bluuebunny/crossref_metadata_2025 huggingface dataset:
4440 Enhanced radiation therapy using chlorin-e6 conjugated gold nanoparticles
Authors: Jenkins Samir V , Griffin Robert J.
Published: July 2020

OBJECTIVES/GOALS:

Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized structurally and mechanistically. The gold particles should enhance radiation activity by closer proximity to the photosensitizer and by increasing particle accumulation in the tumor.

METHODS/STUDY POPULATION:

Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol, then covalently conjugated to chlorin e6, a known FDA-approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species was measured after X-irradiation. Enhanced cell killing was evaluated clonogenically in addition to assessment of in vivo efficacy and tumor pathology.

RESULTS/ANTICIPATED RESULTS:

Conjugation of the particle to the photosensitizer was achieved, and the molecule was detected by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates increased cell killing during radiation treatment, whereas neither the particle alone nor the photosensitizer significantly affected clonogenic survival at the same concentrations. Breast tumors grown in immunocompetent mice showed increased necrotic tissue after a single 20 gy treatment in the presence of the conjugate.

DISCUSSION/SIGNIFICANCE OF IMPACT: Radiation therapy is widely used clinically, but dosage is limited largely to prevent injury to adjacent normal tissue. By increasing the local effect of radiation therapy, our gold conjugate has the potential to augment the effective radiation dose in the tumor, thereby reducing damage to healthy tissue and providing a more effective therapy.
4186 Single IRB and the CTSI: Liaison Model for the IRB Reliance Process
Authors: Caldwell Christine Sego , Trullinger Amy J. , Denne Scott
Published: July 2020

OBJECTIVES/GOALS: Navigating the NIH Single IRB Policy has been challenging for investigators, study teams, and Human Research Protection Programs (HRPP). In response, the Indiana Clinical and Translational Sciences Institute (CTSI) created an innovative Single IRB Project Manager role (sIRB PM), uniquely placed within the Indiana CTSI. METHODS/STUDY POPULATION: The Single IRB Project Manager role was created in 2018 by the Indiana CTSI in response to the NIH Single IRB Policy for Multi-Site Research. The role of the sIRB PM is to serve as a liaison between the Indiana University HRPP, lead site, coordinating center, and participating sites when Indiana University serves as the Single IRB. This model has proven useful to both the IRB and lead site, notably in the following ways:

At study start-up, the sIRB PM can handle complicated communications among sites and the IRB at the same time the lead site is responsible for many other administrative tasks related to start-up. By absorbing the workload of IRB approval for multiple sites, the sIRB PM provides the lead site more capacity to handle other essential tasks.

The sIRB PM translates new terminology and facilitates processes that are new for sites.

RESULTS/ANTICIPATED RESULTS: Early assessment of this program is predominantly positive. The sIRB PM currently supports 24 external sites. In an NIA-funded 13 site study, all sites were added within 9 months of initial IRB approval of the protocol. This role fills a gap that benefits:

IRB staff by allowing them to fulfill their duties of screening and review while leaving some of the reliance organization to the sIRBPM.

Lead PI by allowing them to focus on conducting the research instead of the many administrative tasks required for single IRB review.

Participating sites by having a liaison to enter their amendments and reportable events into an otherwise closed IRB software system.

All parties by having the sIRB PM manage document organization, storage, and distribution study-wide.

DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI sIRB PM role effectively shifts administrative work caused by the sIRB mandate by merging research coordinator experience with regulatory experience while building upon an existing strong relationship with the HRPP. Future focus is on process education, standardizing pricing structure, and ensuring sufficient budget support in grants.
4265 Effect of individual characteristics, healthcare access, and built environment on care coordination outcomes related to cardiovascular disease risk factors
Authors: Patil Sonal J. , Wang Yan , Johnson Angela , Mehr David , Foraker Randi , Kruse Robin
Published: July 2020

