Clinical and Translational Science Award (CTSA) hub websites are a critical communication gateway to assist the clinical and translational science community and promote CTSA hub offerings. The objective of this funded pilot project was to create a website and online database for the CTSA consortium that allows users to conduct structured searches among the 50 + CTSA hub websites. The result is CTSA Search Solutions, an online, searchable database that includes access to 50 + CTSA hub websites with 80+ structured search term options and over 800 links collected, organized, and published. Hubs can be searched by name and filtered by a specific CTSA topic, state, region, or even number of years funded to make detailed comparisons with the data identified. The home page for each hub can be accessed directly from the search page. The CTSA Search Solutions online database will allow for a wide breadth of CTSA personnel (core leads, researchers, administrators, communicators, and evaluators) to find consolidated information to learn about specific CTSA hub program highlights, as well as conduct research into program hub outputs and best practices across the nationwide CTSA consortium.

OBJECTIVES/GOALS: FXT/AS is a devastating, rare neurological syndrome that negatively impacts movement and cognition and is suspected to induce mitochondria dysfunction. Currently, no effective pharmacological treatments for FXTAS exist. The goal is to restore mitochondrial viability using endocannabinoid-like compounds in a cell culture model of FXTAS. METHODS/STUDY POPULATION: To establish a cell model of mitochondrial dysfunction, fibroblast baby hamster kidney (BHK-21) cell lines were treated with glucose oxidase (GluOx) at varying concentrations and times. Mitochondrial viability was assessed by the colorimetric Janus B Green Assay, which stains the mitochondria and enables assessment of cell numbers and the presence of oxygen in anchorage-dependent cell culture. Upon establishing this model of mitochondrial dysfunction, we next investigated the ability of three novel mitochondrial antioxidants (e.g., macamides) to protect mitochondrial viability. RESULTS/ANTICIPATED RESULTS: GluOx treatment of BHK-21 cells caused a dose- and time-dependent increase in oxidative stress. The data demonstrated significant disruption in the morphology of BHK-21 cells at a high glucose concentration, i.e., 40 nM, between 2 and 24 hours post-exposure. The morphology data were confirmed by the Janus B Green colorimetric assay. In examining the effects of glucose on mitochondrial viability, we demonstrated that at 15, 30, 35, and 40 nM, glucose significantly decreased mitochondria viability compared to the untreated, with 40 nM having the greatest effect. Under these conditions of mitochondrial dysfunction, co-incubation of the cells with the 0.5 uM MAM69 macamide attenuated the GluOx-induced increase in oxidative stress, with 0.5 uM MAM69 alone showing no effect on mitochondria viability. DISCUSSION/SIGNIFICANCE: This study illustrates the efficacy of macamides, natural occurring endocannabinoid like-compound, as novel prognostic and therapeutic candidates in the treatment of mitochondrial dysfunction that is associated with FXTAS. The use of BHK-21 fibroblast cells provides a rapid screening model to test for pharmacological therapeutic efficacy.

OBJECTIVES/GOALS: Highly Active Antiretroviral Therapy (HAART) is beneficial for managing HIV infection, however the long-term use of HAART may be problematic for healthy weight maintenance. The aim of the study was to investigate the association of race, weight status, and co-morbidities among individuals with HIV. METHODS/STUDY POPULATION: Self-reported data from 283 participants who completed the Symptom Checklist, the Co-Morbidity Questionnaire, and the Sociodemographic Questionnaire were included in the data analyses. Data were analyzed using Latent Class Analysis on JMP 13. Approximately 50% of participants self-identified as Black, 69% as male, and 35% as having AIDS. Participants’ age ranged from 25 to 66 years (mean age = 43.70 years, SD = 8.14). Participants were grouped by race (self- reported Black or non-Black), and then each group was clustered based on the top three most prevalent symptoms. The clusters identified were least symptomatic, weight gain, and weight loss. RESULTS/ANTICIPATED RESULTS: The non-Black weight gain cluster reported a higher incidence of AIDS (70.6% vs 38.2%), nausea (70.6% vs 17.6%), diarrhea (70.6% vs 26.5%), and shortness of breath (58.8% vs 20.6%) compared to the Black weight gain cluster. The Black weight loss cluster reported a higher incidence of cardiovascular symptoms including chest palpitations (42.2% vs 2.7%), chest pain (44.4% vs 8.1%), and shortness of breath (73.3% vs 35.1%) and a higher incidence of all GI symptoms with the most prominent being diarrhea (71.1% vs 48.6%) compared to the non-Black weight loss cluster. DISCUSSION/SIGNIFICANCE OF IMPACT: Future studies supporting these results will assist practitioners to target treatments that may prevent adverse health outcomes for individuals with HIV on HAART. Further studies will also assist with setting standards that allow practitioners to provide personalized care for individuals with HIV on HAART.

OBJECTIVES/GOALS: Using multi-state discharge data, to identify predictors of frequent emergency department (ED) use among the homeless patients seen in emergent care, and to compare frequent versus less frequent homeless ED users for their risk of serious health services utilization outcomes. METHODS/STUDY POPULATION: Based on the State Emergency Department Database and the State Inpatient Database, homeless individuals (n = 88,541) who made at least one ED visit in four states (Florida, Maryland, Massachusetts, and New York) in 2014. In this retrospective cross-sectional analysis, patient-level demographic and clinical factors were assessed as predictors for increased ED use. Risks of opioid overdose, opioid-related hospital admission/ED visit, in-hospital mortality, mechanical ventilation, and number of hospitalizations were compared between individuals with 4 or more vs. 2-3 vs. 1 ED visit(s), adjusting for potential confounders including hospital fixed effects (allowing for within hospital comparisons). RESULTS/ANTICIPATED RESULTS: Higher rates of ED use were associated with Medicare coverage <65; primary diagnosis of alcohol abuse, asthma, or abdominal pain; and co-morbidity of alcohol abuse, psychoses, or chronic pulmonary disease. Individuals with ≥4 visits had significantly higher adjusted risk of opioid overdose (3.7% vs. 1.2% vs. 1.0%), opioid-related hospitalizations/ED visits (17.9% vs. 8.5% vs. 6.6%), mechanical ventilation (9.8% vs. 7.0% vs. 4.7%), and greater # of hospitalizations (3.2 vs. 1.3 vs. 0.8) compared to individuals with 2-3 or 1 ED visit. Individuals with ≥4 and 2-3 ED visits had similar but increased risks of in-hospital mortality compared to individuals with 1 ED visit (2.8% vs. 2.8% vs. 2.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Homeless patients who were high ED users were more likely to be hospitalized and have other adverse outcomes. These findings encourage targeted interventions (i.e. housing) for the high-utilizer homeless population to reduce the burden of serious outcomes and costs for the patient and society.

OBJECTIVES/GOALS: The trabecular meshwork (TM) and Schlemm’s canal (SC), located within the iridocorneal angle (ICA), form the main outflow pathway and a major target for glaucoma treatments. We characterized the human ICA in vivo with Optical Coherence Tomography (OCT) imaging using a customized goniolens and a commercial OCT device (Heidelberg Spectralis). METHODS/STUDY POPULATION: Imaging these structures is difficult due to the optical limitations of imaging through the cornea at high angles. Therefore, a clinical gonioscopy lens was modified with a 12mm plano-convex lens placed on its anterior surface to focus light on the ICA structures, and capture returning light. Each subjects’ eye was anesthetized with 1 drop of Proparacaine 0.5%. The goniolens was coupled to the eye with gonio-gel and it was held by a 3D adjustable mount. OCT volume scans were acquired on 10 healthy subjects. The linear polarization of the OCT was rotated with a half-waveplate to measure dependence of the ICA landmarks on polarization orientation. RESULTS/ANTICIPATED RESULTS: The TM was seen in 9 of 10 subjects. Polarization rotation modified the brightness of the band of extracanalicular limbal lamina (BELL) and corneoscleral bands due to the birefringent nature of the collagenous structures, increasing the contrast of SC. SC width was 99 ± 20µm varying in size over space, including a subject with SC narrowing in the inferior-temporal quadrant. DISCUSSION/SIGNIFICANCE: This clinically suitable gonioscopic OCT approach has successfully been used to image the human ICA in 3D in vivo, providing detailed characterization of the TM and SC as well as enhancing their contrast against their birefringent backgrounds by rotating the polarization of the imaging beam.

