bluuebunny/crossref_metadata_2025 huggingface dataset:
4523 Assessing Depression in Puerto Rican Hispanic Patients Hospitalized with Heart Failure
Authors: Gonzalez-Cordero Ariel
Published: July 2020

OBJECTIVES/GOALS: Heart failure and depression are important public health problems. Depression has been identified as an independent risk factor for increased cardiovascular morbidities. It is estimated that 1 out of every 5 patients living with heart failure suffer from depression. (Kop, W. J.) Studies have found that Hispanic patients have a higher rate of heart failure than non-Hispanic whites. Current guidelines recommend that proper screening tools must be used to identify and manage major depression disorder in HF patients, however many of these patients go unrecognized in the medical setting. The prevalence, management, and outcomes of depression among PuertoRican Hispanics living with heart failure is unknown. Objective: The purpose of this study is to evaluate the relationship between heart failure and depression in Hispanics with heart failure METHODS/STUDY POPULATION: To this end, we will perform a secondary analysis of data from the PR CardiovascularSurveillance Study (PRCSS). We will extract personal data from 4,461 medical records of patients admitted with heart failure (ICD-9 Codes 428) at 21 hospitals in Puerto Rico, during the years 2007, 2009 and 2011. For statistical methods, we will implement chi-square and t-tests at a significance level of 0.05 RESULTS/ANTICIPATED RESULTS: We expect to see older aged women with higher NYHA and pro-BNP levels to be associatedwith diagnosis of major depression disorder and worse in-hospital outcomes DISCUSSION/SIGNIFICANCE OF IMPACT: With this study, we would like to raise awareness about depression in patients with heart failure, and its role in improving patient outcomes. Moreover, we would like to determine if there are gender-specific health disparities among Puerto Rican Hispanics with heart failure
4258 Black women’s narratives: A mixed-methods exploration of microaggressions and mental health
Authors: Colburn Alexandria , de St. Aubin Ed
Published: July 2020

OBJECTIVES/GOALS: This social justice-oriented, multi-method study aims to gain an understanding of the unique sources of stress and resilience impacting Black women in Milwaukee. As clinical researchers, it is imperative that we understand the mechanisms underlying the relationship between marginalized identities and substantial health disparities. METHODS/STUDY POPULATION: Participants were Black women, diverse in age, income, and sexual orientation to emphasize an intersectional approach (current N = 87 of 160). Our interdisciplinary team collected two interrelated data types: narrative and survey. Participants completed a 1.5-hour life story interview in which they were asked to share stories from their lives, their backgrounds, plans for the future, forces that shaped their stories, and how their identities have influenced their experiences. Interviews were done one-on-one and conducted by Black women interviewers. They were also asked to complete an online survey protocol including measures of stress, trauma, microaggressions, coping, and well-being. Transcribed life story interviews will be coded utilizing grounded theory, an intensive qualitative analysis method. RESULTS/ANTICIPATED RESULTS: The presentation will focus on the unique methodological approach, which emphasizes community empowerment through collaboration and cultural competency. Data collection is still in progress, but initial relationships between key variables will be discussed. It is anticipated that greater frequency and appraisal of microaggressions will significantly predict higher reported stress, anxiety, and depression. Within-group diversity will be examined as well. Relevant themes emerging from grounded theory will also be presented. Results will directly inform community outreach aimed at improving the lives of Black women. DISCUSSION/SIGNIFICANCE OF IMPACT: This study sheds light on unique, identity-related stressors believed to contribute to mental and physical health disparities. It also builds on current theories, filling voids in the research literature by taking a psychosocial perspective, emphasizing the voices of participants, and channeling the findings to specific programs in the community.
4483 Activity and Abundance of Mucus-degrading Microbes in Inflammatory Bowel Disease
Authors: Ostrowski Matthew , Martens Eric C.
Published: July 2020

OBJECTIVES/GOALS: This study seeks to culture and characterize mucus-degrading microbes from the microbiome of inflammatory bowel disease (IBD) patients. METHODS/STUDY POPULATION: Stool will be collected from IBD patients and healthy first-degree relatives, then enriched for mucin-degrading microbes through growth on porcine rectal mucin. Dilution plating in both liquid and solid culture formats will be employed to isolate strains capable of growth on mucin. Cultures that are positive for mucin degradation will be identified with 16S rRNA sequencing; unique isolates will be genome sequenced and transcriptionally profiled on simple monosaccharides and mucin in order to identify putative mucin-degrading genes. The abundance of novel enzymes, pathways, and microbes will be compared in healthy and IBD patient populations using existing datasets in the literature. RESULTS/ANTICIPATED RESULTS: We expect to isolate previously uncultured mucin-degrading microbes, which will likely include new strains and possibly new species of bacteria. Through the transcriptomic characterization of mucin-degrading pathways, we will expand the lexicon of known mucin-degrading enzymes and pathways used by bacteria in the human colon. We expect mucin-degrading microbes to be more abundant and active in IBD patients compared to healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: There is no cure for IBD and treatment relies heavily on suppressing a patient’s immune system. This research seeks to understand the contribution of the gut microbiota in the pathogenesis of IBD, which may lead to future therapeutic targets.
4511 Bio-Compatible Implantable Oxygen Sensor Technology with Real-Time Monitoring of Surgical Flaps and Reimplantation
Authors: Patel Preet , Ibrahim Mohamed , Klitzman Bruce
Published: July 2020