OBJECTIVES/GOALS: We examined how individual characteristics and characteristics of the socioeconomic and built environment were associated with care coordination’s effect on cardiovascular disease (CVD) risks to identify geographic areas that may benefit from supplementary clinic-community linkages. METHODS/STUDY POPULATION: We analyzed data with geocoded residential addresses and data from electronic health records for 9946 adults from a Centers for Medicare & Medicaid Services funded innovation project from 7/1/2013 to 3/30/2015. Variables included patient-level demographics, Elixhauser comorbidity index, total time with a nurse care manager, and neighborhood factors such as poverty indicators, walkability, and social capital index. Outcomes were change in CVD risk factors, hemoglobin A1C, blood pressure (BP), and low-density lipoprotein (LDL). Generalized linear models were used to assess the effect of nurse care management program on outcomes after controlling for confounding factors. RESULTS/ANTICIPATED RESULTS: We report preliminary models that include patient demographics (age, sex, race), health care utilization, nurse care manager contact time, Elixhauser comorbidity index, neighborhood education status, percent of population below 200% federal poverty level, median home value, walkability score of the residential address, and social capital index. After adjusting for all mentioned variables, in adults with HbA1C more than 7.5% at baseline, females had worsening HbA1C by 0.53% over the study period. Additionally, LDL values in females worsened over the study period by 4.8 mg/dL after adjusting for all variables. No clinically significant changes were noted for BP. DISCUSSION/SIGNIFICANCE OF IMPACT: Women’s HbA1C and LDL worsened despite nurse care management and may benefit from additional community-based interventions or interventionists. In future analyses, we anticipate that CVD risk will worsen for patients with higher fast food proximity and with greater geographic distance from their PCP.
4169 The influence of serious mental illness on medical care of patients with lower back pain in the emergency department
Authors: Lee Courtney , McNeil Ian , Guillory Sylvia , Bailey Stacyann
Published: July 2020

OBJECTIVES/GOALS: To determine whether length of stay (LOS) and opioid prescribing differ among patients who present to the emergency department (ED) with low back pain (LBP) and serious mental illness (SMI+) compared to patients without SMI (SMI−). METHODS/STUDY POPULATION: Eligible patients that visited the ED within the Mount Sinai Health Care System from 2016-2019 were identified from the Mount Sinai Data Warehouse. Data on patient demographics, number of medications prescribed, and length of stay (LOS) were compared between the groups. Patients were excluded if English was not their primary language and if the LOS exceeded 24 hours. The final dataset consisted of 940 patients (SMI+: n = 181; SMI−: n = 759). RESULTS/ANTICIPATED RESULTS: SMI+ cases included patients with a diagnosis of depression (n = 152), anxiety (n = 134), schizophrenia (n = 9), bipolar (n = 1), and/or post-traumatic stress disorder (n = 33); 26% of cases had a single diagnosis, 66% with two, and the remaining 8% had three diagnoses. There was no significant difference in pain scores between the two groups (SMI-: 7.0 ± 0.1; SMI+: 6.8 ± 0.3; p = 0.6). We found no significant differences in LOS between the groups (SMI-: 3.9 ± 0.1 hours; SMI+: 3.8 ± 0.2 hours; p = 0.8), nor was there a significant difference in number of medications prescribed (SMI-: 1.7 ± 0.9; SMI+: 1.7 ± 0.6; p = 0.4). Further analysis revealed that the odds of receiving an opiate prescription in the SMI- group was 0.92 (95% CI: 0.54,1.55). DISCUSSION/SIGNIFICANCE OF IMPACT: Comparable opioid prescribing and LOS exist in patients with and without serious mental illness who are seeking treatment for low back pain in the ED. Despite similarities in approaches to care, more information is needed to determine if other social determinants influence these practices.
4085 TL1 Team Approach to Predicting Short-term and Long-term Effects of Spinal Cord Stimulation
Authors: See Kyle , Mahealani Judy Rachel Louise , Coombes Stephen , Fang Ruogu
Published: July 2020

OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for patients with chronic back pain. Technological advances have led to renewed optimism in the field, but mechanisms of action in the brain remain poorly understood. We hypothesize that SCS outcomes will be associated with changes in neural oscillations. METHODS/STUDY POPULATION: The goal of our team project is to test patients who receive SCS at 3 times points: baseline, at day 7 during the trial period, and day 180 after a permanent system has been implanted. At each time point participants will complete 10 minutes of eyes closed, resting electroencephalography (EEG). EEG will be collected with the ActiveTwo system, a 128-electrode cap, and a 256 channel AD box from BioSemi. Traditional machine learning methods such as support vector machine and more complex models including deep learning will be used to generate interpretable features within resting EEG signals. RESULTS/ANTICIPATED RESULTS: Through machine learning, we anticipate that SCS will have a significant effect on resting alpha and beta power in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: This collaborative project will further the application of machine learning in cognitive neuroscience and allow us to better understand how therapies for chronic pain alter resting brain activity.
4398 A Computational Psychiatry Approach to Addiction Using Neuroeconomics Translated Across Species
Authors: Sweis Brian , Camchong Jazmin , Abram Samantha , Haynos Ann , Specker Sheila , Lim Kelvin , MacDonald Angus , Thomas Mark , Redish David
Published: July 2020

