A Novel Mutation in LXRα Uncovers a Role for Cholesterol Sensing in Limiting Metabolic Dysfunction-Associated Steatohepatitis (MASH).

Liver x receptor alpha (LXRα, Nr1h3) functions as an important intracellular cholesterol sensor that regulates fat and cholesterol metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing.

Quantifying the administration and monitoring time burden of several disease-modifying therapies for relapsing multiple sclerosis in the United Kingdom: A time and motion study.

Background: The treatment landscape for relapsing multiple sclerosis (MS) has changed dramatically in recent decades, including an increasing number of high-efficacy disease-modifying therapies (DMTs) with varied administration and monitoring requirements. Coupled with greater focus on earlier treatment, these factors have resulted in stretching of the capacity of MS specialist services and allied healthcare professionals (HCPs). To assist with the effective planning of MS services in the UK NHS, this study quantified the administration and monitoring time burden associated with high-efficacy DMTs (alemtuzumab, cladribine tablets, fingolimod, natalizumab, and ocrelizumab) for relapsing MS.

Real-world use of cladribine tablets (completion rates and treatment persistence) in patients with multiple sclerosis in England: The CLARENCE study.

Background: Treatment with cladribine tablets, a high-efficacy disease-modifying therapy (DMT), has been available in England since 2017 for patients with highly active relapsing multiple sclerosis (MS). Real-world data on treatment completion, persistence and switching in patients treated with cladribine tablets are beginning to emerge, but only small single and multicentre cohorts have reported so far. This longitudinal retrospective observational study (CLARENCE) evaluated a large cohort (>1900) of patients with highly active relapsing MS, receiving cladribine tablets across England, to determine rates of treatment completion, persistence and switching in the real world.

Differentiated experiences of financial precarity and lived precariousness among international students in Australia.

Empirical research on international student migrants has sometimes homogenised this group, framing it as predominantly made up of privileged members of the global middle-class. This has led to calls to acknowledge and address the precarity faced by international students in their respective host countries more comprehensively. This study aims to explore how levels of financial precarity vary among international students in Australia, and how this in turn contributes to varying levels of precariousness in the personal spheres of students' lives.