Public Health Commons^™

Of Vascular Defense, Hemostasis, Cancer, And Platelet Biology: An Evolutionary Perspective, David G Menter, Vahid Afshar-Kharghan, John Paul Shen, Stephanie L Martch, Anirban Maitra, Scott Kopetz, Kenneth V Honn, Anil K Sood

Faculty, Staff and Student Publications

We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets …

Crare Coding Variants In Rcn3 Are Associated With Blood Pressure, Karen Y He, Tanika N Kelly, Heming Wang, Jingjing Liang, Luke Zhu, Brian E Cade, Themistocles L Assimes, Lewis C Becker, Amber L Beitelshees, Lawrence F Bielak, Adam P Bress, Jennifer A Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S De Vries, Ravindranath Duggirala, Ervin R Fox, Nora Franceschini, Anna L Furniss, Yan Gao, Xiuqing Guo, Jeffrey Haessler, Yi-Jen Hung, Shih-Jen Hwang, Marguerite Ryan Irvin, Rita R Kalyani, Ching-Ti Liu, Chunyu Liu, Lisa Warsinger Martin, May E Montasser, Paul M Muntner, Stanford Mwasongwe, Take Naseri, Walter Palmas, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Wayne H-H Sheu, Daichi Shimbo, Jennifer A Smith, Beverly M Snively, Lisa R Yanek, Wei Zhao, John Blangero, Eric Boerwinkle, Yii-Der Ida Chen, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Myriam Fornage, Jiang He, Lifang Hou, Robert C Kaplan, Sharon L R Kardia, Eimear E Kenny, Charles Kooperberg, Donald Lloyd-Jones, Ruth J F Loos, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Kari E North, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, D C Rao, Susan Redline, Alex P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Russell Tracy, Ramachandran S Vasan, Samoan Obesity, Lifestyle And Genetic Adaptations Study (Olaga) Group, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Alanna C Morrison, Daniel Levy, Aravinda Chakravarti, Donna K Arnett, Xiaofeng Zhu

Faculty, Staff and Student Publications

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of …

Applying Evidence-Based Intervention (Ebi) Mapping To Identify The Components And Logic Of Colorectal Cancer Screening Interventions, Jacob Szeszulski, Derek W Craig, Timothy J Walker, Maya Foster, Patricia Dolan Mullen, Maria E Fernandez

Faculty, Staff and Student Publications

Implementation of evidence-based interventions (EBIs) can help to increase colorectal cancer screening (CRCS). Potential users of CRCS EBIs are often unclear about the specific features, logic, and core elements of existing EBIs, making it challenging to use or adapt them. We used EBI Mapping, a systematic process developed from Intervention Mapping that identifies an EBI's components and logic, to characterize existing CRCS EBIs from the National Cancer Institute's Evidence-Based Cancer Control Programs website. The resulting information can facilitate intervention adoption, adaptation, and/or implementation. Two trained coders independently coded intervention materials to describe intervention components and logic (n = 20). We …

Differences In Psychosocial Constructs Among Elementary School Staff That Implement Physical Activity Programs: A Step In Designing Implementation Strategies, Jacob Szeszulski, Timothy J Walker, Michael C Robertson, Maria E Fernandez

Faculty, Staff and Student Publications

Multiple types of school staff members (e.g., classroom teachers, principals) are involved in implementing physical activity programs (e.g., classroom-based, gym), but factors specific to their job responsibilities may inhibit their ability to implement programming effectively. Thus, implementation strategies tailored by job type may be needed. We compare perceptions of behavioral constructs related to implementation of school-based physical activity programs, by job type, among school staff. School staff (n = 139), including principals/assistant principals (n = 21), physical education teachers (n = 41), and classroom teachers (n = 77), from elementary schools (n = 25), completed a cross-sectional survey measuring perceptions …

Fully Resolved Assembly Of Cryptosporidium Parvum, Vipin K Menon, Pablo C Okhuysen, Cynthia L Chappell, Medhat Mahmoud, Medhat Mahmoud, Qingchang Meng, Harsha Doddapaneni, Vanesa Vee, Yi Han, Sejal Salvi, Sravya Bhamidipati, Kavya Kottapalli, George Weissenberger, Hua Shen, Matthew C Ross, Kristi L Hoffman, Sara Javornik Cregeen, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck

Faculty, Staff and Student Publications

BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies.

FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from …

The Association Between Rest-Activity Rhythms And Glycemic Markers: The Us National Health And Nutrition Examination Survey, 2011-2014, Qian Xiao, Charles E Matthews, Mary Playdon, Cici Bauer

Faculty, Staff and Student Publications

OBJECTIVES: Previous studies conducted in mostly homogeneous sociodemographic samples have reported a relationship between weakened and/or disrupted rest-activity patterns and metabolic dysfunction. This study aims to examine rest-activity rhythm characteristics in relation to glycemic markers in a large nationally representative and diverse sample of American adults.

METHODS: This study used data from the National Health and Nutrition Examination Survey 2011-2014. Rest-activity characteristics were derived from extended cosine models using 24-hour actigraphy. We used multinomial logistic regression and multiple linear regression models to assess the associations with multiple glycemic markers (i.e., glycated hemoglobin, fasting glucose and insulin, homeostatic model assessment of …

Translating Research Into Practice-Implementation Recommendations For Pediatric Rheumatology; Proceedings Of The Childhood Arthritis And Rheumatology Research Alliance 2020 Implementation Science Retreat, Cagri Yildirim-Toruner, Rajdeep Pooni, Y Ingrid Goh, Emily Becker-Haimes, James W Dearing, Maria E Fernandez, Esi M Morgan, Gareth Parry, Jon M Burnham, Stacy P Ardoin, Fatima Barbar-Smiley, Joyce C Chang, Peter Chiraseveenuprapund, Vincent Del Gaizo, Guy Eakin, Lisa C Johnson, Yukiko Kimura, Andrea M Knight, Melanie Kohlheim, Erica F Lawson, Mindy S Lo, Nancy Pan, Andrea Ring, Tova Ronis, Rebecca E Sadun, Emily A Smitherman, Alysha J Taxter, Janalee Taylor, Richard K Vehe, Sheetal S Vora, Jennifer E Weiss, Emily Von Scheven, Mas For The Carra Implementation Science Workgroup

Faculty, Staff and Student Publications

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. …

Comparison Of Sexually Transmitted Infections And Adverse Perinatal Outcomes In Underserved Pregnant Patients Before Vs During The Covid-19 Pandemic In Texas, Irene A Stafford, Jennie O Coselli, Danielle F Wilson, Courtney Y Wang, Baha M Sibai

Faculty, Staff and Student Publications

This cohort study assesses the rates of sexually transmitted infections (STI) and associated adverse perinatal outcomes among underserved pregnant patients during the COVID-19 pandemic in a public health system in Southeastern Texas.

A Large-Scale Transcriptome-Wide Association Study (Twas) Of 10 Blood Cell Phenotypes Reveals Complexities Of Twas Fine-Mapping, Amanda L Tapia, Bryce T Rowland, Jonathan D Rosen, Michael Preuss, Kris Young, Misa Graff, Hélène Choquet, David J Couper, Steve Buyske, Stephanie A Bien, Eric Jorgenson, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Kari E North, Bing Yu, Alexander P Reiner, Yun Li, Laura M Raffield

Faculty, Staff and Student Publications

Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort. We found 239 significant gene-trait associations with hematological measures; we replicated 71 associations at p < 0.05 in a TWAS meta-analysis consisting of up to 35,900 Europeans from the Women's Health Initiative, Atherosclerosis Risk in Communities Study, and BioMe Biobank. Additionally, we attempted to refine this list of candidate genes by performing conditional analyses, adjusting for individual variants previously associated with hematological measures, and performed further fine-mapping of TWAS loci. To facilitate interpretation of our findings, we designed an R Shiny application to interactively visualize our TWAS results by integrating them with additional genetic data sources (GWAS, TWAS from multiple reference panels, conditional analyses, known GWAS variants, etc.). Our results and application highlight frequently overlooked TWAS challenges and illustrate the complexity of TWAS fine-mapping.

Genetic Errors Of Immunity Distinguish Pediatric Nonmalignant Lymphoproliferative Disorders, Lisa R Forbes, Olive S Eckstein, Nitya Gulati, Erin C Peckham-Gregory, Nmazuo W Ozuah, Joseph Lubega, Nader K El-Mallawany, Jennifer E Agrusa, M Cecilia Poli, Tiphanie P Vogel, Natalia S Chaimowitz, Nicholas L Rider, Emily M Mace, Jordan S Orange, Jason W Caldwell, Juan C Aldave-Becerra, Stephen Jolles, Francesco Saettini, Hey J Chong, Asbjorg Stray-Pedersen, Helen E Heslop, Kala Y Kamdar, R Helen Rouce, Donna M Muzny, Shalini N Jhangiani, Richard A Gibbs, Zeynep H Coban-Akdemir, James R Lupski, Kenneth L Mcclain, Carl E Allen, Ivan K Chinn

Faculty, Staff and Student Publications

BACKGROUND: Pediatric nonmalignant lymphoproliferative disorders (PLPDs) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD.

