Faculdade de Medicina e Ciências Biomédicas
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Percorrer Faculdade de Medicina e Ciências Biomédicas por Objetivos de Desenvolvimento Sustentável (ODS) "04:Educação de Qualidade"
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- Activity induced genes expression is impaired in polyglutamine spinocerebellar ataxiasPublication . Torquato Afonso, Inês; Vilhena Catarino Brito, David; Bading, Hilmar; Nóbrega, ClévioPolyglutamine Spinocerebellar ataxias (SCAs) are a group of 6 incurable genetic disorders, caused by an expansion of the trinucleotide cytosine-adenine-guanine in their causative genes, which produces a protein with an expanded glutamine region. This project focuses on the study of Spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) (1), which are rare dominantly inherited disorders that primarily impair the cerebellum therefore leading to motor ataxia. Activity-induced inhibitor of death (AID), are a group of pro-survival 9 genes which were found to be neuroprotector in several neurological disorders, including stroke, glaucoma, AD, HD, and ALS (2). In this project, we aim to investigate about the relevance of the expression of AID genes for cerebellum function and whether their expression levels are impaired in SCA2 and SCA3
- AI-enhanced adaptive testing with cognitive diagnostic feedback and its association with performance in undergraduate surgical education: a pilot studyPublication . Gonçalves, Nuno Silva; Collares, Carlos; Pêgo, José MiguelBackground: Effective feedback in the cognitive domain is essential for surgical education but often limited by resource constraints and traditional assessment formats. Artificial Intelligence (AI) has emerged as a catalyst for innovation, enabling automated feedback, real-time cognitive diagnostics, and scalable item generation, thereby transforming how future surgeons learn and are assessed. Methods: An item bank of 150 multiple-choice questions was developed using AI-assisted item generation and difficulty estimation. A formative Computerized Adaptive Testing (CAT), balanced across three cognitive domains (memory, analysis, and decision) and surgical topics, was delivered via QuizOne® 3–5 days before the summative Progress Test. A total of 147 students participated, of whom 116 completed the formative CAT. Performance correlations, group comparisons, analysis of covariance (ANCOVA), and regression analyses were conducted. Results: Students who voluntarily completed CAT showed higher Progress Test scores, though causality cannot be established due to self-selection bias (p = 0.021), with the effect persisting after adjusting for prior academic performance (ANCOVA p = 0.041). Memory skills were the strongest predictors of summative outcomes (R2 = 0.180, β = 0.425), followed by analysis (R2 = 0.080, β = 0.283); decision was not significant (R2 = 0.029, β = 0.170). Conclusion: AI-enhanced CAT–Cognitive Diagnostic Modeling (CDM) represents a promising formative approach in undergraduate surgical education, being associated with higher summative performance and providing individualized diagnostic feedback. Refining feedback presentation and enhancing decisionmaking assessment could further optimize its educational impact.
- Biomarkers for predicting malignant transformation of premalignant lesions of the larynx: a systematic reviewPublication . Rodrigo, Juan P.; Lima-Souza, Reydson Alcides de; López, Fernando; Stenman, Göran; Agaymy, Abbas; Quer, Miquel; Paleri, Vinidh; Leivo, Ilmo; Nadal, Alfons; Zidar, Nina; Mariano, Fernanda V.; Hellquist, Henrik; Gale, Nina; Ferlito, AlfioBackground/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts.
- Chromenone derivatives as CRM1 inhibitors for targeting glioblastomaPublication . Princiotto, Salvatore; Jiménez, Lucía; Domínguez, Lucía; Sequeira, João G. N.; Mourato Paulo, Cristiana Isabel; Orea-Soufi, Alba; da Silva Santos, Bruno Filipe; Dallavalle, Sabrina; Machuqueiro, Miguel; ferreira, Bibiana; Link, WolfgangGlioblastoma (GBM) is one of the most aggressive and deadly cancers. Due to the complexity and redundancy within signaling networks in GBM, targeted inhibitors of specific pathways have shown only limited success. The nuclear export receptor chromosome region maintenance 1 (CRM1) has recently emerged as a promising therapeutic target, as its inhibition can simultaneously disrupt multiple key oncogenic drivers. Herein, whether chromenone derivatives, known for detecting thiol-containing molecules, can function as CRM1 inhibitors is explored. Several chromenonebased derivatives are synthesized and it is demonstrated that they inhibit CRM1-driven nuclear export in a structure- and dose-dependent manner. A preliminary structure–activity relationship is established, providing a rationale for selective CRM1 binding based on molecular docking studies. Additionally, it is showed that the active chromenone derivatives effectively inhibit the nuclear export of endogenous nuclear export signal-containing substrates in GBM cells. Several of these compounds exhibit selective cytotoxicity againstGBM cell lines, highlighting their potential as targeted therapies for GBM.
- Description of the Hamburg Alexander Leukodystrophy Cohort—Insights into Practical Classification and the Care SituationPublication . Kokaly, Nadia; Guerreiro, Helena; Bredow, Janna; Dreha-Kulaczewski, Steffi; Ohlenbusch, Andreas; Köhler, Wolfgang; Reinhardt, Tabea; Schön, Gerhard; Volk, Alexander E.; Sigel, Helen; Bley, AnnetteBackground: Alexander disease (AxD) is a rare severe leukodystrophy that has no cure to date. A pathogenic gain-of-function variant in the GFAP gene affects the astrocytes and subsequently the function of the white matter in the CNS. Methods: We retrospectively analyzed the most frequent symptoms of nine AxD cases, classified them according to published classifications, and described the need of care and support. Results: The description of the courses of disease of nine cases with AxD reflects the broad spectrum of different phenotypes of AxD, with often occurring apnoea. Data about care and support for AxD patients indicate a high and heterogeneous need of support. Treatment with steroids reduced symptoms in two patients. Some patients showed lasting improvement during their course of disease. Conclusions: The course of AxD is very heterogeneous. Thus, we extracted relevant key features to describe the severity of the disease, namely feeding problems, epilepsy, age-appropriate motor function, failure to thrive, age-appropriate language and apnoea. We recommend early evaluation for clinical care and support. For some AxD patients, treatment with steroids may alleviate symptoms. Further development of efficient treatments is necessary
- Developing a toolkit for building a community hospital clinical research programPublication . Rego, Kian; Orlando, Elaina; Archambault, Patrick; Geagea, Anna; Mitra, Anish R.; Vazquez-Grande, Gloria; Marticorena, Rosa M.; Patterson, Lisa; DiDiodato, Giulio; Rewa, Oleksa G.; Senaratne, Janek; Law, Madelyn; Binnie, Alexandra; Tsang, JenniferPurpose Although health research in Canada is primarily conducted in academic hospitals, most patients receive their care in community hospitals. The benefits of increasing research capacity in community hospitals include improved study recruitment, increased generalizability of results, broader patient access to novel therapies, better patient outcomes, enhanced staff satisfaction, and improved organizational efficiency.
- Development and psychometric validation of the Minho suture assessment scale (Minho-SAS) for medical studentsPublication . Gonçalves, Nuno Silva; Sousa, Rita Matos; Collares, Carlos; Pereira, Vítor Hugo; Pêgo, José Miguel; Anderson, M. BrownellIntroduction: Even though mastery of suturing is a core technical skill in surgical education, existing tools for its assessment often lack psychometric validation or are not specifically designed for undergraduate training. The aim of this study was to develop and validate the Minho Suture Assessment Scale (Minho-SAS), a structured instrument to evaluate fundamental suturing competencies in medical students. The research question was whether the Minho-SAS demonstrates validity and reliability as a psychometric tool. Methods: The development process involved collaboration with multidisciplinary surgical teams and experienced practitioners to ensure content validity. Data from a cohort of medical students were utilized for psychometric evaluation. Dimensionality was assessed using parallel analysis, Bayesian information criterion, unidimensional congruence, item unidimensional congruence, explained common variance, item explained common variance and mean of item residual absolute loadings. Validity based on internal structure was assessed with Rasch model analysis and factor analysis from the tetrachoric correlation matrix. Reliability was assessed using Rasch model standard errors of measurement to obtain a conditional reliability curve and Cronbach's alpha and McDonald's omega internal consistency coefficients. Results: Analyses supported a unidimensional structure for the Minho-SAS. The single-factor solution explained 39.96% of variance, and Rasch measures accounted for 29.15% (16.43% by persons, 12.72% by items). Residual correlations, factor loadings, and item fit statistics were within acceptable ranges. Reliability indices were satisfactory: Rasch reliability = 0.706; McDonald's omega = 0.889; Cronbach's alpha = 0.883. Conclusion: The Minho-SAS is a robust instrument specifically tailored for assessing fundamental suturing skills among medical students. Rasch model analysis yielded less favorable results than factor analysis, yet still acceptable. While demonstrating considerable potential, further exploration of Minho-SAS across diverse populations and educational settings is crucial to affirm its broader applicability and impact in medical education and clinical practice.