OBJECTIVES/SPECIFIC AIMS: Cardiac radiation exposure following anti-cancer (CA) thoracic radiotherapy (RT) treatment increases risk of heart failure in a dose-dependent manner with a predominantly restrictive cardiomyopathy phenotype and is characterized by a diffuse fibrosis within the myocardium. The peak oxygen pulse (O2Pulse) determined at cardiopulmonary exercise testing (CPET) is the quotient of oxygen consumption (VO2) divided by the heart rate (HR) at peak exercise. Through deduction of the Fick equation (VO2 = cardiac output (CO) x arteriovenous oxygen difference) it provides a noninvasive estimate of the stroke volume response to exercise. Knowledge of the relationship between cardiac radiation dose and O2Pulse may provide mechanistic insight into the cardiac reserve of the CA survivor following thoracic RT. METHODS/STUDY POPULATION: Patients without a history of cardiovascular disease with a history of thoracic RT for CA treatment with significant incidental heart exposure (≥5 Gray (Gy) to ≥10% of the heart volume) underwent treadmill CPET to determine cardiorespiratory fitness and cardiac magnetic resonance (CMR) imaging to quantify central hemodynamics and for myocardial tissue characterization. The mean cardiac radiation dose (MCRD) and %volume of heart dose was determined from dose-volume histograms reflective of the dose contributions from all RT treatments for each patient. The oxygen pulse (milliliters (mL) of O2 per heart beat) was determined by dividing the absolute VO2 by the HR (beats per minute, bpm) at peak exercise and reported as %-predicted values to account for age and gender differences. Data are reported as number (%) or median (interquartile range). A stepwise multivariate linear regression model was created from significant univariate RT and CMR variables to determine independent predictors of %O2Pulse. RESULTS/ANTICIPATED RESULTS: Thirty patients (age = 63 [57-67] years, 18 [60%] female, 2.0 [0.1-28.7] years since completion of RT) underwent study procedures. The peak VO2=1376 mL·min-1 (62% of predicted) and peak HR = 150 (122-164) bpm resulted in a peak O2Pulse of 9.2 mL/beat (82% of predicted). The MCRD = 5.6 [3.7-17.8] Gy was inversely associated with %O2Pulse at univariate analysis (R = −0.514, p < .01), but was not retained at multivariate analysis. The CMR-derived CO ([4.9 (4.09-5.90) Liters/minute], β = +.374, p < .01), CMR-extracellular volume ([ECV, 26.9 (24.8-29.2)%], β = −.536, p < .01), and volume of the heart exposed to ≥30 Gy ([2.5 (0-15.0)Gy], (β = −.345, p = .01) were retained in the model (R2 = .709, F(3,19) = 15.438, p < .001) and were independent predictors of the %O2Pulse. DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with significant heart exposure following RT, %O2Pulse (a surrogate of stroke volume response to exercise) is inversely associated with cardiac radiation dose and is related to central hemodynamics (CO) and markers of diffuse fibrosis (ECV).

Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.

Objectives/Goals: Differences in gait patterns related to post-traumatic (PTOA) and idiopathic (IDIO) knee osteoarthritis (OA) in aging adults is not well understood. Therefore, the purpose of this study was to assess the impact of knee OA phenotype (PTOA vs IDIO) on the knee total joint moment (TJM) during walking in aging adults with and without end-stage knee OA. Methods/Study Population: Six adults with PTOA and six adults with IDIO were tested prior to knee replacement. Data from 12 healthy, asymptomatic adults were used as control data. All subjects underwent 3D gait analysis at a self-selected speed. TJM was calculated as the square root of the sum of the squared planar internal sagittal, frontal, and transverse plane knee moments across the stance phase. The corresponding sagittal, frontal, and transverse plane moments at the peak TJM in the 1st (TJM1) and 2nd (TJM2) half of the stance phase were extracted. A repeated-measures ANOVA was used to assess group differences in biomechanical parameters of the dominant (control group) and surgical (OA groups) limb, while knee pain (VAS: 0 – 10) during the walking task for the PTOA and IDIO groups was compared using an independent t-test (alpha=0.05). Results/Anticipated Results: Both the PTOA and IDIO groups walked at slower speeds compared to the control group (p<0.01). There was a main effect of knee OA phenotype on frontal plane TJM (p=0.003). The PTOA group exhibited a significantly lower frontal plane moment at TJM2 compared to the control (p=0.047) and IDIO (p=0.019) groups. There were no differences in sagittal, frontal, or transverse plane knee loading at TJM1 nor any differences in sagittal and transverse plane knee loading at TJM2 (p > 0.05). In addition, there were no differences in self-reported knee pain during walking between the PTOA and IDIO groups (p=0.25). Discussion/Significance of Impact: People with PTOA exhibit more rapid knee joint degeneration than those with IDIO. Lower frontal plane loading during TJM2 in PTOA may be associated with a more rapid decline in knee muscle function. Further evaluation of knee muscle function in PTOA and IDIO will provide better insight into these differences in gait patterns between PTOA and IDIO.

