OBJECTIVES/GOALS: The primary research goal was to identify brain alterations reliably associated with obesity using coordinate-based meta-analysis. A secondary goal was to compare brain alterations in metabolically healthy (MHO) and unhealthy (MUO) obesity. METHODS/STUDY POPULATION: Source data were peer-reviewed studies reporting locations of gray-matter alterations in group-average, case-control contrasts (obese vs. non-obese) cohorts, performed in a whole-brain, voxel-wise manner. Both voxel-based morphometry and voxel-based physiology studies were included. Three coordinate-based meta-analyses were performed: Pooled (MUO + MHO), MHO, and MUO. RESULTS/ANTICIPATED RESULTS: Thirty-two studies reporting a total of 50 case-control contrasts (MHO, 23; MUO, 27) met inclusion criteria, representing 3,368 participants (obese, 1,781; non-obese, 1587). The pooled analysis yielded 8 cerebral foci (3 nuclear, 5 cortical) in regions implicated in reward-seeking, cognitive, and interoceptive behaviors. MHO yielded 7 cerebral foci (4 nuclear, 3 cortical), partially overlapping Pooled results, with similar behavioral loadings. The MUO pattern was distinct, with 3 cerebellar and 1 occipital foci. DISCUSSION/SIGNIFICANCE: Brain alterations occurred reliably in obesity. The dominant pattern (Pooled & MHO) involved cerebral reward-system circuits, evident even in metabolically healthy obesity. Cerebellar alterations occurred exclusively in metabolically unhealthy obesity, a pattern previously reported in metabolic syndrome.

OBJECTIVES/GOALS: The purpose of this study is to develop a clinically relevant mouse model of Radiation-Induced Heart Disease (RIHD) and characterize the resulting phenotype to find biomarkers and therapeutic targets as well as to understand the changes in cellular and molecular mechanisms of bioenergetics. METHODS/STUDY POPULATION: We used a two-beam method in the axillary region targeting the heart to irradiate male BALB/c mice at an isodose of 22, 16 and 8 Gray (Gy). We examined cardiac damage (i.e., vacuolization), inflammation, and DNA damage at 10 days post irradiation using histology and immunohistochemistry of heart tissue and cardiac function at day 35 by echocardiography. Additionally, cardiac tissue of mice irradiated at 22 Gy was collected at day 10 and day 35 post irradiation and sent for RNA sequencing. Data from RNA sequencing was analyzed using gProfiler, GSEA, and Cytoscape to enrich and visualize differentially expressed genes. RT-qPCR was performed to validate findings of significantly differentially expressed genes. RESULTS/ANTICIPATED RESULTS: Significantly increased phosphorylation of H2A.X indicated that irradiated mice were undergoing DNA double strand break repair indicating cardiac damage. Additionally, we found that regulators of mitochondrial function were decreased in the heart at day 10 for all doses. We found that mice that received 22 Gy developed cardiomyopathy at day 35 based on increased global longitudinal strain (GLS). Radiation decreased T cells, macrophages, and mast cells in the heart of irradiated mice by RT-qPCR at day 10 indicating damage to immune cells by radiation at all doses. Thus, we successfully created a clinically relevant model of RIHD in male BALB/c mice. DISCUSSION/SIGNIFICANCE: Patients undergoing radiation therapy for thoracic malignancies can develop cardiomyopathy (DCM) due to radiation damage. Previously published animal models utilized mouse strains resistant to developing DCM (female mice, C57BL/6 strain) and used high doses of radiation. Establishing a translational model is crucial for prevention of RIHD.

