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Background: Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1mutations for functional studies to understand their contribution to cancer development and metastasis. Methods: Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and recurring hotspot mutations in EPHreceptors. From these, 15 recurring EPHB1mutations were stably expressed in colorectal cancer followed by 3D confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis using the Sciomics platform. Results: Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. Furthermore, the 3D-protein structure-based bioinformatics analysis showed comparatively more robustness by identifying 63% (5 out of 8 selected 3D-anlysed mutants) vs the 43% (3 out of 7 selected 2D-analysed mutants) EPHB1mutants with compartmentalisation phenotypes. Conclusions: This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, and demonstrated the utility for 3D-protein structure-based mutation analysis in characterization of putative cancer genes.

The eGROUNDWATER project aims to improve sustainable, participatory groundwater management in the Mediterranean region by developing and testing Enhanced Information Systems (EIS) that integrate citizen science and information and communication technology (ICT) tools. A key component of the EIS is a mobile app that will allow farmers and other groundwater users to report groundwater levels in their wells and the amount of water used for irrigation and other purposes. At the same time, the app will provide users with information about the state of the aquifer and recommendations for sustainable water use (for example, short-term and seasonal predictions of irrigation water needs).The eGROUNDWATER app has the potential to be a valuable tool for improving the sustainable use and management of aquifers in the Mediterranean region. By gathering real-time data from a wide range of users, the app will help to create a more complete and accurate picture of groundwater conditions and usage. Policymakers and resource managers can use this information to make informed decisions about the allocation and use of water resources. It can also help to identify potential problems and areas where conservation efforts may be needed.The development of an app that meets the needs of the users required first to understand their perspectives and experiences related to the groundwater body. eGROUNDWATER has organized interviews and meetings in each case study to characterize the vision of the different agents on the groundwater bodies, and to try to build a collective framing of the current groundwater status and use in the area. On these meetings, the users identified lack of information about the aquifer as a critical issue to solve in order to advance towards a sustainable management of the resource.In addition to providing valuable data and information, the eGROUNDWATER app has the potential to engage and educate farmers and other users about the importance of sustainable water management. The app can foster a sense of ownership and responsibility for the aquifer's health among users, as it offers personalized feedback and information about the use of water and the aquifer’s health. This, in turn, could lead to more responsible water use practices and help to preserve groundwater resources for the long-term.The eGROUNDWATER project and its accompanying mobile app offer a promising approach to improving the sustainable use and management of aquifers in the Mediterranean region. The engagement of stakeholders in the development process and the collection and sharing of useful data and information through the app can help promoting education and awareness about water resource management. These efforts can help to foster a greater understanding of the importance of these resources and encourage more sustainable use of aquifers in the region, significantly contributing to the long-term sustainability of Mediterranean aquifers.Acknowledgements:This study has received funding from the eGROUNDWATER project (GA n. 1921) a project from the PRIMA programme, supported by Horizon 2020, the European Union's Framework Programme for Research and Innovation.

Introdução: A qualidade dos cuidados relativos à gestação, ao parto e ao puerpério contribui para a saúde materno-infantil. Métodos: Estudo quantitativo, exploratório e transversal, que levantou o perfil de 87 puérperas e avaliou o seu grau de satisfação com a assistência gravídico-puerperal. Resultados: As puérperas tinham entre 20 e 29 anos (47,1%), companheiro(a) (90,8%), ensino médio completo (32,2%) e atividade profissional (42,5%). A maioria teve até duas gestações (63,2%), sendo 40,2% a taxa de cesariana no último parto. Discussões: Constatou-se maior satisfação quanto ao atendimento recebido na internação em comparação ao pré-natal, o que se relacionou à presença de acompanhante no parto e ao contato permanente com o recém-nascido. Informações sobre amamentação foram avaliadas como muito satisfatórias, enquanto a maior insatisfação relacionou-se à falta de espaço para relatar sentimentos e preocupações nas consultas pré-natais. Conclusões: Esses achados indicam a importância de abordar os aspectos emocionais e relacionais no acompanhamento pré-natal e ao nascimento.

In the application of machine learning to real-life decision-making systems, e.g., credit scoring and criminal justice, the prediction outcomes might discriminate against people with sensitive attributes, leading to unfairness. The commonly used strategy in fair machine learning is to include fairness as a constraint or a penalization term in the minimization of the prediction loss, which ultimately limits the information given to decision-makers. In this paper, we introduce a new approach to handle fairness by formulating a stochastic multi-objective optimization problem for which the corresponding Pareto fronts uniquely and comprehensively define the accuracy-fairness trade-offs. We have then applied a stochastic approximation-type method to efficiently obtain well-spread and accurate Pareto fronts, and by doing so we can handle training data arriving in a streaming way.

Estudos relatam uma íntima relação entre o crescimento de transtornos de ansiedade e depressão na população jovem e a rotina acadêmica, especialmente quando considerado o curso de medicina. Paralelamente, devido à facilidade de acesso e à crença na ausência de malefícios, faz com que os fitoterápicos atuantes no sistema nervoso central sejam uma alternativa bastante procurada por esse público. Dessa forma, o objetivo dessa pesquisa foi traçar o perfil de consumo de produtos naturais de origem vegetal para ação no sistema nervoso central em acadêmicos de medicina em uma universidade pública no nordeste do Brasil. Para tanto, as informações foram coletadas por meio de questionário online contendo perguntas específicas a partir de uma abordagem direta aos acadêmicos de medicina de uma universidade pública do nordeste brasileiro, considerando os fatores de inclusão e exclusão, sendo registrado na Plataforma Brasil do Ministério da Saúde – CAAE nº 50027121.0.0000.5011. O estudo contou com 125 participantes, onde 59 participantes afirmaram utilizar ou já terem utilizado fitoterápicos para o sistema nervoso central, sendo a Passiflora incarnata e a Valeriana officinalis as espécies mais utilizadas. Práticas inadequadas foram constatadas como a automedicação e a troca de receita. Problemas com a faculdade se mostraram como importantes estressores psicossociais e incentivadores para utilização de psicofármacos naturais. Por fim, a pesquisa apresentou semelhanças com a literatura e evidencia uma ampla utilização, sem o devido aconselhamento profissional, de fitoterápicos entre os estudantes de medicina. Studies report a close relationship between the increase of anxiety and depression disorders in the young population and academic routine, especially when considering the medical course. At the same time, due to the easy access and the popular belief of harmlessness, nervous system acting herbal medicines are being much sought after by this group. Thus, this research aimed to trace the consumption profile of central nervous system acting natural products in medical students at a public university in northeastern Brazil. To this end, information was collected through an online form containing specific direct questions to medical students from a public university in northeastern, considering the inclusion and exclusion factors. It was registered on the Brazil Platform of the Ministry of Health. – CAAE No. 50027121.0.0000.5011. The study had 125 participants, where 59 participants claimed to use or have used nervous system acting herbal medicines, with Passiflora incarnata and Valeriana officinalis being the most used species. Inadequate practices were found, such as self-medication and prescription change. College related issues proved to be important psychosocial stressors and incentives for the use of natural psychotropic drugs. Finally, the research presented similarities with the literature, evidencing a wide use, without proper professional advice, of herbal medicines among medical students. Estudios reportan una íntima relación entre el crecimiento de los trastornos de ansiedad y depresión en la población joven y la rutina académica, especialmente cuando se considera la carrera de medicina. Al mismo tiempo, por la facilidad de acceso y la creencia en la ausencia de daño, hace que los medicamentos a base de hierbas que actúan sobre el sistema nervioso central sean una alternativa muy buscada por este público. Por lo tanto, el objetivo de esta investigación fue rastrear el perfil de consumo de productos naturales de origen vegetal para la acción sobre el sistema nervioso central en estudiantes de medicina en una universidad pública en el noreste de Brasil. Para ello, se recolectó información a través de un cuestionario en línea que contenía preguntas específicas de un abordaje directo a estudiantes de medicina de una universidad pública del nordeste de Brasil, considerando los factores de inclusión y exclusión, siendo registrado en la Plataforma Brasil del Ministerio de Salud – CAAE No 50027121.0.0000.5011. El estudio contó con 125 participantes, donde 59 participantes afirmaron usar o ya usaron medicamentos a base de hierbas para el sistema nervioso central, siendo Passiflora incarnata y Valeriana officinalis las especies más utilizadas. Se encontraron prácticas inadecuadas, como la automedicación y el cambio de recetas. Los problemas con la universidad demostraron ser factores estresantes psicosociales importantes e incentivos para el uso de psicofármacos naturales. Finalmente, la investigación presentó similitudes con la literatura y evidencia un amplio uso, sin el debido asesoramiento profesional, de fitoterápicos entre los estudiantes de medicina.

The differential growth and yield response of plant species to rising carbon dioxide concentrations and climatic change may alter species diversity within biomes. The Pampa Biome in South America is an important grassland biome of agronomic and environmental importance.

Made available in DSpace on 2022-04-29T08:41:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The pulp and paper industry is increasingly seeking a sustainable and conscientious development, minimizing the environmental impacts caused by it. Therefore, reducing efficiently the number of stages used in the bleaching process can mean less consumption of water and chemical reagents, contributing to the reduction of harmful waste to the environment. Thus, this study sought to evaluate the pulp quality and some physical-mechanical properties (smoothness, tear and tensile indexes) of two new bleaching sequences A∗DP and A∗E∗DP and compare them with the reference D0(E+P)D1P. To do so, industrial eucalyptus Kraft pulp pre-delignified with oxygen was used. The bleached pulp was refined to 1200, 1800 and 2400, in PFI mill and tested according to TAPPI standards to determine smoothness, tear and tensile indexes. Based on the results obtained, it was verified that the sequences studied are viable for using in bleaching plants, which allowed a reduction in the chlorine dioxide consumption and presented satisfactory smoothness, tear and tensile indexes for paper. Universidade Júlio de Mesquita Filho (Unesp) Campus Experimental de Itapeva, Rua Geraldo Alckmin, 519, Vila N. Sra. Fátima, Itapeva Universidade Júlio de Mesquita Filho (Unesp) Campus Experimental de Itapeva, Rua Geraldo Alckmin, 519, Vila N. Sra. Fátima, Itapeva

Objectives: Due to COVID-19 pandemic, social distancing policies were enacted worldwide, including by the Portuguese official authorities. However, the impact of these measures on maxillofacial trauma and fracture surgical repair remains poorly understood. The aim of this study was to evaluate and compare the incidence and aetiology of facial fractures submitted to surgical repair during 1-year of COVID-19 pandemic versus the previous 4 years, in a level III Trauma Centre located in Lisbon, Portugal. Materials and methods: All emergency episodes registered in our hospital between March 2016 and February 2021 that resulted in patient admittance for surgical treatment of facial fracture were included. Comparative analysis was performed for variables such as fracture type and aetiology. Results: Analysis showed that surgeries performed during the 1st year of COVID-19 were reduced by 37.5 %. Considering only the 75-day lockdown period at the beginning of the pandemic, reduction was even more pronounced and reached -66.7 %. Significant diffe­rences in the aetiology were also found, with physical assault and sport accidents relative frequency decreasing. Moreover, despite being systematically the second most common cause of fracture, during lockdown, fall ranked first, over physical assault. The relative frequency of nasal fractures, the most common facial fracture treated in our hospital, decreased during both the 1st year of COVID-19 and the lockdown period, while mandible fractures ranked first during lockdown. Conclusions: Our study shows that COVID-19 pandemic and enacted policies have significantly changed the epidemiology of maxillofacial trauma.

Using tail bounds, we introduce a new probabilistic condition for function estimation in stochastic derivative-free optimization which leads to a reduction in the number of samples and eases algorithmic analyses. Moreover, we develop simple stochastic direct-search and trust-region methods for the optimization of a potentially non-smooth function whose values can only be estimated via stochastic observations. For trial points to be accepted, these algorithms require the estimated function values to yield a sufficient decrease measured in terms of a power larger than 1 of the algoritmic stepsize. Our new tail-bound condition is precisely imposed on the reduction estimate used to achieve such a sufficient decrease. This condition allows us to select the stepsize power used for sufficient decrease in such a way to reduce the number of samples needed per iteration. In previous works, the number of samples necessary for global convergence at every iteration k of this type of algorithms was O(Delta_k^{-4}), where Delta_k is the stepsize or trust region radius. However, using the new tail-bound condition, and under mild assumptions on the noise, one can prove that such a number of samples is only O(Delta_k^{-2 - eps}), where eps > 0 can be made arbitrarily small by selecting the power of the stepsize in the sufficient decrease test arbitrarily close to 1. The global convergence properties of the stochastic direct-search and trust-region algorithms are established under the new tail bound condition.