Objectives/Goals: Congenital cytomegalovirus (cCMV) continues to be the primary infectious cause of fetal anomalies. The role of fetal natural killer (NK) cells in response to cCMV remains largely unexplored. This study seeks to investigate how fetal NK cells respond to human cytomegalovirus (HCMV) during gestation. Methods/Study Population: Umbilical cord blood and corresponding umbilical cord tissues were collected from fetuses that had no complications during gestation. These samples, provided by the Medical College of Wisconsin Tissue Bank, were processed within 24 hours after live birth. Single-cell suspensions were prepared from the samples, and fetal NK cells were isolated and exposed to HCMV antigen peptides VMAPRTLFL, VMAPRTLIL, VMAPQSLLL, and the human self-peptide ALALVRMLI. These peptides were presented on HLA-E*01:03 BV421-conjugated tetramers produced by the National Institutes of Health Tetramer Core Facility. Additionally, fetal NK cells were also prepared for single-cell RNA sequencing (scRNA-seq), and cells were filtered and clustered based on the number of uniquely expressed genes. Results/Anticipated Results: Through unbiased clustering, our scRNA-seq analysis identified five unique fetal NK cell subsets in umbilical cord blood and four in the corresponding umbilical cord tissue. Notably, fetal NK cells exposed to HCMV during gestation were primarily mature NK cell subsets, while those from unexposed fetuses were mostly immature subsets. Additionally, HCMV-exposed fetal NK cells exhibited a strong recall response to the HCMV antigen, with a notably higher frequency and elevated production of IFN-γ. Conversely, naïve fetal NK cells from fetuses unexposed to HCMV produced significantly lower levels of IFN-γ. Finally, we identified a distinct subset of fetal NK cells that emerge following exposure to the HCMV antigen. Discussion/Significance of Impact: In this study, we show that HCMV infection can influence the formation of specific NK cell subsets and re-exposure to the HCMV antigen can trigger a recall response. These insights could pave the way for the development of innovative NK cell-based immunotherapies aimed at preventing fetuses from developing symptomatic cCMV.

ABSTRACT IMPACT: Study findings can guide improvements of the Summer Food Service Program to maximize the program’s desired effects on child summer nutrition and related health outcomes. OBJECTIVES/GOALS: The Summer Food Service Program (SFSP) addresses food insecurity during summer months. Project specific aims are to: 1. Describe characteristics of children participating in the SFSP. 2. Determine the nutritional quality of the SFSP foods. 3. Evaluate changes in children’s food insecurity, diet quality, and body mass index by SFSP participation. METHODS/STUDY POPULATION: A single group, prospective, staggered cohort design will be used for the proposed study. Two cohorts of 30 (N=60) elementary students and their parents will be recruited during the 2021-22 and 2022-23 school year. Each participant will complete a measurement session at three time-points: Baseline (spring), Post-Program (program end), and Follow-Up (following spring). Parents will complete an online survey about household food insecurity and family socio-demographic characteristics. Children will complete three 24-hour dietary recall interviews, and their heights, weight and percent body fat will be measured. The menus of at least ten SFSP sites will be analyzed to determine the nutritional adequacy of the site menus by using the Healthy Eating Index-2015. RESULTS/ANTICIPATED RESULTS: Study hypotheses are as followed: Aim 1. Not all of the children participating in the SFSP are from food-insecure or low-income households. Aim 2. Meals served at the SFSP will be higher in sugar and fat and lower in fruits and vegetables compared to recommendations in the 2015-2020 Dietary Guidelines for Americans. Additionally, the Healthy Eating Index-2015 score of the SFSP menus will be lower than that of the National School Lunch Program menus. Aim 3. Consistent SFSP participation will have a positive effect on reducing food insecurity, but not on increasing diet quality and reducing body mass index and percent body fat in children. DISCUSSION/SIGNIFICANCE OF FINDINGS: Program user information will determine if the program is reaching the target audience. Program managers will utilize menu analysis results to improve their menu nutritional quality. Changes in food insecurity, diet quality and anthropometric measures will inform whether the program needs to be improved to prevent any untoward excess weight gain.

