OBJECTIVES/GOALS: The purpose of this retrospective cohort study was to evaluate the impact of mental illness on first-time transcatheter aortic valve replacement (TAVR) and repeat TAVR (viv-AVR) outcomes including postoperative atrial fibrillation (POAF/AFL), as well as trends over time. METHODS/STUDY POPULATION: Using de-identified data reports from the New York Statewide Planning and Research Cooperative System (SPARCS) database from 2005-2018, multivariate logistics models were used to predict endpoints including POAF, the Society of Cardiothoracic surgeon (STS) endpoint (MM), and 30-day readmission (READMIT) in patients with and without mental illness. The TAVR procedure was approved for high-risk patients after 2012, and intermediate-risk patients after 2016, indicting a need to analyze the two populations separately. Multivariate analysis was only conducted on the first-time TAVR patients because of the small n in the viv-TAVR population. RESULTS/ANTICIPATED RESULTS: After 2012, 13.05% (1,810/13,870) of patients undergoing TAVR and 20.83% (15/72) undergoing viv-TAVR were diagnosed with a mental illness before the procedure. After 2016, 15.59% (1,485/9,524) TAVR patients and 20.00% (11/55) viv-TAVR patients had a preoperative diagnosis of mental illness. Multivariate analysis showed that mentally ill patients did not have significant differences in rates of POAF, 30-day readmission, and 30-day composite outcomes when compared to patients without mental illnesses following TAVR procedures after 2012 and 2016. Patients with POAF after both 2012 and 2016 were significantly less likely to be mentally ill, Black, and Hispanic. DISCUSSION/SIGNIFICANCE: Of the mentally ill patients who underwent TAVR, there was no significant difference in short-term outcomes after 2012 vs. 2016, compared to patients without mental illnesses. The small number of mentally ill patients undergoing TAVR may point to provider bias as a contributor to this high selectivity, and further evaluation would be of clinical use.

OBJECTIVES/GOALS: The study aims to identify and measure metabolites in irradiation-induced senescent pre-adipocytes induced by the increased secretion of pro-inflammatory cytokines. Through untargeted metabolomics, we seek to understand the alterations to metabolism and mitochondrial activity that occur during irradiation-induced senescence. METHODS/STUDY POPULATION: First, commercially available human primary subcutaneous pre-adipocytes were cultured in vitro, and irradiated to induce senescence. To confirm senescence, cells were stained for beta-galactosidase, which was positive in senescent pre-adipocytes. The cells and their conditioned cultured media were then collected and frozen for untargeted metabolomics to profile metabolites. The sample analysis is currently underway and will be conducted using central carbon isotope tracing and chromatograph mass spectrometry. Principal Component Analysis, fold change analysis, and heat maps will be used to detect and report the changes in metabolite signals. Oxygen consumption rate and extracellular acidification rate measurements are in progress at present using the Agilent Seahorse XF Cell Mito Stress Test. RESULTS/ANTICIPATED RESULTS: We expect that metabolites of central carbon metabolism and oxidative phosphorylation will be upregulated. The concentrations of metabolites of pathways altered by the pro-inflammatory cytokines that have been identified to be secreted by senescent cells are expected to be altered. The metabolites measured in conditioned culture media will provide insight into the changes to the cellular microenvironment caused by senescence. Finally, we anticipate that mitochondrial function, and both aerobic and anaerobic metabolism will be altered in senescent pre-adipocytes compared to controls. Through the present study, we will achieve a better understanding the metabolic alterations that occur as part of cell senescence in pre-adipocytes. DISCUSSION/SIGNIFICANCE: Adipose tissue dysfunction due to the accumulation of senescent cells has been linked to chronic diseases such as diabetes and insulin resistance, and inflammaging. Through this study, we expect to provide new insight into the metabolic alterations of senescence and offer a backbone for prospective translational human studies and clinical trials.

