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Articles 20311 - 20340 of 25139
Full-Text Articles in Entire DC Network
Health Care Utilization And Costs Associated With Functional Status In Patients With Psoriatic Arthritis, Steven Sison, Peter Hur, Nina Kim, Esther Yi, Kaleb Michaud
Health Care Utilization And Costs Associated With Functional Status In Patients With Psoriatic Arthritis, Steven Sison, Peter Hur, Nina Kim, Esther Yi, Kaleb Michaud
Faculty, Staff and Student Publications
BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) has been validated and widely used in psoriatic arthritis (PsA) clinical trials for the assessment of patient functional status. Significant improvements in the HAQ-DI have been reported in response to therapeutic interventions; however, few US studies have evaluated the economic impact of functional disability in patients with PsA.
OBJECTIVE: To evaluate the association of functional status with health care resource utilization (HCRU) and total health care costs in US patients diagnosed with PsA.
METHODS: This retrospective study included adult patients with PsA enrolled in FORWARD between July 2009 and June 2019 who …
Development Of A Novel Pharmacophore Model To Screen Specific Inhibitors For The Serine-Threonine Protein Phosphatase Calcineurin
Faculty, Staff and Student Publications
Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required …
Trends In The Diversity Of Pediatric Faculty: 2000 To 2020
Trends In The Diversity Of Pediatric Faculty: 2000 To 2020
Faculty, Staff and Student Publications
OBJECTIVE: Academic medicine diversity is important for addressing health disparities and training the next generation. A recent study highlighted the lack of diversity among pediatric trainees over time. However, trends in US pediatric faculty diversity have not been clearly illuminated. The aim of this study is to evaluate pediatric faculty diversity trends and compare racial/ethnic representation between pediatric faculty and the US population.
METHODS: Repeat cross-sectional study of the Association of American Medical Colleges Faculty Roster of pediatric faculty from 2000 to 2020. Trends in sex, race, ethnicity, and rank were compared with the Cochran-Armitage test. Data on faculty race/ethnicity …
Is Prior Hip Arthroscopy Associated With Higher Complication Rates Or Prolonged Opioid Claims After Total Hip Arthroplasty? A Matched Cohort Study, Wendell W Cole
Faculty, Staff and Student Publications
BACKGROUND: Hip arthroscopy (HA) procedures have increased exponentially in recent years. Their effect on outcomes after subsequent total hip arthroplasty (THA) remains unclear.
PURPOSE: To compare rates of complications and opioid claims after elective THA among patients with prior HA versus controls.
STUDY DESIGN: Cohort study; Level of evidence, 3.
METHODS: Patients who underwent THA were identified in the PearlDiver database. Arthroplasty performed for hip fractures and hip avascular necrosis were excluded. Within this population, patients with HA before arthroplasty (n = 3156) were propensity score matched 1:1 with controls on age, sex, US region, and several comorbidities. Rates of …
Ureteroscopy Under Conscious Sedation: A Proof-Of-Concept Study, Brian Peters
Ureteroscopy Under Conscious Sedation: A Proof-Of-Concept Study, Brian Peters
Faculty, Staff and Student Publications
INTRODUCTION: Ureteroscopy (URS) is commonly performed under general anesthesia (GA) to maximize patient tolerability and minimize surgical complications; however, given the improvements in endoscopic technology and risks associated with GA, alternate forms of anesthesia have been postulated. We aimed to evaluate the outcomes of URS under conscious sedation.
METHODS: We completed a retrospective cohort study from November 2019 to June 2020 at a tertiary-level hospital. All URSs that were performed under urologist-directed conscious sedation were included. Our primary outcome was the ability to complete URS, defined as success rate. Secondary outcomes included: stone-free rate, intraoperative complication rate, hospital admission rate, …
Machine Learning-Based Prediction Of Masked Hypertension Among Children With Chronic Kidney Disease, Susan L Furth
Machine Learning-Based Prediction Of Masked Hypertension Among Children With Chronic Kidney Disease, Susan L Furth
Faculty, Staff and Student Publications
BACKGROUND: Ambulatory blood pressure monitoring (ABPM) is routinely performed in children with chronic kidney disease to identify masked hypertension, a risk factor for accelerated chronic kidney disease progression. However, ABPM is burdensome, and developing an accurate prediction of masked hypertension may allow using ABPM selectively rather than routinely.