OBJECTIVES/GOALS: Decision-making impairments in addiction can arise from dysfunction in distinct neural circuits. Such processes can be dissociated by measuring complex, computationally distinct behaviors within an economic framework. We aim to characterize computational changes conserved across models of addiction. METHODS/STUDY POPULATION: We used neuroeconomic tasks capable of dissociating neurally separable decision processes using behavioral analyses equally applicable to humans and rodents. We tested 12 human cocaine-users and 9 healthy controls on the Web-Surf task designed to match the rodent Restaurant Row task on which 27 mice were trained and then exposed to saline (n = 10), cocaine (n = 7), or morphine (n = 10). All subjects foraged for rewards (humans: entertaining videos; mice: food) of varying costs (1-30s delays) and subjective value (humans: genres; mice: flavors) by making serial accept or reject decisions while on a limited time budget, balancing the utility of wanting desirable rewards despite conflicting costs. RESULTS/ANTICIPATED RESULTS: When encountering unique offers for rewards with a delay above one’s willingness to wait, cocaine-treated mice like cocaine-exposed humans were less likely to appropriately reject economically disadvantageous offers. Furthermore, these mice and humans did so despite spending more time deliberating between future options. In contrast, morphine-treated mice displayed distinct impairments when given the opportunity to correct past mistakes, a process we previously demonstrated was uniquely sensitive to alterations in strength of synaptic connectivity of the infralimbic-accumbens shell circuit in mice. We anticipate human opioid-users will mirror these latter, computationally distinct findings. DISCUSSION/SIGNIFICANCE OF IMPACT: These data elucidate facets of addiction shared across species yet fundamentally distinct between disease subtypes. Our translational approach can help shed light on conserved pathophysiological mechanisms in order to identify novel diagnostic parameters and computational targets for intervention.
4378 Dynamic Influences on Population Health Management by Asthma Community Health Worker (CHW) Programs: An Agent Based Modeling Approach
Authors: Kramer Bradley , Jones-Smith Jessica , Weiner Bryan
Published: July 2020

OBJECTIVES/GOALS: Twenty years of evidence show CHW home-visits for asthma improve population health and lower overall health care system costs by reducing costly Emergency Department (ED) visits. We built a model to communicate these results to decision makers and demonstrate how program modifications can improve CHW program sustainability and long-term cost savings. METHODS/STUDY POPULATION: This CHW program simulation model (CHWsim) examines program level outcomes of sustainability and costs. CHWsim is populated with individuals in an asthma registry with frequent ED visits. The simulation shows the uptake of the CHW program, and the less frequent use of ED visits based on empirical data from a recent randomized controlled trial (RCT). CHWsim is interactive, allowing for parameter adjustments to programming and robust quantitative evaluation of those changes. We study sustainability using parameters based on number of CHWs, case load, frequency and duration of program. For cost outcomes, we use empirical data from a published return on investment study to demonstrate the cost of CHW programming vs. health care systems savings from reduced ED visits. RESULTS/ANTICIPATED RESULTS: We demonstrate a basic model that successfully simulates a recent RCT (n = 551), replicating the primary outcome of reduced ED visits within the Confidence Intervals. The model is validated by reproducing results of other RCTs. Results will also be presented from an in-process expanded model that simulates the intervention in a broader population (n = 4000). We test two programmatic changes and demonstrate how these modifications might improve health outcomes (reduced ED visits) that translate into cost savings to the system. 1) In the original trial, we served only one household member; in the model, we treat the full household, serving several individuals at the same time. 2) We also consider the assumption that a short annual visit might sustain the known 12-month health effect across many years. DISCUSSION/SIGNIFICANCE OF IMPACT: CHWsim uses individual level local data and patient characteristics to demonstrate the impact of program efficiencies to improve CHW program sustainability and reduce health care system costs without expensive new RCTs. CHWsim has the potential to improve CHW program delivery and influence funders to provide support.
4042 Enhancing Scientific Rigor, Reproducibility, and Reporting in Translational Science Training and Practice
Authors: Vaughan Roger , Covey Matthew , Romanick Michelle , Carvalloza Anthony , Coller Barry S.
Published: July 2020

OBJECTIVES/GOALS: Irreproducible and incompletely reported research lead to misallocated resources, wasted effort in pursing inappropriate avenues of investigation, and loss of public trust. To address this challenge, we employed a Team Science approach to create a multi-modal program to support Rigor, Reproducibility, and Reporting in Translational Science. METHODS/STUDY POPULATION: We conducted literature searches to reveal sources of irreproducibility and recommended corrective actions, invited leaders in the field to give lectures on opportunities to support reproducible science, and worked with the Rockefeller team science leadership group to instill an overarching rigor approach, infused into all training efforts. This multifaceted program was labeled R3 (R-cubed) for Enhancing Scientific Rigor, Reproducibility, and Reporting. RESULTS/ANTICIPATED RESULTS: Didactic Courses:

Introduction to Biostatistics and Critical Thinking – focus on pitfalls in inferential statistics, consequences of poor research, and errors in published research.

