bluuebunny/crossref_metadata_2025 huggingface dataset:
4571 Examination of the relationship between age, program duration and risk profiles among sex-trafficked youth in a specialty court
Authors: Cook Mekeila
Published: July 2020

OBJECTIVES/GOALS: Youth experience worse health and behavioral outcomes the longer they are in the juvenile justice system. This study examines whether age at entry and length of time in a specialty juvenile court program predicts citations, bench warrants, and running away among sex-trafficked girls. METHODS/STUDY POPULATION: Domestic minor sex trafficking (DMST) is exploitation and abuse of children for commercial sexual purposes in exchange for money or other goods/services. Historically, the response to DMST has been punitive, resulting in youth being cited and detained for offenses like prostitution. The specialty court offers enhanced physical/mental health services to trafficked youth. Data come from case files in the specialty court for program participants from 2012-2014 (N = 184). Descriptive, bivariate, and Poisson regression analyses were performed to examine risk profile measures: bench warrants, citations, running away, and foster placements. RESULTS/ANTICIPATED RESULTS: All were (cis)female, 74% were African-American, 96%, US citizens, with average age of 16. Participants lived in approximately 4.5 group homes or foster placements prior to program entry; 56% of youth had run away. Youth also averaged nearly two bench warrants before specialty court participation. Bivariate analysis indicates older age at entry into juvenile court was associated with fewer episodes of running away (p<.02) and new citations (p<.001). Poisson regression estimated older age at entry into the juvenile justice system was associated with fewer bench warrants, citations, foster placements, but not running away while in the program. Additionally, longer duration between time at first citation and entry into the program was associated with fewer bench warrants, running away, and citations. DISCUSSION/SIGNIFICANCE OF IMPACT: Younger girls may be particularly vulnerable to trafficking and recidivism without early and persistent intervention. Youth experiencing sex trafficking need to be diverted away from juvenile justice to comprehensive trauma informed services.
4480 Full STEM Ahead: An Innovative Approach to Translate Science into the School-community
Authors: Hivner Elizabeth , Calo William , Hoke Alicia , Keller Chelsea , Kraschnewski Jennifer
Published: July 2020

OBJECTIVES/GOALS: To provide a translation of health sciences and research to a low-income population and elevate the role of science in personal health and career pathways through the implementation of a STEM-focused, researcher-led, school-community event. METHODS/STUDY POPULATION: Through a strong school district partnership, families from two urban, low-income, high-minority middle schools were invited to attend an academic-community event entitled, Full STEM Ahead in Lancaster, Pennsylvania. Thirty-five Penn State and community partners engaged participants in discovery-focused learning through activity stations. Topic areas included: 3D printing in medicine, herd immunity, HPV cancer prevention, lung health, and germ prevention. Evaluation data from participants and organizational partners was collected to assess process outcomes and qualitative feedback. This event was part of a randomized controlled trial to improve attitudes toward adolescent vaccination. RESULTS/ANTICIPATED RESULTS: Seventy-four parents and students participated in the two-hour event. Evaluation data indicated that 100% of participants who completed the evaluation rated the event as “good” or “excellent” and agreed that they “learned something new.” Specific qualitative feedback indicated that participants enjoyed the STEM information and various learning activities offered. School district leadership hopes to continue the partnership to host the event in future years and expand to other schools, offering an opportunity for academic-community collaboration. DISCUSSION/SIGNIFICANCE OF IMPACT: This event was an innovative approach to connect low-income communities with science and potentially effective in engaging participants in learning. Similar opportunities should be explored to bridge the gap between research and community engagement, especially to increase research awareness.
4409 Indiana Clinical & Translational Science Monon Collaborative – Community Impact Hubs
Authors: Wiehe Sarah , Craig David , Wilcox Matthew , Hardwick Emily , Lawrence Carrie , Schicho Fiona , Hudson Brenda
Published: July 2020

OBJECTIVES/GOALS:

Conduct an environmental scan of Marion County (Indianapolis) neighborhoods using electronic medical record data, state health data, and social and economic data

Develop strong network of community collaborators

Conduct a thorough assessment for each targeted neighborhood by listening and understanding the pressing health issues in the community and working together to design and deliver solutions

METHODS/STUDY POPULATION:

Identify measures in the 3 domains of vulnerability, health and assets for the targeted neighborhoods and conduct bivariate descriptive statistics and multivariable regression analyses to investigate association between measures of vulnerability and health outcomes.

Initiate relationships with leaders and residents in targeted neighborhoods

Locate organizations working in targeted neighborhoods through online mapping software and word-of-mouth at neighborhood events, and created a spreadsheet with contact information.

Conduct multidisciplinary assessment (i.e. key informant interviews, focus groups, town hall meetings) of the targeted neighborhood.

Iteratively synthesize assessments to develop areas of interest and relevance to the community.

Develop a road map for solutions identified by the community.