OBJECTIVES/GOALS: Diffusion MRI can identify microstructural brain changes and can provide insight into neural development and to potentially prognosticate speech and language outcomes in children with SNHL. The goal of our study was to investigate MRI-based microstructural changes along the brainstem regions of the auditory pathway in pediatric patients with SNHL. METHODS/STUDY POPULATION: We reviewed cohort of pediatric patients with SNHL who obtained MRI at 3T between 2011 and 2019. We identified 16 pediatric patients (age RESULTS/ANTICIPATED RESULTS: We identified significant differences in FA values of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs 0.422 ± 0.052; p=0.009). No other FA or MD values were significantly different between the two groups. Among younger children (ï‚£5 years), MD was significantly decreased in the SNHL cohort compared to controls in the IC (0.918 ± 0.051 vs 1.120 ± 0.142; p5 years), there were no significant differences in MD (1.124 ± 0.198 vs 0.997 ± 0.103; p = 0.119). There were no significant differences in MD or FA in the white matter fibers of the IC-SON tract. DISCUSSION/SIGNIFICANCE: This study is the first to assess microstructural changes in brainstem auditory pathway regions among children with SNHL. Longitudinal studies are warranted to assess the predictive value of these MRI-based findings for long-term outcomes and the efficacy of intervention.

OBJECTIVES/GOALS: Craniosynostosis is the premature fusion of one or more cranial sutures that produces brain growth constraints and typically requires surgical treatment. We present an age- and sex-specific method to evaluate surgical outcomes using non-invasive 3D photogrammetry that brings objectivity to the current approach for clinical assessment. METHODS/STUDY POPULATION: First, we created standardized head anatomy representations for 2,020 patients (1,081 males, 939 females, age 3.14 ± 3.05 years) without cranial pathology from their computed tomography (CT) images based on our previous methods. We used principal component regression stratified by sex to establish age-specific normative ranges of anatomical variability and we designed a new metric called cranial shape abnormality (CSA) index that calculates the number of standard deviations from normality of a given patient’s head anatomy. We calculated our CSA index in a group of 56 patients (44 male, 12 female) with sagittal craniosynostosis who underwent sagittal craniectomy from their pre- (22 ± 30 days before surgery) and post-surgical (267 ± 63 days after surgery) 3D photograms to evaluate surgical outcomes. RESULTS/ANTICIPATED RESULTS: We observed a reduction in the CSA index from 1.28 ± 0.26 before surgery to 0.87 ± 0.22 after surgery (p < 0.001 with a paired Wilcoxon test). The CSA index decreased in 53 of 56 patients (94.6%), who consistently showed head shape improvements after corrective surgery during clinical evaluation. Linear temporal regression indicates a CSA index decrease of 0.43 ± 0.05 during the first year after surgery. We found no significant correlation between a patient’s age at surgery and the patient’s CSA index after surgery (Pearson’s correlation coefficient 0.17, p = 0.20) or the patient’s change in CSA index before and after surgery (Pearson’s correlation coefficient 0.22, p = 0.11), suggesting that sagittal craniectomy is equally effective for all patients who are between 85 and 331 days old at the time of surgery. DISCUSSION/SIGNIFICANCE: Our new CSA index is a sex- and age-specific metric of head shape anomalies built upon the observed statistical distributions in the normative pediatric population. Our metric can objectively evaluate pre- and post-surgical head shapes and will allow the investigation of the reported variability in surgical outcomes among patients and procedures.

OBJECTIVES/GOALS: MGMT methylation status is used to predict the response to TMZ. However, a subpopulation of patients lacking MGMT methylation still respond to TMZ. We applied omics approaches and functional studies to a cohort of GBM patients to identify novel markers that may more accurately predict TMZ response. METHODS/STUDY POPULATION: We applied a combination of omics approaches and functional studies to a cohort of GBM patients to search for novel markers that would predict the response to TMZ treatment more accurately than traditional markers. Using a set of 47 primary and secondary GBM tumor samples, we employed comparative transcriptomics, whole exome sequencing, data independent acquisition (DIA) proteomics, and phosphoproteomics to look for DNA mutations and changes in gene expression and/or protein expression that correlated to response or non-response to TMZ. Subsequently, we performed functional studies and analyzed patient treatment data to validate our results. RESULTS/ANTICIPATED RESULTS: This study is in early stage, but we anticipate that our combination of methods may allow us to identify and validate at least one novel biomarker for TMZ response in patient GBM. For example, comparative transcriptomics or phosphoproteomics may identify a previously unrecognized gene or protein over/under-expression in a subset of patients. In this case we will validate findings using western blotting, IHC staining, and through siRNA of target gene/protein on patient derived GBM cells to examine if removal of this marker leads to TMZ sensitivity. We will further confirm prediction of marker correlation through comparison with matched patient treatment data. DISCUSSION/SIGNIFICANCE: The identification of improved biomarkers to predict response to TMZ treatment is a discovery that could rapidly become standard of care for GBM patients. It would ensure that all responders receive TMZ and avoid exposing nonresponders unnecessarily to TMZ and its potential side effects.

