OBJECTIVES/SPECIFIC AIMS: Cannabinoids suppress gastric acid secretion, ameliorate gastric inflammation, and promote gastric ulcer healing, all of which are triggered by H pylori (Hp). Our aim was to determine the relationship between cannabis use and: 1) H pylori infection (HPI) among community residents 2) clinical peptic ulcer disease (PUD) and its complications among hospitalized patients. METHODS/STUDY POPULATION: We performed case-control studies with records from the NHANES III (n=4,556) and HCUP-NIS 2014 (n=4,555,029), and respectively identified subjects with seropositivity for H pylori and clinical PUD, and their cannabis usage status. In the NHANES III, we estimated the adjusted prevalence rate ratio (aPRR) of having HPI with cannabis use, using generalized estimating equations. In the NIS, we propensity-matched cannabis users to non-users in ratio 1:1 (68,073:68,073) and measured the aPRR of having PUD and its complications (SAS 9.4). RESULTS/ANTICIPATED RESULTS: In NHANES III, associated with decreased HPI seropositivity were cannabis ever-users (aPRR: 0.79[0.66-0.95]), greater than 10 times lifetime usage (0.65[0.5-0.84]) and recent 31-day usage (0.67[0.48-0.98]), compared to never usage. In the HCUP-NIS, cannabis users had decreased risk for total PUD (aPRR: 0.74[0.61-0.89]), duodenal PUD (0.48[0.35-0.60]) and PUD complications including hemorrhage (0.58[0.37-0.90]), perforation (0.66[0.51-0.87]), but not obstruction (1.75[0.51-5.98]). DISCUSSION/SIGNIFICANCE OF IMPACT: Cannabis usage is related to a reduced likelihood of having HPI in the community and also mitigate against having complicated presentations to the hospital. More translational studies are needed to illuminate the details of this relationship, given the high worldwide prevalence of both cannabis use and HPI.

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) affects 1 in 3 Americans and can exist in 2 histological subtypes: simple hepatic steatosis (SHS) and nonalcoholic steatohepatitis (NASH), a clinically aggressive variant. Fatigue is the most common complaint in patients with NAFLD but the etiology of fatigue is unknown. Thus, the goal of this study was to objectively evaluate fatigue via maximal cardiopulmonary exercise testing and identify determinants of exercise intolerance in NAFLD. METHODS/STUDY POPULATION: In total, 14 subjects with histologically confirmed NAFLD were prospectively enrolled. Subjects with cirrhosis or those with known history of heart failure (systolic or diastolic) were excluded. Fatigue was quantified via the Duke Activity Status Index (DASI) questionnaire. A symptom-limited treadmill cardiopulmonary exercise test was performed in all subjects to measure exercise time (ET) and peak oxygen consumption (peak VO2). Doppler-echocardiography was performed to measure systolic and diastolic function. RESULTS/ANTICIPATED RESULTS: The DASI score and ET was significantly reduced in patients with NASH (n=10) when compared to those with SHS [40.2 (IQR=24.2–50.7) vs. 58.2 (IQR=50.7–58.2), p=0.04]; [9.1 (IQR=6.4–12.2) vs. 13.1 (IQR=12.5–13.1) min, p=0.02, respectively] reflecting moderate fatigue and impaired overall exercise capacity. The ET was directly linked to peak VO2 (R=+0.79, p<0.001), VO2 at anaerobic threshold (R=+0.73, p=0.003), and inversely to ventilatory efficiency index (R=−0.785, p=0.001) suggesting impaired cardiorespiratory fitness in those with reduced ET. ET was also linked to several parameters of diastolic dysfunction including left atrial volume index (R=−0.798, p<0.001), and the ratio of early transmitral pulse-wave Doppler flow velocity (E) to early mitral annulus tissue Doppler velocity E’ (E/E’) (R=−0.608, p=0.036), suggesting a role of diastolic dysfunction in patients with NAFLD with exercise intolerance. DISCUSSION/SIGNIFICANCE OF IMPACT: Cardiac abnormalities drive cardiorespiratory fitness and exercise intolerance in patients with NAFLD. These findings are exaggerated in patients with NASH suggesting a link between disease severity in NAFLD, exercise intolerance and diastolic dysfunction.

The mission of the National Center for Advancing Translational Science (NCATS) is to speed the development of drugs from discovery to approval to dissemination and implementation. The Medical University of South Carolina and the South Carolina Clinical and Translational Research Institute host a NCATS funded predoctoral T32 training grant (TL1) with a focus on translational research. Doctoral (PhD) trainees working at the bench usually have limited opportunity for clinical interactions to gain a clinical perspective on the diseases that are the focus of their dissertation research. To provide TL1 trainees with an opportunity to see how their research could be translated into improved patient care, we developed a mentored clinical exposure experience named the Translational Sciences Clinic. Trainees spend one-half day a week in a clinic related to their basic science research for one semester interacting with patients and clinical mentors and discuss the most recent literature related to the patient’s clinical problem with their clinical mentor. Trainees deemed the rotation to be one of the most rewarding experiences that they had as a part of their predoctoral training. Participating clinical mentors were also very enthusiastic and agreed that they would be willing to mentor similar trainees again.

Objectives/Goals: To discuss the challenges faced by National Drug Early Warning System (NDEWS; PI Cottler) in monitoring emerging drug trends and disseminating data to maximize public health impact. Drug trends are constantly in flux, with various communities facing different harms. To provide salient information, NDEWS must triangulate data from multiple sources. Methods/Study Population: In 2020, NDEWS was funded at University of Florida through a cooperative agreement with NIDA. A Scientific Advisory Group meets regularly for overall guidance, and 17 Sentinel Sites provide local perspectives. Now in its fifth year, NDEWS has utilized traditional data such as death reporting and drug seizures and has launched several novel surveillance components. Rapid Street Reporting conducts anonymous surveys of drug use in a Sentinel Site or hotspot each month. Machine learning methods applied to Reddit reveal new trends and novel substances. County-level alerts are generated by analysis of 911-dispatch data accessed through biospatial.io. Wastewater-based epidemiology provides city-level data. Findings are disseminated primarily through email weekly briefings and by peer-reviewed articles. Results/Anticipated Results: In its first iteration, NDEWS has expanded available data sources and worked to integrate data to reveal trends that impact communities across the USA. These patterns vary substantially over time and by region and population, complicating analysis, but inclusion of multiple data sources is imperative for a full understanding of the landscape. NDEWS continues to explore novel routes of disseminating information to those who need it, including contacting local health departments with high overdose rates. Establishing networks for bidirectional communication with stakeholder groups such as toxicologists and educational affiliates is underway. NDEWS seeks to deepen ties with survivors unions (those with lived experience) and harm reduction organizations, which can be difficult due to mistrust of research. Discussion/Significance of Impact: Monitoring the rapidly changing drug landscape in the USA is challenging, and its importance has only grown in recent years as new substances arise and adulterated drug supply has become the norm, promulgating the rise of dangerous substances such as fentanyl and xylazine. Ensuring that information filters out to those who use substances is critical.