RESULTS/ANTICIPATED RESULTS: The results from the environmental scan conducted will be displayed in a report and visual “map” of health outcomes and health determinants, including assets and barriers for the targeted neighborhoods. The research team will use results from the environmental scan coupled with listening activities including attendance at community events, key informant interviews and focus groups to develop relationships and strong collaborations with the targeted neighborhood stakeholders. The relationship building between the research team and community will provide increased trust and engagement that will further enhance the effectiveness of the assessments completed with the targeted neighborhood. The assessments will help to empower communities to develop sustainable solutions and drive future work that will lead to future grant applications and larger-scale implementation in other community impact hub neighborhoods. DISCUSSION/SIGNIFICANCE OF IMPACT: Through the community impact hub work, we will develop collaborative efforts with targeted neighborhoods with the greatest health inequities in the Marion County area. In partnership with these neighborhoods, we will build a foundation – a network of community collaborators and a focused plan – upon which we will improve the health outcomes of residents while learning best practices on how to do so.
4073 Parents of Faith Support School-Based Sex Education: A Louisiana Study
Authors: Boos Elise Walsh , Canfield Caitlin , Brown Lissane , Bardell Kristie
Published: July 2020

OBJECTIVES/GOALS: Louisiana state law does not require sex-education (SE) in public schools. Locally and nationally, religious identity and beliefs are often invoked to oppose access to sexual and reproductive healthcare and education. This study aimed to explore support for SE among Louisiana parents, focusing on how religiosity may influence parent support for SE. METHODS/STUDY POPULATION: Participants included 1,197 Louisiana parents and caregivers of children in grades K-12 who completed a web-based survey. Multivariate logistic regression analysis was used to determine associations between covariates and support for SE. RESULTS/ANTICIPATED RESULTS: Sixty-eight percent of parents reported that their overall approach to life is based on their religion or faith. Of those parents, 77% agreed that schools should be required to offer SE. In multivariate analysis, parents who reported that their whole approach to life is based on their religion on faith were 26% less likely to support required SE compared to parents whose whole approach to life was not based on their religion; however, this difference was not statistically significant (adjusted OR 0.74, 95% CI 0.44-1.24). Although support for required SE declined as religiosity increased, a strong majority of parents support requiring SE in Louisiana schools, regardless of religiosity. DISCUSSION/SIGNIFICANCE OF IMPACT: Contrary to opposition claims, strong support for SE exists among Louisiana parents and caregivers of faith. Parents and leaders of faith may be engaged as partners in advocacy for SE as well as other sexual and reproductive health issues.
4301 Racial/Ethnic variations in discharge destination after inpatient care: A risk-adjusted analysis of a large regional dataset
Authors: Ghosh Arnab Kumar , Ibrahim Said
Published: July 2020

OBJECTIVES/GOALS: While there are many well-documented factors for racial/ethnic variation in discharge destination, less is known about the role hospital processes play. We hypothesize that variation in hospital processes -defined as the patient length of stay (LOS) adjusted for known confounders - explains racial/ethnic variation in discharge destination. METHODS/STUDY POPULATION: Our sample was 176,686 discharges from 165 hospitals in 2014 using the New York State Inpatient Dataset from the Healthcare Cost and Utilization Project, merged with the 2014 American Hospital Association Annual Survey to build a file of inpatient discharges with patient, disease and socio-economic characteristics. We excluded patients under 18 years, those with LOS of zero, those who died, those admitted to critical access hospitals, and patients from hospitals that lacked sufficient number of minority patients. We used a generalized linear mixed effects model to create an in-hospital risk-adjusted LOS by modelling the relationship between the interaction of race and discharge destination and LOS, controlling for known confounders such as patient, disease and between-hospital characteristics. RESULTS/ANTICIPATED RESULTS: Mean age of sample was 56.5 years, 57.3 % female, 54.9% white, 18.9% black and 13.1% Hispanic; 64.3% were discharged home, 15.8% to a skilled nursing or other intermediate care facility, 15.5% to home with home care and 2.4% left against medical advice. The top 3 discharge diagnoses were vaginal delivery (6.3% of discharges), psychosis (4.7%), and major joint replacement (2.9%). In adjusted analysis compared to white patients, black and Hispanic patients did not have an risk of increased LOS after being discharged to non-home destinations vs. discharged home, (black patients, adjusted OR [AOR], 0.97; 95% CI: 0.94-1.00, p = 0.08; Hispanic patients, AOR, 1.01; 95% CI: 0.98 – 1.05, p = 0.5). However, being black compared to white and discharge to non-home destinations significantly increased LOS. DISCUSSION/SIGNIFICANCE OF IMPACT: In this large sample of patients admitted for inpatient care in 2014 in New York, we found no independent effect between race and discharge destination on a patient’s LOS after controlling for patient, disease and between-hospital characteristics. However race/ethnicity increased LOS, suggesting its effect may play a role on in-hospital processes CONFLICT OF INTEREST DESCRIPTION: Dr. Ghosh has no relevant relationships with commercial interests to disclose Dr. Ibrahim has no relevant relationships with commercial interests to disclose
4295 The Impact of Social Determinants of Health on Hepatocellular Carcinoma Outcomes
Authors: Nephew Lauren Devore , Rawl Susan , Desai Archita , Orman Eric , Ghabril Marwan , Patidar Kavish , Chalasani Naga
Published: July 2020

