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IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFEnhancing Equity on Crisis Lines: Understanding the Background, Practices and Learning Needs of Responders in Canada.
Community Ment Health J
January 2025
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Understanding the current state of equity, diversity, and inclusion (EDI) within the crisis line sector is essential to enhancing accessibility and acceptability of crisis line services for all. Through an intersectional lens, we examined 9-8-8 crisis line workers' personal and work demographics, training, resources, perceived competencies in supporting diverse populations. We conducted an electronic survey of crisis line responders and leadership in Canada.
View Article and Find Full Text PDFAnti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1.
Proc Natl Acad Sci U S A
January 2025
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells.
View Article and Find Full Text PDFA National Assessment of Pediatric Surgical Critical Care Fellowship Structure: Defining the Training Experience.
J Pediatr Surg
December 2024
University of Michigan Department of Surgery, Division of Pediatric Surgery, 1540 East Hospital Drive Ann Arbor, MI 48109-4211, USA. Electronic address:
Background: Pediatric Surgical Critical Care (PSCC) is a unique specialty incorporating fundamental principles of surgical, neonatal, and pediatric critical care. This study aims to characterize the current landscape of PSCC training to identify opportunities for educational standardization and improvement.
Methods: An anonymous electronic survey-based assessment was distributed to the program directors (PDs) of all current ACGME-accredited PSCC fellowships (n = 14).
A Longitudinal Exploration of -Related Hemiplegic Migraine in Children Using Electronic Medical Records.
Neurol Genet
February 2025
Division of Neurology, Children's Hospital of Philadelphia, PA.
Background And Objectives: Since the initial description of related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.
Methods: We analyzed HM and seizure history from electronic medical records in individuals with -related HM, delineating frequency and severity of events in monthly increments through a standardized approach.
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