bluuebunny/crossref_metadata_2025 huggingface dataset:
2174
Authors: Klonoski Joshua , Facelli Julio C.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This poster presents preliminary results of using in silico approaches to predict a priori, based on sequence alone, the pathogenesis of novel influenza A virus. METHODS/STUDY POPULATION: Here we analyzed the structure of the NS1 protein of 11 strains of well characterized influenza A virus with known pathogenesis, reported in the literature as LD50 values, and published sequences. We performed homology comparison of these sequences using the ExPASy SIM alignment tool for protein sequences and then predicted their 3D structures using the I-TASSER method for protein structure prediction. We retained the best 20 I-TASSER models for the NS1 sequences considered here and compared their structures with that of the X-ray crystallographic structure of the NS1 protein in the A/blue-winged teal/MN/993/1980 (H6N6). The average RMS between this experimental structure and the best 20 I-TASSER models was used as a measure of structural similarity between the 3D structures among the proteins. RESULTS/ANTICIPATED RESULTS: The sequence homology shows modest correlation between sequence and pathogenicity. Linear correlations with R values as large as 0.6 where observed for the full sequence homology and the homology of the RBD domains of the proteins. The correlations with the other protein domains were significant lower. We did not found overall correlation between the 3D structures and pathogenesis of all the variants considered here, but the initial results suggest that correlations do exists for different subgroups of viruses. In future work we will use advanced data mining methods to better understand clustering and correlation between structure and pathogenesis. DISCUSSION/SIGNIFICANCE OF IMPACT: The results presented in this poster demonstrate, as proof of concept, the use of in silico approaches to determine pathogenesis of viruses with substantial impact on human health. The ability of computationally predicting pathogenesis of rapidly mutating viruses can be an effective way to accelerate the development prevention strategies because computational methods are relatively inexpensive and much more scalable than in vivo approaches.
2342
Authors: Johnson Kimberly D. , Gillespie Gordon L. , Vance Kimberly
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The aim of this study was to determining how interruptions affect the triage process. METHODS/STUDY POPULATION: Prospective, observational study, where 118 triage interviews were observed. RESULTS/ANTICIPATED RESULTS: In total, 57% of triage interviews were interrupted. The most common interruption was by other nurses; however, 7% of the interruptions were by the triage nurse themselves. When an interruption occurred during the triage process, 67% of the time the triage nurse would stop the triage assessment and attend to the interrupter. In the interrupted interviews, 17% of the entire triage time was dedicated to addressing interruptions. Some interruptions (ie, additionally staff entering to conduct ECG) had a positive impact by expediting care during the triage process; where other interruptions delayed patient care. DISCUSSION/SIGNIFICANCE OF IMPACT: Interruptions increased the total triage time and contributed to patient treatment delays, as well as led to errors in nursing assessment. Understanding the classifications of triage interruptions and the impact on patient outcomes will allow researchers to develop interventions to mitigate the impact of these interruptions.
2377
Authors: Kanna Balavenkatesh , Castro-Rivas Erida , Roques Euripides , Magabo Shirley , Washington Tina , Faiz Mohammad , Tiwari Namita , Faraci Andrea , Guzman Edgardo
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: More than 2 out of 3 adults in the United States are overweight or obese. Obesity disproportionately affects minority populations. There is limited data on obesity and CVD risks among inner-city minority cab drivers in New York City (NYC). The goal is to study perceptions, knowledge and health behaviors of Hispanic livery cab drivers of NYC that contributes to obesity. METHODS/STUDY POPULATION: We conducted an observational study of focus groups related to perception, knowledge, or behavior among Latino livery cab drivers of NYC. Direct transcription of the taped recordings into concepts were grouped into themes and common themes were categorized. The sample size of the focus groups was based on the saturation point where common themes emerged. RESULTS/ANTICIPATED RESULTS: In total, 25 Latino livery cab drivers were enrolled. Of those, 24 were men. Mean age is 53 years (21–69); body mass index (BMI) is 31 (22.8–38.7) kg/m2; 50% had hypertension and 27% had diabetes. Eight dominant themes emerged. Cab drivers were aware of their increased risk for CVD which most of them attributed to work stress, sedentary lifestyle, and poor eating habits “on-the-go”. In particular, they mentioned a tendency of having “Pipa,” a Spanish term denoting increased abdominal girth, which they equated to early death. Family and social support was an important facilitator in changing unhealthy behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows that minority cab drivers are generally obese or overweight and aware of their personal risk factors for CVD including central obesity. Social and family support may be key to improving their lifestyle. An evidenced-based health model that includes family education and decision support will be tested in our next study phase to understand if it can improve body weight.
