OBJECTIVES/GOALS: Diabetes is a group of chronic metabolic diseases and significant gaps remain in our understanding of disease etiology, treatment regimens, and diabetes-related complications. The objective of study is to demonstrate how informatics techniques can leverage real-world data for diabetes research and identify barriers for implementation. METHODS/STUDY POPULATION: We evaluated informatics applications of real-world data in diabetes research conducted by the Facelli Research Group. The types of real-world data were categorized into clinical records, diabetes-related repositories, wearable sensors, and other data sources. Translational informatics applications were characterized into thematic groups of 1.) use of electronic health records, registries, and claims and other data sources to generate real-world evidence, 2.) evolution of novel methods to accelerate generation and use of real-world data, and 3.) infrastructure to support the generation and use of real-world data in translational science. A literature review is being conducted to identify additional articles meeting these themes focused on diabetes research. RESULTS/ANTICIPATED RESULTS: 6 research projects were included for analysis. The diabetes-focus spanned type 1 diabetes, type 2 diabetes, and general diabetes mellitus. Informatics methods included machine learning and data mining while real-world data sources included electronic medical records, the Environmental Determinants of Diabetes in the Young (TEDDY) study, continuous glucose monitors, and the U.S. Environmental Protection Agency (EPA) air pollution monitors. Overall, computability of real-world data, linkage of medical concepts to standardized terminologies, volume of data, and adoption of novel artificial intelligence methods were major determinants of successful implementation. Future work will systematically evaluate informatics applications of real-world data in diabetes from the academic community at large. DISCUSSION/SIGNIFICANCE: Translational informatics approaches are poised to leverage real-world data and better understand diabetes etiology, treatment regimens, and diabetes-related complications. By understanding barriers and opportunities for informatics methods, we can expedite translational applications in diabetes research.

OBJECTIVES/GOALS: We aim to share information about the Trailblazer Award Pilot Grants, which support collaborative, community engaged research projects with potential to improve health equity in Indiana, and achievements of awardees in terms of publications and funded external grants. We also share plans to expand the impact of the pilot grant process. METHODS/STUDY POPULATION: Data on publications and funded grant applications resulting from Trailblazer Award-funded projects were obtained from progress reports completed by the projects’ principal investigators. Awardees submit annual progress reports throughout the project and five years following the close of the project. On these progress reports, awardees list the publications that they have submitted, and their publication status, and external grants submitted and funded. Because some progress reports were never submitted, and projects which began in 2021 or 2022 are not complete, and are therefore likely to have additional publications and grants result from their projects, our results likelyunderestimate the number of publications and grants resulting from these projects. RESULTS/ANTICIPATED RESULTS: Below are a number of charts which illustrate the outcomes of Trailblazer Award projects from years 2015 through 2022, including: the number of applications received as compared to the number of applications funded; the academic institutions of the academic partners on awarded projects throughout the state of Indiana; the general topic areas of all funded projects; and the number of publications and funded grants resulting from Trailblazer Award-funded projects, as reported by awardees. We have found that, in recent years, while the amount of publications by awardees have stayed roughly the same, the numbers of funded external grants resulting from Trailblazer-funded projects have decreased somewhat. [blob:https://acts.slayte.com/8404bbca-3054-4f57-9d36-cd8d6152841b] [blob:https://acts.slayte.com/6b43bd70-fe90-494a-be1a-c091a6ab924d][blob:https://acts.slayte.com/b0e2b7f6-1604-4379-94df-efccdc2e51c2][blob:https://acts.slayte.com/c1a591a7-2a0e-4f6d-ade1-027bb389ef68] DISCUSSION/SIGNIFICANCE: We will implement changes for Trailblazer projects, including hosting workshops on disseminating findings and applying for external funding, and helping awardees to form partnerships within their topic area. We believe providing these resources to awardees will increase publications and grant funding, thereby allowing their work to continue.#_msocom_1.

ABSTRACT IMPACT: Our goal is to identify bacterial biomarkers of adverse Clostridioides difficile infection outcomes OBJECTIVES/GOALS: We characterized microbiota features of Clostridioides difficile infections (CDIs) and will investigate the association between bacterial taxa and adverse outcomes, which includes severe and recurrent CDIs. METHODS/STUDY POPULATION: 1,517 stool samples were collected from patients diagnosed with a CDI at the University of Michigan along with 1,516 unformed and 910 formed stool control samples. We characterized the microbiota of the 3,943 stool samples by sequencing the V4 region of the 16S rRNA gene and used the Dirichlet Multinomial Mixtures method to cluster samples into community types. Severe CDI cases were defined using the Infectious Diseases Society of America criteria and recurrent CDIs were defined as CDIs that occurred within 2-12 weeks of the primary CDI. We will use machine learning to examine whether specific bacterial taxa can predict severe or recurrent CDIs. We will test 5 machine learning models with 80% training and 20% testing data split. RESULTS/ANTICIPATED RESULTS: Similar to findings from a previous study with 338 samples, we found there was no difference in diversity between CDI cases and unformed controls (Inverse Simpson index, p > 0.5) and samples from the 3 groups (CDIs, unformed controls, and formed controls) clustered into 12 community types. To investigate the bacterial taxa that are important for predicting adverse CDI outcomes, we will select the best machine learning model based on performance and training time and examine how much each feature contributes to performance. We anticipate the large number of CDI cases in our cohort and robust machine learning approaches will enable us to identify more bacteria associated with adverse outcomes compared to other studies that have attempted to predict CDI recurrence with fewer CDI cases. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adverse CDI outcomes are a significant source of the morbidities, mortalities, and healthcare costs associated with CDIs. Identifying bacterial biomarkers of severe and recurrent CDIs could enhance our ability to stratify patients into risk groups and may lead to the development of more targeted therapeutics.

OBJECTIVES/GOALS: Adolescents with congenital heart defects (CHD) have an elevated risk for future cardiovascular events, but information about their risk for e-cigarette use (“vaping”) is unknown. This study aims to present preliminary findings on gender differences in the association of impulsive behavior and vaping susceptibility from an ongoing investigation. METHODS/STUDY POPULATION: Adolescents with CHD (12-18 years; N=63) reported their vaping susceptibility and completed subjective (UPPS-P)/objective (Iowa Gambling Task; IGT) assessments of impulsive behavior previously associated with tobacco use. The UPPS-P includes 5 facets: 1) negative urgency (impulsivity under negative emotions), 2) positive urgency (impulsivity under positive emotions), 3) lack of premeditation (acting without thinking), 4) lack of perseverance (inability to focus), and 5) sensation seeking (seeking thrilling experiences). The IGT is a computerized task that creates conflict between immediate reward and delayed punishment via selections from advantageous/disadvantageous card decks. Linear regressions stratified by gender determined associations between vaping susceptibility and impulsivity. RESULTS/ANTICIPATED RESULTS: Nearly 30% (29.7%) of adolescents with CHD were susceptible to vaping. Negative urgency was associated with vaping susceptibility among females (β = 0.44, p = .035) but not males (β = 0.25, p = .128). Positive urgency was associated with vaping susceptibility among males (β = 0.37, p = .021) and trended toward significance among females (β = 0.40, p = .058). Lack of premeditation was associated with vaping susceptibility among males (β = 0.36, p = .025) but not females (β = 0.15, p = .490). The association between lack of perseverance and vaping susceptibility trended toward significance among males (β = 0.30, p = .064) but not females (β = -0.18, p = .413). IGT performance was not associated with susceptibility to vaping among either gender. UPPS-P facets and IGT performance were not significantly correlated. DISCUSSION/SIGNIFICANCE: The association of impulsivity and vaping susceptibility appears to be characterized by emotion-based rash action (positive/negative urgency) for females and by decreased conscientiousness (lack of premeditation/perseverance) for males. If replicated, the findings have implications for assessment of vaping risk and tailored intervention.

