OBJECTIVES/SPECIFIC AIMS: 1. To identify novel genetic modifiers that result in a mild bleeding phenotype in patients with FVIII <1%. 2. To examine the feasibility of a practice model that incorporates the principles and methods for both obtaining consent for NGS and returning individual research results from the sources described above. METHODS/STUDY POPULATION: 1. We plan a 3-step approach for identifying novel genetic modifiers of hemophilia: a. Obtain samples from individuals with an extremely mild bleeding phenotype: The study will be narrowed to patients with confirmed FVIII <1%, a null mutation in the gene for FVIII, and a mild bleeding phenotype according to a detailed bleeding history. b. Identify variants that modify phenotype: Whole exome sequencing will be performed, followed by a focused analysis of genes known or suspected to be involved in thrombosis and hemostasis and prediction of variant impact using algorithms that account for conservation and deleteriousness of all variants. c. Verify the impact of novel variants in independent samples: In silico (analyze genetic databases for suspected variants), in vivo (assess bleeding in animal models of hemophilia after introducing presumed modifier variants). 2. We will employ a model for obtaining informed consent and communicating individual genetic research results and results with potential clinical impact to research participants: a. The informed consent process will be performed after potential participants read a pamphlet entitled “Genetic Research at The Rockefeller University Hospital and Center for Clinical and Translational Science.” The pamphlet includes 16 questions that the potential participants are urged to ask the investigator, including, “What will you look for in my genetic information?”, “Will I receive results from this study?”. Potential participants will also be informed of the meaning of clinically actionable variants, either pathogenic variants related to phenotype or secondary (“incidental”) findings (i.e. variants unrelated to phenotype, the knowledge of which could lead to actions that may improve health). Participants who do not want to receive information about potentially actionable variants will be excluded from the study to avoid a situation where the investigator has clinically important information that cannot be shared with the participant. b. Genetic testing will be performed in a CLIA-certified lab to allow investigators to share the results with the study participants. c. Results will be reported to study participants according to a standard operating procedure (SOP) that classifies the report of variants according to the relation to phenotype and the pathogenic potential. d. Participant satisfaction with the informed consent process and the return of results will be assessed by a questionnaire for obtaining participants’ perceptions of their research experience, based on a standard set of validated research participation experiences measures (Kost RG et al, J Clin Transl Sci. 2018;2:31). RESULTS/ANTICIPATED RESULTS: Samples from individuals with severe null mutation hemophilia and a mild bleeding phenotype will be enriched in genetic modifier variants. After completing participation, participants will express satisfaction with the informed consent process and the results of the return of genetic information. DISCUSSION/SIGNIFICANCE OF IMPACT: Genetic risk assessment to predict bleeding risk has the potential to provide hemophilia patients with tailored therapy, allowing for very early initiation of treatment (prophylactic thrice weekly IV administration of FVIII) in patients with a high bleeding risk and deferring this costly and burdensome treatment in patients who are expected to be mild bleeders. Genetic modifier variants of hemophilia may be found to predict thrombosis in non-hemophiliac patients and profoundly impact the treatment of venous thrombosis. A structured process for obtaining consent for NGS and return of genetic results to study participants can protect them from uncertain genetic information. Moreover, this process will prevent a situation in which investigators have knowledge about clinically actionable variants but they are not allowed to report them to the participants or do not have a process for doing so. Sharing individual research results and results with clinical significance with participants of studies that involve whole exome sequencing can promote transparency and engagement of participants throughout the research enterprise.

Objectives/Goals: We will conduct a 12-week pilot randomized controlled trial (RCT) to test the feasibility, acceptability, and preliminary efficacy of a staged-intensity whole foods intervention on hemoglobin A1c (HbA1c) change in adults, diet quality change (via the 2020 healthy eating index [HEI-2020]) in adults and offspring, and diet adherence and social determinants of health (SDOH) considerations via focus groups. Methods/Study Population: In this two-arm, parallel RCT, 30 adults with prediabetes (25–59 years) and their offspring (6–18 years) will be randomized to receive the 1) 12-week whole foods intervention which includes a 2-week feeding period (all foods/recipies provided), a 6-week customizable feeding period (3 dinners/recipies weekly), and a 4-week maintenance period (no food/recipies). The control group will receive standard of care (i.e., single RD-led diet counseling session). Primary outcomes include feasibility (≥80% retention and completion of study outcome measures) and acceptability (≥75% adult self-reported diet satisfaction). Intervention effects include 1) HbA1c change at 12-weeks in adults and 2) adult/offspring HEI-2020 scores assessed via diet records. Focus groups will assess influences of SDOH on diet adherence. Results/Anticipated Results: We have received Institutional Review Board approval, and recruitment is planned for January 2025. We will enroll 30 families from the greater Nashville, TN area. An intent-to-treat analysis will be conducted to test the preliminary effects of the whole foods diet intervention on the 12-week change in HbA1c (adults only) and 2020-HEI diet quality scores during the intervention period (adults and offspring). Focus groups will be conducted to understand how individual and family needs/preferences and SDOH may be perceived barriers or facilitators of diet adherence. Data generated from this study will be used to guide a fully powered RCT of our whole foods intervention to assess long-term effects on additional diabetes and metabolic outcomes and assessment of SDOH influences to support long-term adherence. Discussion/Significance of Impact: A healthy diet pattern is an effective nonpharmacological solution to prevent T2D, but only if it can be maintained. A family-centered whole foods diet pattern that uses “food as medicine” and considers how individual and family needs/preferences, and SDOHs could be an effective and sustainable multigenerational solution to prevent T2D in families.

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation <51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend<0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.

ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

OBJECTIVES/GOALS: This study evaluates the impact of an updated and expanded training for social and behavioral health researchers. Participants’ experience with training modules focused on community engagement is a focus of this evaluation as is the application of this training by participants in teams. METHODS/STUDY POPULATION: The Social and Behavioral Research training series for health researchers and team members was first created by faculty and staff of the Michigan Institute for Clinical and Health Research in 2018. This training was updated and expanded in 2021 with support from the National Institutes of Health to include new material regarding community-engaged health research as well as updates concerning technology and new federal regulations. Past participants of the training were invited to retake the training, as were clinical and translational researchers at University of Michigan who were new to the training. Surveys were sent to all participants after completing the training and a focus group of research staff was conducted to identify how they utilized the training in support of their teams. RESULTS/ANTICIPATED RESULTS: It is anticipated that at least 100 individuals will participate in the evaluation of the Social and Behavioral Research training between October 2022 and February 2023. Data extracted from U-M’s learning management platform will demonstrate how well participants performed on key knowledge checks embedded in the modules and how quickly they progressed through the sections of the training. These results will be compared to benchmarks derived from evaluations of the prior course which were conducted in 2018. A focus group of at least 10 individuals will demonstrate how health research staff utilized the training and associated resources to advance the scientific work of their study teams. DISCUSSION/SIGNIFICANCE: Comprehensive training programs for research best practices in social and behavioral health need to have tailored and up-to-date information for this group of researchers and staff. The results of this evaluation will demonstrate how this program contributed to the professional development of the health research workforce.

OBJECTIVES/GOALS: Frontiers CTSI developed applications to ensure its science teams have technological tools to advance their community engagement and trial management. The Trial Finder app is a mobile application that allows users to navigate available trials. The Accrual app will help study teams monitor their recruitment performances in real time. METHODS/STUDY POPULATION: The Data Science team at the University of Kansas Medical Center (KUMC) had previously developed similar applications for The University of Kansas Cancer Center. Both retrieve information from KUMC’s clinical trial management system and ClinicalTrials.gov. This was replicated to include KUMC Pulmonary Critical Care (PCC) and KUMC Neuromuscular (NM) trials. Frontiers CTSI is working with both groups for piloting and feedback. Recruiting and marketing strategies for investigators to add their trials to both apps will be done through existing communication channels and be highlighted on Frontiers trial resource website. Recruiting and marketing strategies of the Frontiers Trial Finder app to the external community will have a focus on, but not limited to, paid social media advertising. RESULTS/ANTICIPATED RESULTS: The Trial Finder app can help providers search for trials their patient may be eligible for during clinic visits and to engage with the community by allowing anyone to download and browse on their Android/iOS device. Built in REDCap forms are used to capture contact information. The Accrual app is a web-based application that helps study teams monitor their recruitment performances in real time and provide an opportunity to adjust strategies. It uses an in-house algorithm to predict if trials will meet timeline goals. This data is conveniently laid out on a single web page so that science teams can overview all their trials’ recruitment performances simultaneously. The next phase of developing these applications is to market their use within Frontiers CTSI and its community catchment area. DISCUSSION/SIGNIFICANCE: Through collaboration, Frontiers CTSI is developing resources to support community engagement and trial management. New innovative applications like these ensure all the main stakeholders involved with clinical trial execution are always engaged and have access to iterative contemporary technologies that support their research.

OBJECTIVES/GOALS: 1) Assess the patient-reported, perceived change in olfactory function after bimodal visual-olfactory training (OT) 2) Assess change in olfactory function after bimodal visual-olfactory training with a smell identification test 3) Assess which scents are most important to people with olfactory dysfunction (OD) METHODS/STUDY POPULATION: The participants are adults with subjective or clinically diagnosed OD with post-surgical or traumatic etiologies within the last 5 years. At the first of two study visits, participants complete the University of Pennsylvania Smell Identification Test (UPSIT) and complete general health (SF-36) and olfactory-related quality-of-life questionnaires. From a list of 34 scents, participants chose the 4 scents most important to them and smelled the scents twice daily for 3 months. Olfactory testing and the quality-of-life questionnaires were repeated at the final visit. RESULTS/ANTICIPATED RESULTS: 10 participants have enrolled in the study. There was one screen fail and one withdrawal. Six participants are currently undergoing OT and two have completed the study. Seven participants have post-surgical etiology and three have post-traumatic etiology of their OD. Of the two participants who have completed the study, one had an UPSIT score improvement from 25 to 33 out of the 40 questions correct. The minimally clinically important difference on the UPSIT is 4. She reports improvement subjectively. The second participant had a UPSIT score change from 25 to 24 and reports ability to smell is neither better nor worse. DISCUSSION/SIGNIFICANCE OF IMPACT: Traumatic and post-surgical, particularly post-transphenoidal hypophysectomy, are common etiologies of OD and no effective treatments exist. The results from our pilot study will help better inform the best way to undergo OT, how effective it is, and the planning of future studies.

OBJECTIVES/GOALS: modonko1@jhmi.edu METHODS/STUDY POPULATION: Michelle Odonkor RESULTS/ANTICIPATED RESULTS: I accept DISCUSSION/SIGNIFICANCE: No, I do not want my poster published JCTS.

OBJECTIVES/SPECIFIC AIMS: We recently reported that PRMT5 epigenetically activates androgen receptor (AR) in prostate cancer cells. Because targeting AR signaling through androgen deprivation therapy is clinically used as a radiosensitization approach to treat high-risk prostate cancer, our finding raised an exciting possibility that targeting PRMT5 may improve RT for prostate cancer patients. Contrary to our expectation, targeting PRMT5 sensitized both AR expressing and AR negative (AR−) prostate cancer cell lines to radiation. The goal of our study was therefore to determine the role of PRMT5 in repair of IR-induced DSBs and to translate these findings to improving radiation therapy for cancer patients in general (not just prostate cancer patients). METHODS/STUDY POPULATION: The majority of experiments were basic science experiments analyzing PRMT5’s role in the DNA damage response in normal and cancer cell lines. For example, to extend our findings and determine if PRMT5’s role in DSB repair is conserved across multiple cell types, we performed similar experiments in AR− prostate cancer cells, luminal breast cancer cells, glioblastoma cells, and human embryonic kidney cells. To determine the clinical significance of our finding, we also analyzed mRNA expression of PRMT5, AR, and both PRMT5 and AR target genes involved in DSB repair across 43 clinical cancer data sets. RESULTS/ANTICIPATED RESULTS: (1) Targeting PRMT5 sensitizes prostate cancer cells to IR in an AR-independent manner, (2) PRMT5 regulates the repair of IR-induced DSBs in an AR-independent manner, (3) RNA-seq analysis reveals that PRMT5 likely regulates genes involved in the DNA damage response, (4) PRMT5 activates expression of several genes in the DDR including those involved in DSB repair, (5) PRMT5 functions as an epigenetic activator of genes involved in DDR, (6) PRMT5 is required for NHEJ, HR, and G2-Arrest upon IR treatment, (7) Upregulation of PRMT5 correlates with formation and repair of IR-induced DSBs, (8) PRMT5’s role in repair of IR-induced DSBs is conserved in several normal and cancer cell types, and (9) PRMT5 expression correlates with expression of DSB repair proteins in clinical cancer samples. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, we provide evidence that PRMT5 is a master epigenetic regulator of IR-induced DSB repair through epigenetic activation of multiple target genes involved both HR and NHEJ as well as G2 arrest. Interestingly, the majority of genes regulated by PRMT5 are well-characterized, “core repair proteins” involved in HR (RAD51, BRCA1, BRCA2, RAD51D, and RAD51AP1), NHEJ (NHEJ1, Ku80, XRCC4, and DNAPKcs), and G2 arrest (Cdk1, CDC25C, CCNB2, and WEE1), which may explain why PRMT5 is essential to repair IR-induced DSBs in several cell lines. Although AR may also regulate DSB repair via both HR and NHEJ, several pieces of evidence in our study suggest that PRMT5 also regulates DSB repair independent of AR. First, PRMT5 targeting sensitizes both AR+ and AR− prostate cancer cells to IR. Second, exogenous expression of AR only partially rescues the impairment of IR-induced DSB repair by PRMT5 knockdown. Third, PRMT5 knockdown increases IR-induced DSB in AR− DU145 cells and several other cancer cell lines and normal cells. Fourth, PRMT5 expression correlates positively with the expression of its target genes in multiple human cancer tissues. During preparation of this project, Braun et al. reported that PRMT5 post-translationally regulates the splicing out of detained-introns (DI)s of genes to modulate gene expression. However, analysis of their data showed that the majority of DEGs we identified either do not contain DIs or DI splicing was not affected by targeting PRMT5. In addition, Clarke et al. reported that PRMT5 participates in the DSB repair choice process and promotes HR through methylation of RUVBL1. It is therefore likely that PRMT5 regulates repair of IR-induced DSB via multiple mechanisms. As PRMT5 is overexpressed in many human cancers and its overexpression correlates with poor prognosis, our findings suggest that increased DSB repair by PRMT5 overexpression in these human cancers may confer survival advantages particularly following DNA damaging treatment. Because targeting DSB repair has been proven to be a valid therapeutic approach for cancer treatment, our findings here also suggest that PRMT5 targeting may be explored as a monotherapy or in combination therapy with RT or chemotherapy for cancer treatment.

OBJECTIVES/GOALS: There is a high burden of lung cancer in persons living with HIV (PLWH). The role that HIV status, by levels of immune function and viral load, has on survival from lung cancer is not fully understood. The study’s objectives were to assess 1) the association of HIV with survival in non-small cell lung cancer (NSCLC) and 2) prognostic factors in PLWH with NSCLC. METHODS/STUDY POPULATION: Participants were from a cohort of lung cancer patients diagnosed between 2004-2017 in the Bronx, NY, with vital status ascertainment at least annually. We compared survival from NSCLC diagnosis between HIV-negative patients (HIV-, N = 2881) and PLWH (N = 88), using Cox regression, accounting for clinical and sociodemographic factors including smoking status. In three separate comparisons to HIV-, PLWH were dichotomized by CD4 count (<200 vs. ≥200 cells/μL), CD4/CD8 ratio (median, <0.43 vs. ≥0.43) and HIV viral load (VL) suppression (<75 vs. ≥75 copies/mL). In PLWH only, we assessed the relationships of CD4 count, CD4/CD8 ratio, and VL at diagnosis with survival adjusting for age, sex, and cancer stage. CD4 count and CD4/CD8 ratio were also examined as time-varying variables using a counting process approach. RESULTS/ANTICIPATED RESULTS: PLWH were younger (median 56 years, IQR 51-52 vs. 68, IQR 60-76) and more likely to be current smokers (58% vs. 37%) at diagnosis than HIV- patients. Median survival was lower in PLWH [1.1 years, 95% confidence interval (95%CI): 0.6-1.3] than in HIV- [1.6 (1.5-1.7)]. Survival comparing PLWH with higher CD4/CD8 to HIV- was similar [hazard ratio (HR), 95%CI: 0.63 (0.37-1.07)], but those with lower CD4/CD8 experienced worse survival (HR = 1.74, 95%CI: 1.07-3.89). Among PLWH, having a CD4 count < 200 cells/μL was associated with over twice the risk of death compared to those with CD4 ≥ 200 cells/μL (HR = 2.37, 95%CI: 1.14-4.92). VL and CD4/CD8 ratio were not associated with survival. Lower time-updated CD4 count was also associated with worse survival (HR = 2.19 for CD4 <200 vs. >200 cells/μL, 95%CI: 1.16-4.13). DISCUSSION/SIGNIFICANCE OF IMPACT: Among persons with NSCLC, CD4/CD8 ratio nearest diagnosis was shown to distinguish mortality risk in PLWH compared with HIV- patients. In addition, PLWH with low CD4 had worse prognosis than PLWH who had higher CD4 counts. These results suggest HIV immune status to be an essential component influencing survival in lung cancer.

