Public Health Commons^™

Demographic And Regional Trends Of Mortality In Patients With Aortic Dissection In The United States, 1999 To 2019, Salik Nazir, Robert W Ariss, Abdul Mannan Khan Minhas, Rochell Issa, Erin D Michos, Yochai Birnbaum, George V Moukarbel, P Kasi Ramanathan, Hani Jneid

Faculty, Staff and Students Publications

Background Aortic dissection (AoD) is associated with high morbidity and mortality. However, the burden of AoD mortality is not well characterized, and contemporary data and mortality trends in different demographic and geographic subgroups have not been described. Methods and Results Trends in AoD mortality were assessed using a cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Crude and age-adjusted mortality rates (AAMR) per 1 million people with associated annual percent changes were determined. Joinpoint regression was used to assess trends in the overall sample and different demographic (sex, race and ethnicity, …

Food Assistance Use Among Food Bank Clients Affected By Type 2 Diabetes, Eliza Short, Jayati Sharma, Debbe I Thompson, Douglas Taren, Rhonda Gonzalez, Melanie Hingle

Children’s Nutrition Research Center Staff Publications

Objective: To understand the perspectives of food bank clients affected by type 2 diabetes (T2DM).

Design: Semi-structured in-depth interviews conducted with food bank clients.

Setting: Arizona regional food bank.

Participants: Twenty English- and Spanish-speaking food bank clients with T2DM or living with a person with T2DM, aged 45-83 years, majority female, Hispanic, and food insecure.

Phenomenon of interest: Food bank use and preferences, and how these related to T2DM management.

Analysis: A hybrid thematic analysis combining inductive and deductive reasoning.

Results: Three organizing themes emerged from the analysis. First, food assistance was influenced by food preferences and the ability to …

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 …

Colonic Epithelial Angiotensin-Converting Enzyme 2 (Ace2) Expression In Blacks And Whites: Potential Implications For Pathogenesis Covid-19 Racial Disparities, Mart De La Cruz, David P Nunes, Vaishali Bhardwaj, Deepika Subramanyan, Caroline Zaworski, Priya Roy, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites.

METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent …

Changes In Physical Activity Associated With The Covid-19 Pandemic In Individuals With Overweight And Obesity: An Interrupted Time Series Analysis With Historical Controls, Michael C Robertson, Che Young Lee, Ivan Haw-Chong Wu, Yue Liao, Margaret Raber, Nathan Parker, Thuan Le, Leticia Gatus, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The objective of this study was to investigate changes in physical activity patterns associated with the COVID-19 pandemic in individuals with overweight and obesity who were participating in a school district worksite weight loss program. We conducted comparative design interrupted time series analyses on physical activity device (Fitbit) data from the 2018-2019 and 2019-2020 school years (N = 211). We administered a questionnaire in 2020 to supplement device data. After the stay-at-home orders in 2020, participants tended to decrease their weekly step count (B = -1315.7, SE = 627.7, p = .045), decrease their weekly "Lightly active minutes" (B = …

Newborn Screening: Review Of Its Impact For Cystinosis, Katharina Hohenfellner, Ewa Elenberg, Gema Ariceta, Galina Nesterova, Neveen A Soliman, Rezan Topaloglu

Faculty, Staff and Students Publications

Newborn screening (NBS) programmes are considered to be one of the most successful secondary prevention measures in childhood to prevent or reduce morbidity and/or mortality via early disease identification and subsequent initiation of therapy. However, while many rare diseases can now be detected at an early stage using appropriate diagnostics, the introduction of a new target disease requires a detailed analysis of the entire screening process, including a robust scientific background, analytics, information technology, and logistics. In addition, ethics, financing, and the required medical measures need to be considered to allow the benefits of screening to be evaluated at a …

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 …

Spatially Resolved Transcriptomics Of High-Grade Serous Ovarian Carcinoma, Elaine Stur, Sara Corvigno, Mingchu Xu, Ken Chen, Yukun Tan, Sanghoon Lee, Jinsong Liu, Emily Ricco, Daniel Kraushaar, Patricia Castro, Jianhua Zhang, Anil K Sood

