OBJECTIVES/GOALS: Our preclinical data demonstrate that the principal effects of nilotinib, a multi-tyrosine kinase inhibitor, in models of neurodegeneration is clearance of misfolded proteins via autophagy. Here we aimed to evaluate the effects of nilotinib on microRNAs in the cerebrospinal fluid of Parkinson’s disease patients. METHODS/STUDY POPULATION: Cerebrospinal fluid (CSF) was collected as part of an open label phase I (NCT02281474) (n = 12, 300 mg nilotinib taken orally once daily for 6 months), and a phase II randomized, double-blind, placebo-controlled study (NCT02954978) (n = 75, randomized 1:1:1 into placebo, 150 mg or 300 mg nilotinib taken orally once daily for 12 months). RNA was isolated from CSF and Indexed sequencing libraries were prepared from total RNA plus miRNA. Next generation whole-genome sequencing (single-end 1x75 bp, 25 million raw reads per sample) was performed to identify miRNAs significantly differentially expressed (fold-change ≥ 2, Benjamini-Hochberg FDR p-value ≤ 0.05 or Empirical Bayes FDR ≤ 0.05) with treatment compared to baseline. RESULTS/ANTICIPATED RESULTS: Next generation whole-genome sequencing of microRNAs in the CSF demonstrated that nilotinib significantly increases microRNAs that specifically regulate expression of autophagy and ubiquitination genes in individuals with Parkinson’s disease. In the open label phase I, samples, 28 microRNAs found to regulate autophagy and ubiquitination genes, were significantly altered with treatment (Benjamini-Hochberg FDR p-value ≤ 0.05). In the phase II randomized, double-blind, placebo-controlled study samples, we verified several of those 28 candidate microRNAs had been significantly deferentially expressed with treatment (Empirical Bayes FDR p-value ≤ 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data provide robust evidence that nilotinib’s effects on misfolded protein clearance is via autophagy and CSF miRNA sequencing is a valid biomarker of nilotinib’s effects in a definitive phase III study to investigate nilotinib in Parkinson’s and other neurodegenerative diseases. CONFLICT OF INTEREST DESCRIPTION: Charbel Moussa is listed as an inventor on several Georgetown University patents for the use of tyrosine kinase inhibitors as a treatment for neurodegenerative diseases

OBJECTIVES/GOALS: Artificial Intelligence (AI) is gaining popularity in a variety of disciplines. While clinical applications for AI have increased in recent years, the use of AI in pediatric congenital heart disease (CHD) is limited. The goal of this systematic review was to assess how AI is currently used in this patient population and to describe knowledge gaps. METHODS/STUDY POPULATION: A systematic search was performed up to July 2023 using PubMed and Scopus databases and revealed 814 articles. Upon initial screening, 161 duplicates, 76 non-AI articles, and an additional 318 irrelevant articles were removed. A total of 259 full-text articles were reviewed for relevance. Articles that did not include a retrospective or prospective review of human subject data were excluded. Articles that had only results in the adult, prenatal, or non-CHD population were excluded. The remaining 68 articles were included in this review. RESULTS/ANTICIPATED RESULTS: Of the 68 articles in this review, 19 were performed within cardiac surgery, 41 were within cardiology, and the remaining 8 included articles were combined cardiac surgery and cardiology. Upon initial review, 24 used AI for diagnostic purposes, 40 for predicting survival or adverse outcomes, 2 for developing training tools, and 2 for surveillance of CHD trends. We anticipate that upon further review of these 68 articles, there will be a wide variety in the types of AI models that were used. The results will reveal a multitude of challenges and limitations that future studies will need to further address. DISCUSSION/SIGNIFICANCE: While technical innovations in pediatric CHD have dramatically improved survival rates, we have hit a plateau in improving the complications of these patients. AI has created an opportunity to build new diagnostic, predictive, teaching, and surveillance tools for advancing CHD care, but it seems we still have a long way to go.

