bluuebunny/crossref_metadata_2025 huggingface dataset:
68127 High Sensitivity Troponins Predicts Mortality in Patients Who Present to the ED with Severe Sepsis or Septic Shock
Authors: Williams Kendrick , Tucker Ryan , Cranford James , Fung Christopher
Published: March 2021

ABSTRACT IMPACT: Our may suggest that delta hsTrop could be of prognostic value in patients with sepsis. OBJECTIVES/GOALS: - METHODS/STUDY POPULATION: We analyzed data of those presenting to the ED over an 18-month period with sepsis and at least one episode of hypotension after 1 liter of IV fluids. We performed a retrospective analysis using a cohort derived from modified inclusion and exclusion criteria from the CLOVERS study. The outcomes of patients found to have a delta (at least 6 pg/dL) in high sensitivity troponin T were compared to patients who did not have a delta or have a troponin level measured. We examined demographic and treatment characteristics of this cohort and the incidence of adverse outcomes were determined. We used multivariable logistic regression analysis to test the association of hsTrop and mortality. RESULTS/ANTICIPATED RESULTS: 778 patients met criteria to be included in the cohort. 279 patients had a change in high sensitivity troponins, an incidence of 35.9%. Patients with a delta were more likely to be older, male, and have a higher Charlson index than patients without a delta or those that had no troponin measured. They were also more likely to have a history of chronic lung disease, heart failure and hypertension. Change in high sensitivity troponins were associated with higher in-hospital mortality. When adjusted for age, gender, and Charlson Index, the association between a positive delta troponin and mortality remained statistically significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: In patients with severe sepsis and septic shock, the presence of a positive or negative delta hsTrop at 2 hours is associated with increased mortality. Measurement of high sensitivity troponin early in the patient’s hospital course may have prognostic utility.
76865 Clinical Outcomes of Chronic Myelomonocytic Leukemia in the VA Healthcare System
Authors: Achar Rohan , Anwar Talha , Parkin Brian
Published: March 2021

ABSTRACT IMPACT: Through a comprehensive analysis of patterns of care and outcomes in Veterans with chronic myelomonocytic leukemia, we will identify Veteran-specific determinants of survival that will allow for more personalized decision-making in this underserved population. OBJECTIVES/GOALS: Little is known about outcomes of Veterans with chronic myelomonocytic leukemia (CMML), a malignancy with high morbidity and mortality. In this study, we will describe patterns of care, identify factors that impact survival, and compare outcomes in this cohort to those of the civilian population. METHODS/STUDY POPULATION: We will conduct a comprehensive retrospective review of approximately 1,000 Veterans with CMML. We will construct a database of demographics, clinical characteristics, disease characteristics, treatment regimens, and outcomes in this cohort. Adult Veterans with a diagnosis of CMML determined by ICD-O-3 coding who were treated through the VA after 1990 and have sufficient electronic health data will be included in this study. Veterans receiving the majority of their care for CMML at non-VA hospitals or clinics will be excluded. Data on veterans will be obtained and validated from VA clinical databases and chart review. Data on the civilian population will be obtained from SEER registries. RESULTS/ANTICIPATED RESULTS: We will first describe the baseline patient characteristics and distribution of disease in this cohort and illustrate the landscape of their CMML care. We will subsequently describe the impact of baseline patient characteristics on pathological features of disease, patterns of care, response to therapy, and survival. We anticipate we will identify several Veteran-specific factors that influence treatment and are prognostic or predictive of survival. After drawing conclusions about the Veteran cohort alone, we will compare baseline characteristics and survival outcomes between the Veteran and civilian populations. We predict we will identify significant differences between these two cohorts. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will help inform Veteran care by identifying clinical features and patient characteristics that are prognostic or predictive of survival. This will open the door for more accurate risk stratification and personalized treatment that could improve outcomes in this underserved population.
39607 Mapping the Draining Lymph Nodes in Central Nervous System Malignancies
Authors: Coxon Andrew T. , Siegel Barry A. , Johanns Tanner M. , Dunn Gavin P.
Published: March 2021