Faculty, Staff and Students Publications

Bulk and single-cell RNA sequencing do not provide full characterization of tissue spatial diversity in cancer samples, and currently available in situ techniques (multiplex immunohistochemistry and imaging mass cytometry) allow for only limited analysis of a small number of targets. The current study represents the first comprehensive approach to spatial transcriptomics of high-grade serous ovarian carcinoma using intact tumor tissue. We selected a small cohort of patients with highly annotated high-grade serous ovarian carcinoma, categorized them by response to neoadjuvant chemotherapy (poor or excellent), and analyzed pre-treatment tumor tissue specimens. Our study uncovered extensive differences in tumor composition between the …

Skp2 Stabilizes Mcl-1 And Confers Radioresistance In Colorectal Cancer, Xinfang Yu, Li Zhou, Wenbin Liu, Lijun Liu, Feng Gao, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Overexpression of Skp2 plays a critical role in tumorigenesis and correlates with poor prognosis in human malignancies. Thus, Skp2 has been proposed as an attractive target for anti-tumor interventions. The expression of Skp2 in human colorectal cancer (CRC) and the role of Skp2 in tumorigenic properties and irradiation sensitivities of CRC cells were examined by anchorage-dependent and -independent growth assays, immunoblot, flow cytometry, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiments. Skp2 is highly expressed in CRC patient tissues. Blocking Skp2 expression reduces the tumorigenic properties of CRC cells in vitro and in vivo. Depletion of …

American Heart Association's Life's Simple 7: Lifestyle Recommendations, Polygenic Risk, And Lifetime Risk Of Coronary Heart Disease, Natalie R Hasbani, Symen Ligthart, Michael R Brown, Adam S Heath, Allison Bebo, Kellan E Ashley, Eric Boerwinkle, Alanna C Morrison, Aaron R Folsom, David Aguilar, Paul S De Vries

Faculty, Staff and Students Publications

BACKGROUND: Understanding the effect of lifestyle and genetic risk on the lifetime risk of coronary heart disease (CHD) is important to improving public health initiatives. Our objective was to quantify remaining lifetime risk and years free of CHD according to polygenic risk and the American Heart Association's Life's Simple 7 (LS7) guidelines in a population-based cohort study.

METHODS: Our analysis included data from participants of the ARIC (Atherosclerosis Risk in Communities) study: 8372 White and 2314 Black participants; 45 years of age and older; and free of CHD at baseline examination. A polygenic risk score (PRS) comprised more than 6 …

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 …

Triglyceride-Rich Lipoproteins, Apolipoprotein C-Iii, Angiopoietin-Like Protein 3, And Cardiovascular Events In Older Adults: Atherosclerosis Risk In Communities (Aric) Study, Aliza Hussain, Caroline Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Xiaoming Jia, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS AND RESULTS: In 6359 participants (mean age …

Genetic Variants Associated Mrna Stability In Lung, Jian-Rong Li, Mabel Tang, Yafang Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

BACKGROUND: Expression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs).

RESULTS: Here, we presented a computational framework that takes advantage of recently developed methods to infer the mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the …

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, …

Understanding Young Adult Tobacco And Marijuana Use, Shazia Rangwala

Dissertations and Theses (Open Access)

In 2015, young adults in the United States (U.S.) reported co-use of tobacco and marijuana at a much higher rate than exclusive use of marijuana. While there is some qualitative research specific to using tobacco and marijuana separately, there is a lack of qualitative research studying poly/dual or co-use of these products and to understand the complex interactions between the varied modes of delivery for tobacco and marijuana. Qualitative research in this area is important especially due to the major developmental shifts that occur as youth transition into young adulthood. The proposed study is a descriptive analysis of qualitative data …

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 …

Depression Among Medical Students In The United States During The Covid-19 Pandemic: The Role Of Communication Between Universities And Their Students, Alexandra Ecker, Abbey B Berenson, Sandra J Gonzalez, Roger Zoorob, Jacqueline M Hirth

Faculty, Staff and Students Publications

OBJECTIVE: Medical students are vulnerable to stress and depression during medical school and the COVID-19 pandemic may have exacerbated these issues. This study examined whether the risk of depression was associated with COVID-19 pandemic-related medical school communication.

METHODS: A 144 - item pilot cross-sectional online survey of medical students in the US, was carried out between September 1, 2020 and December 31, 2020. Items on stress, depression, and communication between students and their medical schools were included. This study examined associations of student perceptions of universities' communication efforts and pandemic response with risk of developing depression.

RESULTS: The sample included …

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 …