Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Herpes Simplex Virus-2 Hepatitis: A Case Report and Review of the Literature

Herpes simplex virus (HSV) is a rare cause of hepatitis in pregnancy and the chronically immunosuppressed, with a high propensity to progress to acute liver failure (ALF) and death. Patients typically present with a nonspecific clinical picture that often delays diagnosis and treatment, contributing to the high mortality rate. We present a case of a young female on chronic prednisone and hydroxychloroquine for systemic lupus erythematosus (SLE) who was diagnosed with HSV-2 hepatitis after presenting with right-sided chest and abdominal discomfort. Despite early clinical deterioration, prompt initiation of therapy with intravenous acyclovir and methylprednisolone led to rapid improvement

The relations between growth mindset, motivational beliefs, and career interest in math intensive fields in informal STEM youth programs

Past research has shown that growth mindset and motivational beliefs have an important role in math and science career interest in adolescence. Drawing on situated expectancy-value theory (SEVT), this study extends these findings by investigating the role of parental motivational beliefs (e.g., expectancy beliefs, utility values) and parent growth mindset in math on adolescent career interest in math-intensive fields (e.g., mathematics, computer science, statistics, and engineering; MCSE) through adolescent motivational beliefs in math. Structural equation modeling was used to test the hypothesized model using data from 290 adolescents (201 girls, 69.3%; Mage = 15.20), who participate in informal STEM (science, technology, engineering, mathematics) youth programs, and their parents (162 parents, 87.7% female) in the United Kingdom and the United States. As hypothesized, adolescent expectancy beliefs, utility values, and growth mindset in math had a significant direct effect on MCSE career interest. Further, there was a significant indirect effect of parental expectancy beliefs in math on MCSE career interest through adolescents’ expectancy beliefs. Similarly, there was a significant indirect effect from parental utility values in math to MCSE career interest through adolescents’ utility values. The findings suggest that parents’ math motivational beliefs play a critical role in adolescent math motivational beliefs and their career interest in math-intensive fields.</p

The relations between growth mindset, motivational beliefs, and career interest in math intensive fields in informal STEM youth programs

Past research has shown that growth mindset and motivational beliefs have an important role in math and science career interest in adolescence. Drawing on situated expectancy-value theory (SEVT), this study extends these findings by investigating the role of parental motivational beliefs (e.g., expectancy beliefs, utility values) and parent growth mindset in math on adolescent career interest in math-intensive fields (e.g., mathematics, computer science, statistics, and engineering; MCSE) through adolescent motivational beliefs in math. Structural equation modeling was used to test the hypothesized model using data from 290 adolescents (201 girls, 69.3%; Mage = 15.20), who participate in informal STEM (science, technology, engineering, mathematics) youth programs, and their parents (162 parents, 87.7% female) in the United Kingdom and the United States. As hypothesized, adolescent expectancy beliefs, utility values, and growth mindset in math had a significant direct effect on MCSE career interest. Further, there was a significant indirect effect of parental expectancy beliefs in math on MCSE career interest through adolescents’ expectancy beliefs. Similarly, there was a significant indirect effect from parental utility values in math to MCSE career interest through adolescents’ utility values. The findings suggest that parents’ math motivational beliefs play a critical role in adolescent math motivational beliefs and their career interest in math-intensive fields.</p

The relations between growth mindset, motivational beliefs, and career interest in math intensive fields in informal STEM youth programs.

Acknowledgements: We thank the sites where the study was conducted, the adolescents for participating in the study, and our research assistants for their assistance with preparing the data.Past research has shown that growth mindset and motivational beliefs have an important role in math and science career interest in adolescence. Drawing on situated expectancy-value theory (SEVT), this study extends these findings by investigating the role of parental motivational beliefs (e.g., expectancy beliefs, utility values) and parent growth mindset in math on adolescent career interest in math-intensive fields (e.g., mathematics, computer science, statistics, and engineering; MCSE) through adolescent motivational beliefs in math. Structural equation modeling was used to test the hypothesized model using data from 290 adolescents (201 girls, 69.3%; Mage = 15.20), who participate in informal STEM (science, technology, engineering, mathematics) youth programs, and their parents (162 parents, 87.7% female) in the United Kingdom and the United States. As hypothesized, adolescent expectancy beliefs, utility values, and growth mindset in math had a significant direct effect on MCSE career interest. Further, there was a significant indirect effect of parental expectancy beliefs in math on MCSE career interest through adolescents' expectancy beliefs. Similarly, there was a significant indirect effect from parental utility values in math to MCSE career interest through adolescents' utility values. The findings suggest that parents' math motivational beliefs play a critical role in adolescent math motivational beliefs and their career interest in math-intensive fields

Reciprocal Associations Between Science Efficacy, STEM Identity and Scientist Career Interest Among Adolescent Girls within the Context of Informal Science Learning.

Acknowledgements: This research was funded by the National Science Foundation (1831593) in the United States and the Wellcome Trust and ESRC (206259/Z/17/Z) in the United Kingdom. The authors would like to thank the youth who participated in the study.Limited research has explored the longitudinal pathway to youth career interests via identity and efficacy together. This study examined the longitudinal associations between science efficacy, STEM (science, technology, engineering and math) identity, and scientist career interest among girls who are historically considered as an underrepresented group among scientists. The sample included 308 girls (M age = 15.22, SD age = 1.66; 42.8% White) from six STEM youth programs, each at a different informal science learning site within the U.K. and the U.S. Longitudinal structural equation modelling demonstrated that science efficacy consistently predicted STEM identity and scientist career interest, and similarly, STEM identity consistently predicted science efficacy over a two-year period. Scientist career interest at 12 months predicted science efficacy at 24 months. The coefficients of efficacy predicting STEM identity and scientist career interest were significantly larger compared to STEM identity and scientist career interest in predicting science efficacy from 12 months to 24 months. Further mediation analysis supported a significant pathway from STEM identity at 3 months to scientist career interest at 24 months via 12-month science efficacy. The findings highlight that science efficacy and STEM identity for girls relate to their scientist career interest and these longitudinal associations are reciprocal. This study suggests that science efficacy and STEM identity mutually influence each other, and enhancing science efficacy and STEM identity is key to promoting adolescents' interest in being a scientist

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research