Digital Commons Network^™

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Oropharyngeal Cancer Outcomes Correlate With P16 Status, Multinucleation And Immune Infiltration, David C Wilde, Patricia D Castro, Kaustav Bera, Syeling Lai, Anant Madabhushi, German Corredor, Can Koyuncu, James S Lewis, Cheng Lu, Mitchell J Frederick, Allan M Frederick, Avery E Haugen, Jose P Zevallos, Erich M Sturgis, Justin Shi, Andrew T Huang, David J Hernandez, Heath D Skinner, Jan O Kemnade, Wendong Yu, Andrew G Sikora, Vlad C Sandulache

Faculty, Staff and Students Publications

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells …

Factors Associated With Parental Acceptance Of Covid-19 Vaccination: A Multicenter Pediatric Emergency Department Cross-Sectional Analysis, Brigitte M Baumann, Robert M Rodriguez, Amy M Delaroche, David Rayburn, Stephanie A Eucker, Nicole L Nadeau, Lisa A Drago, Danielle Cullen, Sarah Dennis Meskill, Suzanne Bialeck, Michael Gillman

Faculty, Staff and Students Publications

STUDY OBJECTIVE: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients.

METHODS: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance.

RESULTS: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents …

Early Growth Response 1 Transcription Factor Is Essential For The Pathogenic Properties Of Human Endometriotic Epithelial Cells, Vineet K Maurya, Maria M Szwarc, Rodrigo Fernandez-Valdivia, David M Lonard, Song Yong, Niraj Joshi, Asgerally T Fazleabas, John P Lydon

Faculty, Staff and Students Publications

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the …

Chronic Granulomatous Disease-Like Presentation Of A Child With Autosomal Recessive Pkcδ Deficiency, Anna-Lena Neehus, Karen Tuano, Tom Le Voyer, Sarada L Nandiwada, Kruthi Murthy, Anne Puel, Jean-Laurent Casanova, Javier Chinen, Jacinta Bustamante

Faculty, Staff and Students Publications

BACKGROUND: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).

MATERIAL AND METHODS: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.

RESULTS: Consistent with a history suggestive of …

Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott

Faculty, Staff and Students Publications

Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell "glucolipotoxicity" can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is …

Evolution Of The Ao Spine Sacral And Pelvic Classification System: A Systematic Review, Barry Ting Sheen Kweh, Jin W. Tee, F. Cumhur Oner, Klaus J. Schnake, Emiliano N. Vialle, Frank Kanziora, Shanmuganathan Rajasekaran, Marcel Dvorak, Jens R. Chapman, Lorin M. Benneker, Gregory Schroeder, Alexander R. Vaccaro

Rothman Institute Papers

OBJECTIVE: The purpose of this study was to describe the genesis of the AO Spine Sacral and Pelvic Classification System in the context of historical sacral and pelvic grading systems.

METHODS: A systematic search of MEDLINE, EMBASE, Google Scholar, and Cochrane databases was performed consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all existing sacral and pelvic fracture classification systems.

RESULTS: A total of 49 articles were included in this review, comprising 23 pelvic classification systems and 17 sacral grading schemes. The AO Spine Sacral and Pelvic Classification System represents both the evolutionary …

A Multitask Deep Learning Approach For Pulmonary Embolism Detection And Identification, Xiaotian Ma, Emma C Ferguson, Xiaoqian Jiang, Sean I Savitz, Shayan Shams

Faculty, Staff and Student Publications

Pulmonary embolism (PE) is a blood clot traveling to the lungs and is associated with substantial morbidity and mortality. Therefore, rapid diagnoses and treatments are essential. Chest computed tomographic pulmonary angiogram (CTPA) is the gold standard for PE diagnoses. Deep learning can enhance the radiologists'workflow by identifying PE using CTPA, which helps to prioritize important cases and hasten the diagnoses for at-risk patients. In this study, we propose a two-phase multitask learning method that can recognize the presence of PE and its properties such as the position, whether acute or chronic, and the corresponding right-to-left ventricle diameter (RV/LV) ratio, thereby …

Stem Cell Transplantation For Systemic Sclerosis, Sebastian Bruera, Harish Sidanmat, Donald A Molony, Maureen D Mayes, Maria E Suarez-Almazor, Kate Krause, Maria Angeles Lopez-Olivo

Faculty, Staff and Students Publications

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.

OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).

SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February …

Implication Of Melanocortin Receptor Genes In The Familial Comorbidity Of Type 2 Diabetes And Depression., Mutaz Amin, Jurg Ott, Rongling Wu, Teodor T Postolache, Claudia Gragnoli

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

The melanocortin receptors are G-protein-coupled receptors, which are essential components of the hypothalamic–pituitary–adrenal axis, and they mediate the actions of melanocortins (melanocyte-stimulating hormones: α-MSH, β-MSH, and γ-MSH) as well as the adrenocorticotropin hormone (ACTH) in skin pigmentation, adrenal steroidogenesis, and stress response. Three melanocortin receptor genes (MC1R, MC2R, and MC5R) contribute to the risk of major depressive disorder (MDD), and one melanocortin receptor gene (MC4R) contributes to the risk of type 2 diabetes (T2D). MDD increases T2D risk in drug-naïve patients; thus, MDD and T2D commonly coexist. The five melanocortin receptor genes might confer risk for both disorders. However, they …

Whole Genome Sequence Association Analysis Of Fasting Glucose And Fasting Insulin Levels In Diverse Cohorts From The Nhlbi Topmed Program, Daniel Dicorpo, Sheila M Gaynor, Emily M Russell, Kenneth E Westerman, Laura M Raffield, Timothy D Majarian, Peitao Wu, Chloé Sarnowski, Heather M Highland, Anne Jackson, Natalie R Hasbani, Paul S De Vries, Jennifer A Brody, Bertha Hidalgo, Xiuqing Guo, James A Perry, Jeffrey R O'Connell, Samantha Lent, May E Montasser, Brian E Cade, Deepti Jain, Heming Wang, Ricardo D'Oliveira Albanus, Arushi Varshney, Lisa R Yanek, Leslie Lange, Nicholette D Palmer, Marcio Almeida, Juan M Peralta, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Lawrence F Bielak, Chung-Shiuan Chen, Yii-Der Ida Chen, Won Jung Choi, Mark O Goodarzi, James S Floyd, Marguerite R Irvin, Rita R Kalyani, Tanika N Kelly, Seonwook Lee, Ching-Ti Liu, Douglas Loesch, Joann E Manson, Ryan L Minster, Take Naseri, James S Pankow, Laura J Rasmussen-Torvik, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Elizabeth Selvin, Jennifer A Smith, Daniel E Weeks, Huichun Xu, Jie Yao, Wei Zhao, Stephen Parker, Alvaro Alonso, Donna K Arnett, John Blangero, Eric Boerwinkle, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Ravindranath Duggirala, Jiang He, Susan R Heckbert, Sharon L R Kardia, Ryan W Kim, Charles Kooperberg, Simin Liu, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Alanna C Morrison, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alan R Shuldiner, Kent D Taylor, Ramachandran S Vasan, Karine A Viaud-Martinez, Jose C Florez, James G Wilson, Robert Sladek, Stephen S Rich, Jerome I Rotter, Xihong Lin, Josée Dupuis, James B Meigs, Jennifer Wessel, Alisa K Manning

Faculty, Staff and Student Publications

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, …

Ketamine For Acute Pain After Trauma: The Kapt Randomized Controlled Trial, Thaddeus J Puzio, James Klugh, Michael W Wandling, Charles Green, Julius Balogh, Samuel J Prater, Christopher T Stephens, Paulina B Sergot, Charles E Wade, Lillian S Kao, John A Harvin

Faculty, Staff and Student Publications

BACKGROUND: Evidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain.

METHODS: This is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

Persistent Ethnicity-Associated Disparity In Anti-Tumor Effectiveness Of Immune Checkpoint Inhibitors Despite Equal Access, Marcus A Florez, Jan O Kemnade, Nan Chen, Wendy Du, Anita L Sabichi, Daniel Y Wang, Quillan Huang, Courtney N Miller-Chism, Aparna Jotwani, Albert C Chen, David Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of …

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …

Characteristics Of Eating Behavior Profiles Among Preschoolers With Low-Income Backgrounds: A Person-Centered Analysis, Jennifer Orlet Fisher, Sheryl O Hughes, Alison L Miller, Mildred A Horodynski, Holly E Brophy-Herb, Dawn A Contreras, Niko Kaciroti, Karen E Peterson, Katherine L Rosenblum, Danielle Appugliese, Julie C Lumeng

Children’s Nutrition Research Center Staff Publications

Background: Individual differences in eating behaviors among young children are well-established, but the extent to which behaviors aggregate within individuals to form distinct eating behavior profiles remains unknown. Our objectives were to identify eating behavior profiles among preschool-aged children and evaluate associations with temperament and weight.

