OBJECTIVES/GOALS: Lack of diversity within clinical trials is well known, but there is little data on the use of investigational products through other pathways, such as expanded access. This project sought to determine the demographic diversity of patients benefiting from expanded access at Michigan Medicine. METHODS/STUDY POPULATION: Previous quality improvement reviews provided the list of 271 patients for whom a single-patient, expanded access request had been approved by the FDA and University of Michigan IRBMED between 2005 and 2021. Demographic information was collected through the EMERSE tool, including age, legal sex, race, ethnicity, and zip code. These data were cross-referenced with available regulatory documentation on product requested, treatment area, and date of request. Descriptive statistics were performed using Excel. RESULTS/ANTICIPATED RESULTS: Patients who were approved to use an investigational product through expanded access at Michigan Medicine showed a wide geographic distribution, including 48 Michigan counties, 20 states, and 1 province. All age groups were served, with those between 30-49 underrepresented and those under 10 and over 60 overrepresented. Race data generally followed the proportions of the Michigan state census, including 76% white and 14% black or African American (expected: 79% and 14%) and 48% female (expected: 50%). On further breakdown, populations differed by specialty and county. DISCUSSION/SIGNIFICANCE: The distribution of Michigan Medicine patients with approved expanded access requests was similar to the population of Michigan with respect to age, sex, and race. Further research is needed to determine if this reflects equitable use or if these results are generalizable to other institutions.

OBJECTIVES/GOALS: The purpose of the project was to create a Tableau dashboard to track metrics on requests for research data at Atrium Health Wake Forest Baptist. The objectives included: 1) define and identify request fulfillment metrics, 2) build a dashboard to capture metrics, and 3) integrate the dashboard into metrics tracking and reporting activities. METHODS/STUDY POPULATION: Project managers and team leaders in the Office of Informatics collaborated to determine which measures would be most relevant and impactful to report on. Metrics that were collected included: total count of tickets fulfilled over time, number of tickets currently open, sum of outstanding quoted hours, quoted hours vs. actual hours needed to fulfill ticket, and hours billed. Tableau's direct connection feature was used to extract the Trac ticket data from its Postgres database and the dashboard was published to Tableau Server. After the initial draft was created, several rounds of revisions were made as new data insights were discovered through further investigation of the data. RESULTS/ANTICIPATED RESULTS: Each morning, Tableau Server runs an automatic refresh of the data. On the dashboard homepage, users can see a quick view of all available metrics; to minimize noise, only the current statuses, active tickets, and stats for the most recent monitoring periods are displayed. Many of the charts give the user the option to link out to a page with related supplemental information (historic data, ticket status history, etc.). With the help of the dashboard, project managers and team leaders can now monitor how long tickets are in each status, increase quote accuracy using the hours quoted and hours billed charts, and examine ticket complexity over time. DISCUSSION/SIGNIFICANCE: Prior to dashboard creation, metrics were sparse and difficult to assemble. By providing information on the quantity, size, and complexity of data requests, the dashboard enables the Office of Informatics to monitor how the process is functioning overall, make informed decisions about resource allocation, and provide quick interventions.

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.

OBJECTIVES/GOALS: CTSA Program hubs provide a wide range of research support services (funding, training, consultations, etc.) to individuals and teams. The CTSA Program hub at Columbia University seeks to identify best practices across CTSA hubs in how they facilitate researchers to identify, navigate, and access services at complex academic medical centers. METHODS/STUDY POPULATION: o A landscape analysis across CTSA Program hub websites was conducted during December 2021-February 2022, with the goal of assessing the availability of research navigation services and the ease of accessing and requesting research support services at each hub. Websites of 66 CTSA hubs were accessed and browsed for the following: 1) if a research navigation or concierge service was available; 2) how to request and apply to use common services such as pilot funding, biostatistics, clinical research services; 3) if there was a contact form and/or email address for general inquiries. Binary coding (1=Yes, 2=No) was used to track and summarize if these features were available, and then further classification and observations were noted into the full data set. RESULTS/ANTICIPATED RESULTS: The landscape analysis determined that 68% of CTSA hubs offer a form of research navigation including consultative models (personalized guidance, studios) and web-based models (self-service web portals, graphics, toolkits). Consultative models could be classified into three levels of support ranging from general information sharing to providing scientific expertise to convening more intensive studio sessions. 92% of CTSA hubs have at least 1 system in place for researchers to request services with a majority of hubs using a mix of tools and systems. In addition, 36% of hubs have additional general contact forms and 75% have general email addresses to assist researchers in obtaining more information. DISCUSSION/SIGNIFICANCE: There is a relative lack of data and information on the effectiveness of different research navigation models across the CTSA network, and barriers for researchers to identify services remain (Elworth et al). Our team is planning additional evaluations including interviews with leaders at other CTSA hubs and researchers and trainees at Columbia.

