Digital Commons Network^™

The Technical Landscape For Patient-Centered Cds: Progress, Gaps, And Challenges, Prashila Dullabh, Krysta Heaney-Huls, David F Lobach, Lauren S Hovey, Shana F Sandberg, Priyanka J Desai, Edwin Lomotan, James Swiger, Michael I Harrison, Chris Dymek, Dean F Sittig, Aziz Boxwala

Faculty, Staff and Student Publications

Supporting healthcare decision-making that is patient-centered and evidence-based requires investments in the development of tools and techniques for dissemination of patient-centered outcomes research findings via methods such as clinical decision support (CDS). This article explores the technical landscape for patient-centered CDS (PC CDS) and the gaps in making PC CDS more shareable, standards-based, and publicly available, with the goal of improving patient care and clinical outcomes. This landscape assessment used: (1) a technical expert panel; (2) a literature review; and (3) interviews with 18 CDS stakeholders. We identified 7 salient technical considerations that span 5 phases of PC CDS development. …

Asthma And Technology In Emerging African American Adults (The Athena Project): Protocol For A Trial Using The Multiphase Optimization Strategy Framework, Alan Baptist, Wanda Gibson-Scipio, April Idalski Carcone, Samiran Ghosh, Angela J Jacques-Tiura, Amy Hall, Karen Kolmodin Macdonell

Faculty, Staff and Student Publications

BACKGROUND: Asthma causes substantial morbidity and mortality in the United States, particularly among African American emerging adults (AAEAs; aged 18-30 years), but very few asthma programs have targeted this population. Interventions that provide education and address underlying motivation for managing asthma may be the most effective. However, intensive face-to-face interventions are often difficult to implement in this population.

OBJECTIVE: The purpose of this study is to develop an effective mobile asthma management intervention to improve control among AAEAs.

METHODS: We will assess the ability of multiple technologic components to assist and improve traditional asthma education. The first component is the …

Pattern Differentiation And Tuning Shift In Human Sensory Cortex Underlie Long-Term Threat Memory, Yuqi You, Lucas R Novak, Kevin J Clancy, Wen Li

Faculty, Staff and Student Publications

The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system 1, but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit 2-4. Through non-human research, the sensory cortex has emerged as a critical substrate for long-term threat memory 5-9, underpinned by sensory cortical pattern separation/completion 10,11 and tuning shift 12,13. In humans, research has begun to associate the human sensory cortex with long-term threat memory 14,15, but the lack of mechanistic insights obscures a direct linkage. Towards that end, …

Characterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson's Diseasecharacterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Jeremiah K H Lim, Ali Shahandeh, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, …

Polygenic Transcriptome Risk Scores For Copd And Lung Function Improve Cross-Ethnic Portability Of Prediction In The Nhlbi Topmed Program, Xiaowei Hu, Dandi Qiao, Wonji Kim, Matthew Moll, Pallavi P Balte, Leslie A Lange, Traci M Bartz, Rajesh Kumar, Xingnan Li, Bing Yu, Brian E Cade, Cecelia A Laurie, Tamar Sofer, Ingo Ruczinski, Deborah A Nickerson, Donna M Muzny, Ginger A Metcalf, Harshavardhan Doddapaneni, Stacy Gabriel, Namrata Gupta, Shannon Dugan-Perez, L Adrienne Cupples, Laura R Loehr, Deepti Jain, Jerome I Rotter, James G Wilson, Bruce M Psaty, Myriam Fornage, Alanna C Morrison, Ramachandran S Vasan, George Washko, Stephen S Rich, George T O'Connor, Eugene Bleecker, Robert C Kaplan, Ravi Kalhan, Susan Redline, Sina A Gharib, Deborah Meyers, Victor Ortega, Josée Dupuis, Stephanie J London, Tuuli Lappalainen, Elizabeth C Oelsner, Edwin K Silverman, R Graham Barr, Timothy A Thornton, Heather E Wheeler, Topmed Lung Working Group, Michael H Cho, Hae Kyung Im, Ani Manichaikul

Faculty, Staff and Student Publications

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and …

Vikela Ekhaya: A Novel, Community-Based, Tuberculosis Contact Management Program In A High Burden Setting, Alexander W Kay, Micaela Sandoval, Godwin Mtetwa, Musa Mkhabela, Banele Ndlovu, Tara Devezin, Welile Sikhondze, Debrah Vambe, Joyce Sibanda, Gloria S Dube, Robert H Stevens, Bhekumusa Lukhele, Anna M Mandalakas

Faculty, Staff and Student Publications

BACKGROUND: The prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.

