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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 PDFImpact of corticosteroids on improving lung compliance in a patient with pulmonary microscopic polyangiitis.
BMJ Case Rep
January 2025
Pulmonary and Critical Care Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Microscopic polyangiitis (MPA) is a small-vessel vasculitis characterised by systemic infiltration, with a primary focus on the renal and pulmonary systems. One of its more lethal pulmonary manifestations is diffuse alveolar haemorrhage (DAH), although the spectrum of lung pathology in MPA is vast and calls for immediate immunosuppressive therapy. Our case looks at an older woman initially presenting with MPA-induced rapid progressive glomerulonephritis.
View Article and Find Full Text PDFHyperthyroidism crisis and complex pancytopenia: A case report.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology, First Affiliated Hospital of Army Medical University, Chongqing 400038.
Antithyroid drugs can cause neutropenia or agranulocytosis, rarely pancytopenia in hyperthyroidism therapy. The treatment is difficult and lethality is high when granulocytopenia or pancytopenia combined with hyperthyroidism crisis. First Affiliated Hospital of Army Medical University treated a patient who had pancytopenia caused by methimazole with systemic lupus erythematosus, secondary hyperthyroidism crisis and agranulocytosis.
View Article and Find Full Text PDFPhenotypic Expansion: Fetus With Cole-Carpenter Type 2 Presenting With Novel Neonatal Lethal Skeletal Dysplasia.
Am J Med Genet A
January 2025
Children's Hospital of Philadelphia, Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment, Philadelphia, Pennsylvania, USA.
We report a 28-year-old G2P0 at 24 weeks 5 days who presented for evaluation secondary to suspected skeletal dysplasia in her fetus. Fetal ultrasound imaging demonstrated foreshortened long bones by 9-10 weeks, multiple bowing deformities and fractures, 11 foreshortened paired ribs with fractures, decreased skull mineralization, frontal bossing, enlarged cavum septum pellucidi, and severe fetal growth restriction (< 2%). Findings were concerning for life limiting condition with thoracic circumference < 2.
View Article and Find Full Text PDFEvaluation of clinical risk stratification to determine benefit from long-term versus short-term androgen deprivation in high-risk localized prostate cancer.
Prostate Cancer Prostatic Dis
January 2025
South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia.
Background: Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT).
Methods: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials.
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