Digital Commons Network^™

Genomic Correlates Of Outcome In Tumor-Infiltrating Lymphocyte Therapy For Metastatic Melanoma, Caitlin A Creasy, Yuzhong Jeff Meng, Marie-Andrée Forget, Tatiana Karpinets, Katarzyna Tomczak, Chip Stewart, Carlos A Torres-Cabala, Shari Pilon-Thomas, Amod A Sarnaik, James J Mulé, Levi Garraway, Matias Bustos, Jianhua Zhang, Sapna P Patel, Adi Diab, Isabella C Glitza, Cassian Yee, Hussein Tawbi, Michael K Wong, Jennifer Mcquade, Dave S B Hoon, Michael A Davies, Patrick Hwu, Rodabe N Amaria, Cara Haymaker, Rameen Beroukhim, Chantale Bernatchez

Faculty, Staff and Student Publications

Purpose: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL) historically yields a 40%-50% response rate in metastatic melanoma. However, the determinants of outcome are largely unknown.

Experimental design: We investigated tumor-based genomic correlates of overall survival (OS), progression-free survival (PFS), and response to therapy by interrogating tumor samples initially collected to generate TIL infusion products.

Results: Whole-exome sequencing (WES) data from 64 samples indicated a positive correlation between neoantigen load and OS, but not PFS or response to therapy. RNA sequencing analysis of 34 samples showed that expression of PDE1C, RTKN2, and NGFR was enriched in responders who had improved …

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 …

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 …

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 …

Building Capacity For Cancer Research In The Era Of Covid-19: Implementation And Results From An International Virtual Clinical Research Training Program In Zambia, Kevin Diao, Dorothy C Lombe, Catherine K Mwaba, Juliana Wu, Darya A Kizub, Carrie A Cameron, Elizabeth Y Chiao, Susan C Msadabwe, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: The incidence of cancer in sub-Saharan Africa is increasing rapidly, yet cancer research in the region continues to lag. One contributing factor is limited exposure to clinical research among trainees. We describe implementation and results of a virtual clinical research training program for Zambian clinical oncology fellows developed jointly by the Cancer Diseases Hospital in Zambia and the MD Anderson Cancer Center to address this need.

Methods: The clinical research training program consisted of 14 weekly virtual lectures, development of research questions by Zambian clinical oncology fellows, assignment of faculty and peer mentors, longitudinal mentorship of research protocols, and …

Chromatin State Dynamics Confers Specific Therapeutic Strategies In Enhancer Subtypes Of Colorectal Cancer, Elias Orouji, Ayush T Raman, Anand K Singh, Alexey Sorokin, Emre Arslan, Archit K Ghosh, Jonathan Schulz, Christopher Terranova, Shan Jiang, Ming Tang, Mayinuer Maitituoheti, Scot C Callahan, Praveen Barrodia, Katarzyna Tomczak, Yingda Jiang, Zhiqin Jiang, Jennifer S Davis, Sukhen Ghosh, Hey Min Lee, Laura Reyes-Uribe, Kyle Chang, Yusha Liu, Huiqin Chen, Ali Azhdarinia, Jeffrey Morris, Eduardo Vilar, Kendra S Carmon, Scott E Kopetz, Kunal Rai

Faculty, Staff and Student Publications

Objective: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.

Design: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and …

Venetoclax Combined With Induction Chemotherapy In Patients With Newly Diagnosed Acute Myeloid Leukaemia: A Post-Hoc, Propensity Score-Matched, Cohort Study, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Sanam Loghavi, Ken Furudate, Lianchun Xiao, Sherry Pierce, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Marina Konopleva, Naveen Pemmaraju, Uday Popat, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Courtney D Dinardo, Tapan M Kadia

Faculty, Staff and Student Publications

Background: Venetoclax combined with intensive chemotherapy has been shown to be safe with promising activity in fit patients with newly diagnosed acute myeloid leukaemia. The aim of this study was to compare the activity of venetoclax plus intensive chemotherapy with intensive chemotherapy alone.

