Public Health Commons^™

Predicted Gene Expression In Ancestrally Diverse Populations Leads To Discovery Of Susceptibility Loci For Lifestyle And Cardiometabolic Traits, Heather M Highland, Genevieve L Wojcik, Mariaelisa Graff, Katherine K Nishimura, Chani J Hodonsky, Antoine R Baldassari, Alanna C Cote, Iona Cheng, Christopher R Gignoux, Ran Tao, Yuqing Li, Eric Boerwinkle, Myriam Fornage, Jeffrey Haessler, Lucia A Hindorff, Yao Hu, Anne E Justice, Bridget M Lin, Danyu Lin, Daniel O Stram, Christopher A Haiman, Charles Kooperberg, Loic Le Marchand, Tara C Matise, Eimear E Kenny, Christopher S Carlson, Eli A Stahl, Christy L Avery, Kari E North, Jose Luis Ambite, Steven Buyske, Ruth J Loos, Ulrike Peters, Kristin L Young, Stephanie A Bien, Laura M Huckins

Faculty, Staff and Student Publications

One mechanism by which genetic factors influence complex traits and diseases is altering gene expression. Direct measurement of gene expression in relevant tissues is rarely tenable; however, genetically regulated gene expression (GReX) can be estimated using prediction models derived from large multi-omic datasets. These approaches have led to the discovery of many gene-trait associations, but whether models derived from predominantly European ancestry (EA) reference panels can map novel associations in ancestrally diverse populations remains unclear. We applied PrediXcan to impute GReX in 51,520 ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) participants (35% African American, 45% Hispanic/Latino, 10% Asian, …

Gestational Age Variation In Human Placental Drug Transporters, Laura Goetzl, Nune Darbinian, Nana Merabova, Lindsay C Devane, Sammanda Ramamoorthy

Faculty, Staff and Student Publications

Patient and providers' fear of fetal exposure to medications may lead to discontinuation of treatment, disease relapse, and maternal morbidity. Placental drug transporters play a critical role in fetal exposure through active transport but the majority of data are limited to the 3rd trimester, when the majority of organogenesis has already occurred. Our objective was to define gestational age (GA) dependent changes in protein activity, expression and modifications of five major placental drug transporters: SERT, P-gp, NET, BCRP and MRP3. Apical brush border membrane fractions were prepared from fresh 1st, 2nd and 3rd trimester human placentas collected following elective pregnancy …

Estimation And Inference Of Predictive Discrimination For Survival Outcome Risk Prediction Models, Ruosha Li, Jing Ning, Ziding Feng

Faculty, Staff and Student Publications

Accurate risk prediction has been the central goal in many studies of survival outcomes. In the presence of multiple risk factors, a censored regression model can be employed to estimate a risk prediction rule. Before the prediction tool can be popularized for practical use, it is crucial to rigorously assess its prediction performance. In our motivating example, researchers are interested in developing and validating a risk prediction tool to identify future lung cancer cases by integrating demographic information, disease characteristics and smoking-related data. Considering the long latency period of cancer, it is desirable for a prediction tool to achieve discriminative …

Host Diversity And Behavior Determine Patterns Of Interspecies Transmission And Geographic Diffusion Of Avian Influenza A Subtypes Among North American Wild Reservoir Species, Joseph T Hicks, Kimberly Edwards, Xueting Qiu, Do-Kyun Kim, James E Hixson, Scott Krauss, Richard J Webby, Robert G Webster, Justin Bahl

Faculty, Staff and Student Publications

Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies and geographic viral transition patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of transition between species were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between …

Birth Defect Co-Occurrence Patterns In The Texas Birth Defects Registry, Renata H Benjamin, Angela E Scheuerle, Daryl A Scott, Maria Luisa Navarro Sanchez, Peter H Langlois, Mark A Canfield, Hope Northrup, Christian P Schaaf, Joseph W Ray, Scott D Mclean, Han Chen, Michael D Swartz, Philip J Lupo, A J Agopian

Faculty, Staff and Student Publications

BACKGROUND: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood.

METHODS: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects.

RESULTS: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of …

Development Of Training Curriculum To Improve Patient Communication Skills And Social Support Among Community Health Workers, Jennifer Holcomb, Gayla M Ferguson, Logan Thornton, Linda Highfield

Faculty, Staff and Student Publications

BACKGROUND: Effective provider communication skills are important for patient decision-making and understanding, particularly for those with low health literacy. A gap exists in training methods and curriculum for community health workers (CHWs). Brief description of activity: Through a clinical and academic partnership, pilot training curriculum focused on patient communication skills was developed to align with CHW scope of work.

IMPLEMENTATION: The curriculum was implemented in three 2-hour training sessions over WebEx with seven state-certified CHWs. The goal was for CHWs to understand the key elements and application of active listening, Teach Back, and action planning in a clinical setting. The …

Centers For Mendelian Genomics: A Decade Of Facilitating Gene Discovery, Samantha M Baxter, Jennifer E Posey, Nicole J Lake, Nara Sobreira, Jessica X Chong, Steven Buyske, Elizabeth E Blue, Lisa H Chadwick, Zeynep H Coban-Akdemir, Kimberly F Doheny, Colleen P Davis, Monkol Lek, Christopher Wellington, Shalini N Jhangiani, Mark Gerstein, Richard A Gibbs, Richard P Lifton, Daniel G Macarthur, Tara C Matise, James R Lupski, David Valle, Michael J Bamshad, Ada Hamosh, Shrikant Mane, Deborah A Nickerson, Heidi L Rehm, Anne O'Donnell-Luria

Faculty, Staff and Student Publications

PURPOSE: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration.

METHODS: Over the past 10 years, the National Institutes of Health-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution.

