Dual Inhibition of Mast Cells and Thymic Stromal Lymphopoietin Using a Novel Bispecific Antibody, CDX-622.

Background: Mast cells (MCs) respond to an array of allergens that drive allergic and inflammatory diseases. Stem cell factor (SCF), the ligand for the receptor KIT, is required for MC survival and function. Thymic stromal lymphopoietin (TSLP) is an alarmin that promotes Type 2 inflammation in asthma and other inflammatory diseases.

Liver Lymphatic Dysfunction as a Driver of Fibrosis and Cirrhosis Progression.

The liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient lymphatic drainage is essential for liver homeostasis, but its role in liver disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates for increased lymph production, but impaired lymphatic drainage in advanced stages may lead to complications such as ascites and portal hypertension.

Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation.

Background And Aims: Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport Guanosine diphosphate-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans.

Supporting adolescents' participation in muscle-strengthening physical activity: protocol for the 'Resistance Training for Teens' (RT4T) hybrid type III implementation-effectiveness trial.

Introduction: In Australia, only 22% of male and 8% of female adolescents meet the muscle-strengthening physical activity guidelines, and few school-based interventions support participation in resistance training (RT). After promising findings from our effectiveness trial, we conducted a state-wide dissemination of the '' (RT4T) intervention from 2015 to 2020. Despite high estimated reach, we found considerable variability in programme delivery and teachers reported numerous barriers to implementation.

A cluster randomised controlled trial to assess the effectiveness of a multi-strategy sustainability intervention on teachers' sustained implementation of classroom physical activity breaks (energisers): study protocol.

Background: Governments internationally have invested hugely in the implementation and scale-up of school-based physical activity interventions, but have little evidence of how to best sustain these interventions once active implementation support ceases. This study will assess the effectiveness of a multi-strategy sustainability intervention on classroom teachers' sustainment of energisers (short 3-5 min physical activity breaks during class-time) scheduled across the school day from baseline to 12 and 24-month follow-up.

Methods: A cluster randomised controlled trial will be conducted in 50 primary schools within the Hunter New England, Illawarra Shoalhaven, Murrumbidgee and Northern New South Wales (NSW) Local Health Districts of NSW Australia.

Evaluating the scaling up of an effective implementation intervention (PACE) to increase the delivery of a mandatory physical activity policy in primary schools.

Background: Physically Active Children in Education (PACE) is an effective implementation intervention for increasing the number of minutes classroom teachers schedule physical activity each week. To date, evaluations of PACE have included a smaller number of schools from only one region in New South Wales Australia. If PACE is to have population-wide benefits we must be able to deliver this support to a larger number of schools across multiple regions.

Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans.

Background & Aims: OATP1B3/SLCO1B3 is a human liver-specific transporter for the clearance of endogenous compounds (eg, bile acid [BA]) and xenobiotics. The functional role of OATP1B3 in humans has not been characterized, as SLCO1B3 is poorly conserved among species without mouse orthologs.

Methods: Slc10a1-knockout (Slc10a1), Slc10a1 (endogenous mouse Slc10a1 promoter-driven human-SLCO1B3 expression in Slc10a1 mice), and human SLCO1B3 liver-specific transgenic (hSLCO1B3-LTG) mice were generated and challenged with 0.

Unique DUOX2ACE2 small cholangiocytes are pathogenic targets for primary biliary cholangitis.

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease.

Investigating the direct and indirect effects of a school-based leadership program for primary school students: Rationale and study protocol for the 'Learning to Lead' cluster randomised controlled trial.

Background: Leadership is a valuable skill that can be taught in school, and which may have benefits within and beyond the classroom. Learning to Lead (L2L) is a student-led, primary school-based leadership program whereby older 'peer leaders' deliver a fundamental movement skills (FMS) program to younger 'peers' within their own school.

Aim: The aims of the study are to determine the efficacy of a peer-led FMS intervention on: (i) peer leaders' (aged 10 to 12 years) leadership effectiveness (primary outcome), leadership self-efficacy, well-being, and time on-task in the classroom; (ii) peers' (aged 8 to 10 years) physical activity levels, actual and perceived FMS competency, cardiorespiratory fitness, muscular power, and executive functioning; and (iii) teachers' (referred to as 'school champions') work-related stress and well-being.

Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling.

Background And Aims: Bile acids trigger a hepatic inflammatory response, causing cholestatic liver injury. Runt-related transcription factor-1 (RUNX1), primarily known as a master modulator in hematopoiesis, plays a pivotal role in mediating inflammatory responses. However, RUNX1 in hepatocytes is poorly characterized, and its role in cholestasis is unclear.

A systematic review and meta-analysis of the benefits of school-based, peer-led interventions for leaders.

The aim of our systematic review and meta-analysis was to quantitatively synthesise the effects of school-based peer-led interventions on leaders' academic, psychosocial, behavioural, and physical outcomes. Eligible studies were those that: (i) evaluated a school-based peer-led intervention using an experimental or quasi-experimental study design, (ii) included an age-matched control or comparison group, and (iii) evaluated the impact of the intervention on one or more leader outcomes. Medline, Sportdiscus, Psychinfo, Embase, and Scopus online databases were searched on the 24th of October, 2022 which yielded 13,572 results, with 31 included in the narrative synthesis and 12 in the meta-analysis.

Cluster randomised controlled trial to determine the impact of an activity enabling uniform on primary school student's fitness and physical activity: study protocol for the Active WeAR Everyday (AWARE) study.

Unlabelled: IntroductionMulticomponent school-based physical activity (PA) interventions can improve students' cardiorespiratory fitness (CRF) and PA. Due to the complex nature of such interventions when delivered at scale their effect sizes markedly reduce. Modifying student school uniforms, so that they are more PA enabling, may be a simple intervention that could enhance student health.

SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.

Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD.

Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis.

Chronic liver diseases, e.g., cholestasis, are negatively impacted by inflammation, which further aggravates liver injury.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH).

Patients And Methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication.

Scale-up of the Physical Activity 4 Everyone (PA4E1) intervention in secondary schools: 24-month implementation and cost outcomes from a cluster randomised controlled trial.

Background: Physical Activity 4 Everyone (PA4E1) is an evidence-based program effective at increasing adolescent physical activity (PA) and improving weight status. This study aimed to determine a) the effectiveness of an adapted implementation intervention to scale-up PA4E1 at 24-month follow-up, b) fidelity and reach, and c) the cost and cost-effectiveness of the implementation support intervention.

Methods: A cluster randomised controlled trial using a type III hybrid implementation-effectiveness design in 49 lower socio-economic secondary schools, randomised to a program (n = 24) or control group (n = 25).

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis.

Adjunct Fenofibrate Up-regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis.

Accumulation of cytotoxic bile acids (BAs) during cholestasis can result in liver failure. Glucuronidation, a phase II metabolism pathway responsible for BA detoxification, is regulated by peroxisome proliferator-activated receptor alpha (PPARα). This study investigates the efficacy of adjunct fenofibrate therapy to up-regulate BA-glucuronidation and reduce serum BA toxicity during cholestasis.