Teses de Doutoramento
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Browsing Teses de Doutoramento by Field of Science and Technology (FOS) "Ciências Médicas::Outras Ciências Médicas"
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- Cinnamic acid terminated dendrimers – Synthesis, characterization, biological evaluation and NMR metabolomics analysisPublication . Olival, Ana Cristina Dias; Rodrigues, João Manuel Cunha; Tomás, Helena Maria Pires GasparGiven the widespread use and enormous therapeutic potential of nanoparticles, the study of their biological effects is a relevant and current issue. In this project, were synthesized new cinnamic acid-terminated PAMAM G4NH2 dendrimers (CATDEN) to target the monocarboxylate transporter (MCTs) overexpressed in cancer cells. The cinnamic acid chosen was alpha-cyano-4-hydroxycinnamic acid, given its effectiveness in vitro and in vivo in inhibiting MCTS. The metabolic profile of cell extracts and cell culture supernatants were studied by NMR metabolomics methods to evaluate the dendrimer’s mechanism of action. After statistical analysis, the results showed that all cell lines were affected by the treatment with the PAMAM G4NH2, with the assays in human osteosarcoma cells (CAL 72) showing higher discrimination between treated and non-treated cells. The results suggested that native dendrimer and CATDEN influence metabolic alterations in energy production (glucose metabolism) and protein synthesis (amino acid catabolism). This finding indicates that the cytotoxicity associated with PAMAM may result from the depletion of the components of the medium. Furthermore, CATDEN dendrimers were also used to encapsulate the anticancer drug DOX. Our results indicated that in CATDEN, even with a lower encapsulation capacity (probably due to steric hindrance), the release of DOX is similar to that of the commercial dendrimer not functionalized with cinnamic acid. The cytotoxicity of both dendrimer/DOX complexes is shown to be superior when compared to free DOX.
- From design to evaluation: a human-centered approach to AI-powered remote cognitive training for stroke patientsPublication . Paulino, Teresa da Conceição Madureira; Cameirão, Mónica da SilvaStroke is a leading cause of long-term disability worldwide, often resulting in cognitive impairments that significantly impact patients' quality of life and independence. This doctoral thesis presents the design, development of the client-side modules, and evaluation of the NeuroAIreh@b platform, a remote cognitive training system specifically tailored for stroke survivors. The focus of this thesis is dual. First, a focus on a comprehensive human-centered design approach was used to design the modular platform that addresses the specific needs of stroke patients and healthcare professionals. Second, the automation of cognitive training through the development of the software module Reh@Sync allows the training to be performed remotely with reduced need for therapist intervention. The system integrates a set of cognitive training apps that incorporate activities of daily living, enhancing ecological validity and potential skill transfer to real-life situations. One of the key innovations of the Reh@Sync is the implementation of personalization and difficulty adaptation features, which use cognitive profiles and machine learning models to tailor interventions to the individual patient's needs and abilities. Moreover, the engineered system can universally integrate independent apps beyond the cognition dimension, making it a multipurpose system for multidimensional training. The design process involved multiple stakeholders and employed various techniques, including requirements engineering, ideation sessions, prototyping, and iterative usability evaluations. The development phase resulted in a modular system capable of integrating multiple cognitive training apps while maintaining customizability for individual users. The results of a feasibility study with 10 chronic stroke survivors who used the system for 4 weeks showed high levels of adherence, usability, and user satisfaction, indicating the potential for widespread adoption in home based rehabilitation settings. Regarding clinical outcomes after the intervention, we observed significant improvements for a subgroup that showed baseline cognition below the norm. Evaluation of the automation process revealed that the system efficiently personalized and adapted the training to each participant's profile. This research contributes to the fields of cognitive rehabilitation, informatics engineering, and human-computer interaction by providing a detailed account of the design, engineering, and development process of an automated remote cognitive training system for stroke survivors. The findings support the feasibility of self-administered digital cognitive training and highlight areas for future improvements, including expanding the difficulty range to accommodate higher-functioning individuals and incorporating a wider variety of content to enhance engagement.