Digital Commons Network^™

A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci For Oral Cancer In Taiwan, Da-Tian Bau, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, Fuu-Jen Tsai

Faculty, Staff and Student Publications

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The …

The Gdf15-Gfral Axis Mediates Chemotherapy-Induced Fatigue In Mice, Brandon Chelette, Chinenye L Chidomere, Robert Dantzer

Faculty, Staff and Student Publications

Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral …

Tissue-Resident Memory T Cells Trigger Rapid Exudation And Local Antibody Accumulation, Pamela C Rosato, Sahar Lotfi-Emran, Vineet Joag, Sathi Wijeyesinghe, Clare F Quarnstrom, Hanna N Degefu, Rebecca Nedellec, Jason M Schenkel, Lalit K Beura, Lars Hangartner, Dennis R Burton, David Masopust

Faculty, Staff and Student Publications

Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells (TRM) in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in …

Executive Function In Autism: Association With Adhd And Asd Symptoms, Rachel R Lee, Anthony R Ward, David M Lane, Michael G Aman, Katherine A Loveland, Rosleen Mansour, Deborah A Pearson

Faculty, Staff and Student Publications

There is substantial comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), and there are well-documented executive functioning (EF) deficits in both populations. An important question concerns whether EF deficits in children with ASD are related to severity of ASD, ADHD, or both. We examined ADHD and ASD symptoms in relation to ratings of EF in the home and classroom. The sample comprised 64 children (55 males) diagnosed with ASD (mean age = 9.26 years; mean FSIQ = 92). Analyses indicated that parent and teacher ratings of EF (except Shift and Emotional Control) were consistently related to ADHD …

Ct Colonography Is The Perfect Colorectal Screening Test That Unfortunately Few People Use Yet, David H Kim

Faculty, Staff and Student Publications

Take-home points

• • Computed tomography colonography (CTC) is the perfect test among the colorectal cancer screening options.
• • The excellent performance of CTC is on par with colonoscopy for both cancers and precancerous polyps, yet without the risks associated with perforation and sedation.
• • CTC presents an opportunity to serve as an important filter and send the small numbers of high-risk lesions for immediate removal while allowing the identification of the few true precursor targets from the large majority of benign polyps.
• • This selective polypectomy strategy at CTC minimizes complications and waste of resources while maintaining advanced neoplasia detection …

Telehealth Trials To Address Health Equity In Stroke Survivors, Anjail Z Sharrief, Amy K Guzik, Erica Jones, Munachi Okpala, Mary F Love, Tamra Ishan Jayenda Ranasinghe, Cheryl Bushnell

Faculty, Staff and Student Publications

Telehealth has seen rapid expansion into chronic care management in the past 3 years because of the COVID-19 pandemic. Telehealth for acute care management has expanded access to equitable stroke care to many patients over the past two decades, but there is limited evidence for its benefit for addressing disparities in the chronic care of patients living with stroke. In this review, we discuss advantages and disadvantages of telehealth use for the outpatient management of stroke survivors. Further, we explore opportunities and potential barriers for telehealth in addressing disparities in stroke outcomes related to various social determinants of health. We …

Metallosis And Nonunion: A Case Series And Literature Review, Muzaffar Mushtaq, Owais A Qureshi, Anmol Dua, Sabina Khan, Meesa Mehraj

Faculty, Staff and Student Publications

Metallosis, defined as the presence of free metal particles in the tissue, including bone and soft tissue, is a rare phenomenon seen in orthopedic practice. It is more commonly seen in arthroplasty surgeries, but its occurrence in the presence of other metal implants is also well recognized. Multiple hypotheses are suggested to explain the genesis of metallosis, but it is traditionally believed that abnormal contact between the metal surfaces leads to abrasive wear causing the release of metal particles into the surrounding tissue eliciting foreign body reactions from the body's immune system. The consequences can be local effects, which can …

Inter-Observer Variability Of Expert-Derived Morphologic Risk Predictors In Aortic Dissection, Martin J Willemink, Domenico Mastrodicasa, Mohammad H Madani, Marina Codari, Leonid L Chepelev, Gabriel Mistelbauer, Kate Hanneman, Maral Ouzounian, Daniel Ocazionez, Rana O Afifi, Joan M Lacomis, Luigi Lovato, Davide Pacini, Gianluca Folesani, Ricarda Hinzpeter, Hatem Alkadhi, Arthur E Stillman, Anna M Sailer, Valery L Turner, Virginia Hinostroza, Kathrin Bäumler, Anne S Chin, Nicholas S Burris, D Craig Miller, Michael P Fischbein, Dominik Fleischmann

Faculty, Staff and Student Publications

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning.

METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a …

Effects Of Subnormothermic Regulated Hepatic Reperfusion On Mitochondrial And Transcriptomic Profiles In A Porcine Model, Joohyun Kim, Michael A Zimmerman, Woo Young Shin, Brent T Boettcher, Ju-Seog Lee, Jong-In Park, Muhammed Ali, Meiying Yang, Jyotsna Mishra, Catherine E Hagen, Joseph E Mcgraw, Angela Mathison, Harvey J Woehlck, Gwen Lomberk, Amadou K S Camara, Raul A Urrutia, David F Stowe, Johnny C Hong

Faculty, Staff and Student Publications

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model.

SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation.

METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), …

Erratum: "Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment", Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada

Faculty, Staff and Student Publications

No abstract provided.

Incidence Of Postoperative Complications Following Pancreatectomy For Pancreatic Cystic Lesions Or Pancreatic Cancer, Eileen C Donovan, Laura R Prakash, Yi-Ju Chiang, Morgan L Bruno, Jessica E Maxwell, Naruhiko Ikoma, Ching-Wei D Tzeng, Matthew H G Katz, Jeffrey E Lee, Michael P Kim

Faculty, Staff and Student Publications

Background: In contrast to pancreatic ductal adenocarcinoma (PDAC), the risks of pancreatectomy for mucinous pancreatic cysts (MCs) are balanced against the putative goal of removing potentially malignant tumors. Despite undergoing similar operations, different rates of perioperative complications and morbidity between MC and PDAC patient populations may affect recommendations for resection. We therefore sought to compare the rates of postoperative complications between patients undergoing pancreatectomies for MCs or PDAC.

Methods: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for MCs or PDAC from July 2011 to August 2019. Patient demographics, complications, and perioperative data were …

Phase Ii Trial Of Weekly Erlotinib Dosing To Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis, N Jewel Samadder, Nathan Foster, Ryan P Mcmurray, Carol A Burke, Elena Stoffel, Priyanka Kanth, Rohit Das, Marcia Cruz-Correa, E Vilar, Gautam Mankaney, Navtej Buttar, Selvi Thirumurthi, Danielle K Turgeon, Michael Sossenheimer, Michelle Westover, Ellen Richmond, Asad Umar, Gary Della'zanna, Luz M Rodriguez, Eva Szabo, David Zahrieh, Paul J Limburg

Faculty, Staff and Student Publications

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Design, setting and participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres.

Exposures: Participants self-administered 350 mg of erlotinib …

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …

An Integrated Multi-Omics Analysis Of Sleep-Disordered Breathing Traits Implicates P2xr4 Purinergic Signaling, Nuzulul Kurniansyah, Danielle A Wallace, Ying Zhang, Bing Yu, Brian Cade, Heming Wang, Heather M Ochs-Balcom, Alexander P Reiner, Alberto R Ramos, Joshua D Smith, Jianwen Cai, Martha Daviglus, Phyllis C Zee, Robert Kaplan, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Sina A Gharib, Susan Redline, Tamar Sofer

Faculty, Staff and Student Publications

Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find …

Gene Expression Profiling Of Circulating Tumor Cells Captured By Microcavity Array Is Superior To Enumeration In Demonstrating Therapy Response In Patients With Newly Diagnosed Advanced And Locally Advanced Non-Small Cell Lung Cancer, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Pablo Lopez Bravo, Wei Qiao, Suyu Liu, Luyang Yao, Steven H Lin, James M Reuben

Faculty, Staff and Student Publications

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC.

Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase …

Blastoid B-Cell Neoplasms: Diagnostic Challenges And Solutions, Lianqun Qiu, Sa A Wang, Guilin Tang, Wei Wang, Pei Lin, Jie Xu, C Cameron Yin, Mahsa Khanlari, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

Blastoid B-cell neoplasms mainly include B-lymphoblastic leukemia/lymphoma (B-ALL), blastoid mantle cell lymphoma, and high-grade B-cell lymphoma with blastoid morphologic features (blastoid HGBL). Distinguishing blastoid HGBL from B-ALL can be challenging and we previously developed six-point flow cytometry-focused and three-point immunohistochemistry-focused scoring systems to aid in differential diagnosis. However, the six-point scoring system was derived from bone marrow cases and occasional cases may have a misleading score using either system. In this study, we assessed 121 cases of blastoid-HGBL (37 BM and 84 extramedullary) to validate the six-point scoring system in all tissue types and to further compare the two scoring …

Rare Variants Of Dermatofibrosarcoma Protuberans: Clinical, Histologic, And Molecular Features And Diagnostic Pitfalls, Celestine M Trinidad, Sintawat Wangsiricharoen, Victor G Prieto, Phyu P Aung

Faculty, Staff and Student Publications

Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor. Most variants are associated with a high risk of local recurrence and a low risk of metastasis. The classic histomorphology of this tumor is made up of uniform, spindle-shaped cells, arranged in a storiform pattern. Tumor cells characteristically infiltrate the underlying subcutis in a honeycomb pattern. Less common variants of DFSP have been identified: myxoid, pigmented, myoid, granular cell, sclerosing, atrophic, and fibrosarcomatous. Only the fibrosarcomatous variant has been shown to differ significantly from classic DFSP in terms of clinical outcome; fibrosarcomatous DFSP has been shown to be associated with a …

Kynureninase Upregulation Is A Prominent Feature Of Nfr2-Activated Cancers And Is Associated With Tumor Immunosuppression And Poor Prognosis, Ricardo A León-Letelier, Ali H Abdel Sater, Yihui Chen, Soyoung Park, Ranran Wu, Ehsan Irajizad, Jennifer B Dennison, Hiroyuki Katayama, Jody V Vykoukal, Samir Hanash, Edwin J Ostrin, Johannes F Fahrmann

Faculty, Staff and Student Publications

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding gene NFE2L2 or a loss of function of its suppressor, Kelch-like ECH-associated protein 1 (KEAP1). NRF2 activation exerts pro-tumoral effects in part by altering cancer cell metabolism. Previously, we reported a novel mechanism of NRF2 tumoral immune suppression through the selective upregulation of the tryptophan-metabolizing enzyme kynureninase (KYNU) in lung adenocarcinoma. In the current study, we explored the relevance of NRF2-mediated KYNU upregulation across multiple cancer types. Specifically, …

Glycolysis Regulates Kras Plasma Membrane Localization And Function Through Defined Glycosphingolipids, Junchen Liu, Ransome Van Der Hoeven, Walaa E Kattan, Jeffrey T Chang, Dina Montufar-Solis, Wei Chen, Maurice Wong, Yong Zhou, Carlito B Lebrilla, John F Hancock

Faculty, Staff and Student Publications

Oncogenic KRAS expression generates a metabolic dependency on aerobic glycolysis, known as the Warburg effect. We report an effect of increased glycolytic flux that feeds into glycosphingolipid biosynthesis and is directly linked to KRAS oncogenic function. High resolution imaging and genetic approaches show that a defined subset of outer leaflet glycosphingolipids, including GM3 and SM4, is required to maintain KRAS plasma membrane localization, with GM3 engaging in cross-bilayer coupling to maintain inner leaflet phosphatidylserine content. Thus, glycolysis is critical for KRAS plasma membrane localization and nanoscale spatial organization. Reciprocally oncogenic KRAS selectively upregulates cellular content of these same glycosphingolipids, whose …

Author Correction: Federated Learning Enables Big Data For Rare Cancer Boundary Detection, Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S Alexander, Joseph Lombardo, Joshua D Palmer, Adam E Flanders, Adam P Dicker, Haris I Sair, Craig K Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A Vogelbaum, J Ross Mitchell, Joaquim Farinhas, Joseph A Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C Pinho, Divya Reddy, James Holcomb, Benjamin C Wagner, Benjamin M Ellingson, Timothy F Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B Martins, Bernardo C A Teixeira, Flávia Sprenger, David Menotti, Diego R Lucio, Pamela Lamontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W Lui, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E Sloan, Vachan Vadmal, Kristin Waite, Rivka R Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V M Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R Van Der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M J Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W Schouten, Hendrikus J Dubbink, Arnaud J P E Vincent, Martin J Van Den Bent, Pim J French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B Chambless, Akshitkumar Mistry, Reid C Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G H Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu, Adeleye Dorcas, Farouk Dako, Amber L Simpson, Mohammad Hamghalam, Jacob J Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y Moraes, Michael A Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S Barnholtz-Sloan, Jason Martin, Spyridon Bakas

Faculty, Staff and Student Publications

No abstract provided.

