Digital Commons Network^™

Pim1 Promotes Hepatic Conversion By Suppressing Reprogramming-Induced Ferroptosis And Cell Cycle Arrest, Yangyang Yuan, Chenwei Wang, Xuran Zhuang, Shaofeng Lin, Miaomiao Luo, Wankun Deng, Jiaqi Zhou, Lihui Liu, Lina Mao, Wenbo Peng, Jian Chen, Qiangsong Wang, Yilai Shu, Yu Xue, Pengyu Huang

Faculty, Staff and Student Publications

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two …

Clonal Hematopoiesis Is Associated With Increased Risk Of Severe Neurotoxicity In Axicabtagene Ciloleucel Therapy Of Large B-Cell Lymphoma, Neeraj Y Saini, David M Swoboda, Uri Greenbaum, Junsheng Ma, Romil D Patel, Kartik Devashish, Kaberi Das, Mark R Tanner, Paolo Strati, Ranjit Nair, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan P Iyer, Raphael Steiner, Nitin Jain, Loretta Nastoupil, Sanam Loghavi, Guilin Tang, Roland L Bassett, Preetesh Jain, Michael Wang, Jason R Westin, Michael R Green, David A Sallman, Eric Padron, Marco L Davila, Frederick L Locke, Richard E Champlin, Guillermo Garcia-Manero, Elizabeth J Shpall, Partow Kebriaei, Christopher R Flowers, Michael D Jain, Feng Wang, Andrew P Futreal, Nancy Gillis, Sattva S Neelapu, Koichi Takahashi

Faculty, Staff and Student Publications

To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P = 0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade …

Follicular Lymphoma Microenvironment Characteristics Associated With Tumor Cell Mutations And Mhc Class Ii Expression, Guangchun Han, Qing Deng, Mario L Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J Nomie, Alexander Bagaev, Edwin R Parra, Luisa M Solis Soto, Simrit Parmar, Fredrick B Hagemeister, Sairah Ahmed, Swaminathan P Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H Fowler, Christopher R Flowers, Paolo Strati, Jason R Westin, Sattva S Neelapu, Loretta J Nastoupil, Francisco Vega, Linghua Wang, Michael R Green

Faculty, Staff and Student Publications

Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with …

Two Mental Models Of Integrated Care For Advanced Liver Disease: Qualitative Study Of Multidisciplinary Health Professionals, Jennifer Arney, Caroline Gray, Anne M Walling, Jack A Clark, Donna Smith, Jennifer Melcher, Steven Asch, Fasiha Kanwal, Aanand D Naik

Faculty, Staff and Student Publications

OBJECTIVES: The purpose of this paper is to present two divergent mental models of integrated advanced liver disease (AdvLD) care among 26 providers who treat patients with AdvLD.

SETTING: 3 geographically dispersed United States Veterans Health Administration health systems.

PARTICIPANTS: 26 professionals (20 women and 6 men) participated, including 9 (34.6%) gastroenterology, hepatology, and transplant physicians, 2 (7.7%) physician assistants, 7 (27%) nurses and nurse practitioners, 3 (11.5%) social workers and psychologists, 4 (15.4%) palliative care providers and 1 (3.8%) pharmacist.

MAIN OUTCOME MEASURES: We conducted qualitative in-depth interviews of providers caring for patients with AdvLD. We used framework analysis …

Erdheim-Chester Disease With Isolated Cns Involvement: A Systematic Review Of The Literature, Anam Haque, Carlos A Pérez, Thejasvi A Reddy, Rajesh K Gupta

Faculty, Staff and Student Publications

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic …

A New Statistical Model For Longitudinal Ecological Momentary Assessment Data On Dual Use Of Electronic And Combustible Cigarettes, James Yang, Jacky Kuo, Wei-Chung Su, Douglas E Jorenby, Megan E Piper, Anne Buu

Faculty, Staff and Student Publications

No abstract provided.

Persistent Disparities In Colorectal Cancer Screening: A Tell-Tale Sign For Implementing New Guidelines In Younger Adults, Po-Hong Liu, Nina N Sanford, Peter S Liang, Amit G Singal, Caitlin C Murphy

Faculty, Staff and Student Publications

BACKGROUND: In May 2021, the U.S. Preventive Services Task Force began recommending initiating colorectal cancer screening at age 45 (vs. 50) years.

METHODS: We estimated prevalence of colorectal cancer screening (by colonoscopy, sigmoidoscopy, CT colonography, or stool-based tests) in adults ages 50 to 75 years using data from the National Health Interview Survey in 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018. For each survey year, we estimated prevalence by age, race/ethnicity, educational attainment, family income, and health insurance. We also compared increases in prevalence of screening from 2000 to 2018 in 5-year age groups (50-54, 55-59, 60-64, 65-69, …

Ethnic Disparities In Early-Onset Gastric Cancer: A Population-Based Study In Texas And California, Anna Tavakkoli, Sandi L Pruitt, Anh Q Hoang, Hong Zhu, Amy E Hughes, Thomas A Mckey, B Joseph Elmunzer, Richard S Kwon, Caitlin C Murphy, Amit G Singal

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of gastric cancer are increasing in young adults (age <50 >years), particularly among Hispanic persons. We estimated incidence rates of early-onset gastric cancer (EOGC) among Hispanic and non-Hispanic White persons by census tract poverty level and county-level metro/nonmetro residence.

METHODS: We used population-based data from the California and Texas Cancer Registries from 1995 to 2016 to estimate age-adjusted incidence rates of EOGC among Hispanic and non-Hispanic White persons by year, sex, tumor stage, census tract poverty level, metro versus nonmetro county, and state. We used logistic regression models to identify factors associated with distant stage diagnosis.

RESULTS: Of …

Human Papillomavirus Vaccine Effectiveness By Number Of Doses: Updated Systematic Review Of Data From National Immunization Programs, Lauri E Markowitz, Mélanie Drolet, Rayleen M Lewis, Philippe Lemieux-Mellouki, Norma Pérez, Mark Jit, Julia M Brotherton, Gina Ogilvie, Aimée R Kreimer, Marc Brisson

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies.

METHODS: We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding.

RESULTS: Overall, 35 studies were included; all except one were conducted within the context of …

The Emerging Spectrum Of Cardiopulmonary Pathology Of The Coronavirus Disease 2019 (Covid-19): Report Of 3 Autopsies From Houston, Texas, And Review Of Autopsy Findings From Other United States Cities, Manish Bodas, Bharathiraja Subramaniyan, Harry Karmouty-Quintana, Peter F Vitiello, Matthew S Walters

Faculty, Staff and Student Publications

The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors …

Biomolecular Condensation: A New Phase In Cancer Research, Anupam K Chakravarty, Daniel J Mcgrail, Thomas M Lozanoski, Brandon S Dunn, David J H Shih, Kara M Cirillo, Sueda H Cetinkaya, Wenjin Jim Zheng, Gordon B Mills, S Stephen Yi, Daniel F Jarosz, Nidhi Sahni

Faculty, Staff and Student Publications

Multicellularity was a watershed development in evolution. However, it also meant that individual cells could escape regulatory mechanisms that restrict proliferation at a severe cost to the organism: cancer. From the standpoint of cellular organization, evolutionary complexity scales to organize different molecules within the intracellular milieu. The recent realization that many biomolecules can "phase-separate" into membraneless organelles, reorganizing cellular biochemistry in space and time, has led to an explosion of research activity in this area. In this review, we explore mechanistic connections between phase separation and cancer-associated processes and emerging examples of how these become deranged in malignancy.

SIGNIFICANCE: One …

Impact Of Social Determinants Of Health On Anticoagulant Use Among Patients With Atrial Fibrillation: Systemic Review And Meta-Analysis, Rasha Khatib, Nicole Glowacki, John Byrne, Peter Brady

Faculty, Staff and Student Publications

BACKGROUND: A growing body of literature now exists examining associations between social determinants of health (SDOH) and adverse outcomes in patients with atrial fibrillation; however, little is available on anticoagulant prescriptions and the impact of SDOH.

PURPOSE: Evaluate the impact of SDOH on anticoagulant prescriptions in patients with atrial fibrillation.

DATA SOURCES: Medline and Embase databases up to January 2021.

STUDY SELECTION: Noninterventional studies were included if they reported associations between at least 1 of 14 SDOH domains and anticoagulant prescription in patients with atrial fibrillation. Two investigators independently screened and collected data.

DATA EXTRACTION: Two investigators independently screened and …

Smyd3 Impedes Small Cell Lung Cancer Sensitivity To Alkylation Damage Through Rnf113a Methylation-Phosphorylation Cross-Talk, Valentina Lukinović, Simone Hausmann, Gael S Roth, Clement Oyeniran, Tanveer Ahmad, Ning Tsao, Joshua R Brickner, Alexandre G Casanova, Florent Chuffart, Ana Morales Benitez, Jessica Vayr, Rebecca Rodell, Marianne Tardif, Pascal W T C Jansen, Yohann Couté, Michiel Vermeulen, Pierre Hainaut, Pawel K Mazur, Nima Mosammaparast, Nicolas Reynoird

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of …

Association Study Between Polymorphisms In Dna Methylation-Related Genes And Testicular Germ Cell Tumor Risk, Chiara Grasso, Maja Popovic, Elena Isaevska, Fulvio Lazzarato, Valentina Fiano, Daniela Zugna, John Pluta, Benita Weathers, Kurt D'Andrea, Kristian Almstrup, Lynn Anson-Cartwright, D Timothy Bishop, Stephen J Chanock, Chu Chen, Victoria K Cortessis, Marlene D Dalgaard, Siamak Daneshmand, Alberto Ferlin, Carlo Foresta, Megan N Frone, Marija Gamulin, Jourik A Gietema, Mark H Greene, Tom Grotmol, Robert J Hamilton, Trine B Haugen, Russ Hauser, Robert Karlsson, Lambertus A Kiemeney, Davor Lessel, Patrizia Lista, Ragnhild A Lothe, Chey Loveday, Coby Meijer, Kevin T Nead, Jérémie Nsengimana, Rolf I Skotheim, Clare Turnbull, David J Vaughn, Fredrik Wiklund, Tongzhang Zheng, Andrea Zitella, Stephen M Schwartz, Katherine A Mcglynn, Peter A Kanetsky, Katherine L Nathanson, Lorenzo Richiardi

Faculty, Staff and Student Publications

Background: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation.

Methods: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the …

Does A Multiple Myeloma Polygenic Risk Score Predict Overall Survival Of Patients With Myeloma?, Angelica Macauda, Alyssa Clay-Gilmour, Thomas Hielscher, Michelle A T Hildebrandt, Marcin Kruszewski, Robert Z Orlowski, Shaji K Kumar, Elad Ziv, Enrico Orciuolo, Elizabeth E Brown, Asta Försti, Rosalie G Waller, Mitchell J Machiela, Stephen J Chanock, Nicola J Camp, Marcin Rymko, Małgorzata Raźny, Wendy Cozen, Judit Várkonyi, Chiara Piredda, Matteo Pelosini, Alem A Belachew, Edyta Subocz, Kari Hemminki, Malwina Rybicka-Ramos, Graham G Giles, Roger L Milne, Jonathan N Hofmann, Jan Maciej Zaucha, Annette Juul Vangsted, Hartmut Goldschmidt, S Vincent Rajkumar, Waldemar Tomczak, Juan Sainz, Aleksandra Butrym, Marzena Watek, Elżbieta Iskierka-Jazdzewska, Gabriele Buda, Dennis P Robinson, Artur Jurczyszyn, Marek Dudziński, Joaquin Martinez-Lopez, Jason P Sinnwell, Susan L Slager, Krzysztof Jamroziak, Rui Manuel Vieira Reis, Niels Weinhold, Parveen Bhatti, Luis G Carvajal-Carmona, Daria Zawirska, Aaron D Norman, Grzegorz Mazur, Sonja I Berndt, Daniele Campa, Celine M Vachon, Federico Canzian

Faculty, Staff and Student Publications

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival.

Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association …

Diverse Stem Cells For Periodontal Tissue Formation And Regeneration, Mizuki Nagata, Jeryl D English, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

The periodontium is comprised of multiple units of mineralized and nonmineralized tissues including the cementum on the root surface, the alveolar bone, periodontal ligament (PDL), and the gingiva. PDL contains a variety of cell populations including mesenchymal stem/progenitor cells (MSCs) termed PDLSCs, which contribute to periodontal regeneration. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitors in their native environment, particularly regarding how they contribute to homeostasis and repair of the periodontium. The current concept is that mesenchymal progenitors in the PDL are localized to the perivascular niche. Single-cell RNA sequencing (scRNA-seq) analyses reveal …

County-Level Social Vulnerability And Breast, Cervical, And Colorectal Cancer Screening Rates In The Us, 2018, Cici Bauer, Kehe Zhang, Qian Xiao, Jiachen Lu, Young-Rock Hong, Ryan Suk

Faculty, Staff and Student Publications

IMPORTANCE: Area-level factors have been identified as important social determinants of health (SDoH) that impact many health-related outcomes. Less is known about how the social vulnerability index (SVI), as a scalable composite score, can multidimensionally explain the population-based cancer screening program uptake at a county level.

OBJECTIVE: To examine the geographic variation of US Preventive Services Task Force (USPSTF)-recommended breast, cervical, and colorectal cancer screening rates and the association between county-level SVI and the 3 screening rates.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used county-level information from the Centers for Disease Control and Prevention's PLACES and SVI data …

Genome-Wide Association Analyses Of Physical Activity And Sedentary Behavior Provide Insights Into Underlying Mechanisms And Roles In Disease Prevention, Zhe Wang, Andrew Emmerich, Nicolas J Pillon, Tim Moore, Daiane Hemerich, Marilyn C Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S Ahluwalia, Traci M Bartz, Amy R Bentley, Lawrence F Bielak, Mike Chong, Audrey Y Chu, Diane Berry, Rajkumar Dorajoo, Nicole D Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M Hall, Toomas Haller, Fernando P Hartwig, David A Hillis, Ville Huikari, Nancy Heard-Costa, Christina Holzapfel, Anne U Jackson, Åsa Johansson, Anja Moltke Jørgensen, Marika A Kaakinen, Robert Karlsson, Kathleen F Kerr, Boram Kim, Chantal M Koolhaas, Zoltan Kutalik, Vasiliki Lagou, Penelope A Lind, Mattias Lorentzon, Leo-Pekka Lyytikäinen, Massimo Mangino, Christoph Metzendorf, Kristine R Monroe, Alexander Pacolet, Louis Pérusse, Rene Pool, Rebecca C Richmond, Natalia V Rivera, Sebastien Robiou-Du-Pont, Katharina E Schraut, Christina-Alexandra Schulz, Heather M Stringham, Toshiko Tanaka, Alexander Teumer, Constance Turman, Peter J Van Der Most, Mathias Vanmunster, Frank J A Van Rooij, Jana V Van Vliet-Ostaptchouk, Xiaoshuai Zhang, Jing-Hua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie N Balslev-Harder, Sebastian E Baumeister, John Beilby, John Blangero, Dorret I Boomsma, Soren Brage, Peter S Braund, Jennifer A Brody, Marcel Bruinenberg, Ulf Ekelund, Ching-Ti Liu, John W Cole, Francis S Collins, L Adrienne Cupples, Tõnu Esko, Stefan Enroth, Jessica D Faul, Lindsay Fernandez-Rhodes, Alison E Fohner, Oscar H Franco, Tessel E Galesloot, Scott D Gordon, Niels Grarup, Catharina A Hartman, Gerardo Heiss, Jennie Hui, Thomas Illig, Russell Jago, Alan James, Peter K Joshi, Taeyeong Jung, Mika Kähönen, Tuomas O Kilpeläinen, Woon-Puay Koh, Ivana Kolcic, Peter P Kraft, Johanna Kuusisto, Lenore J Launer, Aihua Li, Allan Linneberg, Jian'an Luan, Pedro Marques Vidal, Sarah E Medland, Yuri Milaneschi, Arden Moscati, Bill Musk, Christopher P Nelson, Ilja M Nolte, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Christine Power, Olli T Raitakari, Mägi Reedik, Alex P Reiner, Paul M Ridker, Igor Rudan, Kathy Ryan, Mark A Sarzynski, Laura J Scott, Robert A Scott, Stephen Sidney, Kristin Siggeirsdottir, Albert V Smith, Jennifer A Smith, Emily Sonestedt, Marin Strøm, E Shyong Tai, Koon K Teo, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Andre G Uitterlinden, Jagadish Vangipurapu, Natasja Van Schoor, Uwe Völker, Gonneke Willemsen, Kayleen Williams, Quenna Wong, Huichun Xu, Kristin L Young, Jian Min Yuan, M Carola Zillikens, Alan B Zonderman, Adam Ameur, Stefania Bandinelli, Joshua C Bis, Michael Boehnke, Claude Bouchard, Daniel I Chasman, George Davey Smith, Eco J C De Geus, Louise Deldicque, Marcus Dörr, Michele K Evans, Luigi Ferrucci, Myriam Fornage, Caroline Fox, Theodore Garland, Vilmundur Gudnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo L Horta, Elina Hyppönen, Marjo-Riitta Jarvelin, W Craig Johnson, Sharon L R Kardia, Lambertus A Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimäki, Loic Le Marchand, Patrik K E Magnusson, Nicholas G Martin, Mads Melbye, Andres Metspalu, David Meyre, Kari E North, Claes Ohlsson, Albertine J Oldehinkel, Marju Orho-Melander, Guillaume Pare, Taesung Park, Oluf Pedersen, Brenda W J H Penninx, Tune H Pers, Ozren Polasek, Inga Prokopenko, Charles N Rotimi, Nilesh J Samani, Xueling Sim, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Nicholas J Timpson, Rob M Van Dam, Nathalie Van Der Velde, Cornelia M Van Duijn, Peter Vollenweider, Henry Völzke, Trudy Voortman, Gérard Waeber, Nicholas J Wareham, David R Weir, Heinz-Erich Wichmann, James F Wilson, Andrea L Hevener, Anna Krook, Juleen R Zierath, Martine A I Thomis, Ruth J F Loos, Marcel Den Hoed

Faculty, Staff and Student Publications

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle …

Alcohol And Cannabis Co-Use And Longitudinal Gray Matter Volumetric Changes In Early And Late Adolescence, Xi Luo, James J Yang, Anne Buu, Elisa M Trucco, Chiang-Shan R Li

Faculty, Staff and Student Publications

Background: Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross-sectional findings, and omitted potential sex differences.

Methods: Using data based on 724 adolescents (370 females) curated from the NCANDA study, we investigated how gray matter volumes (GMVs) decline longitudinally as a result of alcohol and cannabis use. The impacts of alcohol and cannabis co-use and how these vary across assigned sex at birth and age were examined. Brain imaging data comprised the GMVs of 34 regions of interest and the …

Genetic Analyses Of The Electrocardiographic Qt Interval And Its Components Identify Additional Loci And Pathways, William J Young, Najim Lahrouchi, Aaron Isaacs, Thuyvy Duong, Luisa Foco, Farah Ahmed, Jennifer A Brody, Reem Salman, Raymond Noordam, Jan-Walter Benjamins, Jeffrey Haessler, Leo-Pekka Lyytikäinen, Linda Repetto, Maria Pina Concas, Marten E Van Den Berg, Stefan Weiss, Antoine R Baldassari, Traci M Bartz, James P Cook, Daniel S Evans, Rebecca Freudling, Oliver Hines, Jonas L Isaksen, Honghuang Lin, Hao Mei, Arden Moscati, Martina Müller-Nurasyid, Casia Nursyifa, Yong Qian, Anne Richmond, Carolina Roselli, Kathleen A Ryan, Eduardo Tarazona-Santos, Sébastien Thériault, Stefan Van Duijvenboden, Helen R Warren, Jie Yao, Dania Raza, Stefanie Aeschbacher, Gustav Ahlberg, Alvaro Alonso, Laura Andreasen, Joshua C Bis, Eric Boerwinkle, Archie Campbell, Eulalia Catamo, Massimiliano Cocca, Michael J Cutler, Dawood Darbar, Alessandro De Grandi, Antonio De Luca, Jun Ding, Christina Ellervik, Patrick T Ellinor, Stephan B Felix, Philippe Froguel, Christian Fuchsberger, Martin Gögele, Claus Graff, Mariaelisa Graff, Xiuqing Guo, Torben Hansen, Susan R Heckbert, Paul L Huang, Heikki V Huikuri, Nina Hutri-Kähönen, M Arfan Ikram, Rebecca D Jackson, Juhani Junttila, Maryam Kavousi, Jan A Kors, Thiago P Leal, Rozenn N Lemaitre, Henry J Lin, Lars Lind, Allan Linneberg, Simin Liu, Peter W Macfarlane, Massimo Mangino, Thomas Meitinger, Massimo Mezzavilla, Pashupati P Mishra, Rebecca N Mitchell, Nina Mononen, May E Montasser, Alanna C Morrison, Matthias Nauck, Victor Nauffal, Pau Navarro, Kjell Nikus, Guillaume Pare, Kristen K Patton, Giulia Pelliccione, Alan Pittman, David J Porteous, Peter P Pramstaller, Michael H Preuss, Olli T Raitakari, Alexander P Reiner, Antonio Luiz P Ribeiro, Kenneth M Rice, Lorenz Risch, David Schlessinger, Ulrich Schotten, Claudia Schurmann, Xia Shen, M Benjamin Shoemaker, Gianfranco Sinagra, Moritz F Sinner, Elsayed Z Soliman, Monika Stoll, Konstantin Strauch, Kirill Tarasov, Kent D Taylor, Andrew Tinker, Stella Trompet, André Uitterlinden, Uwe Völker, Henry Völzke, Melanie Waldenberger, Lu-Chen Weng, Eric A Whitsel, James G Wilson, Christy L Avery, David Conen, Adolfo Correa, Francesco Cucca, Marcus Dörr, Sina A Gharib, Giorgia Girotto, Niels Grarup, Caroline Hayward, Yalda Jamshidi, Marjo-Riitta Järvelin, J Wouter Jukema, Stefan Kääb, Mika Kähönen, Jørgen K Kanters, Charles Kooperberg, Terho Lehtimäki, Maria Fernanda Lima-Costa, Yongmei Liu, Ruth J F Loos, Steven A Lubitz, Dennis O Mook-Kanamori, Andrew P Morris, Jeffrey R O'Connell, Morten Salling Olesen, Michele Orini, Sandosh Padmanabhan, Cristian Pattaro, Annette Peters, Bruce M Psaty, Jerome I Rotter, Bruno Stricker, Pim Van Der Harst, Cornelia M Van Duijn, Niek Verweij, James F Wilson, Dan E Arking, Julia Ramirez, Pier D Lambiase, Nona Sotoodehnia, Borbala Mifsud, Christopher Newton-Cheh, Patricia B Munroe

Faculty, Staff and Student Publications

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and …

Evaluation Of A 2-1-1 Telephone Navigation Program To Increase Cancer Control Behaviors: Results From A Randomized Controlled Trial, Maria E Fernandez, Lara S Savas, John S Atkinson, Katherine Ball Ricks, Lynn N Ibekwe, Inimfon Jackson, Philip E Castle, David Jobe, Sally W Vernon

Faculty, Staff and Student Publications

PURPOSE: to evaluate the effectiveness of a telephone navigation intervention for increasing use of cancer control services among underserved 2-1-1 callers.

DESIGN: Randomized controlled trial.

SETTING: 2-1-1 call centers in Houston and Weslaco, Texas (located in the Rio Grande Valley near the Mexican border).

PARTICIPANTS: 2-1-1 callers in need of Pap test, mammography, colorectal cancer screening, smoking cessation counseling, and/or HPV vaccination for a daughter (n = 1,554). A majority were low-income and described themselves as Black or Hispanic.

INTERVENTION: Participants were randomly assigned to receive either a cancer control referral for the needed service(s) with telephone navigation from a …

Gaseous Air Pollutants And Dna Methylation In A Methylome-Wide Association Study Of An Ethnically And Environmentally Diverse Population Of Us Adults, Katelyn M Holliday, Rahul Gondalia, Antoine Baldassari, Anne E Justice, James D Stewart, Duanping Liao, Jeff D Yanosky, Kristina M Jordahl, Parveen Bhatti, Themistocles L Assimes, James S Pankow, Weihua Guan, Myriam Fornage, Jan Bressler, Kari E North, Karen N Conneely, Yun Li, Lifang Hou, Pantel S Vokonas, Cavin K Ward-Caviness, Rory Wilson, Kathrin Wolf, Melanie Waldenberger, Josef Cyrys, Annette Peters, H Marike Boezen, Judith M Vonk, Sergi Sayols-Baixeras, Mikyeong Lee, Andrea A Baccarelli, Eric A Whitsel

Faculty, Staff and Student Publications

Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in …

Clinical Epidemiology Of Carbapenem-Resistant Enterobacterales In The Greater Houston Region Of Texas: A 6-Year Trend And Surveillance Analysis, Bekana K Tadese, Charles Darkoh, Stacia M Desantis, Osaro Mgbere, Kayo Fujimoto

Faculty, Staff and Student Publications

OBJECTIVES: Carbapenem-resistant Enterobacterales (CRE) remain an urgent public health priority in the United States. CRE poses a major threat to patients in healthcare and a potential risk to the community. This study examined the epidemiological trends, clinical, and microbiological data of CRE in the Greater Houston region of Texas.

METHODS: A multi-institutional retrospective observational study was conducted using surveillance data collected from 2015 to 2020. Predictors of incidence rates of CRE were determined by a negative binomial regression fit using a generalized estimation equation.

RESULTS: Over a 6-year period, 4236 CRE cases were reported, of which Klebsiella pneumoniae accounted for …

The Impact Of The Covid-19 Pandemic On Adolescent Mental Health And Substance Use, Jeff R Temple, Elizabeth Baumler, Leila Wood, Shannon Guillot-Wright, Elizabeth Torres, Melanie Thiel

Faculty, Staff and Student Publications

PURPOSE: The aim of this study is to determine whether COVID-19-induced financial impact, stress, loneliness, and isolation were related to perceived changes in adolescent mental health and substance use.

METHODS: Data were from Baseline (2018) and Wave 3 (2020; mean age = 14.8; 50% female) of 1,188 adolescents recruited from 12 Texas public middle schools as part of a randomized controlled trial. Participants were primarily Black (23%), Latinx (41%), Asian (11%), and White (9%). We assessed mental health and substance use (Baseline and Wave 3) and pandemic-related physical interaction, loneliness, stress, family conflict, and economic situation (Wave 3).

