Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&sort=principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1393&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15414", "attributes": { "award_id": "1U24AI183849-01", "title": "The Bacterial and Viral Bioinformatics Resource Center (BV-BRC)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32022, "first_name": "WIRIYA", "last_name": "Rutvisuttinunt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-18", "end_date": "2029-06-30", "award_amount": 3600000, "principal_investigator": { "id": 32023, "first_name": "RICK L.", "last_name": "STEVENS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 289, "ror": "https://ror.org/024mw5h28", "name": "University of Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "The mission of the NIH/NIAID Bioinformatics Resource Center (BRC) program is to accelerate basic and applied infectious disease research by providing access to cutting edge bioinformatic tools, knowledgebases, and expertise, ensuring that our knowledge of pathogenesis can be translated into diagnostics, therapeutics and a public health response that mitigates the morbidity and mortality resulting from infectious diseases. The current NIH/NIAID-funded Bacterial and Viral Bioinformatics Resource Center (BV-BRC; Contract No. 75N93019C00076) supported this mission by providing a bioinformatics knowledgebase and analysis platform covering all bacterial and viral pathogens. In response to the NIAID notice of funding opportunity, RFA-AI-23- 032, our proposal intends to maintain, improve, and expand the BV-BRC to combat future infectious disease threats, while maintaining our commitment to enhance diversity, equity, inclusion, and accessibility, fostering a more inclusive scientific community, and ensuring equitable access to bioinformatics resources. BV-BRC will support bacteria, archaea, viruses, bacteriophages, as well as metagenomic analyses, with particular emphasis on the microbiomes and viromes related to infectious disease and public health. BV-BRC will continue to support the basic scientific research necessary to understand the biology of these organisms, their pathogenesis, and disease processes; support development of diagnostics and therapeutics to combat pathogenic organisms; and provide a rapid response framework to effectively deal with the inevitable and unpredictable outbreaks and pandemics. To support these overarching goals, we propose to extend and enhance BV-BRC through the following four key elements: 1) Maintain and enhance the BV-BRC knowledgebase to support exponential growth of data and usage and provide integrated access to omics data, metadata, analysis services and visualization tools, private user workspace, and user documentation to allow users to analyze public and private data and share or publish results; 2) Develop innovative tools and technologies to provide comprehensive services for viral and bacterial bioinformatics, metagenomics, drug development, and developing AI-driven natural language-based user interface for interacting with data and tools, with emphasis on improving user experience; 3) Offer critical bioinformatics expertise, outreach, and training to the community, with emphasis on fostering opportunities for students and researchers from minority and underserved communities by providing freely accessible training material and conducting training for instructors from underrepresented institutions, with particular focus on Minority Serving Institutions (MSIs); and 4) Provide cutting-edge support to rapidly respond to emerging needs, outbreaks, and pandemic preparedness by building on the tools and procedures developed during COVID-19 and Mpox pandemics and enhancing them to improve readiness and response to future outbreaks and pandemics.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15417", "attributes": { "award_id": "1R01AI188576-01", "title": "SCH: Improving Early Prediction and Decision-Making for Sepsis with Human-AI Collaboration", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)", "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23983, "first_name": "Nancy L.", "last_name": "Ernst", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-17", "end_date": "2028-05-31", "award_amount": 300000, "principal_investigator": { "id": 32024, "first_name": "Jeffrey M", "last_name": "Caterino", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 29277, "first_name": "Ping", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32025, "first_name": "Lace M.", "last_name": "Padilla", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32026, "first_name": "Dakuo", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 778, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Early prediction and timely decision-making of acute diseases are critical to enabling early intervention and improving clinical outcomes (for example, a sepsis patient may benefit from a 4% higher chance of survival if diagnosed 1 hour earlier). Developing machine learning (ML) models for clinical decision-making on Electronic Health Records (EHRs) presents several significant challenges: 1) existing models are trained mostly on EHR data from intensive care units (ICUs), which are not generalizable for sepsis onsets in emergency rooms and hospital wards; 2) most existing tools simply output prediction result as a risk score, without sufficient explanation or confidence interval for it, which is not trustworthy for physicians; 3) existing systems often ignore the human workflow by neither providing actionable insights to physicians nor enabling interactive explorations from physicians, which limits their clinical usages. To address these challenges, we propose a Human-Centered Artificial Intelligence (HCAI) system to collaborate with human domain experts in the high-stake and high-uncertainty decision-making process. Specifically, we 1) create a deidentified database with complete visits and long-term EHR history for patients with sepsis risk; 2) develop early sepsis risk prediction models with uncertainty quantification and active sensing; 3) design and implement a physician-centered AI prediction module and user interface for early sepsis human-AI decision making; and 4) design and conduct controlled usability evaluations to quantitatively and qualitatively measure the clinical outcome and user satisfaction. This project integrates human-AI collaboration design, novel ML algorithms, and data visualization tools for improving early prediction and decision-making for sepsis, which hold great promise for leading new insights into human-AI systems for clinical decision support. RELEVANCE (See instructions): Sepsis, which can be caused by bacteria, fungi, or in the case of COVID-19, a virus, is a life-threatening condition with high mortality rates and expensive treatment costs. This project will develop a physician- centered deep-learning algorithm to predict sepsis onset and a user interface for effective human-AI collaboration. As a result, this work relates to the mission of the NIAID and will make a relevant public health impact by delivering early, life-saving care to the bedside of sepsis patients, and will lead to a useful clinical decision support tool for physicians.