National Institutes of Health

Endogenous anti-Ebola virus GP 1,2 antibodies interfere with detection of secreted glycoprotein in the blood of EVD patients

ABSTRACT Ebola disease (EBOD) is a highly infectious disease with severe hemorrhagic symptoms. It is caused by orthoebolaviruses , which include the Ebola virus ( Orthoebolavirus zairense ) (EBOV) causing Ebola virus disease (EVD), the most lethal EBOD to humans. Through co-trans...

Structure-based identification and biological evaluation of a novel MAPKAPK2 inhibitor for pancreatic cancer

Pancreatic cancer remains a lethal malignancy with few effective treatment options. MAPKAPK2, a downstream effector of p38 signaling, represents a potential target for disrupting tumor survival pathways. Structure-guided computational screening has become an important strategy fo...

Pharmacokinetics of Efavirenz in Pregnancy and Postpartum with and Without First-line Tuberculosis Drugs: Results from IMPAACT P1026s

Efavirenz (EFV) pharmacokinetics (PK) may be influenced by both pregnancy-related physiological changes and concurrent treatment for drug-sensitive tuberculosis (DS-TB), and intensive 24-h EFV PK data during rifampin (RIF)/ isoniazid (INH) treatment in pregnant women living with...

Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry-specific manner. Here, we utilise gen...

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the...

What Is Pediatric Melanoma? Clinical and Genomic Features and the Role of Next‐Generation Sequencing in Tumor Classification

Pediatric melanoma is rare and often poses diagnostic challenges because benign and malignant melanocytic tumors in children can share overlapping clinicopathologic features. Epidemiologic and genomic studies have provided important insights into the etiology of pediatric melanoc...

Distinct Plasma Proteomic Signatures Distinguish MASLD From Non‐Steatotic Individuals but Not From MetALD

ABSTRACT Background and Aims Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease, yet accurate early detection remains challenging. A particular diagnostic obstacle is distinguishing MASLD from metabolic dysfunction and alcohol‐rel...

Comparative Effectiveness of Tocilizumab and Tumor Necrosis Factor Inhibitors in Takayasu Arteritis: Age‐Related Differences in Treatment Response

OBJECTIVE: Comparative, prospective data on biologics for Takayasu arteritis (TAK) are limited. We compared tumor necrosis factor inhibitors (TNFi) and tocilizumab (TCZ) in a combined cohort, assessed demographic and cytokine influences, and evaluated longitudinal outcomes. METHO...

Population state changes the transfer value of organized variation in a finite-population model

Historically acquired variation biases can facilitate adaptation, but their value may change as a population moves through a new environment. We studied a two-dimensional model comparing an inherited variation orientation with a quarter-turned control of identical covariance eige...

Environmental recurrence changes the transmission advantage of private memory in a finite-budget population model

Using stored information may help a strategy spread without improving every population-performance endpoint. We distinguish these outcomes in an abstract 32-individual, 32-bit population model with private one-record memory, inherited strategy labels and an equal objective-evalua...

A randomized phase 2 placebo-controlled trial of clobetasol solution for oral chronic graft-versus-host disease therapy

Chronic graft-versus-host disease (cGVHD) affects multiple organ systems and frequently the mouth. There is an unmet need for more effective topical therapy to adequately control cGVHD in the oral cavity. Clobetasol is a super-potent synthetic glucocorticoid formulated here as an...

Environmental recurrence changes the transmission advantage of private memory in a finite-budget population model

Using stored information may help a strategy spread without improving every population-performance endpoint. We distinguish these outcomes in an abstract 32-individual, 32-bit population model with private one-record memory, inherited strategy labels and an equal objective-evalua...

Cerebellar α-synucleinopathy contributes to Parkinsonian gait and balance impairment in mouse models

Postural instability and gait difficulty (PIGD) represent a debilitating clinical subtype of Parkinson’s disease (PD) that is largely refractory to dopaminergic replacement therapy. While clinical imaging implies that the cerebellum is involved in these axial deficits, the specif...

Structural insight into the activation of adenosine A2AR/A2BR by the dual-agonist MRS3997

Abstract A 1 R, A 2A R, A 2B R, and A 3 R adenosine receptors comprise a G protein-coupled receptor (GPCR) subfamily that regulates many bodily processes. Subtype-selective agonists potentially treat inflammatory and ischemic conditions. The dual A 2A R/A 2B R agonist MRS3997 pro...

RNF5 Regulates HERP1 and OS9 Stability and Modulates Processing of an ERAD Substrate

Endoplasmic reticulum-associated degradation (ERAD) must dynamically adapt to cellular protein-folding demands, yet mechanisms regulating ERAD-associated adaptors remain incompletely defined. Here, we identify the E3 ubiquitin ligase RNF5 as a regulator of the ERAD adaptors HERPU...

Multiscale Regulation of Meiotic Recombination in Mammals

Meiotic recombination is a multilayered process that shapes genetic diversity while safeguarding genome stability. In mammals, the final distribution of crossovers and non-crossovers emerges from the integration of sequence-specific hotspot specification, chromosome architecture,...

An amygdaloreticular pathway promotes motor programs of ingestion

Despite internal cues signaling fullness, animals can continue eating when motivated by context or palatability. The neural pathways and signals enabling the override of these fullness cues remain unclear. Here, we examine a collateralized amygdaloreticular network, focusing on c...

Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder

Abstract Background Down syndrome regression disorder (DSRD) causes a rapid loss of cognitive, behavioral, and daily living skills, usually in adolescents and young adults with Down syndrome. Because people with Down syndrome have a high lifetime risk of Alzheimer’s disease, we e...

The completion gap framework: age-associated weight gain as passive convergence between meal completion and energy demand

Abstract Age-associated weight gain is commonly attributed to behavioral or metabolic changes. We propose the completion gap framework, in which meal-completion requirements and physiological energy demand are only partially coupled. Persistent mismatch between these variables pr...

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...