OBJECTIVES/GOALS: This project presents the Post-doctoral Master of Science in Clinical and Translational Research (MSc) program’s outcomes in 20 years of its implementation. This program is a joint offering between the Schools of Health Professions and School of Medicine of the University of Puerto Rico. METHODS/STUDY POPULATION: This study consists of secondary data analysis of academic and administrative documents. It also includes data from the Annual Evaluation retreats reports and an Alumni Follow-up Survey using an electronic questionnaire. All 121 Scholars admitted to the program from academic years 2003 to 2023 were included in the sample. Data analysis included descriptive statistical analysis of quantitative data and qualitative content analysis regarding recruitment/admissions, faculty composition, curriculum design, Scholars’ outcomes, and program’s financial support sources. Quantitative data were analyzed using the statistical software SPSS. RESULTS/ANTICIPATED RESULTS: Scholars of the program had been recruited from the UPR-MSC and several partner institutions with diverse backgrounds, disciplines, and research areas. Faculty and committee members have representation from the six MSC-Schools and partner institutions. The academic Program structure has changed over the years, and currently, more than 65% of the courses are offered online. Several financial sources have been identified to support the scholars. The Scholars’ portfolios of grant submission and publication productivity evidence the program’s success. Graduates have also been successful in advancing to positions that foster research impacting Hispanics. DISCUSSION/SIGNIFICANCE: The Post-doctoral Master’s in Clinical and Translational Research program (MSc) has contributed to the formation of committed Hispanic clinical and translational researchers impacting minorities and contributing to diversity in the research workforce.

ABSTRACT IMPACT: We seek to determine which lymph nodes drain the human brain. OBJECTIVES/GOALS: Lymphatic vessels train lymphatic fluid from the central nervous system (CNS), but the specific lymph nodes that these vessels drain to remains unknown in humans. We intend on using technetium tilmanocept (TcTM)to map the draining lymph nodes of the CNSin humans. METHODS/STUDY POPULATION: Patients having a tumor resected are eligible for the trial. All patients will have TcTM injected intracranially after tumor resection. Six patients will be enrolled in Cohort 1 to define the time course of drainage to the lymph nodes. Patients in Cohort 1 will be imaged with planar LS within 7 hours of injection and the following day. Either 12 or 24 patients will be enrolled into Cohort 2 to localize the draining lymph nodes with SPECT-CT. The optimal imaging timepoint from Cohort 1 will be used for Cohort 2. Patients in Cohort 2 will be stratified depending on if their tumor is in the frontal, parietal, occipital, or temporal lobe. RESULTS/ANTICIPATED RESULTS: We anticipate that we will detect TcTMin the deep cervical lymph nodes after injection into the brain. It is unclear exactly which lymph nodes the tracer will go to. We hypothesize that the results among patients will be similar, but interindividual variation is a possibility. Furthermore, patients with disease in different lobes of the brain may have different lymph drainage patterns. DISCUSSION/SIGNIFICANCE OF FINDINGS: We seek to answer a fundamental question of human anatomy: what lymph nodes drain the human brain? Additionally, knowing which nodes drain the human brain could shape future research of immunotherapy in patients with brain cancer or autoimmune disease such as multiple sclerosis.

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

OBJECTIVES/GOALS: We developed a state-wide program to support early career faculty in preparing mentored career development awards, and connect them to resources, mentorship, and career development opportunities. We aimed to build self-efficacy along multiple axes, including research design and grantsmanship, and to facilitate networking with mentors and peers. METHODS/STUDY POPULATION: The program recruited four cohorts of faculty over the course of four years, for a total of 32 faculty participants (63% physician scientists). Participants were selected by a Steering Committee, and represented a variety of specialties from 19 departments across Brown University, University of Rhode Island, and affiliated hospitals. Participation required an institutional commitment of 20% minimum protected time to engage in research and a year-long curriculum that included biweekly didactic sessions, project development support, individual consultations, feedback on drafts, and internal study section review. Participants completed pre-, interim-, and final-assessments, which collected measures of self-efficacy, professional development needs, program satisfaction, and formative feedback. RESULTS/ANTICIPATED RESULTS: Over the first 3 years, 21 participants completed the program, 43% have received NIH or VA K/CDA awards so far, and 48% received other federal or non-federal awards. Over 25 faculty from across institutions participated in leadership and didactics, with even greater participation on mentorship teams, panels, and grant review. All cohorts showed improvements in measures of self-efficacy in grantsmanship and research and reported high satisfaction with program activities. Participants found individualized proposal feedback and internal study sections to be most valuable, and frequently cited the value of peer-learning opportunities. Challenges for scholars include mentorship challenges, competing priorities/protected time, and various external factors that impacted individual research progress. DISCUSSION/SIGNIFICANCE: The program has successfully supported cohorts of junior clinical and translational faculty from across the state in launching their independent research careers. The program may serve as a model for IDeA state inter-institutional collaboration in developing diverse faculty cohorts in the early stages of preparing their career development award.

