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.

Objectives/Goals: Mayo Clinic’s Clinical Trials Beyond Walls™ (CTBW) program collaborates with study teams to implement decentralized elements in clinical trials, enabling participation from home or local settings. In cancer treatment trials, traditional paper pill diaries are replaced with real-time digital tracking solutions to monitor chemotherapy adherence. Methods/Study Population: The CTBW team developed a solution to deliver electronic pill diaries to research participants using the electronic health record (EHR) system Epic and patient portal MyChart1. The solution includes a portal message to remind participants to take chemotherapy. Medication dose, date taken, and reasons for missed doses (e.g., “I forgot” or “side effects were bothersome”) are captured. An automated in-basket notification system alerts the study team when predefined conditions are met. Configurable medication schedules ensure diaries are sent according to the prescribed frequency. Reports were generated to allow study teams to monitor all participant diaries. Results/Anticipated Results: The CTBW team implemented this digital pill diary in neuro-oncology trial NCT066250472. We anticipate the pill diary in the patient portal will enhance chemotherapy adherence by capturing real-time data in a platform widely used by Mayo Clinic patients. This patient-reported data is stored in the EHR, where it is accessible to providers and study teams. This allows for continuous monitoring, which facilitates a streamlined review of potential adverse events, improved compliance visibility, and timely treatment adjustments compared to paper-based or external solutions. The system also streamlines data entry, reducing human error and eliminating manual transcription. The created language and workflow templates allow the CTBW to scale this approach to future cancer trials Discussion/Significance of Impact: Decentralized clinical trial participants may never visit Mayo Clinic, making digital recording essential. The EHR-based digital pill diary enables continuous monitoring within a familiar system for providers and patients, increasing study team visibility, and allowing for earlier intervention in cases of non-compliance or adverse events.

Objectives/Goals: Create a supportive Clinical Research Coordinator (CRC) and Clinical Research Nurse consortium at UF. Facilitate mentorship groups to enhance knowledge on key topics. Build strong professional relationships among members. Empower members through collaboration. Develop future leaders and mentor in clinical research. Methods/Study Population: The CRC Group Mentorship Program at UF’s Gainesville and Jacksonville campuses addresses mentorship needs identified in a recent needs assessment, reflecting strong interest among CRC/CRNs. Small groups are formed using the Group Mentorship and Co-Mentoring Circles models, meeting bimonthly for six months on shared research interests. Co-lead mentors guide learning, peer support, communication skills, and goal setting while tracking progress. Mentees engage in peer learning, skill development, and networking. A dedicated Microsoft Teams platform provides resources to enhance confidence in Joint Task Force Clinical Trial Competencies and fosters collaboration through Q&A sessions, activities, assessments, and meetings, improving real-time and asynchronous interactions. Results/Anticipated Results: To measure mentor program impact, pre- and post-program surveys assess changes in knowledge, skills, and confidence among mentors and mentees, providing insights into effectiveness and areas for improvement. Monthly, the program features two meetings focusing on Joint Task Force competencies: a workshop for all groups on essential mentorship and CRC/CRN competencies, followed by evaluations, quizzes, and continuing education credits. The second meeting is group-specific, led by co-lead mentors, requiring submissions that demonstrate the application of learned knowledge and skills. This structure ensures continuous relevance and quality enhancement in future programs. Discussion/Significance of Impact: The program meets CRCs and CRNs’ critical needs through structured mentorship, fostering a supportive environment. It promotes continuous learning and professional development, enhancing job satisfaction and ensuring the sustainability of valuable research professionals.