Methods: This was a post-hoc propensity score matched analysis of prospective clinical trials (NCT03214562, NCT02115295, and NCT01289457) in patients at The University of Texas MD Anderson Cancer Center, Texas, USA between March 29, 2010, and June 15, 2021. Eligible patients were aged 18 years and older, and had newly diagnosed acute myeloid leukaemia …

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. …

Targeting The Notch1-Myc-Cd44 Axis In Leukemia-Initiating Cells In T-All, Sujan Piya, Yaling Yang, Seemana Bhattacharya, Priyanka Sharma, Huaxian Ma, Hong Mu, Hua He, Vivian Ruvolo, Natalia Baran, R Eric Davis, Abhinav K Jain, Marina Konopleava, Hagop Kantarjian, Michael Andreeff, M James You, Gautam Borthakur

Faculty, Staff and Student Publications

The NOTCH1-MYC-CD44 axis integrates cell-intrinsic and extrinsic signaling to ensure the persistence of leukemia-initiating cells (LICs) in T-cell acute lymphoblastic leukemia (T-ALL) but a common pathway to target this circuit is poorly defined. Bromodomain-containing protein 4 (BRD4) is implicated to have a role in the transcriptional regulation of oncogenes MYC and targets downstream of NOTCH1, and here we demonstrate its role in transcriptional regulation of CD44. Hence, targeting BRD4 will dismantle the NOTCH1-MYC-CD44 axis. As a proof of concept, degrading BRD4 with proteolysis targeting chimera (PROTAC) ARV-825, prolonged the survival of mice in Notch1 mutated patient-derived xenograft (PDX) and genetic …

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 …

Landscape Of Notch1 Mutations And Co-Occurring Biomarker Alterations In Chronic Lymphocytic Leukemia, Fatima Zahra Jelloul, Richard Yang, Sofia Garces, Rashmi Kanagal-Shamanna, Chi Y Ok, Sanam Loghavi, Mark J Routbort, Zhuang Zuo, C Cameron Yin, Kristen Floyd, Roland L Bassett, William Wierda, Nitin Jain, Philip Thompson, Rajyalakshmi Luthra, L Jeffrey Medeiros, Keyur P Patel

Faculty, Staff and Student Publications

NOTCH1 is one of the most frequently mutated genes in chronic lymphocytic leukemia and has emerged as a marker of poor prognosis. In addition to coding NOTCH1 mutations involving exon 34, non-coding NOTCH1 mutations involving the 3' UTR have been described in a limited number of chronic lymphocytic leukemia (CLL) patients and were associated with adverse outcomes. In this study, 1574 CLL patients were assessed using targeted sequencing with a 29 gene panel and the results were correlated with prognostic characteristics. NOTCH1 mutations were detected in 252 (16%) patients, including both coding (220/252, 14%), non-coding (24/252, 1.5%) and a mixture …

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 …

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 …

Association Of Flame-Retardant Clothing With Mycosis Fungoides: A Retrospective Analysis, Katherine E Park, Vignesh Ramachandran, Jessica Tran, Tejas P Joshi, Naveen Garg, Madeleine Duvic

Faculty, Staff and Student Publications

Introduction: Mycosis fungoides (MF), the most prevalent form of cutaneous T-cell lymphoma (CTCL), has been associated with a variety of environmental and occupational exposures. Flame-retardant clothing (FRC), in contrast to flame-resistant clothing, is chemically treated and may constitute a previously unrecognized occupational hazard.

Objectives: To report an association between FRC and MF.

Methods: After encountering several young male patients whose onset of MF coincided with the occupational use of FRC and occupation as fire fighters, we did a retrospective search. Additional biopsy proven MF patients with use of FRC were identified by the EPIC electronic medical record using the search …