OBJECTIVES/GOALS: Pregnant African American (Black women) have higher rates of adverse pregnancy outcomes compared to other races and routine monitoring of lipid levels is not currently in practice in prenatal care. We hypothesized that lipid profiles would show variation across pregnancy indicative of specific requirements during gestation and fetal development. METHODS/STUDY POPULATION: We used an untargeted lipidome analysis approach to investigate lipid metabolism with the progression of pregnancy. Pregnant Black women were recruited at prenatal clinics in Midwest (Metro Detroit, Michigan and Columbus, Ohio), women under 18 or above 45 years of age were not enrolled due to metabolic changes associated with these age groups. Women signed the consent forms and plasma samples were collected at 8-18 weeks at (T1), 22-29 weeks (T2) and 30-36 weeks (T3) of pregnancy. Samples from sixty-three women (mean age 27.41 ± 5.61 years) who had term birth (completed 37 weeks of pregnancy) were subjected to “shotgun” Orbitrap high resolution/ accurate mass spectrometry. Mixed-effects models were used to quantify systematic changes in relative lipid abundances over time using R lme4 and ggplot2 packages. RESULTS/ANTICIPATED RESULTS: Total lipids and some major lipid classes showed a significant increase with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase throughout pregnancy, while sphingolipids and total sterol lipids displayed a more pronounced increase at the T3 timepoint. Acylcarnitines, hydroxy acylcarnitines and Lyso phospholipids levels significantly decrease from T1 to T3. One of the interesting finding was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggesting a possible role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids- Linoleic Acid, Arachidonic Acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, Docosahexaenoic acid. DISCUSSION/SIGNIFICANCE: Mapping lipid trends during pregnancy could lend support to a precision health approach to reduce perinatal health disparities among pregnant Black women. The findings from this study will be used to identify biomarkers and study associations with social and environmental factors responsible for adverse perinatal outcome in pregnant Black women.

OBJECTIVES/SPECIFIC AIMS: Many CTSA network activities aim to promote collaboration. Who should we target, and how should we evaluate short-term success? This study examined the validity of recently developed collaboration readiness indices among early career scholars, an important and understudied portion of the translational workforce. METHODS/STUDY POPULATION: Participants were 107 scholars within 10 years of completing terminal degree or residency (mean age = 38; 69% female; 29% MD) who applied to one of two week-long NCATS-funded Innovation Labs (www.buffalo.edu/innovationlabs.html). Measures included the MATRICx (Mallinson etal., 2016), which assesses 17 collaboration motivators and 31 threats; the Transdisciplinary Orientation Scale (TDO; Misra etal., 2015), an assessment of attitudes and behaviors theorized to predict effective collaboration; and a brief measure of one’s perceived ability to succeed in different aspects of collaboration (i.e., self-efficacy; see teamscience.net). RESULTS/ANTICIPATED RESULTS: Factor analyses of individual measures and evaluation of cross-scale correlations suggest that collaboration readiness is multi-dimensional. Factor analysis of the MATRICx suggests 3 moderately-correlated facets of motivators (benefits to world, self, and others rs = +.50 to +.62) and threats (process concerns, external barriers, and leadership style, rs = +.29 to +.53). Most correlations between motivator and threat scales (except process concerns) were modest, suggesting they reflect relatively independent aspects of collaboration readiness. The TDO scales seemed to capture a different aspect of collaboration readiness; correlations with MATRICx motivator and threat scales were mostly modest (rs = -.26 to +.43). As expected, collaboration self-efficacy was positively related to collaboration motivators and TDO (rs = +.41 to +.59) and negatively related to collaboration threats (particularly process threats, r = -.47). Participants typically scored in the upper half of the TDO, MATRICx motivator, and collaboration self-efficacy scale ranges, and in the lower half of the MATRICx threat scale ranges. DISCUSSION/SIGNIFICANCE OF IMPACT: Collaboration readiness is a reasonable short-term target of efforts to promote collaboration. However, this work suggests that no single scale captures the entire conceptual space, and multiple measures should be assessed. The implications for efforts to enhance collaboration are intriguing. In samples already high in collaboration readiness, these measures will have limited ability to detect positive change. However, assessment of collaboration readiness may be particularly useful in identifying scholars who could most benefit from collaboration-enhancement programs (i.e., scholars with moderate scores on one or more of these metrics) and in personalizing intervention (e.g., selectively targeting TDO, collaboration motivators, and/or collaboration self-efficacy, and/or perceived threats to collaboration).

OBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.