2382
Authors: Espejo Maria , Kanna Balaventkatesh , Castro-Rivas Erida , Magabo Shirley , Washington Tina , Faiz Mohammad , Trimble LaShaun , Tiwari Namita , Roques Euripides , Faraci Andrea , Guzman Edgardo
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Compared to others, African-Americans (AA) have a higher prevalence of hypertension. Although, hypertension control has been well studied in clinical settings, a significant number of AA patients have uncontrolled hypertension. We conducted a qualitative study on CVD risk perceptions, knowledge, and behaviors among hypertensive AA in the South Bronx, NY. METHODS/STUDY POPULATION: Hypertensive AA participants, 18 years and older were recruited at a community-based hospital clinic. Focus groups with open-ended questions on CVD knowledge, perception, and behaviors was conducted. Responses were transcribed and transcript was analyzed using open code method. Concepts were formulated, which were then categorized into dominant themes. The sample size was based on the saturation point related to emerging common themes. RESULTS/ANTICIPATED RESULTS: There were 21 patients participated in 3 focus group sessions. The median age was 59 years; BMI median of 31.5 kg/m2; 76% were female. In total, 57% had controlled BP and 67% were diagnosed with diabetes mellitus; 8 themes emerged of which unhealthy diet was dominant. Participants acknowledged eating fried foods and meat seasoned with salt contributed to their hypertension. Their food choices were based on family tradition and economical cost more than nutritional value. DISCUSSION/SIGNIFICANCE OF IMPACT: This study reveals that inner city hypertensive AA patients have misperceptions, gaps in knowledge, and barriers to healthy behaviors. We propose to partner with them using shared decision making to raise awareness, knowledge and change in behaviors to prevent CVD in community settings.
2192
Authors: Abraham Ruvalcaba Carlos , Monroy Roger , Tell Lisa A. , Fiorello Christine V. , Last Jerold , Delplanque Jean-Pierre
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This study investigates the process configuration parameters involved in targeted drug delivery to the avian respiratory system. Previously, direct intratracheal aerosol delivery in an avian model using a commercial atomizer was found to result in delivery of a high portion of the total dose into one lung lobe. We hypothesize that controlling process configuration will decrease the asymmetric distribution. METHODS/STUDY POPULATION: A 3D printed model of an avian trachea and mainstream bronchi was constructed to create a representative model for direct instillation of aerosols. Construction of the model respiratory tract included the trachea and the first mainstream bronchi bifurcation to measure left/right (L/R) distribution of aerosol delivered. Both liquid aerosol delivery (LAD) using a commercial atomizer and dry aerosol delivery (DAD) using a custom-built dry powder insufflator device were tested. Two experimental variables were controlled: (1) retraction distance from the carina and (2) centering of device shaft in the lumen of the trachea. Measurement of device efficiency (dose delivered to the 3D model at as fraction of total dose), aerosol delivery efficiency (dose captured at L/R bifurcations as a fraction of total dose), and aerosol lateralization (L/R) was conducted. RESULTS/ANTICIPATED RESULTS: The aerosol delivery efficiency for both LAD and DAD devices [73.9% (95% CI: 68.2–79.2) and 73.4% (95% CI: 55.5–91.3), respectively] did not have an appreciable difference. However, the LAD device had a higher efficiency as compared with the DAD device. The L/R distribution for the DAD device was found to be highly dependent on both retraction distance and shaft centering. Appreciable improvement in the L/R distribution was seen using the DAD device by increasing the retraction distance distal to the carina. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of targeted drug delivery to treat pulmonary pathogens requires a careful design, manufacture, and therapeutic positioning of devices. In particular, clinically relevant animal models and treatment regimes requires a sound understanding of the physical processes controlling aerosol distribution in the respiratory system. By using a simulated respiratory model, many of the physical parameters of drug delivery can be tested before using a live animal model. This is especially important from an animal welfare perspective as well as an animal subject availability aspect.
2424
Authors: D’Orazio Brianna M. , da Rosa Joel Correa , Tobin Jonathan N.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) recurrence ranges from 16% to 43% and presents significant challenges to clinicians, patients, and families. The number of emergency department visits for SSTIs increased from 1993 to 2005 from 0.48 to 1.16 ED visits per 100 US residents (95% CI 0.94 to 1.39; p<0.001); high safety-net status EDs saw a 4-fold increase in visits. The CA-MRSA Project (CAMP2) comparative effectiveness research (CER) study aims to evaluate a home-based intervention implemented by Community Health Workers (CHWs) or “promotoras” to prevent recurrence and transmission of CA-MRSA in primarily low-income, minority patients presenting to primary care with SSTIs. The intervention disseminates and implements methods found effective in the REDUCE MRSA trial. The present analysis was conducted using publically available data set to characterize the national patterns of healthcare utilization for treatment of SSTIs. METHODS/STUDY POPULATION: An analysis was conducted using data downloaded from the CDC National Ambulatory Medical Care Survey (NAMCS) and the CDC National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 (most recent data available) to evaluate the addition of Emergency Departments (EDs) as compared to Ambulatory Care as recruitment sources for a clinical trial to reduce CA-MRSA SSTI recurrence and household transmission. “Low-income” population was defined using “Expected Source of Payment” categories “Medicaid” and “Uninsured,” and ICD-9-CM dermatologic diagnosis codes for SSTIs and ICD-9-CM Procedure Codes for Incision and Drainage (I&D) were used to define a visit for SSTI treatment. RESULTS/ANTICIPATED RESULTS: In all patients, I&D was performed at a higher rate in EDs as compared with the ambulatory care setting (49.57 vs. 1.44 per 10,000 US residents in Medicaid and Uninsured; 44.48 vs. 5.24 per 10,000 US residents in all other insurance types). Nationally, low-income patients are 4 times more likely to have I&D procedure performed (OR 4.05, 95% CI 0.614–26.759, p<0.0001) and 5 times more likely to be diagnosed with an SSTI (OR 5.10, 95% CI 2.987–8.707, p<0.001) in the ED setting. DISCUSSION/SIGNIFICANCE OF IMPACT: These results confirm that low income patients seek primary care for SSTIs in both EDs and ambulatory care, such as Federally Qualified Health Centers (FQHCs). This also confirms the trend we have experienced in FQHCs in NYC, many of whom refer patients to the ED for the I&D procedure, and those patients return to the FQHC for follow-up. Thus, the most comprehensive test of using CHWs to disseminate and implement the findings from the REDUCE MRSA trial would engage both EDs and Ambulatory Care/FQHCs for patient identification and recruitment.
2450
Authors: Gatebe Kironji Antony , Cheng Tina , Jones Vanya , Lindstrom Johnson Sarah , Fein Joel , Ryan Leticia
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To identify factors associated with urban youth and parent perceptions of the preventability (PoP) of the youth’s medically attended assault injuries in order to guide future violence prevention strategies. METHODS/STUDY POPULATION: Assault-injured youth (n=180; ages 10–15; 60% male; 96% African-American) and their parents were recruited from 2 pediatric emergency departments (EDs) in Baltimore and Philadelphia between June 2014 and June 2016. Data on demographics, circumstances of injury, injury severity, and perceptions of the injury were collected from chart review and in-person interviews with youth and parents using previously validated instruments. Within youth and parent groups, we compared those who reported “definitely true” when asked if the event that brought them to the ED could have been prevented to those who reported “maybe true” or “unlikely” using χ2 testing. RESULTS/ANTICIPATED RESULTS: In total, 68 (37.8%) youth and 123 parents (68.3%) reported that the injury was definitely preventable. Youth who were injured indoors [OR 2.13 (95% CI 1.17, 3.88), p=0.013] or considered their injury not serious [OR 4.82 (95% CI 1.78, 13.11), p=0.002] were more likely to perceive injury preventability and those who reported being the victim were less likely to perceive injury preventability [OR 0.26 (95% CI 0.01, 0.67), p=0.005]. Bullying and use of weapons were not associated with youth PoP. Parents were significantly more likely to perceive preventability when the person/people involved were known by the youth [OR 1.94 (95% CI 1.04, 3.62), p=0.037] and when the injury occurred indoors [OR 1.96 (95% CI 1.04, 3.69), p=0.038]. Similar to youth, parental report of bullying was not associated with parent PoP. Injury severity, and victim role of their child were also not associated with parent PoP. DISCUSSION/SIGNIFICANCE OF IMPACT: A prior violent injury is a major risk factor for future injuries and homicides. Through our work we were able to identify factors associated with youth and parent perception of preventability of injuries in a high risk population. Youth who felt victimized were less likely to perceive their injury as preventable. In addition, parents were more likely to perceive the injury as preventable when their injured child knew those involved in the incident. This work can inform violence prevention strategies and potentially identify opportunities to reduce intentional injuries in urban youth.
2194
Authors: Khanjyan Michael , Nguyen Vien , Kazangian Eric , Browne Shane , Healy Kevin , Ameri Kurosh , Yeghiazarians Yerem
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: A major limitation of cardiac stem cell transplantation following myocardial infarction (MI) is poor retention of cells in the ischemic microenvironment. Our study aims to better understand and promote the survival and differentiation of human cardiosphere-derived cells (hCDCs) in anoxia, a feature of infarcted myocardium. METHODS/STUDY POPULATION: We previously demonstrated that TGFβ1 and heparin-containing hydrogels (TH-hydrogel) can promote murine CDC survival. In this study, hCDCs were incubated in either normoxia or anoxia for 8 hours with and without TH-hydrogel. In addition, hCDCs without TH-hydrogel were assessed in 16 hours of anoxia. Following incubation, hCDCs were assayed for viability using calcein dye and immunostained for CD31, a marker of endothelial differentiation. RESULTS/ANTICIPATED RESULTS: hCDCs incubated for 8 hours in anoxia in both models equally demonstrated increased survival up to 30% when compared with cells incubated in normoxia. However, in contrast to hCDCs alone, hCDCs with TH-hydrogel additionally demonstrated increased differentiation into endothelial cells in both anoxia and normoxia. We found that hCDCs alone were able to upregulate CD31 only when subjected to 16 hours of anoxia. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrate a new, previously unknown response of hCDCs to anoxia. This induces increased viability and differentiation of hCDCs into endothelial cells. The differentiation in anoxia was time dependent and could be expedited with use of TH-hydrogel. Anoxic preconditioning of hCDCs together with the TH-hydrogel system may improve the therapeutic potential of stem cell transplantation following MI.
2484
Authors: Mayo-Gamble Tilicia , McBride Murry Velma , DeBaun Michael R.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Despite the high prevalence of individuals diagnosed with sickle cell disease (SCD) in Tennessee, comprehensive care and education for patients with SCD is not as widely available as healthcare services for individuals managing other chronic illnesses. We aimed to engage SCD stakeholders in patient-centered outcomes research (PCOR) as a mechanism for advancing care and translational research for this rare disease population. METHODS/STUDY POPULATION: Through a partnership with the Sickle Cell Foundation of Tennessee, we implemented Community Health Ambassadors to systematically engage patient partners with SCD and their caregivers, aged 18–50 from rural and urban communities throughout Tennessee, in PCOR to establish a sustainable infrastructure, focused on connecting the SCD community through a service providing community-based organization to offer (1) information on how to connect with other families; and be informed about SCD community activities, or educational offerings; (2) training in basic research principals; and (3) opportunities to contribute to PCOR, including feedback on effective and practical ways for providing input on research efforts through patient centered input, comparing urban and rural area preferences. Community ambassadors utilized health fairs, clinic days at various hospitals and community centers, and social media to spread awareness of the project, in addition to boosting the recruitment process. RESULTS/ANTICIPATED RESULTS: A statewide SCD network was developed to offer social support and increase access to education, medical care, and engagement in research activities. Findings include: recruitment of 150 patients and 35 executive committee members (local physicians, community leaders, adults with SCD and parents of children with SCD). DISCUSSION/SIGNIFICANCE OF IMPACT: Most rural and urban families affected by SCD have no systematic way to engage in, or lend their expertise to, PCOR. A statewide network of patient partners, community stakeholders, researchers, and medical professionals will ultimately increase the standard of care for patients, and provide valuable insight for SCD research. The opportunity to create the underpinnings for coordinated patient-centered education for patients with SCD and their caregivers holds promise for developing a scalable PCOR process model for replication and implementation in other states and emulate this model with other rare disease populations.
2501
Authors: Shaheen Magda , Teklehaimanot Senait
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Examine mental health service use and its correlates among depressed group in a national sample of population≥20 years old. METHODS/STUDY POPULATION: Analysis of data for adult≥20 years old from the NHANES 2006–2012. Depression was assessed using the 9-item PHQ. The use of mental health and antidepressant drug were used to indicate the service use. We utilized multiple logistic regressions to determine the independent association between service use and each independent variable (demographics, health status, food security, chronic conditions, and depression severity) controlling for other independent variables. Data were presented as adjusted odds ratio (AOR), 95% confidence interval (95% CI), and p-value of statistical significance. p-value of<0.05 indicates statistical significance. RESULTS/ANTICIPATED RESULTS: Of the 17,824 subjects, 22% had mild to severe depression. Among the depressed group, 25% used antidepressant, 17% used mental health service. For the use of mental health services among the depressed group, African-American (AA), ≥60 years old, uninsured and foreign born were less likely to use the mental health service relative to other groups [AOR=0.58 (95% CI=0.45–0.75), 0.21 (95% CI=0.14–0.33), 0.61 (95% CI=0.45–0.83), 0.41 (95% CI=0.17–0.99), respectively, p<0.05]. For the use of antidepressant drug among the depressed group, AA, Hispanics, uninsured and foreign born were less likely to use antidepressant drug relative to other groups [OR=0.26 (95% CI=0.20–0.33), 0.42 (95% CI=0.31–0.57), 0.41 (95% CI=0.31–0.56), 0.20 (95% CI=0.10–0.78), respectively, p<0.05). For the use of mental health services and/or antidepressant drug among the depressed group, 40–59 years old, AA, Hispanics, uninsured, foreign born were less likely to use mental health services and/or antidepressant drug relative to other groups [OR=0.52 (95% CI=0.38–0.72), 0.35 (95% CI=0.28–0.43), 0.52 (95% CI=0.40–0.69), 0.53 (95% CI=0.41–0.68), 0.30 (95% CI=0.13–0.68), respectively, p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our study showed that minority (AA and Hispanics), foreign born and uninsured with depression were less likely to use mental health services and/or antidepressant drug relative to other groups. Culturally and linguistically adapted intervention that involves community and providers to increase awareness about depression and the available services/treatment among minority, immigrant, and uninsured population are needed.
2526
Authors: Christine Kugler Kari , Tanner Amanda E. , Wyrick David L. , Milroy Jeffrey J. , Chambers Brittany D. , Ma Alice , Collins Linda M.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to develop an effective and efficient STI preventive intervention among college students following the principles and phases of MOST. METHODS/STUDY POPULATION As part of the preparation phase, an explicit conceptual model, drawing heavily on theory and prior research, was used to translate the existing science into 5 candidate intervention components (ie, descriptive norms, injunctive norms, expectancies, perceived benefits of protective behavioral strategies, and self-efficacy). For the optimization phase, in Fall 2016 all first-year students (n=3547) from 4 universities were recruited to participate. Students were randomized to 1 of 32 different experimental conditions that included a combination of the candidate intervention components. Component effectiveness was evaluated using data from an immediate post-intervention survey on respective component mediators (eg, alcohol and sex-related descriptive norms). After a second factorial experiment (Fall 2017), only those intervention components that meet the pre-specified criteria of day ≥0.15 will be included in the optimized intervention. The evaluation phase will evaluate the effectiveness of the optimized STI preventive intervention via a randomized-control trial (Fall 2018). RESULTS/ANTICIPATED RESULTS: Preliminary results from the first factorial experiment suggest that descriptive norms and injunctive norms intervention components were significantly effective in reducing post-intervention perceived alcohol prevalence (β=−0.28, p<0.001) and approval of alcohol (β=−0.33, p<0.001), and sex-related norms (β=−0.23, p<.001). These results, in combination with process data, are being used to inform revisions of the intervention components to be included in a second factorial screening experiment. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates how an iterative approach to engineering an STI preventive intervention using MOST can affect the behaviors of college students and serve as a foundation for other translational science.
