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Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.  相似文献   
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目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库(CNKI)和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献,应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇,英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示,张爱华是中医药领域代谢组学研究发文量最多的作者,并形成了核心研究团队。发文机构显示,中国医学科学院是该领域的重要研究机构,机构间合作紧密。中、英文文献关键词分析显示,研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。  相似文献   
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In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.  相似文献   
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International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...  相似文献   
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Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.  相似文献   
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Journal of Immigrant and Minority Health - COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to...  相似文献   
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