Digital Commons Network^™

Modulating A Prebiotic Food Source Influences Inflammation And Immune-Regulating Gut Microbes And Metabolites: Insights From The Be Gone Trial, Xiaotao Zhang, Ehsan Irajizad, Kristi L Hoffman, Johannes F Fahrmann, Fangyu Li, Yongwoo David Seo, Gladys J Browman, Jennifer B Dennison, Jody Vykoukal, Pamela N Luna, Wesley Siu, Ranran Wu, Eunice Murage, Nadim J Ajami, Jennifer L Mcquade, Jennifer A Wargo, James P Long, Kim-Anh Do, Johanna W Lampe, Karen M Basen-Engquist, Pablo C Okhuysen, Scott Kopetz, Samir M Hanash, Joseph F Petrosino, Paul Scheet, Carrie R Daniel

Faculty, Staff and Student Publications

BACKGROUND: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention.

METHODS: This low-risk, non-invasive dietary intervention trial was conducted at MD Anderson Cancer Center (Houston, TX, USA). Following a 4-week equilibration, patients were randomized to continue their usual diet without beans (control) or to add a daily cup of study beans to their usual diet (intervention) with immediate crossover at 8-weeks. Stool and fasting blood were collected every 4 …

Whole-Genome Sequencing Uncovers Two Loci For Coronary Artery Calcification And Identifies Arse As A Regulator Of Vascular Calcification, Paul S De Vries, Matthew P Conomos, Kuldeep Singh, Christopher J Nicholson, Deepti Jain, Natalie R Hasbani, Wanlin Jiang, Sujin Lee, Christian L Lino Cardenas, Sharon M Lutz, Doris Wong, Xiuqing Guo, Jie Yao, Erica P Young, Catherine Tcheandjieu, Austin T Hilliard, Joshua C Bis, Lawrence F Bielak, Michael R Brown, Shaila Musharoff, Shoa L Clarke, James G Terry, Nicholette D Palmer, Lisa R Yanek, Huichun Xu, Nancy Heard-Costa, Jennifer Wessel, Margaret Sunitha Selvaraj, Rebecca H Li, Xiao Sun, Adam W Turner, Adrienne M Stilp, Alyna Khan, Anne B Newman, Asif Rasheed, Barry I Freedman, Brian G Kral, Caitlin P Mchugh, Chani Hodonsky, Danish Saleheen, David M Herrington, David R Jacobs, Deborah A Nickerson, Eric Boerwinkle, Fei Fei Wang, Gerardo Heiss, Goo Jun, Greg L Kinney, Haakon H Sigurslid, Harshavardhan Doddapaneni, Ira M Hall, Isabela M Bensenor, Jai Broome, James D Crapo, James G Wilson, Jennifer A Smith, John Blangero, Jose D Vargas, Jose Verdezoto Mosquera, Joshua D Smith, Karine A Viaud-Martinez, Kathleen A Ryan, Kendra A Young, Kent D Taylor, Leslie A Lange, Leslie S Emery, Marcio S Bittencourt, Matthew J Budoff, May E Montasser, Miao Yu, Michael C Mahaney, Mohammed S Mahamdeh, Myriam Fornage, Nora Franceschini, Paulo A Lotufo, Pradeep Natarajan, Quenna Wong, Rasika A Mathias, Richard A Gibbs, Ron Do, Roxana Mehran, Russell P Tracy, Ryan W Kim, Sarah C Nelson, Scott M Damrauer, Sharon L R Kardia, Stephen S Rich, Valentin Fuster, Valerio Napolioni, Wei Zhao, Wenjie Tian, Xianyong Yin, Yuan-I Min, Alisa K Manning, Gina Peloso, Tanika N Kelly, Christopher J O'Donnell, Alanna C Morrison, Joanne E Curran, Warren M Zapol, Donald W Bowden, Lewis C Becker, Adolfo Correa, Braxton D Mitchell, Bruce M Psaty, John Jeffrey Carr, Alexandre C Pereira, Themistocles L Assimes, Nathan O Stitziel, John E Hokanson, Cecelia A Laurie, Jerome I Rotter, Ramachandran S Vasan, Wendy S Post, Patricia A Peyser, Clint L Miller, Rajeev Malhotra

Faculty, Staff and Student Publications

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Contemporary Use Of Coronary Physiology In Cardiology, Ayman Elbadawi, Ramy Sedhom, Mohamed Ghoweba, Abdelazeem Mohamed Etewa, Waleed Kayani, Faisal Rahman

Faculty, Staff and Students Publications

Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain …

Gene Transcription Regulation By Er At The Single Cell And Allele Level, Fabio Stossi, Alejandra Rivera Tostado, Hannah L Johnson, Ragini M Mistry, Maureen G Mancini, Michael A Mancini

Faculty, Staff and Students Publications

In this short review we discuss the current view of how the estrogen receptor (ER), a pivotal member of the nuclear receptor superfamily of transcription factors, regulates gene transcription at the single cell and allele level, focusing on in vitro cell line models. We discuss central topics and new trends in molecular biology including phenotypic heterogeneity, single cell sequencing, nuclear phase separated condensates, single cell imaging, and image analysis methods, with particular focus on the methodologies and results that have been reported in the last few years using microscopy-based techniques. These observations augment the results from biochemical assays that lead …

Complex Evolutionary History With Extensive Ancestral Gene Flow In An African Primate Radiation, Axel Jensen, Frances Swift, Dorien De Vries, Robin M D Beck, Lukas F K Kuderna, Sascha Knauf, Idrissa S Chuma, Julius D Keyyu, Andrew C Kitchener, Kyle Farh, Jeffrey Rogers, Tomas Marques-Bonet, Kate M Detwiler, Christian Roos, Katerina Guschanski

Faculty, Staff and Students Publications

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented …

Endometrial Tgfβ Signaling Fosters Early Pregnancy Development By Remodeling The Fetomaternal Interface, Sydney E Parks, Ting Geng, Diana Monsivais

Faculty, Staff and Students Publications

The endometrium is a unique and highly regenerative tissue with crucial roles during the reproductive lifespan of a woman. As the first site of contact between mother and embryo, the endometrium, and its critical processes of decidualization and immune cell recruitment, play a leading role in the establishment of pregnancy, embryonic development, and reproductive capacity. These integral processes are achieved by the concerted actions of steroid hormones and a myriad of growth factor signaling pathways. This review focuses on the roles of the transforming growth factor β (TGFβ) pathway in the endometrium during the earliest stages of pregnancy through the …

Recommendations To Improve Quality Of Probiotic Systematic Reviews With Meta-Analyses, Lynne V Mcfarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard

Faculty, Staff and Students Publications

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing.

Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity.

Evidence review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where …

Metabolic Dysfunction, Triglyceride-Glucose Index, And Risk Of Severe Asthma Exacerbation, Kristen A Staggers, Charles Minard, Michelle Byers, Drew A Helmer, Tianshi David Wu

Faculty, Staff and Students Publications

BACKGROUND: Metabolic conditions may worsen asthma. There is a need to define a composite biomarker of metabolic dysfunction that has relevance to asthma outcomes.

OBJECTIVE: To determine the association of the triglyceride-glucose index (TyG), a biomarker of metabolic syndrome and insulin resistance, with risk of severe asthma exacerbation.

METHODS: A 5-year retrospective cohort of patients with asthma receiving health care from the US Veterans Health Administration from January 1, 2015, to December 31, 2019, was constructed. Fasting TyG values were extracted. Patients were followed for a severe asthma exacerbation, defined as an asthma-related corticosteroid prescription fill or an emergency encounter …

Microbial Stimulation Of Oxytocin Release From The Intestinal Epithelium Via Secretin Signaling, Heather A Danhof, Jihwan Lee, Aanchal Thapa, Robert A Britton, Sara C Di Rienzi

Faculty, Staff and Students Publications

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, …

Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-Tumor Immunity And Multinucleation Levels Following Completion Of Radiation, Patricia Castro, Germán Corredor, Can Koyuncu, Luke A Nordstrom, Michelle Tiji, Taylor Leavitt, James S Lewis, Anant Madabhushi, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal. Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology.

