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.

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.

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the “inspiring Diverse Researchers in Virginia” (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

Although team science has expanded with far-reaching benefits, universities generally have not established criteria to recognize its value in faculty promotion and tenure. This paper recommends how institutions might weigh a faculty member’s engagement in team science in the promotion and tenure process. Seventeen team science promotion and tenure criteria are recommended based on four sources – an evaluation framework, effectiveness metrics, collaborative influences, and authorship criteria. Suggestions are made for adaptation of the 17 criteria to committee guidelines, faculty team science portfolios, and the roles of individuals and institutions participating in large, cross-disciplinary research projects. Future research recommendations are advanced.

OBJECTIVES/SPECIFIC AIMS: To assess the effect of cannabis on impaired judgment and health outcomes among heart failure patients in the emergency room. METHODS/STUDY POPULATION: Patients with heart failure presenting to the emergency room. Cannabis with confounders such as income level, insurance type, tobacco use, and age. Discharged against medical advice to assess impaired judgment. Hospitalization rates, length of stay, and death rate to assess health outcomes. Multivariate logistic regression to access the odds of each of these outcomes from cannabis RESULTS/ANTICIPATED RESULTS: Cannabis is associated with impaired outcome (increase in discharge against medical advice). Cannabis have poorer health outcome in terms of more hospitalizations from the emergency department. Cannabis also have better health outcome in terms of shorter length of stay and death rate among cannabis users Versus nonusers. DISCUSSION/SIGNIFICANCE OF IMPACT: This is crucial to inform health care providers to ensure better counseling of cannabis users. This result should also be considered to interpret other publications that shows better outcomes in patients taking cannabis. Cannabis users might only seem to have a better outcome because they tend to discharge against medical advice and thereby die outside the hospital, etc.

OBJECTIVES/SPECIFIC AIMS: Exosomes are living nanoscale vesicles that can shuttle large amounts of bioactive cargo for intercellular communication. The potential of these nanovesicles to serve as both biomarkers for disease diagnosis and vehicles for delivery of therapeutics has only begun to be explored. To realize these potentials, molecular tools for effective exosome tracking and capturing must be invented in order to advance basic research and clinical translation. METHODS/STUDY POPULATION: We utilize a surface display strategy that enables exosome modification in living mammalian systems. By reconfiguring the surface protein CD63 or viral envelope glycoprotein VSV-G, we generate 3 topologically distinctive protein chimeras for exosome imaging and capture in mammalian systems. RESULTS/ANTICIPATED RESULTS: We have shown that these genetically encoded protein chimeras have the ability to correctly target and integrate into exosomes in cultured human cells. Furthermore, we have demonstrated that the secreted exosomes could be successfully captured by an affinity peptide intentionally displayed on the outer surface of exosomes. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study highlights the potential of these fusion proteins for exosome tracking and provides novel genetic tools for exosome research and translation, one of which is loading protein therapeutics for targeted delivery.

Objectives/Goals: To assess the effect on the immune response to COVID-19 in children exposed to pesticides. The hypothesis is that increased pesticide exposure results in different immunological response to COVID-19. The goal of the proposal is to improve scientific knowledge on factors affecting COVID-19 and identify a modifiable factor to reduce these disparities. Methods/Study Population: A cross-sectional analysis of children (aged 5–17 years) with asthma to assess pesticide exposure and immune markers of SARS-CoV-2. SARS-CoV-2 infection or vaccination was determined with blood exposome RNA analyses assessed from blood samples taken at baseline. Immunological response was measured using neutralizing, phagocytizing, and NK-activating antibody responses biomarkers using plasma antibody isotyping, effector functions, T-cell activation-induced marker (AIM), and recall cytokine secretion assays on lysed, whole blood. Pesticide exposure was assessed as concentration of four urinary metabolites in a spot urine sample adjusted for creatinine. Unadjusted regression models were created to assess the effect of 3-phenoxy benzoic acid, a common pyrethroid pesticide, on immune markers. Results/Anticipated Results: Children’s (N = 30) average age was 10 years (interquartile range: 8–11) A majority of children were male (63%) and Non-Hispanic Black (73%). The majority of children had markers of SARS-CoV-2 infection (77%). Of the 4 pesticide metabolites assessed, only 3-PBA was commonly found (77% of samples > LOQ). Higher urinary concentrations of 3-PBA are associated with a significant (p Discussion/Significance of Impact: Significant associations in cytokine and inflammatory marker may indicate a Th2-skewed response, and dysregulated cytokine responses can lead to severe disease. A suggested increase in T-cell activation markers (e.g., CD4, CD8) may indicate potential exhaustion if excessively activated.

