Pathology Commons^™

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 …

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 …

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 …

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 …

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: …

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, …

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 …

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

Faculty, Staff and Students Publications

BACKGROUND: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period.

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures …