Objectives/Goals: Approximately 250,000 anterior cruciate ligament (ACL) tears occur annually in the USA. Symptoms generally improve after ACL reconstruction (ACLR), but 20% of athletes do not return to sport. It is not clear how biomechanical function and mental health impact return to activity, so the purpose of this study is to evaluate their effect on return to activity following ACLR. Methods/Study Population: Patients age 18 years and older who have undergone primary ACLR at a single institution who are one year out from their initial procedure will be recruited by email. Patients will be excluded if they had a concomitant or subsequent ligamentous knee injury in the follow-up period since their index procedure. Additionally, patients will be excluded if they do not have access to a mobile phone with video recording capability. The primary outcome will be joint angle kinematics and postural balance metrics derived from patient recorded mobile-phone videos while performing several provocative exercises (sit-to-stand, Star Excursion Balance test). Patients will also be given surveys assessing knee symptoms, psychological readiness for return to sport, mental health, athletic history, and current return to sport level. Results/Anticipated Results: We predict that psychological readiness for return to sport following ACL injury and biomechanical postural stability will each be independently associated with return to sport timing following ACLR. Additionally, we anticipate that psychological readiness, as measured by higher ACL-Return to Sport Index scores, will be more strongly associated with return to sport compared to biomechanical movement quality (better gross postural control on skeletal modeling). In other words, higher psychological readiness for return to sport will have a stronger independent association with return to sport level compared to biomechanical movement quality measures. Discussion/Significance of Impact: This study also aims to define return to sport in terms of biomechanics and psychological readiness in an athletically heterogenous population. Additionally, we will test the feasibility of patient-led, remote, mobile, marker less motion capture for assessment of biomechanical function and distribution of patient-reported outcome measures.

ABSTRACT IMPACT: This study will be the first to explore the relationship between preeclampsia and breast cancer risk using the largest cohort of Black women in the US, and it will guide future research and potentially inform clinical practice to reduce breast cancer disparities in this population. OBJECTIVES/GOALS: Black women are disproportionately impacted by preeclampsia. This disorder induces hormonal changes that may contribute to diseases such as breast cancer. However, there is a lack of clear data on the relationship between preeclampsia and breast cancer, and few previous studies included Black women. This study will work to fill this knowledge gap. METHODS/STUDY POPULATION: We prospectively assessed the association between preeclampsia during pregnancy and risk of breast cancer in 43,040 parous women in the Black Women’s Health Study, a nationwide cohort of Black women who were ages 21 -69 at enrollment in 1995. Through 2017, we confirmed 1,968 incident diagnoses of invasive breast cancer. Approximately 6% of parous women reported a diagnosis of preeclampsia; characteristics of the population at baseline are shown in Table 1. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of breast cancer overall. We used age as the time scale and adjusted for breast cancer risk factors including parity, age at first birth, age at menarche, and body mass index (BMI) at age 18. RESULTS/ANTICIPATED RESULTS: : Compared to parous women without a history of preeclampsia, women with a history of preeclampsia in any pregnancy were not at an increased risk of breast cancer overall (HR 0.98; 95% CI 0.81, 1.18). These preliminary results suggest that history of preeclampsia is not an important risk factor for breast cancer overall in Black women. Our analyses are ongoing to evaluate whether the association may vary by estrogen receptor status or within subgroups of the population defined by age, menopausal status, BMI, and time since last pregnancy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will provide unprecedented knowledge on the association between hypertensive diseases during pregnancy and incidence of breast cancer in the largest cohort of Black women in the U.S.

ABSTRACT IMPACT: Identifying differential COVID-19 progression across the disease continuum may help policymakers and service providers better identify or predict gaps in services and resources and develop precision strategies to support COVID-19 patients where the need is mostly needed. OBJECTIVES/GOALS: Single institution studies have documented COVID-19 disproportionally affected US racial and ethnic minority groups compared to Whites. However, few population-wide data studied severity and death in multiracial populations. We aim to examine the current disparity in the COVID-19 continuum, including hospitalizations, severity, and death. METHODS/STUDY POPULATION: Data on 67,094 laboratory documented COVID-19 cases nested from the state-wide ‘OneFlorida’ research consortium through August 3, 2020, were assessed to decide differences and disparities in COVID-19 outcomes. A COVID-19 outcome continuum outlining the proportions of cases transitioning from diagnosis to death was constructed (Figure 1). OneFlorida partners provide health care to more than 40% of Floridians in the nation’s third-largest and very diverse state. OneFlorida partners encompass hospitals, practice/clinic settings, and physicians, which provide care for 15 million patients across all of Florida’s 67 counties. It is part of the Patient-Centered Outcomes Research Institute (PCORI). RESULTS/ANTICIPATED RESULTS: Among cases, 25,443 (37.9%) were non-Hispanic Whites, 11,709 (17.5%) were non-Hispanic Blacks, and 16,119 (24.0%) were Hispanics. Among COVID-19 patients, Blacks and Hispanics had a higher frequency of emergency department (ED) visits (45.7% and 46.0%, respectively), whereas admission rates were higher in Blacks (15.6%) and Whites (15.9%) than in Hispanics (11.5%). Blacks had the highest rates of intubation (3.6%) and in-hospital deaths (2.7%) compared to Whites (2.5% and 2.3%, respectively) and Hispanics (1.3% and 1.4%, respectively), Figure 1. When rates were indexed to the state census data, Blacks had the worst rates across the disease continuum (infection to death). In comparison, Hispanics had higher rates of ED visits but lower rates of intubation and death, Table 1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Outcomes continuum is a useful tool at an individual-level to assess care outcomes and at population-level as a framework to analyze the proportion of population with COVID-19 that progress to each successive disease stage. This will help policymakers to better identify gaps in services and develop precision strategies to support COVID-19 patients.