OBJECTIVES/GOALS: Aim1: To develop a natural language processing (NLP) algorithm to effectively identify statin associated muscle symptoms (SAMS) in patients’electronic health records (EHRs). Aim2: To develop a machine learning model based on clinical features within EHRs that predict the likelihood of SAMS occurrences. METHODS/STUDY POPULATION: A retrospective cohort of adult patients initiated on statins within the Minnesota Fairview Healthcare System EHRs from 2010 to 2020 will be analyzed. NLP-PIER (Patient Information Extraction for Research) platform will be used to search and identify patients who developed SAMS after statin initiation. Manual annotation of clinical notes will be completed to validate the accuracy of identified SAMS cases. Then, a selection of clinical features within the EHRs will be input as predictors for machine learning algorithms development. Select machine learning classifiers will be deployed to generate models for the prediction of SAMS and the best-performing model will be selected based on model performance. RESULTS/ANTICIPATED RESULTS: The expected outcomes include generation of a fine-tuned NLP algorithm that can rigorously identify SAMS occurrences within EHRs. Further, we anticipate having a practical risk model that accurately predicts patients’risks of developing SAMS when taking statins. DISCUSSION/SIGNIFICANCE: The positive and translational impact of our research will be to equip healthcare providers with such informatics tools to improve statin adherence, ultimately promoting patient optimal health and outcomes by maximizing the tolerance and thus realizing the therapeutic benefits of statins.

OBJECTIVES/GOALS: Development of a user friendly home kit that enables kidney transplant recipients to process urine at home and post the lysate containing RNA to a Core Laboratory would simplify urinary cell mRNA profiling and facilitate longitudinal monitoring. We report our home processing protocol and investigation of its diagnostic performance characteristics. METHODS/STUDY POPULATION: We developed a home processing protocol (HPP) consisting of urine filtration and lysis of urinary cells, both performed at home by the kidney transplant recipients (KTR) themselves, followed by isolation of total RNA from the lysate and mRNA enrichment using a silica-membrane-based cartridge, both performed at the Core Laboratory. Using the HPP, total RNA was isolated from kidney allograft biopsy-matched urines and absolute copy numbers of CD3εmRNA, CXCL10 mRNA, and 18S rRNA, components of the Clinical Trials in Organ Transplantation 04 (CTOT-04) three-gene TCMR diagnostic signature, and urinary cell BKV VP1 mRNA copy number, were measured using customized RT-qPCR assays. RESULTS/ANTICIPATED RESULTS: CTOT-04 three-gene TCMR diagnostic signature scores in urine processed using HPP discriminated KTR with TCMR (12 TCMR biopsies from 11 KTR) from KTR with no TCMR/BKVN (29 No TCMR/No BKVN biopsies from 29 KTR) (P=0.0005, Mann-Whitney test), and AUROC was 0.84 (95% CI, 0.69 to 0.98). TCMR was diagnosed with sensitivity of 67% (95% CI, 35 to 89) at a specificity of 86% (95% CI, 67 to 95) using the CTOT-04 validated cutpoint of -1.213 (P=0.0016,Fisher exact test). BKV VP1 mRNA copy number in urine processed with HPP discriminated KTR with BKVN (n=7) from KTR with no TCMR/BKVN (n=29) and AUROC was 1.0 (95% CI, 1.00 to 1.00). BKVN was diagnosed with a sensitivity of 86% (95% CI, 42 to 99) at specificity of 100% (95% CI, 85 to 100) with the previously validated cutpoint of 6.5x10^8 BKV VP1 mRNA copies/μg of RNA (P DISCUSSION/SIGNIFICANCE: Urine processed using the HPP predicted TCMR and BKVN in KTR. The HPP represents not only a significant advance towards portability of urinary cell mRNA profiling but also should improve patient management by minimizing visits for urine collection.