ABSTRACT IMPACT: We seek to determine which lymph nodes drain the human brain. OBJECTIVES/GOALS: Lymphatic vessels train lymphatic fluid from the central nervous system (CNS), but the specific lymph nodes that these vessels drain to remains unknown in humans. We intend on using technetium tilmanocept (TcTM)to map the draining lymph nodes of the CNSin humans. METHODS/STUDY POPULATION: Patients having a tumor resected are eligible for the trial. All patients will have TcTM injected intracranially after tumor resection. Six patients will be enrolled in Cohort 1 to define the time course of drainage to the lymph nodes. Patients in Cohort 1 will be imaged with planar LS within 7 hours of injection and the following day. Either 12 or 24 patients will be enrolled into Cohort 2 to localize the draining lymph nodes with SPECT-CT. The optimal imaging timepoint from Cohort 1 will be used for Cohort 2. Patients in Cohort 2 will be stratified depending on if their tumor is in the frontal, parietal, occipital, or temporal lobe. RESULTS/ANTICIPATED RESULTS: We anticipate that we will detect TcTMin the deep cervical lymph nodes after injection into the brain. It is unclear exactly which lymph nodes the tracer will go to. We hypothesize that the results among patients will be similar, but interindividual variation is a possibility. Furthermore, patients with disease in different lobes of the brain may have different lymph drainage patterns. DISCUSSION/SIGNIFICANCE OF FINDINGS: We seek to answer a fundamental question of human anatomy: what lymph nodes drain the human brain? Additionally, knowing which nodes drain the human brain could shape future research of immunotherapy in patients with brain cancer or autoimmune disease such as multiple sclerosis.
77286 Intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis
Authors: Gabriel Emmanuel , Kim Minhyung , Fisher Daniel , Mangum Catherine , Attwood Kristopher , Ji Wenyan , Mukhopadhyay Debabrata , Bagaria Sanjay , Robertson Matthew , Dinh Tri , Knutson Keith , Skitzki Joseph , Wallace Michael
Published: March 2021

ABSTRACT IMPACT: Investigation of tumor-associated blood vessels may serve as an imaging biomarker of response to systemic therapy and cancer outcomes. OBJECTIVES/GOALS: Aberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC) and generate clinical utility. METHODS/STUDY POPULATION: During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). RESULTS/ANTICIPATED RESULTS: Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).
42855 A Phenomics Approach to the Categorization and Refinement of Heart Failure
Authors: Reza Nosheen , Bone William , Singhal Pankhuri , Verma Anurag , Murthy Ashwin C. , Denduluri Srinivas , Adusumalli Srinath , Ritchie Macrylyn D. , Cappola Thomas P.
Published: March 2021

ABSTRACT IMPACT: Measuring and analyzing qualitative and quantitative traits using phenomics approaches will yield previously unrecognized heart failure subphenotypes and has the potential to improve our knowledge of heart failure pathophysiology, identify novel biomarkers of disease, and guide the development of targeted therapeutics for heart failure. OBJECTIVES/GOALS: Current classification schemes fail to capture the broader pathophysiologic heterogeneity in heart failure. Phenomics offers a newer unbiased approach to identify subtypes of complex disease syndromes, like heart failure. The goal of this research is to use data-driven associations to redefine the classification of the heart failure syndrome. METHODS/STUDY POPULATION: We will identify < 10 subphenotypes of patients with heart failure using unsupervised machine learning approaches for dense multidimensional quantitative (i.e. demographics, comorbid conditions, physiologic measurements, clinical laboratory, imaging, and medication variables; disease diagnosis, procedure, and billing codes) and qualitative data extracted from an integrated health system electronic health record. The heart failure subphenotypes we identify from the integrated health system electronic health record will be replicated in other heart failure population datasets using unsupervised learning approaches. We will explore the potential to establish associations between identified subphenotypes and clinical outcomes (e.g. all-cause mortality, cardiovascular mortality). RESULTS/ANTICIPATED RESULTS: We expect to identify < 10 mutually exclusive phenogroups of patients with heart failure that have differential risk profiles and clinical trajectories. DISCUSSION/SIGNIFICANCE OF FINDINGS: We will attempt to derive and validate a data-driven unbiased approach to the categorization of novel phenogroups in heart failure. This has the potential to improve our knowledge of heart failure pathophysiology, identify novel biomarkers of disease, and guide the development of targeted therapeutics for heart failure.
37319 A Technology Evaluation Framework for Rural Health Research
Authors: Fehrmann Joshua
Published: March 2021

ABSTRACT IMPACT: As technologies emerge at an increasing pace, the product developed through this work will guide rural health experts through a repeatable method of technology evaluation and selection at a faster and more reliable pace than otherwise possible. OBJECTIVES/GOALS: New technologies are emerging at an increasing pace, which leads to the question: ‘how is one to select a specific technology for their research?’ In response, this project endeavored to develop a technology evaluation and selection framework for rural health researchers. METHODS/STUDY POPULATION: The approach selected for this project included three phases. Phase one was to gain an understanding of rural health challenges, health-related emerging technologies, and rural health resources. Phase two involved using the information from phase one to select and adapt a set of technology foresight and forecasting analysis tools to be compiled within a framework. The third phase of the project was to prototype the framework, obtain researcher feedback, and iteratively implement improvements. Recommendations for the future of the framework were also developed during the third phase. RESULTS/ANTICIPATED RESULTS: The resulting product is the ‘Rural Health: Evaluation and Selection of Technology (RHEST) Framework.’ The RHEST Framework is a guide made available to use to aid in technology selection during the development of a new rural health project. The framework guides researchers through various stages, including ideation, analysis, and decision. Technology analysis tools are introduced in each stage, with links to additional information. The guide also contains a resource catalog for quick information look-up to find data sources, funding opportunities, and expert connections. Quantitative and qualitative data captured indicate that the product would add value for rural health researchers. DISCUSSION/SIGNIFICANCE OF FINDINGS: The initial version of the RHEST framework is limited in value because it is a static document and the primary audience are researchers. The value potential could improve considerably, however, if the framework were expanded to be a dynamic resource available to rural health care providers.
58896 Feasibility of a Parent Navigator Program for Parents of Justice-Involved Youth
Authors: Dir Allyson L. , Wiehe Sarah , Aalsma Matthew C.
Published: March 2021