METHODS: To create a prediction model for masked hypertension using clinic blood pressure (BP) and other clinical characteristics, we analyzed 809 ABPM studies with nonhypertensive clinic BP among the participants of the Chronic Kidney Disease in Children study.
RESULTS: Masked hypertension was identified in 170 (21.0%) observations. We created prediction models for …
An Ultra-Brief Screening Scale For Pediatric Obsessive-Compulsive Disorder: The Oci-Cv-5, Amitai Abramovitch, Jonathan S Abramowitz, Dean Mckay, Heining Cham, Kennedy S Anderson, Lara J Farrell, Daniel A Geller, Gregory L Hanna, Sharna Mathieu, Joseph F Mcguire, David R Rosenberg, S Evelyn Stewart, Eric A Storch, Sabine Wilhelm
An Ultra-Brief Screening Scale For Pediatric Obsessive-Compulsive Disorder: The Oci-Cv-5, Amitai Abramovitch, Jonathan S Abramowitz, Dean Mckay, Heining Cham, Kennedy S Anderson, Lara J Farrell, Daniel A Geller, Gregory L Hanna, Sharna Mathieu, Joseph F Mcguire, David R Rosenberg, S Evelyn Stewart, Eric A Storch, Sabine Wilhelm
Center for Medical Ethics and Health Policy Staff Publications
Background: Obsessive-compulsive disorder (OCD) is an often disabling and chronic condition that is normally assessed using diagnostic interviews or lengthy self-report questionnaires. This makes routine screening in general health settings impractical, and as a result OCD is often under-(or mis-)recognized. The present study reports on the development of an ultra-brief version of the Obsessive-Compulsive Inventory-Child Version (OCI-CV) which may be administered routinely as a screener for pediatric OCD.
Method: A total of 489 youth diagnosed with OCD, 259 non-clinical controls, and 299 youth with other disorders completed the OCI-CV and other indices of psychopathology. Using item analyses, we extracted five …
Improved Right Ventricular Systolic Function After Cardiac Resynchronization Therapy In Patients With Heart Failure, Hakimeh Sadeghian, Ali Kazemisaied, Mehrnaz Rezvanfard, Arash Jalali, Afsaneh Sadeghian, Haleh Ashraf, Farbod Semnani, Amirhossein Ghaseminejad Raeini
Improved Right Ventricular Systolic Function After Cardiac Resynchronization Therapy In Patients With Heart Failure, Hakimeh Sadeghian, Ali Kazemisaied, Mehrnaz Rezvanfard, Arash Jalali, Afsaneh Sadeghian, Haleh Ashraf, Farbod Semnani, Amirhossein Ghaseminejad Raeini
The Texas Heart Institute Journal
Background
Since the introduction of cardiac resynchronization therapy (CRT) to improve left ventricular function, the effect of CRT on the right ventricle in patients with heart failure has not been well described.