ABSTRACT IMPACT: Antibiotic stewardship guidelines should consider the barriers clinicians in low- and middle-income countries face due to limited biomarkers for determining the etiologic pathogen for viral infections like respiratory syncytial virus (RSV) that have a similar presentation to bacterial infections. OBJECTIVES/GOALS: We aimed to evaluate antibiotic administration practices in children who were hospitalized at a government-run hospital in Amman, Jordan, where point-of-care testing is limited. We hypothesized those with RSV are more likely to be administered antibiotics during their hospitalization than children without RSV. METHODS/STUDY POPULATION: We conducted a cross-sectional cohort study in Jordanian children hospitalized with history of acute respiratory symptoms and/or fever from 2010 to 2013. Admitting diagnoses were dichotomized into suspected viral- (e.g., bronchiolitis) and bacterial-like infection (e.g., sepsis, pneumonia). Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) and 95% confidence intervals for macrolides, broad-, and narrow-spectrum antibiotics during hospitalization. Sensitivity and specificity of admission diagnoses and laboratory results were compared. RESULTS/ANTICIPATED RESULTS: Children with a suspected viral-like admission diagnosis, compared to those with suspected bacterial-like, were 89% less likely to be administered a narrow-spectrum antibiotic (POR: 0.11; p<0.001). There were slight differences by sex with males having a lower prevalence than females of narrow-spectrum or broad-spectrum antibiotic administration; but they had a higher prevalence of macrolide administration. Overall, children with RSV had a 30% probability (sensitivity) of being assigned to a suspected viral infection; whereas RSV-negative children had an 85% probability (specificity) of being assigned to a suspected bacterial infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: Children with a suspected viral-like infection were less likely to receive an antibiotic; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.

OBJECTIVES/GOALS: The grant writing process provides investigators with critical thinking, problem solving, and communication skills, crucial for personal and professional development. However, opportunities for junior faculty to learn these skills are highly variable. Thus, we developed a grant writing program to assist in the preparation of an NIH R proposal. METHODS/STUDY POPULATION: The R Club Grant Program was implemented in 2021 for junior faculty of the University of Cincinnati’s College of Medicine and Center for Clinical & Translational Science & Training (CCTST). The program consists of a series of workshops (e.g., How to Craft a Specific Aims Page, How to Construct a Competitive R01 Proposal) utilizing examples of successful proposals and grant review criteria to demonstrate how to translate a conceptual framework into a research proposal (level 1). All participants can receive constructive feedback on a Specific Aims page from an experienced grant writer (level 2), and for a select cohort, the program provides comprehensive scientific content edits and iterative feedback on a full research proposal, with a focus on grantsmanship, presentation, and overall competitiveness (level 3). RESULTS/ANTICIPATED RESULTS: Over three NIH grant cycles, the program to date has provided 38 early-career investigators with multi-level grant writing support. All participants attended the workshops and received supporting documents, 21 received feedback on a Specific Aims page, and 6 received one-on-one writing assistance on their full research proposal. Of the 6 investigators who received the greatest level of support, 3 have received NIH scientific review, with a 66.6% funding success rate for either an original (R01, n=1) or subsequent overlapping (R35, n=1) proposal. In a survey sent to workshop attendees, 100% of respondents (n=23) reported ( Strongly Agreed or Agreed ) that the training was a worthwhile investment in their professional development and 96% stated that they will be able to apply the knowledge and skills learned. DISCUSSION/SIGNIFICANCE: Initial evaluation measures suggest that grant writing support programs have great potential to enhance funding success rates. As the program evolves it will be crucial to evaluate both qualitative and quantitative feedback measures to ensure efforts are directed to the appropriate level(s) of service to maximize the funding success of our faculty.