Objectives/Goals: Injury to the medial knee ligaments (sMCL, dMCL, POL) and anterior cruciate ligament (ACL) can cause anteromedial rotatory instability (AMRI). AMRI can cause knee instability and ACL graft failure, but it is unclear how the sMCL, dMCL, POL, and ACL resist AMRI. We aimed to characterize the in-situ forces of the sMCL, dMCL, POL, and ACL under loading conditions involved with AMRI. Methods/Study Population: We characterized the in situ forces of the sMCL, dMCL, POL, and ACL under 1) isolated external tibial rotation torque (ER), 2) isolated anterior tibial force (Ant), and 3) combined ER+Ant loading. Twenty-eight human cadaveric knees (18 male; mean age, 48±13; 21–65 years) were tested on a robotic manipulator with force sensing. Tibiofemoral kinematics were recorded under isolated ER (4Nm, 0–90°), isolated Ant (134N at 0–90°), and combined ER+Ant (4Nm+100N at 15, 30, 90°). The sMCL, dMCL, POL, and ACL were dissected in random order. The in situ force (N) in the sMCL, dMCL, POL, and ACL at the peak applied load for each loading condition was calculated using superposition and compared with Kruskal–Wallis tests with post hoc pairwise testing using a Bonferroni–Holm correction for multiple comparisons (α = 0.05). Results/Anticipated Results: Under isolated ER, the force in the sMCL (32–52N) from 0°-90° exceeded that of the ACL, dMCL, and POL at each flexion angle (p0.05). Force in the ACL was the second highest (26–6N from 0°-90°). Force in the dMCL and POL was low (≤12N). Under isolated Ant, the ACL carried the highest force at all flexion angles (≥113N) (p0.05), but at 90° the sMCL carried the highest force of all ligaments (p0.05). At 90°, force in the dMCL diminished (Discussion/Significance of Impact: We show that the sMCL is the major stabilizer to external rotation torques and combined anterior and external loading conditions related to anteromedial rotatory instability across the arc of knee flexion, while the dMCL, POL, and ACL play a less prominent role, with the exception of the ACL and dMCL near full extension.

Objectives/Goals: The impact of the program on alumni students was measured in a 2023 survey, which assessed key factors and student perspectives on motivation to apply/remain in the program, their engagement activities, how they used the skills acquired in RAP upon graduating, and if they were currently serving in a health profession and/or clinical research. Methods/Study Population: Survey questions were based upon specific components of CTSI-RAP that make it unique. Covered topics related to motivation for participation, meaningful experiences, program effectiveness, future use of RAP knowledge/training, and current career roles in the health professions and/or clinical research. The survey was built and analyzed in REDCap and deployed May–July 2023. The study received exempt certification from the IRB. The survey was sent to 123 alumni from the 2013 to 2021 cohorts. Bounced e-mails were followed up on and two reminder e-mails were sent to initial non-responders. Identifiable demographic information was separated from program evaluation questions for analysis. A subanalysis was performed to determine program impact on students who identified as underserved or disadvantaged. Results/Anticipated Results: Respondents included 82/123 (66.7%) alumni. The survey took approximately 15 minutes. Most of the students 64/82 (78.0%) had 1 year or less research experience. The top three motivating factors for joining the RAP program were gaining clinical research experience, exposure to healthcare settings, and interest in pursuing a healthcare related career. Most alumni rated the overall effectiveness of the RAP program as very or somewhat valuable and the majority felt that the program ranked high or very high among their undergraduate experiences. The program was very influential or influential in defining their long-term plans and goals. Just under half felt that their career aspirations were changed or influenced by the program, which was especially true for those who identified as underserved/disadvantaged. Discussion/Significance of Impact: CTSI-RAP alumni highly value their experience in the program. They have benefitted professionally and are motivated to keep their connection to the program alive. With a decade of clinical research excellence and programming, CTSI-RAP’s impact is well established as a proven model benefiting both students and the clinical research infrastructure.

