In recent times, there have been calls from within the developing nations for increased ownership by governmental research bodies and universities of the priority research setting and research that aligns with national health strategies. This is a review paper of the studies that have been published on clinical trials in developing countries, with a focus mainly on Pakistan. The literature review used online databases such as PubMed, Scopus, and Google Scholar, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov trial registries to search for clinical trials conducted in Pakistan between January 2000 and December 2022 and analyzed. The results revealed that clinical research in Pakistan is hindered by a number of barriers, including a lack of funding, skilled personnel, and regulatory issues. Lack of funding is a common obstacle, and the majority of funding for clinical trials originates from Western countries or pharmaceutical companies established in the West. In conclusion, clinical studies in developing countries, especially in Pakistan, are hindered by a plethora of barriers, and to improve the current state, increasing funding, streamlining ethical approval procedures, simplifying regulatory systems, addressing cultural and religious concerns, and participating in global efforts to bridge the gap in health-based research are crucial.

OBJECTIVES/SPECIFIC AIMS: A brain-machine interface (BMI) is a device implanted into the brain of a paralyzed or injured patient to control an external assistive device, such as a cursor on a computer screen, a motorized wheelchair, or a robotic limb. We hypothesize we can utilize electrical stimulation of subdural electrocorticography (ECoG) electrodes as a method of generating the percepts of somatosensation such as vibration, temperature, or proprioception. METHODS/STUDY POPULATION: There will be 10 subjects, who are informed, willing, and consented epilepsy patients undergoing initial surgery for placement of subdural ECoG electrodes in the brain for seizure monitoring. ECoG will be used as a platform for recording high-resolution local field potentials during real-touch behavioral tasks. In addition, ECoG will also be used to electrically stimulate the human cerebral cortex in order to map and understand how varying stimulation parameters produce percepts of sensation. RESULTS/ANTICIPATED RESULTS: To determine how tactile and proprioceptive signals are integrated in S1, we will perform spectral analysis of the broadband local field potentials to look for increased power in specific frequency bands in the ECoG recordings while touching or moving the hand. To explore generating artificial sensation, the subject will be asked to perform a variety of tasks with and without the aid of stimulation. We anticipate the subject’s performance will be enhanced with the addition of artificial sensation. DISCUSSION/SIGNIFICANCE OF IMPACT: Many patients might benefit from a BMI, such as those with stroke, amputation, spinal cord injury, or brain trauma. The current generation of BMI devices are guided by visual feedback alone. However, without somatosensory feedback, even the most basic limb movements are difficult to perform in a fluid and natural manner. The results from this project will be crucial to developing a closed loop motor/sensory BMI.

OBJECTIVES/SPECIFIC AIMS: The goal of the present study was to advance our understanding of how alcohol use may contribute to physical inactivity among university students by investigating this association at a day-to-day level. METHODS/STUDY POPULATION: In total, 57 university students (Mage=20.27; 54% male) completed daily diary questionnaires using a cellphone application, which prompted them each evening to report minutes of moderate/vigorous physical activity engaged in, and number of alcoholic drinks consumed, as well as intended minutes of physical activity for the following day. Longitudinal mixed-level modeling was used to disentangle within person and between-person effects of alcohol use on physical activity behavior and intentions. Separate models were run to investigate lagged effects of previous day alcohol use. We controlled for sex and age in all models. RESULTS/ANTICIPATED RESULTS: Results indicated that participants’ usual alcohol use (between-person) was not associated with physical activity behavior or intentions. At the within-person level, day-to-day variance in alcohol use was negatively associated with both physical activity behavior (γ=−0.34, p=0.003) and intentions to engage in physical activity the following day (γ=−0.70, p<0.001). The lagged model indicated that previous day alcohol use negatively predicted PA behavior (γ=−0.33, p=0.004). DISCUSSION/SIGNIFICANCE OF IMPACT: Previous studies have largely been constrained to cross-sectional designs, and have surmised that there exists a positive association between alcohol use and physical activity due to trait-level differences between university students. We advance this literature by using ecological momentary assessment to investigate the within-person effects of alcohol use on physical activity at a day-to-day level while controlling for between-person variance. Contrary to existing literature, we found that on days when students consumed relatively more alcohol than they typically report, they: (a) report fewer minutes of physical activity on the same day, (b) plan to engage in relatively less physical activity on the subsequent day, and (c) engage in less physical activity on the subsequent day. By advancing our understanding of how alcohol use may curtail other health behaviors such as physical activity, we inform interventions that aim to target these behaviors in conjunction, or as part of a multiple behavior change intervention.

OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.

OBJECTIVES/GOALS: In 2010, an estimated 65% of antipsychotic prescriptions were given to youth for off-label indications. It is unclear whether subsequent calls for reduced pediatric prescribing led to a decrease in off-label use. This study examined the diagnostic characteristics of the current pediatric population using antipsychotics in the United States. METHODS/STUDY POPULATION: Data from the Clinformatics Data Mart, a database containing longitudinal patient information between 2010-2019 from commercial healthcare insurance claims in the United States was used in this study. We conducted a case-control study, in which antipsychotic initiators were matched 1:1 to non-initiators on age, sex, and insurance enrollment. There were 26,375 included antipsychotic initiators with matched non-initiator controls between the ages of 6-17. Conditional logistic regression was used to examine the odds of being an antipsychotic user among those with past-year psychiatric diagnoses that have been previously found to be associated with antipsychotic use. RESULTS/ANTICIPATED RESULTS: Disorders with psychotic features were associated with the greatest differences in odds of antipsychotic prescription receipt. Specifically, children with bipolar or manic disorders had 145-fold greater odds of antipsychotic receipt than did those without bipolar or manic disorders (OR = 145.45, 95% CI = [95.64, 221.22]), whereas those with schizophrenia had 106-fold greater odds (OR = 105.89, CI = [67.40, 166.37]). However, these disorders occurred in only 12% and 8%, respectively, of the antipsychotic recipients. The most common disorders among those with antipsychotic receipt were depressive disorders and ADHD, which occurred in 46% and 43% of the recipients, respectively. Additionally, conduct disorder was present in 20% of recipients. DISCUSSION/SIGNIFICANCE: As expected, bipolar disorder and schizophrenia were strongly associated with initiation of pediatric antipsychotic treatment. Yet, most initiators did not have a diagnosis for either psychotic disorder or any other FDA-approved indications. This study highlights the critical need for further research on antipsychotic use among youth.

OBJECTIVES/GOALS: To increase vaccination rates in Black and Latino communities, specifically in South LA and the Eastside of LA. METHODS/STUDY POPULATION: Multimedia campaign combined with vaccine navigation and assistance, led by the SC CTSI and conducted by an interdisciplinary team from 14 schools at USC and CHLA, >160 community partners. RESULTS/ANTICIPATED RESULTS: VaccinateLA was a highly interdisciplinary and multifaceted project that demonstrated increased vaccination rates in Black and Latino communities in South LA and Eastern part of LA. We vaccinated over 1000 people, facilitated vaccines for almost 10k people and reached 1.37M people through our digital campaign. DISCUSSION/SIGNIFICANCE: We have used community vaccine navigators, pop-up clinics, narrative storytelling and other unique approaches to encourage vaccine uptake in communities of color. We plan to expand activities to parents and children in these communities, encourage booster uptake, and evaluate and disseminate the program widely.

OBJECTIVES/GOALS: The rapid spread of Monkeypox (MPV) across the US may trigger stress reactions that increase the risk of developing secondary trauma among those most at risk of exposure. The present study aimed to investigate the degree to which vicarious MPV exposure (i.e., knowing people who acquired MPV), was associated with symptoms of secondary traumatization. METHODS/STUDY POPULATION: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual, and gender minority persons aged 19–39 in September 2022. Multiple linear regression was used to examine the association between proximity to MPV and secondary traumatic stress (STS) symptoms. RESULTS/ANTICIPATED RESULTS: Study findings demonstrated that MPV morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with MPV. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of MPV-related STS. Our multiple linear regression results demonstrated a positive association between an individual’s indirect exposure to MPV via their interpersonal relationships and STS symptoms. DISCUSSION/SIGNIFICANCE: Findings suggest that the more adults’interpersonal relationships are saturated with people who have acquired MPV, the more likely they are to develop symptoms of secondary traumatization. These findings provide initial evidence that secondary exposure to MPV via one’s social network may undermine adults’mental health.

OBJECTIVES/GOALS: In this study, we established a high-throughput chemical screening platform to identify small molecules that facilitates efficient differentiation of stem cells derived β (SC-β) cells. Using this platform, we identified several compounds that potentially increase the differentiation efficiency. METHODS/STUDY POPULATION: Differentiation of human embryonic stem cells (HUES8) into SC-β was carried out using previously published protocols in a 3D cell suspension. Single cells were replated in Matrigel-coated well plates at the start of different stages depending on experiments. Differentiation medium supplemented with small molecules at a final concentration of 2 M and 0.2 M was used throughout the stage. All the cells were then fixed and permeabilized. Immunocytochemical staining was performed. Images of each well were taken and analyzed. Numbers of the total cell, insulin-positive cell, NKX6.1-positive cell, and co-positive cell were recorded. Candidate compounds were validated using flow cytometry or ICC. RESULTS/ANTICIPATED RESULTS: We identified several hit compounds that significantly increase the NKX6.1 positive cell percentage compared to the DMSO-treated controls when treated at the PP1 cell stage. Follow up assays demonstrated that at least one of these putative hits reproducibly increased NKX6.1 expression. In addition, we identified other compounds that significantly increase the insulin and NKX6.1 copositive SC-β cell population when treated at the later PP2 cell stage during the differentiation. We expect a dosage-dependent response when the candidate hits are validated using more accurate assays. DISCUSSION/SIGNIFICANCE OF IMPACT: We established a high-throughput screening platform to identify small molecules that increase the efficiency of SC-β direct differentiation. Successful generation of SC-β allows cell replacement therapy in diabetes patients, and a better understanding of pancreatic biology and development.

OBJECTIVES/SPECIFIC AIMS: Several clinical studies have established a correlation between changes in relative bacterial populations in the gut and Parkinson disease. However, few published experiments have been able to parse out whether these associations are causative or correlative. Our aim is to determine how bacteria in the gut may impact the health and resilience of dopaminergic signaling. Our experiment is designed to serve as a proof-of-principle that controlled alterations to the gut microbiome alters mechanisms in dopamine homeostasis in the midbrain. METHODS/STUDY POPULATION: Bacterial inoculation 8–10-week-old germ-free male mice (C57BL/6) were exclusively used in this experiment. Mice were orally gavaged every 3 days (D0, 3, 6, and 9) with 100 µL novel bacterial suspension (~108 CFU resuspended in PBS with 1.5% NaHCO3) or vehicle and were sacrificed on D11. Tissue preparation—brains were quickly extracted and the striatum was isolated and homogenized in either RIPA buffer with protease inhibitors (for Western blot analysis) or in 0.1 N HClO4 (for HPLC processing). The homogenates were processed through fractional centrifugation to remove cellular debris. Lysate samples were frozen at −80°C until ready for analysis. Protein expression quantification—expression of proteins were measured using intensity of bands from Western blots. Lysates were denatured prior to loading with LB with 10% β-mercaptoethanol and 30-minute incubation at 37°C. All immunoblots were normalized to immunoreactivity to α-tubulin. Immunoblot intensity was determined using the ImageJ software. Dopamine/dopamine metabolite quantification HPLC analysis was used to determine dopamine and dopamine metabolite concentration. Aliquots of the lysate were injected onto a C18 column using a mobile phase consisting of 50 mM H2NaO4P·H2O, 0.72 mM sodium octyl sulfate, 75 µM Na2 EDTA, and 10% acetonitrile (pH 3.0). The mobile phase was pumped through the system at 0.3 mL/minute. RESULTS/ANTICIPATED RESULTS: Measured total dopamine concentration through HPLC analysis in the striatum showed no significant differences in the bacteria-treated group relative to the control group. The metabolites DOPAC and HVA had an elevated measured concentration in the bacteria-treated group relative to the control group. Western blot analysis showed decreased immunoreactivity for DAT and TH in the bacteria-treated group compared with the control group. There was no significance difference in the immunoreactivity for VMAT2. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that dopamine signaling dynamics in the midbrain can be altered by changes in the gut flora in mice. These results further substantiate the impact of the gut-brain axis and may even point to a potential avenue of bolstering the resilience of dopaminergic neurons in preventing the onset of PD. Further experiments must be performed to understand the mechanism of the observed changes and to determine if these changes have any salutary effect.