OBJECTIVES/GOALS: The Learning Health System (LHS) framework at Columbia University Irving Medical Center (CUIMC) aims to optimize health system performance through enhancing the patient and care team experience, reducing inequities, costs and improving population health outcomes, through a collaborative, interdisciplinary and data driven approach. METHODS/STUDY POPULATION: In alignment with the Quintuple Aim, the LHS program at CUIMC is composed of five critical components: data integration (particularly using Epic EHR and real-time informatics data), utilization of evidence-based practices, a methodology for continuous improvement, and leadership commitment. Our methodology incorporates an iterative process improvement project cycle into an integrated infrastructure and governance of an academic medical center and its hospital partners to fulfill rapid project design and implementation. The LHS at CUIMC aims to bring a cultural shift through stakeholder engagement, symposia, training, accelerated pilot award opportunities, and building external partnership engagement. RESULTS/ANTICIPATED RESULTS: At CUIMC, our definition of a successful integration of a LHS framework is a cultural shift in thinking, method, and continuous improvement. The LHS program has developed multidisciplinary teams that are involved in defining and sharing data, design, and project management resources. In 2021, the first annual symposium was launched and brought together over 200 stakeholders from across the organization to support continuous education, training, and scaling of the framework. As a result of this foundation, two pilot initiatives have been funded and launched, the innovation accelerator model developed and is supporting over ten unique innovative and transformative clinical and operational programs, and several research grant applications have been submitted citing learning health system methodologies. DISCUSSION/SIGNIFICANCE: Our LHS framework has broken down silos and institutional barriers, creating a network of stakeholder groups. Our interdisciplinary approach has enabled us to create sustainable processes, resources and training on rapid, rigorous design, evaluation and implementation of interventions using real-time informatics data and digital health tools.

OBJECTIVES/GOALS: The goal of this project is to develop a strategy to collect and extract published evidence in real time and to house and model these data for efficient downstream application to Program activities such as targeted reviews, grant evaluation and partner engagement. METHODS/STUDY POPULATION: We created the World Trade Center Health Effects Library in 2016. Today, this living review is ongoing and is fueled by daily systematic searches of online publication databases. Each day we screen new references for health effects of 9/11. The publication must include measurements, reports, or discussion of 9/11 health effects. If a publication meets these criteria, it is categorized by outcome and funding category. Primary outcome category data, reference metadata, and funding data are then made immediately available for programmatic analysis. All reference data are entered into a data pipeline and modelled for targeted reviews. RESULTS/ANTICIPATED RESULTS: The WTC Health Effects Library curates 1932 references and adds an average of 60 new references each year on a wide range of study populations, exposures, and conditions. The completeness of the library has been verified by comprehensive literature searches for 9/11 health outcomes conducted externally and by CDC Library staff. As a result, the curated library is a proven alternative to a lengthy literature search and allows the Program and stakeholders to explore the data and engage immediately in targeted reviews on curated topics. The data that are collected in the screening and categorization process are merged with publication metadata and funding data to inform a data pipeline that supports outputs such as interactive visuals, charts, reports, and curated bibliographies for structured review. DISCUSSION/SIGNIFICANCE: This living review allows the Program to rapidly conduct focused reviews, to evaluate grants, and to communicate accurate data to partners. By using the curated data, we have reduced the time required to perform mandated evidence reviews by weeks, have conducted two structured reviews, and defined gaps in research maturity and health equity.

