uBibliorum
Digital Repository of the University of Beira Interior
Recent Submissions
Analysis of the Clinical Pathways of Oncological Patients: A comparison of realities for future improvement at “Unidade Local de Saude” at Guarda, Portugal
Publication . Quesada, Mario Forrester; Granadeiro, Luiza Augusta Tereza Gil Breitenfeld
; Aperta, Jorge Manuel Gonçalves
Background
Cancer is a leading cause of death among elderly populations, with cases continuing to rise as life expectancy increases. This growing burden has prompted a shift in oncology care from a disease-focused approach to a patient-centered model that prioritizes quality of life alongside tumor response. Ensuring safe, effective, and well-coordinated cancer treatment—along with supportive and complementary therapies—has become a key priority. Additionally, optimizing healthcare system efficiency is essential to managing costs, improving accessibility, and ensuring equitable cancer care. In this context, understanding patient demographics and the structure of oncology clinical pathways is crucial for enhancing care delivery.
Methods
This study examines the Oncology Clinical Pathway (OCP) at a Portuguese local health unit (Unidade Local de Saúde, ULS-Guarda) to evaluate cancer diagnosis, treatment, and management. The first phase involves a retrospective analysis of medical records from oncology patients treated between 2013 and 2017 across ULS-Guarda’s network, which includes two regional hospitals and 14 primary healthcare centers. This analysis assesses patient demographics, tumor types, and duration of care. The second phase focuses on healthcare professionals’ perspectives regarding the clinical pathway. Using a qualitative approach, structured questionnaires were distributed to key stakeholders—including physicians, nurses, hospital pharmacists, and community pharmacists—to evaluate coordination between services, management practices, process timelines, and overall perceptions of cancer care.
Results and Discussion
The collected data was analyzed to identify variations in experiences and perspectives among healthcare professionals. Findings highlighted the strengths and weaknesses of the oncology clinical pathway, including care transitions, coordination between different healthcare providers, and the role of available platforms in patient management. Additionally, the study explored the impact of the COVID-19 pandemic on oncology services, revealing disruptions and challenges in patient care delivery.
Conclusion
The study highlights significant demographic, economic, and healthcare challenges in the Beira Interior region, impacting the development of an effective Clinical Pathway. The analysis of the Oncological Clinical Pathway (OCP) revealed coordination gaps and the need for standardized protocols and multidisciplinary collaboration. The COVID-19 pandemic underscored the necessity of adaptable healthcare systems, with professionals demonstrating resilience in patient management. Disparities in access and care coordination were identified, particularly in community pharmacies. Strengthening healthcare infrastructure, improving training, and fostering collaboration among institutions are crucial to enhancing cancer care and patient outcomes in the region.
Detection of Stealthy Distributed Denial of Service Attacks Using Artificial Intelligence Methods
Publication . Rios, Vinícius de Miranda; Freire, Mário Marques; Magoni, Damien
Distributed Denial of Service (DDoS) attacks have been used to disrupt various online activities. The significant traffic volume of these distributed attacks has enabled the identification of signatures and behavior profiles that fostered the development of detection mechanisms for mitigating these attacks. However, as new attack types emerge, such as low-rate Denial of Service (DoS) attacks, new detection mechanisms need to be developed to combat these evolving threats effectively.
Many detection mechanisms rely primarily on statistical analysis to identify low-rate DoS attacks in data traffic. However, these methods often exhibit a high rate of false negatives
and are only applicable to small-scale data. Artificial intelligence techniques have been widely employed in various fields, including social network analysis and disease monitoring,
and have gradually gained prominence in the field of cybersecurity in recent years.
This thesis focuses on studying and developing detection mechanisms that exhibit effective performance against two specific types of low-rate DoS attacks: the Reduction of Quality (RoQ) attack and the Slowloris attack. For the RoQ attack, we examine the traffic transmission format to create a similar one, as there is no existing software capable of
generating this type of attack traffic on the internet. For the Slowloris attack, we utilized free and open-source software specifically developed for this purpose. Subsequently, we analyze the traffic from both attacks and extract features that can be used by detection mechanisms.
In this thesis, two approaches have been developed for classifying and detecting RoQ and Slowloris attacks: one approach is based on the separate use of a set of traditional Machine Learning (ML) algorithms and the second approach is based on fuzzy logic plus one traditional ML algorithm (that previously led to good classification results) and Euclidean distance. For the RoQ attack detection, the first approach uses eleven separate machine learning algorithms, namely K-Nearest Neighbors (K-NN), Multilayer Perceptron Neural Network (MLP), Support Vector Machine (SVM), Multinomial Naive Bayes (MNB), Gaussian Naive Bayes (GNB), Decision Tree (DT), Random Forest (RF), Gradient Boosting
(XGB), Logistic Regression (LR), AdaBoost, and Light Gradient Boosting Machine (LGBM), while the second approach consists in our proposed method which combines fuzzy logic, the MLP algorithm, and the Euclidean distance method. For the Slowloris attack detection, the first approach utilizes nine machine learning algorithms, namely KNN, GNB, MLP, SVM, DT, MNB, RF, XGB, and LGBM, while the second approach consists in our proposed method which combines fuzzy logic, the RF algorithm, and the Euclidean distance method. Both approaches utilize previously selected features to classify the data traffic as either attack traffic or legitimate traffic. The obtained results show that some ML algorithms (namely MLP and RF) as well as our approach based on fuzzy logic, one ML algorithm, and Euclidean distance are good candidates to be used to classify RoQ and Slowloris attacks, but the latter approach with a slightly longer runtime for detecting them.
From production to purification: Towards an integrative process for recombinant pre-miRNA-29b as biopharmaceutical
Publication . Carapito, Ana Rita Mugeiro; Sousa, Fani Pereira de; Martins, Mara Guadalupe Freire; Sponchioni, Mattia
Recent advances in RNA research have greatly demonstrated the potential of RNA-based therapies, offering innovative ways to target a variety of diseases with enhanced specificity. Unlike traditional small-molecule drugs, RNA therapeutics like small-interfering RNA and microRNA (miRNA) can precisely regulate gene expression and target specific biological pathways. For instance, recent studies demonstrate that miRNA-29 regulates some pathological routes associated with Alzheimer's disease (AD), a neurodegenerative disorder affecting millions of people around the world. MiRNA-29 plays a crucial role in processes like amyloid-β peptides (Aβ) formation, which contributes to memory loss and neuronal cell damage. Low levels of miRNA-29 are linked to increased production and activity of the enzyme β-secretase (BACE1), which leads to higher production of Aβ and, consequently, β-plaque formation. Given its important functions, restoring or increasing miRNA-29 levels in AD patients can be a promising strategy for AD treatment. Current research is investigating the use of recombinant miRNA-29b precursor (pre-miRNA-29b) to silence BACE1 expression and decrease Aβ levels, aiming to develop novel approaches to slow the progression of AD.
Given this, biopharmaceuticals production and subsequent purification constitute an important process that needs to be in full accordance with criteria established by regulatory entities. Regarding RNA production, the standard technique is through chemical synthesis, however this strategy comes with some disadvantages, namely the biomolecules length that can be correctly produced and the low production levels. Recombinant production is the alternative method that is more cost-effective and applicable for large-scale production. Escherichia coli is the most widely used and studied host, nonetheless, Rhodovulum sulfidophilum (R. sulfidophilum) presents interesting characteristics considering nucleic acids production, that comprise the ability to secrete nucleic acids to the extracellular medium, without secreting RNases. The recovery of recombinantly produced nucleic acids from the extracellular medium might be a great advantage for the further downstream processing because the contaminants, such as cell debris and endotoxins, are not present, as usually are in the intracellular samples.
The downstream process is the most expensive stage of the whole bioprocess, and usually, several chromatographic steps are required to achieve the intended purity and quality. Given this, there is a high demand for specific and efficient purification strategies. Multimodal chromatography is currently under thorough research as it can lead to the same specificity for target compounds as it is observed for affinity chromatography, without using biological ligands that greatly increase the process cost. Ionic Liquids (ILs) are molten salts that can present this multimodal character when used as ligands immobilized onto the stationary phase, being recently studied for nucleic acids purification. The different moieties of the cation in an IL can allow the exploitation of different types of interactions with the target molecule. Therefore, this Doctoral Thesis explores a promising and alternative recombinant host for the production of pre-miRNA-29b, as well as its purification using newly synthesized resins, aiming for the development of a whole bioprocess.
Initially, a DNA vector was designed to produce the target pre-miRNA-29b in R. sulfidophilum. In this study, the impact of the plasmid on bacterial growth was analysed and compared to the non-transformed strain. The transformed strain has shown a global growth about 5 times lower than the non-transformed strain, but this did not impact negatively the target RNA production. An optimization of the extracellular extraction protocol was also conducted during this study, comparing a protocol with ethanol or isopropanol as precipitation agents. The results proven that the protocol using isopropanol as precipitation agent was more efficient reaching a concentration of 0.7 μg of pre-miRNA-29b per liter of medium.
After successfully developing an efficient pre-miRNA-29b production system, it became important to develop a purification strategy. For this, four different silica-based Ionic Liquids (SILs) were synthesized and evaluated on their ability for nucleic acids separation. An initial screening of binding and elution conditions with a low molecular weight RNA sample was performed by using both ionic and hydrophobic conditions, to select the more promising support for further purification assays. The support SSi[C3C3NH2Im]Cl was selected, proving to be highly efficient in separating different species of DNA (genomic and plasmidic) from RNA. Then, it became important to test this support regarding its ability for pre-miRNA-29b purification from other types of RNAs. Given that this approach is more challenging due to the high physical and chemical similarity among small RNAs, four different ILs were employed in this stage to act as competition agents aiming to enhance target selectivity. From the four tested ILs, the 1-ethylimidazolium chloride was proven to have a higher impact on the pre-miRNA-29b selectivity improvement, achieving 76% purity.
