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Articles 331 - 360 of 598
Full-Text Articles in Health Services Research
Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan
Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan
Faculty, Staff and Students Publications
Introduction: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood.
Materials and methods: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function.
Results: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age …
A Non-Parametric Approach To Predict The Recruitment For Randomized Clinical Trials: An Example In Elderly Inpatient Settings, Alejandro Villasante-Tezanos, Yong-Fang Kuo, Christopher Kurinec, Yisheng Li, Xiaoying Yu
A Non-Parametric Approach To Predict The Recruitment For Randomized Clinical Trials: An Example In Elderly Inpatient Settings, Alejandro Villasante-Tezanos, Yong-Fang Kuo, Christopher Kurinec, Yisheng Li, Xiaoying Yu
Faculty, Staff and Student Publications
BACKGROUND: Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement.
METHODS: We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was …
Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse
Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse
Faculty, Staff and Student Publications
Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials.
Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV.
Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase …
Genetics And Genomics Of Pulmonary Fibrosis: Charting The Molecular Landscape And Shaping Precision Medicine, Ayodeji Adegunsoye, Jonathan A Kropski, Juergen Behr, Timothy S Blackwell, Tamera J Corte, Vincent Cottin, Allan R Glanville, Marilyn K Glassberg, Matthias Griese, Gary M Hunninghake, Kerri A Johannson, Michael P Keane, John S Kim, Martin Kolb, Toby M Maher, Justin M Oldham, Anna J Podolanczuk, Ivan O Rosas, Fernando J Martinez, Imre Noth, David A Schwartz
Genetics And Genomics Of Pulmonary Fibrosis: Charting The Molecular Landscape And Shaping Precision Medicine, Ayodeji Adegunsoye, Jonathan A Kropski, Juergen Behr, Timothy S Blackwell, Tamera J Corte, Vincent Cottin, Allan R Glanville, Marilyn K Glassberg, Matthias Griese, Gary M Hunninghake, Kerri A Johannson, Michael P Keane, John S Kim, Martin Kolb, Toby M Maher, Justin M Oldham, Anna J Podolanczuk, Ivan O Rosas, Fernando J Martinez, Imre Noth, David A Schwartz
Faculty, Staff and Students Publications
Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis and clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the …
How Is Diagnostic Uncertainty Communicated And Managed In Real World Primary Care Settings?, Jessica Russell, Laura Boswell, Athena Ip, Jenny Harris, Hardeep Singh, Ashley N D Meyer, Traber D Giardina, Afsana Bhuiya, Katriina L Whitaker, Georgia B Black
How Is Diagnostic Uncertainty Communicated And Managed In Real World Primary Care Settings?, Jessica Russell, Laura Boswell, Athena Ip, Jenny Harris, Hardeep Singh, Ashley N D Meyer, Traber D Giardina, Afsana Bhuiya, Katriina L Whitaker, Georgia B Black
Faculty, Staff and Students Publications
Background: Managing diagnostic uncertainty is a major challenge in primary care due to factors such as the absence of definitive tests, variable symptom presentations and disease evolution. Maintaining patient trust during a period of investigative uncertainty, whilst minimising scope for diagnostic error is a challenge. Mismanagement can lead to diagnostic errors, treatment delays, and suboptimal patient outcomes.
Objective: Our aim was to explore how UK primary care physicians (GPs) address and communicate diagnostic uncertainty in practice.
Design: This qualitative study used video and audio-recordings. Verbatim transcripts were coded with a modified, validated tool to capture GPs' actions and communication in …
Pan-Cancer Proteogenomics Expands The Landscape Of Therapeutic Targets, Sara R Savage, Xinpei Yi, Jonathan T Lei, Bo Wen, Hongwei Zhao, Yuxing Liao, Eric J Jaehnig, Lauren K Somes, Paul W Shafer, Tobie D Lee, Zile Fu, Yongchao Dou, Zhiao Shi, Daming Gao, Valentina Hoyos, Qiang Gao, Bing Zhang
Pan-Cancer Proteogenomics Expands The Landscape Of Therapeutic Targets, Sara R Savage, Xinpei Yi, Jonathan T Lei, Bo Wen, Hongwei Zhao, Yuxing Liao, Eric J Jaehnig, Lauren K Somes, Paul W Shafer, Tobie D Lee, Zile Fu, Yongchao Dou, Zhiao Shi, Daming Gao, Valentina Hoyos, Qiang Gao, Bing Zhang
Faculty, Staff and Students Publications
Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor …
Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer
Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer
Faculty, Staff and Student Publications
BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.
METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …
Analyzing Heterogeneity In Biomarker Discriminative Performance Through Partial Time-Dependent Receiver Operating Characteristic Curve Modeling, Xinyang Jiang, Wen Li, Kang Wang, Ruosha Li, Jing Ning
Analyzing Heterogeneity In Biomarker Discriminative Performance Through Partial Time-Dependent Receiver Operating Characteristic Curve Modeling, Xinyang Jiang, Wen Li, Kang Wang, Ruosha Li, Jing Ning
Faculty, Staff and Student Publications
This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. …
A Qualitative Exploration To Inform An Oral Health Training For Disability Care Workers In Burkina Faso, Ave Põld, Dan Filwendé Kientega, Jocelyne Valérie Garé, Michael Lorenz
A Qualitative Exploration To Inform An Oral Health Training For Disability Care Workers In Burkina Faso, Ave Põld, Dan Filwendé Kientega, Jocelyne Valérie Garé, Michael Lorenz
Faculty, Staff and Student Publications
AIM: To explore enablers and barriers to the creation of an oral health training for care workers at specialized centres for children with disabilities in Ouagadougou.
DESIGN: This was a formative study informed by the Theoretical Domains Framework using qualitative methods.
METHODS: Qualitative observations and 14 semi-structured interviews were conducted with care workers from six specialized centres for disability.
RESULTS: Carer workers emphasized that a successful oral health training must account for available resources and competencies in each specific centre. Part of the training must be dedicated to oral hygiene targeted for people with disabilities and provide knowledge about risk …
Validation Of Electronic Diagnostic Codes For Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Carlos H Schenck, Mehrnaz Azarian, Ricardo E Jorge, Amir Sharafkhaneh, Javad Razjouyan
Validation Of Electronic Diagnostic Codes For Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Carlos H Schenck, Mehrnaz Azarian, Ricardo E Jorge, Amir Sharafkhaneh, Javad Razjouyan
Faculty, Staff and Students Publications
We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of veterans with rapid eye movement sleep behavior disorder. The charts of 139 randomly sampled veterans with ≥ 1 ICD-9 and ICD-10 code(s) for rapid eye movement sleep behavior disorder were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) patients with rapid eye movement sleep behavior disorder electronic diagnoses had not undergone polysomnography, and 29 (20.9%) had polysomnography reports without commentary on rapid eye movement sleep without atonia. Sleep centers are therefore encouraged …
Safety And Efficacy Outcomes Of Early Cessation Of Anti-Pd1 Therapy In Patients 80 Years Or Older: A Retrospective Cohort Study, Kylie Fletcher, Alessio Cortellini, Teja Ganta, Roma Kankaria, Haocan Song, Fei Ye, Rebecca Irlmeier, Neha Debnath, Anwaar Saeed, Maluki Radford, Asrar Alahmadi, Akiva Diamond, Christopher Hoimes, Carolyn J Presley, Dwight H Owen, Sarah Abou Alaiwi, Amin H Nassar, Giuseppe Lamberti, Fabiana Perrone, Sebastiano Buti, Raffaele Giusti, Marco Filetti, Vito Vanella, Domenico Mallardo, Tamara A Sussman, Domenico Galetta, Foteini Kalofonou, Ella Daniels, Paolo A Ascierto, David J Pinato, Caroline Nebhan, Stephanie Berg, Toni K Choueiri, Thomas U Marron, Yinghong Wang, Abdul Rafeh Naqash, Douglas B Johnson
Safety And Efficacy Outcomes Of Early Cessation Of Anti-Pd1 Therapy In Patients 80 Years Or Older: A Retrospective Cohort Study, Kylie Fletcher, Alessio Cortellini, Teja Ganta, Roma Kankaria, Haocan Song, Fei Ye, Rebecca Irlmeier, Neha Debnath, Anwaar Saeed, Maluki Radford, Asrar Alahmadi, Akiva Diamond, Christopher Hoimes, Carolyn J Presley, Dwight H Owen, Sarah Abou Alaiwi, Amin H Nassar, Giuseppe Lamberti, Fabiana Perrone, Sebastiano Buti, Raffaele Giusti, Marco Filetti, Vito Vanella, Domenico Mallardo, Tamara A Sussman, Domenico Galetta, Foteini Kalofonou, Ella Daniels, Paolo A Ascierto, David J Pinato, Caroline Nebhan, Stephanie Berg, Toni K Choueiri, Thomas U Marron, Yinghong Wang, Abdul Rafeh Naqash, Douglas B Johnson
Faculty, Staff and Students Publications
Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (< 12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of < 12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.