OBJECTIVES/GOALS: The goals of the proposed project are to 1) identify the critical components of trust required by Black Women to build a visible expression of trust within their reproductive health space, and 2) incorporate the elements of trust identified into a mindfulness-based communication tool, for reproductive health care providers. METHODS/STUDY POPULATION: We will be applying a mixed-methods approach inclusive of questionnaires and focus groups. Aim 1: Our study population consists of persons who identify as 18+ Black Women in Alachua County, Florida.Aim 2: Our Population within the reproductive health space (e.g., ob-gyn, midwives, nurse practitioners, etc…) at the University of Florida Shands Hospital. RESULTS/ANTICIPATED RESULTS: We anticipate that our results will fully engage with our Black Women in dialogues about key components of trust they want to experience and have within their reproductive space. This will inform the development of the mindfulness-based tool which will be incorporated with continuous insights with our Black Women. The proposed research project will contribute to the call for health equity. We aim to address this barrier by recognizing the agency of Black women to conceptualize trust on their terms, which we then would incorporate into applied trainings of reproductive health providers to establish trust. Health equity will take a considerable amount of social change at many levels and this study aims to better understand the process. DISCUSSION/SIGNIFICANCE: Structural racism and health disparities are linked with the disproportionate loss of Black women and associated negative birth outcomes. Our work will provide needed insights regarding mistrust in patient-provider relationships. Inform the development of a feasible tool challenging implicit bias in health provider spaces.

OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.

OBJECTIVES/SPECIFIC AIMS: The prevalence of BPH, coupled with associated disability ranging from quality of life impairments to hospitalization, has spurred decades of research into its pathophysiology, diagnosis, treatment, and outcomes. For these reasons, we conducted a study to characterize the current landscape of BPH literature, including the most commonly cited articles impacting the field. METHODS/STUDY POPULATION: We used the Web of ScienceTM databases to conduct a bibliometric analysis of the top 100 leading BPH articles. Bibliometric analyses are quantitative approaches examining the impact of academic literature. We used the following search terms: ‘benign prostatic hyperplasia’ and ‘benign prostatic enlargement.’ We identified and characterized the 100 most-cited BPH articles including their citations, journal, author, year, and country through September 2018. RESULTS/ANTICIPATED RESULTS: The top 100 BPH articles were published between 1978 and 2012. The number of citations ranged from 143 to 2,158 across 26 different journals, including 9 urology-specific journals. The Journal of Urology (5-year impact factor: 4.91) was the most published journal with 26 articles, followed by European Urology (5-year impact factor: 15.66) with 16, and Urology (5-year impact factor: 2.39) with 13. The oldest 10 articles in the top 100 mainly focused on BPH etiology/pathogenesis, while the newest 10 articles mainly focused on medical treatment. The 1990’s was the most productive decade accounting for nearly half of the top 100 articles (n=46). Eight authors had two or more first author publications, and 8 institutions had five or more publications in the top 100. Thirteen different countries were represented in the top 100 articles, with the US (n = 64), Italy (n=7), and Germany (n=5) being the most common. The articles were published in the following Web of Science Categories: Urology & Nephrology (n=68), Medicine, General & Internal (n=15), and Endocrinology & Metabolism (n=7). DISCUSSION/SIGNIFICANCE OF IMPACT: This study represents the first bibliometric analysis of the leading 100 BPH articles impacting the academic literature. The literature focus has evolved from BPH pathogenesis/etiology to treatment, and was primarily published in 3 specialty journals. Our findings highlight the most impactful BPH literature, and may be used to guide research and funding priorities for this increasingly common condition.

