OBJECTIVES/GOALS: Seeking ways to support teams in the preparation for and the implementation of the new National Institutes of Health (NIH) Policy for Data Management and Sharing (DMSP), the integrated Translational Health Research Institute of Virginia (iTHRIV) partnered with the UVA Health Sciences Library to develop training and resources for researchers. METHODS/STUDY POPULATION: Health sciences librarians and iTHRIV (an NIH-NCATS supported Clinical Translational Research Institute) convened a Working Group, inviting representatives from central and unit-specific research support offices (e.g. the Comprehensive Cancer Center), research compliance, regulatory affairs, sponsored programs, institutional review boards, libraries, and data science to review and discuss the DMSP requirements. After an initial orientation to the policy, the group reviewed existing public resources and solicited feedback about steps to best support UVA researchers in compliance. Leveraging the broad expertise of the group, the team provides guidance to researchers on writing the DMS plan and choosing a data repository, and provides tools and templates to support implementation of the policy. RESULTS/ANTICIPATED RESULTS: A library-created website provided policy guidance, including links to NIH-hosted information, resources created by other institutions, and new UVA-specific templates and suggested proposal language. Librarians led a webinar on the new policy and UVA resources which included a speaker from UVA regulatory affairs to describe the new DMSP requirements, and a tour of the new guide. The guide has been viewed over 5000 times to date and librarians have provided consultations and training to individuals and departments. Current plans include developing a user satisfaction survey, reviewing DMSP feedback from submitted proposals, and incorporating lessons learned into the website and future training. DISCUSSION/SIGNIFICANCE: The collaboration between iTHRIV and the Health Sciences Library to support the NIH Data Management and Sharing Policy was a successful partnership that provided leadership at the institutional level to communicate with and engage researchers and utilized the library’s web presence, expertise, and service model to provide direct support.

Objectives/Goals: The NIH Office of Data Science and Strategy created Data COUNTS (Collect Once, Use Numerous TimeS) to transform real-world data into actionable insights for translational research. The NEurOinformatics Network (NEON) applies this principle with neurology and national cohort use cases. Methods/Study Population: UNMC and Nebraska Medicine are deploying Data COUNTS to standardize data capture, ensure interoperability, and maximize reuse across research, clinical care, and operations. Teams integrate electronic health records, neuroimaging, biomarkers, wearable sensors, and social drivers of health into federated pipelines. HL7 FHIR and the OMOP Common Data Model maintain interoperability and reproducibility. Use cases include neurological disorders (multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease), cancer outcomes through SEER, diabetes, and rural health disparities. Integration with the National Clinical Cohort Collaborative (N3C) leverages anchor variables and harmonized pipelines to connect local and national datasets for generalizable analytics and collaborative science. Results/Anticipated Results: By linking with CTSA, IDeA-CTR, SEER, N3C, and other national health data, this initiative strengthens Learning Health System infrastructure, accelerates precision medicine, and advances population health. Beginning at NM and UNMC, the model will extend to regional systems, especially in rural and underserved areas. Use cases in neurology, cancer, diabetes, and rural health demonstrate local impact, while SEER and N3C provide scalable pathways for harmonization and national integration. Discussion/Significance of Impact: Nebraska’s leading health system generates multimodal datasets that, connected with SEER and N3C through Data COUNTS principles, enable predictive modeling, explainable AI, and digital twins. These use cases operationalize a scalable framework for translational science.

