The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further support the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis.
Purpose: The aim of this study was to evaluate radiology imaging volumes at distinct time periods throughout the coronavirus disease 2019 (COVID-19) pandemic as a function of regional COVID-19 hospitalizations.Methods: Radiology imaging volumes and statewide COVID-19 hospitalizations were collected, and four 28-day time periods throughout the COVID-19 pandemic of 2020 were analyzed: pre-COVID-19 in January, the "first wave" of COVID-19 hospitalizations in April, the "recovery" time period in the summer of 2020 with a relative nadir of COVID-19 hospitalizations, and the "third wave" of COVID-19 hospitalizations in November. Imaging studies were categorized as inpatient, outpatient, or emergency department on the basis of patient location at the time of acquisition. A Mann-Whitney U test was performed to compare daily imaging volumes during each discrete 28-day time period.Results: Imaging volumes overall during the first wave of COVID-19 infections were 55% (11,098/20,011; P < .001) of pre-COVID-19 imaging volumes. Overall imaging volumes returned during the recovery time period to 99% (19,915/20,011; P ¼ .725), and thirdwave imaging volumes compared with the pre-COVID-19 period were significantly lower in the emergency department at 88.8% (7,951/8,955; P < .001), significantly higher for outpatients at 115.7% (8,818/7,621; P ¼ .008), not significantly different for inpatients at 106% (3,650/3,435; P ¼ .053), and overall unchanged when aggregated together at 102% (20,419/20,011; P ¼ .629).Conclusions: Medical imaging rebounded after the first wave of COVID-19 hospitalizations, with relative stability of utilization over the ensuing phases of the pandemic. As widespread COVID-19 vaccination continues to occur, future surges in COVID-19 hospitalizations will likely have a negligible impact on imaging utilization.
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