Objectives/Goals: To create raciolinguistically sensitive emotion recognition assessment materials, we will (i) identify the prosodic cues that signal differences between raciolects (Black vs. White American English) and (ii) identify the prosodic cues that signal different emotions (angry, happy, and sad). Methods/Study Population: Research evaluating prosodic differences between raciolects and emotions both implicate pitch. For example, Black speakers tend to produce speech lower in pitch, and sad speech tends to be narrower in pitch range. In our study, 50 Black and 50 White American healthy adults will hear manipulated recordings of Black and White speakers uttering pseudoword strings that vary by mean pitch and pitch range. In the race task, participants will choose whether the stimulus was produced by a Black or White speaker. In the emotion task, they will choose whether the stimulus sounded happy, angry, or sad. Linear mixed-effects models will be used to determine the pitch correlates for each emotion by race. Results/Anticipated Results: If mean pitch (high, low) and pitch range (wide, narrow) function as acoustic correlates for emotions but differ by race, we expect the following: first, members in each participant group (Black, White) will converge on correlates that differentiate emotions and race; and second, the emotion correlates will differ between groups. Preliminary results using stimuli from only White speakers suggest convergence across groups for emotions (angry: low mean pitch, happy: high mean pitch, and sad: narrow pitch range) but not race. Ongoing data collection including stimuli from White and Black speakers will be used to conduct planned comparisons as well as test same-race, different-race differences. Discussion/Significance of Impact: Characterizing the prosodic differences in emotion recognition between races helps us understand disparities in post-stroke aprosodia. Additionally, developing a linguistically informed strategy for assessing deficits between dialects can be readily implemented across diverse linguistic communities.

OBJECTIVES/GOALS: The Professional Development Core (PDC) of the Hispanic Alliance for Clinical and Translational Research (The Alliance) has implemented a multifaceted program to support Early-Stage Investigators (ESI) and mid-career investigators to increase productivity and achieve success in their research endeavors. METHODS/STUDY POPULATION: Since 2021, PDC launched an educational program tailored for ESI or mid-career investigators, addressing specific gaps in research competencies. A needs assessment survey gathered information from these investigators, and its results served as the foundation for the program’s design. In addition, recognizing the need for excellence in mentoring, PDC spearheaded a program to provide a certification curriculum for new or experienced mentors. Experienced researchers were encouraged to participate in the certification process with ample opportunities to discuss their mentoring experiences and the incorporation of new approaches that emphasize diversity and inclusion. A structured mentored research experience with support for protected time for the investigator and the mentors was also implemented. RESULTS/ANTICIPATED RESULTS: Four investigators and their mentors have received the Mentor-Mentee Award (100% PhD, 75% female, 50% Assistant Professor, 75% ESI, 75% with mentors from the mainland United States). Their program’s evaluation will be presented. Thirty-two (32) researchers have participated in the courses in Health Disparity and Scientific Communication. Support for grant writing was offered through a three-pronged approach: a webinar series, a course in Grantsmanship and a grant’s bootcamp. Twenty-four (24) mentors were certified, and over 30 training activities were offered to supply knowledge in areas previously identified in the needs assessment. We will present the complete curriculum, courses offerings, participants’ profiles, and productivity outcomes. DISCUSSION/SIGNIFICANCE: Alliance educational and mentoring supportive network increased the diversity of CTR workforce and prepared qualified researchers to address the Hispanics health needs. Collaborations with mainland researchers have expanded the PDC program’s reach and contributed to the enhancement of the Hispanic contribution to the health research ecosystem.

OBJECTIVES/SPECIFIC AIMS: The food reward circuitry regulates hedonic eating especially in relation to palatable hypercaloric foods, which can lead to chronic overeating and consequent overweight and obesity. Evidence supports that there is considerable overlap within the brain reward circuitry between palatable hypercaloric food intake and substance addiction. The goal of this study was to identify associations between addiction-related genes and body mass index. We hypothesized that addiction-related genes potentially participate in the food reward circuitry if they are associated with obesity traits. METHODS/STUDY POPULATION: A secondary analysis was conducted with 1093 African American adolescents and young adults from the New Mother’s Study. Anthropometric, genetic, demographic and lifestyle measurements were available at the 18-year follow-up assessments. A total of 1350 single nucleotide polymorphisms mapped to 127 addiction-related genes were assessed. A total of 186 ancestry informative markers were used to adjust for population stratification. Generalized estimating equation models were used to identify genetic associations, including additive, dominant, and recessive models, and control for correlations within families. RESULTS/ANTICIPATED RESULTS: The participants ranged from 15 to 23 years of age. Of them, 42.7% were overweight or obese. Significant associations with body mass index were identified for 13 single nucleotide polymorphisms mapped to 11 addiction-related genes, including LEP (p 0.027–<0.001). Most of these genes are involved in dopaminergic, opioidergic, serotonergic pathways, and stress. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results support the role of dopaminergic and opioidergic pathways in the food reward circuitry, and suggest a potential involvement of serotonergic pathways and genes related to stress in the food reward circuitry. Further investigation of the identified genes will facilitate delineation and understanding of the brain food reward system and its relationship with obesity.

OBJECTIVES/GOALS: African-Americans have a 3-fold higher risk of end-stage kidney disease (ESKD) compared to Whites due in part to APOL1 risk alleles. Whether resistant hypertension (RH) magnifies the risk of ESKD among African Americans beyond APOL1 is not known. We examined the interaction between RH and race on ESKD risk and the independent effect of RH beyond APOL1. METHODS/STUDY POPULATION: We designed a retrospective cohort of 240,038 veterans with HTN, enrolled in the Million Veteran Program with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2. The primary exposure was incident RH (time-varying). The primary outcome was incident ESKD during a 13.5 year follow up: 2004-2017. Secondary outcomes were myocardial infarction (MI), stroke, and death. Incident RH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 antihypertensive drugs, including a thiazide, or use of 4 or more drugs. Poisson models were used to estimate incidence rates and test additive interaction with race and APOL1 genotype. Multivariable Cox models (with Fine-Gray competing-risks models as sensitivity analyses) were used to examine independent effects. RESULTS/ANTICIPATED RESULTS: The cohort comprised 235,046 veterans; median age was 60 years; 21% were African-American and 6% were women, with 23,010 incident RH cases observed over a median follow-up time of 10.2 years [interquartile range, 5.6-12.6]. Patients with RH had higher incidence rates [per 1000 person-years] of ESKD (4.5 vs. 1.3), myocardial infarction (6.5 vs. 3.0), stroke (16.4 vs. 7.6) and death (12.0 vs. 6.9) than non-resistant hypertension (NRH). African-Americans with RH had a 2.6-fold higher risk of ESKD compared to African-Americans with NRH; 3-fold the risk of Whites with RH, and 9.6-fold the risk of Whites with NRH [p-interaction<.001]. Among African-Americans, RH was associated with a 2.2-fold (95%CI, 1.86-2.58) higher risk of incident ESKD in models adjusted for APOL1 genotype and in the subset of African-Americans with no APOL1 risk alleles, RH was associated with an adjusted 2.75-fold (95% CI: 2.00-3.50) higher risk of incident ESKD. DISCUSSION/SIGNIFICANCE OF IMPACT: RH was independently associated with a higher risk of ESKD and cardiovascular outcomes, especially among African-Americans. This elevated risk is independent of APOL1 genotype. Interventions that achieve BP targets among patients with RH could curtail the incidence of ESKD and cardiovascular outcomes in this high-risk population. CONFLICT OF INTEREST DESCRIPTION: None.

OBJECTIVES/GOALS: There is a critical need to provide quality training for study teams. Materials need to be flexible and available at the learner’s preferred time and format. DIAMOND was developed to provide nimble education offerings that respond to the changing landscape of clinical and translational research. METHODS/STUDY POPULATION: In 2018 four CTSA institutions (the University of Michigan, the Ohio State University, Rochester University, and Tufts University) collaborated to launch the DIAMOND portal. Developed as a CTSA-wide web-based platform, DIAMOND allows members of clinical and translational research teams to widely share and access training and education resources. In 2022 a MICHR-led update of DIAMOND used principles of user centered design to improve the platform. New features include updated search functions to quickly find and sort training materials, tagging training materials to the characteristics of a translational scientist, and development of user controlled customized playlists. RESULTS/ANTICIPATED RESULTS: DIAMOND currently includes 217 training resources developed by 30 CTSA hubs and private industry. The platform has over 600 page views per day from users across the U.S. and internationally. DIAMOND includes an easy-to-use form to upload new materials to the platform. Contributors are asked to include key words and select competency domains and characteristics of a translational scientist that apply to their materials. Other new features include tagging materials to streamline and improve search results, the ability to sort materials by competency domain or characteristics of a translational scientist, and the ability for users to create and share customized, personalized playlists. DISCUSSION/SIGNIFICANCE: DIAMOND is an important tool to support workforce development for study teams. Updates to the flexible digital platform meet the needs and preferences of adult learners and busy health professionals. Lessons learned from the design process and future plans for the platform will be explored.

