ABSTRACT IMPACT: The model of the Clinical Research Support Center at the University of Minnesota of streamlining clinical trial infrastructure can be leveraged by the larger clinical trial community to create valuable efficiencies and facilitate faster initiation of research activities by supporting researchers from concept to dissemination. OBJECTIVES/GOALS: Substantial time, energy, and money are spent bridging disparate resources in research. We describe how the University of Minnesota’s (UMN) Clinical Research Support Center (CRSC) streamlines trial infrastructure, creating valuable efficiencies to support researchers from concept to dissemination. METHODS/STUDY POPULATION: The CRSC, established in 2018 through the Clinical and Translational Science Award (CTSA) program, brings resources together in a single, centralized, and convenient location to help researchers navigate the UMN clinical research startup process and specifically to assist with the development and initiation of a research study from feasibility assessment to project opening. Diverse expertise in components of human subject research is available to support the broad scope of projects at a large institution like the UMN. We present how CRSC services, when coordinated by Clinical Research Specialists, have been used to improve access to clinical research resources during the start up process. RESULTS/ANTICIPATED RESULTS: Since inception in 2018, the CRSC has provided support to over 1700 studies with 437 research projects referred to a Clinical Research Specialist within the CRSC. Of those projects, 97 (22.2%) received comprehensive support from the following expert groups: regulatory guidance (n=74), biostatistics (n=68), clinical (hospital or clinic) partners (n=60), recruitment (n=36), budget development assistance (n=30), and (bio)informatics (n=27). Successful examples of synergies to streamlining study start up include shortening the window between protocol development support from Clinical Research Specialists and IRB submission preparation through to Regulatory Specialists to 3 days. DISCUSSION/SIGNIFICANCE OF FINDINGS: Providing cross-functional support to research teams through the CRSC increases the likelihood of quicker and successful execution and completion of research initiation and subsequently impacts the dissemination of that research to patients and the broader community.

OBJECTIVES/GOALS: Duke University developed a Project Tracker system to provide transparency into the complex study start-up process for Industry sponsored clinical trials. Partnering with process owners, investigators, research teams, and IT developers, we aimed to reduce timelines for IRB approval, Contract Execution, and Billing/Calendar setup. METHODS/STUDY POPULATION: In 2019, a partnership of administrative stakeholders and IT developers began engaging with the primary populations involved in study start-up: research study teams (STs) and research administrators (RAs). A series of workgroups and feedback sessions revealed common themes with a slightly different scope: STs were interested in the progress of individual projects awaiting approval whereas RAs needed an aggregate view of start-up metrics over time and a way to help troubleshoot delays for individuals. Both groups were hindered by data captured across multiple systems, limited understanding of the entire approval process, and an absence of reliable indicators for delays or outstanding requirements. RESULTS/ANTICIPATED RESULTS: In mid-2021, we delivered a Project Tracker system comprised of two main components, accessible via Dukes myRESEARCHhome portal: 1) a Tableau metrics dashboard for RAs that aggregates retrospective data quarterly, visualizing time to completion of approval workflow milestones with defined outliers, filterable by investigator, unit, or sponsor. 2) a project status tracker for STs (with a complementary view for RAs) that consolidates status information for projects awaiting approval, visualizing the process in a linear fashion with clear indicators of progress and steps awaiting study team action. This involved defining the milestones for each workflow, mapping milestones to application variables, combining the variables in a common data mart, and developing the interfaces with user-centered design. DISCUSSION/SIGNIFICANCE: Given its recent implementation, the impact of the tool on start-up timelines cannot yet be determined. However, our development process led to key insights: a simplified process visualization limited to key milestones allows STs and RAs to understand responsibilities, address delays and data discrepancies, and reinforce institutional process.

