2,542 research outputs found

    Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

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    IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

    Gestão do trabalho interprofissional no projeto terapêutico singular: proposta de modelo de processo de trabalho

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    Objetivo: propor um modelo para organização das atividades de um Projeto Terapêutico Singular (PTS) no contexto da estratégia da Saúde da Família (ESF), facilitando a colaboração interprofissional. Método: Trata-se de pesquisa qualitativa. Utilizou-se a estratégia de pesquisa-ação, envolvendo uma equipe multiprofissional de saúde e ações de colaboração interprofissional para aprimorar a prática. A pesquisa-ação foi escolhida por mostrar-se adequada para estudos em cenários sociais, em contextos diversos. Os pesquisadores e a equipe acordaram que a discussão do PTS ocorresse em reuniões amplas para favorecer a discussão, reflexão e propostas de ações para o caso. O trabalho de campo envolveu aproximadamente 20 reuniões com a equipe que geravam subsequentes momentos reflexivos da pesquisa. Essa dinâmica favoreceu a proposta do modelo. As etapas do trabalho da pesquisa foram reconhecimento do problema, planejamento, implementação e avaliação. Resultado: Nas reuniões do trabalho coletivo, a equipe pesquisadora percebeu problemas no processo do PTS, tais como: falta de clareza dos objetivos; planejamento e direcionamento das ações colaborativas interprofissionais pouco efetivos para envolver paciente e família no cuidado de saúde. Nesse contexto, propôs-se um modelo de PTS com quatro etapas: Discussão do caso, Designação, Execução e Encerramento ou nova abordagem do processo de atenção. Conclusão: O modelo proposto é uma contribuição teórica e necessita de mais estudos empíricos para validar sua aplicação no âmbito da ESF. Identificou-se, como limitante para a gestão do cuidado para o PTS, a falta de formação pré- e pós-graduada em educação interprofissional dos participantes. No entanto, o modelo se justifica na medida que ajuda a construir ações interprofissionais, recomendadas pelo Sistema Único de Saúde (SUS) e órgãos internacionais da saúde (OMS e OPAS)

    Armadillo repeat-containing kinesin represents the versatile plus-end-directed transporter in Physcomitrella

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    Kinesin-1, also known as conventional kinesin, is widely used for microtubule plus-end-directed (anterograde) transport of various cargos in animal cells. However, a motor functionally equivalent to the conventional kinesin has not been identified in plants, which lack the kinesin-1 genes. Here we show that plant-specific armadillo repeat-containing kinesin (ARK) is the long sought-after versatile anterograde transporter in plants. In ARK mutants of the moss Physcomitrium patens, the anterograde motility of nuclei, chloroplasts, mitochondria and secretory vesicles was suppressed. Ectopic expression of non-motile or tail-deleted ARK did not restore organelle distribution. Another prominent macroscopic phenotype of ARK mutants was the suppression of cell tip growth. We showed that this defect was attributed to the mislocalization of actin regulators, including RopGEFs; expression and forced apical localization of RopGEF3 partially rescued the growth phenotype of the ARK mutant. The mutant phenotypes were partially rescued by ARK homologues in Arabidopsis thaliana, suggesting the conservation of ARK functions in plants

    A Study on the Evaluation Framework for Community Engagement in American Higher Education

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    50442223 (科研費)南山大学アメリカ高等教育におけるコミュニティ・エンゲージメントの評価に関する研究 2018~2022年度科学研究費助成事業 (基盤研究 (C) (一般)) 研究成果報告書33917 (科研費)202218K02744 (科研費)research repor

    Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array

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    Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM

    Relationships between Teleworking and Travel Behavior in the Brazilian COVID-19 Crisis

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    The COVID-19 pandemic caused a significant shift towards teleworking, resulting in changes in travel patterns. The relationship between teleworking and individual travel behavior is crucial for transportation planning and policymaking. Thereby, this article investigates the relationships between teleworking, COVID-19, and mobility patterns in Brazil during two different periods of the COVID-19 pandemic. Given the exceptional nature of recent events, it is crucial to conduct studies related to teleworking during the pandemic crisis to contribute relevant information and evidence to the literature on this phenomenon. Such research has the potential to provide new insights and perspectives that enhance our understanding of the challenges and opportunities associated with teleworking. Two different approaches were used in the methodological procedure. The first approach used exploratory analysis to study public aggregated data related to the beginning of the pandemic, followed by a cluster analysis and a multinomial logit model. The second approach, relative to a longer relaxation period of sanitary/health measures, collected disaggregated self-reported data using an online survey, which were analyzed through non-parametric tests. The results show a strong relationship between the teleworking regime and the frequency of trips, especially for work purposes. It also highlights the influence of economic development and the region of Brazil in the kind of work regime. The continuation of studies, such as this one, in current periods is important for analyzing possible impacts, such as the reduction in congestion, vehicle emissions, and to enable the use of teleworking as a demand management policy

    Involvement of the L-DOPA receptor GPR143 in acute and chronic actions of methylphenidate

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    Methylphenidate (MPH) and methamphetamine (METH) are the current treatments of choice for attention deficit/hyperactivity disorder. We previously reported that METH induces the release of dopamine (DA) and of the neurotransmitter candidate L-3,4-dihydroxyphenylalanine (L-DOPA). In contrast, we here found that MPH increased the DA release while it did not affect the L-DOPA release from the dorsolateral striatum. Nevertheless, MPH-induced hyperlocomotion was reduced in Gpr143 (L-DOPA receptor) gene-deficient (Gpr143−/y) mice. The rewarding effect and increased c-fos expression induced by MPH were also attenuated in Gpr143−/y mice. Together, these findings suggest that GPR143 is involved in the acute and chronic actions of MPH

    Growth and division mode plasticity is dependent on cell density in marine‐derived black yeasts

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    The Autoantibody Array Assay: A Novel Autoantibody Detection Method

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    Systemic sclerosis (SSc) and dermatomyositis (DM) are autoimmune collagen diseases. Specific autoantibodies are known to be involved in their pathogeneses, each presenting with a different clinical manifestation. Although immunoprecipitation is the gold standard method for detecting autoantibodies, it is difficult to perform in all cases owing to the use of radioisotopes. In this study, we developed a new detection method for SSc and DM autoantibodies (A-cube) using cell-free protein synthesis and examined its validity. Proteins were synthesized using wheat germ cell-free protein synthesis. A total of 100 cases of SSc, 50 cases of DM, and 82 healthy controls were examined. The validity of the method was examined by a comparison with existing test results. Anti-centromere antibody, anti-topoisomerase I antibody, anti-RNA polymerase III antibody, anti-U1RNP anti-body, anti-Jo-1 antibody, anti-TIF1γ antibody, anti-Mi-2 antibody, and anti-ARS antibody were tested for. The results suggested that A-cube is comparable with existing testing methods or has a high sensitivity or specificity. In addition, there was a case in which the diagnosis was reconsidered using the A-cube. The quality of the A-cube was ensured, and its usefulness for a comprehensive analysis was demonstrated. The A-cube can therefore contribute to the clinical assessment and treatment of SSc and DM
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