Objectives/Goals: The expanding emphasis on translational science necessitates a rethinking of traditional academic formats. To align with the central themes of CTS, we have redesigned our PhD journal club and WIP sessions, introducing novel and innovative approaches that enhance the relevance of these activities to real-world scientific and clinical challenges. Methods/Study Population: The newly adapted journal club format for CTS Predoctoral students at Mayo Clinic maintains the traditional focus on literature review but now incorporates a structured analysis of the clinical implications and potential applications of the research. This innovation aims to foster a deeper understanding of how basic research findings can be translated into improved patient outcomes and healthcare practices. Similarly, the WIP sessions have been restructured to offer an engaging and dynamic learning environment designed to empower clinical and translational science predoctoral students to effectively present their research while emphasizing the challenges they have overcome, demonstrating the translational potential of their findings, and enhancing their communication skills. Results/Anticipated Results: Feedback from participants demonstrates strong support for the new format. Students report a greater engagement with the material and a clearer understanding of how their research can contribute to improving patient outcomes. Discussion/Significance of Impact: These changes accommodate the diverse projects in CTS and embody a commitment to pushing the boundaries of knowledge in CTS. This dual transition marks a significant advancement in preparing PhD students for careers in translational science, ensuring that their research is not only rigorous but also impactful in the real world.

Objectives/Goals: As a priority area in translational science, rural health research can benefit from informatics methods for conducting thematic and environment scans. This study demonstrates an efficient approach to gaining insights about the rural health research literature by automated bibliometrics analysis. Methods/Study Population: We developed an automated pipeline to retrieve the 1972–2023 PubMed publications indexed with the MeSH terms “Rural Health” and “United States”. The article metadata in XML format were downloaded and parsed, including title, year, journal, author institutions, and MeSH terms. Each institution address was augmented by Google Maps API to obtain the county and latitude/longitude coordinates. Summary statistics were computed for the publication years, journals, author departments, and locations. A topic network was generated from the frequent co-occurring MeSH terms. The institutions were linked to Rural-Urban Continuum Codes and labeled on a map to visualize their geographic distribution. Results/Anticipated Results: A total of 4564 articles on rural health were analyzed. Two salient peaks of publications were revealed, one around 1978 and the other around 1993. The top author departments include Family Medicine, Nursing, Pediatrics, and Epidemiology. The five leading institutions reside in Chapel Hill, Minneapolis, Iowa City, Seattle, and Atlanta. The geographic distribution shows few institutions that reside in deep rural areas are well published on rural health, although the most scholarly productive institutions do seem adjacent to some moderately rural pockets. The frequently identified topics pertain to age group, study design, and specific concepts such as health services accessibility. Discussion/Significance of Impact: The two publication peaks in history were likely linked to certain policy milestone or seminal publication. Primary care and epidemiology departments have been most active in rural health research. Of concern, the geographic distribution of authors suggests under-investment in rural institutions.

Objectives/Goals: Academic research centers struggle to recruit and retain a diverse, competent clinical and translational science (CTS) workforce. The clinical research professional career pathway is particularly underrecognized among undergraduates, despite offering multiple career opportunities. Methods/Study Population: To address these challenges, two undergraduate outreach programs were developed. First, an undergraduate certificate program in CTS (UC-CTS) was designed to equip students with the skills and knowledge needed to enter the workforce immediately after graduation. Second, a “CTS Roadshow” was launched to build awareness of CTS careers within a variety of undergraduate programs and majors. In this recruitment initiative, principal investigators (PIs) and CRPs visit classrooms to share information about CTS career pathways and offer insights into the roles, responsibilities, and professional opportunities available in the field. Results/Anticipated Results: The UC-CTS program launched in Fall 2024 as a 12-credit certificate that includes two paid internships: one in patient care and one in research. Currently, the program has 5 students enrolled with an anticipated increase in enrollment to 20 students by Spring 2025. Similarly, the CTS Roadshow has reached an increasing number of students each year. Since its inception in Spring 2023, the CTS Roadshow has introduced over 750 undergraduates across 21 courses to CTS careers. The CTS Roadshow has engaged students from a variety of majors, including biology, psychology, medical sciences, legal, finance, accounting, and pre-health programs, increasing awareness of and interest in CTS careers. Discussion/Significance of Impact: Both programs aim to expose students to CTS careers early in their education, better preparing them for full-time CTS roles after graduation. A rise in qualified applicants pursuing CTS careers locally and regionally is expected, improving job satisfaction and retention through enhanced preparation for the career field.

Objectives/Goals: Our research addresses critical gaps by examining the prevalence, blood concentrations, and health implications of xylazine abuse, with a focus on its cardiotoxic effects. We aim to map the geographic distribution of xylazine use across Puerto Rico and characterize its impact on cardiomyocytes at relevant exposure levels. Methods/Study Population: To accurately detect and quantify xylazine in blood samples, we will employ chromatographic techniques coupled with mass spectrometry (UPLC/MS or GC/MS). The xylazine prevalence across the island will be mapped based on health system classifications. Samples will be categorized according to the eight healthcare regions of Puerto Rico, as defined by the “Administración de Seguros de Salud” (ASES), ensuring comprehensive geographic representation. We will investigate the expression profiles of proteins associated with cardiac injury and dysfunction in human cardiomyocytes and in the blood of drug users. Blood samples will be provided by “Iniciativa Comunitaria.” We will assess the xylazine effects on human cardiomyocyte viability and identify key biomarkers of cardiotoxicity induced by xylazine exposure. Results/Anticipated Results: In previous research, we demonstrated that xylazine induces cell death in endothelial cells through both extrinsic and intrinsic pathways. We also observed an increase in reactive oxygen species (ROS) levels after drug exposure, indicating oxidative stress as a potential mechanism of toxicity. Additionally, DNA damage was detected. Given the known relationship between endothelial damage and cardiomyocyte dysfunction in drug-induced cardiotoxicity, we hypothesize that xylazine concentrations vary regionally within Puerto Rico and that chronic xylazine abuse will elevate markers of cardiac injury and dysfunction at common user doses. Discussion/Significance of Impact: The increasing xylazine abuse, particularly in Puerto Rico, represents a critical public health challenge. Our study will fill a knowledge gap by providing crucial data on xylazine’s cardiotoxicity and mapping its geographic prevalence, with the potential to advise healthcare approaches and improve care for drug-using Hispanic populations.

Objectives/Goals: Aged keratinocytes are less proliferative than adult, and aged skin heals more slowly. We examined the proliferation kinetics of aged and adult human keratinocytes. We then tested whether an extrinsic agent, sh-oligopeptide-72, can ameliorate these defects. Methods/Study Population: We used live cell imaging (LCI) to examine the proliferation kinetics of aged (73–92y) and adult (34–49y) passage zero human keratinocytes. We then incubated aged keratinocytes with a peptide, sh-oligopeptide-72 (purported to improve keratinocyte proliferation), or vehicle (PBS). Lineage trees of cell divisions were constructed to determine cell cycle duration and the proliferation/differentiation outcomes of each division. To assess wound healing, cells were isolated from 3 patients, 82–92y, and plated in 2-well culture dishes with inserts. Wells were treated with sh-oligopeptide-72 (100 ng/ml) or vehicle (PBS). At confluence, the insert was removed leaving a well-defined 500 μm gap. The time until 100% closure of the defect was obtained using LCI and the wound healing size tool. Results/Anticipated Results: There was no significant difference in the number of stem cell (SC) colonies between aged and adult keratinocytes. However, aged keratinocytes produced more aged committed progenitor (CP) colonies (P<0.0001). Adult CP, but not stem, colonies were significantly larger than aged (P = 0.0001), and this was associated with earlier terminal differentiation (P = 0.0005). Aged SC and CP colonies exhibited a higher proportion of differentiation divisions, and their cell cycle duration (CCD) was increased. Sh-oligopeptide-72 rescued the increased terminal differentiation as well as decreased the CCD in SC colonies. Sh-oligopeptide decreased the mean closure time of the wound assays (143h vs. 204h, P = 0.04). Discussion/Significance of Impact: Sh-oligopeptide-72 reversed many of the proliferation defects that develop in aged SC colonies. Wound assays show that this results in improved keratinocyte function. These results suggest that the age-related changes in growth dynamics can be modified in response to extrinsic signals in vitro.

