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: Human-centered design (HCD) provides a practical, collaborative approach to integrating diverse perspectives throughout the translational research process. We highlight two CTSAs with established HCD teams who are utilizing varied approaches to accelerate the use of HCD in health intervention design and community engagement. METHODS/STUDY POPULATION: The CTSAs at the University of Michigan (MICHR) and the University of Pittsburgh (Pitt CTSI) have dedicated teams of human-centered designers that assist investigators with the application of HCD in their studies. MICHR’s service approach utilizes facilitated Design Sprints with study teams, guiding them from early conception of a research question through the co-design of interventions and innovations with end-users. Pitt CTSI’s training and consultation approach employs a two-day intensive training with group coaching sessions that provide investigators and research staff with skills and knowledge needed to implement HCD within translational research projects. Both hubs offer consultations on methodology for investigators interested in pursuing funding for studies utilizing HCD. RESULTS/ANTICIPATED RESULTS: Research teams at both hubs are pursuing HCD to co-design health research interventions and mHealth technologies with end-users locally and internationally, to facilitate meaningful engagement within advisory boards and collaboratives, and to enhance team science. To date, MICHR has conducted 13 research study-focused Design Sprints with 73 participants, as well as providing consultations to 26 research teams. Pitt CTSI has trained 164 investigators and staff and provided 146 consultations with research teams. Requests for HCD training have increased at MICHR while requests for HCD service provision have increased at Pitt CTSI. Both hubs are now building capacity to enact a more holistic approach to HCD that combines service delivery and training approaches to better meet the needs of investigators. DISCUSSION/SIGNIFICANCE: Increasing CTSA hub capacity to support the use of HCD in translational research by offering service and training opportunities can position investigators to conduct high impact health research that elevates the voices of those most likely to benefit from interventions, treatments, and innovations.

OBJECTIVES/GOALS: Chronic kidney disease (CKD) affects nearly 40% of adults with diabetes. Our objective is to assess trends in risk factor control and use of 2022 ADA and KDIGO guideline-recommended medications. METHODS/STUDY POPULATION: Using data from 1988 to 2020 from the National Health and Nutrition Examination Survey, we will examine trends in sociodemographic risk factors and glycemic, blood pressure, and lipid control among adults with CKD and diabetes. Glycemic control will be defined as a hemoglobin A1c (HbA1c)<7%, blood pressure control will be examined at cutoffs of 130/80 and 120/80 mmHg, and lipid control will be defined as a fasting triglyceride level ≥150 mg/dL, a low-density lipoprotein (LDL) <100 mg/dL without atherosclerotic cardiovascular disease (ASCVD), or LDL<70 mg/dL if they have ASCVD. We will assess changes in the use of commonly used antidiabetic, antihypertensive, and lipid-lowering medications. RESULTS/ANTICIPATED RESULTS: We hypothesize that from 1988-2020, blood pressure control has improved while glycemic and lipid control has not improved among adults with diabetes and CKD. We expect decreases in sulfonylurea use and increases in DPP-4 inhibitor, metformin, ACE inhibitor, angiotensin receptor blocker, statin, and insulin use over time among those with diabetes and CKD. In addition, there is likely a significant gap between those who are eligible to use newer medications like SGLT2 inhibitors or GLP-1 receptor agonists and who are currently using them within this subpopulation. DISCUSSION/SIGNIFICANCE: This study will examine adherence to guideline-recommended management and identify gaps in care for adults with CKD and diabetes, which may inform how best to optimize medication use for cardiorenal protection in this high-risk patient population.