Scientific Writing – teaches methods and procedures in writing to ensure reproducibility. Lecture Series

Established nine lectures on topics related to R3, including Data Management, Statistical Methods, Genomic Analyses, Data Repositories, Data Sharing, Pharmacy Formulation, and e-lab notebooks. Website

Creating a comprehensive website as repository for research, methods, programs, updates, and improvements related to R3. KL2 Clinical Scholars Seminars and Navigation

Scholars participate in seminars and tutorials to discuss opportunities to improve R3 across the research life-course.

DISCUSSION/SIGNIFICANCE OF IMPACT: Striving for research reproducibility takes focused energy, discipline, and vigilance, but the effort is worthwhile as rigorous and reproducible science is the prerequisite for successful translation of great discoveries into improved health. CONFLICT OF INTEREST DESCRIPTION: none
4545 Identifying Symptom Pattern Trajectories among Heart Failure Patients in a Palliative Care Trial: A Work In Progress
Authors: Stockdill Macy Lynn , Lee Christopher , Dionne-Odom J. Nicholas , Aouizerat Bradley , Durant Raegan , Azuero Andres , Bakitas Marie
Published: July 2020

OBJECTIVES/GOALS: This work-in-progress aims to: 1) identify and differentiate symptom pattern trajectories in a sample of older adult heart failure (HF) patients over 24 weeks, and 2) examine associations between sociodemographic/clinical/physiological characteristics, dyadic health, and symptom trajectories. METHODS/STUDY POPULATION: ENABLE CHF-PC, a palliative care RCT (NCT02505425), was conducted at a Southeastern US medical center. Between 2016-2018, 415 older adult HF patients and 159 family caregivers were randomized to receive a psychoeducational intervention or usual care. Baseline sociodemographic information (age, gender, rurality, etc.) were collected. Outcome variables of interest include symptoms (Kansas City Cardiomyopathy Questionnaire (KCCQ), Functional Assessment of Chronic Illness Therapy-Palliative 14, Hospital Anxiety and Depression Scale (HADS)) and dyadic health (PROMIS-SF Global Health). We have calculated baseline descriptive statistics. Future work includes latent growth mixture modeling to identify distinct symptom trajectories and univariate associations with patient level factors. RESULTS/ANTICIPATED RESULTS: Of 415 patient participants, mean age was 64, 53% were male; 55% were African American; 26% were rural dwellers; 46% had +15.8) and low anxiety (6.7+3.6) and depressive symptoms (5.7+4.3) on the HADS. Of 159 family caregivers participants, the mean age was 57.9, 85.4% were female, 51.9% were African-American, and 65.2% were the patient’s spouse/partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Limited data describes HF symptom pattern trajectories.How co-occurring symptoms affect quality of life or are affected by personal or situational factors are not well-understood. This study will help to identify factors and symptom phenotypes that may serve as targets for future interventions.
4340 Piloting Implementation and Dissemination of Best Practice Guidelines Using BPM+Health
Authors: McClay James , Goyal Pawan
Published: July 2020

OBJECTIVES/GOALS: Clinical translational studies inform clinical practice patterns through dissemination of clinical practice guidelines (CPG). In EM practices change to rapidly for timely local EHR implementation. We test the OMG BPM+Health specification for rapid deployment of best practices relevant to EM. METHODS/STUDY POPULATION: The OMG Business Process Management for Healthcare (BPM+Health) specification combines BPMN™ with Case Management Model and Notation (CMMN™) and Decision Model and Notations (DMN™) to “disseminate and leverage evidence-based best-practices at the point of care.” The American College of Emergency Physicians (ACEP) Board-certified Emergency Physicians modeled practice guidelines in the BPM+ modeling language during on-line meetings. Two common emergency conditions were selected for initial pilot testing: 1) evaluation and treatment of first trimester bleeding in pregnant patients, and 2) the evaluation and treatment of non-traumatic low back pain. RESULTS/ANTICIPATED RESULTS: The protocols were successfully modeled during four on-line meetings in less than 2 months. Process steps from initial evaluation to disposition were implemented using BPMN™. When clinicians need to evaluate the patient to collect data for decision making the inputs and outputs were modeled in CMMN™. Decision logic is represented as DMN™. The software tool linked the components for easy browsing and authoring the logic. The Physicians easily followed the displayed logic. The practice recommendations from each policy were successfully modeled, using the standard BPM+ notation to support rapid implementation in EHRs. Detailed implementation specifications will be shared. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot project demonstrated the feasibility of the OMG approach to solving Clinical Practice Guideline Implementation and Dissemination Barriers. Ongoing work by involved specialty societies will be necessary to demonstrate the scalability and sustainability of this approach.
4152 Special Delivery: Home Delivery of Healthy Food to Young Women during Pregnancy
Authors: Locher Ione , Waselewski Marika , Chang Tammy
Published: July 2020

OBJECTIVES/GOALS: Most pregnant youth (ages 14-24) gain more weight during pregnancy than recommended by clinical guidelines. We aim to describe the feasibility and acceptability of home grocery delivery of fruits, vegetables, and healthy snacks to promote healthy weight gain in this vulnerable population. METHODS/STUDY POPULATION: Participants were low-income pregnant youth in Michigan. Each participant was sent biweekly grocery deliveries consisting of $35 worth of fresh fruits, vegetables, and healthy snacks via the app-based delivery service, Shipt. Between deliveries, participants were prompted to respond to weekly text message-based surveys of a 24-hour food recall. This validated nutritional assessment quantifies consumption of fruit and vegetable servings. In addition, participants were asked to send daily photos and descriptions of foods they were eating. This study was approved by the University of Michigan Institutional Review Board. RESULTS/ANTICIPATED RESULTS: To date, 27 participants have been enrolled. Thirteen participants have completed their participation, 4.3 months on average, and were sent an average of 10 grocery deliveries each. In total, over 200 deliveries have been sent with 86% confirmed by the study participant (179/207). Additional outcomes to be assessed include: 1) text message response rates by participants and 2) content from photos and text descriptions of food eaten by participants. The 24-hour recall and text and photo messaging provided in-context data about grocery utilization. DISCUSSION/SIGNIFICANCE OF IMPACT: Grocery delivery is both feasible and acceptable to our youth participants. Use of grocery delivery constitutes a novel intervention to promote healthy weight gain in pregnancy for vulnerable populations through improving access to healthy food options.
4189 The Changing Health and Social Circumstances of Women Leaving Jails: A Three-year Longitudinal Study
Authors: Assimonye Stephanie , Ramaswamy Megha , Glenn Jason , Smith Sharla
Published: July 2020

OBJECTIVES/GOALS: To characterize the various social and health trajectories of women released from jail, and how these trajectories influence women’s risky sexual and drug behaviors. To identify areas in which prevention programs and community interventions can be implemented to improve social and health outcomes. METHODS/STUDY POPULATION: The present study analyzes data collected as part of the sexual health empowerment (SHE Project) health literacy intervention. Participants were recruited from three county jails in the greater Kansas City area. At baseline, participants completed a survey that assessed participants’ sociodemographic characteristics and social histories prior to incarceration. Women were recruited between 2014-2016 and followed up annually after program completion to complete follow-up surveys to assess long-term health and social circumstances. The present study is a secondary analysis of baseline and follow-up data. Final analyses will include survey data from 126 women. RESULTS/ANTICIPATED RESULTS: In this study, we use Hobfoll’s Conservation of Resources (COR) Theory to conceptualize the impacts of stress on the social and health behaviors of justice-involved women in the years following release from jail. We hypothesize that “loss spirals”, a term coined by Stevan Hobfoll, creates psychological stress that drive justice-involved women to assume behaviors that will generate more resources and help to cope with the stress. We expect to find that women struggle to maintain ties to stable housing, employment, and support, which we believe to be central to “loss spirals.” Additionally, we expect to find that these “loss spirals” are associated with sexual and drug health risks. DISCUSSION/SIGNIFICANCE OF IMPACT: This study aims to define a succinct longitudinal timeline assessing biopsychosocial outcomes of women released from jail in order to improve prevention and intervention techniques for the improvement in social and health circumstances of women leaving jail and their reduction in recidivism.
4373 Defining the role of non-canonical PIK3CA mutations in head and neck squamous cell carcinoma
Authors: Lee Michelle Ji-Eun , Jin Nan , Cho Janice , Kwok-shing Patrick , Mills Gordon B. , Johnson Daniel E. , Grandis Jennifer R.
Published: July 2020

OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.
4578 Early life stress promotes chronicity of experimental colitis
Authors: Muir Rachel Quinn , Klocke Barbara J. , McPherson Kasi C. , Foote Jeremy B. , Pollock Jennifer S. , Maynard Craig L.
Published: July 2020

OBJECTIVES/GOALS: The overall goal of this study was to determine the effect of early life stress (ELS) on the intestinal CD4+ T cell immune compartment, at homeostasis and after induction of experimental Inflammatory Bowel Disease (IBD). METHODS/STUDY POPULATION: We used a mouse model of ELS, maternal separation with early weaning (MSEW). We used IL-10 reporter mice to enable analysis of IL-10-producing cells. Mice were examined on postnatal day 28 to determine the impact of ELS on gut regulatory T cells. Plasma levels of corticosterone (rodent stress response hormone) was determined by ELISA. Colitis was induced in MSEW and normal rear (NR) mice via intraperitoneal injection of α-IL-10R every 5 days until day 15. Mice were euthanized on days 20 and 30. Colonic tissue sections were stained for histological analysis. Remaining tissue was further processed for flow cytometric analysis of CD4+ T cells and innate lymphoid cells. RESULTS/ANTICIPATED RESULTS: Plasma corticosterone was elevated in MSEW mice compared to their NR counterparts at 4 weeks of age. We observed that the MSEW stress protocol does not affect the baseline colonic CD4+ T cell or innate lymphoid cell populations. There was a reduction in the intestinal CD4+ T cells and regulatory T cells on day 20 in α-IL-10R MSEW mice compared to NR counterparts. This difference disappeared by day 30. Histological scoring showed no difference in disease severity between α-IL-10R treated MSEW and NR mice on day 20. However, on day 30, when α-IL-10R NR mice are recovering from colitis, MSEW mice showed persistent histological inflammation, mainly attributable to sustained epithelial damage. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that ELS prolongs intestinal inflammation and impairs epithelial repair. Future studies will focus on elucidating the mechanisms responsible for ELS-dependent impairment of mucosal repair in experimental colitis.
4242 Evaluating the effect of a compliant stent-graft prototype on effective stiffness in a cadaveric aorta
Authors: Kizilski Shannen B , Coletti Filippo , Faizer Rumi , Barocas Victor H.
Published: July 2020

OBJECTIVES/GOALS: High aortic stiffness is associated with increased cardiovascular morbidity and mortality. The purpose of this work is to demonstrate the potential of our compliant stent-graft design to therapeutically increase aortic compliance over a standard aortic stent-graft. METHODS/STUDY POPULATION: The aorta from a human cadaver will be excised and placed into a pulse duplicator circuit. The stiffness of the system will be estimated using the pulse wave velocity (PWV), which will be calculated using the time delay between pressure measurements at proximal and distal locations in the system. Baseline measurements with the unstented aorta will be compared to two cases: (1) with a standard stent-graft placed, and (2) with our compliant stent-graft prototype in the descending thoracic aorta. PWV is calculated as the distance between the pressure sensors divided by the time delay. Faster PWV is associated with a stiffer vessel, or lower aortic compliance. RESULTS/ANTICIPATED RESULTS: Prior work in vitro showed that the compliant stent-graft reduced peak and pulse pressures compared a standard, rigid stent-graft. We also expect the compliant device to exhibit lower PWV compared to a rigid stent-graft. Depending on the aortic tissue stiffness, the compliant stent-graft could raise or lower PWV compared to no stent. Mean pressure in the compliant case is likely to be slightly higher than the other two cases because the compliant stent-graft’s narrower lumen increases flow resistance. Although mean pressure will be higher, peak pressure should be lower than in the standard stent-graft because the added compliance decreases overall pressure swing between systole and diastole. DISCUSSION/SIGNIFICANCE OF IMPACT: Lower PWV in the compliant stent-graft over the standard stent-graft will indicate its potential to therapeutically lower aortic stiffness in patients needing aortic stenting. Positive outcomes from this study will be a step toward the eventual translation of a compliant stent-graft to clinical use.
4287 Extracellular vesicles as biomarkers for early detection of pancreatic cancer
Authors: Hinzman Charles P , Bansal Shivani , Li Yaoxiang , Banerjee Partha , Cheema Amrita
Published: July 2020

OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients.
4418 Optimization and Validation of a Silk Scaffold-Based Neural Tissue Construct
Authors: Gu Ben Jiahe , Jgamadze Dennis , Man Guoming (Tony) , Chen Han-Chiao Isaac
Published: July 2020