RESULTS: We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Beyond generating a list of gene-phenotype relationships …

Knowledge, Attitudes, Willingness To Pay, And Patient Preferences About Genetic Testing And Subsequent Risk Management For Cancer Prevention, Fangjian Guo, Jacqueline M Hirth, Erika L Fuchs, Leslie E Cofie, Veronica Brown, Yong-Fang Kuo, Maria E Fernandez, Abbey B Berenson

Faculty, Staff and Student Publications

Knowledge, attitudes, and patient preferences about genetic testing and subsequent risk management for cancer prevention among average risk populations are understudied, especially among Hispanics. This study was to assess these items by conducting an in-person survey in this understudied population. We conducted in-person surveys using a self-administered, structured questionnaire among young women in 2017. Survey questions were adapted from other validated surveys. This study had 677 participants in the final analyses. Data were collected in 2017 and analyzed in 2018 and 2019. Participants had little knowledge about genes or breast cancer risk, but most felt that genetic testing for cancer …

New Insights Into The Genetic Etiology Of Alzheimer's Disease And Related Dementias, Céline Bellenguez, Fahri Küçükali, Iris E Jansen, Luca Kleineidam, Sonia Moreno-Grau, Najaf Amin, Adam C Naj, Rafael Campos-Martin, Benjamin Grenier-Boley, Victor Andrade, Peter A Holmans, Anne Boland, Vincent Damotte, Sven J Van Der Lee, Marcos R Costa, Teemu Kuulasmaa, Qiong Yang, Itziar De Rojas, Joshua C Bis, Amber Yaqub, Ivana Prokic, Julien Chapuis, Shahzad Ahmad, Vilmantas Giedraitis, Dag Aarsland, Pablo Garcia-Gonzalez, Carla Abdelnour, Emilio Alarcón-Martín, Daniel Alcolea, Montserrat Alegret, Ignacio Alvarez, Victoria Álvarez, Nicola J Armstrong, Anthoula Tsolaki, Carmen Antúnez, Ildebrando Appollonio, Marina Arcaro, Silvana Archetti, Alfonso Arias Pastor, Beatrice Arosio, Lavinia Athanasiu, Henri Bailly, Nerisa Banaj, Miquel Baquero, Sandra Barral, Alexa Beiser, Ana Belén Pastor, Jennifer E Below, Penelope Benchek, Luisa Benussi, Claudine Berr, Céline Besse, Valentina Bessi, Giuliano Binetti, Alessandra Bizarro, Rafael Blesa, Mercè Boada, Eric Boerwinkle, Barbara Borroni, Silvia Boschi, Paola Bossù, Geir Bråthen, Jan Bressler, Catherine Bresner, Henry Brodaty, Keeley J Brookes, Luis Ignacio Brusco, Dolores Buiza-Rueda, Katharina Bûrger, Vanessa Burholt, William S Bush, Miguel Calero, Laura B Cantwell, Geneviève Chene, Jaeyoon Chung, Michael L Cuccaro, Ángel Carracedo, Roberta Cecchetti, Laura Cervera-Carles, Camille Charbonnier, Hung-Hsin Chen, Caterina Chillotti, Simona Ciccone, Jurgen A H R Claassen, Christopher Clark, Elisa Conti, Anaïs Corma-Gómez, Emanuele Costantini, Carlo Custodero, Delphine Daian, Maria Carolina Dalmasso, Antonio Daniele, Efthimios Dardiotis, Jean-François Dartigues, Peter Paul De Deyn, Katia De Paiva Lopes, Lot D De Witte, Stéphanie Debette, Jürgen Deckert, Teodoro Del Ser, Nicola Denning, Anita Destefano, Martin Dichgans, Janine Diehl-Schmid, Mónica Diez-Fairen, Paolo Dionigi Rossi, Srdjan Djurovic, Emmanuelle Duron, Emrah Düzel, Carole Dufouil, Gudny Eiriksdottir, Sebastiaan Engelborghs, Valentina Escott-Price, Ana Espinosa, Michael Ewers, Kelley M Faber, Tagliavini Fabrizio, Sune Fallgaard Nielsen, David W Fardo, Lucia Farotti, Chiara Fenoglio, Marta Fernández-Fuertes, Raffaele Ferrari, Catarina B Ferreira, Evelyn Ferri, Bertrand Fin, Peter Fischer, Tormod Fladby, Klaus Fließbach, Bernard Fongang, Myriam Fornage, Juan Fortea, Tatiana M Foroud, Silvia Fostinelli, Nick C Fox, Emlio Franco-Macías, María J Bullido, Ana Frank-García, Lutz Froelich, Brian Fulton-Howard, Daniela Galimberti, Jose Maria García-Alberca, Pablo García-González, Sebastian Garcia-Madrona, Guillermo Garcia-Ribas, Roberta Ghidoni, Ina Giegling, Giaccone Giorgio, Alison M Goate, Oliver Goldhardt, Duber Gomez-Fonseca, Antonio González-Pérez, Caroline Graff, Giulia Grande, Emma Green, Timo Grimmer, Edna Grünblatt, Michelle Grunin, Vilmundur Gudnason, Tamar Guetta-Baranes, Annakaisa Haapasalo, Georgios Hadjigeorgiou, Jonathan L Haines, Kara L Hamilton-Nelson, Harald Hampel, Olivier Hanon, John Hardy, Annette M Hartmann, Lucrezia Hausner, Janet Harwood, Stefanie Heilmann-Heimbach, Seppo Helisalmi, Michael T Heneka, Isabel Hernández, Martin J Herrmann, Per Hoffmann, Clive Holmes, Henne Holstege, Raquel Huerto Vilas, Marc Hulsman, Jack Humphrey, Geert Jan Biessels, Xueqiu Jian, Charlotte Johansson, Gyungah R Jun, Yuriko Kastumata, John Kauwe, Patrick G Kehoe, Lena Kilander, Anne Kinhult Ståhlbom, Miia Kivipelto, Anne Koivisto, Johannes Kornhuber, Mary H Kosmidis, Walter A Kukull, Pavel P Kuksa, Brian W Kunkle, Amanda B Kuzma, Carmen Lage, Erika J Laukka, Lenore Launer, Alessandra Lauria, Chien-Yueh Lee, Jenni Lehtisalo, Ondrej Lerch, Alberto Lleó, William Longstreth, Oscar Lopez, Adolfo Lopez De Munain, Seth Love, Malin Löwemark, Lauren Luckcuck, Kathryn L Lunetta, Yiyi Ma, Juan Macías, Catherine A Macleod, Wolfgang Maier, Francesca Mangialasche, Marco Spallazzi, Marta Marquié, Rachel Marshall, Eden R Martin, Angel Martín Montes, Carmen Martínez Rodríguez, Carlo Masullo, Richard Mayeux, Simon Mead, Patrizia Mecocci, Miguel Medina, Alun Meggy, Shima Mehrabian, Silvia Mendoza, Manuel Menéndez-González, Pablo Mir, Susanne Moebus, Merel Mol, Laura Molina-Porcel, Laura Montrreal, Laura Morelli, Fermin Moreno, Kevin Morgan, Thomas Mosley, Markus M Nöthen, Carolina Muchnik, Shubhabrata Mukherjee, Benedetta Nacmias, Tiia Ngandu, Gael Nicolas, Børge G Nordestgaard, Robert Olaso, Adelina Orellana, Michela Orsini, Gemma Ortega, Alessandro Padovani, Caffarra Paolo, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Gina Peloso, Alba Pérez-Cordón, Jordi Pérez-Tur, Pierre Pericard, Oliver Peters, Yolande A L Pijnenburg, Juan A Pineda, Gerard Piñol-Ripoll, Claudia Pisanu, Thomas Polak, Julius Popp, Danielle Posthuma, Josef Priller, Raquel Puerta, Olivier Quenez, Inés Quintela, Jesper Qvist Thomassen, Alberto Rábano, Innocenzo Rainero, Farid Rajabli, Inez Ramakers, Luis M Real, Marcel J T Reinders, Christiane Reitz, Dolly Reyes-Dumeyer, Perry Ridge, Steffi Riedel-Heller, Peter Riederer, Natalia Roberto, Eloy Rodriguez-Rodriguez, Arvid Rongve, Irene Rosas Allende, Maitée Rosende-Roca, Jose Luis Royo, Elisa Rubino, Dan Rujescu, María Eugenia Sáez, Paraskevi Sakka, Ingvild Saltvedt, Ángela Sanabria, María Bernal Sánchez-Arjona, Florentino Sanchez-Garcia, Pascual Sánchez Juan, Raquel Sánchez-Valle, Sigrid B Sando, Chloé Sarnowski, Claudia L Satizabal, Michela Scamosci, Nikolaos Scarmeas, Elio Scarpini, Philip Scheltens, Norbert Scherbaum, Martin Scherer, Matthias Schmid, Anja Schneider, Jonathan M Schott, Geir Selbæk, Davide Seripa, Manuel Serrano, Jin Sha, Alexey A Shadrin, Olivia Skrobot, Susan Slifer, Gijsje J L Snijders, Hilkka Soininen, Vincenzo Solfrizzi, Alina Solomon, Yeunjoo Song, Sandro Sorbi, Oscar Sotolongo-Grau, Gianfranco Spalletta, Annika Spottke, Alessio Squassina, Eystein Stordal, Juan Pablo Tartan, Lluís Tárraga, Niccolo Tesí, Anbupalam Thalamuthu, Tegos Thomas, Giuseppe Tosto, Latchezar Traykov, Lucio Tremolizzo, Anne Tybjærg-Hansen, Andre Uitterlinden, Abbe Ullgren, Ingun Ulstein, Sergi Valero, Otto Valladares, Christine Van Broeckhoven, Jeffery Vance, Badri N Vardarajan, Aad Van Der Lugt, Jasper Van Dongen, Jeroen Van Rooij, John Van Swieten, Rik Vandenberghe, Frans Verhey, Jean-Sébastien Vidal, Jonathan Vogelgsang, Martin Vyhnalek, Michael Wagner, David Wallon, Li-San Wang, Ruiqi Wang, Leonie Weinhold, Jens Wiltfang, Gill Windle, Bob Woods, Mary Yannakoulia, Habil Zare, Yi Zhao, Xiaoling Zhang, Congcong Zhu, Miren Zulaica, Lindsay A Farrer, Bruce M Psaty, Mohsen Ghanbari, Towfique Raj, Perminder Sachdev, Karen Mather, Frank Jessen, M Arfan Ikram, Alexandre De Mendonça, Jakub Hort, Magda Tsolaki, Margaret A Pericak-Vance, Philippe Amouyel, Julie Williams, Ruth Frikke-Schmidt, Jordi Clarimon, Jean-François Deleuze, Giacomina Rossi, Sudha Seshadri, Ole A Andreassen, Martin Ingelsson, Mikko Hiltunen, Kristel Sleegers, Gerard D Schellenberg, Cornelia M Van Duijn, Rebecca Sims, Wiesje M Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert

Faculty, Staff and Student Publications

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly …

Mrna Coronavirus Disease 2019 Vaccine-Associated Myopericarditis In Adolescents: A Survey Study, Utkarsh Kohli, Lavina Desai, Devyani Chowdhury, Ashraf S Harahsheh, Alexandra B Yonts, Annette Ansong, Arash Sabati, Hoang H Nguyen, Tarique Hussain, Danyal Khan, David A Parra, Jennifer A Su, Jyoti K Patel, Christina Ronai, Monique Bohun, Bishara J Freij, Matthew J O'Connor, Joseph W Rosanno, Aamisha Gupta, Arash Salavitabar, Adam L Dorfman, Jesse Hansen, Olivia Frosch, Elizabeth L Profita, Shiraz Maskatia, Deepika Thacker, Shubhika Shrivastava, Tyler H Harris, Brian Feingold, Stuart Berger, Michael Campbell, Salim F Idriss, Srikant Das, Markus S Renno, Ken Knecht, S Yukiko Asaki, Sunil Patel, Ravi Ashwath, Renata Shih, John Phillips, Bibhuti Das, Preeti Ramachandran, Eyal Sagiv, Aarti H Bhat, Jonathan N Johnson, Nathaniel W Taggart, Jason Imundo, Natasha Nakra, Shashank Behere, Anjlee Patel, Avichal Aggarwal, Saif Aljemmali, Sean Lang, Sarosh P Batlivala, Daniel E Forsha, Gregory P Conners, Jana Shaw, Frank C Smith, Linda Pauliks, Joseph Vettukattil, Kenneth Shaffer, Stefanie Cheang, Sonia Voleti, Rajesh Shenoy, Rukmini Komarlu, Shea J Ryan, Christopher Snyder, Neha Bansal, Madhu Sharma, Jeffrey A Robinson, Sandra R Arnold, Christine M Salvatore, Madan Kumar, Michael A Fremed, Julie S Glickstein, Melissa Perrotta, William Orr, Tamika Rozema, Muthayipalayam Thirumoorthi, Charles J Mullett, Jocelyn Y Ang

Faculty, Staff and Student Publications

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Pgc1Α/Β Expression Predicts Therapeutic Response To Oxidative Phosphorylation Inhibition In Ovarian Cancer, Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R Marszalek, Christopher P Vellano, Roberta Pastorelli, Mariarosa Bani, Alessandra Decio, Raffaella Giavazzi

Faculty, Staff and Student Publications

Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling …

Effect Of Perfluorocarbon Composition On Activation Of Phase-Changing Ultrasound Contrast Agents, Trevor M Mitcham, Dmitry Nevozhay, Yunyun Chen, Linh D Nguyen, Gianmarco F Pinton, Stephen Y Lai, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US.

