Objectives/Goals: This research aims to harness electronic health records (EHR) combined with machine learning (ML) to predict necrotizing enterocolitis (NEC) in preterm infants using data up to their first 14 days of life. We aim to provide interpretable results for clinical decisions that can reduce infant mortality rates and complications from NEC. Methods/Study Population: Through a retrospective cohort study using data from the University of Florida Integrated Data Repository and One Florida, we will develop machine learning models suitable for sequential data to predict NEC. Our inclusion criteria include very low birth weight (VLBW; < 1500g) infants born < 32 weeks gestation and EHR data availability from the first 14 days of life. We will include infants with NEC and infants without NEC to train our ML model. Exclusion criteria include infants diagnosed with spontaneous intestinal perforation and severe congenital anomalies/defects requiring surgery. Results/Anticipated Results: We anticipate that our model will provide an accurate and dynamic prediction for the risk of NEC in neonates using data up to the first 14 days of life. Our model will be interpretable to identify key risk factors and can integrate real-world clinical insights to increase early detection and improve patient outcomes. Discussion/Significance of Impact: The development of a model to predict NEC could be used in neonatal intensive care guidelines and protocols and could ultimately decrease mortality, reduce complications, improve the overall quality of care, and lower healthcare costs associated with NEC.

OBJECTIVES/GOALS: to investigate the potential impact of grandparental factors and multigenerational epigenetic inheritance on the development of ASD METHODS/STUDY POPULATION: Our study recruited participants from the CHARGE (Child Autism Risks from Genetics and the Environment) study, including grandparents, parents, and children. A questionnaire was used to gather information about the participants’ exposure to environmental factors. Saliva samples werecollected from 349 participants. Newborn dried blood spotsfrom probands and parents are still being collected from the California New born Registry. DNA was extracted from 349 saliva samples from 85 families and subjected to whole genome bisulfite sequencing (WGBS) to analyze DNA methylation. Sequence alignments and bioinformatic analyses will be performed using R packages called DMRichR and Comethyl. RESULTS/ANTICIPATED RESULTS: Sequence alignments and bioinformatic analyses are ongoing, utilizing DMRichR to identify individual genomic loci associated with ASD in each of the three generations and Comethyl to compare correlation patterns between methylation marks and selected variables, including grand parental exposures. New born blood spot collections of parents and probands are ongoing and will be used to identify potential ASD epigenomic signatures that are tissue and life-stage independent. DISCUSSION/SIGNIFICANCE: This research will provide new insights into the increased prevalence and underlying etiology of ASD that should pave the way for future research in the field. DNA Methylation signatures can help create molecular biomarkers which can be used together with behavioral clinical tests for diagnosis of ASD.

Objectives/Goals: We aim to develop new tissue-engineered ear tissue that more closely mimics native elastic cartilage and maintains its topographic form for reconstructive auricular surgery. By integrating decellularized cartilage (DCM) into chondrocyte-seeded collagen matrices, we seek to improve structural stability to support future clinical translation. Methods/Study Population: Bovine auricular chondrocytes were isolated via enzymatic digestion, expanded to passage 3, and encapsulated at 25 million cells/mL into four construct formulations composed of 1% type I collagen mixed with varying amounts of DCM: (1) 100% collagen, (2) 70% collagen + 30% DCM, (3) 40% collagen + 60% DCM, and (4) 10% collagen + 90% DCM. DCM was prepared by zesting ovine rib cartilage into ~0.5 mm³ flakes, followed by chemical and enzymatic decellularization. Constructs were packed into 3D-printed scaffolds and cultured for 0, 1, or 2 months. At each timepoint, constructs were assessed for gross volume, volume retention (normalized to baseline), and angle at the dome–base interface as a geometric surrogate for shape retention. Histology evaluated cell distribution and cartilage-specific matrix deposition. Results/Anticipated Results: At baseline, volumes were comparable across groups. By 1 and 2 months, constructs with higher DCM content yielded significantly greater volume retention. At 2 months, mean retention in the 90% DCM group was 94.0%±6.2%, compared to 64.7%±4.1% in 30% DCM (p<0.01) and 74.7%±5.9% in 0% DCM (p<0.05). Angle analysis likewise showed that higher DCM preserved sharper dome–base curvature. Mean angle change at 2 months was 3.0°±3.6° in 90% DCM versus 17.6°±5.7° (70% DCM, p<0.01), 16.3°±5.7° (30% DCM, p<0.05), and 21.6°±8.1° (0% DCM, p<0.001). In all groups, histology confirmed chondrocyte viability, and inclusion of DCM did not hinder cell distribution in collagen. These findings suggest DCM reinforces construct stability, and we anticipate similar volume and shape retention in upcoming in vivo rat studies. Discussion/Significance of Impact: Incorporating DCM improves in vitro form retention in bioengineered ear cartilage without impeding cell viability, suggesting DCM can act as an internal rebar to resist contraction and preserve geometry. By continuing to advance this construct translationally, next in vivo, we aim to enable its eventual use in clinical ear reconstruction.

Objectives/Goals: To address the disparity in type 2 diabetes within the Latino community, we utilized digital story telling narrative-based videos created by and for individuals with lived experiences. Methods/Study Population: We utilized digital story telling narrative-based videos created by and for individuals with lived experiences. The targeted population is the Latino community. Results/Anticipated Results: Our qualitative results were discordant with the quantitative findings. Rather than four distinct patterns based on self-efficacy and HbA1c levels, we found five common themes across the groups: (1) trauma shapes readiness for change; (2) caregiving responsibilities can hinder self-management; (3) persistence is key to long-term T2D control; (4) social support is essential; and (5) self-advocacy and a desire for knowledge drive success. These results highlight the multifaceted challenges Latino/Hispanic individuals face in managing type 2 diabetes, where overlapping social and cultural factors influence both self-efficacy and health outcomes. Discussion/Significance of Impact: Interventions for Latino/Hispanic communities should be well informed and family/community-centered, and that will strengthen the persistence, support network, and patient empowerment to translate confidence into sustained glycemic control.

Educational tools for application of team science competencies in clinical research are needed. Our interdisciplinary group developed and evaluated acceptability of a virtual world game-based learning tool simulating a multisite clinical trial; performance hinges on effective intrateam communication. Initial implementation with clinical research trainees (n=40) indicates high satisfaction and perceived relevance to team science and research career goals. Game-based learning may play an important role in team science training.

Diversity, equity, and inclusion (DEI) are fundamentally important concepts for advancing clinical and translational science (CTS) education. CTS education spans a wide range of disciplines from cell biology to clinical and community/population research. This large scope both in terms of intellectual areas and target groups requires an understanding of existing educational approaches for DEI as we translate DEI from mere concepts into equitable actions within CTS education. In this  review, we provide the readers with the most common DEI educational approaches, including cultural humility, bias training, and improving mentoring to diversify the workforce. DEI educational materials can achieve maximal success and long-term impact when implemented as institutional-wide interventions, and the materials are not seen as an isolated or independent curriculum. Approaches, strategies, and programs to achieve this are many. However, many questions remain unanswered about what the best approach, strategies, and programs are to be implemented in institutional-wide education that will be embedded in CTS education.

Objectives/Goals: The Standards for Reporting Implementation Studies (StaRI) are the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network 27-item checklist for Implementation Science. This study quantifies StaRI adherence among self-defined Implementation Science studies in published Learning Health Systems (LHS) research. Methods/Study Population: A medical librarian-designed a search strategy identified original Implementation Science research published in one of the top 20 Implementation Science journals between 2017 and 2021. Inclusion criteria included studies or protocols describing the implementation of any intervention in healthcare settings. Exclusion criteria included concept papers, non-implementation research, or editorials. Full-text documents were reviewed by two investigators to abstract and judge StaRI implementation and intervention adherence, partial adherence, or non-adherence. Results/Anticipated Results: A total of 330 documents were screened, 97 met inclusion criteria, and 47 were abstracted including 30 research studies and 17 protocols. Adherence to individual StaRI reporting items ranged from 13% to 100%. Most StaRI items were reported in >60% of manuscripts and protocols. The lowest adherence in research studies was noted around economic evaluation reporting for implementation (16%) or intervention (13%) strategies, harms (13%), contextual changes (30%), or fidelity of either the intervention (34%) or implementation (53%) approach. Subgroup analyses were infrequently contemplated or reported (43%). In protocols, the implications of the implementation strategy (41%) or intervention approach (47%) were not commonly reported. Discussion/Significance of Impact: When leveraging implementation science to report reproducible and sustainable practice change initiatives, LHS researchers will need to include assessments of economics, harms, context, and fidelity in order to attain higher levels of adherence to EQUATOR’s StaRI checklist.

