Objectives/Goals: Competencies of a principal investigator (PI) in clinical research are crucial for ensuring the success, integrity, and ethical conduct of a study. This protocol aims to assess training offerings focused on improving clinical investigator competency and build a set of best practices for training. Methods/Study Population: The authors have started by creating a committed group of key opinion leaders at Rutgers Health and across industry to advise on the process. A mixed-method assessment of the current state of clinical investigator training/education in the conduct of T1-T4 clinical trials is currently being conducted to identify existing practices. An evaluation and assessment of key competencies will be initiated. Education and training objectives and modules will subsequently be developed from this process. The program will be piloted to early career clinicians, faculty, fellows, investigators within NJACTS, and other CTSAs and later assessed for efficacy. Results/Anticipated Results: A summary and descriptive statistics of the landscape of training opportunities and the variabilities of these offerings to address the needs of these investigators is projected to exhibit the gaps in knowledge and skill set required for a PI to effectively conduct a clinical trial. This will serve as the basis for developing a micro-credential (PI Badge) by the NJACTS’ Workforce Development group. Variability across educational offerings from academic institutions, sponsor/CRO protocol/study training, and online courses may not foster applicable skills. This badge is focused on addressing a clinician’s understanding of the roles and responsibilities as they align to the Principal Investigator commitments listed in the FDA form 1572. Discussion/Significance of Impact: Whether or not micro credentialing will enhance principal investigator competency, this mixed-method assessment is poised to identify a common benchmark for success. The ability to deal with increasing protocol complexity requires investigators to be more adept at implementation and compliance to sustain their ability to conduct clinical trials.

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: Kentucky (KY) is a high priority ending the HIV epidemic state, with high rates of new HIV diagnoses tied to injection drug use. The overall goal of this pilot is to launch sentinel surveillance of bloodborne infections and drug compounds among people who inject drugs (PWID) to monitor trends in near-real time and inform rapid community response. Methods/Study Population: In collaboration with the Clark County, KY, syringe service program (SSP), the pilot study involves two 1-month waves of data collection: enrolling eligible SSP participants and conducting anonymous behavioral surveys, collection of participants’ syringes, laboratory testing of syringes to detect HIV and hepatitis C (HCV), drug residue testing through National Institute of Standards and Technology, and statistical modeling approaches to produce outputs of bloodborne infection and drug detection. Syringes are tested from each enrolled individual for: 1) HIV antibody; 2) HCV antibody; 3) HIV and HCV PCR; 4) HIV antigen; and 5) drug residue. Collaboration with community and PWID stakeholders will identify optimal messaging for reporting results. Results/Anticipated Results: The first wave community-facing pilot was conducted in September–October 2024. 29 survey responses were obtained; median age of the sample is 42 years, 55.2% are gender female; 37.9% reported unstable housing in the past week. Primary drugs of injection reported via survey in the prior month were methamphetamine (62.1%), heroin (13.8%), fentanyl (13.8%), buprenorphine (10.3%), meth and fentanyl in combination (3.4%). PWID reported returning 900 used syringes and a median of 15 per participant visit. At most recent testing, 69.0% reported a positive HCV test; 0% reported a positive HIV test. Some level of drug checking with fentanyl test strips in past month was reported by 51.7%. Initially, 20 syringes were tested for drug compounds; results are pending. HIV and HCV detection testing will be completed by early 2025. Discussion/Significance of Impact: Early results document proof of concept for our sentinel surveillance study; all individuals screened were willing to participate in surveys and syringe collection. New methods to identify risk for disease outbreaks and emerging drugs can inform rapid allocation of prevention resources at a community level, especially where testing is infrequent.

Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.

Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.