Methods
We evaluated the effect of CRT on right ventricular systolic function in 20 patients (80% men; mean [SD] age, 58.5 [9.8] y) with cardiomyopathy and right ventricular systolic dysfunction (New York Heart Association class III or IV, left ventricular ejection fraction ≤35%, and QRS interval ≥120 ms). The median follow-up time was 15 months. Right ventricular systolic function, defined as a tricuspid annular plane systolic excursion (TAPSE) …
Subclavian Steal Phenomenon Associated With Vascular Ring In An Infant Who Had A Prenatally Diagnosed Right Aortic Arch With An Atretic Aberrant Left Subclavian Artery, Daiji Takajo, Jennifer Blake, Sanjeev Aggarwal
Subclavian Steal Phenomenon Associated With Vascular Ring In An Infant Who Had A Prenatally Diagnosed Right Aortic Arch With An Atretic Aberrant Left Subclavian Artery, Daiji Takajo, Jennifer Blake, Sanjeev Aggarwal
The Texas Heart Institute Journal
Vascular ring is a rare congenital anomaly in which the abnormal origin of the aorta or its branches and pulmonary arteries leads to encircling and compression of the trachea and esophagus. A right aortic arch (RAA) with an aberrant left subclavian artery is one of the most common forms of vascular ring. Here, we report a case of a prenatally diagnosed vascular ring resulting from an RAA with an aberrant left subclavian artery. When the infant was 7 months of age, the development of noisy breathing prompted further evaluation with cardiac magnetic resonance imaging that showed an atretic left subclavian …
A Case Of Perifollicular Macular Amyloidosis
A Case Of Perifollicular Macular Amyloidosis
Faculty, Staff and Student Publications
Macular amyloidosis is a common type of primary localized cutaneous amyloidosis. We present a case report of a 74-year-old patient with no significant past medical history who was evaluated for dark macules and pruritus for over a year. On exam, follicular-based brown macules on the upper and lower back, bilateral shoulders, and bilateral dorsal upper arms were noted. The morphology and distribution of follicular-based macules was unusual, so the differential included follicular lichen planus, follicular eczema, and macular amyloidosis. Punch biopsy showed deposits of eosinophilic fibrillary material along with pigmentary incontinence in the papillary dermis, consistent with macular amyloidosis. Additionally, …
Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Alexa Levey
Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Alexa Levey
Faculty, Staff and Student Publications
Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.
Minimal Impact Of The Covid-19 Pandemic On Disease Activity And Health-Related Quality Of Life In Patients With Ankylosing Spondylitis Receiving Bimekizumab: Exploratory Analyses From A Phase 2b Open-Label Extension Study, John D Reveille, Marga Oortgiesen, Natasha De Peyrecave, Atul Deodhar
Minimal Impact Of The Covid-19 Pandemic On Disease Activity And Health-Related Quality Of Life In Patients With Ankylosing Spondylitis Receiving Bimekizumab: Exploratory Analyses From A Phase 2b Open-Label Extension Study, John D Reveille, Marga Oortgiesen, Natasha De Peyrecave, Atul Deodhar
Faculty, Staff and Student Publications
OBJECTIVE: The impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health-related quality of life (HRQoL) through the pandemic in patients with AS.
METHODS: In the open-label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID-19 pandemic …
Coronary-To-Coronary Bypass Grafting In Aortoarteritis: A Case Report
Coronary-To-Coronary Bypass Grafting In Aortoarteritis: A Case Report
Faculty, Staff and Student Publications
Takayasu's arteritis (TA) is an idiopathic vasculitis affecting the aorta and its major branches. In TA, coronary artery involvement is rare and it mainly consists of stenosis or occlusion of the coronary ostia. In TA, as the arterial tree is diseased, often, arterial grafts are unsuitable for grafting so the saphenous vein grafts (SVG) are commonly used. We present a case of a young female with TA with an ostial left main stenosis who has undergone a right coronary-to-left anterior descending artery SVG and put on immunosuppression and steroids. She was asymptomatic with a patent graft during 7 years follow-up.
Post–Lung Transplantation Outcomes And Ex Vivo Histopathological Findings In Severe Post-Covid-19 Pulmonary Disease—A Single-Center Experience, Rodrigo Hasbun
Post–Lung Transplantation Outcomes And Ex Vivo Histopathological Findings In Severe Post-Covid-19 Pulmonary Disease—A Single-Center Experience, Rodrigo Hasbun
Faculty, Staff and Student Publications
BACKGROUND: A significant proportion of patients with severe and persistent coronavirus disease 2019 (COVID-19) require continuous ventilatory support and occasional extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS). Lung transplantation is a treatment option for patients who develop severe ARDS.
METHODS: Our lung transplant database was retrospectively reviewed for patients who underwent lung transplantation for COVID-19 pulmonary disease at Memorial Hermann Hospital, Texas Medical Center, Houston, Texas, from January 2020 to March 2022. We evaluated outcomes of patients who were followed in our clinic at least 6 months post-transplant. Pretransplant patient characteristics, COVID-19-related treatment, histopathology results, and postdischarge …
Modulation Of The Association Between Age And Death By Risk Factor Burden In Critically Ill Patients With Covid-19, Rupal Mehta
Modulation Of The Association Between Age And Death By Risk Factor Burden In Critically Ill Patients With Covid-19, Rupal Mehta
Faculty, Staff and Student Publications
Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death.
DESIGN: Multicenter cohort study.
SETTING: ICUs at 68 hospitals across the United States.
PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between …
Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Johanna T Fifi, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth
Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Johanna T Fifi, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth
Faculty, Staff and Student Publications
Background: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).
Methods: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …
Problematic Online Gaming. Is It Real And Does It Matter To Our Teenagers?, Kevin Kaplan Md, David Spielberg, Binal Kancherla, Daniel Glaze, O'Brian Smith, Timothy Vece, Marianna Sockrider
Problematic Online Gaming. Is It Real And Does It Matter To Our Teenagers?, Kevin Kaplan Md, David Spielberg, Binal Kancherla, Daniel Glaze, O'Brian Smith, Timothy Vece, Marianna Sockrider
Journal of Applied Research on Children: Informing Policy for Children at Risk
Background: Video games and social media have become an ubiquitous part of our society. Video games have been associated with both positive and negative health consequences. There is a growing body of literature supporting the idea that users can develop problematic interactive media use. We hypothesized that teenagers who screened positive for internet gaming disorder would have correlations with other psychosocial and behavioral concerns when compared to their peers.
Methods: An urban cohort of high school students aged 14-18 years completed validated self-reported questionnaires to screen for internet gaming disorder, risk of depression, daytime sleepiness, and quality of life measures. …
Virtual Global Health In Graduate Medical Education: A Systematic Review, Nathaniel E Hayward, Shaina Hecht, Priya Agrawal, Amy Chambliss, Jessica Evert, Heather Haq, Stephanie M Lauden, George Paasi, Mary Schleicher, Megan Song Mchenry
Virtual Global Health In Graduate Medical Education: A Systematic Review, Nathaniel E Hayward, Shaina Hecht, Priya Agrawal, Amy Chambliss, Jessica Evert, Heather Haq, Stephanie M Lauden, George Paasi, Mary Schleicher, Megan Song Mchenry
Faculty, Staff and Students Publications
OBJECTIVES: To synthesize recent virtual global health education activities for graduate medical trainees, document gaps in the literature, suggest future study, and inform best practice recommendations for global health educators.
METHODS: We systematically reviewed articles published on virtual global health education activities from 2012-2021 by searching MEDLINE, EMBASE, Cochrane Library, ERIC, Scopus, Web of Science, and ProQuest Dissertations & Theses A&I. We performed bibliography review and search of conference and organization websites. We included articles about primarily virtual activities targeting for health professional trainees. We collected and qualitatively analyzed descriptive data about activity type, evaluation, audience, and drivers or barriers. …
Phage Resistance Accompanies Reduced Fitness Of Uropathogenic Escherichia Coli In The Urinary Environment, Mallory B Ballard, Marlyd E Mejia, Vicki Mercado-Evans, Emmaline R Heckmann, Belkys C Sanchez, Barbara W Trautner, Anthony W Maresso, Kathryn A Patras
Phage Resistance Accompanies Reduced Fitness Of Uropathogenic Escherichia Coli In The Urinary Environment, Mallory B Ballard, Marlyd E Mejia, Vicki Mercado-Evans, Emmaline R Heckmann, Belkys C Sanchez, Barbara W Trautner, Anthony W Maresso, Kathryn A Patras
Faculty, Staff and Students Publications
Urinary tract infection (UTI) is among the most common infections treated worldwide each year and is caused primarily by uropathogenic Escherichia coli (UPEC). Rising rates of antibiotic resistance among uropathogens have spurred a consideration of alternative treatment strategies, such as bacteriophage (phage) therapy; however, phage-bacterial interactions within the urinary environment are poorly defined. Here, we assess the activity of two phages, namely, HP3 and ES17, against clinical UPEC isolates using in vitro and in vivo models of UTI. In both bacteriologic medium and pooled human urine, we identified phage resistance arising within the first 6 to 8 h of coincubation. …
Changes In Apparent Diffusion Coefficient (Adc) In Serial Weekly Mri During Radiotherapy In Patients With Head And Neck Cancer: Results From The Predict-Hn Study, Sweet Ping Ng, Carlos E Cardenas, Houda Bahig, Baher Elgohari, Jihong Wang, Amy C Moreno, Adam S Garden, Jack Phan, G Brandon Gunn, Steven J Frank, Yao Ding, Lumine Na, Ying Yuan, Diana Urbauer, Abdallah S R Mohamed, David I Rosenthal, William H Morrison, Michael P Macmanus, Clifton D Fuller
Changes In Apparent Diffusion Coefficient (Adc) In Serial Weekly Mri During Radiotherapy In Patients With Head And Neck Cancer: Results From The Predict-Hn Study, Sweet Ping Ng, Carlos E Cardenas, Houda Bahig, Baher Elgohari, Jihong Wang, Amy C Moreno, Adam S Garden, Jack Phan, G Brandon Gunn, Steven J Frank, Yao Ding, Lumine Na, Ying Yuan, Diana Urbauer, Abdallah S R Mohamed, David I Rosenthal, William H Morrison, Michael P Macmanus, Clifton D Fuller
Faculty, Staff and Student Publications
Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy.
Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time.
Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that …
Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Richard B Clark
Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Richard B Clark
Faculty, Staff and Student Publications
Mycobacterium abscessus group (MAG) are rapidly growing acid-fast bacteria that consist of three closely related species: M. abscessus (Ma), M. bolletii (Mb), and M. massiliense (Mm). Differentiation of these species can be difficult but is increasingly requested owing to recent infectious outbreaks and their differential drug resistance. We developed a novel and rapid pyrosequencing method using short signature sequences (35 to 45 bp) at a hypervariable site in the rpoB gene to differentiate the three MAG species, along with M. chelonae (Mc), and M. immunogenum (Mi). This method was evaluated …
Integrated Relationship Of Nasopharyngeal Airway Host Response And Microbiome Associates With Bronchiolitis Severity, Robert J Freishtat, Juan C Celedón, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa
Integrated Relationship Of Nasopharyngeal Airway Host Response And Microbiome Associates With Bronchiolitis Severity, Robert J Freishtat, Juan C Celedón, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa
Faculty, Staff and Students Publications
Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell …
Endophenotype Effect Sizes Support Variant Pathogenicity In Monogenic Disease Susceptibility Genes, Giorgio Melloni, Victor Nauffal, Amelia W Hall, Sophia Gunn, Christina A Austin-Tse, James P Pirruccello, Shaan Khurshid, Heidi L Rehm, Emelia J Benjamin, Eric Boerwinkle, Jennifer A Brody, Adolfo Correa, Brandon K Fornwalt, Namrata Gupta, Christopher M Haggerty, Stephanie Harris, Susan R Heckbert, Charles C Hong, Henry J Lin, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Wendy Post, Bruce M Psaty, Susan Redline, Kenneth M Rice, Stephen S Rich, Jerome I Rotter, Peter F Schnatz, Elsayed Z Soliman, Nona Sotoodehnia, Eugene K Wong, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Marc S Sabatine, Christian T Ruff, Kathryn L Lunetta, Patrick T Ellinor, Steven A Lubitz
Endophenotype Effect Sizes Support Variant Pathogenicity In Monogenic Disease Susceptibility Genes, Giorgio Melloni, Victor Nauffal, Amelia W Hall, Sophia Gunn, Christina A Austin-Tse, James P Pirruccello, Shaan Khurshid, Heidi L Rehm, Emelia J Benjamin, Eric Boerwinkle, Jennifer A Brody, Adolfo Correa, Brandon K Fornwalt, Namrata Gupta, Christopher M Haggerty, Stephanie Harris, Susan R Heckbert, Charles C Hong, Henry J Lin, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Wendy Post, Bruce M Psaty, Susan Redline, Kenneth M Rice, Stephen S Rich, Jerome I Rotter, Peter F Schnatz, Elsayed Z Soliman, Nona Sotoodehnia, Eugene K Wong, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Marc S Sabatine, Christian T Ruff, Kathryn L Lunetta, Patrick T Ellinor, Steven A Lubitz
Faculty, Staff and Student Publications
Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P < 0.001 for each trait) and discriminate pathogenic from non-pathogenic variants (area under the curve 0.82-0.84 across endophenotypes). An effect size threshold of ≥ 0.5 times the endophenotype standard deviation nominates up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes with pathogenic potential. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.
Association Between Fall History And Gait, Balance, Physical Activity, Depression, Fear Of Falling, And Motor Capacity: A 6-Month Follow-Up Study, Catherine Park, Md Moin Uddin Atique, Ramkinker Mishra, Bijan Najafi
Association Between Fall History And Gait, Balance, Physical Activity, Depression, Fear Of Falling, And Motor Capacity: A 6-Month Follow-Up Study, Catherine Park, Md Moin Uddin Atique, Ramkinker Mishra, Bijan Najafi
Center on Aging Staff Publications
Maintaining function in older adults is key to the quality of life and longevity. This study examined the potential impact of falls on accelerating further deterioration over time in gait, balance, physical activity, depression, fear of falling, and motor capacity in older adults. 163 ambulatory older adults (age = 76.5 ± 7.7 years) participated and were followed for 6 months. They were classified into fallers or non-fallers based on a history of falling within the past year. At baseline and 6 months, all participants were objectively assessed for gait, balance, and physical activity using wearable sensors. Additional assessments included psychosocial …
Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Julie De Backer, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz
Comparative Risks Of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease, Julie De Backer, Anji T Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott Lemaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M Milewicz
Faculty, Staff and Student Publications
BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.
OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.
METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, …
Molecular Analysis Of Short- Versus Long-Term Survivors Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Emine Bayraktar, Graziela Zibetti Dal Molin, Sherry Y Wu, Lingegowda S Mangala, Ying Wang, Sara Corvigno, Hu Chen, Han Liang, Shelley S Tworoger, Douglas A Levine, Susan K Lutgendorf, Jinsong Liu, Kathleen N Moore, Keith A Baggerly, Beth Y Karlan, Anil K Sood
Molecular Analysis Of Short- Versus Long-Term Survivors Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Emine Bayraktar, Graziela Zibetti Dal Molin, Sherry Y Wu, Lingegowda S Mangala, Ying Wang, Sara Corvigno, Hu Chen, Han Liang, Shelley S Tworoger, Douglas A Levine, Susan K Lutgendorf, Jinsong Liu, Kathleen N Moore, Keith A Baggerly, Beth Y Karlan, Anil K Sood
Faculty, Staff and Student Publications