OBJECTIVE: The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes.

METHODS: PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant Epstein-Barr virus (EBV) infection. Fifty-one subjects from …

Spatial Epidemiology: An Empirical Framework For Syndemics Research, Shikhar Shrestha, Cici X C Bauer, Brian Hendricks, Thomas J Stopka

Faculty, Staff and Student Publications

Syndemics framework describes two or more co-occurring epidemics that synergistically interact with each other and the complex structural social forces that sustain them leading to excess disease burden. The term syndemic was first used to describe the interaction between substance abuse, violence, and AIDS by Merrill Singer. A broader range of syndemic studies has since emerged describing the framework's applicability to other public health scenarios. With syndemic theory garnering significant attention, the focus is shifting towards developing robust empirical analytical approaches. Unfortunately, the complex nature of the disease-disease interactions nested within several social contexts complicates empirical analyses. In answering the …

Efficacy And Safety Of Covid-19 Convalescent Plasma In Hospitalized Patients: A Randomized Clinical Trial, Mila B Ortigoza, Hyunah Yoon, Keith S Goldfeld, Andrea B Troxel, Johanna P Daily, Yinxiang Wu, Yi Li, Danni Wu, Gia F Cobb, Gillian Baptiste, Mary O'Keeffe, Marilou O Corpuz, Luis Ostrosky-Zeichner, Amee Amin, Ioannis M Zacharioudakis, Dushyantha T Jayaweera, Yanyun Wu, Julie V Philley, Megan S Devine, Mahalia S Desruisseaux, Alessandro D Santin, Shweta Anjan, Reeba Mathew, Bela Patel, Masayuki Nigo, Rabi Upadhyay, Tania Kupferman, Andrew N Dentino, Rahul Nanchal, Christian A Merlo, David N Hager, Kartik Chandran, Jonathan R Lai, Johanna Rivera, Chowdhury R Bikash, Gorka Lasso, Timothy P Hilbert, Monika Paroder, Andrea A Asencio, Mengling Liu, Eva Petkova, Alexander Bragat, Reza Shaker, David D Mcpherson, Ralph L Sacco, Marla J Keller, Corita R Grudzen, Judith S Hochman, Liise-Anne Pirofski, Lalitha Parameswaran, Anthony T Corcoran, Abhinav Rohatgi, Marta W Wronska, Xinyuan Wu, Ranjini Srinivasan, Fang-Ming Deng, Thomas D Filardo, Jay Pendse, Simone B Blaser, Olga Whyte, Jacqueline M Gallagher, Ololade E Thomas, Danibel Ramos, Caroline L Sturm-Reganato, Charlotte C Fong, Ivy M Daus, Arianne Gisselle Payoen, Joseph T Chiofolo, Mark T Friedman, Ding Wen Wu, Jessica L Jacobson, Jeffrey G Schneider, Uzma N Sarwar, Henry E Wang, Ryan M Huebinger, Goutham Dronavalli, Yu Bai, Carolyn Z Grimes, Karen W Eldin, Virginia E Umana, Jessica G Martin, Timothy R Heath, Fatimah O Bello, Daru Lane Ransford, Maudry Laurent-Rolle, Sheela V Shenoi, Oscar Bate Akide-Ndunge, Bipin Thapa, Jennifer L Peterson, Kelly Knauf, Shivani U Patel, Laura L Cheney, Christopher A Tormey, Jeanne E Hendrickson

Faculty, Staff and Student Publications

IMPORTANCE: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.

OBJECTIVE: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.

DESIGN, SETTING, AND PARTICIPANTS: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation.

INTERVENTIONS: A unit of …

Machine Learning For Predicting Risk Of Early Dropout In A Recovery Program For Opioid Use Disorder, Assaf Gottlieb, Andrea Yatsco, Christine Bakos-Block, James R Langabeer, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

BACKGROUND: An increase in opioid use has led to an opioid crisis during the last decade, leading to declarations of a public health emergency. In response to this call, the Houston Emergency Opioid Engagement System (HEROES) was established and created an emergency access pathway into long-term recovery for individuals with an opioid use disorder. A major contributor to the success of the program is retention of the enrolled individuals in the program.

