Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer.

Androgen receptor (AR) splice variants, of which ARv7 is the most common, are increased in castration-resistant prostate cancer, but the extent to which they drive AR activity is unclear. We generated a subline of VCaP cells (VCaP16) that is resistant to the AR inhibitor enzalutamide (ENZ). AR activity in VCaP16 is driven by ARv7, independently of full-length AR (ARfl), and its cistrome and transcriptome mirror those of ARfl in VCaP cells.

Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Renin-independent aldosteronism and metabolic dysfunction-associated steatotic liver disease and cirrhosis: A genetic association study.

Background & Aims: Renin-independent aldosteronism (RIA) refers to a spectrum of autonomous aldosterone hypersecretion. We aimed to explore the genetical relationship between RIA and metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis.

Methods: We included 125357 participants from the cohort of United Kingdom Biobank.

Comparison of Management and Outcomes of Hip Fractures Among Low- and High-Income Patients in Six High-Income Countries.

Background: There is a perception that income-based disparities are present in most countries but may differ in magnitude. However, there are few international comparisons that describe income-based disparities across countries and none that focus on hip fractures.

Objective: To compare treatment patterns and outcomes of high- and low-income older adults hospitalized with hip fracture across six high-income countries.

The association of statin therapy with reduced intracranial aneurysm recurrence after endovascular coiling: a post hoc propensity score-matched analysis of a randomized clinical trial.

Objective: Endovascular intracranial aneurysm (IA) management has significantly evolved over the last 2 decades. Despite these advancements, the aneurysm recanalization rate after coil embolization remains a concern. Statins have been found to affect vascular repair and remodeling; therefore, the authors hypothesized that patients receiving statin therapy at the time of coil embolization would have lower aneurysm recurrence and retreatment rates compared with patients not receiving statin therapy.

Integrating Generative Artificial Intelligence Into Medical Education: Curriculum, Policy, and Governance Strategies.

The rapid advancement of generative artificial intelligence (GAI) is poised to revolutionize medical education, clinical decision-making, and health care workflow. Despite considerable interest and a surfeit of newly available tools, medical educators largely lack both competencies and guidance on how to incorporate the new and rapidly evolving world of GAI into the core medical school curriculum and experiences of undergraduate medical education. This Scholarly Perspective highlights the need for medical schools to adapt to this new paradigm by implementing policies, governance, and curricula that address the ethical, technical, and pedagogical implications of GAI.

Evaluation of a Self-collected Device for Human Papillomavirus Screening to Increase Cervical Cancer Screening.

Objective: The authors compared the performance of a novel self-collect device with clinician-collected samples for detection of high-risk human papillomavirus (hrHPV).

Materials And Methods: Eighty-two (82) participants were recruited from 5 clinical sites in the United States. Each participant performed self-collect sampling using the self-collect device followed by a standard of care clinician-collected sample.

Early versus late infectious complications following chimeric antigen receptor-modified T-cell therapy.

Despite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution.

Presenteeism and Absenteeism Before and After Carpal Tunnel Release or Open Reduction and Internal Fixation for Distal Radius Fracture.

Purpose: The use of a person's hands is crucial to their ability to succeed at work. Hand pathologies can impact work success by increasing absenteeism (ie, not being able to go to work) and presenteeism (ie, being able to work but in a reduced capacity). In this study, we quantified employed patients' presenteeism and absenteeism following carpal tunnel release or surgical fixation of a distal radius fracture (DRF).

Biochemical Alterations and Motor Dysfunctions in Corpus Striatum of Rats Brain Exposed to Azo Dyes.

Azo food dyes are prohibited in most countries, but their injudicious use is still reported particularly in the developing Nations. Continuous use of contaminated food raises health concerns and given this the present study designed to investigate the effects of 3 non-permitted azo dyes (metanil yellow - MY, malachite green - MG, and sudan III - SIII) on neurobehavioral, neurochemicals, mitochondrial dysfunction, oxidative stress, and histopathological changes in the corpus striatum of rats. Rats were grouped and treated with MY (430 mg/kg), MG (13.

Effect of the COVID-19 pandemic on unmet healthcare needs after hospital discharge in acute respiratory failure survivors: A multicenter prospective cohort study.

Survivors of acute respiratory failure (ARF) have complex healthcare needs postdischarge, frequently resulting in unmet needs. This prospective multicenter study explores the association between COVID-19 status and unmet healthcare needs in survivors of ARF following hospital discharge. We analyzed patient characteristics and unmet healthcare needs by COVID-19 status using a multivariable regression model with propensity weights.

"Bringing greater research fluency into our educational vision": A qualitative research study on improving Traditional Chinese Medicine research education.

The main objective of this qualitative analysis is to increase the quality of Traditional Chinese Medicine (TCM) research education. Subject matter experts and stakeholders were sent a list of possible topics to include in a research course and were asked to comment on it, add or subtract topics, and suggest appropriate research papers to use, lessons learned in their topic areas and possible stand-alone topics for inclusion in other courses. Their feedback was used to revise the topic list, create a list of foundational research papers to include in a research course and devise a list of stand-alone topics that could be included in the general TCM research curriculum.

Machine Perfusion for Recovery of Brain Death Donor Hearts from Extended Distances.

The emerging ex vivo machine perfusion (MP) enables the extension of ex situ intervals, potentially expanding the heart transplant (OHT) donor pool. From October 18, 2018, to June 30, 2023, isolated OHT using donation after brain death (DBD) from extended distances (>500 miles) were identified in the United Network for Organ Sharing database, and categorized into cold storage (non-MP, N = 1,212) and MP group (N = 152). The MP utilization rate for DBD hearts from extended distances surged from 0% in 2018 to 27.

Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis.

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy-lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly CKD patients remains unknown.

Pleuropulmonary blastoma and DICER1-related tumor predisposition: from clinicopathologic observations to clinical trial.

Purpose Of Review: Pleuropulmonary blastoma (PPB) is a rare primary lung neoplasm of infancy and childhood. The purpose of this review is to highlight recent developments in our understanding of PPB and research strategies to facilitate future rare cancer research.

Recent Findings: The International PPB/DICER1 Registry has recently assembled the largest-ever cohorts of type I and Ir PPB and type II and III PPB.

Bending properties of human cartilaginous ribs and costal cartilage material vary with age, sex, and calcification.

Costal cartilage plays an important functional role in the rib cage, but its mechanical properties have not been well characterized. The objective of this study is to characterize the properties of human costal cartilage and examine the effects of age, sex, rib level, and degree of calcification. We obtained cadaveric costal cartilage samples of ribs 3-6 with intact perichondrium from 24 donors (12 females and 12 males) evenly distributed by age (range 47-94 yr).

Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.

The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted in various preclinical investigations, yet the mechanism of action in humans remains unknown. To decipher the combinatory mode of action of TLR8 agonism and PD-1 blockade, we employed a unique, open-label, phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC) patients. Matched pre- and post-treatment tumor biopsies from the same lesion were obtained.

Feasibility of Alerting Systems and Family Care Partner Support for Postoperative Delirium Prevention.

Background: The objective of this study was to determine whether postoperative pager alerts to the Hospital Elder Life Program (HELP), a delirium prevention service, would accelerate program enrollment for older surgical patients. This study also tested feasibility of family care partner interventions for delirium prevention.

Methods: This single-center, pilot clinical trial factorially randomized 57 non-cardiac surgical patients ≥70 years of age to 4 arms: (1) standard care, (2) pager alerts to accelerate HELP enrollment, (3) family care partner-based delirium prevention interventions, or (4) a combined arm with both HELP and family interventions.

Regulation of injury-induced skeletal myofiber regeneration by glucose transporter 4 (GLUT4).

Background: Insulin resistance and type 2 diabetes impair cellular regeneration in multiple tissues including skeletal muscle. The molecular basis for this impairment is largely unknown. Glucose uptake via glucose transporter GLUT4 is impaired in insulin resistance.