OBJECTIVES/GOALS: Obesity is associated with increased incidence of breast cancer (BC), yet is not included in many lifetime-risk calculators. Obesity may impact breast cancer screening sensitivity. Retrospective studies show that bariatric surgery is associated with a lower risk of BC, but the effects of surgical weight loss on breast tissue are poorly understood. METHODS/STUDY POPULATION: We proposed a mixed-methods before and after study design to investigate the effects of surgical weight loss on breast tissue via pre- and post-weight loss breast tissue biopsies and imaging. In addition, we aimed to better understand barriers to BC screening for patients with obesity by conducting qualitative interviews. With institutional review board approval, we have begun recruiting 14 cisgender women who plan to undergo Roux-en-Y gastric bypass or sleeve gastrectomy. Participants must be at least 40 years old, with no prior history of breast biopsies or breast cancer and will undergo comprehensive breast cancer screening including mammography with quantitative density assessment, breast MRI, as well as breast core biopsies. RESULTS/ANTICIPATED RESULTS: We hypothesize that obesity and its associated metabolic changes lead to altered breast stroma, including increased inflammation, and tissue stiffness, with subsequent risk of carcinogenesis. If true, we expect to find obese women will have measurably increased inflammatory markers in their breast tissue, which are reduced after bariatric surgery. We expect that change in mammographic density may correlate with fibroglandular volume change on MRI; there are little data on change in background parenchymal enhancement in the setting of obesity and weight change and quantifying this will provide preliminary data for future work. Last, we expect that undergoing BC screening will be easier for patients after weight loss due to constraints of imaging equipment and potential bias in the screening process. DISCUSSION/SIGNIFICANCE: Screening for BC is paramount to improving outcomes yet people with obesity are screened less with worse outcomes. Studying the effects of weight loss on the breast may improve interpretation of breast imaging in the setting of obesity and identify markers of risk. Understanding barriers to screening may help us develop strategies to improve screening.

OBJECTIVES/GOALS: The SC CTSI Quality by Design (QbD) program aims to improve the execution of clinical research studies identifying and addressing possible issues before implementation. The program’s overall goal is to optimize operational design to achieve an 80% on-time completion rate. METHODS/STUDY POPULATION: Adapted from the Clinical Trials Transformation Initiative, our QbD program applies principles of quality management, project management, and team science to SC CTSI-funded studies. The process begins with a Design Studio for systematic review of critical-to-quality factors and a discussion of risks and mitigation plans. Studio attendees generally include the research team, SC CTSI faculty, and at least one community member. Outcomes include mitigation plans, a study project plan, and continued support from the project-tailored advisory board. We will iteratively evaluate satisfaction, quality improvement, and study completion rates. RESULTS/ANTICIPATED RESULTS: In an evaluation of the pilot phase, QbD participants responded that careful planning and expert input added value to their studies. The QbD process improved the quality of their studies, and all participants plan to apply QbD tools and resources to future studies. Beyond quality improvement, other anticipated outcomes include higher on-time study completion rates and uptake of QbD resources by other research teams. We also plan to assess the comparative benefit of QbD by study type. DISCUSSION/SIGNIFICANCE: Broader application of the CTSI QbD program has the potential for widespread benefit on research processes and outcomes. Studies implemented with minimal avoidable errors are more likely to complete on time, helping ensure efficient use of valuable resources and participant time.

OBJECTIVES/GOALS: To increase public awareness and access to research opportunities at the University of Minnesota (UMN) utilizing StudyFinder, a public-facing website that features actively enrolling UMN research studies and directly connects website visitors with study teams. METHODS/STUDY POPULATION: Promote the University of Minnesota CTSI’s StudyFinder website to the public via social media ad campaigns and community outreach. Upon completion of the latest StudyFinder enhancement project in 2021, CTSI focused 2022 efforts on marketing and promotion of the site. CTSI created three StudyFinder social media ad campaigns in January, June, and October. CTSI also planned outreach events during the week of Clinical Trials Day, the Minnesota State Fair (1.8M attendees over 12 days), and the UMN’s Urban Research and Outreach-Engagement Center Community Day. RESULTS/ANTICIPATED RESULTS: Website traffic data from Google Analytics indicated a 72.76% increase in StudyFinder sessions from 2021 (Jan 1, 2021 to Nov 1, 2021) to 2022 (Jan 1, 2022 to Nov 1, 2022), with 16,262 sessions to 28,094 sessions, respectively. Direct emails from potential participants to study teams increased 89% in that same timeframe, from 3,082 emails to 5,819 emails. Targeted marketing campaigns and attending community events can improve the visibility of an institution’s research and connections of potential research participants to research teams. DISCUSSION/SIGNIFICANCE: Recruitment remains a main challenge in clinical and translational research. StudyFinder is an important patient-facing tool to connect individuals to specific studies. Future directions include expanding marketing efforts, events, and public feedback.

