bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of enzymes as a feed additive in aquaculture
Authors: Liang Qingping , Yuan Mingxue , Xu Liping , Lio Elia , Zhang Fang , Mou Haijin , Secundo Francesco
Published: April 2022

Modern aquaculture must be sustainable in terms of energy consumption, raw materials used, and environmental impact, so alternatives are needed to replace fish feed with other raw materials. Enzyme use in the agri-food industry is based on their efficiency, safety, and protection of the environment, which aligns with the requirements of a resource-saving production system. Enzyme supplementation in fish feed can improve digestibility and absorption of both plant- and animal-derived ingredients, increasing the growth parameters of aquacultural animals. Herein we summarized the recent literature that reported the use of digestive enzymes (amylases, lipases, proteases, cellulases, and hemicellulases) and non-digestive enzymes (phytases, glucose oxidase, and lysozyme) in fish feed. In addition, we analyzed how critical steps of the pelleting process, including microencapsulation and immobilization, can interfere with enzyme activity in the final fish feed product.
The Intersection of Telemedicine and Wilderness Care: Past, Present, and Future
Authors: Davis Christopher B. , Lorentzen Anne Katherine , Patel Hemali , Cheung Dickson , Wright Angela , Lemery Jay , Penninga Luit
Published: April 2022

Wilderness medicine and telemedicine seemingly exist at opposite ends of the clinical continuum. However, these 2 specialties share a common history and the literature abounds with examples of successful deployment of telemedicine to resource limited settings. The recent widespread adoption of telemedicine has important ramifications for wilderness providers. Telemedicine is inherently reliant on some sort of technology. There is a wide spectrum of complexity involved, but in general these systems rely on a hardware component, a software component, and a network system to transmit information from place to place. Today, connectivity is nearly ubiquitous through access to cellular networks, Wi-Fi, or communication satellites. However, bandwidth, defined as the amount of data which can be transmitted through a given connection over time, remains a limiting factor for many austere settings. Telemedicine services are typically organized into 4 categories: 1) live/interactive; 2) store and forward; 3) remote patient monitoring; and 4) mHealth. Each of these categories has an applicable wilderness medicine use case which will be reviewed in this paper. Though the regulatory environment remains complex, there is enormous potential for telemedicine to enhance the practice of wilderness medicine. Drones are likely to transform wilderness medicine supply chains by facilitating delivery of food, shelter, and medicines and are able to enhance search and rescue efforts. Remote consultations can be paired with remote patient monitoring technology to deliver highly specialized care to austere environments. Early feasibility studies are promising, but further prospective data will be required to define future best practices for wilderness telemedicine.
200 Benefits and Challenges of Human-Centered Design: Perspectives from Research Teams
Authors: Norman Marie , Hamm Megan E. , Schenker Yael , Mayowski Colleen A. , Hierholzer William , Rubio Doris M. , Reis Steven E.
Published: April 2022

OBJECTIVES/GOALS: The use of Human Centered Design (HCD) to improve the quality of team science is a recent application, and HCDs benefits and challenges have not been rigorously evaluated. We conducted a qualitative study with health sciences researchers trained in HCD methods to determine how they applied HCD methods and perceived its benefits and challenges. METHODS/STUDY POPULATION: The University of Pittsburgh offered HCD training to three cohorts of research scientists (staff as well as faculty) over a three-year period. The training was provided by the LUMA Institute, a premier HCD design firm with a highly regarded training program. We then evaluated this training by conducting 1-hour, semi-structured interviews with trainees from three training cohorts. Interviews focused on perceptions of the training, subsequent uses of HCD, barriers and facilitators, and perceptions of the utility of HCD to science teams. Data analysis was conducted using Braun and Clarkes process for thematic analysis. RESULTS/ANTICIPATED RESULTS: We interviewed 18 researchers (nine faculty and nine staff) trained in HCD methods and identified distinct themes regarding HCD use and its perceived benefits and challenges. Trainees found HCD relevant to research teams for stakeholder engagement, research design, project planning, meeting facilitation, and team management. They also described benefits of HCD in five distinct areas: creativity, egalitarianism, structure, efficiency, and visibility. We also identified challenges, including tensions between HCD approaches and academic culture. DISCUSSION/SIGNIFICANCE: Our data suggest that HCD has the potential to help researchers work more inclusively and collaboratively on interdisciplinary teams and generate more innovative and impactful science. The application of HCD methods is not without challenges; however, we believe these challenges can be overcome with institutional investment.
205 Targeting Homologous Repair to Overcome Genotoxic Therapy Resistance in Pancreatic Cancer
Authors: Wolfe Adam , Zuniga Oscar , West Kirk , Leung Justin
Published: April 2022

OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is a relatively radioresistant disease, and inhibition of DNA homologous recombination (HR) repair in combination with radiation therapy (RT) is a potentially attractive strategy to overcome radioresistance. We have found that the expression of the HR protein RAD18 is upregulated in PDAC cells. METHODS/STUDY POPULATION: Standard clonogenic assays, Î³H2aX foci staining, HR-GFP reporter assay, and western blot analysis of DNA damage response proteins were performed in MIA-PaCa2 (MP2) and PANC-1 cells following knockdown of RAD18 in cells via short hairpin RNA (shRNA). Drug targeting of RAD18 was achieved through the use of a USP-7 inhibitor, P5091. Cells with or without stable knockdown of RAD18 were implanted orthotopically in the pancreas of athymic nude mice and treated with sham radiation or radiation to a dose of 20 Gy in 5 daily fractions once tumors reached 100-150 mm3. RESULTS/ANTICIPATED RESULTS: Stable knockdown of RAD18 in MP2 and PANC-1 resulted in decreased radiation clonogenic survival in vitro (dose enhancement factor (DEF)=1.52 and 1.51, respectively), decreased DNA repair after radiation as measured by the increased number of Î³H2aX nuclear foci assay at 6, 12, and 24 hours (all p<0.05), decreased HR activation following DNA damage via an HR-GFP reporter assay (p=0.039), and increased tumor growth delay following radiation in vivo (p<0.001). P5091 treatment of both MP2 and PANC-1 resulted in efficient knockdown of RAD18, which was confirmed through western blotting, qRT-PCR, and luciferase reporter assays. P5091 increased radiosensitization, yH2aX nuclear foci remained elevated at 12 and 24 hours (p<0.05), and HR repair was also reduced (p=0.014). DISCUSSION/SIGNIFICANCE: Herein, we show the HR repair protein RAD18, and that modulation of RAD18 expression correlates with in vitro and in vivo radiosensitization through altered HR-mediated DNA repair. USP7 inhibition successfully reduced RAD18 expression and resulted in enhanced radiosensitization.
206 The Role of Mechanosensitive Ion Channels in Primary Open Angle Glaucoma
Authors: Liu Wendy , Zhu Ying , Jakobs Tatjana , Wiggs Janey
Published: April 2022

OBJECTIVES/GOALS: Intraocular pressure is the most significant risk factor for glaucoma. Mechanosensitive proteins may have a critical role in transducing mechanical stimuli that ultimately lead to death of retinal ganglion cells. Our goal is to use genetic and functional approaches to discover mechanosensitive ion channels that mediate the progression of glaucoma. METHODS/STUDY POPULATION: Association data, obtained using a logistic regression model that included age, gender and population substructure as co-variates, for 2,576 SNPs located in the PIEZO1 and PIEZO2 genomic regions were extracted from the NEIGHBORHOOD genome-wide association study results for primary open angle glaucoma (POAG) (3,853 cases and 33,480 controls) and the subset of cases with intraocular pressure (IOP) measurements > 21mmHg (high-tension, HTG) (1868 cases and 33,480 controls). Rare coding PIEZO1 and PIEZO2 variants were evaluated using logistic regression and SNP data from the Human Exome array in 2606 POAG cases and 2606 controls and the subset of 1868 HTG cases and 2606 controls. Immunohistochemistry was used to characterize the expression of Piezo1 and Piezo2 in mouse eye sections. RESULTS/ANTICIPATED RESULTS: Exome data analysis identified two protein-altering variants associated with lower glaucoma risk (P<0.05): a PIEZO1 missense allele (Arg1527His; OR= 0.18, P= 0.001) and a variant disrupting a splice donor site (c.1107+1G>C; OR=0.38, P= 0.02), that prematurely truncates the protein. Investigation of the NEIGHBORHOOD GWAS dataset identified nominal association with common PIEZO2 variants (minor allele frequency > 0.3) in POAG overall (top SNP rs264179, P= 0.008) and in the HTG subgroup (top SNP rs264160, P= 0.001). The associated PIEZO2 SNPs are significantly associated with gene expression in lymphocytes (P< 1x10-8) with the risk allele correlated with decreased gene expression. Piezo1 and Piezo2 are expressed in many ocular tissues in the mouse, including cornea, ciliary body and retina. DISCUSSION/SIGNIFICANCE: We identify rare, protein-altering PIEZO1 variants associated with lower glaucoma risk and show that Piezo1 and Piezo2 are broadly expressed in the eye. Common variants influencing PIEZO2 expression also show nominal association with POAG risk. Inhibition of Piezo1 or augmentation of Piezo2 could be novel therapeutic strategies for glaucoma.
207 Omega-3 and omega-6 fatty acids attenuate platelet reactivity in postmenopausal women
Authors: Yamaguchi Adriana , Stanger Livia , Prieur Amanda , Tav Rachel , Freedman Cody , Holman Theodore R. , Holinstat Michael
Published: April 2022