OBJECTIVES/GOALS: Clinical Issue/ Practice Problem: A high turnover rate for research nurses was identified between 2017-2022 in the clinical research center at an urban Midwest academic health center. Inexperienced staff and high turnover are barriers to maintaining high-quality research integrity, efficacy, and safety for research projects and participants. METHODS/STUDY POPULATION: Project Implementation: A formal mentorship program was developed based on a curriculum from the International Association of Clinical Research Nursing Scope and Standards of Practice. The six-week project was implemented for research nurses with less than 2 years of experience. Mentees were paired with senior research nurses and met one-on-one weekly. Mentees completed the Anticipated Turnover Scale (ATS) survey in week 1 and week 6. All program participants completed a final evaluation survey. RESULTS/ANTICIPATED RESULTS: Outcomes: There was a one-point average reduction in pre- and post-ATS survey scores. This result supports the theory that mentees were less likely to leave their research role after a formal mentorship program. Qualitative results from the final evaluation survey demonstrate the program had a positive impact and benefits for both the mentees and the mentors. DISCUSSION/SIGNIFICANCE: Clinical Implications: By decreasing turnover rates, a highly competent and knowledgeable research nursing staff is attained to ensure appropriate nursing action and safety profiles for novel therapies.

OBJECTIVES/GOALS: Acidity and the lactate-to-pyruvate ratio correlate with immunotherapy resistance. AcidoCEST MRI and hyperpolarized magnetic resonance spectroscopy (HP-MRS) measure extracellular pH and lactate-to-pyruvate ratio. We will establish a baseline for these biomarkers then observe changes after combination esomeprazole and immunotherapy. METHODS/STUDY POPULATION: We used multiple melanoma models created via serial in vivo passage under immunotherapeutic pressure (FVAX, CTLA-4, PD-1, PD-L1). We used four of these corresponding to 25%, 50%, 75% and 100% resistance (TMT, F2, F3, and F4, respectively). HP-MRS was performed two weeks post implantation in male BL6 mice with AcidoCEST MRI 2-3 days later. Tumors were implanted in additional mice and grown for 1 week. We used esomeprazole as a possible immunotherapy sensitizer. Esomeprazole (or PBS) alone and in combination with immune checkpoint blockade (ICB; αCTLA-4, αPD-1) was then conducted every 3 days for 3 doses. ICB was administered 3h after esomeprazole. AcidoCEST MRI was performed the day after the final dose of combination therapy and 3h after esomeprazole (or PBS) alone. HP-MRS was performed 2-3 days after acidoCEST MRI. RESULTS/ANTICIPATED RESULTS: There was a statistical increase in the lactate-to-pyruvate ratio of the F4 group compared with TMT, F2, and F3 groups (p < 0.05). The TMT, F2, and F3 groups did not differ significantly. The extracellular pH (pHe) of the TMT group was statistically lower than the F2 and F4 groups (p < 0.05). The pHe did not differ significantly between the TMT and F3 groups nor the F2, F3, and F4 groups. The lactate-to-pyruvate ratio and pHe after combination treatment with esomeprazole and ICB did not differ compared to PBS+ICB control. Treatment with esomeprazole alone generated higher lactate-to-pyruvate ratio compared with PBS alone. Tumor volume curves and survival curves of mice bearing F4 tumors treated with esomeprazole combination with ICB showed no difference compared with PBS+ICB, PBS alone, and esomeprazole alone. DISCUSSION/SIGNIFICANCE: We differentiated between the 100% and 25% resistant models with both pHe and lactate-to-pyruvate ratio, although the pHe was counterintuitive. Esomeprazole was ineffective, but other potential sensitizers exist. A non-invasive clinical imaging tool and sensitizer would permit more personalized treatment plans so treatment is more effective.

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: The objectives of the ICPC Course were 1) to define elements needed to 'build' a solid framework for the creation of an effective informed consent document; 2) to examine various regulatory references and their importance in the context of the informed consent process; and 3) to review helpful tips and best practices of the informed consent process. METHODS/STUDY POPULATION: This 7-week course was a multi-disciplinary effort by the Miami CTSI, the Regulatory and Monitoring Support Office and the Human Subjects Research Office (HSRO), as part of their co-op partnership. The CTSI’s Network of Clinical Research Professionals (NCRP) (over 1995 members and established to offer and enhance education, training, and overall career development and networking for the U’s diverse research workforce) served as the target audience. The lead HSRO official was the course content developer and served as instructor. The Director of the HSRO served as the certificate & program coordinator. Additionally, this course indirectly fulfilled part of the requirements of the Institution’s AAHRPP re-accreditation. RESULTS/ANTICIPATED RESULTS: 70 persons attended all sessions and received their certificate. A post-course survey was deployed (n=70). 69 respondents were extremely satisfied with course content; 67 were likely to recommend the course to a colleague. Feedback highlights include: appreciation for time taken to organize/offer the course; presenter knowledge and preparation; and that case studies/examples were up-to-date and applicable. As an added incentive to participate in the course, both the School of Nursing and the Medical School provided CEU credits and the Society of Clinical Research Associates (SOCRA) accepted documentation of candidate participation in continuing education programs for recertification. DISCUSSION/SIGNIFICANCE: Based on a need identified through a multi-disciplinary process, a successful Informed Consent Professional Certificate Course was created and implemented. Respondents indicate extremely high satisfaction with the course and felt it was very relevant and applicable to their practice.

OBJECTIVES/GOALS: ICD-10 coding inconsistencies hinder timely recognition and treatment of metabolic syndrome (MetS), posing a significant risk for cardiometabolic disease progression. This study employed a digital phenotype for MetS and compared odds for medication and lifestyle intervention compared to those coded for MetS. METHODS/STUDY POPULATION: MetS is a cluster of cardiometabolic risk factors that increase risk for numerous adverse clinical outcomes. Patients with MetS were identified through electronic medical records on TriNetX LLC using the standard ICD-10 code or through a digital phenotype, involving grouping codes for the individual components. Percentage of patients with MetS not captured with the standard code was identified. In addition, disparities in blood pressure, glucose, lipid-lowering medication, and lifestyle intervention between the coding schemas were assessed, shedding light on healthcare inequities and informing targeted interventions. Odds ratios (RR) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: Patient demographics and lab values were similar between the standard code and digital phenotype cohorts. Of the 4.3 million individuals aged 50 to 80 identified as having MetS using the digital phenotype in the TriNetX research network, only 1.78% of participants shared the standard code. Individuals with the digital phenotype for MetS were at lower odds in receiving glucose lowering medication (OR: 2.11, 95% CI: 1.98–2.13, p <0.001) and exercise or nutrition-based intervention advice (OR: 1.76, 95% CI: 1.55–1.96, p <0.001) after controlling for demographics and lab values for each MetS component. DISCUSSION/SIGNIFICANCE: This project utilized TriNetX to create a digital phenotype for MetS, and suggests most patients are not coded for it using the standard ICD-10 system. This is troublesome given those with the standard code are less likely to receive certain interventions.

OBJECTIVES/GOALS: Our project aims to assess the composition or characteristics of research papers that score high on alternative metrics. These alternative metrics including the number of newspaper mentions, social media mentions, and the attention score as catalogued on Altmetric, a tool used to document community attention for a given research paper. METHODS/STUDY POPULATION: Our study intends to 1) Utilize topic modeling to identify prevalent themes on Altmetric, and 2) Apply network analysis to elucidate the interconnectedness among universities, funding sources, journals, and publishers associated with high-attention papers. 3) Examine how these patterns vary when attention metrics shift, such as social media mentions, newspaper mentions, or the Altmetric score. We'll first perform this analysis on all types of papers and then limit the networks to Biomedical and Clinical Sciences, and Public and Allied Health Sciences to help inform what health topics garner attention. RESULTS/ANTICIPATED RESULTS: Our initial Altmetric topic models revealed sustained attention for COVID-19 and vaccination-related publications well beyond the pandemic (specifically, papers from January 2023). Health topics like cancer, dementia, and obesity also garnered high attention. Additionally, political papers (elections, democracy), climate change, and battery research had notable attention values. Further analysis needs to be done to explain why these topics gain attention and the type of attention they garner. We will construct networks to see the relationship between attention and entities like universities, funding sources, journals, and publishers. This will identify whether certain clusters of these entities produce papers with high attention or if attention is distributed evenly amoung them. DISCUSSION/SIGNIFICANCE: To gauge the broader impact of scholarly research alternative metrics beyond citations are needed. Altmetric is used widely by CTSA’s to measure the community interest in research. Understanding the types of research that gain traction on Altmetric can help researchers understand how to garner interest from the community.

OBJECTIVES/GOALS: Early life pain/stress impacts infants’ neurodevelopmental outcomes. Mitochondrial dysfunction may interface between infants’ stress and neurodevelopment. The study aims to investigate the associations between pain/stress, proteins associated with mitochondrial dysfunction, and neurobehavioral responses in preterm infants. METHODS/STUDY POPULATION: A prospective cohort study was conducted with 33 preterm infants enrolled between September 2017 and July 2022 at two affiliated NICUs in Hartford and Farmington, CT. Daily pain/stress experienced during NICU was documented. At 36-38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale (NNNS) and buccal swabs for Mass spectrometry-based proteomics analysis. Lasso statistical methods were conducted to study the association between protein abundance and infants’ NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. RESULTS/ANTICIPATED RESULTS: During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions, including leptin receptor binding activity, glutathione disulfide oxidoreductase activity, and response to oxidative stress, lipid metabolism, phosphate, and proton transmembrane transporter activity, were negatively associated with neurobehavioral outcomes. In contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be positively associated with neurodevelopmental outcomes. In addition, mitochondrial dysfunction-related proteins (SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2, ABLIM1, UNC45A, Keratins, MUC1, and CYB5B) were found to be associated with neurobehavioral outcomes. DISCUSSION/SIGNIFICANCE: Mitochondrial dysfunction-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Buccal proteins could be used to predict potential neurobehavioral outcomes. In addition, individualized skin integrity protection should be provided to preterm infants during their NICU stay.

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: We aimed to conduct an updated genome-wide meta-analysis of keloids in expanded populations, including those most afflicted by keloids. Our overall objective was to improve understanding of keloid development though the identification and further characterization of keloid-associated genes with genetically predicted gene expression (GPGE). METHODS/STUDY POPULATION: We used publicly available summary statistics from several large-scale DNA biobanks, including the UK Biobank, FinnGen, and Biobank Japan. We also leveraged data from the Million Veterans Program and performed genome-wide association studies of keloids in BioVU and eMERGE. For each of these datasets, cases were determined from ICD-9/ICD-10 codes and phecodes. With these data we conducted fixed effects meta-analysis, both across ancestries and stratified by broad ancestry groups. This approach allowed us to consider cumulative evidence for genetic risk factors for keloids and explore potential ancestry-specific components of risk. We used FUMA for functional annotation of results and LDSC to estimate ancestry-specific heritability. We performed GPGE analysis using S-PrediXcan with GTEx v8 tissues. RESULTS/ANTICIPATED RESULTS: We detected 30 (23 novel) genomic risk loci in the cross-ancestry analysis. Major risk loci were broadly consistent between ancestries, with variable effects. Keloid heritability estimates from LDSC were 6%, 21%, and 34% for European, East Asian, and African ancestry, respectively. The top hit (P = 1.7e-77) in the cross-ancestry analysis was at a replicated variant (rs10863683) located downstream of LINC01705. GPGE analysis identified an association between decreased risk of keloids and increased expression of LINC01705 in fibroblasts (P = 3.6e10-20), which are important in wound healing. The top hit in the African-ancestry analysis (P = 5.5e-31) was a novel variant (rs34647667) in a conserved region downstream of ITGA11. ITGA11 encodes a collagen receptor and was previously associated with uterine fibroids. DISCUSSION/SIGNIFICANCE: This work significantly increases the yield of discoveries from keloid genetic association studies, describing both common and ancestry-specific effects. Stark differences in heritability support a potential adaptive origin for keloid disparities. Further work will continue to examine keloids in the broader context of other fibrotic diseases.

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: This study examined youth tobacco use, disaggregated by sexual and gender minority (SGM) identity and race, in Massachusetts before and after the state implemented a flavored tobacco restriction. We assessed if the policy differentially impacted groups that have had higher rates of flavored tobacco use (i.e., SGM and African Americans [AAs]). METHODS/STUDY POPULATION: Data for this analysis came from the 2019 and 2021 Massachusetts Youth Risk Behavior Survey (YRBS), a biennial, national survey conducted among high school students, provided by the Massachusetts Department of Elementary and Secondary Education. Changes in current use of cigarettes and e-cigarettes between 2019 and 2021 were examined for the entire sample and by SGM identity and race/ethnicity. Current cigarette use and current e-cigarette use were defined as reporting any use of the product in the past 30 days. We received confirmation from the IRB that because the data are de-identified and available to the public, this research is considered Not Human Subjects Research. RESULTS/ANTICIPATED RESULTS: Between 2019 and 2021, current cigarette use and current e-cigarette use decreased for the entire sample (3.78% to 2.79% and 27.69% to 15.74%, respectively). Decreases were also observed after disaggregating results, but smaller changes were observed among minoritized groups (i.e., SGM and AAs), particularly for e-cigarettes. Current e-cigarette use decreased 25.56% among individuals identifying as SGM (28.14% to 20.95%) compared to a 49.33% decrease among non-SGM individuals (27.63% to 14.0%). Among all races, AAs had the lowest prevalence of current e-cigarette use in 2019 (15.10%), but also saw the lowest percentage decrease (17.68%). Among whites, current e-cigarette use decreased 45.75% from 32.33% in 2019 to 17.54% in 2021. DISCUSSION/SIGNIFICANCE: After implementation of Massachusetts’ flavored tobacco restriction, current cigarette and e-cigarette use declined among Massachusetts youth overall and among groups that have been most affected by flavored tobacco. However, minoritized groups (i.e., SGMs, AAs) had lower percentage decreases compared to non-minoritized groups.

OBJECTIVES/GOALS: The objectives of this workshop were to: (1) provide learners with a space to become aware of and discuss the history of the LGBTQ+ community in medical and public health research; (2) apply frameworks for LGBTQ+ inclusivity in research, inspired by lived experience and multimedia; and (3) assess LGBTQ+ research inclusivity best practices. METHODS/STUDY POPULATION: The CTSC provided the LGBT Community Center of Greater Cleveland (Center) with access to academic resources via an affiliate account and insights on the clinical and translational science research process. Members of the CTSC Research Equity, Accessibility, Diversity, and Inclusion team met regularly with the education and programming team at the Center to review research findings for workshop segments, ideate and provide feedback on activities, and strategize to ensure a psychologically safe virtual environment for learners. Zoom registration was used for workshop registration. An evaluation survey, created by the LGBT Community Center of Greater Cleveland (Center), was deployed by the CTSC to learners after the workshop. Respondents reported that the LGBTQ+ terminology focus was most valuable. RESULTS/ANTICIPATED RESULTS: To maximize investment in and scale theLGBTQ+ Inclusivity For Researchers workshop, the LGBT Community Center of Greater Cleveland offered a shortened version to their Youth Participatory Action Research group and will continue to offer the workshop in their suite of program/educational offerings. The CTSC plans to offer opportunities to co-host the workshop at its hospital system partner institutions, with room to tailor content based on internal LGBT resources (e.g., gender care offered at the institution). We hope to see a remarkable increase in LGBTQ+ identifying researchers, LGBTQ+ participation in research studies and clinical trials, and LGBTQ+ research topics/ideas/questions in response to CTSC pilots, local, national, and global funding opportunities. DISCUSSION/SIGNIFICANCE: LGBTQ+ people are less likely to have a regular health care provider—impeding screening, diagnosis, and treatment. This is reflected in health research where clinical research participation may follow a diagnosis. By providing tools for LGBTQ+ research inclusion, we will catalyze more research with LGBTQ+ people—as researchers and participants.

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: The objectives of the Academy of Community Reviewers (ACR) serve to: (1) provide comprehensive education and training to community members about clinical research and the community review process for clinical research grants; and (2) collaborate with the community in the development of the training to ensure benefice and meaningful engagement. METHODS/STUDY POPULATION: This training targets community members who will serve as future grant reviewers for The Ohio State University Center for Clinical Translational Science (CCTS) pilot grant submissions, other grant submissions and as expert consultants on other projects needing community perspectives. In 2019 and 2020, this training was offered as a live session. Thirty-eight community reviewers were trained and have served as grant reviewers and consultants on over 70 projects. Based on feedback of former graduates, time demands, logistics, and technology advances warranted transitioning the course to an online learning platform. ACR graduates were consulted in course redesign and updates. Course revisions include material on DEIA, implicit bias and health equity in clinical research with narrated lectures. RESULTS/ANTICIPATED RESULTS: Each of the 7 modules (including a total of 15 submodules) will have a brief summary knowledge check. The module “How to incorporate diversity, equity, inclusion and accessibility in health research” will invite trainees to independently explore their own social identity and biases through a guided exercise. The last (7th) module will have interactive opportunities for submitting grant reviews and participation in an online grant review session, geared to The Ohio State University CCTS. ACR graduates have been invited to consult on educational material and pilot the new course. Demographic, knowledge assessments and module evaluations will be collected. An overall course evaluation and focus group interviews with graduates will also be analyzed for quality improvement and contributions in grant reviews. DISCUSSION/SIGNIFICANCE: The increased accessibility of the ACR course will foster more inclusive community engagement and support the development of clinical and translational research that is innovative, efficient, equitable, and relevant to its beneficiaries. This in depth community reviewer training has been designed to be used and customized to other CTSA Hubs.

OBJECTIVES/GOALS: Participating in out-of-school activities (i.e., sports) is associated with improved physical and mental health, but racial/ethnic and income disparities persist. Our goal was to describe parent perspectives to understand how to enhance family engagement in these activities, especially in low-income Black and Latinx communities. METHODS/STUDY POPULATION: We recruited parents through a large urban parks and recreation department located in Los Angeles County (LAC) and two community-based organizations who provide services primarily to low-income Black and Latinx residents in LAC. We conducted semi-structed English or Spanish interviews with parents of children ages 6-17 about the impact of activities on families, experiences making it difficult or easier for their child to be involved, and recommendations to meet their needs and facilitate family engagement. We coded the interviews using Dedoose and then performed thematic analysis. RESULTS/ANTICIPATED RESULTS: We completed 34 interviews (17 English, 17 Spanish). Parents shared these central ideas about out-of-school activities: (1) they support families and promote healthy child development; (2) they must create a safe environment and promote a sense of belonging for all families; and (3) service delivery changes reduced barriers, but activities often remained inaccessible. Barriers included lack of awareness about low-cost options, online enrollment, financial costs, waitlists, program timing, inaccessible parks/pools, safety, inconsistent quality, few opportunities for families to participate together, and a desire for more inclusive practices around race, culture, language, gender, children with special needs, and parent involvement. Parents offered recommendations to increase family engagement. DISCUSSION/SIGNIFICANCE: Involving parents in optimizing out-of-school activities may improve access, uptake, and quality of these health-promoting activities in low-income Black and Latinx communities.