OBJECTIVES/GOALS: Impaired vascular function, a subclinical marker of cardiovascular disease, has been identified in prediabetes. Dietary nitrate supplementation has been shown to improve vascular function. However, this has not been studied in prediabetes. The purpose was to determine the effects of dietary nitrate on vascular function in prediabetes. METHODS/STUDY POPULATION: Five individuals with prediabetes (4 men, 1 woman; 55 ± 17 yr; HbA1c = 5.8 ± 0.2) participated in a double-blind, placebo-controlled, repeated measures study. Participants were randomly assigned to a 3-day nitrate supplementation (nitrate-rich beetroot juice, 12.9 mmol, 140 mL), or a placebo supplementation (nitrate-depleted beetroot juice, 0.05 mmol, 140 mL). Following supplementation, participants reported to the lab for measures of vascular function in the lower limb. Doppler ultrasonography was used to measure flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (RH) of the superficial femoral artery in response to a 5-min bout of leg ischemia. RESULTS/ANTICIPATED RESULTS: FMD did not differ between the nitrate-rich (2.87 ± 2.01%) and placebo (2.24 ± 1.69%) conditions (p = 0.48; d = 0.35). Furthermore, peak RH did not differ between the nitrate-rich (1503 ± 443 ml/min) and placebo (1762 ± 414 ml/min) conditions (p = 0.36; d = 0.46). DISCUSSION/SIGNIFICANCE: These preliminary results suggest that dietary nitrate supplementation in the form of beetroot juice does not improve vascular function in individuals with prediabetes.

Participant recruitment for research is a persistent bottleneck that can be improved by leveraging electronic health records (EHRs). Despite emerging evidence for various EHR-driven approaches, guidance for those attempting to select and use such approaches is limited. The national Recruitment Innovation Center established the EHR Recruitment Consult Resource (ERCR) service line to support multisite studies through implementation of EHR-driven recruitment strategies. As the ERCR, we evolved a guide through 17 consultations over 3 years with multisite studies recruiting in diverse biomedical research domains. We assessed literature and engaged domain experts to identify five key EHR-driven recruitment strategies: direct to patient messages, candidate lists for mailings/calls, direct to research alerts, point of care alerts, and participant registries. Differentiating factors were grouped into factors of study population, study protocol and recruitment workflows, and recruitment site capabilities. The decision matrix indicates acceptable or preferred strategies based on the differentiating factors. Across the ERCR consultations, candidate lists for mailing or calls were most common, participant registries were least frequently recommended, and for some studies no EHR-driven recruitment was recommended. Comparative effectiveness research is needed to refine further evidence for these and potentially new strategies to come.

Inadequate training in the interpersonal skills of conducting informed consent conversations has long been noted as a challenge for clinical research recruitment and retention. To address this critical gap, Tufts Clinical and Translational Science Institute developed regular trainings for clinical research coordinators and other research staff on the practical skills of communicating informed consent using community members as simulated patients for role-playing exercises. In this paper, we assess the reach and effectiveness of these trainings and describe the impact of employing community stakeholders as simulated patients. We found that by embedding community members in the trainings, clinical research coordinators get to hear diverse perspectives, experience a range of patient responses, and learn from the lived experience of the communities that research tries to serve. Utilizing community members as trainers also helps to dismantle traditional power dynamics by demonstrating the organization’s commitment to inclusiveness and community engagement. Based on these findings, we suggest that training on informed consent include more simulated consent exercises that feature interaction with community members who can provide real-time feedback to coordinators.

OBJECTIVES/GOALS: The objective of the study is to compare two horizontal bone augmentation techniques (bone expansion and bone splitting) that are currently used for horizontally deficient maxillary ridges. Bone expanded in millimeters (mm), implant stability, and patient satisfaction will be compared with each technique. METHODS/STUDY POPULATION: This pilot (prospective cohort) study will be divided in two sites, a private practice and the Oral and Maxillofacial Surgery (OMS) Clinic at the University of Puerto Rico, School of Dental Medicine. A total of 20 patients will be selected, 10 patients in each site. In both sites, pre-operative and post-operative Cone Beam CT radiographs will be taken to measure bone width. Implant stability will be measured using an Osstell. 2 weeks post-surgery, a patient satisfaction questionnaire will be given to patients. A two-sample T test will be used to compare techniques statistically. RESULTS/ANTICIPATED RESULTS: We anticipate that bone expansion will be as good as (non-inferiority) bone splitting in terms of bone expanded in millimeters to desire width, and implant diameter will not be compromised. We also expect that implants placed with the bone manipulation technique will have a higher implant stability at baseline and less pain, discomfort and swelling in terms of patient satisfaction. DISCUSSION/SIGNIFICANCE OF IMPACT: Our contributions here are expected to illustrate clinical and radiographic bone expansion techniques that will enhance implant placement treatment for implantologists and patient’s experience.