ABSTRACT IMPACT: This study highlights the importance of creatine in developmental myelination and remyelination to investigate whether creatine provides a therapeutic value during a central nervous system (CNS) demyelinating insult with a potential value in patients with Multiple Sclerosis. OBJECTIVES/GOALS: Creatine is vital for ATP buffering in the brain. Interestingly, the cells that generate myelin express the main enzyme for creatine synthesis, Gamt. Patients with Gamt mutations display intellectual delays and impaired myelination. Therefore, we hypothesize that creatine is essential for developmental myelination and improves remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the guanidinoacetate methyltransferase (Gamt) gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. We used immunohistochemistry techniques to look at the corpus callosum, the main white matter tract in the brain, and evaluate the number of oligodendrocytes (OL), glial cells responsible for generating myelin. We also used the cuprizone model of toxic demyelination to investigate whether dietary creatine and cyclocreatine, a planar analog of creatine that more efficiently crosses the blood-brain barrier, can enhance remyelination. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (+/-0.47%, n=3) co-localization of Gamt within mature OL during postnatal (P) day P14 with no co-localization in neurons or other glial cells. This suggests that mature OL are the main cells making creatine in the CNS. Next, we show that knocking out Gamt leads to a significant reduction in OL in the developing corpus callosum, at P14 and P21 (P14: 0.007, n=3; P21: 0.04, n=3). We also show that creatine supplementation causes a trending increase in mature OL density in the corpus callosum following cuprizone demyelination (2% creatine; p=0.052; n=4). Interestingly, cyclocreatine supplementation significantly increased mature OL density in the corpus callosum following cuprizone demyelination (0.1% cyclocreatine; p=0.034; n=4). DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies highlight the important role creatine plays in developmental myelination and remyelination to investigate whether creatine and cyclocreatine provide a therapeutic value during a CNS demyelinating insult. This work investigates a potential therapeutic value of creatine to patients with Multiple Sclerosis.

OBJECTIVES/SPECIFIC AIMS: Black patients with hepatocellular carcinoma (HCC) receive fewer curative therapies and have higher mortality than other groups. Reducing this disparity will require an in-depth understanding of patient comorbidities, tumor characteristics, and social determinants of health. Our objectives are to a) perform a multi-center retrospective cohort study of black and white patients diagnosed with HCC in the Indianapolis area. b) prospectively enroll black and white patients with HCC to collect clinical characteristics as well as data on the social determinants of health. METHODS/STUDY POPULATION: A retrospective chart review of patients with a diagnosis of HCC from 2010-2017 from five area Indianapolis hospitals will be performed. Demographics, comorbidities, liver disease severity, and tumor characteristics will be collected using the Indiana Network for Patient Care database and compared between black and white patients. Concomitantly, a prospective cohort of black and white patients will be enrolled and surveyed to collect data on socioeconomic status and income adequacy, literacy, functional status, substance abuse history, social support, activation, and adherence. The primary outcomes are the receipt of curative therapies for HCC including liver transplantation, resection or ablation. The secondary outcome is mortality. Multivariable logistic regression models will be used to explore disparities seen in the primary and secondary outcomes. RESULTS/ANTICIPATED RESULTS: These preliminary results include Indiana University Hospital (IUH) findings; a multicenter analysis is underway. The IUH cohort included 1,032 (86%) white and 164 (14%) black patients. Black and white patients had similar Model for End-Stage Liver Disease and Child-Pugh scores. There was a trend toward larger tumor size (5.3 cm vs. 4.7 cm; P = 0.05) in black patients; however, Barcelona Clinic Liver Cancer staging and Milan criteria were similar. Black patients were less likely to undergo liver transplantation than white patients—a disparity that was not attenuated (odds ratio [OR], 0.43; 95% confidence interval [CI]: 0.21-0.90) on multivariable analysis. Substance abuse was more frequently cited as the reason black patients within Milan criteria failed to undergo transplantation than white patients. Survival was similar between the two groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Racial differences in patient and tumor characteristics were small in our single center analysis and did not explain the disparity in liver transplantation. This analysis however only reflects 25% of patients diagnosed with HCC in the Indianapolis metropolitan, highlighting the need for a multicenter study. Higher rates of substance abuse in black patients within Milan criteria who failed to undergo transplantation suggest social factors contribute to this disparity and highlight the need for a prospective study that can explore these and other social factors.

