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The PTP provides improved visual display of a predictive model's discriminative accuracy, which can enhance the practical application of predictive models for medical decision making.Individuals infected with the severe acute respiratory syndrome (SARS)-related coronavirus 2 (SARS-CoV-2) develop a critical and even fatal disease, called Coronavirus disease-19 (COVID-19), that eventually evolves into acute respiratory distress syndrome. The gravity of the SARS-CoV-2 pandemic, the escalating number of confirmed cases around the world, the many unknowns related to the virus mode of action, and the heterogenous outcome of COVID-19 disease in the population ask for the rapid development of alternative approaches, including repurposing of existing drugs, that may dampen virus infectivity. SARS-CoV-2 infects human cells through interaction with sialylated receptors at the surface of epithelial cells, such as angiotensin-converting enzyme 2 (ACE2). Glycan composition on virus entry receptors has been shown to influence the rate of infection of SARS-CoV-2 and spreading of virions has recently been linked to altered lysosomal exocytosis. These processes could concurrently involve the lysosomal system and its glycosidases. We hypothesize that modulating the activity of one of them, the lysosomal sialidase NEU1, could impinge on both the sialylation status of ACE2 and other host receptors as well as the extent of lysosomal exocytosis. Thus NEU1-controlled pathways may represent therapeutic targets, which could impact on SARS-CoV-2 susceptibility, infectivity, and spread.Over the course of a few weeks in March, COVID-19 upended the daily lives of Americans. Academic Medical Centers became a center-point for the response to the virus. Leaders within academic medical centers faced twin challenges of responding to the needs of the patients we serve while managing radical changes within their own institutions, including the educational mission. In this article, we describe some key themes identified and lessons learned as educational leaders during this time. We draw from the experiences of two institutions- one public and one private. These lessons learned fall into the broad categories of leadership decision-making and communication and included the importance of principled decision-making, a connected leadership team, and effective communication both within leadership and to the broader institutional community. The consequences of these responses resulted in a renewed recognition for us as educational leaders of the interdependence of our tripartide academic fates, the importance of academic medical centers as anchor institutions and advocates for our community, and the resilience and ingenuity of our students. We provide examples of these lessons and themes and make recommendations for how to approach educational decision-making in the "new normal" of living with COVID-19 for the immediate future.Washington University School of Medicine began a curriculum renewal process in 2017 with a goal of implementing the Gateway Curriculum in 2020. In this article, we describe the vision of this curriculum and the infrastructure that was built to support it. We also describe the impact of COVID-19 on the legacy curriculum and the Gateway Curriculum as well as the lessons learned to date.At the University of California, Irvine, School of Medicine (UCISOM), the COVID-19 pandemic is accelerating the transition of face-to-face didactic lectures to online platforms. Institutions nationwide have opted to transition their lectures into remote instruction for the upcoming Fall 2020 academic year. UCISOM's pre-clerkship Medical Immunology course in the Spring 2020 serves as a template for other medical courses to successfully transform lecture content into virtual presentations. see more To help facilitate successful large-scale transition to online courses, UCI developed institutional support and implemented a Division of Teaching Excellence and Innovation (DTEI) Fellowship and iMedEd programs to support medical educators throughout Summer. Previously developed E-learning modules for renal and acid-base physiology serve as the foundation for novel pulmonary E-learning modules at UCISOM. In preparation for the new academic year, in a collaboration between faculty, UCISOM's top performing second-year medical students (MS2s) and DTEI fellows worked together during the summer to transition UCISOM's Medical Physiology and Pathophysiology course online. With over 100 first-year medical students attending the Medical Physiology course over live synchronous Zoom instruction, formative and summative assessments were incorporated into Canvas modules along with peer-led review sessions and new E-learning modules to educate and monitor student progress. The course will maintain existing in-person active learning activities for students to get hands-on experience using the latest medical devices while maintaining social distancing. Successful transition to online medical education at UCISOM will depend on increasing use of formative assessments, increased utilization of peer-led review sessions, and efficient communication to help foster self-directed learning.Mitochondria-associated membranes (MAMs) are essential to mitochondria. This study was to determine whether endotoxemia rearranges MAMs in the heart, and whether Beclin-1 regulates this process. Wild-type mice and mice with a cardiac-specific overexpression of Beclin-1 (Becn1-Tg), or a heterozygous knockout of Beclin-1 (Becn1 +/-) were given lipopolysaccharide (LPS) challenge. In the heart, the ultrastructure of MAMs was examined by electron microscopy and the histology evaluated by immunostaining. Additionally, MAMs were isolated by ultracentrifugation, and their content and function were quantified. The effects of Beclin-1-activating peptide (TB-peptide) on MAMs were also examined. Data showed that endotoxemia decreased both the total mass and the function of MAMs, and these deficiencies became worse in Becn1 +/- mice but were alleviated in Becn1-Tg and TB-peptide-treated mice. Responses of myocardial MAMs to LPS and to TB-peptide were additionally examined in AC16 human cardiomyocytes. In vitro findings recaptured the effects of LPS and TB-peptide in cardiomyocytes; the challenge of LPS reduced the level and activity of MAMs, and TB-peptide attenuated this defect.