13,267 research outputs found

    Classification related to immunogenic cell death predicts prognosis, immune microenvironment characteristics, and response to immunotherapy in lower-grade gliomas

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    BackgroundImmunogenic cell death (ICD) is a form of cell death that elicits immune responses against the antigens found in dead or dying tumor cells. Growing evidence implies that ICD plays a significant role in triggering antitumor immunity. The prognosis for glioma remains poor despite many biomarkers being reported, and identifying ICD-related biomarkers is imminent for better-personalized management in patients with lower-grade glioma (LGG).Materials and methodsWe identified ICD-related differentially expressed genes (DEGs) by comparing gene expression profiles obtained across Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) cohorts. On the foundation of ICD-related DEGs, two ICD-related clusters were identified through consensus clustering. Then, survival analysis, functional enrichment analysis, somatic mutation analysis, and immune characteristics analysis were performed in the two ICD-related subtypes. Additionally, we developed and validated a risk assessment signature for LGG patients. Finally, we selected one gene (EIF2AK3) from the above risk model for experimental validation.Results32 ICD-related DEGs were screened, dividing the LGG samples from the TCGA database into two distinct subtypes. The ICD-high subgroup showed worse overall survival (OS), greater immune infiltration, more active immune response process, and higher expression levels of HLA genes than the ICD-low subgroup. Additionally, nine ICD-related DEGs were identified to build the prognostic signature, which was highly correlated with the tumor-immune microenvironment and could unambiguously be taken as an independent prognostic factor and further verified in an external dataset. The experimental results indicated that EIF2AK3 expression was higher in tumors than paracancerous tissues, and high-expression EIF2AK3 was enriched in WHO III and IV gliomas by qPCR and IHC, and Knockdown of EIF2AK3 suppressed cell viability and mobility in glioma cells.ConclusionWe established novel ICD-related subtypes and risk signature for LGG, which may be beneficial to improving clinical outcome prediction and guiding individualized immunotherapy

    History, Features, Challenges, and Critical Success Factors of Enterprise Resource Planning (ERP) in The Era of Industry 4.0

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    ERP has been adopting newer features over the last several decades and shaping global businesses with the advent of newer technologies. This research article uses a state-of-the-art review method with the purpose to review and synthesize the latest information on the possible integration of potential Industry 4.0 technologies into the future development of ERP. Different software that contributed to the development of the existing ERP is found to be Material Requirement Planning (MRP), Manufacturing Resource Planning (MRPII), and Computer Integrated Manufacturing (CIM). Potential disruptive Industry 4.0 technologies that are featured to be integrated into future ERP are artificial intelligence, business intelligence, the internet of things, big data, blockchain technology, and omnichannel strategy. Notable Critical Success Factors of ERP have been reported to be top management support, project team, IT infrastructure, communication, skilled staff, training & education, and monitoring & evaluation. Moreover, cybersecurity has been found to be the most challenging issue to overcome in future versions of ERP. This review article could help future ERP researchers and respective stakeholders contribute to integrating newer features in future versions of ERP

    A chromosome-scale genome assembly of Castanopsis hystrix provides new insights into the evolution and adaptation of Fagaceae species

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    Fagaceae species dominate forests and shrublands throughout the Northern Hemisphere, and have been used as models to investigate the processes and mechanisms of adaptation and speciation. Compared with the well-studied genus Quercus, genomic data is limited for the tropical-subtropical genus Castanopsis. Castanopsis hystrix is an ecologically and economically valuable species with a wide distribution in the evergreen broad-leaved forests of tropical-subtropical Asia. Here, we present a high-quality chromosome-scale reference genome of C. hystrix, obtained using a combination of Illumina and PacBio HiFi reads with Hi-C technology. The assembled genome size is 882.6 Mb with a contig N50 of 40.9 Mb and a BUSCO estimate of 99.5%, which are higher than those of recently published Fagaceae species. Genome annotation identified 37,750 protein-coding genes, of which 97.91% were functionally annotated. Repeat sequences constituted 50.95% of the genome and LTRs were the most abundant repetitive elements. Comparative genomic analysis revealed high genome synteny between C. hystrix and other Fagaceae species, despite the long divergence time between them. Considerable gene family expansion and contraction were detected in Castanopsis species. These expanded genes were involved in multiple important biological processes and molecular functions, which may have contributed to the adaptation of the genus to a tropical-subtropical climate. In summary, the genome assembly of C. hystrix provides important genomic resources for Fagaceae genomic research communities, and improves understanding of the adaptation and evolution of forest trees

    Bayesian networks for disease diagnosis: What are they, who has used them and how?

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    A Bayesian network (BN) is a probabilistic graph based on Bayes' theorem, used to show dependencies or cause-and-effect relationships between variables. They are widely applied in diagnostic processes since they allow the incorporation of medical knowledge to the model while expressing uncertainty in terms of probability. This systematic review presents the state of the art in the applications of BNs in medicine in general and in the diagnosis and prognosis of diseases in particular. Indexed articles from the last 40 years were included. The studies generally used the typical measures of diagnostic and prognostic accuracy: sensitivity, specificity, accuracy, precision, and the area under the ROC curve. Overall, we found that disease diagnosis and prognosis based on BNs can be successfully used to model complex medical problems that require reasoning under conditions of uncertainty.Comment: 22 pages, 5 figures, 1 table, Student PhD first pape

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    On the Mechanism of Building Core Competencies: a Study of Chinese Multinational Port Enterprises

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    This study aims to explore how Chinese multinational port enterprises (MNPEs) build their core competencies. Core competencies are firms’special capabilities and sources to gain sustainable competitive advantage (SCA) in marketplace, and the concept led to extensive research and debates. However, few studies include inquiries about the mechanisms of building core competencies in the context of Chinese MNPEs. Accordingly, answers were sought to three research questions: 1. What are the core competencies of the Chinese MNPEs? 2. What are the mechanisms that the Chinese MNPEs use to build their core competencies? 3. What are the paths that the Chinese MNPEs pursue to build their resources bases? The study adopted a multiple-case study design, focusing on building mechanism of core competencies with RBV. It selected purposively five Chinese leading MNPEs and three industry associations as Case Companies. The study revealed three main findings. First, it identified three generic core competencies possessed by Case Companies, i.e., innovation in business models and operations, utilisation of technologies, and acquisition of strategic resources. Second, it developed the conceptual framework of the Mechanism of Building Core Competencies (MBCC), which is a process of change of collective learning in effective and efficient utilization of resources of a firm in response to critical events. Third, it proposed three paths to build core competencies, i.e., enhancing collective learning, selecting sustainable processes, and building resource base. The study contributes to the knowledge of core competencies and RBV in three ways: (1) presenting three generic core competencies of the Chinese MNPEs, (2) proposing a new conceptual framework to explain how Chinese MNPEs build their core competencies, (3) suggesting a solid anchor point (MBCC) to explain the links among resources, core competencies, and SCA. The findings set benchmarks for Chinese logistics industry and provide guidelines to build core competencies

    DIN Spec 91345 RAMI 4.0 compliant data pipelining: An approach to support data understanding and data acquisition in smart manufacturing environments

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    Today, data scientists in the manufacturing domain are confronted with a set of challenges associated to data acquisition as well as data processing including the extraction of valuable in-formation to support both, the work of the manufacturing equipment as well as the manufacturing processes behind it. One essential aspect related to data acquisition is the pipelining, including various commu-nication standards, protocols and technologies to save and transfer heterogenous data. These circumstances make it hard to understand, find, access and extract data from the sources depend-ing on use cases and applications. In order to support this data pipelining process, this thesis proposes the use of the semantic model. The selected semantic model should be able to describe smart manufacturing assets them-selves as well as to access their data along their life-cycle. As a matter of fact, there are many research contributions in smart manufacturing, which already came out with reference architectures or standards for semantic-based meta data descrip-tion or asset classification. This research builds upon these outcomes and introduces a novel se-mantic model-based data pipelining approach using as a basis the Reference Architecture Model for Industry 4.0 (RAMI 4.0).Hoje em dia, os cientistas de dados no domínio da manufatura são confrontados com várias normas, protocolos e tecnologias de comunicação para gravar, processar e transferir vários tipos de dados. Estas circunstâncias tornam difícil compreender, encontrar, aceder e extrair dados necessários para aplicações dependentes de casos de utilização, desde os equipamentos aos respectivos processos de manufatura. Um aspecto essencial poderia ser um processo de canalisação de dados incluindo vários normas de comunicação, protocolos e tecnologias para gravar e transferir dados. Uma solução para suporte deste processo, proposto por esta tese, é a aplicação de um modelo semântico que descreva os próprios recursos de manufactura inteligente e o acesso aos seus dados ao longo do seu ciclo de vida. Muitas das contribuições de investigação em manufatura inteligente já produziram arquitecturas de referência como a RAMI 4.0 ou normas para a descrição semântica de meta dados ou classificação de recursos. Esta investigação baseia-se nestas fontes externas e introduz um novo modelo semântico baseado no Modelo de Arquitectura de Referência para Indústria 4.0 (RAMI 4.0), em conformidade com a abordagem de canalisação de dados no domínio da produção inteligente como caso exemplar de utilização para permitir uma fácil exploração, compreensão, descoberta, selecção e extracção de dados

    One emoji, many meanings: A corpus for the prediction and disambiguation of emoji sense

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    In this work, we uncover a hidden linguistic property of emoji, namely that they are polysemous and can be used to form a semantic network of emoji meanings. Our key contributions to this direction of study are as follows: (1) We have developed a new corpus to help in the task of emoji sense prediction. This corpus contains tweets with single emojis, where each emoji has been labelled with an appropriate sense identifier from WordNet. (2) Experiments, which demonstrate that it is possible to predict the sense of an emoji using our corpus to a reasonable level of accuracy. We are able to report an average path-similarity score of 0.4146 for our best emoji sense prediction algorithm. (3) We further show that emoji sense is a useful feature in the emoji prediction task, where we report an accuracy of 58.8816 and macro-F1 score of 46.6640, beating reasonable baselines in this task. Our work demonstrates that importance of considering the meaning behind emoji, rather than ignoring them, or simply treating them as extra wordforms

    RAMPVIS: Answering the Challenges of Building Visualisation Capabilities for Large-scale Emergency Responses

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    The effort for combating the COVID-19 pandemic around the world has resulted in a huge amount of data, e.g., from testing, contact tracing, modelling, treatment, vaccine trials, and more. In addition to numerous challenges in epidemiology, healthcare, biosciences, and social sciences, there has been an urgent need to develop and provide visualisation and visual analytics (VIS) capacities to support emergency responses under difficult operational conditions. In this paper, we report the experience of a group of VIS volunteers who have been working in a large research and development consortium and providing VIS support to various observational, analytical, model-developmental, and disseminative tasks. In particular, we describe our approaches to the challenges that we have encountered in requirements analysis, data acquisition, visual design, software design, system development, team organisation, and resource planning. By reflecting on our experience, we propose a set of recommendations as the first step towards a methodology for developing and providing rapid VIS capacities to support emergency responses
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