Science Advances

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...

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...

Human milk oligosaccharides (HMOs) are bioactive components in human milk that influence infant health, yet their role in growth trajectories remains unclear. This study examined associations between concentrations of individual HMOs and child growth outcomes: length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores--at 24 months of age in a population-based cohort from Leon, Nicaragua. Data were analyzed from 295 mother-infant dyads. HMO concentrations in human milk coll...

Relapsed and/or refractory disease remains the leading cause of death in AML, highlighting the need for broadly applicable, high-sensitivity approaches to MRD detection. We developed AML-CAPP-Seq (Cancer Personalized Profiling by Deep Sequencing), a personalized hybrid-capture assay that tracks both canonical AML drivers and patient-specific variants identified by whole-exome sequencing. In 56 patients with longitudinal plasma and matched peripheral blood and bone marrow samples, AML-CAPP-Seq en...

BackgroundLong-term fasting is a promising strategy for improving human health and reducing cardiometabolic risk. Emerging evidence suggests that the gut microbiome may mediate many of these benefits, but the role of its viral component, dominated by bacteriophages, remains poorly understood. MethodsUsing shotgun metagenomic data from a single-arm, monocentric fasting intervention, this study profiled the gut virome (n=89 individuals, n=241 samples) before and after 9.8 days of fasting ([~]250 ...

Allogeneic hematopoietic cell transplantation (allo-HCT) hinges on a delicate trade-off between graft-versus-tumor control and graft-versus-host disease (GvHD), mediated by donor T-cell recognition of antigens presented by recipient human leukocyte antigen (HLA) molecules. We hypothesized that, beyond allele-level matching, sequence divergence at peptide-binding grooves across donor and recipient HLA loci shapes these responses. To this end, we evaluated the effect of HLA evolutionary divergence...

ObjectivesThe therapeutic efficacy of rituximab has reduced the discriminatory power of the International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL), particularly within intermediate-risk categories. To address this "risk dilution," we aimed to develop and internally validate the AB-IPI (Albumin-BCL2 Refined Prognostic Index) using a hypothesis-driven approach that integrates tumor burden, host fitness, and tumor biology. MethodsThis multi-center retrospective study analyze...

A role for substance P in promoting neurogenic inflammation and pain has been described in sickle cell disease (SCD). However its origin and contribution to SCD pathophysiology remain unclear. We measured substance P level in plasma from 225 patients with SCD and observed the highest concentrations during acute chest syndrome (ACS). Therefore, we tested the hypothesis that substance P may induce ACS. In transgenic sickle mice, unlike control mice, intravenous injection of substance P caused leth...

Accurate quantification of individual exposure to air pollutants remains a major challenge in environmental health, as fixed-site monitoring fails to account for mobility, indoor environments, and physiological variability. We deployed TracMyAir, a smartphone-based digital health platform designed to generate time-resolved, personalized exposure and inhaled dose estimates for PM2.5 and ozone under real-world conditions. In an exploratory study of 18 adults contributing more than 1,500 participan...

Fanconi anemia (FA) is an inherited disorder classically characterized by childhood-onset bone marrow dysfunction and lifelong cancer predisposition. FA is caused by pathogenic variants in any one of 23 genes identified so far. Of these, FANCA is the most frequently mutated and accounts for disease in two-thirds of all patients with FA. The spectrum of FANCA pathogenic variants (mutations) is broad, and genotype-phenotype correlation is often unclear. Here we describe the natural history of cyto...

BackgroundSepsis-induced mortality is frequently driven by the systemic dissemination of pore-forming toxins (PFTs), such as Staphylococcus aureus alpha-hemolysin. Biomimetic "nanosponges" which are nanoparticles coated in red blood cell (RBC) membranes have emerged as a promising detoxification strategy. However, current methods rely largely on empirical iteration, often failing to optimize the competitive binding kinetics required to outcompete native RBCs in a high-flow hemodynamic environmen...

Collective interaction of individuals in various settings is crucial for exposure to infections, encompassing complex viral interplay and amplifying infectious risk through phenomena such as social reinforcement, clustering and superspreading events, during the COVID-19 pandemic. However, standard epidemic models often inadequately capture such heterogeneity, overlooking the higher-order social structural. Spatiotemporal variation in transmission, an essential feature of the pandemic, remains po...

BackgroundChikungunya virus (CHIKV) infection can cause significant and long-term morbidity. CHIKV typically appears in explosive outbreaks then vanishes for decades, but evidence from longitudinal studies suggests that it may persist in some populations through low levels of subclinical infection. These epidemiologic dynamics complicate prediction of CHIKV outbreaks and intervention trial planning. Songkhla province in southern Thailand is a promising location for vaccine trials due to its rece...

BackgroundSickle Cell Anaemia (SCA), a genetic blood disorder caused by a single mutation in the beta globin gene, displays a highly variable clinical course. Hydroxyurea (HU), an effective treatment, has an unclear mechanism of action. Plasma proteins can act as biomarkers for understanding disease states and response to HU treatment in SCA patients. MethodsPlasma proteome profiling of 31 healthy individuals and 76 SCA patients, including those with and without HU treatment, was performed usin...

Dengue virus (DENV), comprising four distinct serotypes (DENV-1 to DENV-4), poses a major public health challenge in tropical regions. Infection with one serotype confers long-term immunity to that serotype alone, while subsequent heterologous infections are associated with increased risk of severe disease, necessitating vaccines that induce durable, balanced immunity across all serotypes. However, achieving such balance immunity remains a central challenge for dengue vaccine development. Using ...

BackgroundUnderstanding the associations among biopsychosocial factors is essential for improving research and treatment of chronic low back pain (CLBP). Here we characterized interrelations among biopsychosocial domains using network analysis and identified the most influential features in CLBP. MethodsData came from Quebec Low Back Pain Study, comprising 4,489 CLBP participants. We modeled relationships among baseline biopsychosocial features as networks, where nodes represent features and ed...

Eculizumab, a humanized monoclonal antibody targeting the complement lytic pathway protein C5, has demonstrated high efficacy in the treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. However, recent reports have highlighted patients who exhibit a lack of treatment response, necessitating an increase in the recommended dose or a reduction in the dosing interval. In this study, we employe...

Millions of outdoor workers cannot avoid wildfire smoke, likely leading to inequalities in exposure and health risk. We characterized work-related exposure to wildfire PM2.5 for 3,108 contiguous US counties during 2006-2019. Despite experiencing less ambient exposure to wildfire PM2.5, counties with higher portions of non-Hispanic Black and Hispanic Americans experienced higher work-related exposure. We also find suggestive evidence that the effect of ambient smoke fine particulate matter (PM2.5...

Emerging infectious diseases often circulate undetected until they cause clinical illness, creating serious risks for public health and biosecurity. The U.S. blood supply, with millions of routinely collected and quality-controlled donations, offers an untapped national resource for proactive pathogen surveillance. We propose integrating metagenomic sequencing (MGS) into existing blood and plasma collection workflows to detect novel or unexpected viruses in deidentified residual samples. This ap...

Why some surgical participants experience pain that extends beyond the original site of injury while others do not remains poorly understood. Both pain intensity and widespread pain contribute to recovery and quality of life, yet their psychosocial correlates are often examined separately. Using data from two large pre-surgical cohorts--participants preparing for knee replacement or thoracic surgery--we examined associations between sociodemographic and psychosocial factors, pain intensity at su...