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Stratification and Survival Prediction for Amyotrophic Lateral Sclerosis Patients 肌萎缩侧索硬化症患者的分层和生存预测
Yixiao Huang, Xiaoli Wu, Rosa H. M. Chan
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引用次数: 0
Transcutaneous Cervical Vagus Nerve Stimulation Reduces Respiratory Variability in the Context of Opioid Withdrawal. 经皮颈迷走神经刺激可降低阿片类药物戒断时的呼吸变异性
Asim H Gazi, Anna B Harrison, Tamara P Lambert, Malik Obideen, Justine W Welsh, Viola Vaccarino, Amit J Shah, Sudie E Back, Christopher J Rozell, J Douglas Bremner, Omer T Inan

Opioid withdrawal's physiological effects are a major impediment to recovery from opioid use disorder (OUD). Prior work has demonstrated that transcutaneous cervical vagus nerve stimulation (tcVNS) can counteract some of opioid withdrawal's physiological effects by reducing heart rate and perceived symptoms. The purpose of this study was to assess the effects of tcVNS on respiratory manifestations of opioid withdrawal - specifically, respiratory timings and their variability. Patients with OUD (N = 21) underwent acute opioid withdrawal over the course of a two-hour protocol. The protocol involved opioid cues to induce opioid craving and neutral conditions for control purposes. Patients were randomly assigned to receive double-blind active tcVNS (n = 10) or sham stimulation (n = 11) throughout the protocol. Respiratory effort and electrocardiogram-derived respiration signals were used to estimate inspiration time (Ti), expiration time (Te), and respiration rate (RR), along with each measure's variability quantified via interquartile range (IQR). Comparing the active and sham groups, active tcVNS significantly reduced IQR(Ti) - a variability measure - compared to sham stimulation (p = .02). Relative to baseline, the active group's median change in IQR(Ti) was 500 ms less than the sham group's median change in IQR(Ti). Notably, IQR(Ti) was found to be positively associated with post-traumatic stress disorder symptoms in prior work. Therefore, a reduction in IQR(Ti) suggests that tcVNS downregulates the respiratory stress response associated with opioid withdrawal. Although further investigations are necessary, these results promisingly suggest that tcVNS - a non-pharmacologic, non-invasive, readily implemented neuromodulation approach - can serve as a novel therapy to mitigate opioid withdrawal symptoms.

阿片类药物戒断的生理效应是阿片类药物使用障碍(OUD)康复的主要障碍。先前的研究表明,经皮颈迷走神经刺激(tcVNS)可以通过降低心率和感知症状来抵消阿片戒断的一些生理效应。本研究旨在评估经皮颈迷走神经刺激对阿片类药物戒断的呼吸表现的影响,特别是呼吸时间及其可变性。OUD 患者(21 人)在两小时的治疗过程中接受了阿片类药物急性戒断治疗。该方案包括诱发阿片渴求的阿片线索和用于对照的中性条件。在整个治疗过程中,患者被随机分配接受双盲活性 tcVNS 刺激(10 人)或假刺激(11 人)。呼吸努力和心电图衍生呼吸信号用于估算吸气时间(Ti)、呼气时间(Te)和呼吸频率(RR),并通过四分位数间距(IQR)量化每个测量值的变异性。比较主动组和假刺激组,与假刺激相比,主动 tcVNS 显著降低了变异性指标 IQR(Ti)(p = 0.02)。与基线相比,主动组的 IQR(Ti) 中位变化比假刺激组的 IQR(Ti) 中位变化少 500 毫秒。值得注意的是,之前的研究发现 IQR(Ti) 与创伤后应激障碍症状呈正相关。因此,IQR(Ti)的降低表明,tcVNS能降低与阿片类药物戒断相关的呼吸应激反应。尽管还需要进一步的研究,但这些结果令人鼓舞地表明,tcVNS 这种非药物、非侵入性、易于实施的神经调节方法可以作为一种新型疗法来缓解阿片类药物戒断症状。
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引用次数: 0
Genomics transformer for diagnosing Parkinson's disease. 用于诊断帕金森病的基因组转换器。
Diego Machado Reyes, Mansu Kim, Hanqing Chao, Juergen Hahn, Li Shen, Pingkun Yan