2532
Authors: Thompson Keeshaloy , Brown Milton
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The central goal is to predict the metabolites of varenicline and predictively evaluate their propensities for eliciting an increased binding effect in the brain. METHODS/STUDY POPULATION: Molecular modeling computational software and other cheminformatic tools present a strategic in silico strategy to predict a complete metabolic transformation for the varenicline molecule. Molecular docking tools help to highlight key interactions of the varenicline with key metabolizing enzymes that are differentially expressed across a population. This will assist in validating clinical models for smoking cessation. RESULTS/ANTICIPATED RESULTS: Differentialized binding results depending on whatever metabolite is produced. DISCUSSION/SIGNIFICANCE OF IMPACT: Products of metabolism of varenicline may differ in individuals and across groups, thus, binding effects and the propensity for adverse effects may differ in individuals.
2542
Authors: Srivastava Arnav , Patel Hiten , Kates Max , Schwen Zeyad , Joice Gregory , Semerjian Alice , Gorin Michael , Pierorazio Phillip , Allaf Mohammad E.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Due to increased experience and favorable outcomes, the use of partial nephrectomy (PN) to treat renal cell carcinoma has grown in the past decade, with expansion to larger tumors. Performing PN for larger tumors could potentially increase the number of patients up-staged to pT3a after surgery, who may have instead been treated with radical nephrectomy (RN), if known preoperatively. We aimed to estimate the proportion of patients up-staged to T3a disease after PN stratified by size. We also compared size-stratified survival outcomes of up-staged patients to those with T1a, T1b, or T2 kidney cancer. METHODS/STUDY POPULATION: From 1998 to 2013, patients undergoing PN or RN were identified from Surveillance Epidemiology and End Results registries. The proportion of patients receiving PN found to have pT3a disease was quantified by size. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease with appropriately size-stratified pT3a patients. Also, PN patients with pT3a disease were compared to size-stratified RN patients with pT3a disease. Comparisons by size were performed within pT3a patients receiving PN. RESULTS/ANTICIPATED RESULTS: From a total of 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a increased along with increasing tumor size: 4.2% for T1a, 9.5% for T1b, and 19.5% for T2. Among patients receiving PN, adjusted survival analysis demonstrated worse CSS for up-staged pT3a patients Versus appropriately stratified pT1a (CSS: HR=1.87, p=0.02), pT1b (CSS: HR=1.91, p=0.01), and pT2 (CSS: HR=2.33, p=0.01) patients. However, when assessing OS, only the size-stratified comparison of up-staged pT3a Versus pT1a disease demonstrated worse OS for the up-staged cohort (OS: HR=1.25, p=0.04). Comparing PN and RN for pT3a disease, size-adjusted analysis revealed no statistical difference in CSS or OS. Lastly, among patients undergoing PN with pT3a disease, patients with larger tumors, measuring 4–7 cm (CSS: HR=2.83, p<0.01; OS: HR=1.44, p=0.04) or 7–16 cm (CSS: HR=8.22, p<0.01; OS: HR=2.64, p<0.01), experienced worse survival than those with smaller pT3a tumors, <4 cm. DISCUSSION/SIGNIFICANCE OF IMPACT: A greater proportion of patients appear to experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse cancer specific survival after PN compared to those with similarly sized localized tumors. Furthermore, the up-staged pT3a patients after PN appear to experience similar survival to pT3a patients undergoing RN. However, pT3a patients undergoing PN had worse survival with increasing tumor size, reinforcing the need for improvements in preoperative staging and identifying patients at risk of up-staging.
2275
Authors: Marquis Bryce J. , Carvahlo Eugenia , Hurren Nicholas , Wolfe Robert R. , Borsheim Elisabet
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This study will assess the effect of essential amino acid (EAA) supplementation on plasma triglyceride (TG) in elderly adults. We will also explore the mechanisms mediating EAA mediated changes in fat metabolism and to suggest promising routes to refine therapy of hypertriglyceridemia. METHODS/STUDY POPULATION: In total, 7 nondiabetic male and female subjects ages 50–75 years with elevated plasma TG levels (130–500 mg/dL) were recruited to participate in an acute (5 h) and long-term (8 wk) EAA supplementation study. We measured changes in regional and whole body fat metabolism, including changes in body composition, plasma TG levels, whole body fat metabolic rates, tissue mitochondrial respiratory capacity, and metabolomic profiles before and after supplementation. RESULTS/ANTICIPATED RESULTS: Long-term EAA supplementation decreased fasted plasma TG levels by 19% (p<0.01). Metabolomics of skeletal muscle found acute EAA supplementation resulted in increased EAA metabolic products while long-term supplementation resulted in increased anaplerosis [flux into the tricarboxylic acid cycle (TCA) intermediate pool] and anaplerotic substrates [propionyl (p<0.01) and succinyl (p<0.01) carnitine] and intermediates of long-chain fatty acid metabolism [stearoyl (p<0.01) and myristoyl (p<0.05) carnitine]. However, tissue level respiratory capacity appeared to be unaffected by EAA supplementation. DISCUSSION/SIGNIFICANCE OF IMPACT: EAA supplementation has potential to improve lipid metabolism and plasma TG levels in non-diabetic older adults. Mitochondrial metabolomics suggest that insufficient TCA pool size may limit tissue fatty acid oxidation and may provide an additional route for nutritional therapy.
2290
Authors: Shrestha Elina , Voisin Maud , Barrett Tessa J. , Nishi Hitoo , Pineda-Torra Inés , Fisher Edward A. , Garabedian Michael J.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Accumulation of cholesterol-laden macrophages in arterial walls leads to atherosclerosis. LXRs induce expression of genes that are atheroprotective in macrophages including CCR7, a chemokine receptor that promotes their emigration from the plaque. CCR7 expression has been shown to be negatively regulated by phosphorylation of LXRα at S198 and is reduced in diabetic mice that show impaired plaque regression. I hypothesized that LXRα phosphorylation at S198 diminishes macrophage emigration from atherosclerotic plaque and contributes to impaired regression in diabetes. METHODS/STUDY POPULATION: Inducible LXRα S198A phosphorylation deficient knock in mouse were used as donors for bone marrow transplantation into mice prone to develop atherosclerosis. Plaques were developed by placing mice on western diet; and regression was induced by lowering their lipid levels. Aortic plaques were then analyzed by using morphometric, histological, and molecular analyses in control and diabetic mice expressing either LXRα WT or LXRα S198A during regression. RESULTS/ANTICIPATED RESULTS: Surprisingly, lack of phosphorylation increased plaque macrophage content and impaired regression under normoglycemic condition; however, it did not exacerbate diabetic regression. Plaques in diabetic mice were associated with increased LXRα S198 phosphorylation. Consistent with this, LXRα phosphorylation is enhanced in macrophages cultured under hyperglycemic conditions indicating glucose-dependent regulation of LXRα phosphorylation. Monocyte trafficking studies reveal that lack of phosphorylation and diabetes independently increase recruitment of monocytes in the plaque that might contribute to increased macrophage content. Importantly, I found that diabetes also increases macrophage retention in the plaque, which is reversed in the absence of phosphorylation. We predict that this increased retention results from inhibition of emigration of plaque macrophages through enhanced phosphorylation in diabetes. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that inhibiting LXRα phosphorylation could be beneficial in diabetic atherosclerosis to reverse the accumulation of macrophages in the plaque. This study imparts insight on regulation of plaque macrophage trafficking through LXRα S198 phosphorylation.
2337
Authors: Mancilla Trevi A. , Aune Gregory J.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Our research strives to understand the pathophysiology of doxorubicin cardiotoxicity, focusing on the understudied nonmyocyte cardiac cells. Our understanding will enable researchers to develop protective or alternative therapies for cancer patients and treatments for cancer survivors. METHODS/STUDY POPULATION: Early studies have been carried out in isolated primary cardiac fibroblasts. Cells were treated with varying doses of doxorubicin. Cell viability, proliferation, and reactive oxygen species generation have all been studied. Future studies will focus on mitochondrial assessment in treated cells and confirmation of findings in animal models. Potential therapies discovered in these studies will also be conducted in animal models. RESULTS/ANTICIPATED RESULTS: Our results show a direct effect of doxorubicin on cardiac fibroblasts in vitro. Treated cells show a decreased rate of proliferation and increased production of reactive oxygen species. Similarly to cardiomyocytes, we hypothesize that reactive oxygen species damage the mitochondria of cardiac fibroblasts thereby altering their function and playing a role in doxorubicin cardiotoxicity. DISCUSSION/SIGNIFICANCE OF IMPACT: Current therapies have not been able to adequately protect patients from the cardiotoxicity of doxorubicin and other anthracyclines. A complete understanding of how doxorubicin damages cardiac tissue will only be possible by studying all cell types of the heart. With a better understanding, alternative therapies can be developed to prevent or treat doxorubicin cardiotoxicity without sacrificing the efficacy of doxorubicin in treating cancer.
2422
Authors: Grippin Adam , Sayour Elias , Dobson Jon , Mitchell Duane A.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Immune-based therapies hold great promise for treatment of refractory tumors. However, development is limited by a lack of identified immune correlates to vaccination. We recently showed that dendritic cells (DCs) prolong progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, and that DC migration to site draining lymph nodes robustly correlates with both PFS and OS. While this appears to be a reliable immune correlate, the complexity of routine labeling for PET and SPECT prohibits validation in a large clinical study. We therefore seek to develop a safe, translatable reporter that can be imaged with a widely available imaging modality. METHODS/STUDY POPULATION: The cationic liposome 1,2-doleoyl-3-trimethylammonium-propane (DOTAP) was loaded with MRI-imageable iron oxide nanoparticles (IONPs) with or without the neutral molecules PEG and cholesterol. The resulting nanoparticles were loaded with RNA to form RNA-NPs that were characterized with transmission electron microscopy (TEM) and used to transfect DCs in vitro; 4.7 T MRI was then used to image particles or cells in agarose gel phantoms. RESULTS/ANTICIPATED RESULTS: TEM images of RNA-NPs indicate the presence of IONP-loaded liposomes. In vitro transfection experiments demonstrate that iron oxide does not reduce RNA-NP-mediated transfection of DCs. Additionally, small amounts of either PEG or cholesterol within RNA-NPs increased transfection of DC2.4s and enhanced T-cell priming by bone marrow-derived dendritic cells. A series of 4.7 T MRI images of particles in cells, spleens, and LNs demonstrated quantifiable differences in particle density between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that IONP-loaded RNA-NPs can be imaged with MRI and manipulated to augment DC function. Future work will include in vivo imaging in mice and safety studies to facilitate translation into first-in-human studies. Successful completion of this project would provide a powerful clinical tool to improve and track patient responses to immune therapy.