OBJECTIVES/GOALS: To determine if incorporating specific laboratory values and plasma biomarkers (club cell secretory protein (CC16), matrix metalloproteinase 3 (MMP3), interleukin 8 (IL-8), protein C) to the Lung Injury Prediction (LIP) Score improves the predictive value for development of acute respiratory distress syndrome (ARDS) in ICU patients. METHODS/STUDY POPULATION: Adult patients admitted to the ICU on supplemental oxygen over baseline requirement with a LIP Score ≥6 will be included. Patients admitted to the ICU >24 hours, end-stage renal disease, decompensated heart failure, or <100 µL plasma available will be excluded. Whole blood will be collected from the core lab, centrifuged, and plasma will be stored at -80°C. Protein biomarkers will be measured using enzyme-linked immunosorbent assay. Baseline characteristics, laboratory values, ventilator parameters, and clinical outcomes will be collected from the medical record. ARDS will be defined by the Berlin criteria. Machine learning methods will be used to identify the model with the highest predictive accuracy. Area under the receiver operating characteristic curve of each model will be compared to the LIP Score. RESULTS/ANTICIPATED RESULTS: Research is in progress. Plasma samples and clinical data have been collected for 148 of the 160 samples required to achieve power. Biomarker analysis will take place after sample collection is complete. We anticipate a machine learning model incorporating laboratory values and one or more plasma biomarkers into the LIP Score will outperform the baseline LIP Score for prediction of ARDS development. DISCUSSION/SIGNIFICANCE: Delayed diagnosis and intervention contribute to poor ARDS outcomes. Current predictive models for ARDS have low accuracy and enriching these models with plasma biomarkers may increase their predictive value. Development of accurate models may facilitate earlier ARDS diagnosis and intervention as well as enrichment strategies for ARDS trials.

ABSTRACT IMPACT: This study will generate preliminary data to address a critical, care transition-related patient safety gap involving medication use among children with medical complexity. OBJECTIVES/GOALS: The objectives of this study are: (1) to understand care transition-related medication safety risks for children with medical complexity (CMC), and (2) through a participatory, human centered design (PD) approach, to develop an early prototype intervention to address identified safety risks. METHODS/STUDY POPULATION: The study population includes children with medical complexity (CMC), a medically fragile pediatric population with intensive healthcare needs. CMC rely on multiple and complex medication regimens and/or medical devices for optimal functioning. Parents of CMC report multiple unmet healthcare needs. For Aim 1, we will conduct observations and interviews with ˜15 clinicians as well as semi-structured interviews with ˜30 family caregivers during three care transition experiences: from Cardiac ICU to home, Neonatal ICU to home, and those between primary care/specialty clinic to home. For Aim 2, we will conduct participatory design sessions with up to 5 participants (separately for clinicians and family caregivers) from each of the three care transition settings to co-design a prototype intervention. RESULTS/ANTICIPATED RESULTS: The study is currently recruiting family caregivers of CMC for aim 1 research activities, with interviews planned to be completed in February/March 2021. Transcribed interviews will be used to inform development of patient journey maps. A patient journey map helps to visually depict healthcare services through the patient and family lens, and highlights important ‘touch points’ along the patient journey (e.g., decisions, encounters, constraints, emotional states, etc.) that shape the patient and family experience. The journey map will distill findings from qualitative data and generate a concise visual story focused on the medication use experience of CMC as they transition between the hospital and their home. Individual journey maps will also be combined to generate a consolidated journey map. DISCUSSION/SIGNIFICANCE OF FINDINGS: An-in-depth understanding of medication safety risks unique to the context of CMC care would be essential to develop interventions that are useful, scalable, and sustainable. This is even more important because current interventions are primarily adopted from adult care settings with mixed outcomes.

OBJECTIVES/GOALS: Antibodies play an important role in the pathogenesis of a wide range of diseases, including cancer, autoimmune diseases, and infections. There are currently no reliable methods to isolate and study specific plasma cell subpopulations as antibody production sources. We aim to develop methods to study plasma cells in high resolution. METHODS/STUDY POPULATION: We will use molecular cloning to engineer fusion proteins that would bind plasma cell proteins to study these cells based on their surface features. The first phase of our study consists of assessing the efficacy of this plasma cell isolation method in established cell lines (e.g., RPMI 8226) and also antibody-secreting cell lines that we are establishing as a part of this study. In the second phase of the study, we will assess the efficacy of this method by studying antigen-specific plasma cell populations in the bone marrow aspiration samples of 20 healthy volunteers using various assays, including ELISPOT, flow cytometry, and fluorescent microscopy. RESULTS/ANTICIPATED RESULTS: We have designed the constructs and have completed the cloning. The final plasmids have been verified using various restriction enzymes and Sanger sequencing. Following the transfection of Freestyle HEK 293F cells and isolation of respective proteins, we expect to be able to utilize these engineered proteins to differentiate various antibody-secreting plasma cells. We will use cell lines for proof-of-concept experiments and will subsequently move this method to human bone marrow samples. We expect to be able to visualize multiple specific antibody-secreting plasma cell populations using fluorescent microscopy and utilize this method to isolate them by cell sorting via flow cytometry. DISCUSSION/SIGNIFICANCE: We expect to be able to use this method to target specific plasma cell clones in the advancement of precision medicine regarding the treatment of plasma cell disorders (e.g., multiple myeloma) and also expand its use in other areas, such as antibody discovery and the assessment of the humoral immune responses in infectious diseases.

Objectives/Goals: The study focuses on developing a wound patch that employs a biocompatible matrix which incorporates mesenchymal stem cells (MSCs) with wound healing and antimicrobial properties, along with antimicrobial metallic nanoparticles covered with keratinocytes derived from induced pluripotent stem cells to replicate the skin’s barrier function. Methods/Study Population: In vitro experiments will be conducted to combine bacteria with MSCs and metallic nanoparticles to assess whether bacterial killing is improved by this combination. The MSCs will then be evaluated in the presence of the nanoparticles to confirm that their functionality and phenotype are not altered. To verify the cells’ functional integrity, they will undergo trilineage differentiation, surface marker phenotypic testing, and evaluation of their capacity to inhibit lymphocyte proliferation in the presence of the nanoparticles. Subsequently, this living bandage will be created using a biomatrix embedded with induced pluripotent stem cell-derived keratinocytes and tested on a canine wound model to study the impact on healing. The model will assess the rate of healing and cellular response at weekly intervals until healed. Results/Anticipated Results: The combination of mesenchymal stem cells and antimicrobial nanoparticles works synergistically to enhance bacterial killing in vitro with S. aureus. The presence of the nanoparticles in combination with MSC did not affect the ability of the MSC to undergo trilineage differentiation. We anticipate that the surface phenotype will be similarly unaffected. In addition, we expect that the presence of the nanoparticles should not interfere with the ability of MSC to suppress lymphocyte proliferation. Utilization of the wound patch in the in vivo canine wound model is expected to enhance healing and prevent infection. We expect that we will observe a shift in the cellular composition of the wound with less inflammatory cells and more M2 or wound healing anti-inflammatory monocytes. Discussion/Significance of Impact: The incidence of resistant infections with no pharmacologic therapy available are on the rise. The development of an antimicrobial living bandage that increases the body’s ability to fight off infection, while providing a barrier to reinfection would provide a new way to treat infections regardless of their acquired antibacterial resistance.

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to evaluate the impact of the research and the scientific collaborations as shown in research publication supported by the PRCTRC. METHODS/STUDY POPULATION: Manuscripts published from 2010 to 2017 were retrieved from the Science Citation Index database. Our search criteria included manuscripts: 1) with the PRCTRC grant number and 2) with a PMCID number. Scientometric indicators including h-index (HI), average citation (AC), collaboration coefficient (CC), collaboration index (CI) and degree of collaboration (DC) were calculated using the Web of Science Platform and Stata software for statistical inquiry. Joinpoint was used to calculate the annual percent change (APC). RESULTS/ANTICIPATED RESULTS: A total of 316 publications were identified from 2010-2017, with an average of 39.5 publications per year, and a total of 2,383 citing articles without self-citations. During this period a significant growth (APC = ¬15.3%, p < 0.05) of scientific production was observed. The overall HI was 28, and the AC per item was 9.31. Regarding collaboration, the overall CC was 0.82, the CI was 6.93, and the DC was 99.3. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrated that the PRCTRC scientific production increased statistically significantly. Application of the scientometric indicators allows the PRCTRC assess the research productivity and collaboration to design and implement interventions according to program experience and needs.

