Objectives/Goals: Failure to achieve recruitment goals results in termination of ~20% of clinical trials and delays >85% of trial timelines. We aim to develop an electronic heath record (EHR)-based recruitment tool to ease identification of participants. We sought to determine whether criteria listed on clinicaltrials.gov could support selection of tool variables. Methods/Study Population: To inform the variables to include in the EHR-based recruitment tool, we data scraped clinicaltrials.gov to identify key inclusion and exclusion criteria common across a variety of diabetes clinical trials. We included actively recruiting or recently active phase 2 and 3 clinical trials of adults aged >18 years of age in the USA. We classified identified variables as clinically relevant or not and compared clinically relevant terms with inclusion and exclusion criteria (~20 variables) that were individually identified by three diabetes clinical trialists and two clinical research coordinators (CRCs). Results/Anticipated Results: We reviewed 203 clinical trials listed on clinicaltrials.gov. We identified 115 terms, 91 of which were clinically relevant. Three of 3 clinical trialists, 1 of 2 CRCs, and all trials listed age as a key variable. Consistent with data scraping, all trialists and CRCs identified glucose-lowering medications and kidney function as important criteria. Gender, ethnicity, and race were less commonly noted on clinicaltrials.gov and listed by 2 of 3 trialists and one CRC. Cardiovascular conditions (e.g., history of myocardial infarction), thyroid function tests, and contraceptive requirements were common criteria on clinicaltrials.gov, but only one trialist and one CRC identified these variables. Active infections (e.g., HIV) and c-peptide were not highlighted by trialists or CRCs but common on clinicaltrials.gov. Discussion/Significance of Impact: An EHR-based recruitment tool may facilitate identification of trial participants, but identifying key variables to include is essential. We found that data scraping for variables on clinicaltrials.gov mostly aligned with expert opinion, suggesting that automating variable selection via extraction from clinicaltrials.gov may be acceptable.

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: Translational researchers often struggle to navigate a complex constellation of institutional resources spanning the IRB to bioinformatics units. We had two aims 1) Systematically map all institution-wide research support units and 2) leverage this database within a generative AI virtual concierge tailored to local investigator queries and needs. Methods/Study Population: This study leveraged mixed methods approach. First, we conducted needs assessments of local study teams to identify barriers to translation, revealing that research resources are often unknown to study teams. Second, we identified all investigators, institutional units, and offices offering such resources that we call research support units (RSUs). RSUs were surveyed, collecting contact information (leadership, website, physical location), services provided, type of research supported, and performance metrics. Third, the resource database was integrated into a large language model (LLM, e.g., ChatGPT4o) using a retrieval augmented generation (RAG) system within an R Shiny application called virtual concierge. Queries and responses are recorded for quality improvement. Results/Anticipated Results: Needs assessment focus groups consisted of clinical and basic science investigators, study team members (e.g., clinical research assistants), core directors, and administrators (n = 26). Six sessions were conducted in Spring 2024. A major resultant theme was difficulty finding RSUs “by trial and error” and lacking a “clear defined pathway” for accessing RSUs. This prompted a survey-based environmental scan to identify institutional research resources. There were 122 diverse RSUs ranging from the IRB, to grant writing, to single cell sequencing. Each research unit offered a median of 6 service types, totaling 410 service types overall. The resultant Virtual Concierge meaningfully responds to investigator resource queries with appropriate contact and access information. Usability testing is underway. Discussion/Significance of Impact: Linking researchers with translational resources requires mutual understanding, timely communication, and coordination across teams. We systematically filled these information gaps between investigators and institutional resources. Our Virtual Concierge AI bot can help researchers navigate resources through the translational process.

