Pathology Commons^™

The Mars Complex: A Critical Mediator Of Immune Regulation And Homeostasis, Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular …

Pharmacological Inhibition Of The Map2k7 Kinase In Human Disease, H Daniel Lacorazza

Faculty, Staff and Students Publications

The MAP2K7 signaling pathway activates the c-Jun NH2-terminal protein kinase (JNK) in response to stress signals, such as inflammatory cytokines, osmotic stress, or genomic damage. While there has been interest in inhibiting JNK due to its involvement in inflammatory processes and cancer, there is increasing focus on developing MAP2K7 inhibitors to enhance specificity when MAP2K7 activation is associated with disease progression. Despite some progress, further research is needed to fully comprehend the role of MAP2K7 in cancer and assess the potential use of kinase inhibitors in cancer therapy. This review examines the role of MAP2K7 in cancer and the development …

Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry

Faculty, Staff and Students Publications

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as “DLBCL-NOS with MYC rearrangement” using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World …

Molecular Profiling Of A Hepatocellular Neoplasm Not Otherwise Specified (Hcn-Nos) Demonstrates Distinct Molecular Features In Hepatoblastoma And Hcc-Like Components, Yan Chen Wongworawat, Stephen F Sarabia, Martin Urbicain, Paola Francalanci, Pavel Sumazin, Rita Alaggio, Dolores H López-Terrada

Faculty, Staff and Students Publications

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features. In this study, we characterized an HCN-NOS diagnosed in a 3-year-old patient presenting with a liver mass, in which both HB and HCC histological components were amendable to macro-dissection and molecular profiling. The …

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Translational And Oncologic Significance Of Tertiary Lymphoid Structures In Pancreatic Adenocarcinoma, Zachary Gao, Joseph Azar, Huili Zhu, Sophia Williams-Perez, Sung Wook Kang, Celia Marginean, Mark P Rubinstein, Shalini Makawita, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with poor survival and limited treatment options. PDAC resistance to immunotherapeutic strategies is multifactorial, but partially owed to an immunosuppressive tumor immune microenvironment (TiME). However, the PDAC TiME is heterogeneous and harbors favorable tumor-infiltrating lymphocyte (TIL) populations. Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop within non-lymphoid tissue under chronic inflammation in multiple contexts, including cancers. Our current understanding of their role within the PDAC TiME remains limited; TLS are complex structures with multiple anatomic features such as location, density, and maturity that may impact clinical outcomes such as …

Structure And Funding Of Clinical Informatics Fellowships: A National Survey Of Program Directors, Tushar N Patel, Aaron J Chaise, John J Hanna, Kunal P Patel, Karl M Kochendorfer, Richard J Medford, Dara E Mize, Edward R Melnick, Jonathan D Hron, Kenneth Youens, Deepti Pandita, Michael G Leu, Gregory A Ator, Feliciano Yu, Nicholas Genes, Carrie K Baker, Douglas S Bell, Joshua M Pevnick, Steven A Conrad, Aarti R Chandawarkar, Kendall M Rogers, David C Kaelber, Ila R Singh, Bruce P Levy, John T Finnell, Joseph Kannry, Natalie M Pageler, Vishnu Mohan, Christoph U Lehmann

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.

METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, …

Fungal Empyema Thoracis, A Rare But An Emerging Entity: A Retrospective Case Series From Pakistan, Nousheen Iqbal, Akbar Shoukat Ali, Aqusa Zahid, Kauser Jabeen, Muhammad Irfan

Section of Pulmonary & Critical Care

Background and objective: Fungal empyema is a rare entity which is associated with high mortality. It is mostly seen in immune-compromised hosts. However, there is limited data available on fungal empyema from developing countries regarding risk factors, treatment, and outcome. This study was conducted to determine the risk factors, clinical features, treatment, and outcome of fungal empyema.
Methods: A retrospective observational study was performed on proven fungal empyema cases, admitted at Aga Khan University Hospital, Karachi, Pakistan during January 2018 to May 2021. We excluded all those patients with polymicrobial bacterial and fungal empyema or with negative pleural fluid cultures. …