Objectives/Goals: Define how CKD and iron therapy influence tubular epithelial cell (TEC) iron handling through parallel kidney and urine studies in mice and patients, uncovering cellular signatures that predict injury or recovery and may guide individualized iron therapy in CKD. Methods/Study Population: We used two mouse models of CKD and fresh urine samples from pediatric CKD patients and healthy controls to assess tubular iron handling. Kidney tubular epithelial cells (TECs; CD45−AQP1+) were analyzed by flow cytometry for labile iron pool (LIP) using FerroOrange and sorted into LIP^hi and LIP^low subsets for RNA-seq. Expression of injury markers such as KIM1 and NGAL was used to evaluate tubular stress, linking iron accumulation to epithelial injury and adaptive responses. By combining mouse CKD models with patient urine analysis, we traced how kidney tubular epithelial cells (TECs) manage iron across species. Results/Anticipated Results: In CKD mouse models, tubular epithelial cells (TECs) showed reduced labile iron pool (LIP) and increased ferroptosis, with a smaller population of iron-overloaded cells exhibiting elevated KIM-1 and EMT-related transcriptional changes. Iron chelation lowered LIP in tubular cells and iron therapy exasperated KIM-1 expression. Urinary TECs mirrored tissue findings, with LIP and KIM-1 levels reflecting systemic iron status and CKD severity. In human CKD, urinary LIPHI TECs expressed higher KIM-1 and injury-associated signatures, validating urinary TEC profiling as a noninvasive readout of tubular health. In both species, iron handling and toxicity proceeded differently depending on the nature of the damage (tubular or glomerular), identifying urinary TECs as a noninvasive window into kidney iron toxicity. Discussion/Significance of Impact: Chronic kidney disease affects 10–15% of the world population, and anemia is a common complication. Iron therapy is toxic to kidney cells, contributing to tubular injury. Our studies identify urinary cells as a noninvasive test of renal iron status and link iron handling to injury, enabling safer, personalized therapy to slow kidney damage in patients.

OBJECTIVES/GOALS: Silicosis is a highly fatal progressive fibrotic disease of the lungs characterized by accumulation and persistence of fibroblasts that excessively deposit Collagen1a1. We sought to eliminate Collagen1a1-expressing fibroblasts through a targeted genetic ablation strategy and hypothesized that this would arrest the progression of Silicosis. METHODS/STUDY POPULATION: Silicosis was induced with a single intratracheal (i.t.) instillation of silica particles ( RESULTS/ANTICIPATED RESULTS: Targeted ablation of Col1a1+ fibroblast in established Silicosis resulted in a decrease in: 1) Col1a1+ fibroblasts by flow cytometry and within fibrotic nodules by immunofluorescent staining, 2) total lung collagen content by histology and hydroxyproline assay, 3) tissue-associated disease by microCT and an increase in arterial oxygen saturation by pulse oximetry. Cessation of targeted Col1a1+ fibroblast ablation resulted in a rebound effect in Silicosis disease progression. Following ablation, Col1a1+ fibroblasts expanded by proliferation (Ki67+) and total lung collagen levels returned to pre-ablation levels. DISCUSSION/SIGNIFICANCE: Silicosis is a often fatal disease with no FDA approved therapies. These results suggest that targeted loss of Col1a1+ fibroblasts in Silicosis is sufficient to arrest disease progression. Thus, it is essential to understand how targeted loss of pro-fibrotic fibroblasts can alter disease progression as a tool to develop novel therapeutic strategies.