Despite having similar histologic features, patients with high-grade serous ovarian carcinoma (HGSC) often experience highly variable outcomes. The underlying determinants for long-term survival (LTS, ≥10 years) versus short-term survival (STS, < 3 years) are largely unknown. The present study sought to identify molecular predictors of LTS for women with HGSC. A cohort of 24 frozen HGSC samples was collected (12 LTS and 12 STS) and analyzed at DNA, RNA, and protein levels. OVCAR5 and OVCAR8 cell lines were used for in vitro validation studies. For in vivo studies, we injected OVCAR8 cells into the peritoneal cavity of female athymic nude mice. From RNAseq analysis, 11 genes were found to be differentially expressed between the STS and LTS groups (fold change > 2; false discovery rate < 0.01). In the subsequent validation cohort, transmembrane protein 62 (TMEM62) was found to be related to LTS. CIBERSORT analysis showed that T cells (follicular helper) were found at higher levels in tumors from LTS than STS groups. In vitro data using OVCAR5 and OVCAR8 cells showed decreased proliferation with TMEM62 overexpression and positive correlation with a longevity-regulating pathway (KEGG HSA04213) at the RNA level. In vivo analysis using the OVCAR8-TMEM62-TetON model showed decreased tumor burden in mice with high- vs. low-expressing TMEM62 tumors. Our results demonstrate that restoring TMEM62 may be a novel approach for treatment of HGSC. These findings may have implications for biomarker and intervention strategies to help improve patient outcomes
Fiber Bragg Grating Array For Shape Reconstruction In Structural Elements, Arnaldo Leal-Junior
Fiber Bragg Grating Array For Shape Reconstruction In Structural Elements, Arnaldo Leal-Junior
Faculty, Staff and Student Publications
This paper presents the development, analysis and application of a fiber Bragg grating (FBG) array for two-dimensional (2D) shape reconstruction in a cantilever beam. The structural elements made of Pinus wood and Nylon 6.0 were numerically analyzed using the finite element method for the strain distribution when constant loading is applied at the free end of the beam. In addition, the temperature compensation method is proposed to decouple the temperature cross-sensitivity in the deflection analysis. In this case, the temperature sensitivities of all sensing elements of the 5-FBG array were obtained. An additional FBG was encapsulated in a silicone mold …
Contributions Of Circulating Micrornas For Early Detection Of Lung Cancer, Jody Vykoukal, Johannes F Fahrmann, Nikul Patel, Masayoshi Shimizu, Edwin J Ostrin, Cristina Ivan, Mark D Thornquist, Matt J Barnett, Ziding Feng, George A Calin, Samir M Hanash
Contributions Of Circulating Micrornas For Early Detection Of Lung Cancer, Jody Vykoukal, Johannes F Fahrmann, Nikul Patel, Masayoshi Shimizu, Edwin J Ostrin, Cristina Ivan, Mark D Thornquist, Matt J Barnett, Ziding Feng, George A Calin, Samir M Hanash
Faculty, Staff and Student Publications
There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) …
Evaluation Of Vicinity-Based Hidden Markov Models For Genotype Imputation
Evaluation Of Vicinity-Based Hidden Markov Models For Genotype Imputation
Faculty, Staff and Student Publications
BACKGROUND: The decreasing cost of DNA sequencing has led to a great increase in our knowledge about genetic variation. While population-scale projects bring important insight into genotype-phenotype relationships, the cost of performing whole-genome sequencing on large samples is still prohibitive. In-silico genotype imputation coupled with genotyping-by-arrays is a cost-effective and accurate alternative for genotyping of common and uncommon variants. Imputation methods compare the genotypes of the typed variants with the large population-specific reference panels and estimate the genotypes of untyped variants by making use of the linkage disequilibrium patterns. Most accurate imputation methods are based on the Li-Stephens hidden Markov …
Assessing Age-Specific Vaccination Strategies And Post-Vaccination Reopening Policies For Covid-19 Control Using Seir Modeling Approach
Faculty, Staff and Student Publications
As the availability of COVID-19 vaccines, it is badly needed to develop vaccination guidelines to prioritize the vaccination delivery in order to effectively stop COVID-19 epidemic and minimize the loss. We evaluated the effect of age-specific vaccination strategies on the number of infections and deaths using an SEIR model, considering the age structure and social contact patterns for different age groups for each of different countries. In general, the vaccination priority should be given to those younger people who are active in social contacts to minimize the number of infections, while the vaccination priority should be given to the elderly …