OBJECTIVES/GOALS: In 2020 the Georgia CTSA Clinical Research Center site at Emory University developed a highly trained, credentialed research coordinator pool with a goal to expand the pool to include clinical research coordinators from our partner institutions with the ability to work across institutional barriers in support of Georgia CTSA investigators. METHODS/STUDY POPULATION: Fall 2022, an Emory Investigator requested Georgia CTSA Biorepository samples with supporting clinical data for a NIH funded study. This provided a pilot opportunity to utilize clinical research nursing support offered by the UGA Clinical and Translational Research Unit (CTRU). De-identified samples were collected from our Biorepository while Emory’s coordinators and lab collaborated with UGA’s nursing support for data collection. Our obstacle for cross-institutional support was access to Emory Healthcare (EHC) medical records that would be needed by the UGA nurses, but partnerships created with the Georgia CTSA allowed us to overcome this, granting access to the electronic medical records (EMR) needed to complete the study. RESULTS/ANTICIPATED RESULTS: As expected, the process of credentialing and gaining access to the EHC EMR for the UGA team was the most time-consuming in the development of the pool. Discussions began in June 2021 to determine needs to allow the UGA research nurses to support the Emory coordinator pool. Requirements included acquiring an EHC network ID, completion of required Emory research training, letters of support from the Georgia CTSA outlining the collaboration between institutions, and a credentialing application. All steps were completed in May 2022 and the team began to identify studies that could benefit from this collaboration. Given that all credentialing and access needs were in place, the team was able to initiate the study and complete all study requirements, from sample identification to data collection and clean up, in five weeks. DISCUSSION/SIGNIFICANCE: Workforce shortages of experienced clinical research coordinators make it imperative to overcome barriers presented by institutional rules in order to efficiently utilize available resources to conduct high quality research. The CTSAs provide the perfect opportunity for partner institutions to develop processes to allow support across sites.

OBJECTIVES/GOALS: The goal of the Hatchery is a new approach to de-risk innovative life science ideas within an entrepreneurial setting. The Hatchery creates value by vetting the initial potential through experimental testing. METHODS/STUDY POPULATION: In this study we took a functioning wet laboratory space that was vacant due to principle investigator movement, and created a pipeline for its use in life science startup formation. A functioning laboratory can remain unoccupied for a notable period with transitions of research leadership. At the same time, a life science startup company who is testing core principles of their technology need wet lab space at an affordable cost. Our solution called the Hatchery provides startup companies a state-of-the-art wet laboratory space, next to a research hospital, for a very short duration of time and minimal fee. This novel approach allows preliminary validation of a technology for initial NIH SBIRs and STTRs funding pathways. RESULTS/ANTICIPATED RESULTS: Initial findings demonstrated the effectiveness of the Hatchery method. Our pilot study included five different life science startups company tenants. Each company was enabled to de-risk technologies and secure a phase 1 SBIR/ STTR funding or resulted in an exit via acquisition. DISCUSSION/SIGNIFICANCE: Entrepreneurship is a growing approach for testing and expanding new research areas. The Hatchery model makes use of existing space and infrastructure, can scale with an entrepreneurial community, and can serve as critical pilot data for a more permanent space commitment.

OBJECTIVES/GOALS: Evaluate effectiveness of participant recruitment service to improve study enrollment through customer feedback surveys and recruitment data obtained by research teams utilizing services. Use survey information to conduct gap analysis of additional support needed for participant recruitment. METHODS/STUDY POPULATION: Participant enrollment is often cited as one of the most challenging aspects of clinical research. In 2021, the Indiana CTSI used project management techniques to design and pilot a Team Science approach for providing participant recruitment support to clinical research teams. This service called the Indiana CTSI Recruitment Concierge Service (RCS) is comprised of recruitment, community engagement, social media, communications, and project management expertise. Additional experts are chosen to participate based on the study needs (regulatory, population insight, informatics, clinical services, etc.) RCS customers are comprised of study teams from a variety of areas and research experience. These customers are sent surveys to evaluate the support they received and provide suggestions for improvement. RESULTS/ANTICIPATED RESULTS: The RCS assisted 72 study teams in 2021 and 85 (as of November) in 2022. These studies were referred via word of mouth as no advertising of the service had been done to date. All customers were provided a study specific consultation with recommendations of services and resources that would assist their study. Some services recommended were: local study listing and volunteer registry (All IN for Health), digital marketing support, materials design expertise, community engagement and healthcare patient recruitment guidance. The overall feedback from RCS customers has been positive with most teams indicating the support improved their study recruitment and/or engagement plan. RCS will use information obtained to develop a strategy for prioritizing services due to the overwhelming number of requests received. DISCUSSION/SIGNIFICANCE: Using project management techniques and a Team Science approach, the Indiana CTSI was able to develop a comprehensive participant recruitment service that integrates clinical research operations, community engagement, and informatics expertise to design study specific recruitment plans and coordination of services.

