Medicine and Health Sciences Commons^™

Spatial Heterogeneity Of T Cell Repertoire Across Nsclc Tumors, Tumor Edges, Adjacent And Distant Lung Tissues, Qikang Hu, Meredith L Frank, Yang Gao, Liyan Ji, Muyun Peng, Chen Chen, Bin Wang, Yan Hu, Zeyu Wu, Jina Li, Lu Shu, Qiongzhi He, Yingqian Zhang, Xuefeng Xia, Jianjun Zhang, Xin Yi, Alexandre Reuben, Fenglei Yu

Faculty, Staff and Student Publications

BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients.

METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed …

Translating Energy Balance Research From The Bench To The Clinic To The Community: Parallel Animal-Human Studies In Cancer, Miriam B Garcia, Keri L Schadler, Joya Chandra, Steven K Clinton, Kerry S Courneya, Zobeida Cruz-Monserrate, Carrie R Daniel, Andrew J Dannenberg, Wendy Demark-Wahnefried, Mark W Dewhirst, Carol J Fabian, Stephen D Hursting, Melinda L Irwin, Neil M Iyengar, Jennifer L Mcquade, Kathryn H Schmitz, Karen Basen-Engquist

Faculty, Staff and Student Publications

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer …

Strengthening Deep-Learning Models For Intracranial Hemorrhage Detection: Strongly Annotated Computed Tomography Images And Model Ensembles, Dong-Wan Kang, Gi-Hun Park, Wi-Sun Ryu, Dawid Schellingerhout, Museong Kim, Yong Soo Kim, Chan-Young Park, Keon-Joo Lee, Moon-Ku Han, Han-Gil Jeong, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance.

METHODS: We used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and …

Clinical Insights Into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, And Future Directions, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or …

Pre-Epithelialized Cryopreserved Tracheal Allograft For Neo-Trachea Flap Engineering, Ning Zeng, Youbai Chen, Yewen Wu, Mengqing Zang, Rene D Largo, Edward I Chang, Mark V Schaverien, Peirong Yu, Qixu Zhang

Faculty, Staff and Student Publications

Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection.

Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique …

Stem Cell Theory Of Cancer: Origin Of Metastasis And Sub-Clonality, Shi-Ming Tu, Cesar Moran, William Norton, Niki M Zacharias

Faculty, Staff and Student Publications

Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and …

Chd1, A Multifaceted Epigenetic Remodeler In Prostate Cancer, Haoyan Li, Loraine Gigi, Di Zhao

Faculty, Staff and Student Publications

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1's …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Targeting T Cell Checkpoints 41bb And Lag3 And Myeloid Cell Cxcr1/Cxcr2 Results In Antitumor Immunity And Durable Response In Pancreatic Cancer, Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y Maeda, John A Zebala, Denise J Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y Alan Wang, Nicholas E Navin, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is considered non-immunogenic, with trials showing its recalcitrance to PD1 and CTLA4 immune checkpoint therapies (ICTs). Here, we sought to systematically characterize the mechanisms underlying de novo ICT resistance and to identify effective therapeutic options for PDAC. We report that agonist 41BB and antagonist LAG3 ICT alone and in combination, increased survival and antitumor immunity, characterized by modulating T cell subsets with antitumor activity, increased T cell clonality and diversification, decreased immunosuppressive myeloid cells and increased antigen presentation/decreased immunosuppressive capability of myeloid cells. Translational analyses confirmed the expression of 41BB and LAG3 in human PDAC. Since …

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

Segmentation Stability Of Human Head And Neck Cancer Medical Images For Radiotherapy Applications Under De-Identification Conditions: Benchmarking Data Sharing And Artificial Intelligence Use-Cases, Jaakko Sahlsten, Kareem A Wahid, Enrico Glerean, Joel Jaskari, Mohamed A Naser, Renjie He, Benjamin H Kann, Antti Mäkitie, Clifton D Fuller, Kimmo Kaski

Faculty, Staff and Student Publications

BACKGROUND: Demand for head and neck cancer (HNC) radiotherapy data in algorithmic development has prompted increased image dataset sharing. Medical images must comply with data protection requirements so that re-use is enabled without disclosing patient identifiers. Defacing, i.e., the removal of facial features from images, is often considered a reasonable compromise between data protection and re-usability for neuroimaging data. While defacing tools have been developed by the neuroimaging community, their acceptability for radiotherapy applications have not been explored. Therefore, this study systematically investigated the impact of available defacing algorithms on HNC organs at risk (OARs).

METHODS: A publicly available dataset …

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …

The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) …

Impact Of Region-Of-Interest Size On Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification For Paraffin-Embedded Tumor Tissues, Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Representative regions of interest (ROIs) analysis from the whole slide images (WSI) are currently being used to study immune markers by multiplex immunofluorescence (mIF) and single immunohistochemistry (IHC). However, the amount of area needed to be analyzed to be representative of the entire tumor in a WSI has not been defined.

Methods: We labeled tumor-associated immune cells by mIF and single IHC in separate cohorts of non-small cell lung cancer (NSCLC) samples and we analyzed them as whole tumor area as well as using different number of ROIs to know how much area will be need to represent the …

Exploration Of Cancer Associated Fibroblasts Phenotypes In The Tumor Microenvironment Of Classical And Pleomorphic Invasive Lobular Carcinoma, Harsh Batra, Qingqing Ding, Renganayaki Pandurengan, Heladio Ibarguen, Neus Bota Rabassedas, Aysegul Sahin, Ignacio Wistuba, Edwin Roger Parra, Maria Gabriela Raso

Faculty, Staff and Student Publications

UNLABELLED: As the second most common subtype of breast carcinoma, Invasive Lobular Carcinoma (ILC) microenvironment features have not been thoroughly explored. ILC has different histological subtypes and elucidating differences in their microenvironments could lead to a comprehensive development of cancer therapies. We designed a custom-made cancer associated fibroblast (CAFs) panel and used multiplex immunofluorescence to identify the differences in tumor microenvironment between Classic ILC and Pleomorphic ILC.

MATERIALS AND METHODS: Multiplex immunofluorescence were performed on formalin fixed paraffin embedded tissues using Opal-7 color kit. The antibodies used for phenotyping CAFs were Pan CK (AE1/AE3), CD45, A-SMA, FAP, S100, Thy-1 with …

Respire: A Technological Tool To Navigate Mechanical Ventilation In Patient Care And Educational Settings, Swara Chokshi

Undergraduate Research Posters

Around the world, more than 20 million patients rely on mechanical ventilators annually; however, not enough individuals understand how to operate ventilators, posing a risk to the health of many. Moreover, it is increasingly difficult to determine optimal mechanical ventilator settings in a timely fashion, especially in low-resource countries and critical care areas. Respire is a mobile application that bridges this gap in a twofold manner: it is designed to assist healthcare workers around the world navigate and use mechanical ventilators effectively as well as educate the general public about mechanical ventilation. Respire offers a user-friendly yet educational interface that …

Tnik Regulation Of Interferon Signaling And Endothelial Cell Response To Virus Infection, Khanh M Chau, Abishai Dominic, Eleanor L Davis, Sivareddy Kotla, Estefani Turcios Berrios, Arsany Fahim, Ashwin Arunesh, Shengyu Li, Dongyu Zhao, Kaifu Chen, Alan R Davis, Minh T H Nguyen, Yongxing Wang, Scott E Evans, Guangyu Wang, John P Cooke, Jun-Ichi Abe, David P Huston, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (

SUMMARY: Our findings suggest that …

Association Of Hearing Loss And Tinnitus Symptoms With Health-Related Quality Of Life Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Marc-Elie Nader, Paul W Gidley, Raj Pratihar, Shirin Jivani, Adam S Garden, Frank E Mott, Ryan P Goepfert, Christopher Wallace Ogboe, Camille Charles, Clifton D Fuller, Stephen Y Lai, G Brandon Gunn, Erich M Sturgis, Ehab Y Hanna, Katherine A Hutcheson, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors.

METHODS: This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome …

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M Gaynor, Yaowu Liu, Han Chen, Margaret Sunitha Selvaraj, Ryan Sun, Rounak Dey, Donna K Arnett, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Jeffrey Haessler, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Ani Manichaikul, Lisa W Martin, Stephen T Mcgarvey, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Ramachandran S Vasan, Cristen J Willer, James G Wilson, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Lipids Working Group, Jerome I Rotter, Pradeep Natarajan, Gina M Peloso, Zilin Li, Xihong Lin

Faculty, Staff and Student Publications

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Targeting Nuclear Hormone Receptors For The Prevention Of Breast Cancer, Cassandra L Moyer, Powel H Brown

Faculty, Staff and Student Publications

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for …

Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache

Faculty, Staff and Student Publications

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively.

STUDY DESIGN: Retrospective analysis of prospective cohort.

SETTING: Tertiary care Veterans Health Administration (VHA) medical center.

METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively …

Neurocognitive Correlates Of Cerebellar Volumetric Alterations In Youth With Pediatric Bipolar Spectrum Disorders And Bipolar Offspring, Kirti Saxena, Alessio Simonetti, Christopher D Verrico, Delfina Janiri, Marco Di Nicola, Antonello Catinari, Sherin Kurian, Johanna Saxena, Benson Mwangi, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: Emerging evidence points towards the involvement of the cerebellum in the processing of emotions and pathophysiology of mood disorders. However, cerebellar and related cognitive alterations in youth with pediatric bipolar disorder (PBD) and those at high risk to develop the disorder, such as bipolar offspring (BD-OFF) are not clearly defined.

OBJECTIVE: To investigate cerebellar gray and white matter volumes, cognition, and their relationship in youth with PBD and BD-OFF.

METHODS: Thirty youth (7 to 17 years, inclusive) with PBD, 30 BD-OFF and 40 healthy controls (HC) were recruited. Study participants underwent a computer-based cognitive battery assessing affective processing, executive …