OBJECTIVES/GOALS: Clinical indicators predictive of venous thromboembolism (VTE) in trauma patients at multiple time points are not well outlined, particularly at time of discharge. We aimed to describe and predict inpatient and post-discharge risk factors of VTE after trauma using a multi-variate regression model and best of class machine learning (ML) models. METHODS/STUDY POPULATION: In a prospective, case-cohort study, all trauma patients (pts) who arrived as level 1 or 2 trauma activations, from June 2018 to February 2020 were considered for study inclusion. A subset of pts who developed incident, first time, VTE and those who did not develop VTE within 90 days of discharge were identified. VTE were confirmed either by imaging or at autopsy during inpatient stay or post-discharge. Outcomes were defined as the development of symptomatic VTE (DVT and/or PE) within 90 days of discharge.A multi-variate Cox regression model and a best in class of a set of 5 different ML models (support-vector machine, random-forest, naives Bayes, logistic regression, neural network]) were used to predict VTE using models applied a) at 24 hours of injury date or b) on day of patient discharge. RESULTS/ANTICIPATED RESULTS: Among 393 trauma pts (ISS=12.0, hospital LOS=4.0 days, age=48 years, 71% male, 96% with blunt mechanism, mortality 2.8%), 36 developed inpatient VTE and 36 developed VTE after discharge. In a weighted, multivariate Cox model, any type of surgery by day 1, increased age per 10 years, and BMI per 5 points were predictors of overall symptomatic VTE (C-stat 0.738). Prophylactic IVC filter placement (4.40), increased patient age per 10 years, and BMI per 5 points were predictors of post-discharge symptomatic VTE (C-stat= 0.698). A neural network ML model predicted VTE by day 1 with accuracy and AUC of 0.82 and 0.76, with performance exceeding those of a Cox model. A naīve Bayesian ML model predicted VTE at discharge, with accuracy and AUC of 0.81 and 0.77 at time of discharge, with performance exceeding those of a Cox model. DISCUSSION/SIGNIFICANCE: The rate of inpatient and post-discharge VTEs remain high. Limitations: single institution study, limited number of patients, internal validation only, with the use of limited number of ML models. We developed and internally validated a ML based tool.Future work will focus on external validation and expansion of ML techniques.

OBJECTIVES/GOALS: Neonatal hypoglycemia is seen in 65% of maternally diabetic pregnancies, and can lead to severe neurological damage. Neonatal glycemia may also be an indicator of placental function in these pregnancies. The purpose of this study is to identify patterns of neonatal glycemia, and associated endothelial dysfunction, by maternal diabetes subtype. METHODS/STUDY POPULATION: Pregnancies with maternal Type 1 (T1DM), Type 2 (T2DM), and gestational diabetes mellitus (GDM) are being enrolled. Maternal hemoglobin A1c (HbA1c) and umbilical cord insulin/glucose are being collected from 20 pregnancies in each group, 10 of which also undergo placental/umbilical cord tissue collection. Following delivery, neonatal blood glucose levels are also collected every 3-4 hours (4+ measurements) to determine rate of glycemic change. Linear regression modeling will be used to determine associations with placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic subtype and between normoglycemic and hypoglycemic neonates. Endothelial gene expression will be compared using paired t-tests with Benjamini-Hochberg correction. RESULTS/ANTICIPATED RESULTS: Thus far, 5 T1DM, 10 T2DM, and 13 GDM samples have been collected. Gestational age at delivery and birth weight were similar between groups (38.1 ± 1.05 weeks; 3.6 ± 0.59 kilograms) and delivery method is evenly distributed (Cesarean section or vaginal delivery). Currently, with limited cohort size, no association is evident between maternal HbA1c and umbilical cord glucose/insulin (p=0.114) or neonatal hypoglycemia diagnosis (p=0.674) when controlled for gestational age and infant birthweight. We hypothesize that, with pending analyses, maternal HbA1c and umbilical cord insulin levels will correlate negatively with the rate of neonatal glycemic change, and positively with the level of inflammatory and angiogenic transcription identified in placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Characterization of postnatal glucose control is key to prognosis and risk stratification of infants of diabetic mothers. Understanding placental response to glucose, as well as sequela in the fetal endothelium, is also critical to understanding the pathogenesis of neonatal hypoglycemia and other adverse outcomes of diabetic pregnancy.