Changes in weight and physical function for older African American women in Take Off Pounds Sensibly (TOPS): Study protocol for a randomized clinical trial.

Background: Obesity and frailty are positively linked. Compared to other groups, older African American women have the highest rates of both obesity and frailty. Several academic weight loss interventions have shown that older adults can lose weight and improve physical function through diet and exercise.

Training T-shaped translational scientists.

Unlabelled: To evaluate the design of I-Corps@NCATS as a translational scientist training program, we mapped specific elements of the program's content and pedagogy to the characteristics of a translational scientist, as first defined by Gilliland et al. []: systems thinker, process innovator, boundary spanner, team player, and skilled communicator. Using a mixed-methods evaluation, we examined how the I-Corps@NCATS training program, delivered across twenty-two Clinical and Translational Science Award Hubs, impacted the development of these key translational scientist characteristics.

Rapid luminescence-based screening method for SARS- CoV-2 inhibitors discovery.

The COVID-19 pandemic has emphasized the necessity for rapid and adaptable drug screening platforms against live pathogenic viruses that require high levels of biosafety containment. Conventional antiviral testing is time-consuming and labor-intensive. Here, we outline the design and validation of a semi-automated drug-screening platform for SARS-CoV-2 that utilizes multiple liquid handlers, a stable A549 cell line expressing ACE2 and TMPRSS2 receptors, and a recombinant SARS-CoV-2 strain harboring the nano-luciferase gene.

Advancements in molecular imaging probes for precision diagnosis and treatment of prostate cancer.

Prostate cancer is the second most common cancer in men, accounting for 14.1% of new cancer cases in 2020. The aggressiveness of prostate cancer is highly variable, depending on its grade and stage at the time of diagnosis.

Geriatrics-Focused vs Traditional Primary Care in the Veterans Affairs Health Care System.

Importance: Older adults often require specialized health care expertise, but the effects of geriatrics-focused models of primary care have not been fully evaluated.

Objective: To compare the effects of geriatrics-focused primary care vs traditional primary care for older patients in the Veterans Affairs (VA) health care system.

Design, Setting, And Participants: In this cohort study, geriatrics-focused primary care and traditional primary care patient dyads matched on variables associated with geriatrics-focused primary care entry and outcomes were enrolled from VA medical centers with operational geriatrics-focused primary care clinics serving 500 or more patients annually in fiscal year 2016.

Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates as Imidazoline Receptor Ligands with Anti-Alzheimer and Analgesic Properties.

Imidazoline receptors (I-IRs) are altered in Alzheimer's disease (AD) patients and are associated with analgesia. I-IRs are not structurally described, and their pharmacological characterization relies on their modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates endowed with relevant affinities for I-IRs in human brain tissues.

Discovery of a heparan sulfate binding domain in monkeypox virus H3 as an anti-poxviral drug target combining AI and MD simulations.

Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (MD) simulations, we identified a novel, positively charged α-helical domain in H3 that is essential for HS binding.

Extracellular RNA communication: A decade of NIH common fund support illuminates exRNA biology.

The discovery that extracellular RNAs (exRNA) can act as endocrine signalling molecules established a novel paradigm in intercellular communication. ExRNAs can be transported, both locally and systemically in virtually all body fluids. In association with an array of carrier vehicles of varying complexity, exRNA can alter target cell phenotype.

Preventing Postpartum Anxiety and Obsessive-Compulsive Disorder Over the Internet: An Open-Trial Pilot Study.

Anxiety disorders are the most common postpartum psychiatric conditions, yet limited research exists on the prevention of postpartum anxiety and obsessive-compulsive disorder (OCD). Postpartum anxiety leads to significant problems in both mother and child, such as maternal depression, difficulty breastfeeding, interference with parent-infant bonding, and childhood anxiety. In the current study, we tested the feasibility, acceptability, and initial efficacy of an Internet-delivered postpartum anxiety and OCD prevention program, "Preventing Postpartum Onset Distress" (P-POD), in a sample of 15 pregnant women in their third trimester.

MVCL-DTI: Predicting Drug-Target Interactions Using a Multiview Contrastive Learning Model on a Heterogeneous Graph.

Accurate prediction of drug-target interactions (DTIs) is pivotal for accelerating the processes of drug discovery and drug repurposing. MVCL-DTI, a novel model leveraging heterogeneous graphs for predicting DTIs, tackles the challenge of synthesizing information from varied biological subnetworks. It integrates neighbor view, meta-path view, and diffusion view to capture semantic features and employs an attention-based contrastive learning approach, along with a multiview attention-weighted fusion module, to effectively integrate and adaptively weight the information from the different views.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Enhancing representation of special populations: An approach to the inclusion of women veterans in VA clinical trials.