METHODS: We have identified an increase in dropout from the program after 90 and 120 days. Based on more than 700 program participants, we developed a machine learning …

Common Genetic Variants Contribute To Risk Of Transposition Of The Great Arteries, Doris Škorić-Milosavljević, Rafik Tadros, Fernanda M Bosada, Federico Tessadori, Jan Hendrik Van Weerd, Odilia I Woudstra, Fleur V Y Tjong, Najim Lahrouchi, Fanny Bajolle, Heather J Cordell, A J Agopian, Gillian M Blue, Daniela Q C M Barge-Schaapveld, Marc Gewillig, Christoph Preuss, Elisabeth M Lodder, Phil Barnett, Aho Ilgun, Leander Beekman, Karel Van Duijvenboden, Regina Bokenkamp, Martina Müller-Nurasyid, Hubert W Vliegen, Thelma C Konings, Joost P Van Melle, Arie P J Van Dijk, Roland R J Van Kimmenade, Jolien W Roos-Hesselink, Gertjan T Sieswerda, Folkert Meijboom, Hashim Abdul-Khaliq, Felix Berger, Sven Dittrich, Marc-Phillip Hitz, Julia Moosmann, Frank-Thomas Riede, Stephan Schubert, Pilar Galan, Mark Lathrop, Hans M Munter, Ammar Al-Chalabi, Christopher E Shaw, Pamela J Shaw, Karen E Morrison, Jan H Veldink, Leonard H Van Den Berg, Sylvia Evans, Marcelo A Nobrega, Ivy Aneas, Milena Radivojkov-Blagojević, Thomas Meitinger, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John F Smythe, Luis Altamirano-Diaz, Jane Lougheed, Berto J Bouma, Marie-A Chaix, Jennie Kline, Anne S Bassett, Gregor Andelfinger, Roel L F Van Der Palen, Patrice Bouvagnet, Sally-Ann B Clur, Jeroen Breckpot, Wilhelmina S Kerstjens-Frederikse, David S Winlaw, Ulrike M M Bauer, Seema Mital, Elizabeth Goldmuntz, Bernard Keavney, Damien Bonnet, Barbara J Mulder, Michael W T Tanck, Jeroen Bakkers, Vincent M Christoffels, Cornelis J Boogerd, Alex V Postma, Connie R Bezzina

Faculty, Staff and Student Publications

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA.

METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients …

Effects Of Road Traffic On The Accuracy And Bias Of Low-Cost Particulate Matter Sensor Measurements In Houston, Texas, Temitope Oluwadairo, Lawrence Whitehead, Elaine Symanski, Cici Bauer, Arch Carson, Inkyu Han

Faculty, Staff and Student Publications

Although PM2.5 measurements of low-cost particulate matter sensors (LCPMS) generally show moderate and strong correlations with those from research-grade air monitors, the data quality of LCPMS has not been fully assessed in urban environments with different road traffic conditions. We examined the linear relationships between PM2.5 measurements taken by an LCPMS (Dylos DC1700) and two research grade monitors, a personal environmental monitor (PEM) and the GRIMM 11R, in three different urban environments, and compared the accuracy (slope) and bias of these environments. PM2.5 measurements were carried out at three locations in Houston, Texas (Clinton Drive largely with diesel trucks, US-59 …

Active Living After Cancer: Adaptation And Evaluation Of A Community-Based Physical Activity Program For Minority And Medically Underserved Breast Cancer Survivors, Irene M Tami-Maury, Yue Liao, Maria L Rangel, Leticia A Gatus, Eileen H Shinn, Ashley Alexander, Karen Basen-Engquist

Faculty, Staff and Student Publications

BACKGROUND: An expanding body of research documents the benefits of physical activity for cancer survivors' physical functioning and quality of life, but few successful models provide community-based physical activity programs to cancer survivors. This report presents an evaluation of Active Living After Cancer, an evidence-based physical activity program for breast cancer survivors, adapted for community delivery to minority and medically underserved survivors.