Objectives/Goals: To assess the feasibility, safety, and preliminary efficacy of implementing a supervised, outpatient aerobic and strength exercise regimen in newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL). We hypothesize that early implementation of exercise is feasible and may prevent well-known cardiometabolic late effects. Methods/Study Population: We will enroll 10–20 children (both males and females) with newly diagnosed ALL between the ages of 11–21 years to participate in a 12-month supervised, structured outpatient exercise regimen (STRONGER ALL). This regimen will consist of low- to moderate-intensity aerobic and strength exercises (either in person or coached virtually per patient preference) 3 times a week. This study will include 2 physical fitness assessments: 1) baseline and 2) end of study. Assessments will include resting energy expenditure, peak oxygen uptake, bone density, upper and lower extremity strength, flexibility, and questionnaires (feasibility and quality of life). Additionally, blood and urine specimens will undergo metabolomic analysis to identify biomarkers predictive of future cardiometabolic outcomes. Results/Anticipated Results: We expect that early implementation of STRONGER ALL in children undergoing chemotherapy will be feasible and preliminarily effective at mitigating risk factors for long-term cardiometabolic outcomes in survivors. Feasibility will be defined by recruitment capability (at least 50% of eligible patients agree to enroll), acceptance/compliance (at least 50% of participants complete the program with participation in at least 50% of sessions), data acquisition (collection and outcomes measures are appropriate), and practicability (program shows promise of being successful with pediatric ALL patients as measured by validated surveys administered to patients and caregivers). We anticipate that ALL patients participating in STRONGER ALL will have improved fitness and quality of life. Discussion/Significance of Impact: Evidence on the benefits of physical activity for ALL patients has not changed clinical practice. We aim to overcome the translational science barrier of patient- and system-level blockade in implementation of exercise in children with ALL. The evidence generated from this research may also be generalizable to other childhood cancer survivors.

OBJECTIVES/GOALS: The Association of Clinical and Translational Science (ACTS) chartered a Diversity, Equity, and Inclusion (DEI) Committee to prioritize activities to support, develop and report on metrics for measuring progress toward DEI goals. This poster aims to describe the formative process toward prioritizing DEI in society’s efforts. METHODS/STUDY POPULATION: In 2021, the ACTS chartered the DEI Committee. Two ACTS Board of Directors members chair the committee, and members represent 10 academic institutions committed to prioritizing DEI. Members participated in a Human-Centered Design process to develop the committee’s mission, goals, and activities. The committee determined areas of opportunity for ACTS to increase DEI by identifying challenges to support DEI in clinical and translational science. The chairs facilitated a discussion using Mural to foster an interactive strategy to engage members in conversations that respected individual experiences, promoted a discussion of actions that ACTS as a society, and determining metrics for measuring DEI. RESULTS/ANTICIPATED RESULTS: We plan to present the committee’s efforts to create the ACTS mission statement and strategies to priority to DEI. We will describe current and future activities to engage historically underrepresented members and academic institutions in ACTS programs. Based on the committee’s work, ACTS has taken systematic approaches toward social justice and is beginning to determine new ways of engaging members. DISCUSSION/SIGNIFICANCE: Scientific societies that prioritize DEI increases equity and belonging across members. ACTS is at the forefront of advocacy, policy, and social justice effort. The DEI committee is positioned to aid ACTS in increasing DEI across the clinical and translational science spectrum.

