Digital Commons Network^™

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.

Artificial Intelligence In Clinical And Translational Science: Successes, Challenges And Opportunities, Elmer V Bernstam, Paula K Shireman, Funda Meric-Bernstam, Meredith N Zozus, Xiaoqian Jiang, Bradley B Brimhall, Ashley K Windham, Susanne Schmidt, Shyam Visweswaran, Ye Ye, Heath Goodrum, Yaobin Ling, Seemran Barapatre, Michael J Becich

Faculty, Staff and Student Publications

Artificial intelligence (AI) is transforming many domains, including finance, agriculture, defense, and biomedicine. In this paper, we focus on the role of AI in clinical and translational research (CTR), including preclinical research (T1), clinical research (T2), clinical implementation (T3), and public (or population) health (T4). Given the rapid evolution of AI in CTR, we present three complementary perspectives: (1) scoping literature review, (2) survey, and (3) analysis of federally funded projects. For each CTR phase, we addressed challenges, successes, failures, and opportunities for AI. We surveyed Clinical and Translational Science Award (CTSA) hubs regarding AI projects at their institutions. Nineteen …

Verticox: Vertically Distributed Cox Proportional Hazards Model Using The Alternating Direction Method Of Multipliers, Wenrui Dai, Xiaoqian Jiang, Luca Bonomi, Yong Li, Hongkai Xiong, Lucila Ohno-Machado

Faculty, Staff and Student Publications

The Cox proportional hazards model is a popular semi-parametric model for survival analysis. In this paper, we aim at developing a federated algorithm for the Cox proportional hazards model over vertically partitioned data (i.e., data from the same patient are stored at different institutions). We propose a novel algorithm, namely VERTICOX, to obtain the global model parameters in a distributed fashion based on the Alternating Direction Method of Multipliers (ADMM) framework. The proposed model computes intermediary statistics and exchanges them to calculate the global model without collecting individual patient-level data. We demonstrate that our algorithm achieves equivalent accuracy for the …

Examining Rural-Urban Differences In Fatalism And Information Overload: Data From 12 Nci-Designated Cancer Centers, Jakob D Jensen, Jackilen Shannon, Ronaldo Iachan, Yangyang Deng, Sunny Jung Kim, Wendy Demark-Wahnefried, Babalola Faseru, Electra D Paskett, Jinxiang Hu, Robin C Vanderpool, Deann Lazovich, Jason A Mendoza, Sanjay Shete, Linda B Robertson, Rajesh Balkrishnan, Katherine J Briant, Benjamin Haaland, David A Haggstrom, Bernard F Fuemmeler, Rural Workgroup Of The Population Health Assessment In Cancer Center Catchment Areas Consortium

Faculty, Staff and Student Publications

BACKGROUND: Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.

METHODS: Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (

RESULTS: Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too …

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 …

Rapunzel Syndrome Complicated By Escherichia Coli Sepsis, Bowel Perforation, And Pancreatitis In An 11-Year-Old Malnourished Female, Rhea Daniel, Mary Arbuthnot, Srinivas Ramireddy, Supriya Nair

Faculty, Staff and Student Publications

The most common presenting symptoms of Rapunzel syndrome include abdominal pain (37%), nausea and vomiting (33.3%), obstruction (25.9%), and peritonitis (18.3%). Less commonly, patients may present with weight loss (7.4%) or intussusception (7.4%). Exceedingly rare complications of Rapunzel syndrome include gastric ulceration, obstructive jaundice, and acute pancreatitis as well as other malabsorptive-related complications including protein-losing enteropathy, iron deficiency, and megaloblastic anemia. This report details the case of an 11-year-old female with Rapunzel syndrome complicated by sepsis, a rare complication reported in only 2% of patients.

Medical Management Of Infants With Supraventricular Tachycardia: Results From A Registry And Review Of The Literature, Nathan Wei, Avani Lamba, Sonia Franciosi, Ian H Law, Luis A Ochoa, Christopher L Johnsrude, Sit Yee Kwok, Teng Hong Tan, Santokh S Dhillon, Anne Fournier, Stephen P Seslar, Elizabeth A Stephenson, Andrew D Blaufox, Michel Cabrera Ortega, Jeffrey N Bone, Ash Sandhu, Carolina A Escudero, Shubhayan Sanatani

Faculty, Staff and Student Publications

BACKGROUND: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT.

METHODS: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. …

The Impact Of Age And Sex On Aortic Dissection Outcomes: A True Controversy Or Lack Of Standardization?, Erin F Mccaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B Fitzpatrick, Sanjana Gupta, Noah F Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K Ramdial, Erna Forgó, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A Khader, Sean C Bendall, Matt Van De Rijn, Daniel Kalman, Deepak Kaushal, Robert L Hunter, Niaz Banaei, Adrie J C Steyn, Purvesh Khatri, Michael Angelo

Faculty, Staff and Student Publications

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1

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 …

Improving Transcatheter Aortic Valve Interventional Predictability Via Fluid-Structure Interaction Modelling Using Patient-Specific Anatomy, Vijay Govindarajan, Arun Kolanjiyil, Nils P Johnson, Hyunggun Kim, Krishnan B Chandran, David D Mcpherson

Faculty, Staff and Student Publications

Transcatheter aortic valve replacement (TAVR) is now a standard treatment for high-surgical-risk patients with severe aortic valve stenosis. TAVR is being explored for broader indications including degenerated bioprosthetic valves, bicuspid valves and for aortic valve (AV) insufficiency. It is, however, challenging to predict whether the chosen valve size, design or its orientation would produce the most-optimal haemodynamics in the patient. Here, we present a novel patient-specific evaluation framework to realistically predict the patient's AV performance with a high-fidelity fluid-structure interaction analysis that included the patient's left ventricle and ascending aorta (AAo). We retrospectively evaluated the pre- and post-TAVR dynamics of …

(#Womeninddw) Persistent Speaker Gender Gap At The Premier Digestive Disease Event, Zubair Khan, Rabia Rukhshan, Asmeen Bhatt, Sushovan Guha, Srinivas Ramireddy, Prithvi Patil, Ricardo Badillo, Roy Tomas Davee, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020.

METHODS: The data for DDW 2018-2020 were collected via the online web-based planner. The gender of speakers …

Quantitative Estimation Of Protein In Sprouts Of Vigna Radiate (Mung Beans), Lens Culinaris (Lentils), And Cicer Arietinum (Chickpeas) By Kjeldahl And Lowry Methods, Nayab Batool Rizvi, Samina Aleem, Mohammad Rizwan Khan, Sadia Ashraf, Rosa Busquets

Faculty, Staff and Student Publications

Protein scarcity is the most vital cause of long-lasting diseases and even untimely deaths in some developing nations. The application of protein in food is advantageous from the point of view of non-toxicity, biocompatibility, and dietary benefits. This study aimed to determine the protein contents of the sprouts of

Transcribed Ultraconserved Regions Are Associated With Clinicopathological Features In Breast Cancer, Erika Pereira Zambalde, Douglas Adamoski, Daniela Fiori Gradia, Iris Rabinovich, Ana Carolina Rodrigues, Cristina Ivan, Enilze M S F Ribeiro, George Adrian Calin, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Ultraconserved regions (UCRs) are 481 genome segments, with length longer than 200 bp, that are 100% conserved among humans, mice, and rats. The majority of UCRs are transcriptionally active (T-UCRs) as many of them produce non-coding RNAs. In a previous study, we evaluated the expression level of T-UCRs in breast cancer (BC) patients and found that 63% of transcripts correlated with some clinical and/or molecular parameter of BC. In this study, we delved into the expression levels of 12 T-UCRs and correlated them with clinicopathological parameters, immunohistochemical markers, and overall survival in two breast cancer cohorts: TCGA and Brazilian patients. …

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 …

The Power And Challenge Of Lipid (A)Symmetry Across The Membrane And Cell, Heather E Webber, Joy M Schmitz

Faculty, Staff and Student Publications

Current treatments for substance use disorders (SUDs) are far from ideal, with no U.S. Food and Drug Administration-approved pharmacotherapies to treat stimulant and other use disorders. New approaches are urgently needed to combat the increasing prevalence of SUDs and overdose deaths. It is widely accepted that addiction is a chronic disease of the brain involving changes in neural circuitry associated with cognitive and reward functioning. Brain stimulation techniques are novel methods that can modulate these circuits directly and thus hold considerable promise for treating SUDs.

Sociodemographic And Clinical Characteristics Associated With Improvements In Quality Of Life For Participants With Opioid Use Disorder, Assaf Gottlieb, Christine Bakos-Block, James R Langabeer, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Background: The Houston Emergency Opioid Engagement System was established to create an access pathway into long-term recovery for individuals with opioid use disorder. The program determines effectiveness across multiple dimensions, one of which is by measuring the participant's reported quality of life (QoL) at the beginning of the program and at successive intervals.

Methods: A visual analog scale was used to measure the change in QoL among participants after joining the program. We then identified sociodemographic and clinical characteristics associated with changes in QoL.

Results: 71% of the participants (n = 494) experienced an increase in their QoL scores, …

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 …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

Lncrnafunc: A Knowledgebase Of Lncrna Function In Human Cancer, Mengyuan Yang, Huifen Lu, Jiajia Liu, Sijia Wu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

The long non-coding RNAs associating with other molecules can coordinate several physiological processes and their dysfunction can impact diverse human diseases. To date, systematic and intensive annotations on diverse interaction regulations of lncRNAs in human cancer were not available. Here, we built lncRNAfunc, a knowledgebase of lncRNA function in human cancer at https://ccsm.uth.edu/lncRNAfunc, aiming to provide a resource and reference for providing therapeutically targetable lncRNAs and intensive interaction regulations. To do this, we collected 15 900 lncRNAs across 33 cancer types from TCGA. For individual lncRNAs, we performed multiple interaction analyses of different biomolecules including DNA, RNA, and protein levels. …

Fusiongdb 20: Fusion Gene Annotation Updates Aided By Deep Learning, Pora Kim, Hua Tan, Jiajia Liu, Haeseung Lee, Hyesoo Jung, Himanshu Kumar, Xiaobo Zhou

Faculty, Staff and Student Publications

A knowledgebase of the systematic functional annotation of fusion genes is critical for understanding genomic breakage context and developing therapeutic strategies. FusionGDB is a unique functional annotation database of human fusion genes and has been widely used for studies with diverse aims. In this study, we report fusion gene annotation updates aided by deep learning (FusionGDB 2.0) available at https://compbio.uth.edu/FusionGDB2/. FusionGDB 2.0 has substantial updates of contents such as up-to-date human fusion genes, fusion gene breakage tendency score with FusionAI deep learning model based on 20 kb DNA sequence around BP, investigation of overlapping between fusion breakpoints with 44 human …

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