OBJECTIVES/GOALS: Childhood Sjögren’s disease (cSD) is a rare autoimmune disease. Despite the profound impact on children and their families, pediatric-specific clinical trials to inform therapeutic strategies in cSD are lacking. In 2022 we participated in the Trial Innovation Network (TIN) Design Lab with the purpose of designing a series of N-of-1 trials for cSD. METHODS/STUDY POPULATION: New medications have the potential to be safe/effective treatments for cSD but must be evaluated in randomized trials. To overcome limitations of traditional parallel-group designs given the rarity of cSD, we developed an N-of-1 trial approach. Our proposal was selected by the Tufts TIN Design Lab. The Design Lab multi-stakeholder process involved parents of and patients with cSD, pediatric and adult rheumatologists, and experts in clinical trial design and outcomes. We engaged all stakeholders in protocol development to maximize the impact of the proposed approach on clinical care, ensure a successful recruitment plan, and inform the choice of endpoints as there are no widely accepted cSD outcome measures to determine treatment efficacy. RESULTS/ANTICIPATED RESULTS: Using the Design Lab methodology, we clarified the N-of-1 study goals and engaged in an iterative process to develop a “briefing book” that ensured a sound premise for our study. We reviewed and accumulated published literature to support our focus on mucosal/glandular manifestations, identified potential interventions to be used in the N-of-1 trials, and enumerated possible outcomes, including outcomes important to patient/parents. This work culminated in a full-day Design Lab event that included multiple stakeholders who provided expertise from different perspectives on the full drug development pathway. Study design feedback focused on three specific areas. 1) Inclusion and exclusion criteria; 2) Identification of outcome measures; 3) Treatment and washout periods. DISCUSSION/SIGNIFICANCE: To address the critical need and move treatment of cSD forward, we are designing a prototype N-of-1 trial in children with rheumatic disease. We will continue to engage stakeholders by using a series of Delphi surveys and an in-person meeting to create composite outcome measures to test cSD therapies in personalized trials.

OBJECTIVES/GOALS: The purpose of this study is to evaluate average pain scores in patients with Hidradenitis Suppurativa (HS) and determine if racial disparities influence HS-related pain management. METHODS/STUDY POPULATION: We surveyed 3,140 adult patients about demographics, HS, pain levels, medical history, and health-related quality of life. Among respondents (N=162), pain scores (0-10) were grouped as high (8+, N=54) and low (<7, N=108). We used logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS/ANTICIPATED RESULTS: Respondents were female (88.9%), Black race (59.4%), with a median age of 36 (IQR 25-42) and a mean pain score of 7 (IQR 5-8). Half (48.2%) of respondents disagreed or strongly disagreed with, “I am satisfied with how my pain related to HS is being managed by my doctors.” Independent risk factors for high pain included Black race (aOR=7.95, 95% CI 3.11-20.26), history of prescribed pain medications (aOR=2.37, 95% CI 1.06-5.30), and former/current tobacco use (aOR=4.12, 95% CI 1.76-9.64). DISCUSSION/SIGNIFICANCE: The preliminary data support the hypothesis that race influences HS-related pain. In addition, less education, a history of prescription pain medication use, and tobacco use are all independent risk factors contributing to higher pain scores in patients with HS. Further analysis will be conducted to evaluate racial influences on pain management.

OBJECTIVES/GOALS: To describe and evaluate an innovative university-community vaccination and food access model for minority, immigrant, and underserved individuals experiencing food insecurity during a global pandemic. METHODS/STUDY POPULATION: The Purdue University Center for Health Equity and Innovation (CHEqI) partnered with the two largest food banks in the Midwest and Walgreens to offer free COVID-19 and Flu vaccinations alongside food distribution. Goals included addressing food insecurity, increasing vaccine access, and decreasing vaccine hesitancy. CHEqI acquired funding, recruited volunteers and interpreters, assessed interest and addressed vaccine hesitancy. Food bank/pantry partners distributed food and provided access to clientele and marketing assistance. Walgreens procured, administered, and documented vaccinations. The Model accommodated drive-through and indoor processes. Unidentifiable observational and self-report data were collected. Descriptive statistics were computed to characterize program outcomes. RESULTS/ANTICIPATED RESULTS: A total of 11 vaccination events occurred between June and October 2021 at three food bank/pantry locations. Of these 11 events, nine (82%) were drive-through and two (18%) took place indoors, eight (72%) offered COVID-19 vaccinations only, and three (27%) offered both COVID-19 and Flu vaccinations. Food was distributed to a total of 5,108 families and 416 vaccines (314 COVID, 102 Flu) were administered. Of the 396 individuals who received at least one vaccine, 20 (5%) received both a COVID and Flu vaccine. Of the 386 individuals who received at least one vaccine and reported their sex, 194 (50%) identified as female and the average age of those who received at least one vaccine was 45 years old. Of those who reported race (N = 228) or ethnicity (N = 253), 43% identified as Black or African American and 53% identified as LatinX. DISCUSSION/SIGNIFICANCE: Findings offer an innovative vaccination and food access model for diverse individuals experiencing food insecurity during a global pandemic. By drawing on cost effective, accessible, and culturally contextualized practices to optimize the reach and quality of vaccination services we can improve access barriers and mitigate health disparities.

