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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFElevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.
J Clin Invest
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.
View Article and Find Full Text PDFCharacterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations.
JCI Insight
January 2025
Dianne Hoppes Nunnally Laboratory Research Division, Joslin Diabetes Center, Boston, United States of America.
Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).
Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.
Reporting of concomitant and rescue topical therapies in atopic dermatitis randomised controlled trials evaluating a systemic treatment: a scoping review.
Br J Dermatol
January 2025
Centre of Evidence Based Dermatology, School of Medicine, Faculty of Medicine & Health Sciences, University of Nottingham, UK.
Background: Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they may nullify or exaggerate treatment responses.
View Article and Find Full Text PDFAttention-aware differential learning for predicting peptide-MHC class I binding and T cell receptor recognition.
Brief Bioinform
November 2024
School of Computer Science, Northwestern Polytechnical University, Xi'an, 710129 Shaanxi, China.
The identification of neoantigens is crucial for advancing vaccines, diagnostics, and immunotherapies. Despite this importance, a fundamental question remains: how to model the presentation of neoantigens by major histocompatibility complex class I molecules and the recognition of the peptide-MHC-I (pMHC-I) complex by T cell receptors (TCRs). Accurate prediction of pMHC-I binding and TCR recognition remains a significant computational challenge in immunology due to intricate binding motifs and the long-tail distribution of known binding pairs in public databases.
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