OBJECTIVES/SPECIFIC AIMS: This study aims to identify genetic biomarkers of GDM and facilitate the understanding of its molecular underpinnings. METHODS/STUDY POPULATION: We identified a cohort of mothers diagnosed with GDM in our longitudinal birth study by mining Electronic Health Records of participants utilizing PheCode map with ICD-9 and ICD-10 codes. We verified each case using ACOG’s GDM diagnosis criteria. RESULTS/ANTICIPATED RESULTS: Whole genome sequencing (WGS) data were available for 111 confirmed cases (out of 205) and 706 controls (out of 1,429) from different ancestries (412 EUR, 256 AMR, 56 EAS, 26 SAS and 18 AFR; 49 OTHER). SAS had the highest incidence of GDM at 38.46% and EUR had the lowest at 6.55%. We performed logistic regression using computed ancestry, age and BMI as covariates to determine if any variants are associated with GDM. The top variant (rs139014401) was found in an intron of DFFB gene, which is p53-bound and regulates DNA fragmentation during apoptosis. We will investigate the robustness of 49 identified variants and will separate the cohort by ancestry to detect population-specific differences in the top loci. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of molecular biomarkers in GDM across different ancestral backgrounds will address a gap in current GDM research. Findings may enhance screening and enable clinicians to identify those at risk for developing GDM earlier in the pregnancy. Early management of mothers at risk may lead to better health outcomes for mother and baby.

OBJECTIVES/GOALS: The Indiana CTSI Strategy Committee charged the Racial Justice and Health Equity Taskforce to identify priorities with short-term and long-term goals consistent with the I-CTSI mission. In addition, I-CTSI leadership asked for a general description of current state and the resources necessary to achieve the proposed goals. METHODS/STUDY POPULATION: The Taskforce applied an inclusive excellence model to the way we look at the I-CTSI structure, policies, and programs while performing an environmental scan within and across I-CTSI partner institutions. In order to reach equitable solutions and consensus, listening tours were held with partner stakeholders guided by the SOAR framework for strategic planning. This approach allowed us to assess current resources, needs, and gaps across the system, along with a baseline of measures currently monitored. Taskforce members openly discussed strengths and opportunities for enhancement of current programs and services. In addition, these conversations offered an opportunity to disrupt existing practices and through collective agency we identified priority areas that promote equity, diversity and inclusion. RESULTS/ANTICIPATED RESULTS: The Taskforce identified recurring themes in conversations with all partners, which led to the formation of three working groups that examined recruitment broadly: workforce, staffing, and research participation; professional development across all stakeholders from community members to I-CTSI staff; and data-centered metrics informing current state, decision-making, and accountability. Recommendations included these priorities, content, and implementation strategies. The Taskforce delivered a report to the I-CTSI leadership fostering the promotion of diversity, equity and inclusion along with a systematic collection of gender, race, and ethnicity data for individuals utilizing I-CTSI services and resources requiring additional metrics and tracking. DISCUSSION/SIGNIFICANCE: The pandemic shed light on the manner in which marginalized groups are rendered particularly vulnerable to death and disease by systemic and structural racism. The I-CTSI recognized that we cannot advance population health without attending to root causes of inequity and that includes our internal structure. We offer a potential model for other CTSAs.

