Underrepresented Minority Populations Research Articles

Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations.

The autosomal dominant cancer predisposition disorders hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) are genetic conditions for which early identification and intervention have a positive effect on the individual and public health. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC and LS. Participants were recruited from three geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; Jacksonville, FL). Participants underwent Exome+ sequencing (Helix Inc, San Mateo, CA) and return of results for specific genetic findings: HBOC (BRCA1 and BRCA1) and LS (MLH1, MSH2, MSH6, PMS2, and EPCAM). Chart review was performed to collect demographics and personal and family cancer history. To date, 44,306 participants have enrolled in Tapestry. Annotation and interpretation of all variants in genes for HBOC and LS resulted in the identification of 550 carriers (prevalence, 1.24%), which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM). More than half of these participants (52.1%) were newly diagnosed carriers with HBOC and LS. In all, 39.2% of HBOC/LS carriers did not satisfy National Comprehensive Cancer Network (NCCN) criteria for genetic evaluation. NCCN criteria were less commonly met in underrepresented minority populations versus self-reported White race (51.5% v 37.5%, P = .028). Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have LS and HBOC cancer predisposition syndromes.

P044 Enabling skin research participation of under-represented ethnic minority populations: a codesigned inclusion toolkit

P044 Enabling skin research participation of under-represented ethnic minority populations: a codesigned inclusion toolkit

Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.

Abstract PO5-05-07: Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam

Abstract Background The cyclin-dependent kinases (CDK)4/6 inhibitors (CDK4/6i) palbociclib and ribociclib have been available in Viet Nam since 2021 for the treatment of hormone receptor-positive metastatic breast cancer (MBC). Data regarding CDK4/6i benefit in Vietnamese MBC are sparse. This study evaluated the impact of CDK4/6i in first-line HR+/HER2− MBC using real-world experience at Ho Chi Minh City Oncology Hospital. Methods A single-institution study analyzed retrospective data from 108 patients treated with palbiciclib or ribociclib with endocrine therapy in first-line in HR+/HER2– MBC patients at Ho Chi Minh city oncology hospital. Patient characteristics, PFS, treatment response, and toxicity profiles were analyzed. Results Baseline patients’ characteristics are detailed in Table 1.The median follow-up was 12.5 months (95% CI: 10.9-13.3). Best responses by the line of therapy are in Table 2. The median PFS has still not been reached. The PFS rates at 6, 12 and 18 months were 94.4%, 93.5% and 91.5%, respectively. Patients with bone-only metastasis have a better PFS than visceral metastasis (p = 0.059). Patients with recurrent disease had shorter PFS (p = 0.083) than those presenting with de novo metastasis. The most common reasons for toxicity were neutropenia (92.6%), anemia (35.2%), thrombopenia (22.2%) and the incidence of diarrhea was only 2,8%. None were related to QTc-prolongation Conclusion The real-world effectiveness and safety with CDK4/6 inhibitors in our institution HR+/HER2– MBC patients mimics that observed in the clinical trials. This finding supports the use of CDK4/6i in combination with endocrine therapy as standard of care for HR+/HER2- MBC in Viet Nam. The study also suggests the need for more study of under-represented minority populations. Further studies are ongoing to validate these findings incorporating additional cancer centers. Keywords: advanced/metastatic breast cancer, Asia, CDK4/6 inhibitors, real world Table 1. Patient Demographics and Baseline Disease Characteristics (N=108) Characteristics N (%) Age, y: Median 52 Stage Recurrent from earlier stage, stages 0–III 67 (62) De novo, newly diagnosed stage IV at enrolment 41 (38) DFI &amp;lt; 12 months 5 (4.6) 12-24 months 12 (11.1) &amp;gt; 24 months 51 (47.2) No. of metastatic sites 1 49 (45.4) 2 37 (34.3) ≥ 3 22 (20.4) Metastasis pattern Bone only 30 (27.8) Other 78 (72.2) CDK4/6i Palbociclib 35 (32.4) Ribociclib 73 (67.6) Partner ET AIs 94 (87) Fulvestrant 14 (13) Table 2. Best responses of therapy (N=108) Best responses (N,%) CR 2 (1.9) PR 29 (26.9) SD 67 (62.1) PD 10 (9.3) Total 108 (100) ORR 31 (28.8) CBR 76 (70.3) Table. Citation Format: Hoang-Quy Nguyen, Hong-Duc Phan-Thi, Thi-Hong-Van Le. Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-07.

