The CRISPR/CAS9 technology as a tool for cancer research and therapy

ABSTRACT : CRISPR-Cas9 is a novel gene editing tool that came from the immune system of bacteria against viruses, modified to become one of the most efficient technologies in molecular medicine. The main goal of this final degree project is to systematically review the state of-the-art about the CRISPR-Cas9-based gene-editing tools and their applications in cancer therapy and investigation. A total of 142 articles were used, with any type of design published from 2010 to 2021 with a 3.0 or higher Journal Impact Factor. In investigation, the CRISPR-Cas9-based technology can form knock-outs, knock-ins and chromosomal rearrangements mimicking carcinogenesis and, additionally, can be used to screen for these modifications with CRISPR-Cas9 libraries. Most of its potential is focused towards therapy, with clinical trials on-the-go, being most of the efforts directed to correct the inactivation of tumor-suppressor-genes, to delete fusion oncogenes and to counteract viral proteins in viral driven cancers. In immunotherapy, it contributes to the programming of CAR-T cells and the inhibition of immune checkpoints. Finally, CRISPR-Cas9 can screen for mutations responsible for drug resistance, helping to establish an alternative to poorly responsive tumors. Even though the risk of off-target mutations is the main disadvantage, CRISPR-Cas9 gives hope for high precision medicine.RESUMEN : CRISPR-Cas9 es una nueva herramienta de edición de genes derivada del sistema inmune de las bacterias contra los virus, modificada para establecerse como una de las más eficientes estrategias disponibles en la medicina molecular. El objetivo principal de este trabajo de fin de grado es recordar los mecanismos de reparación del ADN y revisar sistemáticamente el funcionamiento del CRISPR-Cas9 y sus aplicaciones en terapia e investigación del cáncer. Se usaron 142 artículos publicados desde 2010 hasta 2021 incluyendo todo tipo de diseño, con un Factor de Impacto superior a 3.0. En investigación, CRISPR-Cas9 puede eliminar genes (knock-outs), inserción de genes (knock-ins) y reordenar cromosomas en modelos carcinogénicos, aparte de su utilidad para rastrear mutaciones con genotecas específicas. En terapia, su uso se ha dirigido al desarrollo de ensayos clínicos, encaminados fundamentalmente a restablecer genes supresores de tumores, suprimir fusiones oncogénicas o inactivar proteínas tumorales virales. En inmunoterapia, ayuda a programar las células CAR-T e inhibir los puntos de control. Finalmente, CRISPR-Cas9 puede detectar mutaciones implicadas en la resistencia a agentes quimioterápicos, constituyéndose una alternativa en tumores de mal pronóstico. Aunque su mayor desventaja sean las mutaciones generadas fuera del sitio diana, CRISPR-Cas9 ofrece esperanzas hacia una medicina de alta precisión.Grado en Medicin

Arterite de Takayasu: relato de um caso em mulher de meia idade.

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Departamento de Clínica Médica, Curso de Medicina, Florianópolis, 198

Breaking rules: taking Complex Ontology Alignment beyond rule­based approaches

Tese de mestrado, Ciência de Dados, Universidade de Lisboa, Faculdade de Ciências, 2021As ontologies are developed in an uncoordinated manner, differences in scope and design compromise interoperability. Ontology matching is critical to address this semantic heterogeneity problem, as it finds correspondences that enable integrating data across the Semantic Web. One of the biggest challenges in this field is that ontology schemas often differ conceptually, and therefore reconciling many real¬world ontology pairs (e.g., in geography or biomedicine) involves establishing complex mappings that contain multiple entities from each ontology. Yet, for the most part, ontology matching algorithms are restricted to finding simple equivalence mappings between ontology entities. This work presents novel algorithms for Complex Ontology Alignment based on Association Rule Mining over a set of shared instances between two ontologies. Its strategy relies on a targeted search for known complex patterns in instance and schema data, reducing the search space. This allows the application of semantic¬based filtering algorithms tailored to each kind of pattern, to select and refine the most relevant mappings. The algorithms were evaluated in OAEI Complex track datasets under two automated approaches: OAEI’s entity¬based approach and a novel element¬overlap–based approach which was developed in the context of this work. The algorithms were able to find mappings spanning eight distinct complex patterns, as well as combinations of patterns through disjunction and conjunction. They were able to efficiently reduce the search space and showed competitive performance results comparing to the State of the Art of complex alignment systems. As for the comparative analysis of evaluation methodologies, the proposed element¬overlap–based evaluation strategy was shown to be more accurate and interpretable than the reference-based automatic alternative, although none of the existing strategies fully address the challenges discussed in the literature. For future work, it would be interesting to extend the algorithms to cover more complex patterns and combine them with lexical approaches