OBJECTIVES/GOALS: This study examined racial-ethnic differences in antipsychotic initiation within psychiatric diagnostic groups. This is a follow-up to our prior work, which reported that, overall, youth from minority backgrounds had 30-65% lower odds of initiating antipsychotics compared to White youth. METHODS/STUDY POPULATION: This study used 2009-2021 data from Optum’s® Clinformatics® Data Mart, a database containing longitudinal patient information from nationwide commercial insurance claims. We created three separate samples of antipsychotic users and matched non-user controls between the ages of 6-17 years old. These groups contained individuals with clinically diagnosed ADHD, conduct disorder, and depressive disorder, respectively. We used conditional logistic regression to estimate the odds of antipsychotic initiation based on race-ethnicity within each diagnostic group. RESULTS/ANTICIPATED RESULTS: There were no racial-ethnic differences in the odds of antipsychotic initiation among youth diagnosed with ADHD. Among youth with depression diagnoses, Asian youth had 19% lower odds of initiating antipsychotics and Hispanic youth had 11% lower odds compared with White youth. Similar results were observed for conduct disorders, with Asian and Black youth having approximately 10% lower odds of initiating antipsychotic treatment and Hispanic youth having 18% lower odds relative to White youth. DISCUSSION/SIGNIFICANCE: Previously observed lower rates of antipsychotic initiation among racial-ethnic minority groups may be at least partially due to factors leading to disparities in diagnosis. Further research is needed to evaluate factors that may lead to differential antipsychotic use, as the disparities may occur upstream of receiving clinical diagnoses.

OBJECTIVES/GOALS: While the current management of single ventricle repairs has drastically prolonged life expectancy, the repair fails over time primarily through pathologic inflammation and fibrosis. Our goal is to demonstrate that cardio-omentopexy can decrease inflammation and fibrosis in swine after cryoinjury. METHODS/STUDY POPULATION: A cryoinjury is created using a liquid nitrogen cooled probe to the right ventricle of 15-20kg swine for three minutes. In half the groups the omentum is attached to the heart over the area of the injury. The swine are recovered and monitored for 4 or 8 weeks at which time they are euthanized. The injured area is evaluated via histological and immunohistochemical testing for markers of inflammation and scarring including collagen type, scar area, macrophage activity. RESULTS/ANTICIPATED RESULTS: Currently, we have successfully validated the animal model to create myocardial scar validated by histological testing. We anticipate that the addition of omentopexy to cryoinjury will decrease scar area, fibrosis and markers of chronic inflammation. Additionally, we expect an increase in myocytes in the area of injury. We expect that this will occur through the anti-inflammatory and protective mechanism of the omentum. DISCUSSION/SIGNIFICANCE: Cardio-omentopexy, if able to decrease fibrosis and preserve myocytes, may provide a useful adjunct to the treatment of single ventricle repair by prolonging the longevity of the repair. Additionally, as these repairs often require a ventriculotomy, decreasing the operative scar may preserve myocardial function.

