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Challenging mechanistic paradigms in copper monooxygenase
Full text linkThis work explores the structure and function of an important copper monooxygenase: peptidylglycine alpha-amidating monooxygenase. The canonical reaction mechanism of this enzyme is discussed, including its strengths and weaknesses. Ultimately, on the basis of spectroscopic, structural, and kinetic methods an alternative hypothesis is suggested
Ethical and operational considerations in clinician adoption of predictive AI-enabled clinical decision support tools
Full text linkThis capstone examines why predictive AI-enabled clinical decision support tools continue to face resistance at the bedside and how that hesitation impacts patients’ confidence in their care. Through qualitative interviews and thematic analysis, it examines four ethical pressure points, such as autonomy, privacy, fairness, and accountability, as well as workflow frictions that shape clinicians’ trust and, by extension, patients’ trust in AI-guided decisions. The project then outlines governance, communication, and design fixes through AI ethics review boards, question-prompt lists for clinicians and patients, and co-design workflows to make AI adoption both ethically sound and practically workable
Validation of small field treatment planning using Brainlab elements
Full text linkThe purpose of this thesis is to validate the cranial and multiple brain METS module in Brainlab Elements treatment planning system (TPS) and document the validation process for small fields. Measured data from water and solid phantoms were compared against calculated PDDs, profiles, output factors, and planar doses, following MPPG 5.b and TG-119-based tests
An ontology-based framework for evaluating evidence quality and certainty
No full textCurrently, diverse scientific evidence evaluation tools, terms, and guidelines exist, but they are fragmented and inconsistently tied to foundational theory. This paper proposes an ontology-based framework defining core evaluative concepts (internal validity, construct validity, precision, consistency, meta-analytic internal validity, and reporting transparency) and systematically maps existing evaluation instruments onto these domains. The framework highlights overlaps and gaps, such as limited attention to construct validity, and clarifies distinctions between concepts like external validity and generalizability
Cancer molecular subtyping: a machine learning approach
No full textMolecular phenotypes, or subtypes, can describe cancer as distinct diseases within primary tissues-of-origin. Machine learning (ML) can be applied to this molecular taxonomy of cancer for classifying newly diagnosed samples in supporting clinical decision making and informing development of molecular therapeutics
Profiling extracellular vesicles in Niemann Pick disease type c
No full textThis work summarizes a doctoral research project on the role of extracellular vesicles (EVs) in the rare disease Niemann Pick Disease Type C (NPC). It established miRNA expression, surface protein profiles, size, and concentration of EVs from cerebrospinal patient (CSF) and dermal fibroblasts from NPC patients and age-matched controls. These findings reveal novel biological processes at work in a childhood disease that currently has no cure
Delineating resistance mechanisms to gilteritinib combination therapy in AML: shifts in cell state, signaling and mutations
No full textAcute myeloid leukemia (AML) is a malignancy with a poor survival rate, primarily due to resistance to chemotherapy.Combination therapy using gilteritinib with venetoclax, has been explored as a novel strategy to overcome resistance mechanisms. Gilteritinib plus venetoclax combination therapy, especially in the context of F691L mutations, maintains a primitive cell state characterized by increased LSPCs, GMP, and GMP-like cells in both in vitro and patient samples
