Objectives/Goals: Retention in care is vital for people living with HIV. We used human-centered design (HCD) to engage a community-based research panel over a 5-year period, allowing us to incorporate their insights on research guidance and interpretation of findings to investigate correlates of HIV care outcomes. Methods/Study Population: We recruited a diverse panel of individuals who were living with HIV, HIV clinicians, and/or providing non-clinical HIV services in Marion County, Indiana. We conducted biannual sessions using a variety of HCD tools and activities to engage participants. Each session took about three hours, and panelists were compensated for their participation. Due to the COVID-19 pandemic, sessions were initially held virtually. Sessions were designed for project discussion and to facilitate exploration of concerns and challenges facing receipt of HIV services. Our HCD approach put participants in the center of discussion and empowered them to externalize ideas and collaborate meaningfully with our team. Results/Anticipated Results: Since project inception, 48 individuals have joined the panel. Thirty-five are actively engaged, participating in one or more of six sessions conducted to date. We have learned much from the panel. One example is that a residential move might be a risk or protective factor for retention in care and the amount of time one had lived with HIV is a crucial factor. Panel insights have helped guide and prioritize analyses, aided in identification of data missing from our ecosystem, helped interpret results, provided feedback on future interventions, led to a quality improvement project with the local health department, and led to a presentation at a local health equity conference. Discussion/Significance of Impact: Community engagement is essential to impactful and sustainable research. HCD was a successful approach to engage our panel to inform interventions more relevant to the community. We anticipate these methods will be important for others conducting community-engaged research.

Objectives/Goals: The STEM-Coaching and Resources for Entrepreneurial Women (CREW) Program was developed to promote systemic change in entrepreneurship by engaging women faculty and post-doctoral fellows through educational opportunities, mentorship, and professional coaching to close the gender gap in entrepreneurial leadership. Methods/Study Population: We solicited applications from women at the junior faculty or post-doctoral fellowship stage. Applications were reviewed by the CREW leadership and mentors. Applicants accepted into the program participated in monthly large group coaching sessions, one-one-one coaching, and small group mentoring sessions. Applicants also completed an online entrepreneurship course and participated in a shark tank-like competition during annual innovation awareness month. Coaches were professionally credentialed and oriented to the biomedical context. Entrepreneurial experts served as mentors. Our program evaluation used the RE-AIM framework. The evaluation included assessments of the program’s ability to reach a diverse population, satisfaction with program offerings, and changes in entrepreneurship outcomes. Results/Anticipated Results: To date, three cohorts consisting of 35 women from 13 states participated in the program. Results from Cohort 1 show significant improvements in self-assessed confidence in entrepreneurial activities and high satisfaction with the program. All measures of confidence showed increases, with the largest gains in the areas of “estimating customer demand for new products or services”; “Clearly and concisely explaining my business idea in everyday terms”; and “Getting others to identify with and believe in my vision and plans for a new business”. The percentage of participants who have invention disclosures significantly increased from 33.3% to 83.3% after completing the program. The percentage who launched start-up companies also increased from 17% to 33%. Cohort 2 results will be available before the conference. Discussion/Significance of Impact: Participants in the CREW program showed improvement in all measures of evaluation. The program is unique in complementing mentoring with coaching. Because the coaching component takes a holistic approach by encouraging women to craft a vision for their work and life, it provides value that will last beyond entrepreneurship activities.