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of fish oil (âμ-3 fatty acids) or evening primrose oil (âμ-6 fatty acids) supplementation on platelet reactivity in postmenopausal women. METHODS/STUDY POPULATION: Postmenopausal women were recruited from the Ann Arbor community and the University of Michigan Medicine Center. All subjects were recruited under study protocols approved by the University of Michigan IRB between November 2015 and March 2017. We conducted a randomized, double-blind, two-period crossover trial, consisting of a 60-day supplementation period followed by a 14-day washout period in between and at the end of the study. Subjects were treated daily in random order with 2g of fish oil supplement and 2g of evening primrose oil. Blood was drawn at baseline, post-supplementation, and after washout. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion and activation of basal integrin âºIIbÎ23 were assessed following supplementation and washout period. RESULTS/ANTICIPATED RESULTS: The study started with 90 postmenopausal women. A total of 78 subjects completed the study, with 12 subjects dropping out due to non-compliance and medical reasons. Supplementation with fish oil attenuated the thrombin receptor PAR4-induced platelet aggregation, whereas primrose oil supplementation attenuated aggregation mediated by PAR4 or collagen. Supplementation with âμ-3 or âμ-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin âºIIbÎ23 activation. Post-washout following supplementation with primrose oil, the thrombin receptor PAR1-induced platelet aggregation was similarly attenuated. For either treatment, the observed effects post supplementation on dense granule secretion and basal integrin activation were sustained after the washout. DISCUSSION/SIGNIFICANCE: Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. This study indicates that supplementation with âμ-3 and âμ-6 fatty acids may offer significant protection for postmenopausal women against cardiovascular diseases and occlusive thrombotic events by reducing platelet reactivity.
209 A CTS Team Approach to Modeling Migration and Suppression of CCR2+/CX3CR1+ Myeloid Cells in Glioblastoma
Authors: Anderson Hannah , Takacs Gregory P. , Kreiger Christian , Luo Defang , Rong Libin , Harrison Jeffrey K. , Stepien Tracy
Published: April 2022

OBJECTIVES/GOALS: Evaluate the migration and immune suppressive functions of CCR2+/CX3CR1+ myeloid-derived suppressor cells (MDSCs). Integrate experimental data and biologically relevant mathematical models of infiltrating MDSCs in the context of glioblastoma (GBM). METHODS/STUDY POPULATION: CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from CCR2(+/RFP)/CX3CR1(+/GFP) glioma-bearing mice to evaluate their immune-suppressive phenotype and ability to migrate to CCL2 and CCL7. Fluorescent imaging and quantification were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and MDSC densities. A system of ordinary differential equations was constructed to represent the temporal dynamics of glioma cells, T cells, and MDSCs within the tumor microenvironment. The Approximate Bayesian Computation method was used to determine probability distributions of important parameters, such as the suppression rate of T cells by MDSCs. RESULTS/ANTICIPATED RESULTS: CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor-bearing mice suppress CD8+ T cell proliferation and IFNÎ³ production. CCR2+/CX3CR1+ cells migrate to recombinant and KR158B glioma sourced CCL2 and CCL7. Parameter values determined by the Approximate Bayesian Computation method agreed with parameter values from experimental data. This result further validated the structure and results of the mathematical model when performing computer simulations; thus, we can predict CCR2+/CX3CR1+ M-MDSC infiltration over time. DISCUSSION/SIGNIFICANCE: The immune-suppressive microenvironment in GBM contributes to poor outcomes despite standard of care. This study integrates biological and mathematical models to better understand infiltrating immune-suppressive cells, namely CCR2+/CX3CR1+ M-MDSCs. Future directions include modeling immunotherapies.
213 Extrapulmonary Gas Exchange Through Peritoneal Perfluorocarbon Perfusion
Authors: Leibowitz Joshua L. , Naselsky Warren , Doosthosseini Mahsa , Aroom Kevin , Shah Aakash , Bittle Gregory J. , Hahn Jin-Oh , Fathy Hosam K. , Friedberg Joseph S.
Published: April 2022

OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.
214 A TL1 Team Approach: Physician Strategies to Promote Physical Activity Among Youth with Comorbid Asthma and Overweight/Obesity
Authors: Koskela-Staples Natalie C. , Yourell Jacqlyn L. , Doty MS Jennifer L. , Fedele David A.
Published: April 2022