OBJECTIVES/GOALS: Patients suffering from respiratory failure have few options to support oxygenation and carbon dioxide removal aside from mechanical ventilation. Our objective was to test a novel extrapulmonary mechanism of gas exchange via peritoneal oxygenated perfluorocarbon (PFC) in a large animal model. METHODS/STUDY POPULATION: Using two 50 kg swine, hypoxia was modeled with subatmospheric oxygen and hypercarbia induced with acute hypoventilation. Through a midline laparotomy, cannulas were placed into the peritoneal space to allow for PFC infusion and circulation. After abdominal closure, these cannulas were connected to a device capable of draining, oxygenating, and infusing PFC. One animal was subjected to acute hypoxia (12% FiO2) and another animal to acute hypoventilation (4 breaths per minute). Primary outcomes were times for SpO2 to reach 75 mmHg, respectively. Trials were performed without PFC and with PFC dwelling or circulating through the peritoneal space, during which abdominal and bladder pressures were monitored and maintained under 20 mmHg by regulation of the PFC volume contained in the animal. RESULTS/ANTICIPATED RESULTS: In the animal subjected to acute hypoxia (12% FiO2), survival time improved from 5:55 to 20:00 (min:sec) after 2.5 liters of oxygenated PFC was instilled in the peritoneal space. Oxygen percent saturation of PFC before and after dwelling in the peritoneal space was measured at 100% before and 70% after dwelling in the animal during this hypoxic period corresponding with a gas transfer of 300 mL of oxygen over the 20-minute trial (i.e., 15 mL/min). Continual PFC circulation did not further extend the survival time during hypoxic conditions over PFC dwelling in the abdomen. In the animal that was acutely hypoventilated, there were no detectable differences in the rate of CO2 accumulation as measured by EtCO2 or direct blood pCO2 measurements with PFC dwelling or circulating through the peritoneal space. DISCUSSION/SIGNIFICANCE: Oxygenated PFC dwelling in the peritoneal space increased the duration of systemic arterial blood saturation remaining greater than 50% during normobaric hypoxic (12% FiO2) conditions but did not appreciably clear blood carbon dioxide during hypoventilation. Future experiments will focus on maximizing the rate of systemic oxygen uptake.

OBJECTIVES/GOALS: A stroke can impair neural communication between sensory and motor pathways thus compromising walking function. Paired associative stimulation (PAS) is a useful assay of sensorimotor integration (SMI) with limited use post-stroke. The objective of this study will be to determine lower extremity PAS effectiveness and reliability post-stroke. METHODS/STUDY POPULATION: This study will use a pre-post, cross-sectional design. Ten healthy controls and 10 individuals with chronic stroke (>6 months) will be recruited. PAS protocols will be individualized to account for between-subject variability in sensorimotor signaling by first measuring cortical sensory signaling using electroencephalography. Post-stroke participants will then receive PAS targeting the paretic tibialis anterior muscle; healthy controls will receive PAS targeting the non-dominant TA. Changes in cortically derived muscle responses will be characterized by absolute motor-evoked potential amplitude (MEPAmp) change, elicited by transcranial magnetic stimulation, over two sessions separated by >24 hours. Clinical measures of sensorimotor function and walking ability will also be performed. RESULTS/ANTICIPATED RESULTS: By individualizing PAS protocols, we expect to see significant increases in MEPAmp pre to post PAS, determined using paired t-tests. We also anticipate reliable PAS-induced increases in MEPAmp, which will be assessed using two reliability statistics: intraclass correlation coefficient and coefficients of variation of method error. Lastly, the increases in MEPAmp will be correlated with measures of sensorimotor function and walking ability, anticipating that greater increases in MEPAmp will be related to better walking ability and sensorimotor functioning. Correlations will be assessed via a Pearson’s correlation. A preset alpha = 0.05 will be used to determine significant findings. DISCUSSION/SIGNIFICANCE: The importance of this study is that establishing individualized PAS protocols could potentially provide a reliable and clinically relevant measure of SMI. Understanding post-stroke lower extremity SMI is necessary for furthering targeted and personalized interventions to combat walking deficits.