Objectives/Goals: This study aimed to identify preferences for nutrient-dense foods with critical nutrients associated with reduced neuroinflammation and perinatal depression risk. Aim two evaluated the acceptability of daily intake and preparation methods of select foods in Black American pregnant and postpartum people living in food apartheid in St. Louis. Methods/Study Population: The study included a mixed-methods sequential explanatory design with data collection at the YWCA of Metro St. Louis during Early Head Start programming with 21 participants living in geographies with low grocery-to-convenience store ratios. We conducted an open-ended online survey to determine participants’ preferences for specific foods with high nutrient density. Food preferences were subjected to nutrient analyses using FoodData Central, and foods with the highest concentrations of critical nutrients associated with reduced neuroinflammation and perinatal depression risk were identified. We presented results during a focus group with participants who completed the survey and evaluated the acceptability of daily intake and preparation methods. Results/Anticipated Results: Preferred food choices with the highest concentrations of critical nutrients associated with reduced neuroinflammation and perinatal depression risk included dark red kidney beans, black beans, pinto beans, black-eyed peas, peanuts, almonds, pistachios, walnuts, pecans, carrots, spinach, red bell pepper, sweet potatoes, and salmon. Participant justifications for low acceptance of daily intake included allergic reactions, “dry” or “slimy” texture, undesirable taste or appearance, absence of cravings, preferring alternatives, complicated preparation methods, and financial tradeoffs. Participant justifications for high acceptance included desirable taste and texture, diverse modification and preparation options, and nutrient composition critical for anemia treatment. Discussion/Significance of Impact: The study identified nutrient-dense food preferences within a sample vulnerable to nutrient-poor alternatives and health consequences. Participant acceptance of nutrient-dense intake was contingent upon recipes fulfilling cravings, acceptance among persons preparing meals, and diverse options to prevent boredom with preparation methods.

Objectives/Goals: Objective: To examine whether familial longevity modifies the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD) in older adults. Goals include assessing the impact of familial longevity on 1) CVD prevalence, 2) CVD incidence, and 3) mortality among individuals with CKD. Methods/Study Population: An observational, longitudinal study. We examined 1,236 Ashkenazi Jewish adults (ages 65–94) from the LonGenity cohort. Estimated glomerular filtration rate (eGFR) was the independent variable, calculated using the CKD-EPI equation 2021. CVD prevalence, incidence, and mortality were our outcomes. CVD was defined as a composite of MI, PCI, CABG, or stroke. Exceptional longevity was defined as living past 95 years, grouping participants into OPEL (offspring of parents with exceptional longevity, n = 576) and OPUS (offspring of parents with usual survival, n = 604). Stratified logistic regression and Cox proportional hazards models assessed eGFR’s association with CVD, testing effect modification through eGFR × OPEL interaction terms. Median follow-up was 5.5 years. Results/Anticipated Results: A significant association was observed between eGFR and CVD prevalence in OPUS, but not in OPEL. No significant link was found between eGFR and CVD incidence or mortality in either group. Familial longevity did not modify the association between eGFR and CVD prevalence, nor the composite of CVD incidence and mortality, as the interaction term was nonsignificant. The LonGenity cohort’s health status may have influenced these results due to selection and survivor biases, limiting generalizability. Further research is needed to clarify familial longevity’s role in kidney function and cardiovascular outcomes. Discussion/Significance of Impact: Our findings suggest that kidney function, as measured by eGFR, may be associated differently with cardiovascular risk in those with and without familial longevity. The study highlights potential limits of familial longevity in modifying CVD risk associated with CKD, underscoring the need for tailored CVD prevention strategies.

Objectives/Goals: Accurately stratifying patients with clinically isolated syndrome by risk of developing multiple sclerosis is of great clinical importance. Though numerous prediction models attempt to achieve this goal, no systematic review exists to independently evaluate these models. We aim to systematically identify and assess the risk of bias in all such models. Methods/Study Population: Studies developing or validating prediction models to assess risk of developing MS in patients with CIS who are not receiving an MS-indicated disease-modifying therapeutic will be identified via a systematic literature search. Studies will be evaluated for overall risk of bias using PROBAST (Prediction model Risk Of Bias Assessment Tool). Briefly, data sources, predictor, and outcome definition and assessment, applicability, and analysis will be assessed for each model in each identified study, and an overall risk of biased judgment will be assigned. Identified studies, predictors incorporated, results, and risk of bias assessment with accompanying rationale will be summarized in the final report. Results/Anticipated Results: Based on an initial exploratory search, we anticipate that most, if not all, identified prediction models will have high risk of bias. We anticipate that many studies will have limited applicability due to the use of outdated diagnostic criteria for definition of outcomes, or high risk of bias concerns originating from their analysis due to insufficient volume of included participants or poor model validation practices. We further anticipate that most, if not all, of the identified prediction models will have limited potential to be translated to use in a clinical setting. Discussion/Significance of Impact: Understanding how to identify patients with high-risk CIS may inform and improve clinician treatment decisions, patient outcomes, and future research study design. This work may also reveal flaws in current prediction models for CIS, opening new avenues of research and prompting development of improved prognostic models for patients with CIS.

Objectives/Goals: Citizen Science (CS) recognizes the vital role that community members play in research, centering their unique lived experiences and perspectives across the research cycle. We aim to enhance community-engaged research (CEnR) by adapting a CS Program at the University of Illinois Chicago (UIC) Center for Clinical and Translational Science (CCTS). Methods/Study Population: The CS Program, launched in response to COVID-19, was designed/piloted for Chicago community members interested in research careers, developing evidence-based practice skills, and/or partnering with academic, community, and/or public health organizations. To inform program adaptation, we are conducting a landscape assessment, including 1) inventory/annotation of existing curricular materials, 2) review of peer-reviewed literature, 3) website extraction of existing CS programs’ key components, and 4) interviewing key informants. An Advisory Board of prior CS instructors/alumni will guide curriculum adaptation, coordination, and fidelity. We will also identify strategic internal/external UIC organizational partnerships to collaborate on establishing, developing, and conducting the program. Results/Anticipated Results: Literature describes common CS program typology as a continuum, from research done “with the people” to research conducted “by the people” (King et al, 2016). Our program will equip CS to engage across these conceptual continuums. We plan to launch the UIC CCTS CS Program by Fall 2025 and have 10 online modules with a disability justice lens. Topics will range from Critical Thinking and the Research Process to Structural Violence and Evaluation Frameworks. Grounded in liberatory pedagogy, sessions will be taught by UIC faculty, staff, and community partners, each containing a lecture, interactive activities, and assessments. Participants will earn a certificate applicable to related jobs (e.g., academic/community research), supplement community health worker training, precursor to health degrees, and more. Discussion/Significance of Impact: Through the CS Program, we aim to center community expertise and lived experience within research, foster bi-directional collaborations and relationships, and build community capacity. We are evaluating this project adaptation and implementation to create a blueprint for institutions to enhance their community-engaged research.

Objectives/Goals: To investigate interventional clinical trial participation overall and by race, gender, and age. Methods/Study Population: We used Epic Cosmos, an aggregated, de-identified EHR platform including over 270 million patients, to examine overall clinical trial participation and the race, gender, and age composition of participants versus non-participants. Patients ≥5 years old with known race and gender and at least one healthcare encounter between 2021 and 2024 were included. Interventional trial enrollment was identified by a “research flag” indicating current or past participation in an interventional study within an Epic system contributing data to Cosmos. Race was categorized as American Indian, Asian, Black, Native Hawaiian, or White. Age-adjusted relative representation (RR) ratios were used to compare participation, with RR >1 indicating over-representation and RR Results/Anticipated Results: Of 130,455,189 patients meeting eligibility criteria, 0.52% (673,425) of patients were active or inactive in an interventional clinical trial. Results are shown in the figure below. The poorest representation was from Asian and NH/PI persons. Representation was most similar to the patient population for whites and AI/AN persons. Black males participated less and women, more than predicted by patient composition. Older patients participated more frequently than younger (age, mean (SD), y, 53 (22) vs. 46 (23); p Discussion/Significance of Impact: This is the first study we know of describing interventional trial participation in the USA across millions and millions of patients. Further research is needed to clarify whether these differences are due to the nature of the studies themselves (e.g., OB/GYN trials including only women, etc.) versus disparities in recruitment or otherwise.

Objectives/Goals: To design and implement programming that better prepares graduate students for diverse roles in a variety of workforce environments, our study models the training landscape and programming needs of graduate students in behavioral, clinical, and biomedical graduate programs at a large Midwestern school of medicine and public health. Methods/Study Population: We conducted six focus groups (two graduate program manager focus groups and four graduate student focus groups), to assess the programming, career development, and training needs of graduate students. Using a grounded theory approach, we first engaged in open coding of a sample of transcripts. After developing a codebook, we continued with an iterative coding process interspersed with coder meetings to discuss emerging and changing codes. Using the framework of landscape analysis allowed our coding and modeling to go beyond graduate student needs and study the varying relationships and contexts that impact graduate students throughout their training, such as relationship to supervisor or institutional policies. Results/Anticipated Results: Preliminary results indicate that students wrestle with their status as both students and workers. Specifically, conflict arises between graduate and supervisor expectations around time spent in class, lab, and other career development activities based on these divergent roles. Students and program managers also note the disparities that arise from the university’s lack of standard, formalized policy on labor issues, such as paid leave. Data also suggest that students on training grants note the difference in access to career development resources compared to colleagues. In many cases, students themselves coordinate ad hoc programming to better suit their career and professional development needs, although this work is not a required aspect of their training. Discussion/Significance of Impact: We characterize current graduate training landscapes, which continue to shift as graduate student bodies diversify, unionize, and express interest in increasingly varied biomedical careers. Data from multiple perspectives facilitate creating, implementing, and evaluating supportive training programs that meet identified student needs.

Objectives/Goals: Despite persistent health disparities, rural individuals are underrepresented in clinical trials, due in part to access barriers. We investigated if targeted strategies enhanced recruitment, engagement, and retention of rural adolescents in the TEENS+ randomized clinical trial, a 4-month family-based behavioral weight loss intervention. Methods/Study Population: Adolescents (12–16 y) and parents with obesity were eligible for TEENS+. Treatment converted to virtual in COVID-19, allowing eligibility to expand to more rural areas. We leveraged Informatics, a practice-based research network, and direct marketing to identify potential rural participants. Targeted engagement strategies included: rural physician outreach, physician-endorsed letters, providing tablets and mobile hotspots, reimbursing travel, and offering in-person or remote assessment visits. Chi-square tests evaluated differences in screener completion and enrollment of rural families before (T0) and after (T1) changes were made. Noninferiority tests evaluated rural vs. nonrural retention and engagement (% attendance, % dietary self-monitoring) and engagement based on digital tool receipt. Results/Anticipated Results: N = 211 dyads enrolled (n = 54 in T1: 48% male; 41% Black). Screener completion by rural families significantly increased from T0 (9.8%) to T1 (15.1%; p = .043). Yet, there was no significant change in rural adolescent enrollment (T0 = 10%; T1 = 9%; p = .844). Sixteen adolescents (30%) received study tablets, and none needed mobile hotspots. Mean adolescent attendance was 75%±28% for group and 94%±18% for individual sessions, with no significant differences based on rural status or tablet use. Rural adolescent self-monitoring (via app) was 28%, compared with 50% for non-rural adolescents (p = .074). Retention was 94% at 4m and 89% at 8m for T1 participants, with no differences based on rural status. At the primary endpoint (12 m), retention was significantly higher for rural (100%) vs. non-rural (87%) participants; p = .013. Discussion/Significance of Impact: Rural adolescent screener hits increased yet enrollment was unchanged. However, rural attendance was comparable and retention exceeded, compared to nonrural participants. Strategies to yield equitable representation and engagement in clinical trials are essential for geographic generalizability and to reduce rural health disparities.

Objectives/Goals: To discuss the challenges faced by National Drug Early Warning System (NDEWS; PI Cottler) in monitoring emerging drug trends and disseminating data to maximize public health impact. Drug trends are constantly in flux, with various communities facing different harms. To provide salient information, NDEWS must triangulate data from multiple sources. Methods/Study Population: In 2020, NDEWS was funded at University of Florida through a cooperative agreement with NIDA. A Scientific Advisory Group meets regularly for overall guidance, and 17 Sentinel Sites provide local perspectives. Now in its fifth year, NDEWS has utilized traditional data such as death reporting and drug seizures and has launched several novel surveillance components. Rapid Street Reporting conducts anonymous surveys of drug use in a Sentinel Site or hotspot each month. Machine learning methods applied to Reddit reveal new trends and novel substances. County-level alerts are generated by analysis of 911-dispatch data accessed through biospatial.io. Wastewater-based epidemiology provides city-level data. Findings are disseminated primarily through email weekly briefings and by peer-reviewed articles. Results/Anticipated Results: In its first iteration, NDEWS has expanded available data sources and worked to integrate data to reveal trends that impact communities across the USA. These patterns vary substantially over time and by region and population, complicating analysis, but inclusion of multiple data sources is imperative for a full understanding of the landscape. NDEWS continues to explore novel routes of disseminating information to those who need it, including contacting local health departments with high overdose rates. Establishing networks for bidirectional communication with stakeholder groups such as toxicologists and educational affiliates is underway. NDEWS seeks to deepen ties with survivors unions (those with lived experience) and harm reduction organizations, which can be difficult due to mistrust of research. Discussion/Significance of Impact: Monitoring the rapidly changing drug landscape in the USA is challenging, and its importance has only grown in recent years as new substances arise and adulterated drug supply has become the norm, promulgating the rise of dangerous substances such as fentanyl and xylazine. Ensuring that information filters out to those who use substances is critical.

Objectives/Goals: This study aimed to enhance clinical trial data management through large language model information retrieval and generation techniques within the clinical trial reporting workflow. We focused on improving compliance with reporting, reducing human labor, and promoting standardized reporting structure and data quality oversight. Methods/Study Population: We used approved study protocols from UC Davis IRB-approved investigator-initiated studies compared to the same studies reported to ClinicalTrials.gov. Our baseline data extraction system employs commercial large language models (LLMs) and retrieval augmented generation (RAG) to isolate data sources within the secure extraction environment. We stratified protocol documents into easy, complex, and random categories based on study focus, document complexity, the extent of amendments or modifications, and completion metrics from ClinicalTrials.gov. We developed a pilot web-based architecture to capture variations in categorization, labeling, and reporting style and compared generated extraction data. We primarily focused on qualitative evaluation through a review of expert staff. Results/Anticipated Results: Our results revealed significant variations in reporting quality, with dependencies stemming from multiple authors and stages throughout the clinical trial protocol lifecycle. Based on these variations, we used prompt engineering to improve the pilot application’s output compliance with the protocol registration and results system (PRS) structured data format for various study types. We piloted the assisted workflow with prospective studies by partnering with study investigators and the clinical trial office staff to assist in review and clinical trial reporting creation. Initial studies reported by our system were approved and released to the public by PRS staff. We are refining content generation and workflows to different components of studies and evaluating their use in quality and training areas. Discussion/Significance of Impact: Our system fosters collaboration, efficient review, and compliance with clinical trial reporting standards. It supports the promise of AI-driven assistance in clinical trial management, design, and reporting. We focus on the multiple stakeholders, expertise, and data flows in the organizational management of clinical and translational science.

Objectives/Goals: This study aims to harmonize quality indicators (QIs) across University of Toronto-affiliated microbiology labs to establish universal benchmarks that enhance performance, patient safety, and health outcomes. Harmonized QIs will enable effective comparisons and enhance the consistency of care. Methods/Study Population: The study employed the Delphi method, a structured and iterative process to build consensus. An expert panel of clinical microbiology trainees, medical microbiologists, trainees, and site leads from five University of Toronto-affiliated microbiology labs was assembled. Initial insights were gathered through surveys and a comprehensive scoping review of the literature. The study involved two rounds of feedback, a SurveyMonkey-based survey, with a defined consensus of 75% agreement among participants. Followed by an implementation survey conducted through REDCap to assess how these QIs were adopted in practice and identify barriers to implementation. Results/Anticipated Results: The study achieved consensus on nine high-impact quality indicators, including blood culture volume and contamination rates, cerebrospinal fluid transport time, and turnaround times for Gram stain results. Blood culture contamination and positivity rates garnered the highest agreement, at 100% and 91%, respectively. While some indicators were widely accepted and implemented, others faced resistance due to feasibility concerns. The study also identified significant variability in the level of adoption across the participating laboratories, pointing to operational challenges and the need for further efforts to address these barriers. Discussion/Significance of Impact: This study highlights the importance of QI harmonization in improving lab services and patient safety. It reveals challenges in standardizing practices but promotes uniformity in QIs, laying the groundwork for better inter-lab collaboration, consistent outcomes, and improvements in microbiology.

Objectives/Goals: The Wake Forest Clinical and Translational Science Institute (CTSI) has integrated academic goals of T0-T4 translation, scholarship, and education into our Academic Learning Health System (aLHS) framework. Our Translation Research Academy (TRA) provides rigorous training for outstanding and diverse K12 and early-career faculty to develop LHS core competencies. Methods/Study Population: The TRA Forum is the main vehicle for delivering an aLHS-oriented curriculum. Currently, the program includes six K12 scholars and 18 other early-career research faculty with facilitated access to CTSI resources. The TRA Forum is a 2-year seminar series that meets twice a month to discuss topics relevant to the aLHS, leadership, and career development. Inclusion of first- and second-year scholars facilitates peer mentorship, allowing Year 2 scholars to share insights with new scholars. Forum sessions are developed around adult learning theory: Each participant is asked to contribute their experience to discussions, and sessions focus on real-world examples. Results/Anticipated Results: Scholar and faculty commitment is very high. For the first 30 min., scholars present their work in small groups. This extends the range of disciplines exposed (64% of TRA graduates found this very helpful) and promotes translational traits of boundary crosser, team player, and systems thinker. Participants view the TRA as an opportunity to form internal peer networks, promote peer mentoring, and establish new collaborations. The remaining 60 minutes are used for education. Sessions include nominated topics and those providing a solid foundation in core aLHS competencies and characteristics of translational scientists. Educational sessions (97%) were rated as helpful or very helpful. Discussion/Significance of Impact: TRA scholars receive rigorous training in a highly supportive environment to produce aLHS researchers with skills to transcend boundaries, innovate systems, create new knowledge, and rigorously evaluate results.

Objectives/Goals: This study objective is to evaluate the prevalence and risk factors of burnout in practicing radiologists, with a focus on personal as well as systemic factors. It aims to identify and assess the existing strategies to mitigate burnout, enhance radiologist performance, and improve the quality of patient care. Methods/Study Population: The present study is a systematic review that summarizes existing literature on burnout in radiology, examining its prevalence, risk factors, and effect on diagnostic accuracy, decision-making, and job satisfaction. The review will synthesize validated evidence for emotional exhaustion, depersonalization, and professional fulfillment. The review discusses trends and solutions that have emerged from analysis of data within differing countries, subspecialties, and career stages, focusing on elevated risk of burnout in radiologists. It also assesses downstream effects on patient care quality such as missed diagnoses and increased medical errors. The review also discusses potential strategies for mitigating these negative effects on healthcare delivery. Results/Anticipated Results: The anticipated results of this review are expected to reveal significant variability in burnout rates across radiology subspecialties and practice settings, with prevalence ranging from 33% to 88% (Fawzy et al., 2023). Emotional exhaustion and depersonalization emerge as the most reported symptoms as consistently highlighted in previous studies. Major contributors such as workload, administrative burdens, and technological isolation (e.g., remote work and reduced face-to-face interaction) are anticipated. Radiologists in high-demand areas like interventional radiology and those in private practice may show higher burnout levels than those in academic settings. Protective factors, like exercise, supportive environments, and work-life balance, are expected to reduce burnout levels. Discussion/Significance of Impact: This study calls attention to the importance of addressing radiologist burnout as a key institutional priority. Early and effective interventions are essential for improving job satisfaction, reducing medical errors resulting in enhanced patient care. Addressing burnout is crucial for maintaining a sustainable and effective radiology workflow.

Objectives/Goals: Global surgical education is largely driven by high-income countries (HICs), with curricula not tailored to the needs of low- and middle-income countries (LMICs). This study assessed country-specific needs for global surgical curricula and used generative AI to develop tailored curricula. Methods/Study Population: A curriculum framework was developed using expert opinion. Using a focused needs assessment survey, we evaluated international medical students’ and trainees’ needs for structured global surgery curricula, covering research, education, data and develop tailored curriculum templates for each country, ensuring alignment with the distinct needs of respective LMIC and HIC respondents. The AI-generated curricula were then compared across countries to identify variations in content and focus areas. Results/Anticipated Results: A total of 145 respondents from 18 countries and 6 continents participated, with 94 from LMICs and 51 from HICs. Four countries [Uganda (n = 31), Nigeria (n = 34), the USA (n = 23), and the UK (n = 23)] had more than 10 respondents, with the creation of a country specific global surgery curriculum. Curricula developed by HIC trainees focused on access to resources and infrastructure, future directions of global surgical research, and the role of medical students and early career development with a decreased focus on the history of global surgery. LMIC country-based curriculum focused on introducing the concepts of global surgery, quantifying the burden and epidemiology of surgical disease and had a greater emphasis on case studies and use cases, with decreased focus on resources and collaboration. Discussion/Significance of Impact: The research introduces a “precision education” approach that could help close the surgical education access gap globally. Further pilot and qualitative studies are necessary to validate the feasibility of AI-generated needs-based curricula.

Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

Objectives/Goals: The study is designed to co-develop a genetics education digital platform with community participants. Diverse populations, especially African American communities, are less likely to participate in genetic testing and clinical trials. To increase participation and community input, we want community participants across Louisiana. Methods/Study Population: A cross-sectional, mixed-methods study will be conducted to assess interest in learning about genetics through a digital education platform and to adapt the platform based on participant feedback. Specific Aim 1 will be achieved by recruiting a diverse cohort and collecting demographic data to identify participants’ characteristics. For Specific Aim 2, 35 community participants will be enrolled as a co-design team to complete 5-week educational modules. Feedback from focus groups will guide iterative platform refinements, ensuring the platform is culturally tailored and user-friendly. Results/Anticipated Results: For Specific Aim 1, we anticipate that the majority of participants will express interest in learning about genetics through the digital platform, with demographic data revealing a diverse participant pool, predominantly from African American and Hispanic communities. For Specific Aim 2, we expect that all 35 co-design team members will complete the 5-week modules. Feedback from the focus groups is anticipated to highlight the need for more user-friendly navigation, culturally tailored content, and enhanced visuals. These insights will guide the refinement of the digital platform for improved engagement and accessibility. Discussion/Significance of Impact: This study addresses a critical translational barrier – underrepresentation of African descended communities in genetic testing. By developing a culturally tailored, digital platform to engage these populations, the project aims to reduce health disparities, enhance genetic literacy, and foster inclusivity in genomic research.

Objectives/Goals: Our research goal is to translate medical guidelines for adolescent-centered contraceptive counseling into improved clinical practice. Here, we describe the process of co-designing a training program for adolescent-serving primary care clinicians with teen, caregiver, and clinician advisory boards. Methods/Study Population: We recruited teens, caregivers, and clinicians residing in North Carolina to participate in three virtual advisory boards separated by role. Eligible teen advisors were assigned female at birth and 15–19 years old; eligible clinicians provided care for teen patients; and all groups were purposively sampled to reflect diverse identities and experiences. At each advisor meeting, we used human-centered design techniques to elicit participant priorities, generate training content and engagement strategies, and obtain feedback on the final training program. We conducted a focus group at our final meetings and used rapid qualitative analysis to understand our advisors’ experiences participating in program co-development. Results/Anticipated Results: We partnered with 20 advisors with diverse identities across geographic location, race and ethnicity, sexuality, and experiences with disability. During 15 meetings from January to May 2024 (five with each advisor group), we developed a 3-hour virtual, synchronous training for adolescent-serving primary care providers to improve their contraceptive counseling skills. The curriculum includes five interactive modules and a resource toolkit. Advisors described motivations to participate (e.g., chance to share their perspective, desire to make change), positive experiences with the advisory boards (e.g., opportunities to learn, to connect with others), and opportunities for improvement (e.g., better technology orientation). Discussion/Significance of Impact: We describe developing a successful longitudinal partnership with three community advisory boards and co-creating a training program that incorporates community-led priorities and perspectives, including youth. This approach can be adapted for other clinician training programs seeking to center community voices.

Objectives/Goals: This study examines prevalence of complete sample size justifications in publications in the top five clinical neurology journals. Secondary goals include comparing study designs and clinical populations to explore whether some may be more likely to include inadequate sample size considerations. Methods/Study Population: Recent studies (n  =  125) in Lancet Neurology, Alzheimer’s and Dementia, JAMA Neurology, Acta Neuropathology, and Brain will be evaluated. For each journal, the 25 most recent empirical articles between 2022 and 2023 will be examined for their inclusion of a justification and reproducible sample size calculation. Inclusion of components of an ideal sample size justification will be evaluated: effect size to be detected (standardized or unstandardized), alpha, power, and from where values were derived. Prevalence and completeness will be compared among study designs, clinical populations, and with regard to journal reporting requirements. Results/Anticipated Results: At the pilot review stage, 17 of 25 included studies had any kind of sample size justification, and only 3 studies had enough information to reproduce their sample size calculations. Retrospective studies included a sample size justification more frequently (81.8% vs. 57.1%), but prospective studies had more complete sample size justifications, when present. We hypothesize that sample size calculations will be more complete in reports of clinical trials and prospective cohort studies, compared to retrospective and cross-sectional designs. Based on our previous research, we do not expect that journal reporting requirements will affect completeness of sample size justifications. Discussion/Significance of Impact: Translational decision-making is informed in part by the robustness of current research. Transparency of sample size considerations in publications can contribute to the formation of less biased opinions of translational readiness and, subsequently, more efficient and effective translation.

Objectives/Goals: With qualitative interviews we aim to 1-Describe barriers and facilitators for post-transplant lymphoproliferative disease (PTLD) survivors’ access to late effects (LE) care. 2-Investigate clinicians’ perceptions of current and ideal PTLD LE care. Our long-term goal is to develop and pilot implementation strategies to standardize PTLD LE care. Methods/Study Population: Study population: We will recruit 20–25 PTLD survivors or their caregivers and 10–15 health care workers (HCW) from oncology, LE, and solid organ transplant (SOT) teams at St. Louis Children’s Hospital (SLCH). PTLD is a lymphoma-like cancer that occurs in solid organ transplant (SOT) recipients. PTLD survivors experience LE from cancer, yet many do not receive LE care. Research strategy: We will conduct qualitative semi-structured interviews based on the Consolidated Framework for Implementation Research (CFIR). A preliminary codebook will be based on CFIR and refined through transcript review. Team-based coding includes double coding and checking for intercoder reliability. We will generate coding reports to understand themes and identify barriers and facilitators of LE care. Results/Anticipated Results: We hypothesize survivors, caregivers, and HCWs will identify actionable factors to inform future studies to optimize LE care. We will examine the CFIR inner setting (resources, communication, and structural characteristics), outer setting (local attitudes and external pressures), innovation domain (adaptability, evidence base, and relative advantage), individuals domain (need, opportunity, and motivation), and implementation process domain. Our contribution will be novel. 1-This is the first assessment of barriers and facilitators for LE care in pediatric PTLD survivors. 2-We will consider input from HCWs across various disciplines delivering care to PTLD survivors. 3-We anticipate identifying unique contextual factors in PTLD survivors that will influence implementation of evidence-based LE care. Discussion/Significance of Impact: Pediatric cancer survivors experience LE. Coordinated care mitigates LE. PTLD survivors experience a high burden of LE, but less than 10% of PTLD survivors at SLCH follow in LE clinic. No studies have evaluated ideal delivery of LE care for PTLD survivors. Our findings will inform an implementation trial to improve delivery of LE care for PTLD survivors.