Differential Ets1 Binding To T:G Mismatches Within A Cpg Dinucleotide Contributes To C-To-T Somatic Mutation Rate Of The Idh2 Hotspot At Codon Arg140, Jie Yang, Esha Gupta, John R Horton, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Cytosine to thymine (C>T) somatic mutation is highly enriched in certain types of cancer, and most commonly occurs via deamination of a 5-methylcytosine (5mC) to thymine, in the context of a CpG dinucleotide. In theory, deamination should occur at equal rates to both 5mC nucleotides on opposite strands. In most cases, the resulting T:G or G:T mismatch can be repaired by thymine DNA glycosylase activities. However, while some hotspot-associated CpG mutations have approximately equal numbers of mutations that resulted either from C>T or G>A in a CpG dinucleotide, many showed strand bias, being skewed toward C>T …

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%), …

Ovarian Cancer Reporting Lexicon For Computed Tomography (Ct) And Magnetic Resonance (Mr) Imaging Developed By The Sar Uterine And Ovarian Cancer Disease-Focused Panel And The Esur Female Pelvic Imaging Working Group, Atul B Shinagare, Elizabeth A Sadowski, Hyesun Park, Olga R Brook, Rosemarie Forstner, Sumer K Wallace, Jeanne M Horowitz, Neil Horowitz, Marcia Javitt, Priyanka Jha, Aki Kido, Yulia Lakhman, Susanna I Lee, Lucia Manganaro, Katherine E Maturen, Stephanie Nougaret, Liina Poder, Gaiane M Rauch, Caroline Reinhold, Evis Sala, Isabelle Thomassin-Naggara, Herbert Alberto Vargas, Aradhana Venkatesan, Olivera Nikolic, Andrea G Rockall

Faculty, Staff and Student Publications

Objectives: Imaging evaluation is an essential part of treatment planning for patients with ovarian cancer. Variation in the terminology used for describing ovarian cancer on computed tomography (CT) and magnetic resonance (MR) imaging can lead to ambiguity and inconsistency in clinical radiology reports. The aim of this collaborative project between Society of Abdominal Radiology (SAR) Uterine and Ovarian Cancer (UOC) Disease-focused Panel (DFP) and the European Society of Uroradiology (ESUR) Female Pelvic Imaging (FPI) Working Group was to develop an ovarian cancer reporting lexicon for CT and MR imaging.

Methods: Twenty-one members of the SAR UOC DFP and ESUR FPI …

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 …

The Microrna-183/96/182 Cluster Inhibits Lung Cancer Progression And Metastasis By Inducing An Interleukin-2-Mediated Antitumor Cd8+ Cytotoxic T-Cell Response, Samrat T Kundu, B Leticia Rodriguez, Laura A Gibson, Amanda N Warner, Mabel G Perez, Rakhee Bajaj, Jared J Fradette, Caleb A Class, Luisa M Solis, Frank R Rojas Alvarez, Ignacio I Wistuba, Lixia Diao, Fengju Chen, Mohit Sachdeva, Jing Wang, David G Kirsch, Chad J Creighton, Don L Gibbons

Faculty, Staff and Student Publications

Here, Kundu et al. investigated the role of the microRNA-183/96/182 cluster (m96cl) in lung cancer and used a novel conditional m96cl mouse to establish that loss of m96cl accelerated the growth of K-Ras mutant autochthonous lung adenocarcinomas. Overall, the authors identified a novel mechanistic role of the m96cl in the suppression of lung cancer growth and metastasis by inducing an IL2-mediated systemic CD8+ CTL immune response.

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 …

Benefits Of, Barriers To, And Needs For An Artificial Intelligence-Powered Medication Information Voice Chatbot For Older Adults: Interview Study With Geriatrics Experts, Meghana Gudala, Mary Ellen Trail Ross, Sunitha Mogalla, Mandi Lyons, Padmavathy Ramaswamy, Kirk Roberts

Faculty, Staff and Student Publications

BACKGROUND: One of the most complicated medical needs of older adults is managing their complex medication regimens. However, the use of technology to aid older adults in this endeavor is impeded by the fact that their technological capabilities are lower than those of much of the rest of the population. What is needed to help manage medications is a technology that seamlessly integrates within their comfort levels, such as artificial intelligence agents.

OBJECTIVE: This study aimed to assess the benefits, barriers, and information needs that can be provided by an artificial intelligence-powered medication information voice chatbot for older adults.

METHODS: …