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
    人类主要病原体肺炎链球菌已成为140多年来密集的临床和基础科学研究的主题。在多个实例中,这些努力在我们对细菌发病机理的基本生物学原理和基本原则的理解上取得了重大突破,免疫学,疫苗学,和遗传学。肺炎链球菌的发现已导致多项重大公共卫生胜利,挽救了数百万人的生命。肺炎链球菌的研究今天仍在继续,这种细菌被用来剖析宿主对疾病过程的影响,作为一个强大的细胞生物学模型,并更好地了解人类对共生细菌的影响。在这里,我们回顾了主要的发现,即,拼图碎片,用肺炎链球菌制成的,多年来,他们走到一起,塑造了我们对这种细菌生物学的理解,以及医学和现代分子生物学的实践。
    The major human pathogen Streptococcus pneumoniae has been the subject of intensive clinical and basic scientific study for over 140 years. In multiple instances, these efforts have resulted in major breakthroughs in our understanding of basic biological principles as well as fundamental tenets of bacterial pathogenesis, immunology, vaccinology, and genetics. Discoveries made with S. pneumoniae have led to multiple major public health victories that have saved the lives of millions. Studies on S. pneumoniae continue today, where this bacterium is being used to dissect the impact of the host on disease processes, as a powerful cell biology model, and to better understand the consequence of human actions on commensal bacteria at the population level. Herein we review the major findings, i.e., puzzle pieces, made with S. pneumoniae and how, over the years, they have come together to shape our understanding of this bacterium\'s biology and the practice of medicine and modern molecular biology.
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  • 文章类型: Journal Article
    物联网(IoT)包括数十亿个传感器和执行器(我们称为IoT设备),它们从物理世界中收集数据,并通过互联网将其发送到IoT应用程序,以提供智能IoT服务和产品。部署,管理,和维护物联网设备以单独使用物联网应用程序是低效的,并且涉及巨大的成本和精力,往往超过收益。另一方面,使大量物联网应用程序能够共享可用的第三方物联网设备,由各种物联网设备提供商独立部署和维护,降低物联网应用开发成本,时间,和努力。为了实现正的成本/收益比,有必要通过提供有效的物联网设备发现来支持全球第三方物联网设备的共享,使用,物联网应用和第三方物联网设备之间的支付。全球物联网设备共享的解决方案必须如下:(1)可扩展以支持大量第三方物联网设备,(2)可互操作,以处理物联网设备及其数据的异构性,(3)物联网拥有,即,不属于特定的个人或组织。本文调查了支持发现的现有技术,使用,并为第三方物联网设备付费。为了确保这项调查是全面的,本文介绍了我们的方法论,这是受系统文献网络分析(SLNA)的启发,将系统文献综述(SLR)方法与引文网络分析(CNA)相结合。最后,本文概述了实现全球物联网设备共享的新研究的研究空白和方向。
    The Internet of Things (IoT) includes billions of sensors and actuators (which we refer to as IoT devices) that harvest data from the physical world and send it via the Internet to IoT applications to provide smart IoT services and products. Deploying, managing, and maintaining IoT devices for the exclusive use of an individual IoT application is inefficient and involves significant costs and effort that often outweigh the benefits. On the other hand, enabling large numbers of IoT applications to share available third-party IoT devices, which are deployed and maintained independently by a variety of IoT device providers, reduces IoT application development costs, time, and effort. To achieve a positive cost/benefit ratio, there is a need to support the sharing of third-party IoT devices globally by providing effective IoT device discovery, use, and pay between IoT applications and third-party IoT devices. A solution for global IoT device sharing must be the following: (1) scalable to support a vast number of third-party IoT devices, (2) interoperable to deal with the heterogeneity of IoT devices and their data, and (3) IoT-owned, i.e., not owned by a specific individual or organization. This paper surveys existing techniques that support discovering, using, and paying for third-party IoT devices. To ensure that this survey is comprehensive, this paper presents our methodology, which is inspired by Systematic Literature Network Analysis (SLNA), combining the Systematic Literature Review (SLR) methodology with Citation Network Analysis (CNA). Finally, this paper outlines the research gaps and directions for novel research to realize global IoT device sharing.
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  • 文章类型: Journal Article
    背景:医疗保健中的决策越来越复杂;特别是在信息密度很高的医院环境中,例如,急诊科,肿瘤科,还有精神科.本研究旨在从记录的数据中发现决策,以改善决策过程。
    方法:选择设计科学研究方法(DSRM)来设计用于发现和可视化决策的工件(算法)。解释了DSRM的不同活动,从问题的定义到工件的评估。在设计和开发活动中,算法本身被创建。在论证和评估活动中,该算法用真实的合成数据集进行了测试。
    结果:结果显示了用于发现和可视化决策的算法的设计和仿真。模糊分类器算法适用于(1)从决策日志中发现决策和(2)使用决策模型和符号标准可视化决策。
    结论:在本文中,我们表明,可以从决策日志中发现决策,并将其可视化,以改善医疗保健专业人员的决策过程或支持方案和指南的定期评估.
    BACKGROUND: Decision-making in healthcare is increasingly complex; notably in hospital environments where the information density is high, e.g., emergency departments, oncology departments, and psychiatry departments. This study aims to discover decisions from logged data to improve the decision-making process.
    METHODS: The Design Science Research Methodology (DSRM) was chosen to design an artifact (algorithm) for the discovery and visualization of decisions. The DSRM\'s different activities are explained, from the definition of the problem to the evaluation of the artifact. During the design and development activities, the algorithm itself is created. During the demonstration and evaluation activities, the algorithm was tested with an authentic synthetic dataset.
    RESULTS: The results show the design and simulation of an algorithm for the discovery and visualization of decisions. A fuzzy classifier algorithm was adapted for (1) discovering decisions from a decision log and (2) visualizing the decisions using the Decision Model and Notation standard.
    CONCLUSIONS: In this paper, we show that decisions can be discovered from a decision log and visualized for the improvement of the decision-making process of healthcare professionals or to support the periodic evaluation of protocols and guidelines.
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  • 文章类型: Journal Article
    背景:精细菌的一个拷贝,许多真菌的命名是基于已知的工作发生在苏格兰的格拉斯哥大学植物学系,但建筑物在2001年被大火摧毁,以及这项重要工作的下落,如果它存在,丢失了。本文报道了其重新发现。
    结果:精细菌的格拉斯哥副本,未剪裁的Fries\'工作的第一版,位于格拉斯哥博物馆的原始橱柜中,在大火发生前几年被转移到那里,其标本现已数据库化。它是这一重要科学工作的少数现有未剪裁副本之一,也是第一版保存最完好的副本之一。
    结论:第一版精细菌的发现强调了早期真菌学家为重要藏品保留特殊保护的重要性。它还使全世界感兴趣的真菌学家知道格拉斯哥存在未切割的东西,第一版副本。
    BACKGROUND: A copy of Scleromyceti Sueciae, a work on which the nomenclature of many fungi is based was known to occur in Scotland\'s Glasgow University Botany Department but the buildings were devastated by fire in 2001 and the whereabouts of this important work, if it existed, was lost. Its re-finding is reported herein.
    RESULTS: The Glasgow copy of Scleromyceti Sueciae, an uncut first edition of Fries\' work, was located in the Glasgow Museums in its original cabinet being transferred there years before the fire and its specimens being now databased. It is one of the few existing uncut copies of this important scientific work and one of the best-preserved copies of the first edition.
    CONCLUSIONS: The discovery of this first edition of Scleromyceti Sueciae emphasizes the significance to reserve special conservation for important collections by early mycologists. It also allows interested mycologists world-wide to know of the existence in Glasgow of an uncut, first edition copy.
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  • 文章类型: Editorial
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  • 文章类型: Editorial
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  • 文章类型: Review
    串联重复DNA序列构成了人类基因组的显著比例。虽然以前被认为是功能惰性的,这些序列现在被广泛认为是遗传多样性的重要贡献者。然而,这些序列的多态性质可以导致扩展超过基因特异性阈值,引起疾病。迄今为止,已经发现了50多个致病性重复扩增,由于测序技术和相关的生物信息学工具的进步,其中许多是在过去十年中发现的。常用的诊断平台,包括Sanger测序,毛细管阵列电泳,和Southern印迹通常是低通量,并且通常无法准确确定重复大小,composition,和表观遗传签名,这在表征重复扩展时很重要。专门设计用于询问短读数测序的生物信息学工具的快速发展和长读数单分子测序的发展使得能够进行针对重复扩增障碍的新一代高通量测试。在这次审查中,我们讨论了在识别和表征引起疾病的重复扩展方面的一些挑战,以及有望将基因组医学的前景转化为受这些疾病影响的个人和家庭的技术进步.
    Tandem repeat DNA sequences constitute a significant proportion of the human genome. While previously considered to be functionally inert, these sequences are now broadly accepted as important contributors to genetic diversity. However, the polymorphic nature of these sequences can lead to expansion beyond a gene-specific threshold, causing disease. More than 50 pathogenic repeat expansions have been identified to date, many of which have been discovered in the last decade as a result of advances in sequencing technologies and associated bioinformatic tools. Commonly utilised diagnostic platforms including Sanger sequencing, capillary array electrophoresis, and Southern blot are generally low throughput and are often unable to accurately determine repeat size, composition, and epigenetic signature, which are important when characterising repeat expansions. The rapid advances in bioinformatic tools designed specifically to interrogate short-read sequencing and the development of long-read single molecule sequencing is enabling a new generation of high throughput testing for repeat expansion disorders. In this review, we discuss some of the challenges surrounding the identification and characterisation of disease-causing repeat expansions and the technological advances that are poised to translate the promise of genomic medicine to individuals and families affected by these disorders.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    发现戊型肝炎的故事起源于20世纪70年代末,我极端相信发展中国家的黄疸和怀孕之间的关系有一个隐藏的传奇,有机会大规模流行的病毒性肝炎,1978年11月袭击了Gulmarg克什米尔地区。根据挨家挨户调查收集的数据,一种新疾病的存在,非A流行病,非乙型肝炎,由迄今未知的肝炎病毒引起,已宣布。这个消息受到了国际社会的炒作和怀疑。在1980年代初期,世界敬畏地看着人类自我实验的极端例子导致了VLP的鉴定。1990年,来自负责流行病非A的病毒的cDNA克隆,分离非乙型肝炎。多年来,我们经历了三个模糊的时代,希望,和戊型肝炎研究的炒作,并进行了几项开创性的研究,以了解HEV的生物学和戊型肝炎的表现。在戊型肝炎研究的漫长而曲折的道路上,已经达到了许多里程碑,以了解结构,生物学以及代理人的多样性,在发达国家改变病原体的行为,以及高效疫苗的发现。
    The story of the discovery of hepatitis E originated in the late 1970s with my extreme belief that there was a hidden saga in the relationship between jaundice and pregnancy in developing countries and the opportunity for a massive epidemic of viral hepatitis, which hit the Gulmarg Kashmir region in November 1978. Based on data collected from a door-to-door survey, the existence of a new disease, epidemic non-A, non-B hepatitis, caused by a hitherto unknown hepatitis virus, was announced. This news was received by the world community with hype and skepticism. In the early 1980s, the world watched in awe as an extreme example of human self-experimentation led to the identification of VLP. In 1990, a cDNA clone from the virus responsible for epidemic non-A, non-B hepatitis was isolated. Over the years, we traversed three eras of ambiguity, hope, and hype of hepatitis E research and conducted several seminal studies to understand the biology of HEV and manifestations of hepatitis E. Many milestones have been reached on the long and winding road of hepatitis E research to understand the structure, biology, and diversity of the agent, changing the behavior of the pathogen in developed countries, and the discovery of a highly effective vaccine.
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