OBJECTIVES/GOALS: To assemble publicly-available, proprietary, and geocoded datasets about social, environmental, behavioral, and psychological exposures experienced by children with asthma, to provide a technical overview of data aggregation, management, and integration processes utilized, and to build predictive models using sociome and clinical data. METHODS/STUDY POPULATION: Publicly-available data involving census information, crime, green space, building permits, vacant and abandoned buildings, traffic (City of Chicago data portal), pollution and weather (National Oceanic and Atmospheric Administration), and noise (Array of Things project) were assembled. We placed a local instance of the Pelias geocoder on the UChicago Center for Research Informatics HIPAA-compliant infrastructure. The UChicago Clinical Research Data Warehouse will be leveraged to obtain clinical information for children diagnosed with asthma at UChicago Medicine between 2007 and 2021. The address of each child will be subjected to geocoding, and this information will be aligned with imported sociome data. A model will be built to account for each sociome elements contribution to asthma outcomes. RESULTS/ANTICIPATED RESULTS: Here we are creating sustainable and scalable ways for collecting, standardizing, and sharing real-world sociome data, simultaneously linking those data back to patient information. With this work, we aim to demonstrate feasibility of a data-commons-as-a-service for clinical and sociome data and to provide technical specifications and descriptions of processes employed. Creating generalizable and scalable infrastructure to support research of social and environmental impacts on clinical outcomes is critical, and our work will provide a framework to be used in other disease states. Further, this infrastructure will facilitate the application of advanced analytical tools and visualization platforms to accelerate the study of diseases and lead to new insights into factors influencing outcomes. DISCUSSION/SIGNIFICANCE: Beyond focusing on and treating biological mechanisms of disease, advancing health also requires addressing adverse consequences of sociome factors on clinical outcomes. We describe an innovative process to comprehensively codify and quantify such information in a way suitable for large scale co-analysis with biological and clinical data.

OBJECTIVES/SPECIFIC AIMS: The goals of this study were (1) to evaluate the effect of proarrhythmic drugs on calcium transient and (2) to use three-dimensional human engineered cardiac tissue (hECT) technology to evaluate cardiac contractile properties in response to pharmacological challenge with proarrhythmic drugs. METHODS/STUDY POPULATION: Calcium transient was measured in subject-specific iPSC-CMs by using the IonOptix system in Sotalol treated vs. untreated conditions. We fabricated human engineered cardiac tissues (hECT) in a custom designed bioreactor using low- and high-sentitive subject-specific iPSC-CMs. Contractile function of the hECT was evaluated at baseline and after Sotalol [300 µM] administration. The change in beat rate was recorded under spontaneous beating conditions; changes in other twitch parameters, including time to relaxation, were recorded under electrical stimulation. Time to relaxation served as an indicator of action potential duration (APD), which has a temporal correlation with the QT interval. RESULTS/ANTICIPATED RESULTS: The low-sensitive iPSC-CM showed a considerable drop in overall peak height of the calcium transient, in the presence of 100 µM Sotalol. The high-sensitive line, however, showed a more pronounced drop in peak height. Sotalol treatment also induced a more pronounced increase in the exponential decay time constant (tau) in the high-sensitive line compared to the low-sensitive line. The hECT fabricated with high sensitive hiPSC-CM showed a larger decrease in spontaneous beat rate in response to Sotalol (0.41 vs 0.23 fold decrease), with a higher increase in time to relaxation (1.8 vs 1.3 fold increase), compared to hECT from low sensitive hiPSC-CM. Moreover, while the low-sensitive hECT showed a positive correlation between time to relaxation and developed force, as expected after Sotalol stimulation; the high-sensitive hECT failed to show a positive inotropic response. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest subject-specific iPSC-CMs and hECT, can be used to model functional abnormalities observed in diLQTS in response to Sotalol, and offer novel insights into human-based screening assays for toxic drug reactions. Success of this study may help identify key components underlying diLQT susceptibility to ultimately develop novel therapeutic agents.

OBJECTIVES/GOALS: During and after cancer treatment, cancer-related fatigue (CRF) is a debilitating symptom reported by up to 80% of cancer patients Our understanding of the pathology underlying CRF is limited. Preliminary RNA sequencing data suggest that increased levels of KIR3DL1, the natural killer cell (NK) immunoglobulin-like receptor 3DL1a, may be associated with CRF. METHODS/STUDY POPULATION: Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACT-F). Functional validation of the NK cell finding was performed from whole blood obtained from fatigued and non-fatigued subjects. NK cells were isolated from freshly collected whole blood using a human NK cell isolation kit based on CD56 microbead positive selection. NK cell function was assessed using the NK cell direct cytotoxicity assay. Briefly, isolated NK cells were co-cultured in a 2:1 ratio with calcein AM-labelled K562 cells, which are NK cell-sensitive due to the very low MHCI expression. NK cell-mediated cytotoxicity was assessed with Cytation 1 Cell Imaging Multi-Mode reader. Flow cytometric protocols were used to examine NK subset differences between the fatigued and non-fatigued groups. RESULTS/ANTICIPATED RESULTS: NK cells isolated from the fatigued group exhibited decreased cytotoxicity at 12.28% compared to NK cells isolated from non-fatigued controls at a mean of 40.6% cytotoxicity. Flow cytometry analysis revealed a decrease in the CD56dim CD16bright population in the fatigued group (87.1% of CD56+CD4- cells) compared to the control (91.4% of CD56+CD4- cells). Furthermore, there was a decrease in NKG2A expression in mature NK cells (CD56dim CD16bright) isolated from the fatigued group compared to the non-fatigued group. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from the pilot study suggest that there was a decrease in NK cell cytotoxicity in the fatigued group. In addition, there may be a shift in NK cell subpopulations associated with fatigue. Findings from this pilot study suggest that impaired NK cell function may be associated with CRF pathogenesis.