Abstract 16: County-Level Racial Residential Segregation and Sedentary Behavior in US Adults

Introduction: Sedentary behavior (SB) is highly prevalent and shows an increasing trend in United States (US) adults, resulting in adverse health outcomes, such as cardiovascular disease, cancer, and diabetes. Yet, potential environmental determinants of SB, including racial residential segregation, remain understudied. Hypothesis: County-level segregation will be associated with sedentary time in a nationwide sample of US adults, and this relationship will be moderated by sex. Methods: We analyzed data from 2637 US adults aged 20-75 years (mean age [45.1 years], female [50.6%] from the population-based AmeriSpeak panel in 2019. Participants completed the Activities Completed over Time in 24-hours (ACT24) previous-day recall, a validated population-level measure of total daily SB (hours/day). County segregation was expressed as the isolation index at the county level for non-Hispanic (NH) White, NH Black, and Hispanic adults (vs all other races/ethnicities). The isolation index ranges from 0 to 1, with a higher value indicating higher segregation and therefore, a higher average probability of contact among residents of the minority group and, thus, a lower probability of contact among residents of the minority group and all other races/ethnicities. We used survey-weighted linear regression models to assess the relationships of race-specific isolation index with time spent in SB, adjusting for age, sex, marital status, education, occupation, household income, body mass index, census region, and county-level poverty. Additionally, we stratified these relationships by sex. Results: Overall, US adults reported a mean of 9.5 hours/day of sedentary time. Counties with higher NH White isolation showed a significant inverse relationship with sedentary time (β = -1.52, 95% confidence interval [-2.75, -0.29], p = 0.017). Counties with higher NH Black isolation showed a non-significant inverse relationship with sedentary time (β = -0.30 [-2.53, 1.94], p = 0.790), and counties with higher Hispanic isolation showed a non-significant positive relationship (β = 0.32, [-1.64, 2.28], p = 0.743). In sex-stratified analysis, only NH White isolation among White females showed a significant inverse relationship with sedentary time (β = -2.14 [-4.19, -0.09], p = 0.041). Conclusions: NH White adults, particularly females, residing in more segregated counties reported less sedentary time in this population-based nationwide sample of US adults. SB was not strongly associated with isolation for NH Black and Hispanic adults. Future studies could aim to replicate (or not) our findings with larger samples of underrepresented minority populations and further explore potential mechanisms for sex related variation in the association between residential segregation and sedentary behavior.

Understanding Ethnoracial Disparities and Advancing Mental Health Equity Through Clinical Psychological Science: Introduction to Special Issue

Mental health disparities persist in countries such as the United States and across the world. Research with disparity populations is underrepresented in mainstream clinical psychological journals, and existing science has not focused on group specific lived experiences. Achieving mental health equity requires examination of determinants of psychopathology and health disparities and personal and cultural attributes that promote mental health. Clinical psychological science ideally also encourages and values research with underrepresented minority and underserved populations, novel and underused study designs, and research produced by diverse scholars. Our special issue highlights research that considers systematically culture specific processes, examines not only individual- but also community-level factors that relate to psychopathology and mental-health care, and challenges structural limitations in the current literature. We review these articles that incorporate innovative and community engaged approaches and showcase the importance of diversity in researcher and research participant demographics and perspectives in the advancement of equity in clinical psychological science.

Evaluation of the Effectiveness of a Bilingual Nutrition Education Program in Partnership with a Mobile Health Unit.