OBJECTIVES/GOALS: Identify causes for clinical research professional turnover Define data collection methods for exit interviews Provide institutions with resources to collect and analyze exit interviews Employ strategies to maximize the impact of exit interviews on retention METHODS/STUDY POPULATION: The Clinical Research Professional Taskforce (CRPT) exit interview Subgroup has met monthly since January 2023. Action items were agreed to and minutes were kept and reviewed at subsequent virtual working meetings. All members were given opportunity to speak and contribute. After a landscape analysis, conducted via survey, five institutions agreed to provide examples of their exit interview questions. Members spoke at length about goals, methods, collection techniques, institutional involvement, lessons learned and practical applications that could become best practices. RESULTS/ANTICIPATED RESULTS: The Subgroup aggregated all questions into categories and developed sample questions incorporating all data without using any word for word. In order to allow for quantitative assessment and standardized reporting the Subgroup formulated questions to be responded to utilizing a Likert scale with free text fields for select questions where further information is needed. The Subgroup developed best practices describing decision-making metrics, understanding reasons for turnover and reporting data back to leadership. Practical aspects such as method and time of survey collection, anonymity, and training staff are also included. DISCUSSION/SIGNIFICANCE: We are hopeful that sample questions and best practices will be helpful and widely utilized. Understanding the causes and impacts of CRP turnover are critical to meeting the current needs of clinical research. Further work is being done to calculate the cost of turnover to make the business case.

OBJECTIVES/SPECIFIC AIMS: The goal of this project is to study fetal pulmonary vasculature in a CDH animal model, to understand how FETO affects developing vasculature, and to develop a modifiable fetal tracheal occlusive therapeutic device that avoids previously seen sequelae of FETO, like alveolar distension, decreased surfactant production, and decreased Type II Pneumocytes. The primary outcome is lung volume/kilogram. The secondary outcomes are contrast-enhanced ultrasound perfusion metrics (Time to Peak, Mean Transit Time, Wash-in Rate, Wash-in Perfusion Index), pulmonary vascular density, Lung Injury Histology Scores, and Lung Compliance upon ventilation. METHODS/STUDY POPULATION: Congenital diaphragmatic hernias will be modeled by surgical hernia creation via maternal laparotomy and hysterotomy at gestational age 72 - 74 days. The ewe will undergo a second laparotomy at 105 - 115 days gestational age. After a second hysterotomy is made, the fetus will be removed from the amniotic sac, though placental circulation will be maintained (EXIT Procedure). The animal is cannulated via the umbilical vein and arteries onto the pumpless ECMO circuit. The balloon and pressure sensor complex is placed into the trachea via direct laryngoscopy, and the fetus aseptically sealed into the Biobag. The wires of the tracheal occlusive device (balloon catheter and pressure sensor) will egress via the port of the Biobag. The fetus remains in the Biobag for fourteen days, with the tracheal occlusive device in place for ten days, followed by a four day recovery period. Daily contrast-enhanced ultrasounds and pulmonary artery dopplers are performed. Upon study completion, the fetus is intubated and placed on a conventional ventilator. A full necropsy is then performed, with perfusion fixation of the lungs via the pulmonary artery. RESULTS/ANTICIPATED RESULTS: Hypothesis 1: Modifiable Tracheal Occlusion will have statistically different effects on developing lung parenchyma, surfactant production, and abundance of Type II Pneumocytes Hypothesis 2: Modifiable Tracheal Occlusion will have lower levels of pulmonary hypertension than negative control animals, as measured by contrast-enhanced ultrasound (pulmonary artery velocity and washout time). DISCUSSION/SIGNIFICANCE OF IMPACT: This project will provide insight into the development of pulmonary hypertension in the CDH fetus. It will provide insight into the physiology of FETO, a novel therapy for congenital diaphragmatic hernias, and will demonstrate the utility of the EXTEND System for fetal treatments that are not possible in the maternal uterus.

Community research advisory councils (C-RAC) bring together community members with interest in research to support design, evaluation, and dissemination of research in the communities they represent. There are few ways for early career researchers, such as TL1 trainees, to develop skills in community-engaged research, and there are limited opportunities for C-RAC members to influence early career researchers. In our novel training collaboration, TL1 trainees presented their research projects to C-RAC members who provided feedback. We present on initial evidence of student learning and summarize lessons learned that TL1 programs and C-RACs can incorporate into future collaborations.

This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.

Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

Objectives/Goals: Acute myeloid leukemia (AML) is the second most common leukemia among pediatric populations. Approximately 15% of pediatric AML cases have KMT2A gene rearrangements (KMT2A-r), which confers a worse prognosis. Our goal is to better characterize the biologic landscape of KMT2A-r pediatric AML. Methods/Study Population: This study utilizes deidentified peripheral blood and/or bone marrow samples banked in the Children’s Mercy Tumor Bank Biorepository. We investigated four KMT2A-r pediatric AML patients and six patients with other AML subtypes using samples collected at diagnosis and remission that were stored in the “tumor bank.” In addition, we assessed 47 tumor bank samples from patients with other leukemia subtypes. We performed differential expression (DE) analysis on bulk RNA sequencing comparing KMT2A-r and all other AML subtypes, as well as single-cell RNA sequencing and proteomic analysis on the larger cohort. We then coalesced these data to better identify processes and pathways that are dysregulated in KMT2A-r AML, specifically aiming to find those that were contributing to leukemogenesis. Results/Anticipated Results: Transcriptomic analysis showed that HOXA10 and MEIS1, two genes associated with immature myeloid populations and KMT2A-r leukemias, were more highly transcribed in AMLs than other leukemias. In addition, our DE analysis showed significantly higher transcription of ITGA7, a gene shown to correlate with poorer prognosis in AML, in our KMT2A-r samples when compared to other AML subtypes. FAM46C, a tumor suppressor gene contributing to mRNA stabilization, was less highly expressed in KMT2A-r AML when compared to other AML subtypes. Of note, low expression of FAM46C is associated with poorer survival and treatment response in multiple myeloma, and our findings suggest it may also be relevant to AML. Proteomic analysis is currently in process. Discussion/Significance of Impact: Transcriptomic analysis identifies unique molecular features of pediatric KMT2A-r AML. We anticipate that our proteomic data will do the same and will also corroborate our RNA findings. Taken in combination, these results will provide a more complete picture of the specific mechanisms contributing to this aggressive leukemic subtype.

OBJECTIVES/GOALS: Our vision is to build community amongst the Midwest CTSAs, harnessing our collective expertise to collaborate on translational science challenges and meet the needs of our region. We aim to create opportunities to network, share ideas, brainstorm solutions, address translational science topics, and achieve a range of deliverables. METHODS/STUDY POPULATION: Three individuals from the Chicago CTSAs (NUCATs, CCTS, and ITM) had been networking for a year and desired to increase opportunities to collaborate amongst other CTSAs. We developed an initial vision for a new group that would extend across the region, and we invited the TIN POCs from 16 Midwest CTSAs to join. In September, 2022, the group was launched with 20 members from 12 CTSAs. We hosted 12 monthly meetings via Zoom to discuss various topics (i.e., staffing, career training, e-consent, research design, and recruitment tools) via round tables or presentations. We developed a Google Sites website with resources, a discussion forum, and a group calendar. We solicited feedback via survey and follow-up discussion (i.e., most valuable about the group and what can be improved). RESULTS/ANTICIPATED RESULTS: During the past year, our membership grew to more than 30 participants, representing 16 CTSAs in nine Midwest states (IL, IA, IN, MI, MN, MO, KT, OH, WI). We engaged a total of 45 individuals at our meetings, with an average of 11 participants per meeting. Our discussions were lively and stimulated additional conversations, requests for guidance, sharing resources, etc., beyond the meetings. Feedback from the group was overwhelmingly positive. Members found many aspects of the group to be valuable (i.e., learning initiatives, processes, and best practices at other CTSAs) and provided practical suggestions for improvement (i.e., themes across a quarter or year). Members expressed interest in additional collaborations such as subcommittees, papers, and other initiatives. DISCUSSION/SIGNIFICANCE: We created a regional CTSA community that is very enthusiastic to convene, share innovations developed at their CTSA hubs, and assist one other. Future directions include an in-person retreat in the spring. Our approach can serve as a potential roadmap for developing regional CTSA collaborative groups across the nation.