OBJECTIVES/GOALS: CTSA Search Solutions (https://ctsa-search.rutgers.edu/search/) is a database that allows users to systematically conduct structured searches among the 60+ CTSA hub websites for information related to NCATS goals and CTSA hub activities. It was created with the objective of providing a novel process to evaluating and benchmarking CTSA hubs. METHODS/STUDY POPULATION: The CTSA Search Solutions database is an information tool that includes structured search terms relating to 3 main CTSA categories: NCATS goals, CTSA activities, and COVID 19 information. Subcategories from these topics were also identified and organized. Each CTSA hub website was systematically searched for content related to each of the identified terms and categories. The uniform resource locator (URL) for the primary webpage that provided content for each term was collected and stored in the CTSA Search Solutions database for user friendly access. URLs are validated monthly for changes or discrepancies. RESULTS/ANTICIPATED RESULTS: The final database includes access to 63 CTSA Hub websites with 89 structured search term options and over 800 links collected, organized, and published. Hub content can be searched by state, region, or even hub age to make detailed comparisons with the data identified. The CTSA Search Solutions tool allows researchers, administrators, evaluators, and community partners to find the needed links, to learn about specific CTSA hub program highlights as well as conduct research into program hub outputs and best practices across the nationwide CTSA continuum. DISCUSSION/SIGNIFICANCE: On the most practical level, CTSA Search Solutions has the potential to help hub evaluators identify the content of hubs in their first cycle compared to those in their 3rd Cycle. It can help core leads determine common best practices. It can help researchers understand the variety of COVID 19 outreach among the CTSA continuum.

ABSTRACT IMPACT: We are developing the 3D perfusion system for use with patient-derived bacteria to further characterize the mechanism behind bacterial-induced inflammation and cancer. OBJECTIVES/GOALS: We previously reported the adherent invasive E. coli NC101 promote colorectal cancer (CRC) in mice. FimH, a mannose-specific adhesin on type 1 fimbriae, is involved in bacterial surface adhesion. Herein, we investigated the role of FimH in E. coli NC101-induced adherence and carcinogenesis in a novel 3D perfusion culture imaging plate. METHODS/STUDY POPULATION: E. coli NC101 gene fimH was deleted byï ŲRed Recombinase System. Biofilm formation was assessed by crystal violet and congo red staining. 5 dpf (wild-type strain) zebrafish embryos were infected in 6x107 cfu/ml wild type (WT) or fimH-deleted (ï ,,fimH) E. coli NC101 for 24hr and gut dissected for bacterial culture. A 2D/3D infection culture system for IEC-6 and HT-29 cells was infected for 4 hr and imaged and then DNA damage examined by comet assay, cell cycle andÎ3H2AX accumulation. Germ-free (GF) Il10-/- (colitis) mice were orally gavaged with 108 cfu WT orï ,,fimH E. coli NC101 for 16 weeks. E. coli colonization were quantified by plate culture and qPCR. Lipocalin2 was quantified by ELISA. PCNA and β-catenin were evaluated by immunohistochemistry (IHC). RESULTS/ANTICIPATED RESULTS: Biofilm formation was reduced by more than 40% (p<0.05) in E. coli NC101ï ,,fimH compared to WT strain. Zebrafish larvae showed a 41% decrease in intestinal colonization ofï ,,fimH compared to WT (p<0.05). E. coli NC101-induced DNA damage was reduced by 67% (p<0.0001) in HT-29 cells infected withï ,,fimH compared to WT strain. Using the 3D infection system, a 46% decrease in yH2AX (p<0.05) and 42% decrease in G2 cell cycle arrest (p<0.05) was observed inï ,,fimH infected IEC-6 cells compared to WT strain. Furthermore, ï ,,fimH infected Il10-/- mice showed decreased colonization (p<0.01), decreased intestinal inflammation (p<0.05), decreased stool lipocalin2 level (p<0.01), and reduction of PCNA positive cells in the intestine (p<0.05) compared to mice infected with WT strain. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adhesin protein FimH is required by E. coli NC101 to colonize and promote colitis and carcinogenesis both in a 3D perfusion culture and in mice and may serve as potential therapeutic target.

Although mentoring is critical for career advancement, underrepresented minority (URM) faculty often lack access to mentoring opportunities. We sought to evaluate the impact of peer mentoring on career development success of URM early career faculty in the National Heart Lung and Blood Institute-sponsored, Programs to Increase Diversity Among Individuals Engaged in Health-Related Research-Functional and Translational Genomics of Blood Disorders (PRIDE-FTG). The outcome of peer mentoring was evaluated using the Mentoring Competency Assessment (MCA), a brief open-ended qualitative survey, and a semi-structured exit interview. Surveys were completed at baseline (Time 1), 6 months, and at the end of PRIDE-FTG participation (Time 2). The following results were obtained. Between Time 1 and Time 2, mentees’ self-assessment scores increased for the MCA (p < 0.01) with significant increases in effective communication (p < 0.001), aligning expectations (p < 0.05), assessing understanding (p < 0.01), and addressing diversity (p < 0.002). Mentees rated their peer mentors higher in the MCA with significant differences noted for promoting development (p < 0.027). These data suggest that PRIDE-FTG peer mentoring approaches successfully improved MCA competencies among URM junior faculty participants with faculty ranking peer mentors higher than themselves. Among URM faculty, peer mentoring initiatives should be investigated as a key strategy to support early career scholar development.

