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BackgroundThe COVID-19 pandemic sparked a surge of research publications spanning epidemiology, basic science, and clinical science. Thanks to the digital revolution, large data sets are now accessible, which also enables real-time epidemic tracking. However, despite this, academic faculty and their trainees have been struggling to access comprehensive clinical data. To tackle this issue, we have devised a clinical data repository that streamlines research processes and promotes interdisciplinary collaboration. ObjectiveThis study aimed to present an easily accessible up-to-date database that promotes access to local COVID-19 clinical data, thereby increasing efficiency, streamlining, and democratizing the research enterprise. By providing a robust database, a broad range of researchers (faculty and trainees) and clinicians from different areas of medicine are encouraged to explore and collaborate on novel clinically relevant research questions. MethodsA research platform, called the Yale Department of Medicine COVID-19 Explorer and Repository (DOM-CovX), was constructed to house cleaned, highly granular, deidentified, and continually updated data from over 18,000 patients hospitalized with COVID-19 from January 2020 to January 2023, across the Yale New Haven Health System. Data across several key domains were extracted including demographics, past medical history, laboratory values during hospitalization, vital signs, medications, imaging, procedures, and outcomes. Given the time-varying nature of several data domains, summary statistics were constructed to limit the computational size of the database and provide a reasonable data file that the broader research community could use for basic statistical analyses. The initiative also included a front-end user interface, the DOM-CovX Explorer, for simple data visualization of aggregate data. The detailed clinical data sets were made available for researchers after a review board process. ResultsAs of January 2023, the DOM-CovX Explorer has received 38 requests from different groups of scientists at Yale and the repository has expanded research capability to a diverse group of stakeholders including clinical and research-based faculty and trainees within 15 different surgical and nonsurgical specialties. A dedicated DOM-CovX team guides access and use of the database, which has enhanced interdepartmental collaborations, resulting in the publication of 16 peer-reviewed papers, 2 projects available in preprint servers, and 8 presentations in scientific conferences. Currently, the DOM-CovX Explorer continues to expand and improve its interface. The repository includes up to 3997 variables across 7 different clinical domains, with continued growth in response to researchers’ requests and data availability. ConclusionsThe DOM-CovX Data Explorer and Repository is a user-friendly tool for analyzing data and accessing a consistently updated, standardized, and large-scale database. Its innovative approach fosters collaboration, diversity of scholarly pursuits, and expands medical education. In addition, it can be applied to other diseases beyond COVID-19.

Abstract Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors important for its function remain unclear. Renalase is a pro-survival, anti-inflammatory flavoprotein found to be critical in other tissues. We examined the potential role of renalase in placental development. PCR, bulk RNA sequencing, immunohistochemistry, and immunofluorescence for renalase and its binding partners, PMCA4b and PZP, were performed on human placental tissue from second-trimester and full-term placentas separated into decidua, placental villi and chorionic plates. Quantification of immunohistochemistry was used to localize renalase across time course from 17 weeks to term. Endogenous production of renalase was examined in placental tissue and organoids. Renalase and its receptor PMCA4b transcripts and proteins were present in all layers of the placenta. Estimated RNLS protein levels did not change with gestation in the decidual samples. However, placental villi contained more renalase immunoreactive cells in fetal than full-term placental samples. RNLS co-labeled with markers for Hofbauer cells and trophoblasts within the placental villi. Endogenous production of RNLS, PMCA4b, and PZP by trophoblasts was validated in placental organoids. Renalase is endogenously expressed throughout placental tissue and specifically within Hofbauer cells and trophoblasts, suggesting a potential role for renalase in placental development and function. Future studies should assess renalase’s role in normal and diseased human placenta.

The molecular and cellular pathogenesis of leptospirosis remains poorly understood. Based on comparative bacterial genomics data, we recently identified the hypothetical PF07598 gene family as encoding secreted exotoxins (VM proteins) that mediate cytotoxicity in vitro. To address whether VM proteins mediate in vivo leptospirosis pathogenesis, we tested the hypothesis that VM protein immunization of mice would protect against lethal challenge infection and reduce bacterial load in key target organs. C3H/HeJ mice were immunized with recombinant E. coli-produced, endotoxin-free, leptospiral VM proteins (derived from L. interrogans serovar Lai) in combination with the human-compatible adjuvant, glucopyranoside lipid A/squalene oil-in-water. Mice receiving full length recombinant VM proteins were protected from lethal challenge infection by L. interrogans serovar Canicola and had a 3-4 log10 reduction in bacterial load in the liver and kidney. These experiments show that immunization with recombinant VM proteins prevents leptospirosis clinical pathogenesis and leads to markedly reduced key target organ infection in this animal model. These data support the role of leptospiral VM proteins as virulence factors and suggest the possibility that a VM protein-based, serovar-independent, pan-leptospirosis vaccine may be feasible.

Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN.