OBJECTIVES/SPECIFIC AIMS: To outline 4 categories of ethics needs identified at a translational science center. To map how research ethics has been further integrated into the center’s culture in response to these needs. To provide insights into how research ethics can be integrated into the translational team science environment. METHODS/STUDY POPULATION: The Institute for Translational Sciences (ITS) at the University of Texas Medical Branch is studied on an organizational level using polyphonic organizational theory and the results of an ethics needs assessment completed in 2010. RESULTS/ANTICIPATED RESULTS: The results will be a map indicating how research ethics has been further integrated into the culture of the ITS in response to the needs identified to ensure the responsible practice of translational science. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful translational science requires shared understanding of communication and values. Achieving agreement in these areas requires the development of strategies for communicating and reinforcing common goals. Research ethics has often been considered an “add on” rather than a “part of” science. Through integrating ethics into various aspects of translational science, the ITS has taken important steps toward achieving the goal of culture change. The map of how the ITS has integrated ethics into organizational activities and structures will serve as a model for other organizations and institutions.

Objectives/Goals: Advance translational understanding of how families with young children from low SES backgrounds engage with music and how these experiences shape interest in music enrichment programs. By identifying family perceptions and barriers, this work will inform the design of responsive music interventions to promote developmental outcomes. Methods/Study Population: This is a qualitative study of semi-structured interviews. Families had at least one child who was ≤ 2-years old and an income which qualified for the Women, Infants, and Children’s (WIC) program. Exclusion criteria included children (≤ 2-years old) with chronic health diagnosis (e.g., cerebral palsy). Audio recordings were transcribed and coded using the inductive approach of thematic analysis. N = 15 included in the final analysis. The sample consisted of primarily black (53%) and multi-race (20%) families who reported an annual income below the 2023 poverty threshold for the number of family members living in the home (73%). Participating parents were mothers (94%), single (73%), and had a high school education or below (87%). Results/Anticipated Results: The home music environment: Parents’ own musical background influences decisions on music they select for their children. Parents prefer children’s songs that sound like the music they prefer to listen to (e.g., pop, hip-hop). Parent–child music interactions mostly include listening to and watching music shows vs. singing together. Parent interest/perception of community music programs: Parents have interest in community music programs and are interested in social and educational benefits to their child. Parent perceived barriers: Parents were not aware of music programs in their community. Social barriers include irregular work schedules, co-parenting, transportation, and balancing the demands of multiple children. Discussion/Significance of Impact: Understanding how families from low SES backgrounds engage with and access community-based music programs will inform equitable and scalable strategies to promote early developmental enrichment through music, bridging research and community impact.

OBJECTIVES/GOALS: People engaging in high-risk substance use or experiencing food insecurity or housing instability are at increased risk to develop end-stage kidney disease. This study will examine associations between these risk factors, patient indicators of socioeconomic position, and hospitalization rates and quality of life after initiation of hemodialysis. METHODS/STUDY POPULATION: The proposed study will leverage a prospective cohort design. We will enroll a convenience sample of 330 participants from the same large dialysis organization. Participants will complete measures of socioeconomic position (age, gender, race, ethnicity, education, income, occupation and community poverty); substance use; food insecurity; housing instability; and quality of life at baseline. We will follow participants for 6 months and extract hospitalization counts from the dialysis facility medical record. RESULTS/ANTICIPATED RESULTS: We will generate risk scores (low, medium, high) from measures of substance use, food insecurity and housing instability. We will conduct multiple logistic regression to generate odds ratios comparing risk group membership by indicators of socioeconomic position. We anticipate that low or medium-risk groups will differ from high risk groups by indicators of socioeconomic position. We will conduct Poisson regression to generate incidence rate ratios for 6-month hospitalization rates comparing low or medium-risk and high-risk groups. Lastly, we will conduct multiple linear regression to generate beta coefficients for changes in quality of life scores comparing low or medium-risk and high-risk groups. We anticipate that high-risk groups will have higher hospitalization rates and lower quality of life scores. DISCUSSION/SIGNIFICANCE OF IMPACT: As the prevalence of end-stage kidney disease continues to increase, there is a need for tertiary prevention interventions that reduce costly inpatient utilization and improve health-related quality of life. The proposed study will lay groundwork for the development of interventions to improve patient outcomes and reduce Medicare spending.

Objectives/Goals: Parenting programs overlook the needs of Latina mothers affected by intimate partner violence (IPV). To address this, we aim to adapt the Attachment and Biobehavioral Catch-up (ABC) parenting program. Objective: to understand core parenting challenges and strengths, identify implementation needs, and deliver a contextually responsive protocol. Methods/Study Population: Guided by the ADAPT-ITT framework, we are conducting semi-structured interviews with Latina mothers (n = 12–15) and service providers (n = 5-10) to inform the adaptation of ABC while maintaining its core components (10 dyadic sessions focused on following the child’s lead, nurturing children when distressed, and avoiding frightening behaviors). To date, we have interviewed four mothers in Spanish. Two bilingual coders are conducting the thematic analysis using Nvivo. The results presented here are preliminary, based on 80% inter-rater reliability, and derive from transcript review and interviewer memos; final themes will be confirmed through the planned coding process Results/Anticipated Results: We identified the following themes: parenting challenges: persistent safety worries after IPV; heavy caregiving responsibilities with limited time and money; custody/visitation disrupting children’s routine; immigration related stress and co-parent conflict; and symptoms of depression/anxiety. Parenting strengths include a strong commitment to protection, existing routines, and faith/community support. Anticipated adaptations include acknowledging mothers’ protective strengths while integrating brief, accessible content that normalizes stress responses and offers practical co-regulation tools (e.g., grounding breathing exercises) to strengthen parent–child connection. Discussion/Significance of Impact: Early insights suggest that pairing ABC with content that honors mothers’ protective strengths, normalizes stress responses, and offers accessible co-regulation tools could fill a critical gap in contextually responsive support for Latino families, potentially strengthening parent–child relationships and increasing service access.

ABSTRACT IMPACT: The broad goal of this investigation is to inform the development of culturally sensitive HIV prevention strategies to reduce specific challenges pertaining to PrEP uptake and utilization for Latino men. OBJECTIVES/GOALS: HIV is a significant public health concern affecting Latinos in the U.S. Daily use of pre-exposure prophylaxis (PrEP) effectively prevents HIV infection and has the potential to curb HIV epidemics. The objective of this study is to examine how sociocultural variables impact PrEP-related services among HIV-negative Latinxs. METHODS/STUDY POPULATION: The current study is a mixed-method investigation. Participants will include Latinx adult patients seeking services at an HIV community clinic. Approximately 150 participants will be recruited for the study. Participants who are eligible will complete sociocultural, mental health and PrEP-related measures. For the applied aim, community stakeholders will be recruited who serve the Latinx community. Upon completion of data collection, the data analytic plan is as follows: Aim 1, to establish the relationship between each sociocultural variable and PrEP uptake/utilization, preliminary analyses (i.e., correlations and regression analyses considering co-variates) will be conducted. Aim 2, grounded theory techniques will be conducted to establish community-informed practices to increase the use of PrEP. RESULTS/ANTICIPATED RESULTS: Relatively little is known about cultural factors that may impede PrEP uptake among Latinx MSM. Several researchers have identified specific factors such as language, acculturation, familismo, and similar cultural norms as significant barriers to care (Page et al., 2017). It is expected that each of these variables will contribute significant variance to willingness to use PrEP. Specifically, negative relationships are expected between fatalism and machismo and lower stages on the PrEP Contemplation Ladder. Comparably, a negative relationship is expected between the Hispanic acculturation subscale and lower stages on the PrEP Contemplation Ladder. It is however, hypothesized that there will be a positive relationship between familism and the non-Hispanic acculturation sub-scale. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite important advances in health to prevent HIV infection, HIV rates among Latinx MSM continue to rise. This investigation will have the potential to inform the development of culturally sensitive prevention strategies. By collecting qualitative data from key community stakeholders, this project will also directly inform a CBPR prevention.

OBJECTIVES/GOALS: Using a cell culture model, we will determine the effects of phosphate on primary lung cell cultures and use our results to delineate a pathway through which these changes are carried out. Using animal models, we will determine the effects of phosphate on inflammatory and fibrotic lung injury, both in the presence and absence of CKD. METHODS/STUDY POPULATION: For our in vitro experiments, human lung fibroblasts were treated with concentrations of 1 to 5 mM sodium phosphate and FGFR inhibitors. Expression levels of interleukin (IL)-1beta, IL-6, and IL-8 were analyzed by qPCR and secretion of these cytokines was measured by ELISA. Phosphorylation of PLCy and ERK was measured by western blot. Using an in vivo approach, we placed C57Bl/6 mice on a high phosphate (3%) diet to elevate serum phosphate levels in the absence of kidney injury and administered bleomycin via oropharyngeal aspiration to generate an acute inflammatory response. Serum FGF23 levels were measured by ELISA and serum analysis for phosphate and renal function were obtained. Furthermore, expression of FGF23 pathway and inflammatory markers were analyzed in murine lung tissue using qPCR and western blotting. RESULTS/ANTICIPATED RESULTS: Augmented phosphate concentrations led to increased cytokine expression and secretion from human lung fibroblasts as well as a concomitant increase in PLCy and ERK phosphorylation. Inhibition of FGFR1 reversed the effects of phosphate on the inflammatory cytokines and PLCy/ERK phosphorylation. Serum FGF23 levels were significantly upregulated in mice on a high phosphate diet and further increased in mice subjected to a high phosphate diet with exposure to bleomycin. Both serum phosphate and creatinine levels were significantly elevated as well. Additionally, high phosphate and bleomycin increased local FGF23 expression in murine lung tissue, when compared to controls or each stimulus alone. DISCUSSION/SIGNIFICANCE: Phosphate has a significant impact on inflammation and fibrosis in the lung, indicating that the existence of pulmo-renal crosstalk exaggerates pulmonary injury and that there are biological pathways that may be targeted therapeutically to mediate these effects. These results could have a substantial impact on the quality of life for CKD patients.

Objectives/Goals: Research mistrust is well documented. So is community engagement’s potential to foster trust. We share the community engaged development and implementation of informational sessions on research and the protections for participants, aiming at enhancing community members’ knowledge of research. Methods/Study Population: Drawing from a pool of community members who had participated in research projects with a community engaged (CE) research center, we established a four-member Research Partner Committee (RPC) to work with the Center’s research team (CE Team) in the co-creation of materials for an informational session covering two main topics: the fundamentals of biomedical research and of protections for research participants.. The RPC and CE Team also co-developed two sets of pre- and post-tests to evaluate knowledge acquisition at session implementation. Community partners assisted in recruiting their constituents to participate in the sessions and provided convenient sites for the presentations. Results/Anticipated Results: The CE Team and RPC met 7 times to co-create the research and protections presentations (e.g., research definition, importance, inclusion of diverse populations, reasons we have protections, Institutional Review Boards, and informed consent). They also co-developed a 7- and a 9- item pre-post test, respectively. Five informational sessions, implemented by the CE Team with RPC members as observers drew 49 participants (96% African American, 73% female). 55.1% and 75.5% of participants showed a positive change in knowledge after the research and the protections presentations, respectively. 91% agreed to be notified about future research studies at the center. Discussion/Significance of Impact: Engaging community members in dialogue around research and the reasons for mistrust in research encourages relationship development. This engagement equips community members with knowledge to join in conversations around medical studies and make informed decisions about participation in research.

OBJECTIVES/SPECIFIC AIMS: ClinicalTrials.gov (CTgov) compliance has received much international attention as a significant regulatory, scientific, and ethical responsibility. Compliance rates for both industry and academia are held up for scrutiny by transparency advocates, but solutions for achieving compliance in academia have proven to be—because of its focus on innovation and multiple disciplines—significantly more complex than those employed by industry. Added challenges for academic medical centers (AMCs) are both increased researcher responsibilities under the new NIH Policy on Clinical Trial Dissemination and system-wide changes to requirements for “clinical trial only” Funding Opportunity Announcements. At Stanford University, a multifaceted approach toward improving CTgov outreach, education, and reporting led to a dramatic turnaround in compliance over 17-month period. METHODS/STUDY POPULATION: Stanford University School of Medicine’s Senior Associate Dean for Research and PI of Stanford’s CTSA applied a 3-part strategy to address unacceptable rates of results reporting. The strategy included (1) regular compliance reports to department chairs, (2) establishment of a central office, Clinical Research Quality (CRQ), to provide consistent training and support, and (3) interdepartmental cooperation across the school and university. Compliance reports, identifying all studies late for results reporting were sent monthly to all department chairs, with heightened focus on departments that conduct the most clinical trials. Senior leadership described the process in executive meetings and set improvement goals. Reports included multiple data points to help departments mobilize resources and identify trends; half-way through the period, soon-to-be late study records were included. CRQ hired 2 fulltime employees tasked with all aspects of managing the CTgov process and designed a portfolio of activities including: (1) a master list of all Stanford studies in the CTgov system; (2) a process for generating and distributing monthly reports; (3) an education program; and (4) support services, including an administrator working group. RESULTS/ANTICIPATED RESULTS: Since December 2015, Stanford has had the second-highest compliance rate improvement out of the 20 schools of medicine that receive the most NIH funding (+ 62%). DISCUSSION/SIGNIFICANCE OF IMPACT: Managing ClinicalTrials.gov compliance requires a high degree of technical knowledge of regulations, NIH policy, and the CTgov system. But without an equally high degree of engagement from senior leadership, results would not have been achieved. Central resources are critical to set policy and establish consistent processes, but without regular and repeated interactions between faculty, a multitude of administrators and staff, more central resources would have been required. By working simultaneously “down from the top” and “up from the bottom,” communication and education expanded rapidly, ineffective efforts were quickly transformed, and what began as an irritating and cumbersome problem became an occasion for collaboration and celebration of increased transparency.

ABSTRACT IMPACT: This study will be used to culturally tailor interventions to reduce maternal and infant health disparities in a Marshallese community. OBJECTIVES/GOALS: Inadequate prenatal care is associated with adverse birth outcomes including preterm births, low birth weight infants, and neonatal mortality. Marshallese Pacific Islanders are less likely to receive early and consistent prenatal care compared to other racial/ethnic groups and are thus at a higher risk for maternal and infant health disparities. METHODS/STUDY POPULATION: This article used a qualitative comparative analysis method to compare and contrast the perceived barriers to prenatal care for the prospective of Marshallese mothers and Maternal Health Care Providers (MHCPs). RESULTS/ANTICIPATED RESULTS: Marshallese mothers and MHCPs identified the same structural barriers to prenatal care: health insurance, transportation, and language. The socio-cultural barriers to prenatal care were depicted quite differently by Marshallese mothers verses MHCPs. DISCUSSION/SIGNIFICANCE OF FINDINGS: While the description of structural barriers were consistent among Marshallese mothers and MHCPs, the socio-cultural barriers and the value assigned to those barriers was quite different. Understanding the perspectives from both lenses is an important step towards addressing the barriers to prenatal care among Marshallese.

OBJECTIVES/GOALS: The aim of this study is to analyze electronic health record (EHR) data using Mapper PLUS (MP), a new mathematical model, to classify acute myocardial infarction (MI) patients by risk of major adverse events (AE). We tested MP’s ability to define patient subgroups with distinctive risk for death, heart failure or recurrent MI after revascularization. METHODS/STUDY POPULATION: An EHR retrospective analysis of 797 MI patients and 29 variables (i.e., laboratory tests, imaging, vitals, and clinical traits) collected at the time of hospitalization was conducted. All patients received percutaneous coronary intervention and standard pharmacotherapy. MP analysis produced a multi-dimensional nodal graph of the patients based on similarities found within variables. Two algorithms, Walk Likelihood and Walk Likelihood Community Finder were applied to the graph which formed joint clusters according to spatial distance within nodes. The final output was three clusters for risk level evaluation. Risk level (low vs. high) was relative to the average risk of AEs for the entire cohort one year post MI. RESULTS/ANTICIPATED RESULTS: Of three patient subgroups, one (n= 318) had a >1 fold change for the probability of survival without AE when compared to the overall cohort and thus was defined as the low-risk group. The second group (n=304) had DISCUSSION/SIGNIFICANCE: MP stratifies patients into three groups according to predictive variables which relate to the risk for AE following an acute MI treatment. This is a new topological method for patient classification based on minimal input strictly from pre-collected EHR data. More cohort studies are needed to validate MP to classify patients for precision medicine.

OBJECTIVES/SPECIFIC AIMS: Perineal urethral sling placement is an option for men with mild to moderate post-prostatectomy stress urinary incontinence (SUI). However, men with persistent incontinence after sling placement often require secondary artificial urinary sphincter (AUS) placement, made difficult by the sling occupying the proximal bulbar urethra. This proximal section has a thicker corpus spongiosum which may mitigate cuff-induced ischemia and subsequent urethral atrophy. The authors report a series of AUS placements after failed sling, using sling revision or removal to access the proximal urethra. METHODS/STUDY POPULATION: Cutting the sling arms during urethral cuff placement increased urethral exposure and mobility. If feasible, completely removing the sling allowed the most proximal cuff site; but if dissection was felt unsafe, the mesh was left in situ and the cuff placed distally. This study is a retrospective cohort design of patients with SUI who underwent AUS placement after failed sling from 2010 to 2016. Variables included baseline patient characteristics, SUI severity, intraoperative variables, and postoperative outcomes. AUS failure, defined as infection, erosion or urethral atrophy, was analyzed at 12 and 96 months using univariate and multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Over the study period, 29 patients underwent AUS placement after failed sling. At the time of AUS placement, mean urethral circumference was 6.2 cm and 68% of patients had a 4.5 cm cuff placed; no cases required a 3.5 cm cuff. Seventy-three percent of cases were after transobturator sling placement (27% bone-anchored) and 45% of slings were explanted. AUS failure rate at 12 and 96 months was 17.8% and 45%, respectively; atrophy was the most common indication. Prior transobturator sling placement had lower rates of both 12 month (9.1% vs. 57%, p=0.006) and 96 month (36% vs. 71%, p=0.11) failure, though the latter was not statistically significant. Sling explant was not a significant predictor of 12 month (p=0.12) or 96 month failure (p=0.17). DISCUSSION/SIGNIFICANCE OF IMPACT: Sling revision during AUS placement helps expose the wider proximal urethra, allowing larger cuff size placement. This procedure appears safe, with low rates of erosion and short-term failure—albeit with high rates of long-term urethral atrophy possibly due to more significant dissection causing devascularization. However, sling removal was not a significant predictor of failure. The transobturator sling’s smaller profile may result in less trauma to urethra—possibly explaining the improved outcomes.

OBJECTIVES/GOALS: At UNC-Chapel Hill’s CTSA hub – the NC Translational and Clinical Sciences Institute (NC TraCS) – we conducted a participatory evaluation of a new community and patient advisory board (CPAB) to assess member experiences, and the outcomes and early impacts of their work on institutional programming related to equity and inclusivity in research. METHODS/STUDY POPULATION: NC TraCS staff conducted informal interviews with CPAB members to discuss how they envision success in their work, ideas for measuring progress towards their goals, and how they have seen similar work measured by others. These conversations guided the development of outcomes, indicators, and data collection methods for the CPAB evaluation plan. CPAB member satisfaction, experiences, and perceptions of accomplishments were assessed via an online survey. Concurrently, an Outcome Harvesting approach was used, through which NC TraCS staff retrospectively identified key outcomes of the CPAB’s work through team discussion of programmatic changes and review of internal documents and data. RESULTS/ANTICIPATED RESULTS: CPAB members (n=10) were highly satisfied with meetings, group dynamics, activities and accomplishments, and 90% of members felt that NC TraCS was very responsive to their feedback. Key outcomes included: 1) co-creating a shared vision, goals, and operational policies for the CPAB; 2) co-developing a training series for research teams about patient and community engagement; 3) disseminating best practices for co-developing advisory boards; 4) providing guidance to improve NC TraCS consultations, services, and resources related to enhancing equitable participation in research (e.g., developing an Equity in Research Framework); and 5) contributing to institutional initiatives related to diversity, equity, and inclusion (e.g., improving compensation processes for research participants and partners). DISCUSSION/SIGNIFICANCE: Evaluations of CPABs often focus on process measures, while assessments of outcomes and impacts are lacking. Our evaluation data highlight the early outcomes and value of a newly formed CPAB. Furthermore, our approach can inform the creation and evaluation of equity-focused advisory boards within other research institutions.

OBJECTIVES/GOALS: The goal of this study is to evaluate the role of WNT5A and WNT5a-AS1 in sex-differences of GBM progression. In our preliminary studies, we found that a long non-coding RNA WNT5A-AS1 is overexpressed in male GBM patients. We also found that WNT5A-AS1s expression shows a negative correlation with overall survival within male patients. METHODS/STUDY POPULATION: We will define the mechanism by which WNT5A-AS1 regulates WNT5a-mediated glioma stem cell (GSC) maintenance by assessing the effects of inhibiting WNT5A-AS1 expression on transcriptional activity and stemness in GSCs. We will determine if there are distinct Wnt-signaling patterns in male and female isogenic murine astrocytes by examining the expression of downstream proteins in the Wnt signaling pathway and how inhibition of WNT5A-AS1 alters this expression. We will then examine the impact of WNT5A-AS1 on temozolomide (TMZ) resistance in-vitro and in-vivo. We will assess the cell viability and survival of GBM PDX cells upon treatment with TMZ in vitro. Next, we will assess the capacity of knockdown of WNT5A-AS1 to increase sensitivity to TMZ-induced cell death and prolong survival in vivo in intracranial models. RESULTS/ANTICIPATED RESULTS: We hypothesize that WNT5A-AS1 targets Wnt5a and regulates its expression. We anticipate that knockdown of WNT5A-AS1 will upregulate WNT5A expression. We also expect that inhibiting WNT5A-AS1 will alter GSC stem maintenance and functional effects. We expect to see an increase in downstream Wnt5a signaling proteins in males vs females when treated with exogenous Wnt5a. We hypothesize that knockdown of both, WNT5A-AS1 and WNT5A will alter the expression of downstream proteins. We hypothesize that knockdown of WNT5A-AS1 will decrease tumor growth and therapeutic resistance to TMZ while increasing survival in patient derived xenographs in vivo and in vitro. DISCUSSION/SIGNIFICANCE: This study will provide insight into the mechanisms underlying the difference in GBM onset and progression between male and female patients, which is clinically important. We will also characterize the biological role WNT5A-AS1 which is currently unknown to date and elucidate differential role of GSCs in GBM progression between male and female.

OBJECTIVES/GOALS: This project aims to ensure that the age ranges of participants in OHSU studies for specific diseases match the demographics of the populations the diseases occur in, as mandated by the new NIH Inclusion of Individuals Across the Lifespan as Participants in Research Involving Human Subjects policy. METHODS/STUDY POPULATION: This study involves retrospective and prospective data. The retrospective phase (“Look Back”), reviewed all investigator-initiated OHSU studies between 2017 and 2018 with prospective consent that were disease related (N = 63). Age range per IRB protocol and per subject enrollment were graphically compared to disease demographics to determine if study age ranges were a “match” or “mismatch” to disease demographics (0 = mismatch, 1 = partial match, 2 = full match). This data will inform the upcoming prospective phase of the study, when the study team will reach out to primary investigators of enrolling studies with education and resources, and track whether this reduces demographic “mismatch.” RESULTS/ANTICIPATED RESULTS: Of the studies, 51 were evaluated in the “Look Back” analysis. 40 studies were full matches for age inclusion matching disease demographics (78%), 40 for disease prevalence range (78%), and 38 for enrolling subjects within the disease demographic range (74%). Studies received the lowest scores in enrolling subjects that match disease prevalence, with 19 earning full points (37%) and 17 earning 0 points (33%). Limitations include difficulty in finding and applying disease demographic and prevalence ranges. In addition, in this data, 12 of the original 63 total studies could not be scored because no subjects had been enrolled or prevalence ranges were not in line with clinical expertise. DISCUSSION/SIGNIFICANCE OF IMPACT: This study highlights that many trials exclude older subjects at the upper age ranges. Future analysis of the prospective phase of the study will allow us to assist research teams in closing these gaps and will determine the Policy’s impact on the recruitment of older adults into research.

OBJECTIVES/GOALS: Persons with Parkinson’s disease (PwPD) have set-shifting impairments that may limit motor learning of protective responses to prevent falls. This study compares the effect of blocked versus random practice schedules on acquisition and retention of protective stepping stability in PwPD & age-matched controls. METHODS/STUDY POPULATION: Twenty PwPD & 20 age-matched controls will be randomly assigned to random or blocked practice groups to experience slip and trip-like perturbations which induce stepping responses. Blocked practice is repeating a task (e.g., slip) several times before the next task, while random practice is randomly practicing two or more tasks (e.g., slips & trips). Each subject will wear a safety harness to prevent falls, each fitted with a load cell that indicates when a fall would have occurred. We will assess the anterior-posterior and mediolateral margin of stability at 1st protective step, step length, and in-task fall incidence before, 10 minutes, and two days after practice. We will also compare outcomes between participants in the blocked vs. random practice schedule using two ANOVA. RESULTS/ANTICIPATED RESULTS: To date, we have recruited three control subjects. We anticipate that blocked practice will be superior to random practice for protective stepping acquisition and retention PwPD. Existing literature on motor learning of voluntary tasks indicates that PwPD have difficulty acquiring and retaining motor skills via random practice due to the higher cognitive processing required than blocked practice. Furthermore, since the basal ganglia’s set-shifting role is crucial for random practice, it is expected that random practice will limit protective steps acquisition and retention in PwPD. In healthy control, while blocked practice is better for acquisition, random practice will be superior for retention. DISCUSSION/SIGNIFICANCE: The study’s findings will provide knowledge that may foster the development of robust balance rehabilitation protocols to improve postural responses in PwPD and reduce delayed and ineffective stepping responses that results in falls among PwPD.

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: Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients. METHODS/STUDY POPULATION: A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes (ABCB1, ABCG2, CYP3A4, CYP3A5, CYP2J2) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant. RESULTS/ANTICIPATED RESULTS: A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs in both unadjusted and covariate-adjusted Cox regression models. DISCUSSION/SIGNIFICANCE: The effects of these eight genetic variants on exposure to DOACs may not be strong enough to translate into differences in clinical outcomes. Especially if the genetic inheritance underlying the risk of bleeding from DOACs is polygenic, reinforcing the need for further genomic studies on this subject.

OBJECTIVES/GOALS: The primary aim of this study is to explore the relationship between neighborhood deprivation index as measured by the Social Vulnerability Index (primary predictor) and anxiety and depression in primary caregivers of hospitalized children, measured using the Hospital Anxiety and Depression Scale (primary outcome). METHODS/STUDY POPULATION: Design: This descriptive, comparative, non-intervention, cross-sectional substudy is is a secondary analysis of survey data collected from parents of hospitalized children staying at Ronald McDonald Houses. Regression models will examine the relationship between a parent’s social determinants of health and their anxiety and depression in the context of their child’s hospitalization. Setting/Study population: Parents/primary caregivers were recruited from the following sites: RMH of the Greater Philadelphia Region, RMH of San Diego, RMH of Greater Cincinnati, RMH of the Bluegrass (Lexington, KY), and RMH of Alabama. RESULTS/ANTICIPATED RESULTS: In the DAG below I hypothesize the associations between the variables and anxiety and depression based on what has been reported in the literature. The analysis is in progress. [blob:https://acts.slayte.com/50293cb7-4274-49bb-998d-7601dffd23cb] DISCUSSION/SIGNIFICANCE: Parents of hospitalized children experience a high burden of anxiety and depression. Pre-existing indicators of social determinants of health may contribute or compound parental anxiety and depression. A better understanding of this association can lead to improved screening and interventions to better support parents and their children.

Objectives/Goals: Incorporating community voice ensures that research meets real world needs and enhances community trust and engagement. The objective of this program is to train community members on research to become community scientists and strengthen their role as partners in research, advancing the translation of discoveries into community practice. Methods/Study Population: Based on the University of Florida Citizen Scientist model, Mayo Clinic launched a Community Scientist (CS) program in 2021 as a one-day event. It expanded to a 4-week program in 2022, an 8-week program with a 6-week experiential assignment in 2023−2024 and added asynchronous training in 2025. The CS curriculum integrates didactic and experiential assignments with pre/post evaluations implemented in 2023 and expanded in 2024 to include post evaluations for the 6-week experiential assignment. Participants represented three Mayo Clinic regions (Arizona, Florida, Midwest), reflecting different geographies and backgrounds. Evaluations assessed participants’ knowledge, confidence, and engagement in multiple topics such as genomics, ethics, biobanking, and researcher–community collaboration. Results/Anticipated Results: 30 CS participants completed training once evaluations were implemented, and the CS participants’ familiarity with the role of a community scientist increased from 20% to 90%. Understanding of genomics and biobanking increased from <20% to 80% and knowledge of research ethics and IRB processes increased from 30% to 75%. Participants agreed that the experiential assignment deepened their understanding (82%), confidence (80%), and ability (70%) to partner with researchers. High satisfaction scores (89%) from the CS participants supported the program’s value and 100% noted readiness to engage as a CS in research. Overall results demonstrate the program’s scalability and effectiveness while also noting the need for consistent evaluation for program improvement. Discussion/Significance of Impact: The CS program empowers communities with knowledge and confidence to engage with research teams, advocate locally and partner with investigators. Strong gains and consistent growth across domains highlight the CS program’s potential as a scalable model for meaningful community engagement in research.

Objectives/Goals: The goal of the RC2 Systems Marketing Analysis for Research Translation (SMART) special innovation program is to develop and test a structured approach for working with research teams and communities to accelerate the translation of clinical and community innovations to address health inequities by integrating social marketing with community-based system dynamics. Methods/Study Population: The SMART program is a consultancy service for CTS teams focused on selecting and tailoring implementation strategies for advancing equity. We use social marketing for understanding the alignment of practice innovation feature sets with community priorities for advancing health equity; and community-based system dynamics to understand and refine the dynamics of scaling up and sustaining the implementation of innovations with sufficient reach to address regional health inequities. The program is implemented as community-engaged group model-building workshops with research teams, with follow-up marketing analyses and computer simulation of implementation strategies of innovations and development of implementation roadmaps. We use developmental program evaluation to revise the SMART program. Results/Anticipated Results: Anticipated results from piloting the SMART innovation program with four research teams include (1) design matrices pre and post-workshop for each innovation; (2) system dynamics simulation models and analyses of implementation and scale-up of innovations; (3) analysis of the SMART program for highest impact, with priors for estimating subsequent SMART program performance; and (4) a revised SMART program based on results from the developmental program evaluation. Discussion/Significance of Impact: This work highlights the feasibility and benefits of combining methods that have been cited in implementation science for understanding the complexity of implementation to accelerate the translation of innovations into clinical and community settings for advancing health equity.