METHODS: Survivors were recruited from health care and community settings. The program consisted of 12 weekly group sessions providing training in cognitive and behavioral skills for behavior change, brief physical activity, and cancer survivorship-related content. At the baseline …

New Approaches For Testing Non-Inferiority For Three-Arm Trials With Poisson Distributed Outcomes, Samiran Ghosh, Erina Paul, Shrabanti Chowdhury, Ram C Tiwari

Faculty, Staff and Student Publications

With the availability of limited resources, innovation for improved statistical method for the design and analysis of randomized controlled trials (RCTs) is of paramount importance for newer and better treatment discovery for any therapeutic area. Although clinical efficacy is almost always the primary evaluating criteria to measure any beneficial effect of a treatment, there are several important other factors (e.g., side effects, cost burden, less debilitating, less intensive, etc.), which can permit some less efficacious treatment options favorable to a subgroup of patients. This leads to non-inferiority (NI) testing. The objective of NI trial is to show that an experimental …

Genetic Determinants Of Telomere Length From 109,122 Ancestrally Diverse Whole-Genome Sequences In Topmed, Margaret A Taub, Matthew P Conomos, Rebecca Keener, Kruthika R Iyer, Joshua S Weinstock, Lisa R Yanek, John Lane, Tyne W Miller-Fleming, Jennifer A Brody, Laura M Raffield, Caitlin P Mchugh, Deepti Jain, Stephanie M Gogarten, Cecelia A Laurie, Ali Keramati, Marios Arvanitis, Albert V Smith, Benjamin Heavner, Lucas Barwick, Lewis C Becker, Joshua C Bis, John Blangero, Eugene R Bleecker, Esteban G Burchard, Juan C Celedón, Yen Pei C Chang, Brian Custer, Dawood Darbar, Lisa De Las Fuentes, Dawn L Demeo, Barry I Freedman, Melanie E Garrett, Mark T Gladwin, Susan R Heckbert, Bertha A Hidalgo, Marguerite R Irvin, Talat Islam, W Craig Johnson, Stefan Kaab, Lenore Launer, Jiwon Lee, Simin Liu, Arden Moscati, Kari E North, Patricia A Peyser, Nicholas Rafaels, Christine Seidman, Daniel E Weeks, Fayun Wen, Marsha M Wheeler, L Keoki Williams, Ivana V Yang, Wei Zhao, Stella Aslibekyan, Paul L Auer, Donald W Bowden, Brian E Cade, Zhanghua Chen, Michael H Cho, L Adrienne Cupples, Joanne E Curran, Michelle Daya, Ranjan Deka, Celeste Eng, Tasha E Fingerlin, Xiuqing Guo, Lifang Hou, Shih-Jen Hwang, Jill M Johnsen, Eimear E Kenny, Albert M Levin, Chunyu Liu, Ryan L Minster, Take Naseri, Mehdi Nouraie, Muagututi'a Sefuiva Reupena, Ester C Sabino, Jennifer A Smith, Nicholas L Smith, Jessica Lasky Su, James G Taylor, Marilyn J Telen, Hemant K Tiwari, Russell P Tracy, Marquitta J White, Yingze Zhang, Kerri L Wiggins, Scott T Weiss, Ramachandran S Vasan, Kent D Taylor, Moritz F Sinner, Edwin K Silverman, M Benjamin Shoemaker, Wayne H-H Sheu, Frank Sciurba, David A Schwartz, Jerome I Rotter, Daniel Roden, Susan Redline, Benjamin A Raby, Bruce M Psaty, Juan M Peralta, Nicholette D Palmer, Sergei Nekhai, Courtney G Montgomery, Braxton D Mitchell, Deborah A Meyers, Stephen T Mcgarvey, Nhlbi Care Network, Angel Cy Mak, Ruth Jf Loos, Rajesh Kumar, Charles Kooperberg, Barbara A Konkle, Shannon Kelly, Sharon Lr Kardia, Robert Kaplan, Jiang He, Hongsheng Gui, Frank D Gilliland, Bruce D Gelb, Myriam Fornage, Patrick T Ellinor, Mariza De Andrade, Adolfo Correa, Yii-Der Ida Chen, Eric Boerwinkle, Kathleen C Barnes, Allison E Ashley-Koch, Donna K Arnett, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology And Hemostasis Working Group, Topmed Structural Variation Working Group, Cathy C Laurie, Goncalo Abecasis, Deborah A Nickerson, James G Wilson, Stephen S Rich, Daniel Levy, Ingo Ruczinski, Abraham Aviv, Thomas W Blackwell, Timothy Thornton, Jeff O'Connell, Nancy J Cox, James A Perry, Mary Armanios, Alexis Battle, Nathan Pankratz, Alexander P Reiner, Rasika A Mathias

