Pathology Commons^™

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 …

Patient-Derived Ovarian Cancer Models Provide Insight Into Cancer Cell-Intrinsic And Immune Cell-Dependent Effects On Therapeutic Response, Parisa Nikeghbal

Biomedical Sciences ETDs

Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and resistance to chemotherapy. This dissertation applies patient-derived organoids (PDOs), xenograft-derived organoids (PDXOs), and humanized xenografts (huPDX) to investigate therapeutic responses and immune interactions. Organoids were shown to retain critical features of the original malignancy. Across platinum-sensitive, -resistant, and -refractory cases, both PDOs and PDXOs exhibited drug sensitivities that aligned with patients’ clinical classifications. Building on this foundation, a drug screen revealed novel strategies. Auranofin restored platinum sensitivity in Notch3-active models, afatinib broadly reduced viability, and adavosertib–gemcitabine and sorafenib–topotecan combinations produced synergy. Extending this work, immune interactions …

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, …

Multivariate Optical Imaging Of The Oxygen-Metabolism Axis, Jesse D. Ivers

Graduate Theses and Dissertations

Metabolic reprogramming is a characteristic hallmark of multiple pathologies and promotes disease progression, survival, and severity. Current methods to investigate metabolic reprogramming, however, require reductions of dimensionality both because of instrumentation limitations and analysis tools. This work aims to define a blueprint for high dimensional study of the oxygen metabolism axis to enable more sensitive study metabolic reprogramming. We hypothesized (1) multivariate imaging of metabolic and oxygenation metrics in ex vivo tissue sections would elucidate differences in resistant and sensitive head and neck squamous cell carcinoma (HNSCC) xenografts that traditional uni-variate methods miss and (2) an engineered hyperspectral darkfield microscopy …

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 …

The Evaluation Of Anti-Factor Xa Levels In Hospitalised Patients Receiving Low Molecular Weight Heparin (Lmwh): A Prospective Study, Tandzile Thandwayinkosi Simelane

Master of Medicine in Clinical Pathology

Background 

Patients admitted to the hospital have been reported to have coagulation abnormalities due to various factors including immobilisation, preexisting disease, and current illness. The overall incidence of venous thromboembolism (VTE) in critically ill patients varies from 15% to well over 50%, even with the use of prophylactic measures in most patients. Low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are the recommended drugs for VTE prophylaxis in inpatient care. Although not standardly recommended, the laboratory can offer monitoring of anti-Factor Xa using the gold standard method of chromogenic anti-Factor X assay. The anti-Factor Xa levels are notably affected …

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 …

Optimum Volume Of Serious Fluid For The Detection Of Malignancy: A Systematic Review, Sarah Atieno Okech

Master of Medicine in Anatomic Pathology

No abstract provided.

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 …

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 …

Elucidating The Impact Of Ribosome Biogenesis On Breast Cancer, Amr Rafat Elhamamsy

All ETDs from UAB

Ribosome biogenesis, a complex and multi-step process that occurs predominantly in the nucleolus, plays a critical role in cellular function by mediating protein synthesis through the assembly of ribosomal RNAs (rRNAs) and ribosomal proteins into functional ribosomes. In cancer, dysregulation of this process is linked to the development of specialized ribosomes (onco-ribosomes) that support oncogenic translation programs, enhancing tumor progression and therapeutic resistance. This dissertation explores the interplay between ribosome biogenesis and cancer, focusing particularly on the role of RNA Polymerase I (RNA Pol I) activity under hypoxic conditions and rRNA modifications in breast cancer. My first study elucidates the …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

The Impact Of State-Mandated Certification Of Surgical Technologists On Surgical Site Infection Rates: Evaluating Policy, Practice, And Patient Outcomes, Katherine E. Geiger

Graduate Student Theses, Dissertations, & Professional Papers

Abstract

Chairperson: Matthew Schertz, Ph.D.

Committee Member: Morgen J Alwell, Ph.D.

Committee Member: Jill Davis, M.Ed.

