Science Advances

Besides severe respiratory distress, recent reports in Covid-19 patients have found a strong association between platelet counts and patient survival. Along with hemodynamic changes such as prolonged clotting time, high fibrin degradation products and D-dimers, increased levels of monocytes with disturbed morphology have also been identified. In this study, through an integrated analysis of bulk RNA-sequencing data from Covid-19 patients with data from single-cell sequencing studies on lung tiss...

The ability of CD8+ T cells to protect against infection and malignant transformation diminishes with age. Novel means to assess cellular functional deficits in vivo are being made available such as total-body positron emission tomography (PET) and radiotracers with long half-lives. Here, we determined radiolabeled human CD8+ T cells isolated from young and old individuals with zirconium-89 (89Zr) and assessed their biological status in vitro and distribution in vivo. MethodsFresh and cryoprese...

Clonal haematopoiesis of indeterminate potential (CHIP) is the acquisition of somatic mutations in leukaemia-associated genes in haematopoietic progenitors with age. It increases the risk of haematological malignancy (HM), cardiovascular disease (CVD) and mortality mediated by CHIP-associated inflammation, with larger clones posing higher risks. Statins have been found to reduce the risk of progression from myelodysplastic syndrome to acute myeloid leukaemia and have also shown efficacy in vitro...

Artificial intelligence (AI) applied to single-cell data has the potential to transform our understanding of biological systems by revealing patterns and mechanisms that simpler traditional methods miss. Here, we develop a general-purpose, interpretable AI pipeline consisting of two deep learning models: the Multi- Input Set Transformer++ (MIST) model for prediction and the single-cell FastShap model for interpretability. We apply this pipeline to a large set of routine clinical data containing ...

Blood Plasma Viscosity (PV) is an established biomarker for numerous diseases. While PV colloquially refers to the shear viscosity, there is a second viscosity component--the bulk viscosity--that describes the irreversible fluid compressibility on short time scales. The bulk viscosity is acutely sensitive to solid-like suspensions, and obtainable via the longitudinal viscosity from acoustic attenuation measurements. Whether it has diagnostic value remains unexplored yet may be pertinent given th...

1.Indoor airborne particulates are well-known health hazards and filtration is one common method of reducing exposures. Based on our previously developed Regional Shelter Analysis methodology and parameters that characterize the existing US building stock, we perform a high-level assessment of the potential benefits of upgrading existing filters in furnace and in heating, ventilation, and air conditioning systems using off-the-shelf filters. We use three metrics to assess the improvement: Buildi...

Preterm labor is a serious issue that can lead to preterm birth, posing significant risks to both the mother and the neonate. Despite the high incidence of approximately 15 million preterm births worldwide per year, there is a lack of sufficient strategies for predicting and preventing preterm labor. Here, we found that exosomal miRNAs in maternal vaginal discharge can serve as biomarkers for early diagnosis of life-threatening conditions in both the mother and neonate. Our non-invasive biopsy o...

Mobile monitoring campaigns to estimate long-term air pollution levels are becoming increasingly common. Still, many campaigns have not conducted temporally-balanced sampling, and few have looked at the implications of such study designs for epidemiologic exposure assessment. We carried out a simulation study of fixed-site air quality monitors to better understand how different mobile monitoring designs involving short-term stationary measurements at fixed locations impact the resulting exposure...

Prebiotic, probiotic, and combined (synbiotic) interventions often show variable outcomes across individuals, driven by complex interactions between introduced biotics, the endogenous microbiota, and the host diet. Predicting individual-specific success or failure of probiotic and prebiotic therapies remains a major challenge. Here, we leverage microbial community-scale metabolic models (MCMMs) to forecast probiotic engraftment and microbiota-mediated short-chain fatty acid (SCFA) production in ...

Iron deficiency (ID) in children caused by dietary deprivation can be alleviated in [~]40% cases with iron-fortified nutritional solutions. Devising more effective nutritional solutions requires a quantitative understanding of iron homeostasis, which is lacking. Here, we developed a physiologically-based mathematical model of paediatric iron homeostasis that recapitulates ID due to dietary deprivation and its alleviation using nutritional solutions. The model integrates key cellular and systemic...