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: A limited number of Hispanic researchers compete successfully for NIH career development and research grants. We adapted an established K Club model from the University of Pittsburgh with high success rates to Hispanics in Puerto Rico (PR). The K to R Club’s goal is to increase the successful submission of K- and R-type NIH grants in the HCTRECD Program. Methods/Study Population: K to R Club is an inviting environment that exposes scholars to established funded investigators in PR from all career stages. It creates a forum to discuss different grant mechanisms and explains the selection, submission, and review process. The Club promotes the right mentor selection and mentoring team. It facilitates networking with principal investigators local/external to share their success stories, career development experiences, and grant submission tips. It offers mock review sessions of sections of the grant proposal to provide feedback from invited established investigators during the grant writing process. The Club meets 1–2 times per month in-person or virtual for 1 hour and anonymous evaluations were submitted after each session. Results/Anticipated Results: K to R Club 1st year had 11 sessions with 15 invited speakers. Sessions included: 1 Kickoff, 2 funding opportunities, 2 coaching, 7 successful stories of Diversity Supplement, and F99/K00, K22, K23, K99/R00, R01, and R21 awardees. The highest attendance was for the Kickoff (48). Evaluations response rates ranged from 15 to 62 with the highest participation from women (78% vs. 22% men). Most respondents were PhD (45%) and MD (29%). K to R Club sessions were rated as excellent (84%), 74% agreed that the sessions changed their knowledge very much, and 78% reported it changed their ability to apply for funding very much. Interest in submitting NIH supplements in 12 months was higher (68%) vs. 6 months (48%). Interest in requesting mock reviews for K or R grants in 6 months (91%) vs. 12 months (17%). Discussion/Significance of Impact: The 1st year of the K to R Club had an active attendance and increased the interest in submission of NIH grants. We are working on strategies to increase evaluations’ response rates to improve and address future session needs due to the low response rates recorded. Currently, the semester is full of mock review sessions for grant applications (4 Ks and 1 R01).

Objectives/Goals: The UCLA Clinical and Translational Science Institute (CTSI) training programs have been optimized by clinical research experts since 2013. They inculcate an interest in clinical and translational research careers. The acquisition of new skillsets and early exposure to potential career opportunities often influence lifetime decision-making. Methods/Study Population: The first program, in 2013, was the CTSI Research Associates Program (CTSI-RAP), which exposes undergraduate students to clinical research opportunities. RAP students are now mentoring high school students in the Mentoring and Advocacy in Teaching Clinical and Health-Related Research (MATCH) program. The Fiat Lux seminar is a research course designed to allow freshman students to explore diverse interests. The Leveraging Amazing Undergraduates in Clinical Research at UCLA Health (LAUNCH) program continues the workforce development pipeline by recruiting and training recent graduates to enter clinical research study coordinator careers. Each of these programs has their own stellar track records in terms of high interest and satisfaction and are assessed by annual evaluations from stakeholders. Results/Anticipated Results: CTSI-RAP is in its 11th year and a recent 10-year impact survey demonstrated the value of the program to students and their career decision-making especially those who are underserved and/or disadvantaged. The MATCH program arose from the interest of RAP students to mentor STEM high school students from local disadvantaged schools and is now in its 4th year across the state. The Fiat Lux freshman seminar began with a clinical research essentials emphasis, followed by an FDA/regulatory focus, and is now evolving to highlighting specific innovative areas of research with this year’s course spotlighting Cellular & Gene Therapy/Regenerative Medicine. LAUNCH is now in its third year, having been inspired by graduating RAP students wishing to continue in clinical research and feedback from their own focus groups. Discussion/Significance of Impact: The UCLA CTSI has supported these highly successful workforce development pipeline programs, which have had a demonstrated impact on students and the overall institutional clinical research infrastructure. Their stellar reputations generate high interest at UCLA and serve as model programs for implementation at other academic medical centers.

Objectives/Goals: Short-chain fatty acids (SCFAs) exert protective effects against calcium oxalate (CaOx) urinary stone formation in experimental rodent models, yet these effects are not understood in natural stone formers. This study will define the impact of SCFAs on stone risk factors along the gut–kidney axis in a natural canine model of CaOx stone disease. Methods/Study Population: A randomized, placebo-controlled, clinical trial will be performed using a crossover study design. Twenty dogs that are natural CaOx stone formers will be fed a standardized diet and randomized to receive either a daily prebiotic fiber (inulin) that stimulates SCFA production or a placebo. We will perform fecal shotgun metagenomics and SCFA quantification before and after each intervention (four timepoints) to identify how inulin and SCFAs enrich or deplete pathways relevant to stone formation within the gut microbiome. RT-qPCR will be performed to determine the effects of SCFAs on intestinal oxalate transporter gene expression (SLC26A3 and SLC26A6). At each timepoint, urinary shotgun metagenomics and quantification of urine biochemical profiles used to predict stone risk will also be performed. Results/Anticipated Results: We anticipate that prebiotic stimulation of SCFAs with inulin will reduce stone risk factors along the gut–urinary axis in a natural canine model of urinary stone disease. Specifically, we anticipate that prebiotic stimulation of SCFAs will 1) modify gut and urinary microbial communities to promote pathways considered protective against stone formation, 2) alter the expression of oxalate transporters (SLC26A3, SLC26A6) to reduce net oxalate absorption, and 3) reduce stone-promoting metabolites (e.g., oxalate) in the urine. Discussion/Significance of Impact: By defining the impact of prebiotic fibers and SCFAs on the gut–urinary axis in a natural animal model of CaOx urolithiasis, we will lay the foundation for novel nutritional strategies to prevent CaOx stone disease in both humans and animals.