This special communication provides an approach for applying implementation science frameworks to a Clinical and Translational Science Institutes (CTSIs) community engagement (CE) program that measures the use of implementation strategies and outcomes that promote the uptake of CE in research. Using an iterative multi-disciplinary group process, we executed a four-phased approach to developing an evaluation plan: 1) creating an evaluation model adapted from Proctor’s conceptual model of implementation research; 2) mapping implementation strategies to CTSI CE program interventions that support change in research practice; 3) identifying and operationalizing measures for each strategy; and 4) conducting an evaluation. Phase 2 employed 73 implementation strategies across 9 domains generated by the Expert Recommendations for Implementing Change project. The nine domains were used to classify each CE program implementation strategy. In Phase 3, the group used the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to define measures for each individual strategy. Phase 4 demonstrates the application of this framework and measures Year 1 outcomes for the strategy providing interactive assistance, which we implemented using a centralized consultation model. This approach can support the CTSA program in operationalizing CE program measurement to demonstrate which activities and strategies may lead to benefits derived by the program, institution, and community.

The COVID-19 pandemic changed the clinical research landscape in America. The most urgent challenge has been to rapidly review protocols submitted by investigators that were designed to learn more about or intervene in COVID-19. International Review Board (IRB) offices developed plans to rapidly review protocols related to the COVID-19 pandemic. An online survey was conducted with the IRB Directors at Clinical and Translational Science Awards (CTSA) institutions as well as two focus groups. Across the CTSA institutions, 66% reviewed COVID-19 protocols across all their IRB committees, 22% assigned protocols to just one committee, and 10% created a new committee for COVID-19 protocols. Fifty-two percent reported COVID-19 protocols were reviewed much faster, 41% somewhat faster, and 7% at the same speed as other protocols. Three percent reported that the COVID-19 protocols were reviewed with much better quality, 32% reported slightly better quality, and 65% reported the reviews were of the same quality as similar protocols before the COVID-19 pandemic. IRBs were able to respond to the emergent demand for reviewing COVID-19 protocols. Most of the increased review capacity was due to extra effort by IRB staff and members and not changes that will be easily implemented across all research going forward.

OBJECTIVES/GOALS: Provide recruitment support via a coordinated application of strategic operations, participant engagement practices, and informatic capabilities best practices. Improve study success through the discovery of optimal recruitment practices, development of needed services, leverage of existing resources, infrastructure and guidance. METHODS/STUDY POPULATION: The optimization effort utilized a variety of methods for engaging participants and obtaining information related to the recruitment needs of study teams. Information was collected from an advisory board and through surveys of a diverse group of investigators and research coordinators examining recruitment barriers as well as current and possible future recruitment services. A workflow of the investigative teams recruitment experience was created to identify strengths, gaps and areas for improvement. This information was used to develop a set of recommendations for the Indiana CTSI leadership. Three pillars were tasked with tackling specific areas through an integrative and collaborative approach: (1) study planning and operations, (2) informatics, and (3) participant engagement and health literacy. RESULTS/ANTICIPATED RESULTS: Key resulting recommendations included: creating a recruitment navigator to direct clients to the most appropriate service(s), adding a community engaged staff member and a digital public engagement specialist to the recruitment services team, redesigning the website navigations, creating participant payment guidelines, creating participant engagement principles guidelines, improving informatics support, and continual evaluation of best practices and innovations in recruitment support. An intake and follow-up survey were created for clients to assess services offered, those used, and ultimately the success of those services in improving recruitment measures. DISCUSSION/SIGNIFICANCE: The optimization efforts have shown a positive response from study teams demonstrated by an uptick of support requests. By taking an intensive strategic planning approach to streamlining recruitment services, the Indiana CTSI has leveraged existing resources to better serve clients in need of critical recruitment assistance.

OBJECTIVES/GOALS: Atrial fibrillation (AF) not only is the most common sustained cardiac arrhythmia in clinical practice placing patients at increased risk for thromboembolic events. Hispanics despite having a higher risk factor burden for developing AF have a lower overall incidence and prevalence of AF when compared to Non-HispanicWhites (NHW). European ancestry in the African American population was found to be an independent predictor for developing AF. Consequently, we have decided to evaluate if European ancestry is an independent risk factor for Puerto Rican Hispanics(PRH) METHODS/STUDY POPULATION: This project is a secondary analysis of a Puerto Rican population sample (n = 250) fromThePharmacogenetics of Warfarin in Puerto Ricans StudyandAGenomic Approach for Clopidogrel in CaribbeanHispanics; and1000GenomeProject to establish a control group of healthy PRH population. We will evaluate the presence of 111 known single nucleotide polymorphisms(SNP)associated with AF Europeans and determine the frequency in PRH population sample.Using admixture informatic markers (AIM) analysis will determine the percentage of admixture. Statistical analysis will include the use of Pearson Product-MomentCoefficient correlation analysis and multivariate regression. For admixture will use Maximum LikelihoodEstimation Markov Chain Monte Carlo models RESULTS/ANTICIPATED RESULTS: We anticipate that higher-frequency of AF associated European SNPs and overall higher percentage of European admixture will be associated with atrial fibrillation in PRH patients. DISCUSSION/SIGNIFICANCE OF IMPACT: The expected outcomes for this study are to identify the frequency of known genetic loci associated with AF Europeans and validate their use PRH population for machine learning risk factor models.

OBJECTIVES/GOALS: To examine the relationship between epigenetic age acceleration (EAA) and depressive symptoms in a cohort of African American women (AAW) with cardiometabolic conditions (CMC) including hypertension, diabetes, obesity; and to explore clinical phenotypes of depressive symptoms in this population. METHODS/STUDY POPULATION: This secondary analysis utilized genomic and longitudinal clinical data from AAW in the InterGEN cohort (n = 250). EWAS data was used to estimate EAA based on the Horvath method, which incorporates the DNA methylation statuses at 353 specific CpG sites and regresses this epigenetic age on chronological age to determine EAA. Pearson’s correlations and linear regression will be used to examine the relationship between EAA and depressive symptoms and a linear mixed model will investigate this relationship over four time points during a two-year period. Clinical phenotyping of depressive symptoms will be explored using a cluster analysis. RESULTS/ANTICIPATED RESULTS: Analysis is underway and will be complete by the time of presentation. We hypothesize that higher EAA will associate with higher depressive symptoms and poorer trajectories over time. We expect that this relationship may be meditated by the presence of CMCs. Exploratory analysis of clinical phenotyping is expected to provide descriptive evidence with respect to specific depressive symptoms or clusters which are most associated with EAA and CMCs. These results will address several gaps. To our knowledge, this is the first study to examine the relationship of EAA and depressive symptoms considering the role of CMC, in a historically understudied population with disproportionate risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression limits life quality and quantity and is highly comorbid in CMC. AAW have high risk of comorbidity, and this study furthers knowledge of depression and aging with a clinically accessible marker and aids recognition of a heterogenous phenotype in an undertreated population.

OBJECTIVES/GOALS: Many left hemisphere stroke survivors have a reading disorder (alexia), which is experienced as decreasing well-being. Therapies produce inconsistent results, demonstrating a need for treatment response predictors. We are investigating neural correlates of reading computational models to identify biomarkers to improve therapeutic outcomes. METHODS/STUDY POPULATION: Artificial neural network models of reading, mapping between orthography (visual word form), phonology (auditory word form), and semantics (word meaning), are trained to read single words at a healthy, adult capacity. The models are independently damaged to reflect the individual orthography-to-semantics, semantics-to-phonology, and orthography-to-phonology deficits of a sample of left hemisphere stroke survivors (n = 85). These deficits are measured with cognitive tests assessing the intactness of mappings between representations. Model damage is enacted by removing percentages of the connections between representations. For each type of deficit, the percentages of links removed are entered into a voxel-based lesion symptom mapping analysis to identify areas of cortex associated with that mapping. RESULTS/ANTICIPATED RESULTS: We anticipate that the neural correlates of model layers will be localized to a mostly left-lateralized network. Increased damage to the links between semantics and phonology in the model will likely be related to lesions involving the left posterior superior temporal sulcus and inferior frontal gyrus (IFG). Damaged orthography-to-semantic links will be related to the left fusiform gyrus (FG) and IFG. Finally, damage to the orthography-to-phonology links will be related to the left FG and superior temporal gyrus. DISCUSSION/SIGNIFICANCE: Mapping components of language models onto the brain will improve our understanding of the neural networks supporting language processing. Identifying these neural correlates may also produce biomarkers that can be used in predicting reading impairment at the acute stage or optimizing therapy in the chronic stage of stroke.