ABSTRACT IMPACT: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system OBJECTIVES/GOALS: The goals of the study are to (1) develop a parent-peer navigator program utilizing community-based participatory design; and (2) implement and assess the feasibility of a parent peer navigator program in an urban juvenile justice system. METHODS/STUDY POPULATION: The EPIS framework will guide development and implementation of the navigator program as well as measurement of the implementation process, including measurements of feasibility and acceptability. In the Exploration phase, qualitative interviews with juvenile justice staff, parents of justice-involved youth, and members of the local family advisory board will inform program needs. In the preparation stage, I will work closely with the family advisory board to develop the actual parent navigator program protocol, including a training plan for navigators and their specific roles. I will conduct an open trial in the implementation phase, measuring program feasibility and acceptability among parents, navigators, juvenile justice staff, parents, and youth utilizing mixed methods. RESULTS/ANTICIPATED RESULTS: Results will inform feasibility of implementing the program as well as acceptability of the program based on mixed methods data from parents of justice-involved youth, juvenile justice staff, family advisory board members, and other community stakeholders. Results will potentially inform conduct of a larger scale pilot hybrid implementation-effectiveness study. DISCUSSION/SIGNIFICANCE OF FINDINGS: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system.
47745 Low-risk Adenoma Surveillance Decision-making: Perspectives from Patients and Providers
Authors: Maratt Jennifer K. , Matthias Marianne , Gowan Tayler , Imperiale Thomas
Published: March 2021

ABSTRACT IMPACT: I hope that our work will improve surveillance endoscopy experiences, by engaging both patients and providers. OBJECTIVES/GOALS: A large proportion of colonoscopies are performed for post-polypectomy surveillance. Data show that there is overuse of surveillance for low-risk adenomas (LRAs), which can be attributed to patient and provider factors. The objective is to understand patient and provider perspectives for decision-making for LRA surveillance colonoscopy. METHODS/STUDY POPULATION: Semi-structured, one-on-one virtual interviews of patients and providers are currently being conducted at Richard L. Roudebush VA Medical Center and Eskenazi Health. Using a criterion sampling approach, we identified patients 50-75 years of age who had a screening colonoscopy with finding of LRAs, and providers in primary care and gastroenterology, at each site. We plan to recruit at least 8 patients and 8 providers from each site until thematic saturation. Domains that will be covered include: perceived involvement with surveillance decision-making; experiences with, and preferences for, communication about test results; and barriers and facilitators to undergoing colonoscopy. A 3-phase approach, comprising immersion, reduction, and interpretation, is being used to collect and analyze data. RESULTS/ANTICIPATED RESULTS: This study is currently in the recruitment phase and results will be forthcoming. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding decision-making for LRA surveillance colonoscopy will inform future interventions to improve endoscopic resource use and efficiency while improving patient and provider experiences with endoscopic care coordination.
56656 Programmatic Enhancements to Advance Racial Equity in Indiana (IN) CTSI
Authors: Edmonds Brownsyne Tucker , Robb Sheri , Hurley Thomas , Carroll Aaron
Published: March 2021

