Objectives/Goals: To investigate interventional clinical trial participation overall and by race, gender, and age. Methods/Study Population: We used Epic Cosmos, an aggregated, de-identified EHR platform including over 270 million patients, to examine overall clinical trial participation and the race, gender, and age composition of participants versus non-participants. Patients ≥5 years old with known race and gender and at least one healthcare encounter between 2021 and 2024 were included. Interventional trial enrollment was identified by a “research flag” indicating current or past participation in an interventional study within an Epic system contributing data to Cosmos. Race was categorized as American Indian, Asian, Black, Native Hawaiian, or White. Age-adjusted relative representation (RR) ratios were used to compare participation, with RR >1 indicating over-representation and RR Results/Anticipated Results: Of 130,455,189 patients meeting eligibility criteria, 0.52% (673,425) of patients were active or inactive in an interventional clinical trial. Results are shown in the figure below. The poorest representation was from Asian and NH/PI persons. Representation was most similar to the patient population for whites and AI/AN persons. Black males participated less and women, more than predicted by patient composition. Older patients participated more frequently than younger (age, mean (SD), y, 53 (22) vs. 46 (23); p Discussion/Significance of Impact: This is the first study we know of describing interventional trial participation in the USA across millions and millions of patients. Further research is needed to clarify whether these differences are due to the nature of the studies themselves (e.g., OB/GYN trials including only women, etc.) versus disparities in recruitment or otherwise.

OBJECTIVES/SPECIFIC AIMS: This research project aims to: 1) describe the incidents of workplace violence that have been reported to CalOSHA through the Workplace Violent Incident Reporting System for Hospitals; 2) determine if there are any relationships between the types of violent incidents reported and the unit or hospital where the event occurred; 3) describe what mitigation strategies facility representatives report having utilized immediately following a violent incident, such as changes to practice or involvement of law enforcement. METHODS/STUDY POPULATION: Reports submitted to CalOSHA pursuant to the Workplace Violent Incident Reporting System for Hospitals are considered public record and are available through the state’s Public Records Act (PRA) mandate. Records from 7/1/17 – 9/30/18 were obtained through the CalOSHA PRA request process. Descriptive statistics and correlations were calculated using Stata. RESULTS/ANTICIPATED RESULTS: Records reporting 11,116 individual events of violence were analyzed. These results do not include reports submitted by the five California State Hospitals, a group of facilities which treated nearly 13,000 patients in 2017, many of whom have a psychiatric diagnosis and are undergoing treatment mandated by judicial decision. For each record, 111 variables were reported, including description of the event itself, characteristics of the workers involved, factors which may have triggered the event, and what measures were taken to mitigate the situation during and after the incident. All events identified an aggressor; 10,357 (93%) described this individual as a patient. 11,048 reports had a unit or hospital location listed to describe where the incident occurred. Of these, 9393 (84.5%) were inpatient, behavioral health, or surgical units. A physical injury was reported in 3672 events (33%) and stress/psychological impairment was reported in 536 (5%) of the incidents. Police officers were deployed to the scene following the incident in 1122 (10%) of reported events, resulting in arrest of the perpetrator in 402 (3.6%) of the reported incidents. DISCUSSION/SIGNIFICANCE OF IMPACT: While the impulse to address the high prevalence of workplace violence towards healthcare providers has led to deserved attention from policy makers, safety regulators, and healthcare unions, plans for ensuring that new initiatives are achieving their desired effect for workers have yet to fully materialize. An ongoing concern is that incidents are known to be under-reported through official mechanisms, leading to challenges in determining the scope of the problem itself and evaluating the efficacy of interventions to address it. CalOSHA’s new reporting requirement and online interface provides a new channel for improving validity of prevalence data, as early findings indicate that less serious events are being reported through the system. In addition, information describing how hospital leaders report responding to incidents in their immediate aftermath will provide needed insight into what additional efforts are needed to support victims of violence given the unique challenges present in the healthcare industry.

