Objectives/Goals: The standard care for malignant gliomas includes maximal tumor resection, but challenges arise near functional (speech) areas. Direct cortical stimulation (DCS) identifies functional (nonresectable) cortex. We aim to identify electrophysiologic (via subdural electrode recordings [ECOG]) biomarkers of DCS-positive (functional) areas. Methods/Study Population: Our lab maintains one of the largest datasets of electrophysiology analysis of glioma infiltrated brain cortex in the USA. Recordings of intraoperative brain mapping were analyzed to identify cortical sites that were found to be positive (functional) during DCS. DCS positive and negative (nonfunctional) sites were aligned to corresponding subdural electrodes. Future analysis: We plan to compare the temporal and spectral electrophysiologic variations associated with cortical sites found to be DCS positive versus negative during brain mapping. We plan to train machine learning classifiers that utilize these electrophysiologic biomarkers to discriminate between DCS positive and negative sites. Results/Anticipated Results: In total, our database comprised of 110 resections with brain mapping (DCS) and ECOG, including 4 patients who underwent a second procedure for resection. Eight patients were excluded as their resections were for brain metastases, not glioma. Our final cohort was comprised of 98 glioma resections, including 4 patients who underwent surgery twice for recurrence. During these resections, a total of 1393 sites were mapped via DCS for language function (including picture naming, word reading, and sentence syntax tasks). Of these 1393 sites, 100 sites were found to be DCS positive (7.1% positivity rate). (Currently in the process of conducting analysis comparing electrophysiologic features and biomarkers of DCS positive versus negative sites.) Discussion/Significance of Impact: This research is ongoing. Identifying electrophysiologic biomarkers of critical DCS-positive regions may provide a durable alternative to stimulation mapping. Due to its resource intensity, DCS has access barriers. Future neurosurgeons may use biomarkers from subdural electrode recordings to plan safer cortical resections.

Objectives/Goals: • To determine the impact of liraglutide on inflammation and organ injury during sepsis. • To investigate the protective effects of liraglutide on microvascular dysfunction in a clinically relevant model of sepsis. • To provide evidence for the potential therapeutic use of GLP-1 receptor agonists in endothelial dysfunction in sepsis. Methods/Study Population: Sepsis was induced in mice (N = 34) by intraperitoneal injection of cecal contents (1.8 mg/g body weight) and 24-hour hyperoxia (FiO2 90–95%). Mice received saline or liraglutide (0.1 mg/kg) at 6 and 18 hours post-injection and fluids and antibiotics at 12 hours. At 24 hours, mice were euthanized for plasma, bronchoalveolar lavage (BAL), and tissue collection. Plasma inflammatory markers, organ injury markers, and BAL components were measured. In vitro, primary human lung microvascular endothelial cells (HLMVECs) were treated with saline or liraglutide for 24 hours before exposure to saline or LPS (100 ng/mL). HLMVEC barrier dysfunction was evaluated using express permeability testing (XPerT) and electric cell-substrate impedance sensing (ECIS) to measure transendothelial electrical resistance (TER). Results/Anticipated Results: In murine sepsis, illness severity scores and lung injury were improved in mice pretreated with liraglutide (N = 10). Plasma blood urea nitrogen (BUN; P = 0.0036), alanine transaminase (ALT; P = 0.0311) and vascular inflammatory markers MCP-1 (P = 0.0172), ICAM-1 (P = 0.0356), and Pecam-1 (P = 0.0493) in plasma were reduced in mice treated with liraglutide. In HLMVECs, liraglutide (1.5 nM) significantly reduced LPS-induced barrier dysfunction measured by XPerT assay (P = 0.0030) and ECIS (P = 0.0075). Discussion/Significance of Impact: Liraglutide reduces illness severity, vascular inflammation, and organ injury in a two-hit model of sepsis. Liraglutide has direct effects in the microvascular endothelium, limiting LPS-mediated barrier dysfunction. These findings support a protective role for GLP-1 receptor agonism in sepsis, mediated through the microvasculature.

Objectives/Goals: Discovery Day aims to bring diverse and underrepresented groups of potential biomedical research participants into research spaces to increase transparency, knowledge of the research process, trust in research, and interest in STEM fields. Methods/Study Population: Discovery Days are one-day events held on Saturdays at a large hospital in the Midwest. Attendees are recruited through flyers, social media, and other media. Recruitment targets communities that are predominantly underrepresented in research, such as Black/African American and Hispanic/Latino. Events included lunch, presentations, interactive lab demonstrations, Q&A sessions, and a tour of the BioBank research facility. Families completed surveys assessing demographics, trust in research, understanding of research, and interest in STEM careers. Descriptive statistics were used to summarize findings. Results/Anticipated Results: At a Discovery Day held in May 2024, 58 individuals attended. Each family (N  =  30) completed a 15-item survey. Most (70%) participants identified with diverse racial and ethnic backgrounds, with the largest group identifying as Black/African American. Five diverse neighborhoods were represented, as expected for our recruitment strategy. Following Discovery Day, 73.3% of participants reported their trust in research increased, and 93.1% of participants indicated their understanding of research increased. 37.5% reported interest in learning about STEM jobs or internships, and 100% of participants would recommend Discovery Day to friends and family. Discussion/Significance of Impact: We hope that by increasing transparency and trust around the research process, community members that may benefit from research (e.g., genetic research on chronic diseases) may be more likely to participate. Additional findings and future goals for Discovery Day will be discussed.

Objectives/Goals: pT217-tau is a novel fluid biomarker that predicts onset of Alzheimer’s disease (AD) symptoms, but little is known about how pT217-tau arises in brain, as soluble pT217-tau is dephosphorylated postmortem in the humans. Aging macaques naturally develop tau pathology with the same qualitative pattern and sequence as humans, including cortical pathology. Methods/Study Population: The etiology of pT217-tau in aging brains can be probed in rhesus macaques, where perfusion fixation allows capture of phosphorylated proteins in their native state. We utilized multi-label immunofluorescence and immunoperoxidase and immunogold immunoelectron microscopy to examine the subcellular localization of early-stage pT217-tau in entorhinal cortex (ERC) and dorsolateral prefrontal cortex (dlPFC) of aged rhesus macaques with naturally occurring tau pathology and assayed pT217-tau levels in blood plasma using an ultrasensitive nanoneedle approach. Results/Anticipated Results: pT217-tau labeling is primarily observed in postsynaptic compartments, accumulating in: 1) dendritic spines on the calcium-storing smooth endoplasmic reticulum spine apparatus near asymmetric glutamatergic-like synapses and 2) in dendritic shafts, where it aggregated on microtubules, often “trapping” endosomes associated with Aβ42. The dendrites expressing pT217-tau were associated with autophagic vacuoles and dysmorphic mitochondria, indicative of early neurite degeneration. We observed trans-synaptic pT217-tau trafficking between neurons within omega-shaped bodies and endosomes, specifically near excitatory, but not inhibitory synapses. We also examined pT217-tau in blood plasma in macaques across age-span and observed a statistically significant age-related increase in pT217-tau. Discussion/Significance of Impact: We provide direct evidence of pT217-tau trafficking between neurons near synapses to “seed” tau pathology in higher brain circuits, interfacing with the extracellular space to become accessible to CSF and blood. The expression of pT217-tau in dendrites with early signs of degeneration may help to explain why this tau species can herald future diseases.

Objectives/Goals: To identify gaps in policy that influence enrollment trends of patients with multimorbidity in Phase III clinical trials. We aim to propose policy recommendations for increasing use of real-world evidence (RWE) that increases safety and efficacy information for patients with multimorbidities. Methods/Study Population: Conduct a systematic policy analysis on the current regulatory landscape of RWE, referencing the 2020 FDA Guidance “Enhancing the Diversity of Clinical Trial Populations.” Evaluate guidelines using the Department of Health and Human Services’ (HHS) 2016 Regulatory Impact Assessment (RIA) Framework. Utilize the Center for Drug Evaluation and Research’s New Molecular Entity Database to identify novel hypertensive drugs approved after 2006, and assess clinical studies’ alignment with the 2020 Guidance. Review additional policies, FDA guidelines, and ICH documents to establish baseline compliance. Two case studies will evaluate past policy impacts on drug development. Assess costs and benefits of increasing multimorbid patient enrollment to inform a policy framework. Results/Anticipated Results: Anticipated results include all components of the HHS’s RIA and a policy framework informed by the assessment. To identify problems, an analysis of clinical trial exclusion criteria in novel hypertensive drugs will be conducted to show diversity and enrollment gaps in regulatory policy, referencing the FDA’s 2020 Guidance. The RIA’s cost–benefit analysis will highlight costs faced for utilizing RWE and expanding enrollment criteria in Phase III studies. The cost–benefit analysis, RIA, and case studies will inform a policy framework that explains dynamics between stakeholders and outline policies that increase clinical trial representation in ways that are less burdensome to sponsors and patients. Discussion/Significance of Impact: By understanding the barriers to enrolling participants with multimorbid conditions, we can outline incentives to increase diverse trial populations, helping healthcare providers choose more treatments for complex conditions. This research supports policy recommendations to make drugs more representative of conditions the population faces.

Objectives/Goals: This study looks to better understand and call attention to the inequalities found within medical treatment options for individuals suffering from preeclampsia during pregnancy in the USA. The goal is to map the terrain of clinical trials and evaluating existing medicare/medicaid covered services on a both national and state levels. Methods/Study Population: The study population for this research was limited to: pregnant women, ages 18–45, both pregnant and postpartum suffering from preeclampsia. We began looking at clinical trials targeting preeclampsia treatment conducted within the United States between 2019 and 2024. Using our study population parameters, we searched clinicaltrials.gov. These trials’ inclusionary and exclusionary factors were noted, along with participant race. The drug intervention medication used during these clinical trials was compared to those prescribed by doctors via the current national standard of care. We then looked at Medicaid coverage provided to expecting mothers on a state-to-state basis and nationally regulated level. These factors included coverage on ultrasounds, low-dose aspirin, blood pressure monitors, and more. Results/Anticipated Results: Preliminary findings demonstrate the need for more federally regulated policies and programs set in place to help combat the lack of resources faced by expecting mothers across the nation. This research will expose factors contributing to a lack of successful and completed clinical trials and lack of drug intervention innovations taking place to combat the rise in maternal deaths. This study will also focus on the importance of more education and awareness for communities such as African American mothers and those facing multiple gestational pregnancies who are at much higher risk of complications during their pregnancies. We also anticipate a large correlation between a lack of proper childbirth education and mothers who experience complications during birth. Discussion/Significance of Impact: Within the past two decades, rates of preeclampsia have grown 25% within the USA. It affects 5–8% of all pregnancies, and with maternal death rates rising, it is crucial to highlight the alarming lack of government regulation. It is imperative to provide awareness to mothers from disadvantaged backgrounds to treat this preventable condition.

Objectives/Goals: Knowledge about predictive factors for immune-related endocrinopathies can help identify appropriate populations for specific screening approaches, provide recommendations for ICI therapy selection, guide clinical monitoring strategies to improve patient outcomes, and guide research efforts to provide equitable healthcare for all patients. Methods/Study Population: This is an analysis of the demographic and clinical data available of patients from DiRECT Cohort, a longitudinal study that prospectively follows adult cancer patients who self-identify as Black or White and undergo anti-PD-(L)1 ICI therapy. Endocrinopathies were graded using the CTCAE criteria. Kaplan–Meier method was used to calculate the incidence within the first year of treatment. Bivariate analysis (Chi-square and log-rank test) examined the associations between patient demographics, clinical characteristics, and endocrinopathies. Results/Anticipated Results: Among 955 patients, 13.20% developed endocrinopathies of any grade, most commonly hyper-/hypothyroidism and adrenal insufficiency, and 5.97% were at grade ≥2. Younger age (7.59% in age 30 vs. 4.72% in BMI ≤30, p = 0.022) showed significant associations. No significant difference was found in the incidence of grade ≥2 endocrinopathies by race (13.3 % in White and 10.79% in Black patients, p = 0.732). No association was found with cancer stage or comorbidities. Discussion/Significance of Impact: ICIs can lead to (irAEs). Endocrinopathies are a common type of irAEs, presenting a unique challenge. However, the current literature lacks real-time data and a comprehensive comparative analysis of variables like race. Identifying and understanding these variables ensures equatable access to safe and effective healthcare for all patients.

Objectives/Goals: Pregnancy increases vulnerability to stress and mental health symptoms, particularly among Hispanic women in Puerto Rico (PR), a population with unique socioenvironmental adversities, such as poverty and natural disasters. This study examined the relationships between life adversities and psychological distress in this at-risk population. Methods/Study Population: Participants (n = 50) in this cross-sectional study were recruited from an obstetrician’s office in Southern PR. All participants provided written consent and completed the Adverse Life Experiences Scale (ALES, Cronbach’s alpha = 0.71) to identify lifelong adversities faced and the overall duration (chronicity). Measures of psychological distress included the Perinatal Anxiety Screening Scale (PASS, Cronbach’s alpha = 0.96), the Edinburg Postnatal Depression Scale (EDPS, Cronbach’s alpha = 0.87), the Perceived Stress Scale (PSS, Cronbach’s alpha = 0.79), and the Brief Resilience Scale (BRS, Cronbach’s alpha = 0.86). Descriptive and Spearman’s rho correlation analyses were conducted. Results/Anticipated Results: The mean age of the participants was 27.90 years (SD = 6.05), with most in the first trimester (66.0%). On average, participants reported 4.32 (SD = 3.1) out of 23 lifetime adversities. The most common adversities were natural disasters (60.0%), loss of a beloved (58.0%), and financial difficulties (38.0%). Nearly half (44.0%) experienced five or more adversities. A significant number of participants met the clinical threshold for anxiety (38.0%, PASS), depression risk (22.0%, EPDS), moderate-to-severe perceived stress (52.0%, PSS), and low resilience (24.0%, BRS). The overall duration of adversities was significantly associated with anxiety (rs = 0.50, p = 0.001) and stress (rs = 0.50, p = 0.007). Discussion/Significance of Impact: Hispanic pregnant women in PR face high levels of adversity and distress, which can negatively affect both maternal health and fetal development, influencing long-term child outcomes. Early identification and targeted interventions addressing adversities, can improve maternal mental health and child health-development outcomes.

Objectives/Goals: Planning research studies can be daunting for early-career investigators. The UW Madison Institute for Clinical and Translational Research (ICTR) has many services to assist, but navigating them can be convoluted. Therefore, we developed a method to streamline services for investigators. Methods/Study Population: Investigators were reaching out to ICTR research support services for assistance in the wrong order, delaying their study progress. To streamline ICTR services and improve investigator support, we developed the ICTR COllaborative Network (ICON) that meets weekly to discuss investigator needs and how best ICTR services can assist them. This group consists of members from ICTR’s Research and Protocol Development Program, the Recruitment and Retention Resource Center, and the Collaborative Center for Health Equity. After discussion and decision-making, a member of the group schedules a studio, bringing key services together at one time to help investigators more efficiently. Results/Anticipated Results: The group has worked with 22 investigators, decreasing the time to study implementation. One investigator indicated ICON saved her team over four months of work. Other investigators indicated the assistance with finding community partners and collaborators was essential to their success. We expect ICON, with its goal to streamline regulatory submissions and study planning, will continue to help investigators improve organization during study start up and execution, while enhancing recruitment strategies. This will result in quicker study completion and the capability to move forward with future projects and grant submissions. Discussion/Significance of Impact: ICON streamlined the consult process, improved efficiency of study planning, and brought together various experts for studio meetings with investigators. This efficient method can improve study function and execution for early-career investigators resulting in improved study success.

Objectives/Goals: Given the challenges that early career research scientists face, especially preparing for promotion and tenure, the decision on whether to join a research team can be fraught. We developed a novel training to support informed decision-making regarding new scientific teaming opportunities. Methods/Study Population: A team science workshop entitled “Should I join this research team” was designed for early career investigators from varied disciplinary backgrounds. Learning objectives for attendees included 1) describing the role of team science in translational research, 2) determining if teaming opportunities are a good fit, and 3) crafting thoughtful responses to requests. The training was initially delivered to 38 attendees (11 K scholars) during a virtual national meeting. We adapted this training for in-person delivery to K and T scholars at our CTSA regional partners. Instructional methods shared across virtual and in-person modalities included self-reflection, think and share activities, and scenario application. In-person delivery also included short video clips and small group discussions. Results/Anticipated Results: Multiple Likert-scale items were completed by workshop participants before and after completing the workshop to evaluate attendees’ confidence in their perceived abilities to explain strengths and limitations of team science, identify characteristics of effective science teams, evaluate a team invitation, assess costs and benefits, negotiate collaborative team invitations, etc. Preliminary data from the virtual workshop suggests that 54.6% of scholars were either not at all or only slightly confident in evaluating a teaming invitation. After the workshop, 45.5% reported being very confident, and 9.1% reported extreme confidence in evaluating a team invitation. Evaluation of the in-person training, along with a comparison of virtual and in-person learning outcomes will also be presented. Discussion/Significance of Impact: Our multimodal training is designed to equip early career investigators with the tools needed to evaluate and respond effectively to research team invitations. We believe this novel training will result in informed teaming decisions for early career research scientists.

Objectives/Goals: The gut microbiome and its metabolites, such as short-chain fatty acids (SCFA), are dysregulated in rheumatoid arthritis (RA); however, the significance of this observation and its implications in pathogenesis and therapeutics is unclear. Here, we explore the role of the SCFA, butyrate, in treatment efficacy in new-onset rheumatoid arthritis. Methods/Study Population: We designed a proof-of-principle study to determine the effects of butyrate supplementation in new-onset RA (NORA) patients that fulfilled 2010 ACR/EULAR RA criteria. We evaluated the effects of methotrexate (MTX) plus butyrate in NORA (n = 17; 1 gm butyrate, 3 times daily) compared to MTX alone (n = 19) over 4 months. MTX responders were defined by a change in disease activity score (DAS)-28 ESR of > 1.8 at 4 months. Fecal samples were collected at baseline and followed up for 16s rRNA sequencing and metabolite quantification by 1H NMR spectroscopy. Unpaired-t, paired-t, Wilcox and Fisher’s exact test were performed as appropriate. Results/Anticipated Results: MTX responders in the MTX-only group had a higher concentration of fecal butyrate than nonresponders at baseline (p = 0.045). Fecal butyrate concentration decreased over time in treatment responders in MTX group (p = 0.05), whereas butyrate concentration remained similar in MTX/butyrate group. Prior to treatment, both MTX and MTX/butyrate groups demonstrated similar levels of gut bacterial alpha diversity (Shannon index), yet only the MTX/butyrate group demonstrated a significant increase in alpha diversity by 4 months (p = 0.022). LefSe analysis demonstrated increased abundances of Bacteroides, Clostridium, and Phascolarctobacterium in responders in the MTX/butyrate group by 4 months. Ten (52.6%) patients in MTX and 11 (64.7%) in MTX/butyrate group were considered MTX responders by 4 months (p = 0.516). Discussion/Significance of Impact: Butyrate supplementation increased gut microbial diversity in patients and led to increased abundance of Bacteroides, which has been implicated in efficacy of methotrexate, a first line medication in rheumatoid arthritis. Butyrate may have implications for the maximization of therapeutic effectiveness in rheumatoid arthritis.

Objectives/Goals: To describe the evaluation processes of screening services implemented in community pharmacies. Methods/Study Population: A systematic literature review will be conducted from the last 20 years in Ovid Medline, APA PsycINFO, Clinialtrials.gov, and International Pharmaceutical Abstracts. Inclusion criteria are written in English, describes a clinical or health-related screening service in a community pharmacy, and evaluation of said health screening service is included. Approximately 950 articles have been initially identified. Two authors will screen each title, abstract, and full text for inclusion. Subsequent data extraction will occur including elements of 1) evaluation framework, 2) evaluation outcomes assessed, and 3) evaluation results. All elements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed. Quality of articles will be assessed using the MMAT. Results/Anticipated Results: Results are expected to show limited evaluation of screening services in pharmacies. Clinical conditions included in the screening services are expected to vary greatly. High-quality evaluations will be noted as templates for future evaluation of screening services in community pharmacies. Discussion/Significance of Impact: This systematic review will describe the current literature on evaluation of health screening services in community pharmacies. This will give readers an overview of how evaluations are currently being carried out in this setting, as well as provide them with templates of high-quality evaluations for future evaluation of screening services.

Objectives/goals: This project will focus on identifying the barriers that result in low adherence to quality care indicators that establish effective and efficient pediatric emergency care. The overall objective is to understand motivations behind adherence (or lack thereof) and find solutions to facilitate compliance. Methods/Study Population: This study will use a mixed-methods design to investigate the barriers. Quantitative data will be collected through a survey provided to healthcare providers involved in pediatric emergency care, including physicians, nurses, and administrative staff in both pediatric and general hospitals. Qualitative data will be collected through semi-structured interviews with a group of respondents to gain insight on their experience regarding compliance. Quantitative data will be analyzed using statistical analyses while qualitative data will undergo a thorough thematic analysis. Both sets of data will be reviewed to identify themes and differences in barriers across hospital types and healthcare roles. Results/Anticipated Results: We will have gathered insights and perspectives from key stakeholders that are relevant to our study to ensure a comprehensive understanding of any potential implications that may arise from our study. We anticipate that the specific results will highlight key differences in adherence between pediatric and general hospitals. The study is expected to identify specific barriers hindering compliance with established guidelines in both settings. The results may be used to increase adherence to critical quality indicators and improve patient care. Discussion/Significance of Impact: Pediatric injury care prioritizes the immediacy of care for children with acute illness and injury. With certain hospital protocols not being adhered to, there is a risk of wasting crucial time and resources that can affect patient care outcomes. The results would provide recommendations to improve and increase efficiency in pediatric injury care.

Objectives/Goals: Trainees in clinical and translational science (CTS) take courses in biostatistics, epidemiology, and other quantitative areas. To be most successful, trainees require competency in algebra. We developed a quantitative assessment and study guide to assess trainee’s quantitative skills and provide review material to address weaknesses. Methods/Study Population: The Tufts CTS Graduate Program is the training core of the Tufts CTSI and its associated pre- and post-doctoral T32 awards. Approximately 10 trainees with a range of backgrounds (e.g., physicians, medical students, master’s-level researchers, and basic science PhDs) and varying math education experiences matriculate each year. We wanted to address the resulting range of quantitative skills to help students succeed in our program. In Spring 2023, we met with faculty teaching quantitative courses to identify core algebra concepts needed to succeed in their classes. A graduate student in computational mathematics with extensive tutoring experience then drafted assessment questions, a comprehensive study guide, and brief cheat sheet. The material was reviewed and revised with input from quantitative faculty. Results/Anticipated Results: We developed a 20-item quantitative assessment covering properties of operators; identity elements and inverses; simplification of arithmetic and algebraic expressions; solving algebraic equations; functions; equations of a line; and exponents/logarithms. A cheat sheet provided trainees with a brief refresher for these topics. A study guide provided more detailed instruction, example exercises and solutions, and referenced publicly available, online resources (e.g., Khan Academy). During the introductory summer course for the Tufts CTS Program, trainees were allowed to use the cheat sheet and were given 1 hour to complete the assessment. Trainees who got questions incorrect were directed to relevant sections in the study guide. We anticipate collecting formal feedback to evaluate the material. Discussion/Significance of Impact: Trainees must have adequate foundational algebra skills to succeed in CTS graduate programs and as future researchers. Developing a quantitative assessment allowed us to identify areas of weakness resulting from educational disparities or reflecting other aspects of their backgrounds and to provide material to reinforce their preparation.

Objectives/Goals: We aim to develop an intuitive interface to understand the possible relationships between data from different RNA-Seq technologies. It can help novice users and educators to understand, analyze, explain, and visualize such datasets from diverse platforms, all without the need for additional software installations or strong programming expertise. Methods/Study Population: An online interactive interface is developed, integrating robust algorithms for three distinct types of analyses: DESeq2 for bulk RNA-seq, CIBERSORTx for deconvolution, and Seurat for single-cell analysis, with plans to include more algorithms. It allows a demo mode for training using the sample datasets and option for tailored analysis using user’s partially processed data. The interface provides capability to process bulk RNA-seq data from raw counts or a differential gene list. Further, deconvolution analysis for bulk RNA-seq data can be done using raw counts and single-cell data analysis can be performed using processed sequence reads, organized into three key files: barcodes, matrix, and features. Users also have an option to download the results as a zipped file, for samples from human and mouse studies. Results/Anticipated Results: Users with an active internet connection can access the interface from any major web browser. They can adjust parameters – such as genome type, cutoff thresholds, and batch effect correction – according to their specific needs. Bulk RNA-seq results are presented in the form of volcano plots, heat-maps, clusters, gene expression across samples, DEGs, and enrichment plots from KEGG and GO analyses. Deconvolution analysis can be performed using either the “LM22” signature matrix (for human leukocyte cell types) or Derm22 (for skin-specific cell types). The single-cell workflow provides results including quality control metrics, UMAP clustering, gene expression plots/tables, and cluster annotation using CellTypist. Comprehensive details on methods and tutorials are available in the GitHub repository. Discussion/Significance of Impact: Although multiple workflows are available to process bulk and single cell RNA-Seq data along with deconvolution methods to bridge the gap between the two, this is the first online interface to provide the capability to explore and analyze data from all three approaches in one place, without requiring strong computational expertise or resources.

Objectives/Goals: This study tests the REDCap Clinical Data Interoperability Service (CDIS) for streamlined data extraction from electronic health records (EHRs) for research. Managed by Clinical and Translational Science Institute, IU Health, and Eskenazi Health, CDIS offers real-time data syncing, automated workflows, and HIPAA-compliant data security. Methods/Study Population: The REDCap CDIS uses the Fast Health Interoperability Resource (FHIR) Application Programming Interface (API) to extract data from EHRs. It includes the Clinical Data Pull (CDP), which automatically pulls EHR data into user-defined REDCap fields, and the Clinical Data Mart (CDM), which collects longitudinal patient data. Three use cases were selected to assess the CDIS’s effectiveness in extracting data from the IUH Cerner and Eskenazi Epic EHR systems. The technical team set up clinical data mapping and adjudication processes, simplifying complex manual data extraction. Results/Anticipated Results: The CDIS successfully achieved real-time data synchronization during pilot testing with each EHR system. We extracted demographics, drugs, procedures, labs, and conditions. The mapping interface supports many-to-one data point mapping for the study data dictionary, and the adjudication process ensures data quality before integration into the REDCap database. The CDIS also improved data security and HIPAA compliance. An implementation intake process was developed for Indiana University investigators, allowing them to use the service for affordable clinical data extraction from EHR systems. Discussion/Significance of Impact: The implementation and testing of the REDCap CDIS demonstratesits effectiveness in streamlining EHR data extraction for research. The CDIS facilitates real-time data synchronization, automated workflows, and enhanced data security, offering a cost-effective solution through collaborative oversight with research teams.

Objectives/Goals: Youth-onset diabetes and its risk factors are increasing in ethnic and racial minority communities. Our mixed-methods study aimed to explore the associations between participation in a community youth sports program and key diabetes risk factors in youth, including mental health, physical activity, nutrition, and weight status. Methods/Study Population: We used a single cohort, mixed-methods design focused on the Community Leadership Revolution (CLR) Academy, a local youth sports program. Participants, ethnic and racial minority youth ages 5–14, were recruited to assess their mental health, physical activity, and nutrition using validated and reliable questionnaires. Weight status was measured via bioelectrical impedance. Group interviews with youth and individual interviews with staff provided context for the quantitative results. A thematic analysis of the qualitative data will further explore how CLR Academy may impact diabetes risk factors. Results/Anticipated Results: We recruited 24 CLR participants (16 boys/8 girls) and 4 CLR staff (3 males/1 female). Sixteen youth identified as African-American, while the rest identified as multiracial. Correlations revealed that higher attendance at CLR Academy was negatively associated with mental health scores, specifically total, externalizing, and hyperactive scores (all p < 0.01). Higher CLR attendance was negatively associated with physical activity during spare time (p < 0.05), waist circumference (p< 0.05), and waist-to-height ratio (p < 0.01). Being a girl was associated with lower diet quality and physical activity (both p < 0.05). Qualitative data highlighted life skills and supportive relationships in CLR as key factors in improving health outcomes. Thematic analysis is ongoing to clarify these relationships. Discussion/Significance of Impact: This study highlights how participation in programs like CLR Academy may improve ethnic and racial minority youth diabetes risk factors. Staff and participant insights on mechanisms driving these health improvements may offer strategies that can be applied to similar programs focused on reducing marginalized youth’s diabetes risk.

Objectives/Goals: The informed consent (IC) process is similar between clinical trials and expanded access (EA), which allows clinical use of investigational products outside studies. Physicians face unique barriers to IC in clinical environments. This project assesses IC documentation, identifies potential barriers, and evaluates efforts to improve compliance. Methods/Study Population: This is a continuous quality improvement project. To assess the compliance of IC processes for EA patients, informed consent documents signed by EA patients in 2023 were collected and reviewed against institutional standards. Five components of each form were evaluated, and the number and type of noncompliant documentation were tracked. Five physicians who provided EA treatments in 2023 were interviewed and the transcripts were analyzed to identify barriers to physician’s and teams’ IC processes. Efforts made to address these barriers and improve the compliance of informed consent documentation are being tracked and trends in compliance are being evaluated. Results/Anticipated Results: Sixty seven (67) signed informed consent documents for EA treatments were systematically reviewed and 34% were found to be compliant in all key aspects assessed. Analyses of interview notes, transcripts, and memos identified barriers to informed consent processes for expanded access treatments, including the infrequent or irregular occurrence of EA treatments making it difficult for care teams to develop and maintain their understanding of IC process and resources. Efforts made to improve compliance by pre-populating available information into informed consent documentation and removing unnecessary boxes in these forms may have driven improvement in compliance with further efforts underway. Discussion/Significance of Impact: This project evaluated the compliance of IC documentation for EA treatments and identified drivers affecting physicians’ IC processes for these patients. Different strategies to improve the compliance of IC documentation were evaluated and potential best practices for EA support were identified.

Objectives/Goals: Rural disparities in chronic disease burden are well documented. However, the impact of individual socioeconomic status on these rural disparities in prevalence and control status of chronic diseases remains less understood. We aim to assess the association of prevalence and control status of chronic diseases among adults with rurality and socioeconomic status (SES). Methods/Study Population: The Expanded Rochester Epidemiology Project medical records linkage system identified prevalence of asthma, diabetes, hypertension, and mood disorder using ICD codes between 2014 and 2019 among adults in 27 Upper Midwest counties. Uncontrolled status was defined by presence of ED visit or hospitalization with corresponding ICD-9/10 codes. SES was measured by HOUSES index, a validated individual-level SES measure, and rural status was defined by primary Rural Urban Commuting Area codes of 4–10. Hierarchical logistic regression models were used to examine the association of rurality with prevalence and control status of the four chronic diseases, adjusting for age, sex, race/ethnicity, and presence of general medical exam extracted by CPT codes (Model 1) and additionally SES measured by HOUSES (Model 2). Results/Anticipated Results: Among 455,802 adults, 42.8% were rural residents and 87.4% were Non-Hispanic White. Model 1 (without HOUSES) showed higher prevalence and lower control rates of chronic diseases in rural residents, except for asthma. In Model 2, accounting for SES, urban residents were more likely to have an uncontrolled mood disorder, hypertension, and diabetes, and there were no differences in prevalence of chronic diseases that existed between rural and urban residents. Lower SES measured by HOUSES was consistently and significantly associated with higher prevalence and uncontrolled status of chronic diseases (p-value Discussion/Significance of Impact: Patient’s SES explains rural disparities in prevalence (null association with rurality once SES is accounted) and changes the directionality of association for uncontrolled status in Upper Midwest, highlighting the importance of considering SES in rural disparities research.

Objectives/Goals: The University of Illinois Chicago’s Center for Clinical and Translational Science has implemented an innovative approach to program evaluation. We blend high-impact quantitative and in-depth qualitative approaches to identify local and national impacts and areas for improvement that are not captured solely by traditional quantitative methods. Methods/Study Population: CCTS manages service requests and investigator demographics through an in-house system that our evaluation program utilizes to report on service requests, investigator satisfaction, and investigator demographics to service groups, CTSA and campus leadership, and other stakeholders throughout the year. Through this system, we are able to regularly survey and interview investigators about their experiences and solicit feedback about the service process. During interviews, we focus on questions about receiving services, recommendations for CCTS and colleagues, and plans to work with CCTS in the future. This mixed-methods approach helps us lay the foundation to expand evaluation beyond reporting and establish a robust CQI program that focuses both on CCTS staff needs and improving investigator experiences. Results/Anticipated Results: Soliciting both quantitative and qualitative feedback from investigators has enabled our service groups to make significant changes to their internal processes to ensure that investigators are aware of services and supports available. Our quantitative data show us that investigators return time and again to CCTS for services and supports. Yet the feedback we receive through short, targeted interviews also helps identify challenges that investigators experience that could improve the services they come to us to receive. We have already used this system to recommend improved marketing of existing services within certain service groups that were highly requested by investigators, which increased utilization of that service. Discussion/Significance of Impact: Our mixed-method approach to evaluation allows us to easily and rapidly identify areas for improvement within our service groups, an instrumental part of implementing a CQI program that is focused on staff-identified areas of improvement. This approach can be easily replicated by other CTSA hubs with minimal impact to existing resources.