ABSTRACT IMPACT: We present new programs aimed at training, retaining and preparing a diverse cadre of scientists to lead the field in transforming population health and advancing health equity OBJECTIVES/GOALS: To mitigate biases inherent to the R01 grant funding process, trainees from backgrounds underrepresented in medicine (URM) may benefit from enhanced mentorship and a longer ‘runway’ to funding. As such, we have deployed two synergistic programs that aim to support URM retention and advancement. METHODS/STUDY POPULATION: The URM Program for Advising in Research and Development (UPwARD) pairs URM trainees with 2 mentors: 1) an institutional leader from outside their discipline to serve as an internal advocate and 2) an external eminent scholar who will facilitate the scholar’s development and prominence within their discipline. Additionally, the KL2 Program to Launch URM Success (KL2 PLUS) offers URM trainees a third year of funding to focus on scholarship, grant writing and leadership development. Four specific training components of KL2 PLUS include: 1) PLUS II Seminar Series, 2) Faculty Success Program, 3) attendance at the AAMC Minority Faculty Leadership Conference, and 4) CTSI Committee Service. RESULTS/ANTICIPATED RESULTS: Along with measures of productivity (papers, grants, K to R transition), we will utilize social network analyses and measures of collaboration, retention, and future CTSI engagement to evaluate the programs “success’‘ as both are designed to enhance trainee scholarly development and expand their professional and social networks. UPwARD does so by supporting engagement with external mentors at professional meetings and travel to present work across institutions. PLUS writing accountability groups will enhance publication rates and grant submissions, while also building connections with other URM faculty. Trainees also serve on IN CTSI committees to groom talent for future IN CTSI leadership. DISCUSSION/SIGNIFICANCE OF FINDINGS: Systemic inequities underlie the ‘leaky pipeline’ challenge we face in cultivating a diverse cadre of senior scientists and independent investigators. With intentional programming and targeted investments, IN CTSI aims to advance more equitable funding outcomes and diverse leadership.
70925 A TL1 team approach to investigate attention and learning at the intracranial network level and assess the effect different cognitive rehabilitation strategies have on measures of attention and learning
Authors: Long Sarah , Tocci Catherine , Kalamangalam Giridhar , Gunduz Ayse , Perlstein William
Published: March 2021

ABSTRACT IMPACT: Access to intracranial recording in our epileptic sample provides a unique opportunity to characterize neurological activation patterns associated with attention and implicit learning; this foundational physiological understanding will serve to better guide cognitive rehabilitation techniques in TBI patients that aim to improve functioning across these cognitive domains. OBJECTIVES/GOALS: 1) Investigate the network level interactions of attention and learning during an attention network task (ANT) and an implicit learning contextual cueing (CC) task. 2) Assess the effect that attention rehabilitation strategies have on behavioral and neural responses pre/post-attentional intervention. METHODS/STUDY POPULATION: This study involves refractory epilepsy patients (rEP) with implanted intracranial electrodes and moderate-to-severe traumatic brain injury (m/sTBI) survivors. In rEP, we are identifying network level modulations of cortical regions via the ANT, which probes components of attention (alerting, orienting, and executive control) and a CC task that probes implicit learning. We hypothesize that modulation of attention and learning can be seen at the neuronal level. In TBI we will assess improvement following two behavioral attention rehabilitation paradigms; and use our results from epileptic patients to guide measurement of treatment-related neuroplastic change via scalp electroencephalography. RESULTS/ANTICIPATED RESULTS: Preliminary behavioral results from the rEP cohort are in line with previous studies and the intracranial data is suggestive of region- and task-specific modulations in memory and attention related systems. Following completion of recruitment, we expect to more concretely identify regions and networks that exhibit modulatory effects associated with attention and implicit learning. Additionally, we anticipate that deficits in attention will be mitigated following training and hypothesize that implicit learning rate will improve in TBI patients as a result of both attentional rehabilitation paradigms. DISCUSSION/SIGNIFICANCE OF FINDINGS: Characterizing intracranial activity in epilepsy patients will give electrophysiology data unattainable in TBI patients. This intracranial perspective will enable us to propose mechanisms of action that may result from our interventions and enable critique of current rehabilitation treatments.
91348 A mixed methods analysis of hurdles to productivity among T and K awardees
Authors: Schneider Margaret , Jones Lisa , Woodward Amanda
Published: March 2021

ABSTRACT IMPACT: Recommendations for increasing trainee productivity will be highlighted. OBJECTIVES/GOALS: Using a combination of qualitative (interview) and quantitative (publications tracking) data, we undertook to describe the hurdles and concerns impeding academic accomplishments among T and K awardees at one CTSA hub and to examine whether hurdles at 6 months would predict academic output within one year following completion of the training program. METHODS/STUDY POPULATION: Semi-structured interviews were conducted with 29 trainees (28 TL1 and 8 KL2) 6 months into their training. Interview transcripts were analyzed using Atlas.ti to identify hurdles (factors that had already impeded research progress) and concerns (future challenges anticipated by the trainee). PubMed searches yielded the number of publications within one year of exiting the training program. Frequencies of hurdles and concerns were examined to characterize the factors most likely to impact trainee progress during the first 6 months of their training program. Among 18 trainees who had completed their training, the mean number of publications within one year of exiting the program (identified via verified PubMed searches) was compared across the total number of hurdles reported at 6 months (range = 0 to 3). RESULTS/ANTICIPATED RESULTS: The thematic analysis yielded 19 categories of hurdles and 14 categories of concerns. The top three hurdles were technological challenges (e.g., issues with equipment or data reduction; reported by 63% of trainees), professional competing responsibilities (40%), and navigating collaborations (30%). The top three concerns were future funding (33%), potential as an independent researcher (27%), and institutional context (e.g., departmental structure; 23%). The number of hurdles reported at 6 months significantly predicted number of publications one year post-exit (F (3,14) = 3.14, p < .05). Trainees reporting zero hurdles generated a mean of 8.67 publications; those with 3 hurdles generated a mean of 2.4 publications. DISCUSSION/SIGNIFICANCE OF FINDINGS: Future concerns were completely different from past hurdles, suggesting that the issues impeding research progress are not anticipated. Results suggest trainees would benefit from training related to how to balance competing professional responsibilities and navigate collaborations and that early attention to hurdles may enhance productivity.
55059 Developing the COmmuNity kNowlEdge to aCtion Toolkit (CONNECT) to reduce breast cancer screening disparities Let’s CONNECT
Authors: Haynes David , Hughes Kelly
Published: March 2021