ABSTRACT IMPACT: Identifying racial disparities in septic shock mortality, a common and lethal condition, can inform future research and policy efforts aimed at understanding the drivers these disparities and addressing the underlying factors in order to reduce disparities and improve health. OBJECTIVES/GOALS: Septic shock is a major public health problem with significant mortality. Existing data indicate racial disparities in sepsis incidence, but evidence is limited on differences in septic shock outcomes. Our objective was to determine the association between race and septic shock mortality in a statewide cohort while controlling for clinical factors. METHODS/STUDY POPULATION: This was a retrospective analysis of septic shock patients in the One Florida Data Trust between 2012-18. Data was collected regarding age, sex, race, insurance status, and selected comorbid conditions [liver disease, hypertension, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), end-stage renal disease (ESRD), and human immunodeficiency virus infection (HIV)]. To account for severity of illness, we assigned Sequential Organ Failure Assessment scores for components based on laboratory values (labSOFA), and collected data on mechanical ventilation use and initial lactate.

The primary outcome was 90-day mortality. The Least Absolute Shrinkage and Selection Operator (LASSO) method was used for variable selection for the multivariable regression model. RESULTS/ANTICIPATED RESULTS: There were 13,932 septic shock patients with a mean (SD) age of 61(16) years. Of these, 68% identified as white, 28% as black, 2.1% as Hispanic, and 2.0% as other races. 90-day mortality was 32% (n=4,437) and 59% required mechanical ventilation. Significant independent predictors of mortality in the regression model were age (OR 1.04; p<0.01), black race (1.72; p<0.01), lactate (1.10; p<0.01), mechanical ventilation (3.62; p<0.01), labSOFA (1.18; p<0.01), history of liver disease (1.75; p<0.01), hypertension (0.70; p<0.01), COPD (0.87; p<0.01), CHF (1.18; p<0.01), HIV (1.30; p=0.05), and the interaction between age and black race. Black patients had 1.72 times the odds of mortality compared to white patients. For every one-year decrease in age, black patients had a 1% increased odds of mortality (OR 1.01; p < 0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Black patients have increased odds of dying from septic shock compared to white patients after controlling for age, selected comorbid conditions, and markers of illness severity. Future work is needed to move beyond demonstrating septic shock disparities and towards understanding the underlying factors.

COVID-19 has widened the existing digital divide, especially for people from socially and economically deprived communities. We describe a program evaluation using a community participatory approach to develop self-reported items of patient experience with technology inclusive of digital access and literacy. The feedback received from Community Advisory Boards and Community Engagement Studio members led to the evaluation and refinement of the individual items. The community-based participatory approach highlighted in our paper to develop these items could serve as a model for other screening tool development for enhancing equity and inclusiveness in clinical care and research.

Successful translation involves the coupled application of knowledge-generating research with product development to advance a device, drug, diagnostic, or evidence-based intervention for clinical adoption to improve human health. Critical to the success of the CTSA consortium, translation can be more effectively accomplished by training approaches that focus on improving team-emergent knowledge skills and attitudes (KSAs) linked to performance. We earlier identified 15 specific evidence-informed, team-emergent competencies that facilitate translational team (TT) performance. Here, we examine the SciTS literature describing developmental, temporal dynamics, and adaptive learning stages of interdisciplinary teams and integrate these with real-world observations on TT maturation pathways. We propose that TTs undergo ordered developmental phases, each representing a learning cycle that we call Formation, Knowledge Generation, and Translation. We identify major activities of each phase linked to development goals. Transition to subsequent phases is associated with a team learning cycle, resulting in adaptations that enabling progression towards clinical translation. We present known antecedents of stage-dependent competencies and rubrics for their assessment. Application of this model will ease assessment, facilitate goal identification and align relevant training interventions to improve performance of TTs in the CTSA context.