ABSTRACT IMPACT: This work investigates C. difficile strains in soil as a potential exposure for gut colonization and community-acquired infection of C. difficile. OBJECTIVES/GOALS: Identifying environmental sources of C. difficile can inform how non-hospital reservoirs can potentially contribute to C. difficile exposure and subsequent gastrointestinal colonization. The objective of the study was to identify C. difficile and toxin genes across various soil sources. METHODS/STUDY POPULATION: This was a cross-sectional study utilizing soil samples obtained throughout Texas, USA. All samples were collected between August and November of 2019 and 2020. Samples were taken from human and animal high contact areas, such as recreational parks. Samples were stored at -80oC until processing. DNA extractions were performed using the DNeasy Powersoil Pro Kit (Qiagen) per manufacturer’s instructions. Real-time PCR was also performed on extracted DNA using the Microbial DNA qPCR Multi-Assay Kit for Clostridium difficile Pathogenicity (Qiagen) for the identification of C. difficile, toxin A (TcdA), and toxin B (TcdB) genes. RESULTS/ANTICIPATED RESULTS: A total of 137 soil samples including dry dirt, sand, and wet soil near water sources were collected and processed for the presence of C. difficile. These included samples from parks and trails (42.3%), water sources (36.5%), and other public spaces (21.2%). C. difficile was identified in 59 (43.1%) soil samples: 6 (4.4%) with Toxin A and 2 (1.5%) with toxin B production. C. difficile was most prevalent among samples taken from parks and trails (50.0%), followed by other public spaces (48.3%), and water sources (32.0%). The median (IQR) Cq value for the C. difficile gene was 39.24 (33.45-40.47) among samples that tested positive. DISCUSSION/SIGNIFICANCE OF FINDINGS: We identified a high prevalence of Clostridioides difficile in soil samples, though toxin gene detection prevalence was low. Future studies will analyze other sources, including water and varying surface samples to obtain a comprehensive view of C. difficile in the environment.

Objectives/Goals: Our goal is to enhance communication and documentation in collaborative biostatistics by refining data management and metadata processes. We aim to capture critical data collection and generation information, improve transparency and reproducibility, and foster stronger researcher partnerships for more effective collaborations. Methods/Study Population: Traditional statistical analysis plans (SAP) often miss essential contextual knowledge from collaborators, leading to gaps that hinder reproducibility and limit future data use. Biostatistics teams at the University of Kentucky have updated their strategies to better capture important details about data origins and collection processes. By focusing on clear, comprehensive documentation early in the research process, we aim to preserve foundational data insights and improve collaboration efficiency. Our Biostatistics, Epidemiology, and Research Design (BERD) team has established best practices for addressing data management structures with collaborators across medical and healthcare fields – covering all project stages, from initial data collection to metadata creation and dataset finalization. Results/Anticipated Results: We will detail the processes used to improve data management structures and the observed results of these processes. For example, initiating deeper discussions about data origins and collection processes as early as possible in the collaboration has resulted in a more comprehensive project narrative that lays the foundation for effective collaboration. By engaging with project leaders early in the process, we can confirm that critical details about how data were collected and processed are documented, improving both the transparency and reproducibility of research findings. Streamlining the processes of capturing this information makes it more accessible and useful for those with limited statistical backgrounds, which is particularly relevant for faculty and staff in BERD communities and Clinical and Translational Science Awards Programs. Discussion/Significance of Impact: Nuanced data documentation structures are crucial for transforming raw data into meaningful, reusable datasets. Our initiatives promote clear communication, enhanced efficiency, and streamlined workflows. Translational science researchers can benefit from improving data management and metadata to boost long-term collaborative success.