Medical Pathology Commons^™

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

A Functional K+ Channel From Tetraselmis Virus 1, A Member Of The Mimiviridae, Kerri Kukovetz, Brigitte Hertel, Christopher R. Schvarcz, Andrea Saponaro, Mirja Manthey, Ulrike Burk, Timo Greiner, Grieg F. Steward, James L. Van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh

Nebraska Center for Virology: Faculty Publications

Potassium ion (K+) channels have been observed in diverse viruses that infect eukaryotic marine and freshwater algae. However, experimental evidence for functional K+ channels among these alga-infecting viruses has thus far been restricted to members of the family Phycodnaviridae, which are large, double-stranded DNA viruses within the phylum Nucleocytoviricota. Recent sequencing projects revealed that alga-infecting members of Mimiviridae, another family within this phylum, may also contain genes encoding K+ channels. Here we examine the structural features and the functional properties of putative K+ channels from four cultivated members of Mimiviridae. While all four proteins contain variations …

In Vitro Susceptibility Of Treponema Pallidum Subsp Pallidum To Doxycycline, Diane G Edmondson, Gary P Wormser, Steven J Norris

Faculty, Staff and Student Publications

Doxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of T. pallidum subsp. pallidum (Nichols, SS14, UW231B, and UW249B). The Nichols strain cultured in vitro with doxycycline was also tested for infectivity in rabbits, and the minimum bactericidal concentration (MBC) was found to be ≤0.1 μg/ml …

Educational Case: A Case Of Transfusion-Transmitted Babesiosis: Diagnostic Perspectives Across The Clinical Laboratory., Kaitlyn Dykes, Alexis R. Peedin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Immune-Related Gene Expression And Cytokine Secretion Is Reduced Among African American Colon Cancer Patients, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Joussette Alvarado, Li Li, Mubarak Akadri, Kaylene Barrera, Maria Munoz-Sagastibelza, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Xuefeng Wang, John M. Carethers, Jennie L. Williams, Laura A. Martello

School of Medicine Faculty Publications

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized “The Cancer Genome Atlas” (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic …

Comparison Of Sars-Cov-2 Detection From Nasopharyngeal Swab Samples By The Roche Cobas 6800 Sars-Cov-2 Test And A Laboratory-Developed Real-Time Rt-Pcr Test, Elisabet Pujadas, Nnaemeka Ibeh, Matthew M Hernandez, Aneta Waluszko, Tatyana Sidorenko, Vanessa Flores, Biana Shiffrin, Numthip Chiu, Alicia Young-Francois, Michael D Nowak, Alberto E Paniz-Mondolfi, Emilia M Sordillo, Carlos Cordon-Cardo, Jane Houldsworth, Melissa R Gitman

Faculty, Staff and Student Publications

The urgent need to implement and rapidly expand testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has led to the development of multiple assays. How these tests perform relative to one another is poorly understood. We evaluated the concordance between the Roche Diagnostics cobas 6800 SARS-CoV-2 test and a laboratory-developed test (LDT) real-time reverse transcription-polymerase chain reaction based on a modified Centers for Disease Control and Prevention protocol, for the detection of SARS-CoV-2 in samples submitted to the Clinical Laboratories of the Mount Sinai Health System. A total of 1006 nasopharyngeal swabs in universal transport medium from persons under …

Yttrium-90 Selective Internal Radiotherapy As Bridge To Curative Hepatectomy For Recurrent Malignant Solid Pseudopapillary Neoplasm Of Pancreas: Case Report And Review Of Literature, Adam R Dyas, David Thor Johnson, Erin Rubin, Richard D Schulick, Piyush Kumar Sharma

Faculty, Staff and Student Publications

Recurrent malignant solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors with unpredictable clinical and histopathological features. There is a lack of consensus regarding utilization of adjuvant modalities in conjunction with or in lieu of curative metastatectomy. We present a remarkable case where Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was successfully utilized to elucidate underlying tumor biology and aid resection of a large multifocal recurrent metastatic SPNP in the right hemi-liver of a 59-year-old female. Thus, in cases where curative metastatectomy remains the treatment goal in management of recurrent and/or metastatic SPNPs, Y-90 SIRT is a safe and …

Limbic-Predominant Age-Related Tdp-43 Encephalopathy Differs From Frontotemporal Lobar Degeneration, John L. Robinson, Sílvia Porta, Filip G. Garrett, Panpan Zhang, Sharon X. Xie, Eunran Suh, Vivianna M. Van Deerlin, Erin L. Abner, Gregory A. Jicha, Justin M. Barber, Virginia M-Y Lee, Edward B. Lee, John Q. Trojanowski, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, age-related TDP-43 encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer’s disease neuropathological changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, and frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). A practical challenge is that different autopsy cohorts are composed of disparate groups of research volunteers: hospital- and clinic-based cohorts are enriched for FTLD-TDP cases, whereas community-based cohorts have more LATE-NC cases. Neuropathological methods also differ across laboratories. Here, …

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …

Evaluating Soluble Axl As A Biomarker For Glioblastoma, Daniel Raymond

All NMU Master's Theses

AXL, a receptor tyrosine kinase, is known to promote malignant phenotypes in various types of cancer. AXL overexpression is commonly observed in glioblastoma and correlates with a worse prognosis. Detectable in most biological fluids, the extracellular domain of AXL, sAXL, is the product of enzymatic cleavage by ADAM10/17. Here we used ELISA, BCA and BCG assays to characterize blood serum from 23 newly diagnosed GBM patients which was collected roughly 24 hours before and after surgery as well as every three months post-surgery, corresponding to follow-up treatment visits. Immunoblotting was used to determine relative AXL expression in 13 patient tumor …

Symmetric Inverse Consistent Nonlinear Registration Driven By Mutual Information, Wen Fury, Keun Woo Park, Zhuhao Wu, Eunhee Kim, Moon-Sook Woo, Yu Bai, Lynn E Macdonald, Susan D Croll, Sunghee Cho

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months.