Objectives/Goals: To develop a personalized computational framework integrating computational fluid dynamics (CFD) and topology optimization for designing intracranial aneurysm implants. The primary objective is to reduce intra-aneurysmal blood flow velocity and enhance thrombus formation for improved treatment outcomes. Methods/Study Population: Patient-specific aneurysm geometries were extracted from pre-treatment rotational angiograms. A CFD-driven topology optimization framework was employed to design implants that reduce intra-aneurysmal flow velocity. The fluid dynamics were modeled using Navier–Stokes equations and the structural integrity of the implants was ensured by linear elasticity equations. The solid isotropic material with penalization (SIMP) method was applied to optimize the implant’s porous architecture, balancing flow reduction with structural support. COMSOL Multiphysics software was used to implement the optimization. Results/Anticipated Results: The optimized implants demonstrated significant reductions in intra-aneurysmal blood flow velocity and improved hemodynamic conditions. Flow velocity within the aneurysm was reduced by 77%, and the fluid energy dissipation ratio showed a 78.9% improvement compared to pretreatment conditions. The optimized porous structures were tailored to the aneurysm’s specific geometry, providing personalized designs that improve flow stasis and thrombus formation. Further validation of the implants will be performed in vitro and in vivo to assess their effectiveness and biocompatibility. Discussion/Significance of Impact: This personalized implant design framework could lead to better treatment outcomes by reducing aneurysm recurrence and complications compared to current devices. It provides a pathway for improved occlusion rates and patient-specific solutions for intracranial aneurysms.

Objectives/Goals: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies. This study explores whether the Niclosamide derivative HJC0152 can act as an immune modulator to reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy efficacy. Methods/Study Population: Niclosamide-derived HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human and murine TNBC cell lines, as well as primary mouse MDSC cells, were treated with HJC0152. PD-L1 expression in TNBC cells and key immunosuppressive markers in MDSCs (Arg1, Arg2, and iNOS) were evaluated. The immunosuppressive function of MDSCs was further assessed using a T cell co-culture assay. In vivo studies are planned to assess the therapeutic efficacy of HJC0152 in combination with anti-PD-1 therapy using syngeneic TNBC mouse models. Results/Anticipated Results: HJC0152 exhibits improved solubility compared to Niclosamide and displays potent anticancer activity both in vitro and in vivo. RNA-Seq analysis of human TNBC cells treated with HJC0152 revealed significant downregulation of PD-L1 gene expression, which was further validated at the protein level by Western blot analysis. In addition, HJC0152 suppressed Arg1 expression in mouse MDSCs, a key mediator of immunosuppressive myeloid cell function. Together, PD-L1 and Arg1 pathways represent critical mechanisms of tumor immune evasion, and our findings highlight HJC0152 as a promising immune modulatory agent capable of enhancing the efficacy of immune checkpoint blockade in TNBC. Discussion/Significance of Impact: This study presents a novel immunotherapy strategy for TNBC using HJC0152, which downregulates tumor-derived PD-L1 and inhibits Arg1 signaling in MDSCs. As the first investigation of HJC0152 combined with anti-PD-1 in TNBC models, it may support future clinical trials and offer a new therapeutic option for TNBC patients.

OBJECTIVES/GOALS: The objectives are 1) to describe the creation and implementation of a Clinical Research Feasibility Program at the University of Miami Miller School of Medicine (UMMSOM), and 2) to share early findings demonstrating its effectiveness in improving research operations which may be helpful for other academic medical centers. METHODS/STUDY POPULATION: Many clinical trials are closed prematurely because of low accrual or not being able to meet the target enrollment. The Miami CTSI and UMMSOM Executive Dean for Research office collaborated to establish the Research Feasibility Committee (RFC) focusing on clinical trial selection with upfront feasibility and recruitment planning. Program implementation included: 1) selecting faculty with successful clinical trial track records as committee members; 2) developing processes, tools, and governance; 3) feasibility pilot testing; and 4) feasibility program roll out and refinement. The feasibility review process starts with the PI/Designee completing a REDCap study intake form, followed by an administrative review to ensure completeness of the form. The RFC chair assigns reviewers for the studies. RESULTS/ANTICIPATED RESULTS: The RFC went live on September 1, 2022 reviewing industry sponsor clinical research studies. The RFC conducts a systematic feasibility assessment of the study protocol, operational requirements, enrollment barriers, institutional resources, and study budget (if available) for all applicable research studies prior to IRB submission and contract negotiation at the UMMSOM. To date, the RFC has received over 270 submissions. Based on feedback from users, the committee has made changes to improve the comprehension of questions and added questions to ensure capturing of critical information to assess study feasibility. Initial metrics suggest simply implementing the review process has decreased the number of clinical trial submissions: average number of studies per quarter was 41 pre-RFC vs 24 post RFC. DISCUSSION/SIGNIFICANCE: The development and implementation of the RFC involved many stakeholders from the research enterprise. Clear and frequent communication to the research community was a key factor in the program’s success. The next phase is assessing the impact of the RFC, such as preserving vital resources for trials more likely to be successful.