METHODS: Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants' homes.

RESULTS: In total, 945 contacts from …

Iv Sotalol Use In Pediatric And Congenital Heart Patients: A Multicenter Registry Study, Lindsey E Malloy-Walton, Nicholas H Von Bergen, Seshadri Balaji, Peter S Fischbach, Jason M Garnreiter, S Yukiko Asaki, Jeffrey P Moak, Luis A Ochoa, Philip M Chang, Hoang H Nguyen, Akash R Patel, Christa Kirk, Ashley K Sherman, Jennifer N Avari Silva, J Philip Saul

Faculty, Staff and Student Publications

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. …

A Community-Led Mobile Health Clinic To Improve Structural And Social Determinants Of Health Among (Im)Migrant Workers, Shannon Guillot-Wright, N Miles Farr, Ellie Cherryhomes

Faculty, Staff and Student Publications

BACKGROUND: Community-led interventions that address structural and social determinants of health are lacking among (im)migrant workers, especially seafood workers. This lack of medical attention is especially alarming given their high rate of injury and death.

METHODS: Community-based participatory research (CBPR), a relational model that values the participants as equal partners in research, dissemination, and implementation, guided the interviews and mobile clinic. Seafood workers were engaged throughout data collection, analysis, and interpretation and played a significant role in moving the findings from research into actionable change.

RESULTS: to address the lack of healthcare options for (im)migrants, and at the request of …

Comparison Of Collaborative Goal Setting With Enhanced Education For Managing Diabetes-Associated Distress And Hemoglobin A1c Levels: A Randomized Clinical Trial, Lechauncy Woodard, Amber B Amspoker, Natalie E Hundt, Howard S Gordon, Brian Hertz, Edward Odom, Anne Utech, Javad Razjouyan, Suja S Rajan, Nipa Kamdar, Jasmin Lindo, Lea Kiefer, Praveen Mehta, Aanand D Naik

Faculty, Staff and Student Publications

IMPORTANCE: Type 2 diabetes is a prevalent and morbid condition. Poor engagement with self-management can contribute to diabetes-associated distress and hinder diabetes control.

OBJECTIVE: To evaluate the implementation and effectiveness of Empowering Patients in Chronic Care (EPICC), an evidence-based intervention to improve diabetes-associated distress and hemoglobin A1c (HbA1c) levels after the intervention and after 6-month maintenance.

DESIGN, SETTING, AND PARTICIPANTS: This hybrid (implementation-effectiveness) randomized clinical trial was performed in Veterans Affairs clinics across Illinois, Indiana, and Texas from July 1, 2015, to June 30, 2017. Participants included adults with uncontrolled type 2 diabetes (HbA1c level >8.0%) who received primary care …

The Genomic Alterations In Glioblastoma Influence The Levels Of Csf Metabolites, Wilfredo De Jesús-Rojas, José Muñiz-Hernández, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, Arnaldo J Santos-López, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) has been linked to more than 50 genes that cause a spectrum of clinical symptoms, including newborn respiratory distress, sinopulmonary infections, and laterality abnormalities. Although the RSPH4A (c.921+3_6delAAGT) pathogenic variant has been related to Hispanic groups with Puerto Rican ancestry, it is uncertain how frequently other PCD-implicated genes are present on the island. A retrospective chart review of n = 127 genetic reports from Puerto Rican subjects who underwent genetic screening for PCD variants was conducted from 2018 to 2022. Of 127 subjects, 29.1% subjects presented PCD pathogenic variants, and 13.4% were homozygous for the RSPH4A …

Suppression Of Microrna 124–3p And Microrna 340–5p Ameliorates Retinoic Acid-Induced Cleft Palate In Mice, Hiroki Yoshioka, Akiko Suzuki, Chihiro Iwaya, Junichi Iwata

Faculty, Staff and Student Publications

The etiology of cleft lip with or without cleft palate (CL/P), a common congenital birth defect, is complex, with genetic and epigenetic, as well as environmental, contributing factors. Recent studies suggest that fetal development is affected by maternal conditions through microRNAs (miRNAs), a group of short noncoding RNAs. Here, we show that miR-129-5p and miR-340-5p suppress cell proliferation in both primary mouse embryonic palatal mesenchymal cells and O9-1 cells, a neural crest cell line, through the regulation of Sox5 and Trp53 by miR-129-5p, and the regulation of Chd7, Fign and Tgfbr1 by miR-340-5p. Notably, miR-340-5p, but not miR-129-5p, was upregulated …