OBJECTIVES/GOALS: Characterizing and analyzing research studies presents several challenges given the various ways studies may be labeled or organized. The Medical Subject Headings (MeSH) thesaurus is a hierarchical vocabulary that can index and organize research foci using common business intelligence tools to enable rapid exploration of research portfolios. METHODS/STUDY POPULATION: Metadata from ClinicalTrials.gov on 455,437 trials were downloaded and all MeSH terms associated with trials in the condition_browse section were loaded into a database. The corresponding MeSH trees for each term were then identified and mapped to their ancestor terms within the tree. Trials were then indexed based on top four hierarchical levels for each associated MeSH term. Trials performed at the University of Miami (UM) were identified based on locations associated with the trial as well as matching National Clinical Trial (NCT) numbers identified from internal research administration systems. Business intelligence software (Microsoft PowerBI) was applied to the corresponding dataset to enable end user exploration and analysis of the trials within ClinicalTrials.gov. RESULTS/ANTICIPATED RESULTS: A total of 3,271 studies associated with UM were identified, of which, 3,054 (93.3%) had at least one condition MeSH term linked. A total of 7,711 MeSH terms were associated with the trials overall, representing 1,112 unique MeSH terms; the most common terms were carcinoma (164), lymphoma (155), HIV Infections (139), neoplasms (136), and leukemia (122). Utilizing MeSH hierarchy, trials were characterized were categorized into 36 different trees. The most common top tree nodes were neoplasms (1,181), followed by pathological conditions/signs and symptoms (913), immune system diseases (574), nervous system diseases (513), and digestive system diseases (483). Within trees, a total of 184, 681, and 1057 different MeSH terms were specified at the second, third, and fourth nodes in the hierarchy respectively. DISCUSSION/SIGNIFICANCE: Utilizing existing metadata from trials posted on ClinicalTrials.gov and MeSH tree structures can enable organizations to readily explore the foci of clinical trials research. High rates of MeSH term association to research study conditions are necessary to ensure adequate representation of research foci.

OBJECTIVES/GOALS: Diversity and interdisciplinarity are required for successful and transformational CTR. The Title V Coop developed a training curriculum for underrepresented in CTR health professions faculty and students, successfully integrating them in CTR teams. The curriculum exposed students to theory and then a practicum. METHODS/STUDY POPULATION: The curriculum and practicum included basic aspects of training in research including responsible conduct of research and the design of a proposal. The practicum focused on the organizing of a research team identified as a Clinical and Translational Mentoring Team (CTMT) and the implementation of the proposed project. Emphasis was placed on the importance of the mentor-mentee relationship, including peer mentoring. Participants were recruited from across all post-secondary institutions in Puerto Rico emphasizing the participation of faculty(UgF) and students (UgS) from undergraduate programs in health professions and the participation of graduate students GS) as peer mentors. Research mentors for each of the CTMTs were selected from faculty members that are established researchers. RESULTS/ANTICIPATED RESULTS: Twenty-seven (27) proposals from the CTMTs were approved. A total of one hundred and eight (108) participants were or are still engaged in the proposed research. Thirty-four faculty (34) members participated as mentors and three (3) peer reviewed publications have been done. Health professions and science fields represented by the participants include: Nursing, radiology technician, audiologist, medical students, basic science in biology or chemistry, public health and industrial microbiology among others. We will showcase the diversity in research topics and teams composition and their accomplishments. DISCUSSION/SIGNIFICANCE: The Title V Coop has been successful in integrating individuals from academic programs underrepresented in research into interdisciplinary and interprofessional research teams, launching a model for diversity and interdisciplinarity and representation of health professionals at all levels of research.