Objectives/Goals: This research aims to modify an existing regulatory benchmarking framework, initially designed for medical products, to assess cosmetic product regulations in different countries. This tool will provide qualitative and quantitative comparisons of global regulatory approaches to cosmetics. Methods/Study Population: The World Health Organization’s global benchmarking tool (GBT) was selected as a suitable template for the adapted methodology. The GBT contains a comprehensive set of functions, indicators, and sub-indicators defining the high regulatory maturity standard. Although the 269 sub-indicators are tailored to the regulation of medical products, they can be intentionally adapted for other products. Relevant indicators specific to cosmetic regulation will be identified to construct a customized benchmarking tool. This tool will then be used to assess the regulatory maturity of selected countries and regulatory authorities, including the United States, the European Union, Japan, India, Brazil, China, Ethiopia, and Nigeria. Results/Anticipated Results: Preliminary analysis indicates a lack of harmonized standards for regulatory maturity across the global cosmetic market. The recent passage of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) has strengthened the United States’ regulatory framework, incorporating 11 of 13 adapted maturity indicators. The United States joins the European Union (10/13 indicators) and Japan (8/13 indicators) as leaders in cosmetic safety and manufacturing transparency. Common basic policies included good manufacturing practice regulations, while more advanced regulations cover adverse event reporting and premarket requirements. Discussion/Significance of Impact: Cosmetics, supplements, and homeopathic products lack transparency regarding safety and quality requirements. This project establishes a benchmark for cosmetic product regulation, addressing a historic gap in oversight. The benchmark supports regions with less developed regulatory policies to enhance cosmetic safety and quality standards.

Objectives/Goals: The demands on MICHR’s Evaluation team are profuse and varied. Quarterly team meetings were used to keep track projects, identify new projects, and relay important new initiatives from MICHR leadership. The MICHR Translational Innovation team took on the task of assessing the Evaluation team’s processes to design better workflow and effectiveness. Methods/Study Population: The process included 5 stages, Empathize, Define, Ideate, Prototype and Test. Sixteen interviews were conducted with MICHR faculty and staff. Interviews were coded and summarized. Seventeen themes were mapped and distilled into 5 key insights. From the key insights, design principles were identified to guide a design session with Translational Innovation staff and Evaluation staff. New work processes were proposed, designed, and tested by both teams. The Evaluation team “test-drove” the prototype and iterative design sessions were conducted to determine which new elements were successful. The Evaluation team was positioned to begin utilizing the newly designed process at the beginning of MICHR’s new grant year. Results/Anticipated Results: The MICHR Evaluation team is instrumental to the development, conduct, and dissemination of Clinical & Translational Science (CTS), a primary objective of MICHR’s work. Three types of evaluation projects were identified through the design process: required reporting, CQI/program improvement, and CTS/impact evaluation. The service design process enabled the Evaluation team, and MICHR program leads to better identify and prioritize collaborations between the Evaluation and program teams that improved the quantity and quality of MICHR CTS outputs. Discussion/Significance of Impact: Generating CTS is critical to the missions of NCATS and MICHR. Thoughtfully designing processes that facilitate and increase CTS output that can be shared and duplicated across the consortium is invaluable.

Objectives/Goals: Early childhood obesity is a major concern for Latin American children in the U.S., with gut barrier dysfunction as a key risk factor. Diet plays a role in gut development, but few studies have focused on Latin American infants. Our objective is to identify culturally relevant introductory foods that promote in vitro gut barrier development and function. Methods/Study Population: Pooled human milk (2.5 mL) from 6-month postpartum Hispanic mothers was combined with fruit and vegetable baby food products (2.5 g) and subjected to a 3-phase in vitro digestion system that simulates oral, gastric, and intestinal digestion. Digesta products were then anaerobically fermented for 24-hours using human stool inoculum, centrifuged, and filter sterilized. Intestinal epithelial cells (Caco-2, ATCC) were grown to confluence on 0.4 μm polystyrene transwell inserts using a DMEM + 10% FBS medium and allowed to differentiate for 21-days. Highly differentiated monolayers were treated with a 1:4 dilution of fermenta with medium in triplicate. The cell experiment was conducted twice. Cell layer integrity was measured using transepithelial electrical resistance (TEER) 24- and 48-hours after treatment. Results/Anticipated Results: Dietary intake data from the What We Eat in America database indicated that the top 3 fruit and vegetable exposures for infants with Mexican or Hispanic ethnicity were banana, apple, and carrot. Commercial baby food purees of these fruits and vegetables, in addition to baby foods with blueberry and spinach (Natural for Baby, Gerber Products Company) were acquired for digestion and fermentation experiments. Caco-2 cell experiments with these foods are ongoing. We expect Caco-2 monolayer incubated with fermenta from human milk and fruit or vegetables will have greater TEER values due to increased integrity of the cell layer as compared to those with breast milk alone. We also expect that exposure to fruit and vegetable fermenta will increase gene expression of tight junctions compared to exposure to media and human milk. Discussion/Significance of Impact: Using an in vitro digestion and fermentation system coupled with cell culture studies, we are identifying cellular mechanisms that link individual fruits and vegetables to gut barrier function. This will support translational work focused on mitigating obesity development in vulnerable populations.

