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/Goals: We aim to identify how IDH mutant (IDHm) gliomas use exosomes to modulate the local and systemic immune system. We will do so by characterizing differential miRNA expression between IDHm and IDH wild type (IDHwt) exosomes and identifying the specific immune cell population targeted by exosomes in vivo. Methods/Study Population: Exosome RNA will be isolated from cultured patient glioma samples and perform small RNA sequencing to investigate differential expression of miRNA between IDHwt and IDHm exosomes. We will then utilize miRNA target databases in conjunction with bioinformatic pathway analysis to generate potential target regulatory pathways. To identify the in vivo effect of tumor exosomes, we will generate a novel glioma mouse model that has been genetically engineered to release labeled exosomes using the RCAS retroviral system. We will collect peripheral blood and tumor tissue for flow cytometric immune profiling and single-cell RNA sequencing. The transcriptomic data will be analyzed to identify subsets of immune populations that have taken up the labeled exosomes and assess the resulting expression changes in those cells. Results/Anticipated Results: From the small RNA sequencing and bioinformatics analysis, we expect to find several unique miRNA expressed in IDHm exosomes that induce immunosuppressive pathways in local and systemic immune cell populations when compared to IDHwt exosomes. Furthermore, using our novel murine model, we expect to be able to track endogenously released exosomes in the local tumor microenvironment and in the circulating blood. We hypothesize that IDHm exosomes specifically target precursor myeloid cells within the local and peripheral circulating immune populations and induce the expansion of monocytes, M2 macrophages, and mono-MDSCs. Discussion/Significance of Impact: Immunosuppression in IDHm glioma has hindered the development of adequate therapies to treat this fatal disease. Our study will illuminate the mechanism by which tumor exosomes can suppress immune surveillance. These results will help identify new therapeutic targets to sensitize the immune system against glioma cells.

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: 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/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/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.

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: This study aimed to investigate the role of artificial intelligence (AI) in translational science, including personalization of interventions and drug development. Methods/Study Population: A comprehensive literature search was conducted via PubMed, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), Cochrane Library, Medline, and Web of Science. The risk of bias in the eligible studies was assessed using the risk of bias in nonrandomized studies. Data were systematically extracted and analyzed. Results/Anticipated Results: The literature search yielded 2129 records, from which 20 studies that met the eligibility criteria were included. Meta-analysis demonstrated the high specificity of AI-based diagnostics, reassuring the reliability of AI. Furthermore, AI applications significantly improved biomarker identification through machine learning algorithms, enhancing prognostic accuracy and treatment personalization. Moreover, AI showed enhanced diagnostic precision with high sensitivity and specificity in cancer detection, further validating its role in healthcare. AI-driven risk stratification was used in chemotherapy decisions. Discussion/Significance of Impact: This study highlights the transformative power of AI in translational oncology research with applications in drug development and personalized patient care in cancer treatment and research.

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 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: 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.