Objectives/Goals: Efficacy-and-Effectiveness Too (EE2) randomized clinical trials pair a controlled efficacy cohort with a pragmatic effectiveness cohort. We will deliver a Bayesian EE2 framework with interim go/no-go rules and adaptive cross-cohort borrowing for time-to-event endpoints. Methods/Study Population: We formalize three approaches: 1) simultaneous: both cohorts start together, and interim looks apply predictive success probability (PSP) to enable early efficacy or futility stopping within each cohort; 2) staggered: the trial begins with the efficacy cohort and, at 50% information, initiates the effectiveness cohort only if the PSP under a retained-effect assumption (e.g., ≥70% of the efficacy log-HR retained) exceeds a prespecified threshold; 3) sequential: the efficacy trial is completed first, and the effectiveness trial is designed using the efficacy posteriors. Across approaches, the Bayesian method relies on piecewise-exponential modeling with Gamma-Poisson conjugacy, Negative-Binomial predictive counts, and power or commensurate priors with robust discounting. Results/Anticipated Results: Operating characteristics (type I error, power, bias/coverage, borrowing Effective Sample Size) will be evaluated through simulation studies across heterogeneity scenarios and prior-data conflict. We will re-analyze the RUBY and NRG-GY018 endometrial trials (endpoints: Progression-Free Survival and Overall Survival) as EE2 case studies (efficacy: mismatch repair-deficient tumors; effectiveness: mismatch repair-proficient tumors) using dynamic borrowing and the appropriate interim logic to demonstrate feasibility, robustness, and gains in precision. We anticipate improved precision for each cohort and for the combined effect and stable decisions under partial retention. Discussion/Significance of Impact: This work provides the first end-to-end Bayesian EE2 toolkit spanning simultaneous, staggered, and sequential implementations, with interim rules, principled borrowing, and software, to accelerate the generation of generalizable evidence while safeguarding against prior-data conflict, advancing efficient, patient-centered translation.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to understand factors that are associated with identifying which eligible pregnant women in Baltimore City accept a referral for HV services. Taking into account demographic and obstetrical variables, we will examine the extent to which 13 medical and 14 psychosocial risk factors differentiate pregnant women who (1) accepted a HV referral, (2) could not be located, or (3) refused a HV referral. METHODS/STUDY POPULATION: In this observational study, we will use secondary data on 8172 pregnant women collected by Health Care Access Maryland (HCAM) between 2014 and 2016. HCAM is the single point of entry for all pregnant women in Baltimore City into HV. HV eligibility includes being a pregnant woman, residing in Baltimore City, being uninsured or receiving Medicaid, and being identified by a prenatal care provider who completed an assessment profile of the woman’s medical and psychosocial risk (prenatal risk assessment). The outcome variable, HV engagement status (ie, accepted referral, could not be located, refused referral), will be based on HCAM discharge codes. Medical risk factors include BMI, hypertension, anemia, asthma, sickle cell, diabetes, vaginal bleeding, genetic risk, sexually transmitted disease, last dental visit >1 year ago, and taking prescription medications. Psychosocial risk factors include current pregnancy unintended; <1 year since last delivery; late entry to prenatal care (>20 wk gestation); mental, physical, or developmental disability; history of abuse or violence within past 6 months; tobacco use; alcohol use; illegal substance use within the past 6 months; resides in home built before 1978; homelessness; lack of social/emotional support; exposure to long-term stress; lack of transportation; and history of depression or mental illness. All risk factor variables are categorical (yes/no). Control variables will include demographics (eg, age, race, ethnicity, marital status, educational level) and OB history (eg, history of preterm labor, history of fetal or infant death). We will conduct descriptive statistics to characterize the sample and look for interrelatedness among the risk factors. Where there is a high level of inter-relatedness we will consider combining or omitting variables to reduce redundancy. We will use multinomial regression to examine which medical and psychological factors are associated with referral category. RESULTS/ANTICIPATED RESULTS: We hypothesize that (a) women with more medical risk factors will be more likely to accept a referral for HV services, (b) women with more psychosocial risk factors will be more likely to refuse HV or not be located, and (c) certain risk factors, such as depression/mental illness, history of abuse/violence, illegal substance use, homelessness, and exposure to long-term stress will be the strongest predictors of not accepting HV referral and/or not being located. DISCUSSION/SIGNIFICANCE OF IMPACT: The translation of effective randomized control trials (RCTs) to successful implementation in community-based programs can be challenging. Community-based programs serving low-income communities typically lack the same resources available to recruit and retain participants in RCTs. And, exclusion criteria applied in RCTs are often not applied in real world implementation which can open program to participants with more complex social and medical characteristics. Findings from this study will inform the translation of evidence-based HV programs into real world settings through an enhanced understanding of the characteristics of women who are not engaged by HV programs. This will inform development of improved outreach methods that may more effectively engage at-risk women for prenatal HV services.

OBJECTIVES/GOALS: Underrepresented (UR) biomedical researchers leave research positions at a disproportionate rate. We aim to identify factors associated with confidence in career progression and intent to continue clinical research training in UR post-doctoral fellows and early-career faculty. METHODS/STUDY POPULATION: Building Up is a cluster-randomized trial at 25 academic institutions. In September-October 2020, 224 participants from the Building Up study completed the pre-intervention assessment, which included questions on demographics, science identity, mentoring competency, confidence in career progression, and intent to continue clinical research training. Using multinomial logistic regression controlling for gender and race/ethnicity, we identified factors associated with confidence in career progression, and intent to continue clinical research training. Statistically significant findings are reported. RESULTS/ANTICIPATED RESULTS: The cohort (N=219) is 80% female, 33% non-Hispanic Black, and 34% Hispanic. Having mentors that address diversity was associated with belief that career advancement is as open to them as anyone else (OR=1.7) and confidence in ability to overcome professional barriers (OR=1.4). Higher science identity (OR=4.0) and having mentors who foster independence (OR=1.7) were associated with confidence in ability to progress in career. Higher science identity was also associated with confidence in ability to overcome professional barriers (OR=2.2) and intent to continue studying biomedical sciences (OR=3.4). Being faculty (OR=3.8), higher science identity (OR=3.8), and having mentors that align expectations (OR=2.3) were associated with intent to continue clinical research training. DISCUSSION/SIGNIFICANCE: These findings suggest that science identity and mentoring play key roles in confidence in career progression and intent to continue clinical research training. These factors are important to consider in retaining UR early-career biomedical researchers.