Objectives/Goals: To guide UCSF in adopting a justice-based, patient-informed model of health data sharing that moves beyond traditional regulatory frameworks that focus on individual privacy and do not address public good and health equity; to create a roadmap for UCSF to implement transparent, community-engaged data governance that is both responsible and effective. Methods/Study Population: We conducted 24 hours of observation at outpatient clinics and 75 in-depth interviews with multiple stakeholder groups: patients, community advisors, and UCSF faculty and staff involved in managing and governing health and research-generated data. We used an ethnographic approach to investigate health data sharing policies and practices and explore perspectives on data governance. We were particularly interested in how data sharing is explained to patients, and what patients and community members know and think about how patient data may be used other than for clinical care. We explored faculty, staff, patient, and community member perspectives about the potential involvement of patients/communities in data governance. We also reviewed UCSF websites with information about data use and sharing policies. Results/Anticipated Results: Policy Awareness: Clear communication and improved guidelines for data use policies will enhance awareness among patients, the public, and researchers, boosting UCSF’s credibility as a data steward. Risks/Benefits: Data sharing drives scientific and clinical progress but raises concerns about privacy, profiteering, and unequal benefit distribution. Improving the Data Ecosystem: Safe data sharing and public benefit can be strengthened through centralized governance and better communication. Key growth areas include deidentification, external sharing criteria, and leakage prevention. Shared Governance: Patients and community advisors favor shared governance with public involvement, while UCSF informants were equivocal. All are concerned about equitable representation and technical training challenges. Discussion/Significance of Impact: Our recommendations to University leadership: Improve communication of data sharing policies to patients and the public. Involve patients and the public in data governance. Support investigators to ensure understanding and compliance with data use policies. Hold UCSF and collaborators accountable for transparency, equity, and public benefit.

Objectives/Goals: Male urogenital tract development is influenced by hormonal signals, which may be disrupted by endocrine-disrupting chemicals like lead. This observational study investigates the potential link between lead exposure and hypospadias rates in Puerto Rican boys, focusing on regional hotspots of hypospadias. Methods/Study Population: Lead levels from water plants across Puerto Rico were analyzed using PR Aqueduct and Sewer Authority water quality certificates. Hypospadias rates in seven health regions were obtained from the Puerto Rico Department of Health’s Birth Defects Prevention and Surveillance System. Data were from Puerto Rican boys born to women aged 15 years or older from 2017 to 2022. Rates were calculated using 2020 Census data, and statistical analyses were conducted using Intellectus. Results/Anticipated Results: Significant differences in hypospadias rates and lead levels were found across health regions, with the highest rates observed in Bayamón and Arecibo (5 cases per-100,000 births). Bayamón had the highest average lead concentration (14.33 ppb). A Kruskal–Wallis test showed significant regional variation in lead levels (χ²(6)  =  16.82, p  =  0.010) and hypospadias rates (χ²(6)  =  16.53, p  =  0.011). Post hoc analyses revealed key differences between regions, notably Bayamón and Metro. Discussion/Significance of Impact: These findings suggest a potential spatial link between prenatal lead exposure and hypospadias risk, underscoring the need for targeted public health interventions. Future studies will explore anti-Müllerian hormone expression in lead-exposed Sertoli cells to better understand the biological mechanisms behind these patterns.

