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Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 46...

The increasing presence of antibiotics in urban wastewater has raised significant concerns. Therefore, wastewater treatment plants (WWTPs) face questions about their ability to reliably and effectively remove antibiotics. In this study, data from ten representative WWTPs were systematically evaluated to assess antibiotic occurrence, removal efficiencies, seasonal variations, and ecological risks, revealing the prevalent instability in antibiotic removal capacities of traditional WWTPs. The...

Advances in genomic technologies have revolutionized the diagnosis of rare genetic diseases, leading to the emergence of precision therapies. However, there remains significant effort ahead to ensure the promise of precision medicine translates to improved outcomes. Here, we discuss the challenges in advancing precision child health and highlight how international collaborations such as the International Precision Child Health Partnership, which embed research into clinical care, can maximize...

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Background: The Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases (SUCCEED) study was created to better understand COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Knowing the frequency of COVID-19 breakthrough infections is important, particularly in IMID. Our objective was to assess these events in IMID. Methods: We prospectively studied IMID participants who had received ≥three COVID-19 vaccine doses. Individuals provided...

The T cell antigen coupler (TAC) receptor is a novel synthetic receptor designed to maximize the therapeutic potential of T cells in the absence of tonic signaling or receptor-related toxicities. Prior studies indicated that TACs provide safe and long-lasting anti-tumor immunity in multiple preclinical models of solid tumors supported by mounting clinical evidence. TAC receptors function by targeting a cancer associated surface antigen while recapitulating natural T cell receptor (TCR)...

Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated...

Small molecules that induce non-apoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here, we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of non-apoptotic cell death in sarcomas and other cancer cells. This lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR). TECR is canonically...

Prostate cancer is characterized by profound heterogeneity in its clinical trajectory. While genomic heterogeneity has been well-characterized, epigenomic heterogeneity remains less understood. To fill this gap, we compiled 2,149 multi-ancestric prostate methylomes spanning normal tissue through localized disease of varying grades to poly-metastatic disease, most with multi-omic DNA and/or RNA characterization. We identify four subtypes that varied by stage, grade and mutational subtype. We...

CONCLUSIONS: The AutoPipeline feature will improve the accessibility of raw clinical datasets on public archives, such as the Cancer Imaging Archive (TCIA), the largest public repository of cancer imaging, allowing machine learning researchers to process analysis-ready formats without requiring deep domain knowledge.

CONCLUSION: These results suggest that translation of TNFAIP3 and NFKBIA may be inhibited in PsA CD8^(+) T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types.

Single-cell RNA sequencing maps gene expression heterogeneity within a tissue. However, identifying biological signals in this data is challenging due to confounding technical factors, sparsity, and high dimensionality. Data factorization methods address this by separating and identifying signals in the data, such as gene expression programs, but the resulting factors must be manually interpreted. We developed Single-Cell Interpretable REsidual Decomposition (sciRED) to improve the...

Migrant agricultural workers employed through Canada's Temporary Foreign Worker Program face serious occupational health and safety hazards, with compounded difficulties in accessing workers' compensation (WC) if they are sick or injured by the job. Little is known, however, about their ability to return to work (RTW) upon recovery-a fundamental right included in the conception of WC, but complicated by their restrictive work permits and precarious immigration status. Based on interviews with...

Patient sex influences a wide range of cancer phenotypes, including prevalence, response to therapy and survival endpoints. Molecular sex differences across the central dogma have been identified that may drive these phenotypic differences. Despite a growing catalog of specific genomic, transcriptomic and proteomic sex differences in a range of cancer types, their functional consequences remain unclear. To assess how patient sex impacts cancer cell function, we evaluated 1,209 cell lines...

The tangential expansion of the human cerebral cortex, indexed by its surface area (SA), occurs mainly during prenatal and early postnatal periods, and is influenced by genetic factors. Here we investigate the role of rare copy number variants (CNVs) in shaping SA, and the underlying mechanisms, by aggregating CNVs across the genome in community-based cohorts (N = 39,015). We reveal that genome-wide CNV deletions and duplications are associated with smaller SA. Subsequent analyses with gene...

BACKGROUND: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.