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15418", "attributes": { "award_id": "1R01HL175474-01", "title": "Non-conventional signaling by α5 integrin in blood and endothelial cells", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22468, "first_name": "Deborah", "last_name": "Philp", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-15", "end_date": "2028-06-30", "award_amount": 718854, "principal_investigator": { "id": 32027, "first_name": "Jieqing", "last_name": "Zhu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1016, "ror": "", "name": "VERSITI WISCONSIN, INC.", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "– Integrins interact with their ligands to induce intracellular signals that mediate cellular activities such as cell adhesion, spreading, and migration, which are the essential cellular activities for the function of blood and endothelial cells. These signaling events are typically mediated by the cytoplasmic tail of integrin β subunit, while the role of α integrin cytoplasmic tail in integrin function remains relatively underexplored. Our research found that the fibronectin receptor integrin α5β1, via its α cytoplasmic tail, is involved in the formation of tunneling nanotubes (TNTs), a novel type of cellular structure for cell-to-cell communication. Remarkably, our research found that the α5β1-mediated TNT formation can be induced by the spike protein of coronavirus SARS- CoV-2. We observed the spike-induced and α5-dependent TNT formation in model cell lines and primary human blood and endothelial cells. Furthermore, we found that α5β1 integrin can mediate the spike-induced proinflammatory response in human blood and endothelial cells, which may contribute to the thrombotic events in COVID-19. TNTs are long actin-rich cell membrane protrusions that have been increasingly recognized as functional subcellular structures for long-distance dynamic intercellular connection. Functioning as conduits between connected cells, TNTs can transport cytoplasmic components like small molecules, proteins, vesicles, and mitochondria intercellularly. Accumulating evidence suggests that TNTs are involved in the progress of many pathological conditions such as cancer, inflammation, and neurodegenerative diseases. Bacteria and virus pathogens also exploit TNTs for cell-to-cell transmission. TNTs can form under cell stress conditions such as inflammation and virus infection. However, the cellular mechanisms regulating TNT formation remain largely unknown. This is mainly because little to nothing is known about the cell surface receptors directly responsible for TNT biogenesis. Our discovery of α5β1 integrin as a functional signaling receptor for TNT formation provides a powerful platform for investigating TNT biology. Mechanistically, we found that both α5β1-mediated TNT formation and proinflammatory response require the participation of α5 cytoplasmic tail, suggesting that these two processes are interconnected events. Moreover, our protein interaction data suggest a direct binding between α5β1 and the spike protein, which is independent of the classical integrin recognition Arg-Gly-Asp (RGD) motif. Based on these promising data, this application aims to elucidate the cellular mechanisms governing the non-conventional signaling function of α5β1 integrin in TNT formation and inflammation in blood and endothelial cells. Multifaced biochemical, biophysical, structural and cell biology approaches will be used to identify intracellular molecules and signaling pathways involved in the α5β1-mediated TNT formation (Aim 1) and inflammation (Aim 2) and to characterize the non-RGD dependent α5β1 and ligand interaction (Aim 3). The outcome of this study will advance both integrin and TNT biology and uncover potential therapeutic targets for modulating TNTs and inflammation in various diseases.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15420", "attributes": { "award_id": "3U01AA026817-05S1", "title": "S-adenosylmethionine treatment in alcoholic cirrhosis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 10229, "first_name": "Gary", "last_name": "Murray", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-01", "end_date": "2025-08-31", "award_amount": 273786, "principal_investigator": { "id": 32028, "first_name": "Bin", "last_name": "Gao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32029, "first_name": "Suthat", "last_name": "Liangpunsakul", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 32030, "first_name": "Shelly Chi-Loo", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2527, "ror": "https://ror.org/03eftgw80", "name": "Indiana University Indianapolis", "address": "", "city": "", "state": "IN", "zip": "", "country": "United States", "approved": true }, "abstract": "Alcoholic cirrhosis is a leading cause of morbidity and mortality in the US. One of the key drivers in its pathogenesis is the reduction in hepatic methionine adenosyltransferase 1A (MAT1A) expression resulting in the reduction in hepatic S-adenosylmethionine (SAMe) levels. The reduction in SAMe level leads to several adverse intracellular consequences, which include promoting the inflammatory cascades in immune cells such as macrophages by lipopolysaccharides (LPS), oxidative stress and endoplasmic reticulum (ER) stress. This project involves two academic centers in the United States (Cedars-Sinai Medical Center in Los Angeles and Indiana University Hospital), a research institute in Spain (CIC bioGUNE), and NIAAA intramural liver research scientist (Dr. Bin Gao) to examine SAMe in humans with alcoholic cirrhosis. We proposed a randomized double-blind placebo controlled trial to determine the efficacy of SAMe (1,200 mg/day given in two divided dose) and its mechanistic effects in patients with alcoholic cirrhosis (Child class A and B) in the real world setting. The primary endpoint will be the mortality of any causes between groups. The target enrollment of our clinical trial is 196 participants (176 patients with alcohol-associated cirrhosis and 20 controls). The approval for funding of our study started on September 20, 2019. However, our study was significantly impacted by the COVID-19 pandemic in 2020 and 2021. The administrative hold on research activities due to the pandemic prohibited us to enroll patients as we anticipated. To date, 112 participants (~57%) were enrolled. Our enrollment continues to improve and meet the monthly target enrollment starting around the beginning of Yr 3 of the project (~September 2021, the time when the overall COVID-19 pandemic was improving). Given the trajectory of the enrollment, we anticipated that we should be able to complete our enrollment around August 2026. Our current funding ends on 8/31/24. This supplemental application is to allow us to complete the clinical trial, currently being funded by 1U01AA02681.