Objectives/Goals: • Investigate culturally-specific beliefs, caregiving approaches, care preferences, and unmet needs among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) care partners supporting persons living with dementia • Apply identified findings toward culturally-adapting caregiving resources for AANHPI dementia care partners Methods/Study Population: Qualitative data from the Better Together Dementia Care Study and Asian American, Native Hawaiian, and Pacific Islander (AANHPI) Dementia Caregiving Study were analyzed to investigate culturally-specific beliefs, caregiving approaches, preferences, and unmet needs of AANHPI dementia care partners. Both studies remotely conducted and recorded semi-structured interviews (1.5–2.5 hours), with care partners and providers though interview protocols were distinct. Transcripts were AI-generated, through Zoom or Trint, and analyzed using thematic content analysis by two coders. Apriori codes drawn from literature and inductively-identified codes were identified and coded. Preliminary findings informed sociocultural strategies used to adapt existing care partner resources for use in these groups. Results/Anticipated Results: Preliminary analysis of care partner (CP) interviews (N = 8; 4 romantic partners, 4 adult children), revealed differences in caregiving experiences and networks. CPs supporting care receivers (CR) who had emigrated away from extended family networks reported a lack of instrumental support. Most CR (7/8) had adult children, many of whom (6/8) provided some care, though half of CR-child relationships were distant or had past difficulties. Romantic partners were primary CPs while co-caregiving with children; Adult children served as primary CPs for unpartnered CRs (n = 4). Adapted CP resources integrated these findings, acknowledging the complexities of fulfilling traditional filial expectations in light of difficult past relationships. Formal services were framed as an extension of family-coordinated care. Discussion/Significance of Impact: Care partners of immigrants may have limited local family support and may benefit from formal services. Adult children may provide care, though this may be complicated by poor past relationship quality. AANHPI care partners may benefit from culturally-adapted resources which address these issues, though resource acceptability-testing is needed.

Objectives/Goals: Increased numbers of senescent cells have been detected in both traumatic brain injury and epilepsy, suggesting them as targets for therapeutic intervention for treating posttraumatic epilepsy (PTE) and underscoring the need for innovative methods to identify and target senescent cells as a means of alleviating pathology. Methods/Study Population: C57BL/6 mice will receive a single controlled cortical impact (CCI) before having their brains removed at 1 week, 2 weeks, 4 weeks, 1 month, 2 months, and 4 months post injury (n = 5 per time point). Brain sections will then be co-labelled for glial and senescent markers to observe which cells begin to express senescent markers at various time points. We will also perform single-cell RNA sequencing to observe genetic changes associated with both TBI and epileptogenesis. Mice will also be treated with navitoclax, a BCL2 inhibitor being investigated as a senolytic agent, to determine if treatment results in decreased senescence and epileptogenesis, as well as improved behavioral outcomes. Results/Anticipated Results: Preliminary data revealed that senescent microglia begin to arise in the mouse hippocampus as early as 1 week post injury and continue to increase in concentration over the course of the following month, with up to 25% of microglia expressing p16, a known marker of senescence. We anticipate that further staining will reveal senescent astrocytes and neurons in a similar time-dependent manner. Further, we hypothesize that the single-cell sequencing of microglia from injured mice will reveal alterations to the expression of genes associated with neuronal excitability, inflammation, and/or synaptic modeling, features known to be associated with epilepsy. Finally, we anticipate treatment with navitoclax will alleviate the senescent phenotype, resulting in decreased epileptogenesis and improved behavioral outcomes. Discussion/Significance of Impact: Considering the lack of any studies examining senescent cell prevalence in PTE, these data will be the first to identify these cells as etiological factors in PTE onset, as well as druggable targets for improving pathological outcomes in PTE patients.

