discovery

Discovery
  • 文章类型: Journal Article
    目的:植物性饮食与较低的慢性病风险相关。大规模蛋白质组学可以识别植物饮食的客观生物标志物,并提高我们对将植物性饮食与健康结果联系起来的途径的理解。本研究调查了四种不同植物性饮食的血浆蛋白质组[整体植物性饮食(PDI),原素食饮食,健康的植物性饮食(hPDI),和不健康的植物性饮食(uPDI)]在社区动脉粥样硬化风险(ARIC)研究中,并在弗雷明汉心脏研究(FHS)后代队列中复制了该发现。
    方法:ARIC研究参与者在第3次(1993-1995年)时使用完整的食物频率问卷(FFQ)数据和蛋白质组学数据分为内部发现(n=7690)和复制(n=2543)数据集。使用多变量线性回归来检查基于植物的饮食指数(PDIs)与发现样品中的4955种单个蛋白质之间的关联。然后,在ARIC研究中内部复制的蛋白质在FHS中进行了外部复制测试(n=1358)。对饮食相关蛋白进行通路过度表达分析。C统计量用于预测蛋白质是否改善了对植物性饮食指数的预测,超出了参与者的特征。
    结果:在ARIC发现中,在错误发现率(FDR)<0.05的情况下,共观察到837例饮食-蛋白质关联(PDI=233;原素食者=182;hPDI=406;uPDI=16).其中,453饮食-蛋白质关联(PDI=132;原素食=104;hPDI=208;uPDI=9)在内部复制。在FHS,167/453饮食-蛋白质关联可用于外部复制,其中8种蛋白质(PDI=1;前素食=0;hPDI=8;uPDI=0)复制。补体和凝血级联,细胞粘附分子,和视黄醇代谢过度。用于PDI的C-C基序趋化因子25和用于hPDI的8种蛋白质适度但显著地改善了这些指数的单独和共同的预测(对于所有测试,C统计量差异的P值<0.05)。
    结论:使用大规模蛋白质组学,我们确定了植物性饮食的潜在候选生物标志物,以及可能部分解释植物性饮食与慢性病之间关联的途径。
    OBJECTIVE: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.
    METHODS: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics.
    RESULTS: In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests).
    CONCLUSIONS: Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.
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  • 文章类型: Journal Article
    属于MysmenidaePetrunkevitch家族的13种蜘蛛,1928年从西双版纳热带植物园(XTBG)报道,梦伦镇,蒙腊县,中国云南省。一个属和五个物种被记录为科学新物种:Mengmenabannagen。11月。等。sp.11月。孟门育林sp。11月。(‰),Mosuheguomusp.11月。Mysmenaluosoosp.11月。和Mysmenadaisp.11月。(乙醇胺)。提出了一种新的组合:Mosuzhengi(Lin&Li,2008)梳子。11月。前MysmenaSimon,1894).Microdipoenamenglunensis的雌性(Lin&Li,2008),MysmenaarcilongaLin&Li,2008,MysmenafurcaLin&Li,2008年,以及MysmenarostellaLin&Li,第一次描述了2008年。对三个已知物种进行了重新检查和拍照:GaoligongataeniataLin和Li,2014年,Mysmenabiangulata(Lin&Li,2008),和Mysmenacornigera(Lin&Li,2008).提供了这13种霉菌的形态学诊断和插图。
    Thirteen spider species belonging to the family Mysmenidae Petrunkevitch, 1928 are reported from Xishuangbanna Tropical Botanical Garden (XTBG), Menglun Township, Mengla County, Yunnan Province of China. One genus and five species are documented as new to science: Mengmenabanna gen. nov. et. sp. nov. (♂♀), Mengmenayulin sp. nov. (♀), Mosuheguomu sp. nov. (♂♀), Mysmenaluosuo sp. nov. (♂♀), and Mysmenadai sp. nov. (♀). One species is proposed as a new combination: Mosuzhengi (Lin & Li, 2008) comb. nov. (♂♀, ex Mysmena Simon, 1894). The females of Microdipoenamenglunensis (Lin & Li, 2008), Mysmenaarcilonga Lin & Li, 2008, Mysmenafurca Lin & Li, 2008, and Mysmenarostella Lin & Li, 2008 are described for the first time. Three known species are re-examined and photographed: Gaoligongataeniata Lin & Li, 2014, Mysmenabiangulata (Lin & Li, 2008), and Mysmenacornigera (Lin & Li, 2008). Morphological diagnoses and illustrations are provided for these thirteen mysmenid species.
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  • 文章类型: Multicenter Study
    背景:进行高质量的卒中试验既复杂又昂贵。通常,这些试验争夺研究人员的注意力和患者的可用性。同时将患者纳入一项以上的研究有可能加速招募到个体研究中。DISCOVERY是一个多中心,缺血性或出血性卒中后认知障碍和痴呆的初始队列研究。应现场调查人员的要求,DISCOVERY委员会审查个别研究,以批准可能同时参与DISCOVERY的研究.本报告的目的是总结委员会审查的研究的特征和结果,以进行可能的共同注册。
    方法:此分析涵盖了由发现招募和保留核心的现场管理委员会(SMC)从2020年07月01日至2022年04月26日审查的研究。每个研究的特征包括研究类型,后续访问的数量和长度,以及是否有协议要求的抽血,脑成像研究,或者认知测试.对患者负担和与Discovery的科学重叠进行了评分。主要结果是SMC批准共同注册。
    结果:回顾了59项研究,SMC发现69.5%(n=41,21项临床试验;20项观察性研究)适合于联合纳入.更高的患者负担和与DISCOVERY的科学重叠降低了共同注册的批准率。
    结论:在DISCOVERY研究网络中同时进行大量不同的卒中研究。然而,约三分之二的研究被认为适合考虑共同纳入.未来的研究应该研究共同注册如何提高试验网络效率。
    BACKGROUND: Conducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment.
    METHODS: This analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll.
    RESULTS: 59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment.
    CONCLUSIONS: A large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.
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  • 文章类型: Journal Article
    背景:知识图是生物医学和许多其他领域中知识表示的一种常见形式。我们开发了一种基于生物医学知识图的开放式系统,称为在面向知识的途径(ROBOKOP)中链接的生物医学对象上的推理。ROBOKOP由前端用户界面和后端知识图组成。ROBOKOP用户界面允许用户提出问题并探索答案子图。用户还可以通过对底层知识图的直接Cypher查询来提出问题,它目前包含大约600万个节点或生物医学实体,以及描述节点之间关系的1.4亿条边或谓词,来自30多个精选数据源。
    目的:我们旨在将ROBOKOP应用于来自美国国家环境健康科学研究所的环境多态性登记处(EPR)的工作场所暴露和免疫介导疾病的调查数据。
    方法:我们分析了EPR调查数据,确定了工作场所化学品暴露与免疫介导疾病之间的45种关联,根据研究参与者的自我报告(n=4574),在错误发现率校正后,20个关联在P<0.05时显著。然后,我们使用ROBOKOP(1)通过确定ROBOKOP知识图中是否存在合理的连接来验证关联,以及(2)提出可能解释它们的生物学机制,并作为后续测试的假设。我们强调以下三个示例性关联:一氧化碳-多发性硬化症,氨哮喘,和异丙醇过敏性疾病。
    结果:ROBOKOP成功返回了在驱动示例上下文中提出的三个查询的答案集。答案集包括潜在的中介基因,以及可能解释观察到的关联的支持性证据。
    结论:我们展示了ROBOKOP在现实世界中的应用,以产生工作场所化学品暴露与免疫介导的疾病之间关联的机制假设。我们预计ROBOKOP将在许多生物医学领域和其他科学学科中得到广泛应用,加快发现和生成机械假设,开放的自然。
    BACKGROUND: Knowledge graphs are a common form of knowledge representation in biomedicine and many other fields. We developed an open biomedical knowledge graph-based system termed Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP). ROBOKOP consists of both a front-end user interface and a back-end knowledge graph. The ROBOKOP user interface allows users to posit questions and explore answer subgraphs. Users can also posit questions through direct Cypher query of the underlying knowledge graph, which currently contains roughly 6 million nodes or biomedical entities and 140 million edges or predicates describing the relationship between nodes, drawn from over 30 curated data sources.
    OBJECTIVE: We aimed to apply ROBOKOP to survey data on workplace exposures and immune-mediated diseases from the Environmental Polymorphisms Registry (EPR) within the National Institute of Environmental Health Sciences.
    METHODS: We analyzed EPR survey data and identified 45 associations between workplace chemical exposures and immune-mediated diseases, as self-reported by study participants (n= 4574), with 20 associations significant at P<.05 after false discovery rate correction. We then used ROBOKOP to (1) validate the associations by determining whether plausible connections exist within the ROBOKOP knowledge graph and (2) propose biological mechanisms that might explain them and serve as hypotheses for subsequent testing. We highlight the following three exemplar associations: carbon monoxide-multiple sclerosis, ammonia-asthma, and isopropanol-allergic disease.
    RESULTS: ROBOKOP successfully returned answer sets for three queries that were posed in the context of the driving examples. The answer sets included potential intermediary genes, as well as supporting evidence that might explain the observed associations.
    CONCLUSIONS: We demonstrate real-world application of ROBOKOP to generate mechanistic hypotheses for associations between workplace chemical exposures and immune-mediated diseases. We expect that ROBOKOP will find broad application across many biomedical fields and other scientific disciplines due to its generalizability, speed to discovery and generation of mechanistic hypotheses, and open nature.
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  • 文章类型: Journal Article
    Widespread application of omic technologies is evolving our understanding of population health and holds promise in providing precise guidance for selection of therapeutic interventions based on patient biology. The opportunity to use hundreds of analytes for diagnostic assessment of human health compared to the current use of 10-20 analytes will provide greater accuracy in deconstructing the complexity of human biology in disease states. Conventional biochemical measurements like cholesterol, creatinine, and urea nitrogen are currently used to assess health status; however, metabolomics captures a comprehensive set of analytes characterizing the human phenotype and its complex metabolic processes in real-time. Unlike conventional clinical analytes, metabolomic profiles are dramatically influenced by demographic and environmental factors that affect the range of normal values and increase the risk of false biomarker discovery. This review addresses the challenges and opportunities created by the evolving field of clinical metabolomics and highlights features of study design and bioinformatics necessary to maximize the utility of metabolomics data across demographic groups.
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  • 文章类型: Journal Article
    Stomach cancer is one of the leading causes of cancer death worldwide, despite its incidence and mortality falling in many places. The discovery in 1984 that a bacterial infection with Helicobacter pylori could cause stomach and duodenal ulcers prompted work in its role in causing gastritis, and led to the first prospective study in 1991 by Forman et al., showing that infection with H.pylori increased the risk of stomach cancer in those infected by almost three-fold. Prior to then, it was hypothesized that stomach was caused by poor diets. While diets may still play a role, the falls in stomach cancer incidence have been associated with reductions in population prevalence of H. pylori. Discovery of the link was accelerated by the use of stored sera from other unrelated studies, and the use of serological assays. Since those discoveries the treatment landscape of gastric disorders has changed significantly, with a rapid uptake of antibiotic and proton pump inhibitors (triple) therapies in those who are H. pylori positive. Over time we have seen falls in gastric cancer, peptic and duodenal ulcers and in many of the procedures previously used to cure peptic ulcer disease, such as vagotomies and gastrectomies. Further still, an oral vaccine against H. pylori, first trialled in China, holds much promise of being the third vaccine against a cancer causing infection. If successful this would lead to a further reduction in H. pylori related conditions, and ultimately gastric cancer, an otherwise lethal disease.
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