Since the aim is to develop a method suitable for a biopharmaceutical production and purification, it would be needed to achieve higher purity levels than what was verified with SSi[C3C3NH2Im]Cl. Therefore, a commercial multimodal resin, Capto Q ImpRes was chosen to analyse and compare its performance to the previous newly synthesized support. Both intra- and extracellular RNA samples were tested regarding pre-miRNA-29b purification, and a Design of Experiments (DoE) was established for each sample. Screening assays with intracellular RNA sample were made to identify the factors to be implemented in the DoE. Sodium chloride concentration and pH were defined, and it was possible to establish conditions that uncover a balance between the recovery and purity of the target. For intracellular RNA samples, the DoE effectively identified optimal purification parameters, attaining recovery rates up to 73% and purity levels around 78%. However, these two responses shown to be almost inversely proportional. Nonetheless, it was possible to achieve the optimal point with a recovery of 48.21% and purity of 51.15%. On the other hand, purifying extracellular pre-miRNA-29b presented substantial challenges, exhibiting significant inconsistencies in purity and difficulties in identifying the target molecule, probably due to the low concentration of pre-miRNA in the extracellular extract and the difficulty in detection.
To search for an alternative that could lead to an improved selectivity for the biopharmaceutical under study, a set of several oligonucleotides were designed to interact with the target. Initially, 13 oligonucleotides were designed to interact through base complementarity with different regions of the target. Each oligonucleotide was linked to a carbon chain (6 or 12 carbons) with an amino group, resulting in 26 different ligands. After data analysis, some ligands showed higher specificity for their target sites, while others demonstrated versatility in recognizing multiple sites. Based on this, 4 oligonucleotides were identified as the most promising for further experimental testing.
Overall, in this doctoral thesis, a bioprocess was developed starting with the upstream stage with recombinant production of the pre-miRNA-29b, followed by the downstream stage exploiting different approaches applicable to target purification. The work opens the route for the development of an integrated production and purification process for pre-miRNA-29b, with great potential for large-scale translation.
Design of Communication and Control for Swarms of Aquatic Surface Drones
Publication . Christensen, Anders Lyhne; Oliveira, Sancho; Postolache, Octavian; Oliveira, Maria João de; Sargento, Susana; Santana, Pedro; Nunes, Luis; Velez, Fernando J.; Sebastião, Pedro; Costa, Vasco; Duarte, Miguel; Gomes, Jorge; Rodrigues, Tiago; Silva, Fernando
The availability of relatively capable and inexpensive hardware components has made it feasible to consider large-scale systems of autonomous aquatic drones for maritime tasks. In this paper, we present the CORATAM and HANCAD projects, which focus on the fundamental challenges related to communication and control in swarms of aquatic drones. We argue for: (i) the adoption of a heterogeneous approach to communication in which a small subset of the drones have long-range communication capabilities while the majority carry only short-range communication hardware, and (ii) the use of decentralized control to facilitate inherent robustness and scalability. A heterogeneous communication system and decentralized control allow for the average drone to be kept relatively simple and therefore inexpensive. To assess the proposed methodology, we are currently building 25 prototype drones from off-the-shelf components. We present the current hardware designs and discuss the results of simulation-based experiments involving swarms of up to 1,000 aquatic drones that successfully patrolled a 20 km-long strip for 24 hours.
LTE-Advanced Radio and Network Optimization: Basic Coverage and Interference Constraints
Publication . Velez, Fernando J.; Sousa, Sofia; Acevedo Flores, Jessica; Robalo, Daniel; Mihovska, Albena; Prasad, Ramjee
In cellular optimization, the UL and DL the values from carrier-to-noise-plus-interference ratio (CNIR) from/at the mobile station are very important parameters. From a detailed analysis of its variation with the coverage and reuse distances for different values of the Channel Quality Indicator (CQI) and given ITU-R propagation models, an evaluation of the possible range for the reuse factor of LTE-A is performed for the DL. By considering CQI and reference CNIR requirements recommended by 3GPP, DL peak bit rates along with the Transport Block Size assumed for single stream and bandwidths of 10 and 20 MHz, PHY and supported throughputs are analysed. HetNets with Carrier Aggregation are considered, where macro cells operating at 800 MHz provide coverage and small cells (SCs) operating at 2.6 GHz provide throughput enhancement at hotspots. A clear decrease is shown for the supported throughput for the longest coverage distances in NLoS propagation conditions. In the given range of coverage distances, the same maximum value occurs for the supported throughput for K=3 and 7, both for macro and SCs.