OBJECTIVES/GOALS: Poor housing conditions and quality can be linked with residents’environmental exposures, which may contribute to a variety of adverse health outcomes. This systematic literature review will examine literature around housing, environmental exposure, and health; and policy implications to reduce the impact of housing on environmental exposures. METHODS/STUDY POPULATION: This systematic literature review will identify and evaluate published peer-reviewed articles as well as governmental and NGO policy briefs relating to connections between housing quality and condition, neighborhood characteristics, and environmental exposures (e.g., lead poisoning, secondhand smoke, PFAS chemicals) in the United States; and will particularly focus on health implications of such environmental exposures, racial/ethnic and socioeconomic disparities in exposure, and current and future policy recommendations to alleviate the association between housing and environmental risk. A computerized literature search of relevant electronic databases (e.g., PubMed, Sociological Abstracts, EPA database, Congressional database) for literature published after 2000 will be conducted. RESULTS/ANTICIPATED RESULTS: The findings from this literature review will be split up into categorizations around (1) the contribution of housing/neighborhoods on resident environmental exposure; (2) geospatial and demographic inequality (historic and current) around housing/neighborhood conditions contributing to disproportionate environmental exposures for low-income and minoritized residents; (3) health implications of environmental exposures; (4) prior policy addressing the connections between housing/neighborhoods and environmental risk; and (5) future policy recommendations to improve housing/neighborhood quality and minimize environmental exposures for residents. DISCUSSION/SIGNIFICANCE: This project will illuminate connections between housing conditions and environmental exposures, health implications of these exposures, and contribute to advancing understanding of potential policies to reduce adverse environmental health impacts of poor housing conditions for residents (particularly for low-income, minoritized groups).

OBJECTIVES/GOALS: To apply implementation science strategies to evaluate the impact of the 2016 Pennsylvania (PA) Medicaid payment policy change on hospital-level access to immediate postpartum long-acting reversible contraception (IPP LARC), an evidence-based strategy to increase contraceptive access; to identify differences by rurality and academic status. METHODS/STUDY POPULATION: We conducted a web-based, IRB-exempt survey of Labor and Delivery (L&D) leaders at all PA hospitals in Summer-Fall 2022, assessing hospital characteristics, contraceptive practices, and facilitators/barriers to IPP LARC implementation, using concepts from health services studies of small subsets of implementing hospitals; we translate these concepts into policy evaluation by sampling the complete population of Pennsylvania hospitals with active L&D units. L&D hospitals were characterized as sustainers if they implemented by 2019 and continued to provide IPP LARC, as implementers if they implemented IPP LARC in 2020-22, and non-implementers if they had not started the process. We use the Center for Rural Pennsylvania definition of rural: counties with RESULTS/ANTICIPATED RESULTS: We collected data from 48/74 (64.9%) hospitals with L&D units. Hospitals were heterogenous with 18/48 (37.5%) in rural counties and 15/48 (31.3%) identifying as academic. A minority of hospitals provide IPP LARC, with 17/48 (35.4%) offering implants and 16/48 (33.3%) offering intrauterine devices (IUD) immediately postpartum. Before the PA Medicaid payment policy change, few offered implants [4/48 (8.3%)] or IUDs [1/48 (2.1%)]. Non-rural hospitals implemented IPP LARC more often and on an earlier timeline than rural hospitals: [7/30 (23.3%) v 3/18 (16.7%)] sustainers, [5/30 (16.6%) v 2/18 (11.1%)] implementers. Common facilitators include clinical champions, meeting patient needs, and adequate knowledge. Planned analyses include implementation barriers, and impact of external implementation support. DISCUSSION/SIGNIFICANCE: Despite unmet need in rural populations for evidence-based contraception, rural hospitals were less likely to implement IPP LARC. Implementation support should be designed to meet the needs of rural hospitals. Implementation science methods can be translated to evaluate the impact of healthcare policy on access to care.