Mechanisms Of Neurodevelopmental Toxicity Of Topiramate, John W Steele, Vaishnav Krishnan, Richard H Finnell
Mechanisms Of Neurodevelopmental Toxicity Of Topiramate, John W Steele, Vaishnav Krishnan, Richard H Finnell
Faculty, Staff and Students Publications
Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate …
The Interaction Of Endorepellin And Neurexin Triggers Neuroepithelial Autophagy And Maintains Neural Tube Development, Lei Lu, Meizhu Bai, Yufang Zheng, Xiukun Wang, Zhongzhong Chen, Rui Peng, Richard H Finnell, Tongjin Zhao, Chengtao Li, Bo Wu, Yunping Lei, Jinsong Li, Hongyan Wang
The Interaction Of Endorepellin And Neurexin Triggers Neuroepithelial Autophagy And Maintains Neural Tube Development, Lei Lu, Meizhu Bai, Yufang Zheng, Xiukun Wang, Zhongzhong Chen, Rui Peng, Richard H Finnell, Tongjin Zhao, Chengtao Li, Bo Wu, Yunping Lei, Jinsong Li, Hongyan Wang
Faculty, Staff and Students Publications
Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare genetic variants of HSPG2 in 10% cases compared to only 4% in controls among a cohort of 369 NTDs. Endorepellin, a peptide cleaved from the domain V of Perlecan, is known to promote angiogenesis and autophagy in endothelial cells. The roles of enderepellin in neurodevelopment remain unclear so far. Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the …
Demystifying The Virtualization Process: A Call For Standard Reporting Of Virtual Modifications To Evidence-Based Psychotherapies, Using The Frame Model, Derrecka M Boykin, Tracey L Smith, Barbara Rakel, Merlyn Rodrigues, Jennie Embree, Ken Woods, Angelic D Chaison, Lilian Dindo
Demystifying The Virtualization Process: A Call For Standard Reporting Of Virtual Modifications To Evidence-Based Psychotherapies, Using The Frame Model, Derrecka M Boykin, Tracey L Smith, Barbara Rakel, Merlyn Rodrigues, Jennie Embree, Ken Woods, Angelic D Chaison, Lilian Dindo
Faculty, Staff and Students Publications
The sudden onset of the coronavirus disease led to a rapid expansion of video telehealth to deliver mental healthcare. Although video telehealth was not a new clinical practice, there was limited guidance on how best to modify evidence-based psychotherapies (EBPs) for virtual delivery (a process also referred to as virtualization). The virtualization process for EBPs remains unclear as newly emerging reports on this topic do not consistently report modification decisions. This commentary calls attention to the need to improve documentation practices to allow a greater understanding of modifications needed to maximize the positive effects of EBPs transported to a virtual …
Msl2 Variants Lead To A Neurodevelopmental Syndrome With Lack Of Coordination, Epilepsy, Specific Dysmorphisms, And A Distinct Episignature, Remzi Karayol, Maria Carla Borroto, Sadegheh Haghshenas, Anoja Namasivayam, Jack Reilly, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley Mcconkey, Maria Shvedunova, Andrea K Petersen, Kari Magnussen, Christiane Zweier, Georgia Vasileiou, André Reis, Juliann M Savatt, Meghan R Mulligan, Louise S Bicknell, Gemma Poke, Aya Abu-El-Haija, Jessica Duis, Vickie Hannig, Siddharth Srivastava, Elizabeth Barkoudah, Natalie S Hauser, Myrthe Van Den Born, Uri Hamiel, Noa Henig, Hagit Baris Feldman, Shane Mckee, Ingrid P C Krapels, Yunping Lei, Albena Todorova, Ralitsa Yordanova, Slavena Atemin, Mihael Rogac, Vivienne Mcconnell, Anna Chassevent, Kristin W Barañano, Vandana Shashi, Jennifer A Sullivan, Angela Peron, Maria Iascone, Maria P Canevini, Jennifer Friedman, Iris A Reyes, Janell Kierstein, Joseph J Shen, Faria N Ahmed, Xiao Mao, Berta Almoguera, Fiona Blanco-Kelly, Konrad Platzer, Ariana-Berenike Treu, Juliette Quilichini, Alexia Bourgois, Nicolas Chatron, Louis Januel, Christelle Rougeot, Deanna Alexis Carere, Kristin G Monaghan, Justine Rousseau, Kenneth A Myers, Bekim Sadikovic, Asifa Akhtar, Philippe M Campeau
Msl2 Variants Lead To A Neurodevelopmental Syndrome With Lack Of Coordination, Epilepsy, Specific Dysmorphisms, And A Distinct Episignature, Remzi Karayol, Maria Carla Borroto, Sadegheh Haghshenas, Anoja Namasivayam, Jack Reilly, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley Mcconkey, Maria Shvedunova, Andrea K Petersen, Kari Magnussen, Christiane Zweier, Georgia Vasileiou, André Reis, Juliann M Savatt, Meghan R Mulligan, Louise S Bicknell, Gemma Poke, Aya Abu-El-Haija, Jessica Duis, Vickie Hannig, Siddharth Srivastava, Elizabeth Barkoudah, Natalie S Hauser, Myrthe Van Den Born, Uri Hamiel, Noa Henig, Hagit Baris Feldman, Shane Mckee, Ingrid P C Krapels, Yunping Lei, Albena Todorova, Ralitsa Yordanova, Slavena Atemin, Mihael Rogac, Vivienne Mcconnell, Anna Chassevent, Kristin W Barañano, Vandana Shashi, Jennifer A Sullivan, Angela Peron, Maria Iascone, Maria P Canevini, Jennifer Friedman, Iris A Reyes, Janell Kierstein, Joseph J Shen, Faria N Ahmed, Xiao Mao, Berta Almoguera, Fiona Blanco-Kelly, Konrad Platzer, Ariana-Berenike Treu, Juliette Quilichini, Alexia Bourgois, Nicolas Chatron, Louis Januel, Christelle Rougeot, Deanna Alexis Carere, Kristin G Monaghan, Justine Rousseau, Kenneth A Myers, Bekim Sadikovic, Asifa Akhtar, Philippe M Campeau
Faculty, Staff and Students Publications
Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding …
Full-Length Αiibβ3 Cryo-Em Structure Reveals Intact Integrin Initiate-Activation Intrinsic Architecture, Tong Huo, Hongjiang Wu, Zeinab Moussa, Mehmet Sen, Valerie Dalton, Zhao Wang
Full-Length Αiibβ3 Cryo-Em Structure Reveals Intact Integrin Initiate-Activation Intrinsic Architecture, Tong Huo, Hongjiang Wu, Zeinab Moussa, Mehmet Sen, Valerie Dalton, Zhao Wang
Faculty, Staff and Students Publications
Integrin αIIbβ3 is the key receptor regulating platelet retraction and accumulation and a proven drug-target for antithrombotic therapies. Here we resolve the cryoEM structures of the full-length αIIbβ3, which covers three distinct states along the activation pathway. Firstly, we obtain the αIIbβ3 structure at 3Å resolution in the inactive state, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the ligand-binding domain tucked in a specific angle proximity to the TM region. After the addition of a Mn2+ agonist, we resolve two coexisting structures representing two new states between inactive and active state. Our structures show …
Ai Driven Analysis Of Mri To Measure Health And Disease Progression In Fshd, Lara Riem, Olivia Ducharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A Jacobs, Doris G Leung, Seth D Friedman, Silvia S Blemker
Ai Driven Analysis Of Mri To Measure Health And Disease Progression In Fshd, Lara Riem, Olivia Ducharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A Jacobs, Doris G Leung, Seth D Friedman, Silvia S Blemker
Faculty, Staff and Student Publications
Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image …
Caregiver Recruitment Strategies For Interventions Designed To Optimize Transitions From Hospital To Home: Lessons From A Randomized Trial, Allison M Gustavson, Molly J Horstman, Jodie A Cogswell, Diane E Holland, Catherine E Vanderboom, Jay Mandrekar, William S Harmsen, Brystana G Kaufman, Cory Ingram, Joan M Griffin
Caregiver Recruitment Strategies For Interventions Designed To Optimize Transitions From Hospital To Home: Lessons From A Randomized Trial, Allison M Gustavson, Molly J Horstman, Jodie A Cogswell, Diane E Holland, Catherine E Vanderboom, Jay Mandrekar, William S Harmsen, Brystana G Kaufman, Cory Ingram, Joan M Griffin
Faculty, Staff and Students Publications
