Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgrounds.

Somatic mosaicism (SM), the presence of somatic mutations, is classified as clonal hematopoiesis (CH) when it occurs in hematopoietic cells at an age-related rate. CH is associated with risk for hematologic malignancies and cardiovascular disease, but most studies are predominately based on individuals of European ancestry. Using peripheral blood whole exome sequencing data from 125,748 individuals of diverse genetic ancestries, we cataloged 503,703 SM mutations based on low variant allele frequency distributions and 89,361 CH variants based on age-skewing.

Clonal Hematopoiesis in Patients With Human Immunodeficiency Virus and Cancer.

Background: Cancer-related deaths for people with human immunodeficiency virus (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH.

Clonal Hematopoiesis as a Molecular Risk Factor for Doxorubicin-Induced Cardiotoxicity: A Proof-of-Concept Study.

Purpose: The main dose-limiting toxicity of anthracyclines is cardiotoxicity. Clonal hematopoiesis (CH), somatic mutations in hematopoietic stem or progenitor cells in patients without hematologic malignancy, is also associated with risk for adverse cardiovascular events and worse outcomes overall. We hypothesize that CH increases risk for doxorubicin-induced cardiotoxicity (DIC).

Pilot Study of Donor-Engrafted Clonal Hematopoiesis Evolution and Clinical Outcomes in Allogeneic Hematopoietic Cell Transplantation Recipients Using a National Registry.

Improved treatment options, such as reduced-intensity conditioning (RIC), enable older patients to receive potentially curative allogeneic hematopoietic cell transplantation (HCT). This progress has led to increased use of older HLA-matched sibling donors. An unintended potential risk associated with older donors is transplantation of donor cells with clonal hematopoiesis (CH) into patients.

Copper-Catalyzed Bisannulations of Malonate-Tethered -Acyl Oximes with Pyridine, Pyrazine, Pyridazine, and Quinoline Derivatives for the Construction of Dihydroindolizine-Fused Pyrrolidinones and Analogues.

A copper-catalyzed bisannulation reaction of malonate-tethered -acyl oximes with pyridine, pyrazine, pyridazine, and quinoline derivatives has been developed for the concise synthesis of structurally novel dihydroindolizine-fused pyrrolidinones and their analogues. The present reaction shows excellent regioselectivity and stereoselectivity. Theoretical calculations reveal that the coordination effect of the carbonyl group in the nucleophilic substrate determines the excellent regioselectivity.

Seasonality in a tidal reach: Existence, impact and a possible approach for design flood level estimation.

Heterogeneity caused by seasonality could lead to the estimation error of the design flood level (DFL). This research intended to examine the existence of seasonality in the extreme water levels in a tidal reach and to quantify its impact on the DFL estimation. The mixed-distribution, a commonly used method for design value estimation with heterogeneous samples, was tested.