There are limited reports of community-based nutrition education with culinary instruction that measure biomarkers, particularly in low-income and underrepresented minority populations. Teaching kitchens have been proposed as a strategy to address social determinants of health, combining nutrition education, culinary demonstration, and skill building. The purpose of this paper is to report on the development, implementation, and evaluation of Journey to Health, a program designed for community implementation using the RE-AIM planning and evaluation framework. Reach and effectiveness were the primary outcomes. Regarding reach, 507 individuals registered for the program, 310 participants attended at least one nutrition class, 110 participants completed at least two biometric screens, and 96 participants attended at least two health coaching appointments. Participants who engaged in Journey to Health realized significant improvements in body mass index, blood pressure, and triglycerides. For higher risk participants, we additionally saw significant improvements in total and LDL cholesterol. Regarding dietary intake, we observed a significant increase in cups of fruit and a decrease in sugar sweetened beverages consumed per day. Our findings suggest that Journey to Health may improve selected biometrics and health behaviors in low-income and underrepresented minority participants.

Palliative Care Clinical Trials in Underrepresented Ethnic and Racial Minorities: A Narrative Review.

Introduction: A growing number of patients with serious illness who would benefit from palliative care are part of ethnoracial minority groups. Nevertheless, large disparities in provision of palliative services exist for minoritized populations. Furthermore, there is a relative dearth of palliative care research focused on minority groups and how best to provide high-quality, culturally tailored palliative care. The aim of this narrative review is to summarize the existing literature regarding palliative care clinical trials in underrepresented minority populations, describe methodological approaches, and provide guidance on future palliative care-focused clinical trials. Methods: We used the Scale for the Assessment of Narrative Review Articles (SANRA) and Cochrane's guidelines on conducting reviews. We used PubMed and Clinicaltrials.gov to review published, full-text articles or protocols (1950-2022), and limited to palliative care interventions focused on ethnoracial minority populations. We included randomized clinical trials (RCTs), including pilot and feasibility trials, protocols of RCTs, and studies that report RCT methodology. Two reviewers independently assessed eligibility. Results: Our search yielded 585 publications; of these, 30 met the full-text review criteria and 16 studies met our criteria for inclusion. We deemed nine articles as having low risk of bias and four as having high risk of bias. Discussion: Commonly used methodologic approaches for clinical trials in underrepresented minority populations included the following: the use of written and visual materials that were no higher than a sixth-grade reading level, the use of patient and lay health navigators, bilingual and multicultural study staff and study materials, race-concordant staff, the option of in-person and virtual visits that accommodated the patient and family's schedule, recruitment from faith communities, and the use of community-engaged research principles. Future palliative care clinical trials should expand on the strategies described in this article, adopt effective strategies currently used in nonpalliative care interventions, and innovate around the principles of community-engaged research.

An Introduction to Faculty Diversity, Equity, and Inclusion for Excellence in Nurse Education: Literature Review.

The diversity of the world's population is increasing, along with the health inequities of underrepresented minority populations. To provide high-quality care to all patients, nurses require an understanding of diversity, equity, and inclusion (DEI) as well as how to implement best practices. Nurse educators are the ones to lead the way for DEI education for students. This paper aims to describe the findings of a literature review that introduces DEI concepts for excellence in nurse education and their related benefits. Best practices for actions to address DEI in nursing education will be described. After institutional review board approval, a literature search yielded 61 articles using 15 distinct keywords in 4 global, peer-reviewed literature databases. Melynk and Fineout-Overholt's (2023) Levels of Evidence guided the process of selecting 26 peer-reviewed articles and resources. Common themes for best practices in DEI were identified. These themes included recruiting underrepresented minority nursing faculty, incorporating DEI into an institution's mission statement, addressing DEI topics in curricula, providing leadership, having a DEI strategic plan, developing education, developing data-based interventions, instilling policy change, partnering in outreach, targeting impact on hiring committees, recognizing DEI work, and providing mentorship. In summary, this literature review provides several strategies to address DEI for nurse educators. Committing to DEI efforts and improving diversity in the nurse educator workforce are integral steps in improving the quality and inclusivity of nursing education and ultimately improving the health of our communities.

