National Institutes of Health

ReMeDy : A Flexible Statistical Framework for Region‐Based Detection of DNA Methylation Dysregulation

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily thr...

Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis From Uganda

Abstract Objective Severe tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature o...

Open-Source Software Suite for Cell Detection and Segmentation in Adaptive Optics Retinal Imaging

Purpose: The purpose of this study was to present a suite of open-source software tools for automated and interactive annotation (detection and segmentation) of retinal cells from adaptive optics (AO) images. Methods: Three related software packages were developed, implementing m...

The role of chloride ions in serotonin transport

Abstract The human serotonin (5-HT + ) transporter SERT facilitates 5-HT + transport into cells by coupling it to Na + symport and K + antiport. Although extracellular Cl − is also essential for transport, Cl − co-transport has been disputed, raising questions about the role of C...

Divergent complication patterns of type 2 diabetes in African individuals who are lean versus overweight or obese: a multi-cohort analysis

Abstract Aims/hypothesis Nearly 40% of African adults with type 2 diabetes are lean (BMI <25 kg/m 2 ). Emerging evidence suggests that type 2 diabetes in African individuals who are lean may represent a distinct phenotype driven by impaired insulin secretion rather than insulin r...

Prediagnostic circulating 25-hydroxyvitamin D and prostate cancer-specific survival: a collaborative pooled analysis of 13 prospective studies

Abstract Background Previous research suggests higher risk of prostate cancer diagnosis in men with high vitamin D serology, but there are limited data related to prostate cancer survival. In this study, we examine the associations between prediagnostic circulating levels of 25-h...

The global cardiovascular-kidney-liver-metabolic burden from 1990 to 2023

Background The cardiovascular-kidney-liver-metabolic (CKLM) framework represents the multi-organ interplay of systemic metabolic disorders that drive the global burden of cardiovascular diseases (CVD). Methods This study is a descriptive epidemiological analysis of the Global Bur...

16S ribosomal RNA modification drives transcript-specific translation efficiency

ABSTRACT Bacterial ribosomal RNAs (rRNAs) are decorated with conserved nucleotide modifications, but the functionality of these modifications is often underexplored. MraW (RsmH) is a 16S rRNA methyltransferase that fine-tunes ribosomal function. We identified a loss-of-function a...

Aspiration and silent aspiration in Niemann-Pick disease type C1: longitudinal findings from the NIH natural history study

Abstract Background Niemann–Pick disease type C1 (NPC1) is a rare neurodegenerative disorder in which dysphagia is common and aspiration pneumonia is a leading cause of mortality. Aspiration may be clinically apparent or silent, reflecting impaired airway sensation and protective...

VIProDesign: viral protein panel design for highly variable viruses to evaluate immune responses and identify broadly neutralizing antibodies

Motivation: Highly mutable viruses continuously evolve, with some posing major pandemic risks. However, standardized neutralization assays and up-to-date viral panels are often lacking, limiting evaluation of immunogens and identification of broadly neutralizing antibodies. Closi...

Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness

Abstract Many bipolar disorder (BD) patients are non-responsive to lithium. The mechanisms underlying lithium (non-)responsiveness are largely unknown. By using gene-set enrichment analysis methods, we found that core clock gene-sets are significantly associated with lithium resp...

Tramadol Co‐Administration with Oxycodone or Hydrocodone Increases Opioid Burden without Improving Postoperative Pain Control

Tramadol is frequently co-prescribed with oxycodone or hydrocodone after surgery under the assumption that its dual mechanism of action provides an opioid-sparing benefit. However, evidence supporting this practice is limited and inconsistent. We conducted a secondary analysis of...

Bone marrow failure syndromes across the age spectrum: diagnostic and therapeutic principles

Bone marrow failure syndromes (BMFS) are a diverse group of disorders that commonly present with pancytopenia and require a structured approach to evaluation. Initial assessment focuses on excluding reversible causes, followed by consideration of inherited and acquired conditions...

Proliferative control of the saccular-stage developing mouse lung requires the histone methylation activity of KMT2D

KMT2D, the histone methyltransferase and core component of the COMPASS/MLL4 complex, has been implicated in developmental diseases such as Kabuki Syndrome, interstitial lung disease, and congenital diaphragmatic hernia, with clear links to pediatric pulmonary disorders. Despite t...

Potent type-specific de novo antibodies complement broadly reactive imprinted antibodies in immune responses to SARS-CoV-2 variants

Abstract For rapidly mutating viruses such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune memory recalled by antigenically drifted variants primarily comprises antibodies that cross-react to the priming strain rather than de novo eli...

Endothelial Cell Proteins as Biomarkers in Susac Syndrome

ABSTRACT Objective Susac syndrome (SS) is a rare CD8 + T cell–mediated microangiopathy affecting the brain, retina, and auditory labyrinth. Endothelial injury is thought to be a central mechanism; however, no circulating disease biomarkers are known. We performed targeted proteom...

Autonomous AI in prostate cancer: the road ahead towards clinical implementation

Abstract Artificial Intelligence (AI) for detecting clinically significant prostate cancer (csPCa) on MRI has achieved diagnostic performance comparable to that of radiologists. By autonomously interpreting examinations, AI could improve workflow efficiency and help address incre...

An autoinflammatory CDC42 variant M45L demonstrates the mechanism of pyrin inflammasome activation

CDC42 is an evolutionarily conserved guanosine triphosphatase (GTPase) regulating critical cellular and immune processes. Variants in CDC42 therefore cause a spectrum of developmental phenotypes, including hematological and immunological symptoms. Here, we identify a previously u...

Lipidomic and transcriptomic remodeling underlies early retinal pathogenesis in dry age-related macular degeneration

Abstract Dry age-related macular degeneration (AMD) is initiated by retinal pigment epithelium (RPE) dysfunction, yet early metabolic mechanisms linking RPE injury to photoreceptor dysfunction remain unclear. Using a physiologically relevant mouse model, we performed cell-type–re...

Duration of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest

Importance Therapeutic hypothermia is widely used for neuroprotection following cardiac arrest, but clinical trials have not consistently demonstrated improved neurological outcomes, and the optimal duration of cooling remains uncertain. Objective To determine the duration of the...