METHODS: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain …

Case Report On Leiomyosarcoma Of The Vulva: A Rare Pathology, Samantha A. Smith, Nadim Bou Zgheib, Andrea M. Vallejos, Jonathan D. Cuda

Marshall Journal of Medicine

Leiomyosarcoma (LMS) of the vulva is rare. However it is the most common histologic subtype of vulvar sarcoma, accounting for approximately 1% of all vulvar malignancies. ^[1-8] Whether genetics and epigenetics play a role in pathogenesis is unclear. ^[1] The tumor is slow-growing with non-specific symptoms, has high metastatic potential, and follows a bimodal age distribution. ^[1-8] Diagnosis and prognosis are based upon immunohistochemical expression and criteria from early literature. ^[1,3,5-7] The most common therapeutic approach involves radical vulvectomy with lymph node resection. The value of adjuvant chemotherapy and radiation remains unknown. ^[1,3,5-8] Our case describes a 46-year-old Caucasian G2P2 …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Educational Case: Mantle Cell Lymphoma, Brenda Mai, Karan Saluja, Zhihong Hu, Nghia D Nguyen, Amer Wahed, Xiaohong Iris Wang, Lei Chen

Faculty, Staff and Student Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Malignant Hyperthermia For The Nurse Anesthetist, Victor Clark

Nursing Student Class Projects (Formerly MSN)

Malignant Hyperthermia (MH) is a rare, autosomal dominant skeletal muscle disorder that can have an insidious onset in susceptible patients exposed to the triggering agents succinylcholine, halothane, desflurane, sevoflurane, and isoflurane. MH can occur in patients who have received anesthesia with these agents in the past (Nagelhout & Plaus, 2018, p 775). Patients with a family history of MH or associated skeletal muscle disorder must be treated as MH-susceptible until proven otherwise. Failure to detect an MH crisis can lead to kidney failure, profound acidosis, coagulopathies, rhabdomyolysis, cardiac dysrhythmias, cardiovascular collapse, and death (Seifert et al., 2015). It is the …

Epstein Barr Virus-Immortalizedｂlymphocytes Exacerbate Experimental Autoimmune Encephalomyelitis In Xenograft Mice, Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha C. Fernando, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans …

Fall Prevention Assessment In The Intermediate Care Patient Population, Dawn Rose

Doctor of Nursing Practice Final Manuscripts

Fall Prevention Assessment in the Intermediate Care Patient Population

Falls cause greater than 600,000 deaths per year and are the most common injury in people over 65 years of age. Fall prevention in the acute care setting has been identified as key goal in the most recent JCAHO review process. Falls on an intermediary care unit lead to an increased rate of morbidity, delayed discharge, and excess cost expenditure.

Even with appropriate evidence-based tools in place, Hospital A’s intermediate care unit, recorded an increased rate of falls; the highest rate in its health care system. An investigation identified factors contributing …

Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao

School of Medicine Faculty Publications

Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in …

Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions, Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Targeting Natural Killer Cells For Improved Immunity And Control Of The Adaptive Immune Response., Stephen Pierce, Eric S. Geanes, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Natural killer (NK) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the innate immune system. Recently, NK cells have also emerged as key regulators of adaptive immunity and have become a prominent therapeutic target for cancer immunotherapy and infection control. NK cells display a diverse array of phenotypes and function. Determining how NK cells develop and are regulated is critical for understanding their role in both innate and adaptive immunity. In this review we discuss current research approaches into NK cell adaptive immunity and how these cells are being harnessed for improving …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations and Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang

Faculty, Staff and Student Publications

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …

Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa

School of Medicine Faculty Publications

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, …

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …

Anxiety In Alzheimer's Disease, Zachary Cooper

Senior Honors Theses

Researchers familiar with Alzheimer’s disease have often noted the presence of comorbid anxiety symptomatology. Likewise, the occurrence of anxiety before the development of Alzheimer’s disease has been prevalent enough to warrant attention. This review seeks to elaborate on the pathophysiology behind these two conditions, and to accentuate overlapping aspects that promote a causal relationship between these two pathologies on the macroscopic and cellular levels. Subsequent evidence will show that these pathologies are not independent of each other, and that cellular mechanisms of pathology hint at their interrelatedness. Areas requiring further research that would clarify the relationship between Clinical Anxiety and …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …

Artificial Intelligence And Digital Microscopy Applications In Diagnostic Hematopathology, Hanadi El Achi, Joseph D Khoury

Faculty, Staff and Student Publications

Digital Pathology is the process of converting histology glass slides to digital images using sophisticated computerized technology to facilitate acquisition, evaluation, storage, and portability of histologic information. By its nature, digitization of analog histology data renders it amenable to analysis using deep learning/artificial intelligence (DL/AI) techniques. The application of DL/AI to digital pathology data holds promise, even if the scope of use cases and regulatory framework for deploying such applications in the clinical environment remains in the early stages. Recent studies using whole-slide images and DL/AI to detect histologic abnormalities in general and cancer in particular have shown encouraging results. …