PURPOSE: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical …

An Efficient Magnetic Resonance Image Data Quality Screening Dashboard, Evan D H Gates, Adrian Celaya, Dima Suki, Dawid Schellingerhout, David Fuentes

Faculty, Staff and Student Publications

Purpose: Complex data processing and curation for artificial intelligence applications rely on high-quality data sets for training and analysis. Manually reviewing images and their associated annotations is a very laborious task and existing quality control tools for data review are generally limited to raw images only. The purpose of this work was to develop an imaging informatics dashboard for the easy and fast review of processed magnetic resonance (MR) imaging data sets; we demonstrated its ability in a large-scale data review.

Methods: We developed a custom R Shiny dashboard that displays key static snapshots of each imaging study and its …

Rest-Activity Profiles Among Us Adults In A Nationally Representative Sample: A Functional Principal Component Analysis, Qian Xiao, Jiachen Lu, Jamie M Zeitzer, Charles E Matthews, Pedro F Saint-Maurice, Cici Bauer

Faculty, Staff and Student Publications

BACKGROUND: The 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status.

METHODS: The current analysis used data from …

Rest-Activity Profiles Among Us Adults In A Nationally Representative Sample: A Functional Principal Component Analysis, Qian Xiao, Jiachen Lu, Jamie M Zeitzer, Charles E Matthews, Pedro F Saint-Maurice, Cici Bauer

Faculty, Staff and Student Publications

BACKGROUND: The 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status.

METHODS: The current analysis used data from …

Durable Reduction Of Clostridioides Difficile Infection Recurrence And Microbiome Restoration After Treatment With Rbx2660: Results From An Open-Label Phase 2 Clinical Trial, Robert Orenstein, Erik R Dubberke, Sahil Khanna, Christine H Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L Dupont, Dale N Gerding, Ken F Blount, Sarah Mische, Adam Harvey

Faculty, Staff and Student Publications

BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.

METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered …

Elucidating Mechanisms Of Genetic Cross-Disease Associations At The Procr Vascular Disease Locus, David Stacey, Lingyan Chen, Paulina J Stanczyk, Joanna M M Howson, Amy M Mason, Stephen Burgess, Stephen Macdonald, Jonathan Langdown, Harriett Mckinney, Kate Downes, Neda Farahi, James E Peters, Saonli Basu, James S Pankow, Weihong Tang, Nathan Pankratz, Maria Sabater-Lleal, Paul S De Vries, Nicholas L Smith, Amy D Gelinas, Daniel J Schneider, Nebojsa Janjic, Nilesh J Samani, Shu Ye, Charlotte Summers, Edwin R Chilvers, John Danesh, Dirk S Paul

Faculty, Staff and Student Publications

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, …

Using Implementation Mapping To Develop And Test An Implementation Strategy For Active Learning To Promote Physical Activity In Children: A Feasibility Study Using A Hybrid Type 2 Design, Timothy J Walker, Harold W Kohl, John B Bartholomew, Charles Green, Maria E Fernández

Faculty, Staff and Student Publications

BACKGROUND: Incorporating physical movement in the teaching of academic content (active learning) is a promising approach to improve children's health and academic performance. Despite documented benefits, implementation of active learning remains challenging for schools. The aims of this study are to develop an implementation strategy to support the delivery of active learning in elementary schools and examine the impact of the developed implementation strategy on the implementation and effectiveness of active learning.

METHODS: Aim 1 will use Implementation Mapping, which is a multi-step approach that guides the use of theory, stakeholder input, and existing literature to develop a scientifically based …

Use Of The Deep Learning Approach To Measure Alveolar Bone Level, Chun-Teh Lee, Tanjida Kabir, Jiman Nelson, Sally Sheng, Hsiu-Wan Meng, Thomas E Van Dyke, Muhammad F Walji, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

AIM: The goal was to use a deep convolutional neural network to measure the radiographic alveolar bone level to aid periodontal diagnosis.

MATERIALS AND METHODS: A deep learning (DL) model was developed by integrating three segmentation networks (bone area, tooth, cemento-enamel junction) and image analysis to measure the radiographic bone level and assign radiographic bone loss (RBL) stages. The percentage of RBL was calculated to determine the stage of RBL for each tooth. A provisional periodontal diagnosis was assigned using the 2018 periodontitis classification. RBL percentage, staging, and presumptive diagnosis were compared with the measurements and diagnoses made by the …

Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Klebsiella Pneumoniae Complex Among Patients From Different Global Regions (Crackle-2): A Prospective, Multicentre, Cohort Study, Minggui Wang, Michelle Earley, Liang Chen, Blake M Hanson, Yunsong Yu, Zhengyin Liu, Soraya Salcedo, Eric Cober, Lanjuan Li, Souha S Kanj, Hainv Gao, Jose M Munita, Karen Ordoñez, Greg Weston, Michael J Satlin, Sandra L Valderrama-Beltrán, Kalisvar Marimuthu, Martin E Stryjewski, Lauren Komarow, Courtney Luterbach, Steve H Marshall, Susan D Rudin, Claudia Manca, David L Paterson, Jinnethe Reyes, Maria V Villegas, Scott Evans, Carol Hill, Rebekka Arias, Keri Baum, Bettina C Fries, Yohei Doi, Robin Patel, Barry N Kreiswirth, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Cesar A Arias, David Van Duin, Multi-Drug Resistant Organism Network Investigators

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.

METHODS: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability …

Clonal Hematopoiesis Is Associated With Higher Risk Of Stroke, Romit Bhattacharya, Seyedeh M Zekavat, Jeffrey Haessler, Myriam Fornage, Laura Raffield, Md Mesbah Uddin, Alexander G Bick, Abhishek Niroula, Bing Yu, Christopher Gibson, Gabriel Griffin, Alanna C Morrison, Bruce M Psaty, William T Longstreth, Joshua C Bis, Stephen S Rich, Jerome I Rotter, Russell P Tracy, Adolfo Correa, Sudha Seshadri, Andrew Johnson, Jason M Collins, Kathleen M Hayden, Tracy E Madsen, Christie M Ballantyne, Siddhartha Jaiswal, Benjamin L Ebert, Charles Kooperberg, Joann E Manson, Eric A Whitsel, Nhlbi Trans-Omics For Precision Medicine Program, Pradeep Natarajan, Alexander P Reiner

Faculty, Staff and Student Publications

Background and purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.

Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Jane Alookaran, Yuying Liu, Thomas A Auchtung, Amirali Tahanan, Manouchehr Hessabi, Parisa Asgarisabet, Mohammad H Rahbar, Nicole Y Fatheree, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Assessing The Contribution Of Rare Variants To Complex Trait Heritability From Whole-Genome Sequence Data, Pierrick Wainschtein, Deepti Jain, Zhili Zheng, Topmed Anthropometry Working Group, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, L Adrienne Cupples, Aladdin H Shadyab, Barbara Mcknight, Benjamin M Shoemaker, Braxton D Mitchell, Bruce M Psaty, Charles Kooperberg, Ching-Ti Liu, Christine M Albert, Dan Roden, Daniel I Chasman, Dawood Darbar, Donald M Lloyd-Jones, Donna K Arnett, Elizabeth A Regan, Eric Boerwinkle, Jerome I Rotter, Jeffrey R O'Connell, Lisa R Yanek, Mariza De Andrade, Matthew A Allison, Merry-Lynn N Mcdonald, Mina K Chung, Myriam Fornage, Nathalie Chami, Nicholas L Smith, Patrick T Ellinor, Ramachandran S Vasan, Rasika A Mathias, Ruth J F Loos, Stephen S Rich, Steven A Lubitz, Susan R Heckbert, Susan Redline, Xiuqing Guo, Y -D Ida Chen, Cecelia A Laurie, Ryan D Hernandez, Stephen T Mcgarvey, Michael E Goddard, Cathy C Laurie, Kari E North, Leslie A Lange, Bruce S Weir, Loic Yengo, Jian Yang, Peter M Visscher

Faculty, Staff and Student Publications

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error …

Community-Clinic Linkages For Promoting Hiv Prevention: Organizational Networks For Prep Client Referrals And Collaborations, Rebecca L Mauldin, Tamara Al Rawwad, Muhammad Amith, Lisa M Kuhns, John A Schneider, Kayo Fujimoto

Faculty, Staff and Student Publications

Community-clinic linkages may help communities increase HIV pre-exposure prophylaxis (PrEP) uptake. Referrals from community-based organizations may be particularly important for linking Black men who have sex with men (MSM) to PrEP. This study describes PrEP referral and HIV/STI prevention networks among organizations that serve MSM in Houston, TX (N = 40), and Chicago, IL (N = 28), and compares network positions of organizations based on percentage of Black/African American clients. A majority of organizations conducted PrEP awareness/promotion activities, but fewer made PrEP referrals, with little overlap between the collaboration and referral networks. The networks tended to have a …

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes In 454,193 Individuals Across 13 Cohorts, Daniel Dicorpo, Jessica Leclair, Joanne B Cole, Chloé Sarnowski, Fariba Ahmadizar, Lawrence F Bielak, Anneke Blokstra, Erwin P Bottinger, Layal Chaker, Yii-Der I Chen, Ye Chen, Paul S De Vries, Tariq Faquih, Mohsen Ghanbari, Valborg Gudmundsdottir, Xiuqing Guo, Natalie R Hasbani, Dorina Ibi, M Arfan Ikram, Maryam Kavousi, Hampton L Leonard, Aaron Leong, Josep M Mercader, Alanna C Morrison, Girish N Nadkarni, Mike A Nalls, Raymond Noordam, Michael Preuss, Jennifer A Smith, Stella Trompet, Petra Vissink, Jie Yao, Wei Zhao, Eric Boerwinkle, Mark O Goodarzi, Vilmundur Gudnason, J Wouter Jukema, Sharon L R Kardia, Ruth J F Loos, Ching-Ti Liu, Alisa K Manning, Dennis Mook-Kanamori, James S Pankow, H Susan J Picavet, Naveed Sattar, Eleanor M Simonsick, W M Monique Verschuren, Ko Willems Van Dijk, Jose C Florez, Jerome I Rotter, James B Meigs, Josée Dupuis, Miriam S Udler

Faculty, Staff and Student Publications

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.

RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) …

Cancer Incidence, Mortality, Years Of Life Lost, Years Lived With Disability, And Disability-Adjusted Life Years For 29 Cancer Groups From 2010 To 2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Jonathan M Kocarnik, Kelly Compton, Frances E Dean, Weijia Fu, Brian L Gaw, James D Harvey, Hannah Jacqueline Henrikson, Dan Lu, Alyssa Pennini, Rixing Xu, Emad Ababneh, Mohsen Abbasi-Kangevari, Hedayat Abbastabar, Sherief M Abd-Elsalam, Amir Abdoli, Aidin Abedi, Hassan Abidi, Hassan Abolhassani, Isaac Akinkunmi Adedeji, Qorinah Estiningtyas Sakilah Adnani, Shailesh M Advani, Muhammad Sohail Afzal, Mohammad Aghaali, Bright Opoku Ahinkorah, Sajjad Ahmad, Tauseef Ahmad, Ali Ahmadi, Sepideh Ahmadi, Tarik Ahmed Rashid, Yusra Ahmed Salih, Gizachew Taddesse Akalu, Addis Aklilu, Tayyaba Akram, Chisom Joyqueenet Akunna, Hanadi Al Hamad, Fares Alahdab, Ziyad Al-Aly, Saqib Ali, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Amir Almasi-Hashiani, Nihad A Almasri, Sadeq Ali Ali Al-Maweri, Sami Almustanyir, Nivaldo Alonso, Nelson Alvis-Guzman, Hubert Amu, Etsay Woldu Anbesu, Robert Ancuceanu, Fereshteh Ansari, Alireza Ansari-Moghaddam, Maxwell Hubert Antwi, Davood Anvari, Anayochukwu Edward Anyasodor, Muhammad Aqeel, Jalal Arabloo, Morteza Arab-Zozani, Olatunde Aremu, Hany Ariffin, Timur Aripov, Muhammad Arshad, Al Artaman, Judie Arulappan, Zatollah Asemi, Mohammad Asghari Jafarabadi, Tahira Ashraf, Prince Atorkey, Avinash Aujayeb, Marcel Ausloos, Atalel Fentahun Awedew, Beatriz Paulina Ayala Quintanilla, Temesgen Ayenew, Mohammed A Azab, Sina Azadnajafabad, Amirhossein Azari Jafari, Ghasem Azarian, Ahmed Y Azzam, Ashish D Badiye, Saeed Bahadory, Atif Amin Baig, Jennifer L Baker, Senthilkumar Balakrishnan, Maciej Banach, Till Winfried Bärnighausen, Francesco Barone-Adesi, Fabio Barra, Amadou Barrow, Masoud Behzadifar, Uzma Iqbal Belgaumi, Woldesellassie M Mequanint Bezabhe, Yihienew Mequanint Bezabih, Devidas S Bhagat, Akshaya Srikanth Bhagavathula, Nikha Bhardwaj, Pankaj Bhardwaj, Sonu Bhaskar, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Sadia Bibi, Ali Bijani, Antonio Biondi, Catherine Bisignano, Tone Bjørge, Archie Bleyer, Oleg Blyuss, Obasanjo Afolabi Bolarinwa, Srinivasa Rao Bolla, Dejana Braithwaite, Amanpreet Brar, Hermann Brenner, Maria Teresa Bustamante-Teixeira, Nadeem Shafique Butt, Zahid A Butt, Florentino Luciano Caetano Dos Santos, Yin Cao, Giulia Carreras, Ferrán Catalá-López, Francieli Cembranel, Ester Cerin, Achille Cernigliaro, Raja Chandra Chakinala, Soosanna Kumary Chattu, Vijay Kumar Chattu, Pankaj Chaturvedi, Odgerel Chimed-Ochir, Daniel Youngwhan Cho, Devasahayam J Christopher, Dinh-Toi Chu, Michael T Chung, Joao Conde, Sanda Cortés, Paolo Angelo Cortesi, Vera Marisa Costa, Amanda Ramos Cunha, Omid Dadras, Amare Belachew Dagnew, Saad M A Dahlawi, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Aso Mohammad Darwesh, José Das Neves, Fernando Pio De La Hoz, Asmamaw Bizuneh Demis, Edgar Denova-Gutiérrez, Deepak Dhamnetiya, Mandira Lamichhane Dhimal, Meghnath Dhimal, Mostafa Dianatinasab, Daniel Diaz, Shirin Djalalinia, Huyen Phuc Do, Saeid Doaei, Fariba Dorostkar, Francisco Winter Dos Santos Figueiredo, Tim Robert Driscoll, Hedyeh Ebrahimi, Sahar Eftekharzadeh, Maha El Tantawi, Hassan El-Abid, Iffat Elbarazi, Hala Rashad Elhabashy, Muhammed Elhadi, Shaimaa I El-Jaafary, Babak Eshrati, Sharareh Eskandarieh, Firooz Esmaeilzadeh, Arash Etemadi, Sayeh Ezzikouri, Mohammed Faisaluddin, Emerito Jose A Faraon, Jawad Fares, Farshad Farzadfar, Abdullah Hamid Feroze, Simone Ferrero, Lorenzo Ferro Desideri, Irina Filip, Florian Fischer, James L Fisher, Masoud Foroutan, Takeshi Fukumoto, Peter Andras Gaal, Mohamed M Gad, Muktar A Gadanya, Silvano Gallus, Mariana Gaspar Fonseca, Abera Getachew Obsa, Mansour Ghafourifard, Ahmad Ghashghaee, Nermin Ghith, Maryam Gholamalizadeh, Syed Amir Gilani, Themba G Ginindza, Abraham Tamirat T Gizaw, James C Glasbey, Mahaveer Golechha, Pouya Goleij, Ricardo Santiago Gomez, Sameer Vali Gopalani, Giuseppe Gorini, Houman Goudarzi, Giuseppe Grosso, Mohammed Ibrahim Mohialdeen Gubari, Maximiliano Ribeiro Guerra, Avirup Guha, D Sanjeeva Gunasekera, Bhawna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Reyna Alma Gutiérrez, Nima Hafezi-Nejad, Mohammad Rifat Haider, Arvin Haj-Mirzaian, Rabih Halwani, Randah R Hamadeh, Sajid Hameed, Samer Hamidi, Asif Hanif, Shafiul Haque, Netanja I Harlianto, Josep Maria Haro, Ahmed I Hasaballah, Soheil Hassanipour, Roderick J Hay, Simon I Hay, Khezar Hayat, Golnaz Heidari, Mohammad Heidari, Brenda Yuliana Herrera-Serna, Claudiu Herteliu, Kamal Hezam, Ramesh Holla, Md Mahbub Hossain, Mohammad Bellal Hossain Hossain, Mohammad-Salar Hosseini, Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Mowafa Househ, Mohamed Hsairi, Junjie Huang, Fernando N Hugo, Rabia Hussain, Nawfal R Hussein, Bing-Fang Hwang, Ivo Iavicoli, Segun Emmanuel Ibitoye, Fidelia Ida, Kevin S Ikuta, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Lalu Muhammad Irham, Jessica Y Islam, Rakibul M Islam, Sheikh Mohammed Shariful Islam, Nahlah Elkudssiah Ismail, Gaetano Isola, Masao Iwagami, Louis Jacob, Vardhmaan Jain, Mihajlo B Jakovljevic, Tahereh Javaheri, Shubha Jayaram, Seyed Behzad Jazayeri, Ravi Prakash Jha, Jost B Jonas, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Mikk Jürisson, Ali Kabir, Danial Kahrizi, Leila R Kalankesh, Rohollah Kalhor, Feroze Kaliyadan, Yogeshwar Kalkonde, Ashwin Kamath, Nawzad Kameran Al-Salihi, Himal Kandel, Neeti Kapoor, André Karch, Ayele Semachew Kasa, Srinivasa Vittal Katikireddi, Joonas H Kauppila, Taras Kavetskyy, Sewnet Adem Kebede, Pedram Keshavarz, Mohammad Keykhaei, Yousef Saleh Khader, Rovshan Khalilov, Gulfaraz Khan, Maseer Khan, Md Nuruzzaman Khan, Moien A B Khan, Young-Ho Khang, Amir M Khater, Maryam Khayamzadeh, Gyu Ri Kim, Yun Jin Kim, Adnan Kisa, Sezer Kisa, Katarzyna Kissimova-Skarbek, Jacek A Kopec, Rajasekaran Koteeswaran, Parvaiz A Koul, Sindhura Lakshmi Koulmane Laxminarayana, Ai Koyanagi, Burcu Kucuk Bicer, Nuworza Kugbey, G Anil Kumar, Narinder Kumar, Nithin Kumar, Om P Kurmi, Tezer Kutluk, Carlo La Vecchia, Faris Hasan Lami, Iván Landires, Paolo Lauriola, Sang-Woong Lee, Shaun Wen Huey Lee, Wei-Chen Lee, Yo Han Lee, James Leigh, Elvynna Leong, Jiarui Li, Ming-Chieh Li, Xuefeng Liu, Joana A Loureiro, Raimundas Lunevicius, Muhammed Magdy Abd El Razek, Azeem Majeed, Alaa Makki, Shilpa Male, Ahmad Azam Malik, Mohammad Ali Mansournia, Santi Martini, Seyedeh Zahra Masoumi, Prashant Mathur, Martin Mckee, Ravi Mehrotra, Walter Mendoza, Ritesh G Menezes, Endalkachew Worku Mengesha, Mohamed Kamal Mesregah, Tomislav Mestrovic, Junmei Miao Jonasson, Bartosz Miazgowski, Tomasz Miazgowski, Irmina Maria Michalek, Ted R Miller, Hamed Mirzaei, Hamid Reza Mirzaei, Sanjeev Misra, Prasanna Mithra, Masoud Moghadaszadeh, Karzan Abdulmuhsin Mohammad, Yousef Mohammad, Mokhtar Mohammadi, Seyyede Momeneh Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Nagabhishek Moka, Ali H Mokdad, Mariam Molokhia, Lorenzo Monasta, Mohammad Ali Moni, Mohammad Amin Moosavi, Yousef Moradi, Paula Moraga, Joana Morgado-Da-Costa, Shane Douglas Morrison, Abbas Mosapour, Sumaira Mubarik, Lillian Mwanri, Ahamarshan Jayaraman Nagarajan, Shankar Prasad Nagaraju, Chie Nagata, Mukhammad David Naimzada, Vinay Nangia, Atta Abbas Naqvi, Sreenivas Narasimha Swamy, Rawlance Ndejjo, Sabina O Nduaguba, Ionut Negoi, Serban Mircea Negru, Sandhya Neupane Kandel, Cuong Tat Nguyen, Huong Lan Thi Nguyen, Robina Khan Niazi, Chukwudi A Nnaji, Nurulamin M Noor, Virginia Nuñez-Samudio, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Chimedsuren Ochir, Oluwakemi Ololade Odukoya, Felix Akpojene Ogbo, Andrew T Olagunju, Babayemi Oluwaseun Olakunde, Emad Omar, Ahmed Omar Bali, Abidemi E Emmanuel Omonisi, Sokking Ong, Obinna E Onwujekwe, Hans Orru, Doris V Ortega-Altamirano, Nikita Otstavnov, Stanislav S Otstavnov, Mayowa O Owolabi, Mahesh P A, Jagadish Rao Padubidri, Keyvan Pakshir, Adrian Pana, Demosthenes Panagiotakos, Songhomitra Panda-Jonas, Shahina Pardhan, Eun-Cheol Park, Eun-Kee Park, Fatemeh Pashazadeh Kan, Harsh K Patel, Jenil R Patel, Siddhartha Pati, Sanjay M Pattanshetty, Uttam Paudel, David M Pereira, Renato B Pereira, Arokiasamy Perianayagam, Julian David Pillay, Saeed Pirouzpanah, Farhad Pishgar, Indrashis Podder, Maarten J Postma, Hadi Pourjafar, Akila Prashant, Liliana Preotescu, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Raghu Anekal Radhakrishnan, Venkatraman Radhakrishnan, Ata Rafiee, Fakher Rahim, Shadi Rahimzadeh, Mosiur Rahman, Muhammad Aziz Rahman, Amir Masoud Rahmani, Nazanin Rajai, Aashish Rajesh, Ivo Rakovac, Pradhum Ram, Kiana Ramezanzadeh, Kamal Ranabhat, Priyanga Ranasinghe, Chythra R Rao, Sowmya J Rao, Reza Rawassizadeh, Mohammad Sadegh Razeghinia, Andre M N Renzaho, Negar Rezaei, Nima Rezaei, Aziz Rezapour, Thomas J Roberts, Jefferson Antonio Buendia Rodriguez, Peter Rohloff, Michele Romoli, Luca Ronfani, Gholamreza Roshandel, Godfrey M Rwegerera, Manjula S, Siamak Sabour, Basema Saddik, Umar Saeed, Amirhossein Sahebkar, Harihar Sahoo, Sana Salehi, Marwa Rashad Salem, Hamideh Salimzadeh, Mehrnoosh Samaei, Abdallah M Samy, Juan Sanabria, Senthilkumar Sankararaman, Milena M Santric-Milicevic, Yaeesh Sardiwalla, Arash Sarveazad, Brijesh Sathian, Monika Sawhney, Mete Saylan, Ione Jayce Ceola Schneider, Mario Sekerija, Allen Seylani, Omid Shafaat, Zahra Shaghaghi, Masood Ali Shaikh, Erfan Shamsoddin, Mohammed Shannawaz, Rajesh Sharma, Aziz Sheikh, Sara Sheikhbahaei, Adithi Shetty, Jeevan K Shetty, Pavanchand H Shetty, Kenji Shibuya, Reza Shirkoohi, K M Shivakumar, Velizar Shivarov, Soraya Siabani, Sudeep K Siddappa Malleshappa, Diego Augusto Santos Silva, Jasvinder A Singh, Yitagesu Sintayehu, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Matthew J Soeberg, Ahmad Sofi-Mahmudi, Houman Sotoudeh, Paschalis Steiropoulos, Kurt Straif, Ranjeeta Subedi, Mu'awiyyah Babale Sufiyan, Iyad Sultan, Saima Sultana, Daniel Sur, Viktória Szerencsés, Miklós Szócska, Rafael Tabarés-Seisdedos, Takahiro Tabuchi, Hooman Tadbiri, Amir Taherkhani, Ken Takahashi, Iman M Talaat, Ker-Kan Tan, Vivian Y Tat, Bemnet Amare A Tedla, Yonas Getaye Tefera, Arash Tehrani-Banihashemi, Mohamad-Hani Temsah, Fisaha Haile Tesfay, Gizachew Assefa Tessema, Rekha Thapar, Aravind Thavamani, Viveksandeep Thoguluva Chandrasekar, Nihal Thomas, Hamid Reza Tohidinik, Mathilde Touvier, Marcos Roberto Tovani-Palone, Eugenio Traini, Bach Xuan Tran, Khanh Bao Tran, Mai Thi Ngoc Tran, Jaya Prasad Tripathy, Biruk Shalmeno Tusa, Irfan Ullah, Saif Ullah, Krishna Kishore Umapathi, Bhaskaran Unnikrishnan, Era Upadhyay, Marco Vacante, Maryam Vaezi, Sahel Valadan Tahbaz, Diana Zuleika Velazquez, Massimiliano Veroux, Francesco S Violante, Vasily Vlassov, Bay Vo, Victor Volovici, Giang Thu Vu, Yasir Waheed, Richard G Wamai, Paul Ward, Yi Feng Wen, Ronny Westerman, Andrea Sylvia Winkler, Lalit Yadav, Seyed Hossein Yahyazadeh Jabbari, Lin Yang, Sanni Yaya, Taklo Simeneh Yazie Yazie, Yigizie Yeshaw, Naohiro Yonemoto, Mustafa Z Younis, Zabihollah Yousefi, Chuanhua Yu, Deniz Yuce, Ismaeel Yunusa, Vesna Zadnik, Fariba Zare, Mikhail Sergeevich Zastrozhin, Anasthasia Zastrozhina, Jianrong Zhang, Chenwen Zhong, Linghui Zhou, Cong Zhu, Arash Ziapour, Ivan R Zimmermann, Christina Fitzmaurice, Christopher J L Murray, Lisa M Force

Faculty, Staff and Student Publications

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite …

Brain Stereotactic Radiosurgery Using Mr-Guided Online Adaptive Planning For Daily Setup Variation: An End-To-End Test, Eun Young Han, He Wang, Tina Marie Briere, Debra Nana Yeboa, Themistoklis Boursianis, Georgios Kalaitzakis, Evangelos Pappas, Pamela Castillo, Jinzhong Yang

Faculty, Staff and Student Publications

Online magnetic resonance (MR)-guided radiotherapy is expected to benefit brain stereotactic radiosurgery (SRS) due to superior soft tissue contrast and capability of daily adaptive planning. The purpose of this study was to investigate daily adaptive plan quality with setup variations and to perform an end-to-end test for brain SRS with multiple metastases treated with a 1.5-Tesla MR-Linac (MRL). The RTsafe PseudoPatient Prime brain phantom was used with a delineation insert that includes two predefined structures mimicking gadolinium contrast-enhanced brain lesions. Daily adaptive plans were generated using six preset and six random setup variations. Two adaptive plans per daily MR image …

Younger Age Of Stroke In Low-Middle Income Countries Is Related To Healthcare Access And Quality, Mohammad H Rahbar, Martin Medrano, Franck Diaz-Garelli, Cosme Gonzalez Villaman, Sepideh Saroukhani, Sori Kim, Amirali Tahanan, Yahaira Franco, Gelanys Castro-Tejada, Sarah A Diaz, Manouchehr Hessabi, Sean I Savitz

Faculty, Staff and Student Publications

Stroke is the second leading cause of mortality globally with higher burden and younger age in low-middle income countries (LMICs) than high-income countries (HICs). However, it is unclear to what extent differences in healthcare access and quality (HAQ) and prevalence of risk factors between LMICs and HICs contribute to younger age of stroke in LMICs. In this systematic review, we conducted meta-analysis of 67 articles and compared the mean age of stroke between LMICs and HICs, before and after adjusting for HAQ index. We also compared the prevalence of main stroke risk factors between HICs and LMICs. The unadjusted mean …

Elucidating The Clinical Spectrum And Molecular Basis Of Hyal2 Deficiency, James Fasham, Siying Lin, Promita Ghosh, Francesca Clementina Radio, Emily G Farrow, Isabelle Thiffault, Jennifer Kussman, Dihong Zhou, Rick Hemming, Kenneth Zahka, Barry A Chioza, Lettie E Rawlins, Olivia K Wenger, Adam C Gunning, Simone Pizzi, Roberta Onesimo, Giuseppe Zampino, Emily Barker, Natasha Osawa, Megan Christine Rodriguez, Teresa M Neuhann, Elaine H Zackai, Beth Keena, Jenina Capasso, Alex V Levin, Elizabeth Bhoj, Dong Li, Hakon Hakonarson, Ingrid M Wentzensen, Adam Jackson, Kate E Chandler, Zeynep H Coban-Akdemir, Jennifer E Posey, Siddharth Banka, James R Lupski, Sarah E Sheppard, Marco Tartaglia, Barbara Triggs-Raine, Andrew H Crosby, Emma L Baple

Faculty, Staff and Student Publications

PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice displaying similar phenotypes. In this study, we better define the phenotype and pathologic disease mechanism.

METHODS: Clinical and genomic investigations were undertaken alongside molecular studies, including immunoblotting and immunofluorescence analyses of variant/wild-type human HYAL2 expressed in mouse fibroblasts, and in silico modeling of putative pathogenic variants.

RESULTS: Ten newly identified individuals with this condition were investigated, and they were associated with 9 novel pathogenic variants. Clinical studies defined genotype-phenotype correlations and …

Tissue-Targeted Crispr-Cas9-Mediated Genome Editing Of Multiple Homeologs In F0 Generation Xenopus Laevis Embryos, Mark E Corkins, Bridget D Delay, Rachel K Miller

Faculty, Staff and Student Publications

Xenopus laevis frogs are a powerful developmental model that enables studies combining classical embryology and molecular manipulation. Because of the large embryo size, ease of microinjection, and ability to target tissues through established fate maps, X. laevis have become the predominant amphibian research model. Given that their allotetraploid genome has complicated the generation of gene knockouts, strategies need to be established for efficient mutagenesis of multiple homeologs to evaluate gene function. Here we describe a protocol to utilize CRISPR-Cas9-mediated genome editing to target either single alleles or multiple alloalleles in F0 X. laevis embryos. A single guide (sg) RNA is …