ABSTRACT IMPACT: By restoring the gut microbiota in patients with acute myeloid leukemia exposed to antibiotics, we will reduce infections during and after curative-intent chemotherapy. OBJECTIVES/GOALS: Infection is a leading cause of death in acute myeloid leukemia (AML). Antibiotics disrupt the gut microbiota, promoting secondary infections. Through a double-blind randomized placebo-controlled phase 2 trial, we will determine whether microbiota restoration using fecal microbiota transplantation (FMT) prevents infections in AML patients. METHODS/STUDY POPULATION: 72 intensively treated AML patients at our institution are randomized in a 2:1 ratio to FMT (arm A) or placebo (arm B). After completing each course of antibacterial antibiotics, patients receive one study treatment. Up to 3 study treatments are administered over 3 months. FMT is delivered as a third-party oral product containing microbiota (˜5x10^11 bacteria) in 4-6 capsules. Stool samples are collected before and after each study treatment. The primary endpoint is 4-month overall infection rate. 16S rRNA gene sequencing of stool samples is used to determine specific taxa that are under- or over-represented in samples preceding infections and compare the two arms for key microbiome features including diversity and composition. Bloodstream infection within 7 days after FMT counts towards stopping rule. RESULTS/ANTICIPATED RESULTS: Five patients have been enrolled: 4 have received 1 dose and 1 received 2 doses. The only adverse event (possibly related to study treatment) has been grade 1 abdominal pain in 1 patient. Notably, no bloodstream infection has occurred. All planned samples have been collected and are sequenced in batches. We expect arm A patients to experience fewer infections and fewer intestinal blooms of pathobionts, and both arms to experience intestinal blooms before specific infections. An interim efficacy analysis will be performed at half total enrollment. DISCUSSION/SIGNIFICANCE OF FINDINGS: Current supportive care during intensive chemotherapy is fundamentally anti-microbial and results in dysbiosis, with detrimental consequences. We will establish the evidence for FMT as a restorative strategy in AML patients. This is the first randomized placebo-controlled trial of repeated FMT, with potential implications to other cancers.

OBJECTIVES/GOALS: The objectives of the ICPC Course were 1) to define elements needed to 'build' a solid framework for the creation of an effective informed consent document; 2) to examine various regulatory references and their importance in the context of the informed consent process; and 3) to review helpful tips and best practices of the informed consent process. METHODS/STUDY POPULATION: This 7-week course was a multi-disciplinary effort by the Miami CTSI, the Regulatory and Monitoring Support Office and the Human Subjects Research Office (HSRO), as part of their co-op partnership. The CTSI’s Network of Clinical Research Professionals (NCRP) (over 1995 members and established to offer and enhance education, training, and overall career development and networking for the U’s diverse research workforce) served as the target audience. The lead HSRO official was the course content developer and served as instructor. The Director of the HSRO served as the certificate & program coordinator. Additionally, this course indirectly fulfilled part of the requirements of the Institution’s AAHRPP re-accreditation. RESULTS/ANTICIPATED RESULTS: 70 persons attended all sessions and received their certificate. A post-course survey was deployed (n=70). 69 respondents were extremely satisfied with course content; 67 were likely to recommend the course to a colleague. Feedback highlights include: appreciation for time taken to organize/offer the course; presenter knowledge and preparation; and that case studies/examples were up-to-date and applicable. As an added incentive to participate in the course, both the School of Nursing and the Medical School provided CEU credits and the Society of Clinical Research Associates (SOCRA) accepted documentation of candidate participation in continuing education programs for recertification. DISCUSSION/SIGNIFICANCE: Based on a need identified through a multi-disciplinary process, a successful Informed Consent Professional Certificate Course was created and implemented. Respondents indicate extremely high satisfaction with the course and felt it was very relevant and applicable to their practice.

OBJECTIVES/SPECIFIC AIMS: Bladder cancer patients being considered for immune checkpoint blockade are often judged on immunohistochemical staining for the checkpoint target protein PD-L1 in the original surgery or biopsy sample. However, sampling error or the clinical evolution of most patients’ cancer can render the original PD-L1 assessment no longer accurate. In contrast, circulating tumor cells (CTCs) allow serial noninvasive sampling of the current tumor status throughout a patient’s clinical course including those with the highest metastatic potential. We therefore sought to develop a method for quantifying PD-L1 expression in CTCs towards addressing inherent limitations of current UC management. METHODS/STUDY POPULATION: This work utilizes both cancer cell lines as well as patient samples. Positive and negative control cancer cell lines were assessed via “industry standard” antibodies for PD-L1 expression via Western blots and immunofluorescence, and a threshold-based method was developed for reliable quantification. PDL-1 expression was additionally verified via interferon-mediated up-regulation. CTCs isolated from bladder cancer patient samples via a density centrifugation method were then assessed for PD-L1 via the same antibodies. RESULTS/ANTICIPATED RESULTS: We will show preliminary preclinical and clinical data that validates the sensitivity and specificity of our assay. A case study will be presented that illustrate the potential useful of the novel approach we describe and which should be complementary to current clinical practices. In a patient with metastatic bladder cancer, this method effectively detected the PD-L1 expression in CTCs taken at a time coincident to when the patient derived an excellent response to the PD-L1 checkpoint inhibitor Pembrolizumab. DISCUSSION/SIGNIFICANCE OF IMPACT: This work highlights the potential utility of CTCs in the management of bladder cancer. It may be the case that this assay in conjunction with current methods of patient selection for immunotherapy may allow for better response prediction than either method alone.