Alternative model to deliver germline genetic testing to patients with advanced prostate cancer (PCa).

123 Background: Genomic testing is now standard-of-care (SOC) for PCa patients with both therapeutic and hereditable consequences. National guidelines recommend germline testing in all high-risk and advanced PCa patients, regardless of age or family history. Yet, many systemic barriers prevent patients from receiving germline testing promptly, including the burden of appointments, comorbidities, transportation, provider knowledge of genetic testing, and insufficient genetics workforce that limits timely referral to genetic counselors. Methods: We developed a streamlined, alternative genetic care delivery model to improve rates of germline genetic testing for PCa patients. A multidisciplinary team (genitourinary medical oncologists, advanced practice RN, and genetic counselors) developed a tailored pre- and posttest counseling curriculum for PCa patients undergoing germline testing that was delivered by oncology providers. Pretest counseling was incorporated into SOC counseling for somatic tumor genomic testing performed to personalize therapeutics. Systematic posttest counseling was delivered by oncology providers, and men with germline pathogenic/likely pathogenic (P/LP) variants were referred to certified genetic counselors for formal genetic counseling. We retrospectively collected data on PCa patients treated at an academic oncology practice who underwent paired germline/somatic testing through a commercial lab accompanied by tailored pre/posttest counseling, including demographics, clinical characteristics, and germline test results. We performed quarterly audits to monitor quality metrics. Results: From September 2021 to May 2023, seventy-five PCa patients underwent paired germline/somatic tumor testing. The racial/ethnically diverse patient population (self-identified) included 81% Black, 13% Hispanic, and 6% non-Hispanic White men. At the time of analysis, 64 tests had resulted; 9.4% of patients (n=6) had a P/LP germline variant, and 31.2% of patients (n=20) tested negative. The majority of patients (59.4%, n=38) had a variant of unknown significance (VUS). Additional data will be available at the time of presentation. Conclusions: Providing paired germline/somatic tumor testing with tailored pre/posttest education delivered by oncology providers, and formal genetic counseling reserved for patients with P/LP germline variants, is an efficient way to provide guideline-directed genetic services for PCa patients. Given the frequency of VUS, education for pre/posttest counseling is essential, particularly in under-represented minority populations. The frequency of actionable mutations is reduced in underrepresented minority PCa patients compared with reports in the literature, reflecting limitations of current germline testing/bioinformatics platforms and the need for greater inclusion of diverse populations in future studies.

Respondent Driven Sampling Method of Recruitment for a Case Control Study of Gastric Cancer Risk.

Gastric cancer (GC) disproportionately affects ethnic minorities in the US including Asians and Pacific Islanders. Research with minority groups who are at high risk are needed to provide more effective treatment. Successful recruitment of minorities to research must overcome obstacles of language, access, fear and mistrust. Respondent Driven Sampling (RDS) is a sampling strategy designed to recruit underrepresented minority populations using social networks. However, there are no reports of RDS being used for a case-control study. Our pilot study examined the feasibility of using RDS as a recruitment strategy to enroll a large number of participants to develop a GC screener. Our preliminary work showed that 750 cases and 5,250 controls would be needed to fully develop this tool. GC cases, who also served as the seeds, were asked to refer 2 more people to participate as controls in our study. Our pilot goal was to recruit 8 GC cases (as seeds) and 112 controls using three waves of referrals and recruitment. Twenty-seven GC cases were contacted of which 10 refused, 4 expressed interested to participate in the survey but were unwilling to recruit controls. Thirteen cases were recruited but only 5 Complete the survey. Of these 5, 3 cases did not pass on referral coupons and only 2 of the participants gave coupons to 3 potential controls. Our study revealed the limitations of using RDS with cancer patients to support recruitment. GC patients' constrained social networks, inadequate incentives or other factors may have contributed to the lack of success with using RDS in this setting.