OBJECTIVES/SPECIFIC AIMS: Every year, approximately 800,000 Americans suffer a stroke. Supportive social environments are recognized as an important factor contributing to successful stroke recovery, yet, stroke lesions can affect brain areas important for socioemotional functioning, which could impair a patient’s ability to maintain their social relationships. Specifically, emotion recognition, a fundamental socioemotional skill, is predominantly right-lateralized and may be impacted by right-hemisphere stroke. This research tests for emotion recognition impairments after right-hemisphere stroke and examines whether such deficits are associated with worse reported social support. METHODS/STUDY POPULATION: Twenty right-hemisphere stroke patients (9 female, 11 male) and 23 age-matched healthy control subjects (9 female, 14 male) completed laboratory testing including the Geneva Emotion Recognition Test Short. Subjects additionally completed a measure of self-reported social support using the Older Americans Resources and Services questionnaire. Emotion recognition accuracy was calculated using overall accuracy and valence accuracy (i.e. correctly rating a positive emotion as positive). RESULTS/ANTICIPATED RESULTS: Right-hemisphere stroke patients had lower overall emotion recognition accuracy than controls (patients; M = 37.8%, SD = 18.9%. controls; M = 48.5%, SD = 14.6%, t(41)=2.11, p=.041). Furthermore, patients had significantly lower valence accuracy (patients; M = 84.5%, SD = 10.7%. controls; M = 90.0%, SD = 5.2%, t(41)=2.19, p =.035), indicating that they more often mistook a positive emotion as a negative emotion, and vice-versa. Finally, within the right-hemisphere patient group, overall emotion recognition accuracy was trending to be positively correlated with self-reported social support (rho = 0.397, p =.083), suggesting that poor emotion recognition skills may be associated with worse social outcomes in the real-world. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings indicate that right-hemisphere stroke is associated with impaired emotion recognition. Future research could investigate whether an emotion recognition training may be beneficial for right-hemisphere stroke patient recovery.

ABSTRACT IMPACT: In a global pandemic where data development and dissemination are integral to combating the disease, the Clinical Research Support Center at the University of Minnesota provides a model of comprehensive virtual support, helping to attain and disseminate novel research on COVID-19, its individual and community impact, and treatment initiatives/outcomes. OBJECTIVES/GOALS: The pandemic created massive disruption to the conduct of clinical research with an unprecedented reorientation towards COVID-19. In this fast-paced environment, the Clinical Research Support Center (CRSC) rapidly developed innovative means of supporting diverse research initiatives. METHODS/STUDY POPULATION: The CRSC rapidly transitioned into a virtual environment and developed tools for the clinical research community to enhance remote clinical trial start up. This includes supporting remote consent, eBinders, COVID-19 research training for clinical staff, and easier identification of potential participants for COVID-19 studies; all through virtual support. Support provided research teams guidance on study protocols, regulatory requirements, informatics, biostatistics, financial management, recruitment strategies to support critical, urgent COVID-19 research. We outline proactive examples of how the CRSC now provides support to research teams through the pandemic. RESULTS/ANTICIPATED RESULTS: From March-November 2020, 116 COVID-19 projects received virtual support from the CRSC for COVID-19 research: disease understanding (n=27), treatment (n=23), pandemic impact (n=20), clinical care innovation (n=18), disease control and surveillance (n=10), prevention (n=9), detection (n=5), and impact on minorities (n=4). The diversity of these studies demonstrates the demand for and benefit from multidisciplinary expertise supporting study design and implementation. Through successful articulation and acceleration of research activities, the CRSC met the need for speed and rapidly adapted to new challenges created by the pandemic. DISCUSSION/SIGNIFICANCE OF FINDINGS: In a global pandemic where rapidly changing barriers to research is ongoing, through multidisciplinary efforts, the CRSC continues to provide comprehensive, virtual support to attain and disseminate novel research on COVID-19, its individual and community impact, and treatment initiatives/outcomes.

