Browsing by Issue Date, starting with "2025-09"
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- Hair as a monitoring tool for psychoactive substancesPublication . Simão, Ana Aysa Rocha da; Alba, María Eugenia Gallardo; Barroso, Mário Jorge Dinis; Andraus, Maristela HaddadThe global prevalence of substance use and its severe health, social, and economic consequences remain significant public health concerns. The continuous emergence of new psychoactive substances (NPS), alongside the widespread use of traditional drugs, exacerbates the challenges faced by forensic and clinical toxicologists. These substances often evade conventional detection methods due to their rapid evolution, posing significant risks to users and complicating monitoring efforts. Understanding substance use patterns and their impacts is essential for informing prevention strategies, shaping public policies, and implementing harm reduction initiatives. Hair analysis has emerged as a powerful tool in toxicological investigations, offering unique advantages over traditional biological matrices such as blood and urine. Its extended detection window enables the assessment of chronic and historical drug use, while its resistance to adulteration ensures reliability. As a non-invasive collection method, hair analysis facilitates large-scale studies, making it particularly suitable for exploring poly-drug use and evaluating the prevalence of both classical drugs and NPS across diverse populations. Quantitative hair analysis complements self-reported data, addressing discrepancies and enhancing the accuracy of substance use research. [...]
- Identificação de causas genéticas do hipogonadismo hipogonadotrófico congénito utilizando a sequenciação de nova geraçãoPublication . Carriço, Josianne Nunes; Lemos, Manuel Carlos Loureiro de; Gonçalves, Catarina Inês Nunes PiresO desenvolvimento pubertário é um processo fisiológico complexo que resulta da interação entre o sistema neuroendócrino, fatores genéticos e ambientais. Inicia-se com a reativação do eixo Hipotálamo-Hipófise-Gónadas, levando à produção de gonadotrofinas, hormonas sexuais e consequente desenvolvimento dos carateres sexuais secundários. O Hipogonadismo Hipogonadotrófico Congénito (HHC) é uma doença endócrina rara que, na adolescência, se manifesta clinicamente com ausência completa ou parcial do desenvolvimento dos caracteres sexuais secundários. Na idade adulta, os sintomas incluem ausência de virilização e disfunção erétil no sexo masculino, amenorreia primária no sexo feminino, ausência de líbido e infertilidade em ambos os sexos. O HHC caracteriza-se pela ausência ou diminuição da produção, secreção ou ação da hormona libertadora de gonadotrofinas. Em 50 a 60% dos casos associa-se a anosmia/hiposmia (Síndrome de Kallmann) ou a outras anomalias congénitas. O diagnóstico do HHC baseia-se na anamnese, observação de sinais clínicos, levantamento de sintomas e exames laboratoriais e imagiológicos. Contudo, desde o início do século XXI, o conhecimento sobre as causas genéticas do HHC tem avançado na mesma medida que o desenvolvimento das tecnologias de sequenciação genética. A disponibilidade das tecnologias de sequenciação de nova geração (NGS) proporcionou grandes avanços no diagnóstico molecular destes doentes. Este estudo teve como objetivo investigar as causas genéticas do HHC em doentes portugueses, utilizando a NGS, ferramentas in silico e técnicas de biologia molecular. Foram estudados 81 doentes com HHC e 263 controlos portugueses. O ADN genómico foi extraído dos leucócitos do sangue periférico e submetido à sequenciação do exoma completo. A partir das bases de dados OMIM® e Pubmed, identificaram-se 169 genes relacionados com o fenótipo de HHC, que foram incluídos num painel virtual. As variantes encontradas nesses genes foram filtradas com base na frequência populacional e localização no genoma, sendo classificadas conforme os critérios do American college of medical genetics and genomics e da Association for molecular pathology (ACMG-AMP) em cinco níveis, de benignas a patogénicas. Para avaliar o impacto de variantes com potencial para alterar o splicing, utilizou-se o método de minigene. A análise das variantes germinativas permitiu identificar a causa genética do HHC em 24 dos 81 doentes estudados (29,6%). As variantes causais estavam distribuídas por 10 dos 169 genes presentes no painel genético virtual analisado. Os genes GNRHR, FGFR1, ANOS1 e CHD7 foram os mais frequentemente afetados. Notavelmente, a ampliação do painel genético não resultou num aumentou considerável da taxa de diagnóstico. No entanto, é importante destacar que este estudo expandiu o espectro mutacional da doença, identificando várias variantes até então nunca descritas. A maioria das variantes encontradas foi classificada como de significado indeterminado (VUS), mas a taxa de VUS não diferiu significativamente entre doentes e controlos, com exceção do gene EGF, onde foram encontradas VUS exclusivamente nos doentes. Concluímos que a maioria dessas variantes raras não estão diretamente relacionadas com o fenótipo estudado, refletindo provavelmente o fundo genético da população portuguesa. Em relação à oligogenia, observou-se uma frequência de 6,2% entre os doentes (5/81), um valor estatisticamente mais elevado quando comparado com os controlos. O estudo funcional de uma variante identificada no gene CHD7 (NM_017780.4: c.4354G>T, p.Val1452Leu), resultou no aumento da taxa de diagnóstico para 30,9%, demonstrando a importância dos estudos funcionais na reclassificação de VUS. Este trabalho enfatizou a complexidade genética do HHC, reforçando a importância de uma compreensão aprofundada da doença, seja para estabelecer o diagnóstico e/ou o prognóstico, para ajudar no aconselhamento genético e tratamento, seja para o esclarecimento dos processos biológicos, que potencialmente poderão contribuir para o desenvolvimento de terapias dirigidas no futuro.
