Objectives/Goals: The University of Minnesota’s two-year TL1 program provides flexible and individualized education and training for a diverse cohort of scholars committed to pursuing impactful careers in clinical and translational science (CTS). The program aims to strengthen the nation’s biomedical workforce by developing scientists skilled in clinical and translational research. Methods/Study Population: The TL1 program recruits PhD candidates and postdoctoral fellows from a wide variety of graduate programs in colleges and departments across the University. To date, we have trained 26 predoctoral and 9 postdoctoral Scholars in 3 cohorts. Scholars represent dozens of disciplines and the full translational spectrum. These interdisciplinary cohorts are in a unique position to realize the fundamental characteristics of a translational scientist. Entrance/exit surveys and exit interviews provide program leadership with information for quality improvement and areas scholars believe contribute the most to their education and training in CTS. Results/Anticipated Results: Entrance/exit surveys indicated Scholar-perceived benefits of training in an interdisciplinary program, including growth in translational scientist characteristics (e.g., Boundary Crosser, Team Player). Exit interviews showed Scholars appreciated the cohort model bringing together trainees from many different research areas. They valued exposure to varied perspectives, talking through challenges and solutions with each other, and learning others shared similar issues. They valued the Scholar community they developed. Several felt siloed in their careers before the program and reported that TL1 participation connected them to others outside their own area of focus, expanded their knowledge about different research methods and revealed more pathways for translation. Discussion/Significance of Impact: Recruiting and training a diverse interdisciplinary cohort of pre- and postdoctoral TL1 Scholars promoted synergy in translational research, science skills and competencies, and transformed the perspectives of Scholars’ views on the importance of interdisciplinary collaboration to accelerate science.

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

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

Objectives/Goals: 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: 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: The goal of this study is to investigate the peri-metastatic rims of peritoneal lesions to determine features that predict malignancy using both imaging processing techniques and machine learning. This information will subsequently be added to our existing knowledge of peritoneal lesions to improve classification accuracy as benign or malignant. Methods/Study Population: The study population consists of 521 imaged lesions from 163 subjects with cancers of GI-origin with biopsy results as well as the clinical subject information and follow up. All images were obtained during staging laparoscopy by the senior author (TS). On the images, the central lesion as well as the surrounding peri-metastatic rim will be segmented as regions of interest (ROIs). Image processing will be used to calculate a variety of metrics for these two regions. A general estimating equation approach will be used to determine significance of these metrics compared to the dependent outcome of malignancy determined on the pathology report as the ground truth. These ROIs and significant metrics will then be used to improve the accuracy of a machine learning model to classify these lesions as benign or malignant. Results/Anticipated Results: Our previous research showed that experts performed this task at only a 52% accuracy rate (classifying lesions as malignant or benign based on imaging). A previous machine-learning model on a much smaller dataset was able to achieve by contrast an area under the curve of 0.78. We anticipate that by including a larger dataset in addition to including the peri-metastatic rim, we will be able to improve the accuracy of the the model in this task while uncovering significant biomarkers as well that can be used in future studies. Discussion/Significance of Impact: Classifying peritoneal lesions determines the correct treatment for cancer patients whether chemo-radiation, definitive surgery or palliative surgery. This project aims to develop an improved model that can perform this task using nonlabeled laparoscopic imaging with a particular focus on the diagnostic value of the peri-metastatic rim.

Objectives/Goals: The goal of this poster is to 1) describe the development of a graduate certificate program for community-engaged research for health (CEnRH) in a Clinical and Translational Science Awards-funded institution; 2) describe the initial impact of the program; and 3) discuss strengths, implications, and potential improvements for the future. Methods/Study Population: The CEnRH graduate certificate is a 12-credit, postbaccalaureate program offered at the University of Cincinnati co-created by faculty from the Community Engagement and Translational Workforce Cores of the CCTST with community partners. The goal is to support learning about community-engaged research (CEnR) and enhances capacity for academic-community partnered research. Student demographics are collected as part of university registration. Quantitative course evaluations are collected each semester. Program evaluations including qualitative data are collected from students enrolled in the program during and upon completion of the certificate. Results/Anticipated Results: The CEnRH curriculum includes 3 existing courses/electives in the College of Medicine and Psychology and three new courses in social justice and action research methodologies. Notably, the committee advocated for a scholarship to cover tuition for the certificate program to promote access for community partners. Since the fall of 2022, 17 students have enrolled in the CEnRH program, including 9 Faculty/Staff within CCTST institutions, 2 University of Cincinnati PhD Students, 5 Fellows, and 1 Community Member (who receives the scholarship). Notably, 24% of these students are from underrepresented minority backgrounds. Impact and evaluation data, as well as lessons learned, will be presented. Future directions for the CEnRH program will also be discussed. Discussion/Significance of Impact: The CEnRH is an impactful program for trainees, faculty, and staff who are planning to conduct CEnR, while also strengthening research capacity among community partners and advocates. This certificate program may be especially valuable to academic researchers as more funding agencies require community and stakeholder engagement in their proposals.

Objectives/Goals: Despite significant advancements, adolescent and young adult (AYA) patients with hematologic malignancies continue to have inferior improvement in survival over time compared to their younger and older peers. This project assesses which patient and neighborhood characteristics are associated with clinical trial enrollment in this population. Methods/Study Population: We will perform a retrospective study of individuals, aged 15–39, diagnosed and treated at Children’s Healthcare of Atlanta (CHOA) or Winship Cancer Institute for hematologic malignancies between 2011 and 2023. Our primary exposure variables will be race/ethnicity, the area deprivation index (ADI), and the index of concentration at the extremes (ICE). The primary study outcome will be enrollment in an open frontline therapeutic clinical trial (yes vs. no). Our analyses will estimate the crude and adjusted odds ratio of clinical trial enrollment according to race/ethnicity, ADI, and ICE; these analyses will be adjusted for co-variables of interest (e.g. patient primary language, and insurance provider). As a secondary analysis, we will further subdivide the patients by treatment location and by age tertiles. Results/Anticipated Results: Our study team completed preliminary work looking at institutional clinical trial enrollment in a pediatric-only (Discussion/Significance of Impact: We expect that this study conducted in a large, diverse AYA cohort will reveal key associations about likelihood of clinical trial enrollment. Once these associations are known, we can develop and test interventions –such as augmented social work involvement and assistance with transportation– to mitigate the effect of amenable risk factors.

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: 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: As translational science (TS) emerges as a field, there is a need for research organizations to understand how to develop capacity for and support the advancement of TS. To support such institutional and infrastructural change, this poster outlines a Translational Science Promotion and Research Capacity (T-SPARC) framework. Methods/Study Population: The T-SPARC framework was developed by members of the Duke University Clinical and Translational Science Institute (CTSI) primarily from CTSI Pilots, Team Science, Evaluation, and Administration, all of whom had identified the need for building institutional capacity for TS at our institution. The group reviewed literature on TS to ensure grounding in current knowledge, drafted an initial TS logic model, and then determined the value of developing a framework addressing building TS institutional capacity. The group then identified other frameworks/models related to behavioral, organizational, and system change; examined scholarship addressing the building of research capacity in colleges and universities; and iterated on a TS-focused framework in multiple working sessions. Results/Anticipated Results: The resultant T-SPARC framework provides a foundation to 1) inform the development of interventions and programs advancing TS and 2) evaluate their effectiveness. It outlines: organizational levels for TS capacity building (large-scale systems, research institutions, teams, and individuals); intervention activities (policies and processes, funding, collaboration and partnership, and training); proximal outcomes (knowledge/attitudes, behaviors, resources/infrastructure, and connections); next-stage outcomes (e.g., interdisciplinary team processes, and research infrastructure); and ultimate goals (fewer translational impediments, improved public health, and health equity). It ingrates TS principles as foundational to, and outcomes of, capacity-building efforts. Discussion/Significance of Impact: T-SPARC, as a framework for building capacity in TS, provides added foundation for advancing the conceptualization and practice of TS. Ultimately, T-SPARC seeks to advance broader goals of reducing longstanding challenges in the translational research process and improving health outcomes.

Objectives/Goals: Physical activity (PA) is a well-documented protective factor against many cardiovascular diseases. PA guidelines to reduce these risks and the impact of variability are unclear, and most studies only examine a 7-day activity window. This study aimed to examine factors related to variability in step counts in a 3-year study of adults aged ≥18 years. Methods/Study Population: Included were 6,525 participants from the Michigan Predictive Ability and Clinical Trajectories study, a prospective cohort of community-dwelling adults enrolled between 8/14/2018 and 12/19/2019 who received care at Michigan Medicine and were followed for 3 years. Data were collected from Apple Watches provided to participants via the HealthKit. This secondary analysis included those with ≥4 valid weeks of data (≥4 days with at least 8 hours of wear time). Season was defined as Spring (March 20–June 20), Summer (June 21–September 21), Fall (September 22–December 20), and Winter (December 21–March 19). GEE models against the outcome of variability, defined as weekly standard deviation of step counts, and the predictor of season were adjusted for age, sex, race/ethnicity, weekly average step count, diabetes, and body mass index. Results/Anticipated Results: The average (standard deviation (SD) step counts by season were 7101 (3434) in Spring, 7263 (3354) in Summer, 6863 (3236) in Fall, and 6555 (3211) in Winter. Compared to winter, there was statistically significantly higher variability in all other seasons (p Discussion/Significance of Impact: In this cohort of community-dwelling adults, we found significant differences in variability of physical activity by season, age, and BMI. Future work will examine how this variability impacts the risk of development of cardiovascular disease, incorporating the impact and recovery trajectories of COVID-19 and other acute respiratory infections.

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

Objectives/Goals: 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: • To examine current barriers to research translation that collide with funder imperatives to share research results broadly. • To create community-driven guidance on broadening dissemination of research findings to communities to enhance health literacy and trustworthiness in the research process. Methods/Study Population: The Penn State Community Health Equity & Engagement in Research team, part of our Clinical and Translational Science Institute, completed six semi-structured focus groups in the Fall of 2023 (N = 46, including geographically diverse communities with and without research experience). Focus groups included presentation of evidence-based and novel approaches to lay results dissemination, including lay briefs and data walks, to elucidate experiences with and preferences for receiving research study results. Qualitative data were analyzed using MAXQDA software, with successful (>0.70) kappa coefficient achieved for interrater reliability. Codes and themes were developed inductively. Results/Anticipated Results: Focus group characteristics included N = 39 identifying as women, with a mean age of 56 years old and 10% identifying as Black/African American. Geographic breakdown included 49% rural, 44% suburban, and 7% urban. Thematic analyses demonstrated a perceived lack of trustworthiness and representation in the research process, with several cultural and geographic barriers to research accessibility and results dissemination. The majority of participants did not receive research results from prior studies and identified the importance of trusted community messengers to share findings broadly. Participants prefer receiving lay briefs, with health literate infographics, over published study manuscripts. Data walks featuring key findings presented by researchers within communities were highly desired. Discussion/Significance of Impact: Improving translation of study results in underrepresented communities is a catalyst for increasing engagement, demonstrating trustworthiness, and improving health literacy. The development of evidence-based lay dissemination methodologies can increase translation and bolster efforts to support informed, research-ready communities.

Objectives/Goals: As life expectancy increases in people with HIV, neurocognitive impairment is becoming more common, and women with HIV (WWH) are disproportionately impacted. This work investigated mitochondrial function and oxidative stress in WWH in order to understand the relationship between mitochondrial function and cognition in future studies. Methods/Study Population: Peripheral blood mononuclear cells were isolated from virally suppressed WWH (n = 64) and underwent the Seahorse Cell Mito Stress test to assess different realms of mitochondrial function. Cells were then lysed for direct DNA extraction, and quantitative PCR was performed to understand mitochondrial DNA expression (mtDNA) levels as a measure of oxidative stress. A series of simple linear regressions was then conducted to understand the relationships between mitochondrial function and mtDNA content. Future work will expand this analysis to investigate associations between demographic dynamics, such as trauma history, and mitochondrial function, as well as to understand the relationships between mitochondrial function and cognitive outcomes in WWH. Results/Anticipated Results: In our cross-sectional analysis of mitochondrial dynamics in WWH, we found a significant association between maximum mitochondrial respiration ability and mtDNA content, with greater mtDNA expression associated with increased levels of maximum respiration following stimulation. There was no association between basal respiration and levels of oxidative stress. There was also a significant variation in mitochondrial function in our participants, indicating that future analyses to investigate the source of that variation are warranted. The work presented here sheds light on mitochondrial dynamics in WWH and will be the basis for future studies that will investigate how demographic dynamics may be associated with mitochondrial function, as well as how mitochondrial dynamics may predict cognitive outcomes. Discussion/Significance of Impact: There is significant variation in mitochondrial function in WWH. More analysis is needed to understand what may be associated with these variations, including an investigation of both clinical factors as well as cognitive outcomes. This analysis will inform directions for future mechanistic work aimed at mitigating adverse cognitive outcomes in WWH.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

Objectives/Goals: (1) Conduct a pilot study documenting prevalence of tinnitus in a sample of Puerto Rican adults at the Audiology Clinic of the Medical Sciences Campus-University of Puerto Rico, (2) categorize patterns of tinnitus, (3) document intervention received for tinnitus, and (4) study sociodemographic characteristics of Puerto Rican adult participants with tinnitus. Methods/Study Population: A descriptive retrospective study was performed reviewing 121 clinical records of patients seen at the Audiology Intramural Clinic of the Medical Sciences Campus of the Universidad de Puerto Rico between 2022 and 2023. They were analyzed to determine the prevalence of tinnitus among this cohort. The study was submitted to the Office of Human Participants for revision and approval under the exempt category. The data were used to categorize the type of tinnitus, episodic versus constant, tonal versus non-tonal and the sociodemographic description of the sample. Results/Anticipated Results: From these 121 records, 70.2% (n = 85) were females and 29% (n = 29.8) were males. Subject ages ranged between 21 and 65 years. About 30% reported being single 30.6% (n = 37), followed by 21.5% (n = 26) reporting being married. From the 62 revised clinical records of subjects that reported tinnitus, 24% (n = 29) classified their tinnitus, in terms of how long they experience its presence, as constant, while 14% (n = 17) classified their tinnitus as intermittent. From the 62 revised clinical records, 44 participants (36.4%) described their tinnitus as tonal and 64.6 % as a complex sound of those patients 38 (31.4%) reported the tinnitus as a high-frequency pitch sound. Of the 62 patient records, the majority (98.4%) informed that they never received the treatment for tinnitus. Discussion/Significance of Impact: The results indicate that more than half of adults evaluated in the UPR Audiology Intramural Clinic (51%) had tinnitus. Age range was broad developing at any age but most prevalent in middle-aged females. Manifested permanent as a tonal or a complex sound. About 98.4% informed that they never received treatment, therefore, there is a need to ensure intervention.

Objectives/Goals: To evaluate equity in utilization of free initial health evaluation (IHE) services among members of a limited health care program, the World Trade Center (WTC) Health Program (Program), to inform intervention development and provide insights for similar healthcare programs. Methods/Study Population: We included Program members who newly enrolled during 2012–2022, and who had an IHE or were alive for ≥ 1 year after enrollment. Program administrative and surveillance data collected from January 2012 to February 2024 were used. We evaluated two outcomes: timely IHE utilization (proportion of members completing an IHE within 6 months of enrollment) and any IHE utilization (proportion completing an IHE by February 2024). We described IHE utilization by enrollment year and various members’ characteristics and conducted multivariable logistic regression models to estimate adjusted odds ratios for IHE utilizations to identify factors related to potential inequities for the two member types: Responders, who performed support services, vs. Survivors, who did not respond but were present in the New York disaster area. Results/Anticipated Results: A total of 27,379 Responders and 30,679 Survivors were included. Responders were 89% male, 70% 45–64 years old at enrollment and 76% White. Survivors were 46% female, 54% 45–64 years old at enrollment, and 57% White. Timely IHE utilizations remained relatively stable (~65%) among Responders across time and increased from 16% among Survivors who enrolled in 2017 to 68% among Survivors who enrolled in 2021. Timely IHE utilization was lower for younger members (enrolled Discussion/Significance of Impact: This study highlights Program achievements and gaps in providing equitable IHE services. Strategies to improve members’ equitable IHE utilization can include: adopt/expand flexible scheduling; increase non-English language capacity and cultural competency; and facilitate transportation/assistance for members with accessibility barriers.