OBJECTIVES/GOALS: Diagnostic odyssey is the time it can take to a patient for receiving a diagnosis. Diagnostic process in rare diseases can be complex due to the heterogeneity of symptoms and lack of access to care. We aim to evaluate the association between diagnostic odyssey, perceived stress, and access to care, in parents of Puerto Rican patients with a rare disease. METHODS/STUDY POPULATION: We propose a cross-sectional study in parents of 100 children who received an uninformative whole exome sequencing (WES) report during a scheduled appointment with their geneticist. Discussion of WES results during clinical session, followed by a Perceived Stress Scale (PSS-10) and semi-structured interview to explore the experience of access to care during the diagnostic process will be arranged. Observation and interviews will be recorded. Data analysis and descriptive statistics will be calculated using STATA. Statistical associations (OR) will be estimated using generalized linear models at a 5% significance level. RESULTS/ANTICIPATED RESULTS: We expect to find high perceived stress in parents of Puerto Rican pediatric individuals having rare diseases, especially among single mothers. We will be able to identify limited access to care in Puerto Rico, especially in the testing pre-authorization process and long waits for geneticist appointments. Demand for advanced diagnostics is above the number of medical geneticists available in Puerto Rico, which triggers delayed diagnosis, management, and counseling. Therefore, these could affect the health disparities in our population with rare diseases. DISCUSSION/SIGNIFICANCE: This descriptive study will evaluate perceived stress in parents of pediatric patients living a diagnostic odyssey in Puerto Rico. No study has described perceived stress and access to care in this Hispanic population with undiagnosed conditions. Findings will contribute to a deep understanding of diagnostic process and limited access to care.

OBJECTIVES/GOALS: Adolescence represents a critical period for substance use initiation. Various factors may contribute to trying a sip or single puff of a substance, that could lead to more frequent use. However, less is known about how predictors from multiple domains converge to impact risk for general substance use initiation. METHODS/STUDY POPULATION: The Adolescent Brain Cognitive Development (ABCD) study is a multi-site longitudinal study following youth into early adulthood. The present study included 7,644 ABCD children who reported no lifetime substance use (including any experimentation) at baseline (ages 9–10). Our primary aim was to use a random forest classification model to predict binary substance use initiation, defined as trying any non-prescribed substance (e.g., alcohol, tobacco, cannabis, non-prescribed medications), during a 2-year follow-up after baseline. A total of 402 variables from the following categories were examined as predictors: demographics, peer substance use and availability, mental and physical health, culture and environment, biospecimens, neurocognitive functioning, and structural neuroimaging variables. RESULTS/ANTICIPATED RESULTS: Over a two-year follow-up, 751 (9.8%) of substance-naïve children reported trying a substance by age 11. The most common substance was alcohol, followed by cannabis and tobacco. Mean Decrease Accuracy (MDA) values were used to assess the relative importance of each predictor. The overall accuracy of the model in accurately predicting group membership (no substance use initiation vs. substance use initiation) was 57.66%. Of the top 5 predictors, the most important predictor was intent to use alcohol (MDA = .002). The following top predictors were structural neuroimaging variables: volume and surface area of right lateral occipital lobe (MDA = .0009 and .0008, respectively), surface area of right inferior temporal lobe (MDA = .0007), and surface area of left superior frontal lobe (MDA = .0007). DISCUSSION/SIGNIFICANCE: A combination of intent to use alcohol and structural neuroimaging indices were among the top predictors of substance use initiation. Understanding predictors of early substance use experimentation is important for identifying at-risk youth that may require targeted intervention approaches.

OBJECTIVES/GOALS: Our overall objective is to investigate the relationship between radiologic features of meningioma with recently identified histopathological and molecular biomarkers, and to apply a machine learning (ML) approach to further demonstrate their utility in predicting clinical outcomes. METHODS/STUDY POPULATION: We have enrolled a cohort of 84 patients with meningioma diagnosed on the basis of conventional gadolinium-enhanced MRI imaging features since September 2019. Each patient has demographic and clinical data, Ga-68-DOTATATE MRI/PET SUV and dynamic metrics, DCE-MRI perfusion parameters, and histopathologic data. Various tumor subregions will be segmented semi-automatically and later confirmed by experienced neuroradiologist. Histopathologic data will include histologic grade, mitotic rate, Ki67 proliferative index, and presence of WHO established atypical histologic features, immunohistochemical parameters, and established high-grade molecular features. We will use supervised learning techniques to develop algorithms for predicting molecular features from imaging phenotypes. RESULTS/ANTICIPATED RESULTS: Anticipated results - advancements in understanding the molecular biomarkers of meningiomas has uncovered genetic alterations and epigenetic changes that more accurately determine tumor behavior. Currently, the imaging correlates of these molecular biomarkers are unknown, and utilizing radiographic data to predict prognosis and imaging-based classifications of meningiomas have not yet been investigated. Validated imaging correlates of molecular biomarkers not only provide an in-vivo assessment of tumor biology, but can also be integrated with histopathologic features ( radiopathomics models’) for more accurate disease prognostication. We anticipate that our results will identify surrogate imaging features for some of the recently emerged molecular biomarkers of meningioma. DISCUSSION/SIGNIFICANCE: There is a paucity of data on the importance of imaging phenotypes in determining tumor biology. This work has the potential of significant clinical impact by enabling a priori molecular characterization of meningiomas at the time of new diagnosis or recurrence, thereby allowing a personalized medicine approach to treatment planning.

OBJECTIVES/GOALS: Tropsensor, a noninvasive portable device using infrared spectroscopy, delivers a troponin res ult within five minutes, significantly quicker than standard of care (SOC) assays. This pilot study assesses the correlation of the Tropsensor and high sensitivity cardiac troponin (hs-cTnI) assay results. METHODS/STUDY POPULATION: Patients undergoing cTnI testing with the Abbott Architect STAT (Abbott Laboratories) hs-cTnI assay were recruited at a quaternary-care emergency department (ED). The Tropsensor was applied to the underside of the patients’ wrist within 5 minutes of the SOC blood draw for 5 minutes. The results of the hs-cTnI assays were compared with the raw output of the Tropsensor device to assess the relationship using both Spearman’s and nonlinear logarithmic measures of correlation. Patient demographic data was extracted from the EHR to supplement the data collected for this study. RESULTS/ANTICIPATED RESULTS: 58 patients were recruited with a mean age of 60 years (60% male, 40% female). Due to connection error, 8 patients’data did not get captured by the device. Additionally, due to noise related to suboptimal device contact with the wrist, 24 patients’data (41%) were rejected. Of the 26 patients with usable data, 9 patients had a troponin above the 99th percentile threshold. A nonlinear correlation of 0.64 and Spearman’s rho of 0.59 were observed between the SOC hs-cTnI assay and Tropsensor optical data. DISCUSSION/SIGNIFICANCE: The Tropsensor exhibits 64.4% correlation to the SOC hs-cTnI assay. While further evaluation is needed, this exploratory study provides insight into the potential of a transdermal optical device to be used as a screening tool for AMI in an ED triage situation.

OBJECTIVES/GOALS: Pediatric heart failure is a complex disease presenting as an end-stage condition due to various etiologies and symptoms, causing 14,000 hospitalizations per year in the United States. Currently, there is a lack of objective metrics that are monitored non-invasively. This study explores tools to adapt remote monitoring technologies for pediatrics. METHODS/STUDY POPULATION: The task was determining commercially available and upcoming technologies for remote heart failure monitoring in the pediatric population. Literature and patent reviews were done in various databases with defined eligibility and key terms. Our inclusion criteria were: English peer-reviewed research or review articles, patents filed by cardiac monitoring companies, and independent groups focusing on non-invasive monitoring solutions. Key terms used for the literature search and patent review included pediatric heart failure’, at-home monitoring’, cardiac monitoring’, and non-invasive’. Based on a strong correlation between increased filling pressures and pediatric heart failure, the term filling pressures’ was also included in the search. RESULTS/ANTICIPATED RESULTS: Preliminary searches demonstrate an abundance of adult-use commercially available devices and patents for monitoring heart failure. Yet, there are no FDA-approved devices for use in the pediatric population. Current devices include monitoring metrics such as lung congestion and multi-parametric monitoring to capture heart rate, thoracic impedance, and oxygen saturation levels. In monitoring filling pressures, Abbott CardioMEMs is a leader in measuring pulmonary arterial pressure invasively in adults. Thus, there is a gap for non-invasive monitoring of filling pressures in both pediatric and adult populations. For further review, a larger focus will be placed on non-invasive methods for direct monitoring or extrapolation of cardiac filling pressures. DISCUSSION/SIGNIFICANCE: Current methods of heart failure monitoring are ineffective in serving the pediatric population. Thus, an identified gap exists in non-invasive filling pressure monitoring for pediatric heart failure. This review informs that innovation within this area would address inefficacies within the current paradigm of heart failure monitoring.