OBJECTIVES/GOALS: SGLT2i therapy is currently a cornerstone in heart failure with preserved ejection fraction (HFpEF) therapy. Similarly, H2S has been shown to be beneficial in preclinical models of heart failure. With this in mind, we sought to investigate the effects of the SGLT2i and H2S donor therapy alone or in combination in a rodent model of cardiometabolic HFpEF. METHODS/STUDY POPULATION: Male C57BL/6N mice (9 weeks of age) were fed a high fat, Western diet (HFD) and received L-NG-Nitro arginine methyl ester (L-NAME) in the drinking water (0.5 g/L) to induce HFpEF. At 5 weeks, animals were randomized to either control, H2S donor (SG-1002, 90 mg/kg/d, P.O), Empagliflozin (155 mg/L, P.O), or the combination of SG-1002 and Empagliflozin for an additional 5 weeks while being maintained on HFD and L-NAME. Echocardiography, left ventricular invasive LV and systemic hemodynamics, and exercise capacity testing were performed to assess cardiovascular disease severity. Fasted glucose, circulating triglyceride and cholesterol content were similarly measured to quantify key clinical metabolic parameters. H2S and its metabolite, sulfane sulfur, were quantified to assure adequate H2S donation. RESULTS/ANTICIPATED RESULTS: Administration of SG-1002 restored H2S and sulfane sulfur to normal circulating levels. All treatment groups exhibited similar improvements in LV diastolic dysfunction as measured by E/E’and LVEDP. Combination therapy significantly improved exercise capacity whereas the monotherapy groups did not. Treatment with SG-1002 decreased fasting glucose and circulating cholesterol while all treatment groups displayed decreased circulating triglycerides and body weight compared to HFpEF control. DISCUSSION/SIGNIFICANCE: These data indicate that restoring H2S or treatment with an SGLT2i in this preclinical HFpEF model attenuates pathology. Combination of both drugs exhibited greater benefit than either monotherapy in important HFpEF parameters such as exercise capacity. Further studies are underway to characterize the benefits observed from combination therapy.

OBJECTIVES/GOALS: To determine the impact of regional anesthesia (RA) on rates of breast cancer recurrence, breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use among patients who received regional anesthesia during primary breast cancer surgery. METHODS/STUDY POPULATION: Study population: Patients who underwent primary breast cancer surgery at Emory University and among a national patient cohort. Methods: This is a retrospective analysis of patients who underwent primary breast cancer surgery. Invasive breast cancer specific survival & breast cancer-specific survival will be estimated using Kaplan-Meier method and compared among patient groups. Cox proportional hazards will be utilized to estimate the unadjusted & adjusted risk of breast cancer recurrence and breast cancer-specific mortality between the two groups. RESULTS/ANTICIPATED RESULTS: We will present on our work comparing rates of breast cancer recurrence among patients who received regional anesthesia compared to patients who did not. DISCUSSION/SIGNIFICANCE: This study aims to establish the effect of regional anesthesia on breast cancer recurrence,breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use following primary breast cancer surgery.