OBJECTIVES/SPECIFIC AIMS: Engaging Richmond is a community-university partnership, made up of local residents and university faculty and staff that was established in 2011 with an NIH supplement to a Clinical and Translational Science Research Award at Virginia Commonwealth University (VCU). The primary aims of the supplement were to (1) to conduct community-based participatory research (CBPR) on the leading causes of health disparities perceived by the Richmond community and (2) to thereby highlight community needs and assets and build capacity for future community-engaged research (CEnR). The goal was to prepare a community-focused, community-prioritized, health equity report while building capacity, strengthening relationships, and discovering local barriers to CEnR, and therefore to stimulate, facilitate, and inform future CEnR at VCU. METHODS/STUDY POPULATION: This is a case study exploring the impact of 1 community-university partnership on investigator-initiated research using historical and qualitative data. RESULTS/ANTICIPATED RESULTS: Although Engaging Richmond received only 12 months of support from the NIH supplement that provided its initial funding, the community-university partnership has worked continuously since its formation in 2011. This work has not only helped to build connections with the community and key stakeholders, it has also contributed substantially to the resources available to university faculty pursuing CEnR. Specifically, we find that Engaging Richmond has contributed to investigator initiated research in the following ways, either working as co-investigators or in a consultative capacity: consultation on proposal development (5 projects); assisted with instrument development (4 projects); participant recruitment (7 projects); data collection and analysis (6 projects); dissemination (5 projects). In addition to collaboration on projects, Engaging Richmond has increased institutional capacity for CEnR through its contributions to the Annual Community Engaged Institute at the university and the Center of Clinical and Translational Science’s Community Review Board (CRB). The CRB helps researchers work successfully in a community setting, enhance the research design, help to improve study implementation and assist with translation and dissemination of findings. DISCUSSION/SIGNIFICANCE OF IMPACT: Although community-university partnerships have become much more common over the past several decades, there remains a gap in research evidence on the impact of these partnerships. In their 2004 review, Viswanathan et al. note that community-based participatory research studies infrequently document improved capacity of researchers and research organizations as an outcome, despite the expectation that such improvement will accrue through investment in CEnR. A more recent study assessing the range of community-university partnerships across a research university also noted the lack of processes in place to assess impacts (Holton et al., 2015). While assessments of CEnR impact on communities have become increasingly common as demand for evidence about the effectiveness of community-engaged partnerships has mounted, there does not appear to be a similar trend in assessing the impact of these efforts on faculty research and institutional capacity. By focusing on the impact of 1 community-university partnership that has been sustained for over 5 years, we highlight the ways in which having ongoing partnerships in place can support and strengthen investigator-initiated research, reflecting the flexible, “2-way approach” (Weerts and Sandmann, 2010) at the heart of CEnR.

