Background: Lack of insight into factors that determine purity and quality of human iPSC (hiPSC)-derived neo-cartilage precludes applications of this powerful technology toward regenerative solutions in the clinical setting. Here, we set out to generate methylome-wide landscapes of hiPSC-derived neo-cartilages from different tissues-of-origin and integrated transcriptome-wide data to identify dissimilarities in set points of methylation with associated transcription and the respective pathways in which these genes act.
Methods: We applied in vitro chondrogenesis using hiPSCs generated from two different tissue sources: skin fibroblasts and articular cartilage.
Orthoflaviviruses, including zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, induce severely debilitating infections and contribute significantly to the global disease burden, yet no clinically approved antiviral treatments exist. This review offers a comprehensive analysis of small-molecule drug development targeting orthoflaviviral infections, with a focus on NS2B-NS3 inhibition. We systematically examined clinical trials, preclinical efficacy studies, and modes of action for various viral replication inhibitors, emphasizing allosteric and orthosteric drugs inhibiting NS2B-NS3 protease with in vivo efficacy and in vitro-tested competitive NS2B-NS3 inhibitors with cellular efficacy.
View Article and Find Full Text PDFBackground: Explanations for the genesis and propagation of cholera pandemics since 1817 have remained elusive. Evolutionary pathogen change is presumed to have been a dominant factor behind the 7th "El Tor" pandemic, but little is known to support this hypothesis for preceding pandemics. The role of anomalous climate in facilitating strain replacements has never been assessed.
View Article and Find Full Text PDFBackground: Patients who present in a primary stroke center (PSC) with ischemic stroke are usually transferred to a comprehensive stroke center (CSC) in case of a large vessel occlusion (LVO) for endovascular thrombectomy (EVT) treatment, the so-called 'drip-and-ship' (DS) model. The 'drive-the-doctor' (DD) model modifies the DS model by allowing mobile interventionalists (MIs) to transfer to an upgraded PSC acting as a thrombectomy capable stroke center (TSC), instead of transferring patients to a CSC. Using simulation we estimated time savings and impact on clinical outcome of DD in a rural region.
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