- Dextran as an adjunct in carotid endarterectomy: a systematic review and meta-analysisPublication . Silva-Vieira,Duarte; Pereira-Neves, António; Nzwalo, Hipólito; Myrcha, Piotr; Neves, João RochaBackground: Carotid endarterectomy (CEA) is a widely used surgical procedure to prevent stroke in patients with carotid artery stenosis. Dextran, an antithrombotic agent with antihemostatic properties, has been proposed as an adjunctive therapy to reduce thromboembolic complications during CEA. However, its effectiveness and safety remain controversial. This systematic review and meta-analysis aim to assess the incidence of thromboembolic and hemorrhagic complications in patients undergoing CEA with dextran administration. Methods: A systematic search was conducted in MEDLINE, Scopus, and Web of Science for studies evaluating the postoperative effects of dextran in CEA patients. Random-effects metaanalysis was performed to estimate the pooled incidence of adverse events, and heterogeneity was assessed through meta-regression analysis. The quality of the included studies was evaluated using the National Heart, Lung, and Blood Institute Study Quality Assessment Tool for observational studies and the Cochrane Risk-of-Bias 2 tool for randomized controlled trials (RCTs). Results: Ten studies, including a total of 149,540 patients, met the inclusion criteria. Of these, 9 were observational cohort studies (6 retrospective and 3 prospective), while one was an RCT. The meta-analytical incidence of stroke following CEA with dextran was 0.7% at 30 days post operatively (95% confidence interval, 0.3e1.1%), with moderate heterogeneity (I2 ¼ 50.79%, P ¼ 0.002). Meta-regression analysis indicated that geographic region significantly contributed to heterogeneity (P ¼ 0.010), while other clinical covariates, such as diabetes, hypertension, and coronary artery disease, were not associated with significant variations in outcomes. Dextran was primarily administered selectively to high-risk patients, with variations in dosing protocols across studies. Conclusion: The use of dextran in CEA was associated with a low incidence of thromboembolic events. However, some heterogeneity among studies highlights the need for further large-scale RCTs to clarify its efficacy and safety. Given the potential risks of dextran, including hemorrhage and renal complications, individualized patient selection and standardized administration protocols are recommended.
- Exploring angiogenesis and cardiomyocyte differentiation in left ventricular noncompaction using patient derived hiPSCPublication . Carmo, Sara Martins do; Bragança, JoséLeft ventricular noncompaction (LVNC), is a rare cardiomyopathy characterized by a spongy myocardial structure, hyper-trabeculation and intra-trabecular recesses, resulting from failure of normal embryonic compaction of the myocardium. The prevalence of LVNC varies globally, between 9.5% in paediatric age and 0.05-0.25% in the general population. Multiple genetic mutations are associated with LVNC, affecting sarcomeric, cytoskeletal and mitochondrial functions. This study investigates the genetic mechanisms underlaying LVNC, focusing on mutations involved in heart diseases and their impact in cardiomyocyte differentiation and angiogenesis, with a special focus on ZSCAN10, SCN10A and VE-PTP, found mutated in the patient’s cells used in this study. Cardiomyocytes were differentiated from induced pluripotent stem cells (iPSCs) derived from a LVNC patient and a 1st degree healthy relative. Gene relative expression analysis of samples collected during cardiomyocyte differentiation, highlighted significant differences on in key genes, such as GATA4, ISL1, SOX17, KDR, VE-PTP, VEGFA, TNNT2 and NKX2.5 in patients derived cells compared to control cells. Among those, GATA4, ISL1 and NKX2.5, which were previously showed to cooperate for the differentiation and proliferation of cardiomyocytes, presented a significantly lower expression. SOX17, KDR and VEGFA have functions in cardiac vascularization, and the expression of SOX17 was higher in patient’s cells, while in the same conditions KDR and VEGFA were decreased at critical time points for endothelial cells differentiation. Thus, the expression of these genes, crucial for cardiomyocyte development and angiogenesis, were markedly altered in LVNC-derived cells compared to control cells. A Tube formation assay using endothelial cells from both LVNC-derived and control cells, to assess their ability to form capillary like structures. Remarkable differences were observed, with patient cells showing a delayed and an impaired tube formation, and a reduced vascular network complexity. Overall, our results argue that novel genetic and cellular mechanisms might be altered in the LVNC patient cells analysed.
- Fibrosis-related transcriptome unveils a distinctive remodelling matrix pattern in penetrating ileal Crohn’s diseasePublication . Sousa, Helena Tavares; Ferreira, Marta; Gullo, Irene; Rocha, Ana Mafalda; Pedro, Ana; Leitão, Dina; Oliveira, Carla; Carneiro, Fátima; Magro, FernandoBackground and Aims: Stricturing [B2] and penetrating [B3] ileal Crohn’s disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn’s disease. Methods: Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture[s] [B3s] and 12 without [B3o]. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes, a p-adjusted Results: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn’s disease localisa tion, perianal disease, and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn’s disease fibrogenesis, and eight differentially expressed genes were so in other organs. The most significantly active biological processes and pathways in penetrating disease were response to TGFβ and matrix organisation and degradation, as validated by immunohistochemistry. Conclusions: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn’s disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodelling.
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