Digital Commons Network^™

Evaluating The Efficacy Of Rib-To-Pelvis Growth-Friendly Surgery For The Treatment Of Non-Ambulatory Early-Onset Scoliosis Myelomeningocele Patients, Norman Ramirez, Gerardo Olivella, Ryan E Fitzgerald, John T Smith, Peter F Sturm, Paul D Sponseller, Lawrence I Karlin, Scott J Luhmann, Norberto J Torres-Lugo, Tricia St Hilaire, Pediatric Spine Study Group

Open Access Publications

INTRODUCTION: Early-onset scoliosis (EOS) is a well-known orthopaedic manifestation in patients with myelomeningocele. The rib-based growing system (RBGS) has been proposed as an alternative for these individuals because of the poor outcomes with traditional surgical techniques. We aimed to describe the effect of RBGS in patients with nonambulatory EOS myelomeningocele.

METHODS: We retrospectively reviewed the Pediatric Spine Study Group Multicenter Database for all patients with nonambulatory EOS myelomeningocele treated with RBGS from 2004 to 2019. Demographics, surgical data, radiographic findings, and postoperative complications were obtained. The quality-of-life parameters were assessed postoperatively using the Early-onset Scoliosis Questionnaire-24.

RESULTS: Thirty patients (18 …

A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi

Open Access Publications

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and …

Clinical And Molecular Relevance Of Genetic Variants In The Non-Coding Transcriptome Of Patients With Cytogenetically Normal Acute Myeloid Leukemia, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al

Open Access Publications

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in lncRNA that are expressed in leukemic blasts. Among these variants, we identified a cytosine-to-thymidine variant in the lncRNA RP5-1074L1.4 and a cytosine-to-thymidine variant in the lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15 lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the cytosine-to-thymidine variant. We conclude that recurrent genetic variants of lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.

Phgdh Heterogeneity Potentiates Cancer Cell Dissemination And Metastasis, Matteo Rossi, Patricia Altea-Manzano, Margherita Demicco, Ginevra Doglioni, Laura Bornes, Marina Fukano, Anke Vandekeere, Alejandro M Cuadros, Juan Fernández-García, Carla Riera-Domingo, Cristina Jauset, Mélanie Planque, H Furkan Alkan, David Nittner, Dongmei Zuo, Lindsay A Broadfield, Sweta Parik, Antonino Alejandro Pane, Francesca Rizzollo, Gianmarco Rinaldi, Tao Zhang, Shao Thing Teoh, Arin B Aurora, Panagiotis Karras, Ines Vermeire, Dorien Broekaert, Joke Van Elsen, Maximilian M L Knott, Martin F Orth, Sofie Demeyer, Guy Eelen, Lacey E Dobrolecki, Ayse Bassez, Thomas Van Brussel, Karl Sotlar, Michael T Lewis, Harald Bartsch, Manfred Wuhrer, Peter Van Veelen, Peter Carmeliet, Jan Cools, Sean J Morrison, Jean-Christophe Marine, Diether Lambrechts, Massimiliano Mazzone, Gregory J Hannon, Sophia Y Lunt, Thomas G P Grünewald, Morag Park, Jacco Van Rheenen, Sarah-Maria Fendt

Faculty, Staff and Students Publications

Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs1. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process2,3. Metabolic heterogeneity has also been observed4, yet its role in cancer progression is less explored. Here, we discover that loss of phosphoglycerate dehydrogenase (PHGDH) potentiates metastatic dissemination. Specifically, we find that heterogeneous or low PHGDH expression in primary tumors of breast cancer patients is associated with decreased metastasis free survival time. In mice, circulating tumor cells and early metastatic lesions are enriched with PHGDH low cancer …

Curated Variation Benchmarks For Challenging Medically Relevant Autosomal Genes, Justin Wagner, Nathan D Olson, Lindsay Harris, Jennifer Mcdaniel, Haoyu Cheng, Arkarachai Fungtammasan, Yih-Chii Hwang, Richa Gupta, Aaron M Wenger, William J Rowell, Ziad M Khan, Jesse Farek, Yiming Zhu, Aishwarya Pisupati, Medhat Mahmoud, Chunlin Xiao, Byunggil Yoo, Sayed Mohammad Ebrahim Sahraeian, Danny E Miller, David Jáspez, José M Lorenzo-Salazar, Adrián Muñoz-Barrera, Luis A Rubio-Rodríguez, Carlos Flores, Giuseppe Narzisi, Uday Shanker Evani, Wayne E Clarke, Joyce Lee, Christopher E Mason, Stephen E Lincoln, Karen H Miga, Mark T W Ebbert, Alaina Shumate, Heng Li, Chen-Shan Chin, Justin M Zook, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The repetitive nature and complexity of some medically relevant genes poses a challenge for their accurate analysis in a clinical setting. The Genome in a Bottle Consortium has provided variant benchmark sets, but these exclude nearly 400 medically relevant genes due to their repetitiveness or polymorphic complexity. Here, we characterize 273 of these 395 challenging autosomal genes using a haplotype-resolved whole-genome assembly. This curated benchmark reports over 17,000 single-nucleotide variations, 3,600 insertions and deletions and 200 structural variations each for human genome reference GRCh37 and GRCh38 across HG002. We show that false duplications in either GRCh37 or GRCh38 result in …

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 …

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 …

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 …

Genetic Correlates In Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated With Hyper-Cvad Plus Dasatinib Or Ponatinib, Yuya Sasaki, Hagop M Kantarjian, Nicholas J Short, Feng Wang, Ken Furudate, Hidetaka Uryu, Rebecca Garris, Nitin Jain, Koji Sasaki, Farhad Ravandi, Marina Konopleva, Guillermo Garcia-Manero, Latasha Little, Curtis Gumbs, Li Zhao, P Andrew Futreal, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Recurring genetic abnormalities have been identified in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Among them, IKZF1 deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. However, the molecular determinants for clinical outcomes in ponatinib-treated patients remain unknown. We systematically analyzed genetic alterations in adults with Ph-positive ALL uniformly treated in clinical trials with dasatinib-based regimens or a ponatinib-based regimen and investigated the molecular determinants for treatment outcomes using pretreatment specimens collected from adults with Ph-positive ALL treated with Hyper-CVAD plus dasatinib or ponatinib. DNA sequencing and SNP microarray were performed and recurrent genetic abnormalities …

Molecular, Histological, And Clinical Characteristics Of Oligodendrogliomas: A Multi-Institutional Retrospective Study, Antonio Dono, Kristin Alfaro-Munoz, Yuanqing Yan, Carlos A Lopez-Garcia, Zaid Soomro, Garret Williford, Takeshi Takayasu, Lindsay Robell, Nazanin K Majd, John De Groot, Yoshua Esquenazi, Carlos Kamiya-Matsuoka, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined.

Objective: To evaluate the role of PIK3CA mutations in mODGs.

Methods: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed.

Results: The median age was 37 years, and 61 patients (57%) were male. …

Free Cholesterol Bioavailability And Atherosclerosis, Rei J Abe, Jun-Ichi Abe, Minh T H Nguyen, Elizabeth A Olmsted-Davis, Abrar Mamun, Priyanka Banerjee, John P Cooke, Longhou Fang, Henry Pownall, Nhat-Tu Le

Faculty, Staff and Student Publications

Purpose of review: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.

Recent …

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 …

Iatrogenic Diversion Of Superior Vena Cava Into Left Atrium, Tarun Jain, Jamil F Borgi, James C Lee, Karthikeyan Ananthasubramaniam

The Texas Heart Institute Journal

No abstract provided.

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

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 …

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, …

Characteristics, Treatment, And Control Of Hypertension In Public Primary Healthcare Centers In Nigeria: Baseline Results From The Hypertension Treatment In Nigeria Program, Dike B Ojji, Mark D Huffman, Et Al

2020-Current year OA Pubs

BACKGROUND: There are limited data on large-scale, multilevel implementation research studies to improve hypertension diagnosis, treatment, and control rates at the primary healthcare (PHC) level in Africa. We describe the characteristics, treatment, and control rates of patients with hypertension in public PHC centers in the Hypertension Treatment in Nigeria Program.

METHODS: Data were collected from adults at least 18 years at 60 public PHC centers between January 2020 and November 2020. Hypertension treatment rates were calculated at registration and upon completion of the initial visit. Hypertension control rates were calculated based on SBP and DBPs less than 140/90 mmHg. Regression …

Impact Of Recent Acute Kidney Injury On Creatinine Clearance Estimation In Critically Ill Patients Undergoing Cardiac Surgery, Amaris Fuentes, Jagadeswara R Earla, Tomona Iso, Joshua T Swan

The Texas Heart Institute Journal

Acute kidney injury (AKI), often present in critically ill patients and patients with cardiac dysfunction, may alter estimates of renal function. The impact of recent AKI on the accuracy of the Cockcroft-Gault creatinine clearance equation (CG-CrCl) before cardiac surgery is unknown. This single-center, retrospective study included patients who underwent cardiac surgery from 1 January 2006 through 30 June 2012 and whose 24-hour urine creatinine clearance (24hr-CrCl) was measured in the intensive care unit before surgery. We evaluated CG-CrCl accuracy by calculating absolute differences between 24hr-CrCl and CG-CrCl estimates. Clinical impact was signified by discrepancies in United States Food and Drug …