OBJECTIVES/GOALS: To understand how energy drinks are marketed and regulated and the effects of these policies on adolescent consumption and perceptions of the product. METHODS/STUDY POPULATION: A review of research studies using the PubMed database (PubMed.gov); clinical trials (clinicaltrials.gov); FDA Recall, Market Withdrawals, and Safety Alerts (FDA.gov); and emergency department (ED) visits from reports from the Drug Abuse Warning Network (DAWN) were conducted. A survey is being designed and will be sent to undergraduate and graduate university students through advertised QR codes and university email chains sent out to student organizations and courses. The survey will determine the percentage of respondents who consume caffeine, the frequency in which individuals consume caffeine, and reasons for consuming caffeine. The survey also seeks to understand perceptions and thoughts on energy drinks and caffeine regulation and consumption. RESULTS/ANTICIPATED RESULTS: From January 1st, 2000, to August 5th, 2022, 112 research studies investigated the physiological impact of energy drinks on adolescents, and 13 clinical trials from the age group of 0-17 were conducted. No FDA recalls have been observed for energy drinks or the top 4 brands within the US (by sales; Red Bull, Monster, Bang Energy, Rockstar), though some recalls regarding container manufacturing were made outside the US. ED visits from energy drinks doubled from 2007 to 2011 with 1/10 of them resulting in hospitalization. 58% of the total ED visits were exclusively related to energy drinks. It is anticipated that survey results will indicate trends of frequent caffeine/energy drink consumption among college students for studying, but students will not have a clear understanding of recommended caffeine intake. DISCUSSION/SIGNIFICANCE: Due to the lack of regulations and studies surrounding energy drinks, the dangers (as seen from ER visits) to public health are concerning. Regulatory agencies should invest in developing new protocols or regulations regarding the content of energy drinks as well as find ways to monitor the marketing strategies more closely behind them.

OBJECTIVES/GOALS: Collaborations are at the core of translational science and team science. Differences by gender have been identified in various research contexts from recruitment to retention to promotion. This study assesses the relational associations of translational collaborations, and what role of gender. METHODS/STUDY POPULATION: In 2011 and 2013, clinical and basic sciences investigators at University of Rochester School of Medicine and Dentistry responded to an online survey nominating their research collaborators. Two study years were merged, and name lists were transformed into a collaboration network. Departments were classified into basic sciences (e.g. biochemistry) and clinical (e.g. urology). If respondent and partner were affiliated to different department classes, the collaboration was defined as translational. Multi-level GLM models were developed to assess the associates of the likelihood of translational vs. within discipline collaborations. Partner nominations were nested in respondents. RESULTS/ANTICIPATED RESULTS: 202 respondents were included in the multi-level GLM models. A collaboration was more likely to be translational if the respondent shared more collaborators with the partner (OR:1.13), and respondent was a central actor in collaboration network (OR: 1.2). Translational collaborations were less likely to be reported by clinicians (OR: 0.25). In the model to assess gender match, a collaboration was more likely to be translational if the respondent was male, and nominated a male partner. For both genders, collaboration with a partner of the opposite gender was more likely to be translational if respondent had more shared collaborators with the partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Translational collaborations happen in teams. Gender homophily exits in translational collaborations, and is reduced by shared collaborators; implying the effect of personal connections and community membership. Community-building interventions may increase diversity in translational collaborations.

OBJECTIVES/GOALS: Diabetic Kidney Disease (DKD) is a common diabetes complication, often linked to end-stage renal disease in the United States (US). While autophagy and miRNAs are pivotal, miR-451’s specific role remains understudied. Our study explores its renoprotective effects in an accelerated DKD mouse model. METHODS/STUDY POPULATION: We assessed the effect of miR-451 mimic treatment on Diabetic Kidney Disease (DKD) in BTBR ob/ob mice, known for their rapid DKD-like renal lesions. Mice were divided into four groups: WT (wild-type), BTBR ob/ob, WT+miR-451 (wild-type with miR-451 mimic), and BTBR ob/ob+miR-451 (BTBR ob/ob with miR-451 mimic). MiR-451 mimics were administered at 2mg/kg body weight once weekly for three consecutive weeks. We collected spot urine and monitored blood glucose levels at each time point. After the treatment period, mice were euthanized for kidney and blood samples. Western blot analysis assessed autophagy-related protein markers. Statistical analysis included Student’s t-test and ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: The study assessed the impact of miR-451 mimic treatment in BTBR ob/ob mice. Albumin:creatinine ratio increased fourfold (p=0.01) in BTBR ob/ob mice at 5 weeks. MiR-451 mimic treatment had no impact on body weight. Blood glucose levels were notably higher in both treated and untreated BTBR ob/ob mice at 12 (425±33.1 mg/dL; p=0.04) and 13 weeks (383±25.3 mg/dL; p=0.007). However, a significant drop occurred from week 13 (554.7±10.8 mg/dL) to week 14 (289±13.3 mg/dL; p=0.0002) in BTBR ob/ob miR-451 treated mice. Western blot analysis in whole kidney homogenates showed a 91% reduction (p=0.02) in YWHAZ, a predicted miR-451 target, in treated BTBR ob/ob mice and a 95% reduction (p=0.01) in WT mice. Furthermore, miR-451 mimic treatment led to a 68% increase (p=0.01) in ATG101 and a 44% increase in Beclin-1 in BTBR ob/ob mice. DISCUSSION/SIGNIFICANCE: The study uncovers miR-451-based interventions as a promising avenue to counter Diabetic Kidney Disease by modulating autophagy, potentially introducing novel therapies for at-risk individuals. However, practical DKD treatments will require further research and rigorous clinical validation to harness the full potential of these insights.

OBJECTIVES/GOALS: Vaginal delivery is typically avoided in extremely preterm breech fetuses due to the concern for head entrapment by the cervix. Development of a device to prevent head entrapment would be best addressed by a multidisciplinary approach incorporating engineering principles with clinical obstetrics. METHODS/STUDY POPULATION: Construction of a collaborative multidisciplinary team to address the clinical challenge of preventing head entrapment was initiated through a unique course at the Massachusetts Institute of Technology (Course 2.75, Medical Device Design). The course would provide a structured means by which students (senior undergraduate and graduate students in Mechanical Engineering) would be paired with a clinical advisor and faculty in their department. Weekly team meetings were scheduled to review the clinical context pertinent to the problem and review engineering principles needed to develop a solution. The course also provided a small monetary budget ($4K) for the students to purchase supplies. RESULTS/ANTICIPATED RESULTS: During the semester long course, several iterations of a prototype were designed. Each subsequent rendition was evaluated from both an engineering and manufacturing perspective, as well as clinical appropriateness. The weekly meetings allowed for rapid re-design and assured that all necessary parameters were considered by the entire team. Students also had access to lab facilities and additional mentorship that allowed for supplementary input beyond that generated by core team members. These interactions, along with those of their classmates working on other projects, provided a strong base for exploring subsequent device development. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful medical device development requires a collaborative process and students can be ideal members of these teams as they reside in an environment that is conducive to exploration and novel idea generation. Course-based student led team science platforms can provide an excellent foundation for solving uniquely challenging medical problems.

OBJECTIVES/GOALS: Food and Drug Administration (FDA) warning letters regarding misbranding of products intended to treat, prevent, or diagnose COVID-19 were used as a proxy for assessing misinformation on social media. The FDA database of Warning Letters was used to identify the largest misinformation contributor. METHODS/STUDY POPULATION: On November 9, 2022, the full dataset of warning letters dating back to January 1, 2018 was extracted from the FDA website. Separate datasets were also extracted using the search terms: Facebook’, Twitter’, YouTube’, and Instagram’. The data entries were organized by issuing office and subject. The subjects were then filtered to only include letters related to misbranding of products for COVID-19. Letters regarding medical devices, manufacturing practices, and adulterated products were excluded from the analysis. Cumulative totals were collected for the number of letters issued for each search term. These totals were stratified by year and scaled by platform size for relative comparison. RESULTS/ANTICIPATED RESULTS: The FDA’s Center for Drug Evaluation and Research issued the most letters related to misbranding of COVID-19 products, 153 out of the 2798 entries in the complete dataset. Analysis of the datasets by search term show: 53, 18, 24, and 17 letters were related to Facebook, Twitter, YouTube, and Instagram respectively. Forty-one letters were related to other non-social media sources. Facebook had the most letters issued, however when scaled to account for the size of each respective platform’s approximate user base, Twitter had the largest proportional amount of misinformation regarding agents for the management of COVID-19, followed by Facebook, then Instagram. Most letters were issued in 2020. DISCUSSION/SIGNIFICANCE: In light of COVID-19, many social media sites adopted policies to limit inaccurate information. The success of these efforts have been variable. Although Facebook is the largest absolute contributor assessed, greater attention should be given to the policies of other platforms utilized by the industry.