- Dual-crosslinked injectable in situ forming Alginate/CaCl2/Pluronic F127/ α-Cyclodextrin hydrogels incorporating Doxorubicin and graphene-based nanomaterials for cancer chemo-photothermal therapyPublication . Gonçalves, Joaquim; Melo, Bruna Daniela Lopes ; Pouso, Manuel António do Rosário ; Correia, Ilídio Joaquim Sobreira ; de Melo-Diogo, DuarteInjectable in situ forming hydrogels have been emerging due to their capacity to perform the direct delivery of therapeutics into the tumor site with minimal off-target leakage. Particularly, physical crosslinked injectable in situ forming hydrogels are appealing due to their straightforward preparation that exploits the native jointing capabilities of specific polymers/materials. However, the features of these hydrogels (e.g., injectability, degradation, swelling) are strongly pre-determined by the physical interactions available on the selected polymers/ materials, occasionally yielding undesired outcomes. Thus, the combination of multiple physical crosslinking cues may allow the preparation of hydrogels with enhanced properties. In this work, a dual-crosslinked injectable in situ forming hydrogel was engineered by combining Pluronic F127/α-Cyclodextrin and Alginate/CaCl2 (i.e., combination of host-guest and electrostatic interactions), being loaded with Doxorubicin (chemotherapeutic drug) and Dopamine-reduced Graphene Oxide (photothermal nano-agent) for application in cancer chemophotothermal therapy. When compared to the single-crosslinked hydrogels, the dual-crosslinking contributed to the assembly of formulations with suitable injectability and improved degradation and water absorption behaviors. Moreover, the dual-crosslinked hydrogels presented a good photothermal capacity (ΔT ≈ 14 ◦C), leading to a 1.18-times enhanced Doxorubicin release. In in vitro cell-based studies, the dual-crosslinked hydrogels exhibited an excellent cytocompatibility towards healthy (normal human dermal fibroblasts) and breast cancer (MCF-7) cells. As importantly, the dual-crosslinked hydrogels were able to mediate a chemophotothermal effect that diminished the cancer cells’ viability to just 23 %. Overall, the developed dualcrosslinked injectable in situ forming hydrogels incorporating Doxorubicin and Dopamine-reduced Graphene Oxide are a promising macroscale system for breast cancer chemo-photothermal therapy.
- Quality Evaluation of Point Cloud Coding SolutionsPublication . Prazeres, João Pedro Casanova; Pinheiro, António Manuel GonçalvesPoint clouds experienced a large increase in popularity. From gaming to medical applications, autonomous driving, and urban mapping, point clouds have been widely used in the current technological world. As the demand for point cloud content increases, the need for efficient point cloud coding solutions also increases. Access to such solutions is important for efficient storage and transmission of point cloud data, because they are typically represented by huge amounts of information. It is, however, crucial to have access to quality methods that accurately benchmark point cloud coding solutions. This allows the developers of such solutions to accurately test their codec in several different environments, adjusting the codec development accordingly. In the past, subjective quality models were established to assess the quality of images and videos. Based on this knowledge, new models were developed for point cloud content, though there are crucial differences due to the 3D nature of point clouds. Recently, the growing popularity of learning-based codecs led to a new analysis of the performance of the developed quality models, as the caused distortions tend to be different from those created by the traditional coding technologies. This thesis aims to research those well established subjective quality models in order to assess the performance of point cloud coding solutions, namely the ones that are learningbased. Furthermore, it was also important to understand how the current point cloud objective quality metrics perform in assessing the quality of learning-based point cloud coding solutions. To achieve this goal, several quality studies were conducted under different viewing conditions and considering several state-of-the-art point cloud coding solutions. Furthermore, extensive objective quality metrics benchmarking was conducted across this doctoral program in order to assess their performance in predicting the quality of learning-based point cloud coding solutions. Ultimately, this led to multiple contributions that were proposed and accepted by the scientific community and that were helpful in understanding the performance of point cloud coding solutions, the impact of the display on quality perception, and the performance of objective point cloud quality metrics.