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.

OBJECTIVES/SPECIFIC AIMS: Physical inactivity and mineral imbalances greatly contribute to morbidity and mortality in patients with end-stage renal disease (ESRD). Barriers for engaging in physical activity and adhering to the hemodialysis diet have been reported predominantly with white participants from countries other than Puerto Rico. Therefore, this study’s aims were to explore the barriers and facilitators that Hispanic adults with end-stage renal disease encountered for engaging in physical activity and adhering to the hemodialysis diet. METHODS/STUDY POPULATION: Three focus groups were conducted among 19 adults living with ESRD who received services from a renal center in Puerto Rico. Sessions were recorded, transcribed, and coded first using inductive methods. RESULTS/ANTICIPATED RESULTS: The presence of fatigue, lack of acceptance of the renal condition, and lack of knowledge of appropriate exercises for patients in hemodialysis were the most frequently reported barriers to engage in physical activities. Cost of the renal diet, limited availability of the renal diet products, the restrictive nature and the lack of Puerto Rican taste of the renal diet, and inadequate educational materials were the most frequent barriers to adhere to the hemodialysis diet reported by the sample. The most commonly reported facilitators to engaging in physical activities were having a positive attitude, opportunities for group exercises, and listening to Hispanic music while exercising. Health benefits, family support, having financial resources, availability of community resources, and having willpower were the most commonly reported facilitators to adhere to the hemodialysis diet. DISCUSSION/SIGNIFICANCE OF IMPACT: We identified a number of culturally relevant individual, interpersonal, institutional, and community-related barriers and facilitators to physical activity and adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico. Evidence-based solutions to overcome these barriers and strategies for enhancing these facilitators should be addressed in future studies aimed at increasing the level of physical activity and increasing adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico.

Objectives/Goals: Our objective was to use human-centered design methods to co-develop an intervention that enhances postpartum management of hypertensive disorders of pregnancy and reduces long-term cardiovascular (CV) disease risk. Methods/Study Population: Human-centered design is a problem-solving approach that centers the end-user including patients, clinicians, and community members. We conducted six focus groups with people who experienced HDP, doulas, lactation consultants, perinatal community health workers, midwives, Ob/Gyns, and family physicians (n=26). Design activities included patient journey mapping, group discussion, mad lib creation, rapid solution brainstorming, dot voting, impact/difficulty matrix analysis, and pitch concept development. Focus group sessions explored the patient journey and identified major unmet needs. These results informed the co-design of solutions to address key facilitators and barriers to positive care pathways. Results/Anticipated Results: Participants identified a need for a community-embedded care model that promotes continued engagement after delivery, timely blood pressure (BP) monitoring and management, chronic stress reduction, and a smooth transition to primary care. These findings informed the co-design of a multi-level intervention that includes 1) midwife-led dyadic mom–baby visits that facilitate evidence-based strategies: BP surveillance, medication management, and lifestyle education; 2) remote BP monitoring with bi-directional communication; 3) community-based doula care; 4) a co-located family support specialist that addresses social determinants of health and chronic stress; and 5) facilitated primary care transition. Discussion/Significance of Impact: Using human-centered design enabled the integration of lived experiences, clinical insights, and community perspectives. This participatory process ensures that actionable solutions are responsive to real-world needs and have greater potential to improve CV health.