Supracardiac Total Anomalous Pulmonary Venous Return Repair In A 7-Month-Old Infant, Mislav Planinc, Ivan Malcic, Darko Anic

The Texas Heart Institute Journal

Total anomalous pulmonary venous return is a congenital heart malformation characterized by anomalous pulmonary venous inflow to the right atrium. Surgical repair typically occurs during the first month of life, and survival beyond that age in untreated patients is unlikely. We report an extreme case of supracardiac total anomalous pulmonary venous return in an infant who survived 7 months despite atypical anomalous inflow without atrial-level communication and with right-to-left shunting only through a patent ductus arteriosus. We stabilized the patient's left-sided heart function before surgically repairing the anomalous venous return 2 months later. Three years postoperatively, the patient was well.

A D2 To D1 Shift In Dopaminergic Inputs To Midbrain 5-Ht Neurons Causes Anorexia In Mice, Xing Cai, Hailan Liu, Bing Feng, Meng Yu, Yang He, Hesong Liu, Chen Liang, Yongjie Yang, Longlong Tu, Nan Zhang, Lina Wang, Na Yin, Junying Han, Zili Yan, Chunmei Wang, Pingwen Xu, Qi Wu, Qingchun Tong, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HT

Association Of Physical Activity, Sports, And Screen Time With Adolescent Behaviors In Youth Who Visit The Pediatric Emergency Department, Rohit P Shenoi, James G Linakis, Julie R Bromberg, T Charles Casper, Rachel Richards, Thomas H Chun, Victor M Gonzalez, Michael J Mello, Anthony Spirito

Faculty, Staff and Students Publications

Moderate to vigorous physical activity (MVPA), sports, and reduced screen time are associated with favorable youth risk profiles. We evaluated the association of MVPA, sports, and screen time with adolescent behaviors among pediatric emergency department youth. Adolescents were assessed for alcohol/drug use, risky behavior, conduct disorder, and depressive mood. MVPA was activity for ≥5 days/week and ≥60 minutes/day. Increased screen time was ≥3 hours/day computer/TV use for non-schoolwork. Multivariable regression studied association between MVPA, sports, and increased screen time and outcomes adjusting for demographics and academic achievement. Older age and lower academic achievement were significantly associated with risky behaviors, conduct …

Prevalence And Clinical Correlates Of Antinuclear Antibody In Patients With Gastroparesis, Henry P Parkman, Mark L Van Natta, Ashima Makol, Madhusudan Grover, Richard W Mccallum, Zubair Malik, Kenneth L Koch, Irene Sarosiek, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Thomas L Abell, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders.

AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA.

METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP).

RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), …

Recurrent Parotid Adenocarcinoma Presenting As Diffuse Myocardial Metastatic Disease, Edward A El-Am, Upasana Jarori, Sara J Grethlein, Ronald Mastouri, Abhishek Khemka

The Texas Heart Institute Journal

A 64-year-old man who had undergone treatment for left parotid adenocarcinoma presented with progressive exertional shortness of breath. Evaluation revealed metastatic invasion of the myocardium as a rare presentation of recurrent parotid adenocarcinoma. This case highlights the importance of using multimodal imaging methods in diagnostic evaluation and a collaborative multidisciplinary approach in managing patient care.

Proposed Research Criteria For Prodromal Behavioural Variant Frontotemporal Dementia, Megan S Barker, Jill Goldman, Et Al.

2020-Current year OA Pubs

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal …

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 …

Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li

Department of Medicine Faculty Papers

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy …

Donor-Derived Multiple Leukemia Antigen-Specific T-Cell Therapy To Prevent Relapse After Transplant In Patients With All, Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Natalia Lapteva, Wang Tao, Mengfen Wu, Bambi Grilley, George Carrum, Rammurti T Kamble, Laquisa Hill, Robert A Krance, Caridad Martinez, Priti Tewari, Bilal Omer, Stephen Gottschalk, Helen E Heslop, Malcom K Brenner, Cliona M Rooney, Juan F Vera, Ann M Leen, Premal D Lulla

Faculty, Staff and Students Publications

Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no …

Urine Sediment Exam Provides More Diagnostic Information In Aki Than Novel Urinary Biomarkers: Commentary, Junior Uduman, Jerry Yee

Nephrology Articles

No abstract provided.

Dance Of The Golgi: Understanding Golgi Dynamics In Cancer Metastasis, Rakhee Bajaj, Amanda N Warner, Jared F Fradette, Don L Gibbons

Faculty, Staff and Student Publications

The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been …