Preclinical studies in ovarian cancer have demonstrated upregulation of the Wnt/β-catenin pathway promoting tumor proliferation and chemoresistance. Our objective was to evaluate the effect of the Wnt/β-catenin pathway inhibitor, WNT974, in primary ovarian cancer ascites cells. Ascites cells from patients with papillary serous ovarian cancer were isolated and treated with 1 μM WNT974 ± 100 μM carboplatin. Viability was evaluated with the ATPlite assay. The IC 50 was calculated using a dose-response analysis. Immunohistochemistry (IHC) was performed on ascites cells and tumor. Expression of R-spondin 2 (RSPO2), RSPO3, PORCN, WLS, AXIN2, and three previously characterized RSPO fusion transcripts were assessed using Taqman assays. Sixty ascites samples were analyzed for response to WNT974. The ascites samples that showed a decrease in ATP concentration after treatment demonstrated no difference from the untreated cells in percent viability with trypan blue staining. Flow cytometry demonstrated fewer cells in the G2 phase and more in the G1 and S phases after treatment with WNT974. Combination therapy with WNT974 and carboplatin resulted in a higher percentage of samples that showed ≥ 30% reduction in ATP concentration than either single drug treatment. IHC analysis of Wnt pathway proteins suggests cell cycle arrest rather than cytotoxicity after WNT974 treatment. QPCR indicated that RSPO fusions are not prevalent in ovarian cancer tissues or ascites. However, higher PORCN expression correlated to sensitivity to WNT974 (P = 0.0073). In conclusion, WNT974 produces cytostatic effects in patient ascites cells with primary ovarian cancer through inhibition of the Wnt/β-catenin pathway. The combination of WNT974 and carboplatin induces cytotoxicity plus cell cycle arrest in a higher percentage of ascites samples than with single drug treatment. RSPO fusions do not contribute to WNT974 sensitivity; however, higher PORCN expression indicates increased WNT974 sensitivity.

Background: Biomedical research is essential for optimizing patient care. Research has suggested inadequacies in nonorthopaedic trainees' understanding of study design and biostatistics. This study assesses orthopaedic residents' knowledge of common biostatistical and study design concepts, as well as their confidence in utilizing the medical literature. Methods: A validated survey assessing knowledge and the application of study design concepts was administered to residents at 10 U.S. institutions. The survey tested knowledge as well as confidence and attitudes regarding common biostatistics principles. The association of demographic characteristics, work activities, and confidence and attitude ratings with test performance were examined using t tests and analysis of variance. Results: The survey response rate was 64% (178 of 279). The largest group of participants were men (83%, 137 of 165), were between the ages of 26 and 30 years (59%, 105 of 177), and had graduated medical school within the past 4 to 10 years (43%, 76 of 175). Fifty-three percent (93 of 176) had prior biostatistics training, while 44% (77 of 176) had prior epidemiology training. Less than 5% of biostatistics or epidemiology training had taken place after medical school. Forty-seven percent (83 of 176) were unable to determine a study's design. Thirty-eight percent (67 of 178) could not apply the concept of specificity and sensitivity. Eighty-three percent (147 of 178) could not assess the strength of a relationship using odds ratios. Sixty-nine percent (123 of 178) understood the implications of p values. Previous biostatistics training, but not epidemiology or evidence-based medicine training; inclusion of reading research, attending conferences, and data analysis; as well as a self-reported finding of statistics as important for the analysis of one's own research data were significantly associated with better test performance (p < 0.05). Conclusions: Notable deficits exist in orthopaedic residents' biostatistical knowledge. Greater emphasis is needed to improve biostatistics and research design training. The impact of biostatistics knowledge and/or aptitude on clinical decision-making is an area of suggested research.Research and statistics are essential for optimizing patient care through the production and consumption of sound research. The current literature suggests inadequacies in nonorthopaedic trainees' understanding of the science of research and statistics because of poor development, maintenance, and monitoring of these skills [1][2][3][4][5][6][7][8][9][10][11] . It has been reported that 30% to 90% of the medical literature contains erroneous application and interpretation of statistical methods 6,7,12 . As the reliance on and requirement for evidence-based medicine (EBM) continues to grow, it is crucial that physicians are confident and competent in their *Additional members of the Collaborative Orthopaedic Educational Research Group are listed in a Note at the end of the article. Disclosure:The authors indicated that no exter...