2508
Authors: Blick Sara , Morrell Craig , Ture Sara , Field David J.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To investigate the role of platelet factor-4 (PF4) in B cell differentiation and develop strategies to better modulate B cell differentiation in vitro and in vivo. METHODS/STUDY POPULATION: We use tissue culture and flow cytometry to examine the role of PF4 in B cell differentiation. We use wild type (WT) and PF4−/− mice on a C57Bl6/J background. PF4−/− mice have reduced in vivo B cell differentiation responses. RESULTS/ANTICIPATED RESULTS: We anticipate that our studies will demonstrate that PF4 promotes B cell differentiation in the bone marrow microenvironment. DISCUSSION/SIGNIFICANCE OF IMPACT: The significance of this project may be valuable in developing efficient methods and strategies to increase or limit B cell numbers in vitro and in human disease.
2085
Authors: Namenek Brouwer Rebecca , Moen Rebbecca , Sanderson Iain , Boulware Ebony , O’Dell Johanna , Morris Browning Kellie
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Describe (1) the features of the first release of Duke’s myRESEARCHhome portal for researchers, and 2) the methods and results of adoption strategies METHODS/STUDY POPULATION: Through methods described previously (cite ACTS poster, 2016), the myRESEARCHhome portal team conducted a needs assessment to determine priorities for inclusion in the tool. Based on results of that assessment, the “minimal viable product” launched in June 2016 included the following features, organized into 9 distinct widgets: Access to all web-based research applications; ability to find and request research services; at-a-glance view of financial, protocol, and salary distribution information; access to financial and personnel reports; access to status of agreements and patents; access to CTSA-supported navigation services; visibility into required training and expiration dates; listing of announcements relevant to researchers; customized links area; ability to customize portal. The portal was developed using Ruby on Rails™, with a REACT grid framework. The development team, internal to Duke University, followed industry-standard best practices for development. After the initial release, the team employed several strategies to ensure awareness and adoption. Although written communications were an important factor for awareness, the presentations and hands-on studios proved most important. RESULTS/ANTICIPATED RESULTS: Use of the portal was directly related to in-person outreach efforts. There were small spikes after written communications, but strategies such as presentations, hands-on demonstrations, training sessions, and faculty meetings garnered the steadiest adoption rates. As of early January, 2017, almost 3000 users have interacted with the portal, with numbers rising steadily. There are an estimated 10,000+ faculty, staff, and trainees engaged in research at Duke. DISCUSSION/SIGNIFICANCE OF IMPACT: To maintain high adoption rates with the research community, engagement strategies must be ongoing. In addition to frequent in-person demonstrations, updates via written communications, and attendance at events, the portal team will employ a key adopt strategy—engaging the researchers in ongoing needs assessments. By maintaining the portal’s relevance to the needs of the research community, the tool can better improve the efficiency of research at a large academic medical center.
2140
Authors: Sarder Pinaki , Yacoub Rabi , Tomaszewski John E.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: (i) Digitally quantify pathologically relevant glomerular microcompartmental structures in murine renal tissue histopathology images. (ii) Digitally model disease trajectory in a mouse model of diabetic nephropathy (DN). METHODS/STUDY POPULATION: We have developed a computational pipeline for glomerular structural compartmentalization based on Gabor filtering and multiresolution community detection (MCD). The MCD method employs improved, efficient optimization of a Potts model Hamiltonian, adopted from theoretical physics, modeling interacting electron spins. The method is parameter-free and capable of simultaneously selecting relevant structure at all biologically relevant scales. It can segment glomerular compartments from a large image containing hundreds of glomeruli in seconds for quantification—which is not possible manually. We will analyze the performance of our computational pipeline in healthy and streptozotocin induced DN mice using renal tissue images, and model the structural distributions of automatically quantified glomerular features as a function of DN progression. The performance of this structural-disease model will be compared with existing visual quantification methods used by pathologists in the clinic. RESULTS/ANTICIPATED RESULTS: Computational modeling will reveal digital biomarkers for early proteinuria in DN, able to predict disease trajectory with greater precision and accuracy than manual inspection alone. DISCUSSION/SIGNIFICANCE OF IMPACT: Automated detection of microscopic structural changes in renal tissue will eventually lead to objective, standardized diagnosis, reflecting cost savings for DN through discovery of digital biomarkers hidden within numerical structural distributions. This computational study will pave the path for the creation of new digital tools which provide clinicians invaluable quantitative information about expected patient disease trajectory, enabling earlier clinical predictions and development of early therapeutic interventions for kidney diseases.