METHODS: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of infiltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms.

RESULTS: Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

Serum Biomarkers Of Nociceptive And Neuropathic Pain In Chronic Pancreatitis, Jami L Saloman, Yan Li, Kimberly Stello, Wenhao Li, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were …

Prostate Safety Events During Testosterone Replacement Therapy In Men With Hypogonadism: A Randomized Clinical Trial, Shalender Bhasin, Thomas G Travison, Karol M Pencina, Michael O'Leary, Glenn R Cunningham, A Michael Lincoff, Steven E Nissen, M Scott Lucia, Mark A Preston, Mohit Khera, Nader Khan, Michael C Snabes, Xue Li, Catherine M Tangen, Kevin A Buhr, Ian M Thompson

Faculty, Staff and Students Publications

IMPORTANCE: The effect of testosterone replacement therapy (TRT) on the risk of prostate cancer and other adverse prostate events is unknown.

OBJECTIVE: To compare the effect of TRT vs placebo on the incidences of high-grade prostate cancers (Gleason score ≥4 + 3), any prostate cancer, acute urinary retention, invasive prostate procedures, and pharmacologic treatment for lower urinary tract symptoms in men with hypogonadism.

DESIGN, SETTING, AND PARTICIPANTS: This placebo-controlled, double-blind randomized clinical trial enrolled 5246 men (aged 45-80 years) from 316 US trial sites who had 2 testosterone concentrations less than 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or …

Characterization Of Essential Eggshell Proteins From Aedes Aegypti Mosquitoes, Jun Isoe, Carter J. Simington, Max E. Oscherwitz, Alyssa J. Peterson, Alberto A. Rascón, Brooke B. Massani, Roger L. Miesfeld, Michael A. Riehle

Faculty Research, Scholarly, and Creative Activity

Background: Up to 40% of the world population live in areas where mosquitoes capable of transmitting the dengue virus, including Aedes aegypti, coexist with humans. Understanding how mosquito egg development and oviposition are regulated at the molecular level may provide new insights into novel mosquito control strategies. Previously, we identified a protein named eggshell organizing factor 1 (EOF1) that when knocked down with RNA interference (RNAi) resulted in non-melanized and fragile eggs that did not contain viable embryos. Results: In this current study, we performed a comprehensive RNAi screen of putative A. aegypti eggshell proteins to identify additional proteins that …

The 2023 Model Core Content Of Disaster Medicine, Bryan J Wexler, Carl Schultz, Paul D Biddinger, Gregory Ciottone, Angela Cornelius, Robert Fuller, Roxanna Lefort, Andrew Milsten, James Phillips, Ira Nemeth

Faculty, Staff and Students Publications

Introduction: Disaster Medicine (DM) is the clinical specialty whose expertise includes the care and management of patients and populations outside conventional care protocols. While traditional standards of care assume the availability of adequate resources, DM practitioners operate in situations where resources are not adequate, necessitating a modification in practice. While prior academic efforts have succeeded in developing a list of core disaster competencies for emergency medicine residency programs, international fellowships, and affiliated health care providers, no official standardized curriculum or consensus has yet been published to date for DM fellowship programs based in the United States.

Study objective: The objective …

Temporary Ventricular Assist Device Support With A Catheter-Based Axial Pump: Changing The Paradigm At A Pediatric Heart Center, Sebastian C Tume, Andres A Fuentes-Baldemar, Marc Anders, Joseph A Spinner, Hari Tunuguntla, Michiaki Imamura, Asma Razavi, Edward Hickey, Gary Stapleton, Athar M Qureshi, Iki Adachi

Faculty, Staff and Students Publications

Objective: We report the largest pediatric single-center experience with an Impella (Abiomed Inc) catheter-based axial pump support.

