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PLOS Papers on Breast Cancer Metastasis, Left-Sided Cardiac Defects, SARS-CoV-2 Monitoring

In PLOS Genetics, researchers from the National Institutes of Health and the Frederick National Laboratory for Cancer Research describe ties between breast cancer metastasis and expression of CLIC4, a transforming growth factor beta-regulated chloride intracellular channel 4 gene previously implicated in breast cancer stroma formation. The team saw higher-than-usual CLIC4 expression in breast cancer tumor data from the Cancer Genome Atlas or METABRIC efforts, particularly in cases involving younger women, early stage metastatic disease, or poor outcomes. Based on a series of mouse model, proteomic profiling, and transcriptional analyses on human samples, the authors conclude that "CLIC4 expression in human breast cancers may serve as a prognostic biomarker" and suggest "therapeutic targeting of CLIC4 could reduce primary tumor viability and host metastatic competence."

For another paper in PLOS Genetics, a team at Nationwide Children's Hospital and Ohio State University turn to family-based sequencing strategies to unearth genetic factors behind left-sided cardiac defects. After doing exome sequencing on members of 19 left-sided congenital heart disease-affected families — including dozens of individuals with or without the conditions — the investigators used variant filtering, predictive algorithms, and publicly available annotation data to focus on candidate variants in eight of the families. The suspicious variants fell in new or known heart disease-related genes, the authors report, noting that at least two apparent risk genes turned up in a subset of the participating families. "These findings show that studying families may be more effective than using individuals to find causes of heart defects," they argue. "In addition, this family-based method suggests that changes in more than one gene may be required for a heart defect to occur."

Investigators at the University of Essex, Cranfield University, and elsewhere present findings from a case study using wastewater testing to monitor SARS-CoV-2 levels in more than a dozen UK schools. With qPCR testing on two SARS-CoV-2 genes, the team tested almost 300 samples collected at 16 primary, secondary, and post-secondary schools over the course of nine weeks in 2020, picking up SARS-CoV-2 sequences in more than 47 percent of the samples considered. "[R]egular feedback of results to each school and its wider community may improve engagement with non-pharmaceutical interventions and implementation of infection prevention and control measures," the authors argue, noting that wastewater-based epidemiology "could provide valuable insights on the local epidemiology of COVID-19 in areas/schools with low uptake of school mass testing and a high level of hesitancy to vaccination.