OBJECTIVES/GOALS: Achieving therapy for hepatocellular carcinoma (HCC) involves navigating through a complex cascade of care. Non-HCC cancer mortality has been associated with social determinants of health outside of cancer specific risk. Our objective is to explore the impact of social determinants on HCC outcomes. METHODS/STUDY POPULATION: Patients with HCC were enrolled from 3 hospitals form June, 1 2019 to December 1, 2019. A chart review was done to collect information on liver disease severity and cancer stage. Patients were interviewed to collect information on the following: 1) socioeconomic status (income, education, insurance status, and employment status), 2) literacy (Rapid Estimate of Adult Literacy in Medicine (REALM-R) and Brief Health Literacy Screening Tool (BREIF)), 3) social support (Patent Reported Outcome Measurement Information System (PROMIS) instrumental and information support tool), 4) quality of life (PROMIS global and mental health tool), 5) substance abuse, and 6) linkage to care. RESULTS/ANTICIPATED RESULTS: Data compiled on the social determinants of health revealed (n = 35): 1) 60.0% of patients had incomes below $30,000 per year, 60.0% of patients had not gone past high school for education, and 8.6% had full time employment, 2) the average BREIF score was 10.3 (range 3-15)(4-12 indicate limited literacy). The average REALM-R score was 5.5 (range 0-8) (<6 indicate at risk for poor literacy), 3) patients had strong instrumental (T score 61.4±7.1) and information social support (T score 64.6±4.7) (mean T scores calibrated to a general population mean of 50), 4) patients had poor mental (T score 43.7 ±6.5) and physical quality of life (T score 46.6 ±9.9), 5) 25.7% of patients reported alcohol use in the past 90 days 6) 80.0% of patients reported that their doctor had spoken to them about liver transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: This patient population was well linked to care with good social support. However their literacy, socioeconomic status, mental and global health was poor and substance use history complex. Continued follow up of this cohort is planned to determine how these factors might impact their ability to navigate through the care cascade as well as survival.
4240 The relationship between family structure and quality of life among children with asthma
Authors: Shaheen Magda , Bryant-Horn Arneshia LA’Shelle , Teklehaimanot Senait
Published: July 2020

OBJECTIVES/GOALS: Asthma is a life-long, chronic lung disease that inflames and narrows the airways. Its effects on quality of life in children can be exacerbated. The goal of this study was to investigate the link between asthma, family structure and demographics and how it impacts quality of life in children. METHODS/STUDY POPULATION: We analyzed data from a cross sectional study of the 2016-2017 National Survey of Children’s Health, NSCH, to assess the relationship between determinants of health variables and the outcome variable of parent’s report of child’s perceived health status (quality of life). The study population was children under the age of 18. Data were analyzed using descriptive, bivariate analysis using Chi square, and multiple logistic regression of quality of life and family structure adjusting for confounding variables. RESULTS/ANTICIPATED RESULTS: The study included 5,687 children. Significant predictors of asthmatic children’s quality of life were severity of asthma, self-perceived mental/physical health status of adults, neighborhood safety for children (p <0.05). The interaction between family structure and asthma severity was significant indicating that asthma severity was an effect modifier. Among children with mild asthma, predictors of quality of life were self-perceived mental/physical health status of adults in the household, neighborhood safety of children, physical activity status of children (p<0.05). Among children with severe asthma, predictors were family structure and physical/mental health of adults (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: This study suggests children with severe asthma who are born to single mothers with lower parental reporting of physical/mental health status had a lower quality of life. A longitudinal study could be implemented to target these three measures to improve quality of life among these children. Also, a culturally adapted intervention involving community, parents, and providers is needed to improve the quality of life of the children with asthma.
4095 Concurrent assessment of experimental pain and self-reported pain intensity with acute exercise intervention in fibromyalgia; clarifying or obscuring clinical outcomes?
Authors: Berardi Giovanni , Ptizen Grace , DellaIacono Matthew , Bement Marie Hoeger
Published: July 2020

OBJECTIVES/GOALS: Experimental pain testing is used to identify changes in nociceptive processing and outcomes with intervention. This study investigated exercise induced changes in experimental pain and self-reported pain intensity after an acute bout of exercise in participants with fibromyalgia. METHODS/STUDY POPULATION: Ten females with fibromyalgia (55±10yr) were familiarized to study procedures and underwent submaximal (20% maximal voluntary contraction) intermittent eccentric muscle contractions isolated to the right arm for 10-minutes. Self-reported pain intensity (0-10 numerical pain rating scale [NPRS]) of the exercising arm was measured before, during, and after exercise; whole-body pain intensity was measured before and after exercise. Experimental pain testing included measurement of pressure pain thresholds (kPa [PPTs]); temporal summation (TS) of pressure pain with a constant mechanical pressure; and TS of punctate pressure with repeated application of monofilaments before and after exercise. RESULTS/ANTICIPATED RESULTS: Participants reported minimal to moderate arm pain (3.1±2.1) during exercise. Following exercise, arm pain and whole-body pain significantly increased (3.1±2.2 and 1.6±0.5, respectively) [p<0.05]. No change occurred with PPTs at the bicep (138.9±49.5 to 142.8±55.3), PPTs at the quad (212.0±105.4 to 228.1±100.0), TS of mechanical pressure pain (7.6±2.1 to 7.9±1.5), TS of punctate pressure pain at the bicep (2.6±1.7 to 3.0±1.5), and TS of punctate pressure pain at the quad (3.6±1.5 to 3.7±1.4) before to after exercise respectively [p>0.05]. The change in self-reported arm and whole-body pain did not correlate with the change in experimental pain testing. DISCUSSION/SIGNIFICANCE OF IMPACT: In people with fibromyalgia, there is no relation between self-reported clinical pain and experimental pain following a single exercise session. Further research should identify the influence of exercise training on pain perception and if experimental pain testing translates to clinical insight.
4302 Decreased structural basal ganglia motor loop connections in Vascular Parkinsonism compared to Parkinson’s disease and healthy aging
Authors: Cooper Christine , Rodriguez-Porcel Federico , Turner Travis , Revuelta Gonzalo , Jensen Jens , Hinson Vanessa , Bonilha Leonardo
Published: July 2020

