BACKGROUND Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy associated with disability, morbidity and mortality. Impairment of health-related quality of life (HRQoL) in ENL has been reported using the Dermatology Life Quality Index (DLQI) and the 36-Item Short Form Health Survey (SF-36), the latter validated in people affected by leprosy. Understanding the […]
InSleep46: Deployment of a remote monitoring device for the detection and monitoring dementia risk in older adult populations: a feasibility study
Background: Improvements in health technology offer opportunities for remote disease screening, diagnosis and monitoring. The Withings Sleep Analyzer (WSA), an under mattress ballistocardiograph sensor able to detect body movement, breathing, and cardiac ejection is a promising technology for the non-invasive detection and monitoring of neurodegenerative diseases. InSleep46 aims to evaluate whether the WSA is able […]
Comparative Efficacy and Safety of Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Oral Gepants for Episodic Migraine Prevention: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Background. Calcitonin gene-related peptide (CGRP)-targeted therapies, including injectable monoclonal antibodies (mAbs: erenumab, fremanezumab, galcanezumab, eptinezumab) and oral gepants (atogepant, rimegepant), represent a paradigm shift in episodic migraine prevention. No direct head-to-head trials across the full drug class exist. We conducted a PRISMA-NMA-compliant Bayesian network meta-analysis (NMA) to compare the relative efficacy and tolerability of all […]
Undetected isoniazid resistance leads to rifampin-resistant tuberculosis
Background: Isoniazid resistance is the most common form of drug-resistant tuberculosis (TB) globally. However, WHO-recommended molecular tests available to most TB patients worldwide detect rifampin resistance only, risking under-treatment of isoniazid-resistant, rifampin-susceptible TB (HR-TB) and subsequent emergence of rifampin resistance. Methods: This prospective study (2020-2024) aimed to collect and archive sputum specimens from all adults […]
A RHNO1-ATR/Chk1 positive feedback loop sustains the DNA replication stress response
Elevated DNA replication stress is a common feature of cancer cells, rendering them dependent on ATR/Chk1 signaling, which controls the DNA replication stress checkpoint, for survival. Although the activation of ATR/Chk1 signaling is well-established, how this signal is maintained until replication stress is fully resolved is less understood. Here, we investigated the roles of RAD9 […]
Argonaute-2 slicing of Rtl1 promotes skeletal muscle development and postnatal survival
Argonaute (AGO) proteins associate with small guide RNAs to bind and repress mRNA targets. AGO2 is the primary AGO slicer in mammals, cleaving RNAs that base-pair extensively to its guide RNA. Disrupting the slicing activity of AGO2 in mice causes neonatal lethality, however, the specific cell types and substrates that contribute to this lethality are […]
FBH1 and RAD54L directly interact and cooperate to drive replication fork reversal
Replication fork reversal alleviates DNA replication stress and maintains genome stability. We previously showed that FBH1 and RAD54L cooperate to promote fork reversal in human cells, and that FBH1-dependent fork reversal requires the branch migration activity of RAD54L. However, the molecular basis of this cooperation remained unclear. Here, we identify both a physical and functional […]
Causal Network Mapping of sEEG Identifies Compact Epileptogenic Targets Concordant with Seizure Freedom: Multicenter Validation in 60 Patients
Background and Purpose: Drug resistant epilepsy (DRE) affects approximately 15 million people worldwide, and surgery remains the only curative option. A key challenge in predicting outcomes is the lack of standardized, quantitative tools to help distinguish seizure driver regions from responder regions during stereoelectroencephalography (sEEG) recordings. We validated the CN Suite, a computational platform that […]
Collagen Rope Trick: Cell-Laden Fibre Assembly at 1 Liquid Interfaces
Tissues and organs in living organisms represent centimeter-scale hierarchical architectures comprising nano- to microscale, uniaxially aligned extracellular matrix (ECM) fibres with high mechanical strength, integrated with cellular components, as exemplified in tendon, skin, cartilage, bone, and blood vessels. Here, we present a liquid-liquid interfacial spinning method to produce highly uniaxially aligned, centimeter-scale collagen fibres. The […]
Proteomic Identification of Pig Xenoantigens for Clinical Xenotransplantation
Xenotransplantation using genetically engineered pig organs offers a promising solution to the shortage of donor organs for life-saving transplants. However, human preformed antibodies against unknown pig xenoantigens remain a significant barrier to successful xenotransplantation. Current methods for characterizing these antibodies or xenoantigens are limited to cellular-level crossmatch assays. In this study, we developed a novel […]
Sex-specific associations between metabolic dysregulation and knee pain: a 9-year population-based cohort study
Introduction Knee pain is a highly prevalent condition in the general population and is more common than knee osteoarthritis. Population-based evidence linking metabolic dysfunction to knee pain remains limited, and data on sex-specific effects are scarce. Therefore, we examined sex-specific associations between metabolic dysregulation and knee pain in a population-based cohort. Method We analyzed data […]
Patient and caregiver lived experiences and mental health service engagement during first-episode psychosis in Uganda: a longitudinal mixed-methods study protocol
Introduction: Engagement with mental health services (MHCS) during the first episode of psychosis (FEP) is critical for symptom control, quality of life, and relapse prevention. However, disengagement rates remain high in Uganda with severe consequences for patients and caregivers. This study protocol describes a mixed-methods investigation which aims to examine the relationship between patients and […]