While clinical trials are ongoing using human pluripotent stem cell-derived midbrain dopamine (mDA) neuron precursor grafts in Parkinson's disease (PD), current protocols to derive mDA neurons remain suboptimal. In particular, the yield of TH+ mDA neurons after grafting and the expression of some mDA neuron and subtype-specific markers can be further improved. For example, characterization of mDA grafts by single cell transcriptomics has yielded only a small proportion of mDA neurons and a considerable fraction of contaminating cell populations.
View Article and Find Full Text PDFEvaluating synthetic accessibility of molecules is an integral component of the drug discovery process. While the application of machine learning models to predict whether small molecules are easy or hard to synthesize has gained attention recently, predetermined thresholds and data set imbalances present challenges for these binary classification approaches. In this study, we introduce a novel multiclass fold-ensembled classification approach to predict the minimum number of steps needed to synthesize a small molecule.
View Article and Find Full Text PDFIntroduction: Pancreatic ductal adenocarcinoma (PDAC) of the body/tail is notably different than PDAC in the head of the pancreas. Surgery plus chemotherapy is known to improve outcomes for all PDAC. The sequence of this therapy is well studied in head cancers yet has never been evaluated systematically in relation to distal pancreatectomy (DP).
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