Pathology Commons^™

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

An Inf2-Dependent Actin-Mediated Step In Inositol 1,4,5-Trisphosphate Receptor Cluster Formation And Activity, Maite R. Zavala, Amrapali Ghosh, Suresh K. Joseph, Rajarshi Chakrabarti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intracellular calcium signaling plays a vital role in regulating various cellular processes including gene regulation, motility, metabolism, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER) are a major cation channel that regulates stimulus-induced calcium release from the ER. While several molecular players regulate the activity of IP3R, its regulation by actin filaments was uncharacterized. Here, we show that actin filaments polymerized by the specific actin nucleator INF2 facilitate agonist-induced IP3R activity. Our results demonstrate that INF2-mediated actin filaments regulate the formation and/or stability of IP3R clusters on the ER that have been previously shown to be …

Intrathecal (G4c2)149 Delivery In C9orf72-Deficient Mice Yields Mild Motor Dysfunction And Als/Ftd Pathological Hallmarks, Katelyn Russell, Amelia Shahrabi, Suleyman Akerman, Matthew D. Byrne, Jeffrey Rothstein, Davide Trotti, Brigid Jensen, Aaron Haeusler

Farber Institute for Neuroscience Faculty Papers

A repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet existing mouse models incompletely engage spinal regions implicated in disease. Here, an adeno-associated virus encoding (G4C2)149 repeats was delivered via neonatal intrathecal injection, achieving widespread CNS expression with robust spinal cord targeting. This approach was applied to mice with graded loss of endogenous C9orf72 to interrogate both gain- and loss-of-function mechanisms. Longitudinal motor, behavioral, and pathological analyses revealed that repeat expression primarily drives mild, progressive muscle weakness, whereas coordination deficits were largely genotype dependent. Subtle gait abnormalities and hyperactivity …

Disease-Causing Mfn2 Mutants Impair Mitochondrial Fission Dynamics By Distinct Drp1 Dysregulation, Daniel Lagos, Pamela R. De Santiago, Nicolás Pérez-Bravo, Benjamín Cartes-Saavedra, Josefa Vial-Brizzi, Diego Troncoso-Chandía, Oliver Podmanicky, Rita Horvath, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria undergo fusion and fission. While DRP1 regulates fission, fusion is controlled by OPA1, MFN1, and MFN2. The balance between these processes and the crosstalk between machineries remains poorly understood. MFN2 mutations cause Charcot-Marie-Tooth disease type 2 A (CMT2A), affecting mitochondrial fusion and morphology. However, their role in fission is unclear. Using skin fibroblasts from CMT2A patients (L248H and M376V MFN2 mutations) and wild-type mouse embryonic fibroblasts expressing these variants, we studied how MFN2 mutations impact mitochondrial dynamics beyond fusion. We analyzed mitochondrial morphology and dynamics by live-cell confocal microscopy and tested fusion/fission protein levels, oxygen consumption rate (OCR), extracellular …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Fda Approval Of Tradipitant: A Novel Approach To Motion Sickness Treatment, Haley Brown, Jennifer Cao, Allie Honigford, Leah Heitkamp, Sarah Hiett, Connor Dains, Brenna Hissong, Manoranjan D'Souza

Pharmacy and Wellness Review

Motion sickness is a prevalent neurophysiological condition affecting approximately one-third of the worldwide population, resulting from sensory mismatch and the brain’s internal model of motion. It is characterized by nausea, vomiting, dizziness, and autonomic symptoms during exposure to actual or virtual motion, which may significantly impair daily functioning and quality of life. Current guidelines recommend the prevention and treatment of motion sickness through pharmacologic, herbal, and non-pharmacologic strategies. Scopolamine and first-generation antihistamines are effective pharmacologic options, while ginger has demonstrated some benefit in reducing symptoms as an herbal option. Non-pharmacologic interventions such as habituation training, behavioral techniques, and sensory strategies …

