Canine genome-wide association study identifies as an obesity gene in dogs and humans.

Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers.

Margin thermal ablation eliminates size as a risk factor for recurrence after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps.

Background: Lesion size is an independent risk factor for recurrence following endoscopic mucosal resection of large (≥20 mm) non-pedunculated colorectal polyps. Post-resection margin thermal ablation (MTA) reduces the risk of recurrence. Its impact on the uncommon larger (≥40 mm) lesions is unknown.

Effects of rare coding variants in severe early-onset obesity genes in the population-based UK Biobank study.

Objectives: Clinical case-based studies have identified rare pathogenic variants in several genes as causes of severe early-onset obesity, but their penetrance and interaction with polygenic susceptibility in the general population remain unclear. We analysed the UK Biobank (UKBB) whole exome sequence data to assess the effects of heterozygous variants in nine previously reported genes on adult BMI and recalled childhood adiposity.

Methods: Among 419,581 UKBB participants, we identified heterozygous carriers of coding variants that were i) experimentally-characterised as loss-of-function (LoF), or ii) bioinformatically-predicted as rare (minor allele frequency <0.

Impact of margin thermal ablation after cold-forceps avulsion with snare-tip soft coagulation for non-lifting large non-pedunculated colorectal polyps.

Background And Study Aims: Non-lifting large non-pedunculated colorectal polyps (NL-LNPCPs) account for 15% of LNPCP and are effectively managed by Endoscopic Mucosal Resection with adjunctive Cold-forceps Avulsion with adjuvant Snare-Tip soft coagulation (CAST). However, recurrence rates > 10% at surveillance colonoscopy is a significant limitation. We aimed to compare the outcomes of CAST with MTA versus CAST alone for NL-LNPCPs.

The metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system.

Amphetamine (AMPH) exerts metabolic and cardiovascular effects. The central melanocortin system is a key regulator of both metabolic and cardiovascular functions. Here, we show that the melanocortin system partially mediates AMPH-induced anorexia, energy expenditure, tachycardia, and hypertension.

A comprehensive spatio-cellular map of the human hypothalamus.

The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies. Here we combine single-nucleus sequencing of 433,369 human hypothalamic cells with spatial transcriptomics, generating a comprehensive spatio-cellular transcriptional map of the hypothalamus, the 'HYPOMAP'.

Focused Recommendations for the Management of Metabolic Dysfunction-Associated Steatohepatitis (MASH) by Advanced Practice Providers in the United States.

Metabolic dysfunction-associated steatohepatitis (MASH) has become the dominant cause of liver disease in the United States. With the growing burden of this disease in gastroenterology practices, the identification and treatment of those at risk of developing adverse outcomes (cirrhosis, hepatocellular carcinoma, or liver-related death) has become urgent. In recent years, the development of noninvasive tests (NITs) to identify "at-risk MASH" patients have provided cost-effective algorithms to identify these patients.

The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.

Purpose: Maximal oxygen consumption (VOmax), the predominant index of cardiorespiratory fitness (CRF), is a predictor of whole-body function and longevity in humans. The central cardiac function and the skeletal muscle's capacity to use oxygen are key determinants of VOmax. Murine Double Minute 2 (MDM2), mainly known as an oncogene, could regulate myocardial hypertrophy, skeletal muscle angiogenesis, and oxidative phosphorylation.

Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease.

Background: Association of genetic factors with non-invasive tests (NITs) for MASLD has not been well established.

Methods: Clinical and laboratory data, liver biopsy and/or liver stiffness measurement (LSM) by transient elastography were collected from MASLD patients seen in tertiary care hepatology practices. Minor allele frequency for genomic loci rs641738 (MBOAT7), rs58542926 (TM6SF2), rs738409 (PNPLA3), rs62305723 (HSD1713B) were evaluated for association with high ELF (≥11.

Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health.

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis.

Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice.

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.

Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD.

Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

Aims: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.

Materials And Methods: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R.

Key Performance Indicators and Metrics for the Implementation of an Oral Chemotherapy Adherence Program.

Background: Oral anticancer agents (OAAs) transformed cancer care for patients, extending survival and delaying progression in certain cases. There are multiple pharmacy-driven models to improve patient knowledge and adherence to OAAs. However, a lack of measurable key performance indicators (KPIs) has limited the adoption, implementation, and maintenance of these models.

Real-World Incidence and Severity of Hypertension Caused by Abiraterone Acetate in Patients With Metastatic Prostate Cancer.

Background: Abiraterone acetate (AA) is used in treatment of patients with metastatic prostate cancer. Despite the survival advantage, AA is associated with hypertension due to mineralocorticoid excess syndrome.

Objective: We conducted a single-center retrospective analysis to evaluate the real-world incidence and severity of AA-induced hypertension.

The vagus nerve mediates the physiological but not pharmacological effects of PYY on food intake.

Peptide YY (PYY) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY, but not peripherally administered pharmacological doses.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers.

Genome sequences of B-2979 phages MidnightRain and Gusanita.

Phages MidnightRain and Gusanita, with siphovirus morphology, were isolated on B-2979. MidnightRain's genome consists of 53,674 bp, encoding 101 putative genes and 1 tRNA, whereas Gusanita's genome is 42,742 bp, encoding 68 putative genes and 2 tRNAs.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers.

Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey.

Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women.

Introduction: Post-acute SARS-CoV-2 (PASC) symptoms are often persistent, disruptive, and difficult to treat effectively. Fatigue is often among the most frequently reported symptoms and may indicate a more challenging road to recovery.

Purpose: To describe the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2.

Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis.

Background: Multiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes.

Objective: The objective of this study was to evaluate the predictive value of CSF brain-specific proteins from early in the disease course of MS on long term clinical outcomes.