OBJECTIVES/GOALS: We aimed to find the histology-specific markers that were predictive of post-operative long-term chordoma recurrence (≤1 year) using trained multiple tree-based machine learning (ML) algorithms. METHODS/STUDY POPULATION: We reviewed the records of patients who had treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Patients were excluded if they had no histopathology or recurrence as an outcome. Demographics, type of treatment, clinical and radiological follow-up duration, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict the long-term recurrence based on unseen data using an 80/20 split. The performance of the model was optimized using tenfold cross-validation. RESULTS/ANTICIPATED RESULTS: One hundred fifty-one patients were identified: 58 chordomas from the clivus, 48 chordomas of the mobile spine, and 45 sacrococcygeal. Subtotal Resection followed by radiation therapy, was the most common treatment modality, followed by Gross Total resection, then radiation therapy. The multivariate analysis defines the molecular predictors of recurrence following resection. S100 and pan-cytokeratin is more likely to increase the risk of post-operative recurrence (OR= 3.67; CI= [1.09,12.42], p=0.03). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37 % of encounters and a 90% chance of being classified for recurrence (Accuracy= 77%). Factors predicting long-term recurrence are the patient’s age, type of surgical treatment, location of the tumor, S100, pan-cytokeratin, and EMA. DISCUSSION/SIGNIFICANCE: Our molecular and clinicopathological variables combined with tree-based ML tools successfully demonstrate a high capacity to individually identify the patient’s recurrence pattern with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the histologic drivers of recurrence.

ABSTRACT IMPACT: Brain networks can be explored by delivering brief pulses of electrical current in one area while measuring responses in other areas, and this describes an open-source novel algorithm to carry out this exploration. OBJECTIVES/GOALS: If we focus on a single brain site and observe the average effect of stimulating each of many other brain sites, visually-apparent motifs in the temporal response shape emerge from adjacent stimulation sites. There are no existing approaches to identify and quantify the spatiotemporal structure of these motifs. METHODS/STUDY POPULATION: Individual stimulation trials are correlated with one another, then a correlation-significance matrix quantifying similarity between stimulation sites is decomposed with non-negative matrix factorization, in which the inner dimension is iteratively reduced. The dimensionality reduction identifies stimulation sites that produce a common elicited temporal response, and linear kernel PCA is applied to obtain the robust profile of this response cluster. RESULTS/ANTICIPATED RESULTS: We describe and illustrate a data-driven approach to determine characteristic spatiotemporal structure in these response shapes, summarized by a set of unique ‘basis profile curves’ (BPCs). Each BPC may be mapped back to underlying anatomy in a natural way, quantifying projection strength from each stimulation site using simple metrics. Our technique is demonstrated for an array of implanted brain surface electrodes in a human patient, and our code is shared at https://purl.stanford.edu/rc201dv0636. DISCUSSION/SIGNIFICANCE OF FINDINGS: This framework enables straightforward interpretation of single-pulse brain stimulation data, and can be applied generically to explore the diverse milieu of interactions that comprise the connectome.

OBJECTIVES/GOALS: 1. Describe the importance of community engaged research. 2. Explore the impact of participating in Community Engagement Studios from the perspective of the community expert. 3. Explain how Community Engagement Studios can positively impact clinical and translational sciences. METHODS/STUDY POPULATION: Stakeholders who participate in CE Studios are defined as community experts (CEs); care-givers, patients, researchers, etc. They are not classified as research participants, but rather consultants, who are designated with the task of providing input on the specified research study. CEs were recruited in a variety of formats such as clinics, social media, and other community-based settings. To be eligible for the study, CEs had to participate in at least one CE Studio prior to data collection. Data was collected from an online survey from April to September of 2019. One hundred and fifteen CEs participated in the study. We conducted thematic analysis on a total of 233 participant responses to three open-ended questions assessing attitudes towards research, desire to engage in research, and understanding of research. RESULTS/ANTICIPATED RESULTS: Ten major themes emerged from the data: involvement, togetherness, trust, value, confidence, community engagement, community connectedness, encouraging others to participate, increase knowledge and awareness, and respect. A major overarching theme of inclusion was presented in the data. Findings from this study indicate that CE Studios provide a space for CEs to gain a better understanding of the multi-faceted research process, offer insight into ways to include historically excluded populations, and increase trust, confidence and respect for researchers and the research process. Moreover, community experts felt connected to their community by participating in CE Studios and expressed interest in encouraging others to participate. DISCUSSION/SIGNIFICANCE: CEs are a crucial component of the research process, and their experiences should be utilized and reflected upon as we work to reduce health disparities. CE Studios serve to build trust, identify strategic areas of improvement in research, and provide a foundation to introduce community members to the multiple ways to engage in research.