ABSTRACT IMPACT: Advanced spatial analysis techniques are used to target a community education intervention for Immigrant and African American women to increase breast cancer screening. OBJECTIVES/GOALS: We are addressing breast cancer screening disparities through the development of the COmmuNity kNowlEdge to aCtion Toolkit (CONNECT). CONNECT implements a mixed-methods approach using GIScience, community education, and social media to mitigate the impact of breast cancer screening disparities for Immigrant African and African American women. METHODS/STUDY POPULATION: We used advanced spatial analysis techniques, Spatially Adaptive Filters (SAF) to reveal mammography screening rates below the state level. SAF create screening maps of This new information allows lay health educators to identify and engage their communities in the Breast Cancer Champions program. We transformed and curated existing cancer educational material into culturally relevant educational training for lay health educators. Lay health educators participate in educational trainings and receive stipends for conducting formal and informal breast cancer education and screening events. RESULTS/ANTICIPATED RESULTS: We have identified four principles for designing culturally relevant education materials.

1.

Visual representation of the community in materials

2.

Positive Framing

3.

Statistics and graphs should be minimal

4.

Appropriate reading level and minimizing jargon

Due to COVID-19, our breast cancer champions are engaging with their community in socially responsible ways (i.e., engaging through social media, developing and placing community education flyers, community radio spots). Our social media campaign, which began in October has already attracted over 1000 followers. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite the disruption of COVID-19, our project continues reduce breast cancer screening disparities. We have developed and created culturally appropriate materials and are currently training Champions. By incorporating an online presence into our community outreach, we are increasing the ways we connect with our community.
82913 Engaging women of color virtually: Cultural Impact of Treatment Delays among Women of Color with Uterine Fibroids
Authors: Orellana Minerva , Allyse Megan , Stewart Elizabeth A. , Venable Sateria , Enders Felicity , Balls-Berry Joyce E.
Published: March 2021

ABSTRACT IMPACT: This study will showcase the importance if incorporating patient stakeholders in the development of an interview guide for a women of color with uterine fibroids, an understudied population. OBJECTIVES/GOALS: Black women and Hispanic/Latinas report having greater symptom burden from uterine fibroids (UF), non-cancerous neoplasms, compared to White women. These disparities may be linked to cultural factors resulting in treatment delays. The objective of this study is to provide insights to barriers and facilitators to timely treatment. METHODS/STUDY POPULATION: In partnership with the Fibroid Foundation, a UF advocacy organization, we plan to conduct a virtual community engagement (CE) studio to serve as a first step for a pilot study with a national cohort of Black women and Hispanic/Latinas who receive treatment in the United States for UF. The studios will include a presentation about UF treatment options and a facilitated discussion. The CE team will use past research and constructs from Model of Improvement and Health Belief Model to develop materials for the studio. A qualitative researcher will guide the discussion, a note-taker will take notes, and they will thematically code the notes. The results will be used to create and implement a cross-sectional in-depth qualitative study with a national sample. RESULTS/ANTICIPATED RESULTS: We hypothesize that timely treatment will be impacted by cultural factors, such as health literacy in uterine fibroids and menstruation. We expect that detailed feedback from this national cohort will contribute to greater insight to the experiences of women of color with UF and address barriers and facilitators to treatment. We anticipate the anecdotes will provide information about the influence of culture in seeking treatment for UF. We will utilize this experience to understand the impact of a virtual CE studio in elucidating open discussion among women of color on a challenging and personal topic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Using CE process with advocates and research partners attains a deeper understanding in the development of an interview guide to examine the cultural impact on the treatment of UF for women of color. Understanding cultural barriers and facilitators can help overcome treatments delays in UF along with other gynecological diseases.
81030 Utilizing a synergistic drug combination to target relapsed/refractory FLT3 mutant AML
Authors: Jones LaQuita , Melgar Katelyn , Hoyt Scott , Wunderlich Mark , O’Brien Eric , Perentesis John , Thomas Craig , Starczynowski Daniel
Published: March 2021