Methods: A secondary, cross-sectional analysis of baseline data from 2 cohort studies was conducted involving 1004 children aged 3-4 years and their parents with low-income backgrounds. Children's eating behaviors and temperament were assessed by parental report. Body mass index z-scores and weight status were calculated using measured heights and weights. Latent profile analysis (LPA) …

The Rsph4a Gene In Primary Ciliary Dyskinesia, Ron Nates, Mattan Arazi, Liza Grosman-Rimon, Roy Israel, Jacob Gohari, Leonid Sternik, Erez Kachel

Faculty, Staff and Student Publications

INTRODUCTION: There is no consensus as to which patients should undergo Non-Contrast Chest Computerized Tomography (NCCCT) and carotid arteries Doppler (CD) prior to cardiac surgery. The objective of this study was to examine whether preoperative imaging modalities provide clinical benefits and a change in surgical strategy.

METHODS: We routinely performed NCCCT and CD in all non-urgent cardiac surgery patients. Major NCCCT/CD findings related to cardiovascular findings (aortic calcification/atherosclerosis, carotid artery plaque/stenosis), or other incidental findings (lung kidney, thyroid, adrenal, gastrointestinal sites etc.) were documented. The results were divided into 3 categories: (A) findings requiring both changes in surgical strategy and …

Perceived Effectiveness Of Video Interviews For Orthopaedic Surgery Residency During Covid-19, Jonathan R. Warren, Lafi S. Khalil, Alexander Pietroski, Gabriel B. Burdick, Michael J. Mcintosh, Stuart T. Guthrie, Stephanie J. Muh

Orthopedics Articles

BACKGROUND: During the 2020-21 residency interview season, interviews were conducted through virtual platforms due to the COVID-19 pandemic. The purpose of this study is to assess the general perceptions of applicants, residents and attendings at a single, large, metropolitan orthopaedic residency with regards to the video interview process before and after the interview season.

METHODS: Surveys were sent to all orthopaedic applicants, residents, and attendings before the interview season. Applicants who received interviews and responded to the first survey (46) and faculty who responded to the first survey (28) were sent a second survey after interviews to assess how their …

Influenza Activity And Composition Of The 2022-23 Influenza Vaccine - United States, 2021-22 Season, Angiezel Merced-Morales, Peter Daly, Anwar Isa Abd Elal, Noreen Ajayi, Ekow Annan, Alicia Budd, John Barnes, Arielle Colon, Charisse N Cummings, A Danielle Iuliano, Juliana Dasilva, Nick Dempster, Shikha Garg, Larisa Gubareva, Daneisha Hawkins, Amanda Howa, Stacy Huang, Marie Kirby, Krista Kniss, Rebecca Kondor, Jimma Liddell, Shunte Moon, Ha T Nguyen, Alissa O'Halloran, Catherine Smith, Thomas Stark, Katie Tastad, Dawud Ujamaa, Dave E Wentworth, Alicia M Fry, Vivien G Dugan, Lynnette Brammer

Faculty, Staff and Student Publications

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma, Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Center for Medical Ethics and Health Policy Staff Publications

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Tumor Microenvironment In Pancreatic Ductal Adenocarcinoma: Implications In Immunotherapy, Caitlyn Smith, Wei Zheng, Jixin Dong, Yaohong Wang, Jinping Lai, Xiuli Liu, Feng Yin

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug …

Advanced-Stage Melanoma At Presentation Following The Peak Of The Pandemic: A Covid-19 Cancer Canary In A Coal Mine, Ryan Lamm, Md, Walker Lyons, Md, Winnie So, Rn, Alliric I. Willis, Md, Facs, Msph

Department of Surgery Faculty Papers

Background: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline.

Methods: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables …

Understanding The Role Of Sex On Outcomes For The Cancer Patient Undergoing Treatment With Immune Checkpoint Inhibitors: A Scoping Review Protocol, Amy L Shaver, Nikita Nikita, Swapnil Sharma, Daniel S Lefler, Atrayee Basu-Mallick, Jennifer M Johnson, Meghan L Butryn, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the …

Racial Difference In Bmi And Lung Cancer Diagnosis: Analysis Of The National Lung Screening Trial, Joy Zhao, Julie Barta, Russell K. Mcintire, Christine S. Shusted, Charnita Zeigler-Johnson, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

Background: The inverse relationship between BMI and lung cancer diagnosis is well defined. However, few studies have examined the racial differences in these relationships. The purpose of this paper is to explore the relationships amongst race, BMI, and lung cancer diagnosis using the National Lung Screening Trial (NLST) data.

Methods: Multivariate regression analysis was used to analyze the BMI, race, and lung cancer diagnosis relationships.

Results: Among 53,452 participants in the NLST cohort, 3.9% were diagnosed with lung cancer, 43% were overweight, and 28% were obese. BMI was inversely related to lung cancer diagnosis among Whites: those overweight (aOR = …

Hippo-Taz Signaling Is The Master Regulator Of The Onset Of Triple-Negative Basal-Like Breast Cancers, Hirotoshi Soyama, Miki Nishio, Junji Otani, Toshiko Sakuma, Shintaro Takao, Shigeo Hara, Takaaki Masuda, Koshi Mimori, Shinya Toyokuni, John P Lydon, Kazuwa Nakao, Hiroshi Nishina, Takumi Fukumoto, Tomohiko Maehama, Akira Suzuki

Faculty, Staff and Students Publications

A universal oncogenic driver of basal-like breast cancer (BLBC) has resisted identification. We show that continuous transcriptional coactivator with PDZ-binding motif (TAZ) activation in precancerous murine luminal cells generates luminal cancers that later become BLBCs. Subsequent TP53 alteration, a feature of invasive human BLBCs, accelerates tumor progression. Because BLBC development is inhibited by TAZ inactivation in vivo, our work provides a sound rationale for targeting Hippo-TAZ signaling as therapy for human BLBC. Our mouse model of BLBC represents a powerful tool for evaluating such drugs.

Therapeutic Targeting Of Macrophage Plasticity Remodels The Tumor-Immune Microenvironment, Hee-Jin Jang, Hyun-Sung Lee, Wendong Yu, Maheshwari Ramineni, Cynthia Y Truong, Daniela Ramos, Taylor Splawn, Jong Min Choi, Sung Yun Jung, Ju-Seog Lee, Daniel Y Wang, Joel M Sederstrom, Massimo Pietropaolo, Farrah Kheradmand, Christopher I Amos, Thomas M Wheeler, R Taylor Ripley, Bryan M Burt

Center for Medical Ethics and Health Policy Staff Publications

Although the majority of patients with advanced lung adenocarcinoma (LUAD) are eligible to receive immune checkpoint blockade, approximately 80% of these tumors are resistant to this therapeutic approach. Insights at the single-cell level into mechanisms that drive LUAD tumorigenesis and the relationship of LUAD histologic heterogeneity to response to immune checkpoint blockade could help identify biomarkers and potential combinational approaches to improve immunotherapy efficacy. Here we used a genetically engineered mouse model that replicates the development of human LUAD through a spectrum of pre-invasive to invasive adenocarcinoma histologic subtypes. A systems onco-immunology approach of integrating the analytical power and unique, …

A Narrative Review On Yoga: A Potential Intervention For Augmenting Immunomodulation And Mental Health In Covid-19, Indranill Basu-Ray, Kashinath Metri, Dibbendhu Khanra, Rishab Revankar, Kavitha M Chinnaiyan, Nagaratna Raghuram, Mahesh Chandra Mishra, Bhushan Patwardhan, Manjunath Sharma, Ishwar V Basavaraddi, Akshay Anand, Shrinath Reddy, K K Deepak, Marian Levy, Sue Theus, Glenn N Levine, Holger Cramer, Gregory L Fricchione, Nagendra R Hongasandra

Faculty, Staff and Students Publications

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as …

Predictive Factors And Outcomes For Ibrutinib In Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K Moyo, Nishitha Reddy, Julia Sheets, David M Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P Kenkre, Adam J Olszewski, Jonathon B Cohen, Neil D. Palmisiano, Elvira Umyarova, Ryan A Wilcox, Farrukh T Awan, Juan Pablo Alderuccio, Stefan K Barta, Natalie S Grover, Nilanjan Ghosh, Nancy L Bartlett, Alex F Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% …

A Method For Bridging Population-Specific Genotypes To Detect Gene Modules Associated With Alzheimer's Disease, Yulin Dai, Peilin Jia, Zhongming Zhao, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Genome-wide association studies have successfully identified variants associated with multiple conditions. However, generalizing discoveries across diverse populations remains challenging due to large variations in genetic composition. Methods that perform gene expression imputation have attempted to address the transferability of gene discoveries across populations, but with limited success.

METHODS: Here, we introduce a pipeline that combines gene expression imputation with gene module discovery, including a dense gene module search and a gene set variation analysis, to address the transferability issue. Our method feeds association probabilities of imputed gene expression with a selected phenotype into tissue-specific gene-module discovery over protein interaction …

Cryo-Em Structure Of The Human Kv3.1 Channel Reveals Gating Control By The Cytoplasmic T1 Domain, Gamma Chi, Qiansheng Liang, Akshay Sridhar, John B Cowgill, Kasim Sader, Mazdak Radjainia, Pu Qian, Pablo Castro-Hartmann, Shayla Venkaya, Nanki Kaur Singh, Gavin Mckinley, Alejandra Fernandez-Cid, Shubhashish M M Mukhopadhyay, Nicola A Burgess-Brown, Lucie Delemotte, Manuel Covarrubias, Katharina L Dürr

Department of Neuroscience Faculty Papers

Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and …