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Histopathologic Evaluation and Single-Cell Spatial Transcriptomics of the Colon Reveal Cellular and Molecular Abnormalities Linked to J-Pouch Failure in Patients with Inflammatory Bowel Disease
Publication Year: 2025 Source: bioRxiv PMID: 39974918
BACKGROUND AND AIMS: Total abdominal colectomy (TAC) with a staged ileal pouch-anal anastomosis (IPAA) is a common surgical treatment for ulcerative colitis (UC). However, a significant percentage of patients experience pouch failure, leading to morbidity. This retrospective case-control study identified histopathological features of the TAC specimen associated with pouch failure …
Multiple-testing corrections in selection scans using identity-by-descent segments
Publication Year: 2025 Source: bioRxiv PMID: 39975073 DOI: 10.1101/2025.01.29.635528
Failing to correct for multiple testing in selection scans can lead to false discoveries of recent genetic adaptations. The scanning statistics in selection studies are often too complicated to theoretically derive a genome-wide significance level or empirically validate control of the family-wise error rate (FWER). By modeling the autocorrelation of …
Dynamic μ-PBWT: Dynamic Run-length Compressed PBWT for Biobank Scale Data
Publication Year: 2025 Source: bioRxiv PMID: 39975111 DOI: 10.1101/2025.02.04.636479
Durbin's positional Burrows-Wheeler transform (PBWT) supports efficient haplotype matching and queries given a panel of haplotypes. It has been widely used for statistical phasing, imputation and identity-by-descent (IBD) detection. However, the original PBWT panel doesn't support dynamic updates when haplotypes need to be added or deleted from the panel. Dynamic-PBWT …
Loss of intestinal endosome associated protein sorting nexin 27 disrupts epithelial barrier and promotes inflammation
Publication Year: 2025 Source: bioRxiv PMID: 39975158 DOI: 10.1101/2025.02.05.635995
BACKGROUNDS AND AIMS: SNX27, member of the sorting nexin (SNX) family, carries a unique PDZ domain and mediates recycling of endocytosed transmembrane proteins. SNX27 is critical for neurodevelopmental processes, however its role in intestine remains unexplored. We aim to determine the previously unknown roles of SNX27 in regulating intestinal homeostasis, …
Human colon stem cells are the principal epithelial responders to bacterial antigens
Publication Year: 2025 Source: bioRxiv PMID: 39975165
Intestinal epithelial cells (IECs) are capable of mounting an adequate antimicrobial inflammatory response to pathogens while tolerating commensals. The underlying regulatory mechanisms of immune sensitivity remain incompletely understood, particularly in the context of human IECs. To enhance our understanding of the immune response of IECs to bacterial epithelial barrier breach, …
Haplotype rather than single causal variants effects contribute to regulatory gene expression associations in human myeloid cells
Publication Year: 2025 Source: bioRxiv PMID: 39975189 DOI: 10.1101/2025.01.30.635675
Genome-wide association studies typically identify hundreds to thousands of loci, many of which harbor multiple independent peaks, each parsimoniously assumed to be due to the activity of a single causal variant. Fine-mapping of such variants has become a priority and since most associations are located within regulatory regions, it is …
BTS: scalable Bayesian Tissue Score for prioritizing GWAS variants and their functional contexts across omics data
Publication Year: 2025 Source: bioRxiv PMID: 39975395 DOI: 10.1101/2024.10.30.621077
MOTIVATION: statistics from genome-wide association studies (GWAS) are widely used in fine-mapping and colocalization analyses to identify causal variants and their enrichment in functional contexts, such as affected cell types and genomic features. With the expansion of functional genomic (FG) datasets, which now include hundreds of thousands of tracks across …
The role of mastery in Crohn's disease: a cross-sectional study
Publication Year: 2025 Source: Therap Adv Gastroenterol PMID: 39975481
BACKGROUND: Crohn's disease (CD) is a chronic autoimmune inflammatory bowel disease. It is estimated that approximately 40% of individuals with CD are non-adherent to medical prescriptions. This lack of adherence to treatment plans has been linked to an increased risk of hospitalisation and surgical procedures, which can have a detrimental …
Risk factors and clinical characteristics of Clostridium difficile colonization and infection in patients with inflammatory bowel disease exposed to Vedolizumab: a multicenter retrospective study
Publication Year: 2025 Source: Therap Adv Gastroenterol PMID: 39975482 DOI: 10.1177/17562848251321707
BACKGROUND: Vedolizumab (VDZ), a humanized monoclonal antibody that selectively inhibits the binding of the alpha4beta7 integrin, has been approved for treating inflammatory bowel disease (IBD). Long-term safety studies of VDZ in clinical trials identified Clostridium difficile infection (CDI) as the major opportunistic infection. OBJECTIVES: We aimed to address the incidence …
Dental problems and oral microbiome alterations in ulcerative colitis
Publication Year: 2025 Source: Front Immunol PMID: 39975550
Ulcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis …
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