OBJECTIVES/GOALS: Current surgical flap and replantation monitoring techniques have limitations in detecting the pathologic state, calibration and cost-to-patient issues. Our hypothesis is that novel implantable oxygen sensors can provide a more efficient, accurate, and reliable monitoring of tissue oxygenation. METHODS/STUDY POPULATION: Experimental sensors were used with an exogenous remote used as a reader once implanted (Fig. 1) A rat tissue perfusion model with three regions of an SIEA flap as well as into adjacent control sites was made (Tip, Middle, and Base) Blood flow was greatest at the base, diminishing towards the Tip, thus creating a perfusion gradient. Changes in tissue oxygen tension PO2 were estimated by the steady-state fluorescence of the optical sensors using an IVIS imaging system. The sensors were used to collect data from days 0, 3, and 7 as a reading of Tissue Oxygen Tension (TOT) with ANOVA used to assess for statistical significance in blood oxygen data with respect to relative perfusion status. RESULTS/ANTICIPATED RESULTS: Inspired FiO2 was decreased from 100% to 12% with a corresponding change in the TOT readings from all sensors. (Fig. 2) The tip portion of the flap demonstrated the most profound detection of tissue necrosis, with the middle demonstrating the second most necrosis and the base demonstrating the least with correlating TOT sensor readings. (Fig. 3) Acute vascular compromise of the feeding blood vessels in the pedicle was immediately detected within 70 seconds (*p<0.05). (Fig. 4) DISCUSSION/SIGNIFICANCE OF IMPACT: This study introduces and validates a recent technique to monitor acute vascular occlusion, flap viability, and necrosis in the immediate postoperative period in a validated rodent model. Future directions of this novel technology will aim to reproduce these findings in clinical feasibility studies.
4090 Dysregulation of Skeletal Muscle Mitochondrial Function following Critical Illness: a Translational Approach
Authors: Gill Luther , Simon Liz , Molina Patricia
Published: July 2020

OBJECTIVES/GOALS: The objective of the study was to determine whether CLP altered genes associated with mitochondrial function in the diaphragm. METHODS/STUDY POPULATION: A rodent cecal-ligation and puncture (CLP) model used to mimic sepsis-induced critical illness. The CLP model involved ligation of 50% of the cecum below the ileocecal valve in adult C57BL6 mice, followed by needle puncture of the cecum resulting in mid-grade sepsis. Mice survived for 48 hours or more, following injury. Diaphragm and limb muscles were harvested 24 hours following CLP (N = 6) and following a sham CLP procedure (N = 6). RESULTS/ANTICIPATED RESULTS: Gene expression of mitochondrial related genes (mef2c, myh1, pgc1-α), were significantly decreased in the diaphragm of CLP injured animals when compared to controls. In addition, ubiquitin ligases, genes associated with skeletal muscle atrophy murf1 and atrogin were increased in the diaphragm 24 hours after injury (p< 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that sepsis-induced critical illness significantly impacts the expression of genes implicated in mitochondrial homeostasis and atrophy. Ongoing studies will identify whether CLP injury decreases skeletal muscle mitochondrial function.
4078 Identification of distinct fibroblast populations with unique roles in pancreatic cancer progression and tumor immunity
Authors: Darpolor Josephine Kebbeh , Zheng Xiaofeng , Yang Sujuan , Sugimoto Hikaru , Carstens Julienne , de Sampiao Pedro Correa , LeBleu Valerie , Kalluri Raghu
Published: July 2020

OBJECTIVES/GOALS: The desmoplastic reaction in PDAC involves a significant accumulation of immune cells and fibroblasts.The functional diversity of carcinoma associated fibroblasts (CAFs) remains largely unknown, and identification of immune regulating subsets would have a substantial impact in augmentation of immunotherapy efficacy. METHODS/STUDY POPULATION: Employing histology, FACs, multiplex immunohistochemistry, single cell RNA sequencing (sc-RNA-seq) and genetically engineered mouse models, we demonstrate that aSMA+ cells are a dominant CAF population in PDAC with tumor restraining properties (TS-CAFs), as opposed those of the FAP+ CAFs, which demonstrate tumor promoting activity (TP-CAFs). RESULTS/ANTICIPATED RESULTS: Analysis of bulk tumor depleted of either TS-CAFs or TP-CAFs showed that TS-CAFs predominantly modulate extracellular matrix (ECM) production, facilitate cell-ECM adhesion and regulate adaptive immunity, while TP-CAFs exhibit a lineage that is skewed towards a pro-inflammatory, chemokine secreting phenotype. Further, scRNA-Seq analyses demonstrate that CAFs share distinct gene expression profiles characteristic of lymphocytic and myeloid lineages. Together our data distinguish two populations of CAFs, one which is tumor suppressing with roles in ECM remodeling and another which is tumor promoting with roles in cytokine production, both with immune modulating capabilities. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study identifies a complex network of functionally heterogeneous fibroblasts during PDAC progression with significant immunotherapeutic implication. The identification of distinct fibroblast subsets will allow us to discriminately target fibroblast populations to augment immunotherapy efficacy in pancreatic cancer.
4249 Markers of mitochondrial biogenesis, fusion and architecture are disturbed in PBMC from war veterans with posttraumatic stress disorder (PTSD)
Authors: Andric Silvana , Markovic Aleksandra , Milosevic Mirko , Radovic Sava , Starovlah Isidora , Brkljacic Jelena , Milutinovic Danijela Vojnovic , Matic Gordana , Kostic Tatjana
Published: July 2020

