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As a cost-effective and objective population-wide surveillance tool, wastewater-based epidemiology (WBE) has been widely implemented worldwide to monitor the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentration in wastewater. However, viral concentrations or loads in wastewater often correlate poorly with clinical case numbers. To date, there is no reliable method to back-estimate the coronavirus disease 2019 (COVID-19) case numbers from SARS-CoV-2 concentrations in wastewater. This greatly limits WBE in achieving its full potential in monitoring the unfolding pandemic. The exponentially growing SARS-CoV-2 WBE dataset, on the other hand, offers an opportunity to develop data-driven models for the estimation of COVID-19 case numbers (both incidence and prevalence) and transmission dynamics (effective reproduction rate). This study developed artificial neural network (ANN) models by innovatively expanding a conventional WBE dataset to include catchment, weather, clinical testing coverage and vaccination rate. The ANN models were trained and evaluated with a comprehensive state-wide wastewater monitoring dataset from Utah, USA during May 2020 to December 2021. In diverse sewer catchments, ANN models were found to accurately estimate the COVID-19 prevalence and incidence rates, with excellent precision for prevalence rates. Also, an ANN model was developed to estimate the effective reproduction number from both wastewater data and other pertinent factors affecting viral transmission and pandemic dynamics. The established ANN model was successfully validated for its transferability to other states or countries using the WBE dataset from Wisconsin, USA.

Germline variants in the 30 untranslated region (3'UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS variant, is associated with both cancer risk and altered tumor biology. Here, we test the hypothesis that the KRAS variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS variant-positive EOC patients. As this variant seems to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival. EOC patients with complete clinical data were genotyped for the KRAS variant and analyzed for outcome (n = 536), response to neoadjuvant chemotherapy (n = 25) and platinum resistance (n = 306). Outcome was separately analyzed for women with known BRCA mutations (n = 79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were used to confirm altered sensitivity to chemotherapy associated with the KRAS variant. Finally, the KRAS variant was directly targeted through small-interfering RNA/miRNA oligonucleotides in cell lines and survival was measured. Postmenopausal EOC patients with the KRAS variant were significantly more likely to die of ovarian cancer by multivariate analysis (hazard ratio 1.67, 95% confidence interval: 1.09-2.57, P = 0.019, n = 279). Perhaps explaining this finding, EOC patients with the KRAS variant were significantly more likely to be platinum resistant (odds ratio 3.18, confidence interval: 1.31-7.72, P = 0.0106, n = 291). In addition, direct targeting of the KRAS variant led to a significant reduction in EOC cell growth and survival in vitro. These findings confirm the importance of the KRAS variant in EOC, and indicate that the KRAS variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this study supports the hypo

Recently, a variant allele in the 3′UTR of the KRAS gene (rs61764370 T>G) was shown to be associated with an increased risk for developing non-small cell lung cancer, as well as ovarian cancer, and was most enriched in ovarian cancer patients from hereditary breast and ovarian cancer families. This functional variant has been shown to disrupt a let-7 miRNA binding site leading to increased expression of KRAS in vitro. In the current study, we have genotyped this KRAS-variant in breast cancer index cases from 268 BRCA1 families, 89 BRCA2 families, 685 non-BRCA1/BRCA2 families, and 797 geographically matched controls. The allele frequency of the KRAS-variant was found to be increased among patients with breast cancer from BRCA1, but not BRCA2 or non-BRCA1/BRCA2 families as compared to controls. As BRCA1 carriers mostly develop ER-negative breast cancers, we also examined the variant allele frequency among indexes from non-BRCA1/BRCA2 families with ER-negative breast cancer. The prevalence of the KRAS-variant was, however, not significantly increased as compared to controls, suggesting that the variant allele not just simply associates with ER-negative breast cancer. Subsequent expansion of the number of BRCA1 carriers with breast cancer by including other family members in addition to the index cases resulted in loss of significance for the association between the variant allele and m

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