As a surgical technology instructor, I have witnessed firsthand the impact that certified surgical technologists (CSTs) have on patient safety, particularly in the prevention of surgical site infections (SSIs). This professional paper investigates the relationship between state-mandated certification of surgical technologists and SSI rates, with a focus on how standardized education and credentialing influence clinical outcomes. SSIs remain a significant concern in surgical environments, contributing to increased morbidity, longer hospital stays, and greater healthcare costs. The research presented here examines certification requirements across various …

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. …

Specifically Targeting Muc16 For Fluorescence-Guided Surgery Of Pancreatic Ductal Adenocarcinoma, Kathryn M. Muilenburg

Theses & Dissertations

Pancreatic cancer is a lethal disease with a low 5-year survival rate and a high rate of resection recurrence. However, surgery remains the only treatment with curative potential for pancreatic cancer. Many factors such as high desmoplasia, a lack of intraoperative imaging, and micrometastatic disease contribute to the high rate of incomplete resections in pancreatic cancer. Fluorescence-guided surgery (FGS) is a potential intraoperative tool for application in surgical resection. FGS works through passive or active targeting of a free dye or dye-containing moiety (e.g. antibody, peptide, and nanoparticles) to specifically fluoresce the tumor compared to the surrounding normal, fibrotic, and …

Hydrogen Peroxide Regulates Protein N-Glycosylation, Alexandria Hernandez-Nichols

All ETDs from UAB

N-glycosylation is a co- and post-translational modification wherein a variety of sugars are added to proteins in a linear pathway progressing from high mannose (HM) to hybrid, to complex type N-glycans. This modification is important to the understanding of protein maturation, stability, and function. Studies have shown that changes in cell N-glycomes, in particular, the HM N-glycan category, could be hallmarks of various pathologies. The biosynthetic pathway for N-glycosylation is well studied and the key enzymes involved in the progression of HM to hybrid N-glycans are the a-mannosidases. Little is understood about the regulation of this highly complex post-translational modification …

Reliability Of Popliteal Artery Flow-Mediated Dilation In The Seated Position, Taskina Akhter

Rehabilitation Sciences Theses & Dissertations

Flow-mediated dilation (FMD) is a noninvasive measurement of endothelial function, which is a useful prognostic tool for cardiovascular disease risk. Despite its widespread use since 1992, the reproducibility of FMD varies widely between studies. This variability in reproducibility is especially significant in the case of the popliteal artery due to different methodological approaches. Studies perform popliteal FMD in various body positions, with the prone and seated positions most common. However, no studies have examined the reproducibility of both the seated and prone positions of the popliteal artery FMD. Therefore, the aim of this study is to examine the test-retest and …

The Role Of Dystrophic Microglia In Aging And Disease, Ryan K. Shahidehpour

Theses and Dissertations--Neuroscience

Microglia are the primary immune cells of the central nervous system and are crucial in maintaining homeostasis and defense from disease and injury in the brain. Recent genome-wide association studies (GWAS) have also highlighted microglia as a central player in Alzheimer’s disease (AD). However, the mechanisms of microglia’s influence are poorly understood. Traditionally, microglial subtypes characterized physiologically as “reactive” or “activated” have been linked with disease and injury in the brain. However, morphologically, a recently described microglia category known as “dystrophic,” characterized structurally by fragmented processes and cytoplasmic decay is believed to be more strongly associated with aging and neurodegeneration. …

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Comparison Between Acute Leukaemia Screening Tube And Lineage Specific Panels For The Diagnosis Of Acute Leukaemia At The Aga Khan University Hospital, Nairobi, Douglas Irimu Munga

Master of Medicine in Clinical Pathology

Introduction; Acute leukaemia is a heterogeneous group of haematological malignancies. It is categorized depending on the immature cells that proliferate and replace the normal tissue in the bone marrow. The broad categories are acute myeloid leukaemia if the immature cells are myeloblasts and acute lymphoid leukaemia if lymphoblasts. Other rare categories are blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute leukaemias of ambiguous lineage which include acute undifferentiated leukaemia and mixed phenotype acute leukaemias (MPALs). The classification is important as the treatment and management differ hence a timely and accurate diagnosis is paramount. Multiparameter comparison of the immunophenotype is possible …

Efficient Classification Of Very High Resolution Images, Mohammad I. Nouyed

Graduate Theses, Dissertations, and Problem Reports (ETD)

In recent decades, deep learning approaches have shown significant improvement in various image understanding tasks. However, analysis of high-resolution images remains a major challenge. In this work, we address the challenge of very high-resolution histopathological image (VHRHI) classification using a new information-theoretic discriminative patch selection approach. We show results on a high-resolution image dataset, namely, gigapixel whole slide tissue images for cancer tumors. Then we address how to efficiently classify challenging histopathology images, such as gigapixel whole-slide images for cancer diagnostics with image-level annotation. These ``weak labels'' are applied throughout the image but describe tumor regions of variable sizes and …

