Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon.

The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. This type of unbiased population screening can detect at-risk individuals who may otherwise be missed by conventional medical approaches. However, challenges exist for this type of high-throughput testing in an academic setting, including developing a low-cost high-efficiency test and scaling up the clinical laboratory for processing large numbers of samples. Modifications to our academic clinical laboratory including efficient test design, robotics, and a streamlined analysis approach increased our ability to test more than 1,000 samples per month for HOP using only one dedicated HOP laboratory technologist. Additionally, enrollment using a HIPAA-compliant smartphone app and sample collection using mouthwash increased efficiency and reduced cost. Here, we present our experience three years into HOP and discuss the lessons learned, including our successes, challenges, opportunities, and future directions, as well as the genetic screening results for the first 13,670 participants tested. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%. Our laboratory experience described here may provide a useful model for population screening projects in other states.

Rural research capacity: a co-created model for research success.

PURPOSE: The United States' National Institutes of Health (NIH) have long challenged academia to improve clinical trial enrollment, especially in underrepresented populations; inclusive of geography, age, disability status, racial and ethnic minorities. It has been shown that rural and urban residents enrolled in clinical trials have similar outcomes, yet, rural healthcare systems struggle to provide opportunities to rural residents to participate in clinical trials when infrastructure is limited or unsupportive of research programs and/or research staffing levels are insufficient. To fully address the barriers to clinical trial access in rural areas, it is not adequate to simply open more trials. Community receptivity of research as well as organizational and community capacity must be considered. This project was determined by the Oregon Health and Science University's Institutional Review Board to be generalizable research across the chosen counties and was approved to operate under a waiver of written consent. Participants received a cash incentive in appreciation for their time and verbally agreed to participate after reviewing a project information sheet. METHODS: The research team co-created a community-responsive approach to the receipt, review, and acceptance of clinical trials in a rural community setting. An adapted 5 step Implementation Mapping approach was used to develop a systematic strategy intended to increase the success, and therefore, the number of clinical trials offered in a rural community. RESULTS: The research team and participating rural community members pilot-tested the implementation of a co-designed research review strategy, inclusive of a Regional Cultural Landscape and three co-created project submission and feasibility review forms, with a cancer early detection clinical trial. The proposed clinical trial required engagement from primary care and oncology. Utilizing the research review strategy demonstrated strong researcher-community stakeholder communication and negotiation, which resulted in early identification and resolution of potential barriers, hiring a local clinical research coordinator, and timely trial opening. CONCLUSION: To the knowledge of the research team, the work described is the first to use a community-engaged approach for creating a clinical trial implementation strategy directly supportive of rural-sitting community stakeholders in receiving, reviewing, and approving cancer-related clinical trials in their community. Participating community members and leaders had the chance to negotiate research protocol changes or considerations directly with researchers interested in conducting a cancer clinical trial in their rural setting.

Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project.

Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

How undergraduates historically underrepresented in biomedical sciences value multiple components of a research training program.

To promote diversity in the STEM workforce, undergraduate research training programs incorporating a variety of intervention strategies have been developed to support students from historically underrepresented backgrounds in overcoming numerous systemic barriers to pursuing careers in science. However, relatively little research has focused on how students experience and value these interventions and the ways in which the interventions support student success. The current study analyzed qualitative interviews from participants (n=15) in a comprehensive research training program for undergraduates historically underrepresented in biomedical research to investigate the student perspective on how specific program components address barriers and support their research training, academic progress, and career preparation. Findings indicated that students benefit from authentic research experiences, mentoring, supplemental curriculum, financial assistance, and a supportive program environment. Participants described how the program helped them address financial concerns, navigate academic and career choices, build science identity and efficacy, and feel a sense of belonging within a caring community. The study highlights how multi-faceted research training programs offering a variety of supports can contribute to student retention and development according to the needs and circumstances of individual students.

Contributions Made by Undergraduates to Research Projects: Using the CREDIT Taxonomy to Assess Undergraduate Research Experiences.

The authors developed a novel tool, the CREDIT URE, to define and measure roles performed by undergraduate students working in research placements. Derived from an open-source taxonomy for determining authorship credit, the CREDIT URE defines 14 possible roles, allowing students and their research mentors to rate the degree to which students participate in each role. The tool was administered longitudinally across three cohorts of undergraduate student-mentor pairs involved in a biomedical research training program for students from diverse backgrounds. Students engaged most frequently in roles involving data curation, investigation, and writing. Less frequently, students engaged in roles related to software development, supervision, and funding acquisition. Students' roles changed over time as they gained experience. Agreement between students and mentors about responsibility for roles was high.

Pupil response to social-emotional material is associated with rumination and depressive symptoms in adults with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is marked by repetitive thinking and high rates of depression. Understanding the extent to which repetitive negative thinking in ASD reflects autistic stereotypy versus general depressive thinking patterns (e.g., rumination) could help guide treatment research to improve emotional health in ASD. We compared associations between rumination, depressive symptoms, and pupil response to social-emotional material in adults with ASD and typically developing (TD) adults with and without depression. METHODS: N = 53 verbally fluent young adults were recruited to three cohorts: ASD, n = 21; TD-depressed, n = 13; never-depressed TD-controls, n = 19. Participants completed Ruminative Response Scale and Beck Depression Inventory self-reports and a passive-viewing task employing emotionally-expressive faces, during which pupillary motility was assessed to quantify cognitive-affective load. Main and interactive effects of cohort, emotion condition, and time on pupil amplitude were tested via a linear mixed effects analysis of variance using restricted maximum likelihood estimation. Similar procedures were used to test for effects of rumination and depressive symptoms on pupil amplitude over time within ASD. RESULTS: Responsive pupil dilation in the ASD cohort tended to be significantly lower than TD-depressed initially but increased to comparable levels by trial end. When viewing sad faces, individuals with ASD who had higher depression scores resembled TD-depressed participants' faster, larger, and sustained pupil response. Within ASD, depressive symptoms uniquely predicted early pupil response to sad faces, while rumination and depression scores each independently predicted sustained pupil response. CONCLUSIONS: People with elevated depressive symptoms appear to have faster and greater increases in pupil-indexed neural activation following sad stimuli, regardless of ASD status, suggesting the utility of conceptualizing rumination as depression-like in treatment. Ruminative processes may increase more slowly in ASD, suggesting the potential utility of interventions that decrease reactions before they are uncontrollable. Findings also reinforce the importance of testing for effects of internalizing variables in broader ASD research.