OBJECTIVES/SPECIFIC AIMS: The goal of the study is to evaluate the prognostic importance and accuracies of a biomarker, human epidermal receptor 2 (Her2), for breast cancer recurrence in a cohort study, namely Lifetime after Cancer Epidemiology (LACE). We specifically interested in the role that Her2 plays in prognosis of breast tumor recurrence for women after a previously diagnosed and treated breast cancer. METHODS/STUDY POPULATION: The study cohort includes 2267 women enrolled in LACE who had previously diagnosed breast cancer. Patients were enrolled from each of the 2 LACE registries in California and Utah. The main endpoint of the study is the right-censored time to breast cancer recurrence. Patients’ enrollments were, on average, 2 years after diagnosis of the first breast cancer. The patients’ characteristics at baseline were obtained through self-administered questionnaires. Cox proportional hazard model with time-varying covariates was used to relate the Her2 status (Her2+ and Her2−) to the primary end point (time to breast cancer recurrence). Hazard ratios (HRs) and their 95% confidence interval comparing Her2+ and Her2− arms were estimated. Time-dependent sensitivity and specificity were used to investigate the performance of using Her2 for classifying patients into high and low risk (Her2 + is classified as hi risk and Her− as low risk) of future breast cancer recurrence at time points after baseline. The time-dependent sensitivity was calculated as the proportion of patients being classified as high risk of recurrence who had breast cancer recurrence before a series of pre-specified time points after baseline, and the time-dependent specificity was calculated as the proportion of subjects being classified as low risk of recurrence who did not have breast cancer recurrence at the same time points. RESULTS/ANTICIPATED RESULTS: The average patient follow-up time was 9.8 years, and 18% of the women got positive Her2 test results at baseline. Among 2267 patients in the study cohort, 2031 had records on their Her2 status, among whom 326 (16.1%) patients were Her2+ and 1705 (83.9%) were Her2−. The mean tumor size among the 2031 patient was 2.10±1.22 cm. A majority of the patients (78.9%) were White. Over one-half of these patients were neither current nor past smokers. Only 3% of the patient had a baseline stage IIIA or higher. About 49% of the patients underwent a mastectomy. Radiation therapy was used by 63.5% of the patients, and Tamoxifen users accounted for 78% of the study cohort. We found a statistically significant association between Her2 and breast cancer recurrence (HR=1.33, log-ran p-value=0.006). However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time. We also investigate the effect of combined Her2, estrogen (ER), and progesterone (PR) on breast cancer recurrence and found that patients with Her2+/ER+/PR− had the highest risk of breast cancer recurrence. The hazard of recurrence for this group of patients was 85% higher than patients with Her2−/ER+/PR+. We also investigate the prognostic accuracies of Her2 in terms of time-dependent sensitivity and specificity. Using Her2 as the prognostic biomarker resulted in a specificity consistently over 80% from baseline up until 15 years post-baseline. The time-dependent sensitivity of Her2 was above 90% between baseline and 1.5 years. Then, the sensitivity dropped gradually to 40% from 1.5 years to 3 years post-baseline. For prognosis of breast cancer over 3 years from baseline, the sensitivity was between 30% and 40%. DISCUSSION/SIGNIFICANCE OF IMPACT: As a single biomarker and risk factor, Her2 was statistically significantly associated with the recurrence of breast cancer among patients in the LACE cohort. A composite biomarker by combining Her2, ER, and PR status was also significantly associated with the breast cancer recurrence. However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time, implying that the Her2 status had a high impact on early recurrent breast tumors. Single biomarkers, usually, have very limited ability for prognosis of future events. However, we found that using HER2 as a single biomarker can give a relatively larger specificity consistently over 15 years of the study period. The sensitivity of Her2 is high for detecting early breast cancer recurrence. However, after 2.5 years from baseline, using Her2 for breast cancer recurrence detection is not reliable. Due to the relatively high accuracies of using Her2 status for prognosis of breast cancer recurrence, we conclude that Her2 should be considered in clinical studies related to prognosis of breast cancer recurrence. Future studies will investigate if prognostic accuracies can be improved by combining Her2 with baseline clinical risk factors such as age, tumor size and lymph nodes. In conclusion, our study has the clinical impact on prognosis (or early detection) of breast cancer recurrence among women with previously diagnosed and treated breast cancers.

Objectives/Goals: Aim 1: Assess the correlation between Tuft cell T2R functionality and Th2 sinonasal inflammation, disease burden, and post-surgical outcomes in AERD patients. Aim 2: Determine if hyperfunctional Tuft cell T2Rs enhance denatonium-stimulated inflammatory responses in nasal epithelial air–liquid interface (ALI) cultures from AERD patients. Methods/Study Population: Aim 1: We will conduct a prospective cohort study with 82 AERD patients. Taste sensitivity to denatonium (DB), serving as a proxy for tuft cell T2R functionality, will be assessed using a validated 13-point scale, and correlations with clinical outcomes – SNOT-22, histopathologic, CT, and endoscopic scores – will be analyzed using linear regression. Aim 2: Sinonasal epithelial cells will be collected from AERD patients either hyper- or hyposensitive to DB and from healthy controls. We will establish ALI cultures and expose them to varying DB concentrations. Secretions will be analyzed for antimicrobial peptide release via bacterial kill assays and for IL-25 and β-defensin 2 via ELISA. Tuft cell frequency and baseline IL-25 mRNA expression will be assessed using immunofluorescence and quantitative real-time polymerase chain reaction, respectively. Results/Anticipated Results: We expect that higher DB taste sensitivity in AERD patients will correlate with worse clinical outcomes, reflected by elevated 6-month postoperative SNOT-22 scores, indicating increased symptoms. Additionally, we anticipate that preoperative Lund-MacKay and Lund-Kennedy scores, along with histopathological metrics, will be worse in DB-hypersensitive patients, establishing a link between taste sensitivity and disease burden. In vitro, we predict that AERD patients with DB hypersensitivity will demonstrate significantly higher IL-25 and β-defensin 2 secretion and reduced bacterial colonies in kill assays. We also expect increased tuft-cell frequency and baseline IL-25 mRNA in AERD-derived cultures compared to healthy controls, highlighting T2R functionality’s role in AERD pathogenesis. Discussion/Significance of Impact: This project aims to investigate a putative new role for Tuft cells in AERD pathogenesis by correlating Tuft cell T2R functionality with outcomes in AERD patients and with inflammatory response in vitro. Findings could lead to predictive clinical taste tests and future genotyping studies to identify T2R polymorphisms correlated with AERD severity.

Objectives/Goals: Adolescent suicide is a major and growing public health concern, as suicide-related hospital visits continue to rise. Additionally, brain regions implicated in suicide risk are still undergoing change during adolescence. Here, we explore the longitudinal impact of suicide risk factors on brain functional connectivity during adolescence. Methods/Study Population: Data from the Adolescent Brain and Cognitive Development (ABCD) Study were used for this analysis. The ABCD Study is an ongoing, multi-site, longitudinal study that follows kids starting at 9 years old until they’re 18 years old. The study sample is meant to be representative of the current US population, based on various demographic criteria obtained from the US census. For this study, baseline and Year 2 functional MRI imaging data and parent and youth reports of depression, non-suicidal self-injury (NSSI), and suicidal thoughts and behaviors (STB) from the ABCD Study, were used for this analysis. Clinical and imaging data were added into a statistical model (linear mixed-effects model) to describe how the relationship between suicide risk and brain development changes over time. Results/Anticipated Results: A total of 9653 subjects (51% Female), between the ages of 8.9 – 13.8 years, across two timepoints: Baseline (N=6493) and Year 2 (N=3,160), were included in the analysis. Of this sample, 861 (8.9%) endorsed depression, 1428 (14.8%) NSSI, 2146 (22.2%) STB, and 3012 (31.2%) any of the three suicide risk factors at any timepoint. Results showed a significant interaction between the association of network connectivity and STB group status with age in the approach (B = -15.0, 95%CI [-26.4, -3.8]), avoidance (B = -8.5, 95%CI [-16.3, -0.9]), regulation (B = -14.4, 95%CI [-26.2, -3.1]), approach-avoidance (B = -14.4, 95%CI [-28.3, -0.5]), and approach-regulation (B = -15.6, 95%CI [-28.8, -2.7]) network. Discussion/Significance of Impact: Findings suggest, in early adolescence, presence of STBs is associated with changes in communication in regions involved in reward-(approach), emotion/threat-processing (avoidance), and their cognitive regulation (regulation). The causal relationship is unclear, but it’s an important step to understanding the neural mechanisms of suicide.