CD8+ T cells are critical players in anti-tumor immunity. In higher-risk myelodysplastic neoplasms (HR-MDS) and acute myeloid leukemia (AML), CD8+ T cells exhibit altered functionality, however whether this affects disease course is poorly understood. Herein, we aimed to identify immune cell signatures in the bone marrow (BM) associated with disease progression and treatment outcomes. In-depth immunophenotypic analysis utilizing mass and flow cytometry on 104 pre-treatment BM samples from patien...

The prevalence of obesity is rapidly increasing worldwide and its impact on future generations must be assessed. We recently showed that colostrum from mothers with obesity contained a significantly reduced B lymphocytes (CD19+) fraction. Here, in a subsequent transversal cohort study of 48 mothers, we exhaustively characterize the B lymphocytes subsets present in peripheral blood and colostrum from obese mothers and describe a pervasive alteration of the B lymphocytes compartment of human colos...

BackgroundNatural killer (NK) cells originate from bone marrow precursors and mediate effective anti-tumor responses. Clinical trials of cytokine-primed memory-like (ML) NK cells in acute myeloid leukemia (AML) have demonstrated activity without major toxicity, including graft-versus-host disease or cytokine release syndrome. However, broad application of non-expanded, non-engineered ML NK cells has been hindered by limited availability of NK cells from a single donor, thereby precluding aggress...

ObjectiveAutoimmune diseases (ADs) markedly elevate venous thromboembolism (VTE) risk, yet the shared genetic architecture and tissue-specific regulatory mechanisms of this "Autoimmune-Thrombotic Axis" remain poorly defined. We aimed to characterize the genomic landscape of immunothrombosis to identify causal links and therapeutic targets. Approach and ResultsWe integrated large-scale GWAS data for VTE and 16 ADs using a multi-omics framework, including pleiotropy scanning, local genetic correl...

The recent spread of COVID-19 across the U.S. led to concerted efforts by states to flatten the curve through the adoption of stay-at-home mandates that encourage individuals to reduce travel and maintain social distance. Combining data on changes in travel activity with COVID-19 health outcomes and state policy adoption timing, we characterize nationwide changes in mobility patterns, isolate the portion attributable to statewide mandates, and link these reductions to changes in COVID-19 health ...

MotivationPrecise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-lev...

The human gastrointestinal tract (GIT) is central to human physiology, yet our understanding of the metabolite, microbial, and hormonal spatiotemporal dynamics in humans is limited. Here, we employ naso-enteral intubation to generate a spatiotemporally resolved, multimodal dataset spanning the oral cavity (salivary fluid sampling), stomach, duodenum, and ileum of ten healthy participants. In a randomised trial, participants consumed legume-based meals prepared with varying degrees of structural...

We describe the development and public availability of the National Transportation Noise Exposure Map with the goal of estimating population exposures to various noise levels at the census tract level in the United States. The map was created by overlaying the Bureau of Transportation Statistics National Transportation Noise Map with 5-year block group population estimates from the American Community Survey, and aggregating exposed population estimates to the census tract level. Based on the exp...

Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often due to insufficient milk supply. The molecular causes of low milk production are not well understood. Fresh milk samples from 30 lactating individuals, classified by milk production levels across postpartum stages, were analyzed using genomic and microbiome techniques. Bulk RNA sequencing of milk fat globules (MFG), milk cells, and breast tissue revealed that MFG-derived RN...

The haematological malignancy multiple myeloma is associated with skewed T-cell activation and function. T-cell alterations are detectable in asymptomatic myeloma precursor conditions and have the potential to identify precursor patients at imminent risk of progression. However, what myeloma-associated T-cells alterations represent mechanistically, how they relate to tumour burden and gene expression, and what influences high inter-patient variability in immune composition remains unknown. Here,...