The leukemia stem cell (LSC) hypothesis proposes that a subset of cells in the bulk leukemia population propagates the leukemia.We tested the LSC hypothesis in a mouse model of Notch-induced T-cell acute lymphoblastic leukemia (T-ALL) in which the tumor cells were largely CD4+ CD8+ T cells. LSC activity was enriched but rare in the CD8+ CD4 HSA(hi) immature single-positive T-cell subset. Although our murine T-ALL model relies on transduction of HSCs, we were unable to isolate Notch-activated HSCs to test for LSC activity. Further analysis showed that Notch activation in HSCs caused an initial expansion of hematopoietic and T-cell progenitors and loss of stem cell quiescence, which was followed by progressive loss of long-term HSCs and T-cell production over several weeks. Similar results were obtained in a conditional transgenic model in which Notch activation is induced in HSCs by Cre recombinase. We conclude that although supraphysiologic Notch signaling in HSCs promotes LSC activity in T-cell progenitors, it extinguishes self-renewal of LT-HSCs. These results provide further evidence for therapeutically targeting T-cell progenitors in T-ALL while also underscoring the need to tightly regulate Notch signaling to expand normal HSC populations for clinical applications.
Introduction And Hypothesis: We aimed to analyze the quality of sexual life of patients with apical vaginal wall prolapse who had undergone laparoscopic lateral suspension (LLS) and laparoscopic sacrocolpopexy (LSC).
Methods: We performed a secondary analysis of sexual outcomes of a previous randomized control trial comparing LLS and LSC in 89 women with symptomatic POP stage ≥ II. We evaluated sexually active (SA) and non-sexually active women (NSA) using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR).
Tritium, a radioactive isotope produced naturally through cosmic radiation interactions and anthropogenically through nuclear weapons testing, poses potential environmental risks, particularly within the water cycle. This study measured tritium concentrations in surface water across Thailand to establish a baseline dataset for monitoring potential contamination from nuclear activities and accidents. Surface water samples were collected from 14 large reservoirs during the wet season in October 2023 and the dry season in February 2024, providing a total of 28 samples.
Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment.
Therapies for acute myeloid leukemia (AML) face formidable challenges due to relapse, often driven by leukemia stem cells (LSCs). Strategies targeting LSCs hold promise for enhancing outcomes, yet paired comparisons of functionally defined LSCs at diagnosis and relapse remain underexplored. We present transcriptome analyses of functionally defined LSC populations at diagnosis and relapse, revealing significant alterations in IL-1 signaling.
As a model for the energy-efficient aftertreatment of exhaust gas components, we studied microwave-assisted (MW) CO oxidation over a (La,Sr)CoO (LSC) perovskite oxide catalyst under dry and humidified conditions. We found that the use of a MW-based process can offer multiple advantages over traditional thermocatalysis in this scenario, as the nature of the MW-solid interaction offers quick, adaptive, and energy-efficient heating as well as improved yield and lower light-off temperatures. As found by combined CO and water MW-desorption experiments, the presence of technically relevant amounts of water leads to a competition for surface active sites and thus slows the reaction rate without indications for a fundamental change in the mechanism.