Parkinson's disease (PD) is the second most common neurodegenerative disease and presents a complex etiology with genomic and environmental factors and no recognized cures. Genotype data, such as single nucleotide polymorphisms (SNPs), could be used as a prodromal factor for early detection of PD. However, the polygenic nature of PD presents a challenge as the complex relationships between SNPs towards disease development are difficult to model. Traditional assessment methods such as polygenic risk scores and machine learning approaches struggle to capture the complex interactions present in the genotype data, thus limiting their discriminative capabilities in diagnosis. On the other hand, deep learning models are better suited for this task. Nevertheless, they encounter difficulties of their own such as a lack of interpretability. To overcome these limitations, in this work, a novel transformer encoder-based model is introduced to classify PD patients from healthy controls based on their genotype. This method is designed to effectively model complex global feature interactions and enable increased interpretability through the learned attention scores. The proposed framework outperformed traditional machine learning models and multilayer perceptron (MLP) baseline models. Moreover, visualization of the learned SNP-SNP associations provides not only interpretability to the model but also valuable insights into the biochemical pathways underlying PD development, which are corroborated by pathway enrichment analysis. Our results suggest novel SNP interactions to be further studied in wet lab and clinical settings.

帕金森病(PD)是第二常见的神经退行性疾病,其病因复杂,有基因组和环境因素,尚无公认的治疗方法。基因型数据,如单核苷酸多态性(SNPs),可以作为早期检测PD的前驱因素。然而,PD的多基因性质带来了挑战,因为SNPs与疾病发展之间的复杂关系很难建模。传统的评估方法,如多基因风险评分和机器学习方法,难以捕捉基因型数据中存在的复杂相互作用,从而限制了它们在诊断中的判别能力。另一方面,深度学习模型更适合这项任务。尽管如此,他们也会遇到自己的困难,比如缺乏可解释性。为了克服这些局限性,在这项工作中,引入了一种新的基于变压器编码器的模型,根据PD患者的基因型将其从健康对照中分类。该方法旨在有效地对复杂的全局特征交互进行建模,并通过学习的注意力得分提高可解释性。所提出的框架优于传统的机器学习模型和多层感知器(MLP)基线模型。此外,所学习的SNP-SNP关联的可视化不仅为模型提供了可解释性,而且还提供了对PD发展背后的生化途径的有价值的见解,这一点通过途径富集分析得到了证实。我们的研究结果表明,新的SNP相互作用有待在湿实验室和临床环境中进一步研究。
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引用次数: 0
Analysis of Regions of Interest and Distractor Regions in Breast Biopsy Images. 乳腺活检图像中感兴趣区域和干扰区域的分析。
Ximing Lu, Sachin Mehta, Tad T Brunyé, Donald L Weaver, Joann G Elmore, Linda G Shapiro
This paper studies why pathologists can misdiagnose diagnostically challenging breast biopsy cases, using a data set of 240 whole slide images (WSIs). Three experienced pathologists agreed on a consensus reference ground-truth diagnosis for each slide and also a consensus region of interest (ROI) from which the diagnosis could best be made. A study group of 87 other pathologists then diagnosed test sets (60 slides each) and marked their own regions of interest. Diagnoses and ROIs were categorized such that if on a given slide, their ROI differed from the consensus ROI and their diagnosis was incorrect, that ROI was called a distractor. We used the HATNet transformer-based deep learning classifier to evaluate the visual similarities and differences between the true (consensus) ROIs and the distractors. Results showed high accuracy for both the similarity and difference networks, showcasing the challenging nature of feature classification with breast biopsy images. This study is important in the potential use of its results for teaching pathologists how to diagnose breast biopsy slides.
本文研究了为什么病理学家会误诊诊断具有挑战性的乳腺活检病例,使用了240个完整的幻灯片图像(wsi)的数据集。三位经验丰富的病理学家就每张幻灯片的基准诊断达成了共识,并就诊断最佳的兴趣区域(ROI)达成了共识。一个由87名病理学家组成的研究小组随后诊断了测试组(每个组60张幻灯片),并标记了他们感兴趣的区域。诊断和投资回报率被分类,如果在给定的幻灯片上,他们的投资回报率与共识投资回报率不同,他们的诊断是不正确的,投资回报率被称为分心。我们使用基于HATNet转换器的深度学习分类器来评估真实(共识)roi和干扰物之间的视觉相似性和差异性。结果显示,相似性和差异网络的准确率都很高,这显示了乳房活检图像特征分类的挑战性。这项研究的结果对于指导病理学家如何诊断乳腺活检片具有重要的潜在意义。
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引用次数: 2
Uncertainty-based Self-training for Biomedical Keyphrase Extraction. 基于不确定性的生物医学关键词提取自训练。
Zelalem Gero, Joyce C Ho

