The cytochrome P450 (CYP) enzymes constitute a large polymorphic family that play a huge role in the metabolism of endogenous compounds and in the metabolization of 70–80% of all clinically prescribed medications. Among them, the CYP2C9, CYP2C19, CYP2D6 and CYP4F2 genes are of clinical relevance, as they are highly polymorphic and implicated in the metabolism of several drugs. These genetic polymorphisms which induce variability in CYPs expression present qualitative and quantitative differences between ethnic groups and geographic regions. This review aims to evaluate the allele frequencies, genotypic distribution and predicted CYP2C9, CYP2C19, CYP2D6 and CYP4F2 genetic variants in the European countries. Therefore, a PubMed and a Web of Science search from 1989 to 2021 on the data on the polymorphic prevalence among European countries of the CYP2C9, CYP2C19, CYP2D6 and CYP4F2 genes was performed. After excluding the duplicates, a total of 1179 studies were found. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The present paper is an overview on the frequency CYP genetic variations, facilitating the prediction of a patient's response to medication and, consequently, enabling the selection of personalized medicine

(Introduction) Antibody testing plays a crucial role in identifying individuals previously infected with a specific pathogen. The role of antibody testing gained extreme importance, especially during the COVID-19 pandemic, as monitoring anti-SARS-CoV-2 antibodies provides vital epidemiological and clinical insights into the evolution of coronavirus disease and the stratification of immunized and asymptomatic populations. Therefore, access to a highly portable and user-friendly sensor for point-of-care detection of SARS-CoV-2 antibodies or others contributes to aid in the timely diagnosis of infections or immune responses, immunity monitoring to enable personalized treatments.

Passenger riding comfort is a major concern in railways, particularly in high-speed (HS) networks due its strict requirements. Both the track and vehicle conditions may influence the comfort experienced by the passengers, but other external factors may also do it. Among these factors, the effects caused by crosswinds stand out due to the high levels of vibrations that may cause to the vehicle. However, almost no studies in this regard can be found in the literature, since most of the works do not consider external loads and do not analyse this phenomenon on bridges. Thus, the present work aims to fill this gap, by evaluating the passenger comfort on bridges subjected to crosswinds with different lateral structural behaviours and track conditions. Based on the vehicle's accelerations computed with an in-house dynamic train-track-bridge interaction tool, the Mean and Continuous comfort indexes defined by the European norm EN 12299, as well as the Sperling index, have been assessed for distinct scenarios. The bridge's lateral behaviour shows a negligible effect in the riding comfort, as well as the track quality since the wind load is much more determinant for the carbody vibrations than the track irregularities considered in this work.

This article describes the experimental and numerical evaluation of the dynamic behaviour of the Cascalheira bridge, located on the Northern Line of the Portuguese railway network. The bridge has a short span formed by two filler-beam half-decks, each one accommodating a railway track. The study includes the development of a finite element numerical model in ANSYS® software, as well as in situ dynamic characterization tests of the structure, namely ambient vibration tests, for the estimation of natural frequencies, modes shapes and damping coefficients, and a dynamic test under railway traffic, particularly for the passage of the Alfa Pendular train. The damping coefficients’ estimation was performed based on the Prony method, which proved effective in situations where the classical methods (e.g., decrement logarithm) tend to fail, particularly in the case of mode shapes with closed natural frequencies, as typically happens with the first vertical bending and torsion modes. The updating of the numerical model of the bridge was carried out using an iterative methodology based on a genetic algorithm, allowing an upgrade of the agreement between the numerical and experimental modal parameters. Particular attention was given to the characterization of the ballast degradation over the longitudinal joint between the two half-decks, given its influence in the global dynamic behavior of this type of double-deck bridges. Finally, the validation of the numerical model was performed by comparing the acceleration response of the structure under traffic actions, by means of numerical dynamic analyses considering vehicle-bridge interaction and including track irregularities, with the ones obtained by the dynamic test under traffic actions. The results of the calibrated numerical model showed a better agreement with the experimental results based on the accelerations evaluated in several measurement points located in both half-decks. In the validation process the vertical stiffness of the supports, as well as the degradation of the ballast located over the longitudinal joint between half-decks, was demonstrated to be relevant for the accuracy and effectiveness of the numerical models.

The mucin O-glycan sialyl Tn antigen (sTn, Neu5Acα2-6GalNAcα1-O-Ser/Thr) is an antigen associated with different types of cancers, often linked with a higher risk of metastasis and poor prognosis. Despite efforts to develop anti-sTn antibodies with high specificity for diagnostics and immunotherapy, challenges in eliciting high-affinity antibodies for glycan structures have limited their effectiveness, leading to low titers and short protection durations. Experimental structural insights into anti-sTn antibody specificity are lacking, hindering their optimization for cancer cell recognition. In this study, we used a comprehensive structural approach, combining X-ray crystallography, NMR spectroscopy, computational methods, glycan/glycopeptide microarrays, and biophysical techniques, to thoroughly investigate the molecular basis of sTn recognition by L2A5, a novel preclinical anti-sTn monoclonal antibody (mAb). Our data unequivocally show that the L2A5 fragment antigen-binding (Fab) specifically binds to core sTn moieties. NMR and X-ray structural data suggest a similar binding mode for the complexes formed by the sTn moiety linked to Ser or Thr and the L2A5 Fab. The sugar moieties are similarly oriented in the paratope of mAb, with the Neu5Ac moiety establishing key interactions with the receptor and the GalNAc moiety providing additional contacts. Furthermore, L2A5 exhibits fine specificity toward cancer-related MUC1 and MUC4 mucin-derived sTn glycopeptides, which might contribute to its selective targeting against tumor cells. This newfound knowledge holds promise for the rational improvement and potential application of this anti-sTn antibody in diagnosis and targeted therapy against sTn expressing cancers such as breast, colorectal, and bladder cancer, improving patient care.

Bivalves accumulate toxins produced by microalgae, thus becoming harmful for humans. However, little information is available about their toxicity to the bivalve itself. In the present work, the physiological stress and damage after the ingestion of toxic dinoflagellate species (Gymnodinium catenatum) and a diatom species (Skeletonema marinoi, which is non-toxic to humans but may be to grazers) in the oyster Magallana angulata are evaluated against a control treatment fed with the chlorophyte Tetraselmis sp. Oysters were exposed for two hours to a concentration of 4 × 104 cells/L of G. catenatum and 2 × 107 cells/L of S. marinoi. The biomarkers superoxide dismutase (SOD), catalase (CAT), glutathione S-Transferase, total Ubiquitin (Ubi) and Acetylcholinesterase (AchE) were assessed. The exposure of M. angulata to G. catenatum lead to a reduction in SOD and AchE activity and ubiquitin concentrations when compared to the control treatment. Moreover, it increased CAT activity in the adductor muscle, and maintained its activity in the other tissues tested. This may be related to the combination of reduced metabolism with the deployment of detoxification processes. S. marinoi also lead to a decrease in all biomarkers tested in the gills and digestive glands. Therefore, both species tested caused physiological alterations in M. angulata after two hours of exposure.

Inland wetlands are highly diverse, productive ecosystems at the transition between terrestrial and aquatic environments, providing major services to society. They are also under high human pressure and have suffered a progressive decline in total area globally. Here, we describe the genetic diversity and demography of the endangered Lisbon arched-mouth nase Iberochondrostoma olisiponense occurring in the inland wetlands of a major river in southwestern Europe, within a context of extreme habitat changes. Our results highlight the presence of well-structured small population nuclei with evidence of sporadic gene flow at historical and contemporary time scales. Historical reconstructions suggest population isolation consistent with periods of unsuitable habitat conditions severing population connectivity, while small population sizes may be due to limited available habitat coupled to historical as well as recent restricted connectivity among river tributaries. Habitat contraction or loss due to decreased rainfall associated with climate change is expected to impact inland wetland fish regionally, raising additional conservation concerns on species with low genetic diversity and small effective population sizes as I. olisiponense. This study may serve as a proxy for taxa occurring in similar inland wetland ecosystems and may inform conservation efforts and planning regarding the expected drivers of population demographics, distribution and connectivity.

Naples yellow was widely used across different types of artwork. Technical studies identified a binary Pb–Sb type as well as modified ternary variants with either zinc or tin in the structure. Although these variants were the object of previous experimental studies, a better understanding of the impact of the glazing procedure on the chromatic, chemical and crystallographic characteristics of the pigment is still lacking. In this work, several historical Naples yellow recipes were re-worked and subsequently applied and fired on test tiles, over a white glaze. The results show that the interaction between pigment and glaze produces important modifications to the colour, chemistry and structure of the pigment. Such modifications will strongly impact the reconstruction of historical recipes, with major consequences for identifying Naples yellow variants on artwork and investigating artistic practices.

The carbon-neutrality target set by the European Union for 2050 drives the increasing relevance of green hydrogen as key player in the energy transition. This work uses the JRC-EU-TIMES energy system model to assess opportunities and challenges for green hydrogen trade from North Africa to Europe, analysing to what extent it can support its decarbonization. An important novelty is addressing uncertainty regarding hydrogen economy development. Alternative scenarios are built considering volumes available for import, production costs and transport options, affecting hydrogen cost-effectiveness. Both pipelines and ships are modelled assuming favourable market conditions and pessimistic ones. From 2040 on, all available North African hydrogen is imported regardless of its costs. In Europe this imported hydrogen is mainly converted into synfuels and heat. The study aims to support policymakers to implement effective strategies, focusing on the crucial role of green hydrogen in the decarbonization process, if new competitive cooperations are developed.

There is an actual need for developing materials for wound healing applications with anti-inflammatory, antioxidant, or antibacterial properties in order to improve the healing performance. In this work, we report the preparation and characterization of soft and bioactive iongel materials for patches, based on polymeric poly(vinyl alcohol) (PVA) and four ionic liquids containing the cholinium cation and different phenolic acid anions, namely cholinium salicylate ([Ch][Sal]), cholinium gallate ([Ch][Ga]), cholinium vanillate ([Ch][Van]), and cholinium caffeate ([Ch][Caff]). Within the iongels, the phenolic motif in the ionic liquids plays a dual role, acting as a PVA crosslinker and a bioactive compound. The obtained iongels are flexible, elastic, ionic conducting, and thermoreversible materials. Moreover, the iongels demonstrated high biocompatibility, non-hemolytic activity, and non-agglutination in mice blood, which are key-sought material specifications in wound healing applications. All the iongels have shown antibacterial properties, being PVA-[Ch][Sal], the one with higher inhibition halo for Escherichia Coli. The iongels also revealed high values of antioxidant activity due to the presence of the polyphenol, with the PVA-[Ch][Van] iongel having the highest activity. Finally, the iongels show a decrease in NO production in LPS-stimulated macrophages, with the PVA-[Ch][Sal] iongel displaying the best anti-inflammatory activity (>63% at 200 µg/mL).