The Involvement Of Hepatic Cytochrome P450s In The Cytotoxicity Of Lapatinib, Si Chen, Xilin Li, Yuxi Li, Xiaobo He, Matthew Bryant, Xuan Qin, Feng Li, Ji-Eun Seo, Xiaoqing Guo, Nan Mei, Lei Guo

Faculty, Staff and Students Publications

Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Phi-1, An Endogenous Inhibitor Protein For Protein Phosphatase-1 And A Pan-Cancer Marker, Regulates Raf-1 Proteostasis, Jason Kirkbride, Garbo Nilsson, Jee In Kim, Kosuke Takeya, Yoshinori Tanaka, Hiroshi Tokumitsu, Futoshi Suizu, Masumi Eto

Kimmel Cancer Center Faculty Papers

Raf-1, a multifunctional kinase, regulates various cellular processes, including cell proliferation, apoptosis, and migration, by phosphorylating MAPK/ERK kinase and interacting with specific kinases. Cellular Raf-1 activity is intricately regulated through pathways involving the binding of regulatory proteins, direct phosphorylation, and the ubiquitin-proteasome axis. In this study, we demonstrate that PHI-1, an endogenous inhibitor of protein phosphatase-1 (PP1), plays a pivotal role in modulating Raf-1 proteostasis within cells. Knocking down endogenous PHI-1 in HEK293 cells using siRNA resulted in increased cell proliferation and reduced apoptosis. This heightened cell proliferation was accompanied by a 15-fold increase in ERK1/2 phosphorylation. Importantly, the observed …

Labrad : Vol 48, Issue 2 - December 2023, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Editorial
• Articles
• Navigating Lab Excellence in LARAD
• Lab Resilience in a Changing Climate: Sustainable Strategies for Future-Proof Clinical Laboratories
• Professional Insights from a Pioneer in Autoimmune Disease Testing: The Future of Antinuclear/Anticellular Antibody Testing
• Insights into CCHF and Other Viral Hemorrhagic Fevers
• Bombay Blood Group
• Role and Application of Cytogenetics in Multiple Myeloma
• Low-grade Nasopharyngeal Papillary Adenocarcinoma in a Deceivingly "blue" Biopsy
• Transplant Immunology – Diagnostics
• The Best of the Past
• Farewell Chronicles: Celebrating Dr Anila Rashid's Journey
• The Best of the Past
• Farewell Chronicles: Celebrating Dr Anila Rashid's Journey
• Polaroid
• Chemical Pathology
• Radiology
• Hematology
• Histopathology
• Microbiology
• Molecular Pathology
• Tests …

Prevalence And Missed Cases Of Respiratory Distress Syndrome Disease Amongst Neonatal Deaths Enrolled In The Kenya Child Health And Mortality Prevention Surveillance Network (Champs) Program Between 2017 And 2021, Harun O. Owuor, Victor Akelo, Florence Murila, Dickens Onyango, Magdalene Kuria, Emily Rogena, Gunturu Revathi, Paul Mitei, Solomon Sava, Joyce Were

Pathology, East Africa

Objectives: To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021.

Methods: We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy.

Results: Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels …

Microbiota Dynamics, Metabolic And Immune Interactions In The Cervicovaginal Environment And Their Role In Spontaneous Preterm Birth, Stanely Onyango, Jia Dai Mi, Anjela Koech, Patricia Okiro, Marleen Temmerman, Peter Von Dadelszen, Rachel Marie Tribe, Geoffrey Omuse

Pathology, East Africa

Differences in the cervicovaginal microbiota are associated with spontaneous preterm birth (sPTB), a significant cause of infant morbidity and mortality. Although establishing a direct causal link between cervicovaginal microbiota and sPTB remains challenging, recent advancements in sequencing technologies have facilitated the identification of microbial markers potentially linked to sPTB. Despite variations in findings, a recurring observation suggests that sPTB is associated with a more diverse and less stable vaginal microbiota across pregnancy trimesters. It is hypothesized that sPTB risk is likely to be modified via an intricate host-microbe interactions rather than due to the presence of a single microbial taxon …

Pathomic Features Reveal Immune And Molecular Evolution From Lung Preneoplasia To Invasive Adenocarcinoma, Pingjun Chen, Frank R Rojas, Xin Hu, Alejandra Serrano, Bo Zhu, Hong Chen, Lingzhi Hong, Rukhmini Bandyoyadhyay, Muhammad Aminu, Neda Kalhor, J Jack Lee, Siba El Hussein, Joseph D Khoury, Harvey I Pass, Andre L Moreira, Vamsidhar Velcheti, Daniel H Sterman, Junya Fukuoka, Kazuhiro Tabata, Dan Su, Lisha Ying, Don L Gibbons, John V Heymach, Ignacio I Wistuba, Junya Fujimoto, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials …

Corrigendum To “Epstein-Barr-Virus-Positive Large B-Cell Lymphoma Associated With Breast Implants: An Analysis Of Eight Patients Suggesting A Possible Pathogenetic Relationship” [Modern Pathology 34 (2021) 2154–2167], L Jeffrey Medeiros, Mario L Marques-Piubelli, Valentina F I Sangiorgio, Roberto Ruiz-Cordero, Francisco Vega, Andrew L Feldman, Jennifer R Chapman, Mark W Clemens, Kelly K Hunt, Mark G Evans, Christine Khoo, Stephen Lade, Mark Silberman, Jerzy Morkowski, Edward M Pina, Daniel C Mills, Christopher M Bates, Winston B Magno, Aliyah R Sohani, Beth A Sieling, Joseph M O'Donoghue, Chris M Bacon, Neill Patani, Despina Televantou, Suzanne D Turner, Laura Johnson, Fiona Macneill, Andrew C Wotherspoon, Swaminathan P Iyer, Luis E Malpica, Keyur P Patel, Jie Xu, Roberto N Miranda

Faculty, Staff and Student Publications

No abstract provided.

The Clinicopathologic Features And Molecular Signatures Of Blastoid High-Grade B Cell Lymphoma, Not Otherwise Specified, Lianqun Qiu, Pei Lin, Mahsa Khanlari, Jie Xu, Evan N Cohen, Sofia Garces, Roberto N Miranda, Wei Wang, Hong Fang, Carlos E Bueso-Ramos, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome.

Sars-Cov-2 Seroprevalence In Pregnant Women In Kilifi, Kenya From March 2020 To March 2022, Angela Koech, Geoffrey Omuse, Alex Mugo, Isaac Mwaniki, Joseph Mutunga, Moses Mukhanya, Onesmus Wanje, Grace Mwashigadi, Geoffrey Katana, Marleen Temmerman

Centre of Excellence in Women and Child Health

Background: Seroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.

Methods: We obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, …

Navigating Relapsed Hepatoblastoma: Predictive Factors And Surgical Treatment Strategy, Andres F Espinoza, Kalyani R Patel, Priya B Shetty, Richard S Whitlock, Pavel Sumazin, Xinjian Yu, Stephen F Sarabia, Martin Urbicain, Andras Heczey, Prakash Masand, Sarah E Woodfield, Dolores H López-Terrada, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

Objective: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center.

Methods: A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re-appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging.

Results: …

Endometrial Tgfβ Signaling Fosters Early Pregnancy Development By Remodeling The Fetomaternal Interface, Sydney E Parks, Ting Geng, Diana Monsivais

Faculty, Staff and Students Publications

The endometrium is a unique and highly regenerative tissue with crucial roles during the reproductive lifespan of a woman. As the first site of contact between mother and embryo, the endometrium, and its critical processes of decidualization and immune cell recruitment, play a leading role in the establishment of pregnancy, embryonic development, and reproductive capacity. These integral processes are achieved by the concerted actions of steroid hormones and a myriad of growth factor signaling pathways. This review focuses on the roles of the transforming growth factor β (TGFβ) pathway in the endometrium during the earliest stages of pregnancy through the …

Microbial Products Linked To Steatohepatitis Are Reduced By Deletion Of Nuclear Hormone Receptor Shp In Mice, Ryan Mifflin, Jung Eun Park, Mikang Lee, Prasant Kumar Jena, Yu-Jui Yvonne Wan, Hazel A Barton, Mirjavid Aghayev, Takhar Kasumov, Li Lin, Xinwen Wang, Robert Novak, Feng Li, He Huang, Leah P Shriver, Yoon-Kwang Lee

Faculty, Staff and Students Publications

Deletion of the nuclear hormone receptor small heterodimer partner (Shp) ameliorates the development of obesity and nonalcoholic steatohepatitis (NASH) in mice. Liver-specific SHP plays a significant role in this amelioration. The gut microbiota has been associated with these metabolic disorders, and the interplay between bile acids (BAs) and gut microbiota contributes to various metabolic disorders. Since hepatic SHP is recognized as a critical regulator in BA synthesis, we assessed the involvement of gut microbiota in the antiobesity and anti-NASH phenotype of Shp−/− mice. Shp deletion significantly altered the levels of a few conjugated BAs. Sequencing the 16S …

Exploration Of The Implementation Of An Integrated Electronic Laboratory Information Management System On Quality Diagnostics Service Indicators At A County Level Public Hospital In Western Kenya., Kelly Allen

Capstone Collection

Underinvestment in pathology and laboratory capacity caused by low visibility in research and in prioritization by public health leaders results in limited effective healthcare coverage and an estimated 1.1 million premature deaths annually in Low-and-Middle-Income Countries. Kenya’s public health laboratories provide a median 41% of the Essential Diagnostic List to their patients and in Kisumu County, as much as 44.2% of the population has little to no access to essential diagnostics. The government of Kisumu implemented the county Health Laboratory Strategic Plan 2018-2022 to address this public health challenge. Little information exists on the effectiveness of these initiatives and the …

Educational Case: An Invasive Salivary Gland Tumor: Adenoid Cystic Carcinoma Of The Parotid Gland, Jaime Eberle-Singh, Madalina Tuluc, Joanna Sue Yee Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Nonlinear Model Predictive Control Of Vagal Nerve Stimulation To Regulate Hemodynamic Variables, Oluwasanmi Adeodu, Michelle Gee, Babak Mahmoudi, Rajanikanth Vadigepalli, Mayuresh Kothare

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Various pre-clinical investigations indicate that the electrical stimulation of the cervical branch of the vagus that innervates the heart has therapeutic value in the management of various cardiac diseases. In theory, the design of a closed-loop control mechanism that automatically adjusts vagal nerve stimulation (VNS) parameters based on real-time physiological feedback can eliminate intra-patient variability in VNS outcomes and therefore represents a major step towards patient-specific therapy. This study develops a nonlinear model predictive control (NMPC) approach for VNS of a pulsatile, human cardio-baroreflex system. The manipulated variables are the frequency and amplitude of a charge-balanced biphasic current. The effects …

Wire Snare Close Loop: A Novel Technique To Retrieve Embolized Devices, Manish Bansal, Gary E Stapleton, Srinath T Gowda, Athar M Qureshi

Faculty, Staff and Students Publications

No abstract provided.

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Population-Specific Mutation Patterns In Breast Tumors From African American, European American, And Kenyan Patients, Wei Tang, Jung S. Byun, Tiffany H. Dorsey, Harris G. Yfantis, Anuoluwapo Ajao, Huaitian Liu, Margaret S. Pichardo, Catherine M. Pichardo, Alexandra R. Harris, Shahin Sayed

Pathology, East Africa

Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and African …

Population-Specific Mutation Patterns In Breast Tumors From African American, European American, And Kenyan Patients, Wei Tang, Flora Zhang, Jung S. Byun, Shahin Sayed, Tiffany H. Dorsey, Harris G. Yfantis, Anuoluwapo Ajao, Huaitian Liu, Margaret Pichardo, Catherine Pichardo

Pathology, East Africa

Abstract: Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and …

Highly Invasive Biliary Cancer Presenting As Multiple Extrabiliary Lesions Masquerading As Abscesses, Alexander Lu, Alireza Mojtahedi, Lukman Cheraghvandi, David Wynne, Neda Zarrin-Khameh, Mohammad Ghasemi Rad

Faculty, Staff and Students Publications

Carcinosarcomas of the biliary tract are an extremely rare type of malignancy and may be low on a differential when presenting as multiple metastatic masses. In this case report, we report a case of a female who presented with an aggressive late-stage disease whose initial workup did not indicate a malignant process. Further complicating her care, biopsy samples taken from extra-hepatic masses were culture-positive for Lactobacillus rhamnosu. Given the late stage of the patient’s disease, hospice care was initiated. The patient passed away four months after the initial presentation.