ABSTRACT IMPACT: This study will help to characterize the root causes of racial and ethnic disparities in viral respiratory outbreaks and determine the extent to which this is unique to the COVID-19 pandemic, so that preventative interventions can be designed for future pandemics and epidemics. OBJECTIVES/GOALS: The causes of racial and ethnic disparities in COVID-19 clinical outcomes are multifactorial but include social inequity driven by structural racism. This study seeks to characterize the patterns of these disparities by linking patient-level EHR data with population-level sociodemographic measures. METHODS/STUDY POPULATION: This retrospective review of adult patients tested for SARS-CoV-2 in the UCHealth System will compare rates of COVID-19 infection, hospitalization, in-hospital mortality and 30-day mortality across racial and ethnic groups. Race and ethnicity are determined by patient self-report in the EHR. Univariable and multivariable regression analyses will be used to assess the association of these outcomes with sociodemographic factors. Potential confounders that will be adjusted for include Charlson Co-morbidity Index, disease severity and likelihood of readmission. Using chi-square tests, we will assess differences in the race/ethnicity distributions between this cohort and those from the 2009 H1N1 Pandemic and the 2018-19 influenza season. RESULTS/ANTICIPATED RESULTS: Of the first 459 patients hospitalized for COVID-19 in March and April 2020, race/ethnicity were: 194 Hispanic (42.3%), 104 non-Hispanic Black (22.6%), 83 non-Hispanic white (18.1%), 43 Asian (9.4%), and 35 other or unknown race (7.6%). There were significant differences in the race/ethnicity distribution compared to the cohort of patients hospitalized for viral respiratory infection during the 2018-19 influenza season (n=254, p <0.001): 58 Hispanic (22.8%), 52 non-Hispanic black (20.4%), 116 non-Hispanic white (45.7%), 15 Asian (6%), and 13 other or unknown race (5.1%). Our anticipated results include further adjusted analyses and comparisons to the 2009 pandemic. We will compare COVID-19 prevalence and outcomes by race/ethnicity with other viral infection outbreaks, adjusting for confounders. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial hospitalizations for COVID-19 at our institution are notable for a high proportion of Hispanic patients and smaller proportion of non-Hispanic whites, in contrast to the prior year. Our study will demonstrate the extent to which racial and ethnic disparities are typical in viral respiratory outbreaks, which can guide future interventions.

OBJECTIVES/GOALS: To promote diverse research engagement and address health disparities by creating an inclusive tool to collect sexual orientation and gender identity (SOGI) data from potential participants #_msoanchor_1 METHODS/STUDY POPULATION: The Penn State Community Health Equity & Engagement in Research (CHEER) team, part of our Clinical and Translational Science Institute (CTSI), developed inclusive screening guidance to collect SOGI data from potential research participants to fill an identified gap in the literature. Guidance was developed through an iterative feedback process, leveraging expertise from local, regional, and national organizations, healthcare systems, and leaders throughout Clinical & Translational Science Award hubs. By eliciting expert feedback, CHEER co-developed a comprehensive SOGI data collection form, filling an important gap of inclusivity in the consenting process. Training of this new tool was delivered to CHEER’s far-reaching listserv researchers (internal and external) and community partners. RESULTS/ANTICIPATED RESULTS: Feedback collected from our LGBTQ+ expert partners resulted in a total of five inclusive SOGI screening questions; two ‘Gender Identity’ questions, one ‘Sexual Orientation’ question, and two ‘Sex’ questions, with “prefer not to answer” and “another option not listed” provided. The goal of this effort is to equip research teams with a tool that integrates SOGI characteristics that may be particularly important to determine study eligibility respective to a person’s identity or orientation. Additionally, collecting SOGI data in an inclusive way may increase trust worthiness in research from potential research participants, particularly among the LGBTQ+ community, who have been underrepresented yet experience several inequities and disparities across multiple health outcomes. DISCUSSION/SIGNIFICANCE: CHEER’s goal is to reduce health disparities in underrepresented populations, including the LGBTQ+ community, by promoting inclusivity and engagement in research. Developing a community-driven screening that addresses the unique needs of the LGBTQ+ community successfully bridges a gap in equity across all research participants.

OBJECTIVES/SPECIFIC AIMS: I would like to make clinicians aware about prescription opioid use and glycemic control among patients with diabetes. This is a quality of care issue that increases the disease burden for two conditions opioid dependence and diabetic complications. Big data analytics can bring out this quality of care issue and help in changing clinical practice through precision medicine METHODS/STUDY POPULATION: This is a population health study of patients on prescription opioid pain medications in Erie county medical center and local out patient clinic. The electronic data from the hospital records and Outpatient were collected, merged and de identified. The database was saved in a protected environment and made accessible to researchers through a secure login. The data was queried for the number of patients with diabetes. The glycohemoglobin levels were collected and then the analysis was made RESULTS/ANTICIPATED RESULTS: It was found that only 63 of the 89 patients with DPN and 156 of the 570 patients without DPN had any measurement of HbA1c in our data. It was found that 86 out of 156 patients without DPN had suboptimal glycemic control with a glycohemoglobin level > 7% while 36 out of 63 patients with DPN had a glycohemoglobin > 6.7%. The odds of patients with DPN having poor glycemic control is 0.57 while the odds of having poor glycemic control without DPN is.55. The relative risk being 1.03. DISCUSSION/SIGNIFICANCE OF IMPACT: Our population study revealed suboptimal glycemic control among a large set of patients in Western New York with a diagnosis of diabetes mellitus and a concurrent prescription for an opioid pain medication. A significant percentage of patients in our study population with a diagnosis of DPN might benefit in terms of decreased painful symptoms of neuropathy from monitoring and attempting to improve glycemic control. Additionally, in our patient population, there were no patients with diabetic peripheral neuropathy prescribed pregabalin or duloxetine, the first-line FDA-approved medications for painful DPN, Based on our population study, the quality of care for diabetic patients with DPN who are prescribed opioid pain medications should be monitored closely. First-line, FDA approved anticonvulsants and antidepressants should be considered for the treatment of painful symptoms when necessary. Attention should be directed towards monitoring and improving glycemic control in patients without DPN receiving opioid pain medications to attempt to prevent or delay the microvascular complications of diabetes, including the onset of painful peripheral neuropathy.