OBJECTIVES/GOALS: Septic shock is a lethal condition. Research suggests that overall sepsis mortality varies by race, but less is known about demographic differences in septic shock mortality. Our objectives were to describe the septic shock population using a large, state-wide data repository and identify demographic predictors of septic shock mortality. METHODS/STUDY POPULATION: This was a retrospective review of patients with septic shock in the One Florida Data Trust from 2012-2018. Patients were classified as having septic shock if they received vasopressors and had either 1) an ICD-9 or 10 code for septic shock or 2) an ICD-9 or 10 code for infection and an ICD-9 or 10 code for organ dysfunction. Demographic data and place of residence prior to admission was collected. The primary outcome was 90 day mortality. T-test and chi-square tests were used to test association of individual predictors and mortality. Multiple logistic regression was used to identify predictors of mortality after adjustment for other variables. Level of significance was set at 0.05. SAS v9.4 (Cary, NC) was used for analyses. RESULTS/ANTICIPATED RESULTS: There were 11,790 patients with septic shock. The mean(SD) age was 61(16) years. With regard to race/ethnicity 66% identified as white, 27% as black, 3.7% as Hispanic, and 3.5% as other races (non-white, non-black, non-Hispanic). Most came from home (57%). Overall, 39% died. Mortality varied by race (p<0.01): white 39%, black 39%, Hispanic 31%, other races 51%. In the logistic regression model, age, race, and residence were significant predictors of mortality, after adjustment for other variables. Each additional year of age had a 2.7% increased odds of mortality (OR 1.03; 95% CI 1.02-1.03; p<0.01). Compared to white patients, odds of death were 1.6 times higher for other races (95% CI 1.3-2.0; p <0.01) and non-significantly higher for black patients (OR 1.1; 95% CI 1.0-1.2; p = 0.05). Compared to those from home, odds of death were highest for those from a skilled nursing facility (OR 1.5; p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients who identified as other races had increased mortality from septic shock compared to white patients after adjusting for other variables. Septic shock mortality also increased with age and varied by residence. Further analyses are needed to examine racial disparities and control for comorbidities, severity of illness, and aspects of resuscitation. CONFLICT OF INTEREST DESCRIPTION: The authors report no conflicts of interest, except for Dr. Fernandez, who reports personal payment from Physio-Control, Inc. for speaker fees.

Objectives/Goals: Despite efforts to support healthcare researchers to navigate translational gaps and achieve health impact, impact remains rare. We were interested in determining whether, when, and how researchers were taking actions to optimize the translational potential and impact of their research. We also wanted to identify ways to support optimization. Methods/Study Population: Our sample was drawn from Tufts CTSI’s annual outcomes survey respondents (2017–2022) and included tufts principal investigators who had at least one project that reported an outcome (e.g., publication, presentation, funding application, research products, intellectual property protection, and implementation) on the survey. We excluded individuals no longer based at Tufts, no longer working in research, and holding a non-leadership role in their research. We drew a random sample of 58 researchers from the database. Of these, 11 (19%) were excluded, 32 (55%) did not respond to our invitation, 3 (5%) declined to take part, and 12 (21%) were interviewed. The study was approved by Tufts IRB and semi-structured interviews were recorded via Zoom, transcribed in full, and analyzed using the qualitative software Dedoose. Results/Anticipated Results: We interviewed 12 participants, both male (5) and female (7), from 11 different fields, working in preclinical (2), clinical (6), and public health (4) research at assistant (3), associate (5), and full professor (4) rank. There was variety in the way that researchers conceptualized and anticipated pathways to impact. While researchers almost always described their motivation as connected to improved patient care, their ideas of impact were commonly described as research products or outputs, and there was little attention to planning and executing for real-world use. Researchers spoke about challenges related to competing career demands, institutional barriers, organizational culture, and lack of connections. Strategies to address these challenges included mentorship, collaboration, and policy work. Discussion/Significance of Impact: The disconnect between researchers’ ideas of output and impact was notable, and while researchers sometimes mentioned dissemination via publications and committees, use of dissemination and implementation frameworks were very infrequent. Fragmented approaches and implementation science gaps remain significant barriers to health impact.

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.

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.