OBJECTIVES/GOALS: This study uses diffusion kurtosis imaging (DKI) to investigate the structural profiles of basal ganglia (BG) motor circuitry in Vascular Parkinsonism (VP), Parkinson’s disease (PD), and healthy aging controls (HC). VP is a clinical diagnosis of lower body predominant parkinsonism without significant benefit from levodopa. VP is distinct from PD, yet the concept of VP remains debated due to the inability of prior studies to identify specific causative changes. One reason for this may be limitations in measuring intricate BG connectivity in vivo. Given the predominant lower body parkinsonism symptoms in VP, we hypothesized that VP would be associated with decreased connectivity specifically within the BG motor loop. METHODS/STUDY POPULATION: We obtained DKI brain imaging in subjects with VP (N = 7), PD (N = 21), and HCs (N = 58), the latter of which had cardiovascular risk factors but no neurological symptoms. The VP and PD groups were evaluated by a parkinsonism-focused motor exam and brief cognitive testing. We compared BG motor loop connectivity between groups and investigated for correlation between connectivity and clinical scores. To account for differences in fiber counts due to the different imaging scanners and protocols between cohorts, we used a BG motor loop proportion, which was the ratio of the BG motor loop fiber count over a control loop, the visual processing pathway. We used Kruskal-Wallis rank sum test with post-hoc Dunn tests to assess imaging findings between subject groups, and Pearson’s correlation to look for correlation between clinical scores and fiber counts. RESULTS/ANTICIPATED RESULTS: The whole brain connectome showed the fewest number of fibers in VP, followed by PD, and then HC (p<0.0001). The BG motor loop proportion fiber count of the BG motor loop was lower in the VP group, compared to the PD and HC cohorts (p = 0.031). In the VP group, the whole brain connectome fiber count correlated with a gait and balance subscore of the Movement Disorders Society - Unified Parkinson Disease Rating Scale (R = −0.87, p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study indicates that VP is associated with decreased structural connectivity, with a disproportionate degree of loss in the BG motor circuitry. While the etiology for this susceptibility to injury and preferential damage to BG remains to be defined, these findings can provide an important starting point for a biological understanding of VP, and a potential future marker for diagnosis and tracking disease progression.
4346 Potential Sudden Unexpected Death in Epilepsy (SUDEP) Biomarkers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes with DEPDC5 Loss-of-Function
Authors: Zhao Yanting , Zhang Helen , Parent Jack M. , Isom Lori L.
Published: July 2020

OBJECTIVES/GOALS: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in epilepsy patients. This study aims to determine whether cardiac mechanisms contribute to SUDEP in epilepsy patients with variants in DEPDC5, a gene encoding a member of the mTOR GATOR complex, to identify SUDEP biomarkers. METHODS/STUDY POPULATION: SUDEP has been reported in 10% of epilepsy patients with DEPDC5 loss-of-function variants. We used human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to measure changes in cellular excitability that are known to be substrates for cardiac arrhythmias. CRISPR-derived isogenic DEPDC5 iPSC-CMs and DEPDC5 patient-derived iPSC-CMs were used in this study. Whole-cell patch-clamp was used to measure voltage-gated sodium current (INa) and calcium current (I>Ca) in single iPSC-CMs in voltage-clamp mode; and to measure action potentials (APs) in 3-dimentional iPSC-CM-derived micro-tissues in current-clamp mode. RESULTS/ANTICIPATED RESULTS: CRISPR generated heterozygous deletion of 1 base-pair in the first coding exon of DEPDC5 gene, resulting in a premature stop codon, simulated the variants identified in DEPDC5 epilepsy patients. In CRISPR generated heterozygousDEPDC5 iPSC-CMs, whole-cell voltage-clamp recordings revealed that INa was increased and ICa was reduced compared with isogenic control iPSC-CMs. Whole-cell current-clamp recordings revealed that AP duration at 80% and 90% of repolarization, APD80 and APD90, respectively, were prolonged compared to isogenic control iPSC-CMs. Similar measurements will be performed for iPSC-CMs derived from DEPDC5 patients. DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows that epilepsy patients with non-ion channel gene variants in DEPDC5 have altered CM excitability, which may serve as a substrate for cardiac arrhythmias in DEPDC5 patients. Importantly, this work may allow us to identify biomarkers for SUDEP risk in these patients in the future. CONFLICT OF INTEREST DESCRIPTION: L.L.I. is the recipient of a collaborative research grant from Stoke Therapeutics.
4278 Recovery Time is Exaggerated in Individuals with Degenerative Cervical Myelopathy Following Standing Lateral Waist Pulls
Authors: Boerger Timothy , McGinn Learon , Clare Marisa , Wang Marjorie , Schmit Brian D , Hyngstrom Allison S
Published: July 2020

OBJECTIVES/GOALS: The aim of this study was to quantify balance impairments in stance in individuals with degenerative cervical myelopathy (IwDCM) in response to external perturbations. IwDCM have damage to their spinal cord due to degeneration of the cervical vertebral column, but little is known about balance. METHODS/STUDY POPULATION: Recovery time following a perturbation may be an important measure of balance. Changes in recovery time were measured in 7 IwDCM (2m, 58.59±15.00y) and 6 controls without DCM (2m, 56.91±11.04y) as they stood on an instrumented treadmill and received cued (predictable) and uncued (unpredictable) lateral pulls to the waist at 12% (high) and 6% (low) pull magnitudes. Individuals stood with feet together, shoulder width, and wide. Recovery time was defined as the time following pull onset when the absolute value of the center of pressure velocity returned to <1x baseline standard deviation. Repeated measures ANOVA was performed on recovery time. RESULTS/ANTICIPATED RESULTS: We anticipate that feet together standing, unpredictable, higher magnitude perturbations will be most challenging evidenced by longer recovery times. For waist pull recovery time, there was a trend for a Group x Predictability x Magnitude x Stance Width interaction (p = 0.1) which we anticipate being greater with additional participants. There were significant Group x Predictability x Stance Width (p = 0.01) and Group x Magnitude x Predictability (p = 0.01) interactions. IwDCM had exaggerated recovery times in narrow and wide stances with unpredictable pulls. IwDCM recovered more slowly in response to unpredictable higher magnitude pulls. DISCUSSION/SIGNIFICANCE OF IMPACT: Balance responses in IwDCM are most impaired in narrow stances and when perturbations are unpredictable. Rehabilitation should focus on shortening latency of response timing and increasing power utilization during balance response to promote quicker recovery.
4096 Refined structure of human ferroportin using restraints from mass spectrometry
Authors: Parry Christian S. , Ivanov Andrey , Vazquez-meves Guelaguetza , Alhakami Fatemah A. , Agyepong Jessika , Han Kyungreem , Brooks Bernard R. , Nekhai Sergei
Published: July 2020

OBJECTIVES/GOALS: Mammals require iron for hemoglobin, respiration, immunity and as cofactor in enzymes. But free iron is toxic from the production of reactive oxygen species. Ferroportin is the sole exporter of cellular iron and it crucially determines cellular and systemic iron levels. Labile iron must be tightly regulated. This requires structural understanding. METHODS/STUDY POPULATION: We built structure of human ferroportin (FPN1) using the ab ignition prediction approaches of Rosetta/Robetta and by comparative modeling with distance restraints in MODELLER. Templates selected were from solute carrier protein families of distantly related orthologs and homologs including a proton coupled peptide transporter (PDB ID: 4IKV) and the bacterial iron transporter in outward-open and inward-open states, (PDB ID: 5AYM, 5AYO). Each model was validated by experimental mass spectrometry data. The energy minimized structural model was inserted into a lipid bilayer, placed in a rectangular simulation box, covered with TIP3P water solvent balanced with counterions and conditioned. Finally, we carried out 350 nanoseconds molecular dynamics simulations. RESULTS/ANTICIPATED RESULTS: Our first model of FPN1 (571aa), using Rosetta/Robetta ab initio approach, resembles the structure of the proton-dependent transporter, POT and consists of 12 transmembrane helices. The membrane spanning helices veer away from the orientation in the structure of 4IKV. The alternate model using MODELLER and the method of satisfaction of constraints, returned one template, the structure of Bdellovibrio bacteriovorus iron (Fe2+) transporter homolog (5AYN, 440aa) with sequence identity of 19%. Aligning FPN1 on the template sequence incorporating structural information revealed better conservation (29%). This model also comprises 12 transmembrane helices in two bundles separated by a large intracellular loop. The iron binding site predicted in both models match the structures of distant bacterial homologs. DISCUSSION/SIGNIFICANCE OF IMPACT: We are using these experimentally verified structures and functional data to answer questions about the mechanism of ferroportin iron transport, structural dynamics and the significance of mutations in ferroportin seen in different populations, especially the Q248H mutation found in Africans and black Americans with moderate to high prevalence.
4307 Role of Pre-pregnancy Uterine Natural Killer Cells in Human Embryo Implantation
Authors: Kanter Jessica , Mani Sneha , Gordon Scott , Mainigi Monica
Published: July 2020

OBJECTIVES/GOALS: Human placentation requires complex coordination between maternal and fetal cell types but remains incompletely understood. We hypothesize that uterine natural killer (uNK) cells, an immune cell type that increases in abundance during the implantation window, is essential for appropriate implantation and placentation. METHODS/STUDY POPULATION: We plan to examine stromal cell (SC) decidualization, spiral artery remodeling, and EVT invasion, processes vital for early pregnancy establishment, in the presence or absence of secretory phase uNK cells. Fetal extravillous trophoblasts (EVTs) will be isolated from first trimester pregnancy tissue; maternal SCs, endothelial cells (ECs) and uNK cells will be obtained from secretory phase uterine tissue. SCs will be placed in monoculture and coculture with uNK cells and prolactin will be measured to evaluate decidualization. To study EVT invasion, we will utilize our novel “implantation-on-a-chip” device to determine how addition of uNK cells affects EVT migration through a collagen-matrigel matrix. In this system, we will also examine spiral artery remodeling with or without uNK cells via TUNEL staining. RESULTS/ANTICIPATED RESULTS: We anticipate that uNK cell addition to SCs will lead to a significant increase in SC prolactin levels, suggesting a role of uNK cells in endometrial decidualization. In vitro, we expect the addition of uNK cells will increase EC apoptosis and promote EVT invasion. DISCUSSION/SIGNIFICANCE OF IMPACT: Although decidual NK cells are known to participate in placentation, the role of pre-pregnancy uNK cells is unknown. uNK cell involvement in processes important for the earliest stages of pregnancy would provide a potential marker for abnormal placentation and offer avenues for intervention to decrease placentation associated perinatal morbidity.
4492 The role of creatine in developmental myelination and remyelination
Authors: Rosko Lauren , Smith Victoria N , Huang Jeffrey K.
Published: July 2020

OBJECTIVES/GOALS: Oligodendrocytes (OL) are glial cells of the central nervous system (CNS) responsible for the energy demanding task of generating myelin sheaths during development and remyelination after demyelinating injury. One metabolite shown to significantly increase ATP production in OL is the nitrogenous organic acid, creatine. Creatine plays an essential role in ATP buffering within tissues with highly fluctuating energy demands such as brain and muscle. Interestingly, mature OL, which are the cells capable of myelin production, are the main cells in the CNS expressing the rate-limiting enzyme for creatine synthesis, guanidinoacetate methyltransferase (Gamt). Patients with mutations in Gamt display intellectual disabilities, impaired myelination and seizures. Therefore, we hypothesize that creatine may be essential for developmental myelination and improve remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the Gamt gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. 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. Next, we show that knocking out Gamt leads to a significant reduction in OL in the major CNS white matter tract, the corpus callosum, at P14 and P21 (P14: 0.007, n = 3; P21: 0.04, n = 3). Here, we also investigate whether dietary creatine can enhance remyelination in the cuprizone model of toxic demyelination. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies highlight the important role creatine plays in developmental myelination and investigate whether creatine can provide a therapeutic value during a CNS demyelinating insult.
4292 Epigenetic Age and Depressive Symptoms in African American Women with Cardiometabolic Conditions
Authors: Perez Nicole B , Vorderstrasse Allison , Yu Gary , Taylor Jacquelyn
Published: July 2020

OBJECTIVES/GOALS: To examine the relationship between epigenetic age acceleration (EAA) and depressive symptoms in a cohort of African American women (AAW) with cardiometabolic conditions (CMC) including hypertension, diabetes, obesity; and to explore clinical phenotypes of depressive symptoms in this population. METHODS/STUDY POPULATION: This secondary analysis utilized genomic and longitudinal clinical data from AAW in the InterGEN cohort (n = 250). EWAS data was used to estimate EAA based on the Horvath method, which incorporates the DNA methylation statuses at 353 specific CpG sites and regresses this epigenetic age on chronological age to determine EAA. Pearson’s correlations and linear regression will be used to examine the relationship between EAA and depressive symptoms and a linear mixed model will investigate this relationship over four time points during a two-year period. Clinical phenotyping of depressive symptoms will be explored using a cluster analysis. RESULTS/ANTICIPATED RESULTS: Analysis is underway and will be complete by the time of presentation. We hypothesize that higher EAA will associate with higher depressive symptoms and poorer trajectories over time. We expect that this relationship may be meditated by the presence of CMCs. Exploratory analysis of clinical phenotyping is expected to provide descriptive evidence with respect to specific depressive symptoms or clusters which are most associated with EAA and CMCs. These results will address several gaps. To our knowledge, this is the first study to examine the relationship of EAA and depressive symptoms considering the role of CMC, in a historically understudied population with disproportionate risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression limits life quality and quantity and is highly comorbid in CMC. AAW have high risk of comorbidity, and this study furthers knowledge of depression and aging with a clinically accessible marker and aids recognition of a heterogenous phenotype in an undertreated population.
4429 Powering precision medicine research with the efficient construction of large diverse cohorts
Authors: Petukhova Lynn , Adenu-Mensah Nana Ekua , Shang Ning , Ena Lyudmila , Friedman Carol , Weng Chunhua , Schrimshaw Eric W.
Published: July 2020