OBJECTIVES/GOALS: Our goal is to develop a silk fibroin scaffold-based neural tissue construct and characterize it in a rat model of cortical injury. We aim to optimize the construct for transplantation, test pharmacologic interventions that may enhance its survival, and evaluate its integration with the host brain. METHODS/STUDY POPULATION: To optimize cell density and health, silk fibroin scaffolds varying in porosity and stiffness were seeded with E18 GFP+ rat cortical neurons and imaged at DIV 5. Different seeding methods and loads were similarly tested. Constructs, loaded with an inhibitor of apoptosis (ROCK inhibitor Y-27632) or necroptosis (necrostatin-1) in a fibrin hydrogel, were transplanted into aspiration lesions created in the primary motor cortex of Sprague-Dawley rats, and graft survival was compared to negative control at 2 weeks. Lastly, constructs were transplanted and evaluated via immunohistochemistry at 1, 2, and 4-month time points for survival, differentiation, inflammation, and anatomic integration. RESULTS/ANTICIPATED RESULTS: Scaffolds with smaller pore sizes retained more cells after seeding. Softer scaffolds, which enhance hemostasis at transplantation, did not compromise cell health on live/dead assay. We anticipate that seeding concentrated cell suspensions onto multiple surfaces of the construct will produce the most evenly seeded and cell-dense constructs. Based on a prior pilot study, we anticipate that necrostatin-1 will significantly improve intermediate-term construct survival. We have observed up to 15% cell survival at 1 month with retained neuronal identity and abundant axonal projections into the brain despite evidence of persistent inflammation; we anticipate similar outcomes at later time points. DISCUSSION/SIGNIFICANCE OF IMPACT: Our construct, due to its exceptional longevity in vitro, manipulability, and modularity, is an attractive platform for neural tissue engineering. In the present work, we optimize and validate this technology for transplantation with the goal of addressing the morbidity burden of cortical injury.
4321 Personalization of T cell production for cellular immunotherapy
Authors: Yuan Dennis Jinglun , Shao Shuai , Lee Joanne H , Fernandes Stacey M , Brown Jennifer R , Kam Lance C
Published: July 2020

OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
4528 Sirtuin 3 activation as a potential renoprotective therapy in a mouse model of Alport syndrome
Authors: Jones Bryce , Myakala Komuraiah , Wang Xiaoxin , Libby Andrew , Takahashi Shogo , Bhasin Kanchan , Ranjit Suman , Rosenberg Avi , Levi Moshe
Published: July 2020

OBJECTIVES/GOALS: Sirtuin 3 (Sirt3), a mitochondrial NAD+-dependent deacetylase, is decreased in diverse models of kidney disease, and Sirt3 activation prevents disease progression in many of those models. We are investigating if pharmacological activation of Sirt3 ameliorates kidney disease in a mouse model of Alport syndrome. METHODS/STUDY POPULATION: Alport syndrome is a hereditary orphan disease arising from a defect in the collagen IV α3α4α5 heterotrimer, a component of the glomerular basement membrane. Male and female Col4a3tm1Dec knockout mice and wild type controls on the 129X1/SvJ background were harvested at 9–10 weeks of age. Serum and urine were collected prior to euthanasia; renal pathology was assessed by histology; and renal cortical mRNA and protein levels were assessed by qRT-PCR and western blot, respectively. Studies are ongoing using dietary administration of a Sirt3 activator, nicotinamide riboside (500 mg/kg/day), in Col4a3 transgenic mice on both the 129X1/SvJ and C57BL/6J backgrounds. RESULTS/ANTICIPATED RESULTS: Col4a3−/− mice have elevated BUN (P < 0.0001, both sexes), serum creatinine (P < 0.001, male; P < 0.0001, female), and urinary albumin-to-creatinine ratio (P < 0.0001, both sexes) compared to Col4a3+/+ controls. On histology, Col4a3−/− mice have extensive renal fibrosis compared to Col4a3+/+ controls. Sirt3 expression is decreased in the renal cortices of Col4a3−/− mice at the mRNA (P < 0.0001, male; trend, P = 0.07, female) and protein levels (P < 0.05, male; P < 0.001, female) compared to Col4a3+/+ controls. All experiments had 5–9 mice per group. Results of the prevention study with nicotinamide riboside, a Sirt3 activator, are unknown at the time of abstract submission. DISCUSSION/SIGNIFICANCE OF IMPACT: Col4a3−/− mice have severe renal impairment and decreased renal cortical expression of Sirt3 at the mRNA and protein levels compared to Col4a3+/+ controls. However, it is unknown at this time if pharmacologically activating Sirt3 prevents this renal decline.
PUBLIC SLAVES IN ROME: ‘PRIVILEGED’ OR NOT?
Authors: Luciani Franco
Published: July 2020

In the Roman world, slavery played a crucial role. Besides private slaves, owned by individual masters, and—from the beginning of the Principate—imperial slaves, who were the property of the emperors, there were also the so-called public slaves: non-free individuals who were owned by a community, such as the Roman people as a whole in Rome (serui publici populi Romani), or the citizen body of a colony or a municipium in Italy or in the provinces (serui ciuitatum). Public slaves in Rome were employed for numerous public services and acted under the authority of the Senate as assistants to public magistrates, officers or priests. Similarly, in Italian and in provincial cities, they juridically depended on the decisions of local councils and performed various activities within the civic administration, beholden to the magistrates.
THE COMBINATORICS OF TENSOR PRODUCTS OF HIGHER AUSLANDER ALGEBRAS OF TYPEA
Authors: MCMAHON JORDAN , WILLIAMS NICHOLAS J.
Published: July 2020

We consider maximal non-l-intertwining collections, which are a higher-dimensional version of the maximal non-crossing collections which give clusters of Plücker coordinates in the Grassmannian coordinate ring, as described by Scott. We extend a method of Scott for producing such collections, which are related to tensor products of higher Auslander algebras of typeA. We show that a higher preprojective algebra of the tensor product of twod-representation-finite algebras has ad-precluster-tilting subcategory. Finally, we relate mutations of these collections to a form of tilting for these algebras.
COLONIAL PIG-STICKING, IMPERIAL AGENDAS, AND NATURAL HISTORY IN THE INDIAN SUBCONTINENT
Authors: OOMMEN MEERA ANNA
Published: July 2020

As the sport that purportedly enhanced martial conditioning of the ‘dominant’ race, pig-sticking assumed critical importance for the survival of the British in India. When numerous local insecurities and large-scale anxieties threatened the empire, hunting pursuits involving the wily Indian pig, it was said, made soldiers out of boys; the attendant spectacles of masculinity aimed to exert symbolic dominance over the restive Indian masses. The sport also served as an avenue for upward mobility for the subaltern soldier attempting to upstage aristocratic hunting performances in England and India. While masculinity and symbolic governance have been analysed repeatedly in critiques of hunting, sportsmen's contributions to natural history have seen limited analyses. Here, I show that the local intricacies of pig-sticking motivated a superlative understanding of the Indian wild boar, a tricky, unpredictable customer with a vile temper, and a ready propensity to attack its pursuers. Pig-sticking entailed a multi-faceted immersion with both land and people, incorporating hybrid knowledge-making, shaped within the contact zone of indigenous and colonial encounter. Further, while agreeing with post-colonial critiques on sport and imperialism, I propose looking beyond colonial exceptionalism to situate big-game hunting within the larger scholarship on costly signalling and hunting for prestige among human societies.
Fossil Usnea and similar fruticose lichens from Palaeogene amber
Authors: Kaasalainen Ulla , Rikkinen Jouko , Schmidt Alexander R.
Published: July 2020

Fruticose lichens of the genus Usnea Dill. ex Adans. (Parmeliaceae), generally known as beard lichens, are among the most iconic epiphytic lichens in modern forest ecosystems. Many of the c. 350 currently recognized species are widely distributed and have been used as bioindicators in air pollution studies. Here we demonstrate that usneoid lichens were present in the Palaeogene amber forests of Europe. Based on general morphology and annular cortical fragmentation, one fossil from Baltic amber can be assigned to the extant genus Usnea. The unique type of cortical cracking indirectly demonstrates the presence of a central cord that keeps the branch intact even when its cortex is split into vertebrae-like segments. This evolutionary innovation has remained unchanged since the Palaeogene, contributing to the considerable ecological flexibility that allows Usnea species to flourish in a wide variety of ecosystems and climate regimes. The fossil sets the minimum age for Usnea to 34 million years (late Eocene). While the other similar fossils from Baltic and Bitterfeld ambers cannot be definitely assigned to the same genus, they underline the diversity of pendant lichens in Palaeogene amber forests.
Race and language teaching
Authors: Von Esch Kerry Soo , Motha Suhanthie , Kubota Ryuko
Published: July 2020

In this review article on race and language teaching, we highlight an urgent need for the international educational community to continue to develop a complex understanding of how language teaching and learners’ lives are shaped by our global history of racist practices of colonial expansion, including settler colonialism and transatlantic slavery. We outline the genesis of research on race and language teaching and review literature that reflects a recent increase in scope and range of studies that problematize the workings of race and racism in language teaching and point to hopeful solutions for addressing effects of racial inequities. We conceptualize two key terms, ‘race’ and ‘language,’ then overview theories that appeared most significant in the research literature. We explore five interconnected themes that featured prominently throughout the existing literature on race and language teaching: standard language ideology and racial hegemony, the idealized and racialized native speaker, racial hierarchies of languages and language speakers, racialization and teacher identity, and race-centered approaches to pedagogies and educational practices. We offer a critical analysis of the current status of scholarship on race and language teaching, including gaps and necessary reframing, and conclude with implications for future directions and questions arising from the work.