OBJECTIVES/SPECIFIC AIMS: The objective of this research was to identify and evaluate published research articles that highlight the use of CTSA institutional websites as a research tool or data source for translational science research. METHODS/STUDY POPULATION: A multifaceted systematic search process was engaged for this literature review process using standard literature database searching, digital journal database searching, and pearl growing. All U.S. based studies and reports from 2006 through the present that addressed the application of websites of CTSA institutions for translational science purposes were included in this review. Identified articles were collected, organized, and analyzed using an excel spreadsheet. There were 2 different data collection and organization protocols, one for studies the other for reports. The first data collection protocol was for identified studies that used individual CTSA Institutional websites as a data source for a research topic. The organization processes for each relevant study article included a customized data extraction process that looked to identify a standard group of key elements from each study: (1) The study’s NCATS CTSA Goal. (2) The type of data searched in the CTSA institutional website. (3) The number of CTSA institutional websites searched. (4) The number of sites that had the needed data. (6) The outcomes reported from the research. The second data collection protocol was for identified reports that referenced single CTSA Institutional websites as performing a specific translational informatics functionality either as a portal to Clinical and Translational Science Award tools and resources or as a direct information source. The organizational process for each relevant report article also included a customized data extraction process that looked to identify a standard group of key elements from each report: (1) NCATS / CTSA Goal (2) Tool or Functionality Promoted (3) Description (4) Website used as portal or direct tool. (5) Target Audience. RESULTS/ANTICIPATED RESULTS: The studies were summarized using the standard group of key elements identified for data extraction and summarized in a table. In 5 of the 6 studies, researchers relied on CTSA member individual website content to mine necessary data. One (1) of the studies employed a mixed methods approach to data acquisition and only relied on CTSA member individual website content for CTSA institutions that did not respond to a user survey. One (1) study used a survey to learn about CTSA website content rather than review the websites. In 5 of the 6 studies, researchers reviewed individual CTSA websites for the purposes of determining the number or percentages of CTSA institutions had specific data. One (1) study instead reviewed the individual websites to develop a broader picture of what the CTSA Consortium offered as a group. The percentage of CTSA websites that had the needed data of the researchers ranged from 32% to 100%. The median and mean scores for CTSA websites having the needed data was 66% and 66.5% respectively. One study did not provide specific information for assessment. All 6 studies included research that fell within at least 2 categories of the 5 NCATS CTSA Goal topics. The category most investigated was translational research processes where 5 of the 6 studies investigated how CTSA websites looked to improve the quality and efficiency of translational research. Three (3) studies investigated how CTSA’s cultivated and trained the clinical and translational science workforce. Two (2) studies investigated how CTSA’s engaged patients and communities in the translational research process. Two (2) studies investigated how CTSA’s promoted the integration of underserved populations. One (1) study investigated ways the CTSA’s used their websites to advance the use of cutting-edge informatics. The outcomes reported included (1) the percentage CTSA individual websites that provided information regarding patient recruitment. (2) A list of generic services provided across the CTSA Individual website medium. (3) The number of CTSA individual website education and training programs. (4) The number and quality of informed consent forms presented online. (5) Investigational New Drug (IND) / Investigational Device Exemption (IDE) training methods for CTSA Investigators. (6) The percentage of KL2 Awards used by Child Health Investigators at CTSA Institutions. The reports (rn=9) were also summarized using the standard group of key elements identified for data extraction and summarized in a table. All six articles reported using their Institutional CTSA website as either a portal or a tool to promote clinical and translational science as outlined through NCATS goals. A CTSA website is used as a portal when it provides links to other sites, tools, or programs. A CTSA Website is used as a tool when it provides the functionality within its web design like providing an online application or database, or interactive training pages. In 8 of the 9 articles, authors reported on CTSA institutional website as either a translational informatics portal or providing informatics functionalities. Four (4) of the articles reported the use of their website for engagement, on either the collaborator or patient level, such as advocacy, education, or subject enrollment. Two (2) articles reported the use of their CTSA website for the cultivation and training of a clinical and translational science workforce. Four (4) articles reported on the use of their CTSA website for the purposes of increasing the quality and efficiency of translational research. None of the articles reported how their sites were used to promote the integration of underserved populations. All the reports identified a CTSA institutional website as a tool to leverage or disseminate CTSA capabilities and functionality. The access point and or warehousing of these capabilities was the CTSA institutional website. The target audience for these publications included researchers, clinical research administrators, IT programmers, community collaborators, and research subjects. The articles that reported on the use of CTSA institutional websites for clinical and translational functionality included topics such as: (1) the introduction of an informatics tool that searches clinical notes to identify clinical data for research. (2) the promotion of an online research subject advocacy program. (3) the introduction of an informatics tool portal that allows researchers flexible, efficient and effective means of collaboration and interaction with data. (4) the promotion of a team development project tool. (5) the introduction of a research participant registry and study promotion and education tool. (6) the promotion of an independent informatics tool registry that could connect to all CTSA websites. DISCUSSION/SIGNIFICANCE OF IMPACT: This research shows that CTSA institutional website functionality and content contributes to the CTSA body of research and the advancement NIH translational science goals.