Social Determinants of Health Impacting Access to Renal Dialysis for Racial/Ethnic Minorities.

Although widespread, the burden of disease presented by chronic kidney disease (CKD) is not equally distributed among all demographics. Examining the social determinants of health (SDOH) that relate to barriers to renal dialysis care in CKDcan help to prevent future disparities. There has not been a study addressing the social factors that create barriers to care for ethnic minority patients with CKD. The aim of this scoping review is to address the SDOH that affects access to renal dialysis for ethnic minority patients in the United States.This study was based on the protocol published by the Joanna Briggs Institute. A total of 349 studies were identified from PubMed, EBSCOhost, and Embase. Each article was screened against population, concept, and context criteria in order to be considered for inclusion. The population was determined to be adults of all genders from underrepresented minority populations. The selected concept was SDOH. The context of this study was the United States population. From the articles selected by the search criteria, neighborhood of residence, mental health care access, glomerular filtration rate (GFR) methodology, socioeconomic status (SES), language barriers, immigration status, and military rank were identified as SDOH affecting access to renal dialysis care. While this study identified four social determinants, more research is needed for the investigation of other possible SDOH contributing to disparities related to CKD and access to renal dialysis care.

Promoting educational equity among health science students through a project-based learning writing course at a Hispanic Serving Institution

Background: Overall, high rates of American high school seniors lack writing proficiency (75%) and historically underrepresented minority (URM) populations fare even worse (91% of African American, 89% of Latinx) (U.S. Dept of Education, 2011), which suggests that URM college students enter college with lower writing abilities (Bracco et al., 2021). Co-curricular writing instruction could help eliminate writing skill disparities. The Health Science Intensive Writing Workshop (HSIWW) aimed to increase students’ perceived confidence in their writing abilities, encourage and increase academic help-seeking behaviors and networking skills.&#x0D; Description of Practice: A project-based learning methodology proved the best fit because of its focus on real-world problems and assessments, and emphasis on collaboration and revisions of personal work. &#x0D; Outcomes: Eight upper-division health science undergraduate students participated in the 5-day HSIWW. Descriptive statistics indicated increases in perceived ability, confidence in writing abilities, and academic help-seeking behaviors. &#x0D; Conclusion: To the study team’s knowledge, the HSIWW was unique as a co-curricular, project-based course that used high-impact practices to teach public health writing skills to URM students in higher education. HSIWW’s findings suggest a positive impact on student achievement by improving student performance and scaffolding the academic help-seeking behaviors that help keep students on the path to graduation.

A quantitative synthesis of disparities in the inclusion of racial/ethnic minorities and older women in breast cancer trials.

6557 Background: Trials that inadequately include underrepresented minority (URM) populations widen inequities in cancer care. We assessed reporting patterns, representation, and trends of URM representation in breast cancer (BC) trials. Methods: We analyzed all phase 2/3 trials for age disparity and trials recruiting from the US for racial/ethnic disparity amongst BC RCTs (1990-2021). Enrollment-incidence ratios (EIR), which compare trial proportions (TP) from age subgroups against global estimates of incidence in the corresponding age group (from Global Burden of Disease) and racial/ethnic subgroups against US-population-based incidence in the corresponding racial/ethnic group (from SEER 22), were calculated. Individual-trial EIRs were pooled using random-effects meta-analyses. EIRs of &lt;0.80 indicated meaningful underrepresentation, while EIRs &gt;1.20 indicated meaningful overrepresentation. Meta-regression was used to explore associations between key trial characteristics and EIR, and trends in EIR over the last three decades. Results: Of 842 global trials with 490,657 participants, 232 (27.6%) reported the number of participants in specific age strata and 144 (17.1%) reported outcomes by age. Only 60 trials recruited exclusively from the US. Of these, 41 (68.3%) reported race and 24 (40.0%) reported ethnicity, and 2 (3.3%) analyzed outcomes by race. Older adults aged ≥65 years (TP: 24.3%; EIR: 0.53 [95% CI: 0.47-0.60]) and Hispanic women (TP: 5.3%; 0.54; 0.40-0.75) were underrepresented across global trials and US-only trials respectively. Black women were significantly underrepresented in trials that led to FDA approval (0.38; 0.25-0.58) but not in US-only trials. Stratified analysis by BC subtype (with subtype-specific population incidence) showed underrepresentation of Black women in US-only trials for HER2+ BC (0.66; 0.47-0.93), Hispanic women in ER+ BC (0.42; 0.20-0.90), Asians in triple-negative BC (0.24; 0.11-0.53), and older women in HER2+ BC (0.35; 0.31-0.40) and triple-negative BC (0.36; 0.29-0.45). From 1990-2021, the representation of older women declined significantly (meta-regression coefficient for EIR: -0.4 per 10 years), while Black and Hispanic representation showed no significant change. Black (p = 0.02) and Hispanic representation (p = 0.05) worsened significantly in larger trials. Conclusions: Published reports of BC trials do not consistently report the inclusion of URM. Older and Hispanic women were consistently underrepresented, whereas Black women were underrepresented in large, practice-changing trials. [Table: see text]

