Diseases Commons^™

Origins Of Cancer: Ain’T It Just Mature Cells Misbehaving?, Charles J Cho, Jeffrey W Brown, Jason C Mills

Faculty, Staff and Students Publications

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain …

Patient Perspectives On Using Telemedicine During In-Center Hemodialysis: A Qualitative Study, Trenton M Haltom, Susie Q Lew, Wolfgang C Winkelmayer, Glenn M Chertow, Allison Jaure, Kevin F Erickson

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the United States federal government expanded originating telemedicine sites to include outpatient dialysis units. For the first time, nephrology practitioners across the United States could replace face-to-face visits with telemedicine for patients receiving in-center hemodialysis. This study describes patients' perspectives on the use of telemedicine during in-center hemodialysis.

STUDY DESIGN: A qualitative study.

SETTING & PARTICIPANTS: Thirty-two patients from underserved populations (older, less educated, unemployed, persons of color) receiving in-center hemodialysis who used telemedicine with their nephrologist during the COVID-19 pandemic.

ANALYTICAL APPROACH: Telephone semistructured interviews were …

Severe Febrile Neutropenia And Pancytopenia In A Patient With Advanced Hepatocellular Carcinoma Treated With Atezolizumab And Bevacizumab: A Case Report, Shadi Chamseddine, Michael Lapelusa, Kristen Carter, Van Nguyen, Yehia I Mohamed, Yara Sakr, Cristhiam M Rojas-Hernandez, Rikita I Hatia, Manal Hassan, John A Goss, Khaled M Elsayes, Asif Rashid, Ryan Sun, Hop Sanderson Tran Cao, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course.

CASE DESCRIPTION: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a …

Risk Of Anthracycline-Induced Cardiac Dysfunction In Adolescent And Young Adult (Aya) Cancer Survivors: Role Of Genetic Susceptibility Loci, Lily K Stafford, Xiaohui Tang, Amanda Brandt, Jianzhong Ma, Jose Banchs, J Andrew Livingston, Michael E Roth, Alanna C Morrison, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

There is a known genetic susceptibility to anthracycline-induced cardiac dysfunction in childhood cancer survivors, but this has not been adequately shown in adolescent and young adult (AYA) patients. Our aim was to determine if the previously identified variants associated with cardiac dysfunction in childhood cancer patients affect AYA cancer patients similarly. Forty-five variants were selected for analysis in 253 AYAs previously treated with anthracyclines. We identified four variants that were associated with cardiac dysfunction: SLC10A2:rs7319981 (p = 0.017), SLC22A17:rs4982753 (p = 0.019), HAS3:rs2232228 (p = 0.023), and RARG:rs2229774 (p = 0.050). HAS3:rs2232228 and SLC10A2:rs7319981 displayed significant effects in our AYA …

Aging- And Alcohol-Associated Spatial Transcriptomic Signature In Mouse Acute Pancreatitis Reveals Heterogeneity Of Inflammation And Potential Pathogenic Factors, Rachel R Tindall, Yuntao Yang, Isabella Hernandez, Amy Qin, Jiajing Li, Yinjie Zhang, Thomas H Gomez, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Zhongming Zhao, Daniel Kraushaar, Patricia Castro, Yanna Cao, W Jim Zheng, Tien C Ko

Faculty, Staff and Student Publications

The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via …

Tumor Biomechanical Stiffness By Magnetic Resonance Elastography Predicts Surgical Outcomes And Identifies Biomarkers In Vestibular Schwannoma And Meningioma, Bailey H Duhon, Kristin Thompson, Melanie Fisher, Vivian F Kaul, Han Tn Nguyen, Michael S Harris, Varun Varadarajan, Oliver F Adunka, Daniel M Prevedello, Arunark Kolipaka, Yin Ren

Faculty, Staff and Student Publications

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial …

Clinical And Genomic Profile Of Primary Cranial Neurolymphomatosis, Emily B Wolf, Robin Imperial, Liuyan Jiang, Amit K Agarwal, Han W Tun

Faculty, Staff and Student Publications

Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Remodeling Of Anti-Tumor Immunity With Antibodies Targeting A P53 Mutant, Dafei Chai, Junhao Wang, Chunmei Fan, Jing-Ming Lim, Xu Wang, Praveen Neeli, Xinfang Yu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: p53, the most frequently mutated gene in cancer, lacks effective targeted drugs.