It Is Not A Boerhaave! A Case Of Spontaneous Pneumothorax, Imran Khan, Rukma R Govindu, Hussam Ammar

Faculty, Staff and Student Publications

Spontaneous pneumothorax is a pneumothorax that is not caused by trauma or an apparent precipitating factor. This report presents a case of a 91-year-old man with no history of lung disease who developed pneumothorax after two days of persistent nausea and vomiting. He was misdiagnosed as a case of Boerhaave's syndrome. A chest computed tomography with iohexol oral contrast showed no evidence of esophageal rupture, and an upper endoscopy revealed a small gastric ulcer and no gastric outlet obstruction. The patient was managed conservatively; his spontaneous pneumothorax, nausea, and vomiting resolved.

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 …

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 …

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 …

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 …

Treatment Of Acromioclavicular Joint Instability With A Tunnel-Free Reconstruction Technique, Michelle M Gosselin, Brandon S Denney, James M Gregory

Faculty, Staff and Student Publications

Acromioclavicular joint injuries are a common shoulder injury encountered by orthopaedic surgeons. Many different surgical techniques have been described for the operative treatment of these injuries with no single, clear gold standard technique on which surgeons agree. Among the most common complications after surgical management of acromioclavicular injuries are loss of reduction, infection, fracture of clavicle or coracoid, and need for reoperation. We propose an arthroscopic-assisted, tunnel-free surgical technique using a tibialis anterior allograft combined with a FiberTape Cerclage (Arthrex, Naples, FL) to manage both acute and chronic acromioclavicular joint injuries. No bony tunnels are drilled and no hardware is …

Whole Exome Sequencing Identifies Potential Candidate Genes For Spina Bifida Derived From Mouse Models, Chunyan Wang, Steve Seltzsam, Bixia Zheng, Chen-Han Wilfred Wu, Camille Nicolas-Frank, Kirollos Yousef, Kit Sing Au, Nina Mann, Dalia Pantel, Sophia Schneider, Luca Schierbaum, Thomas M Kitzler, Dervla M Connaughton, Youying Mao, Rufeng Dai, Makiko Nakayama, Jameela A Kari, Sherif El Desoky, Mohammed Shalaby, Loai A Eid, Hazem S Awad, Velibor Tasic, Shrikant M Mane, Richard P Lifton, Michelle A Baum, Shirlee Shril, Carlos R Estrada, Friedhelm Hildebrandt

Faculty, Staff and Student Publications

Spina bifida (SB) is the second most common nonlethal congenital malformation. The existence of monogenic SB mouse models and human monogenic syndromes with SB features indicate that human SB may be caused by monogenic genes. We hypothesized that whole exome sequencing (WES) allows identification of potential candidate genes by (i) generating a list of 136 candidate genes for SB, and (ii) by unbiased exome-wide analysis. We generated a list of 136 potential candidate genes from three categories and evaluated WES data of 50 unrelated SB cases for likely deleterious variants in 136 potential candidate genes, and for potential SB candidate …

An Evaluation Of Seasonal Maternal-Neonatal Morbidity Related To Trainee Cycles, Ayamo Oben, Paula Mcgee, William A Grobman, Jennifer L Bailit, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Mona Prasad, George R Saade, Dwight J Rouse, Sean C Blackwell, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

BACKGROUND:

The existence of the “July phenomenon” (worse outcomes related to the presence of new physician trainees in teaching hospitals) has been debated in the literature and media. Previous studies of the phenomenon in obstetrics are limited by the quality and detail of data.

OBJECTIVE:

To evaluate whether the months of June to August, when transitions in trainees occur, are associated with increased maternal and neonatal morbidity.

STUDY DESIGN:

Secondary analysis of an observational cohort of 115,502 mother–infant pairs that delivered at 25 hospitals from March 2008 to February 2011. Inclusion criteria were an individual who had a singleton, nonanomalous …

Predictive Performance Of Newborn Small For Gestational Age By A Us Intrauterine Versus Birth Weight-Derived Standard For Short-Term Neonatal Morbidity And Mortality, Nathan R Blue, Lisa Mele, William A Grobman, Jennifer L Bailit, Ronald J Wapner, John M Thorp, Steve N Caritis, Mona Prasad, Alan T N Tita, George R Saade, Dwight J Rouse, Sean C Blackwell, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

Objective:

The use of birth weight standards to define small for gestational age (SGA) may fail to identify neonates affected by poor fetal growth since they include births associated with sub-optimal fetal growth. Our objective was to compare intrauterine versus birth weight-derived standards to define newborn SGA to predict neonatal morbidity and mortality.