Cultivating a Sense of Belonging in Allied Health Education: An Approach Based on Mindfulness Anti-Oppression Pedagogy.

To address accreditation standards and to meet a need due to a disparity in health care providers engaged in direct patient care, many institutions of higher education have focused on initiatives to increase the numbers of ethnic and racial minority populations. Despite these efforts, there remains a dearth of diversity in health care. For many underrepresented minority populations (URM), numerous barriers exist to becoming a health professional. Greater levels of discrimination and bias reduce belonging and agency in URM students impacting recruitment and retention. Research has shown that discrimination and bias are antithetical to feeling a sense of belonging on college campuses for URM students. The sense of belonging for URM students has been positively linked to retention and other academic outcomes. Faculty interaction and campus environment have been correlated to sense of belonging. Thus, faculty members as mentors, advisors, and shapers of campus climate have an important role to play in supporting URM students. However, due to socialization in an oppressive society, narratives about race and racism can become entrenched. The entrenchment of racial ideologies, without tools to examine, deconstruct, and reflect, leads to little forward progress. Incorporation of mindfulness anti-oppression pedagogy provides a needed paradigm shift for allied health educators to act with intentionality as they cultivate spaces of belonging for URM students.

Single Cell Transcriptomics of Myeloid Cells in Black Americans with Multiple Sclerosis (P2-3.009)

<h3>Objective:</h3> Identify myeloid cell subsets from peripheral blood and monocyte-derived macrophages associated with MS in Black Americans. <h3>Background:</h3> Prior work in a cohort of patients composed primarily of underrepresented minority populations suggested an association between MS susceptibility and differential DNA methylation of genes that regulate cellular differentiation, proliferation, and invasion. <h3>Design/Methods:</h3> Peripheral blood mononuclear cells (PBMC) were obtained from Black American patients with MS and controls with non-inflammatory neurologic conditions under an IRB-approved protocol (UIC Neuroimmunology Biobank). Single cell libraries for RNAseq were constructed from PBMC (n=9) and monocyte-derived macrophages (MDM, n=6) using the Chromium Next GEM Single Cell 3′ Kit v3.1 and Chromium Next GEM Chip G (10x Genomics). Libraries were sequenced on an Illumina NovaSeq 6000. Expression data was analyzed in R software using the Seurat package (Butler et al., 2018). The SingleR and celldex packages (Aran et al., 2019) were used for identification of human peripheral immune cell types. <h3>Results:</h3> Peripheral blood monocytes from MS patients demonstrated an increase in relative numbers of transitional macrophages. These cells included those from classical CD163+ and non-classical CD16+ monocyte populations. Transcriptomic analysis showed an increase in the expression of a lncRNA (long non-coding RNA), KCNQ1OT1, in these cells. Analysis of MDM revealed expansion of a subset of C1Q1+ macrophages in MS. These cells express high levels of a pattern recognition receptor, FCN1 (ficolin 1). Global transcriptomic analysis revealed increased expression of SNHG5, a small nucleolar RNA host gene, in MS in all macrophage subtypes. <h3>Conclusions:</h3> These results suggest an association between expansion of specific monocyte-macrophage populations in our patient cohort. Increased expression of KCNQ1OT1 in transitional macrophages and SNHG5 in MDM is also consistent with our prior study of epigenetic biomarkers because these non-coding RNA’s are associated with cellular differentiation and proliferation in neoplastic diseases. <b>Disclosure:</b> Mr. Bingen has nothing to disclose. The institution of Dr. Clark has received research support from National Science Foundation. Ms. Wright has nothing to disclose. Fangxiu Xu has nothing to disclose. The institution of Dr. Carrithers has received research support from Biogen.