Objectives/Goals: Children with intestinal failure rely on central venous catheters (CVCs) for at-home delivery of hydration and nutrition to sustain life. CVC associated infections are the leading driver of morbidity in this population. It is currently unknown what challenges caregivers of this patients face for at-home infection prevention tasks. Methods/Study Population: This is a qualitative analysis of the clinical implementation of at-home CVC care. Participants will be caregivers of children with intestinal failure in the Children’s Hospital of Los Angeles’ Intestinal Rehabilitation Program (a program with a large Spanish speaking population). The study team will conduct, record, and transcribe four synchronous remote focus groups using Zoom, two in English and two in Spanish, with 4–6 participants per focus group (n = 16–24). Questions will focus on caregiver experiences of CVC care. Transcripts will be analyzed using rapid qualitative analysis, an implementation science-oriented approach. The study team will review transcripts and summarize key points into matrices to examine relevant themes and quotes efficiently and systematically, using midpoint data analysis. Results/Anticipated Results: Illustrative quotes of all themes and domains discussed by caregivers will provide a person-centered overview of the specific types of facilitators and barriers to infection prevention task performance. Focus groups will be conducted in January 2025 with analysis in February. Facilitators and barriers will be mapped onto the Capability, Opportunity and Motivation behavioral model (COM-B), allowing for additional topics participants introduce by participants. Facilitators and barriers will affect all domains of the COM-B model and may also describe factors that cross multiple domains or fall outside the COM-B domains. Facilitators and barriers may differ between English and Spanish speaking caregivers. Discussion/Significance of Impact: Identifying facilitators of and barriers to infection prevention tasks will allow clinicians to maximize infection prevention efforts and improve quality of life for caregivers of children with intestinal failure. Additionally, this bilingual study will have improved external validity and address potential language-related barriers to care.

Objectives/Goals: Recognizing a critical need for sustained education and community beyond formalized training periods at Columbia University’s NCATS-CTSA, we created the TRANSFORM (TRaining And Nurturing Scholars FOr Research that is Multidisciplinary) Evolution program to preserve the networks cultivated during the KL2 program. Methods/Study Population: We will provide an overview of the genesis, expansion, key components, and programming for the TRANSFORM Evolution program. The program is designed for current and alumni of the KL2 program and late junior faculty that receive our CTSA’s Irving Scholar Award. TRANSFORM Evolution is a faculty and alumni network offering a platform to support the next generation of clinical and translational researchers while fostering a lasting community of collaboration and educational activities throughout a scholar’s career lifespan. Results/Anticipated Results: Salient components include the opportunities for social interaction, such as social/happy hours and member led education/career development sessions pertaining to topics that support thriving in an academic career. The program operates with financial resources and the support of a program manager. Evolution adopts a holistic, long-term approach, focusing on the entire professional lifespan by encouraging the development of enduring opportunities for our alumni. The program is intentionally structured to meet the evolving needs of its participants, through the beginning to more established phases in their professional careers. This continuity underscores the program’s capacity to adapt and remain relevant, informing and supporting sustained career progression and scholarly productivity. Discussion/Significance of Impact: The program has been an instrumental adjuvant in facilitating the transition to each career stage. By cultivating a community rooted in a common foundation – the KL2 and Irving Scholars programs, the program has created a robust support system that is crucial for the career development of clinician-scientists.

