Medical Pathology Commons^™

Computed Tomography Tissue Characterization Of Pediatric Cardiac Tumor, Rafael Zonana Amkie, Amulya Buddhavarapu, Mehul D Patel, Bihong Zhao, Dilachew A Adebo

Faculty, Staff and Student Publications

Little is known about tissue characterization of cardiac tumors by dedicated cardiac computed tomography (CT) protocols in pediatric patients. We report using arterial and delayed CT acquisitions to characterize a large left ventricular free wall tumor in a 12-year-old female with congenital mitral insufficiency and an automatic implantable cardioverter defibrillator. (

Is Β-Lactamase Testing Acceptably Accurate For Predicting Haemophilus Influenzae Susceptibility To Β-Lactams? Epidemiological Data From Philadelphia, Usa, 2017–2023, Arianna B. Morton, Chairut Vareechon, Matthew A. Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Pathobiology Of Myocardial Ischemia And Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation, And Clinical Applications, L Maximilian Buja

Faculty, Staff and Student Publications

This review presents an integrated approach to the analysis of myocardial ischemia and reperfusion injury and the modulating influence of myocardial conditioning during the evolution of acute myocardial infarction (AMI) and other clinical settings. Experimental studies have involved a spectrum of in vitro, ex vivo, and in vivo models, and guidelines have been developed for the conduct of rigorous preclinical studies and for the identification of various forms of cell injury and death in evolving AMI. AMI in vivo is dominated by oncosis (cell injury with swelling) leading to necroptosis and final necrosis of ischemic cardiomyocytes (CMCs), without or with …

Identifying The Serious Clinical Outcomes Of Adverse Reactions To Drugs By A Multi-Task Deep Learning Framework, Haochen Zhao, Peng Ni, Qichang Zhao, Xiao Liang, Di Ai, Shannon Erhardt, Jun Wang, Yaohang Li, Jianxin Wang

Faculty, Staff and Student Publications

Adverse Drug Reactions (ADRs) have a direct impact on human health. As continuous pharmacovigilance and drug monitoring prove to be costly and time-consuming, computational methods have emerged as promising alternatives. However, most existing computational methods primarily focus on predicting whether or not the drug is associated with an adverse reaction and do not consider the core issue of drug benefit-risk assessment-whether the treatment outcome is serious when adverse drug reactions occur. To this end, we categorize serious clinical outcomes caused by adverse reactions to drugs into seven distinct classes and present a deep learning framework, so-called GCAP, for predicting the …

Don't Fear The Artificial Intelligence: A Systematic Review Of Machine Learning For Prostate Cancer Detection In Pathology, Aaryn Frewing, Alexander B. Gibson, Richard Robertson, Paul Urie, Dennis Della Corte

Faculty Publications

The adoption of whole slide image (WSI) scanners in clinical practice was accelerated by US Food and Drug Administration approval in 2017, which allowed primary pathologic diagnoses to be made on scanned images. Images in the digital domain allow the application of pathology artificial intelligence (AI), including clinical decision support with algorithms performing specific diagnoses.1,2 These algorithms, if trained properly, could go beyond the ability of human observation to detect and quantify features that are not recognizable by human perception.1,3,4

Identification Of Immune Biomarkers In Thyroid Cancer, Anupam Kotwal

Theses & Dissertations

Thyroid cancer is the most common endocrine malignancy, estimated to be the second most common cancer in women by 2030. The frequency of differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, is higher in patients with autoimmune thyroid disease but the influence of the immune milieu on thyroid carcinogenesis remains unclear. To address this gap in knowledge, we performed clinical and translational experiments to identify immune biomarkers for the occurrence and prognosis of DTC. Multiparameter flow cytometry of peripheral blood from 32 adults found advanced thyroid cancer either at presentation or during the disease-course to be associated …

Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron

School of Medicine Faculty Publications

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the “first wave” of the pandemic with alpha …

Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford

Faculty, Staff and Student Publications

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in …

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations and Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …

Sindrom Respons Inflamasi Sistemik, Yefta Moenadjat

Department of Surgery Teaching Materials and Monographs

Materi perkuliahan memuat uraian respons inflamasi pascatrauma yang berkembang menjadi sindrom respons inflamasi sistemik, berakhir dengan kegagalan organ multipel ditinjau dari aspek biomolekuler.