Faculty, Staff and Student Publications

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, …

Association Between Perceived Health Risks Of E-Cigarettes And Actual E-Cigarette Use, Based On Cigarette Smoking Status And Sexual And Gender Minority Status Among Us Adults, David Adzrago, Yue Shi, Kayo Fujimoto

Faculty, Staff and Student Publications

BACKGROUND: There is a lack of consensus in the literature about the association between the perceived health risks of e-cigarettes and their actual use, an association that may be based on cigarette smoking status or sexual and gender minority status. This study examined the moderating effect of these variables as well as differences in e-cigarette use between and within perceived harmfulness of e-cigarettes and cigarette smoking among U.S. adults.

METHODS: The data were drawn from the 2020 and 2019 Health Information National Trends Survey (HINTS 5), Cycles 4 and 3, on adults (

RESULTS: Of the study population, 30.75% currently …

Emergence Of Clinical Clostridioides Difficile Isolates With Decreased Susceptibility To Vancomycin, Charles Darkoh, Kadiatou Keita, Chioma Odo, Micah Oyaro, Eric L Brown, Cesar A Arias, Blake M Hanson, Herbert L Dupont

Faculty, Staff and Student Publications

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of hospital-associated antibiotic-related diarrhea and deaths worldwide. Vancomycin is one of the few antibiotics recommended for both nonsevere and severe CDI cases. We sought to determine whether vancomycin nonsusceptible C. difficile strains are circulating in the patient population.

METHODS: Stool samples from patients with CDI were collected from 438 and 98 patients at a large university hospital in Houston, Texas, and Nairobi, Kenya, respectively. The stools were examined for the presence of vancomycin and metronidazole nonsusceptible C. difficile using broth dilution culture, Etest (BioMérieux, France), polymerase chain reaction (PCR), whole-genome sequencing, …

Rare Coding Variants In 35 Genes Associate With Circulating Lipid Levels-A Multi-Ancestry Analysis Of 170,000 Exomes, George Hindy, Peter Dornbos, Mark D Chaffin, Dajiang J Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A Aguilar-Salinas, Lucinda Antonacci-Fulton, Diego Ardissino, Donna K Arnett, Stella Aslibekyan, Gil Atzmon, Christie M Ballantyne, Francisco Barajas-Olmos, Nir Barzilai, Lewis C Becker, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Lori L Bonnycastle, Erwin Bottinger, Donald W Bowden, Matthew J Bown, Jennifer A Brody, Jai G Broome, Noël P Burtt, Brian E Cade, Federico Centeno-Cruz, Edmund Chan, Yi-Cheng Chang, Yii-Der I Chen, Ching-Yu Cheng, Won Jung Choi, Rajiv Chowdhury, Cecilia Contreras-Cubas, Emilio J Córdova, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, John Danesh, Paul S De Vries, Ralph A Defronzo, Harsha Doddapaneni, Ravindranath Duggirala, Susan K Dutcher, Patrick T Ellinor, Leslie S Emery, Jose C Florez, Myriam Fornage, Barry I Freedman, Valentin Fuster, Ma Eugenia Garay-Sevilla, Humberto García-Ortiz, Soren Germer, Richard A Gibbs, Christian Gieger, Benjamin Glaser, Clicerio Gonzalez, Maria Elena Gonzalez-Villalpando, Mariaelisa Graff, Sarah E Graham, Niels Grarup, Leif C Groop, Xiuqing Guo, Namrata Gupta, Sohee Han, Craig L Hanis, Torben Hansen, Jiang He, Nancy L Heard-Costa, Yi-Jen Hung, Mi Yeong Hwang, Marguerite R Irvin, Sergio Islas-Andrade, Gail P Jarvik, Hyun Min Kang, Sharon L R Kardia, Tanika Kelly, Eimear E Kenny, Alyna T Khan, Bong-Jo Kim, Ryan W Kim, Young Jin Kim, Heikki A Koistinen, Charles Kooperberg, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Leslie A Lange, Jiwon Lee, Juyoung Lee, Seonwook Lee, Donna M Lehman, Rozenn N Lemaitre, Allan Linneberg, Jianjun Liu, Ruth J F Loos, Steven A Lubitz, Valeriya Lyssenko, Ronald C W Ma, Lisa Warsinger Martin, Angélica Martínez-Hernández, Rasika A Mathias, Stephen T Mcgarvey, Ruth Mcpherson, James B Meigs, Thomas Meitinger, Olle Melander, Elvia Mendoza-Caamal, Ginger A Metcalf, Xuenan Mi, Karen L Mohlke, May E Montasser, Jee-Young Moon, Hortensia Moreno-Macías, Alanna C Morrison, Donna M Muzny, Sarah C Nelson, Peter M Nilsson, Jeffrey R O'Connell, Marju Orho-Melander, Lorena Orozco, Colin N A Palmer, Nicholette D Palmer, Cheol Joo Park, Kyong Soo Park, Oluf Pedersen, Juan M Peralta, Patricia A Peyser, Wendy S Post, Michael Preuss, Bruce M Psaty, Qibin Qi, D C Rao, Susan Redline, Alexander P Reiner, Cristina Revilla-Monsalve, Stephen S Rich, Nilesh Samani, Heribert Schunkert, Claudia Schurmann, Daekwan Seo, Jeong-Sun Seo, Xueling Sim, Rob Sladek, Kerrin S Small, Wing Yee So, Adrienne M Stilp, E Shyong Tai, Claudia H T Tam, Kent D Taylor, Yik Ying Teo, Farook Thameem, Brian Tomlinson, Michael Y Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Teresa Tusié-Luna, Miriam S Udler, Rob M Van Dam, Ramachandran S Vasan, Karine A Viaud Martinez, Fei Fei Wang, Xuzhi Wang, Hugh Watkins, Daniel E Weeks, James G Wilson, Daniel R Witte, Tien-Yin Wong, Lisa R Yanek, Amp-T2d-Genes, Myocardial Infarction Genetics Consortium, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Nhlbi Topmed Lipids Working Group, Sekar Kathiresan, Daniel J Rader, Jerome I Rotter, Michael Boehnke, Mark I Mccarthy, Cristen J Willer, Pradeep Natarajan, Jason A Flannick, Amit V Khera, Gina M Peloso