OBJECTIVES/SPECIFIC AIMS: Juvenile Polyposis Syndrome (JPS) is an inherited cancer predisposition syndrome sometimes attributed to a germline mutation in SMAD4 or BMPR1A. However, many patients meet clinical criteria for JPS without having a pathogenic alteration in either gene. Herein, we perform a cross-sectional analysis of JPS patients at a pediatric and adult tertiary referral center to understand potential differences in the clinical presentation and outcomes of patients with or without a known causative gene mutation. Additionally, we conduct whole exome sequencing (WES) on a subset of the pediatric patients to evaluate for novel genomic drivers of disease. METHODS/STUDY POPULATION: Data were abstracted from medical charts using IRB-approved protocols at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania (Penn). Records were reviewed for patients with a clinical diagnosis of JPS and genetic testing result and seen at either institution in the last 10 years (2008-2018). Patients recruited for sequencing were consented for blood draw through the CHOP IRB protocol, and had whole exome sequencing completed at 70X depth, with data analyzed through institutional pipeline. RESULTS/ANTICIPATED RESULTS: Records were reviewed for 41 patients at CHOP and 19 patients at Penn, for a total of 60 JPS patients. Mean age of CHOP cohort was 11 years: 58.5% male, mean length of follow up 3.9 years. Mean age Penn cohort was 33 years: 47.4% male, mean length of follow up 9.3 years. In the pediatric cohort, 7 patients (17%) had a mutation in BMPR1A (n=6) or SMAD4 (n=1); in the adult cohort, 15 patients (79%) had a mutation in BMPR1A (n=3) or SMAD4 (n=12). The average number of polyps in the pediatric cohort was not significantly higher in patients with a SMAD4 or BMPR1A mutation (9.3 polyps/year of surveillance with a SMAD4 or BMPR1A mutation, vs 5.7 polyps/year; p=0.19). In combined cohort review, all individuals that required gastrectomy and/or colectomy (n=8) as well as all those who developed gastrointestinal cancer (n=3) had a mutation in SMAD4 or BMPR1A. Of the patients who underwent whole exome sequencing (n=13), potential causative germline mutations were identified in four patients (30.8%); all potential drivers identified were within the TNF/BMP pathway. DISCUSSION/SIGNIFICANCE OF IMPACT: This data from a dual-institution review demonstrates that the rate of SMAD4/BMPR1A mutation in JPS is lower in a pediatric cohort compared to an adult cohort. Furthermore, although individuals with JPS may have similar clinical presentations in childhood regardless of whether or not a causative mutation is present, the presence of a mutation in SMAD4 or BMPR1A is associated with a more severe course of disease in adulthood. Further study and a larger cohort will be required to fully validate these findings. Approximately 30% of patients who underwent germline WES had a potential novel driver identified, with further validation underway.

OBJECTIVES/GOALS: The Informatics Program in the Wake Forest CTSI is experiencing rapid growth. To accommodate an influx of both staff and clinical investigators this program Invests resources in self-service tools to increase researcher capabilities Automates resource intensive activities Creates transparency of operational processes for researchers. METHODS/STUDY POPULATION: Self-service tools (immediate/automated) The i2b2 tool queries clinical data for feasibility numbers and cohort identification; and provides demographic breakdowns of patient sets The Data Puller tool pulls identified patient data (with IRB approval) The SKAN NLP tool pulls aggregate numbers from over 3 million clinical notes Automation A custom-built tracking system automates parts of tracking requests for data and checking IRB protocols Operational transparency The Data Request Dashboard shows requesters information about their request and where it is in the process of being fulfilled The Data Quote tool was constructed leveraging the integrated CTSA informatics network and uses details of the request to estimate how long it will take to complete. RESULTS/ANTICIPATED RESULTS: i2b2 has had over 300 unique users each year; 80% are faculty or research staff, 20% are clinicians or students. From 2017-2021 there have been an average of 300 i2b2 queries and 45 Data Puller pulls each month. SKAN has had 58 unique users since its implementation in late 2020, averaging 5 new users per month. The automated data request tracking system took approximately 30 staff hours to create and saves an average of 4 hours of staff time per week. It also decreases human error by pulling/pushing information directly between systems. The Informatics program has received positive feedback from researchers who use the Data Request Dashboard. The Data Quote Tool is being used to give standardized quotes to researchers. DISCUSSION/SIGNIFICANCE: Investing resources in developing and implementing self-service tools and operational transparency ultimately reduces overall resource consumption, saving staff and investigator time and effort. This enables the Informatics program to maintain a high standard of service while experiencing rapid growth.