OBJECTIVES/GOALS: Developmental dyslexia is a common reading disability (RD) which negatively impacts academic success. To address the role of early language experience on RD, we tested if the reported differences in gray matter volume (GMV) in RD also manifests in poor readers with a bilingual language background. METHODS/STUDY POPULATION: We studied 54 Spanish-English Bilingual Typical Readers with Oral Reading Recognition Test (ORRT) scores above 100 (avg. =113 ± 10), 51 Spanish-English Bilinguals with RD with ORRT scores below 92 (avg. =84 ± 7), 54 English Monolingual Typical Readers with ORRT scores above 100 (avg. =113 ± 10) and 51 English Monolinguals with RD with ORRT scores below 92 (avg. =84 ± 7) from the Adolescent Brain & Cognitive Development Study. All groups had an average age of 12 ± 0.7 years and were matched for sex and self-ratings of English ability. Structural magnetic resonance images were analyzed using Voxel-Based Morphometry and the bilingual and monolingual groups were separately compared in two-sample t-tests (p < 0.05). RESULTS/ANTICIPATED RESULTS: Monolinguals with RD had less GMV than the Monolingual Typical Readers in the right supramarginal gyrus (Brodmanns Area (BA) 40; MNI Coordinates: 69, -27, 39) (p=0.011) similar to the right superior temporal finding reported in the existing literature. However, a comparison of Bilinguals with RD and Bilingual Typical Readers did not show any GMV differences in superior temporal regions. Instead, our Bilinguals with RD had less GMV compared to the Spanish-English Bilingual Typical Readers in the right superior frontal gyrus (BA 11; MNI Coordinates: 21, 44, -24) extending to the middle frontal gyrus (BA 10) (p = 0.014). DISCUSSION/SIGNIFICANCE: Our findings suggest that the neuroanatomical bases of RD in Spanish-English Bilingual children are not the same as those observed for monolinguals, and biological models developed in monolinguals cannot be generalized. This has implications for diagnoses and treatment of RD in bilinguals.

OBJECTIVES/SPECIFIC AIMS: We aimed to assess trends in incidence of genital warts across human papillomavirus (HPV) vaccine-eligible and nonvaccine-eligible age groups to determine the impact of the HPV vaccine among Medicaid enrollees in the state of Tennessee. METHODS/STUDY POPULATION: We analyzed 2006–2014 medical and pharmaceutical claims data from TennCare (Tennessee’s Medicaid program) enrollees aged 15–64 years. Incident cases of genital warts were defined as persons 12 months disease free and: (1) a diagnosis of condyloma acuminatum, or (2) a diagnosis of viral warts and genital-specific procedure, or (3) a prescription for genital warts medication and genital-specific procedure. Mann-Kendall trend tests were performed to assess for significant trends in incidence of genital warts by sex and age group; average annual percent changes were calculated to quantify these trends. RESULTS/ANTICIPATED RESULTS: Our analysis is in progress. We hypothesize that we will observe declines in genital warts among younger, vaccine-eligible age groups and no changes in older, nonvaccine-eligible age groups, with largest declines among females aged 15–19 years from 2006 to 2014. We also expect to see declines among younger males due to herd protection, with greater declines after 2011, when the vaccine was approved for males. DISCUSSION/SIGNIFICANCE OF IMPACT: Significant declines among younger compared with older age groups would suggest HPV vaccine effectiveness for preventing genital warts.