Faculty, Staff and Student Publications

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, …

Effects Of Aerosol Particle Size On The Measurement Of Airborne Pm25 With A Low-Cost Particulate Matter Sensor (Lcpms) In A Laboratory Chamber, Temitope Oluwadairo, Lawrence Whitehead, Elaine Symanski, Cici Bauer, Arch Carson, Inkyu Han

Faculty, Staff and Student Publications

Previous validation studies found a good linear correlation between the low-cost particulate matter sensors (LCPMS) and other research grade particulate matter (PM) monitors. This study aimed to determine if different particle size bins of PM would affect the linear relationship and agreement between the Dylos DC1700 (LCPMS) particle count measurements (converted to PM

Effects Of Aerosol Particle Size On The Measurement Of Airborne Pm25 With A Low-Cost Particulate Matter Sensor (Lcpms) In A Laboratory Chamber, Temitope Oluwadairo, Lawrence Whitehead, Elaine Symanski, Cici Bauer, Arch Carson, Inkyu Han

Faculty, Staff and Student Publications

Previous validation studies found a good linear correlation between the low-cost particulate matter sensors (LCPMS) and other research grade particulate matter (PM) monitors. This study aimed to determine if different particle size bins of PM would affect the linear relationship and agreement between the Dylos DC1700 (LCPMS) particle count measurements (converted to PM2.5 mass concentrations) and the Grimm 11R (research grade instrument) mass concentration measurements. Three size groups of PM2.5 (mass median aerodynamic diameters (MMAD): < 1 µm, 1-2 µm, and > 2 µm) were generated inside a laboratory chamber, controlled for temperature and relative humidity, by dispersing sodium chloride crystals through a nebulizer. A linear regression …

Differential Gene Expression In Cord Blood Of Infants Diagnosed With Cerebral Palsy: A Pilot Analysis Of The Beam Cohort, Maria L V Dizon, Raye-Ann O Deregnier, Steven J Weiner, Michael W Varner, Dwight J Rouse, Maged M Costantine, Ronald J Wapner, John M Thorp, Sean C Blackwell, Nina K Ayala, Antonio F Saad, Steve N Caritis, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …

Covid-19 Mortality May Be Reduced Among Fully Vaccinated Solid Organ Transplant Recipients, Micaela Sandoval, Duc T Nguyen, Howard J Huang, Stephanie G Yi, R Mark Ghobrial, A Osama Gaber, Edward A Graviss

Faculty, Staff and Student Publications

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality from COVID-19 due to their immunosuppressed state and reduced immunogenicity from COVID-19 mRNA vaccines. This investigation examined the association between COVID-19 mRNA vaccination status and mortality among SOT recipients diagnosed with COVID-19.