ABSTRACT IMPACT: This work will estimate current EPT implementation in Minnesota and provide cost-effectiveness analyses of different implementation scenarios to inform STI treatment policy. OBJECTIVES/GOALS: This research aims to 1) assess current implementation of Expedited Partner Therapy (EPT) as treatment for C. Trachomatis (chlamydia) and N. Gonorrhoeae (gonorrhea) among healthcare providers in Minnesota and to 2) simulate the current burden of chlamydia and gonorrhea infections to test the cost-effectiveness of increasing EPT implementation. METHODS/STUDY POPULATION: We will conduct key informant interviews (KII) and an online survey of health providers across the continuum of care for chlamydia and gonorrhea treatment. Based on experience in prior studies, the KII sample size is expected to be about 15 informants. KIIs will be carried out among providers who submitted EPT protocols to the Minnesota Department of Health to understand how EPT is currently being implemented. KII results will inform the online survey of health providers, which will estimate how many providers across the state provide EPT. We will distribute the survey through Minnesota health provider networks to achieve a sample of at least 500 health providers. The KII and survey results will inform model structure and parameter values for a compartmental cost-effectiveness model of EPT. RESULTS/ANTICIPATED RESULTS: Initial results from KII pilots suggest that EPT is primarily provided through a paper script for the sexual partner of a patient who tests positive for CT or NG by the treating provider. Less commonly, a patient’s partner who is already a patient in the health system may receive notification and treatment through the provider. While EPT is legal in Minnesota, concerns about medical liability for adverse reactions and difficulty obtaining paper scripts in electronic workflows are barriers to implementation. The statewide survey will include questions to estimate the likelihood of EPT provision among providers when these concerns are addressed. These figures will be integrated into the cost-effectiveness model to simulate outcomes and costs across different EPT implementation scenarios. DISCUSSION/SIGNIFICANCE OF FINDINGS: The statewide survey will define cost-effectiveness model parameters, including the proportion of providers in the state who currently provide EPT or would be willing to provide EPT under different scenarios. Study findings will be shared with health provider networks and health departments to inform STI treatment procedures and state EPT policies.

ABSTRACT IMPACT: Our work may be able to impact the examination and clinical decision making of a clinician to identify and target movement impairments to treat people with low back pain. OBJECTIVES/GOALS: Test if the magnitude of spinal control impairments is different in two clinical tests of lower limb movement in people with and without low back pain (LBP). The impairment is defined as the time difference between the start of limb to lumbopelvic motion. Also, test if the magnitude of impairments across tests is associated with LBP intensity and function. METHODS/STUDY POPULATION: 18 controls and 21 people with LBP (51.6% F, 34.5 ±11.5 yrs) participated in a cross-sectional, laboratory-based study. Subjects completed the modified Oswestry Disability Questionnaire (LBP-related functional limitation measure; 0-100%) and the Numeric Pain Rating Scale (LBP intensity; average pain prior 7 days; 0-10) self-report surveys and clinical tests of hip medial and lateral rotation performed in prone. A three-dimensional motion capture system was used to capture angular lumbopelvic and hip motion across time. A 2x2 mixed model ANOVA will be used to examine the effects of group, hip rotation test, and group x hip rotation test. Separate bivariate correlations will be used to quantify the association of magnitude of the impairment to (1) average LBP intensity and (2) LBP-related functional limitation. RESULTS/ANTICIPATED RESULTS: We hypothesize that, compared to healthy controls, people with LBP will display a greater magnitude of impairment across the hip medial and lateral rotation tests. In addition, we hypothesize that the magnitude of the difference in impairment between people with LBP vs controls will be larger during the hip lateral rotation test compared to the hip medial rotation test. Finally, we hypothesize that in people with LBP the magnitude of the impairments across tests will be associated with LBP intensity and LBP-related functional limitation. DISCUSSION/SIGNIFICANCE OF FINDINGS: If our hypotheses are supported, the hip rotation tests would further be recognized as a key part of a clinician’s examination and an important target for treatment of LBP.

Objectives/Goals: Ventilator-associated pneumonia (VAP) is an infection caused by bacteria, viruses, or fungi during mechanical ventilation. We analyzed a cohort of COVID-19 patients admitted to the intensive care unit with respiratory failure with different VAP outcomes. We hypothesize that the multiomics data can help predict VAP development within this cohort. Methods/Study Population: We recruited participants from a cohort on a NYU IRB protocol (i22–00616), who had COVID19 respiratory failure, admitted to ICU, and required invasive mechanical ventilation (n = 245). We collected and analyzed research specimens (bronchoalveolar lavage [BAL, n = 213], tracheal aspirates [n = 246], background [n = 18]) and clinical cultures (sputum and BAL) for 245 participants. A panel of experts adjudicated VAP within the cohort, resulting in 92 VAP diagnoses. We annotated metatranscriptome (Illumina NovaSeq) using a Kraken/Bracken database, and KEGG for functional annotation of transcriptome data (Illumina HiSeq). We used edgeR (v.4.0.16) to analyze differential expression of metatranscriptome and transcriptome data. Results/Anticipated Results: We diagnosed VAP in n = 92 (38%) participants. We found significant differences in days of overall hospital stay (p Discussion/Significance of Impact: VAP is a serious complication of mechanical ventilation, and oral commensals alter the lung microbiome and host immunity. We identified a transcriptome-metatranscriptome signature that identifies those at VAP risk. VAP was associate with both pro- and anti-inflammatory gene expression resulting in increased risk for lower airway infection.