Methods: We conducted a retrospective cohort study of all patients with acute decompensated heart failure or cardiogenic shock requiring catheter-based axial pump support between October 2014 and February 2022. The primary outcome per individual encounter (hospital admission) was defined as bridge-to-recovery, bridge-to-durable ventricular assist device support, bridge-to-cardiac transplantation, or death at 6 months after catheter-based axial pump explantation. Adverse events were defined according to the Pediatric Interagency Registry for Mechanical Circulatory Support criteria.

Results: Our final study cohort included 37 encounters with 43 …

Differentiating Desquamating Skin Lesions: A Case Of Methotrexate Epidermal Necrosis, Sahifah Ansari, Dina H Zamil, Edgar Rodriguez, Carly Dunn, Soo Jung Kim

Faculty, Staff and Students Publications

Desquamating skin lesions are a non-specific finding that requires urgent evaluation given the life-threatening severity of one of the potential causes, Stevens-Johnson syndrome (SJS). Methotrexate toxicity, also known in its cutaneous form as methotrexate epidermal necrosis (MEN), is another entity that presents similarly to SJS and is described here in a patient with increased risk due to his age, chronic kidney disease, and increased dose of methotrexate. His diagnosis was complicated by other historical risk factors, including antibiotic use, but was eventually elucidated when he was noted to have bone marrow suppression. Given the pathophysiology of SJS, a T-cell mediated …

Junctional Ectopic Tachycardia Caused By Junctophilin-2 Expression Silencing Is Selectively Sensitive To Ryanodine Receptor Blockade, Qixin Yang, Hanna J Tadros, Bo Sun, Minu-Tshyeto Bidzimou, Jordan E Ezekian, Feng Li, Andreas Ludwig, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4:shJph2 mice serve as a model of nodal arrhythmias driven by ryanodine type 2 receptor (RyR2)–mediated Ca2+ leak. EL20 is a small molecule that blocks RyR2 Ca2+ leak. In a novel in vivo model of JET, Hcn4:shJph2 mice demonstrated rapid conversion of JET to sinus rhythm with infusion of EL20. Primary atrioventricular nodal cells demonstrated increased Ca2+ transient oscillation frequency and increased RyR2-mediated stored Ca2+ leak which was normalized by EL20. EL20 was found to be rapidly degraded in mouse and human plasma, making it a potential novel therapy for …

Dynamic And Functional Linkage Between Von Willebrand Factor And Adamts-13 With Aging: An Atherosclerosis Risk In Community Study, Wei Liu, Kavita Patel, Yi Wang, Michael Nodzenski, Ashley Nguyen, Gayle Teramura, Harrison A Higgins, Ron C Hoogeveen, David Couper, Xiaoyun Fu, Barbara A Konkle, Matthew Shane Loop, Jing-Fei Dong

Faculty, Staff and Students Publications

Background: von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs.

Objective: To identify subjects in the Atherosclerosis Risk in Community study who had persistently low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects.

Methods: We measured VWF antigen, propeptide, adhesive activities, and cleavage by ADAMTS-13 quantified …

Neuroimaging-Based Classification Of Ptsd Using Data-Driven Computational Approaches: A Multisite Big Data Study From The Enigma-Pgc Ptsd Consortium, Xi Zhu, Yoojean Kim, Orren Ravid, Xiaofu He, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Seonjoo Lee, Chadi G Abdallah, Michael Angstadt, Christopher L Averill, C Lexi Baird, Lee A Baugh, Jennifer U Blackford, Jessica Bomyea, Steven E Bruce, Richard A Bryant, Zhihong Cao, Kyle Choi, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Michael D Debellis, Emily L Dennis, Maria Densmore, Terri Deroon-Cassini, Seth G Disner, Wissam El Hage, Amit Etkin, Negar Fani, Kelene A Fercho, Jacklynn Fitzgerald, Gina L Forster, Jessie L Frijling, Elbert Geuze, Atilla Gonenc, Evan M Gordon, Staci Gruber, Daniel W Grupe, Jeffrey P Guenette, Courtney C Haswell, Ryan J Herringa, Julia Herzog, David Bernd Hofmann, Bobak Hosseini, Anna R Hudson, Ashley A Huggins, Jonathan C Ipser, Neda Jahanshad, Meilin Jia-Richards, Tanja Jovanovic, Milissa L Kaufman, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B J Koch, Inga K Koerte, Sheri M Koopowitz, Mayuresh S Korgaonkar, John H Krystal, Ruth Lanius, Christine L Larson, Lauren A M Lebois, Gen Li, Israel Liberzon, Guang Ming Lu, Yifeng Luo, Vincent A Magnotta, Antje Manthey, Adi Maron-Katz, Geoffery May, Katie Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Richard W J Neufeld, Jack B Nitschke, Erin M O'Leary, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, K Luan Phan, Rongfeng Qi, Yann Quidé, Ivan Rektor, Kerry Ressler, Pavel Riha, Marisa Ross, Isabelle M Rosso, Lauren E Salminen, Kelly Sambrook, Christian Schmahl, Martha E Shenton, Margaret Sheridan, Chiahao Shih, Maurizio Sicorello, Anika Sierk, Alan N Simmons, Raluca M Simons, Jeffrey S Simons, Scott R Sponheim, Murray B Stein, Dan J Stein, Jennifer S Stevens, Thomas Straube, Delin Sun, Jean Théberge, Paul M Thompson, Sophia I Thomopoulos, Nic J A Van Der Wee, Steven J A Van Der Werff, Theo G M Van Erp, Sanne J H Van Rooij, Mirjam Van Zuiden, Tim Varkevisser, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xin Wang, Carissa Weis, Sherry Winternitz, Hong Xie, Ye Zhu, Melanie Wall, Yuval Neria, Rajendra A Morey

Faculty, Staff and Students Publications

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls …

Navigating Relapsed Hepatoblastoma: Predictive Factors And Surgical Treatment Strategy, Andres F Espinoza, Kalyani R Patel, Priya B Shetty, Richard S Whitlock, Pavel Sumazin, Xinjian Yu, Stephen F Sarabia, Martin Urbicain, Andras Heczey, Prakash Masand, Sarah E Woodfield, Dolores H López-Terrada, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

Objective: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center.

Methods: A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re-appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging.

Results: …

Microbial Products Linked To Steatohepatitis Are Reduced By Deletion Of Nuclear Hormone Receptor Shp In Mice, Ryan Mifflin, Jung Eun Park, Mikang Lee, Prasant Kumar Jena, Yu-Jui Yvonne Wan, Hazel A Barton, Mirjavid Aghayev, Takhar Kasumov, Li Lin, Xinwen Wang, Robert Novak, Feng Li, He Huang, Leah P Shriver, Yoon-Kwang Lee

Faculty, Staff and Students Publications

Deletion of the nuclear hormone receptor small heterodimer partner (Shp) ameliorates the development of obesity and nonalcoholic steatohepatitis (NASH) in mice. Liver-specific SHP plays a significant role in this amelioration. The gut microbiota has been associated with these metabolic disorders, and the interplay between bile acids (BAs) and gut microbiota contributes to various metabolic disorders. Since hepatic SHP is recognized as a critical regulator in BA synthesis, we assessed the involvement of gut microbiota in the antiobesity and anti-NASH phenotype of Shp−/− mice. Shp deletion significantly altered the levels of a few conjugated BAs. Sequencing the 16S …

Management Of Adults With Anomalous Aortic Origin Of The Coronary Arteries: State-Of-The-Art Review, Mario Gaudino, Antonino Di Franco, Eloisa Arbustini, Emile Bacha, Eric R Bates, Duke E Cameron, Davide Cao, Tirone E David, Ruggero De Paulis, Ismail El-Hamamsy, Kanwal M Farooqi, Leonard N Girardi, Christoph Gräni, Jonathan D Kochav, Silvana Molossi, John D Puskas, Sunil V Rao, Sigrid Sandner, James Tatoulis, Quynh A Truong, Jonathan W Weinsaft, Daniel Zimpfer, Carlos M Mery

Faculty, Staff and Students Publications

As a result of increasing adoption of imaging screening, the number of adult patients with a diagnosis of anomalous aortic origin of the coronary arteries (AAOCA) has grown in recent years. Existing guidelines provide a framework for management and treatment, but patients with AAOCA present with a wide range of anomalies and symptoms that make general recommendations of limited applicability. In particular, a large spectrum of interventions can be used for treatment, and there is no consensus on the optimal approach to be used. In this paper, a multidisciplinary group of clinical and interventional cardiologists and cardiac surgeons performed a …

Benefits And Concerns Of Expanded Carrier Screening: What Do Pregnant Latina Women In Texas Think?, Embedzayi Madhiri, Haocen Wang, Melodie Tedross, Victoria Vidal, Christine Young, Denise Martinez, Wei-Ju Chen, Patricia Robbins-Furman, Robin Page, Nora Montalvo-Liendo, Lei-Shih Chen

Faculty, Staff and Students Publications

The American College of Medical Genetics and Genomics (ACMG) recommends carrier screening for all pregnant women regardless of race or ethnicity. In recent years, the ACMG broadened the guidelines to include expanded carrier screening (ECS) which can screen for 112 conditions. This study seeks to explore the perceptions of pregnant Latina women about the benefits and concerns related to ECS use. Partnering with prenatal clinics in Texas, we conducted semi-structured qualitative interviews with 32 pregnant Latina women in their second or third trimester of pregnancy. NVivo 8 was used to conduct content analysis and emergent coding of the data. Participants …

Associations Between Avocado Intake And Measures Of Glucose And Insulin Homeostasis In Hispanic Individuals With And Without Type 2 Diabetes: Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Mackenzie K Senn, Mark O Goodarzi, Gautam Ramesh, Matthew A Allison, Mariaelisa Graff, Kristin L Young, Gregory A Talavera, Amanda C Mcclain, Tanya P Garcia, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.

METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by …

Machine Learning For Dynamic And Early Prediction Of Acute Kidney Injury After Cardiac Surgery, Christopher T Ryan, Zijian Zeng, Subhasis Chatterjee, Matthew J Wall, Marc R Moon, Joseph S Coselli, Todd K Rosengart, Meng Li, Ravi K Ghanta

Faculty, Staff and Students Publications

OBJECTIVE: Acute kidney injury after cardiac surgery increases morbidity and mortality. Diagnosis relies on oliguria or increased serum creatinine, which develop 48 to 72 hours after injury. We hypothesized machine learning incorporating preoperative, operative, and intensive care unit data could dynamically predict acute kidney injury before conventional identification.

METHODS: Cardiac surgery patients at a tertiary hospital (2008-2019) were identified using electronic medical records in the Medical Information Mart for Intensive Care IV database. Preoperative and intraoperative parameters included demographics, Charlson Comorbidity subcategories, and operative details. Intensive care unit data included hemodynamics, medications, fluid intake/output, and laboratory results. Kidney Disease: Improving …

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

Tumor-Infiltrating Normal B Cells Revealed By Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic And Crucial For Antitumor Immune Responses In Dlbcl, Zijun Y Xu-Monette, Yong Li, Thomas Snyder, Tiantian Yu, Tingxun Lu, Alexandar Tzankov, Carlo Visco, Govind Bhagat, Wenbin Qian, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Yingjun Wang, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, Xiangshan Fan, J Han Van Krieken, Miguel A Piris, Jane N Winter, Qingyan Au, Ilan Kirsch, Mingzhi Zhang, John Shaughnessy, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

PURPOSE: Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance.

EXPERIMENTAL DESIGN: A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex …

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enables Murine Embryo Implantation, Vineet K Maurya, Maria M Szwarc, David M Lonard, Ramakrishna Kommagani, San Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2’s role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2 ^d/d) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2 …