OBJECTIVES/GOALS: Self-monitoring (SM) improves adherence to low-fat low-calorie (LFLC) diet for weight management. Ketogenic diet (KD) is a promising alternative to LFLC, however, it is unclear whether SM improves KD adherence. We examined the association between SM and KD adherence during the first 12 weeks of a 6-month technology-assisted lifestyle intervention. METHODS/STUDY POPULATION: We included 30 (50.8 ± 12.4 years, 70% female) overweight/obese (body mass index: 37.1 ± 7.2 kg/m2) participants in the analysis. They received personalized KD goals with very low-carbohydrate (22–62 g/d), moderate protein (52 -87 g/d), and high-fat (115 - 219g/d) and calorie intake goals (1338–2554 kcal/d). Additionally, participants performed daily diet, exercise, and weight SM. Adherence to KD was measured by (1) self-monitored dietary intake, and (2) percent of days in ketosis state (blood ketone≥0.5 mmol/L) captured by a fingerstick blood ketone meter. SM frequency was defined as percent of days participant logged food intake, wore fitness tracker, and weighed body weight. Pearson correlation coefficients were computed to examine the correlation between SM in diet, exercise, and weight with KD adherence. RESULTS/ANTICIPATED RESULTS: Percentage of days participants SM for diet, exercise, and weight was 58.4 ± 32.2%, 66.4 ± 30.9%, and 59.0 ± 32.6%, respectively. Correlational analysis more frequent diet SM was positively correlated with more days in ketosis (r = 0.58, p = 0.003), higher fat intake (r = 0.68, p = 0.0001), and higher calorie intake (r = 0.67, p = 0.002) within the fat and calorie goals set; more frequent weight SM was positively correlated with more days in ketosis (r = 0.48, p = 0.02), higher fat intake (r = 0.45, p = 0.023), and higher calorie intake (r = 0.44, p = 0.027). DISCUSSION/SIGNIFICANCE: We found that diet and weight SM were positively associated with fat and calorie intake, as well as days in ketosis. Given the reported promising effect of KD on weight loss and the challenges of adhering to KD, our findings suggested that promoting SM on diet and weight might be a promising avenue for improving KD adherence leading to successful weight loss.

OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.

OBJECTIVES/SPECIFIC AIMS: Using a novel biomechanical-based motor speech assessment alongside commonly used clinically-based motor speech assessments, the goal of this study was to describe longitudinal recovery in speech movements and functional speech in a cohort of 5 patients following facial transplantation. METHODS/STUDY POPULATION: Five participants who had received either full or partial face transplantation were included in this study. Each participant received a unique facial graft from their donor, which included varied amounts of soft tissue, facial musculature, nerve, and bone. Two participants were early in the recovery period and were assessed from zero to 24 months post-transplantation. Three participants were late in the recovery period and were assessed from 36 to 60 months post-transplantation. Each participant completed two data collection sessions and the average time between sessions was 20.4 months. At each session, orofacial movements were recorded using a 3D motion capture system. A 4-sensor head marker was used to subtract head movement (translation and rotation) from the facial markers. The analyses in this study were restricted to two markers: midline lower lip and a virtually calculated midline jaw marker. A marker at the top of the nose bridge was used as the origin point. The following kinematic variables were obtained from each lip-jaw movement time-series: peak movement speed (mm/s), and displacement (mm). Each patient was instructed to perform 10 repetitions of the phrase “buy bobby a puppy” at his or her typical speaking rate and volume. Sentence-level intelligibility was obtained using the Sentence Intelligibility Test (SIT) and word-level intelligibility was obtained using the Word Intelligibility Test, using standard procedures. Intelligibility, measured in percentage of words correctly transcribed, and speaking rate, measured in words per minute (wpm), was derived from the SIT sentences for each patient. Intelligibility, measured in percentage of words correctly chosen via multiple choice was derived from the Word Intelligibility Test. RESULTS/ANTICIPATED RESULTS: Effect sizes (Cohen’s d) across the 10 trials of “buy bobby a puppy” were computed to assess the effects of recovery time on range of motion and speed of the lower lip alone, the jaw alone, and the lower lip and jaw together for both range of motion and for speed. The largest effect sizes were observed for increased range of motion and increased speed of the articulators for participants within 24 months of surgery. Smaller effect sizes were observed for these parameters for the participants in the later stages of recovery, with some participants showing declines in range of motion and speed of some but not all articulators. Descriptive statistics indicate that both speech and word intelligibility improvements are most notable in the first two years following transplantation and appear to plateau during the later stages of recovery. Only two out of five of our participants achieved “normal” speech intelligibility (i.e., >97%) at five years post-transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: Biomechanical assessment revealed that kinematic recovery of articulator range of motion and speed appears most significant in the first two years following surgery, but that improvement continues to some degree as far as five-years post-transplant. Clinically-based assessments suggest that gains in intelligibility appear to plateau by 3-years post-surgery.