Objectives/Goals: Optimal hydrocephalus treatment with permanent cerebrospinal fluid (CSF) diversion in myelomeningocele (MMC) patients is not well understood, especially how treatment response varies with time of MMC repair. We evaluate two treatment methods in this population–endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting (VPS). Methods/Study Population: We retrospectively identified patients from St. Louis Children’s Hospital who were diagnosed with MMC prenatally and underwent either prenatal or postnatal repair and subsequently underwent permanent treatment for hydrocephalus (VPS or ETV +/- choroid plexus cauterization) between 2018 and 2024. The primary outcome was failure (defined as need for revision) of procedure and time to failure. All revisions were shunt insertions/revisions. Differences in preoperative and 6-month postoperative head circumference (HC) and WHO standard HC z-score were examined. Differences in preoperative and 6-month follow-up fronto-occipital horn ratios (FOHR), a validated age-independent measure of CSF within the brain, on CT and MRI were additionally examined. Results/Anticipated Results: Eighty-three MMC patients were identified. 46 (55%) underwent CSF diversion: 37 (80.4%, 9 pre- and 28 postnatal) VPS and 9 (19.6%, 5 pre- and 4 postnatal) ETV +/- choroid plexus cauterization. Six (16%) VPS patients required revision vs. 3 (33%) ETV patients (∆17%; 95% CI -9 – 50). Mean time to failure was longer after VPS vs. ETV (516, SD 470 vs. 34, SD 7 days) [∆482; 95% CI 163 – 800]. The decrease between pre- and postoperative FOHR was greater after VPS vs. ETV (6 mo: -0.14, SD 0.10 vs. -0.03, SD 0.07) [∆0.11; 95% CI 0.04 – 0.18]. Differences in pre- and postoperative HC were similar (VPS 5.67, SD 2.91 vs. ETV 4.04, SD 1.66 cm) [∆1.63; 95% CI -0.71 – 3.98]. Greater, but not significant, z-score decreases were seen after VPS vs. ETV (-1.04, SD 2.22 vs. -0.13, SD 1.11) [∆-0.91; 95% CI -2.68 – 0.86]. Similar trends were observed in pre- and postnatal MMC repair groups. Discussion/Significance of Impact: Failure rates in MMC-associated hydrocephalus patients were greater in the ETV group, but no definitive conclusion can be made due to imprecision. Those treated with ETV have less time to failure and smaller FOHR decreases than those treated with VPS, indicating less CSF drainage. Due to the need for more subjects, future research should be multicenter.

Objectives/Goals: SARS-CoV-2 infection has been shown to impact multiple organ systems, including the brain, and is associated with increased cognitive decline in vulnerable populations. The gut microbiome may play a significant role in modulating these effects, as shifts in microbiota composition have been linked to inflammation and systemic disease processes. Methods/Study Population: To explore these interactions, we conducted an acute COVID-19 study using 12-week-old C57 mice intranasally inoculated with 1x10^4 PFU of the Mouse Adapted 10 (MA-10) strain of SARS-CoV-2. On day 5 postinfection, we performed 16S ribosomal RNA sequencing on fecal samples, analyzed using QIIME2 and DeSeq2, to assess microbiome alterations and identify changes in metabolic pathways associated with inflammatory responses. Results/Anticipated Results: Analysis revealed notable shifts in the gut microbiome during the acute phase of COVID-19 infection, with significant alterations in metabolic pathways related to inflammation and immune regulation. These changes suggest that early gut microbiome disruptions may contribute to the host response in acute COVID-19. Discussion/Significance of Impact: Our findings indicate that acute SARS-CoV-2 infection leads to rapid alterations in the gut microbiome, which could underlie inflammatory and immune pathways impacting disease progression. These insights highlight the potential for microbiome-targeted therapies to mitigate acute COVID-19 morbidity and warrant further investigation.

Objectives/Goals: 1. Build a network of stakeholders (WomenWise) empowered as a Community Advisory Board (CAB). 2. Expand knowledge about patient-centered outcomes research (PCOR) and comparative effectiveness research (CER), specifically related to alcohol use in women. 3. Report facilitators, barriers, and CAB members’ experience with developing WomenWise. Methods/Study Population: Female stakeholders from nonprofit organizations (NPOs), persons and family members with lived experience with alcohol misuse, and health professionals were organized into a CAB (n = 17). CAB members receive education on PCOR/CER and sex-related disparities in alcohol treatment and create resources for large-scale community dissemination. Members will also host partnered learning sessions in their community alongside NPOs to teach the public about alcohol misuse in women and engage in PCOR/CER. Surveys and descriptive statistics assess CAB members’ understanding of educational material, engagement, and project feasibility. A Governance Council of co-investigators, collaborators, patient representatives, and a CAB chairperson oversee project progress and completion. Results/Anticipated Results: Two CAB meetings were completed thus far, with five meetings continuing into the next year. The first two CAB meetings were attended by 14/17 (82%) of members. After receiving education on Research Fundamentals, among those completing the survey (11/14), the knowledge assessments scores were very high. The Governance Council began planning the first large-scale community dissemination symposium to be held in Summer 2025, and three additional CAB meetings will be held before the ACTS conference poster presentation. We will share data on the process to initiate this capacity-building project, PCOR/CER education, stakeholder engagement and feedback, challenges and responses, and overall evaluation of the project’s feasibility and sustainability. Discussion/Significance of Impact: Historically, women have been unrepresented in alcohol misuse research, and studies rarely analyze sex and gender differences. WomenWise, a network of women stakeholders knowledgeable about these disparities and PCOR/CER, will lead efforts to educate community members about alcohol treatment disparities and engage them in future research.

Objectives/Goals: This study will assess population heterogeneity in Candida bloodstream infections by quantifying antifungal resistance, fitness, and genomic diversity to understand clonality and develop a high-throughput screening tool to detect population-level resistance to update clinical practice. Methods/Study Population: This study assesses antifungal resistance and population heterogeneity in Candida bloodstream isolates collected through multiple Midwest hospitals. Blood samples are plated to isolate single colonies and population samples, which are then archived. We test resistance to key antifungals using EUCAST guidelines, conduct growth curve assays, and perform whole-genome sequencing to determine genetic diversity. A high-throughput screening method tracks colony growth under different drug conditions using time-lapse imaging and custom analysis software. The findings will reveal the extent of antifungal resistance and genetic variation within infecting populations, informing better clinical management. Results/Anticipated Results: Preliminary analysis of Candida glabrata bloodstream isolates show significant heterogeneity in colony morphology, antifungal resistance, and fitness. Some single colonies exhibit higher minimum inhibitory concentration values for micafungin and fluconazole than the overall population, while others show reduced susceptibility to amphotericin B, highlighting diverse resistance profiles. Growth assays reveal distinct fitness phenotypes within these populations. This variation underscores the limitations of single-colony testing and suggests a need for population-level resistance screening. We anticipate genomic analyses will identify genetic diversity underlying these differences, supporting a more comprehensive clinical approach to treatment. Discussion/Significance of Impact: This study reveals notable intrapopulation heterogeneity in Candida glabrata, including variations in colony morphology, antifungal resistance, and fitness. Findings highlight genomic diversity, introduce a novel screening method for resistance, and emphasize the need for population-level testing in clinical practice.

Objectives/Goals: This study’s objective was to explore how a personal cancer diagnosis impacts the social connectedness (i.e., quality, structure, and functions of social relationships) of adolescent/young adult cancer survivors (AYACS, patients diagnosed with cancer between 15 and 39 years old), to inform intervention development fostering social health. Methods/Study Population: In this qualitative study (part of larger study assessing AYACS’ psychosocial challenges), participants were 15–25 years old at the time of cancer diagnosis and within 6 years of cancer diagnosis. Participants (and consenting parents of participants 18 years old and older) had to have fluency in written and spoken English and access to a computer or smartphone. Qualitative interviewers utilized an interview guide to conduct individual participant interviews. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyze data using a phenomenological approach to explore how a personal cancer diagnosis impacted social connectedness. Qualitative data related to social connectedness (corresponding to code “Relationships and Support”) are presented. Results/Anticipated Results: Three themes emerged through thematic analysis: (1) AYACS experience substantial heterogeneity related to social support needs; (2) AYACS leverage multiple relationships and resources when seeking support after a personal cancer diagnosis; (3) AYACS’ individual experiences were unique in that some noted positive changes, whereas others noted negative changes in relationships within social networks, specifically with peers. Discussion/Significance of Impact: AYACS experience various social support needs, and leverage multiple relationships when seeking social support. These translational findings create a foundation to develop AYACS social programming, foster peer relationships, and incorporate social science methods to aid intervention development to strengthen AYACS’ social connectedness.

Objectives/Goals: To assess the impact of UCLA’s Clinical and Translational Science Institute Research Associates Program (CTSI-RAP), a student-led undergraduate clinical research initiative, on current members’ career interests and development. Methods/Study Population: To evaluate CTSI-RAP’s impact, we surveyed students using the REDCap platform between May and June 2023. The survey captured data on demographics, academic background, motivations for joining, and engagement in clinical research activities. Students also provided self-assessments of how the program influenced their career interests. Both descriptive and qualitative analyses were then used to assess key factors influencing students’ experiences, including the program’s impact on career decisions in healthcare and clinical research. Results/Anticipated Results: Out of 43 students surveyed, 40 responded (93%). Before entering, 84.2% of students had less than one year of research experience, and most students (73.6%) did not have family members in healthcare or research professions. Top reasons for joining were gaining clinical research exposure, healthcare setting experience, and pursuing healthcare careers. Overall, 97% of students stated CTSI-RAP “definitely” or “most probably” confirmed their interest in medicine and 76% of students reported CTSI-RAP has “definitely” or “most probably” solidified their interest in clinical research. 100% of students who have applied for a job, professional school, scholarship, or internship included CTSI-RAP as a meaningful experience, reflecting the program’s mission to provide motivations for a career in medicine and science. Discussion/Significance of Impact: Since its establishment in 2013, CTSI-RAP has expanded from 15 students to more than 50 annually, providing hands-on clinical research and professional development opportunities. The program’s peer-mentorship and student-led approach have proven effective in preparing students for diverse healthcare and research pathways.

Objectives/Goals: There has been a significant increase in the engagement of researchers with persons with lived and living experience, driven by a growing recognition of the invaluable insights and expertise these individuals bring to the research process. However, there remains a need for research teams to learn how to engage with patients and community partners. Methods/Study Population: The EMPOWER project is a collaborative of members with lived/living expertise of substance use during pregnancy. EMPOWER meets three times per month in support of their goals of patient-centered research, changing the narrative through conversations, and building the capacity of persons with lived experience to co-lead research. Through over 4 years of active collaboration and co-learning, EMPOWER has identified and created methods that support meaningful patient engagement and capacity building. Results/Anticipated Results: EMPOWER has identified the following methods that support meaningful engagement and capacity building: Mind-Mapping Exercises, Personal and Collective Journey Mapping, 8-month research training curriculum, Digital Storytelling, Learning Labs, and World Cafe Meetings. These methods have led to a collaborative of 20 individuals with lived experience of substance use to identify research gaps, prioritize research questions, design data collection tools, analyze research data, disseminate research results, and consult with healthcare teams in efforts to improve clinical care. To-date EMPOWER have given over 10 invited presentations and is currently writing manuscripts. Discussion/Significance of Impact: Meaningful patient and community engagement is critical to developing and implementing healthcare interventions. Unfortunately, engagement efforts are often lack in building capacity of patients and community, which impedes their ability to fully engage in all phases of research.

Objectives/Goals: Goals for this work include identifying areas for continuous curricular improvement as well as documenting best practices in multidimensional mentoring in innovation. Programmatic goals include pivoting early career scientists toward translational science solutions that are commercially viable. Methods/Study Population: Using Likert-scaled perception surveys of fellowship participants, preliminary pre- and post-fellowship responses are presented. Preliminary regression analyses are used to identify trends in participants’ ratings across innovation pathways and customer-focused design. Results/Anticipated Results: Focusing on the initial cohort of fellows’ perceptions of their competencies in the areas of technology propositions and industry networking, we observed a near twofold improvement reported competency, suggesting a key strength area for the Fellowship program. Discussion/Significance of Impact: First of its kind at Penn State College of Medicine, the Center for Medical Innovation’s partnership with Clinical and Translational Science Institutesignals enhanced commitment to developing early career fundamental scientists in the areas of intellectual property, customer-focused design, and commercialization. Significance of this work includes capturing best practices.

