USU Teaching Documentation: Dossiers from the Mentoring Program

The nation\u27s land grant institutions were founded on the principle of access for the general public to the knowledge gained through research and creative activity fostered in higher education. Central to our access mission is our dedication to teaching and learning that is informed by research and discovery, both of which must result, at least in part, from our engagement with our external constituents. That teaching and learning informs our research and vice versa; our research informs and aids in our teaching mission. This work, compiled by Professors Maria Luisa Spicer-Escalante and Cathy Ferrand Bullock, is focused on how the best, highly informed teaching is accomplished when done in an intentional manner. That intentional process helps the best university educators thoughtfully build their teaching story in an organized manner. Educators think about how they can successfully reach and engage their appropriate student audiences (or mentees), what they hope to accomplish, and how they intend to accomplish their goals. Further, as learning outcomes are identified and established, first-rate methods for course design, content inclusion, and continuous improvement can be outlined. Those of us who follow these intentional principles may then detail our growth and success along the way as teachers in the development of documents that tell our stories. Undoubtedly, the ability to clearly document and articulate that story will help academic personnel add to their tenure and promotion preparation in a very meaningful way. But as or even more important is the opportunity to describe these journeys with all the efforts, large and small, of improving their product in terms of learning outcomes and student growth and success. The nuggets of wisdom compiled by Professors Spicer-Escalante and Bullock, in USU Teaching Documentation: Dossiers from the Mentoring Program, will help teachers across the board from the new lecturer or assistant professor to the experienced professor dive into their teaching programs and find ways to continuously experiment and refine their approaches to our critically important student audiences. Good luck, teach on, and successfully document some of the most important work you all do! Frank Galey Executive Vice President and Provost Utah State University 2019https://digitalcommons.usu.edu/ua_faculty/1000/thumbnail.jp

Parental Perceptions of the Impact of COVID-19 and Returning to Play Based on Level of Sport

This study examined the impact of COVID-19 on youth sport parents based on competition level to understand how the pandemic affected youth sport and factors associated with youth returning to sport. Survey data were collected from samples of US sport parents in two waves - early in the pandemic (N = 751) and as programs began to resume (N = 707). Data showed elite sport parents were more willing to return. Although most participants returned to play, significant numbers had not resumed participation. Parent comfort was the most important factor associated with resuming. However, parents allowed children to resume play due to perceived external pressure, potentially creating stress among parents regarding sport participation decisions. Attending school in person and household income were associated with the ability to resume sport suggesting the need to provide school sport environments and consider the financial impacts of COVID-19 on sport families

SIAH and EGFR, Two RAS Pathway Biomarkers, are Highly Prognostic in Locally Advanced and Metastatic Breast Cancer

Background: Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS “pathway” activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine. Methods: In this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer. Findings: SIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases. Interpretation: The discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy. Funding: This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT)-Commonwealth Research Commercialization Fund (CRCF) (MF14S-009-LS to A.H. Tang), and National Cancer Institute (CA140550 to A.H. Tang)

A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model

D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus. Idh2R140Q mice displayed significantly elevated 2HG levels and recapitulated multiple defects seen in patients. AGI-026, a potent, selective inhibitor of the human IDH2R140Q-mutant enzyme, suppressed 2HG production, rescued cardiomyopathy, and provided a survival benefit in Idh2R140Q mice; treatment withdrawal resulted in deterioration of cardiac function. We observed differential expression of multiple genes and metabolites that are associated with cardiomyopathy, which were largely reversed by AGI-026. These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.25 page(s