Objectives/Goals: This study assesses the feasibility of a human-to-swine lung transplant model for the evaluation of bioengineered organs. Given the critical organ shortage, this research explores bioengineered organs as a potential solution by evaluating early lung function, immune responses, and technical aspects to develop a model for bioengineered lungs. Methods/Study Population: The study employs a non-survival human-to-swine left lung transplant model in an immunosuppressed Yorkshire swine. A combination of cobra venom factor pretreated with methylprednisolone and Benadryl with scheduled dosing of tacrolimus and mycophenolate over a 24-hour period will be administered. The transplanted human lung is assessed over a 24-hour post-transplant period, with hourly pulmonary vein gas sampling and lung tissue resections. The proposed model will assess the immunological response of swine to human lung tissue as well as the efficacy of the immunosuppression model. Tissue samples are taken at intervals to evaluate for signs of rejection, cellular damage, and the overall function of the transplanted lung. All tissues are preserved in formaldehyde for subsequent immunohistology evaluation. Results/Anticipated Results: We anticipate a successful non-survival swine transplant model with pulmonary function sustained for the full 24-hour study using our proposed immunosuppression regimen. Initial testing with a standard human lung will lay the groundwork to assess the effectiveness of the human-to-swine transplant model. Hourly pulmonary vein gas analyses and tissue biopsies are expected to show minimal immune rejection, supported by the preoperative immunosuppression regimen. Early data indicate that the swine tolerates both the surgical procedure and immunosuppressive therapy well, with manageable hemodynamic stability. This model is expected to yield critical insights into lung viability and will identify areas for optimization for long-term survival studies to test the efficacy of bioengineered organs. Discussion/Significance of Impact: This non-survival swine model offers valuable insights into the acute-phase immune response and functional viability of human-to-swine lung transplant model. The findings will support the development of long-term survival models that will allow the evaluation of bioengineered organs based solely on their functionality as engineered organs.

Objectives/Goals: The Clinical and Translational Research (CTR) pathway aims to increase the number of health science professionals participating in CTR in their careers throughout the WWAMI Region (Washington, Wyoming, Alaska, Montana, and Idaho). Methods/Study Population: The first cohort of thirty-one students started in January 2024 and were organized into three groups that met weekly. One in-person group of students in Anchorage, AK; one in-person group in Seattle, WA; and a group of students from across the WWAMI region convened virtually. Students completed a year-long series of elective courses addressing fundamental concepts of designing, conducting, and presenting the results of a research project. Over the summer between year 1 and year 2 of medical school, students dedicated 8 weeks to full-time research activities under the supervision of their research project mentor. In Fall 2024, students prepared and presented research posters at regional poster sessions and abstracts and oral presentations for submission to the Western Medical Research Conference in January 2025. Results/Anticipated Results: The ultimate goal of the CTR pathway is to increase the number of medical providers across the WWAMI region with significant awareness, interest, and experience in research. Many students hesitate to engage in research due to a perceived lack of necessary skills. The CTR pathway addresses this gap by equipping students with the research competencies needed to participate confidently in scientific inquiry. Feedback from the inaugural cohort has been overwhelmingly positive, with many students highlighting how the CTR pathway enhanced their confidence and knowledge, empowering them to execute their proposed research projects successfully. Our second cohort of students joined the CTR pathway in January 2025. Discussion/Significance of Impact: The CTR pathway positions early medical students to engage in research more deeply during their medical training and prepares them to seek additional training opportunities toward a career in research. The majority of students in the first cohort were located at regional sites and many have interest in practicing in rural or underserved areas.

Objectives/Goals: Children with chronic respiratory technology needs (CRTN) are becoming a dominant patient group in pediatric intensive care units (ICUs). However, little is known about patient-level, long-term outcomes in this population. The lack of such knowledge may lead to inadequate ICU therapies, interventions, or follow-up care. Methods/Study Population: This project will deploy a set of ecological momentary assessment (EMA) modules measuring real-time functioning as well as standardized instruments to measure child and family outcomes including health care utilization, physical functioning, and health-related quality of life following pediatric critical illness in children with CRTN. EMA has particular strength in assessing conditions where individual-level characteristics vary over time, as after critical illness. EMA’s recurrent measurements allow for evaluation of the variables’ temporal course and limit the potential for bias associated with recall surveys. Pulmonary function in children with CRTN in this study will be monitored over time using standardized pulmonary metrics and information from home respiratory machines. Results/Anticipated Results: This work tests the central hypothesis that long-term functional outcomes in children with CRTN are predicted by multimodal data obtained during and shortly after critical illness. To date, 17 families (of a planned 70) have been enrolled. Adherence to EMA modules is high, with 80% completion. Following serial data collection at 3, 6, and 9 months after hospital discharge, phenotypes of recovery (including improvement, stability, or deterioration) will be described. This will include 1) describing the patient demographic and clinical features associated with each long-term outcome trajectory and 2) identifying subgroups with similar outcome trajectories using patient demographics, features of the clinical illness, and EMA data using both traditional biostatistical and causal analysis techniques. Discussion/Significance of Impact: This project will provide important insights into the long-term outcomes following critical illness of children with CRTN while utilizing an innovative methodology. This proposal will provide the necessary information to drive future clinical trials assessing potential interventions at a number of different points to improve outcomes.

