Medicine and Health Sciences Commons^™

Cross-Species Genetic Screens Identify Transglutaminase 5 As A Regulator Of Polyglutamine-Expanded Ataxin-1, Won-Seok Lee, Ismael Al-Ramahi, Hyun-Hwan Jeong, Youjin Jang, Tao Lin, Carolyn J Adamski, Laura A Lavery, Smruti Rath, Ronald Richman, Vitaliy V Bondar, Elizabeth Alcala, Jean-Pierre Revelli, Harry T Orr, Zhandong Liu, Juan Botas, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Many neurodegenerative disorders are caused by abnormal accumulation of misfolded proteins. In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-expanded) ataxin-1 (ATXN1) causes neuronal toxicity. Lowering total ATXN1, especially the polyQ-expanded form, alleviates disease phenotypes in mice, but the molecular mechanism by which the mutant ATXN1 is specifically modulated is not understood. Here, we identified 22 mutant ATXN1 regulators by performing a cross-species screen of 7787 and 2144 genes in human cells and Drosophila eyes, respectively. Among them, transglutaminase 5 (TG5) preferentially regulated mutant ATXN1 over the WT protein. TG enzymes catalyzed cross-linking of ATXN1 in a polyQ-length–dependent manner, …

Analysis Of Stimulant Prescriptions And Drug-Related Poisoning Risk Among Persons Receiving Buprenorphine Treatment For Opioid Use Disorder, Carrie M Mintz, Kevin Y Xu, Ned J Presnall, Sarah M Hartz, Frances R Levin, Jeffrey F Scherrer, Laura J Bierut, Richard A Grucza

2020-Current year OA Pubs

Importance: Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied.

Objectives: To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention.

Design, Setting, and Participants: This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to …

Association Of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events And Health Care Expenditures, Anne M Butler, Derek S Brown, Michael J Durkin, John M Sahrmann, Katelin B Nickel, Caroline A O'Neil, Margaret A Olsen, David Y Hyun, Rachel M Zetts, Jason G Newland

2020-Current year OA Pubs

Importance: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described.

Objective: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

Design, Setting, and Participants: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. …

Comparative Effectiveness Associated With Buprenorphine And Naltrexone In Opioid Use Disorder And Cooccurring Polysubstance Use, Kevin Y Xu, Carrie M Mintz, Ned Presnall, Laura J Bierut, Richard A Grucza

2020-Current year OA Pubs

Importance: Despite prevalent polysubstance use, treatment patterns and outcomes for individuals with opioid use disorder (OUD) and cooccurring substance use disorders (SUD) are understudied.

Objective: To evaluate the distribution of buprenorphine and naltrexone initiation among individuals with OUD with vs without cooccurring SUD and to assess the comparative effectiveness associated with buprenorphine and naltrexone against drug-related poisonings.

Design, Setting, and Participants: This observational comparative effectiveness study used insurance claims from 2011 to 2016 from the US IBM MarketScan databases to study initiation of medications for OUD (MOUD) among treatment-seeking individuals aged 12 to 64 years with a primary diagnosis of …

Factors Associated With Endowed Chair Allocation In Medical Oncology In The United States, Lena Jia, Michael Kevin Rooney, Clare E Jacobson, Kent A Griffith, Christina Mangurian, Reshma Jagsi, Merry Jennifer Markham

2020-Current year OA Pubs

To explore persisting gender disparities across leadership roles in medicine, we examined factors associated with holding endowed chairs in US oncology divisions. In 2019, we identified 95 academic oncology divisions, using the Oncology Division Chiefs and Department Chairs listing in the American Society of Clinical Oncology myConnection forum. We collected public information on gender, degree, total National Institutes of Health funding as principal investigator, H-indices, publication and citation numbers, and graduation year and constructed a multivariable logistic regression model. All statistical tests were 2-sided. We identified 1087 oncology full professors. Of these, 287 (26.4%) held endowed chairs: 60 of 269 …

Translational Approaches To Understanding Resilience To Alzheimer's Disease., Sarah M Neuner, Maria Telpoukhovskaia, Vilas Menon, Kristen M S O'Connell, Timothy J Hohman, Catherine Kaczorowski

Faculty Research 2022

Individuals who maintain cognitive function despite high levels of Alzheimer's disease (AD)-associated pathology are said to be 'resilient' to AD. Identifying mechanisms underlying resilience represents an exciting therapeutic opportunity. Human studies have identified a number of molecular and genetic factors associated with resilience, but the complexity of these cohorts prohibits a complete understanding of which factors are causal or simply correlated with resilience. Genetically and phenotypically diverse mouse models of AD provide new and translationally relevant opportunities to identify and prioritize new resilience mechanisms for further cross-species investigation. This review will discuss insights into resilience gained from both human and …

Survey Of Confidence And Knowledge To Manage Patellofemoral Pain In Readers Versus Nonreaders Of The Physical Therapy Clinical Practice Guideline, Richard W. Willy, Lisa T. Hoglund, Neal R. Glaviano, Lori A. Bolgla, David M. Bazett-Jones

Department of Physical Therapy Faculty Papers

Objectives: To compare beliefs of physical therapists (PTs) who read the clinical practice guideline (CPG) for the management of individuals with patellofemoral pain (PFP) to those who have not read the CPG.

Design: Cross-sectional study.

Setting: Online survey.

Participants: 494 currently licensed/registered PTs or physiotherapists.

Main Outcome Measures: Respondents answered Likert-based or open-ended questions regarding the diagnosis, prognosis, risk factors, and management of individuals with PFP, as well as confidence for managing individuals with PFP, especially the ability to identify beneficial and non-beneficial interventions. We dichotomized responses into participants who read (READERS) and did not read (NonREADERS) the CPG.

Results: …

Nanog Prion-Like Assembly Mediates Dna Bridging To Facilitate Chromatin Reorganization And Activation Of Pluripotency, Kyoung-Jae Choi, My Diem Quan, Chuangye Qi, Joo-Hyung Lee, Phoebe S Tsoi, Mahla Zahabiyon, Aleksandar Bajic, Liya Hu, B V Venkataram Prasad, Shih-Chu Jeff Liao, Wenbo Li, Allan Chris M Ferreon, Josephine C Ferreon

Faculty, Staff and Student Publications

Human NANOG expression resets stem cells to ground-state pluripotency. Here we identify the unique features of human NANOG that relate to its dose-sensitive function as a master transcription factor. NANOG is largely disordered, with a C-terminal prion-like domain that phase-transitions to gel-like condensates. Full-length NANOG readily forms higher-order oligomers at low nanomolar concentrations, orders of magnitude lower than typical amyloids. Using single-molecule Förster resonance energy transfer and fluorescence cross-correlation techniques, we show that NANOG oligomerization is essential for bridging DNA elements in vitro. Using chromatin immunoprecipitation sequencing and Hi-C 3.0 in cells, we validate that NANOG prion-like domain assembly is …

Publication Trends In Telemedicine Research Originating From Canada, Jim S Xie, Keean Nanji, Mohammad Khan, Muhammad F Khalid, Sunir J Garg, Lehana Thabane, Sobha Sivaprasad, Varun Chaudhary

Department of Medicine Faculty Papers

Telemedicine modalities for patient care have seen significant global uptake during the COVID-19 pandemic. This study aimed to bibliometrically evaluate the evolution and current landscape of telemedicine literature in Canada. The Scopus database was searched to identify telemedicine publications for which the first or last author had a Canadian institutional affiliation. Study selection and data abstraction were conducted by two pairs of independent reviewers. Between 1976 and January 2021, 810 of 3,620 retrieved citations were telemedicine publications originating from Canada, including 29 randomized controlled trials and 6 systematic reviews. The annual publication output increased substantially from 1/year in 1976 to …

Recommendations For Effective Documentation In Regional Anesthesia: An Expert Panel Delphi Consensus Project, Hassan M Ahmed, Benjamin P Atterton, Gillian G Crowe, Jaime L Barratta, Mark Johnson, Eugene R. Viscusi, Sanjib Adhikary, Eric Albrecht, Karen Boretsky, Jan Boublik, Dara S Breslin, Kelly Byrne, Alan Ch'ng, Alwin Chuan, Patrick Conroy, Craig Daniel, Andrzej Daszkiewicz, Alain Delbos, Dan Sebastian Dirzu, Dmytro Dmytriiev, Paul Fennessy, H Barrie J Fischer, Henry Frizelle, Jeff Gadsden, Philippe Gautier, Rajnish K Gupta, Yavuz Gürkan, Harold David Hardman, William Harrop-Griffiths, Peter Hebbard, Nadia Hernandez, Jakub Hlasny, Gabriella Iohom, Vivian H Y Ip, Christina L Jeng, Rebecca L Johnson, Hari Kalagara, Brian Kinirons, Andrew Kenneth Lansdown, Jody C Leng, Yean Chin Lim, Clara Lobo, Danielle B Ludwin, Alan James Robert Macfarlane, Anthony T Machi, Padraig Mahon, Stephen Mannion, David H Mcleod, Peter Merjavy, Aleksejs Miscuks, Christopher H Mitchell, Eleni Moka, Peter Moran, Ann Ngui, Olga C Nin, Brian D O'Donnell, Amit Pawa, Anahi Perlas, Steven Porter, John-Paul Pozek, Humberto C Rebelo, Vicente Roqués, Kristopher M Schroeder, Gary Schwartz, Eric S. Schwenk, Luc Sermeus, George Shorten, Karthikeyan Srinivasan, Markus F Stevens, Kassiani Theodoraki, Lloyd R Turbitt, Luis Fernando Valdés-Vilches, Thomas Volk, Katrina Webster, T Wiesmann, Sylvia H Wilson, Morné Wolmarans, Glenn Woodworth, Andrew K Worek, E M Louise Moran

Department of Anesthesiology Faculty Papers

Background and objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia.

Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live …

Outstanding Outcomes In Infants With Kmt2a-Germline Acute Lymphoblastic Leukemia Treated With Chemotherapy Alone: Results Of The Children's Oncology Group Aall0631 Trial, Erin M. Guest, John A. Kairalla, Joanne M. Hilden, Zoann E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Y. Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael Borowitz, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Natural Killer Cells In Liver Transplantation: Can We Harness The Power Of The Immune Checkpoint To Promote Tolerance?, Jennifer Halma, Stephen Pierce, Rebecca Mclennan, Todd Bradley, Ryan T. Fischer

Manuscripts, Articles, Book Chapters and Other Papers

The roles that natural killer (NK) cells play in liver disease and transplantation remain ill-defined. Reports on the matter are often contradictory, and the mechanisms elucidated are complex and dependent on the context of the model tested. Moreover, NK cell attributes, such as receptor protein expression and function differ among species, make study of primate or rodent transplant models challenging. Recent insights into NK function and NK-mediated therapy in the context of cancer therapy may prove applicable to transplantation. Of specific interest are immune checkpoint molecules and the mechanisms by which they modulate NK cells in the tumor micro-environment. In …

Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath

Department of Neurology Faculty Papers

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among 17 patients (mean age …

Implementation Of Preemptive Dna Sequence-Based Pharmacogenomics Testing Across A Large Academic Medical Center: The Mayo-Baylor Right 10k Study, Liewei Wang, Steven E Scherer, Suzette J Bielinski, Donna M Muzny, Leila A Jones, John Logan Black, Ann M Moyer, Jyothsna Giri, Richard R Sharp, Eric T Matey, Jessica A Wright, Lance J Oyen, Wayne T Nicholson, Mathieu Wiepert, Terri Sullard, Timothy B Curry, Carolyn R Rohrer Vitek, Tammy M Mcallister, Jennifer L St Sauver, Pedro J Caraballo, Konstantinos N Lazaridis, Eric Venner, Xiang Qin, Jianhong Hu, Christie L Kovar, Viktoriya Korchina, Kimberly Walker, Harshavardhan Doddapaneni, Tsung-Jung Wu, Ritika Raj, Shawn Denson, Wen Liu, Gauthami Chandanavelli, Lan Zhang, Qiaoyan Wang, Divya Kalra, Mary Beth Karow, Kimberley J Harris, Hugues Sicotte, Sandra E Peterson, Amy E Barthel, Brenda E Moore, Jennifer M Skierka, Michelle L Kluge, Katrina E Kotzer, Karen Kloke, Jessica M Vander Pol, Heather Marker, Joseph A Sutton, Adrijana Kekic, Ashley Ebenhoh, Dennis M Bierle, Michael J Schuh, Christopher Grilli, Sara Erickson, Audrey Umbreit, Leah Ward, Sheena Crosby, Eric A Nelson, Sharon Levey, Michelle Elliott, Steve G Peters, Naveen Pereira, Mark Frye, Fadi Shamoun, Matthew P Goetz, Iftikhar J Kullo, Robert Wermers, Jan A Anderson, Christine M Formea, Razan M El Melik, John D Zeuli, Joseph R Herges, Carrie A Krieger, Robert W Hoel, Jodi L Taraba, Scott R St Thomas, Imad Absah, Matthew E Bernard, Stephanie R Fink, Andrea Gossard, Pamela L Grubbs, Therese M Jacobson, Paul Takahashi, Sharon C Zehe, Susan Buckles, Michelle Bumgardner, Colette Gallagher, Kelliann Fee-Schroeder, Nichole R Nicholas, Melody L Powers, Ahmed K Ragab, Darcy M Richardson, Anthony Stai, Jaymi Wilson, Joel E Pacyna, Janet E Olson, Erica J Sutton, Annika T Beck, Caroline Horrow, Krishna R Kalari, Nicholas B Larson, Hongfang Liu, Liwei Wang, Guilherme S Lopes, Bijan J Borah, Robert R Freimuth, Ye Zhu, Debra J Jacobson, Matthew A Hathcock, Sebastian M Armasu, Michaela E Mcgree, Ruoxiang Jiang, Tyler H Koep, Jason L Ross, Matthew G Hilden, Kathleen Bosse, Bronwyn Ramey, Isabelle Searcy, Eric Boerwinkle, Richard A Gibbs, Richard M Weinshilboum

Faculty, Staff and Student Publications

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping.

METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 …

Complexity Of Ballooned Hepatocyte Feature Recognition: Defining A Training Atlas For Artificial Intelligence-Based Imaging In Nafld, Elizabeth M. Brunt, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Histologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in clinical trials and serves as a key regulatory-approved surrogate endpoint for drug efficacy. High inter/intra-observer variation in ballooning measured using the NASH CRN semi-quantitative score has been reported yet no actionable solutions have been proposed.

METHODS: A focused evaluation of hepatocyte ballooning recognition was conducted. Digitized slides were evaluated by 9 internationally recognized expert liver pathologists on 2 separate occasions: each pathologist independently marked every ballooned hepatocyte and later provided an overall non-NASH NAFL/NASH assessment. Interobserver …

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, …

Health-Related Quality Of Life In Pediatric Acute Recurrent Or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors, See Wan Tham, Fuchenchu Wang, Cheryl E Gariepy, Gretchen A Cress, Maisam A Abu-El-Haija, Melena D Bellin, Kate M Ellery, Douglas S Fishman, Tanja Gonska, Melvin B Heyman, Tom K Lin, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Jaimie D Nathan, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Tonya M Palermo, International Study Group Of Pediatric Pancreatitis: In Search For A Cure (Insppire) And Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Abdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.

METHODS: Data were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.

RESULTS: The sample included …

Bisphenol A Exposure Induces Sensory Processing Deficits In Larval Zebrafish During Neurodevelopment, Courtney Scaramella, Joseph B Alzagatiti, Christopher Creighton, Samandeep Mankatala, Fernando Licea, Gabriel M Winter, Jasmine Emtage, Joseph R Wisnieski, Luis Salazar, Anjum Hussain, Faith M Lee, Asma Mammootty, Niyaza Mammootty, Andrew Aldujaili, Kristine A Runnberg, Daniela Hernandez, Trevor Zimmerman-Thompson, Rikhil Makwana, Julien Rouvere, Zahra Tahmasebi, Gohar Zavradyan, Christopher S Campbell, Meghna Komaranchath, Javier Carmona, Jennifer Trevitt, David Glanzman, Adam C Roberts

2020-Current year OA Pubs

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Efficacy And Safety Of Bempedoic Acid In Patients Not Receiving Statins In Phase 3 Clinical Trials, Ulrich Laufs, Christie M Ballantyne, Maciej Banach, Harold Bays, Alberico L Catapano, P Barton Duell, Anne C Goldberg, Antonio M Gotto, Lawrence A Leiter, Kausik K Ray, Leanne T Bloedon, Diane Macdougall, Yang Zhang, G B John Mancini

2020-Current year OA Pubs

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.

OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.

METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for …

Anthropometric Measures Correspond With Functional Motor Outcomes In Females With Rett Syndrome, Kathleen J Motil, Suzanne Geerts, Fran Annese, Jeffrey L Neul, Tim Benke, Eric Marsh, David Lieberman, Steven A Skinner, Daniel G Glaze, Peter Heydemann, Arthur Beisang, Shannon Standridge, Robin Ryther, Jane B Lane, Lloyd Edwards, Alan K Percy

Children’s Nutrition Research Center Staff Publications

Objective: To characterize growth and anthropometric measurements in females with Rett syndrome and compare these measurements with functional outcomes.

Study design: We obtained longitudinal growth and anthropometric measurements from 1154 females with classic and atypical Rett syndrome seen between 2006 and 2019 in the US Natural History Study. We calculated the Clinical Severity Score, Motor Behavior Assessment score, and arm and leg muscle areas and recorded the functional assessments of arm and hand use and ambulation. We compared growth and anthropometric variables from females with Rett syndrome in regard to normative data. We analyzed Clinical Severity Score, Motor Behavior Assessment, …

Organ Fat In Latino Youth At Risk For Type 2 Diabetes, Janiel L Pimentel, Kiley B Vander Wyst, Erica G Soltero, Armando Peña, Houchun H Hu, Smita S Bailey, Amber Pokorney, Stephanie L Ayers, Ana Martinez Valencia, Micah L Olson, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Purpose: Obesity in youth increases the risk for type 2 diabetes (T2D) and elevated abdominal adipose tissue and organ fat may be particularly deleterious. The purpose of this study was to examine associations among measures of adiposity including total, visceral, and organ fat (hepatic and pancreatic) and whether these measures were independently associated with glycemia in Latino youth at risk for diabetes.

Methods: Latino adolescents (47 boys and 32 girls, 13.7 ± 1.4 years) with obesity (BMIz 2.3 ± 0.3) were assessed for total fat by DXA and visceral and organ fat by 3 T magnetic resonance imaging. Glycemic indicators …

Sustainability Via Active Garden Education: The Sustainability Action Plan Model And Process, Rebecca E Lee, Jacob Szeszulski, Elizabeth Lorenzo, Anel Arriola, Meg Bruening, Paul A Estabrooks, Jennie L Hill, Teresia M O'Connor, Gabriel Q Shaibi, Erica G Soltero, Michael Todd

Children’s Nutrition Research Center Staff Publications

Sustainability of intervention programming is challenging to achieve under real world conditions, since few models exist and many studies do not plan far beyond the funding period. Programming content in early care and education centers (ECECs) is often driven by guidelines. However, implementation is very sensitive to contextual factors, such as the setting and implementer (teacher) characteristics. This paper presents the model, definitions, and methodology used for the sustainability action plan capitalizing on a community-based participatory research (CBPR) approach, developed for a multi-site, multi-level garden-based childhood obesity prevention study, Sustainability via Active Garden Education (SAGE). The Ecologic Model of Obesity …

Toll-Like Receptor 1 Locus Re-Examined In A Genome-Wide Association Study Update On Anti-Helicobacter Pylori Igg Titers, Suk Yee Lam, Michiel C Mommersteeg, Bingting Yu, Linda Broer, Manon C W Spaander, Fabian Frost, Stefan Weiss, Henry Völzke, Markus M Lerch, Ben Schöttker, Yan Zhang, Hannah Stocker, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C Wood, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Russell P Tracy, Edmond K Kabagambe, Marcis Leja, Janis Klovins, Raitis Peculis, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, André Uitterlinden, Ernst J Kuipers, Gwenny M Fuhler, Georg Homuth, Maikel P Peppelenbosch

Children’s Nutrition Research Center Staff Publications

Background & aims: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus.

Methods: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European …

Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation In Patients With Advanced Systolic Heart Failure, Amanda R Vest, William W Wong, Joronia Chery, Alex Coston, Laura Telfer, Matthew Lawrence, Didjana Celkupa, Michael S Kiernan, Gregory Couper, Masashi Kawabori, Edward Saltzman

Children’s Nutrition Research Center Staff Publications

Background: Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support.