OBJECTIVES/SPECIFIC AIMS: Background: Annually, 2.5 million traumatic brain injuries (TBI) occur with nearly 75% classified as mild TBI (mTBI), also known as a concussion. Mild TBI can be subtle and detection requires a high index of suspicion and a regimented evaluation process. This study was done to define the proportion of patients with a possible mTBI evaluated for concussion at a high volume urban trauma center. METHODS/STUDY POPULATION: Methods: A prospective cohort of patients was identified using a 3-question screen at the time of triage: did an injury occur; was the mechanism consistent with mTBI; was there a period of altered mental status. Patients who screened positive were thought to meet a minimum threshold for the evaluation of mTBI. Information about mTBI specific evaluation, management, and education was obtained from the patient’s charts. RESULTS/ANTICIPATED RESULTS: Results: 38,484 patients were screened over 16 weeks, of whom 453 (1.18%) screened positive for a possible mTBI and did not meet exclusion criteria. In total, 198 patients had documented loss of consciousness, 101 were diagnosed with mTBI, and 49 received mTBI discharge instructions. Overall, 32.5% of included patients had mTBI listed in the differential or as a diagnosis and 32.3% with loss of consciousness received a mTBI diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Many patients with a possible mTBI were not evaluated, managed, or educated for their potential injury. Changes in physicians’ approach to mTBI must occur to increase the proportion of patients receiving appropriate evaluation, management, and education. These results define the current reality of mTBI treatment in the Emergency Department and show the need for further experimental studies targeted at physician decision support interventions to improve mTBI care.

OBJECTIVES/GOALS: To assess researchers’ experiences working with community advisory boards (CABs) and how community member/patient stakeholder feedback impacted the research. METHODS/STUDY POPULATION: Researchers (N = 34) who presented their research to a Mayo Clinic CAB (at MN, AZ, or FL) from 2014-2017 were invited to participate in an interview in-person or by phone averaging 10-15 min. Researchers were asked “In what ways did the feedback you received from the CAB influence your research?” The validated structured 7-item interview included domains assessing potential influence that CABs had on the research: 1) Pre-research (e.g., generated ideas), 2) Infrastructure (e.g., budget preparation), 3) Research design, 4) Implementation (e.g., research recruitment), 5) Analysis, 6) Dissemination, and 7) Post-research (e.g., assist in formulating next steps). RESULTS/ANTICIPATED RESULTS: 17 interviews were completed (8 no longer at Mayo, 9 no response). Researchers presented their study to a CAB a mean of 4 years (range 3-5) before the interview. Researchers reported that the CAB had influenced their research in the following domains: 24% in pre-research, 24% infrastructure, 41% study design, 41% implementation, 6% analysis, 24% dissemination, and 18% for post-research activities. The mean total score was = 1.8 (SD = 1.7, range 0-6), of a possible range of 0-7. DISCUSSION/SIGNIFICANCE OF IMPACT: Impact of CAB feedback on the research was moderate. Ways to enhance impact could include follow-up with researchers and CAB members.

OBJECTIVES/GOALS: Fecal incontinence is associated with increased caregiver strain, reduced patient dignity and diminished quality of life. A spectrum of incontinence exists, along with a paucity of available solutions for patients and their caregivers. This research aims to stratify this space and identify gaps within the existing solution landscape. METHODS/STUDY POPULATION: To understand this problem, a literature review was performed with key search terms specific to fecal incontinence. These included, anal incontinence epidemiology, fecal incontinence in nursing homes, and incontinence management. To determine gaps within the existing solution landscape, key search terms related to existing solutions for fecal incontinence were also included. These included, fecal management systems, rectal incontinence therapies, and anorectal incontinence procedures.' To perform a population segmentation, white papers, review articles, and cross-sectional studies were reviewed to break down the burden of incontinence in older adults living in nursing facilities and in the community. RESULTS/ANTICIPATED RESULTS: Two unaddressed populations were identified, the first being independent adults over the age of forty, particularly women, who suffer from frequent, bothersome incontinence. These 1.2 million patients are active, living at home, and they restrict their daily activities due to incontinence. However, there are several durable and effective solutions for patients who have sufficient sphincter tone or who are surgical candidates. The second population identified are caregiver dependent older adults residing in nursing facilities who suffer from severe incontinence. This population of 160,000 is affected more severely by consequences of fecal and are poorly served by solutions that are largely absorptive such as diapers and pads. DISCUSSION/SIGNIFICANCE: Although two populations were identified, caregiver dependent older adults residing in nursing homes were identified to have a significant unmet need within incontinence care. Current solutions are onerous and transient, preventing ease and duration for use by caregivers and nurses.