OBJECTIVES/GOALS: The rates of computational phenotyping algorithm reuse across health systems are low, leading to a proliferation of algorithms for the same trait. We propose a framework for reusing computational phenotyping algorithms and describe the real-world deployment of this framework for the development of the Colorado Diabetes EHR Research Repository. METHODS/STUDY POPULATION: The novel phenotype reuse framework consists of 4 steps: select algorithms that are appropriate for reuse by assessing whether they are fit for purpose; extend the algorithm to account for changes in data and care practice standards; localize the algorithm to use local database standards and terminologies; optimize the algorithm by applying a data driven approach to achieve the desired local performance. To identify individuals with type 1 diabetes (T1D) or type 2 diabetes (T2D), we selected and implemented T2D algorithms in a cohort of adults with any diabetes or pre-diabetes related diagnosis code, medication, or abnormal glucose-related laboratory test in the clinical data warehouse for UCHealth and the University of Colorado. RESULTS/ANTICIPATED RESULTS: We included a total of 926,290 patients who were identified by initial filters. Patients were more likely to be female (53%), identify as non-Hispanic white (69%) and had a median age of 58 years (IQR: 41, 70). Implementation, extension, localization, & optimization through iterative chart review prioritized high sensitivity for all-cause diabetes and high specificity for T1D and T2D. Of the original cohort, 252,946 (27%) were identified by the all-cause diabetes algorithm. Of these 11,688 were identified as T1D and 135,588 as T2D. After optimization the all-cause diabetes algorithm had 88% sensitivity, 90% specificity, 74% positive predictive value (PPV), and 96% negative predictive value (NPV). Our algorithms for T1D and T2D had high specificity (100% and 99%, respectively) and PPV (100 and 96% respectively). DISCUSSION/SIGNIFICANCE: Developing computational phenotyping algorithms is expensive and time consuming, yet algorithm reuse is low due to a lack of practical approaches for reusing algorithms. We demonstrate application of a novel framework for algorithm reuse, yielding good alignment of algorithm performance with study goals for identifying individuals with diabetes.

OBJECTIVES/GOALS: Multiple Organ Failure, often precipitated by Acute Lung Injury, is a life-threatening condition that causes death in military and civilian life. Furthermore, Acute Kidney Injury is very common, increasing morbidity and mortality rates. Therefore, understanding the molecular difference between survivors and non-survivors is urgently needed. METHODS/STUDY POPULATION: A 24-hour unilateral pulmonary contusion porcine model (pneumonectomy) of trauma-induced Multiple Organ Failure (MOF) model (n=17) and separate 48-hour polytrauma injury of bilateral pulmonary contusion, traumatic brain injury, and hemorrhage (polytrauma) MOF model (n=26) was developed at Dr. Batchinsky's AREVA laboratory. Serum was assayed at baseline and 3h or 6h post-trauma for amino acid metabolites using the Zip-Chip platform for mass spectrometry. The IDO1 enzyme activity assay kit (ab235936) was used to measure IDO1 enzyme activity in the tissue. Mass Spectrometry Imaging (MSI) was employed to frozen kidney tissues. Tissues were sectioned to 10- micron thickness. For MSI, the DAN matrix was utilized, and MALDI-MSI images were processed and obtained from METASPACE and SCILS software. RESULTS/ANTICIPATED RESULTS: In the pneumonectomy model, 10 survived, 7 died, and in the polytrauma group, 13 survived, and 13 died. In the pneumonectomy model, there was a significant increase in the serum kynurenine/tryptophan (KYN/TRP) ratio in the non-survivors 3h post-injury. A similar pattern was found in the validation group, which showed a significant increase in the KYN/TRP ratio at 6h post-trauma in non-survivors from the polytrauma model. There was a significant increase in IDO1 enzyme activity in non-survivor kidney tissues and a downregulation of tryptophan (TRP) metabolite in the kidney section in the non-survivor group post-trauma. DISCUSSION/SIGNIFICANCE: An increase in the KYN/TRP ratio post-trauma identified the pigs that suffered early mortality. A decrease in TRP metabolite and an increase in IDO1 enzyme activity in the kidney could contribute to an increase in KYN in the non-survivors. As a result, focusing on therapeutics targeting the KYN/TRP to reduce the incidence and severity of MOF is warranted.