Buku ini merupakan bagian pertama dari seri inflamasi yang disusun dalam bentuk digital dan dipublikasi menurut konsep lisensi Commons Attribution-NonCommercial 4.0 International License untuk tujuan diseminasi.

Sars‑Cov‑2 Entry Into And Evolution Within A Skilled Nursing Facility, Nicole R. Sexton, Parker Parker Cline, Emily N. Gallichotte, Emily Fitzmeyer, Michael C. Young, Ashley J. Janich, Kristy L. Pabilonia, Nicole Ehrhart, Gregory D. Ebel

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the …

Identity, Structure, And Function Of The Mitochondrial Permeability Transition Pore: Controversies, Consensus, Recent Advances, And Future Directions, Paolo Bernardi, Christoph Gerle, Andrew P. Halestrap, Elizabeth A. Jonas, Jason Karch, Nelli Mnatsakanyan, Evgeny Pavlov, Shey-Shing Sheu, Alexander A. Soukas

Center for Translational Medicine Faculty Papers

The mitochondrial permeability transition (mPT) describes a Ca2+-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca2+ efflux. Since its discovery decades ago, intensive efforts …

Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. T., Charles Wood

Nebraska Center for Virology: Faculty Publications

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …

Hhv-6 Myocarditis Progressing To Ventricular Standstill Requiring Cardiac Transplant, Stephanie Golob, Haider Nazeer, Bernard Kadosh, Randal Goldberg, Navneet Narula, Nader Moazami, Shaline Rao, Alex Reyentovich

Faculty, Staff and Student Publications

Human herpesvirus-6 (HHV-6) is an increasingly recognized cause of myocarditis. We present the case of a 46-year-old woman who presented with fulminant HHV-6 myocarditis requiring heart transplantation. (Level of Difficulty: Advanced.)

Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti

School of Graduate Studies Faculty Publications

Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …

A Clinical Review Of Antibiotic Therapy Versus Appendectomy For Treatment Of Acute Uncomplicated Appendicitis, Taylor Mcclard

SIU Journal of Medical Science Scholarly Works

Purpose: The purpose of this manuscript is to review the efficacy of antibiotic therapy in the treatment of acute uncomplicated appendicitis versus standard appendectomy.

Method: A PubMed literature search was conducted with keywords of acute appendicitis, antibiotics, and appendectomy. The publication date was limited to the last five years. Sample size less than 100 people, patient population less than five years of age, and articles examining only acute complicated appendicitis were excluded. Pertinent articles reviewing the efficacy of antibiotics compared to appendectomy serve as the basis for this clinical review.

Results: Antibiotic therapy alone could be a …

Genome-Wide Association Study Of Thoracic Aortic Aneurysm And Dissection In The Million Veteran Program, Derek Klarin, Poornima Devineni, Anoop K Sendamarai, Anthony R Angueira, Sarah E Graham, Ying H Shen, Michael G Levin, James P Pirruccello, Ida Surakka, Purushotham R Karnam, Tanmoy Roychowdhury, Yanming Li, Minxian Wang, Krishna G Aragam, Kaavya Paruchuri, Verena Zuber, Gabrielle E Shakt, Noah L Tsao, Renae L Judy, Ha My T Vy, Shefali S Verma, Daniel J Rader, Ron Do, Joseph E Bavaria, Girish N Nadkarni, Marylyn D Ritchie, Stephen Burgess, Dong-Chuan Guo, Patrick T Ellinor, Scott A Lemaire, Dianna M Milewicz, Cristen J Willer, Pradeep Natarajan, Philip S Tsao, Saiju Pyarajan, Scott M Damrauer

Faculty, Staff and Student Publications

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and …

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 …