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

OBJECTIVES/SPECIFIC AIMS: To explore rural African American parents’ and their community advisors’ perspectives on the Safety Baby Shower’s acceptability, feasibility, and adaptability. METHODS/STUDY POPULATION: Collaborating with a local community organization, we explored community advisors’ and expectant women’s SBS experiences to understand intervention delivery and adoption in a rural underserved community (RUC). The Consolidated Framework for Implementation Research guided our data collection and analysis using focus groups and key informant interviews. We used directed content analysis to generate themes and sub codes. RESULTS/ANTICIPATED RESULTS: Five focus groups (21 participants) and one key informant interview were conducted. Identified barriers that hinder feasibility and acceptability included resources, time/ flexibility, intervention location, cultural norms and beliefs, and the lack of a birthing hospital in the county. “Baby proofing”, “reinforcement products” and “teaching sleep safety on the same day as infant clinical appointment” are expectant mothers’ exemplars for what comes to their minds when asked to think about safety baby showers. To improve feasibility, both community advisors and expectant mothers suggested adaptations ranging from decentralizing or rotating intervention location, using different delivery sites such as churches, scheduling intervention outside business hours, to incorporating intervention into school health fairs and barbeque events. Social media emerged as a facilitator, and integrating safe sleep education into personal baby showers emerged as an implementation strategy. DISCUSSION/SIGNIFICANCE OF IMPACT: The community advisors and expectant mothers identified a wide spectrum of potential adaptations that have potential to improve safe sleep knowledge and practices. In the next study phase, identified themes will inform intervention adaptation and suggested implementation strategies will support uptake of the adapted SBS. Identifying transformative implementation strategies and conducting a community-informed SBS adaptation using a collective decision-making process between intervention experts and local community partners will support improved safety baby shower delivery, adoption and sustainability in RUCs.

