Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Improvement in Serum Eosinophilia is Observed in Clinical Responders to Ustekinumab but not Adalimumab in Inflammatory Bowel Disease.

Introduction: In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biologic therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy.

Interventions to Reduce Loneliness Among Community-dwelling Older Adults: A Network Meta-analysis and Systematic Review.

Objectives: This study aimed to evaluate the effectiveness of interventions in reducing loneliness among community-dwelling older adults.

Design: A network meta-analysis (NMA) and systematic review.

Setting And Participants: Interventional studies were included if they contained original quantitative data on interventions to reduce loneliness among community-dwelling older adults.

Outcomes With Radiation Therapy as Primary Treatment for Unresectable Cutaneous Head and Neck Squamous Cell Carcinoma.

Aims: Unresectable cutaneous squamous cell cancer of the head and neck (HNcSCC) poses treatment challenges in elderly and comorbid patients. Radiation therapy (RT) is often employed for locoregional control. This study aimed to determine progression-free survival (PFS) and overall survival (OS) outcomes achieved with upfront RT in unresectable HNcSCC.

Effect of a Nurse-Led Support Program Using Mobile Application Versus Nurse Phone Advice on Patients at Risk of Coronary Artery Disease: A Randomized Controlled Trial.

Background: Coronary artery disease (CAD) is a major health problem of atherosclerotic cardiovascular (CV) disease and early intervention is regarded important. Given the proven effect of a lifestyle intervention with nursing telephone counselling and mHealth use in health care, yet the comparisons of both support are lacking, this study is proposed.

Objectives: This study aimed to compare the effects of a coronary artery disease (CAD) support program using a mobile application versus nurse phone advice on exercise amount and physical and psychological outcomes for clients at risk of CAD.