OBJECTIVES/GOALS: The aim of this study was to define the transcription profiles of the molecular markers of mitochondrial biogenesis and fusion/architecture, and the markers of mtDNA copy numbers in the peripheral blood mononuclear cells (PBMCs) from war veterans with/without post-traumatic stress disorder (PTSD). METHODS/STUDY POPULATION: The peripheral blood mononuclear cells (PBMCs) from war veterans with/without post-traumatic stress disorder (PTSD) were used to monitor transcription profile of the molecular markers of mitochondrial biogenesis and fusion/architecture, as well as the markers of mtDNA copy numbers. The human male immortalized monocytes were exposed in vitro to hormonal markers of PTSD in order to monitor the effects of each particular hormonal marker on the molecular markers of mitochondrial biogenesis and fusion/architecture, as well as the markers of mtDNA copy numbers. RQ-PCR analyses were used to define transcriptional profile of above mentioned markers. RESULTS/ANTICIPATED RESULTS: The transcription profiles of above mentioned markers were disturbed, with high individual variability within the groups. A significant increase in the expression of the PPARGC1A transcript was observed in a group of subjects with current PTSD, as well as in the subjects with “life-time” PTSD, compared to healthy controls. PPARGC1B, NRF2 and MFN2 transcripts increased only in PBMCs of “life-time"-PTSD, while the level of transcripts for other investigated genes and the ratio of markers of mtDNA copy numbers showed no significant difference between groups. The in vitro results showed parallelism with the results obtained using the PBMCs from the subjects of the PTSD study. DISCUSSION/SIGNIFICANCE OF IMPACT: Although preliminary (the analysis require a larger number of subjects), the results are first findings and a solid base for further extensive multidisciplinary research in order to clarify the molecular mechanisms for the prevention and treatment of trauma-induced pathological conditions.
4121 The beneficial, anti-fibrotic effects of chemokine receptor 2 and 5 antagonists on fat-exposed mouse primary hepatic stellate cells (pHSCs)
Authors: Kruger Annie J. , Bergman Kruger , Gay Martha , Cao Hong , Tucker Robin , Shivapurkar Narayan , Smith Jill P.
Published: July 2020

OBJECTIVES/GOALS: Non-alcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in the world for which no anti-fibrotic therapies exist. We hypothesized that BMS-22 and maraviroc (MVC), chemokine receptor 2 (CCR2) and 5 (CCR5) antagonists, respectively, would diminish the fibrogenic activity of "fat-exposed" murine pHSCs. METHODS/STUDY POPULATION: pHSCs were isolated from livers of 6 week old male mice following 4 weeks on a NASH-inducing choline-deficient high fat diet (CDAHFD, “fat-exposed”) or standard diet (SD) and passaged in vitro. Early passage (6-12) pHSCs were plate-adhered and TGF-b-treated (10ng/mL) to maximally activate their pro-fibrogenic genes, collagen 1α1 (Col1A1), tissue inhibitor of metalloproteinase 1 (TIMP1), or α-smooth muscle actin (ACTA2). CDAHFD and SD pHSCs were then treated for 48 hours with increasing doses of BMS-22 or MVC (range: 0.3-120ng/mL) to determine (1) the degree of attenuation of the pro-fibrogenic response as measured by qPCR of fibrogenic genes (Col1A1, TIMP1,ACTA2); (2) enhancement of a fibrolytic response as measured by qPCR of matrix metalloproteinases (MMP) 2, 9 and 13 genes; and (3) pHSC migration using the scratch assay. Cell viability and CCR2 and CCR5 gene expression in response to escalating doses of antagonists were also measured. RESULTS/ANTICIPATED RESULTS: Plate- and TGF-b activated CDAHFD pHSCs had a 2-fold greater, dose-dependent attenuation of their pro-fibrogenic activity in response to BMS-CCR2-22 and MVC, when compared with plate- and TGF-b activated SD pHSCs, as measured by reductions in collagen 1α1 (Col1A1) and α-smooth muscle actin (ACTA2) gene expression. TIMP1 gene expression was unaffected by drug treatment for 48 hours. Cell viability was not affected up to doses of 30ng/mL of each drug. pHSCs also demonstrated a dose-dependent increase in CCR2, CCR5 and MMP-9 gene expression in response to surface receptor antagonism. Migration assays comparing CDAHFD and SD pHSCs in response to escalating doses of MVC and BMS-22 are ongoing and expected to demonstrate a significantly decreased migratory capacity of CDAHFD pHSCs than SD pHSCs in response to therapy, reflecting the increased susceptibility of the “fat-exposed” pHSCs to anti-fibrotic therapy than normal pHSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-fibrotic drugs that dampen pro-fibrogenic activities of “fat-exposed” pHSCs are urgently needed. CCR2 and CCR5 antagonists, BMS-22 and MVC, respectively, can selectively dampen the pro-fibrogenic response of fat-exposed pHSCs, and must be considered for future trials in human NASH. CONFLICT OF INTEREST DESCRIPTION: Dr. Jill Smith has a patent licensing agreement with Immune Therapeutics, Inc.
4431 Utilization of swept source optical coherence tomography to optimize characterization of cystoid macular edema in preterm infants
Authors: Seely Kai , Mangalesh Shwetha , Winter Katrina , Tai Vincent , Tran-Viet Du , Chiu Stephanie , Toth Cynthia
Published: July 2020