Objectives/Goals: Our goal was to develop a method for creating a streamlined, Clinical and Translational Science Awards (CTSA)-specific translational science scoring rubric to be used to differentiate between translational science and translational research projects during the pilot proposal review process. Methods/Study Population: We created a survey using the 24 Translational Science Principle-based questions sourced from Schneider et al.’s 2023 manuscript in JCTS. Survey respondents were asked to rank the questions from 1 to 24, with “1” being the question that is the most impactful for defining translational science at Penn State. The survey was distributed to our CTSA staff, faculty, and leadership who are well-versed in translational science across all CTSA Cores. The rankings were averaged per question. The five questions with the most impactful average score were selected to be used to evaluate translational science at our CTSA. Results/Anticipated Results: Nine individuals, including faculty, staff, and leadership, across five CTSA Cores completed the survey. The average ranking scores ranged from 6.1 to 20.3. The top five ranked items represented the following four Translational Science Principles: generalizable solutions, efficiency and speed, focus on unmet needs, and cross-disciplinary team science. Importantly, these five items and corresponding translational science principles reflect our CTSA priority areas, the infrastructure support we provide, and the translational research activities conducted at our CTSA. For example, team science is highlighted throughout our CTSA programming, including mini presentations during our CTSA meetings. Discussion/Significance of Impact: This method allows CTSA teams to reflect on their institutional work and share Core-specific perspectives of translational science. This CTSA-specific rubric allows for streamlined translational science pilot proposal evaluation in alignment with site specific CTSA mission and vision.

Objectives/Goals: Opioid use disorder (OUD) in pregnancy and its implications on the maternal-fetal interface has been relatively understudied. Here, we aimed to uncover the impact of maternal OUD on placental structure, function, and inflammatory responses and further stratified our findings by maternal hepatitis C (HCV) infection. Methods/Study Population: To address this knowledge gap, we collected placental tissue from healthy pregnancies (control) and those with opioid use disorder with and without maternal HCV infection. First, placental development was assessed by gross and histological examination of the placenta. Immune cells were then isolated from decidua (maternal) and chorionic villous (fetal) placental tissues, and the frequency and phenotype of immune subsets were determined by flow cytometry. Markers of inflammation, placental perfusion, growth factors, tissue remodeling, and vascularization were measured in placental tissue homogenate by multiplex Luminex assay. Finally, gene expression alterations in placental architecture were assessed by Visium spatial transcriptomics, integrating transcriptomic data with spatial information. Results/Anticipated Results: Our results indicate that maternal OUD impairs placental perfusion/development and is accompanied by increased markers of inflammation in the decidua (IL-1Ra, IL-2, IL-18, IP-10, MIP-1β, and TNFα) and villous (IL-6 and IL-8). Furthermore, markers of angiogenesis and placental development are altered in the decidua, including increased EGF and IL-6Ra, but decreased FLT-1, FLT-4, and bFGF. The abundance of placental immune cells is varied with OUD/HCV, including decreased frequencies of decidual macrophages and NK cells, critical for blood supply to the fetus, and increased abundance of infiltrating maternal macrophages in fetal chorionic villous. Finally, spatial transcriptomics revealed aberrant infiltration of activated immune cells and modified processes associated with inflammation and angiogenesis. Discussion/Significance of Impact: Altogether, these findings suggest a profound impact of maternal OUD with and without maternal HCV infection on the structure, function, and immune landscape of the maternal–fetal interface that can alter fetal development and maturation.

Objectives/Goals: Bacterial dysbiosis has emerged as an accomplice in the progression of many cancers. The pancreas microbiome changes in pancreatic cancer patients. The mechanisms via which components of the microbiome regulate tumor growth is unclear. We seek to determine if bacterial dysbiosis influences cancer cell behavior thereby promoting tumor progression. Methods/Study Population: We performed immunohistochemistry for lipopolysaccharide and observed bacteria preferentially located in close proximity to cancer cells. We utilized an in vitro cell culture system and in vivo mouse models, in the presence and absence of gut bacteria, to assess the effect of bacteria and bacterial metabolites on pro-tumorigenic signaling and transcriptional changes in the cancer cell. We analyzed cancer cells and epithelial cells using RNA sequencing, flow cytometry, and enzyme-linked immunosorbent assay. We also used targeted metabolomics to identify bacterial and cancer cell produced metabolites. Results/Anticipated Results: We found microbial dysbiosis can induce proliferation, an inflammatory response and an increase in tryptophan metabolism via the kynurenine pathway in the pancreatic cancer cell. Along with upregulated expression of IDO1 in vivo, we observe an increase in nicotinic adenine mononucleotide. Also, we observe an increase in nicotinic acid in vitro and nicotinic adenine dinucleotide within the cancer cell compartment in the presence of bacteria and bacteria conditioned media. Due to the critical role in many vital pathways of cell survival, NAD+ production is thought to play a significant role in cancer progression. Nicotinic acid can stimulate NAD production to protect cells from cell death. Discussion/Significance of Impact: Pancreatic cancer is associated with a distinct tumor microbiome and ablation slows disease progression. Our data delineate mechanisms via which microbes modulate the pancreatic cancer cell and provide insight into therapeutic strategies for gut microbial modulation in treating pancreatic cancer.

