National Institutes of Health

High rates of transition to immune active disease in a cohort of strictly defined immune tolerant patients with chronic hepatitis B: results from the RADICAL consortium

Background Patients with immune tolerant (IT) chronic hepatitis B (CHB) have high viral loads, minimal inflammation and minimal fibrosis. Nevertheless, the benign nature of this phase and the need for antiviral therapy remain controversial. Objective We explored the natural histo...

Cellular, molecular and functional characteristics of induced pluripotent stem cell derived neurons from refractory chronic cough patients and healthy controls

The pathophysiology of refractory chronic cough (RCC) and the aetiology of associated cough hypersensitivity syndrome remains unclear, partly due to the absence of a suitable disease-specific sensory neuronal model. This study was designed to investigate whether induced pluripote...

Post-colonial human admixture and natural selection: disentangling signals in complex demographic contexts

Natural selection and admixture are defining population genetic features of modern human populations, yet their interaction has only recently emerged as a major focus in human evolutionary genomics. While the influence of natural selection on population structure and trait divers...

Landscape of approaches for streamlining pre-analytical and early analytical variables for solid tumor next-generation sequencing: A Genomics Organization for Academic Laboratories consortium report

The scope of pre-analytical and early analytical methods used in clinical molecular laboratories can have vast effects on the quality and turnaround time for solid tumor next-generation sequencing assays. To learn more about various approaches, a survey of 24 academic laboratorie...

Epithelial-mesenchymal Wnt crosstalk directs planar cell polarity in the developing cochlea

Cochlear hair cells are precisely oriented by planar cell polarity. Wnt proteins direct planar cell polarity in vertebrates, but their roles in regulating cochlear planar cell polarity remain unclear. Here, we inhibit Wnt secretion by ablating epithelial Wntless and find shortene...

Sex-specific biological aging clocks across organs and omics

Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer’s disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex in...

HLA-B*27-associated arthritis across the ages – bridging the gap

HLA-B*27-associated arthritis comprises a number of different forms of inflammatory arthritis with a common phenotype, encompassed by the term spondyloarthritis. The clinical features and outcomes differ across the age spectrum which has resulted in different classification syste...

A Live Single-Cycle RSV Vaccine with Immune Responses Focused on Prefusion F and the Central Conserved Region of Attachment Protein G

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and children, and a pediatric vaccine is not available. Among various approaches, live vaccines are attractive as they induce broad multi-antigenic responses and have never bee...

Zebrafish larvae swim bladder serves as a model to study Mycobacterium abscessus infection kinetics, host–pathogen interactions and drug efficacy

Mycobacterium abscessus , a nontuberculous mycobacterium (NTM), is a cause of chronic lung infection primarily affecting people with underlying conditions such as cystic fibrosis and other causes of bronchiectasis. Mostly caudal vein infection of zebrafish embryos has been used f...

Oral Fungal Infection Impacts Epithelial Innate Immunity to Promote Local and Distal Squamous Cell Carcinoma Progression

Abstract Fungi have been detected within human tumors and shown to support tumor progression. A better understanding of how intratumoral fungi evade innate immunity, remodel the tumor microenvironment (TME), and promote tumorigenesis may provide insights into cancer pathogenesis...

Neocortical long-range inhibition promotes cortical synchrony and sleep

Abstract Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity 1 . During low-arousal states such as slow-wave sleep, synchronous low-frequency rhythms dominate activity across widespread cortical regions. Although inhibitory neurons are increa...

Neighborhood Contemporary Redlining and Racial Mortgage Lending Bias and Cardiovascular Outcomes in Women With Breast Cancer

BACKGROUND: Studies have demonstrated neighborhood structural inequities are associated with cardiovascular outcomes among breast cancer survivors. We investigated the associations between bias in mortgage lending practices (contemporary redlining and racial lending bias) and car...

TMA-Grid: an open-source, zero-footprint web application for FAIR tissue microarray de-arraying

Tissue microarrays (TMAs) significantly increase analytical efficiency in histopathology and large-scale epidemiologic studies by allowing multiple tissue cores to be scanned on a single slide. The individual cores can be digitally extracted and then linked to metadata for analys...

End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis

Non-homologous end joining (NHEJ) is a major pathway of DNA double strand break (DSB) repair, capable of directly joining both damaged strands of DNA through the coordinated activities of repair factors that detect the termini, physically bridge them together, and perform the che...

Environmental exposures and risks for the idiopathic inflammatory myopathies and its phenotypes: a narrative review

Purpose of review The delineation of myositis-specific autoantibody (MSA) subgroups over the past two decades has reframed environmental research in idiopathic inflammatory myopathies (IIMs), making it plausible to examine discrete exposure-phenotype pairings within serologically...

Intravascular ultrasound–guided versus angiography-guided endovascular interventions for peripheral artery disease: a systematic review and meta-analysis

Abstract Background Endovascular revascularization is a cornerstone therapy for peripheral artery disease (PAD), typically guided by angiography, which may underestimate vessel size and lesion complexity. The clinical benefit of intravascular ultrasound (IVUS) guidance remains un...

Measurement of binding antibodies to SARS-CoV-2 variants elicited by natural infection and COVID-19 vaccines in a sub-Saharan African population

Abstract Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly with respect to antibody (Ab) binding across SARS-CoV-2 variants and for different types of vaccine platforms. We assessed anti-spike (anti-S) antibody binding to nin...

Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation

Oncogenic KRAS and NRAS mutations are common in hematologic malignancies, but how they signal is less well characterized than in carcinomas. To uncover novel RAS biology and potential therapeutic vulnerabilities, we employed a multi-omics screening approach in multiple myeloma to...

Overcoming immune checkpoint inhibitor-mediated T-cell exhaustion with a TCR β chain-directed selective dual T-cell activator

Abstract Background Resistance to immune checkpoint inhibition (ICI) using antibodies against the PD-1/PD-L1 axis remains a significant clinical challenge. Here, we report that combination of anti-PD-1 with a bifunctional fusion molecule, anti-TCRβ-IL-2, comprised of a monovalent...

MUTYH Activity Maintains Telomere Stability in Response to Chronic Telomeric 8-Oxoguanine Damage in Cancer Cells

Telomeres are highly susceptible to oxidative DNA damage, particularly 8-oxoguanine (8-oxoG), which is processed by glycosylase-initiated base excision repair (BER). OGG1 removes 8-oxoG opposite C, and MUTYH removes A misinserted opposite 8-oxoG to prevent mutations. While OGG1 h...