Critical Perspectives on Expanding Racial/Ethnic Diversity in the HIV Research Workforce: Comorbidities and Mentoring.

HIV-related comorbidities in underrepresented minority populations are reframed to include the co-occurring problems of systemic and structural barriers, within the mentoring context as a buffer and as action-oriented. This framework is discussed to improve racial and ethnic minority diversity in the research workforce from the perspectives of HIV comorbidities and mentoring. An integrated and coordinated approach to HIV-related comorbidities and inequities may be helpful when combined with research on the social-structural contributions as drivers to diversify the research workforce. We emphasize how these key research issues (a) provide a platform for training and retraining a highly motivated, diverse workforce and (b) facilitate the empowerment of these trained individuals to conduct rigorous scientific research on social-structural factors to mitigate the effects of these comorbidities. We conclude that a diverse research workforce is necessary but insufficient for improving training-related outcomes or reducing comorbidity effects. Additional considerations are warranted that include systemic approaches and changes at the structural and institutional levels.

Computational integration and meta-analysis of abandoned cardio-(vascular/renal/metabolic) therapeutics discontinued during clinical trials from 2011 to 2022.

Cardiovascular/renal/metabolic (CVRM) diseases collectively comprise the leading cause of death worldwide and disproportionally affect older demographics and historically underrepresented minority populations. Despite these critical unmet needs, pharmaceutical research and development (R&D) efforts have historically struggled with high drug failure rates, low approval rates, and other challenges. Drug repurposing is one approach to recovering R&D costs and meeting unmet demands in therapeutic markets. While there are multiple approaches to conducting drug repurposing, we recognize the importance of bringing together and consolidating discontinued drug information to help identify prospective repurposing candidates. In this study, we have harmonized and integrated information on all relevant CVRM drug assets from U.S. Securities and Exchange Commission (SEC) filings, clinical trial records, PharmGKB, Open Targets, and other platforms. A list of existing therapeutics discontinued or shelved by pharmaceutical/biotechnology companies in 2011-2022 were manually curated and interpreted for insights using information on each drug's genetic target, mechanism of action (MOA), clinical indication, and R&D information including highest phase of clinical development, year of discontinuation, previous repurposing attempts (if any), and other actionable metadata. This study also summarizes the profiles of CVRM drugs discontinued within the past decade and identifies the limitations of publicly available information on discontinued drug assets. The constructed database could serve as a tool for identifying candidates for drug repurposing and developing query methods for collecting R&D information.

Differential DNA methylation associated with multiple sclerosis and disease modifying treatments in an underrepresented minority population.