OBJECTIVES/GOALS: The goal of this study is to evaluate and optimize the characterization of cystoid macular edema (CME) using an investigational swept source (SS)-OCT system. Our knowledge of CME in preterm infants is limited; optimizing its characterization is a critical step in understanding its impact on vision. METHODS/STUDY POPULATION: In this IRB-approved protocol, 118 preterm infants were imaged in the Duke intensive care nursery (ICN) with a novel lightweight, hand-held, high-speed, SS-OCT system following routine clinical eye exams. SS-OCT images were deidentified, automatically segmented using custom software (DOCTRAP), measured for several retinal layer thicknesses, and reviewed by masked expert graders for the presence and severity of CME. Reliability of SS-OCT measures will be assessed, and the association between CME status and retinal layer thicknesses will be calculated using logistic regression modeling. RESULTS/ANTICIPATED RESULTS: The prevalence of CME overall and by severity will be calculated. The distribution of several retinal layer thicknesses will be reported and compared by infant CME status and, when edema is present, by CME severity. Reproducibility and repeatability will be reported for objective variables, and intra-grader and inter-grader agreement will be reported for subjective variables. Multivariate logistic regression coefficients and odds ratios will be calculated for each retinal layer thickness variable. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will use a novel SS-OCT system to identify retinal thickness measures that may be objective markers of CME status. This will refine the characterization of CME and provide a framework for correlating CME with functional outcomes like visual acuity. CONFLICT OF INTEREST DESCRIPTION: SC and CT have unlicensed patents on relevant technologies. CT receives royalties from Alcon and Hemosonics and consultation fees from EMMES.
4089 Clinical Implementation of Monte Carlo Dose Calculation for Patient-Specific Radiotherapy Quality Assurance
Authors: Parenica Holly Marie , Kabat Christopher , Myers Pamela , Kirby Neil , Papaconstadopoulos Pavlos , Papanikolaou Nikos , Stathakis Sotirios
Published: July 2020

OBJECTIVES/GOALS: The Monte Carlo dose calculation method is often considered the “gold standard” for patient dose calculations and can be as radiation dose measurements. Our study aims to develop a true Monte Carlo model that can be implemented in our clinic as part of our routine patient-specific quality assurance. METHODS/STUDY POPULATION: We have configured and validated a model of one of our linear accelerators used for radiation therapy treatments using the EGSnrc Monte Carlo simulation software. Measured dosimetric data was obtained from the linear accelerator and was used as the standard to compare the doses calculated with our model in EGSnrc. We will compare dose calculations between commercial treatment planning systems, the EGSnrc Monte Carlo model, and patient-specific measurements. We will implement the Monte Carlo model in our clinic for routine second-checks of patient plans, and to recalculate plans delivered to patients using machine log files. RESULTS/ANTICIPATED RESULTS: Our Monte Carlo model is within 1% agreement with our measured dosimetric data, and is an accurate representation of our linear accelerators used for patient treatments. With this high level of accuracy, we have begun simulating more complex patient treatment geometries, and expect the level of accuracy to be within 1% of measured data. We believe the Monte Carlo calculation based on machine log files will correlate with patient-specific QA analysis and results. The Monte Carlo model will be a useful tool in improving our patient-specific quality assurance protocol and can be utilized in further research. DISCUSSION/SIGNIFICANCE OF IMPACT: This work can be implemented directly in clinical practice to ensure patient doses are calculated as accurately as possible. These methods can be used by clinics who do not have access to more advanced dose calculation software, ensuring accuracy for all patients undergoing radiotherapy treatments.
4058 Enhanced efficiency of large-scale clinical proteomic studies: when less is more
Authors: Thomas Stefani , Friedrich Betty , Schnaubelt Michael , Chan Daniel W. , Zhang Hui , Aebersold Ruedi
Published: July 2020

OBJECTIVES/GOALS: Large-scale clinical proteomic studies of cancer tissues often entail complex workflows and are resource-intensive. In this study we analyzed ovarian tumors using an emerging, high-throughput proteomic technology termed SWATH. We compared SWATH with the more widely used iTRAQ workflow based on robustness, complexity, ability to detect differential protein expression, and the elucidated biological information. METHODS/STUDY POPULATION: Proteomic measurements of 103 clinically-annotated high-grade serous ovarian cancer (HGSOC) tumors previously genomically characterized by The Cancer Genome Atlas were conducted using two orthogonal mass spectrometry-based proteomic methods: iTRAQ and SWATH. The analytical differences between the two methods were compared with respect to relative protein abundances. To assess the ability to classify the tumors into subtypes based on proteomic signatures, an unbiased molecular taxonomy of HGSOC was established using protein abundance data. The 1,599 proteins quantified in both datasets were classified based on z-score-transformed protein abundances, and the emergent protein modules were characterized using weighted gene-correlation network analysis and Reactome pathway enrichment. RESULTS/ANTICIPATED RESULTS: Despite the greater than two-fold difference in the analytical depth of each proteomic method, common differentially expressed proteins in enriched pathways associated with the HGSOC Mesenchymal subtype were identified by both methods. The stability of tumor subtype classification was sensitive to the number of analyzed samples, and the statistically stable subgroups were identified by the data from both methods. Additionally, the homologous recombination deficiency-associated enriched DNA repair and chromosome organization pathways were conserved in both data sets. DISCUSSION/SIGNIFICANCE OF IMPACT: SWATH is a robust proteomic method that can be used to elucidate cancer biology. The lower number of proteins detected by SWATH compared to iTRAQ is mitigated by its streamlined workflow, increased sample throughput, and reduced sample requirement. SWATH therefore presents novel opportunities to enhance the efficiency of clinical proteomic studies.
4518 Metabolomic Identifiers Predictive of Adverse Events due to Acetaminophen Administration
Authors: Sonn Brandon Joseph , Heard Kennon , Monte Andrew
Published: July 2020

OBJECTIVES/GOALS: Acetaminophen (Tylenol, APAP) toxicity has been well documented and well explored over the last 50 years. However, there has been no investigation into identification of specific metabolites that can predict which patients will have adverse reactions to therapeutic doses of APAP. METHODS/STUDY POPULATION: 205 subjects recruited from the Denver, CO community received the highest recommended daily dosing of APAP, 4 grams, for 16 days. Subjects were grouped by 1) alanine aminotransferase (ALT) at any monitored time point above 60units/L (n = 20) vs 2) no increase in ALT at any time point (n = 185). Blood was collected at days 0, 4, 7, 16, and 31. Samples were run on ultra-high performance liquid chromatography mass spectrometry with 27 heavy-labeled standards for metabolites documented to be associated with APAP metabolism. Data will be analyzed to look for significant changes in metabolite and demographic variable expressions using t-tests, chi square and logistic regression, as appropriate. RESULTS/ANTICIPATED RESULTS: It is expected that there will be greater elevations of conjugated non-toxic APAP metabolites (APAP-glucuronide, APAP-sulfate) in subjects whose ALT did not elevate because of successful hepatoprotection. Conjugated APAP metabolites are expected to only be present in samples taken after APAP therapy initiation confirming exposure as compared to being predictive of toxic response. Increases in lactate and cysteine in pre-exposure samples would allow for prediction of APAP toxicity as they are expected to have increased expression in subjects whose ALT became elevated which is indicative of increased hepatic damage due to oxidative damage. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of metabolites and/or demographic factors associated with toxic response to APAP prior to administration could advise APAP recommendations. Quantification of post-APAP administration metabolites would identify extent of successful hepatoprotective mechanisms.
4267 Noninvasive hybrid ultrasound and photoacoustic imaging for the assessment of liver fibrosis
Authors: Sultan Laith Riyadh , Karmacharya Mrigendra , D’Souza Julia , Kirkham Brooke , Brice Angela K , Wood Andrew KW , Hunt Stephen , Sehgal Chandra
Published: July 2020

OBJECTIVES/GOALS: The detection of liver fibrotic changes at an early and reversible stage is essential to prevent its progression to end-stage cirrhosis and hepatocellular carcinoma. Liver biopsy, which is the current gold standard for fibrosis assessment, is accompanied by several complications due to its invasive nature in addition to sampling errors and reader variability. In this study, we evaluate the use of quantitative parameters extracted from hybrid ultrasound and photoacoustic imaging to detect and monitor fibrotic changes in a DEN rat model. METHODS/STUDY POPULATION: Liver fibrotic changes were induced in 34 Wistar male rats by oral administration of Diethylnitrosamine (DEN) for 12 weeks. 22 rats were imaged with B-mode ultrasound at 3 different time points (baseline, 10 weeks and 13 weeks) for monitoring liver texture changes. Texture features studied included tissue echointensity (liver brightness normalized to kidney brightness) and tissue heterogeneity. 12 rats were imaged with photoacoustic imaging at 4 time points (baseline, 5 wks, 10 wks, and 13 wks) to look at changes in tissue oxygenation. Hemoglobin oxygen saturation (sO2A) and hemoglobin concentration (HbT) in the right and left lobes of the liver were measured. 8 rats were used as controls. Liver tissue samples were obtained following 13 weeks from DEN start time for METAVIR histopathology staging of fibrosis. RESULTS/ANTICIPATED RESULTS: Texture features studied showed an increase with time in DEN rats. Normalized echointensity increased from 0.28 ± 0.06 at baseline to 0.46 ± 0.10 at 10 weeks (p < 0.0005) and 0.53 ± 0.15 at 13 weeks in DEN rats (p < 0.0005). In the control rats, echointensity remained at an average of 0.25 ± 0.05 (p = 0.31). Tissue heterogeneity increased over time in the DEN-exposed rats from a baseline of 208.7 ± 58.3 to 344.6 ± 52.9 at 10 weeks (p < 0.0005) and 376.8 ± 54.9 at 13 weeks (p = 0.06) however it stayed constant at 225.7 ± 37.6 in control rats (p = 0.58). The quantitative analyses of the photoacoustic signals showed that blood oxygen saturation significantly increased with time. At 5 weeks sO2AvT increased by 53.83 % (± 0.25), and HbT by 35.31 % (± 0.07). Following 10 weeks of DEN; sO2AvT by 92.04 % (± 0.29), and HbT by 55.24 % (± 0.1). All increases were significant p < 0.05. In the 13th week, however, the values of all of these parameters were lower than those in the 10th week, however, the decrease was statistically insignificant. DISCUSSION/SIGNIFICANCE OF IMPACT: Quantitative features from B-mode ultrasound and photoacoustic imaging consistently increased over time corresponding to hepatic damage, inflammation and fibrosis progressed. The use of this hybrid imaging method in clinical practice can help meet the significant need for noninvasive assessment of liver fibrosis.
4106 Personalizing Care For Colorectal Cancer: Identifying Novel Opportunities
Authors: Rivers Zachary , Stenehjem David , Lou Emil , Nelson Andrew , Jacobson Pamala , Kuntz Karen
Published: July 2020

OBJECTIVES/GOALS: This project seeks to understand how personalized medicine can optimize care for patients with colorectal cancer. It identifies opportunities for personalized medicine to improve clinical outcomes, and uses cost-effectiveness analysis to assess the clinical and financial impact of this approach. METHODS/STUDY POPULATION: This project uses two methods to understand the impact of personalized medicine. First, this project has used SEER-Medicare data in conjunction with Clinical Pharmacogenetics Implementation Consortium guidelines to identify medications used by patients with colorectal cancer that can be impacted by genetic variants. This data will then be combined with population genetic variant rates to understand the likely impact screening for a given variant will have on medication response and adverse events. Medication use frequencies and genetic variant rates are then used to populate cost-effectiveness models that simulate the clinical and financial outcomes, identifying optimal genes to screen. RESULTS/ANTICIPATED RESULTS: The first result will be a comprehensive overview of treatment patterns for patients with colorectal cancer in the United States, as well as the treatments used for disease-induced comorbidities. The second result will be the identification of genetic variants based on population rates and medication utilization that should be screened in this patient population. The final result will be a breakdown of the clinical and financial outcomes associated with implementing screening for the identified genes. Preliminary results from a two-gene cost-effectiveness analysis demonstrates that screening for variants in those genes improves both clinical and financial outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: This project demonstrates how current treatment approaches can be optimized via personalized medicine. It uses epidemiological methods to identify opportunities to integrate genetic findings from other diseases, and uses cost-effectiveness analysis to understand the impact of transforming care. CONFLICT OF INTEREST DESCRIPTION: Stocks-Aurinia, Syndax, Adaptimmune, Rigel pharma
4565 Sex-Specific Differences in the Genomic Landscape of Pediatric and Adult Glioblastoma
Authors: Ivanov Nikolay A. , Dahmane Nadia , Greenfield Jeffrey P. , Mason Christopher E.
Published: July 2020

OBJECTIVES/GOALS: It has been previously shown that pediatric high-grade glioma (pHGG) survival is different between sexes. We set out to find out whether there are sex-specific differences in the genomic landscapes of pHGG that may underlie this sex disparity. METHODS/STUDY POPULATION: We downloaded Illumina 450k DNAm data from ArrayExpress and GeneExpressionOmnibus. The minfi package was used to process raw DNAm data. Sex chromosomes and CpGs that are common SNPs were removed. Surrogate variables (SVs) were estimated via the sva Bioconductor package. Differentially methylated CpGs were identified by fitting a multiple linear regression model for the DNAm level at each CpG, with independent variables being sex (a binary variable) and the estimated SVs. RNAseq data was downloaded from Cavatica, and differential gene expression analysis was carried out via the DESeq2 package. RESULTS/ANTICIPATED RESULTS: In the pediatric glioblastoma (GBM) DNAm data [58 female & 91 male IDH wt samples; ages 0.1–21 yrs;], we found 7,371 differentially methylated cytosines (DMCs) at FDR≤0.05. Of the DMCs, 289 had DNAm differences between male and female samples ≥10%. The majority of probes (68%) were in CpG islands, shelves, or shores. We also found 4 differentially methylated regions (DMRs) between sexes (FWER≤0.1). In the adult GBM DNAm samples [32 F & 32 M IDH wt samples; ages 22–75 yrs], we found only 117 DMCs at FDR≤0.05, and no DMRs. In the RNAseq dataset [68 F & 54 M pHGG samples, ages 0.08–30.6 yrs], we found 383 differentially expressed genes (at FDR≤0.05), and 16 of them (4%) overlapped a DMC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings demonstrate that pHGG exhibits sex-specific methylome differences. Interestingly, this difference is greater in the pediatric population as compared to adults. The pHGG transcriptome also differs by sex, which may be related to differential DNAm in a minority of cases.
4385 The Pain and Social Experiences Project: Understanding the role of interpersonal trauma in pain
Authors: Pierce Jennifer , Hassett Afton L. , Harris Rick E. , Goesling Jenna , Brummett Chad M.
Published: July 2020

OBJECTIVES/GOALS: Traumatic interpersonal experiences are associated with higher rates of chronic pain, increased pain severity and poorer functioning. The objective of this ongoing project is to obtain prevalence rates for various forms of interpersonal trauma among individuals with chronic pain, and to explore the potential mediating effect of heightened sensory and social sensitivity on the experience of pain. METHODS/STUDY POPULATION: Patients at Michigan Medicine between the ages of 18 and 65 complete an online survey. Patients are being recruited through a tertiary-care, outpatient pain clinic, as well as through an online health research portal. We aim to recruit 700 participants; we currently have 59.6% of our goal (n = 417). Participants also have the option to be included in a registry from which we can recruit for future studies. Approximately 85% of our participants have agreed to be in the registry. RESULTS/ANTICIPATED RESULTS: Preliminary data show that, of the 263 (63.4%) participants for whom data on chronic pain is available, 167 (63.5%) report chronic or persistent pain over the previous 3 months. Of these, 54% reported some form of childhood abuse or neglect. Approximately 41% reported four or more adverse childhood experiences. Additionally, of the 122 participants (73%) who were in a current romantic relationship, 20% reported some form of physical violence victimization from their romantic partner. We anticipate that interpersonal trauma will be associated with poorer perceptions of social relationships, higher sensory sensitivity, and higher perceived stress. DISCUSSION/SIGNIFICANCE OF IMPACT: The PASE Project parent study will be used to better understand prevalence rates for various forms of interpersonal trauma in our chronic pain population. Future analyses and studies will explore alternative pathways linking interpersonal trauma to the experience of pain through sensory and social sensitivity, which will inform interventions aimed at reducing pain among patients with a history of trauma.
4168 Understanding ECM-Based Drug Resistivity in Breast Cancer
Authors: Libring Sarah , Shinde Aparna , Boodaghidizaji Miad , Plummer Alexandra , Ardekani Arezoo , Wendt Michael , Solorio Luis
Published: July 2020

OBJECTIVES/GOALS: Cell-cell (CC) and cell-matrix interactions (CM) are known to affect drug sensitivity of cancer cells, but are not effectively recapitulated using 2D platforms. This research aims to determine how cell and matrix interactions confer drug resistivity in 3 distinct culturing models: 2D (no CM/limited CC), 3D spheroids (CC) and 3D fibronectin (both). METHODS/STUDY POPULATION: We examined four breast cancer cell types. The cells were derived from a nonmetastatic primary tumor (HMLE-E2) or overt bone-metastasis (BM). Transglutaminase 2 (TGM2), a matrix crosslinking protein, is overexpressed in metastatic bone tumors and may play a key role in matrix-conferred drug resistivity. In a gain-of-function model, TGM2 was upregulated in HMLE-E2 cells and compared to shTGM2 knockdown BM cells. Growth rates were analyzed using metabolic activity over 8 days, and drug sensitivity to Neratinib (0-1000 nM) was analyzed via cell titer. To account for the different transport properties of the 3 distinct culture environments, we developed a mathematical model for each condition, allowing us to normalize the drug sensitivity results across models to effectively compare true biological resistivity. RESULTS/ANTICIPATED RESULTS: We observed that increased cellular levels of TGM2 significantly increase the growth rate and drug resistivity of cells on fibronectin matrices. Interestingly, in 2D cultures, TGM2 expression was correlated with higher Neratinib resistivity but did not affect growth rates. In spheroid models without a significant matrix component, that rely solely on cell-cell junctions, high levels of TGM2 were correlated with lower survival rates. Lower levels of TGM2 are correlated with a more epithelial phenotype, and using our mathematical model we have identified significant transport differences between high and low TGM2 spheroids. We theorize that the low TGM2 spheroids have denser packing, which lowers the rate of diffusion and, thus reduces the effective concentration of the drug to the majority of the cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Our studies indicate that the cellular response to drugs can be altered by changes in both transport properties of the tissue and the CM interactions. By systematically investigating the effects of CC interactions and CM interactions, we can use mathematical models to delineate physical means of drug resistivity from a biologically driven resistance.
4500 Providing a System for Practical Monitoring Training for Clinical Trials within Academic Institutions
Authors: Chandramohan Advaita , Kaur Sukhmani , Pacifici Eunjoo
Published: July 2020

OBJECTIVES/GOALS: The goal was to understand the effectiveness of a novel clinical trial educational module and a corresponding initiative designed and disseminated by the Southern California Clinical and Translational Science Institute (SC-CTSI) to increase the quality of clinical trials conducted in academia. METHODS/STUDY POPULATION: The CRCs (Clinical Research Coordinators) for the initiative are asked to complete the online training. Possible study protocols are picked to be monitored by the CRCs. The monitor is instructed to study the protocol extensively and prepare for their monitoring visit. The trained monitor from the initiative then reaches out to the CRC of the study that is to be monitored and carries out the monitoring visit. Afterwards, the monitor sends initiative personnel the monitoring report, which is evaluated to see if the monitor checked everything they should have during the visit. The PI of the study is contacted with highlights from the monitoring report and improvements that they can make. RESULTS/ANTICIPATED RESULTS: The first study monitored was a site of a large NIH-sponsored study where the consent forms were signed electronically. It was found that the monitor could not access the consent forms. Therefore, the monitor could not do source data verification. The PI of the study said that they would be raising this issue with the NIH. During the monitoring visit of the second study chosen for the initiative, patient binders were specifically examined for informed consent and source documentation completeness. The charts of patients were also reviewed. The only deviation found was a missing signature in the Investigator Site File. For the last two studies, data will be reported. DISCUSSION/SIGNIFICANCE OF IMPACT: Monitors were not only able to monitor efficiently, but also able to point out deficiencies in the monitoring practices of large studies. This model could be expanded to other academic institutions to establish quality management systems to ensure data integrity and subject protection.
4349 Survey of Regulatory Reforms to Address Comprehension of Clinical Trial Results
Authors: Kirkland Matthieu , Reyes Christian , Pire-Smerkanich Nancy , Pacifici Eunjoo
Published: July 2020

OBJECTIVES/GOALS: Clinical research is the backbone of the medical community. However, there are few regulations to ensure clinical trial participants can understand their results, leading to volunteers feeling unvalued and unlikely to enroll in trials1. This study examines the need of lay summaries METHODS/STUDY POPULATION: To understand the current landscape of clinical trial summaries, literature searches were conducted using the University of Southern California Library database with keywords Title contains “lay language” OR “lay summary” AND any field contains “Trial” OR “clinical”, and Title contains “natural language processing” AND “clinical trial” OR “Summary”. Studies were deemed relevant if they discussed lay language summaries for health care realms or using Natural Language Processing (NLP) to increase comprehension. Papers published by the Center for Information and Study on Clinical Research Participation (CISCRP) were reviewed and their Associate Director was interviewed. RESULTS/ANTICIPATED RESULTS: Of 67 total results, 14 were determined to be relevant. Ten of the relevant results examined lay language summaries and their regulation and 4 were NLP studies. The European Medicines Agency set regulations mandating clinical trial summaries. However, researchers have difficulty validating to an appropriate reading level2. Difficulty and potential bias halted a U.S. mandate of lay summaries3. The nonprofit CISCRP has partnered with industry to develop unbiased clinical trial summaries resulting in all volunteers feeling appreciated and 91% understanding clinical trial results post summary1. Similarly, NLP software for annotating Electronic Health Records increased comprehension for 77% of patients4. DISCUSSION/SIGNIFICANCE OF IMPACT: In the U.S., a lack of regulations mandating lay summaries may be related to concerns by regulatory agencies that summaries in plain language may introduce bias3. Future looks into integration of NLP systems to clinical trials may create unbiased summaries and allow for FDA regulation.
4027 Collaborative Working Retreats for Interdisciplinary Investigators and Engaged Stakeholders as a Tool for Sparking Creativity and Accelerating the Development of Translational Research Projects
Authors: Borawski Elaine A , Matos Anna Thornton , Goodwin Meredith , Gardenhire Rachel Ann , McIntosh Briana
Published: July 2020

OBJECTIVES/GOALS: As part of the Cleveland CTSA, “Collaborative Working Retreats” have been developed for the purpose of being a catalyst to move groups of interdisciplinary investigators and stakeholders to collaborative research teams with feasible and actionable translational research projects. METHODS/STUDY POPULATION: Groups of interdisciplinary investigators with engaged stakeholder(s) were invited to apply. Selected groups participated in a 4-hour, professionally facilitated retreat, tailored to the unique needs of each team. In addition to the facilitator, a graphic recorder was utilized to capture ideas and aid in decision making by creating a visual narrative linked to the team’s overall vision. Teams were charged with generating three translational research projects and writing a formal Team Action Plan (TAP) by two months post retreat. Retreat participants were asked to complete a survey to evaluate the retreat, and structured interviews were conducted with team leaders 4-6 months post retreat. RESULTS/ANTICIPATED RESULTS: Six groups were awarded retreats, comprised of 48 investigators (representing all schools in the university and 3 of 4 affiliated hospital systems) and 28 stakeholders for a total of 76 participants. 45% completed the followup survey. 77% said they would recommend the service to other teams or would use it again themselves and 97% stated their team benefited from having a facilitator. At 2 month follow up, one team had completed the TAP and subsequently applied for federal funding. However, 4 of the remaining 5 teams indicated that they had made significant progress, attributing progress to their retreat time. Each teams’ progress is being tracked for 2 years, using a newly developed metric. DISCUSSION/SIGNIFICANCE OF IMPACT: Facilitated retreats appear to serve as an important catalyst for progression of translational research projects, providing needed time and support for brainstorming and planning. Lessons learned, pre-retreat work, and tools for tailoring retreat content and tracking progress will be presented.
4375 Developing team science for practical applications of artificial intelligence in health systems to improve value and outcomes: A case study in reducing avoidable emergency department use
Authors: Manuel Vladimir G. , Halperin Eran , Chiang Jeffrey , Taraszka Kodi , Kim Laura , Raja Naveen , Saigal Christopher , Roh Lily , Eskin Eleazer
Published: July 2020

OBJECTIVES/GOALS: Health care systems are complex, dynamic, and varied. Advances in artificial intelligence (AI) are enabling healthcare systems to use their own data to elicit patterns and design suitable interventions. To realize this potential, computer scientists and clinicians need an effective, practical, and replicable approach to collaboration METHODS/STUDY POPULATION: In this study, computer scientists partnered with clinicians to investigate predictors of avoidable emergency department use. The team sought an approach to computational medicine that could increase the relevance and impact of prediction to solve pressing problems in the health system. The team adopted an emergent architecture that engaged system leaders, computer scientists, data scientists, health services researchers, and practicing clinicians with deep ambulatory and inpatient knowledge to form the initial questions that shaped the prediction model; to understand nuances of coding and recording in source data and the implications for models; and to generate insights for promising points of intervention. The team recorded decisions and challenges as it progressed to analyze its function. RESULTS/ANTICIPATED RESULTS: Most avoidance models focus on a narrow time period around target events, or on high cost patients and events. This interdisciplinary team used their insights into the health system’s workflows and patient population to adopt a longitudinal approach to their prediction models. They used AI to build models of behavior in the system and consider prevention points across clinical units, time, and place. The holistic, systemwide focus enabled the team to generate insights that the system leaders and subsequently specific clinical units could apply to improve value and outcomes. A facilitated team process using learning system and cooperative network principles allowed a large and modular interdisciplinary team to build a transparent AI modeling process that yielded actionable insights into hypercomplex workflows. DISCUSSION/SIGNIFICANCE OF IMPACT: An architecture for involving diverse stakeholders in computational medicine projects can increase the relevance and impact of AI for solving care delivery problems in complex health systems. Translational science and computational medicine programs can foster this type of engagement and encourage a whole system perspective.