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15424", "attributes": { "award_id": "1SB1AG087755-01", "title": "Ryan® CompanionBot for Assisting Older Adults with Early-Stage Alzheimer's Disease and Dementia", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 32031, "first_name": "DINESH", "last_name": "John", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-03-01", "end_date": "2026-05-31", "award_amount": 1424731, "principal_investigator": { "id": 32032, "first_name": "Mohammad", "last_name": "Mahoor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2541, "ror": "", "name": "DREAM FACE TECHNOLOGIES, LLC", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The population of Americans age 65 years or older will increase from 58 million in 2021 to 88 million by 2050. By 2050, nearly 14 million older adults are expected to have AD/ADRD. For these individuals, significant care is required, and that care is often provided by family members. A 2022 study estimated that 11 million American family members are providing 16 billion hours of care valued at more than $272 billion. Senior care facilities are another option. The COVID-19 pandemic severely affected senior care facility residents. Despite representing only about 1% of the total population in the U.S., COVID-19 deaths in senior care facilities have made up nearly 40% of total COVID-19 deaths. Senior care facilities often face staffing shortages during and after the pandemic. Currently, 3 in 5 assisted living facilities are concerned that they may have to close due to staffing shortages. The situation with these two caregiving options is alarming; increasing demand for caregivers coupled with short supply has led to higher costs, unfilled needs, and fierce competition for resources. While computer technologies, such as wearable devices, are beginning to partially alleviate the shortage of caregivers, more powerful and personalized tools are needed. To address this urgent need, DreamFace Technologies, LLC invented Ryan® CompanionBot, a novel humanoid socially-assistive robot expertly tailored to the specific needs of older adults with early-stage AD/ADRD. The development of Ryan®, with the support of one NSF and two NIA/NIH SBIR grants, has been informed by 100 customer interviews and several subsequent field tests and clinical trials involving more than 50 older adults with early-stage AD/ADRD. In these tests, Ryan® has effectively delivered companionship, engaging conversations, physical and mental stimulation, daily activity reminders, and valuable assistance to the AD/ADRD-afflicted seniors powered by state-of-the-art artificial intelligence technologies such as facial expression recognition and synthesis, brain games, and empathic conversations while we also learned about several additional capabilities required for commercial success. Furthermore, in the pre-launch phase of the initial version of Ryan®, it has been deployed on a subscription basis at the esteemed senior care facility, Morningstar, which has served as a valuable beta site. In this Commercialization Readiness Pilot (CRP) program, we plan to complete the preparation of Ryan® for full commercialization. Specifically, we will: (1) refine and enhance Ryan®'s software and hardware, making mass manufacturing more efficient and cost-effective while making Ryan®'s operation more robust and easier to adopt by family members, staff, administrators, and caregivers in senior care facilities, (2) develop robust, integrated marketing and sales strategies, (3) develop an Intellectual Property strategy and required privacy policy and legal documents and (4) develop a financing and fundraising strategy for the successful commercialization of Ryan®. Upon the completion of the CRP project, we will have all the essential elements in place for the full commercialization of Ryan® as a transformative solution for senior care, benefiting both individuals diagnosed with early-stage AD/ADRD and caregivers alike.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15425", "attributes": { "award_id": "5G08LM014107-03", "title": "Reading Bees: Adapting and Testing a Mobile App Designed to Empower Families to Read more Interactively with Children in Distinct Geographical and Cultural Contexts", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Library of Medicine (NLM)" ], "program_reference_codes": [], "program_officials": [ { "id": 26724, "first_name": "Meryl", "last_name": "Sufian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-01-23", "end_date": "2026-07-31", "award_amount": 149693, "principal_investigator": { "id": 32033, "first_name": "John S.", "last_name": "Hutton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1215, "ror": "", "name": "UT SOUTHWESTERN MEDICAL CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Many children arrive at kindergarten unprepared to learn to read, at-risk of falling more behind, with major inequities linked to race, geography and poverty (rates >50%). These are amplified during disruptions such as COVID, when access to information and resources is perturbed. Low proficiency is strongly linked to adverse school, vocational and health outcomes, with estimated costs >$350 billion/year. As parents are a child’s “first and most important teachers,” home reading routines have a large impact on these outcomes. However, there are wide disparities in these between high- and low-resource families, fueled by household stressors, cultural differences, literacy challenges and other factors. Marginalized families also often face barriers to access of reliable literacy-promoting information, programs and resources, worsening disparities. Given trusted access to families when parenting routines are shaped, health providers are poised to help mitigate these barriers, yet guidance tends to be general, inconsistent and can fade-out at home. The objective of the proposed project is to enhance, “localize” and test a new, free mobile app designed to provide reliable shared reading guidance and resources for parents (Reading Bees; RB) in an efficient, engaging way. The rationale is that no similar approach exists, RB is free and designed to enhance existing programs, and there is evidence that its features will be useful and effective. Content is evidence-based and has been co-developed with input from community stakeholders and families from disadvantaged backgrounds. Core principles are clarity, credibility, flexibility (e.g., parents set their own goals), responsiveness (child age, family concerns, ZIP), engaging content (tips, videos, resources) and positive reinforcement (“LitCoin” awards). The long-term goal of this project is to use RB to help improve reading and literacy outcomes. To achieve this, teams in 3 culturally distinct areas (OH, WV, FL) will collaborate in a 3-year project. Content will first be added to address needs in each community: lists of local reading-related resources curated by area stakeholders and a Spanish language version of RB. Enhanced, “localized” RB will then be tested with parents in each area, first through focus groups to gauge usefulness and guide refinement, and then by providing RB to parents (ages 0-6) during clinic visits and measuring use over the next 2 months. Outcome measures involve feasibility, acceptance and useflness. The central hypothesis is that local stakeholders will be engaged by the opportunity to highlight resources in their area; families will rate RB content as useful and use RB often, especially to earn LitCoin awards; and improved access to information and resources will fuel better reading and literacy outcomes. This work is significant and innovative as it involves a tech-enabled, user-centered approach that is scalable within existing pediatric, library and program infrastructure and empowers parents to read more interactively and access reliable information. The expected outcome is that this work will provide vital enhancements to RB, show feasibility and usefulness and provide a flexible, collaborative model to “localize” and scale use of RB into other areas.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15426", "attributes": { "award_id": "7G08LM014107-02", "title": "Reading Bees: Adapting and Testing a Mobile App Designed to Empower Families to Read more Interactively with Children in Distinct Geographical and Cultural Contexts", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Library of Medicine (NLM)" ], "program_reference_codes": [], "program_officials": [ { "id": 26724, "first_name": "Meryl", "last_name": "Sufian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-01-23", "end_date": "2026-07-31", "award_amount": 120271, "principal_investigator": { "id": 32033, "first_name": "John S.", "last_name": "Hutton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1215, "ror": "", "name": "UT SOUTHWESTERN MEDICAL CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Many children arrive at kindergarten unprepared to learn to read, at-risk of falling more behind, with major inequities linked to race, geography and poverty (rates >50%). These are amplified during disruptions such as COVID, when access to information and resources is perturbed. Low proficiency is strongly linked to adverse school, vocational and health outcomes, with estimated costs >$350 billion/year. As parents are a child’s “first and most important teachers,” home reading routines have a large impact on these outcomes. However, there are wide disparities in these between high- and low-resource families, fueled by household stressors, cultural differences, literacy challenges and other factors. Marginalized families also often face barriers to access of reliable literacy-promoting information, programs and resources, worsening disparities. Given trusted access to families when parenting routines are shaped, health providers are poised to help mitigate these barriers, yet guidance tends to be general, inconsistent and can fade-out at home. The objective of the proposed project is to enhance, “localize” and test a new, free mobile app designed to provide reliable shared reading guidance and resources for parents (Reading Bees; RB) in an efficient, engaging way. The rationale is that no similar approach exists, RB is free and designed to enhance existing programs, and there is evidence that its features will be useful and effective. Content is evidence-based and has been co-developed with input from community stakeholders and families from disadvantaged backgrounds. Core principles are clarity, credibility, flexibility (e.g., parents set their own goals), responsiveness (child age, family concerns, ZIP), engaging content (tips, videos, resources) and positive reinforcement (“LitCoin” awards). The long-term goal of this project is to use RB to help improve reading and literacy outcomes. To achieve this, teams in 3 culturally distinct areas (OH, WV, FL) will collaborate in a 3-year project. Content will first be added to address needs in each community: lists of local reading-related resources curated by area stakeholders and a Spanish language version of RB. Enhanced, “localized” RB will then be tested with parents in each area, first through focus groups to gauge usefulness and guide refinement, and then by providing RB to parents (ages 0-6) during clinic visits and measuring use over the next 2 months. Outcome measures involve feasibility, acceptance and useflness. The central hypothesis is that local stakeholders will be engaged by the opportunity to highlight resources in their area; families will rate RB content as useful and use RB often, especially to earn LitCoin awards; and improved access to information and resources will fuel better reading and literacy outcomes. This work is significant and innovative as it involves a tech-enabled, user-centered approach that is scalable within existing pediatric, library and program infrastructure and empowers parents to read more interactively and access reliable information. The expected outcome is that this work will provide vital enhancements to RB, show feasibility and usefulness and provide a flexible, collaborative model to “localize” and scale use of RB into other areas.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15430", "attributes": { "award_id": "7I01RX004572-02", "title": "Modifying Adiposity Through Behavioral Strategies to Improve COVID-19 Rehabilitation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-11-01", "end_date": "2029-10-31", "award_amount": null, "principal_investigator": { "id": 32034, "first_name": "KATHLEEN A", "last_name": "GRIFFITH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 26754, "first_name": "ALICE S.", "last_name": "RYAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Findings of post-acute sequelae of Post-COVID Conditions (PCC) manifestations of fatigue, pain, dyspnea, and muscle weakness, provide a strong rationale for rehabilitation; yet few formal studies exist and the effects of severe acute respiratory syndrome coronavirus-2 infection on function are not well described. Notably, two- thirds of Veterans are overweight and obese, rendering excess adiposity a significant risk factor and a high- priority area related to PCC prevention and care. Obesity increases the risk of severe illness in Veterans recovering from PCC, but how it does so is not fully understood. Recent research suggests that excess adipose tissue is associated with adverse changes in adipose cellular function, and that these variations may be involved in the biology of aging and the etiology of aging- related diseases. Adipose tissue contains cells that have undergone cellular senescence, which induces inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. However, the precise role of adipose tissue cellular composition on PCC recovery is limited. Thus, we propose to evaluate the role of obesity and PCC on physical functioning, health-related quality of life (HRQOL), and systemic and adipose tissue inflammatory and cellular senescence profiles in ethnically diverse older Veterans from the Audie Murphy (San Antonio) and Baltimore VA Medical Centers. Further, we propose a randomized controlled trial to determine whether a reduction in body weight and increased physical function by a weight loss intervention (WL), including dietary modification and exercise, in obese Veterans with PCC will reduce systemic and adipose tissue inflammation and senescence, which will have important implications for PCC recovery. We will pursue the following aims: Aim 1: To compare physical function, body composition, HRQOL, PCC symptoms, and adipose tissue molecular profiling in four cohorts of Veterans at baseline: lean PCC naïve, lean with PCC, obese PCC naïve, and obese with PCC (N=150). Aim 2: To compare in Veterans with obesity: a) a 12-week randomized WL vs. weight stability (WS) intervention (30/group) on physical function, body composition, HRQOL, and PCC symptoms together with changes in the global molecular profile in adipose tissue in Veterans with PCC and b) the WL intervention in PCC naïve vs. with PCC (N=30/group) on these outcomes. Older (55-80 years) men and women Veterans will be recruited. We will perform a standard functional battery (maximal aerobic capacity [VO2max; primary outcome], usual gait speed, six min walk distance, timed up and go, and handgrip strength), body composition (dual energy x-ray absorptiometry and computed tomography scans), HRQOL (NIH PROMIS-57), and PCC symptoms (COVID-19 Yorkshire Rehabilitation Scale [C19-YRS]) and adipose tissue will be collected. Further, we will test, in a randomized controlled trial, the hypothesis that a WL intervention, compared to weight stability (WS), improves physical function, body composition, and HRQOL and reduces inflammation and senescent cell burden and to a similar extent as the PCC naïve group with obesity. A deeper understanding of the relationship between adipose tissue and PCC will likely reveal factors that predispose to or protect against aging-related functional declines. Moreover, a better understanding of the effects of a lifestyle intervention on the molecular profile of adipose tissue will help to determine how changes in adipose tissue contribute to PCC and PCC recovery. Lastly, this research will provide important mechanistic insights into how cellular senescence influences the pathophysiology of physical, mental, and social dysfunction in older Veterans. Our findings could provide evidence-based recommendations to promote this type of intervention in Veterans recovering from PCC.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15588", "attributes": { "award_id": "5I01RX004572-03", "title": "Modifying Adiposity Through Behavioral Strategies to Improve COVID-19 Rehabilitation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-11-01", "end_date": "2029-10-31", "award_amount": null, "principal_investigator": { "id": 32034, "first_name": "KATHLEEN A", "last_name": "GRIFFITH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 26754, "first_name": "ALICE S.", "last_name": "RYAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Findings of post-acute sequelae of Post-COVID Conditions (PCC) manifestations of fatigue, pain, dyspnea, and muscle weakness, provide a strong rationale for rehabilitation; yet few formal studies exist and the effects of severe acute respiratory syndrome coronavirus-2 infection on function are not well described. Notably, two- thirds of Veterans are overweight and obese, rendering excess adiposity a significant risk factor and a high- priority area related to PCC prevention and care. Obesity increases the risk of severe illness in Veterans recovering from PCC, but how it does so is not fully understood. Recent research suggests that excess adipose tissue is associated with adverse changes in adipose cellular function, and that these variations may be involved in the biology of aging and the etiology of aging- related diseases. Adipose tissue contains cells that have undergone cellular senescence, which induces inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. However, the precise role of adipose tissue cellular composition on PCC recovery is limited. Thus, we propose to evaluate the role of obesity and PCC on physical functioning, health-related quality of life (HRQOL), and systemic and adipose tissue inflammatory and cellular senescence profiles in ethnically diverse older Veterans from the Audie Murphy (San Antonio) and Baltimore VA Medical Centers. Further, we propose a randomized controlled trial to determine whether a reduction in body weight and increased physical function by a weight loss intervention (WL), including dietary modification and exercise, in obese Veterans with PCC will reduce systemic and adipose tissue inflammation and senescence, which will have important implications for PCC recovery. We will pursue the following aims: Aim 1: To compare physical function, body composition, HRQOL, PCC symptoms, and adipose tissue molecular profiling in four cohorts of Veterans at baseline: lean PCC naïve, lean with PCC, obese PCC naïve, and obese with PCC (N=150). Aim 2: To compare in Veterans with obesity: a) a 12-week randomized WL vs. weight stability (WS) intervention (30/group) on physical function, body composition, HRQOL, and PCC symptoms together with changes in the global molecular profile in adipose tissue in Veterans with PCC and b) the WL intervention in PCC naïve vs. with PCC (N=30/group) on these outcomes. Older (55-80 years) men and women Veterans will be recruited. We will perform a standard functional battery (maximal aerobic capacity [VO2max; primary outcome], usual gait speed, six min walk distance, timed up and go, and handgrip strength), body composition (dual energy x-ray absorptiometry and computed tomography scans), HRQOL (NIH PROMIS-57), and PCC symptoms (COVID-19 Yorkshire Rehabilitation Scale [C19-YRS]) and adipose tissue will be collected. Further, we will test, in a randomized controlled trial, the hypothesis that a WL intervention, compared to weight stability (WS), improves physical function, body composition, and HRQOL and reduces inflammation and senescent cell burden and to a similar extent as the PCC naïve group with obesity. A deeper understanding of the relationship between adipose tissue and PCC will likely reveal factors that predispose to or protect against aging-related functional declines. Moreover, a better understanding of the effects of a lifestyle intervention on the molecular profile of adipose tissue will help to determine how changes in adipose tissue contribute to PCC and PCC recovery. Lastly, this research will provide important mechanistic insights into how cellular senescence influences the pathophysiology of physical, mental, and social dysfunction in older Veterans. Our findings could provide evidence-based recommendations to promote this type of intervention in Veterans recovering from PCC.", "keywords": [ "2019-nCoV", "Acute", "Adipose tissue", "Aerobic", "Area", "Baltimore", "Behavioral", "Biological Assay", "Biology of Aging", "Body Composition", "Body Weight", "COVID-19", "COVID-19 impact", "COVID-19 prevention", "Caring", "Cell Aging", "Cell Cycle Arrest", "Cell Physiology", "Cells", "Chronic", "Diet Modification", "Dual-Energy X-Ray Absorptiometry", "Dyspnea", "Etiology", "Exercise", "Fatigue", "Fatty acid glycerol esters", "Functional disorder", "Gait speed", "Health", "Individual", "Inflammation", "Inflammatory", "Intervention", "Intramuscular", "Laboratories", "Life Style", "Long COVID", "Medical center", "Metabolic dysfunction", "Molecular Profiling", "Muscle Weakness", "Obesity", "Outcome", "Overweight", "Oxidative Stress", "Pain", "Participant", "Patient Self-Report", "Phenotype", "Physical Function", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Predisposing Factor", "Prevention", "Psyche structure", "Randomized", "Randomized Controlled Trials", "Recovery", "Rehabilitation therapy", "Reporting", "Research", "Risk", "Risk Factors", "Role", "SARS-CoV-2 infection", "Sampling", "Scanning", "Symptoms", "Testing", "Thinness", "Tissue Banks", "Tissues", "United States National Institutes of Health", "VO2max", "Variant", "Veterans", "Visceral fat", "Walking", "Weight", "Woman", "X-Ray Computed Tomography", "aging related", "aging related disease", "clinical implementation", "cohort", "cytotoxicity", "disability", "ethnic diversity", "evidence based guidelines", "functional decline", "health related quality of life", "improved", "innovation", "insight", "lifestyle intervention", "men", "novel", "persistent symptom", "pharmacologic", "physical conditioning", "post-COVID conditions", "post-COVID-19", "primary outcome", "recruit", "response", "senescence", "senescence associated secretory phenotype", "senescent cell", "social deficits", "weight loss intervention" ], "approved": true } }, { "type": "Grant", "id": "15440", "attributes": { "award_id": "3R01MD019027-02S1", "title": "Factors Influencing Pediatric Asthma into Adulthood (FIPA2)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 27240, "first_name": "UTIBE RONALD", "last_name": "Bickham-Wright", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-25", "end_date": "2028-04-30", "award_amount": 120454, "principal_investigator": { "id": 32035, "first_name": "LYLE G", "last_name": "BEST", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 9754, "first_name": "Esther", "last_name": "Erdei", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 761, "ror": "", "name": "UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR", "address": "", "city": "", "state": "NM", "zip": "", "country": "United States", "approved": true } ] }, { "id": 32036, "first_name": "Dara", "last_name": "Torgerson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2543, "ror": "", "name": "MISSOURI BREAKS RESEARCH, INC.", "address": "", "city": "", "state": "SD", "zip": "", "country": "United States", "approved": true }, "abstract": "A. Summary of Funded Parent Grant: Factors Influencing Pediatric Asthma into Adulthood (R01MD019027) The prevalence of asthma among American Indian (AI) children is 9.3% as compared to 5.5% in non- Hispanic White children. Asthma disparities become even more pronounced into adulthood, with AI adults having the highest prevalence of asthma as compared to all other racial/ethnic groups in the US, with 60% uncontrolled. Asthma is influenced by social and environmental factors (SEF) including adverse childhood events (ACEs), tobacco smoke, and everyday life stressors that may alter immunological state. ACEs in particular, including abuse, neglect, and household challenges have been associated with immune dysregulation, may have implications for clinical outcomes of respiratory viral infections in children that have been linked to asthma and persistent respiratory symptoms. For example, Infants who develop severe RSV bronchiolitis in the first year of life are more likely to develop asthma, and children with asthma are at increased risk of experiencing complications from respiratory viral infections due to SARS-CoV-2, respiratory syncytial virus (RSV), influenza, and rhinovirus C. In the Factors Influencing Pediatric Asthma (FIPA) study including children from a Northern Plains American Indian community, we found children with asthma experienced an increased clinical burden from RSV infection and had lower levels of serum RSV-specific Immunoglobulin G (IgG) than children without asthma, indicative of immune suppression or dysfunction. However, the complex interplay between social, environmental and immunological response to viral respiratory infections remains largely unknown, and these factors have not been investigated among AI children with respect to their influence on immunological response and asthma development and control of asthma symptoms. In this continued AI community-focused study, we will test the hypothesis that social and environmental factors contribute to asthma susceptibility through stress-induced immune dysregulation, including the alteration of immunological response to viral respiratory infections. We will also investigate the role of viral respiratory infections and SEF