OBJECTIVES/GOALS: An ex-vivo tissue model has been developed to predict target concentrations of tenofovir diphosphate (TFVdp; active metabolite of tenofovir) but has not been utilized to see how vaginal dysbiosis affects TFVdp/dATP exposure in female genital tract (FGT). My central hypothesis is that presence of specific anaerobic bacteria will increase dATP in FGT. METHODS/STUDY POPULATION: De-identified HIV-negative cervical tissues from women undergoing gynecological surgeries will be procured and a punch biopsy will be used to create explants. TFVdp/dATP concentrations were both tested in both aerobic and anaerobic conditions after a 24-hour incubation in tenofovir (TFV) to determine any changes between conditions. TFVdp/dATP in cervical tissue was be measured using LC-MS. Next, media and explants were collected at baseline to characterize donor microbiome for 6 donors. 16S microbiome sequencing was performed on extracted DNA to obtain the relative abundances of each bacteria species present. To test changes in dATP/TFVdp due to the microbiome, explants will be incubated in TFV for 24 hours with Prevotella and Dialister to specifically see how microbiomes dominated by these taxa affect dATP. RESULTS/ANTICIPATED RESULTS: There was no significant difference in TFVdp formation between aerobic and anaerobic conditions after a 24-hour tenofovir incubation (p = 0.2) for 8 donors. dATP was not quantifiable at 24 hours in explants, so explants are being collected before 24hrs during a TFV incubation to determine how quickly dATP depletes after collection. We were able to characterize the donor microbiome in media and tissue at baseline and 24hrs which had inter variability. We did not see any presence of Prevotella or Dialister in any donors. We are working on characterizing bacteria growth over time to see how the donor microbiome would change during a 24 hour experiment in anaerobic conditions. Finally, we anticipate seeing increases in dATP with a Prevotella or Dialister supplemented donor microbiome compared to baseline donor microbiome. DISCUSSION/SIGNIFICANCE: The addition of vaginal dysbiosis to tissue model will increase accuracy of prediction of 100% protective TFVdp concentrations and is likely to provide a translational model that can be used to improve TFV-based PrEP in women and streamline development of future PrEP candidates, bringing more prevention options to women and ending the HIV epidemic.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to evaluate the extent of publication bias in anesthesia and to evaluate the characteristics of studies that are registered and unpublished. METHODS/STUDY POPULATION: We used the advanced search option and the key word “anesthesia” to identify anesthesia related studies in the ClinicalTrials.gov registry. For the purpose of this analysis we have randomly selected 50% of the anesthesia related studies from the year 2008–2013. We have collected information pertaining to drug/device study, origin, type, design, subspecialty, enrollment target, anesthesia type, and adult/ pediatric, sponsored/ investigator initiated, population studied and start and end date. Studies with an ongoing, terminated, or unknown status were excluded from the analysis. For results, we initially searched the results section associated with each study; also we searched for any publication link at the study result area of the registry. For studies with no results and publication links we searched on PubMed, Google Scholar, and Embase by trial registration number, study title, and investigators name for matching manuscripts. In addition, we also analyzed the proportion of studies with positive and negative conclusions. We used descriptive and univariate statistics to report the results. RESULTS/ANTICIPATED RESULTS: Overall, 5448 studies were identified within the queried timeframe. We have included 2649 studies in our final analysis and detailed analysis were performed for 1778 studies with the status “completed.” The mean, standard deviation of subjects enrolled in completed trials was 392.47±6378. Only 162 (9.9%) studies registered were in the pediatric population, and 1616 (90.9%) were in the adult population. Finally, of the reviewed studies, 1486 (83.6%) were investigator-initiated, 207 (11.6%) were sponsored, and 85 (4.8%) were registered as collaborated studies. Among the completed studies only 296 (16.6%) studies posted results to the result section of the registry. Additionally, a link associated with a publication was posted in only 393 (22.1%) of the studies. The proportion of studies with posted results were 208 (14%), 61 (29%) and 27 (31.8%) in investigator-initiated, sponsored, and collaborated studies p<0.001 respectively. In the 1778 studies we reviewed, 954 (53.7%) studies were associated with one publication. In the published studies, 721 (75.6%) studies reported a positive conclusion for their publication. DISCUSSION/SIGNIFICANCE OF IMPACT: Only, 53.7% of anesthesia related studies with a “complete” status in ClinicalTrials.gov were published. Furthermore, investigators fail to fulfill the requirement of making the results available in the results section of the registry. Lack of availability of published literature and the nonavailability of the results from these studies contributes to publication bias and also failure to honor the ethical responsibility of the investigator to share the results of the study with subjects and with the medical community around the world.

OBJECTIVES/GOALS: Achieving therapy for hepatocellular carcinoma (HCC) involves navigating through a complex cascade of care. Non-HCC cancer mortality has been associated with social determinants of health outside of cancer specific risk. Our objective is to explore the impact of social determinants on HCC outcomes. METHODS/STUDY POPULATION: Patients with HCC were enrolled from 3 hospitals form June, 1 2019 to December 1, 2019. A chart review was done to collect information on liver disease severity and cancer stage. Patients were interviewed to collect information on the following: 1) socioeconomic status (income, education, insurance status, and employment status), 2) literacy (Rapid Estimate of Adult Literacy in Medicine (REALM-R) and Brief Health Literacy Screening Tool (BREIF)), 3) social support (Patent Reported Outcome Measurement Information System (PROMIS) instrumental and information support tool), 4) quality of life (PROMIS global and mental health tool), 5) substance abuse, and 6) linkage to care. RESULTS/ANTICIPATED RESULTS: Data compiled on the social determinants of health revealed (n = 35): 1) 60.0% of patients had incomes below $30,000 per year, 60.0% of patients had not gone past high school for education, and 8.6% had full time employment, 2) the average BREIF score was 10.3 (range 3-15)(4-12 indicate limited literacy). The average REALM-R score was 5.5 (range 0-8) (<6 indicate at risk for poor literacy), 3) patients had strong instrumental (T score 61.4±7.1) and information social support (T score 64.6±4.7) (mean T scores calibrated to a general population mean of 50), 4) patients had poor mental (T score 43.7 ±6.5) and physical quality of life (T score 46.6 ±9.9), 5) 25.7% of patients reported alcohol use in the past 90 days 6) 80.0% of patients reported that their doctor had spoken to them about liver transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: This patient population was well linked to care with good social support. However their literacy, socioeconomic status, mental and global health was poor and substance use history complex. Continued follow up of this cohort is planned to determine how these factors might impact their ability to navigate through the care cascade as well as survival.

ABSTRACT IMPACT: Identification of microRNA (miRNA) associated with neuropathic pain after spinal cord injury (SCI) will elucidate underlying epigenetic mechanisms contributing to its development and identify targets for intervention to optimize treatment strategies and outcomes. OBJECTIVES/GOALS: Approximately 70% of individuals with SCI experience neuropathic pain, which is refractory to pharmacologic intervention, and can reduce overall health and wellbeing. This study aims to identify predictive miRNA biomarkers of neuropathic pain after SCI to identify targets for the development of efficacious interventions. METHODS/STUDY POPULATION: Blood samples and clinical outcome measures were collected from adult participants with SCI with neuropathic pain (n = 28) and without neuropathic pain (n = 15). The sample population consisted of a mean age of 39 (SD = 12.12), 8 female (20%), with 13 classified as acute SCI (within 3 months post injury) and 30 as chronic SCI (> 3 years post injury). Pain presence, type, and intensity were assessed with the International Spinal Cord Injury Basic Pain Dataset (ISCIBPDS). Serum miRNA sequencing counts were produced from blood samples. Fold change and independent t-tests assessed differential expression between those with and without neuropathic pain, and those with chronic or acute SCI. Linear regression was performed to explore the relationship between miRNA expression and ISCIBPDS pain intensity ratings. RESULTS/ANTICIPATED RESULTS: In individuals with SCI, significant downregulation of expression of miR-338-5p was present in those with neuropathic pain compared to those without neuropathic pain (fold change = 0.81, p = 0.04). A significant relationship between expression of miR-338-5p and highest reported neuropathic pain intensity on the ISCIBPDS was identified (R2 = 0.15, F = 7.32, p < 0.01). Covariates of sex, age, and years post injury were not found to significantly influence the relationship between miRNA expression and ISCIBPDS intensity ratings. No significant differences in miR-338-5p expression were identified between participants with acute and chronic SCI, or with nociceptive pain ratings, demonstrating specificity of the relationship between miR-338-5p differential expression with pain of a neuropathic nature. DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings, along with validated targets of miR-338-5p in the NF-KB neuroinflammatory signaling pathway, suggest that miR-338-5p may serve a neuroprotective role in modulating neuroinflammation, and that its downregulation may result in maladaptive neuroplastic mechanisms contributing to the development of neuropathic pain after SCI.