Objectives/Goals: This study aims to first understand the expression of the L-type amino acid transporter, Slc7a5, in demyelinated plaques in postmortem multiple sclerosis (MS) CNS tissue. It also seeks to understand the effect of a novel inhibitor of Slc7a5 on remyelination in mice with experimental autoimmune encephalomyelitis. Methods/Study Population: Using single-cell RNA sequencing (scRNA-seq), we will examine the expression of Slc7a5 in demyelinated plaques in postmortem CNS tissue of patients with MS compared to non-lesioned regions (n  =  3/group). Using visually evoked potential (VEP) on mice with experimental autoimmune encephalomyelitis (EAE), we will determine the ability of the Slc7a5 allosteric inhibitor OKY-034 to promote remyelination compared to EAE-only controls (n  =  10/group). Lastly, we will use spatial transcriptomics with scRNA-seq to map transcriptional activity within different populations of cells to determine how OKY-034 changes gene expression in specific cell types compared to EAE-only controls (n  =  3/group). Results/Anticipated Results: A conditional knockout of Slc7a5 showed that microglial activation and oligodendrocyte differentiation were affected in demyelinated lesions. This suggests that it plays a role in numerous cell types in active demyelinated plaques, which is what we expect to find from our scRNA-seq data in post-mortem CNS tissue of patients with MS. Measuring VEP is a noninvasive way to measure remyelination in both clinical and research settings. OKY-034 increases oligodendrocyte differentiation suggesting remyelination, so we expect that administration of OKY-034 in mice with EAE will lead to restored VEP compared to control and EAE-only mice. Lastly, because OKY-034 reduces inflammation, we expect to see a decrease in gene expression for genes involved in an immune response. Discussion/Significance of Impact: Completion of this study will lead to understanding what the effect the allosteric Slc7a5 inhibitor OKY-034 has on remyelination and whether it may serve as a novel therapeutic drug that can be administered orally for the treatment of MS. This could lead to its further development as a treatment for progressive MS.

Objectives/Goals: Evaluate use and reuse of data in biomedical fields to explore how data advances translational benefit for science and patients. Methods/Study Population: In this study, we use the metadata for 5 million data citations in the Data Citation Corpus as a source to analyze the use of datasets from biomedical fields across a number of facets, including date, affiliations, and funders. We identify examples of datasets that have been used across different research fields by analyzing the disciplinary scopes of the datasets and the publications that cite them and explore patterns of reuse of datasets beyond the original research project from which it was created. Results/Anticipated Results: The analysis will provide insights into datasets showing broad usage in biomedical fields, the patterns of data use over time, and the affiliations and funders associated with highly used datasets. The analysis will also dive into examples of datasets showing use across different fields and usage beyond the original project. The results will showcase examples of valuable datasets in translational research and serve as a basis for exploring different considerations around the impact of open datasets. Discussion/Significance of Impact: The exploration of data citations will provide insights into open data showing translational reach and an example of how the Data Citation Corpus can support evaluation of the impact of research data.