METHODS & FINDINGS: A retrospective, registry-based chart review was conducted investigating COVID-19 mortality among immunosuppressed solid organ transplant (SOT) recipients in a large metropolitan healthcare system in Houston, Texas, USA. Electronic health record data was collected from consecutive SOT recipients who received a diagnostic SARS-CoV-2 test between March 1, 2020, and October 1, 2021. …

Desired Resources For Changing Diet Among Persons With Multiple Sclerosis: Qualitative Inquiry Informing Future Dietary Interventions, Stephanie L Silveira, Emma V Richardson, Robert W Motl

Faculty, Staff and Student Publications

BACKGROUND: There are approximately 1 million adults in the United States with multiple sclerosis (MS). Persons with MS are interested in diet as a second-line therapy for improving MS symptoms and disease progression. Examination of desired resources regarding diet among persons with MS is necessary for supporting behavior change.

METHODS: Twenty-five adults with MS completed 1-on-1, online semistructured interviews. An inductive, 6-phase, semantic thematic analysis was applied to identify themes associated with participant preferences for dietary behavior change.

RESULTS: The research team crafted 4 key themes from the data that encompassed participants' desired resources for dietary behavior change. Theme 1, …

The Healthy Native Youth Implementation Toolbox: Using Implementation Mapping To Adapt An Online Decision Support System To Promote Culturally-Relevant Sexual Health Education For American Indian And Alaska Native Youth, Christine M Markham, Stephanie Craig Rushing, Jane Manthei, Michelle Singer, Cornelia Jessen, Gwenda Gorman, Melissa F Peskin, Belinda F Hernandez, Lea Sacca, Gabrielle S Evans, Claudia Luna-Meza, Zoe Merritt, Ross Shegog

Faculty, Staff and Student Publications

BACKGROUND: American Indian and Alaska Native (AI/AN) youth experience serious disparities in sexual and reproductive health, including the highest teen birth rate among racial/ethnic groups, and disproportionate rates of sexually transmitted infections (STI), including HIV. A growing number of evidence-based programs (EBPs) that integrate the strengths and cultural teachings of Native communities exist. Yet, multiple factors, including lack of trained personnel, limited resources, and geographic isolation, may hinder their adoption and implementation. Innovative implementation strategies that facilitate the adoption and implementation of sexual health EBPs in Native communities may help reduce these disparities.

METHODS: We applied Implementation Mapping, a systematic …

Perceptions Of Physical Activity Guidelines Among Wheelchair Users With Multiple Sclerosis, Stephanie L Silveira, Brenda Jeng, Gary Cutter, Robert W Motl

Faculty, Staff and Student Publications

BACKGROUND: Physical activity guidelines provide prescriptive resources for population-level promotion of behavior change to improve health outcomes. The National Multiple Sclerosis Society (NMSS) recently created and disseminated physical activity guidelines for persons with multiple sclerosis (MS) across the disease spectrum.

OBJECTIVE: This study aimed to assess perceptions of the updated NMSS Physical Activity Guidelines among wheelchair users with MS.

METHODS: One hundred thirty-four wheelchair users with MS participated in a cross-sectional study examining health behaviors. Outcomes were measured using an online questionnaire that included items related to demographic and clinical characteristics and a battery of questions regarding perceptions of the …

Application Of Artificial Intelligence And Machine Learning For Hiv Prevention Interventions, Yang Xiang, Jingcheng Du, Kayo Fujimoto, Fang Li, John Schneider, Cui Tao

Faculty, Staff and Student Publications

In 2019, the US Government announced its goal to end the HIV epidemic within 10 years, mirroring the initiatives set forth by UNAIDS. Public health prevention interventions are a crucial part of this ambitious goal. However, numerous challenges to this goal exist, including improving HIV awareness, increasing early HIV infection detection, ensuring rapid treatment, optimising resource distribution, and providing efficient prevention services for vulnerable populations. Artificial intelligence has had a pivotal role in revolutionising health care and has shown great potential in developing effective HIV prevention intervention strategies. Although artificial intelligence has been used in a few HIV prevention intervention …