OBJECTIVES/GOALS: Our long term goal is to identify the socioeconomic and cancer-specific determinants in patients with prostate cancer undergoing prostatectomy that impact their ability to maintain a healthy weight. This study explores the association between participants’health determinants and their indicated degree of self-efficacy and quality of life (QoL). METHODS/STUDY POPULATION: Study population includes participants of the WARRIOR trial (n=40), which included overweight men scheduled radical prostatectomy from the University of Kansas Medical Center. In addition to baseline demographics, the study team will administer a questionnaire based on a socioeconomic position and health-related QoL framework. This questionnaire will assess participants' socioeconomic, cancer-specific, and psychological circumstances at time of surgery and present day. Univariate analyses will be conducted on all variables with bivariate analyses between socioeconomic and clinical items to the outcome of composite self-efficacy scoring. RESULTS/ANTICIPATED RESULTS: We anticipate that participants in the intervention will report higher self-efficacy and emotional/social support than participants in the control group, participants with social vulnerability (lower income, marginalized race/ethnicity, etc) will report decreased self efficacy and poorer QoL compared with participants who are not socially vulnerable, and that participants who previously indicated social vulnerability will report more emotional barriers to weight loss, and lesser weight loss satisfaction, self-esteem, and QoL. DISCUSSION/SIGNIFICANCE: Lifestyle interventions have helped prostate cancer patients lose weight before surgery, but many regain weight. Exploring perceptions of self efficacy as well as learning more about what structural and systemic barriers affect self efficacy is important to inform how to improve our approach for sustained weight loss and health behavior changes.

OBJECTIVES/SPECIFIC AIMS: Engaging patients and consumers in research is a complex process where innovative strategies are needed to effectively translate scientific discoveries into improvements in the public’s health (Wilkins et. al., 2013; Terry et. al., 2013). The Clinical Translational Science Awards (CTSA)—supported by the National Institute of Health (NIH) under the auspices of the National Center for Advancing Translational Sciences (NCATS)—aim to provide resources and support needed to strengthen our nation’s clinical and translational research (CTR) enterprise. In 2008, Stanford University was awarded a CTSA from the NIH, establishing Spectrum (Stanford Center for Clinical and Translational Research and Education) and its Community Engagement (CE) Program aimed at building long-standing community-academic research partnerships for translational research in the local area surrounding Stanford University. To date, the CE Pilot Program has funded 38 pilot projects from the 2009-2017 calendar year. The purpose of this study was to understand, through a unique pilot program, the barriers, challenges, and facilitators to community-engaged research targeting health disparities as well as community-academic partnerships. METHODS/STUDY POPULATION: Investigators conducted a qualitative study of the community engagement pilot program. Previous pilot awardees were recruited via email and phone to participate in a one-hour focus group to discuss their pilot project experience—describing any barriers, challenges, and facilitators to implementing their pilot project. RESULTS/ANTICIPATED RESULTS: The focus group revealed that community engage research through the pilot program was not only appreciated by faculty, but projects were successful, and partnerships developed were sustained after funding. Specifically, the pilot program has seen success in both traditional and capacity building metrics: the initial investment of $652,250.00 to fund 38 projects has led to over $11 million dollars in additional grant funding. In addition, pilot funding has led to peer-reviewed publications, data resources for theses and dissertations, local and national presentations/news articles, programmatic innovation, and community-level impact. Challenges and barriers were mainly related to timing, grant constraints, and university administrative processes. DISCUSSION/SIGNIFICANCE OF IMPACT: The Community Engagement Pilot Program demonstrates an innovative collaborative approach to support community-academic partnerships. This assessment highlights the value and importance of pilot program to increase community engaged research targeting health disparities. Challenges are mainly administrative in nature: pilot awardees mentioned difficulties working on university quarterly timelines, challenges of subcontracting or sharing money with community partners, onerous NIH prior approval process, and limitations to carryover funding. However, pilot grants administered through the program strengthen the capacity to develop larger scale community-based research initiatives.