To keep pace with the increased generation and digitization of documents, automated methods that can improve search, discovery and mining of the vast body of literature are essential. Keyphrases provide a concise representation by identifying salient concepts in a document. Various supervised approaches model keyphrase extraction using local context to predict the label for each token and perform much better than the unsupervised counterparts. However, existing supervised datasets have limited annotated examples to train better deep learning models. In contrast, many domains have large amount of un-annotated data that can be leveraged to improve model performance in keyphrase extraction. We introduce a self-learning based model that incorporates uncertainty estimates to select instances from large-scale unlabeled data to augment the small labeled training set. Performance evaluation on a publicly available biomedical dataset demonstrates that our method improves performance of keyphrase extraction over state of the art models.

为了跟上日益增长的文档生成和数字化的步伐,能够改进大量文献的搜索、发现和挖掘的自动化方法是必不可少的。关键字通过识别文档中的重要概念提供了简洁的表示。各种监督方法使用本地上下文对关键短语提取进行建模,以预测每个令牌的标签,并且比无监督的对应方法执行得更好。然而,现有的监督数据集具有有限的注释示例来训练更好的深度学习模型。相比之下,许多领域有大量未注释的数据,可以利用这些数据来提高关键字提取中的模型性能。我们引入了一种基于自学习的模型,该模型结合不确定性估计从大规模未标记数据中选择实例,以增强小标记训练集。对公开可用的生物医学数据集的性能评估表明,我们的方法比最先进的模型提高了关键词提取的性能。
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引用次数: 3
Transcutaneous Cervical Vagus Nerve Stimulation Lengthens Exhalation in the Context of Traumatic Stress. 经皮颈迷走神经刺激延长创伤应激的呼气。
Asim H Gazi, Srirakshaa Sundararaj, Anna B Harrison, Nil Z Gurel, Matthew T Wittbrodt, Amit J Shah, Viola Vaccarino, J Douglas Bremner, Omer T Inan
Transcutaneous electrical stimulation of the vagus nerve is believed to deliver afferent signaling to the brain that, in turn, yields downstream changes in peripheral physiology, including cardiovascular and respiratory parameters. While the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on these parameters have been studied broadly, little is known regarding the specific effects of tcVNS on exhalation time and the spontaneous respiration cycle. By understanding such effects, tcVNS could be used to counterbalance sympathetic hyperactivity following distress by enhancing vagal tone through parasympathetically favored modulation of inspiration and expiration – specifically, lengthened expiration relative to inspiration. We thus investigated the effects of tcVNS on respiration timings by decomposing the respiration cycle into inspiration and expiration times and incorporating state-of-the-art respiration quality assessment algorithms for respiratory effort belt and electrocardiogram derived respiration signals. This enabled robust estimation of respiration timings from quality measurements alone. We thereby found that tcVNS increases expiration time minutes after stimulation, compared to a sham control (N = 26). This suggests that tcVNS could counteract sympathovagal imbalance, given the relationship between expiration and heightened vagal tone.
经皮电刺激迷走神经被认为向大脑传递传入信号,进而产生下游外周生理变化,包括心血管和呼吸参数。虽然经皮颈迷走神经刺激(tcVNS)对这些参数的影响已被广泛研究,但tcVNS对呼气时间和自主呼吸周期的具体影响尚不清楚。通过了解这些影响,tcVNS可以通过副交感神经偏爱的吸气和呼气调节来增强迷走神经张力,特别是相对于吸气延长呼气,从而抵消焦虑后的交感神经亢进。因此,我们通过将呼吸周期分解为吸气和呼气时间,并结合呼吸努力带和心电图衍生呼吸信号的最先进呼吸质量评估算法,研究了tcVNS对呼吸时间的影响。这使得仅从质量测量就可以可靠地估计呼吸时间。因此,我们发现与假对照相比,tcVNS在刺激后增加了过期时间(N = 26)。这表明tcVNS可以抵消交感迷走神经失衡,考虑到呼气和增强迷走神经张力之间的关系。
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引用次数: 6
KARGA: Multi-platform Toolkit for k-mer-based Antibiotic Resistance Gene Analysis of High-throughput Sequencing Data. KARGA:基于k-mer的抗生素耐药基因分析高通量测序数据的多平台工具包。
Mattia Prosperi, Simone Marini

High-throughput sequencing is widely used for strain detection and characterization of antibiotic resistance in microbial metagenomic samples. Current analytical tools use curated antibiotic resistance gene (ARG) databases to classify individual sequencing reads or assembled contigs. However, identifying ARGs from raw read data can be time consuming (especially if assembly or alignment is required) and challenging, due to genome rearrangements and mutations. Here, we present the k-mer-based antibiotic gene resistance analyzer (KARGA), a multi-platform Java toolkit for identifying ARGs from metagenomic short read data. KARGA does not perform alignment; it uses an efficient double-lookup strategy, statistical filtering on false positives, and provides individual read classification as well as covering of the database resistome. On simulated data, KARGA's antibiotic resistance class recall is 99.89% for error/mutation rates within 10%, and of 83.37% for error/mutation rates between 10% and 25%, while it is 99.92% on ARGs with rearrangements. On empirical data, KARGA provides higher hit score (≥1.5-fold) than AMRPlusPlus, DeepARG, and MetaMARC. KARGA has also faster runtimes than all other tools (2x faster than AMRPlusPlus, 7x than DeepARG, and over 100x than MetaMARC). KARGA is available under the MIT license at https://github.com/DataIntellSystLab/KARGA.

高通量测序被广泛用于微生物宏基因组样品的菌株检测和抗生素耐药性鉴定。目前的分析工具使用精心策划的抗生素耐药基因(ARG)数据库对单个测序读段或组装的contigs进行分类。然而,由于基因组重排和突变,从原始读取数据中识别ARGs可能非常耗时(特别是如果需要组装或比对)并且具有挑战性。在这里,我们提出了基于k-mer的抗生素基因耐药性分析仪(KARGA),这是一个多平台Java工具包,用于从宏基因组短读数据中识别ARGs。KARGA不执行对齐;它使用有效的双重查找策略,对误报进行统计过滤,并提供单独的读取分类以及覆盖数据库阻力组。模拟数据显示,当错误/突变率在10%以内时,KARGA的抗生素耐药性类别召回率为99.89%,当错误/突变率在10% - 25%之间时,召回率为83.37%,而对于重排ARGs,召回率为99.92%。在经验数据上,KARGA比AMRPlusPlus、DeepARG和MetaMARC提供更高的命中分数(≥1.5倍)。KARGA的运行速度也比所有其他工具都快(比AMRPlusPlus快2倍,比DeepARG快7倍,比MetaMARC快100倍)。KARGA在MIT许可下可在https://github.com/DataIntellSystLab/KARGA获得。
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引用次数: 6
A Machine Learning Approach to Predict Acute Ischemic Stroke Thrombectomy Reperfusion using Discriminative MR Image Features. 基于判别性MR图像特征预测急性缺血性卒中取栓再灌注的机器学习方法。
Haoyue Zhang, Jennifer Polson, Kambiz Nael, Noriko Salamon, Bryan Yoo, William Speier, Corey Arnold

Mechanical thrombectomy (MTB) is one of the two standard treatment options for Acute Ischemic Stroke (AIS) patients. Current clinical guidelines instruct the use of pretreatment imaging to characterize a patient's cerebrovascular flow, as there are many factors that may underlie a patient's successful response to treatment. There is a critical need to leverage pretreatment imaging, taken at admission, to guide potential treatment avenues in an automated fashion. The aim of this study is to develop and validate a fully automated machine learning algorithm to predict the final modified thrombolysis in cerebral infarction (mTICI) score following MTB. A total 321 radiomics features were computed from segmented pretreatment MRI scans for 141 patients. Successful recanalization was defined as mTICI score >= 2c. Different feature selection methods and classification models were examined in this study. Our best performance model achieved 74.42±2.52% AUC, 75.56±4.44% sensitivity, and 76.75±4.55% specificity, showing a good prediction of reperfusion quality using pretreatment MRI. Results suggest that MR images can be informative to predicting patient response to MTB, and further validation with a larger cohort can determine the clinical utility.

机械取栓(MTB)是急性缺血性卒中(AIS)患者的两种标准治疗方案之一。目前的临床指南指导使用预处理成像来表征患者的脑血管血流,因为有许多因素可能是患者对治疗成功反应的基础。目前迫切需要利用入院时的预处理成像,以自动化的方式指导潜在的治疗途径。本研究的目的是开发和验证一种全自动机器学习算法,以预测MTB后脑梗死后的最终改良血栓溶解(mTICI)评分。从141例患者的分割预处理MRI扫描中计算出总共321个放射组学特征。再通成功定义为mTICI评分>= 2c。本研究考察了不同的特征选择方法和分类模型。我们的最佳性能模型AUC为74.42±2.52%,灵敏度为75.56±4.44%,特异性为76.75±4.55%,可以很好地预测MRI预处理后的再灌注质量。结果表明,MR图像可以为预测患者对MTB的反应提供信息,并且通过更大的队列进一步验证可以确定临床效用。
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引用次数: 3
Theory-Guided Randomized Neural Networks for Decoding Medication-Taking Behavior. 理论引导的随机神经网络解码服药行为。
Navreet Kaur, Manuel Gonzales, Cristian Garcia Alcaraz, Laura E Barnes, Kristen J Wells, Jiaqi Gong

Long-term endocrine therapy (e.g. Tamoxifen, aromatase inhibitors) is crucial to prevent breast cancer recurrence, yet rates of adherence to these medications are low. To develop, evaluate, and sustain future interventions, individual-level modeling can be used to understand breast cancer survivors' behavioral mechanisms of medication-taking. This paper presents interdisciplinary research, wherein a model employing randomized neural networks was developed to predict breast cancer survivors' daily medication-taking behavior based on their survey data over three time periods (baseline, 4 months, 8 months). The neural network structure was guided by random utility theory developed in psychology and behavioral economics. Comparative analysis indicates that the proposed model outperforms existing computational models in terms of prediction accuracy under conditions of randomness.

长期的内分泌治疗(如他莫昔芬、芳香化酶抑制剂)对预防乳腺癌复发至关重要,但坚持使用这些药物的比率很低。为了开发、评估和维持未来的干预措施,个体水平的建模可以用来了解乳腺癌幸存者服药的行为机制。本文采用跨学科研究,基于三个时间段(基线、4个月、8个月)的调查数据,建立了一个采用随机神经网络的模型来预测乳腺癌幸存者的日常服药行为。神经网络的结构以心理学和行为经济学的随机效用理论为指导。对比分析表明,该模型在随机性条件下的预测精度优于现有计算模型。
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引用次数: 1
Simulating Study Design Choice Effects on Observed Performance of Predictive Patient Monitoring Alarm Algorithms. 模拟研究设计选择对预测性病人监测报警算法观察性能的影响。
David O Nahmias, Christopher G Scully

There are multiple study design choices to be selected in order to perform evaluations of predictive patient monitoring algorithms related to the event and true positive alarm definitions (e.g., how far ahead of the event is a true positive alarm). Often, passively collected patient monitoring datasets from clinical environments are available to perform these types of studies, so that the effects of different study design choices can be simulated to evaluate the robustness of an algorithm to those choices. Here, we simulate the effects of varying alarm and event definition criteria on the reported performance of the early warning score to predict hypotensive events. A total of 432 combinations of study design choices were simulated. Area under the receiver-operating characteristic curve varied from greater than 0.8 to less than 0.5 by adjusting alarm and event definition criteria. Traditional metrics for evaluating diagnostic systems were modulated across a wide range by adjusting study design choices for a predictive algorithm using a patient monitoring dataset. This highlights the importance of examining study design choices for new predictive patient monitoring algorithms and presents an approach to simulate different study designs with retrospective patient monitoring data as part of a robustness evaluation.

为了对与事件和真阳性警报定义(例如,事件发生前多远是真阳性警报)相关的预测性患者监测算法进行评估,需要选择多种研究设计选择。通常,从临床环境中被动收集的患者监测数据集可用于执行这些类型的研究,因此可以模拟不同研究设计选择的效果,以评估算法对这些选择的鲁棒性。在这里,我们模拟了不同的报警和事件定义标准对早期预警评分报告性能的影响,以预测低血压事件。总共模拟了432种研究设计选择组合。通过调整报警和事件定义标准,接收器工作特征曲线下的面积从大于0.8变化到小于0.5。通过调整使用患者监测数据集的预测算法的研究设计选择,对评估诊断系统的传统指标进行了大范围的调整。这突出了研究设计选择对新的预测性患者监测算法的重要性,并提出了一种方法,以回顾性患者监测数据模拟不同的研究设计,作为鲁棒性评估的一部分。
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引用次数: 0
期刊
... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics
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