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

Objectives/Goals: 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: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

Objectives/Goals: Increased follicle-stimulating hormone (FSH) is linked to declines in ovarian and metabolic function in older women. Obesity is both a manifestation and a driver of aging pathologies. In animal models, FSH and insulin resistance (IR) were reduced after 6 mos. of a nutritional therapeutic (GLYLO). Our goal was to translate preclinical evidence to humans. Methods/Study Population: An integrated, precision medicine approach identified a unique phenotype of aging-related debility relative to older females. A non-comparer pilot study was conducted to translate GLYLO preclinical findings to postmenopausal women with obesity (n = 85; >55 years; body mass index [BMI]  = 35.0±4.35; range: 30.3–42.8). Participants meeting the inclusion and exclusion criteria (n = 13) were enrolled and received two capsules of GLYLO (vitamins and natural products) daily for 6 mos. Assessments for FSH, estradiol (E2), IR (homeostatic model [HOMA-IR]), total cholesterol (TC), low- (LDL), high-density lipoproteins (HDL), safety biomarkers (e.g., red cell distribution width [RDW%], mean corpuscular volume [MCV]), and depression (Center for Epidemiologic Studies Depression Scale) were conducted prior to and after 6 mos. Results/Anticipated Results: Mixed-effect models with intent-to-treat analysis were applied to compare outcomes prior to (n = 13) and following (n = 7) the intervention. Significant reductions in FSH were observed (-13.1 [2.47] ∆/SD; p = 0.002)) following the 6-month intervention. Interestingly, BMI, E2 (p = 0.412), HOMA-IR (p = 0.885), TC (p = 0.363), and LDL (p = 0.145) were unchanged, while HDL decreased significantly (-9.7 [3.82] ∆/SD; p = 0.044). Other biomarkers, RDW% (-0.2 [0.05] ∆/SD; p = 0.009) and MCV (-2.3 [0.33] ∆/SD; p = 0004), were significantly reduced. All other safety parameters were not altered. Six participants reported mild to moderate adverse events (acid indigestion) and were lost to follow-up. Depression scores significantly increased (+4.0 [0.75] ∆/SD; p = 0.002)). Results were similar with and without intent to treat analysis. Discussion/Significance of Impact: Decreased FSH, but not IR, was observed following six months of GLYLO in postmenopausal women with obesity. Significant alterations in HDL, depression, RDW%, and MCV warrant further investigation. Findings are limited by the small sample size and loss to follow-up. Randomized, controlled trials are needed to confirm these results.

Objectives/Goals: Germinal matrix hemorrhage (GMH) is a devastating disease of infancy that results in brain-related pathologies. Following rupture of vasculature in the brain, red blood cell (RBC) lysis, and hemoglobin breakdown results in heme/iron-related toxicities. We hypothesize that these cellular pathologies are mediated in part by the complement system. Methods/Study Population: Post-natal mice on day 4 (P4) were subjected to collagenase induced-GMH and treated with various complement inhibitors that function at different points in the complement pathway and differentially prevent the generation of specific complement activation products. The principle bioactive complement activation products are C3 opsonins (C3b, iC3b, and C3d), the proinflammatory anaphylatoxins (soluble C3a and C5a peptides), and the terminal cytolytic membrane attack complex (MAC). Experimental groups consisted of: Wild-type (WT) naïve mice, and WT GMH-mice treated with either PBS (vehicle), CR2-Crry (C3 inhibitor that blocks all activation products), anti-C5 mAb (blocks C5a and MAC), C5aRA (blocks C5a-C5a receptor interaction), or anti-C7 mAb (blocks MAC). Study endpoints were P7 or P14. Results/Anticipated Results: Following GMH, CR2-Crry treatment decreased MAC deposition on RBC and additionally decreased heme oxygenase-1 expression, heme deposition, and iron-induced inflammation measured at P7. In support of a specific role for the MAC, anti-C7 mAb treatment resulted in similar outcomes and was similarly protective. Anti-C7 mAb treatment also reduced hydrocephalus development at a later time point (P14). A similar result was obtained using C7 deficient mice and with anti-C5 mAb treatment. On the other hand, no protective effect was seen with C5aR blockade, and double knock out of C3aR/C5aR also did not provide protection, indicating no role for the anaphylatoxins C3a and C5a and their receptors expressed on leukocytes and endothelial cells in exacerbating deteriorating outcomes. Discussion/Significance of Impact: Our data indicate a key role for the MAC in RBC induced hemolysis after GMH which serves as a driver of inflammation and early GMH pathogenesis. We further show that we can effectively increase precision by targeting solely the MAC complex acutely. Future work will be undertaken to determine temporal roles of individual complement activation products.

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: Micro-credentials (MCs) or digital badges are short programs designed to allow learners to gain knowledge and skills at their own pace to tailor their professional development. This study aims to examine the characteristics of learners completing MCs and explore their motivation for pursuing MCs through the University at Buffalo Clinical and Translational Science Institute (CTSI) program. Methods/Study Population: Currently, the CTSI offers five MCs in Effective Teaching, Good Clinical Practice, Responsible Research, Scientific Communication, and Translational Teamwork. Individuals who completed an MC (2019–2024) were identified by the UB Office of Micro-credentials. An invitation email and two reminders were sent to all individuals who received MCs asking them to complete a short online survey in July-August 2024. The survey included three questions about the type(s) of MCs completed, learners’ motivation for pursuing MCs, and perceived or actual benefits of completing an MC. The questions included multiple choice, select all that apply, and open-ended format, respectively. The survey was sent using Google Forms; data were analyzed using descriptive statistics. We received 25 completed surveys (29% response rate). Results/Anticipated Results: Since 2019, 85 individuals completed MCs at Buffalo CTSI including 21 faculty, 18 trainees, 26 students, and 20 staff. The most popular MC, Responsible Research (65% of completers), is based on the Responsible Conduct of Research series, which consists of modules on authorship ethics, ethical use of animals (IACUC) and human subjects (IRB), conflicts of interest/commitment, and responsible data acquisition and management. We found that 33% of responders were motivated to obtain the MC to advance their career and for professional development, 30% for lifelong learning, and 23% intended to use the badges to showcase their proficiency to potential employers. The greatest benefits reported were to obtain knowledge/skills for their professional career (46%) and improve their ability to receive research funding (14%). Discussion/Significance of Impact: Micro-credentials are valuable learning tools to stay current on changing research requirements, with ability to engage asynchronously. Badges also provide unique professional development opportunities for students and research workforce (staff and community stakeholders) who have limited resources (time and money).

Objectives/Goals: To assess theory of mind and empathy in adolescents with Tourette syndrome (TS) and examine their association with social problems. This study aims to extend research in social cognition to an adolescent cohort with TS and identify a potential modifiable risk factor for social problems in TS that may serve as a novel intervention target. Methods/Study Population: We will enroll 50 adolescents with TS (ages 11–17) and 50 demographically matched controls along with one parent to complete a single in-person study visit. Adolescents with TS will be recruited through the Vanderbilt Center for TS and other Tic disorders. Controls will be recruited using university listservs and flyers posted in community and primary care settings. Adolescents will complete the NEPSY-II to assess theory of mind abilities and the Multifaceted Empathy Test – Juvenile to assess empathy with negative emotions. Parents will complete the Child Behavior Checklist to assess adolescent social problems. Results/Anticipated Results: Based on evidence of low self-other distinction in TS, we hypothesize TS adolescents will make more errors about the mental states of others (theory of mind) and report greater emotional reactions to faces (empathy) compared to controls. Further, greater social problems will be associated with greater disturbances in social cognition. To date, 15 adolescents with TS and 15 matched controls have completed the assessment (67% male; Mage  =  14.33 in both groups). Within this sample, adolescents with TS experienced more social problems than controls (Cohen’s d  =  .74, p  = .03). There were no between-group differences in theory of mind or empathy in this pilot sample. However, higher levels of both theory of mind and empathy were linked to experiencing greater social problems in the TS sample only (p’s < .05). Discussion/Significance of Impact: Preliminary findings suggest that while social cognition did not differ between groups, TS adolescents exhibiting high levels of theory of mind and empathy appear to struggle socially. This work could inform future interventions by highlighting the need to focus on social cognition and how these skills translate into social behaviors.

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: The growing burden of hypertension in the USA disproportionately impacts individuals with lower socioeconomic status and those in rural communities. This study aims to investigate specific social determinants of health associated with uncontrolled hypertension among rural, underserved patients residing in Alabama. Methods/Study Population: A retrospective review of electronic health records data from the UAB Selma Family Medicine clinic was conducted. The deidentified data were entered into the Population Health Assessment Engine (PHATE) to render social characteristics and community vital sign (CVS) scores, a social deprivation index, by census tracts. We provide descriptive statistics and compare the stated factors between patients with controlled and uncontrolled hypertension using logistic regression models. We are conducting phone surveys to gather individualized data on social determinants of health to assess the perceived social needs of patients with hypertension. The Protocol for Responding to & Assessing Patients’ Assets, Risks & Experience tool was used to develop the survey, and survey responses will be compared with the PHATE results. Results/Anticipated Results: Among 2129 patients, 375 (17.6%) had uncontrolled hypertension with a mean age of 58.7 ± 14.4 years. Women comprised 66.7% (250) and 65.1% (1142) of the uncontrolled and controlled hypertension populations, respectively. The prevalence of uncontrolled hypertension was 19.1% among Black patients and 8.2% in White patients. Patients with uncontrolled hypertension had a CVS of 82.37 ± 7.31 and 81.81 ± 8.40 patients with controlled hypertension. Patients with uncontrolled hypertension lived in areas where an average of 46 ± 11% were not employed, 36 ± 9% rented, and 28 ± 1% lived below the federal poverty line (FPL). Adjusting for age, race, and sex, a unit increase in the proportion of people below the FPL was associated with 43% higher odds of uncontrolled versus controlled hypertension (OR  =  1.43, 95% CI 0.44, 4.64). Discussion/Significance of Impact: Rural, underserved patients with hypertension experience multiple adverse social determinants, such as nonemployment rates, low income, and rental housing. Survey results will allow us to compare assessed and individualized social determinants that may be important to address when caring for this population.

Objectives/Goals: This project will enrich our understanding of basal breast carcinogenesis, highlighting the distinct biological differences in breast cancer risk between non-Hispanic Black (NHB) or non-Hispanic White (NHW) women, but also has the potential to provide real-world solutions thereby contributing to reducing health disparities in breast cancer outcomes Methods/Study Population: In the biological investigation, I am utilizing a unique cohort of normal breast tissues from Mayo Clinic patients who underwent breast reduction surgery that have self-identified as NHB or NHW premenopausal women. From these tissues, we are able to subculture human mammary epithelial cells, which we will use for our consequent experiments. For the qualitative study, I aim to recruit up to 40–50 eligible NHB women identified at increased risk for breast cancer and conduct semi-structured qualitative interviews informed by the National Institute on Minority Health and Health Disparities Research Framework. Results/Anticipated Results: Gene expression profiling on our cohort of 15 NHB and 40 NHW premenopausal women identified a gene expression signature in NHB women indicative of elevated Hedgehog signaling, a key factor in triple-negative breast cancer (TNBC) development and progression. I hypothesize that persistent activation of Hedgehog signaling within NHB women instigates the proliferation and transformation of basal stem cells within the breast, thus fueling TNBC development. Understanding the perceptions and experiences of NHB women that are identified as being at an increased risk for BC will aid in the identification of barriers and facilitators to their risk reduction care and in turn provide implementation strategies that could contribute to alleviating the racial disparity seen in TNBC morbidity, mortality, and preventative care. Discussion/Significance of Impact: The significance of this project lies in its dual approach, uncovering basal breast cancer mechanisms in a high-risk group using normal breast tissue and evaluating the perspectives from NHB women to enhance the practical relevance of our findings.

Objectives/Goals: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a spontaneous inflammatory cerebral vasculopathy that mimics complications of Alzheimer’s disease immunotherapies. Our objective is to evaluate imaging and cerebrospinal fluid (CSF) markers of blood–brain barrier (BBB) impairment and inflammation in CAA-ri. Methods/Study Population: We plan to enroll 20 patients total: 1) 10 patients with CAA-ri as defined by Auriel et al (JAMA Neurology 2016) (exposure group). 2) 10 patients with non-inflammatory CAA defined using Boston criteria 2.0 that do not also meet criteria for CAA-ri (control group). The primary outcome will be Ktrans, a parameter of BBB impairment calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of the brain. Secondary outcomes will include DCE-MRI parameter VL, CSF albumin index, CSF fibrinogen, CSF sPDGFR-β, CSF MMP-2, CSF MMP-9, CSF C3, CSF IL1β, CSF IL6, IL8, and TNFα. Statistical comparisons between the exposure and control groups will be made using Wilcoxon rank sum test. Results/Anticipated Results: We anticipate significantly higher levels of BBB impairment and inflammatory biomarkers from DCE-MRI and CSF in subjects with CAA-ri relative to control subjects with non-inflammatory CAA. Discussion/Significance of Impact: Biomarkers are essential to characterize risk factors, pathophysiology, and possible treatment targets in CAA-ri. We plan to use the results of the current study to inform longitudinal studies that will test whether these markers are useful in identifying not only the presence of CAA-ri but also severity, progression, and response to treatment.

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model is a convolutional neural network (CNN) with dropout regularization. It generates a prediction set containing high-probability correct predictions using conformal prediction techniques, which add an uncertainty layer to the CNN. Additionally, gradient-based localization mapping is employed to identify brain regions associated with low uncertainty cases. Results/Anticipated Results: The performance of the computational conformal model is evaluated using training and testing data with varying dropout rates from 0.1 to 0.5. The best results are achieved with a dropout rate of 0.5, yielding a fivefold cross-validated average precision of 72.19% and an F1-score of 70.66%. Additionally, the model provides probabilistic uncertainty quantification along with gradient-based localization maps that identify key brain regions, including the temporal lobe, putamen, caudate, and occipital lobe, relevant to obesity prediction. Comparisons with standard segmented brain atlases and existing literature highlight that our model’s uncertainty quantification mapping offers complementary evidence linking obesity to structural brain regions. Discussion/Significance of Impact: This research offers two significant advancements. First, it introduces a probabilistic model for predicting obesity from structural magnetic resonance imaging data, focusing on uncertainty quantification for reliable results. Second, it improves interpretability using localization maps to identify key brain regions linked to obesity.

Objectives/Goals: Team science (TS) competency is important for translational science team collaboration. However, there are few educators available to assist teams. Asynchronous learning is an effective strategy for delivering TS content. The goal of this project is to expand TS education by providing online access to our learners using online modules. Methods/Study Population: The Collaboration and Team Science (CaTS) team at the University of Cincinnati provides a robust TS education and training program. As the need for team science gains recognition, CaTS has received increased requests for services, leading to a need to broaden TS offerings. To address this demand, the CaTS team created “Team Science 101,” an online, asynchronous, series of 15 modules covering basic team science concepts. Each module consists of an educational recording lasting an average of 20 minutes, optional topic resources, pre- and post-module surveys assessing learners’ confidence and satisfaction, post-module knowledge checks, and evaluation questions. Upon completing all modules, participants receive a completion certificate. Results/Anticipated Results: TS 101 will be piloted with a group of participants who expressed interest in asynchronous TS content and will be adjusted based on the feedback received. The associated pre- and post-module survey, post-module knowledge check, and evaluation questions will be monitored to determine learning levels and improve TS 101 overall. Canvas is the educational platform that houses these modules, allowing for participant follow-up and scalable dissemination. The CaTS team plans to disseminate TS 101 nationally and internationally for anyone interested in this resource. Discussion/Significance of Impact: There is a national effort to collect and curate TS education, training, and toolkits. TS 101 will be a useful educational tool that will expand the reach of team science educators, provide the foundation for educators to explore topics more deeply by building on the module topics, and provide education to broader audiences who lack access to TS experts.

Objectives/Goals: How do we care for a patient whose mental health is deteriorated such that their decision-making capacity may be compromised? The high-potency opioid crisis in Ontario demands that we provide effective care for the affected population. We must also avoid patients having a subjective experience of coercion and must protect their human rights and dignity. Methods/Study Population: Ontario’s legislation governing mental health care will be explored: the Ontario Mental Health, Healthcare Consent, and Substitute Decisions Acts. We will identify best practices/learning across locales. Patients who have been involuntarily treated/confined will be welcomed to voice what the law should contain. International strategies for: coercion reduction practices, advanced care directives, less prohibitionist care culture, and supports for social determinants of health (SDH) may also help Ontarians. Patients, family members, law enforcement, judiciary, community agencies, and healthcare professionals will be invited to contribute via focus groups to drafted mental health care legislative improvements. Thus, we ensure law enforces patient-defined quality care and practical workflows. Results/Anticipated Results: We hope to emerge from our focus group consultation with draft legislative and procedural edits for Ontario’s mental healthcare laws to ensure that the laws protect human rights and that the laws reflect patient-defined needs. We must ensure controls are in place to de-risk power imbalances and limit the incidence of potential procedural misuse. We intend to design legislated procedures to ensure that people don’t get inappropriately involuntarily confined/treated. We will incorporate the perspectives and lived experiences of patients who have experienced involuntary treatment and/or involuntary medical confinement (locally in a focus group(s)) and internationally (in literature) to inform this legislative development. Discussion/Significance of Impact: We will learn from engaged stakeholders about how to shape Ontario’s legislation to support quality mental health care. We hope to identify and draft legislation improvements that voice what patients and their families’ value, drafts informed by evidence-based best practices and informed innovation. Via inclusion, we create a policy that serves.

Objectives/Goals: The importance of interprofessional communication in healthcare is well documented. However, there has yet to be a theoretical framework for understanding this complex phenomenon. The purpose of this project was to develop a situation-specific theory about the culture of communication in the interprofessional healthcare setting. Methods/Study Population: We conducted individual virtual qualitative interviews with 16 healthcare professionals at different levels and from various disciplines. Participants were practicing clinicians at a tertiary care academic medical center. We transcribed audio-recordings of the interviews verbatim and aligned each transcript for accuracy, confidentiality, and representativeness. Data analysis was conducted using dimensional analysis, including open- and theoretical-coding utilizing an explanatory matrix for theory generation. Results/Anticipated Results: Our findings produced a situation-specific theory on the culture of interprofessional communication in the healthcare setting. Participants described the environments in which they practiced in terms of hierarchical system structures and through a conceptual perspective of resource investment. In other words, they viewed their time and their effort as valuable – and notably, scarce – resources, which they invest in patient care, interprofessional communication, and other tasks. There are two key pathways that characterize the culture of interprofessional communication: collaborative communication and transactional interactions, depending on whether an individual perceives the goals of another person, department, or level of the hierarchical institution as aligned with their own goals. Discussion/Significance of Impact: Positive cultures of interprofessional communication in the healthcare setting depend on perceived goal alignment among individuals, departments, and leadership. Future research can explore how perceptions of goal alignment are developed and empirically test this situation-specific theory in other healthcare system settings.

Objectives/Goals: We designed a forum to educate participants about bioethical issues in the application of big data (BD) and artificial intelligence (AI) in clinical and translational research (CTR) in underrepresented populations. We sought to determine changes in participants’ interests in ethics, bias, and trustworthiness of AI and BD. Methods/Study Population: 141 individuals registered for the forum, which was advertised to our partner institutions, minority-serving institutions, and community organizations. Registrants received email instructions to complete an AI Trustworthiness (AI-Trust) survey, a questionnaire with integrated qualitative and quantitative measures designed to better understand learners who engaged with the institution-specific AI/Data Science curriculum. Respondents completed the survey using personal devices via a link and QR code, with anonymized responses and enhanced privacy features. 82 people attended; 22 responded to the survey pre-forum and 22 post-forum. Pre- and post-forum responses were qualitatively compared to assess shifts in attitudes toward AI and BD and related interests in ethics, bias, and trustworthiness. Results/Anticipated Results: We found increased interests post- vs. pre-forum in the use of AI for CTR, AI bias and its effects on underrepresented populations, and ethical risk assessment and mitigation strategies for the use of BD to empower research participants. In contrast, trust in AI was lower post- vs. pre-forum. Moreover, respondents also indicated that the current application of AI in healthcare practice would result in increased racial, economic, and gender bias. In comparison, interest in ethical challenges, bioethical considerations, and trustworthiness regarding use of BD and AI in health research and practice did not differ pre- vs. post-forum. Discussion/Significance of Impact: Interest in the application of BD/AI in CTR increased post-forum, but AI distrust and bias expectations also increased, suggesting that learners become more skeptical and discerning as they become more knowledgeable about the complexity of the ethics of AI and BD use in healthcare, especially its application to underrepresented populations.

Objectives/Goals: Our research group is focused on care of hospitalized persons with opioid use disorder (OUD) in the era of high-potency synthetic opioids (HPSO). In this work, we describe trends in patient-directed discharge (PDD) and inpatient treatment with medications for opioid use disorder (MOUD). We hypothesized that PDD is associated with MOUD dose and timing. Methods/Study Population: Patient data generated in the routine care of patients was automatically abstracted using a SQL query on Epic Clarity tables in the electronic health record (EHR). We included adult patients admitted to Johns Hopkins Hospital between July 1, 2019 and June 30, 2022, with an ICD-10-CM code for a list of opioid-related disorders (F11.X) consistent with OUD. Demographics, prior medication list, clinical care including hospital service, consultation services, COWS scores, length of time in emergency department, time of triage, time until receipt of methadone or buprenorphine, dosage and timing of MOUD, opioid medications other than methadone or buprenorphine, adjuvant medications; prior methadone or buprenorphine treatment and disposition. Query results were validated by manual abstraction of EHR. Results/Anticipated Results: The SQL identification of the cohort of patients with OUD was found to be accurate. Time of triage, discrete orders completed during hospitalization were well represented in the query. The query was able to identify individual opioid medications but unable to summarize total dose in Morphine Milligram Equivalents. The query did not extract accurate information from patient-controlled analgesia pumps due to the continuous nature of the medication rather than discrete doses reflected in the medication administration record. Finally, the query characterized prior treatment with methadone or buprenorphine as a binary variable – dosage and timing of that prior treatment could not be accurately represented. Finally, stimulant use is not reliably collected in the EHR and was unavailable. Discussion/Significance of Impact: Given the rise of HPSO, patients may not tolerate delay of MOUD. Improving the granularity of data collected will offer more insight into the inpatient treatment for OUD. Real-world data have promise but requires extensive technical expertise. Future work is needed to improve capture of derived variables such as total dosage of opioids in MME.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer (BC) with limited treatment options. Mortality rate is especially high in African American (AA) women of reproductive age. High levels of intracellular calcium (Ca2+) have been shown in TNBC cells. This study is to investigate Ca2+ channel blockers (CCBs) as therapy for TNBC. Methods/Study Population: Two human TNBC cell lines obtained from ATCC – HCC1806, and MDA-MB-453 are treated with CCBs, Cilnidipine (Cil), and Mibefradil (Mib), in a concentration- and time-dependent manner. Cell proliferation assays are performed by the MTS cell viability assay. Intracellular Ca2+ levels are measured using the fluorescent dye: Fluro 4-AM. Apoptosis is determined by flow cytometry using Annexin V staining and mitochondrial permeability will be assessed by the Mito JC-1 assay. Expression of Ca2+ signaling genes will be quantitated by real-time polymerase chain reaction (RT-PCR). Potential pathways of CCB efficacy will be identified by ingenuity pathway analysis (IPA). Results/Anticipated Results: Our findings show both CCBs decrease cell proliferation in a concentration- and time-dependent manner to a maximum of 80% vs. control in both TNBC cells. Flow cytometry findings on both TNBC cells treated with both drugs at 20 µM for 24 hours depicts late apoptosis. Interestingly, Mib did not change the intracellular Ca2+ level in HCC1806 cells yet decreased in MDA-MB-453 cells by fivefold, while Cil increased the intracellular Ca2+ level in both cells almost twofold. It is anticipated that Mito JC-1 assay depict decreased mitochondrial potential in both cells. For reverse transcription polymerase chain reaction, it is anticipated that CCB treatment will increase transient receptor potential Ca2+ channels and decrease voltage-gated Ca2+ channels in both cells. IPA analysis is expected to show apoptotic pathways are involved in TNBC via CCB treatment. Discussion/Significance of Impact: TNBC lacks the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Treatment options for TNBC remain severely limited. Our findings that both Cil and Mib can inhibit proliferation of human breast cancer cell lines indicate repurposing CCBs as treatment for TNBC warrants further investigation.