OBJECTIVES/GOALS: People living with HIV, despite antiretroviral therapy (ART), have increased burden of inflammatory and aging-related comorbidities such as periodontitis. Oral microbiota have been linked to periodontitis, but not in the context of HIV. We aim to compare relationships between the oral microbiome and periodontal disease in HIV+ vs healthy controls. METHODS/STUDY POPULATION: In an ongoing cohort study we have been recruiting pre- and post-menopausal women with HIV+ on ART for ≥6 months and HIV- controls matched by menopausal status (target n = 30 per arm; currently HIV+: n = 30 post- and 9 pre-M; HIV-: n = 15 post- and 6 pre-M). Patients age <18 or on antibiotics within 3 mos., except prophylaxis, are excluded. Patients provide saliva, then subgingival plaque collection during a dental examination through scaling from six index teeth. Standard CDC/AAP classifications of periodontitis are used. We will perform 16S rRNA and ITS sequencing to profile bacterial and fungal communities in saliva and plaque. Linear mixed effect regression and differential abundance analyses will be used to identify microbial and mycobial oral signatures of periodontal disease severity in HIV+ and HIV- populations. RESULTS/ANTICIPATED RESULTS: We found a markedly high prevalence of severe periodontal disease in HIV+ women despite ART (59%, compared to 11% in HIV- controls). In post-menopausal women with HIV, saliva bacterial α- and β-diversity in the saliva differed significantly with periodontal disease severity. Fungal α-diversity was also significantly lower in plaque from teeth with severe loss of tissue attachment (CAL ≥4 mm). We identified bacterial and fungal taxa significantly enriched in post-menopausal HIV+ women with severe compared to no or mild periodontitis. We hypothesize, similarly, associations between the oral microbiome and periodontitis in HIV- controls. However, we expect overall diversity metrics to be significantly altered in HIV+ compared to HIV- patients, indicating long-term dysbiosis despite treatment with ART. DISCUSSION/SIGNIFICANCE OF IMPACT: Contrasting associations between the oral microbiome and periodontal disease with respect to HIV will provide evidence for the role of microbiota in accelerated aging phenotype caused by HIV. Our results would also provide rationale for interventions targeting co-morbidities in people living with HIV to account for both inflammation and dysbiosis.

ABSTRACT IMPACT: Lipidomics is emerging as a powerful strategy to identify biomarkers for Major Depressive Disorder, as well as therapeutic targets in lipid metabolic pathways. OBJECTIVES/GOALS: Lipidomics is increasingly recognized in precision psychiatry for global lipid perturbations in patients suffering from Major Depressive Disorder (MDD). We will test the hypothesis that lipid metabolism dysregulation is associated with familial risk of depression. METHODS/STUDY POPULATION: Patients with MDD (G1), children (G2), and grandchildren (G3) have been part of a longitudinal study since 1982. If a parent G2 and grandparent G1 have MDD, G3 is considered a high risk of depression. Biospecimens (saliva and serum) were collected for full exome sequencing and RNA analysis. Samples will also be extracted for lipid content and lipids will be identified by mass spectrometry. A panel of nearly 600 lipid species can reliably be identified and quantified using liquid chromatography paired with tandem mass spectrometry (LC-MS/MS). Dysregulated lipids will be correlated with familial risk of depression in samples of G3. RESULTS/ANTICIPATED RESULTS: We hypothesize that dysregulation of lipids and lipid metabolism will be apparent in biospecimens from the high risk compared to the low risk of depression. Also, alterations in RNA transcriptomics of genes involved in lipid metabolic networks are associated with familial risk of depression. Several differential lipid species were previously identified to be associated with MDD. Reduced phosphatidylcholine(PC), phosphatidylethanolamine(PE), phosphatidylinositol(PI), and increased LysoPC, LysoPE, ceramide, triacylglycerol, and diacylglycerol levels have been correlated to MDD. However, these results need to be replicated in independent studies using lipidomics analysis. DISCUSSION/SIGNIFICANCE OF FINDINGS: It is highly likely that completely novel cellular targets will emerge from these studies by uncovering the convergence of lipidomics and genetic variance of lipid metabolic enzymes as biomarkers for predisposition to MDD as well as potential targets for therapeutic development for MDD.

Over the last year, COVID-19 has emerged as a highly transmissible and lethal infection. As we address this global pandemic, its disproportionate impact on Black, Indigenous, and Latinx communities has served to further magnify the health inequities in access and treatment that persist in our communities. These sobering realities should serve as the impetus for reexamination of the root causes of inequities in our health system. An increased commitment to strategic partnerships between academic and nonacademic health systems, industry, local communities, and policy-makers may serve as the foundation. Here, we examine the impact of the recent COVID-19 pandemic on health care inequities and propose a strategic roadmap for integration of clinical and translational research into our understanding of health inequities.

