3,804 research outputs found

    Engineering stimuli-responsive microparticles for biomedical applications

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    The use of polyphenol-based coating mechanisms has emerged as a facile and versatile method to generate multifunctional thin films for several applications including energy storage, separation, and drug delivery. The scope of this thesis is to investigate the use of two polyphenol-based mechanisms for the assembly of microcapsules for drug delivery: polydopamine and metal-phenolic networks. The mussel-inspired polydopamine has been widely studied for its adhesive and biocompatible properties. The first aspect of this thesis is to investigate the adhesion of polydopamine-coated microparticles to biological tissues. The exploitation of the simple coating mechanism onto micron-sized drug-loaded template is used to improve the retention of the drug delivery system to the target site allowing a sustained release of the therapeutics. The second aspect was to evaluate the biological effect of oligonucleotide-releasing polydopamine-coated microparticles as a tool for the investigation of the suppression of the yes-associated protein on synovial fibroblasts. The third aspect was to exploit the use of metal-phenolic networks to generate enzyme-cleavable microcapsules as endogenous stimuli-responsive drug delivery systems. The use of cell-secreted proteases could be used as a trigger for the degradation and release of therapeutic agents to the desired site. In summary, the use of two classes of polyphenol-based chemistry: polydopamine and metal-phenolic networks are investigated for their use in the biomedical field.Open Acces

    Performance Evaluation of Smart Decision Support Systems on Healthcare

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    Medical activity requires responsibility not only from clinical knowledge and skill but also on the management of an enormous amount of information related to patient care. It is through proper treatment of information that experts can consistently build a healthy wellness policy. The primary objective for the development of decision support systems (DSSs) is to provide information to specialists when and where they are needed. These systems provide information, models, and data manipulation tools to help experts make better decisions in a variety of situations. Most of the challenges that smart DSSs face come from the great difficulty of dealing with large volumes of information, which is continuously generated by the most diverse types of devices and equipment, requiring high computational resources. This situation makes this type of system susceptible to not recovering information quickly for the decision making. As a result of this adversity, the information quality and the provision of an infrastructure capable of promoting the integration and articulation among different health information systems (HIS) become promising research topics in the field of electronic health (e-health) and that, for this same reason, are addressed in this research. The work described in this thesis is motivated by the need to propose novel approaches to deal with problems inherent to the acquisition, cleaning, integration, and aggregation of data obtained from different sources in e-health environments, as well as their analysis. To ensure the success of data integration and analysis in e-health environments, it is essential that machine-learning (ML) algorithms ensure system reliability. However, in this type of environment, it is not possible to guarantee a reliable scenario. This scenario makes intelligent SAD susceptible to predictive failures, which severely compromise overall system performance. On the other hand, systems can have their performance compromised due to the overload of information they can support. To solve some of these problems, this thesis presents several proposals and studies on the impact of ML algorithms in the monitoring and management of hypertensive disorders related to pregnancy of risk. The primary goals of the proposals presented in this thesis are to improve the overall performance of health information systems. In particular, ML-based methods are exploited to improve the prediction accuracy and optimize the use of monitoring device resources. It was demonstrated that the use of this type of strategy and methodology contributes to a significant increase in the performance of smart DSSs, not only concerning precision but also in the computational cost reduction used in the classification process. The observed results seek to contribute to the advance of state of the art in methods and strategies based on AI that aim to surpass some challenges that emerge from the integration and performance of the smart DSSs. With the use of algorithms based on AI, it is possible to quickly and automatically analyze a larger volume of complex data and focus on more accurate results, providing high-value predictions for a better decision making in real time and without human intervention.A atividade médica requer responsabilidade não apenas com base no conhecimento e na habilidade clínica, mas também na gestão de uma enorme quantidade de informações relacionadas ao atendimento ao paciente. É através do tratamento adequado das informações que os especialistas podem consistentemente construir uma política saudável de bem-estar. O principal objetivo para o desenvolvimento de sistemas de apoio à decisão (SAD) é fornecer informações aos especialistas onde e quando são necessárias. Esses sistemas fornecem informações, modelos e ferramentas de manipulação de dados para ajudar os especialistas a tomar melhores decisões em diversas situações. A maioria dos desafios que os SAD inteligentes enfrentam advêm da grande dificuldade de lidar com grandes volumes de dados, que é gerada constantemente pelos mais diversos tipos de dispositivos e equipamentos, exigindo elevados recursos computacionais. Essa situação torna este tipo de sistemas suscetível a não recuperar a informação rapidamente para a tomada de decisão. Como resultado dessa adversidade, a qualidade da informação e a provisão de uma infraestrutura capaz de promover a integração e a articulação entre diferentes sistemas de informação em saúde (SIS) tornam-se promissores tópicos de pesquisa no campo da saúde eletrônica (e-saúde) e que, por essa mesma razão, são abordadas nesta investigação. O trabalho descrito nesta tese é motivado pela necessidade de propor novas abordagens para lidar com os problemas inerentes à aquisição, limpeza, integração e agregação de dados obtidos de diferentes fontes em ambientes de e-saúde, bem como sua análise. Para garantir o sucesso da integração e análise de dados em ambientes e-saúde é importante que os algoritmos baseados em aprendizagem de máquina (AM) garantam a confiabilidade do sistema. No entanto, neste tipo de ambiente, não é possível garantir um cenário totalmente confiável. Esse cenário torna os SAD inteligentes suscetíveis à presença de falhas de predição que comprometem seriamente o desempenho geral do sistema. Por outro lado, os sistemas podem ter seu desempenho comprometido devido à sobrecarga de informações que podem suportar. Para tentar resolver alguns destes problemas, esta tese apresenta várias propostas e estudos sobre o impacto de algoritmos de AM na monitoria e gestão de transtornos hipertensivos relacionados com a gravidez (gestação) de risco. O objetivo das propostas apresentadas nesta tese é melhorar o desempenho global de sistemas de informação em saúde. Em particular, os métodos baseados em AM são explorados para melhorar a precisão da predição e otimizar o uso dos recursos dos dispositivos de monitorização. Ficou demonstrado que o uso deste tipo de estratégia e metodologia contribui para um aumento significativo do desempenho dos SAD inteligentes, não só em termos de precisão, mas também na diminuição do custo computacional utilizado no processo de classificação. Os resultados observados buscam contribuir para o avanço do estado da arte em métodos e estratégias baseadas em inteligência artificial que visam ultrapassar alguns desafios que advêm da integração e desempenho dos SAD inteligentes. Como o uso de algoritmos baseados em inteligência artificial é possível analisar de forma rápida e automática um volume maior de dados complexos e focar em resultados mais precisos, fornecendo previsões de alto valor para uma melhor tomada de decisão em tempo real e sem intervenção humana

    ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

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    BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses

    Centralized scientific communities are less likely to generate replicable results

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    Concerns have been expressed about the robustness of experimental findings in several areas of science, but these matters have not been evaluated at scale. Here we identify a large sample of published drug-gene interaction claims curated in the Comparative Toxicogenomics Database (for example, benzo(a)pyrene decreases expression of SLC22A3) and evaluate these claims by connecting them with high-throughput experiments from the LINCS L1000 program. Our sample included 60,159 supporting findings and 4253 opposing findings about 51,292 drug-gene interaction claims in 3363 scientific articles. We show that claims reported in a single paper replicate 19.0% (95% confidence interval [CI], 16.9–21.2%) more frequently than expected, while claims reported in multiple papers replicate 45.5% (95% CI, 21.8–74.2%) more frequently than expected. We also analyze the subsample of interactions with two or more published findings (2493 claims; 6272 supporting findings; 339 opposing findings; 1282 research articles), and show that centralized scientific communities, which use similar methods and involve shared authors who contribute to many articles, propagate less replicable claims than decentralized communities, which use more diverse methods and contain more independent teams. Our findings suggest how policies that foster decentralized collaboration will increase the robustness of scientific findings in biomedical research

    A review on Natural Language Processing Models for COVID-19 research

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    This survey paper reviews Natural Language Processing Models and their use in COVID-19 research in two main areas. Firstly, a range of transformer-based biomedical pretrained language models are evaluated using the BLURB benchmark. Secondly, models used in sentiment analysis surrounding COVID-19 vaccination are evaluated. We filtered literature curated from various repositories such as PubMed and Scopus and reviewed 27 papers. When evaluated using the BLURB benchmark, the novel T-BPLM BioLinkBERT gives groundbreaking results by incorporating document link knowledge and hyperlinking into its pretraining. Sentiment analysis of COVID-19 vaccination through various Twitter API tools has shown the public’s sentiment towards vaccination to be mostly positive. Finally, we outline some limitations and potential solutions to drive the research community to improve the models used for NLP tasks

    Link prediction for interdisciplinary collaboration via co-authorship network

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    We analyse the Publication and Research (PURE) data set of University of Bristol collected between 20082008 and 20132013. Using the existing co-authorship network and academic information thereof, we propose a new link prediction methodology, with the specific aim of identifying potential interdisciplinary collaboration in a university-wide collaboration network
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