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The objective of this study was to develop a novel copula-based time series (CTS) model to forecast COVID-19 cases and trends based on wastewater SARS-CoV-2 viral load and clinical variables. Wastewater samples were collected from wastewater pumping stations in five sewersheds in the City of Chesapeake VA. Wastewater SARS-CoV-2 viral load was measured using reverse transcription droplet digital PCR (RT-ddPCR). The clinical dataset included daily COVID-19 reported cases, hospitalization cases, and death cases. The CTS model development included two steps: an autoregressive moving average (ARMA) model for time series analysis (step I), and an integration of ARMA and a copula function for marginal regression analysis (step II). Poisson and negative binomial marginal probability densities for copula functions were used to determine the forecasting capacity of the CTS model for COVID-19 forecasts in the same geographical area. The dynamic trends predicted by the CTS model were well suited to the trend of the reported cases as the forecasted cases from the CTS model fell within the 99 % confidence interval of the reported cases. Wastewater SARS CoV-2 viral load served as a reliable predictor for forecasting COVID-19 cases. The CTS model provided robust modeling to predict COVID-19 cases., Competing Interests: Declaration of competing interest All the authors don't have any financial and personal relationships with organizations that could inappropriately influence (bias) their work. The project was supported by the Data Science Seed Grant from Old Dominion University. The funding source had no such involvement in study design, data collection, analysis, and interpretation of data., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plasma leakage is a hallmark process in dengue viral (DENV) infection that occurs due to the loss of vascular integrity in endothelial cells. Endoglin (ENG) and Syndecan-1 (SDC-1) are released by activated endothelial cells; however, the complete dynamics of its expression at the gene and protein levels during the course of DENV infection remains unknown. In the present study, we quantified the mRNA and soluble protein levels of ENG and SDC-1 in dengue cases during febrile, defervescence, and convalescence stages in Dengue without Warning Sign (DWOW-15), Dengue with Warning Sign (DWW-22), and Severe Dengue cases (SD-10) compared to nondengue Other Febrile Illness (OFI-10) and healthy control (HC-8). Respective protein and mRNA levels along with clinical characters were further analyzed for their efficacy in predicting disease outcomes using Support Vector Machine (SVM). We observed a steady and significant (P ≤ 0.01) increase in the levels of protein and mRNA of both the ENG and SDC-1 towards defervescence which is considered a critical phase in both severe and non-severe dengue cases. Importantly during the critical phase, the levels were significantly higher (P ≤ 0.001) in SD cases compared to DWW, DWOW, and OFI controls. However, at the time of admission (febrile), no such significant changes were observed within dengue, OFI, and healthy controls. SVM analysis revealed that the serum levels of ENG and SDC-1 along with other clinical symptoms could predict the disease severity with 100% accuracy. Based on the results we have proposed a mechanism on how ENG and SDC-1 could be involved in vascular dysfunction rather than just being a biomarker., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Signaling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby coordinates cell movement and positioning in normal and oncogenic development. While cell contact-dependent Eph activation frequently leads to cell-cell repulsion, also the diametrically opposite response, cell-cell adhesion, is a probable outcome. However, the molecular principles regulating such disparate functions have remained controversial. We have examined cell-biologic mechanisms underlying this switch by analyzing ephrin-A5-induced cell-morphologic changes of EphA3-positive LK63 pre-B acute lymphoblastic leukemia cells. Their exposure to ephrin-A5 surfaces leads to a rapid conversion from a suspended/nonpolarized to an adherent/polarized cell type, a transition that relies on EphA3 functions operating in the absence of Eph-kinase signaling. Cell morphology change and adhesion of LK63 cells are effectively attenuated by endogenous protein tyrosine phosphatase (PTP) activity, whereby PTP inhibition and productive EphA3-phosphotyrosine signaling reverse the phenotype to nonadherent cells with a condensed cytoskeleton. Our findings suggest that Eph-associated PTP activities not only control receptor phosphorylation levels, but as a result switch the response to ephrin contact from repulsion to adhesion, which may play a role in the pathology of hematopoietic tumors.