OBJECTIVES/GOALS: The goal of our multi-institutional team is in our name Holistic Electrical, ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury†(HEPIUS) Lab. Officially, I am a Ph.D. researcher, but the team has empowered me to share insights from being a former spinal cord patient myself – creating a more direct feedback loop. METHODS/STUDY POPULATION: Human-centered design is a method growing in popularity due to its impact on outcomes. Any translational project aspires to utilize some level of patient perspective. Our team has taken several initiatives to make this a part of our core. The team has a dedicated advisor who suffered a spinal cord injury and underwent the current standard of care. There are also non-traditional and unofficial advocates (like myself) on the team. Although I am fully recovered today without any symptoms from a different spinal cord complication, the team equips me with the time and support needed to share my experiences in clinic. The team gives me the opportunity to champion for the most appropriate approaches during official meetings and periodically in the lab whenever a question arises. RESULTS/ANTICIPATED RESULTS: In this poster we aim to discuss the following points: 1.) Team Culture: Those with patient insights will only share if there is an established healthy culture. 2.) Privacy: Just because someone advocates on the behalf of patients does not mean that they need to divulge personal information 3.) Workflow Structure: Sharing patient insight only reaches as far as the organization permits. Thankfully, my team is open to member perspectives and has benefited from several insights already 4.) The art of listening: Patient insights should be listened to and treated with respect, but not as an undebatable suggestion 5.) Rewarding aspects: Sharing patient insights is a very rewarding experience if you feel comfortable enough to share. DISCUSSION/SIGNIFICANCE: Translational teams often rely on statistics, one-time patient interviews, or dedicated individuals in an advocacy role to help guide the project. This poster is intended to highlight some new ways to practice engagement of patient perspectives, while introducing the intricacies of fostering healthy cultures which promote these voices.

ABSTRACT IMPACT: As scientific research is trending towards greater interdisciplinary and collaboration in order to meet the challenges of contemporary science, which has led to increased recognition of the importance of Team Science, this study will promote team science research within NJ ACTS Consortium as well as across the country. OBJECTIVES/GOALS: The objective of this study is to assess the feasibility of using the NIH Reporter database for developing and tracking team science metrics within the CTSA-funded NJ ACTS Consortium, which consists of RU, PU, and NJIT. The NIH Reporter database provides detailed information on single-PI and multiple-PI R01 grants funded by NIH. METHODS/STUDY POPULATION: 58 multi-PI projects and 344 single-PI projects are currently funded within the NJ ACTS consortium. We will use information from the database on funding levels, institutional composition of projects (e.g., within-consortium projects vs. projects with PIs both within and outside of the consortium), numbers of publications, impact factors of publications, and funding supplements obtained to quantify and track NIH R01 Team Science activity in the consortium. RESULTS/ANTICIPATED RESULTS: Preliminary analysis suggests that it will be both feasible and efficient to use the NIH reporter database to develop Team Science metrics and to augment information in the database with information on PI characteristics such as department/center/school/university, academic discipline, and rank/tenure status, as well and detailed composition of research teams, such as the mix in terms of senior and junior scholars. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will make an important contribution to this movement by demonstrating the feasibility of using the publicly available NIH Reporter Database to quantify the level and success of Team Science in the form of single-PI and multiple-PI R01 grants funded by NIH, which represent extremely important Team Science activities at universities.

OBJECTIVES/GOALS: To develop an untargeted metabolomics assay that can holistically characterize the small molecule signatures of different inborn errors of metabolism (IEM) for biomarker discovery and identification of novel IEMs, with the goal of implementing the assay into the clinical laboratory to improve testing efficiency. METHODS/STUDY POPULATION: A hydrophilic interaction liquid chromatography (HILIC) column and reverse phase (RP) column were assembled in tandem on a SCIEX X500B quadrupole time-of-flight (QTOF) system to create a dual liquid chromatography (LC), tandem mass spectrometry method. The X500B was operated in data-independent acquisition mode with both positive and negative ionization. A mixture of 165 reference standards from eleven compound classes common to IEMs were used to evaluate the capability of the assay to resolve small molecules. Chromatographic resolution for each standard was determined qualitatively by comparison to a reference spectral database. External validation of the assay will be performed by analyzing a commercial library of reference metabolites. RESULTS/ANTICIPATED RESULTS: A total of 88% (146/165) of the standards were detected by the assay. The RP column alone resolved 71% (117/165) of the standards, the HILIC column resolved 33% (55/165), while 17% (29/165) of the standards were resolved by both columns. The HILIC column resolved standards that were more polar, while the RP column resolved more non-polar compounds. To evaluate matrix effects, the reference standard mixture was spiked into pooled plasma. In the presence of plasma 6/146 (4%) of the standards were suppressed to levels below the limit of detection. We expect external validation with the commercial metabolite library will corroborate these results, and that the high-quality spectral data attained from this reference library can be used to improve identification of unknown metabolites in patient samples. DISCUSSION/SIGNIFICANCE: We have shown our untargeted metabolomics assay can detect known biomarkers for IEMs. Clinical implementation of this method could streamline diagnosis of IEMs while simultaneously improving patient outcomes by leveraging the metabolome for biomarker discovery, and improved understanding of IEM mechanisms to inform novel treatment strategies.

OBJECTIVES/GOALS: a. Summarize barriers and best practices related to effective CRP onboarding, training and professional development b. Identify challenges with the assessment of and mentoring for CRP competency growth. c. Describe opportunities to improve the training and professionalization of the CRP career pathway. METHODS/STUDY POPULATION: Qualitative data from a series of UnMeeting breakout sessions and open-text survey questions were analyzed to explore the complex issues at play when developing high-quality onboarding and continuing education opportunities for CRPs at academic health centers. RESULTS/ANTICIPATED RESULTS: Results suggest there are several barriers to providing training to the CRP workforce, including: balancing foundational onboarding with role-based training, managing logistical challenges and institutional contexts, the need for institutional champions, assessing competency, and providing high-quality mentorship. Several of these themes are interrelated. One common thread present throughout all of these themes is the challenge of effective communication and team science training. DISCUSSION/SIGNIFICANCE: Few institutions have solved all of the issues related to training a competent and adaptable CRP workforce, although some have addressed one or more. This study illustrates the need to work collaboratively within and across institutions to overcome training barriers and support a vital and well-qualified workforce.

OBJECTIVES/GOALS: Harmful algal blooms (HABs) are increasing in both frequency and intensity due to climate change. HABs release the toxin microcystin-LR (MC-LR) which enters cells via organic anion-transporting polypeptides (OATPs). In this study, we sought to assess the ability of MC-LR to accumulate in trophoblasts, potentially disrupting placental functions. METHODS/STUDY POPULATION: Intracellular accumulation of MC-LR at exposure concentrations of 0.1, 1, and 10 µM over 6 hrs was evaluated in immortalized JAR placental cytotrophoblasts. Western blotting was used to evaluate protein-bound MC-LR accumulation in JAR cells. The function of OATP transporters in JAR cells was determined by pre-incubating cells with 10µM cyclosporin A, a general OATP inhibitor for 1 hr, and then incubated with 1µM OATP substrate fluorescein for up to 40 min. Fluorescence of fluorescein was measured at Ex/Em: 494nm/515nm by spectrophotometry. RESULTS/ANTICIPATED RESULTS: A concentration-dependent increase of MC-LR bound proteins in JAR cells was observed at 6 hrs with the greatest intracellular accumulation of MC-LR at 10µM. In the transporter experiments, a significant decrease of fluorescein uptake by up to 45% into JAR cells was observed following cyclosporin A inhibition of OATPs. These findings are consistent with the functional expression of OATP transporters in JAR placenta cells. Ongoing studies are evaluating whether the cyclosporin A-mediated inhibition of OATPs also inhibits the uptake of MC-LR. DISCUSSION/SIGNIFICANCE: Although MC-LR is well-known for its hepatotoxic and neurotoxic effects, there is growing interest in examining its potential adverse impacts on female reproductive health, particularly during pregnancy. Active uptake of MC-LR into the placenta could interfere with placental and fetal development.

ABSTRACT IMPACT: This study will provide important insight about effective team formation from coming up with an idea to successfully implementing that idea, as well as will highlight the implementation, evolution, and future directions of a team science initiatives. OBJECTIVES/GOALS: The goal of this study is to describe the feasibility of initiating an ideation forum to catalyze team formation, explore the process by which themes and teams are selected to participate in the forum setting, and assess the progress of participating teams post-forum through internal and external funding and other synergistic research activities. METHODS/STUDY POPULATION: Three ideation forums took place between 2018-2019 at Rutgers University, with a defined process and collection of data. The method of intervention to trigger team science, specifically the methodology employed to identify teams and produce new collaborative ideas, will first be described to show the feasibility of such an event to encourage team formation. In post-hoc analysis, we compare various success matrices of participating teams received seed funding versus teams that didn’t receive any funding to assess the progress of teams in the research ideation forum incubation process. RESULTS/ANTICIPATED RESULTS: Triggering team science through ideation forums is feasible and, in fact, quite productive to creating a durable response in formed teams showing continued productivity in publications, fundraising, and other academic metrics. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our case review can illuminate how academic institutions can support team science research through ideation forums. In addition, this study lays an initial foundation for improvements in ideation forum creation and new metrics that can be shared broadly to compare across other institutions.

OBJECTIVES/SPECIFIC AIMS: The primary aim is to assess differences in therapeutic effect between MSC and EPC EVs on acute ischemic rat hearts through delivery in a biocompatible and shear-thinning hydrogel. Primary outcomes for therapeutic assessment include an in-vitro angiogenesis assay and in-vivo hemodynamic analysis, mainly identifying differences in ejection fraction and contractility. Secondary hemodynamic outcomes include cardiac output, stroke volume, and end-diastolic pressure volume relationship (EDPVR). Secondary structural outcomes include post-mortem scar analysis and immunohistochemistry (IHC) staining for angiomyogenesis. METHODS/STUDY POPULATION: MSCs and EPCs will be cultured according to previously published protocols. EVs will be isolated from cultured cell lines through precipitation methods with polyethylene glycol. EVs will be qualitatively analyzed with nanoparticle tracking analysis (NTA) and flow cytometry. The shear thinning hydrogel (STG) will be constructed using a hyaluronic backbone conjugated to adamantane or beta-cyclodextrin, ultimately facilitating guest-host interactions with shear thinning properties. Controls and treatment groups mixed with the hydrogel will be injected into the border zone of infarcted Wistar rat hearts immediately following a left anterior descending artery ligation. Hemodynamic assessment will be performed at four weeks through left ventricular catheter based pressure-volume recordings. Ex-vivo analysis will include scar thickness assessment using Masson collagen staining and IHC stain for vessel (anti-vonWillebrand factor; anti-Isolectin) and myocyte formation (anti-cardiac Troponin I). RESULTS/ANTICIPATED RESULTS: We hypothesize that, in-vitro, MSC-EVs will demonstrate non-inferior angiogenic potential as compared to EPC-EVs. We posit that MSC-EVs will demonstrate superior therapeutic effect to EPC-EVs in-vivo as measured by functional hemodynamics and structural assessment. We have successfully isolated MSC and EPC EVs and have validated uniformity across EV populations (Figure 1). Preliminary data from the angiogenesis assay (n=3) demonstrated that MSC-EV and EPC-EV produce non-significantly different angiogenic potential as measured by number of vascular meshing extremes (p=0.144) and length of master vascular segment (p=0.193), with significant differences compared to either positive or negative controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Novel regenerative therapies are needed for patients with a history of AMI given current limitations to therapy and sequelae of ischemic heart disease. Delivery of extracellular vesicles through a shear-thinning gel is a novel “off-the-shelf” translational approach to address the current clinical need.

