Adapting Public Health and Health Services Interventions in Diverse, Real-World Settings: Documentation and Iterative Guidance of Adaptations.

When complex public health and health services interventions are implemented in real-world settings, adaptations should be expected, embraced, and studied rather than suppressed and ignored. A substantial amount of recent research has been conducted on the assessment of some types of adaptations, and interest in guiding adaptations to both interventions and implementation strategies is growing. However, there is still a need to investigate the optimal ways to systematically and pragmatically document, analyze, and iteratively guide adaptations as well as to measure the impact of those adaptations on implementation and effectiveness outcomes.

Military Nurses' Deployment Experiences: A Qualitative Metasynthesis.

Introduction: Military medical personnel, including nurses, face a wide array of emotional and psychological issues while deployed. Understanding the challenges military nurses face in the deployed setting may prove useful in effectively preparing nurse leaders for future disaster responses in the military and civilian sectors. The purpose of this metasynthesis is to answer the following research question: What are the experiences of U.

Influenza vaccine effectiveness against hospitalizations and emergency department or urgent care encounters for children, adolescents, and adults during the 2023-2024 season, United States.

Background: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses.

Methods: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024.

Hallmarks of female reproductive aging in physiologic aging mice.

The female reproductive axis is one of the first organ systems to age, which has consequences for fertility and overall health. Here, we provide a comprehensive overview of the biological process of female reproductive aging across reproductive organs, tissues and cells based on research with widely used physiologic aging mouse models, and describe the mechanisms that underpin these phenotypes. Overall, aging is associated with dysregulation of the hypothalamic-pituitary-ovarian axis, perturbations of the ovarian stroma, reduced egg quantity and quality, and altered uterine morphology and function that contributes to reduced capacity for fertilization and impaired embryo development.

High-Risk Infant Developmental Outcome Is Associated with Medical Complexity and Neighborhood Opportunity.

Objective: To assess how medical complexity and neighborhood opportunity jointly affect cognitive, motor, and language Bayley's Scales of Infant Development. Secondary objectives involved identifying the factors contributing to developmental disparities across diverse racial and ethnic groups.

Study Design: Electronic health records from a Southern California high-risk infant follow-up clinic were analyzed for 440 infants from 2014 through 2023 who had either had neonatal intensive care unit stays, prematurity, very low birthweight, or developmental delay risk.

Regulation of human interferon signaling by transposon exonization.

Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2.

Integrated analysis of immunometabolic interactions in Down syndrome.

Down syndrome (DS), caused by trisomy 21 (T21), results in immune and metabolic dysregulation. People with DS experience co-occurring conditions at higher rates than the euploid population. However, the interplay between immune and metabolic alterations and the clinical manifestations of DS are poorly understood.

Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.

Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

Unraveling Sex Differences in Kidney Health and CKD: A Review of the Effect of Sex Hormones.

Sexual dimorphism plays an important role in the pathogenesis and progression of CKD. Men with CKD often exhibit faster kidney function decline, leading to higher rates of kidney failure and mortality compared with women. Studies suggest that sex hormones may influence this apparent dimorphism, although the mechanisms underlying these influences remain poorly understood.

Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes.

Aims/hypothesis: Many studies of type 1 diabetes pathogenesis focus on individuals with high-risk HLA haplotypes. We tested the hypothesis that, among islet autoantibody-positive individuals, lacking HLA-DRB1*04-DQA1*03-DQB1*0302 (HLA-DR4-DQ8) and/or HLA-DRB1*0301-DQA1*0501-DQB1*0201 (HLA-DR3-DQ2) is associated with phenotypic differences, compared with those who have these high-risk HLA haplotypes.

Methods: We classified autoantibody-positive relatives of individuals with type 1 diabetes into four groups based on having both HLA-DR4-DQ8 and HLA-DR3-DQ2 (DR3/DR4; n=1263), HLA-DR4-DQ8 but not HLA-DR3-DQ2 (DR4/non-DR3; n=2340), HLA-DR3-DQ2 but not HLA-DR4-DQ8 (DR3/non-DR4; n=1607) and neither HLA-DR3-DQ2 nor HLA-DR4-DQ8 (DRX/DRX; n=1294).

A Pathway-Level Information ExtractoR (PLIER) framework to gain mechanistic insights into obesity in Down syndrome.

Down syndrome (DS), caused by the triplication of chromosome 21 (T21), is a prevalent genetic disorder with a higher incidence of obesity. Traditional approaches have struggled to differentiate T21-specific molecular dysregulation from general obesity-related processes. This study introduces the omni-PLIER framework, combining the Pathway-Level Information ExtractoR (PLIER) with the omnigenic model, to uncover molecular mechanisms underlying obesity in DS.

A Visual Analytics Framework for Assessing Interactive AI for Clinical Decision Support.

Human involvement remains critical in most instances of clinical decision-making. Recent advances in AI and machine learning opened the door for designing, implementing, and translating interactive AI systems to support clinicians in decision-making. Assessing the impact and implications of such systems on patient care and clinical workflows requires in-depth studies.

The Implementation Climate for Integrating Buprenorphine Prescribing into Rural Primary Care.

Background: Rural communities have been significantly affected by opioid use disorder (OUD) and related harms but have less access to evidence-based medications for opioid use disorder (MOUD), such as buprenorphine. Given the shortage of specialists in these areas, rural primary care is an important setting to expand buprenorphine access, but implementation is limited.

Objective: To explore implementation climate factors that support or hinder buprenorphine implementation in rural primary care.

Transposable element activity captures human pluripotent cell states.

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states.

Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies.

Background: Risk stratification is an essential part of evaluating disease severity in patients with pulmonary arterial hypertension (PAH). This study applied the 4-strata COMPERA 2.0 risk model to the Phase 3 PATENT-1/2 studies of riociguat.

Event-level effects of alcohol, cannabis, and simultaneous alcohol and cannabis use on bystander intentions in response to hypothetical situations among college women.

Bystanders can play an important role in preventing alcohol-related harm (e.g., unintentional injury) or sexual aggression.

Sacituzumab Govitecan in Patients With Relapsed/Refractory Advanced Head and Neck Squamous Cell Carcinoma: Results From the Phase 2 TROPiCS-03 Basket Study.

Purpose: Treatment options for advanced head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and a programmed death-1 (PD-1) inhibitor are limited. Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in HNSCC. Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved for patients with certain previously treated solid tumors.

More than the passage of time: neonatal health and active labor duration, the mediating role of chorioamnionitis.

Background: Labor intervention is intended to prevent perinatal morbidity and mortality. Labor durations traditionally defined as "dystocia" affect primary cesarean delivery rates. However, there is mixed evidence about the association between labor duration and poor neonatal outcomes.

The impact of pancreatic endotherapy on quality of life in chronic pancreatitis.

Background And Aims: Pancreatic endotherapy (PET) offers a treatment option for adverse events of chronic pancreatitis (CP) such as pancreatic duct (PD) strictures, stones, and pseudocysts. Previous studies have primarily focused on how PET affects pain, so the primary aim of this study was to evaluate the effect of PET on quality of life.

Methods: This single-center prospective study assessed quality of life before the initiation of endotherapy using a validated CP-specific quality of life instrument.

Medical language matters: impact of clinical summary composition on a generative artificial intelligence's diagnostic accuracy.

Objectives: Evaluate the impact of problem representation (PR) characteristics on Generative Artificial Intelligence (GAI) diagnostic accuracy.

Methods: Internal medicine attendings and residents from two academic medical centers were given a clinical vignette and instructed to write a PR. Deductive content analysis described the characteristics comprising each PR.

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.