Medicine and Health Sciences Commons^™

Echocardiographic Image Collection And Evaluation In Infants With Chd: Lessons Learned From The Imaging Core Lab For The Residual Lesion Score Study, Jami C Levine, Steven Colan, Felicia Trachtenberg, Edward Marcus, Matthew Ferguson, Anitha Parthiban, Carolyn Taylor, Andreea Dragulescu, Benjamin Goot, Ronald V Lacro, Carol Mcfarland, Shanthi Narasimhan, Matthew O'Connor, Marcus Schamberger, Shubhika Srivistava, Michael Taylor, Meena Nathan

Faculty, Staff and Students Publications

Many factors affect patient outcome after congenital heart surgery, including the complexity of the heart disease, pre-operative status, patient specific factors (prematurity, nutritional status and/or presence of comorbid conditions or genetic syndromes), and post-operative residual lesions. The Residual Lesion Score is a novel tool for assessing whether specific residual cardiac lesions after surgery have a measurable impact on outcome. The goal is to understand which residual lesions can be tolerated and which should be addressed prior to leaving the operating room. The Residual Lesion Score study is a large multicentre prospective study designed to evaluate the association of Residual Lesion …

Failure Rate Of Anti-Tumor Necrosis Factor Α Biologics In Very Early Onset Inflammatory Bowel Disease, Ashleigh Watson, Lina B Karam, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Cognitive, Emotional, And Other Non-Motor Symptoms Of Spinocerebellar Ataxias, Chi-Ying R Lin, Sheng-Han Kuo, Puneet Opal

Faculty, Staff and Students Publications

Purpose of review: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function.

Recent findings: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and …

Psychosocial Moderators Of Polygenic Risk Scores Of Inflammatory Biomarkers In Relation To Grimage, Amanda J F Tamman, Dora Koller, Sheila Nagamatsu, Brenda Cabrera-Mendoza, Chadi Abdallah, John H Krystal, Joel Gelernter, Janitza L Montalvo-Ortiz, Renato Polimanti, Robert H Pietrzak

Faculty, Staff and Students Publications

GrimAge acceleration has previously predicted age-related morbidities and mortality. In the current study, we sought to examine how GrimAge is associated with genetic predisposition for systemic inflammation and whether psychosocial factors moderate this association. Military veterans from the National Health and Resilience in Veterans study, which surveyed a nationally representative sample of European American male veterans, provided saliva samples for genotyping (N = 1135). We derived polygenic risk scores (PRS) from the UK Biobank as markers of genetic predisposition to inflammation. Results revealed that PRS for three inflammatory PRS markers—HDL (lower), apolipoprotein B (lower), and gamma-glutamyl transferase (higher)—were associated …

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Frequency Of Treatment Failure Of Utis In Children With Congenital Urinary Tract Anomalies, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Pearl W Chang, Sanyukta Desai, Michael Tchou, John M Morrison, Jamie D Mudd, Brittany D Casey, Victor Trevisanut, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure.

METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A Shepherd, Marie Florescu, Parneet Cheema, Quincy S C Chu, Sang-We Kim, Daniel Morgensztern, Melissa L Johnson, Sophie Cousin, Dong-Wan Kim, Mor T Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J Ambrose, Sajan Khosla, Avinash Reddy, Deanna L Russell, Mohamed Reda Keddar, James P Conway, J Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J Jewsbury, Sonia Iyer, Simon T Barry, Jan Cosaert, John V Heymach

Faculty, Staff and Student Publications

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure …

Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Student Publications

Background: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined.

Objectives: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales.

Methods: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020.

Results: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with …

The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected …

Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain By Activation Of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 In The Dorsal Root Ganglia, Hee Kee Kim, Qi Wang, Seon-Hee Hwang, Patrick M Dougherty, Jing Wang, Salahadin Abdi

Faculty, Staff and Student Publications

Background: Many chemotherapeutic drugs, including paclitaxel, produce neuropathic pain in patients with cancer, which is a dose-dependent adverse effect. Such chemotherapy-induced neuropathic pain (CINP) is difficult to treat with existing drugs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidative responses and activates phosphorylated Nrf2 (pNrf2). We determined the analgesic effects of bardoxolone methyl (BM), an Nrf2 activator, and the role of pNrf2 on CINP.

Methods: CINP was induced in rats by intraperitoneally injecting paclitaxel on 4 alternate days in rats. BM was injected systemically as single or repeated injections after pain fully developed. RNA transcriptome, …

Surrogate Endpoints In Clinical Trials Of P16-Positive Squamous Cell Carcinoma Of The Oropharynx: An Individual Patient Data Meta-Analysis, Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell, Christopher U Jones, Darrion L Mitchell, Greg Krempl, John A Ridge, Michael F Gensheimer, James A Bonner, Edith Filion, Neal E Dunlap, William A Stokes, Quynh-Thu Le, Pedro Torres-Saavedra, Michelle Mierzwa, Matthew J Schipper

Faculty, Staff and Student Publications

Background: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy.