OBJECTIVES/SPECIFIC AIMS: Lung cancer claims 160,000 lives in the United States every year, and lung adenocarcinoma (LADC) is the most frequent type. Early diagnosis is crucial. Computed tomography (CT) is very sensitive in identifying early-stage lung nodules, but has low specificity. Increased glucose uptake is a hallmark of cancer measurable in vivo by fluorodeoxyglucose (FDG) positron-emission tomography (PET). FDG PET is widely used for cancer staging but has low sensitivity in the diagnosis of solitary lung nodules. We have previously identified an alternative glucose transporter, SGLT2, expressed in different types of cancer but not detected by FDG PET. SGLT2 activity can be measured in vivo with the PET tracer methyl-4-fluorodeoxyglucose (Me4FDG). The objective of this study was to test the hypothesis that SGLT2 is a novel diagnostic and therapeutic target in FDG-negative, early stage LADC. METHODS/STUDY POPULATION: To study glucose transporter expression in LADC, we performed immunohistochemistry with SGLT2- and GLUT1-specific antibodies in human lung pre-malignant lesions and LADC samples. To verify the possibility of detecting SGLT2 activity in vivo, we performed microPET imaging with the SGLT-specific tracer Me4FDG in a Kras-driven, p53-null genetically engineered mouse model and in patient-derived xenografts of LADC. Finally, we performed therapeutic trials in genetically engineered and patient-derived mouse models of LADC with the FDA-approved SGLT2 inhibitor canagliflozin. RESULTS/ANTICIPATED RESULTS: We observed a switch in the modality of glucose transport during lung carcinogenesis: SGLT2 was highly expressed in pre-malignant lesions and well-differentiated LADC, whereas GLUT1 was upregulated in advanced, poorly differentiated lesions. This pattern was observed both in human samples and in murine models. This observation led us to hypothesize that early-stage LADCs are often negative on FDG PET because this imaging modality does not detect the activity of SGLT2, which is expressed in early lesions. Therefore, we performed PET imaging with the tracer Me4FDG, that measures SGLT2 activity, in our mouse model, and observed that Me4FDG accumulated in small nodules that were negative with FDG. We confirmed the functionality of SGLT2 in human LADC by Me4FDG PET in patient-derived xenografts. To investigate the role of SGLT2-mediated glucose uptake in the early stages of LADC development, we treated both genetically engineered mice and patient-derived xenografts with FDA-approved SGLT2 inhibitors, showing that SGLT2 inhibition effectively reduced LADC growth and prolonged survival in mouse models. In addition, Me4FDG uptake predicted response to SGLT2 inhibition. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results show that sodium-dependent glucose transport is a critical metabolic supply strategy in the early stages of lung adenocarcinoma development, and that Me4FDG is a novel biomarker of early LADC and of SGLT-dependent tumor growth. The discovery of SGLT2 in LADC highlighted the need for a re-interpretation of FDG-negative lung nodules, which might rely on SGLT2 for glucose uptake, and therefore may be detected by the new tracer Me4FDG. We anticipate our findings will lead to clinical studies evaluating Me4FDG as a diagnostic tracer for solitary lung nodules and early LADC, and as a biomarker for the selection of patients eligible for treatment with SGLT2 inhibitors.

There is a paucity of educational resources for potential clinical trial participants, particularly resources in plain language, attentive to health literacy principles and translated into native languages. The New England Research Subject Advocacy Group was formed to explore common issues, interests, and concerns related to the experience of participation in clinical research and research participant safety. Specifically, the group sought to increase community awareness and trust through the development and distribution of publicly accessible informational resources. In support of these aims, the group developed a robust library of high-quality, plain-language educational materials covering topics in health research, research participation, and common research procedures, and translated the majority of the materials into an additional 15 languages. These resources have been downloaded over 130,000 times. After English, the most common languages downloaded are Vietnamese, Spanish, and Korean.