Objectives/Goals: Our objective is to examine patient and community perspectives on hospital actions that signify accountability to healthcare equity; part of our overall goal is to identify equity measure concepts representative of community perspectives and priorities for future hospital accountability programs. Methods/Study Population: We conducted a qualitative thematic analysis of secondary data – 32 focus group transcripts from our hospital’s Community Health Needs Assessment (CHNA). A tri-annual CHNA is required of nonprofit hospitals to maintain tax exemption. Diverse participants were recruited from our hospital’s large catchment area. Coding focused on responses to 6 pertinent questions. We adapted the National Committee for Quality Assurance, “Health Equity Measurement Framework for Medicaid Accountability” which consists of 5 domains (access, clinical, experience, structure, and social) to guide the development of our a priori coding tree and subsequent analysis. Two coders double-coded 25% of transcripts. The multidisciplinary research team, including community partners, met iteratively to extract and refine themes. Results/Anticipated Results: We organized our analysis by our conceptual framework’s 5 measurement domains. The “access” and “experience” domains were the most salient for participants. We defined “access” by four sub-domains: financial access, physical access, communication access, and navigability; and “experience” by two subdomains: inclusivity and accomodation. Beyond discussing concepts within these measurement domains, participants debated the “scope” of the hospital’s role with regard to healthcare equity. While some did not think “it was the hospitals” responsibility to give people access to good jobs or fair pay, education…, “other participants felt that healthcare involves not just addressing peoples’ physical health but. their housing… because how can someone take care of their health when they are homeless?” Discussion/Significance of Impact: When asked about hospital accountability to healthcare equity, “access” and “experiences” of care are the most salient measurement domains for patients and communities. The “scope” of the hospital’s role is debated. Policy and health system leaders can apply these perspectives to equity measurement initiatives.

Objectives/Goals: Cardiovascular disease, particularly myocardial infarction (MI), is a leading cause of death in the USA. Previous studies have identified CD8+ T-cells as adverse regulators post-MI. We hypothesized that CD8+ T-cells impair cardiac function by altering scar composition. Methods/Study Population: MI was induced by permanent ligation of the coronary artery in C57BL6/J (WT; 3–7 mo) and CD8atm1mak mice (CD8-/-; 3–7 mo). CD8-/- mice were injected with either vehicle or naïve splenic CD8+ T-cells (2x10^6 cells/injection) via tail vein, 4 hours after ligation. Tissue was collected at Day 7 post-MI for biomechanical testing and further downstream analyses. Granzyme (Gzm)A, B, and K were tested for collagen cleavage using a fluorogenic cleavage assay. Effect on collagen production in TGF-β-activated cardiac fibroblasts was assessed in vitro by stimulating cells with GzmA, B, and K (25 AU) for 24 hours. Results/Anticipated Results: CD8-/- mice had improved ejection fraction and LV dilation at Day 7 post-MI compared to WT and CD8-/- mice resupplemented with splenic CD8+ T-cells (p Discussion/Significance of Impact: Our study demonstrates that CD8+ T-cells regulate cardiac fibrosis partially through Gzm release, resulting in left ventricular biomechanical impairments and increased dilation.

Objectives/Goals: The primary objectives of this project were to create a user-friendly website that • Shares details of ongoing studies in an easily searchable and filterable format. • Provides lay summaries of study results. • Highlights our volunteer registry. • Offers a platform for community engagement and feedback on research interests. Methods/Study Population: The website, developed using DRUPAL 10 and launched in June 2024, was created with input from faculty, staff, research participants, and community partners. It targets potential participants, community members, providers, and other Academic Medical Centers. The development process included focus groups to identify design and feature needs, design iterations and usability testing, and an external accessibility review. Study information is automatically updated from the Study Information Portal (SIP) in OnCore and a custom REDCap survey. Features include a research volunteer registry, study results in lay terms, educational content about research, and multiple ways for community engagement. The site supports English and Spanish and follows best practices for accessibility. Results/Anticipated Results: Community feedback on the site has been very positive, with positive comments about ease of navigation and the improved appearance of the website. It is still early, but we have seen a notable increase in enrollment in the Volunteer Registry since the launch of the website. We track referral sources for the registry, and to date, we have seen 98 individuals enrolled who were directed to us through the website since it launched. This equates to an average of 5 people a week, more than any other referral source. This rate increases to almost 7 per week if we look solely at the period since we started the promotion of the website in early August. As the site awareness expands, we will also be getting feedback from individual studies and are tracking email communication generated from the site as well. Discussion/Significance of Impact: The development of this website represents a significant step toward improving community engagement in clinical research at Duke. By providing a centralized platform for study information, results, and community feedback, we aim to foster a more informed and involved participant base, ultimately enhancing the impact and reach of our research.

Objectives/Goals: Dissemination and implementation scientists often conflate or confuse pragmatic trials and effectiveness-implementation trial designs. This study evaluates the barriers and facilitators affecting these scientists’ collaborative work to design, plan for, and conduct these different kinds of trials. Methods/Study Population: This is a sequential mixed-methods study. For the quantitative evaluation secondary data collection and surveys of roughly 200 investigators constituting an Implementation Science Network were carried out to identify research needs and impacts associated with the Translational Science Benefits Model. Surveys were prepopulated with respondents’ grant awards and prompts to define the study designs being used. Interviews of respondents are being conducted to identify barriers and challenges they faced in conducting different implementation trials and to develop case studies of their resultant research agendas. A peer-reviewed interview protocol designed for Clinical and Translational Research Institutes to conduct case studies of translational research is being used for this qualitative evaluation. Results/Anticipated Results: The 182 ISN members submitted 1590 research proposals since 2020, 52% of which were funded. ISN members responding to surveys (N = 30) self-identified many of these studies as being Hybrid 3 (29%), Hybrid 1 (17%), or Pragmatic trials (7%), although the largest proportion included studies classified “other” (33%), and some could not be classified (12%). Surveys of ISN members also indicated that many want to conduct pragmatic trials (36%) or hybrid trials (8%) but need more opportunities to collaborate (19%). Twelve (40%) ISN members agreed to be interviewed and another 11 (37%) indicated that they would do so in fall 2024 if available. Initial findings suggest that regular interactions with colleagues helped investigators new to the field understand how varied study designs could advance their implementation science. Discussion/Significance of Impact: These findings will show how U-M implementation scientists collaborate to conduct implementation trials. If the kinds of barriers faced by investigators differs by trial type, research supports and initiatives can be tailored to better support all implementation scientists in the CTSA Consortium.

Objectives/Goals: In January 2023, Mayo Clinic set a goal to have 10% of studies open for six months or more without accrual. At that time, Mayo Clinic Florida had 19% non-accruing studies and 18% non-accruing clinical trials. Research administration implemented strategies to improve accrual outcomes. Methods/Study Population: Two strategies were developed to address non-accruing trials: a clean-up approach and a proactive approach. The clean-up approach involves escalating studies that haven’t been enrolled in over 6 months, identifying barriers, and escalating communication with the principal investigator (PI) and research administration alongside a physician partner. The proactive approach targets studies at the 3-month mark to address issues before reaching 6 months without accrual. Both strategies aim to reduce the cost and effort of non-accruing studies by either creating an enrollment plan or closing the study. Results/Anticipated Results: Since implementation, Mayo Clinic Florida’s non-accruing study portfolio decreased by 10%, and its clinical trials non-accruing portfolio decreased by 7% as of October 2024. Research Administration tracks key metrics (reasons for no enrollment, justifications, and actions) to identify trends and mitigate future accrual risks. A REDCap electronic data capture tool hosted at Mayo Clinic (supported by CCaTS grant UL1TR002377)1 notifies principal investigators when their studies are non-accruing. Future plans include establishing an API with Mayo Clinic’s portfolio management system to streamline the process while maintaining awareness and collaboration. Discussion/Significance of Impact: Through increased monitoring, enhanced communication, and deeper collaboration, Mayo Clinic Florida effectively reduced non-accruing studies in its research portfolio. This approach minimizes effort and costs associated with under-enrolled studies while tracking key metrics to inform future study development.