Objectives/Goals: We aim to determine whether inadequate sphingosine-1-phosphate (S1P) production in hyperglycemia is involved in deranged inflammatory response and host defense during methicillin-resistant Staphylococcus aureus (MRSA) skin infection. Methods/Study Population: Using a Phenome-Wide Association Study (PheWAS), we analyzed a disease-agnostic cohort of ~40,000 individuals to identify disease associations with SNPs in genes involved in the S1P pathway. RNA-seq data enabled comparison of key S1P-related genes in diabetic foot ulcer and non-ulcerated diabetic foot skin. For animal data, we infected euglycemic (EG) and hyperglycemic (HG) mice with MRSA and monitored infection resolution over 9 days. Biopsies were taken on days 1, 3, and 9, and S1P levels, lesion size, bacterial load, and cell death were assessed. To evaluate whether S1P can enhance clearance of dead cells/bacteria and promote healing, we treated mice with FTY720, an S1P agonist FDA-approved for multiple sclerosis Results/Anticipated Results: PheWAS analysis suggests that SGPL1 SNP rs111439207 has protective effects against MRSA infection (OR = 1.71, P = 0.0004) and type 1 diabetes (OR = 1.325,P = 0.003). The RNA-seq dataset revealed increased SGPL1 expression (an enzyme responsible for S1P degradation) in the skin of diabetic patients with foot ulcers. In animals, we show that infected HG mice develop larger lesions, higher bacterial loads, and poor abscess formation. We found a correlation between dead cell buildup and a lower ratio of ingested dead cells in the skin by macrophages of HG mice compared to EG mice. Topical S1P treatment decreased lesion size and bacterial load in HG mice. Discussion/Significance of Impact: Our data show increased expression of SGPL1 in diabetic patients. S1P deficiency during MRSA skin infection leads to tissue damage, uncontrolled bacterial growth, and poor resolution of the infection in mice. Topical treatment with S1P agonist is a promising therapeutic approach to enhance patient healing.

Objectives/Goals: To design a flexible, comprehensive framework for Data Science Units to cultivate sustainable, long-term relationships with Clinical and Translational Science Research Units. Best practices for managing Data Science collaborations are presented to improve the quality and efficiency of research conducted throughout academic health centers. Methods/Study Population: Leaders of Data Science Units across six institutions formed a workgroup to develop guidance and best practices for Data Science Units to establish long-term, sustainable collaborations with Clinical and Translational Science Research Units. This guidance is based on tools and protocols developed and employed by the participating units, which range from larger groups with over 20 partnerships to a unit with three partnerships that is actively working to expand. Importantly, partnerships are highly variable, with some partnerships at one institution representing engagement with over 500 faculty, whereas some partnerships at another institution involve the lab of a single investigator. Results/Anticipated Results: We offer guidance in three domains: (1) Identifying the needs for a new partnership, including assessing required effort and data science expertise, setting partnership priorities, developing formal agreements, and identifying goals and metrics; (2) managing data science teams by implementing regular meetings, creating project intake and prioritization processes, and effort monitoring; and (3) evaluating the successes and failures/gaps of the collaboration by measuring the metrics mapped to the goals. For each domain, we provide specific suggestions on which parties should be involved and how frequently the processes should occur. This guidance is applicable both to larger collaborative partnerships and to smaller, single faculty or staff partnerships, whether they are new or well-established. Discussion/Significance of Impact: Effective collaboration between data scientists and clinical and translational investigators is key to advancing data-driven research. The guidance and resources are presented to support Data Science Units in successfully managing long-term collaborations through goal-development, evaluation, and adapting to evolving research needs.

Objectives/Goals: Linking GAINS evaluates a 14-week community-based program combining genomic testing, ancestry education, and culturally tailored nutrition to improve cardiometabolic health, literacy, and behavior among African American adults in Baton Rouge, Louisiana. Methods/Study Population: Sixty African American adults in Baton Rouge will be randomized into genetically blinded (GB) or unblinded (GU) groups. Both complete baseline surveys, biometric assessments, and a 14-week health behavior program with screenings, nutrition education, cooking classes, and exercise. The GU group receives Color Genomics testing and counseling at baseline; GB receives counseling post-intervention. Follow-up measures assess literacy, diet, and cardiometabolic outcomes. Results/Anticipated Results: CHATGPT SAID: We anticipate improvements in genomic literacy, nutrition knowledge, and willingness to undergo genetic testing, particularly among the unblinded group. Participants are expected to adopt healthier eating and physical activity behaviors, leading to modest reductions in BMI and blood pressure and increased trust in genomics and preventive health research. Discussion/Significance of Impact: Linking GAINS shows how combining genomic testing with culturally tailored nutrition education can improve literacy and lifestyle behaviors, offering a scalable model for advancing equitable precision health in African American communities.