OBJECTIVES/GOALS: Youth with comorbid asthma and overweight/obesity (OW/OB) are at risk for increased morbidity. Physical activity (PA) engagement can mitigate risks, but the majority of youth do not meet national PA guidelines. This study examines caregiver and youth perspectives about ways physicians can promote PA in this population. METHODS/STUDY POPULATION: Participants included 20 adolescents (M age = 16.0; 55% male) with asthma and OW/OB and a primary caregiver (90% mothers). Caregivers and adolescents participated in separate semi-structured interviews about adolescent PA engagement, including questions regarding strategies for physicians to promote PA. Interviews were audio recorded, transcribed, and analyzed using NVivo. Two authors assigned conceptual codes to the transcripts to identify key concepts and then met to create a codebook. Authors independently coded 4 transcripts and met to resolve discrepancies. Authors then independently coded 2 additional transcripts (final kappa = .62) and met to reach consensus before dividing the remainder for coding. Codes were collapsed and sorted into themes, and attributes of each theme were determined. RESULTS/ANTICIPATED RESULTS: Dyads discussed the importance of physicians providing general (positive statements) and PA-specific encouragement. Dyads also stated that physicians should encourage teens to set and reach PA-related goals. Caregivers and youth reported that physicians should provide education about the importance of PA and ways to engage in PA, awareness about adolescents weight and its impact on health, and resources (camps, events, and locations). Additionally, caregivers and a teen noted that physicians should talk directly to and address questions toward teens. Dyads mentioned the importance of focusing on overall health (instead of weight) as well. Dyads also noted that physicians should avoid judgmental and shaming statements when talking about weight. DISCUSSION/SIGNIFICANCE: Results provide information about strategies physicians can use to promote PA among adolescents with asthma and OW/OB, a population that is at risk for low PA and poor health outcomes. Findings suggest that physicians may effectively motivate behavior change by providing health guidelines, encouragement, resources, and positive reinforcement.
224 Ends of Endemics: Capturing Viral UTRs in Clinically Relevant Arbovirus Samples
Authors: Morris Victoria , Zhou Y , Yun R , Thompson J , Khan B , Bolling B , Weaver SC , Routh AL
Published: April 2022

OBJECTIVES/GOALS: Whole-genome viral sequencing is vital to inform public health and study evolution. Arboviruses evolve in vectors, reservoir hosts, and humans, and require surveillance at all points. We developed a new rigorous method of sequencing that captures whole viral genomes in field-collected and clinical samples. METHODS/STUDY POPULATION: ClickSeq is a novel method of Next Generation Sequencing (NGS) library synthesis using azido-nucleotides to terminate reverse transcription. The cDNA generated can be ligated to sequencing and indexing primers at room temperature using copper (Cu I) and vitamin C. With this approach, we designed primers located ~250 bp apart along the genomes of the arboviruses Chikungunya 37797, Zika Dakar, Yellow Fever Asibi, Dengue serotype 2, West Nile 385-99, and St. Louis Encephalitis Virus (SLEV) clade II. We tested this method with varying viral titers: lab-infected mosquito pools, field-collected mosquito pools from a Texas West Nile and SLEV outbreak, and patient isolates from a Pakistani CHIKV outbreak. The cDNA was sequenced in the UTMB NGS Core and aligned using bowtie. RESULTS/ANTICIPATED RESULTS: The use of a single protocol to capture whole viral genomes including UTRs for multiple viruses from different sample collection styles is ideal for arboviruses. Primers for multiple viruses were pooled and used to sequence mosquito pools. The Tiled ClickSeq method captured whole viral genomes without the need for host depletion. UTRs were captured even when the viral strain used for primer design differed from the resulting strain. Discreet variants were captured in both the hypervariable nsP3 region and the UTR in the patient isolates from the CHIKV outbreak compared to the 2017 outbreak. Texas WNV and SLEV outbreaks are now defined from the 2020 outbreak and can be further tracked to update public health measures and understand viral evolution. DISCUSSION/SIGNIFICANCE: UTRs impact both human and mosquito fitness, leading to further outbreaks. Tiled ClickSeq aims to capture whole viral genomes with a method and cost that can be implemented by public health researchers to understand disease evolution as it happens to update both public health and basic virology to the effects of evolution on arboviruses.
232 Psychotropic Medication Use Before Cancer Diagnosis Among US Adolescents and Young Adults
Authors: Onasanya Oluwadamilola , dosReis Susan , Castillo Wendy Camelo
Published: April 2022

OBJECTIVES/GOALS: To describe the prevalence of, and factors associated with, psychotropic medication use before cancer diagnosis (solid tumor cancer, lymphoma or leukemia) among AYAs 15 to 39 years of age in the US. METHODS/STUDY POPULATION: Retrospective cohort study in a 10% sample of claims from the IQVIA PharMetricsÂ® Plus for Academics (2006-2020). We included AYAs with no prior cancer diagnosis codes 9 months before their index date – defined as the first of â‰¥2 ICD-9/10-CM primary diagnosis codes for cancer occurring â‰¤60 days apart. We defined psychotropic use as a claim for an antidepressant, anxiolytic/sedative-hypnotic, mood stabilizer, stimulant or antipsychotic medication. Prevalence of psychotropic use overall and by class, was estimated as the proportion of AYAs with at least one claim for a psychotropic in the 9-months prior to the index date. Using Chi-square and T-tests, we compared demographic characteristics, prevalence of mental health disorders, chronic pain and cancer type between psychotropic users and non-users. RESULTS/ANTICIPATED RESULTS: We identified 6,257 AYAs with cancer (thyroid 17%, breast 13%, melanoma 13%), 64% female, mean age 31 (SD 6) years. Twenty-four percent (n=1,506) used a psychotropic in the 9 months prior to the index date. Psychotropic classes used were antidepressants 15%, anxiolytic/sedative-hypnotics 11%, stimulants 3%, mood stabilizers 2% and antipsychotics 1%. Psychotropic use was higher among females than males (27% vs 19%, p <.001), older than younger AYAs (35 to 39 years-old: 26% vs 15 to 19 years-old: 16%, p <.001). Anxiety (25% vs 4%), depression (22% vs 3%) and chronic pain (17% vs 8%) were more common among those with psychotropic use pre-cancer diagnosis (all p <.001). The proportion of AYAs diagnosed with brain cancer was higher among psychotropic users than non-users (7% vs 5%, p <.001). DISCUSSION/SIGNIFICANCE: One in four US AYAs used a psychotropic medication prior to being diagnosed with cancer. Understanding psychotropic medication management patterns for these patients before cancer treatment may help inform comprehensive care.
236 Optimizing Haploidentical Donor Selection for Pediatric Hematopoietic Cell Transplant
Authors: Liberio Nicole , Shaw Bronwen , Yanik Greg , Qayed Muna , Schultz Kirk , Broglie Larisa
Published: April 2022

OBJECTIVES/GOALS: Patients who require a hematopoietic cell transplant (HCT) and dont have an HLA-matched related or unrelated donor may rely on a haploidentical donor. The optimal haploidentical donor and guidance for selection is limited. We aim to determine how donor characteristics affect outcomes following haploidentical-HCT for pediatric patients. METHODS/STUDY POPULATION: This is a retrospective cohort study evaluating the effect of donor age and relationship on post-HCT outcomes in children (0-18y) from 2008-2018. Multivariable logistic regression analysis will identify if donor age or donor relationship affect the development of graft-versus-host-disease (GVHD), while adjusting for other patient, donor, and transplant related variables. Two-year overall survival & event-free survival will be determined using Kaplan-Meier curves, stratified by donor age group and donor relationship, and compared by log-rank testing. Sub-analyses will be performed for myeloablative transplants and reduced intensity conditioning, as well as for malignant and non-malignant diseases. RESULTS/ANTICIPATED RESULTS: Our primary aim to is determine the effect of donor age and the effect of donor relationship to patient on the development of GVHD. We hypothesize that utilization of a younger donor will decrease the incidence of GVHD. Further, we hypothesize that utilizing a sibling haploidentical donor will result in less GVHD than a parental donor. Secondary aims include evaluating the effect of donor age and donor relationship on overall survival, event-free survival, non-relapse mortality, relapse, graft failure and time to engraftment. The results of this study will help us to develop criteria for optimal haploidentical donor selection. If donor selection is optimized, this could result in improved outcomes following haploidentical transplants. DISCUSSION/SIGNIFICANCE: Haploidentical donors are increasingly used as many patients, especially ethnic minorities, do not have an HLA-matched donor. This will be the largest study of haploidentical HCT in children. The data gathered will allow us to identify important donor characteristics to help guide physician decision-making when choosing a haploidentical donor.
242 Characterization of Maternal Stress During Pregnancy
Authors: Dhaliwal Satvinder K. , Wilkening Greta , Lee-Winn Angela , Glueck Deborah , Dabelea Dana , Perng Wei
Published: April 2022

OBJECTIVES/GOALS: 1. To characterize domains of maternal psychosocial stress from the Edinburgh Postnatal Depression Scale (EPDS) and Cohens Perceived Stress Scale (PSS) administered during pregnancy using principal components analysis (PCA). 2. To identify sociodemographic, perinatal, and lifestyle correlates of maternal psychosocial stress domains. METHODS/STUDY POPULATION: Using data from 1,079 pregnant women in the Healthy Start Study who completed both the EPDS and PSS in early pregnancy, we ran PCA and retained factors representative of uncorrelated domains of maternal psychosocial stress based on the Scree plot and Eigenvalues >1. We then used linear regression to identify sociodemographic, perinatal, and lifestyle correlates of each maternal stress domain, followed by multivariable models that mutually adjusted for all characteristics that were statistically significant at alpha = 0.10. RESULTS/ANTICIPATED RESULTS: We identified three domains of maternal psychosocial stress based on PCA results: Feeling Overwhelmed (Domain 1), Anhedonia (Domain 2), and Lack of Control (Domain 3). In unadjusted analyses, lower household income and poor diet quality were associated with higher scores for all three domains. In adjusted analyses, lower household income, being multiparous, inadequate or excessive GWG, and poor diet quality were associated with Feeling Overwhelmed. Older age, Hispanic ethnicity, and poor diet quality were associated with Anhedonia. Non-Hispanic, Black race/ethnicity, lower educational attainment, having a partner born outside the US, larger household size, receiving public assistance, and smoking during pregnancy were associated with Lack of Control. DISCUSSION/SIGNIFICANCE: We identify three unique domains of maternal psychosocial stress that are differentially related to sociodemographic, perinatal, and lifestyle characteristics. Correlates of stress domains shed light on upstream determinants and biological and psychosocial mechanisms through which experiences of stress manifest.
248 Use of a Propensity Score to Examine Association between Rates of In-Hospital Decongestion and Mortality and Cardiovascular Outcomes Among Patients admitted for Acute Heart Failure
Authors: McCallum Wendy , Tighiouart Hocine , Testani Jeffrey M. , Griffin Matthew , Konstam Marvin A. , Udelson James E. , Sarnak Mark J.
Published: April 2022

OBJECTIVES/GOALS: Decongestion, or fluid removal, is an important goal in the management of acute heart failure (AHF) among patients with heart failure with reduced ejection fraction (HFrEF). We sought to examine whether the rate of decongestion is associated with mortality and cardiovascular (CV) outcomes. METHODS/STUDY POPULATION: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial (n=4133), we evaluated the rate of decongestion by using linear mixed models to derive the in-hospital slope of b-type natriuretic peptide (BNP) and hematocrit as proxies of volume overload and hemoconcentration, respectively. A propensity score was developed to match patients from the quartile with most rapid rates of decongestion to the three quartiles with slower rates. Cox proportional hazards regression models were fitted to assess the association between rate of decongestion with risk of all-cause mortality and a composite of CV mortality or AHF hospitalization. RESULTS/ANTICIPATED RESULTS: Slower rates of in-hospital decongestion were associated with increased risk of both outcomes over a median 10-month follow-up. Those with slower rates of BNP decline, in comparison to the propensity-score matched patients with the most rapid rates of BNP decline, had higher hazards of mortality (HR=1.73 [1.23, 2.42]) and the composite outcome (HR=1.48 [1.18, 1.86]). Those with slower rates of hematocrit increase, in comparison to the propensity-score matched patients with the most rapid rates of hematocrit increase, showed a trend toward higher hazard of mortality (HR=1.17 [0.95, 1.43]) and an increased risk of the composite outcome (HR=1.26 [1.08, 1.47]). DISCUSSION/SIGNIFICANCE: Among patients with HFrEF admitted for AHF, slower rates of decongestion are associated with increased risk of mortality, CV mortality and AHF hospitalization. It remains unknown whether more rapid decongestion provides cardiovascular benefit or if it serves as a proxy for less treatment resistant heart failure.
254 Markers of Neurodegeneration Associate with Worse Performance of Complex Daily Tasks
Authors: Keleman Audrey A. , Bollinger Rebecca M. , Ances Beau M. , Stark Susan L.
Published: April 2022

OBJECTIVES/GOALS: In preclinical Alzheimer disease (AD), biomarkers such as amyloid protein, decreased hippocampal volume, and weaker network connections are apparent in the brain, but memory symptoms assessed by paper and pencil tests have not yet appeared. Performance tests of complex daily tasks may be more sensitive and detect early functional impairment. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing cohort study. Cognitively normal (CN) older adults completed 3 standardized complex daily tasks from the Performance Assessment of Self-Care Skills (PASS) in their home. Biomarkers of AD were assessed within 2-3 years of an individuals completion of the PASS and include: amyloid accumulation, hippocampal volume, and resting-state functional connectivity (rs-fc) signature. Associations between performance on PASS tasks and the biomarkers of AD were quantified by Pearson point-biserial correlations, as biomarker data was normally distributed and PASS scores fell between two categories (acceptable or optimal quality of performance). Correlations with a 95% confidence interval (CI) that did not include 0 were considered significant. RESULTS/ANTICIPATED RESULTS: 161 CN participants (mean age 74.3 years, 55% female) were included. Mean score on the 3 PASS tasks ranged from 2.67 [standard deviation (SD): .47] to 2.90 (SD: .16) out of 3. Mean amyloid PET on Centiloid scale was 23.8 (SD: 34.8); mean partial volume corrected hippocampal volume was 7448.5 (SD: 909.8); mean rs-fc signature was .805 (SD: .164). After controlling for age and gender, worse performance of complex daily activities was associated with smaller hippocampal volumes (Pearsons r: 0.302, p=.02, 95% CI: .179 to .416) and weaker rs-fc network connections (Pearsons r: 0.276, p=.03, 95% CI: .078 to .453), but not amyloid accumulation. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks may be associated with markers of neurodegeneration. These findings could lead to a better understanding of functional changes that may occur during the preclinical stage of AD.
259 Proton pump inhibitor use is not significantly associated with severe COVID-19 related outcomes after extensive covariate adjustment
Authors: Shah Shailja C. , Halvorson Alese E. , McBay Brandon , Dorn Chad , Wilson Otis , Denton Jason , Tuteja Sony , Chang Kyong-Mi , Cho Kelly , Hauger Richard L. , Suzuki Ayako , Hunt Christine M. , Siew Edward , Matheny Michael E. , Hung Adriana , Greevy Robert A. , Roumie Christianne L.
Published: April 2022

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.
266 Inpatient Quality Indicators Risk-Adjustment Using Interactions Selected by Machine Learning Methods
Authors: Ray Monika , Romano Patrick S.
Published: April 2022

OBJECTIVES/GOALS: Predictive models for health outcomes often have poor calibration potentially due to interactions that are ignored by standard methods. Using AHRQ models for Inpatient Quality Indicator (IQI) 11 Abdominal Aortic Aneurysm Repair and IQI 09 Pancreatic Resection mortality, we hypothesize that identifying interactions may improve model calibration. METHODS/STUDY POPULATION: We used adult discharge data from 16 states obtained from AHRQ Healthcare Cost and Utilization Project (State Inpatient Database), California Department of Health Care Access and Information, and New York State Department of Health. We used AHRQ’s v2021-1 Clinical Classifications Software Refined (CCSR) with present on admission flags to create features for risk-adjustment. We compared the performance of Least absolute shrinkage and selection operator (LASSO) model and first-order interaction models estimated using Hierarchical Group Lasso Regression (HGLR), after splitting the data into training and test sets. C-statistics, area under the precision-recall curve and Hosmer-Lemeshow calibration plots are reported. Finally, logistic regression models with selected CCSRs were evaluated on the test set. RESULTS/ANTICIPATED RESULTS: IQI 11 has four strata: open and endovascular repair of ruptured aneurysms (39% and 21% mortality, respectively); open and endovascular repair of unruptured aneurysms (6% and 0.8% mortality, respectively). IQI 09 has two strata: with and without pancreatic cancer (2% and 2.5% mortality, respectively). Comparing the HGLR model (with interaction effects) with Lasso models (without interactions), we noticed meaningful improvements in discrimination and calibration. However, for IQI 09, the extremely low mortality rate did not result in good HGLR or LASSO models. Interactions involving CCSRs could be identified using the novel HGLR method, which improved model performance given a heterogeneous population in IQI 11 with a mix of high and low event rates, unlike the more homogeneous patient population in IQI 09. DISCUSSION/SIGNIFICANCE: Standard implementations of regression models fail to address critical issues that arise in healthcare data – (a) quadratic explosion of potential interactions that cannot be manually identified, and (b) categorical variables with multiple levels or values (e.g., age categories). We propose innovative use of HGLR to robustly address these issues.
275 Cost and Benefit Tradeoffs of Preconception Fibroid Treatment with Myomectomy on Obstetric Outcomes: A Cost-Effectiveness Analysis
Authors: Colson-Fearon Darien , Drabo Emmanuel Fulgence , Coleman Jenell
Published: April 2022

OBJECTIVES/GOALS: Fibroids during pregnancy are associated with worse obstetric outcomes. However, theres no recommendation to guide counseling. We aimed to assess the cost-effectiveness of (1) treating prevalent fibroids before pregnancy and (2) screening and treatment of fibroids against the outcomes of postpartum hemorrhage (PPH) and fetal malpresentation. METHODS/STUDY POPULATION: A decision tree model was used to compare (1) preconception myomectomy for prevalent fibroids, without treatment and (2) preconception myomectomy for prevalent cases and universal ultrasound screening with subsequent myomectomy for incident cases. Probabilities and costs, calculated from the U.S. healthcare sectors perspective, were derived from the literature. Effectiveness was measured in incident PPH or malpresentation cases per 1,000 in the population. The incremental cost-effectiveness ratio (ICER) was measured in incremental cost per case averted. One-way and probabilistic sensitivity analyses were conducted to identify influential parameters and assess the impact of parameter uncertainty. RESULTS/ANTICIPATED RESULTS: Treating known fibroids prior to pregnancy averted 65.7 PPH cases at the cost of $8,773,094 and 91.08 malpresentations at the cost of $8,163,315 (ICERs, $133,532 vs $89,628 per case averted, respectively). Universal fibroid screening with treatment of incident and prevalent cases averted 7.34 PPH cases at the cost of $3,725,619 and 2.7 malpresentations at the cost of $3,477,033 (ICERs, US$507,450 vs US$1,335,771 per case averted, respectively). Sensitivity analyses showed cost-effectiveness improved with decreased cost of myomectomy and increased proportion of prevalent and incident cases. DISCUSSION/SIGNIFICANCE: Treatment alone costs $133,532 per PPH averted and $89,628 per malpresentation averted. Likewise, screening with treatment costs $507,450 per PPH averted and $1,335,771 per malpresentation averted. Additionally, ICERs may decrease when focusing on populations where fibroid incidence and prevalence is higher, for example, among Black women.
277 Heart Failure Clinical Trial Enrollment at a Rural Satellite Hospital
Authors: Abbate Antonio , Sedhai Yub Raj , Patel Nimesh K. , Mihalick Virginia , Talasaz Azita , Thomas Georgia , Denlinger Bethany L. , Damonte Juan I. , Buono Marco Del , Federmann Emily , Hardin Mary , Ibe Ikenna , Harmon Mary , Van Tassell Benjamin , Abbate Antonio , Roberts James C.
Published: April 2022

