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The COVID-19 pandemic presents a continued public health challenge. Veterinary diagnostic laboratories in the United States use RT-rtPCR for animal testing, and many laboratories are certified for testing human samples; hence, ensuring that laboratories have sensitive and specific SARS-CoV2 testing methods is a critical component of the pandemic response. In 2020, the FDA Veterinary Laboratory Investigation and Response Network (Vet-LIRN) led an interlaboratory comparison (ILC1) to help laboratories evaluate their existing RT-rtPCR methods for detecting SARS-CoV2. All participating laboratories were able to detect the viral RNA spiked in buffer and PrimeStore molecular transport medium (MTM). With ILC2, Vet-LIRN extended ILC1 by evaluating analytical sensitivity and specificity of the methods used by participating laboratories to detect 3 SARS-CoV2 variants (B.1; B.1.1.7 [Alpha]; B.1.351 [Beta]) at various copy levels. We analyzed 57 sets of results from 45 laboratories qualitatively and quantitatively according to the principles of ISO 16140-2:2016. More than 95% of analysts detected the SARS-CoV2 RNA in MTM at ≥500 copies for all 3 variants. In addition, for nucleocapsid markers N1 and N2, 81% and 92% of the analysts detected ≤20 copies in the assays, respectively. The analytical specificity of the evaluated methods was >99%. Participating laboratories were able to assess their current method performance, identify possible limitations, and recognize method strengths as part of a continuous learning environment to support the critical need for the reliable diagnosis of COVID-19 in potentially infected animals and humans. [ABSTRACT FROM AUTHOR]

Objective. There is insufficient evidence to generate skin cancer screening guidelines at the population level, resulting in arbitrary variation in patient selection for screening skin examinations. This study was aimed at developing an easy-to-use predictive model of nonmelanoma skin cancer (NMSC) risk on screening total body skin examination (TBSE). Methods. This epidemiologic assessment utilized data from a prospective, multicenter international study from primarily academic outpatient dermatology clinics. Potential predictors of NMSC on screening TBSE were identified and used to generate a multivariable model that was converted into a point-based scoring system. The performance characteristics of the model were validated in a second data set from two healthcare institutions in the United States. Results. 8,501 patients were included. Statistically significant predictors of NMSC on screening TBSE included age, skin phototype, and history of NMSC. A multivariable model and point-based scoring system using these predictors exhibited high discrimination (AUC = 0.82). Conclusion. A simple three-variable model, abbreviated as CAP (cancer history, age, phototype) can accurately predict the risk of NMSC on screening TBSE by dermatology. This tool may be used in clinical decision making to enhance the yield of screening TBSE. [ABSTRACT FROM AUTHOR]

Abstract Over 5 million people in the United States suffer from heart failure, due to the limited ability to regenerate functional cardiac tissue. One potential therapeutic strategy is to enhance proliferation of resident cardiomyocytes. However, phenotypic screening for therapeutic agents is challenged by the limited ability of conventional markers to discriminate between cardiomyocyte proliferation and endoreplication (e.g. polyploidy and multinucleation). Here, we developed a novel assay that combines automated live-cell microscopy and image processing algorithms to discriminate between proliferation and endoreplication by quantifying changes in the number of nuclei, changes in the number of cells, binucleation, and nuclear DNA content. We applied this assay to further prioritize hits from a primary screen for DNA synthesis, identifying 30 compounds that enhance proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Among the most active compounds from the phenotypic screen are clinically approved L-type calcium channel blockers from multiple chemical classes whose activities were confirmed across different sources of human induced pluripotent stem cell-derived cardiomyocytes. Identification of compounds that stimulate human cardiomyocyte proliferation may provide new therapeutic strategies for heart failure. Graphical abstract Unlabelled Image Highlights • Novel automated hybrid live/fixed assay for cardiomyocyte proliferation. • Assay distinguishes proliferation from multinucleation and polyploidization. • Assay applied for high-content screening of compounds. • L-type calcium channel blockers induce cardiomyocyte proliferation. [ABSTRACT FROM AUTHOR]