The under-recruitment of historically marginalized populations into clinical trials thwarts equitable inclusion of individuals who could benefit from healthcare innovations and limits the generalizability of results. For decades, the Veterans Health Administration (VA) has conducted large clinical trials that impact clinical guidelines for veterans and civilians alike. Within the VA, women are a numeric minority, and recruitment of this population into trials is challenged by gender-specific care structures, distinct demographic characteristics, and mistreatment such as higher rates of military sexual trauma and harassment on VA grounds.

Effectiveness of Synchronous Postdischarge Contacts on Health Care Use and Patient Satisfaction : A Systematic Review and Meta-analysis.

Background: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.

Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.

Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.

Open Soil Spectral Library (OSSL): Building reproducible soil calibration models through open development and community engagement.

Soil spectroscopy is a widely used method for estimating soil properties that are important to environmental and agricultural monitoring. However, a bottleneck to its more widespread adoption is the need for establishing large reference datasets for training machine learning (ML) models, which are called soil spectral libraries (SSLs). Similarly, the prediction capacity of new samples is also subject to the number and diversity of soil types and conditions represented in the SSLs.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Integrating Model-Informed Drug Development With AI: A Synergistic Approach to Accelerating Pharmaceutical Innovation.

The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model-Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as pharmacokinetics and pharmacodynamics. Artificial intelligence (AI), encompassing techniques such as machine learning, deep learning, and Generative AI, offers powerful tools and algorithms to efficiently identify meaningful patterns, correlations, and drug-target interactions from big data, enabling more accurate predictions and novel hypothesis generation.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

StackDILI: Enhancing Drug-Induced Liver Injury Prediction through Stacking Strategy with Effective Molecular Representations.

Drug-induced liver injury (DILI) is a major challenge in drug development, often leading to clinical trial failures and market withdrawals due to liver toxicity. This study presents StackDILI, a computational framework designed to accelerate toxicity assessment by predicting DILI risk. StackDILI integrates multiple molecular descriptors to extract structural and physicochemical features, including the constitution, pharmacophore, MACCS, and E-state descriptors.

Structural characterization of pyruvic oxime dioxygenase, a key enzyme in heterotrophic nitrification.

Nitrification by heterotrophic microorganisms is an important part of the nitrogen cycle in the environment. The enzyme responsible for the core function of heterotrophic nitrification is pyruvic oxime dioxygenase (POD). POD is a non-heme, Fe(II)-dependent enzyme that catalyzes the dioxygenation of pyruvic oxime to produce pyruvate and nitrite.

Medication adherence in rheumatoid arthritis: implications for cardiovascular disease risk and strategies to address in U.S. veterans.

Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with an increased risk of cardiovascular disease (CVD) and premature mortality. The risk of CVD is closely associated with RA disease activity, and achieving RA remission using disease-modifying anti-rheumatic drugs (DMARDs) can significantly mitigate this risk. However, despite the availability of highly effective DMARDs, many veterans fail to achieve sustained RA remission.

A Brief History of Cell Culture: From Harrison to Organs-on-a-Chip.

This comprehensive overview of the historical milestones in cell culture underscores key breakthroughs that have shaped the field over time. It begins with Wilhelm Roux's seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel's influential contributions, notably the immortalization of chicken heart cells, have marked a significant advancement in cell culture techniques.

Mitochondrial Dysfunction as a Biomarker of Illness State in Bipolar Disorder: A Critical Review.

Mitochondria are organelles involved in different cellular functions, especially energy production. A relationship between mitochondrial dysfunction and mood disorders, especially bipolar disorder (BD), has been reported in the scientific literature, which suggests altered energy production and higher levels of oxidative stress compared to healthy controls. Specifically, in BD, the hypothesis of a biphasic pattern of energy availability has been postulated according to mood states.

Artificial intelligence in lung cancer: current applications, future perspectives, and challenges.

Artificial intelligence (AI) has significantly impacted various fields, including oncology. This comprehensive review examines the current applications and future prospects of AI in lung cancer research and treatment. We critically analyze the latest AI technologies and their applications across multiple domains, including genomics, transcriptomics, proteomics, metabolomics, immunomics, microbiomics, radiomics, and pathomics in lung cancer research.

Beyond symptom reduction: Veterans' goals for posttraumatic stress disorder treatment.

Despite a varied selection of available trauma-focused evidence-based psychotherapies (TF-EBPs) for posttraumatic stress disorder (PTSD), few veterans receive a full course of an evidence-based treatment. A better understanding of and alignment with veterans' PTSD treatment goals could be one way to improve treatment engagement and adherence, consistent with veteran-oriented care within the U.S.