on asthma control, including frequency of symptoms, exacerbations, ER visits/hospitalizations, and use of asthma medications. Aim 1: Identify social and environmental factors (SEF) that contribute to asthma susceptibility, asthma control, and long-term respiratory health in American Indian children. We will follow-up on our previously NIMHD-funded case/control study of 324 children recruited between the ages of 6-17 from 2013- 2017 as they transition into adulthood (now ages 11-27). We will recontact original study participants, evaluating their current asthma status to investigate the role of age and gender on long-term respiratory health including current asthma and asthma control. We will also expand our study to 400 new participants with and without asthma between the ages of 6-17, including Tribal members living in Rapid City, SD, and offspring of original study participants (~30% of original study participants have since become parents). We will obtain detailed measures of SEF, and retrospective information on adverse childhood events (ACE) using an established screener to evaluate their role in asthma susceptibility and asthma control, including comparisons between urban vs. rural and multi-generational effects in this community-engaged study. We hypothesize that domains of biological and behavioral influences acting on the individual and interpersonal levels generate social stress and have an impact on asthma development and control. Aim 2: Investigate the role of SEF on immunological response to viral respiratory infections (VRIs) in AI children with and without asthma. We will investigate the impact of social and environmental factors measured using validated and Tribally-developed surveys on the immune system of AI children with and without asthma, including response to viral respiratory infections (viral-specific serum IgG and IgM concentrations to RSV and other VRI pathogens known to cause long-term respiratory sequelae). We will quantify serological measurements of participants’ humoral immune responses including serum biomarkers of inflammation (Th1/Th2/Th17 cytokines), atopy (serum total IgE), and total immunoglobulins. We will test our hypothesis that interactions with detailed survey measures of SEF with immunological and clinical outcomes of VRIs, including viral responses in participants with and without asthma are the strongest and most significant predictors in our AI participants. Aim 3: Engage with an existing Tribal Community Advisory Board (CAB) using continuous bidirectional process evaluation to develop an intervention and policy framework of asthma prevention. We will engage with the CRST’s dedicated community and Tribal cultural experts and active volunteers in building our local CAB. We will leverage the scientific knowledge gained under this proposal to work with the CAB to create a sustainable, feasible, and Lakota-driven, intervention and policy framework, including the creation of structures to allow integration of social stressers including ACEs into existing referral services and policy initiatives. We will collect detailed information using questionnaires and semi-structured interviews among CAB members and the community about the study development and processes. We recognize that Tribal children with mild, moderate to severe asthma who are experiencing humoral immune response alterations and a combination of SEFs need very targeted and specialized preventive measures that this study will be able to develop and support with implementation. B. RESEARCH PLAN: Environmental Toxicants and Asthma in American Indian Children Background: Viral respiratory infections in early life have been linked to the development of asthma and persistent respiratory symptoms in children 1–3, including respiratory syncytial virus (RSV) of which the majority of children are exposed before age 2. Infants who develop RSV bronchiolitis in the first year of life have a high chance of developing asthma 4, and children with asthma have an increased risk of experiencing complications and lasting respiratory symptoms from infections such as RSV, SARS-CoV-2, influenza, and rhinovirus-C 5–8. The prevalence of asthma among American Indian (AI) children is 9.3% as compared to 5.5% in non-Hispanic White children 9. This is a serious but understudied, pediatric health disparity in the U.S. that becomes even more pronounced into adulthood, with AI adults having the highest prevalence of asthma as compared to all other racial/ethnic groups 9. Asthma has been linked to a number of social and environmental factors 10–15 including exposure to social stress, tobacco smoke, air pollution, and environmental toxicants including per- and perfluoroalkyl substances (PFAS) 16. There is mounting evidence that PFAS, a “forever chemical” in the environment has a deleterious effect on many aspects of health 17, including thyroid and immune activity 18, inflammation in pregnancy 19, fetal growth 20, immune response to childhood vaccines 21 and viral respiratory infections 22,23. Thus, exposure to PFAS and environmental toxins during childhood may have a lasting effect on Tribal health. In summary, we propose to address newly emerging chemical exposures including PFAS in an at-risk, low income, Native American community in consultation with the Cheyenne River Sioux Tribe (CRST), including children living in Rapid City South Dakota and the Cheyenne River Sioux and Oglala Lakota Reservations. In this area of South Dakota, the proportion of children living below the Federal poverty line is 47% and 57% in Ziebach 24 and Dewey 25 Counties, respectively. The adverse health effects of PFAS and environmental toxins due to community-level exposure in this area of high childhood poverty has yet to be investigated, nor their effects on immunological response to viral respiratory infections and immune dysfunction. Preliminary Research: In the Factors Influencing Pediatric Asthma (FIPA) study we found that AI children with asthma living on the Cheyenne River Sioux and Oglala Lakota Reservations were more likely to reside in multi-unit housing, and in residences with rodent or insect infestation resulting in poor indoor air quality as compared to asthma controls 26. Children with asthma also had higher BMI, total leukocyte counts, % eosinophils, total serum IgE, and specific IgE to five common indoor airborne antigens 27. We also found children with asthma to have lower levels of RSV-specific IgG during the winter (Figure 1) and to report increased hospitalizations and RSV diagnoses (Figure 2), suggesting immune dysregulation with clinical implications 28. We hypothesize that exposures to environmental toxins, some of which have been linked to immune dysregulation may play an important role. Figure 1: A. Asthma cases recruited during the winter (RSV season) had significantly lower RSV IgG as compared to asthma cases recruited during the summer (p=2.5x10-6). There was no observed difference in seasonality for asthma controls (p=0.60). B. More children with asthma have low levels of IgG (<40 IU/mL). In unpublished results, Dr. Erdei (co-PI of parent study) detected PFAS in 83% of samples from 50 CRST adults who fish regularly from the Tribe's main public water sources. She has identified an association between PFAS and a number of tissue- specific and antinuclear autoantibodies, and found serum PFAS and other compounds to be predictors of autoimmune markers indicative of a hyperreactive immune response in adults (Figure 3). Consuming locally caught fish as part of AI Figure 2: Children with asthma in the FIPA study report a higher culture and as a dietary source of protein was also clinical burden from RSV. associated with overall elevation of serum PFAS. Similar investigations among children in the CRST will allow us to learn more about PFAS exposure patterns as it relates to immune dysregulation, viral respiratory infections, and its effect on children’s health in the community. Figure 3: Quantile Regression plots in CRST adults showing that A. Perfluorononanoic acid (PFNA) exposures are predictive of anti- native DNA response. B. PFOS and C. PFOA exposures are predictive of thyroid-specific (anti-thyroglobulin) autoimmune response, with PFOA having an immunosuppressive effect. In summary, we hypothesize that exposure to environmental toxins, specifically PFAS, contributes to immune dysregulation and response to viral respiratory infections in American Indian children with asthma. As recruitment for FIPA2 is starting, this is an opportune time for Dr. Spear to lead a study investigating the role of PFAS and environmental toxins on the health of AI children. This opportunity will afford Dr. Spear to narrow in on the role of PFAS on immune dysregulation and response to viral respiratory infections in children with and without asthma, while making new connections with scientists in the field of environmental research. Overall, our study will advance knowledge of the effect of environmental toxins on immune dysregulation of children to inform future policies and interventions. Thus, our specific aims for this diversity supplement are: Specific Aim 1: Measure and identify suspect and PFAS chemicals that are present in American Indian children from Rapid City and the Cheyenne River Sioux/Oglala Lakota Reservations. Specific Aim 2: Perform correlative and predictive modeling between PFAS/suspect chemicals and immunological biomarkers and response to viral respiratory infections in AI children with and without asthma. Approach: We will perform suspect screening and test for levels of 12 PFAS in serum samples of 52 children with and without asthma and living in urban vs. rural (Reservation) locations (Figure 4). We will identify suspect chemicals present in AI children, and perform preliminary correlations with immune biomarkers, viral-specific immunoglobulins, PFAS and suspect chemicals identified. Characterizing the presence and effect of environmental toxins on the immune system is an essential step for understanding environmental health disparities, which the community has been struggling with for decades. Figure 4: Location and summary of serum samples for study to measure PFAS/suspect chemicals in children ages 6-17 years old in FIPA2. Recruitment is beginning 5/2024. We also have stored samples for >300 original FIPA participants at -80C (living on Reservation, only). Specific Aim 1: Measure and identify suspect and PFAS chemicals that are present in American Indian children from Rapid City and the Cheyenne River Sioux/Oglala Lakota Reservations. We will work with the UCSF Bioassay Facility Core to develop a protocol for PFAS and untargeted suspect screening of serum samples from 52 AI children, including 26 asthma cases and 26 matched controls living in an urban (Rapid City SD) vs. rural (Reservation) environment. Specific Aim 2: Perform correlative and predictive modeling between PFAS/suspect chemicals and immunological biomarkers and response to viral respiratory infections in AI children with and without asthma. We will test for a correlation of PFAS/suspect chemicals with levels of immune biomarkers and viral- specific immunoglobulins. Immune biomarkers will include cytokines, Creactive protein, CBCs (white blood cell counts), total serum IgE, and viral specific IgG/IgM (SARs-CoV2, RSV, influenza, and rhinovirus C). Results from this aim will provide insights in to 1) the variability in exposure to environmental toxicants in children living in urban vs. rural (Reservation) locations and 2) the role of exposure to PFAS/suspect chemicals on immune dysregulation and asthma. Statistical analyses: We will examine the distribution of individual PFAS chemicals plus untargeted suspect chemicals to determine the relevant statistical test. In general, for commonly detected chemicals we will utilize linear and logistic regression models (or nonparametric tests) to test for associations between PFAS/suspect chemicals adjusting for multiple covariates selected through an iterative process (e.g. BMI, sex, household size, asthma medications); we will also contrast models with and without an asthma interaction. For rare chemicals we will apply a fisher’s exact test for detected/undetected. ROC curves will be generated for individual chemicals by asthma and location, and cluster analyses will be performed over all chemicals using a principal component analysis (with UMAP projection) and partial least-squares discriminant analysis (PLS-DA) for predictive modeling and Cox regression. Lastly, we will attempt a mediation analysis to evaluate if exposure to PFAS/suspect chemicals contributes to asthma via immune dysregulation. Relevance to the parent grant: The parent grant is centered on identifying social determinants of the environment including adverse childhood experiences that contribute to the development of asthma through altering the immunological response to viral respiratory infections. However, there is substantial evidence to suggest that exposure to environmental toxicants contribute to immune dysregulation in both the context of asthma and general immune function as discussed above. In this proposal, Dr. Spear will focus on the physical environment, specifically the role of exposure and accumulation of environmental toxicants on immune dysregulation in children with and without asthma.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1424, "count": 14236 } } }