2204
Authors: Slattery Susan , Liu Lei , Chai Haitao , Grobman William , Duggan Jennie , Downey Doug , Murthy Karna
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Neonatal hypoxic-ischemic encephalopathy (HIE) is frequently accompanied with physiologic perturbations and organ dysfunction. Markers of these perturbations and their associations with length of stay (LOS) are uncertain. To estimate the association between changes in selected physiologic and/or laboratory values with LOS in newborns with HIE. METHODS/STUDY POPULATION: Using the Children’s Hospitals Neonatal Database (CHND), we identified neonates with HIE at our center born ≥36 weeks’ gestation from 2010 to 2016. Those with major congenital anomalies were omitted. Infants uniformly received therapeutic hypothermia for 72 hours unless death occurred sooner. Inpatient vital signs and selected laboratory markers were collected from our institution’s health informatics, electronic data warehouse (EDW) and then matched to records in CHND. With severity of HIE, gender, and confirmed seizures, each marker’s association with LOS was calculated using multivariable Cox proportional hazards regression equations. These analyses were stratified by mortality. Candidate markers were vital signs, pulse oximetry, creatinine, acidosis (pH), international normalized ratio (INR), and supplemental oxygen (FiO2). RESULTS/ANTICIPATED RESULTS: There were 66 eligible infants (38 males) and 1741 patient-days identified; Severe HIE (48%) and mortality (n=21, 32%) were common. Overall, the median length of stay (mLOS) was 20.5 days (25th–75th centile: 10–31 days), although shorter for nonsurvivors [nonsurvivors mLOS=8 days (5, 20); survivors mLOS=24 days (14, 31), p<0.001). Median birthweight and gestational age were 3.3 kg and 39.4 weeks’ gestation, respectively. In survivors (n=45, 1290 days), regression analyses demonstrated that none of the selected parameters were associated with LOS. Among nonsurvivors (n=21, 451 days), diastolic blood pressure changes [hazard ratio (HR)=0.93, 95% confidence interval (CI)=0.88, 0.97, p=0.04] was related to longer time of survival; conversely, temperature (HR=2.0, 95% CI=1.24, 3.26, p=0.005) was related to shorter survival. Creatinine, pH, INR, FiO2, or other vital signs were unrelated to time-to-death in nonsurvivors. DISCUSSION/SIGNIFICANCE OF IMPACT: In a pilot study of neonatal HIE, changes in physiologic values were related to duration of survival in nonsurvivors, while neither physiologic nor laboratory values were related to survivors’ mLOS. These results both exemplify novel uses for disease-specific, exposure-outcome relationships using EDWs and incorporates required functionalities of required software patches to extract, clean, and report from clinical information captured in electronic health records. We anticipate that text mining with techniques such as natural language processing will augment associations and/or predictions of short-term outcomes.
2246
Authors: McDonough Caitrin W. , Hogan William R. , Shenkman Betsy , Cooper-DeHoff Rhonda M.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Our objective is to create a Resistant Hypertension (RHTN) computable phenotype from electronic health record (EHR)-based data, and to determine the characteristics associated with RHTN within a large, diverse, EHR-based database. METHODS/STUDY POPULATION: The OneFlorida Clinical Research Consortium includes 10 unique health care systems providing care for approximately half of the state (48%, ~10 million). OneFlorida houses a Data Trust which contains longitudinal EHR data and claims data from these providers in a common format, the PCORnet common data model v3.0. For the current project, data from 5 health care systems were considered. All of the adult hypertension (HTN) patients with a HTN diagnosis from an outpatient encounter were extracted from the OneFlorida Data Trust. Additional data such as demographics, prescribing, and vitals information were also extracted. The RHTN computable phenotype was created by constructing a drug exposure variable that took into consideration the number of antihypertensive medications an individual was prescribed at any point in time over the course of the OneFlorida dataset. RHTN was defined as any blood pressure requiring four or more antihypertensive drugs, or uncontrolled blood pressure (≥140/90) on 3 antihypertensive drugs. RHTN cases had to meet the definition criteria twice during the data period, at least 30 days apart. All data extraction, computation phenotype coding, and statistical analyses were conducted using SQL or SAS. RESULTS/ANTICIPATED RESULTS: Our preliminary results show that there were n=342,026 adults with a HTN diagnosis from an outpatient visit in the data set. After the RHTN computable phenotype was constructed, n=11,670 RHTN cases were identified from the n=130,901 HTN individuals with all of the required variables in the data set (8.9% RHTN prevalence). In all, 55% of RHTN cases were Black or African American, compared with the total HTN population (25% Black/African American). RHTN cases also had more prescriptions for loop diuretics, centrally acting agents, α-blockers, and vasodilators compared with the total HTN population. Not surprisingly, the RHTN cases had 26% of the antihypertensive prescriptions in the data set, and the RHTN cases had fewer blood pressure readings that were in control (only 49.4% of readings <140/90). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, our preliminary data shows that it is possible to create the very complicated computable phenotype of RHTN within the OneFlorida Data Trust. We found that the RHTN prevalence in OneFlorida is 8.9% which is consistent with previous studies from NHANES. Although promising, these results require further validation of the computable phenotype and replication in other similar data sets in order to ascertain their true meaning. Once validated, the experience gained from this computable phenotype can be applied to many other phenotypes.