ABSTRACT IMPACT: This work will help to understand a novel therapeutic approach to a common type of acute myeloid leukemia. OBJECTIVES/GOALS: FMS-like tyrosine kinase 3 (or FLT3) mutations occur in ˜30% of acute myeloid leukemia (AML) cases. FLT3 tyrosine kinase domain (TKD) mutations are particularly important in relapsed/refractory FLT3 mutant AML, which portends poor prognosis. This study describes a therapeutic approach to overcoming resistance conferred by FLT3-TKD mutations. METHODS/STUDY POPULATION: To understand the efficacy of a novel type 1 FLT3 inhibitor (NCGC1481), as a monotherapy and combination therapy, several assays were utilized to interrogate functionality of these therapies. Cell lines and patient samples containing aspartate 835 to tyrosine mutations (D835Y, the most common TKD alteration) and phenylalanine 691 to leucine (F691L) were utilized to examine the effects of NCGC1481 with and without other targeted therapies like MEK inhibitors. Specifically, assays measuring viability, cell death using flow cytometry, in vitro clonogenicity, cellular signaling, and xenograft survival were examined in these FLT3-TKD AML models. Synergy was also measured using well described methods, which also allowed for appropriate dose finding for drug combination experiments. RESULTS/ANTICIPATED RESULTS: Our novel type 1 FLT3 inhibitor (NCGC1481) was particularly effective in the most common FLT3 TKD mutant, D835Y. NCGC1481 reduced viability and cell signaling, while also inducing cell death and prolonging xenograft survival in the FLT3-D835Y model system. In contrast, clinically approved FLT3 inhibitors were less effective at suppressing AML cells expressing FLT3-D835Y. In the case of FLT3-F691L, most of the FLT3 inhibitors tested, including NCGC1481, suppressed canonical FLT3 signaling, but did not significantly reduce viability or leukemic clonogenicity. However, when NCGC1481 was combined with other targeted agents like MEK inhibitors, at synergistic doses, eradication of the FLT3-F691L AML clone was substantially increased. DISCUSSION/SIGNIFICANCE OF FINDINGS: In AML, response to FLT3 inhibitor therapy is often short-lived, with resistance sometimes occurring via FLT3-TKD mutations. Given the dismal prognosis of relapsed FLT3 mutant AML, novel therapies are necessary. This study describes efficacy of a novel FLT3 inhibitor, along with its synergistic activity when combined with other targeted agents.
38081 A Whole Blood Signature of Neutrophil Expression and Adaptive Immune Downregulation Characterizes Sepsis Mortality
Authors: Giannini H.M. , Cosgriff C.V. , Lu X.M. , Reilly J.R. , Anderson B.J. , Jones T.K. , Ittner C.A.G. , Weissman A.R. , Agyeum T. , Dunn T. , Shashaty M. , Meyer N.J.
Published: March 2021

ABSTRACT IMPACT: This work identifies host immune perturbations in sepsis mortality that suggests targets for a precision medicine paradigm in the host response to infection. OBJECTIVES/GOALS: To compare the early whole blood transcriptome during sepsis between 30-day survivors and non-survivors in the Intensive Care Unit (ICU), and to evaluate for pathway enrichment that might explain sepsis lethality. METHODS/STUDY POPULATION: We enrolled 162 sepsis patients in the first 24 hours of ICU admission, particularly targeting individuals requiring vasopressors. Peripheral whole blood was collected in PAXgene vacutainers. Isolated RNA was analyzed with Affymetrix Human Genome ST 2.0 microarray. Differential gene expression was performed with Bioconductor/R/limma using log2 fold-change +/-0.6 as a threshold for differential expression, and a Benjamini-Hochberg adjusted p-value <0.05 to declare significance. Functional gene enrichment was performed using the Gene Ontology (GO) database with PANTHER overrepresentation test (Fisher’s Exact) on all transcripts with adjusted p-value <0.05. Pathways analysis was performed with the Reactome Project using the raw fold change and significance data to identify dysregulated pathways. RESULTS/ANTICIPATED RESULTS: There were 58 non-survivors (36% mortality). We identified 39 genes as differentially expressed between sepsis non-survivors and survivors; 31 were upregulated in non-survivors and 8 had reduced expression. Several of the most overexpressed transcripts are neutrophil-specific, including LCN, MPO, OLF4M4, DEFA3, and DEFA4. A functional gene overrepresentation test further supports this finding, as the most enriched gene ontologies were neutrophil-mediated killing, neutrophil cytotoxicity, neutrophil extravasation, and respiratory burst, all demonstrating higher than 10-fold enrichment and FDR < 0.02. Pathway analysis of the peripheral blood transcriptome was notable for immune response derangement, specifically downregulation of both innate and adaptive immune pathways (FDR < 0.00001). DISCUSSION/SIGNIFICANCE OF FINDINGS: We identified increased expression of neutrophil-related genes in sepsis non-survivors, replicating candidates previously identified in pediatric sepsis mortality and ARDS. These immune perturbations in sepsis mortality may represent key targets for eventually employing precision medicine strategies in sepsis.
54478 The NIH Reporter Database: A Wealth of Information for Developing Team Science Metrics?
Authors: Arman Hosen , Razeq Ziyad , Reichmann Nancy , Lattime Edmund , Parekkadan Biju
Published: March 2021