Objectives/Goals: Develop a cervicovaginal mucus replacement to prevent bacterial vaginosis (BV) in pregnant women. Our therapeutic, specialized hydrogel in natural enhancement for vaginal health (SHINE-VH), is formulated through polymer chemistry, tested for efficacy and safety through microbiology, and translated through clinical and translational science. Methods/Study Population: We will develop SHINE-VH with optimized viscoelastic and mucoadhesive properties intended to mimic healthy vaginal mucus. SHINE-VH will be synthesized via robust photoiniferter methods and investigated through shear rheology, sugar binding, and permeability studies. To evaluate the biocompatibility and safety profile of SHINE-VH, we will utilize a series of in vitro models to test its impact on the viability and cytotoxicity of human vaginal epithelial cells. In addition, we will assess the capacity of SHINE-VH to fortify vaginal barrier integrity and modulate anti-inflammatory activities in a 2D epithelial barrier model exposed to BV-associated pathogens. Lastly, employing organ-on-a-chip technology, vaginal swabs from both healthy and suspected BV pregnant patients will be treated with SHINE-VH. Results/Anticipated Results: SHINE-VH will mimic the protective, hydrophilic gel network of natural mucins. The viscoelastic properties of our formulation determined by shear rheology will be tuned through concentration and polymer composition to mimic vaginal mucus. We will also show the facile movement of small molecule nutrients through the SHINE-VH network via sugar-binding and permeability tests. Additionally, we anticipate that the introduction of SHINE-VH, due to their xenobiotic nature as synthetic mucins, will modulate the microbiota by diminishing inflammation, thereby reinforcing the cervicovaginal mucus and cultivating a vaginal microbiome that is more resilient to the disruptive impacts of BV. Such modulation could lead to a marked difference between the SHINE-VH-treated and untreated groups. Discussion/Significance of Impact: BV affects ~30% of women globally and is associated with severe gynecologic and obstetric complications, representing a significant unmet need in women’s health. SHINE-VH offers a novel approach to BV management, aiming to strengthen vaginal mucosal integrity, potentially reducing BV prevalence, and improving women’s health outcomes.

Scientific progress increasingly relies on large, complex biomedical datasets; data management concerns (heterogeneity, volume, sensitivity, and a pervasive lack of standardization) present significant challenges, especially in the context of AI adoption and precision medicine. This fragmented data landscape leads to inefficiencies, hinders interoperability, and impedes the full potential of biomedical innovation. Standards Development Organizations (SDOs) are crucial in addressing these challenges by creating common languages, frameworks, and protocols for biomedical data. This document outlines the critical importance of proactive engagement by translational researchers with SDOs, detailing various modes of participation such as correction, enrichment, alignment of existing standards, and assessing the need for implementation guidance. It identifies key SDOs in the biomedical domain (e.g., HL7, GA4GH) and discusses the processes for engaging with them, including framing requests with compelling justification, ensuring alignment, demonstrating community consensus, and understanding SDO-specific procedures. The authors emphasize that successful engagement requires collaboration with SDO communities, patience, and respect for their processes. Ultimately, robust SDO engagement and continuous feedback are indispensable for fostering a more agile and robust data ecosystem, accelerating biomedical innovation, and translating research into improved health outcomes, thereby building public trust and ensuring reliable, reproducible, and equitable research.

Creating a sustainable residency research program is necessary to develop a sustainable research pipeline, as highlighted by the recent Society for Academic Emergency Medicine 2024 Consensus Conference. We sought to describe the implementation of a novel, immersive research program for first-year emergency medicine residents. We describe the curriculum development, rationale, implementation process, and lessons learned from the implementation of a year-long research curriculum for first-year residents. We further evaluated resident perception of confidence in research methodology, interest in research, and the importance of their research experience through a 32-item survey. In two cohorts, 25 first-year residents completed the program. All residents met their scholarly project requirements by the end of their first year. Two conference abstracts and one peer-reviewed publication were accepted for publication, and one is currently under review. Survey responses indicated that there was an increase in residents’ perceived confidence in research methodology, but this was limited by the small sample size. In summary, this novel resident research curriculum demonstrated a standardized, reproducible, and sustainable approach to provide residents with an immersive research program.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

Diversity remains low among US colleges faculty, with only 3% identifying as Black or Hispanic. Moreover, underrepresented racial minority faculty often face unique challenges and are less likely than their white counterparts to earn higher academic rank, tenure, and funding, especially those who study health equity. We developed a novel program for health-equity focused pre-docs and junior faculty. The Disparities Researchers Equalizing Access for Minorities (DREAM) Scholars is a 24-month career development program led by the Center for Clinical and Translational Science (CCTS) that provides pilot and travel funding, career development seminars, mentoring, and writing retreats. We report the outcomes of the first Scholar cohort (N = 10), pre-docs n = 6; assistant professors, n = 4; seven were Black, one Hispanic, two White, one who identified as non-binary. At the end of the program, Scholars coauthored 34 manuscripts, 9 abstracts and 8 grants. Semi-structured interviews revealed seven major program strengths: funding, support and sense of community, accountability, exposure to translational science, network expansion, and exposure to multidisciplinary peers. Scholars provided feedback useful for subsequent cohorts. The DREAM program provided accountability and fostered a sense of community, expanded professional networks and enhanced scholarly productivity. The program serves as a model for implementation throughout the CCTSs.