OBJECTIVES/GOALS: Pain Catastrophizing is a negative coping mechanism involving rumination, magnification, and helplessness and is associated with worse chronic pain. The neurobiological mechanisms underlying this relationship are poorly understood. We aim to examine the intrinsic activity of a functional pathway in patients with chronic orofacial pain. METHODS/STUDY POPULATION: This is the second phase of a parent study examining genetics, placebos, and the brain in temporomandibular disorders (TMD). We intend to recruit 120 of the original 398 TMD patients for this phase. Participants completed the Graded Chronic Pain Scale to assess TMD pain intensity and disability and the Pain Catastrophizing Scale. Behaviorally, pain catastrophizing scores and pain intensity and disability will be analyzed using structural equation modeling. Resting-state functional magnetic resonance imaging will be used to record intrinsic brain activity. The functional connectivity between the posterior cingulate, anterior insula, and periaqueductal grey will be assessed as a causal pathway relating pain catastrophizing to pain intensity and disability. Mediation analyses will be used to test causality. RESULTS/ANTICIPATED RESULTS: We anticipate that greater engagement in catastrophic thinking about pain increases the functional connectivity strength between the posterior cingulate, anterior insula, and periaqueductal grey, which ultimately leads to heightened perception of pain intensity and disability. Therefore, we expect to see increased functional connectivity in those with high pain catastrophizing levels as compared to those with low pain catastrophizing levels, and that this pathway will mediate the relationship between pain catastrophizing and pain intensity and disability. Further, we predict that helplessness will most strongly correlate with the change in functional connectivity as compared to rumination and magnification. Results will be presented in full at the conference. DISCUSSION/SIGNIFICANCE: Understanding how pain catastrophizing can influence chronic pain pathways will not only promote a more integrative approach to chronic pain management but will also help identify the mechanisms by which pain itself develops and persists in the particularly vulnerable pain population of TMD.

The COVID-19 pandemic has exacerbated health disparities and rendered them acutely more visible. Special and underrepresented populations need to be fully integrated into the translational research process from the very beginning and all the way through. This article presents findings and rapid analysis mini-case studies from the Environmental Scan (E-Scan) of adaptive capacity and preparedness of Clinical and Translational Science Award hubs, specific to the goal of integrating special and vulnerable populations in different institutional research settings. In our discussion of the findings and case studies, we flexibly apply local adaptive capacity framework concepts and characteristics, and, whenever possible, we present ideas on how to enhance capacity in those areas, based on the challenges and practices identified through the E-Scan. Although the past year has recorded incredible achievements in vaccine development, clinical trials, diagnostics, and overall biomedical research, these successes continue to be hampered by our inability to turn them into achievements equally available and accessible to all populations.

The clinical research units (CRUs) are one of the main spaces where both translational research and science take place. However, there is a lack of information about both best practices for CRU operations and, ultimately, benchmarks to evaluate CRU performance. The Research Unit Network (RUN) was created with the purpose to enable direct communication and collaboration among CRUs. An online survey was administered to further illustrate the functionality and impact of RUN. Thirty-one individual survey responses (39.2%) were included in the final analysis. The members value RUN monthly meetings (87.1%) as the most useful aspect of this network and CRU budgeting (67.7%) and staffing (61.3%) were the most relevant topics discussed. This is followed by EPIC – Research (58.1%), delegation of authority logs, unit signatures, and policies (51.6%), COVID-19 pandemic response (41.9%), the implementation of clinical trial management system (29.0%), and protocol deviations (19.4%). The intermediate goal of RUN is to identify best practices CRUs are establishing, implementing, and sharing these experiences with the goal to adopt them in different CRUs. The network’s long-term goal is to establish standard benchmarks that can be used for evaluating the performance of CRUs across the nation.

Traditional training and funding mechanisms in academic health centers often do not support its faculty, staff, and trainees in evaluating and implementing innovative ideas, necessitating supplemental innovation programming. The University of Michigan (U-M) Frankel Cardiovascular Center partnered with U-M Fast Forward Medical Innovation (FMMI), a biomedical innovation and commercialization unit funded in part by the Clinical and Translational Science Award awarded to the Michigan Institute for Clinical & Health Research, to provide training and resources to advance ideas toward impacting patients. The program recruited faculty, trainees, staff, patients, and family members from multidisciplinary backgrounds. Engaging patients and family members expanded the ideas generated and furthered clinical relevance. Over two years, 11 project teams completed an 11-week, 16-session course on innovation and entrepreneurship concepts that incorporated workshops to progress ideas and develop a pitch for development funding. An increase in knowledge was reported in key innovation topics, such as customer discovery, assessing markets, and intellectual property. Participants reported an increase in project preparation, including obtaining stakeholder support, preparation of a development plan, readiness to apply for funding, and filing invention disclosures. This program can serve as a model for implementing training and funding mechanisms to advance innovative ideas.