OBJECTIVES/GOALS: Heart failure (HF) is a clinical condition that notably affects the lives of patients in rural areas. The partnering of a rural satellite hospital with an urban academic medical center may provide geographically underrepresented populations with HF an opportunity to access controlled clinical trials (CCTs). METHODS/STUDY POPULATION: We report our experience in screening, consenting and enrolling subjects at the VCU Health Community Memorial Hospital (VCU-CMH) in rural South Hill, Virginia, that is part of the larger VCU Health network, with the lead institution being VCU Health Medical College of Virginia Hospitals (VCU-MCV), Richmond, VA. Subjects were enrolled in a clinical trial sponsored by the National Institutes of Health (ClinicalTrials.gov: NCT03797001) and assigned to treatment with an anti-inflammatory drug for HF or placebo. We used the electronic health record and remote guidance and oversight from the VCU-MCV resources using a closed-loop communication network to work with local resources at the facility to perform screening, consenting and enrollment. RESULTS/ANTICIPATED RESULTS: One hundred subjects with recently decompensated HF were screened between January 2019 and August 2021, of these 61 are enrolled to date: 52 (85 %) at VCU-MCV and 9 (15%) at VCU-CMH. Of the subjects enrolled at VCU-CMH, 33% were female, 77% Black, with a mean age of 52ï‚±10 years. DISCUSSION/SIGNIFICANCE: The use of a combination of virtual/remote monitoring and guidance of local resources in this trial provides an opportunity for decentralization and access of CCTs for potential novel treatment of HF to underrepresented individuals from rural areas.
284 Explaining the Transportation Dimension of Food Access
Authors: Grover Raneitra
Published: April 2022

OBJECTIVES/GOALS: Lack of a vehicle and the distant location of supermarkets influence the ease with which people can shop for healthy foods. The aim of this qualitative study is to understand how transportation impacts food access and food purchases of Baltimore residents who do not own an automobile. METHODS/STUDY POPULATION: The Lyft Grocery Access Program was piloted in Baltimore, MD from November 2019 through September 2020. Eligible households resided in Healthy Food Priority Areas, formerly known as food deserts, in south and west Baltimore and also did not own a vehicle. Enrolled households were offered discounted Lyft rides to select supermarkets. Participants for the present study will be purposively recruited via email and phone using contact information that was provided by enrolled households during the pilot program. Each in-depth interview will be conducted via Zoom and recorded, transcribed and analyzed for themes by two trained coders. Data collection and analysis will occur simultaneously. Data collection will cease once data saturation is reached and themes will be derived from the data. RESULTS/ANTICIPATED RESULTS: This study is in progress. Anticipated themes may relate to the food environment, transportation and food access. DISCUSSION/SIGNIFICANCE: Access to healthy foods is an important determinant of health, and how food access is impacted by broader aspects of daily living such as transportation will add to the food access literature. Findings may provide new insights that can help inform food policy and transportation planning in urban communities.
298 Feasibility of A Dietary Sodium Reduction Intervention Using mHealth Technology to Improve Adherence in Hypertensive Patients
Authors: Ko Jisook , Wang Jing
Published: April 2022

OBJECTIVES/GOALS: Despite the large body of evidence concerning the effects of dietary interventions on blood pressure, trials have often reported poor adherence to sodium restriction. We implemented the Sodium Watcher Program-Hypertension (SWPH) program using digital self-monitoring. The purpose of this study was to determine the feasibility of the SWPH program. METHODS/STUDY POPULATION: The SWPH is a pilot two-arm, 2-month randomized controlled trial that enrolls adults with hypertension. The intervention group received personalized feedback on dietary sodium intake and BP and the control group participants received usual care for hypertension. Both groups participated in digital self-monitoring of daily diet and BP over 8 weeks. The primary outcomes were adherence to dietary sodium intake as captured by 24-hour urinary sodium excretion and BP at baseline and at the 2-month follow-up. Feasibility assessment included adherence to dietary sodium intake monitoring and in-home BP monitoring measured by the percentage of days that participant logged their food intake and in-home BP. The preliminary effect on the outcome variables was tested by using a repeated-measures analysis of variance. RESULTS/ANTICIPATED RESULTS: In this feasibility study, we included data from 12 participants (n=9 SWPH, n=3 control) who completed all phases of the study. The patients median age was 56.5 years and 70% were female. The mean baseline BP was 142.7/87.5 mmHg. The mean 24-hour urine sodium of 4853.0 mg (SD=1639.9 mg) with 80% having 24-hour urine sodium >2300 mg at baseline. SWPH group had lower systolic (baseline 142.4 mmHg vs follow-up 124.1 mmHg, p<0.001), diastolic (baseline 87.1 mmHg vs follow-up 77.5 mmHg, p<0.05) BP, and 24-hour urine sodium (baseline 3790.4 mg vs 2609.7 mg, p<0.05) compared with control group. Compared with the control group, the SWPH group had significantly more eligible days of digital food log usage (control 80.0% vs intervention 98.2%, p<0.01) and in-home BP monitor usage (control 77.6% vs intervention 94.6%, p<0.01). DISCUSSION/SIGNIFICANCE: Millions of Americans remain in need of effective interventions to manage their hypertension. Innovative and accessible strategies to sustain a low sodium diet intervention are needed for the majority of individuals not following the low sodium diet. By leveraging digital self-monitoring, a low sodium diet program was feasible and in reducing BP.