Challenges to recruitment of family caregivers exist and are amplified when consent must occur in the context of chaotic healthcare circumstances, such as the transition from hospital to home. The onset of the COVID-19 pandemic during our randomized controlled trial provided an opportunity for a natural experiment exploring and examining different consent processes for caregiver recruitment. The purpose of this publication is to describe different recruitment processes (in-person versus virtual) and compare diversity in recruitment rates in the context of a care recipient's hospitalization. We found rates of family caregiver recruitment for in-person versus virtual were 28% and 23%, respectively …
Sars-Cov-2 Triggers Dickkopf-1 (Dkk-1) Modulation Of T Helper Cells And Lung Pathology In Mice, Yifan Wu, Freedom M Green, Stephen A Shaw, Lauren J Bonilla, Shannon E Ronca, Maria Elena Bottazzi, Farrah Kheradmand, Jill E Weatherhead
Sars-Cov-2 Triggers Dickkopf-1 (Dkk-1) Modulation Of T Helper Cells And Lung Pathology In Mice, Yifan Wu, Freedom M Green, Stephen A Shaw, Lauren J Bonilla, Shannon E Ronca, Maria Elena Bottazzi, Farrah Kheradmand, Jill E Weatherhead
Faculty, Staff and Students Publications
No abstract provided.
Mechanisms Of Gelofusine Protection In An In Vitro Model Of Polymyxin B-Associated Renal Injury, Cole S Hudson, Anirban Roy, Qingtian Li, Aniket S Joshi, Taijun Yin, Ashok Kumar, David Sheikh-Hamad, Vincent H Tam
Mechanisms Of Gelofusine Protection In An In Vitro Model Of Polymyxin B-Associated Renal Injury, Cole S Hudson, Anirban Roy, Qingtian Li, Aniket S Joshi, Taijun Yin, Ashok Kumar, David Sheikh-Hamad, Vincent H Tam
Faculty, Staff and Students Publications
Polymyxins are a last-resort treatment option for multidrug-resistant gram-negative bacterial infections, but they are associated with nephrotoxicity. Gelofusine was previously shown to reduce polymyxin-associated kidney injury in an animal model. However, the mechanism(s) of renal protection has not been fully elucidated. Here, we report the use of a cell culture model to provide insights into the mechanisms of renal protection. Murine epithelial proximal tubular cells were exposed to polymyxin B. Cell viability, lactate dehydrogenase (LDH) release, polymyxin B uptake, mitochondrial superoxide production, nuclear morphology, and apoptosis activation were evaluated with or without concomitant gelofusine. A megalin knockout cell line was …
Exome Sequencing Identifies Novel Genes Underlying Primary Congenital Glaucoma In The National Birth Defects Prevention Study, Elizabeth E Blue, Kristin J Moore, Kari E North, Tania A Desrosiers, Suzan L Carmichael, Janson J White, Jessica X Chong, Michael J Bamshad, Mary M Jenkins, Lynn M Almli, Lawrence C Brody, Sharon F Freedman, Jennita Reefhuis, Paul A Romitti, Gary M Shaw, Martha Werler, Denise M Kay, Marilyn L Browne, Marcia L Feldkamp, Richard H Finnell, Wendy N Nembhard, Faith Pangilinan, Andrew F Olshan, National Institutes Of Health Intramural Sequencing Center, University Of Washington Center For Mendelian Genomics, National Birth Defects Prevention Study
Exome Sequencing Identifies Novel Genes Underlying Primary Congenital Glaucoma In The National Birth Defects Prevention Study, Elizabeth E Blue, Kristin J Moore, Kari E North, Tania A Desrosiers, Suzan L Carmichael, Janson J White, Jessica X Chong, Michael J Bamshad, Mary M Jenkins, Lynn M Almli, Lawrence C Brody, Sharon F Freedman, Jennita Reefhuis, Paul A Romitti, Gary M Shaw, Martha Werler, Denise M Kay, Marilyn L Browne, Marcia L Feldkamp, Richard H Finnell, Wendy N Nembhard, Faith Pangilinan, Andrew F Olshan, National Institutes Of Health Intramural Sequencing Center, University Of Washington Center For Mendelian Genomics, National Birth Defects Prevention Study
Faculty, Staff and Students Publications
Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants.
Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention …
Achieving Equitable Cardiovascular Care For All: Acc Board Of Trustees Health Equity Task Force Action Plan, Paul L Douglass, Dipti Itchhaporia, Biykem Bozkurt, Robert O Roswell, Akshay Khandelwal, Quinn Capers, Kathryn Berlacher, Modele O Ogunniyi, Alison L Bailey, Phillip D Levy, Aubrey J Grant, Jack Tocco, Angela Natcheva, Akua G Asare, Ami B Bhatt, Jennifer H Mieres, Maghee F Disch, Melvin R Echols
Achieving Equitable Cardiovascular Care For All: Acc Board Of Trustees Health Equity Task Force Action Plan, Paul L Douglass, Dipti Itchhaporia, Biykem Bozkurt, Robert O Roswell, Akshay Khandelwal, Quinn Capers, Kathryn Berlacher, Modele O Ogunniyi, Alison L Bailey, Phillip D Levy, Aubrey J Grant, Jack Tocco, Angela Natcheva, Akua G Asare, Ami B Bhatt, Jennifer H Mieres, Maghee F Disch, Melvin R Echols
Faculty, Staff and Students Publications
Advancements in cardiovascular (CV) disease management are notable, yet health inequities prevail, associated with increased morbidity and mortality noted among non-Hispanic African Americans in the United States. The 2002 Institute of Medicine Report revealed ongoing racial and ethnic health care disparities, spearheading a deeper understanding of the social determinants of health and systemic racism to develop strategies for CV health equity (HE). This article outlines the strategic HE approach of the American College of Cardiology, comprising 6 strategic equity domains: workforce pathway inclusivity, health care, data, science, and tools; education and training; membership, partnership, and collaboration; advocacy and policy; and …
Thrombosis Risk Prediction In Lymphoma Patients: A Multi-Institutional, Retrospective Model Development And Validation Study, Shengling Ma, Jennifer La, Kaitlin N Swinnerton, Danielle Guffey, Raka Bandyo, Giordana De Las Pozas, Katy Hanzelka, Xiangjun Xiao, Cristhiam M Rojas-Hernandez, Christopher I Amos, Vipul Chitalia, Katya Ravid, Kelly W Merriman, Christopher R Flowers, Nathanael Fillmore, Ang Li
Thrombosis Risk Prediction In Lymphoma Patients: A Multi-Institutional, Retrospective Model Development And Validation Study, Shengling Ma, Jennifer La, Kaitlin N Swinnerton, Danielle Guffey, Raka Bandyo, Giordana De Las Pozas, Katy Hanzelka, Xiangjun Xiao, Cristhiam M Rojas-Hernandez, Christopher I Amos, Vipul Chitalia, Katya Ravid, Kelly W Merriman, Christopher R Flowers, Nathanael Fillmore, Ang Li
Faculty, Staff and Students Publications
Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the …
Author Reply To Letter By Topkan Et Al Regarding Delays In Starting Postoperative Radiotherapy, Kelsey A Duckett, Byung Joo Lee, Bhisham S Chera, Sidharth V Puram, Vlad C Sandulache, Russel Kahmke, Shaun A Nguyen, Brian Nussenbaum, Anthony J Alberg, Chanita Hughes Halbert, Katherine R Sterba, Evan M Graboyes
Author Reply To Letter By Topkan Et Al Regarding Delays In Starting Postoperative Radiotherapy, Kelsey A Duckett, Byung Joo Lee, Bhisham S Chera, Sidharth V Puram, Vlad C Sandulache, Russel Kahmke, Shaun A Nguyen, Brian Nussenbaum, Anthony J Alberg, Chanita Hughes Halbert, Katherine R Sterba, Evan M Graboyes
Faculty, Staff and Students Publications
No abstract provided.