ABSTRACT IMPACT: Increase understanding of the types of sponsors responding to the COVID-19 pandemic. OBJECTIVES/GOALS: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, treatment, and preventative products, the healthcare community has initiated a staggering number of clinical trials. Clinicaltrials.gov was reviewed to determine the types of sponsors who are conducting COVID-19 studies. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched using terms ‘COVID-19’ and ‘SARS-Cov-2’. Search results were further defined to include only ‘Interventional’ studies. Of these, only studies with sites located in the United States were selected and for which the ‘Condition’ included at least one of the following terms: ‘COVID’, ‘COVID-19’, ‘Coronavirus’, ‘SARS-Cov-2’, ‘SARS’, or ‘2019-nCoV'. Study sponsors were then categorized as: (1) commercial, (2) academic, or (3) other, based on ‘Sponsor’ information within each study listing. A Google search was conducted for any sponsor that was not easily categorized to obtain additional information to support the proper assessment of sponsor type. The types of sponsors were analyzed over time using the ‘First Posted’ date of each study listing. RESULTS/ANTICIPATED RESULTS: A total of 3662 studies were retrieved, of which 2075 were ‘Interventional’ studies. The studies were further reduced to 681 studies by including only United States sites and the desired ‘Condition’. The percentage of studies from this refined dataset, by sponsor type, were found to be 63% academic, 34% commercial, and 3% other. The relationship between time and sponsor type demonstrated that academic sponsors had the highest percentage of study postings in the first month (March) of the COVID-19 pandemic compared to commercial and other sponsors. Following this first month, academic study postings gradually declined, while commercial sponsors had an increase in postings per month into July, followed by a gradual decline. Few other sponsor type postings were made and occurred primarily in August. DISCUSSION/SIGNIFICANCE OF FINDINGS: The number and timing of listings may be a reflection of study intention and regulatory pathway requirements. Additional variables, such as inconsistent terminology, collaborators, funding, and study start date may influence results. Further analysis may reveal how modification of listing information may result in expedited pandemic response.

OBJECTIVES/SPECIFIC AIMS: Current practice frequently dictates hospitalization for TIA and minor stroke (TIAMS) in order to obtain comprehensive evaluation of stroke risk factors and mechanism. Inpatient hospitalization is often done to expedite workup and to coordinate care although may be associated with nosocomial risks and increased healthcare cost. However, a subset of these patients who do not have debilitating deficits may not require inpatient hospitalization. We conducted a pilot study to assess the feasibility of conducting rapid outpatient stroke evaluations in low risk patients with TIAMS without disabling deficits. METHODS/STUDY POPULATION: The rapid access clinic was initiated at a single-site urban tertiary care facility for outpatient evaluation of TIAMS within 24 hours of emergency department (ED) evaluation. Patients were selected using a decision tool identifying presumed low-risk TIAMS seen in the ED. Criteria included medical (e.g., no disabling deficit, no thrombolytic agent given, negative CT for hemorrhagic stroke) as well as social criteria (e.g., patient ability to follow-up as an outpatient). We evaluated rates of noncompliance with post-ED follow-up, need for hospitalization from clinic, and 90 day stroke and health outcome data. RESULTS/ANTICIPATED RESULTS: Between December 2016 and December 2017 a total of 93 TIAMS patients seen in the ED were recommended for the rapid access clinic utilizing the decision tool. Of these patients, 94.5% (86) were evaluated within 24 hours of ED discharge. Only 2 patients (2.4%) who received outpatient evaluation required hospitalization; 61 (71.8%) patients had TIAMS on final evaluation in clinic. DISCUSSION/SIGNIFICANCE OF IMPACT: Our pilot data suggests that for a subset of patients, rapid outpatient evaluation may be a feasible and safe strategy for TIAMS management. Future work exploring such strategies may help improve TIAMS outcomes and reduce ED crowding and unnecessary hospital admissions.

OBJECTIVES/SPECIFIC AIMS: We set out to describe important associations and outcomes among those requiring maintenance renal replacement therapy with the patient volume per provider. METHODS/STUDY POPULATION: Through the combination of several large administrative datasets, including the United States Renal Data System (n=237,485), the American Medical Association Master file (n=6249), and Medicare data limited to 2012, we compared characteristics of patients, by quintile of patient/provider volume. χ2 and logistic regression, adjusted for various patient and provider factors for categorical and continuous variables, was used for baseline comparisons, respectively. Cox regression, adjusted for patient, provider, and socioeconomic variables, was used to calculate risks for important clinical outcomes such as kidney transplant listing, transplant receipt, and all-cause mortality. RESULTS/ANTICIPATED RESULTS: There is a threshold patient volume at which important clinical outcomes, including kidney transplantation and all-cause mortality, may be influenced. Higher patient volume is associated with adverse patient outcome. Those receiving care from providers with the highest patient volumes are less likely to receive kidney transplantation, live in a more rural area, and be non-White. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a need to identify novel and potentially modifiable factors associated with patient outcome among those with end-stage kidney disease on maintenance renal replacement therapy. Provider level variables, such as patient volume, is one such variable. As nephrologists are often tasked with the care of variable numbers of patients on dialysis, a better understanding of this association is an unmet need.

OBJECTIVES/SPECIFIC AIMS: Understand the immunomodulatory effects of anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (G-CSF) on type 1 diabetes patients using samples and in the preclinical model, the nonobese diabetic mouse. METHODS/STUDY POPULATION: Flow cytometry analysis of phase 1 peripheral blood samples treatment of nonobese diabetic mouse with ATG and GCSF and flow cytometry analysis of immune organs (spleen, lymph nodes, blood, bone marrow). RESULTS/ANTICIPATED RESULTS: Changes in both innate and adaptive immune cell subsets including plasmacytoid dendritic cells, naive, memory, effector CD4+ and CD8+ T-cells, and CD4+ T-regulatory cells and CD8+ T-regulatory cells DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding of immune cell targets for immunotherapy in new-onset type 1 diabetes patients.

OBJECTIVES/GOALS: To describe the prevalence of, and factors associated with, psychotropic medication use before cancer diagnosis (solid tumor cancer, lymphoma or leukemia) among AYAs 15 to 39 years of age in the US. METHODS/STUDY POPULATION: Retrospective cohort study in a 10% sample of claims from the IQVIA PharMetrics® Plus for Academics (2006-2020). We included AYAs with no prior cancer diagnosis codes 9 months before their index date – defined as the first of ≥2 ICD-9/10-CM primary diagnosis codes for cancer occurring ≤60 days apart. We defined psychotropic use as a claim for an antidepressant, anxiolytic/sedative-hypnotic, mood stabilizer, stimulant or antipsychotic medication. Prevalence of psychotropic use overall and by class, was estimated as the proportion of AYAs with at least one claim for a psychotropic in the 9-months prior to the index date. Using Chi-square and T-tests, we compared demographic characteristics, prevalence of mental health disorders, chronic pain and cancer type between psychotropic users and non-users. RESULTS/ANTICIPATED RESULTS: We identified 6,257 AYAs with cancer (thyroid 17%, breast 13%, melanoma 13%), 64% female, mean age 31 (SD 6) years. Twenty-four percent (n=1,506) used a psychotropic in the 9 months prior to the index date. Psychotropic classes used were antidepressants 15%, anxiolytic/sedative-hypnotics 11%, stimulants 3%, mood stabilizers 2% and antipsychotics 1%. Psychotropic use was higher among females than males (27% vs 19%, p <.001), older than younger AYAs (35 to 39 years-old: 26% vs 15 to 19 years-old: 16%, p <.001). Anxiety (25% vs 4%), depression (22% vs 3%) and chronic pain (17% vs 8%) were more common among those with psychotropic use pre-cancer diagnosis (all p <.001). The proportion of AYAs diagnosed with brain cancer was higher among psychotropic users than non-users (7% vs 5%, p <.001). DISCUSSION/SIGNIFICANCE: One in four US AYAs used a psychotropic medication prior to being diagnosed with cancer. Understanding psychotropic medication management patterns for these patients before cancer treatment may help inform comprehensive care.