Rapid Adaptation to Prevent Drug Use (RAPD): protocol of a pilot randomized trial to enhance the impact of an evidence-based intervention for youth.

Background: Drug use trends change rapidly among youth, leaving intervention experts struggling to respond promptly. Delays in responses can lead to preventable morbidity and mortality. The COVID-19 pandemic underscored the need for implementation science to facilitate rapid, equitable responses using existing treatment and prevention efforts.

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays.

Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.

Study on the effects of Mogroside V in inhibiting NLRP3-mediated granulosa cell pyroptosis and insulin resistance to improve PCOS.

Objective: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women, contributing to 75% of infertility cases due to ovulatory dysfunction. The condition poses significant health and psychological challenges, making the study of its pathogenesis and treatment a research priority. This study investigates the effects of Mogroside V (MV) on PCOS, focusing on its anti-inflammatory and anti-insulin resistance properties.

Translation of oral health research priorities into research topics in an equity-based priority setting exercise.

Background: In the context of research priority-setting, participants express their research priorities and ideas in various forms, ranging from narratives to explicit topics or questions. However, the transition from these expressions to well-structured research topics or questions is not always straightforward. Challenges intensify when research priorities pertain to interventions or diagnostic accuracy, requiring the conversion of narratives into the Participant, Intervention, Comparator, Outcome (PICO) format.

Genetic variation reveals the therapeutic potential of BRSK2 in idiopathic pulmonary fibrosis.

Background: Current research underscores the need to better understand the pathogenic mechanisms and treatment strategies for idiopathic pulmonary fibrosis (IPF). This study aimed to identify key targets involved in the progression of IPF.

Methods: We employed Mendelian randomization (MR) with three genome-wide association studies and four quantitative trait loci datasets to identify key driver genes for IPF.

Multiplex immunohistochemistry to explore the tumor immune microenvironment in HCC patients with different GPC3 expression.

Objectives: GPC3 has been recognized as a promising target for immunotherapy in hepatocellular carcinoma (HCC). However, the GPC3-targeted immunotherapies have shown limited therapeutic efficacy. The use of anti-PD-1/PD-L1 monoclonal antibodies in HCC treatment is considerably constrained.

Prenatal maternal stress: triangulating evidence for intrauterine exposure effects on birth and early childhood outcomes across multiple approaches.

Background: Maternal stress during pregnancy may impact offspring development via changes in the intrauterine environment. However, genetic and environmental factors shared between mothers and children might skew our understanding of this pathway. This study assesses whether prenatal maternal stress has causal links to offspring outcomes: birthweight, gestational age, or emotional and behavioral difficulties, triangulating across methods that account for various measured and unmeasured confounders.

Medical Students' Observations of High Value and Potentially Wasteful Care Behaviors Modeled During Clinical Rotations.

Background: Medical student exposure to role-modeling of high-value care (HVC) behaviors may shape professional identity formation and future HVC practices.

Objective: To investigate the frequency and characteristics of HVC role-modeling witnessed by medical students during core clinical rotations.

Design: Cross-sectional survey study.

Perceived Discrimination in the Healthcare Setting and Medical Mistrust: Findings from the Health Information National Trends Survey, 2022.

Background: Perceived discrimination and medical mistrust are barriers to care that impact both individual and population health.

Objective: This study aims to characterize the prevalence of perceived racial or ethnic discrimination in healthcare as well as mistrust in the medical system and explore their associations with race and ethnicity.

Design: Cross-sectional study of nationally representative data from the Health Information National Trends Survey (fielded March-November 2022).

Cardiovascular and thromboembolic outcomes with immune checkpoint inhibitors in gastroesophageal cancer: a propensity score-matched cohort study.

Background: Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular and thromboembolic events. However, the incidence of cardiovascular and thromboembolic events associated with ICIs in gastroesophageal cancers is unknown.

Methods: We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 130 participating healthcare institutions.

Wellbeing and quality of life among parents of individuals with Fontan physiology.

Purpose: To examine global and health-related quality of life (QOL) among parents of individuals with Fontan physiology and determine associations with sociodemographic, parent and child-related health, psychological, and relational factors.

Methods: Parents participating in the Australian and New Zealand Fontan Registry (ANZFR) QOL Study (N = 151, Parent Mean age = 47.9 ± 10.

Psychotropic Polypharmacy in Dementia: A Retrospective Analysis for People with Neuropsychiatric Symptoms Referred to an Australian Dementia Support Service.

Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

Epidemiology of Coronavirus Disease 2019-Associated Fungal Infections in the Intensive Care Unit: A Single-Center Retrospective Study.

Introduction: Invasive fungal disease (IFD) is a morbid superinfection that can arise in critically ill patients with COVID-19 infection. Studies evaluating the full spectrum of COVID-19-associated fungal infections remain limited.

Methods: Single-center retrospective study assessing IFD in patients with COVID-19, hospitalized for ≥ 72 h in the intensive care unit (ICU) between 02/25/20 and 02/28/22 (n = 1410).

Society of American Gastrointestinal and Endoscopic Surgeons guidelines development: patient engagement update to standard operating procedure.

Introduction: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee develops evidence-based surgical guidelines. Involvement of patient partners is important to ensure patient concerns and values are adequately addressed and incorporated. This standard operating procedure (SOP) for the process of patient partner involvement within the guidelines is described here.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability.

Tumors lacking the BRCA1 and BRCA2 (BRCA) hereditary breast cancer genes display heightened sensitivity to anti-cancer treatments, such as inhibitors of poly (ADP-ribose) polymerase 1 (PARP1). However, when resistance develops, treatments are lacking. Using CRISPR technology, we discovered that enhancing homologous recombination through increased DNA end resection in BRCA1-deficient cells by loss of the 53BP1-Shieldin complex-which is associated with resistance to PARP inhibitors-also heightens sensitivity to DNA nicks.

MRI features that predict progression of residual disease after ablation of extra-abdominal desmoid fibromatosis.

Objective: To identify MRI features of desmoid tumors (DTs) that predict the growth of residual disease following ablation.

Methods: Patients who underwent MRI-guided ablation for DTs between February 2013 and April 2021 were included in this single-center IRB-approved retrospective study. MRI scans assessed three suspicious tissue features: intermediate T2 signal [+iT2], nodular appearance [+NOD], and contrast enhancement [+ENH].

Comprehensive RNA-seq analysis of benign prostatic hyperplasia (BPH) in rats exposed to testosterone and estradiol.

The imbalance between estrogen and androgen may be an important mechanism of BPH, but the specific mechanism remains unclear. We used mixed sustained-release pellets made of testosterone and estradiol (T + E) to stimulate the establishment of a BPH rat model. Compared to the prostate hyperplasia rat model using only androgens, the new prostate hyperplasia rat model can be observed to have better macroscopic and pathological characteristics of prostate hyperplasia.

Association between extracellular DNA levels, markers of inflammation and left ventricular mass index in children with chronic kidney disease.

Chronic kidney disease (CKD) is associated with chronic low-grade inflammation, but the primary factors triggering this inflammation remain unclear. Extracellular or cell-free DNA (exDNA) originates from virtually all tissues, being released during cell death, and stimulates the innate immune system. Our study was designed as an observational, cross-sectional cohort study of children with CKD (both before and after kidney transplantation) and controls to analyze associations between exDNA, markers of inflammation, and cardiovascular health.

Diversity and consequences of structural variation in the human genome.

The biomedical community is increasingly invested in capturing all genetic variants across human genomes, interpreting their functional consequences and translating these findings to the clinic. A crucial component of this endeavour is the discovery and characterization of structural variants (SVs), which are ubiquitous in the human population, heterogeneous in their mutational processes, key substrates for evolution and adaptation, and profound drivers of human disease. The recent emergence of new technologies and the remarkable scale of sequence-based population studies have begun to crystalize our understanding of SVs as a mutational class and their widespread influence across phenotypes.

PLK3 weakens antioxidant defense and inhibits proliferation of porcine Leydig cells under oxidative stress.

Aging is characterized by cellular degeneration and impaired physiological functions, leading to a decline in male sexual desire and reproductive capacity. Oxidative stress (OS) lead to testicular aging by impairing the male reproductive system, but the potential mechanisms remain unclear. In the present study, the functional status of testicular tissues from young and aged boars was compared, and the transcriptional responses of Leydig cells (LCs) to hydrogen peroxide (HO)-induced senescence were explored, revealing the role of OS in promoting aging of the male reproductive system.

Development of a 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis.

This investigation aimed to develop a radiographic 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis (JIA), and to perform a validation against expert evaluations. Data were collected from a population-based Nordic JIA cohort of 240 patients that received a cone-beam computed tomography (CBCT) scan approximately 17 years after onset of JIA. The cohort was randomized into two groups: A baseline group for establishing the index (n = 210) and a test group (n = 30).