METHODS: We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess the function of mAbs in vitro and in vivo.

RESULTS: These LNP-pE285K-mAbs in the IgG1 format exhibited a robust anti-tumor effect, facilitating the infiltration of immune cells, including CD8+ T, B, and NK cells. scRNA-seq revealed that IgG1 reduces immune inhibitory signaling, increases …

Association Between Helicobacter Pylori Infection, Mismatch Repair, Her2 And Tumor-Infiltrating Lymphocytes In Gastric Cancer, Carlos A Castaneda, Miluska Castillo, Luis A Bernabe, Joselyn Sanchez, Matteo Fassan, Katherine Tello, Ignacio Ivan Wistuba, Ivan Chavez Passiuri, Eloy Ruiz, Juvenal Sanchez, Fernando Barreda, Daniel Valdivia, Yaqueline Bazan, Milagros Abad-Licham, Claudio Mengoa, Hugo Fuentes, Paola Montenegro, Ebert Poquioma, Raul Alatrista, Claudio J Flores, Luis Taxa

Faculty, Staff and Student Publications

BACKGROUND: The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.

AIM: To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC.

METHODS: Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 …

Spatiotemporal Analysis Of Hpv Vaccination And Associated Neighborhood-Level Disparities In Texas-An Ecological Study, Ryan Ramphul, Abigail S Zamorano, Saswati Upadhyay, Manali Desai, Cici Bauer

Faculty, Staff and Student Publications

BACKGROUND: HPV is responsible for most cervical, oropharyngeal, anal, vaginal, and vulvar cancers. The HPV vaccine has decreased cervical cancer incidence, but only 49% of Texas adolescents have initiated the vaccine. Texas shows great variation in HPV vaccination rates. We used geospatial analysis to identify areas with high and low vaccination rates and explored differences in neighborhood characteristics.

METHODS: Using Anselin's Local Moran's I statistic, we conducted an ecological analysis of hot and cold spots of adolescent HPV vaccination coverage in Texas from 2017 to 2021. Next, we utilized a Mann-Whitney U test to compare neighborhood characteristics of vaccination coverage …

Improving Patient Retention Of Medical Information: Lessons From The Contact Dermatitis Clinic, Jennifer Li-Wang, Rajani Katta

Faculty, Staff and Students Publications

Medical communication skills are widely recognized as important, especially for situations in which providers must present complex and detailed information. Although much research focuses on how providers can improve their delivery of medical information, an equally important part of communication is supporting patient retention of the information. We present several methods to improve patient retention of medical information that we have found successful in an allergic contact dermatitis clinic. Some recommendations address information transfer (follow effective structure, teach to different learning styles, provide written instructions, employ the teach-back method). Other methods are effective, focusing on the patient's emotional, social, and …

Contrast-Enhanced Magnetic Resonance Imaging Based T1 Mapping And Extracellular Volume Fractions Are Associated With Peripheral Artery Disease, Asem I Fitian, Michael C Shieh, Olga A Gimnich, Tatiana Belousova, Addison A Taylor, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

BACKGROUND: Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis, but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1 mapping and ECV differ between PAD patients and matched controls.

METHODS AND RESULTS: A total of 37 individuals (18 PAD patients and 19 matched controls) underwent 3.0T CE-MRI. Skeletal calf muscle T1 mapping was performed before and after gadolinium contrast with a motion-corrected modified look-locker inversion recovery (MOLLI) pulse sequence. T1 values were calculated with a three-parameter Levenberg-Marquardt curve fitting algorithm. ECV and T1 maps were quantified …

Durable Objective Response To Lurbinectedin In Small Cell Bladder Cancer With Tp53 Mutation: A Molecular-Directed Strategy, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Sagar A Naik, Vivek Subbiah, Matthew T Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi

Faculty, Staff and Student Publications

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following …

Digital Twin Mathematical Models Suggest Individualized Hemorrhagic Shock Resuscitation Strategies, Jeremy W Cannon, Danielle S Gruen, Ruben Zamora, Noah Brostoff, Kelly Hurst, John H Harn, Fayten El-Dehaibi, Zhi Geng, Rami Namas, Jason L Sperry, John B Holcomb, Bryan A Cotton, Jason J Nam, Samantha Underwood, Martin A Schreiber, Kevin K Chung, Andriy I Batchinsky, Leopoldo C Cancio, Andrew J Benjamin, Erin E Fox, Steven C Chang, Andrew P Cap, Yoram Vodovotz

Faculty, Staff and Student Publications

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting.

METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation.

RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well …

An Essential Gene Signature Of Breast Cancer Metastasis Reveals Targetable Pathways, Yiqun Zhang, Fengju Chen, Marija Balic, Chad J Creighton

Faculty, Staff and Students Publications

BACKGROUND: The differential gene expression profile of metastatic versus primary breast tumors represents an avenue for discovering new or underappreciated pathways underscoring processes of metastasis. However, as tumor biopsy samples are a mixture of cancer and non-cancer cells, most differentially expressed genes in metastases would represent confounders involving sample biopsy site rather than cancer cell biology.

METHODS: By paired analysis, we defined a top set of differentially expressed genes in breast cancer metastasis versus primary tumors using an RNA-sequencing dataset of 152 patients from The Breast International Group Aiming to Understand the Molecular Aberrations dataset (BIG-AURORA). To filter the genes …

Rigor And Reproducibility In Human Brain Organoid Research: Where We Are And Where We Need To Go, Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Cross-Iddrc Human Stem Cell Consortium, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao

Faculty, Staff and Students Publications

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

Feasibility Of Achieving Nutritional Adequacy In Critically Ill Children With Critical Neurological Illnesses (Cnis)?-A Quaternary Hospital Experience, Marwa Mansour, Nicole Knebusch, Jennifer Daughtry, Thomas P Fogarty, Fong Wilson Lam, Renan A Orellana, Yi-Chen Lai, Jennifer Erklauer, Jorge A Coss-Bu

Faculty, Staff and Students Publications

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …

Improved Liver Disease Prediction From Clinical Data Through An Evaluation Of Ensemble Learning Approaches, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

PURPOSE: Liver disease causes two million deaths annually, accounting for 4% of all deaths globally. Prediction or early detection of the disease via machine learning algorithms on large clinical data have become promising and potentially powerful, but such methods often have some limitations due to the complexity of the data. In this regard, ensemble learning has shown promising results. There is an urgent need to evaluate different algorithms and then suggest a robust ensemble algorithm in liver disease prediction.

METHOD: Three ensemble approaches with nine algorithms are evaluated on a large dataset of liver patients comprising 30,691 samples with 11 …

Seroprevalence Of Anti-Sars-Cov-2 Igg Antibodies In Healthcare Personnel In El Salvador Prior To Vaccination Campaigns, José Elías Aguilar Ramírez, Adrianna Maliga, Allison Stewart, Allison Lino, José Eduardo Oliva, Xochitl Sandoval, Emily Zielinski-Gutierrez, Rafael Chacon-Fuentes, Parminder S Suchdev, Susana Zelaya, Mario Sánchez, Delmy Lisseth Recinos, Beatriz López, Ella Hawes, Julie Liu, Shannon E Ronca, Sarah M Gunter, Kristy O Murray, Rhina Domínguez

Faculty, Staff and Students Publications

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike …

Reply To: Correlation Between Right Ventricular Echocardiography Measurements And Functional Capacity In Patients With Pulmonary Arterial Hypertension, Annalisa Caputo, Gianmarco Scoccia

The Texas Heart Institute Journal

No abstract provided.

Postoperative Bioactive Adrenomedullin Is Associated With The Onset Of Ards And Adverse Outcomes In Patients Undergoing Open Thoracoabdominal Aortic Surgery, Panagiotis Doukas, Oliver Hartmann, Jelle Frankort, Birte Arlt, Hanif Krabbe, Michael Johan Jacobs, Andreas Greiner, Jan Paul Frese, Alexander Gombert

Faculty, Staff and Student Publications

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory …

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

An Atlas Characterizing The Shared Genetic Architecture Of Inflammatory Bowel Disease With Clinical And Behavioral Traits, Vikram R Shaw, Jinyoung Byun, Rowland W Pettit, Jason K Hou, Kyle M Walsh, Younghun Han, Christopher I Amos

Faculty, Staff and Students Publications

BACKGROUND: Inflammatory bowel disease (IBD) development is a complex, multifactorial process that involves extrinsic and intrinsic factors such as host genetics, the immune system, the gut microbiome, and environmental risks. To help understand the genetic contribution of clinical, behavioral, psychiatric, and diet-related traits, we aim to provide a deep and comprehensive characterization of the shared genetic architecture between IBD and hundreds of potentially related traits.

METHODS: Utilizing publicly available summary statistics from a previously published IBD genome-wide association study and hundreds of traits from the United Kingdom BioBank (UKBB), we performed linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait …

Strength Of Selection In Lung Tumors Correlates With Clinical Features Better Than Tumor Mutation Burden, Ivan P Gorlov, Olga Y Gorlova, Spyridon Tsavachidis, Christopher I Amos

Faculty, Staff and Students Publications

Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations …

Jak-Stat Signaling And Beyond In The Pathogenesis Of Spondyloarthritis And Their Clinical Significance, Siba P Raychaudhuri, Ruchi J Shah, Sneha Banerjee, Smriti K Raychaudhuri

Faculty, Staff and Student Publications

Purpose of Review

Janus kinase–signal transducers and activators of transcription cell signaling proteins (JAK-STATs) play a key regulatory role in functioning of several inflammatory cytokines. JAK-STAT signaling proteins are the key regulators of the cytokine/cytokine receptor system involved in the pathogenesis of various autoimmune disease including spondyloarthritis (SpA). This article mainly highlights the JAK-STAT signaling system, its association with the relevant cytokine/cytokine-receptor system, and its regulatory role in pathogenesis of SpA. Also, we have briefly addressed the principle for the use JAKi in SpA and the current status of use of JAK inhibitors (JAKi) in SpA.

Recent Findings

Recent developments …

Increased Incidence Of Vestibular Disorders In Patients With Sars-Cov-2, Lawrance Lee, Evan French, Daniel H Coelho, Nauman F Manzoor, Adam B Wilcox, Adam M Lee, Alexis Graves, Alfred Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E Williams, Andrew Southerland, Andrew T Girvin, Anita Walden, Anjali A Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J W Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L Rutter, Julie A Mcmurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M Walters, Ken Wilkins, Kenneth R Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B Palchuk, Melissa A Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A Francis, Penny Wung Burgoon, Peter Robinson, Philip R O Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A Moffitt, Richard L Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T Miller, Saiju Pyarajan, Sam G Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T O'Neil, Soko Setoguchi, Stephanie S Hong, Steve Johnson, Tellen D Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang

Faculty, Staff and Student Publications

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population.

STUDY DESIGN: Retrospective.

SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C).

METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period.

RESULTS: Patients testing positive for COVID-19 were significantly more likely to have …

Understanding The Treatment Paradigm And The Sequencing Of Antiglaucoma Fixed-Dose Combinations In A Tertiary Center In South India, Ronnie George, Praggya Mishra, Balekudaru Shantha, Lingam Vijaya, Nitin Maksane, Neha Gurha

Faculty, Staff and Student Publications

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India.

METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications …

Clinical Features And Genomic Epidemiology Of Bloodstream Infections Due To Enterococcal Species Other Than Enterococcus Faecalis Or E Faecium In Patients With Cancer, Dierdre B Axell-House, Patrycja A Ashley, Stephanie L Egge, Truc T Tran, Claudia Pedroza, Meng Zhang, An Q Dinh, Shelby R Simar, Pranoti V Sahasrabhojane, William R Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Non–Enterococcus faecium, non–E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.

METHODS: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood cultureclearance). Whole-genome sequencing was performed on all …