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 …

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 …

Identification Of Immune Biomarkers In Thyroid Cancer, Anupam Kotwal

Theses & Dissertations

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

Oxidative Damage Together With Post-Occlusive Re-Oxygenation Kinetics, In Calf Muscle, Implicate Microvessels In The Myopathy Of Peripheral Artery Disease, Molly Schieber

Theses & Dissertations

Background:Peripheral Artery Disease (PAD) is characterized by calf muscle fibrosis and myofiber oxidative damage (OxD). Our laboratory has demonstrated architectural changes of calf-muscle microvessels (

Methods:Gastrocnemius biopsies were collected from controls, patients with Stage II PAD, and Stage IV patients with limb-threatening ischemia. Carbonyl adducts (CA; oxidative damage), and Heme Oxygenase-1 (HO-1; anti-OxD in microvessels) were quantified in microvessels (

Results: Post-occlusive re-oxygenation of calf muscle was slowed in Stage II patients versus controls. Kinetic parameters correlated poorly with Ankle-Brachial Index. Microvessel CA was increased in pre- and post-exercise Stage II patients and in Stage IV patients versus …

The Relationship Between “Speak Up” Culture Level, Team Effectiveness, And Organizational Performance Among Clinical Laboratory Professionals, Emmanuel Udasco

Walden Dissertations and Doctoral Studies

The clinical laboratory plays a crucial role in aiding physicians to diagnose disease. With numerous studies on “Speak Up” culture well-documented among providers and nurses surrounding patient safety, gaps in literature exist concerning “Speak Up” culture that address team effectiveness and organizational performance within the clinical lab setting. The purpose of this quantitative correlation study was to investigate the relationship between “Speak Up” culture level, team effectiveness, and organizational performance among health care workers employed in the clinical lab. The high-performance work practices model was utilized as the conceptual framework to ground this study. Research questions assessed the link between …

Relationship Between Crown Like Structures And Body Mass Index In Breast Cancer, Sophie Wanjiru Irungu

Master of Medicine in Anatomic Pathology

Introduction: Breast cancer (BC) is the most common malignancy in women worldwide, including Kenya. Globally, increasing incidences of BC have paralleled those of obesity. The mechanism by which obesity contributes to BC is still an active area of research but white adipose tissue inflammation characterized by crown-like structures (CLS), which are macrophages surrounding dying adipocytes, is considered an important contributor. Objectives: The primary objective was to determine the association between CLS and body mass index (BMI) in BC patients. The secondary objectives were to determine the association of CLS with BC risk factors specifically, age, menopausal status, subtypes of BC, …

Homogeneity Test On Error Rates From Ordinal Scores And Application To Forensic Science, Ngoc Ty Nguyen

Graduate Thesis and Dissertation 2023-2024

The Receiver Operating Characteristic (ROC) curve is used to measure the classification accuracy of tests that yield ordinal or continuous scores. Ordinal scores are common in medical imaging studies and, more recently, in black-box studies on forensic identification accuracy (Phillips et al., 2018). To assess the accuracy of radiologists in medical imaging studies or the accuracy of forensic examiners in biometric studies, one needs to estimate the ROC curves from the ordinal scores and account for the covariates related to the radiologists or forensic examiners. In this thesis, we propose a homogeneity test to compare the performance of raters. We …

Uncovering The Role Of Fat-Infiltrated Axillary Lymph Nodes In Obesity-Related Diseases With Statistical And Machine Learning Analyses, Qingyuan Song

Dartmouth College Ph.D Dissertations

The link between obesity and pathogenesis is a complex and multifaceted area of research that is yet to be fully understood. Ample evidence exists to demonstrate the direct relationship between excessive internal fat and various health conditions such as cancer, and metabolic and cardiovascular diseases. The infiltration of ectopic fat into axillary lymph nodes, observable on breast cancer screening images, has been shown to be correlated with body mass index (BMI) in women undergoing screening. This study aimed to explore the relationship between fat-infiltrated axillary lymph nodes (FIN) and obesity-related diseases, with the goal of evaluating the clinical value of …

The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi

Master of Medicine in Anatomic Pathology

Introduction: Breast Cancer (BC) is the most diagnosed cancer among women worldwide and in Kenya. It is a highly heterogeneous disease requiring patient specific treatment and strategies to monitor response to therapy, especially in the neoadjuvant (NAC) setting. Currently, there are no reliable markers in use that can predict response to chemotherapy among patients receiving NAC. Tumour Infiltrating Lymphocytes (TILs) and Cell free DNA (cfDNA) are biomarkers that could possibly bridge this gap. However, limited studies have been carried out on the African population. With the increasing mortality rates attributable to BC in Sub-Saharan Africa, coupled with the growing preference …