Revisions to the Common Rule and NIH policy require the use of a single Institutional Review Board (sIRB) for the review of most federally funded, multisite research, with the intent of streamlining the review process. However, since initial implementation in 2018, many IRBs and institutions continue to struggle with the logistics of implementing this requirement. In this paper, we report the findings of a workshop held in 2022 to examine why sIRB review remains problematic and propose possible solutions. Workshop participants identified several issues as major barriers, including new responsibilities for study teams, persistent duplicative review processes, the lack of harmonization of policies and practices across institutions, the absence of additional guidance from federal agencies, and the need for greater flexibility in policy requirements. Addressing these problems will require providing additional resources and training to research teams, the commitment of institutional leaders to harmonize practice, and policymakers to critically evaluate the requirement and provide flexibility in applicability.

OBJECTIVES/GOALS: Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. METHODS/STUDY POPULATION: Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. RESULTS/ANTICIPATED RESULTS: Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 0.012; RC, 12925 ± 0.023; n=2; p=2.10e-8]. Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p DISCUSSION/SIGNIFICANCE: MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to increase remission and reduce recurrence for GBM patients.

OBJECTIVES/GOALS: Ask the Experts: A Biomedical Innovation Forum, presented by Fast Forward Medical Innovation (FFMI) at the University of Michigan, provided an opportunity to educate biomedical innovators on life science investment trends and technology assessment criteria. METHODS/STUDY POPULATION: FFMI, in partnership with the U.S. Economic Development Administration, recruited an expert group of panelists to be featured at this virtual event. These life science investment experts provided insight on the strategy, timing, and best method for innovators to engaged investors, the specifics of what investors look for in technologies and project teams, and expectations of investors and project teams after the investment is secured. The panel presentation was followed by a poster presentation highlighting projects from the FFMI Hub at the University of Michigan, allowing innovators to have an open and constructive conversation with experts and attendees. RESULTS/ANTICIPATED RESULTS: There was a total of 73 registrants including academic faculty, biomedical innovators, and life science investment professionals from 21 different academic institutions, private companies, and other organizations. 50 attended the panel presentation and poster session. Results (N=5) of an evaluation of the event revealed that 100% of the respondents strongly agreed or agreed that the event met their expectations, while 80% strongly agreed or agreed that they would recommend the event to a colleague. Feedback from poster presenters was also strong with presenters exclaiming they “enjoyed the panel discussion and getting one-on-one time with the panelists,” as well as “a lot of great advice was given by the experts” and “I really liked the poster presentation part in which I got feedback from the investors.” DISCUSSION/SIGNIFICANCE: The data demonstrates how accelerating technology mining activities, proactively seeking and strengthening external partnerships with investors, and scaling commercialization education programs can have a positive impact on the development and launch of biomedical innovations.

OBJECTIVES/SPECIFIC AIMS: Qualitative approaches help explore poorly understood phenomenon, and are highly engaging, enabling both sides of an encounter greater connection. Historically, Deaf communities have been marginalized and oppressed, with their linguistic needs unrecognized and ignored. As a result, Deaf participants are rarely involved in clinical research. Like other marginalized communities, the Deaf community experiences health disparity compared with others, especially in low- and middle-income settings. The purpose of this project was to assess the feasibility of conducting qualitative research with Deaf Dominicans. METHODS/STUDY POPULATION: We implemented a partnered research process with 59 Deaf community members in the Dominican Republic, conducting preliminary thematic analysis through reviews of interviews and on-site debriefings. RESULTS/ANTICIPATED RESULTS: Participants were highly engaged with the Deaf-Deaf research encounters, indicating satisfaction with both the process and with the opportunity to communicate their needs and interests. Preliminary findings indicated Deaf Dominicans were highly engaged, confirming their interest, and often stated that they felt they were being listened for the first time. Indeed, some participants claimed that this was the first time they communicated their experiences as Deaf Dominicans and appreciated the opportunity to relate this experience to Deaf interviewers. DISCUSSION/SIGNIFICANCE OF IMPACT: This experience confirms that the Deaf Dominican community can be mobilized and will participate in Deaf-Deaf research.