Objectives/Goals: The aging population faces unique health issues, many of which are exacerbated by aging-associated immune function decline. However, the driving mechanisms behind this decline are poorly understood. We use a mouse model to study the relationship between extracellular matrix (ECM) stiffness and cell mobility within the lymph node (LN) as one potential driving mechanism. Methods/Study Population: We will collect LN from young (6 weeks old) mice and acquire LN from aged (11 month old) mice from a collaborator. We will section LN for ex vivo analysis, including quantification and localization of collagen I using immunofluorescent staining, analysis of microrheological properties using multiparticle tracking (MPT) with PEGylated fluorescent nanoparticles, and migration assays to track the movement of B and T cells. Results/Anticipated Results: We hypothesize a positive correlation between collagen deposits and stiffness within murine LNs due to known mechanisms underlying age-related fibrosis. We also hypothesize that areas of increased stiffness (as revealed by MPT) will exhibit decreased cell migration due to physical hindrance to B and T cell mobilization. Furthermore, we hypothesize that aged murine LN will exhibit a significant increase in stiffness and resultant decreased cell mobility when compared to young murine LN, particularly in areas with increased collagen localization. Discussion/Significance of Impact: These studies will elucidate structure–function relationships driving age-associated LN fibrosis and stiffness, and the resultant impedance to cell migration, thus clarifying some of the potential driving mechanisms behind immune aging and providing data capable of informing the development of relevant models and interventions.

Objectives/Goals: Undergraduate Medical Education (UME) may apply Just-in-Time training (JITT) to provide medical students with learning experiences closely aligned with real-time clinical needs. The purpose of this scoping review is to offer an overview of the implementation of JITT training in UME. Methods/Study Population: Following the five-stage framework by Arksey and O’Malley to methodically collect and analyze studies on JITT in UME, five electronic databases were searched, and a supplemental search for grey literature was conducted. Studies exploring the integration of JITT principles into UME clinical training and their time to follow-up after training were included. Bloom’s Taxonomy was used to assess educational goals of JITT interventions. Results/Anticipated Results: The review yielded 21 studies across 4 countries. The majority were cohort studies (13) and randomized control trials (5). Assessment definitions and use of JITT varied widely. Most studies focused on short-term outcomes, defined by being measured immediately after JITT session (15) or at the end of JITT-based rotation or clerkship (3). Three studies evaluated outcomes at a period longer than 2 weeks after completion of session or clerkship. Attitudes (9), followed by skills (8) were the most common educational goals of intervention. The efficacy and utility of JITT in improving educational goal acquisition was demonstrated in 90% (17/19) of the studies with reported outcomes. Discussion/Significance of Impact: The introduction of JITT in UME has been shown to meet the immediate needs of healthcare environments; however, evidence is limited in the evaluation of longer-term outcomes. Further research to determine the impact of JITT on long-term learning retention and education goal acquisition in UME is merited.