Each year our Clinical and Translational Science Award pilot projects program awards approximately $500,000 in translational pilot funding to advance health in South Texas. We identified needs to improve the timeliness, transparency, and efficiency of the review process by surveying applicants. Lean six sigma methodologies, following a “Define, Measure, Analyze, Improve, Control” approach, were used to streamline the pilot project application and review by identifying and removing bottlenecks from process flows. We evaluated the impact of our reorganized review process by surveying applicants and reviewers. Process mapping identified pilot project review as the main source of delay, leading to the implementation of a study section-style review mechanism. After one cycle, 90.3% of pilot applicants and 100% of reviewers were highly satisfied with the new processes and time to award notice was reduced by 2 months. All reviewers familiar with both review processes preferred the study section. We demonstrated how lean six sigma, a methodology not commonly applied in research administration, can be used to evaluate processes in translational science in academic health centers. Through our efforts, we were able to improve timeliness, transparency, and efficiency of the review process.

The University of Pittsburgh (Pitt) Clinical and Translational Science Institute (CTSI) and the nonprofit Bidwell Training Center co-developed a new program for translational workforce diversification and development to foster diversity and inclusion in clinical research. The STricklAnd Research Training (START) program provides students in the Medical Assistant program at Bidwell a career path in clinical research. We created a 12-hour didactic package that covers responsible conduct of human subjects research and good clinical practice as an add-on to existing vocational curriculums. Students have the option of completing a clinical research-related externship at Pitt, which includes mentoring, shadowing, and protocol-specific training on a study team whose intention is to hire them as a clinical research assistant. Those who accept a position at Pitt receive continued mentorship, education, and professional development through Pitt CTSI. In the first three cohorts, two of which had access to research externships at Pitt, 92% of students successfully completed the instruction in clinical research. We plan to expand START to new venues to train and hire local community members from diverse backgrounds who can bring their lived experience to research programs.

A priority of the Northern New England Clinical and Translational Research (NNE-CTR) Network is conducting, promoting, and advancing community-engaged research through its Community Engagement and Outreach (CEO) Core. We sought to measure the CEO Core’s success in strengthening community-level research partnerships using a validated survey platform based on network science to map and track collaborations over time. The survey was completed by 59/76 organizations (77.6% response rate). Key findings included a high level of trust and a modest level of perceived value relative to published benchmarks. Additional specific findings will inform opportunities to improve the network as the NNE-CTR matures.

ABSTRACT IMPACT: Our research focuses on determining rural-urban disparities in chronic obstructive pulmonary disease (COPD) management to improve COPD health outcomes in rural areas. OBJECTIVES/GOALS: Several methods exist to distinguish rural from urban areas, but it is not clear which method relates most directly to rural-urban health care disparities. To address this, we compared different measures of rurality to measures of chronic obstructive pulmonary disease (COPD) processes of care among a national sample of veterans. METHODS/STUDY POPULATION: Retrospective analysis of patients with COPD (2016-2019 by ICD-10 codes) using national Veterans Affairs (VA) data. We assessed rurality by: 1) patient’s residential address, 2) assigned primary care clinic address, and 3) drive time from the patient’s residence to closest primary care clinic. Rurality designations of the residential address and primary care clinic address into urban, rural, and highly rural areas are based on the Rural Urban Commuting Area (RUCA) codes. The dependent variables were binary outcomes of: 1) documentation of a pulmonary clinic encounter and 2) evidence of spirometry to confirm the diagnosis of COPD. RESULTS/ANTICIPATED RESULTS: Of 6,765,951 veterans, 1,157,002 (17%) had COPD (Table 1). Although approximately 40% of patients with COPD reside in addresses that are rural and highly rural, a large majority are assigned to primary care clinics in urban areas (82.8%) and reside within 30 minutes to the closest primary care clinic (76.7%) (Table 2). Compared to defining rurality based on patient’s residential address or drive time to closest primary care, defining rurality based on the assigned primary care clinic address was associated with a larger disparity in rates of pulmonary encounter. In contrast, the drive time from the patient’s residence to the closest primary care was the strongest predictor of receipt of spirometry (Figure 1 and Table 3). DISCUSSION/SIGNIFICANCE OF FINDINGS: Estimates of the severity of rural-urban disparities varied based on the definition of rurality used. For two process measures, definitions of rurality based on where the patient received primary care generated more evidence of disparities than definitions based solely on the patient’s residential address.