OBJECTIVES/GOALS: The goal of this study is to compare plasma neurofilament light (NfL) concentrations in asymptomatic children and young adults that carry the gene expansion (GE group) that causes Huntington’s Disease to similar subjects that do not carry this genetic mutation (GNE group). METHODS/STUDY POPULATION: Subjects from the Kids-HD study in the GE group were divided into groups based on their estimated years to motor onset. Each subgroup was compared to the subjects from the GNE group. Additionally, a group of participants with juvenile HD were compared to the GNE group. These comparisons were made by utilizing linear mixed effects regression models that included a random effect per subject and family and also included the covariates of age and parental socioeconomic status. A post-hoc analysis of subjects in the GE group who were within 20 years from their predicted motor onset was conducted to assess the relationship between striatal volume and plasma NfL concentrations. RESULTS/ANTICIPATED RESULTS: GE participants more than 20 years from their predicted motor onset did not have elevated plasma NfL concentrations relative to the GNE group. However, participants who were 15-20 years from their predicted motor onset had a mean NfL concentration of 1.61 pg/uL compared to 1.31 pg/uL in the GNE group (p = 0.036). Participants who were within 15 years from their predicted motor onset had a mean NfL concentration of 2.08 pg/uL, which was also significantly elevated relative to the GNE group (t = 3.03, p = 0.003). Additionally, the participants with juvenile HD had a mean NfL level of 3.22 pg/uL, which was significantly elevated compared to the GNE group (p<0.0001). NfL concentrations were significantly correlated with striatal volume amongst participants who were within 20 years of onset (p = 0.017). DISCUSSION/SIGNIFICANCE OF IMPACT: The huntingtin protein is essential to neurodevelopment but current gene therapies for HD focus on blocking production of this gene. These results will provide guidance on the optimal timing of administration of gene therapies by identifying neurodegeneration decades prior to motor onset of HD.

OBJECTIVES/GOALS: The Virtual CTSA Visiting Scholars Program allows KL2 scholars to serve as visiting professors at host CTSA consortium institutions. This program facilitates connections with faculty outside scholars home institutions, as well as fostering collaboration among different CTSA hubs. Stanford aimed to incorporate participants into its KL2 program. METHODS/STUDY POPULATION: Stanford is one of 57 host institutions for the Virtual CTSA Visiting Scholars Program. The program includes a virtual meeting between each participant and a chosen faculty at the host institution. Program participants also give a virtual Grand Rounds lecture, open to the entire CTSA consortium. As well as encouraging Spectrum KL2 Scholars to participate in the virtual exchange, the Spectrum KL2 program incorporated the visiting scholars into weekly activities over the course of 3 months. Visiting scholars were invited to participate virtually in KL2 educational sessions, which provide career development training and mentoring. As meetings transitioned to in-person, KL2 scholars were allowed to attend virtually when needed. Hybrid in-person sessions were also conducive to participation by visiting scholars. RESULTS/ANTICIPATED RESULTS: Stanfords Spectrum KL2 program was virtual (Zoom) for academic year 2020-2021 and included 1:1 mentoring sessions, weekly career development seminars, and 1:1 peer virtual lunches to integrate the 9 junior faculty scholars. Visiting scholars joined the weekly Zoom meetings when their schedules allowed. KL2 faculty mentored visiting scholars for 3 months, exchanging ideas and forming collaborations. Each visiting participant was paired with a KL2 Scholar, who provided 1:1 peer mentorship. In addition, visiting scholars presented a work-in-progress seminar, to obtain feedback before the more formal Grand Rounds lecture. For academic year 2021-2022, Spectrum KL2 meetings include virtual and hybrid in-person sessions, allowing visiting scholars to join by Zoom during the 3-month virtual exchange program. DISCUSSION/SIGNIFICANCE: What set Stanfords Virtual CTSA Visiting Scholars Program apart was faculty engagement and mentorship provided to visiting participants. By incorporating visiting scholars virtually into the ongoing KL2 education program, participants could engage fully with mentors and scholars, even surpassing opportunities of pre-pandemic on-site visits.

OBJECTIVES/GOALS: Sleep is critical for healing, however pediatric intensive care unit (PICU) sound is above recommended levels (i.e., 45 A-weighted decibels [dBA]). This observational study identifies sources of PICU sound and compares sources between times of high (i.e., dBA≥45) and low (i.e., dBA < 45) levels. METHODS/STUDY POPULATION: The sound environment of 10 critically ill children 1 to 4 years of age was monitored via a bedside dosimeter and video camera for 48 hours, or until PICU discharge. Dosimeter and video data were uploaded to Noldus Observer XT and time synchronized. A reliable, previously published coding scheme developed to identify sound sources in the adult ICU was modified for the pediatric population. Sound sources (e.g., clinician/family/child [verbal vs. non-verbal] vocalization, patient care, medical equipment) were identified via instantaneous sampling of video data at each minute of recording. The proportion of sampling points with each sound source are compared between times of high and low sound levels, and between day (7:00-18:59) and night (19:00-6:59) shift. RESULTS/ANTICIPATED RESULTS: Video coding is ongoing, with high inter-rater reliability (κ̅=0.99, SD DISCUSSION/SIGNIFICANCE: Medical equipment sound is ubiquitous in the PICU. Clinicians should optimize the PICU sound environment for sleep, including minimizing equipment alarms, conversation, general activity, and screen media during child rest. Large-scale studies are needed to confirm findings from this small cohort.

OBJECTIVES/SPECIFIC AIMS: To develop a social network model of collaborations within and external to the University of Rochester Medical Center (URMC) CTSI using data from the annual Research Performance Progress Report (RPPR) as well as other sources, to provide longitudinal evaluation of the CTSI’s engagement with key stakeholder groups. METHODS/STUDY POPULATION: The annually submitted RPPR follows a specific format with well-defined sections. The Highlights, Milestones and Challenges Report includes areas in which CTSI function leaders provide details about program integration and innovation, including collaborations with other functions or external groups. The Highlights, Milestones and Challenges Report was qualitatively coded to identify function-collaborator dyads. Each entity in the dyad became a node in the network. Nodes were connected by edges named by the dyads. The network included two types of nodes. The first were CTSI internal functions/programs, i.e. the entities that submitted RPPR sections and formed an interconnected sub-network. The second type of nodes were entities external to the CTSI (collaborators, internal or external to the CTSI site). These entities were named by functions submitting RPPR narratives. External nodes with similar meanings were consolidated. Duplicate edges were removed. CTSI-external nodes were grouped into five stakeholder categories: URMC, University of Rochester (UR), community, other CTSA institutions, CTSA consortium. Thus, these nodes were connected to the CTSI internal nodes, but not to each other. A second source of collaboration data was function-reported internal metrics. As part of the internal metric data collection, functions list partners who play a role in improving metric data or who are responsible for providing data. Partners identified in the internal metrics data, but not specified in the RPPR, were added to the network. RESULTS/ANTICIPATED RESULTS: Twenty-three internal CTSI functions submitted an RPPR and represent the CTSI internal nodes. Internal CTSI functions identified 235 collaborations (edges): 125 collaborations with other CTSI internal functions, 57 collaborations with URMC entities, 14 with UR entities, 15 with the external community, 15 with other institutions (CTSA hubs and other universities), and 9 with CTSA consortium entities. Thirty-eight of the collaborations were identified in the internal metrics partners section. In total, the network comprised 104 nodes. Graph density was.022 for full network and.21 for the CTSI internal sub-network. The global clustering coefficient, a measure of connectivity, for the CTSI internal sub-network was.252. DISCUSSION/SIGNIFICANCE OF IMPACT: The RPPR provides an underutilized source of data for annually repeated analyses of internal and external CTSI collaborations and is a way to enhance use of this routinely collected information. Analyses of the network yield metrics for measuring CTSI reach and impact on stakeholder groups over time. For example, measures such as number of nodes representing entities external to CTSI and average vertex degree of the CTSI Internal nodes track aspects of CTSI collaborations. Visualizations using different layouts or highlighting different sub-networks provide a representation of CTSI engagement with the communities of stakeholders as well as insights to relationships between functions, regions of collaboration, and areas of gaps. These data also provide an important new mechanism to engage the CTSI leadership and function leads in understanding how their work contributes to the overall network and synergies they have with each other.