The Saga Of Covid-19 In Chronic Lung Disease: History Repeats Itself, Amir Sharafkhaneh, Javad Razjouyan
The Saga Of Covid-19 In Chronic Lung Disease: History Repeats Itself, Amir Sharafkhaneh, Javad Razjouyan
Faculty, Staff and Students Publications
No abstract provided.
Using Human Intestinal Organoids To Understand The Small Intestine Epithelium At The Single Cell Transcriptional Level, Carolyn Bomidi, Xi-Lei Zeng, Victoria Poplaski, Cristian Coarfa, Mary K Estes, Sarah E Blutt
Using Human Intestinal Organoids To Understand The Small Intestine Epithelium At The Single Cell Transcriptional Level, Carolyn Bomidi, Xi-Lei Zeng, Victoria Poplaski, Cristian Coarfa, Mary K Estes, Sarah E Blutt
Faculty, Staff and Students Publications
Single cell transcriptomics has revolutionized our understanding of the cell biology of the human body. State-of-the-art human small intestinal organoid cultures provide ex vivo model systems that bridge the gap between animal models and clinical studies. The application of single cell transcriptomics to human intestinal organoid (HIO) models is revealing previously unrecognized cell biology, biochemistry, and physiology of the GI tract. The advanced single cell transcriptomics platforms use microfluidic partitioning and barcoding to generate cDNA libraries. These barcoded cDNAs can be easily sequenced by next generation sequencing platforms and used by various visualization tools to generate maps. Here, we describe …
The Frailty Trajectory's Additional Edge Over The Frailty Index: Retrospective Cohort Study Of Veterans With Heart Failure, Javad Razjouyan, Ariela R Orkaby, Molly J Horstman, Parag Goyal, Orna Intrator, Aanand D Naik
The Frailty Trajectory's Additional Edge Over The Frailty Index: Retrospective Cohort Study Of Veterans With Heart Failure, Javad Razjouyan, Ariela R Orkaby, Molly J Horstman, Parag Goyal, Orna Intrator, Aanand D Naik
Faculty, Staff and Students Publications
No abstract provided.
Identifying Interventions To Improve Diagnostic Safety In Emergency Departments: Protocol For A Participatory Design Study, Woosuk Seo, Sun Young Park, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan
Identifying Interventions To Improve Diagnostic Safety In Emergency Departments: Protocol For A Participatory Design Study, Woosuk Seo, Sun Young Park, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan
Faculty, Staff and Students Publications
Background: Emergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks.
Objective: This study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and …
Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley
Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley
Faculty, Staff and Student Publications
BACKGROUND: Adverse childhood experiences (ACEs) are potentially traumatic exposures experienced during childhood, for example, neglect. There is growing evidence that the coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic conditions contributed to an increased risk of ACEs. As public health programs/services are re-evaluated and restored following the state of emergency, it is important to plan using an ACEs-informed lens. The aim of this study was to identify and prioritize initiatives or activities that Public Health Ontario (PHO) could undertake to support Ontario public health units' work towards ACEs-informed pandemic recovery plans.
METHODS: The Child Health and Nutrition Research Initiative method …
Chagas Disease In Immunocompromised Patients, Eva H Clark, Louisa A Messenger, Jeffrey D Whitman, Caryn Bern
Chagas Disease In Immunocompromised Patients, Eva H Clark, Louisa A Messenger, Jeffrey D Whitman, Caryn Bern
Faculty, Staff and Students Publications
As Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various …