ABSTRACT IMPACT: As scientific research is trending towards greater interdisciplinary and collaboration in order to meet the challenges of contemporary science, which has led to increased recognition of the importance of Team Science, this study will promote team science research within NJ ACTS Consortium as well as across the country. OBJECTIVES/GOALS: The objective of this study is to assess the feasibility of using the NIH Reporter database for developing and tracking team science metrics within the CTSA-funded NJ ACTS Consortium, which consists of RU, PU, and NJIT. The NIH Reporter database provides detailed information on single-PI and multiple-PI R01 grants funded by NIH. METHODS/STUDY POPULATION: 58 multi-PI projects and 344 single-PI projects are currently funded within the NJ ACTS consortium. We will use information from the database on funding levels, institutional composition of projects (e.g., within-consortium projects vs. projects with PIs both within and outside of the consortium), numbers of publications, impact factors of publications, and funding supplements obtained to quantify and track NIH R01 Team Science activity in the consortium. RESULTS/ANTICIPATED RESULTS: Preliminary analysis suggests that it will be both feasible and efficient to use the NIH reporter database to develop Team Science metrics and to augment information in the database with information on PI characteristics such as department/center/school/university, academic discipline, and rank/tenure status, as well and detailed composition of research teams, such as the mix in terms of senior and junior scholars. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will make an important contribution to this movement by demonstrating the feasibility of using the publicly available NIH Reporter Database to quantify the level and success of Team Science in the form of single-PI and multiple-PI R01 grants funded by NIH, which represent extremely important Team Science activities at universities.
46733 Strategy for Effective Team Formation: A Case Study of Rutgers’ Big Ideas Initiative
Authors: Razeq Ziyad , Parekkadan Biju , Reichman Nancy , Lattime Edmund
Published: March 2021

ABSTRACT IMPACT: This study will provide valuable insight regarding the effectiveness of a top-down approach for team formation. OBJECTIVES/GOALS: Rutgers’ Big Ideas is a philanthropic initiative designed to gather team science ideas and present them to donors. We intend to evaluate this Team Science intervention and determine its feasibility in catalyzing the inception of team formation. We will explore the composition of teams that are formed using this particular method and team outcomes. METHODS/STUDY POPULATION: Our group will first evaluate the themes that were covered by the initial 210 submissions as well as the 40 ideas chosen to be presented at the Big Ideas Symposium. We will also be taking a look at the donor population that these ideas were presented to. Then, we will evaluate the 8-12 winning teams that were chosen to move forward. We will compare various success metrics of the 8-12 teams that were chosen compared to the 40 ideas that had not been chosen. RESULTS/ANTICIPATED RESULTS: Encouraging team science through an initiative such as the Big Ideas forum is not only feasible, but also highly effective in creating resilient teams that show prolonged productivity in fundraising, publications, and other academic metrics. DISCUSSION/SIGNIFICANCE OF FINDINGS: Team Science is an exciting movement with immense potential. To that extent, this study seeks to discuss ways that academic leadership can inspire and foster effective team science collaboration. Concurrently, our case review lays the groundwork for further improvements to Team Science initiatives.
22566 Identifying metabolic mechanisms linking prenatal acetaminophen exposure to childhood attention-deficit hyperactivity disorder
Authors: Anand Neha S. , Wang Xiaobin
Published: March 2021

