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This study identifies how to screen for harmful alcohol use among gender minority (e.g., transgender and gender-expansive) people using brief screening methods and identifies which screening methods perform best among gender-expansive, transfeminine, and transmasculine subgroups, as screening recommendations are not currently available. Using 2018 Annual Questionnaire data from The PRIDE Study, area under the curve (AUC) values were compared to identify which screening methods ("4 or more" or "5 or more" drinks on one occasion in the past year, or one or more items from the Alcohol Use Disorders Identification Test [AUDIT]) best predicted (i) harmful alcohol use and (ii) one or more past year alcohol dependence symptoms or consequences. Among 1892 participants, "5 or more" drinks on one occasion (AUC ranges: 0.82–0.86) performed better than "4 or more" drinks (AUC ranges: 0.78–0.81) in predicting harmful drinking. The screening methods "4 or more" drinks, "5 or more" drinks, and the consumption items of the AUDIT (AUDIT-C) using a cutoff score of 3 all maximized sensitivity and specificity to predict alcohol dependence symptoms or consequences in gender minority people overall (AUC: 0.77–0.78). Screening for "5 or more" drinks on one occasion within the past year performed as well as or better than other screening methods to detect both harmful drinking and alcohol dependence-related symptoms or consequences. This single-item screening method can identify if more extensive alcohol use assessment is warranted with gender minority people. [ABSTRACT FROM AUTHOR]

Cell-based therapies to treat skeletal muscle disease are limited by the poor survival of donor myoblasts, due in part to acute hypoxic stress. After confirming that the microenvironment of transplanted myoblasts is hypoxic, we screened a kinase inhibitor library in vitro and identified five kinase inhibitors that protected myoblasts from cell death or growth arrest in hypoxic conditions. A systematic, combinatorial study of these compounds further improved myoblast viability, showing both synergistic and additive effects. Pathway and target analysis revealed CDK5, CDK2, CDC2, WEE1, and GSK3β as the main target kinases. In particular, CDK5 was the center of the target kinase network. Using our recently developed statistical method based on elastic net regression we computationally validated the key role of CDK5 in cell protection against hypoxia. This method provided a list of potential kinase targets with a quantitative measure of their optimal amount of relative inhibition. A modified version of the method was also able to predict the effect of combinations using single-drug response data. This work is the first step towards a broadly applicable system-level strategy for the pharmacology of hypoxic damage. [ABSTRACT FROM AUTHOR]

Development of human embryonic stem cell (hESC)-based therapy requires derivation of in vitro expandable cell populations that can readily differentiate to specified cell types and engraft upon transplantation. Here, we report that hESCs can differentiate into skeletal muscle cells without genetic manipulation. This is achieved through the isolation of cells expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), following embryoid body (EB) formation. The ESC-derived cells differentiated into myoblasts in vitro as evident by upregulation of various myogenic genes, irrespective of the presence of serum in the medium. This result is further corroborated by the presence of sarcomeric myosin and desmin, markers for terminally differentiated cells. When transplanted in vivo, these pre-myogenically committed cells were viable in tibialis anterior muscles 14 days post-implantation. These hESC-derived cells, which readily undergo myogenic differentiation in culture medium containing serum, could be a viable cell source for skeletal muscle repair and tissue engineering to ameliorate various muscle wasting diseases. [ABSTRACT FROM AUTHOR]