Study Design:

This was a secondary analysis of a multi-center observational study of 118,422 births. Liveborn singleton, non-anomalous newborns born at 23–41 weeks were included. Those with missing gestational age estimation or without a 1^st or 2^nd trimester ultrasound to confirm dating, birth weight, or …

Hemophilia A: Strategies For Improving Long-Term Holistic Management, Adherence, And Quality Of Life, Miguel A Escobar, Cindy Leissinger, Guy Young

Faculty, Staff and Student Publications

Hemophilia A is a rare inherited bleeding disorder characterized by a deficiency in factor VIII. The evolution of currently approved prophylaxis therapy in hemophilia A will be reviewed, including the clinical value of prophylaxis, real-world experience with prophylaxis, and patient quality-of-life factors that must be considered when choosing treatment options for these patients.

Perifollicular Hypopigmentation In Systemic Sclerosis: Associations With Clinical Features And Internal Organ Involvement, Melody P Chung, Christopher A Mecoli, Jamie Perin, Carrie Richardson, Zsuzsanna H Mcmahan

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether perifollicular hypopigmentation in systemic sclerosis (SSc) is associated with demographics, distinct clinical features, and autoantibody profiles.

METHODS: Patients with SSc were prospectively enrolled, with a standardized data form used to collect anatomic distribution of perifollicular hypopigmentation. Associations between hypopigmentation and features of SSc were assessed.

RESULTS: Of 179 adult patients with SSc, 36 (20%) patients had perifollicular hypopigmentation. Of these 36 patients, 94% (n = 34) were female and 33% (n = 12) had limited cutaneous SSc. In univariable logistic regression, Black race (odds ratio [OR] 15.63, 95% CI 6.6-37.20,

CONCLUSION: Perifollicular hypopigmentation is observed in …

Barriers And Facilitators Of Implementing Automated Radiotherapy Planning: A Multisite Survey Of Low- And Middle-Income Country Radiation Oncology Providers, Gwendolyn J Mcginnis, Matthew S Ning, Beth M Beadle, Nanette Joubert, William Shaw, Christoph Trauernich, Hannah Simonds, Surbhi Grover, Carlos E Cardenas, Laurence E Court, Grace L Smith

Faculty, Staff and Student Publications

Purpose: Global access to radiotherapy (RT) is inequitable, with obstacles to implementing modern technologies in low- and middle- income countries (LMICs). The Radiation Planning Assistant (RPA) is a web-based automated RT planning software package intended to increase accessibility of high-quality RT planning. We surveyed LMIC RT providers to identify barriers and facilitators of future RPA deployment and uptake.

Methods: RT providers underwent a pilot RPA teaching session in sub-Saharan Africa (Botswana, South Africa, and Tanzania) and Central America (Guatemala). Thirty providers (30 of 33, 90.9% response rate) participated in a postsession survey.

Results: Respondents included physicians (n = 10, 33%), …

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 …

Src Stimulates Abl-Dependent Phosphorylation Of The Guanine Exchange Factor Net1a To Promote Its Cytosolic Localization And Cell Motility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh

Faculty, Staff and Student Publications

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), …

Novel And Extendable Genotyping System For Human Respiratory Syncytial Virus Based On Whole-Genome Sequence Analysis, Jiani Chen, Xueting Qiu, Vasanthi Avadhanula, Samuel S Shepard, Do-Kyun Kim, James Hixson, Pedro A Piedra, Justin Bahl

Faculty, Staff and Student Publications

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition.

METHODS: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair-wise node distances.

RESULTS: …

Analyzing Relationships Between Economic And Neighborhood-Related Social Determinants Of Health And Intensive Care Unit Length Of Stay For Critically Ill Children With Medical Complexity Presenting With Severe Sepsis, Hunter Hamilton, Alina N West, Nariman Ammar, Lokesh Chinthala, Fatma Gunturkun, Tamekia Jones, Arash Shaban-Nejad, Samir H Shah

Faculty, Staff and Student Publications

OBJECTIVES: Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community.

METHODS: This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period. Severe sepsis CMC patients were …