Medical Pathology Commons^™

Equine Polyclonal Antibodies Prevent Acute Chikungunya Virus Infection In Mice, Douglas Barker, Xiaobing Han, Eryu Wang, Ashley Dagley, Deborah M. Anderson, Aruni Jha, Scott C. Weaver, Justin Julander, Cory Nykiforuk, Shantha Kodihalli

Office of Research Faculty and Staff Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen that causes chikungunya disease (CHIK); the disease is characterized by fever, muscle ache, rash, and arthralgia. This arthralgia can be debilitating and long-lasting, seriously impacting quality of life for years. Currently, there is no specific therapy available for CHIKV infection. We have developed a despeciated equine polyclonal antibody (CHIKV-EIG) treatment against CHIKV and evaluated its protective efficacy in mouse models of CHIKV infection. In immunocompromised (IFNAR^−/−) mice infected with CHIKV, daily treatment for five consecutive days with CHIKV-EIG administered at 100 mg/kg starting on the day of infection prevented mortality, reduced …

Stroke Survivors' Telemedicine Experiences During The Covid-19 Pandemic: A Phenomenological Investigation, Irene N Kasumba, Kit Tilly, Tao Lin, Steven J Norris, Patricia A Rosa

Faculty, Staff and Student Publications

The highly segmented genome of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease, is composed of a linear chromosome and more than 20 co-existing endogenous plasmids. Many plasmid-borne genes are unique to B. burgdorferi and some have been shown to provide essential functions at discrete points of the infectious cycle between a tick vector and rodent host. In this study, we investigated the role of bba40, a highly conserved and differentially expressed gene on a ubiquitous linear plasmid of B. burgdorferi. In a prior genome-wide analysis, inactivation of bba40 by transposon insertion was linked with a …

Viral Dna Accumulation Regulates Replication Efficiency Of Chlorovirus Osy-Ne5 In Two Closely Related Chlorella Variabilis Strains, Ahmed Esmael, Irina V. Agarkova, David D. Dunigan, You Zhou, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Many chloroviruses replicate in Chlorella variabilis algal strains that are ex-endosymbionts isolated from the protozoan Paramecium bursaria, including the NC64A and Syngen 2-3 strains. We noticed that indigenous water samples produced a higher number of plaque-forming viruses on C. variabilis Syngen 2-3 lawns than on C. variabilis NC64A lawns. These observed differences led to the discovery of viruses that replicate exclusively in Syngen 2-3 cells, named Only Syngen (OSy) viruses. Here, we demonstrate that OSy viruses initiate infection in the restricted host NC64A by synthesizing some early virus gene products and that approximately 20% of the cells produce a …

Cervical Steroid Injections Are Not Effective For Prevention Of Surgical Treatment Of Degenerative Cervical Myelopathy., Mustfa K. Manzur, Andre M Samuel, Avani Vaishnav, Catherine Himo Gang, Evan D Sheha, Sheeraz A Qureshi

Student Papers, Posters & Projects

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: The objective of this study is to determine how often patients with degenerative cervical myelopathy (DCM) and initially treated with cervical steroid injections (CSI) and to determine whether these injections provide any benefit in delaying ultimate surgical treatment.

METHODS: All patients with a new diagnosis of DCM, without previous cervical spine surgery or steroid injections, were identified in PearlDiver, a large insurance database. Steroid injection and surgery timing was identified using Current Procedural Terminology (CPT) codes. Multivariate logistic regression identified associations with surgical treatment.

RESULTS: A total of 686 patients with DCM were identified. …

The Correlation Between Neonatal Intensive Care Unit Safety Culture And Quality Of Care, Karan Sud, Navneet Narula, Elena Aikawa, Eloisa Arbustini, Philippe Pibarot, Giampaolo Merlini, Robert S Rosenson, Surya V Seshan, Edgar Argulian, Amir Ahmadi, Fang Zhou, Andre L Moreira, Nancy Côté, Sotirios Tsimikas, Valentin Fuster, Sam Gandy, Robert O Bonow, Olga Gursky, Jagat Narula

Faculty, Staff and Student Publications

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits …

Evolving Landscape Of Carbapenem-Resistant Pseudomonas Aeruginosa At A Single Centre In The Usa, Aki Sakurai, An Q Dinh, Blake M Hanson, William C Shropshire, Samie A Rizvi, Kirsten Rydell, Truc T Tran, Audrey Wanger, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

OBJECTIVES: The increased identification of carbapenem-resistant

METHODS: A total of 169 CR-PA isolated from clinical specimens at a single centre in Houston, TX, USA were studied. Among them, 61 isolates collected between 1999 and 2005 were defined as historical strains, and 108 collected between 2017 and 2018 were defined as contemporary strains. Antimicrobial susceptibilities against selected β-lactams was determined. WGS data were used for the identification of antimicrobial resistance determinants and phylogenetic analysis.

RESULTS: Non-susceptibility to ceftolozane/tazobactam and ceftazidime/avibactam increased from 2% (1/59) to 17% (18/108) and from 7% (4/59) to 17% (18/108) from the historical to the contemporary collection, …

Nailfold Videocapillaroscopic Alterations As Markers Of Microangiopathy In Covid-19 Patients, Roberta Gualtierotti, Sharon E. Fox, Fernanda Da Silva Lameira, Andrea Giachi, Luca Valenti, Maria Orietta Borghi, Pier Luigi Meroni, Massimo Cugno, Flora Peyvandi

School of Medicine Faculty Publications

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, …

Changes In Nascent Chromatin Structure Regulate Activation Of The Pro-Fibrotic Transcriptome And Myofibroblast Emergence In Organ Fibrosis, Morgan D. Basta, Svetlana Petruk, Ross Summer, Joel Rosenbloom, Peter J. Wermuth, Edward J. Macarak, Alex V. Levin, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. …