Development of a GIS-Based Information System for Watershed Monitoring in Mato Grosso, Central Brazil

This paper describes the conceptual framework and implementation of a prototype for a GIS-based Information System for Watershed Monitoring and Planning in the state of Mato Grosso, Central Brazil. The system was developed to support the implementation of water resources management policies passed by Brazilian federal and state legislatures in 1997.The first phase of the information system development was focused on database design, to create modules for the storage and pre-processing of diverse environmental data sets and for georeferenced registration and control of water users. The GIS environment includes tools for data mining and integrating the NGFlow and QUAL2E models for river runoff and water quality simulation; these tools were successfully validated in the Cuiabá River basin. To guarantee acceptance and continuity of system maintenance in regions under development, GIS applications for watershed management should be component-based. They should also integrate models with robustness for input data that are poor in consistency and quality. Finally, they should be implemented with development tools already used by local technical staff and have a high degree of user friendliness.This paper describes the conceptual framework and implementation of a prototype for a GIS-based Information System for Watershed Monitoring and Planning in the state of Mato Grosso, Central Brazil. The system was developed to support the implementation of water resources management policies passed by Brazilian federal and state legislatures in 1997.The first phase of the information system development was focused on database design, to create modules for the storage and pre-processing of diverse environmental data sets and for georeferenced registration and control of water users. The GIS environment includes tools for data mining and integrating the NGFlow and QUAL2E models for river runoff and water quality simulation; these tools were successfully validated in the Cuiabá River basin. To guarantee acceptance and continuity of system maintenance in regions under development, GIS applications for watershed management should be component-based. They should also integrate models with robustness for input data that are poor in consistency and quality. Finally, they should be implemented with development tools already used by local technical staff and have a high degree of user friendliness

Chemical composition, antibacterial and repellent activities of Azorella trifurcata, Senecio pogonias, and Senecio oreophyton essential oils

The antibacterial and insect-repellent activities of the essential oils (EOs) from Argentinian medicinal plants Azorella trifurcata (Gaertn.) Pers., Senecio cfr. oreophyton J. Remy and Senecio cfr. pogonias Cabrera, were investigated. All EOs showed good repellent properties against Triatoma infestans Klug, the vector of the Chagas disease, with percent repellence values between 60% and 70% at 24 hours compared with positive control N-N diethyl-m-methylbenzamide (DEET) and moderate activity against the bacteria tested with minimum inhibitory concentrations (MICs) values between 31.2 and 2000 μg/ml. The Azorella trifurcata, Senecio pogonias and S. oreophyton EOs, obtained by hydrodistillation, were characterized by GC-FID and GC/MS analyses. Spathulenol (38.2%), myrtenyl acetate (8.4%) and α-terpineol (4.5%), limonene (9.8%) and α-thujene (5.4%) were the main constituents in the EO of Azorella trifurcata. The Senecio pogonias and S. oreophyton EOs are characterized by a high content of monoterpenes hydrocarbons (92% and 95.1%, respectively) with α-pinene, the main component in both oils. To our knowledge, the essential oil composition from Andean medicinal plants A. trifurcata, Senecio pogonias and S. oreophyton collected in central Andean slopes are reported for first time.Fil: López, Sandra Beatriz. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Lima, Beatriz Viviana. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Agüero, María Belén. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López, María Liza. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hadad, Martín Ariel. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zygadlo, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Caballero, Duilio. Provincia de San Juan. Hospital Marcial Quiroga; ArgentinaFil: Stariolo, Raúl Luis. Ministerio de Salud. Secretaría de Programas Sanitarios. Subsecretaría de Programas de Prevención y Promoción. Coordinación Nacional de Control de Vectores; ArgentinaFil: Suero, Eduardo. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentin

Galactosemia, intolerância à lactose e alergia à proteína do leite: compreensão dos mecanismos fisiopatológicos na primeira infância e suas respectivas prescrições nutricionais

