Deubiquitinating enzymes (DUBs) are key regulators of cellular homoeostasis, and their dysregulation is associated with several human diseases. The ovarian tumour protease (OTU) family of DUBs are biochemically well-characterised and of therapeutic interest, yet only a few tool compounds exist to study their cellular function and therapeutic potential. Here we present a chemoproteomics fragment screening platform for identifying novel DUB-specific hit matter, that combines activity-based protein profiling with high-throughput chemistry direct-to-biology optimisation to enable rapid elaboration of initial fragment hits against OTU DUBs.
View Article and Find Full Text PDFObjectives: To investigate through a meta-analysis of comparative studies the impact of donor type (brain death DBD vs circulatory death DCD) on the short- and long-term outcomes of lung transplantation(LTx).
Methods: Literature search (terms "lung transplantation" AND "donation after circulatory death") was performed up to July 2022 and studies comparing outcomes of LTx from DCD versus DBD were selected. Primary endpoints were early and long-term mortality.
Background: Heterogeneity of treatment effects (HTEs) can occur because of either differential treatment compliance or differential treatment effectiveness. This distinction is important, as it has action implications, but it is unclear how to distinguish these two possibilities statistically in precision treatment analysis given that compliance is not observed until after randomization. We review available statistical methods and illustrate a recommended method in secondary analysis in a trial focused on HTE.
View Article and Find Full Text PDFSince nearly 40% of metabolic and bariatric surgery (MBS) patients are individuals with the ability to bear children, many may seek to become pregnant or may be currently lactating when seeking surgery. While many patients plan to breastfeed, MBS patients are at high risk for premature cessation of breastfeeding. Limited literature exists on the impact of MBS on lactation and there are no established guidelines to help clinicians support and educate MBS patients about breastfeeding.
View Article and Find Full Text PDFObjective: Specific modifiable factors (e.g., screen time [ST], sleep duration, physical activity, or social connections) are targets for reducing depression risk in adults.
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