Methods: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as …

Comprehensive Immunogenomic Profiling Of Idh1-/2-Altered Cholangiocarcinoma, Shalini Makawita, Sunyoung Lee, Elisabeth Kong, Lawrence N Kwong, Zeyad Abouelfetouh, Anaemy Danner De Armas, Lianchun Xiao, Karthikeyan Murugesan, Natalie Danziger, Dean Pavlick, Anil Korkut, Jeffrey S Ross, Milind Javle

Faculty, Staff and Student Publications

Purpose: Isocitrate dehydrogenase (IDH)1/2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2-mutated iCCA is largely unknown.

Methods: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune cell infiltration, immune marker expression, and T-cell inflammation. Tissue microarray arrays were subjected to multiplex immunohistochemistry and colocalization …

Tongue Electrical Impedance Myography Correlates With Functional, Neurophysiologic, And Clinical Outcome Measures In Long-Term Oropharyngeal Cancer Survivors With And Without Hypoglossal Neuropathy: An Exploratory Study, Nathan J Hansen, Karin Woodman, Sheila Buoy, Shitong Mao, Carly E A Barbon, Stephen Y Lai, C David Fuller, Katherine A Hutcheson, Benjamin Sanchez

Faculty, Staff and Student Publications

Background: This pilot study analyzed correlations between tongue electrical impedance myography (EIM), standard tongue electromyography (EMG), and tongue functional measures in N = 4 long-term oropharyngeal cancer (OPC) survivors.

Methods: Patients were screened for a supportive care trial (NCT04151082). Hypoglossal nerve function was evaluated with genioglossus needle EMG, functional measures with the Iowa oral performance instrument (IOPI), and multi-frequency tissue composition with tongue EIM.

Results: Tongue EIM conductivity was higher for patients with EMG-confirmed cranial nerve XII neuropathy than those without (p = 0.005) and in patients with mild versus normal EMG reinnervation ratings (16 kHz EIM: p …

Personal History Of Cancer As A Risk Factor For Second Primary Lung Cancer: Implications For Lung Cancer Screening, Sara Nofal, Jiangong Niu, Paul Resong, Jeff Jin, Kelly W Merriman, Xiuning Le, Hormuzd Katki, John Heymach, Mara B Antonoff, Edwin Ostrin, Jia Wu, Jianjun Zhang, Iakovos Toumazis

Faculty, Staff and Student Publications

Background: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening.

Methods: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC …

Analysis Of East Asia Subgroup In Study 309/Keynote-775: Lenvatinib Plus Pembrolizumab Versus Treatment Of Physician's Choice Chemotherapy In Patients With Previously Treated Advanced Or Recurrent Endometrial Cancer, Kan Yonemori, Keiichi Fujiwara, Kosei Hasegawa, Mayu Yunokawa, Kimio Ushijima, Shiro Suzuki, Ayumi Shikama, Shinichiro Minobe, Tomoka Usami, Jae-Weon Kim, Byoung-Gie Kim, Peng-Hui Wang, Ting-Chang Chang, Keiko Yamamoto, Shirong Han, Jodi Mckenzie, Robert J Orlowski, Takuma Miura, Vicky Makker, Yong Man Kim

Faculty, Staff and Student Publications

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.

METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once …

The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett

Faculty, Staff and Student Publications

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence

Watching The Fall Of Roe V Wade: Media Exposure Relates To Us Women's Alcohol Use Intentions, Stacy M Post, Mary C Jobe, Arianne N Malekzadeh, Katarina E Aubuchon, Rebecca K Hoffman, Michelle L Stock, Lisa Bowleg

Faculty, Staff and Student Publications

OBJECTIVE: The Supreme Court of the United States’ decision in Dobbs v. Jackson Women’s Health Organization in June 2022 overturned Roe v. Wade and ended federal protection of abortion rights. Given the drastic policy changes as a result of the ruling and high exposure to media related to abortion, women opposed to the decision may have experienced distress, which could trigger maladaptive coping strategies, such as alcohol use. The present research examined how consuming abortion-related media in the weeks following the Dobbs decision impacted alcohol use intentions among women of reproductive age residing in the 13 “trigger law” states that …

Artificial Intelligence-Based Radiotherapy Contouring And Planning To Improve Global Access To Cancer Care, Laurence E Court, Ajay Aggarwal, Anuja Jhingran, Komeela Naidoo, Tucker Netherton, Adenike Olanrewaju, Christine Peterson, Jeannette Parkes, Hannah Simonds, Christoph Trauernicht, Lifei Zhang, Beth M Beadle, Radiation Planning Assistant Consortium Collaborators, Affiliations Expand

Faculty, Staff and Student Publications

PURPOSE: Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.

METHODS: The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.

RESULTS: For cervical cancer, RPA plans using bony landmarks were scored as …

Lung Cancer In Ever- And Never-Smokers: Findings From Multi-Population Gwas Studies, Yafang Li, Xiangjun Xiao, Jianrong Li, Younghun Han, Chao Cheng, Gail F Fernandes, Shannon E Slewitzke, Susan M Rosenberg, Meng Zhu, Jinyoung Byun, Yohan Bossé, James D Mckay, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Gary E Goodman, John K Field, Michael P A Davies, Sanjay Shete, Loïc Le Marchand, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Ryan Sun, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Angela Cox, Yun-Chul Hong, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Ann G Schwartz, Ivan Gorlov, Kristen S Purrington, Ping Yang, Yanhong Liu, Joan E Bailey-Wilson, Susan M Pinney, Diptasri Mandal, James C Willey, Colette Gaba, Paul Brennan, Jun Xia, Hongbing Shen, Christopher I Amos

Faculty, Staff and Student Publications

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.

RESULTS: Five novel independent loci, GABRA4, intergenic …

Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group

Faculty, Staff and Student Publications

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a …

Imaging Predictors Of 4q12 Amplified And Rb1 Mutated Glioblastoma Idh-Wildtype, Antonio Dono, Jose Torres, Luis Nunez, Octavio Arevalo, Juan Carlos Rodriguez-Quinteros, Roy F Riascos, Arash Kamali, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Introduction: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma.

Methods: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Case Series: Stenotrophomonas Maltophilia In Pediatric Oncology Patients, Sanila Sarkar, Lea M Stitzlein, Emily Rav, Miriam B Garcia, Shehla Razvi, Michael Chang, Ramia Zakhour

Faculty, Staff and Student Publications

Background: Stenotrophomonas maltophilia is a bacterial pathogen that can be fatal in hospitalized and immunocompromised patients with mortality as high as 69%. Pediatric cancer patients often have risk factors that are common for this infection, making them particularly susceptible. Managing S. maltophilia is especially challenging as it has inherent resistance to several antibiotics. Furthermore, soft tissue infections in neutropenic patients may deviate from the typical clinical presentation of S. maltophilia.

Case details: This case series describes an in-depth examination of three cases involving immunocompromised pediatric patients with S. maltophilia infections. Each case exhibited a distinct clinical presentation, encompassing infection of …

Identification Of Pancreatic Cancer Germline Risk Variants With Effects That Are Modified By Smoking, Huili Zhu, Jaihee Choi, Naishu Kui, Tianzhong Yang, Peng Wei, Donghui Li, Ryan Sun

Faculty, Staff and Student Publications

Purpose: Pancreatic cancer (PC) is a deadly disease most often diagnosed in late stages. Identification of high-risk subjects could both contribute to preventative measures and help diagnose the disease at earlier timepoints. However, known risk factors, assessed independently, are currently insufficient for accurately stratifying patients. We use large-scale data from the UK Biobank (UKB) to identify genetic variant-smoking interaction effects and show their importance in risk assessment.

Methods: We draw data from 15,086,830 genetic variants and 315,512 individuals in the UKB. There are 765 cases of PC. Crucially, robust resampling corrections are used to overcome well-known challenges in hypothesis testing …

Genome-Wide Gene-Environment Interaction Analyses To Understand The Relationship Between Red Meat And Processed Meat Intake And Colorectal Cancer Risk, Mariana C Stern, Joel Sanchez Mendez, Andre E Kim, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A Harrison, Jeroen R Huyghe, Catherine M Tangen, Polly A Newcomb, Amanda I Phipps, Claire E Thomas, Eric S Kawaguchi, Juan Pablo Lewinger, John L Morrison, David V Conti, Jun Wang, Duncan C Thomas, Elizabeth A Platz, Kala Visvanathan, Temitope O Keku, Christina C Newton, Caroline Y Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel J B Van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K Tsilidis, D Timothy Bishop, Yohannes Adama Melaku, Brigid M Lynch, Daniel D Buchanan, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Andrew J Pellatt, Li Li, Matthew A M Devall, Peter T Campbell, Demetrius Albanes, Stephanie J Weinstein, Sonja I Berndt, Stephen B Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D Joshi, David A Drew, Jessica L Petrick, Andrew T Chan, Marios Giannakis, Ulrike Peters, Li Hsu, W James Gauderman

Faculty, Staff and Student Publications

Background: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations.

Methods: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan.

Results: Meta-analyses confirmed positive associations between increased consumption of red meat and …

Peroxisome Proliferator-Activated Receptors As Therapeutic Target For Cancer, Yuqing Wang, Feifei Lei, Yiyun Lin, Yuru Han, Lei Yang, Huabing Tan

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-β/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and …

Omics-Based Profiles And Biomarkers Of Respiratory Infections: Are We There Yet?, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsvL

Glycoprotein Nonmetastatic Melanoma Protein B (Gpnmb) Immunohistochemistry Can Be A Useful Ancillary Tool To Identify Perivascular Epithelioid Cell Tumor, Sintawat Wangsiricharoen, Davis R Ingram, Rohini R Morey, Khalida Wani, Alexander J Lazar, Wei-Lien Wang

Faculty, Staff and Student Publications

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa …