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Prediction of Heart Transplant Rejection Using Histopathological Whole-Slide Imaging. 利用组织病理学全切片成像预测心脏移植排斥反应
Adrienne E Dooley, Li Tong, Shriprasad R Deshpande, May D Wang

Endomyocardial biopsies are the current gold standard for monitoring heart transplant patients for signs of cardiac allograft rejection. Manually analyzing the acquired tissue samples can be costly, time-consuming, and subjective. Computer-aided diagnosis, using digitized whole-slide images, has been used to classify the presence and grading of diseases such as brain tumors and breast cancer, and we expect it can be used for prediction of cardiac allograft rejection. In this paper, we first create a pipeline to normalize and extract pixel-level and object-level features from histopathological whole-slide images of endomyocardial biopsies. Then, we develop a two-stage classification algorithm, where we first cluster individual tiles and then use the frequency of tiles in each cluster for classification of each whole-slide image. Our results show that the addition of an unsupervised clustering step leads to higher classification accuracy, as well as the importance of object-level features based on the pathophysiology of rejection. Future expansion of this study includes the development of a multiclass classification pipeline for subtypes and grades of cardiac allograft rejection.

心内膜活检是目前监测心脏移植患者心脏同种异体排斥迹象的金标准。人工分析获取的组织样本成本高、耗时长,而且很主观。计算机辅助诊断使用数字化全切片图像,已被用于对脑肿瘤和乳腺癌等疾病的存在和分级进行分类,我们希望它也能用于预测心脏异体移植排斥反应。在本文中,我们首先创建了一个管道,从心内膜活检组织病理全切片图像中归一化并提取像素级和对象级特征。然后,我们开发了一种两阶段分类算法,首先对单张图片进行聚类,然后利用每个聚类中图片的频率对每张整张幻灯片图像进行分类。我们的研究结果表明,增加无监督聚类步骤可提高分类准确率,同时还可提高基于排斥病理生理学的对象级特征的重要性。这项研究的未来扩展包括为心脏同种异体移植排斥反应的亚型和分级开发一个多类分类管道。
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引用次数: 0
Using Closure Tables to Enable Cross-Querying of Ontologies in Database-Driven Applications. 在数据库驱动的应用程序中使用闭包表实现本体的交叉查询。
Daniel R Harris, Darren W Henderson, Jeffery C Talbert

We demonstrate that closure tables are an effective data structure for developing database-driven applications that query biomedical ontologies and that require cross-querying between multiple ontologies. A closure table stores all available paths within a tree, even those without a direct parent-child relationship; additionally, a node can have multiple ancestors which gives the foundation for supporting linkages between controlled ontologies. We augment the meta-data structure of the ICD9 and ICD10 ontologies included in i2b2, an open source query tool for identifying patient cohorts, to utilize a closure table. We describe our experiences in incorporating existing mappings between ontologies to enable clinical and health researchers to identify patient populations using the ontology that best matches their preference and expertise.

我们证明闭包表是一种有效的数据结构,用于开发数据库驱动的应用程序来查询生物医学本体和需要在多个本体之间交叉查询。闭包表在树中存储所有可用的路径,即使是那些没有直接父子关系的路径;此外,一个节点可以有多个祖先,这为支持受控本体之间的链接提供了基础。我们增强了i2b2(一个用于识别患者队列的开源查询工具)中包含的ICD9和ICD10本体的元数据结构,以利用封闭表。我们描述了我们在整合本体之间的现有映射方面的经验,使临床和健康研究人员能够使用最符合他们偏好和专业知识的本体来识别患者群体。
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引用次数: 3
Detection of Nuclei in H&E Stained Sections Using Convolutional Neural Networks. 卷积神经网络检测H&E染色切片细胞核。
Mina Khoshdeli, Richard Cong, Bahram Parvin

Detection of nuclei is an important step in phenotypic profiling of histology sections that are usually imaged in bright field. However, nuclei can have multiple phenotypes, which are difficult to model. It is shown that convolutional neural networks (CNN)s can learn different phenotypic signatures for nuclear detection, and that the performance is improved with the feature-based representation of the original image. The feature-based representation utilizes Laplacian of Gaussian (LoG) filter, which accentuates blob-shape objects. Several combinations of input data representations are evaluated to show that by LoG representation, detection of nuclei is advanced. In addition, the efficacy of CNN for vesicular and hyperchromatic nuclei is evaluated. In particular, the frequency of detection of nuclei with the vesicular and apoptotic phenotypes is increased. The overall system has been evaluated against manually annotated nuclei and the F-Scores for alternative representations have been reported.

细胞核的检测是一个重要的步骤,在表型分析的组织学切片,通常是在明亮的视野成像。然而,细胞核可以有多种表型,这是很难建模的。研究表明,卷积神经网络(CNN)可以学习不同的表型特征用于核检测,并通过基于特征的原始图像表示提高了性能。基于特征的表示利用拉普拉斯高斯(LoG)滤波器,突出斑点形状的对象。对输入数据表示的几种组合进行了评估,表明通过LoG表示,核的检测是先进的。此外,我们还评估了CNN对泡状核和深染核的疗效。特别是,检出率的细胞核与泡状和凋亡表型增加。整个系统已经对人工注释的核进行了评估,并报告了替代表示的f分数。
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引用次数: 31
Mining standardized neurological signs and symptoms data for concussion identification. 挖掘标准化的神经体征和症状数据,以识别脑震荡。
Janani Venugopalan, Michelle C LaPlaca, May D Wang

The Centers for Disease Control estimate that 1.6 to 3.8 million concussions occur in sports and recreational activities annually. Studies have shown that concussions increase the risk of future injuries and mild cognitive disorders. Despite extensive research on sports related concussion risk factors, the factors which are most predictive of concussion outcome and recovery time course remain unknown. In order to overcome the issue of physician bias and to identify the factors which can best predict concussion diagnosis, we propose a multi-variate logistic regression based analysis. We demonstrate our results on a dataset with 126 subjects (ages 12-31). Our results indicate that among 322 features, our model selected 27-29 features which included a history of playing sports, history of a previous concussion, drowsiness, nausea, trouble focusing as measured by a common symptom list, and oculomotor function. The features picked using our model were found to be highly predictive of concussions and gave a prediction performance accuracy greater than 90%, Matthews correlation coefficient greater than 0.8 and the area under the curve greater than 0.95.

据美国疾病控制中心估计,每年在体育和娱乐活动中发生的脑震荡达 160 万至 380 万次。研究表明,脑震荡会增加未来受伤和轻度认知障碍的风险。尽管对与运动相关的脑震荡风险因素进行了广泛的研究,但最能预测脑震荡结果和恢复时间进程的因素仍然未知。为了克服医生偏见问题,并找出最能预测脑震荡诊断的因素,我们提出了一种基于多变量逻辑回归的分析方法。我们在一个包含 126 名受试者(12-31 岁)的数据集上展示了我们的结果。结果表明,在 322 个特征中,我们的模型选取了 27-29 个特征,其中包括运动史、既往脑震荡史、嗜睡、恶心、根据常见症状列表测量的注意力不集中以及眼球运动功能。使用我们的模型选出的特征对脑震荡具有很高的预测性,预测准确率超过 90%,马修斯相关系数大于 0.8,曲线下面积大于 0.95。
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引用次数: 0
Improving Multi-class Classification for Endomicroscopic Images by Semi-supervised Learning. 通过半监督学习改进内窥镜图像的多类分类
Hang Wu, Li Tong, May D Wang

Optical Endomicroscopy (OE) is a newly-emerged biomedical imaging modality that can help physicians make real-time clinical decisions about patients' grade of dysplasia. However, the performance of applying medical imaging classification for computer-aided diagnosis is primarily limited by the lack of labeled images. To improve the classification performance, we propose a semi-supervised learning algorithm that can incorporate large sets of unlabeled images. Our real-world endo-microscopic imaging datasets consist of 425 labeled images and 2,826 unlabeled ones. With semi-supervised learning algorithms, we improved multi-class classification performance over supervised learning algorithms by around 10% in all evaluation metrics, namely precision, recall, F1 score and Cohen-Kappa statistics.

光学内窥镜(OE)是一种新兴的生物医学成像模式,可帮助医生对患者的发育不良程度做出实时的临床决策。然而,将医学影像分类应用于计算机辅助诊断的性能主要受到缺乏标记图像的限制。为了提高分类性能,我们提出了一种半监督学习算法,该算法可结合大量未标记图像集。我们的真实世界内窥镜成像数据集包括 425 张标注图像和 2826 张未标注图像。利用半监督学习算法,我们在所有评估指标(即精确度、召回率、F1 分数和 Cohen-Kappa 统计量)上都比监督学习算法的多类分类性能提高了约 10%。
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引用次数: 0
Intelligent Mortality Reporting with FHIR. FHIR智能死亡率报告。
Ryan A Hoffman, Hang Wu, Janani Venugopalan, Paula Braun, May D Wang

One pressing need in the area of public health is timely, accurate, and complete reporting of deaths and the conditions leading up to them. Fast Healthcare Interoperability Resources (FHIR) is a new HL7 interoperability standard for electronic health record (EHR), while Sustainable Medical Applications and Reusable Technologies (SMART)-on-FHIR enables third-party app development that can work "out of the box". This research demonstrates the feasibility of developing SMART-on-FHIR applications to enable medical professionals to perform timely and accurate death reporting within multiple different jurisdictions of US. We explored how the information on a standard certificate of death can be mapped to resources defined in the FHIR standard (DSTU2). We also demonstrated analytics for potentially improving the accuracy and completeness of mortality reporting data.

公共卫生领域的一项迫切需要是及时、准确和完整地报告死亡和导致死亡的条件。快速医疗互操作性资源(FHIR)是针对电子健康记录(EHR)的新的HL7互操作性标准,而基于FHIR的可持续医疗应用和可重用技术(SMART)使第三方应用程序开发能够“开箱即用”。这项研究证明了开发fhir智能应用程序的可行性,使医疗专业人员能够在美国多个不同的司法管辖区及时准确地进行死亡报告。我们探讨了如何将标准死亡证明上的信息映射到FHIR标准(DSTU2)中定义的资源。我们还展示了可能提高死亡率报告数据准确性和完整性的分析方法。
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引用次数: 16
Analyzing the Usage of Standards in Radiation Therapy Clinical Studies. 分析放射治疗临床研究中标准的使用情况。
Y Zhen, Y Jiang, L Yuan, J Kirkpartrick, J Wu, Y Ge

Standards for scoring adverse effects after radiation therapy (RT) is crucial for integrated, consistent, and accurate analysis of toxicity results at large scale and across multiple studies. This project aims to investigate the usage of the three most commonly used standards in published RT clinical studies by developing a text-mining based analysis method. We develop and compare two text-mining methods, one based on regular expressions and one based on Naïve Bayes Classifier, to analyze published full articles in terms of their adoption of standards in RT. The full dataset includes published articles identified in MEDLINE between January 2010 and August 2015. A radiation oncology physician reviewed all the articles in the training/validation subset and produced the usage trending data manually as gold standard for validation. The regular-expression based method reported classifications and overall usage trends that are comparable to those of the domain expert. The CTCAE standard is becoming the overall most commonly used standards over time, but the pace of adoption seems very slow. Further examination of the results indicates that the usage vary by disease type. It suggests that further efforts are needed to improve and harmonize the standards for adverse effects scoring in RT research community.

放射治疗(RT)后不良反应评分标准对于大规模、跨多项研究的综合、一致、准确的毒性结果分析至关重要。本项目旨在通过开发一种基于文本挖掘的分析方法,调查已发表的 RT 临床研究中最常用的三种标准的使用情况。我们开发并比较了两种文本挖掘方法,一种是基于正则表达式的方法,另一种是基于奈伊夫贝叶斯分类器的方法,以分析已发表的完整文章在 RT 中采用标准的情况。完整数据集包括 2010 年 1 月至 2015 年 8 月期间在 MEDLINE 中发现的已发表文章。一位放射肿瘤科医生审阅了训练/验证子集中的所有文章,并手动生成了使用趋势数据,作为验证的金标准。基于正则表达式的方法报告的分类和总体使用趋势与领域专家的报告相当。随着时间的推移,CTCAE 标准正在成为最常用的总体标准,但采用的速度似乎非常缓慢。对结果的进一步研究表明,不同疾病类型的使用情况各不相同。这表明需要进一步努力改进和协调 RT 研究界的不良反应评分标准。
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引用次数: 0
On Quantifying Diffusion of Health Information on Twitter. 论Twitter上健康信息的量化传播。
Gokhan Bakal, Ramakanth Kavuluru

With the increasing use of digital technologies, online social networks are emerging as major means of communication. Recently, social networks such as Facebook and Twitter are also being used by consumers, care providers (physicians, hospitals), and government agencies to share health related information. The asymmetric user network and the short message size have made Twitter particularly popular for propagating health related content on the Web. Besides tweeting on their own, users can choose to retweet particular tweets from other users (even if they do not follow them on Twitter.) Thus, a tweet can diffuse through the Twitter network via the follower-friend connections. In this paper, we report results of a pilot study we conducted to quantitatively assess how health related tweets diffuse in the directed follower-friend Twitter graph through the retweeting activity. Our effort includes (1). development of a retweet collection and Twitter retweet graph formation framework and (2). a preliminary analysis of retweet graphs and associated diffusion metrics for health tweets. Given the ambiguous nature (due to polysemy and sarcasm) of health relatedness of tweets collected with keyword based matches, our initial study is limited to ≈ 200 health related tweets (which were manually verified to be on health topics) each with at least 25 retweets. To our knowledge, this is first attempt to study health information diffusion on Twitter through retweet graph analysis.

随着数字技术的日益普及,在线社交网络正在成为主要的交流方式。最近,像Facebook和Twitter这样的社交网络也被消费者、护理提供者(医生、医院)和政府机构用来分享健康相关信息。不对称的用户网络和短消息大小使得Twitter在Web上传播健康相关内容时特别受欢迎。除了自己发推外,用户还可以选择转发其他用户的特定推文(即使他们没有在Twitter上关注这些用户)。因此,一条tweet可以通过关注者-朋友关系在Twitter网络中传播。在本文中,我们报告了我们进行的一项试点研究的结果,该研究旨在定量评估健康相关推文如何通过转发活动在直接关注者-朋友推特图中扩散。我们的工作包括:(1)开发转发收集和Twitter转发图形成框架;(2)对健康推文的转发图和相关扩散指标进行初步分析。考虑到基于关键字匹配收集的推文的健康相关性的模糊性(由于一词多义和讽刺),我们的初步研究仅限于≈200条与健康相关的推文(人工验证为健康主题),每条推文至少有25条转发。据我们所知,这是第一次尝试通过转发图分析来研究Twitter上的健康信息传播。
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引用次数: 10
Phenotyping Hypotensive Patients in Critical Care Using Hospital Discharge Summaries. 利用出院摘要对重症监护中的低血压患者进行表型分析。
Yang Dai, Sharukh Lokhandwala, William Long, Roger Mark, Li-Wei H Lehman

Among critically-ill patients, hypotension represents a failure in compensatory mechanisms and may lead to organ hypoperfusion and failure. In this work, we adopt a data-driven approach for phenotype discovery and visualization of patient similarity and cohort structure in the intensive care unit (ICU). We used Hierarchical Dirichlet Process (HDP) as a nonparametric topic modeling technique to automatically learn a d-dimensional feature representation of patients that captures the latent "topic" structure of diseases, symptoms, medications, and findings documented in hospital discharge summaries. We then used the t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm to convert the d-dimensional latent structure learned from HDP into a matrix of pairwise similarities for visualizing patient similarity and cohort structure. Using discharge summaries of a large patient cohort from the MIMIC II database, we evaluated the clinical utility of the discovered topic structure in phenotyping critically-ill patients who experienced hypotensive episodes. Our results indicate that the approach is able to reveal clinically interpretable clustering structure within our cohort and may potentially provide valuable insights to better understand the association between disease phenotypes and outcomes.

在重症患者中,低血压代表着代偿机制的失败,可能导致器官灌注不足和衰竭。在这项工作中,我们采用了一种数据驱动的方法来发现表型,并将重症监护室(ICU)中患者的相似性和队列结构可视化。我们使用分层 Dirichlet 过程(HDP)作为非参数主题建模技术,自动学习患者的 d 维特征表示,捕捉出院摘要中记录的疾病、症状、药物和检查结果的潜在 "主题 "结构。然后,我们使用 t 分布随机邻域嵌入(t-SNE)算法,将从 HDP 中学习到的 d 维潜在结构转换成成对相似性矩阵,以可视化患者相似性和队列结构。利用 MIMIC II 数据库中一个大型患者队列的出院摘要,我们评估了所发现的主题结构在经历过低血压发作的重症患者表型中的临床实用性。我们的结果表明,这种方法能够揭示队列中临床上可解释的聚类结构,并有可能为更好地理解疾病表型和预后之间的关联提供有价值的见解。
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引用次数: 0
Estimating Patient's Health State Using Latent Structure Inferred from Clinical Time Series and Text. 利用临床时间序列和文本推断的潜在结构估计患者的健康状况。
Aaron Zalewski, William Long, Alistair E W Johnson, Roger G Mark, Li-Wei H Lehman

Modern intensive care units (ICUs) collect large volumes of data in monitoring critically ill patients. Clinicians in the ICUs face the challenge of interpreting large volumes of high-dimensional data to diagnose and treat patients. In this work, we explore the use of Hierarchical Dirichlet Processes (HDP) as a Bayesian nonparametric framework to infer patients' states of health by combining multiple sources of data. In particular, we employ HDP to combine clinical time series and text from the nursing progress notes in a probabilistic topic modeling framework for patient risk stratification. Given a patient cohort, we use HDP to infer latent "topics" shared across multimodal patient data from the entire cohort. Each topic is modeled as a multinomial distribution over a vocabulary of codewords, defined over heterogeneous data sources. We evaluate the clinical utility of the learned topic structure using the first 24-hour ICU data from over 17,000 adult patients in the MIMIC-II database to estimate patients' risks of in-hospital mortality. Our results demonstrate that our approach provides a viable framework for combining different data modalities to model patient's states of health, and can potentially be used to generate alerts to identify patients at high risk of hospital mortality.

现代重症监护病房(icu)在监测危重患者时收集了大量数据。icu的临床医生面临着解释大量高维数据以诊断和治疗患者的挑战。在这项工作中,我们探索使用分层狄利克雷过程(HDP)作为贝叶斯非参数框架,通过结合多个数据来源来推断患者的健康状态。特别是,我们使用HDP将临床时间序列和护理进度记录中的文本结合在一个概率主题建模框架中,用于患者风险分层。给定一个患者队列,我们使用HDP来推断来自整个队列的多模式患者数据共享的潜在“主题”。每个主题都建模为在异构数据源上定义的码字词汇表上的多项分布。我们使用MIMIC-II数据库中超过17,000名成年患者的第一个24小时ICU数据来评估学习主题结构的临床效用,以估计患者在院死亡的风险。我们的研究结果表明,我们的方法提供了一个可行的框架,可以结合不同的数据模式来模拟患者的健康状况,并有可能用于生成警报,以识别医院死亡率高的患者。
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引用次数: 13
期刊
... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics
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