OBJECTIVES/SPECIFIC AIMS: To analyze contemporary study design methods and clinical trial approaches in placebo research. METHODS/STUDY POPULATION: An analysis was conducted on the following studies: I. “Managing” the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models by RN Haden, et al. The objective of the study was to consider elements of the placebo response in the context of two pain models using a “single-blind placebo lead-in” design (SBPLI) by engaging the “placebo response” prior to randomization to active drug and placebo-controlled conditions. The methods of the study included two pilot drug trials using knee osteoarthritis (KOA) and non-radicular low back pain (LBP) subjects, SBPLI protocols were conducted. In the first study, 36 subjects with non-radicular CLBP were enrolled in a double-blind, randomized, placebo-controlled trial of hydromorphone ER. In the second study, a total of 42 subjects with chronic KOA pain were enrolled in a double-blind, randomized, placebo-controlled study of milnacipran. Gender and/or diagnosis affected placebo responses as observed in changes in patient self-reported pain, depressive and pain anxiety symptoms were examined. Additionally, the placebo response on performance-based tests (stair climbing, range of motion (ROM), sit to stand repetitions, and 6-minute treadmill distance) was evaluated. II. Randomized Placebo-Controlled Placebo Trial to Determine the Placebo Effect Size by L. Gerdesmeyer, et al. The objective of the study was to analyze the pure placebo effect on clinical, chronic pain through a blinded RCT. The methods of the study included 182 patients suffering from chronic plantar heel pain for over 6 months, who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. III. Open-label placebo treatment in chronic low back pain: a randomized controlled trial by C. Carvalho, et al. The objective of the study was to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. The methods of the study included 97 randomized participants in a 3-week randomized control trial comparing current treatment plus OLP to current treatment alone (TAU). RESULTS/ANTICIPATED RESULTS: N/a DISCUSSION/SIGNIFICANCE OF IMPACT: The aforementioned studies provide placebo researchers with contemporary and reliable methodologies to examine placebo effects on participants. These methodologies provide scientists with clinical translational research methodology styles based on the foundation of regulatory science.

OBJECTIVES/GOALS: Reveal common immune mechanisms in dysregulated age-related lobular involution (ARLI) and post-partum lobular involution (PPLI) to understand their link to increased breast cancer risk, challenging the traditional view of their distinctiveness. Ultimately, to improve breast cancer risk assessment and personalized prevention METHODS/STUDY POPULATION: The Mayo Clinic Benign Breast Disease (BBD) cohort comprises of ~20,000 women with benign biopsies, including ~1000 women with sequential benign biopsies. Lobular involution (LI) status was assessed by selecting perimenopausal women, ages 45-55, with sequential biopsies, comparing acini number and lobule size between initial and subsequent biopsies. NanoString IO360/ BC360 RNA profiling identified differentially expressed genes associated with dysregulated LI. Using multiplex immunofluorescence (mIF), I'll analyze and spatially map immune biomarkers related to dysregulated ARLI and PPLI in BBD tissue from perimenopausal women who did or did not go on to develop breast cancer, assessing the commonality of ARLI and PPLI markers and exploring their potential as risk biomarkers for breast cancer. RESULTS/ANTICIPATED RESULTS: Preliminary findings link patients who display dysregulated ARLI with an increased breast cancer risk and identify vital PPLI biomarkers in perimenopausal women. I expect the biopsies of women who developed post-menopausal breast cancer (PMBC) and post-partum breast cancer (PPBC) to exhibit elevated levels of dysregulated ARLI immune biomarkers and PPLI biomarkers. Spatially mapping these markers promises to provide a more comprehensive understanding of their interactions, potentially revealing common immunological pathways. These findings could transform our current paradigm of ARLI and PPLI as distinct processes and demonstrate their interconnection in shaping breast cancer risk. DISCUSSION/SIGNIFICANCE: PMBC and PPBC dominate majority of breast cancer cases. Both involve activation of the understudied process of lobular involution, which has been shown to have pro-tumorigenic traits. Elucidating these mechanisms will aid more efficient risk stratification and personalized prevention to reduce incidence and mortality of breast cancer.