OBJECTIVES/GOALS: Our long term goal is to identify the socioeconomic and cancer-specific determinants in patients with prostate cancer undergoing prostatectomy that impact their ability to maintain a healthy weight. This study explores the association between participants’health determinants and their indicated degree of self-efficacy and quality of life (QoL). METHODS/STUDY POPULATION: Study population includes participants of the WARRIOR trial (n=40), which included overweight men scheduled radical prostatectomy from the University of Kansas Medical Center. In addition to baseline demographics, the study team will administer a questionnaire based on a socioeconomic position and health-related QoL framework. This questionnaire will assess participants' socioeconomic, cancer-specific, and psychological circumstances at time of surgery and present day. Univariate analyses will be conducted on all variables with bivariate analyses between socioeconomic and clinical items to the outcome of composite self-efficacy scoring. RESULTS/ANTICIPATED RESULTS: We anticipate that participants in the intervention will report higher self-efficacy and emotional/social support than participants in the control group, participants with social vulnerability (lower income, marginalized race/ethnicity, etc) will report decreased self efficacy and poorer QoL compared with participants who are not socially vulnerable, and that participants who previously indicated social vulnerability will report more emotional barriers to weight loss, and lesser weight loss satisfaction, self-esteem, and QoL. DISCUSSION/SIGNIFICANCE: Lifestyle interventions have helped prostate cancer patients lose weight before surgery, but many regain weight. Exploring perceptions of self efficacy as well as learning more about what structural and systemic barriers affect self efficacy is important to inform how to improve our approach for sustained weight loss and health behavior changes.

OBJECTIVES/GOALS: Sleep is critical for healing, however pediatric intensive care unit (PICU) sound is above recommended levels (i.e., 45 A-weighted decibels [dBA]). This observational study identifies sources of PICU sound and compares sources between times of high (i.e., dBA≥45) and low (i.e., dBA < 45) levels. METHODS/STUDY POPULATION: The sound environment of 10 critically ill children 1 to 4 years of age was monitored via a bedside dosimeter and video camera for 48 hours, or until PICU discharge. Dosimeter and video data were uploaded to Noldus Observer XT and time synchronized. A reliable, previously published coding scheme developed to identify sound sources in the adult ICU was modified for the pediatric population. Sound sources (e.g., clinician/family/child [verbal vs. non-verbal] vocalization, patient care, medical equipment) were identified via instantaneous sampling of video data at each minute of recording. The proportion of sampling points with each sound source are compared between times of high and low sound levels, and between day (7:00-18:59) and night (19:00-6:59) shift. RESULTS/ANTICIPATED RESULTS: Video coding is ongoing, with high inter-rater reliability (κ̅=0.99, SD DISCUSSION/SIGNIFICANCE: Medical equipment sound is ubiquitous in the PICU. Clinicians should optimize the PICU sound environment for sleep, including minimizing equipment alarms, conversation, general activity, and screen media during child rest. Large-scale studies are needed to confirm findings from this small cohort.

OBJECTIVES/GOALS: Treatment options for glioblastoma (GBM) are limited. Prognosis remains dismal, with an 18 month on average survival rate following diagnosis due to treatment resistance and disease recurrence. The goal of this project is to investigate hallmarks of cancer progression that contribute to temozolomide (TMZ) resistance, a first tine treatment for GBM. METHODS/STUDY POPULATION: Two signaling pathways were investigated in TMZ-sensitive and -resistant GBM cell lines and in primary and recurrent patient-derived xenograft (PDX) tumor cells by genetically and pharmacologically inhibiting methionine adenosyltransferase 2A (MAT2A) and adenosylhomocysteinase (AHCY). Cell growth and survival were assessed by measuring protein expression of proliferation, oxidative stress and cell cycle arrest markers. EPIC array analysis and targeted bisulfite sequencing were conducted to identify changes in genome-wide and specific CpG island methylation. The Seahorse XF Analyzer measured mitochondrial respiratory capacity and oxidative metabolism. Induced pluripotent stem cell organoids were co-cultured with PDX tumor cells to determine if treatments mitigate tumor cell invasiveness. RESULTS/ANTICIPATED RESULTS: Compared to parental cells (PC), MAT2A gene expression was increased by 1.7-fold in acquired resistant and de novo resistant GBM cells (RC) [(transcript per million): PC, 7386 ± 0.012; RC, 12925 ± 0.023; n=2; p=2.10e-8]. Compared to TMZ-sensitive cells (TS), TMZ-resistant cells (TR) demonstrated a 56% increase in baseline oxygen consumption rate [(pmol/min): TS, 179 ± 6.7; TR, 279 ± 13; n=18; p=.0012] and 64% increase in maximal respiratory capacity [(pmol/min): TS, 403 ± 29; TR, 659 ± 35; n=6; p DISCUSSION/SIGNIFICANCE: MAT2A and AHCY contribute to TMZ resistance and recurrence by dysregulating methylation programs and upregulating antioxidant programs, respectively. These findings provide a foundation for developing novel combinatory therapeutic strategies and inform clinical studies intended to increase remission and reduce recurrence for GBM patients.

OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.