Influenza C And D Viruses Demonstrated A Differential Respiratory Tissue Tropism In A Comparative Pathogenesis Study In Guinea Pigs, Chithra C. Sreenivasan, Runxia Liu, Rongyuan Gao, Yicheng Guo, Ben M. Hause, Milton Thomas, Ahsan Naveed, Travis Clement, Dana Rausch, Jane Christopher-Hennings, Eric Nelson, Julian Druce, Miaoyun Zhao, Radhey S. Kaushik, Qingsheng Li, Zizhang Sheng, Dan Dan, Feng Li

Nebraska Center for Virology: Faculty Publications

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal …

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Correction: Deadly Combination Of Vaping-Lnduced Lung Injury And Influenza: Case Report, Bindu H Akkanti, Rahat Hussain, Manish K Patel, Jayeshkumar A Patel, Kha Dinh, Bihong Zhao, Shaimaa Elzamly, Kevin Pelicon, Klemen Petek, Ismael A Salas De Armas, Mehmet Akay, Biswajit Kar, Igor D Gregoric, L Maximilian Buja

Faculty, Staff and Student Publications

Following publication of the original article [1], In this article the title was incorrectly given as “Deadly combination of E-cigarettes has become a popular-lnduced lung injury and Influenza: case report” but should have been “Deadly combination of Vaping-lnduced lung injury and Influenza: case report”.

The original article has been updated.

Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca²⁺ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca²⁺] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca²⁺ accumulation, thereby reducing ROS production and stress-induced intracellular Ca²⁺ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca²⁺] in female rat VCMs challenged …

Irritable Bowel Syndrome: Proposed Mechanisms Of Pathophysiology And The Underlying Dysregulation Of Brain-Gut Interaction, Hailey Haddix

Senior Honors Theses

Irritable bowel syndrome (IBS) is a disease of the gastrointestinal tract affecting approximately 11-21% of people worldwide (Xiao et al., 2021). This research focuses on the dysregulation of gut homeostasis in IBS and explains how the pathophysiology of the gut is controlled by the bidirectional brain-gut axis. The mechanisms of the brain-gut axis consist of neuro-immune cross talk, neuro-hormone cross talk, microbiome-gut signaling, and the HPA-axis. Each of these contribute to one or more of the possible phenotypes of gut pathophysiology, which could include intestinal permeability, visceral hypersensitivity, and motility disturbance (Xiao et al., 2021). Stress is also an important …

Acute Kidney Injury In The Elderly, Zachary Palanza

Honors Scholar Theses

Acute kidney injury (AKI) is a significant clinical concern in the elderly, marked by heightened incidence rates, increased morbidity and mortality, and impaired kidney repair mechanisms. AKI often has severe consequences, including extended hospital stays, heightened rates of chronic kidney disease, and elevated healthcare costs. The vulnerability of elderly individuals to AKI is amplified by age-related structural and functional changes in the kidneys, reduced physiological reserve, and increased exposure to nephrotoxic agents. The impaired kidney repair mechanisms observed in the elderly pose further complexities in AKI management. With age, the regenerative capacity of the kidneys diminishes, resulting in incomplete recovery …

Histopathology Of The Mitral Valve Residual Leaflet In Obstructive Hypertrophic Cardiomyopathy, Aaron L Troy, Navneet Narula, Daniele Massera, Elizabeth Adlestein, Isabel Castro Alvarez, Paul M L Janssen, Andre L Moreira, Iacopo Olivotto, Alexandra Stepanovic, Kristen Thomas, Briana Zeck, Luis Chiriboga, Daniel G Swistel, Mark V Sherrid

Faculty, Staff and Student Publications

BACKGROUND: Mitral valve (MV) elongation is a primary hypertrophic cardiomyopathy (HCM) phenotype and contributes to obstruction. The residual MV leaflet that protrudes past the coaptation point is especially susceptible to flow-drag and systolic anterior motion. Histopathological features of MVs in obstructive hypertrophic cardiomyopathy (OHCM), and of residual leaflets specifically, are unknown.

OBJECTIVES: The purpose of this study was to characterize gross, structural, and cellular histopathologic features of MV residual leaflets in OHCM. On a cellular-level, we assessed for developmental dysregulation of epicardium-derived cell (EPDC) differentiation, adaptive endocardial-to-mesenchymal transition and valvular interstitial cell proliferation, and genetically-driven persistence of cardiomyocytes in the …

Head And Neck Tumor Histopathological Image Representation With Pre- Trained Convolutional Neural Network And Vision Transformer, Ranny Rahaningrum Herdiantoputri, Daisuke Komura, Tohru Ikeda, Shumpei Ishikawa

Journal of Dentistry Indonesia

Image representation via machine learning is an approach to quantitatively represent histopathological images of head and neck tumors for future applications of artificial intelligence-assisted pathological diagnosis systems. Objective: This study compares image representations produced by a pre-trained convolutional neural network (VGG16) to those produced by a vision transformer (ViT-L/14) in terms of the classification performance of head and neck tumors. Methods: W hole-slide images of five oral t umor categories (n = 319 cases) were analyzed. Image patches were created from manually annotated regions at 4096, 2048, and 1024 pixels and rescaled to 256 pixels. Image representations were …

A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd

Kimmel Cancer Center Faculty Papers

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of …

Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including …

The Sars-Cov-2 Utr’S Intrudes Host Rbp’S And Modulates Cellular Splicing, Anjali Singh, Kush Kumar Pandey, Shubham Kumar Agrawal, Rupesh K. Srivastava, Sankar Bhattacharyya, Bhupendra Verma

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of posttranscriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3’UTRs of the …