ABSTRACT IMPACT: This study has implications for understanding early developmental mechanisms of ADHD and for guidelines regarding safe use of acetaminophen during pregnancy. OBJECTIVES/GOALS: Prenatal acetaminophen exposure has been associated with childhood attention-deficit hyperactivity disorder (ADHD), but the underlying mechanism is unknown. This prospective birth cohort study aims to identify linkages between specific metabolites in umbilical cord plasma and the association of prenatal acetaminophen exposure and ADHD. METHODS/STUDY POPULATION: The sample was a subset of the Boston Birth Cohort that included 583 mother-newborn dyads followed at Boston Medical Center from 1998 to 2018. Metabolites were measured from cord plasma collected at birth. Based on existing literature, the analyses focused on candidate metabolites involved in neuroendocrine, inflammation, and oxidative stress pathways. The outcome was physician-diagnosed ADHD between the ages of 3 and 16 years. Exploratory analyses and multiple logistic regressions were used to examine the association of these candidate metabolites with both unmetabolized cord plasma acetaminophen levels and with incident risk of ADHD, adjusting for covariates of maternal and child characteristics. RESULTS/ANTICIPATED RESULTS: Of the 583 children, 257 had ADHD and 326 had neurotypical development. Two promising results have been found thus far. 5-methoxytryptophol (5-MTX), a neuroendocrine molecule which also has antioxidant and immunomodulatory properties, was inversely associated with acetaminophen and ADHD risk. For children below the median cord 5-MTX level, the odds of ADHD were 3.29 (95% CI [1.56, 7.16], p=0.002) for the third tertile of acetaminophen compared to the first tertile. This association attenuated among those above the median 5-MTX level: 2.23 (95% CI [0.98, 5.21], p=0.059), suggesting a protective effect. Tryptophan, an essential amino acid and precursor of serotonin, was positively associated with acetaminophen and ADHD. Next steps include mediation analysis with tryptophan and analyses for other metabolites. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies cord plasma metabolites as possible modifiers or mediators linking prenatal acetaminophen exposure and childhood ADHD, which may offer insight into a mechanistic pathway. The study findings have implications for FDA, clinical, and public health guidelines regarding safe use of acetaminophen during pregnancy.
43412 Exploring the link between allostatic load and mortality risk in U.S. Black men of different age groups
Authors: Wallace Duane J. , Thorpe Roland J.
Published: March 2021

ABSTRACT IMPACT: This research study will provide evidence for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men. OBJECTIVES/GOALS: Previous studies have demonstrated a strong association between allostatic load (i.e., stress-induced cumulative biological risk) and mortality in the Black American population. The aim of this study is to examine the association between allostatic load and mortality in Black men and to determine if the relation varies by age. METHODS/STUDY POPULATION: Data from the third National Health and Nutritional Examination Survey (NHANES III, 1988-1994), linked to the 2015 National Death Index Public Release File, will be used for Black male adults 18 years or older. Allostatic load score includes nine biomarkers: albumin, C-reactive protein, total cholesterol, high-density lipoprotein, hemoglobin A1C, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, and pulse rate. The number of variables for which the participant’s scores fall in the quartile of highest clinical risk are added together to create a summary score. Cox proportional-hazard analyses is employed to estimate the associations between allostatic load and all-cause mortality for the total sample and stratified by age, adjusting for selected characteristics. RESULTS/ANTICIPATED RESULTS: We hypothesize that the association of allostatic load with mortality will be greater among younger, compared to older, Black men. Young Black men (ages 25-44) are at particular risk of adverse impacts of chronic stress and allostatic load, due to their experience of chronic discrimination, systemic racism, racial battle fatigue, and mundane, extreme, environmental stress. Furthermore, the allostatic load-mortality association may be attenuated for older Black men due to a survival effect. DISCUSSION/SIGNIFICANCE OF FINDINGS: If the association between allostatic load score and mortality is stronger in young Black men, it would provide evidence for early identification of a group with high risk of premature mortality, and for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men.
51152 Efficacy of Bimodal Visual-Olfactory Training in Patients with COVID-19 resultant Hyposmia or Anosmia Using Patient-Preferred Scents (VOLT Trial - Visual-OLfactory Training)
Authors: Khan Amish Mustafa , Kallogjeri Dorina , Piccirillo Jay F.
Published: March 2021

ABSTRACT IMPACT: Olfactory dysfunction is a defining symptom of COVID-19 infection. As the number of total, confirmed COVID-19 cases approaches 7 million in the United States, it is estimated that there will be up to 500,000 new cases of chronically diminished smell. We offer a promising treatment. OBJECTIVES/GOALS: The primary aim is to explore the main effects and interaction of bimodal visual-olfactory training and patient-preferred scents on olfactory training in patients with post-COVID-19 hyposmia or anosmia. METHODS/STUDY POPULATION: The study will utilize a 2x2 factorial design. The two effects we will explore are unimodal versus bimodal training and conventional versus patient-preferred odors. All 4 arms will undergo 12 weeks of olfactory training. Participants will be assessed pre and post-intervention. Measurements of olfactory function include the objective smell identification test and subjective measures including the Clinical Global Impression Scale and Olfactory Dysfunction Outcomes Rating. Individuals eligible for the study include men and women between 18 and 70 years of age with olfactory dysfunction of at least 3 months duration initially diagnosed within 2 weeks of a COVID-19 infection. Of note, we will enroll nationally. RESULTS/ANTICIPATED RESULTS: We anticipate that the bimodal, patient-preferred scents training group will have the greatest improvement in smell scores, number of responders, and patient-reported sense of smell and health-related quality of life due to an additive interaction between the bimodal visual-olfactory and patient-preferred interventions. DISCUSSION/SIGNIFICANCE OF FINDINGS: The pathophysiology of COVID-19 olfactory dysfunction is mediated through damage to the peripheral and central olfactory pathways. This suggests that interventions most likely to be efficacious target both pathways, as olfactory training does.