Biology subjects

Sunshine, J.

Publications and source records attributed to Sunshine, J..

5 recordsLinked to original sources

bioRxiv2026

Associations Between QuantiFERON-TB Gold Plus IFNγ Concentrations and Progression to Symptomatic Tuberculosis in Global High-Burden TB Settings

IntroductionPredictive biomarkers for symptomatic tuberculosis (TB) progression would transform targeted prevention efforts. Although interferon-gamma release assays (IGRAs), including QuantiFERON(R) TB-Gold Plus (QFT-Plus), have been studied for this purpose, systematic evaluation of the QFT-Plus TB1 and TB2 Interferon-Gamma (IFN{gamma}) concentrations remains limited, particularly in high-burden TB settings. MethodsBaseline TB1 and TB2 IFN{gamma} concentrations from 5,259 participants in TB-endemic regions were analyzed in relation to subsequent TB outcomes over a median of 525 days follow-up. Participants were categorized as controls (no TB), suspected TB (no microbiological confirmation), or laboratory-confirmed TB, including a subset meeting a stringent case definition ([≥]2 positive microbiologic tests). Associations between baseline IFN{gamma} concentrations and progression to symptomatic TB were assessed. ResultsIn the full cohort (IGRA+/-participants), baseline TB2 IFN{gamma} concentrations were significantly higher compared to controls among participants who developed suspected TB (p=0.01), laboratory-confirmed TB (p=0.01), or met the stringent case definition (p<0.0001). In IGRA+ participants, baseline TB2 concentrations were significantly higher than controls in suspected (p=0.01) and laboratory-confirmed (p=0.02) groups. Associations with baseline TB1 IFN{gamma} concentrations and TB progression were observed for participants meeting the stringent case definition within the full cohort (p=0.009). Among stringent definition cases, TB2 concentrations achieved an area under the Receiver Operating Characteristic curve of 0.84, with a sensitivity of 80% and specificity of 78%. ConclusionsQuantitative IFN{gamma} concentrations from QFT-Plus, particularly TB2, were associated with progression to symptomatic TB, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers, and may support biomarker-based stratification in TB clinical research. SummaryIn an exploratory analysis from a global tuberculosis (TB) epidemiology study, higher QuantiFERON-TB Gold Plus IFN{gamma} concentrations were associated with progression to symptomatic TB and met WHO predictive biomarker thresholds, supporting their potential value for risk stratification in TB research.

immunology↗

bioRxiv2025

A Validated Method for Detection of Bifidobacterium infantis Bi-26™ DNA in Stool by Quantitative Real-Time PCR

BackgroundBifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterium enriched in the microbiota of breastfed infants and associated with beneficial effects on infant gut health. Clinical studies evaluating B. infantis supplementation in infants have reported increased colonization, reduced inflammation, enhanced vaccine responsiveness, and improved growth outcomes. To support rigorous evaluation of these effects in further clinical trials, reliable and validated methods for quantifying B. infantis in stool are needed. MethodsWe validated a quantitative real-time PCR (qPCR) assay against a conserved B. infantis genomic target. Assay performance was evaluated using DNA from the B. infantis strain Bi-26TM, spiked infant stool pools, and matrix controls. Validation parameters included linearity, sensitivity, accuracy, within- and between-run reproducibility, recovery, and matrix interference, with acceptance criteria informed by bioanalytical best practices. ResultsThe assay demonstrated robust performance across validation parameters. Linearity was confirmed over at least six orders of magnitude (R2 > 0.99; mean efficiency 96.4%), with a lower limit of quantification of 37.36 genome equivalents / reaction. Analytical sensitivity was high, with a 95% limit of detection of 4.67 genome equivalents / reaction. Accuracy across multiple stool pools met acceptance criteria, with mean deviation from nominal values of 0.39 log10. Reproducibility was strong, with within-run variability of 0.37% and between-run variability of 1.78%. Recovery averaged 41.3%, exceeding the predefined minimum threshold, and matrix interference was minimal. ConclusionsThis study reports a validated qPCR assay suitable for quantifying B. infantis Bi-26 DNA in stool samples collected in stabilized formats. Its robust analytical performance supports its use in clinical and translational research evaluating B. infantis colonization and its health impacts in early infant life.

microbiology↗

bioRxiv2024

The microanatomy of human skin in aging

Aging is a major driver of diseases in humans. Identifying features associated with aging is essential for designing robust intervention strategies and discovering novel biomarkers of aging. Extensive studies at both the molecular and organ/whole-body physiological scales have helped determined features associated with aging. However, the lack of meso-scale studies, particularly at the tissue level, limits the ability to translate findings made at molecular scale to impaired tissue functions associated with aging. In this work, we established a tissue image analysis workflow - quantitative micro-anatomical phenotyping (qMAP) - that leverages deep learning and machine vision to fully label tissue and cellular compartments in tissue sections. The fully mapped tissue images address the challenges of finding an interpretable feature set to quantitatively profile age-related microanatomic changes. We optimized qMAP for skin tissues and applied it to a cohort of 99 donors aged 14 to 92. We extracted 914 microanatomic features and found that a broad spectrum of these features, represented by 10 cores processes, are strongly associated with aging. Our analysis shows that microanatomical features of the skin can predict aging with a mean absolute error (MAE) of 7.7 years, comparable to state-of-the-art epigenetic clocks. Our study demonstrates that tissue-level architectural changes are strongly associated with aging and represent a novel category of aging biomarkers that complement molecular markers. Our results highlight the complex and underexplored multi-scale relationship between molecular and tissue microanatomic scales.

pathology↗

bioRxiv2024

What Does Large-scale Electrodermal Sensing Reveal?

Electrodermal activity (EDA) is a physiological measure that is used to index sympathetic arousal in response to stressors and other perturbations. However, EDA is underutilized in real-world, population-level research and clinical practice because of a paucity of remote measurement capabilities on commodity devices. The current study examined the capabilities of continuous remote measurement of EDA at scale to quantify physiological changes in the context of diurnal and circadian rhythms, demographic differences, high arousal contexts such as public holidays and high arousal moments (e.g., the Super Bowl). We first demonstrated the accuracy of a novel EDA sensor developed for the Fitbit Sense 2 wearable device within a controlled, arousal-inducing experiment. We then retrospectively analyzed 10 million hours of continuous EDA data collected from over 16,000 people. We show that continuously sampled in-situ EDA from Sense 2 has similar population-level diurnal patterns as those established from more tightly controlled in-lab experiments. Following this, variation of SCL across day of the week and season are presented. Finally, EDA dynamics occurring in response to commonly held stressful or exciting events such as Thanksgiving and the Super Bowl are described which we interpret as a natural experiment eliciting autonomic arousal.

physiology↗

bioRxiv2021

Anatomical Structures, Cell Types, and Biomarkers Tables Plus 3D Reference Organs in Support of a Human Reference Atlas

1.This paper reviews efforts across 16 international consortia to construct human anatomical structures, cell types, and biomarkers (ASCT+B) tables and three-dimensional reference organs in support of a Human Reference Atlas. We detail the ontological descriptions and spatial three-dimensional anatomical representations together with user interfaces that support the registration and exploration of human tissue data. Four use cases are presented to demonstrate the utility of ASCT+B tables for advancing biomedical research and improving health.

cell biology↗