OBJECTIVES/GOALS: Knocking down the inflammatory response following joint trauma may halt the cytokine cascade and prevent the resulting cyclic degradation of articular cartilage. MK2 inhibiting (MK2i) peptides are an emerging and promising class of pharmaceutical to treat post-traumatic osteoarthritis (PTOA); however, these peptides are susceptible to proteolytic degradation in the extracellular space. Our objective is to encapsulate MK2i in thermoresponsive hollow nanoparticles (hNPs) to knockdown the inflammatory cytokine IL-6 to prevent the cyclic degradation of articular cartilage. METHODS/STUDY POPULATION: NP Synthesis: N-isopropyl acrylamide (NIPAm) cores was initiated by potassium persulfate (KPS) in aqueous solution with sodium dodecylsulfate (SDS) at 70°C under a nitrogen for 2 hours. Then exposed to oxygen for 45 min, followed by a nitrogen purge. NIPAm, 2-acrylamindo-2-methyl-1-propanesulfonic acid (AMPS), N,N’-bis(acryoyl)cystamine (BAC), and Acrylic Acid (AAc), in fluorescent batches rhodamine b isothiocyanate (RBITC), were polymerized around the core to form the shell. NPs were purified using tangential flow filtration. The NPs were dialyzed at 4°C for 14 days to remove the core and form hNPs. Loading & Release: hNPs and MK2i were incubated at 1 mg/ml at 4°C for 24 h. MK2i released into 1x PBS and analyzed on HPLC. IL-6 Expression: Bovine chondrocytes seeded at 10,000 cell/cm2 were stimulated with 20 ng/ml IL-1b daily and treated once with 100 µg/ml MK2i loaded-NP or 100 µg/ml free MK2i treatment on day 2. Analyzed on bovine IL-6 ELISA. In Vivo Intra Articular Injections: 75 µl of 2 mg/ml hNPsRHB or a PBS control was injected into the right knee of 4-month old Fischer 344 (Envigo) rats. Rats were imaged daily for 7 days then euthanized, legs dissected, and imaged. RESULTS/ANTICIPATED RESULTS: Core removal facilitated increased MK2i release from hNPs, Fig 1A, allowing up to 63% after 5 days in PBS. The hNPs generated here offer a continual sustained release of MK2i and hNPs are non-cytotoxic (data not shown) up to 12 mg/ml. MK2i loaded-NPs significantly knocked down IL-6 production after a single treatment after 2 days, Figure 1B, and continued knockdown for up to 4 days. hNPsRBITC was successfully injected into rat joint space and was retained for at least 7-days compared to pre-injection and PBS control, Fig 1 B-C. DISCUSSION/SIGNIFICANCE OF IMPACT: hNPs protect MK2i from ECM degradation and offer continual sustained release into chondrocytes. Core removal allows for MK2i release in vitro with further sustained release compared to previous non-degradable model. The single MK2i treatment lead to a significant IL-6 knockdown bovine chondrocytes for up to 4 days in hNPs. We were able to successfully inject and retain fluorescently labeled hNPs within rat knees for 7 days. Our translational therapeutic shows the promise of delivering a degradable, non-cytotoxic hNP into the joint space to knockdown the inflammatory response to halt the cyclic progression of articular cartilage degradation and progression of PTOA. CONFLICT OF INTEREST DESCRIPTION: The authors declare the following competing financial interest(s): Moerae Matrix, Inc. has a worldwide exclusive license to the CPP (MK2 inhibitor peptide). A. Panitch owns greater than 5% of Moerae Matrix, Inc.

OBJECTIVES/SPECIFIC AIMS: To understand the mechanisms of how a non-antimicrobial can reshape a commensal microbe community to cure a ubiquitous human disease. METHODS/STUDY POPULATION: Whole genome sequencing of bacterial isolates, metabolomic investigations of previously collected skin microbe isolates from patients, and structural investigations of a protein from these skin microbes. RESULTS/ANTICIPATED RESULTS: Metabolic pathways associated with adaptation to a changing skin microenvironment, novel antimicrobial characterization, and a structural understanding of a novel nutrient acquisition protein. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple angles of this investigation are poised to improve current non-antimicrobial dermatologic treatments and they have the potential to impact microbe-related diseases in other human microenvironments.

OBJECTIVES/GOALS: Patient adherence with antidepressant therapy is a critical aspect of clinical management. Drug molecules often interact with other off-target proteins resulting in adverse events. We utilized an interactome model for predicting the likelihood of adverse drug reactions in order to accurately prescribe antidepressant medications to a patient. METHODS/STUDY POPULATION: We utilized an interactome model to study physical interactions between proteins and biological functions disrupted by major depression to understand how changes in genes alter patient-specific drug efficacy and cause adverse drug-reactions. To study how drugs and diseases propagate through the proteins and biological functions, we harnessed diffusion profiles to represent nodes in the graphical model and used a biased random walks model to illustrate how signals propagate in a heterogeneous biological network. The edge weights were defined for the drug, disease, protein, and biological function node types. The interactions studied included drug-protein, disease-protein, protein-protein, protein-biological function, biological function-biological function. RESULTS/ANTICIPATED RESULTS: Based on previous studies, we anticipate that the genetic variants modulating antidepressant response include 5-HTT, STin2, HTR1A, HTR2A, TPH1 and BDNF. Additionally, genetic variants such as SLC6A4 as well as the HPA pathway may play an important role in antidepressant therapeutic response. With regards to medication drug response, the genes, SLC6A4 and HTR2A, have been known for encoding proteins that affect the synaptic cleft of serotonergic neurons. Also, the gene SLC6A4 has been shown to encode for the serotonin reuptake transporter, which is the main pharmacological target of SSRIs. In female patients with major depression, the polymorphism associated with MAOA gene may be involved in the pharmacological response. DISCUSSION/SIGNIFICANCE: The key to successful depression treatment is early adherence but nearly 60% of patients discontinue antidepressants within three months. By developing a strong understanding of the genes that alter treatment efficacy, we can provide patients with more awareness regarding the most effective treatment plan to minimize adverse events.

OBJECTIVES/GOALS: Negative emotions (NE) play a pivotal role in addiction-related processes, including tobacco lapse during a quit attempt. Some NEs (e.g., shame, guilt) are posited to lead to a spiraling effect, whereby lapse predicts increased NEs leading to further lapse. This study goal is to examine associations between NEs and lapse. METHODS/STUDY POPULATION: This study examined associations between tobacco lapse and 13 distinct NEs among people who use tobacco and are trying to quit in two tobacco cessation studies. In Study 1, 220 adult (ages 18-74) cigarette users who identified as Black (50% female) participated in a 14-day study where ecological momentary assessment (with assessments approximately every 4 hours) was used to assess emotions and lapse in real-time and real-world settings. In Study 2, 288 adult (ages 18-71) cigarette users who were low socioeconomic status (51% White, 14% Black, 10% Hispanic, 49% female) participated in a 14-day study with the same study protocol as Study 1. Between and lagged within-person associations testing links between distinct NEs and lapse were examined with multilevel modeling with logistic links for binary outcomes. RESULTS/ANTICIPATED RESULTS: Results from Study 1 suggested that at the between-person level, disgust (OR =1.22, CI: 1.05, 1.42), nervousness (OR=1.23, CI:1.05,1.43), guilt (OR=1.40, CI: 1.16,1.69), and sadness (OR=1.18, CI:1.02,1.36) were predictive of higher odds of lapse, and at the within-person level, shame (OR=1.23, CI:1.04,1.45) was associated with higher odds of lapse. Results from Study 2 were similar and suggested that at the between-person level, disgust (OR=1.35, CI: 1.16, 1.56) and guilt (OR=1.88, CI:1.07,3.30), and at the within-person level, shame (OR =1.31, CI:1.10,1.55), were associated with higher odds of lapse. DISCUSSION/SIGNIFICANCE: The present study uses real-time, real-world data to demonstrate the role of distinct NEs on momentary tobacco lapse and helps elucidate specific NE that hinder the ability to abstain from tobacco use during a quit attempt. Results suggest that disgust, guilt, and shame play consistent roles in predicting lapse among diverse samples of tobacco users.