OBJECTIVES/SPECIFIC AIMS: The study aims to understand if pro inflammatory epicardial white adipose phenotype is positively associated with coronary atherosclerosis, while the brown adipose phenotype is negatively associated. Primary outcome is association between epicardial fat fraction and coronary atherosclerosis and cardiac function. Secondary outcome is transcriptomic and lipidomic profiling between epicardial, extra pericardial, and subcutaneous depots and how these profiles correlate with fat fraction. METHODS/STUDY POPULATION: Recruited patients undergoing open-heart surgery provided informed consent at their second visit and underwent laboratory testing and imaging (cardiac magnetic resonance including water-fat imaging and coronary calcium computed tomography) prior to their surgery. Cardiac function such as cardiac chamber volume, mass, function, and strain, and depo-specific fat fraction were calculated from cardiac MR and Agatston calcium score and epicardial adipose volume from CT images. At the time of surgery, a tissue specimens from the epicardial, extrapericardial, and subcutaneous depots were obtained for transcriptomic and lipidomic analysis. Linear and logistic regression analyses adjusted for other variables were performed to evaluate significance level between variables. RESULTS/ANTICIPATED RESULTS: 37 subjects were enrolled in the study, 13 (35%) of which were women. Cardiac function and fat fraction was quantified in all patients, whereas tissue analyses were performed in 22 patients. Epicardial and extrapericardial fat fraction were independently associated with coronary atherosclerosis (p-value 0.01 and 0.04 respectively) Only epicardial fat fraction was negatively associated with global circumferential shortening of the left ventricle (0.03), while neither the extrapericardial fat fraction nor epicardial adipose volume were not (p =0.33 and 0.97 respectively) All three adipose depots have unique gene signatures with differentially expressed genes and pathways. RNA sequencing of epicardial, extrapericardial, and subcutaneous depots demonstrated tight clustering of epicardial and subcutaneous signatures based on PCA analysis (Figure 2). 19 lipid classes and 59 lipids showed differential expression between at least 2 of the fat depots (Figure 3). Hierarchal clustering of the lipids showed that epicardial and extrapericardial depots were more closely related than subcutaneous adipose. Plasmenyl-phosphatidylcholines, with an ether-linked fatty acid at the sn-1 position of the lipid, were higher in subcutaneous fat while most other lipids were higher in epicardial fat per tissue weight, such as ceramides (p=0.002). DISCUSSION/SIGNIFICANCE OF IMPACT: Epicardial, extrapericardial, and subcutaneous adipose depots express different lipidome and transcriptome signatures and different pathways. GSEA analysis demonstrated enrichment of genes related to antigen presentation and B cell immunity in epicardial compared to subcutaneous adipose tissue. Epicardial fat fraction is associated with coronary atherosclerosis and decreased left ventricular global circumferential shortening as an early predictor of decreased left ventricular stroke volume. Epicardial fat fraction is also associated with cermides which may play role in the development of coronary atherosclerosis and decreased cardiac function.

OBJECTIVES/GOALS: An environmental scansoughtto understand research processes, areas for improvement, and opportunities for collaborative quality improvement (QI)across the Northwest Participant and Clinical Interactions Network (NW PCI). METHODS/STUDY POPULATION: NW PCI site champions were invited for semi-structured single and group Zoom-based interviews. Interviewers asked participants about local research processes, strengths and weaknesses, existing infrastructure to support QI, and interest in collaborative QI across the Network. Audio transcripts were coded using Dedoose and analyzed with deductive and inductive coding. RESULTS/ANTICIPATED RESULTS: Between February and April 2023, 10 interviews collected data from 7 research decision makers and 7 staff members across 7 sites. Most participants (n=13, 92%) agreed the diagram shown during the interview was representative of the local process. Organizations consistently identified strengths and weaknesses within the domains of study start-up, recruitment, budgets, and compliance. QI infrastructure was inconsistent (n=5, 36%) and all (n=14, 100%) saw potential for success in multisite QI initiatives to enhance efficiency. DISCUSSION/SIGNIFICANCE: NW PCI sites use similar processes, share common strengths and weaknesses, and universally reported interest in collaborating on QI. Study startup was reported as both a strength and weakness within the same organization, requiring unpacking of key elements before pursuing QI initiatives.