Objectives/Goals: This proposal outlines the successful deployment of a research training initiative to support the formation of a Learning Healthcare System. Mayo Clinic Health System (MCHS) rural providers were offered the opportunity to the fundamentals of clinical research via Clinical and Translational Science Awards core curriculum, mentorship, and an online seminar series. Methods/Study Population: MCHS funded 4 key introductory research courses: 1) Manuscript Writing, 2) Grant Writing, 3) Basic Biostatistics, and 4) Essentials of Clinical and Translations Science Program. In addition to course offerings, a Research Interest Group was formed to guide novice rural researchers on topic selection and study design. This cultivated interest to create a 16-month clinical research webinar series offering CME credits. Subsequently, an internal MCHS RFA was launched seeking early-stage investigator pilot proposals focused on rural health. Results/Anticipated Results: In 2023, over 140 MCHS providers enrolled in 324 CCaTS research courses. This training led to the submission of 53 proposals to the inaugural MCHS 2023 RFA, of which 15 were awarded. Additionally, 14 MCHS extramural grants were submitted in 2023. Training efforts expanded in 2024 to include an online research seminar series covering various study topics and providing CME credit, with an approximate attendance up to 196 attendees per session. The second annual MCHS RFA resulted in 4 internal awards, with an additional 22 extramural grant submissions. These collective efforts have increased the number of MCHS first and last author publications and the number of MCHS providers with academic rank. Discussion/Significance of Impact: Leadership’s commitment of resources to educate, mentor, and engage clinicians was crucial to our success and demonstrated a strong return on investment. To maximize impact in community-based practice, continued commitment is needed in the form of protected research time, funding, and research administration support of projects of interest

Objectives/Goals: Unhealthy lifestyle habits may increase medical students’ risk for metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty pancreatic disease (NAFPD). This study aims to investigate how these lifestyle factors affect liver and pancreas health in preclinical medical students using diagnostic ultrasound imaging. Methods/Study Population: Using diagnostic ultrasound imaging, we propose a research study to evaluate the anatomical changes of the liver and pancreas associated with lifestyle among medical students in UCC. Forty-two (42) medical students from the Central University of the Caribbean who are in their preclinical years will be recruited to perform an abdominal ultrasound. To measure the diameter of the right liver lobe, we will employ the craniocaudal measurement method established by Riestra. et al. (2018). The parameter established by Rumack et al. (2011) will be utilized to assess liver texture and categories by Lee JS et al. (2009) to pancreas fat infiltration grades. Results/Anticipated Results: This study expects to reveal a significant correlation between the lifestyles of preclinical medical students and the health of their liver and pancreas, particularly in size and texture. We anticipate identifying specific lifestyle factors – such as dietary habits and physical activity levels – that contribute to the prevalence of hepatic and pancreatic steatosis. Additionally, we expect to highlight the need for targeted interventions to promote healthier lifestyles among medical students to mitigate risks associated with MAFLD and NAFPD. Discussion/Significance of Impact: This study is significant for monitoring changes in liver and pancreas health, preventing complications, and improving health quality while reducing future costs. It may guide the creation of tailored wellness programs for medical students, enhancing their well-being and contributing to better healthcare practices and educational strategies.

Objectives/Goals: Clinical research professionals (CRPs) are vital to the conduct of clinical research and require ongoing, high-quality training to be effective. This poster will explore participating CRPs’ assessments of the impact of the inter-institutional Research Professionals Network (RPN) Workshops on their work and ability to perform their roles. Methods/Study Population: The RPN Workshops are a consortium of four academic medical centers and their affiliates that collaborate to host peer-led workshops for CRP continuing education. CRP presenters and attendees include a wide variety of roles, responsibilities, and levels of experience. From September 2023 to December 2024, workshop attendees received bi-annual evaluations to assess the workshop impact, including skill application and understanding of topics. Responses from these bi-annual evaluations, along with monthly session evaluations, were analyzed to identify key outcomes on the workshops’ impact in regard to participating CRP application of learnings and confidence in their role. Results/Anticipated Results: Preliminary review of the bi-annual RPN Workshop Impact Survey data, alongside monthly workshop evaluation responses from workshop participants, revealed attendees indicated that they valued the topics presented. Key findings indicated that CRPs’ participation in the workshops: reinforced their existing practices,tncreased their confidence in knowledge and/or skills discussed, enhanced their collaboration with CRPs from other institutions, and more detailed results of the analysis will be presented. Discussion/Significance of Impact: Overall results demonstrated increased confidence in CRP roles. Participants valued the inter-institutional collaboration, which is facilitated by the sharing of best practices and diverse perspectives within the workshop format.

