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 […]
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 […]
Exercise Stress Echocardiography Unmasks Subclinical Cardiovascular Dysfunction in Midlife Women Following Hypertensive Disorders of Pregnancy
Background: Hypertensive disorders of pregnancy (HDP) are a risk factor for early cardiovascular disease in women, perhaps related to adverse cardiovascular reactivity to physiologic stress. Objectives: To evaluate the association of HDP subtypes with exercise stress echocardiography parameters. Methods: This retrospective cohort study linked exercise stress echocardiograms with delivery records. HDP was classified as none, […]
Macrophage spatial polarity to T cells predicts prognosis in young women with luminal breast cancer
Purpose: The prognostic role of tumor-infiltrating lymphocytes in luminal breast cancer remains uncertain, partly because density-based metrics do not capture spatial interactions between immune cell subsets. We developed a density-independent spatial metric quantifying macrophage-T cell proximity and assessed its prognostic value. Experimental Design: Using multiplex immunohistochemistry across three breast cancer cohorts (exploratory, n = 17; […]
MiR487a-3p and MiR6855-3p Facilitate Macrophage Pro-inflammatory Polarization and Lipid Accumulation in Atherosclerosis
BACKGROUND: MicroRNAs (miRNAs) regulate macrophage plasticity in atherosclerosis (AS). We tested the hypothesis that miR487a-3p and miR6855-3p accelerate AS by promoting macrophage inflammatory responses and metabolic dysregulation. METHODS: miRNA-seq and mRNA-seq were performed on peripheral monocytes from CAD patients and healthy controls. Macrophages in mouse aortas and human coronary arteries were characterized by flow cytometry […]
Wavelet Decomposition-Based Genomic Analysis of the Human Electrocardiogram
The electrocardiogram (ECG) encodes the electrical activity of the heart across multiple timescales, yet standard clinical analysis collapses this rich signal into a handful of scalar measurements that discard most of the waveform’s structure. Whether the frequency signals lost in this reduction carry heritable biological information relevant to cardiovascular disease risk remains unclear. Here we […]
Identification of amino acid metabolism-related biomarkers in liver fibrosis: a transcriptomic analysis with experimental validation
Background Liver fibrosis (LF) represents a pivotal pathological phase in the advancement of chronic liver disorders toward cirrhosis. Amino acid metabolism reprogramming plays a pivotal role in its pathogenesis, yet the underlying molecular mechanisms remain incompletely understood. Methods Integrating three public datasets (GSE14323, GSE84044, and GSE136103) with amino acid metabolism-related gene sets, we performed consensus […]
Tryptophan-Kynurenine shunt and depletion of indole-producing Firmicutes: A new Gut-Heart axis in Calcific Aortic Stenosis (GUT-CAS)
Introduction: Calcific aortic stenosis (CAS) is a progressive valvular disease characterized by lipid accumulation, inflammation, and osteogenic remodeling. Emerging evidence implicates gut microbiota-derived metabolites in cardiovascular pathology, yet their contribution to valvular disease remains poorly defined. The aim of this study was to investigate gut microbiota and metabolite signatures in patients with CAS and explore […]
The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration
Rare coding variants can have large effects on disease risk and provide direct routes from human genetics to disease mechanisms and therapeutic targets, but their discovery is constrained by sample size, particularly for low-prevalence diseases. Here we establish the Biobank Rare Variant Analysis (BRaVa) consortium, a global rare variant association resource that integrates sequencing and […]
Antigenic seniority and convergent haemagglutinin evolution shaped the immune landscape preceding influenza B/Yamagata’s extinction
Background: In 2020, the B/Yamagata lineage of influenza B disappeared from circulation. Understanding the immunological conditions preceding this loss can help explain why the lineage disappeared and has implications for our understanding of viral evolution and ongoing vaccine policies. Methods: We measured neutralising antibody responses in age- and sex-matched blood donor cohorts collected in 2020, […]
The Dermatology Life Quality Index is a useful patient reported outcome measure in individuals with severe erythema nodosum leprosum: a post-hoc analysis of the Methotrexate and Prednisolone study – MaPs in ENL
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 […]
Explainable AI for Data-Driven Design of High-Dimensional Predictive Studies
Predictive modelling is important for health data analysis and data-driven clinical decision-making. However, predictive studies are challenging to design optimally by hand when tens or even hundreds of features require selection, transformation, or interaction modelling. While complex machine learning models offer high performance, their "black-box" nature limits the clinical trust, transparency, and interpretability required for […]