Black and Hispanic American patients frequently develop earlier onset of multiple sclerosis (MS) and a more severe disease course that can be resistant to disease modifying treatments. The objectives were to identify differential methylation of genomic DNA (gDNA) associated with disease susceptibility and treatment responses in a cohort of MS patients from underrepresented minority populations. Patients with MS and controls with non-inflammatory neurologic conditions were consented and enrolled under an IRB-approved protocol. Approximately 64% of donors identified as Black or African American and 30% as White, Hispanic-Latino. Infinium MethylationEPIC bead arrays were utilized to measure epigenome-wide gDNA methylation of whole blood. Data were analyzed in the presence and absence of adjustments for unknown covariates in the dataset, some of which corresponded to disease modifying treatments. Global patterns of differential methylation associated with MS were strongest for those probes that showed relative demethylation of loci with lower M values. Pathway analysis revealed unexpected associations with shigellosis and amoebiasis. Enrichment analysis revealed an over-representation of probes in enhancer regions and an under-representation in promoters. In the presence of adjustments for covariates that included disease modifying treatments, analysis revealed 10 differentially methylated regions (DMR's) with an FDR <1E-77. Five of these genes (ARID5B, BAZ2B, RABGAP1, SFRP2, WBP1L) are associated with cancer risk and cellular differentiation and have not been previously identified in MS studies. Hierarchical cluster and multi-dimensional scaling analysis of differential DNA methylation at 147 loci within those DMR's was sufficient to differentiate MS donors from controls. In the absence of corrections for disease modifying treatments, differential methylation in patients treated with dimethyl fumarate was associated with immune regulatory pathways that regulate cytokine and chemokine signaling, axon guidance, and adherens junctions. These results demonstrate possible associations of gastrointestinal pathogens and regulation of cellular differentiation with MS susceptibility in our patient cohort. This work further suggests that analyses can be performed in the presence and absence of corrections for immune therapies. Because of their high representation in our patient cohort, these results may be of specific relevance in the regulation of disease susceptibility and treatment responses in Black and Hispanic Americans.

Improving the cancer survivorship journey: Developing a survivorship care transition model for rural and underserved low risk breast and gynecologic cancer patients (511)

<b>Objectives:</b> The rapid growth of cancer survivors in the United States, in combination with oncology service workforce shortage, creates an urgent need to develop effective survivorship care models. While survivorship programs are required by the Commission on Cancer and endorsed by national cancer organizations, the evidence base supporting specific components and delivery models is still lacking, and novel approaches are especially needed in rural care settings with high concentrations of underrepresented minority populations. Our team is working to create effective and innovative cancer survivorship care models for low-risk breast and gynecologic cancer patients. <b>Methods:</b> We conducted exploratory research among low-risk breast and gynecologic cancer survivors and primary care providers to inform a subsequent intervention of navigated care transitions. We convened a Patient Advisory Board (PAB) to review a structured menu of cancer survivorship issues, including access to primary care services, compliance with screening recommendations, treatment of comorbid conditions and identified the range of desired survivorship resources. We conducted five virtual PAB meetings via ZOOM, and participants completed four surveys. In parallel, we conducted semi-structured qualitative interviews with seven primary care providers (Family Physicians and OB/GYNs) to understand preferences of cancer survivor care transition timing and informational needs. Both PAB and Provider sessions/interviews were transcribed and coded for content and thematic analysis. <b>Results:</b> Participants in the PAB provided insight into survivorship experiences and processes to facilitate earlier care transitions. They emphasized the need to begin survivorship planning at an earlier stage of care and advocated for the creation of tailored documents relevant to the care needs of particular stages (e.g., diagnosis, definitive treatment, care transitions). Lastly, they identified other overlooked care needs, including adverse effects on sexual health. Primary care provider data aligned with PAB findings, including the need to initiate enhanced communication with the oncologists immediately following diagnosis. Additionally, providers expressed confidence in managing survivorship care based on responses to structured vignettes of breast and gynecological cancer patients. <b>Conclusions:</b> This formative research identified key factors with regard to the development of processes and informational resources necessary to support cancer survivorship care transitions among underserved and rural breast and gynecologic cancer patients. In alignment with findings from primary care providers, this model would focus on initiating survivorship support at an early stage of care, include a broad "menu" of potential patient care needs, and ensure provider training and awareness related to surveillance and referral pathways. Further research to test the feasibility of this model is underway.