Objectives/Goals: Monensin is FDA approved for use in veterinary medicine. Recent studies pointed to its potent anticancer activity. Since de novo drug discovery process typically takes 10 to 15 years and requires an investment of approximately $1.3 to $3 billion, drug repositioning can bypass several steps in this process and increase the potential for success. Methods/Study Population: Cell viability assays were conducted on human MDA-MB-231, MDA-MB-468, and MCF10A breast cancer cell lines and mouse EO771 and 4T1 breast cancer cell lines. MDA-MB-231 cell line was used in all the studies unless specified otherwise. Time course levels of Bcl-2, Bak, p62, and LC3II were assessed via Western blotting with GAPDH as a loading control. Proteomics analysis was conducted by the IDEA National Resource for Quantitative Proteomics. Time course levels of major histocompatibility complex (MHC) I and II and calreticulin were evaluated using flow cytometry. At least three biological replicates have been conducted for each experiment. Results/Anticipated Results: Monensin and several of its novel analogs were potent toward human and mouse breast cancer cell lines. Furthermore, they induced apoptotic cell death as evidenced by Annexin V/PI assay, downregulation of Bcl-2, and upregulation of Bak in MDA-MB-231 cells. Proteomics analysis revealed that several molecular pathways related to MHC class I and II antigen presentation were significantly altered following treatment with these compounds. Additionally, monensin and its analogs significantly increased the expression of MHC class I and II. Our studies also showed that monensin and its analogs increase the surface calreticulin levels. Treatment of MDA-MB-231 cells with these compounds also resulted in an increase in p62 and LC3II expression, suggesting a disruption of the autophagic process. Discussion/Significance of Impact: These results suggest that monensin and its analogs not only exhibit anti-breast cancer cell activity but also modulate immune-related pathways. By disrupting autophagy and enhancing calreticulin levels, these compounds may potentiate antitumor immune responses, providing a promising avenue for drug repositioning in cancer therapy.

Objectives/Goals: To explore the caregivers’ lived experiences related to facilitators of and barriers to effective primary care or neurology follow-up for children discharged from the pediatric emergency department (PED) with headaches. Methods/Study Population: We used the descriptive phenomenology qualitative study design to ascertain caregivers’ lived experiences with making follow-up appointments after their child’s PED visit. We conducted semi-structured interviews with caregivers of children with headaches from 4 large urban PEDs over HIPAA-compliant Zoom conferencing platform. A facilitator/co-facilitator team (JH and SL) guided all interviews, and the audio of which was transcribed using the TRINT software. Conventional content analysis was performed by two coders (JH and AS) to generate new themes, and coding disputes were resolved by team members using Atlas TI (version 24). Results/Anticipated Results: We interviewed a total of 11 caregivers (9 mothers, 1 grandmother, and 1 father). Among interviewees, 45% identified as White non-Hispanic, 45% Hispanic, 9% as African-American, and 37% were publicly insured. Participants described similar experiences in obtaining follow-up care that included long waits to obtain neurology appointments. Participants also described opportunities to overcome wait times that included offering alternative healthcare provider types as well as telehealth options. Last, participants described desired action while awaiting neurology appointments such as obtaining testing and setting treatment plans. Discussion/Significance of Impact: Caregivers perceived time to appointment as too long and identified practical solutions to ease frustrations while waiting. Future research should explore sharing caregiver experiences with primary care providers, PED physicians, and neurologists while developing plans to implement caregiver-informed interventions.

Objectives/Goals: * Examination of the acute glucose-lowering response to physical activity within a comprehensive behavioral weight loss intervention in adults without T2DM. * Explore whether the acute response to yogadiffers from the acute response to brisk walking and to examine whether these responses vary across the intervention period. Methods/Study Population: Participants in the behavioral weight loss and aerobic exercise group will start with 100 minutes per week of moderate-intensity aerobic activity, increasing every four weeks to 250–300 minutes, spread over five days. Activities will be self-selected, such as walking. Participants in the combined aerobic exercise and yoga group will do aerobic exercise three days a week and yoga two days a week, also progressing from 100 to 250–300 minutes weekly. All participants will follow an energy-restricted diet (1200–1800 kcal/day) and participate in weekly education sessions to learn lifestyle modification skills for successful weight loss. The study will explore differences in acute responses to yoga versus walking and how these vary during the intervention, controlling for initial and changing weight status. Results/Anticipated Results: Primary and secondary outcomes from the parent study will include body weight, BMI, body composition (via DXA), cardiorespiratory fitness, energy intake, and physical activity. Glucose and insulin levels will be measured pre- and post-exercise, with HOMA-IR computed. Continuous glucose monitoring (CGM) will be used to track glucose responses during each session, with the area under the curve (AUC) as the primary metric. The study will also explore advanced CGM analytics in collaboration with the KUMC Diabetes Institute that will include in-depth analyzation of peak and trough change velocity as well as novel correlations betwen glucose dynamics and physical activity patterns with an aim to uncover insights that transcend conventional CGM analyses. Discussion/Significance of Impact: This study uses advanced CGM analytics to examine glucose control during physical activity, collaborating with experts to create comprehensive models for glucose fluctuations. It compares acute responses to walking and yoga, addressing a key gap in research, with potential clinical insights for managing glucose in obesity.

Objectives/Goals: The study focuses on developing a wound patch that employs a biocompatible matrix which incorporates mesenchymal stem cells (MSCs) with wound healing and antimicrobial properties, along with antimicrobial metallic nanoparticles covered with keratinocytes derived from induced pluripotent stem cells to replicate the skin’s barrier function. Methods/Study Population: In vitro experiments will be conducted to combine bacteria with MSCs and metallic nanoparticles to assess whether bacterial killing is improved by this combination. The MSCs will then be evaluated in the presence of the nanoparticles to confirm that their functionality and phenotype are not altered. To verify the cells’ functional integrity, they will undergo trilineage differentiation, surface marker phenotypic testing, and evaluation of their capacity to inhibit lymphocyte proliferation in the presence of the nanoparticles. Subsequently, this living bandage will be created using a biomatrix embedded with induced pluripotent stem cell-derived keratinocytes and tested on a canine wound model to study the impact on healing. The model will assess the rate of healing and cellular response at weekly intervals until healed. Results/Anticipated Results: The combination of mesenchymal stem cells and antimicrobial nanoparticles works synergistically to enhance bacterial killing in vitro with S. aureus. The presence of the nanoparticles in combination with MSC did not affect the ability of the MSC to undergo trilineage differentiation. We anticipate that the surface phenotype will be similarly unaffected. In addition, we expect that the presence of the nanoparticles should not interfere with the ability of MSC to suppress lymphocyte proliferation. Utilization of the wound patch in the in vivo canine wound model is expected to enhance healing and prevent infection. We expect that we will observe a shift in the cellular composition of the wound with less inflammatory cells and more M2 or wound healing anti-inflammatory monocytes. Discussion/Significance of Impact: The incidence of resistant infections with no pharmacologic therapy available are on the rise. The development of an antimicrobial living bandage that increases the body’s ability to fight off infection, while providing a barrier to reinfection would provide a new way to treat infections regardless of their acquired antibacterial resistance.

Objectives/Goals: Our pilot study tests the hypothesis that a hospital-based oral health education and referral program will increase patient knowledge of the importance of oral health, engagement with dental health services, and create a reproducible model to improve access and utilization of routine oral health care services and treatments. Methods/Study Population: Participants recruited for this study will include a pool of eligible patients at an urban university affiliated teaching hospital, 18 years or older, who upon initial screening, reported having not seen a dentist within the past 12 months. Enrolled participants also reported having some form of dental insurance coverage. Our project plans to recruit fifty hospitalized patients from ten inpatient units. Once consented and enrolled, participants will receive a brief education on oral health and be assisted in scheduling a dental appointment with one of the providers from our dental referral network. The dental referral network will consist of local dental providers who agree to treat our study participants. Tracking of ongoing participant dental care engagement will be tracked over a six-month period. Results/Anticipated Results: We anticipate no issue recruiting the 50 planned hospitalized patients. One, the eligible hospitalized patient pool is large, two, data from previous study indicates that a large percentage (~57%) of hospitalized patients at our facility are not receiving adequate dental services and supports. We anticipated that the number of participants who attend their post-discharge dental appointments will be less than 70%. This number reflects averaged rate of missed dental appointments among other populations and considers that our population may have more barriers to appointment attendance. Due to the high prevalence of unmet dental needs among our study population, we anticipate that providers will report patients were seen for many standard dental procedures (cleanings, extractions, fillings, etc.) Discussion/Significance of Impact: The results of this study demonstrate the feasibility of 1) developing and maintaining a dental provider network and 2) utilizing hospital-based teams to promote inpatient engaging with regular oral hygiene and dental appointments. These results show how inpatients visits provide a valuable opportunity to engage adults with unmet dental needs.

Objectives/Goals: NIH requires researchers submit Data Management and Sharing (DMS) Plans with their grant applications. Librarians developed an assessment tool for the plans and completed a pilot assessment in order to leverage the plans and understand current institutional research data management and sharing. Methods/Study Population: The assessment tool includes questions related to evaluations of DMS Plans as well as questions related to the content of the plans. Evaluation questions were adapted from the Federation of American Societies for Experimental Biology evaluation rubric developed for the DataWorks! Data Management Plan (DMP) Challenge. Fields were added to collect information on the content of DMS Plans, including data type, institutional resources, data repositories, data standards, and data dissemination timelines. The assessment tool was tested in a pilot implementation. Seven library workers were trained and completed paired review samples of 27 DMS Plans (54 evaluations total) in order to test for tool reliability. Results/Anticipated Results: Results include findings on the reliability of the tool as well as preliminary results from an assessment of DMS Plans. Findings on the reliability of the tool include assessments of the paired reviewers for each question included in the tool. Paired reviewers generally agreed, but tended to differ on specific questions, including questions pertaining to the data types generated or used in a research project. Questions with high levels of agreement included subjects of study and code sharing practices. Results on the content of the DMS Plans include information such as data repositories used, data oversight responsibilities, and data and metadata standards employed. Discussion/Significance of Impact: DMS Plans present an opportunity to better understand data management and sharing practices, and good data management supports high-quality, reproducible research. Developing and testing assessment tools for these plans is a key step toward understanding and improving current research data management practices.

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: 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: Develop trauma-informed, victim-centered care skills. Foster student-led, translational research on trauma and victim services engage students in public policy and public health engagement support professional growth through research presentation and publication. Methods/Study Population: A review of the 2018–2021 mentorship program that engaged ten graduate students from diverse institutions (seven from San Juan Bautista School of Medicine, one from Interamerican University, one from UPR-Medical Sciences Campus, and one from Ponce Health Sciences University). Students participated in trauma-informed and victim-centered research projects focusing on sexual violence, child abuse, and victim services. They were mentored by Dr. Linda Laras and Dr. Linda Pérez at the Puerto Rico Health Justice Center, receiving hands-on experience through case discussions, literature review, research design, data collection, and presentations at the Start By Believing Symposium. Results/Anticipated Results: From 2018 to 2021, students developed trauma-informed care skills and conducted research on topics such as therapy dogs in courtrooms, victim services, and the impact of child sexual abuse. The results of this mentorship program included a publication in Cureus (10.7759/cureus.13644) and presentations at the Start By Believing Symposium, attended by legal and community professionals. The Fundación Intellectus Sexual Violence Research Scholarship was awarded, and the research earned award winning posters at multiple symposiums, including the SJBSM Interdisciplinary Research Symposium. Discussion/Significance of Impact: This mentorship translates trauma-informed research into real-world applications for sexual violence intervention. Medical students gain practical skills to address trauma in residency, while public health students shape policy. These research efforts have resulted in best practices and policy changes in Puerto Rico.

Objectives/Goals: Obtaining reliable clinical research professional (CRP) employment data within and across Clinical and Translational Science Awards (CTSA) institutions is an ongoing challenge. We describe an intra-institutional approach implemented to generate routine and accurate CRP data reports to monitor and evaluate CRP career progression and assist in formation of an institutional CRP network. Methods/Study Population: A research job family with 47 job series including human, animal, and laboratory research positions was implemented at Virginia Commonwealth University (VCU). However, CRP job satisfaction surveys and evaluations could not be confidently interpreted due to the confounding animal and laboratory research positions. Led by VCU Clinical and Translational Science Awards Workforce Development a cross-functional team was formed to isolate specific CRP positions. The team included CRP front-line staff and managers partnering with VCU Human Resource Information Systems. Identified were 39 unique CRP positions across 13 distinct job series. This identification provides CRP new hire and job specific data for evaluation and tracking as well as the ability for CRP directed communications. Results/Anticipated Results: Initial and monthly HR data reports were used to develop an institutional CRP list-serv for 325–350 allowing for targeted CRP communications within a decentralized environment. Bimonthly HR data reports identify university new hires and internal transfers into any of the 39 unique jobs within 0 – 12 days of hire. Twelve unique data points are provided (name, email, current position hire date, job code, job title, working title, department, division, supervisor’s name, job title, email, and job code) allowing for tracking and analysis of retention rates, career progression, and lateral movement among other outcomes. Collaboration led by VCU Clinical and Translational Science Awards Workforce Development team provides the representative CRP staff, managers, and institutional leadership with a renewed confidence interpreting CRP employment data. Discussion/Significance of Impact: The team science approach to identify and develop routine and real-time reporting of CRP job specific data provides a rich source of information. The information is used to evaluate CRP job satisfaction and factors contributing to CRP retention, engage in future mixed-methods research, and support the formation of an institutional CRP network.

Objectives/Goals: Magnetic resonance imaging (MRI) reports are stored as unstructured text in the electronic health record (EHR), rendering the data inaccessible. Large language models (LLM) are a new tool for analyzing and generating unstructured text. We aimed to evaluate how well an LLM extracts data from MRI reports compared to manually abstracted data. Methods/Study Population: The University of California, San Francisco has deployed a HIPAA-compliant internal LLM tool utilizing GPT-4 technology and approved for PHI use. We developed a detailed prompt instructing the LLM to extract data elements from prostate MRI reports and to output the results in a structured, computer-readable format. A data pipeline was built using the OpenAI Application Programming Interface (API) to automatically extract distinct data elements from the MRI report that are important in prostate cancer care. Each prompt was executed five times and data were compared with the modal responses to determine variability of responses. Accuracy was also assessed. Results/Anticipated Results: Across 424 prostate MRI reports, GPT-4 response accuracy was consistently above 95% for most parameters. Individual field accuracies were 98.3% (96.3–99.3%) for PSA density, 97.4% (95.4–98.7%) for extracapsular extension, 98.1% (96.3–99.2%) for TNM Stage, had an overall median of 98.1% (96.3–99.2%), a mean of 97.2% (95.2–98.3%), and a range of 99.8% (98.7–100.0%) to 87.7% (84.2–90.7%). Response variability over five repeated runs ranged from 0.14% to 3.61%, differed based on the data element extracted (p Discussion/Significance of Impact: GPT-4 was highly accurate in extracting data points from prostate cancer MRI reports with low upfront programming requirements. This represents an effective tool to expedite medical data extraction for clinical and research use cases.

Objectives/Goals: This project investigates how early childhood neighborhood factors influence attention-deficit/hyperactivity disorder (ADHD) outcomes in adolescence. Poor neighborhood conditions have been linked to higher ADHD rates; however, the effects of these factors on academic achievement, social relationships, and risk-taking behaviors remain understudied. Methods/Study Population: A large, diverse, harmonized, cleaned dataset from a national multisite research program (Environmental Influences on Child Health Outcomes (ECHO)) will be used. Neighborhood factors will be measured using geocoded, census-level indices of neighborhood quality: the Child Opportunity Index 3.0. Adolescent outcomes include self and caregiver-reported measures of comorbid psychopathology, risk-taking behavior, and academic and social functioning. A series of regression analyses will be conducted to examine the relationship between these variables. An estimated 6000 children are expected to be included in the analyses. Results/Anticipated Results: We expect that poorer neighborhood conditions, particularly low social and economic resources, will be associated with lower overall functioning in adolescence, and that this relationship will be stronger among adolescents with ADHD relative to those without ADHD. Discussion/Significance of Impact: By identifying risk and protective factors, this project will help identify potential prevention and treatment targets for a substantial number of youth and may inform policy efforts to improve resource equity and reduce existing disparities.

Objectives/Goals: Electronic health record (EHR)-based recruitment can facilitate participation in clinical trials, but is not a panacea to trial accrual challenges. We conducted a root cause analysis to identify EHR-based accrual barriers and facilitators in a pragmatic randomized trial of metformin for those with prostate cancer and glucose intolerance. Methods/Study Population: We quantitatively analyzed enrollment drop-offs among eligible patients who either did not complete a consent (with analysis of EHR-embedded consent process) or who completed a consent but were not enrolled (with analysis of EHR implementation of a Best Practice Alert). We summarized data from the EHR by eligibility, provider encounters, and alerts, and generated CONSORT diagrams and tables to trace the enrollment pathway. We supplemented quantitative findings with a thematic analysis of semi-structured individual interviews with eligible patients (n = 10) and study providers (n = 4) to identify systematic barriers to recruitment and enrollment of eligible patients. Results/Anticipated Results: CONSORT diagram analysis found that 24% of potentially eligible patients (268 of 1130) had an eligible study encounter but were not enrolled. Additionally, BPAs were not triggering for some eligible patients. Interviews revealed that study providers wanted more detailed information about which study arm their patient would be assigned to, and about next steps after enrollment, especially relating to additional lab tests and follow-up care needed. Patient interviews suggested that patients often did not remember completing the consent process and felt overwhelmed with appointments and information; patients expected providers to actively bring up research opportunities during appointments. Discussion/Significance of Impact: While pragmatic EHR-embedded trials are often characterized as lower-burden, these trials still require active engagement by providers, as well as ongoing attention from both research and informatics teams to ensure that EHR-embedded processes are functioning as designed, and that they are effective in recruiting study participants.

Objectives/Goals: In mice, it has been shown that loss of Cib2 (calcium and integrin-binding protein 2) results in progressive retinal disease that recapitulates many characteristics of age-related macular degeneration (AMD). This study aims to characterize transcriptional changes in the retinal pigment epithelium (RPE) that underlie this disease process. Methods/Study Population: RPE tissue samples, pooled from 2–3 mice for each biological group, were collected from Cib2-KO and wildtype (WT) mice at two (young) and eight (aged) months of age. Bulk mRNA sequencing was performed using the Illumina HiSeq 4000. Reads were aligned to the UCSC mouse reference genome and quantified using HTSeq. Significant differentially expressed genes (DEGs) between mouse genotype and age groups were assessed using DESeq. CLICK unsupervised clustering followed by gene ontology analysis was performed to identify cellular processes and molecular pathways affected by loss of Cib2 as well as age. Results/Anticipated Results: CLICK analysis revealed several functional pathways that are differentially expressed between sample groups. For example, in both young and aged mice, pathways upregulated in Cib2-KO samples included calcium signaling, RhoA signaling, and integrin signaling. Uniquely downregulated DEGs in young Cib2-KO animals were related to complement and coagulation cascades, LXR/RXR activation (related to lipid synthesis and transport), and phagosomes. Aged Cib2-KO mice displayed the most significant downregulation of genes in the phototransduction pathway, indicating temporal changes in functional pathways that correlate with disease progression. Next steps in analysis include investigating patterns in RPE- and AMD-signature gene sets that may identify molecular pathways more specific to human disease. Discussion/Significance of Impact: Many current studies investigate the role of complement activation, vesicle trafficking, and ion transport as top contributors to AMD development. We identified DEGs paralleling many of these molecular pathways in Cib2-KO mice, highlighting their potential as a model to study age-related RPE pathologies and evaluate therapeutic interventions.

Objectives/Goals: Skilled clinical research professionals are essential to efficient and effective research teams, but many undergraduate students are not aware of staff-level careers in the field. To address this, the Michigan Institute for Clinical and Health Research launched the Clinical and Health Research Professional (CHRP) Pathways Program. Methods/Study Population: The 10-week hybrid CHRP Pathways Program was piloted in Summer 2024. Undergraduate students interested in research careers were recruited from local universities and community colleges. The program consisted of 8 hours/week of didactic curriculum guided by ECRPTQ competencies and 32 hours/week of mentored work experience on research teams. Classroom activities were completed with participants from a partner program within the university. Surveys were administered at 3 weeks and 10 weeks along with an end-of-program focus group to assess acceptability and self-reported learning outcomes. Results/Anticipated Results: The pilot CHRP Pathways Program enrolled 3 students and was well-received by participating students and mentor research teams. Students agreed that they would recommend the program to their classmates. Students indicated that the program helped them understand the role of a study coordinator, provided insight into research career paths, and helped them form professional relationships. Self-reported confidence levels in a range of research competencies increased. Two students who completed the 10-week program chose to continue working part-time with their research teams while continuing their undergraduate studies. Discussion/Significance of Impact: Experiences like the CHRP Pathways Program provide valuable exposure to staff-level research career opportunities for students engaged in health science studies. They can address an existing workforce gap by equipping college graduates with relevant work experience and basic research competencies.