Objectives/Goals: Colorectal cancer (CRC) is classified into right-sided, left-sided, and rectal cancer. Clinicopathological and molecular features vary along the colorectum, even within subsites, leading to inconsistencies in identifying relevant biomarkers. We created a CRC metabolome map to explore diagnostic and survival heterogeneity across subsites. Methods/Study Population: A total of 372 patient-matched tumor and normal tissue samples were collected from seven colorectal subsites: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). Liquid chromatography–mass spectrometry was used to compare metabolite abundances. Cox proportional hazards regression assessed metabolite impact on survival, adjusted for clinical covariates. Parametric and nonparametric tests were applied to compare the metabolite abundances. An interactive, publicly accessible online platform was developed to allow researchers to explore and generate hypotheses from this data. Results/Anticipated Results: Our study identified 39 and 70 significantly altered metabolites, including bile acids and lysophosphatidylcholines, across tumors and normal mucosa, showing metabolic heterogeneity between CRC subsites. We observed significant linear trends in metabolite gradients from the cecum to the rectum, and it was depended on the disease status. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite. Metabolite differences correlated with survival were unique to each subsite. Additionally, we developed an interactive, publicly accessible CRC metabolome database to share this valuable resource: https://colorectal-cancer-metabolome.com/yale-university. Discussion/Significance of Impact: This study provides the first CRC metabolome map, revealing metabolic differences across colorectal subsites. It challenges the right vs. left CRC classification, highlighting subsite-specific biomarker identification. Findings offer insights for personalized treatments tailored to the tumor type to improve patient outcomes.

Objectives/Goals: This poster details the development, implementation, and assessment of a comprehensive competency-based curriculum crosswalk and training plan aimed at enhancing the mentorship and skill development of translational research mentees within the National Institutes of Health (NIH) KL2 and TL1 Career Development Award programs. Methods/Study Population: The Center for the Improvement of Mentored Experiences in Research (CIMER) Mentoring Up for Early Career Investigators program, first developed by the University of Wisconsin-Madison, was further adapted by the Frontiers Clinical and Translational Science Institute (Frontiers CTSI). A competency crosswalk illustrates connections between a training curriculum and expected competencies. Developing a competency-based training crosswalk is a strategic approach designed to align mentoring practices with established NIH competencies, including the Seven Characteristics of a Translational Scientist, Mentoring Competency Assessment, Responsible Conduct of Research, Translational Teams, and TeamMAPPS. Results/Anticipated Results: The KL2 and TL1 Award Programs serve as ideal platforms for applying the developed curriculum. Implementing a competency-based, evidence-based, and culturally responsive curriculum for research mentee training has shown substantial benefits. Our pilot tests and full-scale implementation within the KL2 and TL1 Award Programs have demonstrated marked improvements in mentee competencies, such as technical skills, research design, and professional development as shown through evaluation feedback. Integrating the new Frontiers CTSI curriculum has fostered more effective and supportive mentoring relationships. Mentees have reported high satisfaction levels with the training program, particularly appreciating the interactive didactics, continuous feedback mechanisms, and reflective practices. Discussion/Significance of Impact: By adopting these recommendations, Clinical and Translational Science Awards (CTSA) and similar programs can improve research mentorship quality and impact, fostering a diverse cohort of skilled researchers. Implementing these strategies in CTSA mentorship programs offers a model for broader application in research training.

Objectives/Goals: Engaging interest holders in research is increasingly common, and guidelines include creating engagement plans. A detailed plan may be especially helpful when researchers perceive engagement as difficult or less relevant. We tested whether a study’s translational stage or an investigator’s years of research experience affect their perceptions. Methods/Study Population: Since 2019, the Tufts Clinical and Translational Science Institute Pilot Studies Program required applicants to submit plans to engage interest holders. Applicants in three cohorts responded to a survey about this requirement, including perceived difficulty developing an engagement plan, perceived relevance of engagement, and self-reported years of research experience (≤5, 6–10, and ≥10 years). Two raters assigned translational stage(s) of proposed studies: T0 (basic science), T.5 (pre-clinical to initial human studies), and T1 through T4. Separate analyses were conducted when multistage studies were coded as the earliest vs. latest stage and for individual stage vs. groups of stages (T0/T.5/T1 vs. T2/T3/T4). The Fisher’s exact statistical test was used to assess associations between variables. Results/Anticipated Results: Analyses included 67 participants. Developing an engagement plan was perceived as more difficult for studies at earlier translational stages when those studies were coded as the earliest applicable stage. This significant association held both when stages were grouped as T0/T.5/T1 and T2/T3/T4 (P  =  .03) and when analyzed as a single stage (P  =  .01); however, when studies were coded as the latest applicable stage, there were no significant associations. Similarly, when multistage studies were coded as the earliest applicable stage, engagement was perceived as less relevant for early-stage studies when grouped (P  =  .04), but not for individual stages or when studies were coded as the latest applicable stage. No significant association between years of research experience and perceived difficulty was identified. Discussion/Significance of Impact: Results show that investigators conducting early-stage research perceive more difficulty engaging interest holders, aligning with prior qualitative studies. These investigators may need more evidence of the value added to early-stage studies, targeted and practical training, and funder requirements to establish a culture of engagement.

Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.

Objectives/Goals: Mood and anxiety disorders are a risk factor (Ozer et al., 2003) for posttraumatic stress disorder (PTSD) following trauma exposure. As such, a latent internalizing dimension may also be a risk factor. We examine how the shared variance between mood and anxiety symptoms (as in HiTOP; Kotov et al., 2021) impacts development of posttraumatic stress (PTS) symptoms, and symptom clusters. Methods/Study Population: Using data from a prior study of individuals who arrived at emergency rooms and were assessed at later time points (AURORA study; McLean et al., 2020), our sample included 1866 participants (1208 females, Mage  =  38.49 years) with available data for the proposed analyses. A latent factor (INTtotal) was operationalized as the shared variance between mood and anxiety symptoms (PROMIS Anxiety and Depression; Cella et al., 2010) as well as PTS symptoms (PCL-5, Weathers et al., 2013). We computed a second internalizing factor excluding PTS symptoms (INTma) to isolate the contribution of baseline affect and anxiety from PTS at baseline. We examined how baseline PTS symptoms, INTtotal, and INTma compare as prospective predictors for PTS symptoms at later time points and how these variables predict individual PTS symptoms. Results/Anticipated Results: Baseline INTma, INTtotal, and PTS symptoms were significant prospective predictors of PTS symptoms across all time points (all with t > 10, p < .005). When focusing on INTma relative to DSM-5 PTSD criterion (American Psychiatric Association, 2013), INTma significantly predicted later symptoms at six months posttrauma pertaining to Criterion D (t  =  18.88, p < .005), negative alterations in cognition and mood, Criterion E (t  =  15.44, p < .005) arousal and reactivity, and Criterion B, intrusion (t  =  15.44, p < .005). INTma significantly predicted symptoms in Criterion C, avoidance, though to a lesser degree (t  =  12.87, p Discussion/Significance of Impact: These findings bolster the utility of examining PTSD risk factors through a transdiagnostic lens. INTma was predictive of later PTS symptoms, independent of baseline PTS. Our analyses reveal clinical implications for the assessment of PTSD, and the tailoring of treatment for patients high in internalizing following trauma exposure.

Objectives/Goals: This poster describes the scientific rationale, needs assessment, programmatic elements, and impact of a community of practice (CoP) focusing on advancing equity in the science and practice of mentorship. Methods/Study Population: In 2023, the University of Wisconsin Institute for Clinical and Translational Research received NIH R13 funding to host a conference, the Science of Effective Mentorship (Asquith, McDaniels, et.al., 2023). Approximately 150 researchers and program leaders from Clinical and Translational Science Awards (CTSA) Hubs and beyond attended. Data were collected before, during, and after the conference, providing the authors with an initial idea of community needs. As a result, a mentorship CoP was formed. In the subsequent 18 months, a steering and advisory committee established a program of virtual, topic-focused virtual events every 3 months as well as a community website, with increasing attendance and utilization. A survey was disseminated after the completion of one year, and a focus group was held during the last virtual gathering. Results/Anticipated Results: The demand for infrastructure to support a national community of practice will be demonstrated. The demographic and positional diversity (e.g. role within a CTSA Hub) will highlight the opportunities of convening this diverse community. Organizational challenges and opportunities will be highlighted. Assessment data will reveal the broad range of needs and interests of participants. Aggregate demographic, professional, and participation data about community of practice members will be shared, as well as the governance and programmatic elements of this community of practice. Evaluation results from the first year of activity will be displayed. Needs for sustainability will be discussed. Discussion/Significance of Impact: CoPs are not new in the CTR space. Membership in a CoP may reduce isolation individuals feel as they negotiate the important work of equity in the biomedical workforce. Members of this community of practice share the expertise and commitment to promoting equity in the biomedical workforce through supporting robust culture of mentorship.