RESULTS: COVID-19-induced …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Faculty, Staff and Student Publications

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

Pivoting The Biosafety Program In Response To Covid-19: Recommendations Of Key Services And Tasks To Consider For The Next Pandemic, Robert J Emery, Scott J Patlovich, Kristin G King, Janelle Rios

Faculty, Staff and Student Publications

INTRODUCTION: With the onset of the COVID-19 pandemic, a rapid adjustment of work tasks was necessary for many biosafety programs (and other safety programs) to address drastic shifts in workload demands amid pandemic-related shutdowns and subsequent needs for supporting COVID-19-related safe work protocols, diagnostic testing, research, vaccine development, and so forth. From a program management standpoint, evaluating and understanding these tasks were critically important to ensure that appropriate support and resources were in place, especially during such unprecedented times of rapid change and significant impact to normal life and routine.

METHODS: Described here are examples of how the biosafety program …

Association Of Social Risk Factors With Mortality Among Us Adults With A New Cancer Diagnosis, Matthew P Banegas, John F Dickerson, Zhiyuan Zheng, Caitlin C Murphy, Reginald Tucker-Seeley, James D Murphy, K Robin Yabroff

Faculty, Staff and Student Publications

This cohort study examines the associations of multiple social risk factors with mortality risk among patients newly diagnosed with cancer in the US.

Agreement Between Sars-Cov-2 Pcr Test Results Using Nasopharyngeal And Mid-Turbinate Specimens Among Asymptomatic Working-Age Adults, Judy Wendt Hess, Faiyaz Bhojani, Derrick Cameron, Mary Freire De Carvalho, Fayaz Momin

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to determine whether mid-turbinate specimens reliably detect active infection in asymptomatic adults undergoing regular COVID-19 PCR testing.

METHODS: Qualitative agreement between 2481 paired nasopharyngeal and mid-turbinate PCR results was assessed. Mean cycle threshold values for each positive result were evaluated as an indicator of active infection.

RESULTS: Overall agreement between nasopharyngeal and mid-turbinate tests was 98.4%. Positive percent agreement was 37.2%, and negative percent agreement was ~100%. Test pairs with lower cycle thresholds (≤30 and ≤25) reached 67% and 100% positive percent agreement, respectively.

CONCLUSIONS: SARS-CoV-2 infections with high viral loads were detected …

Assessing Associations Between Insecure Income And Us Workers' Health: An Ipums-Meps Analysis, Robert D Thomas, John W Davis, Paula M Cuccaro, Gretchen L Gemeinhardt

Faculty, Staff and Student Publications

Gig economy compensation policy initiatives, such as California Prop 22, are increasing the number of US workers receiving piece rate pay (PRP) and other forms of insecure income. However, there is limited evidence about how this trend affects people's health. Using data from the 2008-19 IPUMS Medical Expenditure Panel Survey (MEPS), we examined associations between insecure compensation and US adults' self-reported overall health as well as psychological distress. We report significant associations with three types of insecure income - PRP, hourly, and daily pay - on overall health and psychological distress. These effects were robust to adjustment for suspected confounders, …

Impact Of High, Low, And Non-Optimum Temperatures On Chronic Kidney Disease In A Changing Climate, 1990-2019: A Global Analysis, Li He, Baode Xue, Bo Wang, Ce Liu, David Gimeno Ruiz De Porras, George L Delclos, Ming Hu, Bin Luo, Kai Zhang

Faculty, Staff and Student Publications

BACKGROUND: Although a few studies have reported the relationship between high and low temperatures and chronic kidney disease (CKD), the global burden of CKD attributable to extreme heat and cold in recent decades remains unknown.

METHODS: Based on the Global Burden of Disease Study (GBD) 2019, we obtained data on age-standardized mortality rates (ASMR) and age-standardized rates of disability-adjusted life years (ASDR) per 100 000 population of the CKD attributable to non-optimum temperatures from 1990 to 2019. The annual mean temperature of each country was used to divide each country into five climate zones (tropical, subtropical, warm-temperate, cool-temperate, and boreal). …