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Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.
Gynecol Oncol
January 2025
Duke University, Durham, NC, United States of America. Electronic address:
Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).
Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status.
Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.
Sci Adv
January 2025
Center for Physical Genomics and Engineering, Northwestern University, Evanston, IL 60208, USA.
In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.
View Article and Find Full Text PDFMultiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.
Sci Immunol
January 2025
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.
View Article and Find Full Text PDFPurpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.
View Article and Find Full Text PDFComprehensive characterization of European house dust contaminants: Concentrations and profiles, geographical variability, and implications for chemical regulation and health risk.
Sci Total Environ
December 2024
Flemish Institute for Technological Research (VITO), Unit Materials and Chemistry (MATCH), 2400 Mol, Belgium.
Article Synopsis
- - This study explores the levels and geographical differences of contaminants found in house dust across Europe, identifying over 1200 anthropogenic compounds using advanced techniques like mass spectrometry and suspect screening.
- - The research indicates that contaminant concentrations vary less than threefold within Europe, showing similarities with North American dust due to shared consumer products and materials.
- - It highlights geographical patterns, revealing that certain contaminants increased from north to south (like PAHs and chlorinated paraffins), whereas others, like biocides, decreased; it also emphasizes a significant risk from older, restricted contaminants, like DEHP and PCBs, despite limited toxicity data available for newer compounds.
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