Validation Of A Real-Time Pcr Laboratory Developed Test For The Detection Of Pneumocystis Jirovecii In Bronchoalveolar Lavage Samples, Caitlyn Moon

Honors Scholar Theses

Pneumocystis jirovecii is an opportunistic, host-obligate fungal pathogen responsible for causing P. jirovecii pneumonia (PJP) in humans. PJP is treated with trimethoprim-sulfamethoxazole (TMP-SMX), a strong broad-spectrum antibiotic that carries risk of renal and hepatotoxicity. Therefore, rapid diagnosis or exclusion of PJP is crucial to ensure PJP-positive patients receive effective treatment and PJP-negative patients avoid unnecessary antibiotics. Unlike most microorganisms, P. jirovecii cannot be cultured, presenting complications for the typical methods of diagnosing fungal pathogens. Historically, the gold standard for diagnosis was direct microscopic examination with stains such as methenamine silver and calcofluor white, but this diagnostic technique requires highly skilled …

Trustworthy Multimodal Ai For Medical Imaging: Enhancing Diagnosis, Reasoning, And Human-Agent Interaction In Extended Reality, Jai Prakash Veerla

Computer Science and Engineering Dissertations

The transition from traditional microscopy to digital pathology has digitized diagnostic data, yet clinical workflows remain constrained by two-dimensional screens and passive, opaque analysis tools that fail to capture the spatial complexity of biological systems. While Foundation Models now promise to reason across histology and genomics, a critical disconnect persists between the richness of this data and the limited cognitive bandwidth of clinicians, who currently lack the immersive interfaces and trustworthy agents necessary to utilize it effectively. This dissertation presents a unified framework for "Embodied Agentic AI," establishing a pipeline that augments physician capabilities through immersive visualization, robust security, and …

Educational Case: Hidradenitis Suppurativa, Ryan C. Saal, Linnea Lackstrom Westerkam, Cristo A. Carrasco Mendoza, Paul B. George, Christopher J. Sayed

Department of Medicine Faculty Publications

[Introduction] 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 https://doi.org/10.1016/j.acpath.2023.100086.1¹

Objective SK1.1: Pathophysiology of changes in the skin. Describe the pathophysiologic basis for changes in the color, surface texture, swelling, temperature, and sensitivity of skin.

Competency 2: Organ system pathology, Topic: Skin (SK); Learning Goal 1: …

A Tissue Renewal-Based Mechanism Drives Colon Tumorigenesis, Ryan M. Boman, Gilberto Schleiniger, Christopher Raymond, Juan P. Palazzo, Anne Shehab, Bruce M. Boman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Our Goal is to identify how colorectal cancer (CRC) arises in the single-layered cell epithelium (simple columnar epithelium) that lines the luminal surface of the large intestine. Background: We recently reported that the dynamic organization of cells in colonic epithelium is encoded by five biological rules and conjectured that colon tumorigenesis involves an autocatalytic tissue renewal reaction. Introduction Our objective was to define how altered crypt turnover explains tissue disorganization that leads to adenoma morphogenesis and CRC. Hypothesis: Changes in rate of tissue renewal-based cell polymerization leads to epithelial expansion and tissue disorganization during adenoma histogenesis. Methods: Accordingly, we created …

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Decorin Evokes A Pro-Lysosomal Pathway In Lymphatic Endothelial Cells, Gabriel J. Pascal, Dipon K. Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones, is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal …

The Significance Of Detecting An Unusual Myeloblast Immunophenotype In A Presumptive Clinical Diagnosis Of Myelodysplastic Syndromes, Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais

Open Access Theses & Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and complex malignancy that accounts for 15% of pediatric acute lymphoblastic leukemia (ALL) cases in the United States. Tyrosine kinases control critical cellular processes, including the development, survival, and activation of T cells, and are established drivers of leukemia.Tyrosine kinases involved in hematological disorders include receptor tyrosine kinases and non-receptor tyrosine kinases family members such as SRC, ABL, FAK, and Janus kinases (JAKs). This study primarily focused on JAK1 gain-of-function (GoF) mutations. These mutations are recognized as hyperactivating mutations, maintaining kinase activity of JAKs on and essentially keeping downstream signaling effectors, like …