Methods: We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry …

Plasma Proteome Analyses In Individuals Of European And African Ancestry Identify Cis-Pqtls And Models For Proteome-Wide Association Studies, Jingning Zhang, Diptavo Dutta, Anna Köttgen, Adrienne Tin, Pascal Schlosser, Morgan E Grams, Benjamin Harvey, Ckdgen Consortium, Bing Yu, Eric Boerwinkle, Josef Coresh, Nilanjan Chatterjee

Faculty, Staff and Student Publications

Improved understanding of genetic regulation of the proteome can facilitate identification of the causal mechanisms for complex traits. We analyzed data on 4,657 plasma proteins from 7,213 European American (EA) and 1,871 African American (AA) individuals from the Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative …

Multi-Ancestry Genetic Study Of Type 2 Diabetes Highlights The Power Of Diverse Populations For Discovery And Translation, Anubha Mahajan, Cassandra N Spracklen, Weihua Zhang, Maggie C Y Ng, Lauren E Petty, Hidetoshi Kitajima, Grace Z Yu, Sina Rüeger, Leo Speidel, Young Jin Kim, Momoko Horikoshi, Josep M Mercader, Daniel Taliun, Sanghoon Moon, Soo-Heon Kwak, Neil R Robertson, Nigel W Rayner, Marie Loh, Bong-Jo Kim, Joshua Chiou, Irene Miguel-Escalada, Pietro Della Briotta Parolo, Kuang Lin, Fiona Bragg, Michael H Preuss, Fumihiko Takeuchi, Jana Nano, Xiuqing Guo, Amel Lamri, Masahiro Nakatochi, Robert A Scott, Jung-Jin Lee, Alicia Huerta-Chagoya, Mariaelisa Graff, Jin-Fang Chai, Esteban J Parra, Jie Yao, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Valgerdur Steinthorsdottir, James P Cook, Mart Kals, Niels Grarup, Ellen M Schmidt, Ian Pan, Tamar Sofer, Matthias Wuttke, Chloe Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Meraj Ahmad, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Cécile Lecoeur, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Richard A Jensen, Salman Tajuddin, Edmond K Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, Jack Flanagan, Fernando Abaitua, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Masato Akiyama, Sonia S Anand, Alain Bertoni, Zheng Bian, Jette Bork-Jensen, Ivan Brandslund, Jennifer A Brody, Chad M Brummett, Thomas A Buchanan, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Myriam Fornage, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Christian Fuchsberger, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Mark O Goodarzi, Penny Gordon-Larsen, David Gorkin, Myron Gross, Yu Guo, Sophie Hackinger, Sohee Han, Andrew T Hattersley, Christian Herder, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Marit E Jørgensen, Torben Jørgensen, Yoichiro Kamatani, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Katsuhiko Kohara, Jennifer Kriebel, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Valeriya Lyssenko, Vasiliki Mamakou, K Radha Mani, Thomas Meitinger, Andres Metspalu, Andrew D Morris, Girish N Nadkarni, Jerry L Nadler, Michael A Nalls, Uma Nayak, Suraj S Nongmaithem, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Mark A Pereira, Annette Peters, Fraser J Pirie, Bianca Porneala, Gauri Prasad, Sebastian Preissl, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Kathryn Roll, Charumathi Sabanayagam, Maike Sander, Kevin Sandow, Naveed Sattar, Sebastian Schönherr, Claudia Schurmann, Mohammad Shahriar, Jinxiu Shi, Dong Mun Shin, Daniel Shriner, Jennifer A Smith, Wing Yee So, Alena Stančáková, Adrienne M Stilp, Konstantin Strauch, Ken Suzuki, Atsushi Takahashi, Kent D Taylor, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Brian Tomlinson, Jason M Torres, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Marijana Vujkovic, Niels Wacher-Rodarte, Eleanor Wheeler, Eric A Whitsel, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Toshimasa Yamauchi, Loïc Yengo, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Liang Zhang, Wei Zheng, Finngen, Emerge Consortium, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Craig L Hanis, Patricia A Peyser, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Eleftheria Zeggini, Mitsuhiro Yokota, Stephen S Rich, Charles Kooperberg, James S Pankow, James C Engert, Yii-Der Ida Chen, Philippe Froguel, James G Wilson, Wayne H H Sheu, Sharon L R Kardia, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Leif Groop, Dennis O Mook-Kanamori, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Erwin P Bottinger, Abbas Dehghan, E-Shyong Tai, Josée Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Colin N A Palmer, Simin Liu, Goncalo Abecasis, Jaspal S Kooner, Ruth J F Loos, Kari E North, Christopher A Haiman, Jose C Florez, Danish Saleheen, Torben Hansen, Oluf Pedersen, Reedik Mägi, Claudia Langenberg, Nicholas J Wareham, Shiro Maeda, Takashi Kadowaki, Juyoung Lee, Iona Y Millwood, Robin G Walters, Kari Stefansson, Simon R Myers, Jorge Ferrer, Kyle J Gaulton, James B Meigs, Karen L Mohlke, Anna L Gloyn, Donald W Bowden, Jennifer E Below, John C Chambers, Xueling Sim, Michael Boehnke, Jerome I Rotter, Mark I Mccarthy, Andrew P Morris

Faculty, Staff and Student Publications

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS …

Machine Learning Automated Detection Of Large Vessel Occlusion From Mobile Stroke Unit Computed Tomography Angiography, Alexandra L Czap, Mersedeh Bahr-Hosseini, Noopur Singh, Jose-Miguel Yamal, May Nour, Stephanie Parker, Youngran Kim, Lucas Restrepo, Rania Abdelkhaleq, Sergio Salazar-Marioni, Kenny Phan, Ritvij Bowry, Suja S Rajan, James C Grotta, Jeffrey L Saver, Luca Giancardo, Sunil A Sheth

Faculty, Staff and Student Publications

BACKGROUND: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO.

METHODS: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO …

Manual Therapy For Patients With Radiation-Associated Trismus After Head And Neck Cancer, Holly Mcmillan, Carly E A Barbon, Richard Cardoso, Abigail Sedory, Sheila Buoy, Christine Porsche, Kiara Savage, Lauren Mayo, Katherine A Hutcheson

Faculty, Staff and Student Publications

IMPORTANCE: Trismus is highly prevalent in head and neck cancer (HNC) survivorship. Current standards for trismus treatment include various stretch-based exercise protocols as a primary and single treatment modality with limited evidence regarding the role of manual therapy (MT) for this indication.

OBJECTIVE: To assess the effect size and associations of response to MT to increase oral opening in the setting of radiation-associated trismus.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series was conducted at the University of Texas MD Anderson Cancer Center between 2016 and March 2020 (before COVID-19 interruption) and included 49 disease-free survivors of HNC who were …

Definitive Radiotherapy For Extracranial Oligoprogressive Metastatic Renal Cell Carcinoma As A Strategy To Defer Systemic Therapy Escalation, Brian De, Aradhana M Venkatesan, Pavlos Msaouel, Amol J Ghia, Jing Li, Debra N Yeboa, Quynh-Nhu Nguyen, Andrew J Bishop, Eric Jonasch, Amishi Y Shah, Matthew T Campbell, Jennifer Wang, Amado J Zurita-Saavedra, Jose A Karam, Christopher G Wood, Surena F Matin, Nizar M Tannir, Chad Tang

Faculty, Staff and Student Publications

Objective: To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival.

Patients and methods: We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT. …

Home Cooking Quality Assessment Tool Validation Using Community Science And Crowdsourcing Approaches, Margaret Raber, Nalini Ranjit, Larkin L Strong, Karen Basen-Engquist

Faculty, Staff and Student Publications

Objective: To refine a measure of home cooking quality (defined as the usage level of practices with the potential to influence the nutrient content of prepared foods) and conduct a construct validation of the revised tool, the Healthy Cooking Questionnaire 2 (HCQ2).

Design: Two validation approaches are described: (1) a community science approach used to refine and validate Healthy Cooking Questionnaire (HCQ) constructs, and (2) responses to the revised HCQ (HCQ2) in a sample of Amazon Mechanical Turk (MTurk) workers to determine questionnaire comprehension.

Setting: The Community Scientist Program at the University of Texas MD Anderson Cancer Center facilitated discussion …