The objective of this study is to explain three similar pathologies that manifest in children in their early childhood, contributing to nutritionists and pediatricians and encouraging multidisciplinary work. The rare genetic error that affects neonates and prevents the metabolization of galactose is called classic Galactosemia. The body's immune response to children's early exposure to certain proteins, such as casein and lactoglobulin, is known as cow's milk protein allergy. Finally, lactose intolerance, which is subdivided into primary, secondary and congenital, which is the most common in children, making it impossible to produce the enzyme that would absorb lactose. This article will present a bibliographic review on the possible appropriate therapies to avoid nutritional deficiencies as a result of the need to restrict or exclude milk from their diets. The research used a total of 33 articles found in the Science, Scielo and Google Scholar databases.El objetivo de este estudio es explicar tres patologías cercanas que se manifiestan en los niños en su primera infancia, contribuyendo con nutricionistas y pediatras y fomentando el trabajo multidisciplinar. El raro error genético que afecta a los recién nacidos y que hace imposible el metabolismo de la galactosa se denomina galactosemia clásica. La reacción inmunológica del cuerpo a la exposición temprana de los niños a ciertas proteínas, como la caseína y la lactoglobulina, se conoce como Alergia a la proteína de la leche de vaca. Y por último, la intolerancia a la lactosa, que se subdivide en primaria, secundaria y congénita, es la más común en los niños, haciendo imposible la producción de la enzima que haría la absorción de la lactosa. Se presentará una revisión de la literatura sobre las posibles terapias apropiadas para evitar las deficiencias nutricionales como consecuencia de la necesidad de restringir o excluir los alimentos lácteos en sus dietas. La búsqueda utilizó un total de 33 artículos encontrados en las bases Science, Scielo y Google Academic.O objetivo desse estudo é explicar três patologias próximas que manifestam-se em crianças na sua primeira infância, contribuindo com nutricionistas e pediatras e incentivando um trabalho multidisciplinar. O erro genético raro que acomete os neonatais e impossibilita a metabolização da galactose é denominado como Galactosemia clássica. A reação imunológica do corpo à exposição precoce das crianças a determinadas proteínas, como a caseína e lactoglobulina, é conhecida como Alergia à proteína do leite de vaca. E por fim, a Intolerância à lactose que é subdividida em primária, secundária e congênita, sendo esta a mais comum em crianças impossibilitando a produção da enzima que faria a absorção da lactose. Este artigo apresentará uma revisão bibliográfica sobre as possíveis terapêuticas adequadas para se evitar deficiências nutricionais em consequência da necessidade de restrição ou exclusão do alimento leite nas suas dietas. A pesquisa utilizou um total de 33 artigos encontrados nas bases Science, Scielo e Google Acadêmico

Balanced Scorecard adoption in Portuguese organizations: Contingent and institutional variables

Objeto: Este artículo tiene como objetivo identificar y analizar un conjunto de variables contingentes e institucionales que pueden potencialmente influir en el conocimiento e implementación del Cuadro de Mando Integral (CMI) en las organizaciones portuguesas pertenecientes al sector público y privado. Diseño/metodología: Para comprobar empíricamente las hipótesis de investigación formuladas hemos recurrido a los datos obtenidos mediante la aplicación de un cuestionario postal a 591 organizaciones públicas y 549 organizaciones privadas portuguesas, con una tasa de respuesta total del 31,3%. Aportaciones y resultados: Los resultados obtenidos indican la asociación entre el conocimiento CMI y el grado de formación de los empleados, así como entre la implementación del CMI y la realización de cursos de formación. Por otro lado, no hemos obtenido evidencia empírica respecto a la posible relación entre la implementación del CMI y el grado de comunicación interna, el recurso a consultores externos, cuestiones de “modas de gestión” y la búsqueda de legitimidad. Valor añadido: En la revisión de la literatura no se encontraron elementos bibliográficos sobre los factores contingentes e instituciones determinantes en la adopción del CMI en Portugal, hecho que nos permitió dar a este estudio un enfoque innovador. Además, se ha caracterizado la situación del CMI en Portugal haciendo un estudio comparativo con los resultados obtenidos en estudios llevados a cabo en otros países.Purpose: In this article we aim to identify and analyze a set of contingent and institutional variables that can potentially influence the knowledge and the adoption of the Balanced Scorecard (BSC) in Portuguese public and private organizations. Design/methodology/approach: Hypotheses were tested using data obtained from a questionnaire sent to 591 public organizations and 549 private organizations in Portugal, with an overall response rate of 31.3%. Findings and Originality/value: The results indicate the association between BSC knowledge and the level of training of employees, and between BSC implementation and conducting training courses. On the other hand, we did not obtain empirical evidence regarding the possible relationship between the BSC implementation and the degree of internal communication, the use of external consultants, questions of "management fads" and the search for legitimacy. Originality/value: In the literature review we did not found bibliographic elements about the contingent and institutional factors that determine the BSC adoption in Portugal, a fact that allowed us to give this study an innovative approach. Moreover, the BSC situation in Portugal has been characterized, doing a comparative study with the results of studies conducted in other countries.Peer Reviewe

A imagem de Portugal enquanto destino do turismo equestre: estudo das motivações e do perfil da procura

O turismo equestre registou um crescimento significativo ao longo das últimas duas décadas. Este crescimento deve-se em parte à crescente popularidade dos desportos equestres no mundo desenvolvido e, em parte, à necessidade de diversificar a base de rendimentos da indústria equestre. Tomljenović et al. (2018) refere, no entanto, que a investigação tanto da oferta como da procura de turismo equestre é ainda rara, fragmentada e incomparável, atrasando a criação de um corpo coerente de conhecimentos e o desenvolvimento de um modelo conceptual que proporcionaria uma abordagem sistemática à conceção de estratégias de desenvolvimento do turismo equestre, orientando o empreendedorismo e as ações a nível de destinos. O propósito deste trabalho assenta, principalmente, em conhecer o turismo equestre como produto turístico e como forma de turismo em Portugal, desenvolvendo assim o tópico da imagem que Portugal detém enquanto destino de turismo equestre. Pretende-se dar a conhecer o turismo equestre, as suas características, a sua história, como este está representado em território nacional e, também, desenvolver um estudo sobre o perfil do turista equestre atualmente e sobre as suas motivações. A metodologia teve por base uma revisão de literatura prévia e a realização de 4 entrevistas exploratórias a empresas diretamente ligadas à área do turismo equestre. Foram também realizados inquéritos por questionário a turistas que praticam (ou já praticaram) turismo equestre em Portugal, por forma a não só perceber em que patamar se encontra este tipo de turismo atualmente em território nacional, como também poder construir uma base de dados atualizada sobre o turista equestre. Os resultados permitiram perceber que o turista equestre possui diversos motivos que o levam à prática de atividades equestres em Portugal, entre eles a raça dos cavalos (nomeadamente o Puro-Sangue Lusitano), a qualidade e reputação dos serviços, a qualidade das instalações, dos colaboradores, dos instrutores, a proximidade com os cavalos, a gastronomia, a paisagem e a natureza envolvente, o relaxamento e a fuga à rotina.ABSTRACT: Equestrian tourism has experienced significant growth over the past two decades. This growth is partly due to the increasing popularity of equestrian sports in the developed world, and partly due to the need to diversify the revenue base of the equestrian industry. Tomljenović et al. (2018) notes, however, that research on both the supply and demand of equestrian tourism is still rare, fragmented, and unmatched, delaying the creation of a coherent body of knowledge and the development of a conceptual model that would provide a systematic approach to the design of equestrian tourism development strategies, guiding entrepreneurship and actions at the destination level. The purpose of this work is mainly based on knowing equestrian tourism as a tourism product and as a form of tourism in Portugal, thus developing the topic of the destination image that Portugal holds as a destination for equestrian tourism. We intend to make equestrian tourism known, its characteristics, its history, how it is represented in the national territory and also to develop a study on the profile of the equestrian tourist nowadays and on their motivations through a previous literature review and also through 4 exploratory interviews to some companies directly linked to the area of equestrian tourism, and also questionnaire surveys to tourists who practice (or have practiced) equestrian tourism in Portugal, in order to not only understand at what level we can find this type of tourism currently in national territory, but also to be able to build an updated database on the equestrian tourist. The qualitative and quantitative methodology used in this study allowed us to realize that the equestrian tourist has several reasons that lead him to practice equestrian tourism activities in Portugal, among them the horses (namely the Lusitano breed), the quality and reputation of the services, the quality of the facilities, the staff, the instructors, the proximity to the horses, the gastronomy, the landscape and the surrounding nature, the relaxation and the escape from routine