OBJECTIVES/GOALS: This investigation aimed to develop and validate a subject-specific finite element analysis (FEA) model with subject-specific mechanical loads during walking and to use this method to compare mechanical stresses between transfemoral and transtibial osseointegrated (OI) implants. METHODS/STUDY POPULATION: One patient with a unilateral transtibial OI prosthesis and one with a unilateral transfemoral OI prosthesis participated in motion analysis to collect kinematics and ground reaction forces during overground walking. Subject-specific musculoskeletal models were created, and static optimization was used to estimate muscle and joint reaction forces throughout walking. 3D FEA models of the tibia, femur, and implants were created using ScanIP and exported into ABAQUS CAE. Muscle forces were applied at corresponding origin/insertion locations, determined from the musculoskeletal models [7]. Fixed boundary conditions were applied at proximal joint centers, and bone stresses throughout gait were calculated. OpenSim and FEA derived estimates of joint reaction forces were compared for validation. RESULTS/ANTICIPATED RESULTS: A maximum stress of 65.53 MPa and 60.70 MPa was observed at the bone-implant interface for the transtibial and transfemoral patients (respectively) in the late stance phase of the walking task, corresponding to terminal stance and heel off. Averaged root mean squared errors of the walking task (in the anterior-posterior, inferior-superior, and medial-lateral directions, respectively) for the transtibial and transfemoral patients were (124, 152, 80) N, (71, 80, 30) N, and (190, 62, 30) N, respectively. DISCUSSION/SIGNIFICANCE: The purpose of the above study was to develop a methodology for determining subject-specific mechanical loads during walking using finite element analysis and compare mechanical stresses in patients with transfemoral and transtibial OI. Similar stresses between the two implant types were found.

OBJECTIVES/GOALS: Non-Typhoidal Salmonella causes over 95 million infections globally each year, and no effective vaccine exists to combat infections in humans. The goal of this study is to determine the immune protection provided by a novel extracellular vesicle (EV)-based vaccine generated using lab-strain Salmonella against wastewater-derived Salmonella. METHODS/STUDY POPULATION: We isolated Non-Typhoidal Salmonella (NTS) from raw influent wastewater samples collected from two wastewater reclamation facilities (WRF) in Gainesville, FL. Whole genome sequencing was performed on each isolate and compared to sequences of clinically-derived isolates in FL during our study period to identify a clinical and subclinical isolate for assessing EV based vaccine protection. Mouse serum and stool samples were collected from a cohort of EV-vaccinated mice. Surrogates of protection against Salmonella used anti-Salmonella IgA in the feces of these mice, and anti-Salmonella IgG in serum of the mice, by using ELISAs coated with whole cell lysate collected from the two wastewater-derived isolates. RESULTS/ANTICIPATED RESULTS: We have previously shown that an EV vaccine provides protection against Salmonella enterica Serovar Typhimurium, the serovar used in the generation of the EV vaccine. We anticipate that the EV vaccine generates additional protection against the community-acquired strains, which will be characterized by increases in fecal IgA and serum IgG against two community Salmonella isolates that is similar to responses against the serovar used to generate the EV vaccine (Typhimurium). DISCUSSION/SIGNIFICANCE: This study will improve the translation of our vaccine studies by demonstrating the efficacy of our novel EV vaccine against circulating Salmonella isolates.