Objectives/Goals: People experiencing homelessness (PEH) face excess cervical cancer burden and unique barriers to screening. As part of a broader study addressing cervical cancer disparities in homeless populations in Indiana, our goal was to engage unhoused women in a human-centered design process to inform a homeless shelter-based self-sampling intervention. Methods/Study Population: An established community-academic partnership enabled meaningful engagement of homeless communities in Indiana and informed the need to understand and address cervical cancer disparities in this population. Rapid assessment surveys (n = 202) and in-depth interviews (n = 30) were conducted with PEH at two major shelters in Indianapolis and Lafayette to understand cervical cancer screening coverage, knowledge, attitudes, and practices; barriers and facilitators; and acceptability of human papillomavirus (HPV) self-sampling for onsite shelter-based screening. A human-centered design session with (n = 12) unhoused women further explored motivators and concerns regarding self-sampling and informed key messages and informational materials to encourage uptake of screening. Results/Anticipated Results: At least 37% were overdue for screening (last screened >5 years ago; 50% were last screened >3 years ago), far greater than national (22%) or state (24%) averages. Despite common misconceptions regarding indifference toward preventive healthcare among homeless populations, most (87%) wanted to be screened and believed it is important for their health. Competing priorities for daily survival, transportation, cost, provider mistrust, stigma, and related trauma were common barriers to screening. Enthusiasm for HPV self-sampling centered on convenience, privacy, and comfort in taking one’s own sample at the shelter. Notable concerns included lack of confidence regarding ability to self-sample correctly, unhygienic conditions in shelter restrooms, preference to be seen by a doctor, and the need for education. Discussion/Significance of Impact: The unique challenges of PEH require human-centered strategies to improve cervical cancer screening access. Willingness to be screened and acceptability of HPV self-sampling is high. Identified concerns and preferences will guide implementation of HPV self-sampling delivered by trusted community health workers in homeless shelters in Indiana.

Objectives/Goals: The Fanconi anemia (FA) pathway is responsible for faithful DNA damage repair. FA mutations are common in multiple types of cancer, including HPV-negative head and neck cancers. We sought to identify synthetic lethal genes within this pathway to target treatment of FA-mutant tumors through siRNA- and chemical-compound-based screens. Methods/Study Population: First, we completed siRNA-based and chemical compound-based screening assays to identify gene targets that reduce patient derived Fanconi pathway mutant cell (FA-D2) viability compared to Fanconi pathway proficient cells (FA-D2 + FANCD2). Five aurora kinase (AURK) inhibitors from the compound screen were chosen for further evaluation. Cell lines were treated with AURK inhibitors or siRNA-based AURK knockdown to assess viability, proliferation, DNA repair, and cell cycle progression differences. Patient mutational, mRNA expression, and outcome data were accessed through The Cancer Genome Atlas (TCGA) portal and the Caris CODEai portal. We stratified patients by tumor AURKA and AURKB mRNA levels and assessed differences in patient survival, tumor grade, and DNA repair proficiency. Results/Anticipated Results: In both screens, AURKA came up as a target to selectively reduce the growth of FA-D2 cells compared to FA-D2 + FANCD2 cells. All five AURK inhibitors identified showed selective growth inhibition (~50–75%) in FA-D2 cells at low nanomolar doses. We narrowed our selection to hesperadin, an AURKB-specific inhibitor, which showed the highest selectivity. siRNA knockdown of AURKA and AURKB decreased cell viability by 50% and 20%, respectively. Patients with FA-mutated tumors from the TCGA pan-cancer dataset had high AURKA (twofold) and AURKB (threefold) mRNA expression. AURKA and AURKB tumor mRNA expression was significantly associated with poor patient survival. Homologous recombination deficiency scores were increased ~5-fold (p Discussion/Significance of Impact: We hypothesize that in FA-deficient backgrounds, loss of AURKA or AURKB leads to heightened genomic instability due to cell cycle dysregulation and accumulated DNA damage. Our findings warrant investigation of the therapeutic potential for AURK inhibitors, specifically hesperadin, in FA-mutant head and neck cancers.