Objectives/Goals: We aim to develop an intuitive interface to understand the possible relationships between data from different RNA-Seq technologies. It can help novice users and educators to understand, analyze, explain, and visualize such datasets from diverse platforms, all without the need for additional software installations or strong programming expertise. Methods/Study Population: An online interactive interface is developed, integrating robust algorithms for three distinct types of analyses: DESeq2 for bulk RNA-seq, CIBERSORTx for deconvolution, and Seurat for single-cell analysis, with plans to include more algorithms. It allows a demo mode for training using the sample datasets and option for tailored analysis using user’s partially processed data. The interface provides capability to process bulk RNA-seq data from raw counts or a differential gene list. Further, deconvolution analysis for bulk RNA-seq data can be done using raw counts and single-cell data analysis can be performed using processed sequence reads, organized into three key files: barcodes, matrix, and features. Users also have an option to download the results as a zipped file, for samples from human and mouse studies. Results/Anticipated Results: Users with an active internet connection can access the interface from any major web browser. They can adjust parameters – such as genome type, cutoff thresholds, and batch effect correction – according to their specific needs. Bulk RNA-seq results are presented in the form of volcano plots, heat-maps, clusters, gene expression across samples, DEGs, and enrichment plots from KEGG and GO analyses. Deconvolution analysis can be performed using either the “LM22” signature matrix (for human leukocyte cell types) or Derm22 (for skin-specific cell types). The single-cell workflow provides results including quality control metrics, UMAP clustering, gene expression plots/tables, and cluster annotation using CellTypist. Comprehensive details on methods and tutorials are available in the GitHub repository. Discussion/Significance of Impact: Although multiple workflows are available to process bulk and single cell RNA-Seq data along with deconvolution methods to bridge the gap between the two, this is the first online interface to provide the capability to explore and analyze data from all three approaches in one place, without requiring strong computational expertise or resources.

OBJECTIVES/GOALS: To identify, categorize, and streamline the wide range of commonly encountered barriers in translational research that prevent studies from progressing along the translational research spectrum through a comprehensive needs assessment survey. Results will be utilized to institute potential solutions to overcome these identified barriers. METHODS/STUDY POPULATION: The comprehensive survey consisted of three sections, Demographics and Background, Self-Reporting of Barriers, and Comments and Feedback. An extensive literature review was conducted to develop and compile questions and barrier categories for the survey. The survey content was derived from primary literature sources and supplemented with the NCATS Translational Science course material. The target population for the survey included all researchers engaged in translational research at the NJ ACTS CTSA hub. The hub includes Rutgers, Princeton, and NJIT and all of their affiliated institutions and partnered healthcare systems, such as Robert Wood Johnson Barnabas Health and University Hospital. Results will be analyzed according to the type of research conducted and stage of translation research (T0-T4). RESULTS/ANTICIPATED RESULTS: Examples of the survey barrier categories being analyzed include Regulatory/IRB, Funding, Collaborations and Networking, and Training. Initial analysis (N=106) consisted of these top barriers in the NJ ACTS CTSA hub: obtaining timely IRB approval, inadequate staffing for the research team, and lack of holistic institutional support. After completion of data collection, the survey results will be further analyzed to determine common barriers and patterns in barrier type across the different institutions, schools, positions/roles in research, and translational research stages. Given that the Comments and Feedback section of the survey entailed ranking the top three barriers across the entire survey as a whole, the results will also indicate the relative prevalence of specific barriers and categories. DISCUSSION/SIGNIFICANCE: The impact of the survey and its results is to develop feasible institutional solutions to overcome the prevalent barriers and improve efficiency in all parts of the research process. Possible solutions encompass accessible resources for researchers, longitudinal training programs, consultative services, and workshops for investigators.