Spoken Word Recognition Across Language Boundary: Erp Evidence Of Prosodic Transfer Driven By Pitch, Juan Zhang, Yaxuan Meng, Chenggang Wu, Zhen Yuan

Faculty, Staff and Student Publications

Extensive research has explored the perception of English lexical stress by Chinese EFL learners and tried to unveil the underlying mechanism of the prosodic transfer from a native tonal language to a non-native stress language. However, the role of the pitch as the shared cue by lexical stress and lexical tone during the transfer remains controversial when the segmental cue (i.e., reduced vowel) is absent. By employing event-related potential (ERP) measurements, the current study aimed to further investigate the role of the pitch during the prosodic transfer from L1 lexical tone to L2 lexical stress and the underlying neural responses. …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

A Novel Defined Tlr3 Agonist As An Effective Vaccine Adjuvant, Kwang Hyun Ko, Seung Bin Cha, Seung-Hwan Lee, Hyun Shik Bae, Chul Soo Ham, Min-Gyu Lee, Dong-Ho Kim, Seung Hyun Han

Faculty, Staff and Student Publications

Synthetic double-stranded RNA analogs recognized by Toll-like receptor 3 (TLR3) are an attractive adjuvant candidate for vaccines, especially against intracellular pathogens or tumors, because of their ability to enhance T cell and antibody responses. Although poly(I:C) is a representative dsRNA with potent adjuvanticity, its clinical application has been limited due to heterogeneous molecular size, inconsistent activity, poor stability, and toxicity. To overcome these limitations, we developed a novel dsRNA-based TLR3 agonist named NexaVant (NVT) by using PCR-coupled bidirectional in vitro transcription. Agarose gel electrophoresis and reverse phase-HPLC analysis demonstrated that NVT is a single 275-kDa homogeneous molecule. NVT appears to …

The Improve Trial: Study Protocol For A Pragmatic Cluster Randomised Controlled Trial To Assess The Effectiveness Of Using Lay Health Workers To Improve Uptake And Completion Of Pulmonary Rehabilitation In Patients With Chronic Obstructive Pulmonary Disease, Rui Li, Hosamadin Assadi, Gareth Matthews, Zia Mehmood, Ciaran Grafton-Clarke, Bahman Kasmai, David Hewson, Richard Greenwood, Hilmar Spohr, Liang Zhong, Xiaodan Zhao, Chris Sawh, Rudolf Duehmke, Vassilios S Vassiliou, Faye Nelthorpe, David Ashman, John Curtin, Gurung-Koney Yashoda, Rob J Van Der Geest, Samer Alabed, Andrew J Swift, Marina Hughes, Pankaj Garg

Faculty, Staff and Student Publications

There remains a debate whether the ventricular volume within prolapsing mitral valve (MV) leaflets should be included in the left ventricular (LV) end-systolic volume, and therefore factored in LV stroke volume (SV), in cardiac magnetic resonance (CMR) assessments. This study aims to compare LV volumes during end-systolic phases, with and without the inclusion of the volume of blood on the left atrial aspect of the atrioventricular groove but still within the MV prolapsing leaflets, against the reference LV SV by four-dimensional flow (4DF). A total of 15 patients with MV prolapse (MVP) were retrospectively enrolled in this study. We compared …

Global Impact Of The Covid-19 Pandemic On Stroke Volumes And Cerebrovascular Events: A 1-Year Follow-Up, Thanh N Nguyen, Muhammad M Qureshi, Piers Klein, Hiroshi Yamagami, Robert Mikulik, Anna Czlonkowska, Mohamad Abdalkader, Petra Sedova, Anvitha Sathya, Hannah C Lo, Ossama Yassin Mansour, Husitha Reddy Vanguru, Emilie Lesaine, Georgios Tsivgoulis, Aaron I Loochtan, Jelle Demeestere, Ken Uchino, Violiza Inoa, Nitin Goyal, Andreas Charidimou, James E Siegler, Shadi Yaghi, Diana Aguiar De Sousa, Mahmoud H Mohammaden, Diogo C Haussen, Espen Saxhaug Kristoffersen, Virginia Pujol Lereis, Sergio Daniel Scollo, Bruce C V Campbell, Alice Ma, James Orton Thomas, Mark W Parsons, Shaloo Singhal, Lee-Anne Slater, Rodrigo Tomazini Martins, Chris Enzinger, Thomas Gattringer, Aminur Rahman, Thomas Bonnet, Noemie Ligot, Sylvie De Raedt, Robin Lemmens, Peter Vanacker, Fenne Vandervorst, Adriana Bastos Conforto, Raquel C T Hidalgo, Luciana De Oliveira Neves, Rodrigo Targa Martins, Daissy Liliana Mora Cuervo, Leticia C Rebello, Igor Bessa Santiago, Isabelle Lameirinhas Da Silva, Teodora Sakelarova, Rosen Kalpachki, Filip Alexiev, Luciana Catanese, Elena Adela Cora, Mayank Goyal, Michael D Hill, Michael E Kelly, Houman Khosravani, Pascale Lavoie, Lissa Peeling, Aleksandra Pikula, Rodrigo Rivera, Hui-Sheng Chen, Yimin Chen, Xiaochuan Huo, Zhongrong Miao, Shuiquan Yang, Marina Roje Bedekovic, Marina Bralic, Hrvoje Budincevic, Angel Basilio Corredor-Quintero, Osvaldo E Lara-Sarabia, Martin Cabal, Dusan Tenora, Petr Fibrich, Roman Herzig, Helena Hlaváčová, Emanuela Hrabanovska, David Hlinovsky, Lubomir Jurak, Jana Kadlcikova, Igor Karpowicz, Lukas Klecka, Martin Kovar, David Lauer, Jiri Neumann, Hana Palouskova, Martin Reiser, Petra Rekova, Vladimir Rohan, Ondrej Skoda, Miroslav Škorňa, Lenka Sobotková, Martin Sramek, Lenka Zakova, Hanne Christensen, Nicolas Drenck, Helle Klingenberg Iversen, Thomas Clement Truelsen, Troels Wienecke, Khalid Sobh, Pauli Ylikotila, Kemal Alpay, Daniel Strbian, Patricia Bernady, Philippe Casenave, Maria Dan, Jean-Marc Faucheux, Jean-Christophe Gentric, Elsa Magro, Candice Sabben, Peggy Reiner, Francois Rouanet, Ferdinand O Bohmann, Stefan Boskamp, Joshua Mbroh, Simon Nagel, Christian H Nolte, Peter A Ringleb, Michael Rosenkranz, Sven Poli, Götz Thomalla, Theodoros Karapanayiotides, Ioanna Koutroulou, Odysseas Kargiotis, Lina Palaiodimou, Jose Dominguo Barrientos Guerra, Vikram Huded, Bindu Menon, Shashank Nagendra, Chintan Prajapati, P N Sylaja, Nyoman Angga Krishna Pramana, Achmad Firdaus Sani, Abdoreza Ghoreishi, Mehdi Farhoudi, Elyar Sadeghi Hokmabadi, Tariq Abu Raya, Shani Avnery Kalmanovich, Levite Ronen, Sergiu Ionut Sabetay, Maurizio Acampa, Alessandro Adami, Lucio Castellan, Marco Longoni, Raffaele Ornello, Leonardo Renieri, Claudia Rolla Bigliani, Michele Romoli, Simona Sacco, Andrea Salmaggi, Davide Sangalli, Andrea Zini, Ryosuke Doijiri, Hiroki Fukuda, Toshiyuki Fujinaka, Kyohei Fujita, Hirotoshi Imamura, Nobuyuki Sakai, Takuya Kanamaru, Naoto Kimura, Ryuhei Kono, Kosuke Miyake, Manabu Sakaguchi, Kenichiro Sakai, Kazutaka Sonoda, Kenichi Todo, Fumio Miyashita, Naoki Tokuda, Yuji Matsumaru, Shoji Matsumoto, Nobuyuki Ohara, Seigo Shindo, Yohei Takenobu, Takeshi Yoshimoto, Kazunori Toyoda, Takeshi Uwatoko, Yoshiki Yagita, Takehiro Yamada, Nobuaki Yamamoto, Ryoo Yamamoto, Yukako Yazawa, Yuri Sugiura, Peter Kuria Waweru, Jang-Hyun Baek, Si Baek Lee, Kwon-Duk Seo, Sung-Il Sohn, Anita Ante Arsovska, Yong Chieh Chan, Wan Asyraf Wan Zaidi, Ainul Syahrilfazli Jaafar, Fernando Gongora-Rivera, Manuel Martinez-Marino, Adrian Infante-Valenzuela, Stanislav Groppa, Pavel Leahu, Jonathan M Coutinho, Leon A Rinkel, Diederik W J Dippel, Dianne H K Van Dam-Nolen, Annemarei Ranta, Teddy Y Wu, Tajudeen Temitayo Adebayo, Abiodun H Bello, Ernest Okwundu Nwazor, Taofiki Ajao Sunmonu, Kolawole Wasiu Wahab, Ole Morten Ronning, Else Charlotte Sandset, Amal M Al Hashmi, Saima Ahmad, Umair Rashid, Liliana Rodriguez-Kadota, Miguel Ángel Vences, Patrick Matic Yalung, Jon Stewart Hao Dy, Maria Carissa Pineda-Franks, Christian Oliver Co, Waldemar Brola, Aleksander Debiec, Malgorzata Dorobek, Michal Adam Karlinski, Beata M Labuz-Roszak, Anetta Lasek-Bal, Halina Sienkiewicz-Jarosz, Jacek Staszewski, Piotr Sobolewski, Marcin Wiacek, Justyna Zielinska-Turek, Andre Pinho Araujo, Mariana Rocha, Pedro Castro, Vitor Tedim Cruz, Paulo Venancio Ferreira, Patricia Ferreira, Ana Paiva Nunes, Luisa Fonseca, João Pedro Marto, Teresa Pinho E Melo, Miguel Rodrigues, M Luis Silva, Adela Dimitriade, Cristian Falup-Pecurariu, May Adel Hamid, Narayanaswamy Venketasubramanian, Georgi Krastev, Miroslav Mako, Oscar Ayo-Martin, Francisco Hernández-Fernández, Jordi Blasco, Alejandro Rodríguez-Vázquez, Antonio Cruz-Culebras, Francisco Moniche, Joan Montaner, Soledad Perez-Sanchez, María Jesús García Sánchez, Marta Guillán Rodríguez, Katarina Jood, Annika Nordanstig, Michael V Mazya, Tiago T P Moreira, Gianmarco Bernava, Morin Beyeler, Manuel Bolognese, Emmanuel Carrera, Tomas Dobrocky, Grzegorz Marek Karwacki, Emanuela Keller, Chang Yang Hsieh, Surawan Boonyakarnkul, Anchalee Churojana, Ozlem Aykac, Atilla Ã-Zcan Ozdemir, Arsida Bajrami, Songul Senadim, Syed Irteza Hussain, Seby John, Soma Banerjee, Joseph Kwan, Kailash Krishnan, Robert Lenthall, Ashok Matthews, Ken Wong, Liqun Zhang, Dorothea Altschul, Kaiz S Asif, Zeelalem Bahiru, Kristine Below, José Biller, Sean Ruland, Saqib A Chaudry, Michael Chen, Alex Chebl, Jackie Cibulka, Leon Cistrunk, Judith Clark, Marco Colasurdo, Alexandra Czap, Adam De Havenon, Salvatore D'Amato, Sushrut Dharmadhikari, Kasey B Grimmett, Adam A Dmytriw, Mark R Etherton, Chizoba Ezepue, Mudassir Farooqui, Steven K Feske, Lauren Fink, Ulviyya Gasimova, Amy K Guzik, Maryam Hakemi, Majesta Hovingh, Muhib Khan, Dinesh Jillela, Peter T Kan, Rakesh Khatri, Ayaz M Khawaja, Naim N Khoury, Nicole L Kiley, Benny S Kim, Murali K Kolikonda, Anna Luisa Kuhn, Stephanie Lara, Guillermo Linares, Italo Linfante, Timothy G Lukovits, Sarah Lycan, Shailesh S Male, Laith Maali, John Mancin, Hesham Masoud, Ghada A Mohamed, Andre Monteiro, Fadi Nahab, Krishna Nalleballe, Santiago Ortega-Gutierrez, Ajit S Puri, Yazan Radaideh, Rahul H Rahangdale, Ansaar Rai, Pankajavalli Ramakrishnan, Aravind B Reddy, Diana M Rojas-Soto, Jose Rafael Romero, Natalia S Rost, Aaron Rothstein, Setareh Salehi Omran, Sunil A Sheth, Adnan H Siddiqui, Amy K Starosciak, Nicholas E Tarlov, Robert A Taylor, Michael J Wang, Jared Wolfe, Ka-Ho Wong, Huynh Vu Le, Quy Viet Nguyen, Thong Nhu Pham, Trung Thanh Nguyen, Hoang Thi Phan, Mai Duy Ton, Urs Fischer, Patrik Michel, Davide Strambo, Sheila O Martins, Osama O Zaidat, Raul G Nogueira

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year …

Mixcan: A Framework For Cell-Type-Aware Transcriptome-Wide Association Studies With An Application To Breast Cancer, Xiaoyu Song, Jiayi Ji, Joseph H Rothstein, Stacey E Alexeeff, Lori C Sakoda, Adriana Sistig, Ninah Achacoso, Eric Jorgenson, Alice S Whittemore, Robert J Klein, Laurel A Habel, Pei Wang, Weiva Sieh

Faculty, Staff and Student Publications

Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared …

Epigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinomaepigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinoma, Amin H Nassar, Sarah Abou Alaiwi, Sylvan C Baca, Elio Adib, Rosario I Corona, Ji-Heui Seo, Marcos A S Fonseca, Sandor Spisak, Talal El Zarif, Viktoria Tisza, David A Braun, Heng Du, Monica He, Abdallah Flaifel, Michel Alchoueiry, Thomas Denize, Sayed G Matar, Andres Acosta, Sachet Shukla, Yue Hou, John Steinharter, Gabrielle Bouchard, Jacob E Berchuck, Edward O'Connor, Connor Bell, Pier Vitale Nuzzo, Gwo-Shu Mary Lee, Sabina Signoretti, Michelle S Hirsch, Mark Pomerantz, Elizabeth Henske, Alexander Gusev, Kate Lawrenson, Toni K Choueiri, David J Kwiatkowski, Matthew L Freedman

Faculty, Staff and Student Publications

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional …

Outcomes Of Surgical Treatment For Extradural Benign Primary Spinal Tumors In Patients Younger Than 25 Years: An Ambispective International Multicenter Study, Alexander C Disch, Stefano Boriani, Aron Lazary, Laurence D Rhines, Alessandro Luzzati, Ziya L Gokaslan, Charles G Fisher, Michael G Fehlings, Michelle J Clarke, Dean Chou, Nicole M Germscheid, Klaus-Dieter Schaser, Jeremy J Reynolds, The Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were identified. Patient- and case-related characteristics were collected and statistically analyzed. Results: 161 patients (66f;95m; age 17.0 ± 4.7 years at time of diagnosis) were identified. The most common tumors were osteoblastomas n = 53 (32.9%), osteoid osteomas n = 45 (28.0%), and aneurysmal bone cysts n = 32 (19.9%). The tumor grade, according to the Enneking Classification S1/S2/S3, was 14/73/74 (8.7/45.3/46.0%), …

Resistance Mechanisms To Anti–Epidermal Growth Factor Receptor Therapy In Ras/Raf Wild-Type Colorectal Cancer Vary By Regimen And Line Of Therapy, Christine M Parseghian, Ryan Sun, Melanie Woods, Stefania Napolitano, Hey Min Lee, Jumanah Alshenaifi, Jason Willis, Shakayla Nunez, Kanwal P Raghav, Van K Morris, John P Shen, Madhulika Eluri, Alexey Sorokin, Preeti Kanikarla, Eduardo Vilar, Marko Rehn, Agnes Ang, Teresa Troiani, Scott Kopetz

Faculty, Staff and Student Publications

Purpose: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients.

Methods: We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third …

Integrated Mrna Sequence Optimization Using Deep Learning, Haoran Gong, Jianguo Wen, Ruihan Luo, Yuzhou Feng, Jingjing Guo, Hongguang Fu, Xiaobo Zhou

Faculty, Staff and Student Publications

The coronavirus disease of 2019 pandemic has catalyzed the rapid development of mRNA vaccines, whereas, how to optimize the mRNA sequence of exogenous gene such as severe acute respiratory syndrome coronavirus 2 spike to fit human cells remains a critical challenge. A new algorithm, iDRO (integrated deep-learning-based mRNA optimization), is developed to optimize multiple components of mRNA sequences based on given amino acid sequences of target protein. Considering the biological constraints, we divided iDRO into two steps: open reading frame (ORF) optimization and 5' untranslated region (UTR) and 3'UTR generation. In ORF optimization, BiLSTM-CRF (bidirectional long-short-term memory with conditional random …