Objectives/Goals: The identification of the cascade of molecular and cellular events occurring during the progression of focal segmental glomerulosclerosis in human kidney biopsies from kidney transplant (KTx) recipients (KTR) with normal function or recurrent FSGS to determine potential targets of intervention and therapy. Methods/Study Population: In this study, we evaluate the molecular and cellular events associated with primary FSGS in both native and transplant kidneys. We collected biopsy samples from the native normal kidney (nNK, n = 3), normal functioning allografts (NKTx, n = 3), primary FSGS in the native kidney (nFSGS, n = 1), recurrent FSGS (KTxFSGS, n = 5). KTxFSGS comprises a collection of longitudinal samples with biopsy also collected at the subsequent recurrence. Blood samples were collected during biopsy collection. Biopsies were preserved in RNAlater at the time of collection. 10X genomics chromium single nuclei RNA sequencing (snRNAseq) was performed using isolated nuclei. Data was analyzed using Seurat on R. Conditionally immortalized podocytes were treated with a patient serum to determine the change in expression observed in snRNAseq data. Results/Anticipated Results: Recurrence rates of primary FSGS are high in kidney allograft recipients up to 25–50% in first, and up to 80% in second transplants, often leading to graft loss. Our findings reveal that podocyte detachment is driven by metabolic and structural dysregulation rather than cell death, increasing VEGFA expression and disrupting glomerular endothelial cell growth and permeability. Parietal epithelial cells initially compensate by dedifferentiating toward podocytes but later increase collagen deposition, contributing to glomerular sclerosis. Increased interactions of glomerular cells with B cells exacerbate extracellular matrix deposition and scarring. We also observed tubular sclerosis and disruption of the regenerative potential of proximal tubular cells, with increased interaction with T cells. Discussion/Significance of Impact: These findings offer new insights into the pathogenesis of recurrent FSGS and suggest potential therapeutic targets and establishes a foundation for future studies to further evaluate the role of metabolic dysfunction as the cause of podocyte injury and loss.

OBJECTIVES/GOALS: Ambulatory methods are useful tools to study physical and mental health in everyday life. While many studies show daily activity improves mood, the effects of daily light exposure on mood remain unknown. This study evaluated the effects of daily natural light exposure and activity on daily mood and evaluate whether depression moderate effects. METHODS/STUDY POPULATION: 82 adults with lifetime major depression disorder (25 current) and 49 healthy controls were recruited from the greater Chicago community (N = 131, 62% female, age M = 30.15, SD = 9.94). At baseline, participants completed the Inventory of Depression and Anxiety Symptoms to measure depression symptoms of anhedonia, or loss of pleasure. Positive and negative affect were then measured 3x daily for 14-days via self-report using smartphones while light exposure and activity were continuously recorded from a wrist-worn actigraphy device. Following prior studies, daily natural light exposure was measured as the total number of white light samples greater than 1000 lux each day. Multilevel models were used to separate within-person (daily level) from between-person (subject level) effects. RESULTS/ANTICIPATED RESULTS: Results revealed daily within-person activity (p < .001) and natural light exposure duration (p = .035) were independently associated with increased positive affect. Effects were significantly moderated by baseline anhedonia symptoms (3-way interaction: p = .004). Natural light exposure duration only increased positive affect on lower activity days for high anhedonia and higher activity days for low anhedonia (ps < .018). Significant results remained controlling for between-person light and activity, time of year, age, sex, negative affect, and baseline general depression symptoms. Compared to one’s own daily averages, daily activity and natural light exposure may be independent pathways to boost positive affect, especially for individuals with high anhedonia symptoms. DISCUSSION/SIGNIFICANCE: Results suggest daily natural light exposure may be an accessible, low-cost alternative to independently increase positive affect in depression on days when activity is low. Translational applications are discussed focusing on transdiagnostic implications for physical and mental health conditions that disrupt mood and limit activity.

OBJECTIVES/GOALS: Despite highly effective antiretroviral therapy, people living with HIV (PLWH) experience chronic immune activation and inflammation which may influence the progression of infections such as SARS-CoV-2. Here, we explore the immune response and clinical outcomes in HIV(+) and HIV(-) individuals experiencing acute COVID-19 and long COVID (LC). METHODS/STUDY POPULATION: We performed flow cytometric analyses on peripheral blood mononuclear cells from the following: 1) HIV(-) individuals experiencing acute COVID-19, 2) PLWH experiencing acute COVID-19, and 3) pre-COVID-19 pandemic PLWH. Additionally, we will perform similar analyses for the following: 1) PLWH experiencing LC, 2) PLWH previously infected with SARS-CoV-2 who recovered, 3) pre-COVID-19 pandemic PLWH, and 4) HIV(-) individuals experiencing LC. Flow cytometry panels include surface markers for immune cell populations, activation and exhaustion surface markers (with and without SARS-CoV-2-specific antigen stimulation), and intracellular cytokine staining. We will also analyze how chronic HIV infection and other clinical and demographic factors (e.g., age, CD4 %) impact persistent symptomatic burden. RESULTS/ANTICIPATED RESULTS: Acute COVID-19 results–Overall, PLWH had higher baseline expression of activation markers OX40 and CD137 on CD4+ and CD8+ T cells, along with increased levels of TNFa producing CD8+ T cells. Interestingly, PLWH had increased expression of exhaustion markers PD1 and TIGIT but decreased expression of TIM3 on CD4+ and CD8+ T cells. Additionally, PLWH had decreased levels of IL-2 and IFNg producing CD4+ T cells which suggests functional exhaustion. Long COVID-19 expected results–we hypothesize that the activation and inflammation seen in chronic HIV infection will lead to more immune dysregulation and subsequently worsened symptomatic burden. Additionally, we hypothesize that PLWH may have different frequencies of certain LC manifestations, such as increased rates of neurocognitive impairment. DISCUSSION/SIGNIFICANCE: Our findings suggest that chronic HIV infection influences acute immune response during SARS-CoV-2 infection, and that PLWH have variable expression of exhaustion markers which warrants further study. Additionally, our findings in the LC cohort will aid in characterizing clinical manifestations and immunologic mechanisms of LC in PLWH.

ABSTRACT IMPACT: Disparities are multifactorial in etiology we seek to elucidate the effects of social determinants of health such as race on the outcomes of autologous flap reconstruction. OBJECTIVES/GOALS: Immediate breast reconstruction has increased in recent years yet, racial and socioeconomic disparities in the receipt of postmastectomy breast reconstruction persist. We review the usage of autologous flaps for immediate breast reconstruction in a single institution with a diverse population to determine the effect of radiation on flap survival. METHODS/STUDY POPULATION: The database of a Southeastern tertiary referral center was queried for patients who received autologus flaps for immediate reconstruction following mastectomy. Patients were stratified based on whether they received no radiation (TRAM), neoadjuvant radiation (TRAM + Pre-XRT), or post-reconstruction radiation (TRAM + PMRT). So far, we have identified 91 patients (157 breasts) meeting inclusion criteria from 2006 to 2017. Patient demographics and outcomes were compared based on radiation status. The primary outcome (reconstructive success) was defined as breast reconstruction without flap loss. Comorbidities, socioeconomic status, and method of reconstruction were collected. Statistical analysis included t-tests, chi-square tests and logistic regression were appropriate using R. RESULTS/ANTICIPATED RESULTS: At the moment, we focus on outcomes of transverse rectus abdominus flaps and are adding information on 4 other flap-based methods. There were 68 in the solely TRAM group, 33 in TRAM+Pre-XRT and 56 in TRAM+PMRT with equivalent demographics between all groups for Age, Race and BMI (Table 1). In terms of race most patients self-identified as White (68%), followed by Black (24%) and Other (8%), p=0.172. There was a statistically significant difference in the incidence of tobacco use with the type of radiation used (p=0.007) with the PTRAM+ PMRT group having the highest percentage. When analyzing major and minor complications based on radiation received or reconstructive success there was no significant difference regardless of radiation treatment with the group overall achieving a 97.4% success rate (p=0.229). DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite the known racial disparities in healthcare and the deleterious effects of radiation therapy on wound healing, there was no significant difference found in the incidence of major or minor complications in patients receiving neoadjuvant or post-reconstruction radiation therapy regardless of patient demographics.

OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM.

OBJECTIVES/GOALS: Neuroimaging research has found that childhood maltreatment is related to reduced activation of the nucleus accumbens. The long-lasting impact of this relationship is not as well understood. This study aims to explore the association between childhood emotional neglect and reward-related functional connectivity in an adult trauma sample. METHODS/STUDY POPULATION: Participants (N=169, M age=, 32.2; SD=10.3; women=94) experienced a traumatic injury and were recruited from a Level I Trauma Center. Two-weeks post injury, participants completed the Childhood Trauma Questionnaire (emotional neglect M=10.6; SD=5.2), a self-reported, retrospective account of childhood maltreatment, and underwent a resting-state functional magnetic resonance imaging (fMRI) scan. Whole-brain resting-state left and right nucleus accumbens connectivity analyses were completed using the CONN Toolbox. RESULTS/ANTICIPATED RESULTS: Whole-brain left nucleus accumbens connectivity analyses revealed one significant region (angular gyrus (AG); p DISCUSSION/SIGNIFICANCE: Results suggest that childhood emotional neglect is related to nucleus accumbens connectivity and a brain region associated with memory, attention, and theory of mind in adult survivors of trauma. Early life emotional neglect may be contributing to heightened baseline reward sensitivity–particularly for social rewards (implicated by the AG).

OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.