OBJECTIVES/GOALS: There is an imperative need to initiate translational genetic studies of hidradenitis suppurativa (HS). Such work requires large cohorts and no HS registries exist. Precision medicine initiatives provide new resources and methods for efficiently constructing cohorts, but empirically informed best practice guidelines are needed. METHODS/STUDY POPULATION: Traditional methods for building cohorts rely on clinical encounters to identify patients and collect phenotype data. Precision medicine initiatives aim to decrease the time and cost of data collection by using alternative sources, including electronic health records (EHR) and remote collection of patient-reported data. The public’s use of the Internet to obtain and exchange health-related information coupled with the success of direct-to-consumer genetic companies suggests that it is feasible to remotely ascertain research participants for genetic studies. Importantly, Internet cohorts provide an opportunity to include research participants who are disconnected from healthcare, and thus remain hidden from research that relies on EHR or clinical services. RESULTS/ANTICIPATED RESULTS: First, to conduct studies in EHR we are developing an analytic pipeline for the automated extraction of an accurate HS diagnosis using natural language processing of clinical notes. In our preliminary work we are also using ICD codes to build cohorts in two EHR systems with and without linked genetic data. Second, we have developed Internet advertising campaigns for symptom-based recruitment. Informed consent and patient-reported data is collected on-line through a series of short surveys. Patients who complete the surveys and express interest in participating in genetic studies are sent saliva collection kits and return mailing material. Finally, we have established an HS biobank that has DNA from 300 participants identified through clinical services. Enrollment is on going. DISCUSSION/SIGNIFICANCE OF IMPACT: Our goal is to assemble an HS cohort that is large enough to power genetic discoveries. Our work is generating empirical evidence for precision medicine guidelines and will improve our knowledge about HS. The methods we are developing can be applied to efficiently create new cohorts for genetic studies of other diseases across different clinical areas.
4043 Saliva microRNA for pediatric concussion assessment
Authors: Hicks Steven , Loeffert Jayson , Loeffert Andrea , Onks Cayce , Zhen Kevin , Kim Raymond , Olympia Robert
Published: July 2020

OBJECTIVES/GOALS: There is no objective, biologic tool to detect concussion or guide clinical management. We previously showed that saliva microRNA (miRNA) levels differ in children with concussion and may predict symptom duration. The purpose of this study was to validate the utility of saliva miRNA and define longitudinal trends during the recovery period. METHODS/STUDY POPULATION: We collected concussion symptom burden (SCAT-5), cognitive performance (DANA), balance measures (ClearEdge), and saliva from 150 children (7-21 years) with concussion over 5 time-points: 0-2, 3-6, 7-14, 15-29, and 30-60 days post-injury. Saliva miRNA levels within the 443 concussion samples were quantified with RNA sequencing and compared to 218 samples from age- and sex-matched controls (healthy and post-exercise participants). Non-parametric ANOVA assessed RNA levels across time-points, and between concussions/controls. Machine learning was used to build logistic regression algorithms differentiating concussions/controls, and symptomatic/recovered concussion participants. Relationships between miRNAs and concussion phenotypes were explored with Spearman’s Rank correlations. RESULTS/ANTICIPATED RESULTS: Fifteen miRNAs differed across control and concussion participants (FDR < 0.05). Within concussion participants, all 15 miRNAs trended back toward control levels by 30-60 days post injury. A regression algorithm employing 6 of the 15 miRNAs differentiated control and concussion participants with an area under the curve (AUC) of 0.78 in a training set (n = 244) and 0.84 in a naïve test set (n = 24). Similarly, 6 miRNAs were able to differentiate symptomatic (SCAT-5 symptom score > 7) and asymptomatic concussion participants with an AUC of 0.73 in a training set (n = 219) and 0.76 in a naïve test set (n = 44). Furthermore, 5 miRNAs showed significant (R > 0.3; FDR < 0.05) associations with subjective and/or objective measures of concussion-related symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Saliva miRNAs levels are altered in children with concussion, and display predictable longitudinal trends following injury. Saliva miRNA measurement represents a non-invasive, objective tool that could be rapidly assessed to provide biologic evidence for clinicians managing pediatric concussion. CONFLICT OF INTEREST DESCRIPTION: I serve as a paid consultant and scientific advisory board member for Quadrant Biosciences, who has funded a portion of this work and licensed the findings from the Penn State College of Medicine.
4485 Silicone Implant Shells Increase the Rate of Proliferation of Patient-Derived BIA-ALCL Cells but Not Primary T Cells in an Engineered Biomimetic Breast Platform
Authors: Premaratne Ishani , Wright Matthew , Gadjiko Mariam , Lara Daniel , Samadi Arash , Ginter Paula , Inghirami Giorgio , Brown Kristy , Spector Jason
Published: July 2020

OBJECTIVES/GOALS: We use a tissue engineered, biomimetic, 3D model to study the pathogenesis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the effect of silicone implant shell on proliferation of patient-derived BIA-ALCL to its precursor T cells within the breast microenvironment. METHODS/STUDY POPULATION: Patient-derived breast tissue was processed for component adipocytes, ductal organoids, and stromal vascular fraction. These were suspended within 50 µl of 0.3% type I collagen matrix to which was added 200,000 cells/mL of either patient-derived BIA-ALCL cells or T progenitor cells. These were then plated into 6mm wells. As a control, both BIA-ALCL cells and T progenitor cells were suspended within type I collagen alone at the same seeding density without breast components. Before plating, wells were lined circumferentially with either textured, smooth, or no implant shell. These were 1cm by 2cm pieces dissected from the whole implant. Wells were imaged using confocal microscopy over 8 days. RESULTS/ANTICIPATED RESULTS: Unstimulated T progenitor cell count showed no significant increase in any of the conditions tested. The change in cell count over 8 days was 3.85% in each condition (p = 0.3352). A Tukey’s multiple comparison test comparing each condition revealed no significant increase in cell count over 8 days for all six conditions. Notably, our previous studies have shown proliferation of BIA-ALCL cells to be significantly more robust in the biomimetic platform compared to collagen-only groups, regardless of implant shell type (p < 0.01). BIA-ALCL cells grew nearly 30% faster in textured and smooth shell biomimetic groups compared to biomimetic wells lacking implant shell. DISCUSSION/SIGNIFICANCE OF IMPACT: Towards elucidating BIA-ALCL’s etiopathology, we show that silicone implant shell has a significant effect on proliferation of BIA-ALCL cells, but not their precursor T cells. If breast implant silicone shell is not a sufficient stimulus for T cell proliferation, co-stimulatory factors are required.
4505 Implementation of Real-World Data and Real-World Evidence in Clinical Studies
Authors: Pham Jessica , Pacifici Eunjoo
Published: July 2020

OBJECTIVES/GOALS: Real-world studies have been gaining momentum in providing evidence of treatment effectiveness and hold great potential for facilitating the drug regulatory process. The U.S. Food and Drug Administration (FDA) has recognized this by providing a framework for using real-world data (RWD) to generate real-world evidence (RWE). The objective of this study is to assess the current level of RWE implementation in clinical studies. METHODS/STUDY POPULATION: Using keywords relevant to RWE, we reviewed studies on drugs, biologics, and medical devices published on PubMed in 2018. Information regarding the therapeutic area of focus, intervention type, study design, primary outcome, and data source was recorded. Further analyses of the three main therapeutic areas of study (oncology, cardiology, and infectious diseases) were performed to determine how RWE was being utilized. In addition, a broad “real-world” search was performed on Clinicaltrials.gov, from which we extracted relevant observational and Phase I, II, II/III, III, III/IV, and IV studies. A supplemental PubMed search was used to evaluate published studies in order to identify which field these trials were concentrated in and the outcome of interest.” RESULTS/ANTICIPATED RESULTS: After application of “real-world” search terms to PubMed, 995 hits were generated and of these, 311 studies were excluded. More than half of the studies were observational and retrospective in nature (64%) with 70% examining drug/biologic outcomes. RWE data sources were largely dominated by medical records and claims data. The primary uses of RWE across oncology, cardiology, and infectious diseases included supporting drug product effectiveness, assessing safety, and evaluating treatment patterns. Of the 207 RWE studies identified on ClinicalTrials.gov, 66 were cancer randomized controlled trials (RCTs), a majority of which were used for post-marketing safety evaluations. Further research will be conducted to determine the precise role of RWE in all studies (e.g. historical comparator, label expansion). DISCUSSION/SIGNIFICANCE OF IMPACT: By examining the use of RWE in regulatory decision making, we can inform stakeholders of the extent to which robust RWE studies complement evidence generated by RCTs. Thought to reflect a product’s performance in a broader and more diverse population, RWE can provide greater insight to clinical trial conduct and ultimately transform patient outcomes.
4045 A TL1 Team Approach to Identify Factors Affecting Rural Tobacco Users’ Participation in Research and Quitting Tobacco Use
Authors: Gebru Neo , Damiani Rachel Elisabeth , Krieger Janice , Leeman Robert F
Published: July 2020

OBJECTIVES/GOALS: Guided by the health belief model and social identity theory, we aim to identify socio-cultural and psychological factors that influence rural tobacco users a) participation in research and b) quitting tobacco use. We also explore how citizen scientists are perceived as disseminators of messages. METHODS/STUDY POPULATION: In Phase I of this multi-stage project, we are conducting in-depth interviews with approximately 30 tobacco users. Interviews are on-going, and have been conducted with 16 participants thus far from four rural counties in Florida. The interview consists of semi-structured questions and multiple validated questionnaires. Specifically, we ask a series of questions about participants’ barriers to participating in research, tobacco use history, and internet use and message preferences. Additionally, we include questionnaires on participants’ substance use, nicotine dependence, motivation to quit, and willingness to participate in research studies. RESULTS/ANTICIPATED RESULTS: Initial findings suggest that rural tobacco users have an overall positive perception of research, and many choose to participate in research for altruistic reasons (i.e. they want to help others). Further, participants noted described feeling stigmatized due to their tobacco use. Although most began smoking to fit in with their community, many now feel on the outs. Participants also reported logistical barriers to participating in research, including lack of transportation. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings can inform the development of recruitment materials to resonate with rural adults, including by emphasizing the collective potential to help by participating. This interdisciplinary highlights areas for collaboration to enhance the reach of health education and public health messages.