Differential Impacts On Proteoglycan Expression In The Response To Lens Wounding In Reparative And Pro-Fibrotic Microenvironments, Janice L Walker, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ex vivo lens epithelial explant cultures created through a technique that mimics cataract surgery provided an ideal model with which to compare the impacts on proteoglycan expression in the response to wounding in both reparative promoting and pro-fibrotic microenvironments. On their native basement membrane capsule the injured lens epithelium undergoes regenerative repair, with the wound closing within a few days. Their migration across the wound area is led by a population of activated lens resident immune cells. The same leader cell population also directs the wounded epithelium to migrate off the outside edges of the lens explant across the surrounding …

Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw

Pathology, East Africa

Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from …

Pediatric Myeloid Neoplasms With Ubtf Tandem Duplications: Morphologic, Immunophenotypic, And Clinical Characterization, Mahsa Khanlari, Wei Wang, Yonghui Ni, Paul E Mead, Masayuki Umeda, Tami Westover, Jing Ma, Jeffrey E Rubnitz, Juan M Barajas, Stanley Pounds, Jeffery M Klco

Faculty, Staff and Student Publications

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts …

Diagnostic Pearls And Pitfalls In The Interpretation Of Small Biopsies And Frozen Sections Of The Pancreatobiliary Tract, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Advancing Diagnostic Accuracy And Quality Of Patient Care Through The Implementation Of A Flow Cytometry Quality Assurance Program, Dylan Wang, Hong Fang, Chi Young Ok, Jeffrey L Jorgensen, L Jeffrey Medeiros, Wei Wang, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification, and disease monitoring of hematologic neoplasms. The interpretation of flow cytometry testing can be challenging.

Objective.—: To explore ways to improve diagnostic accuracy and in turn enhance the quality of patient care.

Design.—: A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed. The outcomes of the QA review were categorized into 3 groups: complete agreement, minor discrepancy, and major discrepancy. Each discrepancy underwent a process of documentation, discussion, and resolution. Here we summarize our 3 …

Inflammatory Hyperplastic Mass Mimicking Local Recurrence Following Endoscopic Submucosal Dissection Of A Colonic Adenoma, Isiah Gonzalez, Linda K Green, Salmaan Jawaid, Wasseem Skef

Faculty, Staff and Students Publications

This case presents a hyperplastic inflammatory mass at the resection site of a colorectal tubular adenoma. A 65-year-old man with a history of alcohol-associated liver cirrhosis, >10 lifetime polyps, and a CHEK2 mutation underwent hybrid endoscopic submucosal dissection of a 3 cm lateral spreading tumor, nongranular, Paris 0-IIa polyp in the ascending colon. Postresection pathology confirmed tubular adenoma with negative margins (R0). Six-month surveillance colonoscopy in the community identified a mass at the resection site, initially suspected to be local recurrence. Repeat colonoscopy demonstrated a mass which appeared inflammatory, with a Kudo type II hyperplastic pit pattern on narrow-band imaging …

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …

The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal

Faculty, Staff and Students Publications

BACKGROUND: The Triglyceride-glucose (TyG) index represents a simple, cost-effective, and valid proxy for insulin resistance. This surrogate marker has also been proposed as a predictor of metabolic and cardiovascular disease (CVD). In this descriptive review, we aimed to assess the utility of the TyG index as a predictive biomarker of cardiometabolic diseases.

METHODS: A search was conducted in PubMed, and Web of Science to identify cross-sectional and more importantly prospective studies examining the use of the TyG index as a predictive biomarker. The following terms were utilized in addition to the TyG index: "insulin resistance", "metabolic syndrome", "diabetes"; "cardiovascular diseases". …