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  • 文章类型: News
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  • 文章类型: Journal Article
    提出了一种新的分析,用于逆行示踪剂测量,该示踪剂测量了the猴皮层解剖区域之间的连接。原始数据的原始归一化产生分数链接权重度量,FLNe.这是重新检查,以考虑其他可能的措施,揭示潜在的链接权重。两者产生的预测用于检查网络模块和集线器。在包含权重的情况下,InfoMap算法可以识别the猴皮层中的八个结构模块。使用模块分配和参与系数来识别进出集线器和主要连接器节点。围绕主要枢纽的时间演变网络跟踪揭示了pFC中的中型集群,temporal,听觉和视觉区域;其中最紧密耦合和最重要的是在pFC中。通过检查皮层网络中的最高流量链路提供了补充观点,并揭示了平行的感觉流向pFC,并通过关联区域流向额叶区域。
    A new analysis is presented of the retrograde tracer measurements of connections between anatomical areas of the marmoset cortex. The original normalisation of raw data yields the fractional link weight measure, FLNe. That is re-examined to consider other possible measures that reveal the underlying in link weights. Predictions arising from both are used to examine network modules and hubs. With inclusion of the in weights the InfoMap algorithm identifies eight structural modules in marmoset cortex. In and out hubs and major connector nodes are identified using module assignment and participation coefficients. Time evolving network tracing around the major hubs reveals medium sized clusters in pFC, temporal, auditory and visual areas; the most tightly coupled and significant of which is in the pFC. A complementary viewpoint is provided by examining the highest traffic links in the cortical network, and reveals parallel sensory flows to pFC and via association areas to frontal areas.
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  • 文章类型: Journal Article
    肾脏疾病是世界范围内的主要死亡原因。目前,肾脏疾病的诊断和严重程度的分级主要基于临床特征,不能揭示潜在的分子途径。近来更多的组学研究极大地促进了疾病研究。人工智能(AI)的出现为大数据集的有效集成和解释开辟了道路,以发现临床可操作的知识。这篇综述讨论了人工智能和多组学如何应用和整合,提供在肾脏疾病中开发新的诊断和治疗手段的机会。新技术和新分析管道的结合可以在扩大我们对疾病发病机理的理解方面取得突破,为生物标志物和疾病分类提供新的思路,以及提供精确治疗的可能性。
    Kidney disease is a leading cause of death worldwide. Currently, the diagnosis of kidney diseases and the grading of their severity are mainly based on clinical features, which do not reveal the underlying molecular pathways. More recent surge of ∼omics studies has greatly catalyzed disease research. The advent of artificial intelligence (AI) has opened the avenue for the efficient integration and interpretation of big datasets for discovering clinically actionable knowledge. This review discusses how AI and multi-omics can be applied and integrated, to offer opportunities to develop novel diagnostic and therapeutic means in kidney diseases. The combination of new technology and novel analysis pipelines can lead to breakthroughs in expanding our understanding of disease pathogenesis, shedding new light on biomarkers and disease classification, as well as providing possibilities of precise treatment.
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  • 文章类型: Journal Article
    病原体溢出对应于病原体或寄生虫从原始宿主物种向新宿主物种的传播。疾病的出现。了解在人畜共患周期中导致病原体传播的相互作用因素可以帮助识别病原体的新宿主和导致疾病出现的模式。我们假设生态和生物地理因素驱动宿主相遇,感染易感性,和跨物种溢出传播。在新热带地区使用啮齿动物-外寄生虫系统,共同的外寄生虫协会作为啮齿动物物种之间生态相互作用的代理,我们使用地理范围评估了啮齿动物之间的关系,系统发育相关性,和外寄生虫协会,以确定通才和专家宿主在汉坦病毒传播周期中的作用。在基于外寄生虫共享的网络模型中,总共对50种啮齿动物进行了中心性排名。地理接近性和系统发育相关性是啮齿动物共享外寄生虫物种的预测因子,并且与啮齿动物之间通过共享外寄生虫的网络路径距离较短有关。啮齿动物-外寄生虫网络模型成功预测了七个已知汉坦病毒宿主的独立数据。该模型预测了五种新的啮齿动物是潜在的,南美未识别的汉坦病毒宿主。研究结果表明,外寄生虫的数据,地理范围,野生动物物种的系统发育相关性可以帮助预测易受感染和人畜共患病原体可能传播的新宿主。汉坦病毒是一种高后果的人畜共患病原体,动物对人类,和人与人之间的传播。对新的啮齿动物宿主的预测可以指导特定地区和野生动植物物种的积极流行病学监测,以减轻汉坦病毒从啮齿动物向人类的溢出传播风险。这项研究支持以下观点:啮齿动物之间的体外寄生虫关系是宿主物种相互作用的代理,并且可以告知在野生动植物疾病系统中循环的多种病原体的传播周期。包括具有流行潜力的野生动物病毒,比如汉坦病毒。
    Pathogen spillover corresponds to the transmission of a pathogen or parasite from an original host species to a novel host species, preluding disease emergence. Understanding the interacting factors that lead to pathogen transmission in a zoonotic cycle could help identify novel hosts of pathogens and the patterns that lead to disease emergence. We hypothesize that ecological and biogeographic factors drive host encounters, infection susceptibility, and cross-species spillover transmission. Using a rodent-ectoparasite system in the Neotropics, with shared ectoparasite associations as a proxy for ecological interaction between rodent species, we assessed relationships between rodents using geographic range, phylogenetic relatedness, and ectoparasite associations to determine the roles of generalist and specialist hosts in the transmission cycle of hantavirus. A total of 50 rodent species were ranked on their centrality in a network model based on ectoparasites sharing. Geographic proximity and phylogenetic relatedness were predictors for rodents to share ectoparasite species and were associated with shorter network path distance between rodents through shared ectoparasites. The rodent-ectoparasite network model successfully predicted independent data of seven known hantavirus hosts. The model predicted five novel rodent species as potential, unrecognized hantavirus hosts in South America. Findings suggest that ectoparasite data, geographic range, and phylogenetic relatedness of wildlife species could help predict novel hosts susceptible to infection and possible transmission of zoonotic pathogens. Hantavirus is a high-consequence zoonotic pathogen with documented animal-to-animal, animal-to-human, and human-to-human transmission. Predictions of new rodent hosts can guide active epidemiological surveillance in specific areas and wildlife species to mitigate hantavirus spillover transmission risk from rodents to humans. This study supports the idea that ectoparasite relationships among rodents are a proxy of host species interactions and can inform transmission cycles of diverse pathogens circulating in wildlife disease systems, including wildlife viruses with epidemic potential, such as hantavirus.
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  • 文章类型: Journal Article
    进行了一项调查,以开发一种设计和制造具有嵌入式分布式传感器网络的3-D智能皮肤的过程,用于不可开发(或双重弯曲)表面。智能皮肤是智能结构的传感组件,允许此类结构从其周围环境中收集数据以做出控制和维护决策。这样的智能皮肤需要跨越各种各样的领域,特别是对于那些表面对外部负载或环境变化需要高灵敏度的设备,例如人类辅助机器人,医疗器械,可穿戴健康组件,等。然而,在不可开发的表面上制造和部署分布式传感器网络面临着严峻的挑战。这些挑战包括目标物体的共形覆盖,而不会在传感器互连中造成过高的应力,并确保皮肤传感器部署位置的位置准确性。以及由于变薄而带来的包装挑战,灵活的皮肤形状因子。在这项研究中,从最初的传感器网络设计到最终的集成皮肤组装,开发了用于制造这种3-D智能皮肤的新颖和流线型的过程。具体来说,该过程涉及网络本身的设计(为此开发了基于物理仿真的优化),将网络部署到目标3D表面(为此设计和实施了专用工具),和最终皮肤的组装(为此,开发并实施了基于浸涂的新颖工艺。).
    An investigation was performed to develop a process to design and manufacture a 3-D smart skin with an embedded network of distributed sensors for non-developable (or doubly curved) surfaces. A smart skin is the sensing component of a smart structure, allowing such structures to gather data from their surrounding environments to make control and maintenance decisions. Such smart skins are desired across a wide variety of domains, particularly for those devices where their surfaces require high sensitivity to external loads or environmental changes such as human-assisting robots, medical devices, wearable health components, etc. However, the fabrication and deployment of a network of distributed sensors on non-developable surfaces faces steep challenges. These challenges include the conformal coverage of a target object without causing prohibitive stresses in the sensor interconnects and ensuring positional accuracy in the skin sensor deployment positions, as well as packaging challenges resulting from the thin, flexible form factor of the skin. In this study, novel and streamlined processes for making such 3-D smart skins were developed from the initial sensor network design to the final integrated skin assembly. Specifically, the process involved the design of the network itself (for which a physical simulation-based optimization was developed), the deployment of the network to a targeted 3D surface (for which a specialized tool was designed and implemented), and the assembly of the final skin (for which a novel process based on dip coating was developed and implemented.).
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  • 文章类型: Journal Article
    背景:由于多重耐药生物体(MDROs)引起的医疗保健相关感染,如耐甲氧西林金黄色葡萄球菌(MRSA)和艰难梭菌(CDI),给我们的医疗基础设施带来沉重负担。
    目的:MDROs的筛查是防止传播的重要机制,但却是资源密集型的。这项研究的目的是开发可以使用电子健康记录(EHR)数据预测定植或感染风险的自动化工具,提供有用的信息来帮助感染控制,并指导经验性抗生素覆盖。
    方法:我们回顾性地开发了一个机器学习模型来检测在弗吉尼亚大学医院住院患者样本采集时未分化患者的MRSA定植和感染。我们使用来自患者EHR数据的入院和住院期间信息的临床和非临床特征来构建模型。此外,我们在EHR数据中使用了一类从联系网络派生的特征;这些网络特征可以捕获患者与提供者和其他患者的联系,提高预测MRSA监测试验结果的模型可解释性和准确性。最后,我们探索了不同患者亚群的异质模型,例如,入住重症监护病房或急诊科的人或有特定检测史的人,哪个表现更好。
    结果:我们发现惩罚逻辑回归比其他方法表现更好,当我们使用多项式(二次)变换特征时,该模型的性能根据其接收器操作特征-曲线下面积得分提高了近11%。预测MDRO风险的一些重要特征包括抗生素使用,手术,使用设备,透析,患者的合并症状况,和网络特征。其中,网络功能增加了最大的价值,并将模型的性能提高了至少15%。对于特定患者亚群,具有相同特征转换的惩罚逻辑回归模型也比其他模型表现更好。
    结论:我们的研究表明,使用来自EHR数据的临床和非临床特征,通过机器学习方法可以非常有效地进行MRSA风险预测。网络特征是最具预测性的,并且提供优于现有方法的显著改进。此外,不同患者亚群的异质预测模型提高了模型的性能。
    BACKGROUND: Health care-associated infections due to multidrug-resistant organisms (MDROs), such as methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile (CDI), place a significant burden on our health care infrastructure.
    OBJECTIVE: Screening for MDROs is an important mechanism for preventing spread but is resource intensive. The objective of this study was to develop automated tools that can predict colonization or infection risk using electronic health record (EHR) data, provide useful information to aid infection control, and guide empiric antibiotic coverage.
    METHODS: We retrospectively developed a machine learning model to detect MRSA colonization and infection in undifferentiated patients at the time of sample collection from hospitalized patients at the University of Virginia Hospital. We used clinical and nonclinical features derived from on-admission and throughout-stay information from the patient\'s EHR data to build the model. In addition, we used a class of features derived from contact networks in EHR data; these network features can capture patients\' contacts with providers and other patients, improving model interpretability and accuracy for predicting the outcome of surveillance tests for MRSA. Finally, we explored heterogeneous models for different patient subpopulations, for example, those admitted to an intensive care unit or emergency department or those with specific testing histories, which perform better.
    RESULTS: We found that the penalized logistic regression performs better than other methods, and this model\'s performance measured in terms of its receiver operating characteristics-area under the curve score improves by nearly 11% when we use polynomial (second-degree) transformation of the features. Some significant features in predicting MDRO risk include antibiotic use, surgery, use of devices, dialysis, patient\'s comorbidity conditions, and network features. Among these, network features add the most value and improve the model\'s performance by at least 15%. The penalized logistic regression model with the same transformation of features also performs better than other models for specific patient subpopulations.
    CONCLUSIONS: Our study shows that MRSA risk prediction can be conducted quite effectively by machine learning methods using clinical and nonclinical features derived from EHR data. Network features are the most predictive and provide significant improvement over prior methods. Furthermore, heterogeneous prediction models for different patient subpopulations enhance the model\'s performance.
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  • 文章类型: Journal Article
    土壤-根连续体的微生物在生态系统功能中起着关键作用。黄土高原以其严重的土壤侵蚀和厚厚的黄土而闻名于世,从东南到西北,平均年降水量(MAP)和土壤养分减少。然而,环境因素对四个微生境(块状土壤,根际,根际平面,和内圈)在黄土高原沿环境梯度的土壤-根连续体中仍不清楚。在这项研究中,我们调查了黄土高原从温带到沙漠草原的82个野外地点,中国,为了评估细菌的多样性,composition,社区集会,使用细菌16S重组DNA扩增子测序,沿着环境梯度在土壤-根连续体中同时出现网络。我们发现,微生境解释了该地区细菌多样性和群落组成变化的最大来源。环境因素(例如,MAP,土壤有机碳,和pH值)影响了土壤,根际,和根际平面细菌群落,但是它们对细菌群落的影响随着从土壤到根际平面与根的距离增加而降低,MAP扩大了根际和根际平面与块状土壤的微生物群落差异。此外,随机组装过程驱动了内圈群落,而土壤,根际,根际平面群落主要受确定性过程的变量选择控制,这表明从温带草原到沙漠草原的重要性日益增加。此外,根际平面群落中微生物网络的特性表明沙漠草原中的网络更加稳定,可能赋予微生物群落在较高胁迫环境中的抗性。总的来说,我们的结果表明,土壤-根连续体中的细菌群落在环境梯度上具有不同的敏感性和组装机制。这些模式是由黄土高原与根的邻近度和环境胁迫变化交织在一起的同时形成的。
    Microorganisms of the soil-root continuum play key roles in ecosystem function. The Loess Plateau is well known for its severe soil erosion and thick loess worldwide, where mean annual precipitation (MAP) and soil nutrients decrease from the southeast to the northwest. However, the relative influence of environmental factors on the microbial community in four microhabitats (bulk soil, rhizosphere, rhizoplane, and endosphere) in the soil-root continuum along the environmental gradient in the Loess Plateau remains unclear. In this study, we investigated 82 field sites from warm-temperate to desert grasslands across the Loess Plateau, China, to assess the bacterial diversity, composition, community assembly, and co-occurrence networks in the soil-root continuum along an environmental gradient using bacterial 16S recombinant DNA amplicon sequencing. We discovered that the microhabitats explained the largest source of variations in the bacterial diversity and community composition in this region. Environmental factors (e.g., MAP, soil organic carbon, and pH) impacted the soil, rhizosphere, and rhizoplane bacterial communities, but their effects on the bacterial community decreased with increased proximity to roots from the soil to the rhizoplane, and the MAP enlarged the dissimilarity of microbial communities from the rhizosphere and rhizoplane to bulk soil. Additionally, stochastic assembly processes drove the endosphere communities, whereas the soil, rhizosphere, and rhizoplane communities were governed primarily by the variable selection of deterministic processes, which showed increased importance from warm-temperate to desert grasslands. Moreover, the properties of the microbial networks in the rhizoplane community indicate more stable networks in desert grasslands, likely conferring the resistance of microbial communities in higher stress environments. Collectively, our results showed that the bacterial communities in the soil-root continuum had different sensitivities and assembly mechanisms along an environmental gradient. These patterns are shaped simultaneously by the intertwined dimensions of proximity to roots and environmental stress change in the Loess Plateau.
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  • 文章类型: Journal Article
    对Marmoset皮层连通性数据的网络分析表明,前额叶皮层及其周围存在大量3D聚类。一个多节点,构建了该六节点簇的异质神经质量模型。其参数由可用的实验和模拟数据告知,以便每个神经团块在特征频率带中振荡。节点与定向连接,加权链接来自于Marmoset结构连通性数据。每个节点的链路权重和模型参数不同会产生异质性。用在标准频带中调制的入射脉冲序列刺激集群,会引起各种动态状态转变,持续5-10s,暗示与短期记忆相关的时间尺度。短暂的伽马爆发迅速重置了β诱导的跃迁。θ诱导的过渡态表现为自发的,延迟复位到静止状态。一个额外的,连续的伽马波刺激引起了新的跳动振荡状态。更长或重复的伽马爆发与β振荡相位对齐,提供增加的能量输入和导致更短的过渡时间。这些结果与工作记忆的相关性尚未确定,但他们提出了有趣的机会。
    Network analysis of the marmoset cortical connectivity data indicates a significant 3D cluster in and around the pre-frontal cortex. A multi-node, heterogeneous neural mass model of this six-node cluster was constructed. Its parameters were informed by available experimental and simulation data so that each neural mass oscillated in a characteristic frequency band. Nodes were connected with directed, weighted links derived from the marmoset structural connectivity data. Heterogeneity arose from the different link weights and model parameters for each node. Stimulation of the cluster with an incident pulse train modulated in the standard frequency bands induced a variety of dynamical state transitions that lasted in the range of 5-10 s, suggestive of timescales relevant to short-term memory. A short gamma burst rapidly reset the beta-induced transition. The theta-induced transition state showed a spontaneous, delayed reset to the resting state. An additional, continuous gamma wave stimulus induced a new beating oscillatory state. Longer or repeated gamma bursts were phase-aligned with the beta oscillation, delivering increasing energy input and causing shorter transition times. The relevance of these results to working memory is yet to be established, but they suggest interesting opportunities.
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  • 文章类型: Journal Article
    最近的研究强调了脑岛是人脑网络中的关键枢纽,也是最容易受到主观认知能力下降(SCD)影响的区域。然而,SCD患者岛叶亚区功能连接的变化仍然知之甚少.本研究旨在使用静息态功能磁共振成像(rs-fMRI)阐明SCD患者岛状亚区域内功能连接模式的改变。
    在这项研究中,我们收集了30例SCD患者和28例健康对照(HCs)的rs-fMRI数据.通过定义脑岛的三个子区域,我们绘制了全脑静息状态功能连接(RSFC)图.我们确定了岛屿分区的几种不同的RSFC模式。具体来说,对于积极的连通性,在脑岛内确定了三种认知相关的RSFC模式,提示前后功能细分:(1)脑岛的背侧前区,显示RSFC与执行控制网络(ECN);(2)脑岛的腹侧前区,显示与显著性网络(SN)的功能连通性;(3)沿着脑岛的后部区,显示与感觉运动网络(SMN)的功能连通性.
    与对照相比,SCD患者在脑岛亚区表现出增加的RSFC阳性,表现出补偿性可塑性。此外,这些异常的岛叶亚区RSFCs与SCD患者的认知能力密切相关.
    我们的研究结果表明,不同的岛屿分区表现出具有不同功能网络的RSFC的不同模式,SCD患者受影响不同。
    UNASSIGNED: Recent research has highlighted the insula as a critical hub in human brain networks and the most susceptible region to subjective cognitive decline (SCD). However, the changes in functional connectivity of insular subregions in SCD patients remain poorly understood. The present study aims to clarify the altered functional connectivity patterns within insular subregions in individuals with SCD using resting-state functional magnetic resonance imaging (rs-fMRI).
    UNASSIGNED: In this study, we collected rs-fMRI data from 30 patients with SCD and 28 healthy controls (HCs). By defining three subregions of the insula, we mapped whole-brain resting-state functional connectivity (RSFC). We identified several distinct RSFC patterns of the insular subregions. Specifically, for positive connectivity, three cognitive-related RSFC patterns were identified within the insula, suggesting anterior-to-posterior functional subdivisions: (1) a dorsal anterior zone of the insula that shows RSFC with the executive control network (ECN); (2) a ventral anterior zone of the insula that shows functional connectivity with the salience network (SN); and (3) a posterior zone along the insula that shows functional connectivity with the sensorimotor network (SMN).
    UNASSIGNED: Compared to the controls, patients with SCD exhibited increased positive RSFC to the sub-region of the insula, demonstrating compensatory plasticity. Furthermore, these abnormal insular subregion RSFCs are closely correlated with cognitive performance in the SCD patients.
    UNASSIGNED: Our findings suggest that different insular subregions exhibit distinct patterns of RSFC with various functional networks, which are affected differently in patients with SCD.
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  • 文章类型: Journal Article
    胸苷(7-O-甲基草二醇),一种黄烷酮化合物,分离自大黄鱼和大黄鱼的叶子,具有神经保护作用,抗炎,和抗氧化性能。因此,使用网络药理学确定阿尔茨海默病的潜在靶标是有意义的.我们报告了100个潜在的类固醇目标和673个已知的阿尔茨海默氏症目标中的25个重叠目标。APP,BACE-1和AChE是富含与阿尔茨海默病相关的生物学过程和途径的十个中心靶标之一。随后,分子对接分析表明,胸骨与这些hub基因靶标具有最佳的结合特征,以供进一步考虑。
    Sterubin (7-O-Methyleriodicytol), a flavanone compound isolated from the leaves of Eriodicyton californicum and Eriodicyton angustifolium, has neuroprotective, anti-inflammatory, and antioxidant properties. Therefore, it is of interest to identify the potential targets for Alzheimer disease using network pharmacology. We report 25 overlapping targets among 100 potential targets of sterubin and 673 known targets of Alzheimer. APP, BACE-1, and AChE were among the ten hub targets enriched in biological processes and pathways relevant to Alzheimer\'s disease. Subsequent, molecular docking analysis shows that sterubin have optimal binding features with these hub gene targets for further consideration.
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