dynamics (MD) simulations can be used to evaluate the binding free energy, typically by thermodynamic integration, and to probe binding mechanisms, including the description of protein conformational dynamics. The advantages of MD come at a high computational cost, which limits its use.

Supplemental Intervention for Alcohol Use Disorder Treatment Patients With a Co-Occurring Anxiety Disorder: Technical Development and Functional Testing of an Autonomous Digital Program.

Background: Anxiety disorders are common in alcohol use disorder (AUD) treatment patients. Such co-occurring conditions ("comorbidity") have negative prognostic implications for AUD treatment outcomes, yet they commonly go unaddressed in standard AUD care. Over a decade ago, we developed and validated a cognitive behavioral therapy intervention to supplement standard AUD care that, when delivered by trained therapists, improves outcomes in comorbid patients.

Epithelial Polarity Loss and Multilayer Formation: Insights Into Tumor Growth and Regulatory Mechanisms.

Epithelial tissues serve as critical barriers in metazoan organisms, maintaining structural integrity and facilitating essential physiological functions. Epithelial cell polarity regulates mechanical properties, signaling, and transport, ensuring tissue organization and homeostasis. However, the barrier function is challenged by cell turnover during development and maintenance.

Structure-Dependent Balance between Excited-State Deactivation Pathways in Cross-Conjugated Molecular Photoswitches.

Diaryl thieno-[3,4-]thiophenes (TT) are photoswitchable compounds that operate through reversible photoinduced cyclization/cycloreversion and have been designed specifically for integration within π-conjugated polymers to switchably manipulate polymer electronic properties. Here we report on how cross conjugating the central TT moiety impacts photocyclization dynamics as interrogated using transient absorption spectroscopy (TAS) for a series of switches built with electron-rich substituents that have various electronic interaction strengths with the TT core. For cross-conjugated structures exhibiting a propensity to switch in steady-state photoconversion experiments, ultrafast TAS reveals signatures of rapid dynamics (occurring within <1-10 ps) similar to those observed for unsubstituted switches and that are consistent with photocyclization.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.

Introduction: Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest without considering the underlying fiber geometry.

Methods: We propose a novel macrostructure-informed normative tractometry (MINT) framework to investigate how white matter (WM) microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia.

Life-Space Mobility Is Related to Loneliness Among Living-Alone Older Adults: Longitudinal Analysis With Motion Sensor Data.

Background: Life-space mobility can be a behavioral indicator of loneliness. This study examined the association between life-space mobility measured with motion sensors and weekly vs. annually reported loneliness.

microT-CNN: an avant-garde deep convolutional neural network unravels functional miRNA targets beyond canonical sites.

microRNAs (miRNAs) are central post-transcriptional gene expression regulators in healthy and diseased states. Despite decades of effort, deciphering miRNA targets remains challenging, leading to an incomplete miRNA interactome and partially elucidated miRNA functions. Here, we introduce microT-CNN, an avant-garde deep convolutional neural network model that moves the needle by integrating hundreds of tissue-matched (in-)direct experiments from 26 distinct cell types, corresponding to a unique training and evaluation set of >60 000 miRNA binding events and ~30 000 unique miRNA-gene target pairs.

Machine learning-enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations.

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.

A comprehensive benchmark study of methods for identifying significantly perturbed subnetworks in cancer.

Network-based methods utilize protein-protein interaction information to identify significantly perturbed subnetworks in cancer and to propose key molecular pathways. Numerous methods have been developed, but to date, a rigorous benchmark analysis to compare the performance of existing approaches is lacking. In this paper, we proposed a novel benchmarking framework using synthetic data and conducted a comprehensive analysis to investigate the ability of existing methods to detect target genes and subnetworks and to control false positives, and how they perform in the presence of topological biases at both gene and subnetwork levels.

The iPhylo suite: an interactive platform for building and annotating biological and chemical taxonomic trees.

Accurate and rapid taxonomic classifications are essential for systematically exploring organisms and metabolites in diverse environments. Many tools have been developed for biological taxonomic trees, but limitations apply, and a streamlined method for constructing chemical taxonomic trees is notably absent. We present the iPhylo suite (https://www.

nsP2 Protease Inhibitor Blocks the Replication of New World Alphaviruses and Offer Protection in Mice.

New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses.

Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction in the United States.

Background: The role of Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is still unclear in patients with STEMI undergoing PCI in the current second-generation DES era.

Aims: This study aimed to evaluate the trends and outcomes of IVUS-guided PCI in patients with STEMI.

Methods: We used the National Inpatient Sample (NIS) database from 2016 to 2021.

The Ontogeny of Attitudes Toward Migrants.

Immigration is among the most pressing issues of our time. Important questions concern the psychological mechanisms that contribute to attitudes about immigration. Whereas much is known about adults' immigration attitudes, the developmental antecedents of these attitudes are not well understood.

Management of T cell responses by anesthetic drugs-propofol & isoflurane in perioperative breast cancer patients: A prospective hospital-based study.

Background & objectives The choice of anesthetic for better perioperative conservation of immune responses has always been contentious. This study investigated the differential impact of the intravenous anesthetic, propofol, and the volatile anesthetic, isoflurane on the T cell immune responses, if any, among individuals going through perioperative breast cancer. Methods Perioperative blood samples (preoperative, intraoperative and postoperative) collected from participants with breast cancer in two arms namely isoflurane arm (n=50) and the propofol arm (n=50) were analyzed for T cell immune response using flow cytometry and ELISA.

Anatomy of Risk: Decoding the Predictors of Vascular Access Complications in Transcatheter Aortic Valve Replacement.

Background: Despite advancements in valve implantation devices, vascular access complications (VAC) remain a significant cause of morbidity and mortality for those undergoing transcatheter aortic valve replacement (TAVR). We describe pre-operative imaging analysis of the aortoiliac and femoral arterial beds using the TransAtlantic intersociety consensus (TASC) score, ilio-femoral tortuosity, and procedural characteristics to identify anatomic risk factors predictive of VAC in TAVR.

Methods: Consecutive patients undergoing TAVR from 2012 to 2022 at a single North Dakota hospital were retrospectively reviewed.

I-CONECT intervention effects on weekly time spent outside of home and social contacts among socially isolated older adults.

Background: Socially isolated individuals tend to have less access to cognitively stimulating activities, which could adversely impact their cognitive health. The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) intervention was designed to deliver online conversation sessions to socially isolated older old adults to prevent cognitive decline. The current study examined the intervention efficacy on participants' weekly time spent out-of-home and their social interaction with family and friends.

Lung cancer risk and its potential association with PM in Bagmati province, Nepal-A spatiotemporal study from 2012 to 2021.

Background: Despite examining the role of an association between particulate matter and lung cancer in low-income countries, studies on the association between long-term exposure to particulate matter and lung cancer risk are still contradictory. This study investigates the spatiotemporal distribution patterns of lung cancer incidence and potential association with particulate matter (PM) in Bagmati province, Nepal.

Methods: We performed a spatiotemporal study to analyze the LC - PM association, using LC and annual mean PM concentration data from 2012 to 2021.

"The Heart of the Center": Exploring the Role of the Patient Care Technician in US Dialysis Care.

Rationale & Objective: Dialysis patient care technicians (PCTs) provide essential, frontline care for patients receiving in-center hemodialysis. We qualitatively explored perceptions of the PCT job role, responsibilities, and training among current PCTs, non-PCT dialysis staff, and patients receiving hemodialysis.

Study Design: Focus group study.

Adolescent circadian rhythm disruption increases reward and risk-taking.

Introduction: Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions.