OBJECTIVES/GOALS: In 2022, Chicago created the COVID-19 Response Corps, a cohort of community health workers (CHWs), trained to conduct contact tracing and vaccine outreach. Through an Earn and Learn program, corps members studied community-engaged participatory research, and co-led a rapid assessment with researchers to assess vaccine hesitancy in communities. METHODS/STUDY POPULATION: The Chicago COVID-19 Community Response corps worked to mitigate COVID-19 transmission in disadvantaged neighborhoods by activating CHWs, a diverse public health workforce from communities most affected by health and economic inequities. The Earn and Learn Program allotted 600 corps members up to 7.5 hrs/week of paid capacity building opportunities to learn new skills, pursue training programs, or college courses. Embodying a praxis of participatory action research and intergenerational organizing, corps members co-designed research questions and survey instruments, pilot tested the tools, trained other corps members on how to recruit and collect data, and contributed to the analysis and interpretation of the results. They generated evidenced-informed solutions to address future real-world problems. RESULTS/ANTICIPATED RESULTS: Corps members brought insight, cultural literacy, and lived experience that was invaluable in reaching the priority population of unvaccinated Chicagoans. They enhanced all aspects of the rapid assessment while conducting their work safely and comfortably in neighborhoods that outsiders consider challenging. Community member responses as to why they had not yet received a COVID-19 vaccine included being unable to risk putting what they saw as a rushed or improperly tested product into their bodies, to not being able to risk becoming ill even temporarily due to the potential for lost wages, as well as having other priorities in their lives which took precedence over concern about COVID-19, such as paying bills and feeding their families. DISCUSSION/SIGNIFICANCE: Research and evaluation benefits from the inclusion of CHWs. They are agile agents of change with the potential to replenish and repair trust in a fractured public health system. Engaging CHWs in evaluation work can strengthen community-academic partnerships and enhance the understanding of challenges and solutions to improving community health.

OBJECTIVES/GOALS: The objective of this study was to determine whether pet dogs with multicentric lymphoma (ML), a spontaneous, immunocompetent model for human non-Hodgkin lymphoma (NHL), are exposed to higher concentrations of herbicides and volatile organic compounds (VOCs) compared to matched unaffected control dogs. METHODS/STUDY POPULATION: We are prospectively enrolling dogs with ML within a single high-risk breed, the boxer dog, along with age-matched control boxers sampled within the same season. We are measuring urinary concentrations of the herbicides glyphosate (in Roundup®) and 2,4-D, as well as stable urinary metabolites of the VOCs benzene and 1,3-butadiene. To assess the genotoxic potential of herbicide and VOC exposures, we are using reverse dosimetry to estimate plasma exposures, and exposing healthy canine PBMC’s to these concentrations of herbicides and VOCs in vitroto assess double stranded DNA damage using the Comet Chip assay. RESULTS/ANTICIPATED RESULTS: Preliminary data show significantly higher benzene exposures, measured by the stable benzene metabolite PHMA, and significantly higher 2,4-D exposures at the time of diagnosis in cases versus controls. All dogs had measurable exposures to 1,3-butadiene (measured as its stable metabolite DHBM) and glyphosate.In vitro results show significant genotoxicity thresholds of 0.1 uM for both glyphosate and 2,4-D in dog lymphoid cells. To date, these predicted plasma exposures have not been reached in vivo in boxer dogs with ML or unaffected control boxers. DISCUSSION/SIGNIFICANCE: Canine multicentric lymphoma resembles human NHL and is a potentially useful model of non-occupational chemical risk for NHL in people. The goal of this research is to identify potentially preventable non-occupational chemical risk for lymphoma and support evidence-based remediation strategies to decrease lymphoma risk in both humans and dogs.

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

OBJECTIVES/GOALS: We aim to characterize how Heligmosomoides polygyrus bakeri (H. poly) alleviates murine allergic asthma which shares many characteristics of human asthma. This approach of has already identified helminth-produced human immune cell ligand “mimics” that hold great potential for next-generation clinical biologics METHODS/STUDY POPULATION: We examined the lung tissue of C57BL/6 mice infected with H. poly for changes in the pulmonary microenvironment. At ten days post infection, four infected mice and two co-housed uninfected mice were sacrificed, and their lung tissue harvested for examination of RNA via RT-qPCR. This design allows for the comparison between the lung microenvironments of infected and naīve mice. In future experiments, we intend to characterize what small molecules produced by the helminth drive changes in the lung using germ-free models of H. poly infection. RESULTS/ANTICIPATED RESULTS: We found key differences in lung chemokines between mice infected with H. poly and naīve mice. Using a student t-test with naīve correction for variance, we were able to show significant differences in the expression of E cadherin (p = 0.0355), CXCL10 (p = 0.0025), CX3CL1 (p = 0.0029), CCR2 (p = 0.017), and IDO1 (0.0078). We also found that differences in the expression of CCL5 bordered on significant with a p-value of 0.066. The expression of most of these markers (CXCL10, CCR2, CCL5, and IDO1) was elevated in the lungs of infected mice compared to naīve controls. In contrast, E cadherin and CX3CL1 showed the opposite trend with naīve mice showing greater expression. These clear differences in lung tissue gene expression underscore the connection between the gastrointestinal and pulmonary mucosal immune compartments. DISCUSSION/SIGNIFICANCE: The changes are unexpected for an infection that has been shown to attenuate allergic inflammation in the lung with increases in the IFN-Y responsive genes IDO1 and CXCL10 and inflammatory lung markers, CCL5 and CCR2. In contrast, there were decreases in inflammatory lung marker CX3CL1 and the tight junction protein E cadherin in infected mice.

OBJECTIVES/GOALS: Super refractory status epilepticus (SRSE) is associated with high mortality, often due to withdrawal of life sustaining therapy (WLST) based on perceived poor neurological prognosis. Factors influencing decision making are underreported and poorly understood. We surveyed clinicians who treat SRSE to identify factors that influence WLST. METHODS/STUDY POPULATION: Health care providers (HCP), including physicians, pharmacists, and advanced practice providers, who treat SRSE answered a 51-question survey on respondent demographics, institutional characteristics and SRSE management that was distributed though professional societies. Respondents described approaches to prognostication and rated the importance of clinical factors in the management of two hypothetical clinical cases followed by their prediction of recovery potential for the same two cases. Neurointensivists and other HCP responses were compared using descriptive statistics to differentiate group characteristics; a p-value <0.05 was considered significant. Logistical regression models were employed to identify associations between clinician specific factors and prognostication. RESULTS/ANTICIPATED RESULTS: One-hundred and sixty-four respondents were included in the analysis. Compared to other HCPs (neurologists, epileptologists, neurosurgeons, other intensivists; n=122, 74%), neurointensivists (n=42, 26%) [Odds ratio (OR) 0.3, 95% confidence interval (CI) 0.14-0.68), p=.004)] were less likely to use prognostic severity scores and were less likely to prognosticate likelihood of good functional recovery (OR: 0.28 (95% CI: 0.13-0.62), p=.002) compared to non-neurointensivist HCPs, controlling for potential confounders including professional degree, years of experience, country of practice, and annual volume of SRSE cases. There was, however, significant overlap in factors deemed necessary for determining futility in care escalation. DISCUSSION/SIGNIFICANCE: Neurointensivists value similar clinical factors to other HCPs when evaluating medical futility in SRSE but are less likely to predict definitive outcomes. Pending final survey results, future studies aimed at understanding why neurointensivists may be less likely to decisively prognosticate (i.e. avoiding nihilism) in SRSE may be warranted.

OBJECTIVES/GOALS: To describe the creation, use and outcome of a successful multi-session case study for team science education and training. Creating a case study that spans multiple sessions can aid in emphasizing many team science concepts using one ongoing scenario. METHODS/STUDY POPULATION: We will describe the creation and use of a multi-session case study used in a team science graduate course. This case study incorporates the interpretation and use of assessments that coincide with concepts presented in each session. Participants engage with the case study as a team. The use of this case study allows participants to draw conclusions and make decisions about team interventions using concepts they’ve just learned. The multi-session case study also allows participants to see the outcome of their decisions in the next session. Further, the continuous nature of this case study allows participants to build on their knowledge from session to session and make connections between concepts. RESULTS/ANTICIPATED RESULTS: Incorporating a multi-session case study should help participants better understand team science concepts and practice incorporating the use of those concepts into teams in a more realistic way over time. The case study framework has been used in a team science graduate course for the last two years. The teaching team has incorporated continuous improvement into optimizing the case study over time. We’ll share preliminary results collected over the use of the case study so far along with the improvements made over time. DISCUSSION/SIGNIFICANCE: This education framework is very versatile and can be incorporated into a team science course or series of workshops and provides a real-world situation that allows participants to practice incorporating team science concepts and interventions in a team.

OBJECTIVES/GOALS: The goal of this study is to leverage a national database to see if autologous reconstruction rates differ in patient and clinical characteristics, readmission rates, and overall survival (OS) compared to other forms of reconstruction. Autologous reconstruction has not been looked at in this way before. METHODS/STUDY POPULATION: • Aim 1: Use the National Cancer Data Base to construct three patient cohorts for women under 70 and above 18 treated surgically for breast cancer with A) mastectomy only, B) implant-based reconstruction, and C) autologous breast reconstruction. • Aim 2: Examine receipt rates of surgical intervention in Cohorts A vs. B vs. C based on clinical and patient demographic/socioeconomic characteristics. • Aim 3: Compare readmission and overall survival (OS) rates for Cohorts A vs. B vs. C while controlling for age and other key variables. RESULTS/ANTICIPATED RESULTS: Based on the literature, we expect rates of autologous reconstruction (Cohort C) to be lower for patients of minority backgrounds compared to white individuals. In addition, we do not expect overall survival to differ between implant-based (Cohort B) and Cohort C reconstruction. Still, we expect mastectomy-only (Cohort A) survival to vary from the two cohorts even when adjusting for different clinical factors, as similar but smaller studies have shown. Finally, we expect readmission rates to be higher for Cohort C, compared to Cohorts A & B, as it is a more complicated procedure typically done in academic institutions with skilled surgeons. DISCUSSION/SIGNIFICANCE: Autologous reconstruction is now considered the gold standard due to its ability to restore the breast shape with higher patient satisfaction and superior long-term outcomes. Multiple studies have documented ongoing racial disparities in post-mastectomy breast reconstruction and autologous reconstruction, with lower rates and referrals.

OBJECTIVES/GOALS: Our objective is to develop a Telenephrology dashboard for the 150,000 Veterans that obtain care through the Iowa City Veterans Affairs Health Care System. Our goal is to create a comprehensive and user-friendly tool for monitoring kidney health and facilitating remote nephrology consultations. METHODS/STUDY POPULATION: We structured our intervention according to the five stages of human-centered design: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype and (5) Test. During the empathy stage, the principal investigator spent 10 hours immersed in the clinical setting observing how nephrologists approach a remote nephrology consultation. These observations were augmented by unstructured interviews with clinicians and patients to better understand the process and dynamics. Following this, a rapid ideation workshop was convened to generate creative solutions that balance technical requirements with the needs of clinicians and patients. These led to rapid prototyping and testing to identify what elements of the prototypes worked and which needed improvement. RESULTS/ANTICIPATED RESULTS: Through the empathy and define stages, three needs were identified: (1) clarity in visualizing data, (2) accuracy of information, and (3) balancing standardization with individualization. During the rapid ideation workshop, the concept of a four-frame dashboard was settled upon. This led to the creation of five prototypes, which were tested. These were reconciled and modified to make a final product. This final product, the Telenephrology Dashboard, contains 5 elements that support nephrologists and supporting staff: (1) a graph of kidney function over time, (2) tables synthesizing lab data, (3) options to drill down events to specific times, (4) customization of views, and (5) integration of kidney disease progression models. DISCUSSION/SIGNIFICANCE: A Telenephrology dashboard was created to facilitate remote nephrology consultations through a Human-Centered Design process. Our next steps include determining if this dashboard may improve end-user satisfaction, referring clinician satisfaction, access to specialist care, and patient outcomes.

OBJECTIVES/GOALS: This project presents the Post-doctoral Master of Science in Clinical and Translational Research (MSc) program’s outcomes in 20 years of its implementation. This program is a joint offering between the Schools of Health Professions and School of Medicine of the University of Puerto Rico. METHODS/STUDY POPULATION: This study consists of secondary data analysis of academic and administrative documents. It also includes data from the Annual Evaluation retreats reports and an Alumni Follow-up Survey using an electronic questionnaire. All 121 Scholars admitted to the program from academic years 2003 to 2023 were included in the sample. Data analysis included descriptive statistical analysis of quantitative data and qualitative content analysis regarding recruitment/admissions, faculty composition, curriculum design, Scholars’ outcomes, and program’s financial support sources. Quantitative data were analyzed using the statistical software SPSS. RESULTS/ANTICIPATED RESULTS: Scholars of the program had been recruited from the UPR-MSC and several partner institutions with diverse backgrounds, disciplines, and research areas. Faculty and committee members have representation from the six MSC-Schools and partner institutions. The academic Program structure has changed over the years, and currently, more than 65% of the courses are offered online. Several financial sources have been identified to support the scholars. The Scholars’ portfolios of grant submission and publication productivity evidence the program’s success. Graduates have also been successful in advancing to positions that foster research impacting Hispanics. DISCUSSION/SIGNIFICANCE: The Post-doctoral Master’s in Clinical and Translational Research program (MSc) has contributed to the formation of committed Hispanic clinical and translational researchers impacting minorities and contributing to diversity in the research workforce.

OBJECTIVES/GOALS: Many researchers aim to build trust with communities and participants. Trust building is meant to achieve greater representation across aspects of research whether in participation, or more comprehensively as partners from design to dissemination. We provide practical guidance for trust building activities and the ethical issues that can arise. METHODS/STUDY POPULATION: While trust itself is inherently seen as an ethical good, often little attention is paid to the ethical aspects of trust building exercises themselves and the fact that trust can vary in type. Using a bioethical analysis of trustworthiness, we discuss how to approach trust in different relationships and settings. Explicit communication about the supports/constraints and potential outcomes of new trusted relationships is required for ethical practice. Where relationships are built without appropriate transparency and follow through, or with misunderstandings about potential shared values, priorities, or desired outcomes, significant harms can occur in the short- and long term. Using a bioethical framework and practical examples we provide guidance on how to engage in ethical trust building activities. RESULTS/ANTICIPATED RESULTS: While many people are good at the trust building work they do, this work is often not shared as best practices and is ascribed to individual skill. This is slowly changing and an evidence-base is being developed that can support those new to these activities. Ethical guidance to support trust building practices, especially for those new to these activities, is currently lacking. By providing both a conceptual and normative bioethical analysis grounded in practice, we provide the foundations for new activities and the necessary support for work that explores and determines best practices. This analysis provides an understanding of trust including a taxonomy and a discussion of how different types of trust can be built and can support research activities, as well as problems that can arise. DISCUSSION/SIGNIFICANCE: Trust building activities with communities and participants are crucial to much of translational science and research, but ethical guidance on how to engage in these activities well is lacking. We provide bioethical guidance and offer practical recommendations.

OBJECTIVES/GOALS: Intra-aortic balloon pumps are commonly used as circulatory support in patients with critically reduced cardiac function. The goal of this study is to estimate the incidence of mesenteric ischemia as an understudied vascular complication and to describe the clinical and radiographic characteristics of patients experiencing this complication. METHODS/STUDY POPULATION: We will be conducting a retrospective analysis of the electronic medical records of all patients who underwent intra-aortic balloon pump (IABP) placement between October 2020 and April 2023 at our academic medical center to identify the incidence of mesenteric ischemia. We will describe the clinical course of these patients and characterize them based on demographic features and risk factors for vascular complications including medical comorbidities. Finally, we will assess available chest x-ray and thoracoabdominal CT imaging for adequacy of balloon tip positioning, concordance between balloon size and aortic dimensions, and compromise of any visceral arteries in patients who experienced mesenteric ischemia vs. those who did not. RESULTS/ANTICIPATED RESULTS: We anticipate approximately 150 patients to have recieved IABPs over this period with at least 4 known cases of mesenteric ischemia. We will describe the clinical presentation of these cases and their often fatal outcomes. We expect several known risk factors will be present in these patients, including history of peripheral vascular disease, diabetes, or smoking history. On chest x-ray, we predict balloon tip positioning to be suboptimal (defined as >5cm below the aortic arch) in many patients, both those with mesenteric ischemia and those without, but a greater discordance on CT imaging between balloon size and aortic dimensions with greater evidence of visceral compromise in patients with mesenteric ischemia compared to those without. DISCUSSION/SIGNIFICANCE: Mesenteric ischemia is a serious and poorly studied complication of intra-aortic balloon pumps. Understanding the hospital course, clinical characteristics, and radiographic features present in these patients may guide clinicians in the early recognition and management of this potentially fatal complication.

OBJECTIVES/GOALS: Dietary fiber has been used in other clinical populations to improve mineral disorders, but there is limited data in chronic kidney disease, despite the high prevalence of mineral and bone disorder (known as CKD-MBD). Our objective was to evaluate the effect of dietary fiber based on viscosity and fermentability on CKD-MBD outcomes. METHODS/STUDY POPULATION: 22-week-old male CKD rats (mild-to-moderate CKD) were randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) Inulin (+fermentability, -viscosity), 3) Psyllium husk (-fermentability, +viscosity), or 4) Pectin (+ fermentability, +viscosity). Treatments lasted 10 weeks, and rats were euthanized at 32 weeks of age (kidney failure). Rats were placed in metabolic cages for 3 consecutive days the last week before euthanasia for mineral balance. At euthanasia, blood, tibia, heart, and aorta were collected for CKD-MBD assessment. Additional tissues collected included kidneys and all intestinal segments. RESULTS/ANTICIPATED RESULTS: Our preliminary data indicates that weight trajectories and survival were similar between treatment groups. At 33 weeks of age, kidney weight index (an indirect measurement of kidney function as this animal model develops polycystic kidneys) was lower in the psyllium-treated rats compared to all of the other treatments. Plasma phosphorus was lower with Psyllium and Pectin compared to Cellulose-treated rats. Left ventricular mass index was lower in the Inulin, Psyllium, and Pectin-treated rats compared to the Cellulose-treated rats. Ongoing tissue analyses include biochemical markers of mineral and bone metabolism (parathyroid hormone, fibroblast growth factor-23, and phosphorus balance), bone parameters (dynamic histomorphometry and microCT), and cardiovascular calcification. DISCUSSION/SIGNIFICANCE: Our preliminary data indicate that dietary fiber based on fermentability and viscosity impacts CKD-MBD outcomes and may be an innovative, low-cost intervention that can be trialed in people with CKD for the prevention and treatment of CKD-MBD.

OBJECTIVES/GOALS: This project aims to improve the design of medical technology for global health by addressing gaps in engineering education. Our primary goal is to develop open educational resource’curriculum boosters’ that can be added to existing BME curricula to build skills in transdisciplinary collaboration, practical ethics, and failure resilience. METHODS/STUDY POPULATION: A phasic mixed-method research strategy has been employed. The Needs Analysis includes a systematic review and meta-analysis of existing knowledge regarding the three conceptual pillars of Transdisciplinary Collaboration, Practical Ethics, and Integrated Resilience. The Behavioral Study includes surveys, interviews, observations, and biometric data collection from working engineers, engineering students, global health stakeholders, and clinicians. The Validation Study will be conducted via small group workshops, a semester-long engineering design course, and a summer study-abroad course. Data collected will be analyzed and used to refine the proposed educational strategies. RESULTS/ANTICIPATED RESULTS: The final educational strategies will be structured into 'curriculum boosters' and published as open educational resource materials. The boosters and their supporting data will be made available to other engineering education programs with the goal of promoting widespread adoption and integration of these methods. DISCUSSION/SIGNIFICANCE: The long-term outcome of this ongoing work is to train a new generation of engineers prepared to participate adeptly in the co-design of technological solutions for complex global healthcare challenges by working ‘with, not for,’ clinicians, communities, and other stakeholders in peripheral healthcare settings.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

OBJECTIVES/GOALS: To evaluate the association of maternal delivery history with a brachial plexus birth injury (BPBI) risk in subsequent deliveries, and to estimate the effect of subsequent delivery method on BPBI risk. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of all livebirth deliveries occurring in California-licensed hospitals from 1996-2012. The primary outcome was recurrent BPBI in a subsequent pregnancy. The exposure was prior delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering an infant with BPBI). Multiple logistic regression was used to model adjusted associations of prior delivery history with BPBI in a subsequent pregnancy. The adjusted risk (AR) and adjusted risk difference (ARD) for BPBI between vaginal and cesarean delivery in subsequent pregnancies were determined, stratified by prior delivery history, and the number of cesarean deliveries needed to prevent one BPBI was determined. RESULTS/ANTICIPATED RESULTS: Of 6,286,324 infants delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a BPBI. Higher parity was associated with a 5.7% decrease in BPBI risk with each subsequent delivery (aOR 0.94, 95%CI 0.92, 0.97). Previous shoulder dystocia or BPBI were associated with 5-fold (aOR=5.39, 95%CI 4.10, 7.08) and 17-fold increases (aOR=17.22, 95%CI 13.31, 22.27) in BPBI risk, respectively. Among individuals with a history of delivering an infant with a BPBI , cesarean delivery was associated with a 73.0% decrease in BPBI risk (aOR=0.27, 95%CI 0.13, 0.55), compared with an 87.9% decrease in BPBI risk (aOR=0.12, 95%CI 0.10, 0.15) in individuals without this history. Among individuals with a previous history of BPBI, 48.1 cesarean deliveries are needed to prevent one BPBI. DISCUSSION/SIGNIFICANCE: Parity, previous shoulder dystocia, and previously delivering a BPBI infant are associated with future BPBI risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding BPBI risk and planned mode of delivery.

OBJECTIVES/GOALS: Ebolavirus disease survivors report persistent, debilitating health concerns dubbed Post-Ebola Syndrome (PES). Attention to PES in young survivors is lacking, we describe PES in pediatric EVD survivors in Eastern Sierra Leone. Additionally, we introduce our proposal investigating differential presentations of PES in pediatric survivors. METHODS/STUDY POPULATION: EVD survivors were enrolled a median of 2.5 years after resolution of disease. Survivors were eligible if listed in a national register maintained by the Sierra Leone Association of Ebola Survivors. Household contacts (HCs) were identified by survivors. Participants were assigned into three comparison groups: pediatric (7-11), adolescent (12-17) and young adult (18-25). A self-reported symptom questionnaire, and a physical exam were conducted. Variables were clustered within organ system and compared across groups. RESULTS/ANTICIPATED RESULTS: Pediatric survivors had lower levels of long-term sequelae compared to adolescents and young adults. Symptoms and abnormal physical exam signs increase with age. Musculoskeletal, psychiatric, ophthalmologic, and GI signs and symptoms were significantly different between groups. Pediatric survivors had significantly more persistent sequelae than age-matched HCs with no history of EVD; particularly within the cardiac/GI (p=.006) and psychiatric/neurological (p=.025) clusters. PES is heterogeneous with respect to age, calling for a deeper understanding of age-based differences. Even the youngest group of survivors experienced significantly more sequelae than HCs, highlighting the elevated symptom burden in these children over their peers. DISCUSSION/SIGNIFICANCE: Understanding mechanistic drivers will ultimately improve targeted treatments for PES. We will characterize symptom groups defining PES in children, determine the relationship between accelerated aging and PES in this population, and test how immune profiles associated with accelerated aging relate to the development of PES in children.

OBJECTIVES/GOALS: With a growing intеrеst in tailoring disеasе diagnosis to еach individual as opposеd to a “onе-sizе-fits-all” approach, our aim is to еnhancе thе robustnеss of thе Itеrativе Clustеring for Subtypе Discovеry (iKCAT) algorithm in charactеrizing lung cancеr subtypеs for individualizеd trеatmеnt. METHODS/STUDY POPULATION: Our mеthod еxplorеs thе robustnеss of thе prеviously dеvеlopеd iKCAT algorithm. This itеrativе clustеring mеthod finds robust—homogеnеous and diffеrеntiablе—subtypеs of lung nodulеs through itеrativе K-mеans clustеring that hеlps classify thеm and lеavеs somе data unclustеrеd. This sеt of unclustеrеd or “hard” data rеprеsеnts imagеs that cannot confidеntly bе assignеd to any subtypеs and may rеquirе morе rеsourcеs (е.g., timе or radiologists) to diagnosе. Wе еxplorе thе robustnеss of iKCAT across multiplе fеaturе spacеs, including dеsignеd imagе fеaturеs (which arе еnginееrеd to capturе somе propеrtiеs such as lеvеl of еlongation, еccеntricity and circularity), rеducеd dеsignеd imagе fеaturеs using Principal Componеnt Analysis (PCA) and Uniform Manifold Approximation and Projеction (UMAP). RESULTS/ANTICIPATED RESULTS: Whеn running our еxpеrimеnt on thе 64 imagе fеaturеs, our rеsults consistеntly carvеd out a singlе purе, homogеnеous clustеr ovеr thе coursе of 30 iKCAT runs. From an initial datasеt of 1490 data points, 1430 points wеrе lеft unclustеrеd in this fеaturе spacе. Whеn conducting thе 30 iKCAT runs on thе PCA fеaturе spacе with 10 componеnts, wе found it did not producе any distinct clustеr abovе thе dеfinеd homogеnеity thrеshold. Thе 2D UMAP fеaturе spacе consistеntly gеnеratеd 8 clustеrs with an avеragе homogеnеity of 87. 22% ovеr 30 runs, and only lеft 9 points unclustеrеd. Ovеr 30 iKCAT runs, wе idеntifiеd 8 pеrsistеnt clustеrs or subtypеs, 3 mostly malignant and 5 mostly bеnign clustеrs. DISCUSSION/SIGNIFICANCE: Through our еxpеrimеnt using thе iKCAT algorithm, wе found that iKCAT’s clustеring functionality producеd thе most pеrsistеnt rеsults on thе 2D UMAP fеaturе spacе duе to its high avеragе homogеnеity scorеs and consistеncy in idеntifying clustеrs/subtypеs, hеlping improvе tailorеd disеasе diagnosis.

OBJECTIVES/GOALS: The overall goals of this project are: (1) to demonstrate the utility of staff with cross-disciplinary skills in biostatistics and epidemiology as program managers for CTSA BERD Cores, and (2) examine streamlined processes in project triaging, consultations, and data extractions for CTSA service requests when individuals are in this role. METHODS/STUDY POPULATION: Biostatistics and epidemiology are partnered disciplines incorporated in a variety of research areas, especially in human health sciences and health care. For interdisciplinary teams, including individuals trained in both specialties results in efficient research collaborations. When these individuals are program managers for research navigation, processes become more effective and expedited for project timelines and workflows across the CTSA. Examples of this integration are described in vignettes from project triaging, statistical consultations, and data extractions from CTSA service requests. Process comparisons of previous and current workflows are presented to show the advantages of utilizing this type of program manager within these areas of BERD. RESULTS/ANTICIPATED RESULTS: This project defines three areas of integration for a program manager with cross-disciplinary training in biostatistics and epidemiology: (1) project triaging to statistical teams, (2) study design and analysis consultations, and (3) data extractions. Each of these areas demonstrates prior processes that once would require multiple steps in CTSA service requests (including time, resources, and personnel) and identified common issues (slow response to requests, data re-extractions, and challenges providing statistical support) that are now avoided with a manager with cross-training in biostatistics and epidemiology methods. The advantages and disadvantages of integrating these individuals are also described. DISCUSSION/SIGNIFICANCE: BERD Cores seeking improvements to research navigation processes can gain efficiency by incorporating program managers with cross-disciplinary training in biostatistics and epidemiology. BERD Cores may also use this as a case study for translational science with innovation to longstanding challenges in CTSA research workflows.

OBJECTIVES/GOALS: In this work investigating the epidemiological differences associated with Post Acute Sequelae of SARS-CoV-2(PASC) patho genesis we willassess the sex differences inocular viral persistence and the immunologic profile in tear film obtained from COVID-19 patients. METHODS/STUDY POPULATION: Participants will be enrolled from the NIH funded RECOVER Consortium at the 15 adult hubs in the US and will include those with acute COVID-19 (n=250), followed up at baselineto 48 weeks post infection. RT-PCR will be used to detect viral RNA and electro chemiluminescence assays will be used to detect IgG, IgA1 and IgA2 antibodies.Tear film antibody titers will be measured longitudinally in all participants to assess the kinetics of the immune responses in those who developed PASC and those who did not. Tear film antibody titers will be correlated with antibody titers in the blood and compared between those individuals with or without measurable viral RNA in tear film. RESULTS/ANTICIPATED RESULTS: Logistic regression models will be used assess the association of viral persistence with PASC status controlling for relevant covariates. Linear mixed regression models will be used to assess the association of IgA1/IgA2 with PASC status. We expect to observe delayed clearance of viral RNA and elevation in SARS-CoV-2 specific IgA2/IgA1 in the tear film of patients with PASC compared with those without PASC. Given evidence of increased PASC risk in women we expect to observe higher rates of SARS-CoV-2 ocular viral persistence and higher SARS-CoV-2 specific IgA2/IgA1 ratios in women with COVID-19 when compared to men with COVID-19. DISCUSSION/SIGNIFICANCE: There is concern that PASC will pose a major global health challenge given the scale of the Covid-19 pandemicand the patho genesis remains unclear. This work is highly likely to improve our understanding of the mechanisms of PASC and the reasons why women are more vulnerable to this condition.

OBJECTIVES/GOALS: Diabetic Kidney Disease (DKD) is a common diabetes complication, often linked to end-stage renal disease in the United States (US). While autophagy and miRNAs are pivotal, miR-451’s specific role remains understudied. Our study explores its renoprotective effects in an accelerated DKD mouse model. METHODS/STUDY POPULATION: We assessed the effect of miR-451 mimic treatment on Diabetic Kidney Disease (DKD) in BTBR ob/ob mice, known for their rapid DKD-like renal lesions. Mice were divided into four groups: WT (wild-type), BTBR ob/ob, WT+miR-451 (wild-type with miR-451 mimic), and BTBR ob/ob+miR-451 (BTBR ob/ob with miR-451 mimic). MiR-451 mimics were administered at 2mg/kg body weight once weekly for three consecutive weeks. We collected spot urine and monitored blood glucose levels at each time point. After the treatment period, mice were euthanized for kidney and blood samples. Western blot analysis assessed autophagy-related protein markers. Statistical analysis included Student’s t-test and ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: The study assessed the impact of miR-451 mimic treatment in BTBR ob/ob mice. Albumin:creatinine ratio increased fourfold (p=0.01) in BTBR ob/ob mice at 5 weeks. MiR-451 mimic treatment had no impact on body weight. Blood glucose levels were notably higher in both treated and untreated BTBR ob/ob mice at 12 (425±33.1 mg/dL; p=0.04) and 13 weeks (383±25.3 mg/dL; p=0.007). However, a significant drop occurred from week 13 (554.7±10.8 mg/dL) to week 14 (289±13.3 mg/dL; p=0.0002) in BTBR ob/ob miR-451 treated mice. Western blot analysis in whole kidney homogenates showed a 91% reduction (p=0.02) in YWHAZ, a predicted miR-451 target, in treated BTBR ob/ob mice and a 95% reduction (p=0.01) in WT mice. Furthermore, miR-451 mimic treatment led to a 68% increase (p=0.01) in ATG101 and a 44% increase in Beclin-1 in BTBR ob/ob mice. DISCUSSION/SIGNIFICANCE: The study uncovers miR-451-based interventions as a promising avenue to counter Diabetic Kidney Disease by modulating autophagy, potentially introducing novel therapies for at-risk individuals. However, practical DKD treatments will require further research and rigorous clinical validation to harness the full potential of these insights.