OBJECTIVES/GOALS: Fetal glucose dynamics mediate many of the adverse outcomes seen in infants of diabetic mothers (IDM). The goals of this study are to identify: (1) rates of blood glucose change in normoglycemic and hypoglycemic IDM; (2) their relation to in-utero insulin exposure; and (3) their transcriptional impacts on placental and umbilical vasculature. METHODS/STUDY POPULATION: Using a longitudinal prospective study design, placental/umbilical cord tissue and maternal hemoglobin A1c (HbA1c) are being collected from mothers diagnosed with Type 1, Type 2, or gestational diabetes mellitus. Blood glucose levels are also collected from their infants at birth, and every 3-4 hours for up to 9 hours to determine the rate of change. Linear regression modeling will be used to determine associations between placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic sub-type. Gene expression from endothelial specimens will be compared between diabetic sub-types and between normoglycemic and hypoglycemic infants via paired t-tests using Benjamini-Hochberg procedure for false discovery rate correction. RESULTS/ANTICIPATED RESULTS: We hypothesize the following; (1) glucose levels will have a steeper rate of change in hypoglycemic infants; (2) maternal HbA1c and in-utero insulin levels will correlate with the level of transcriptional change identified in placental and umbilical endothelial samples; (3) a negative association will exist between cord insulin levels and the rate of change in infant glucose levels; and (4) a positive association will exist between cord insulin level and transcriptional change on the placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Identifying gene expression changes in diabetic placental/umbilical endothelium, and the role of insulin/glucose in these changes, is key to managing diabetic vasculopathy and its adverse outcomes. Understanding infant insulin response may also guide management of hypoglycemia and decrease the risk for neonatal intensive care unit admission.

OBJECTIVES/GOALS: Research on the safety of perinatal kratom use - an herb that acts on opioid receptors - is scarce. Our transdisciplinary clinical and translational science (CTS) team is conducting parallel qualitative analyses of subreddit posts related to kratom use during (1) pregnancy and (2) breastfeeding. METHODS/STUDY POPULATION: Pregnancy- and breastfeeding-related keywords are being used to extract posts and selected metadata from the following subreddit communities: r/kratom, r/quittingkratom, r/pregnant, and/or r/breastfeeding. After the removal of duplicate posts, posts written in a non-English language and those that state in the post text and/or title that they were published by minors ( RESULTS/ANTICIPATED RESULTS: Among the eligible posts, the number of unique usernames of the sources publishing the posts; the range of publication dates; and the mean, median, & range of the number of comments per post will be presented. Inter-rater concordance in thematic coding will be computed. A word cloud will be created with the most used nouns from the eligible posts. Verbatim quotes will be shown to illustrate themes depicted in the sample. The quantitative and qualitative analyses will be conducted separately for the posts related to kratom use during pregnancy and breastfeeding. DISCUSSION/SIGNIFICANCE: These findings could assist clinicians in identifying questions that obstetric patients may have regarding the perinatal use of this emerging substance of concern. Further research is needed to validate these findings using other social media data, such as Twitter.

OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.

OBJECTIVES/GOALS: Selinexor is a novel XPO1 inhibitor that blocks nuclear export, thus impairing DNA repair and causing apoptosis. Our goal was to conduct preclinical and clinical studies to test our hypothesis that selinexor’s efficacy is boosted by priming with temozolomide and is associated with a tissue biomarker. METHODS/STUDY POPULATION: We leveraged a team science approach through the NCI Cancer Therapy Evaluation Program (CTEP) to design preclinical experiments, develop a novel RNAseq analysis pipeline, and use pre-existing clinical experience to open an early phase clinical trial for recurrent glioblastoma. Team members included a CTEP medical officer, cancer biologist, pharmacist, industry scientist, translational scientist, and early career clinician scientist mentored by an expert clinician scientist. Based on preclinical results, participants in the clinical trial experimental arm will receive sequential temozolomide 150mg/m2 on days 1-5 and a starting dose of selinexor 60mg on days 8 and 15 of a 28-day cycle. Participants in the control arm will receive monotherapy temozolomide. RESULTS/ANTICIPATED RESULTS: Sequential treatment of U87 cells and intracranial xenografts had superior DNA damage (É£H2A.X, cleaved PARP) and overall survival compared to combination or single-agent (HR 0.25 [95% CI, 0.07-0.84]; p=0.01, log-rank). We used the top-scoring gene pair method to identify an RNAseq signature associated with response to selinexor. We then designed a trial for first recurrent MGMT methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and validation of a molecular signature. Phase 1 dose finding (n=12) will be followed by a randomized phase 2 (n=72); using proportional hazards regression, RHR 0.5 with p DISCUSSION/SIGNIFICANCE: The NCI CTEP Project Team employs team science as a framework to successfully develop multidisciplinary collaborations, build investigator trial experience, and lead the way to future research opportunities. Our trial addresses a significant unmet need to offer novel therapies and molecular biomarkers in glioblastoma.