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Caudal and Thalamic Segregation in White Matter Brain Network Communities in Alzheimer's Disease Population. 阿尔茨海默病人群白质脑网络社区的尾侧和丘脑分离。
Frederick Xu, Duy Duong-Tran, Yize Zhao, Li Shen

Neuroimaging studies have demonstrated that Alzheimer's disease (AD) is closely related to changes in neuroanatomy in the form of damage to both grey matter and white matter. However, the exact nature of AD's relationship with white matter anatomical deterioration is not fully understood at a systemic level. To investigate this knowledge gap, we constructed structural brain networks from ADNI-GO/2 diffusion tensor imaging (DTI) images with brain regions of interest (ROIs) as nodes and white matter connections as edges weighted by fiber density. The cohort consists of healthy control (HC), mild cognitive impairment (MCI), and clinically diagnosed AD subjects. By optimizing consensus modularity of structural brain networks at a subpopulation level to investigate community structure throughout a range of resolution parameters (γ), we observed a split of the reward-based decision-making module in the AD group at γ = 1.3, thus finding a 7th consensus community in the AD consensus brain network partition that was not present in that of MCI or HC populations. Upon further investigation, we found that thalamic and caudal regions were involved in the increased segregation of AD brain networks. These regions are implicated in regulation of decision-making processes, and their segregation from other decision-making regions is a novel finding in white matter biomarker studies of AD. Our study presents novel evidence that AD may be a disconnection syndrome at the mesoscopic structural level, with potential new avenues of exploration into the role of the thalamus and caudate that may reveal neural correlates of cognitive deficits in clinically diagnosed AD.

神经影像学研究表明,阿尔茨海默病(AD)与神经解剖学的变化密切相关,表现为灰质和白质的损伤。然而,阿尔茨海默病与白质解剖退化的关系的确切性质在系统水平上尚不完全清楚。为了研究这种知识差距,我们从ADNI-GO/2扩散张量成像(DTI)图像中构建了结构脑网络,其中大脑感兴趣区域(roi)作为节点,白质连接作为纤维密度加权的边缘。该队列包括健康对照(HC)、轻度认知障碍(MCI)和临床诊断为AD的受试者。通过在亚群体水平上优化大脑网络结构的共识模块化,通过一系列分辨率参数(γ)来研究社区结构,我们观察到AD组中基于奖励的决策模块在γ = 1.3时分裂,从而在AD共识大脑网络分区中发现了MCI或HC群体中不存在的第7个共识社区。在进一步的研究中,我们发现丘脑和尾侧区域参与了AD脑网络分离的增加。这些区域与决策过程的调节有关,它们与其他决策区域的分离是AD白质生物标志物研究中的一个新发现。我们的研究提供了新的证据,表明阿尔茨海默病可能是一种中观结构水平上的断开综合征,为探索丘脑和尾状核的作用提供了潜在的新途径,可能揭示阿尔茨海默病临床诊断中认知缺陷的神经相关因素。
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引用次数: 0
Challenges in the Differential Classification of Individual Diagnoses from Co-Occurring Autism and ADHD Using Survey Data. 使用调查数据对并发自闭症和ADHD的个体诊断进行差异分类的挑战。
Aditi Jaiswal, Dennis P Wall, Peter Washington

Autism and Attention-Deficit Hyperactivity Disorder (ADHD) are two of the most commonly observed neurodevelopmental conditions in childhood. Providing a specific computational assessment to distinguish between the two can prove difficult and time intensive. Given the high prevalence of their co-occurrence, there is a need for scalable and accessible methods for distinguishing the co-occurrence of autism and ADHD from individual diagnoses. The first step is to identify a core set of features that can serve as the basis for behavioral feature extraction. We trained machine learning models on data from the National Survey of Children's Health to identify behaviors to target as features in automated clinical decision support systems. A model trained on the binary task of distinguishing either developmental delay (autism or ADHD) vs. neither achieved sensitivity >92% and specificity >94%, while a model trained on the 4-way classification task of autism vs. ADHD vs. both vs. none demonstrated >65% sensitivity and >66% specificity. While the performance of the binary model was respectable, the relatively low performance in the differential classification of autism and ADHD highlights the challenges that persist in achieving specificity within clinical decision support tools for developmental delays. Nevertheless, this study demonstrates the potential of applying behavioral questionnaires not traditionally used for clinical purposes towards supporting digital screening assessments for pediatric developmental delays.

自闭症和注意力缺陷多动障碍(ADHD)是儿童时期最常见的两种神经发育疾病。提供一个特定的计算评估来区分这两者可能很困难,而且耗时。鉴于这两种疾病的共存率很高,我们需要一种可扩展的、可获得的方法来区分自闭症和ADHD的共存与个体诊断。第一步是确定一组核心特征,这些特征可以作为行为特征提取的基础。我们根据来自全国儿童健康调查的数据训练机器学习模型,以识别自动临床决策支持系统中的目标行为特征。在区分发育迟缓(自闭症或ADHD)与两者都不区分的二元任务上训练的模型,灵敏度为bbb92 %,特异性为>94%,而在自闭症与ADHD、两者都与无的四向分类任务上训练的模型,灵敏度为>65%,特异性为>66%。虽然二元模型的表现是值得尊敬的,但在自闭症和多动症的鉴别分类中相对较低的表现突出了在发育迟缓的临床决策支持工具中实现特异性的挑战。尽管如此,本研究证明了应用传统上不用于临床目的的行为问卷来支持儿科发育迟缓的数字筛查评估的潜力。
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引用次数: 0
RBAD: A Dataset and Benchmark for Retinal Vessels Branching Angle Detection. RBAD:视网膜血管分支角检测的数据集和基准。
Hao Wang, Wenhui Zhu, Jiayou Qin, Xin Li, Oana Dumitrascu, Xiwen Chen, Peijie Qiu, Abolfazl Razi, Yalin Wang

Detecting retinal image analysis, particularly the geometrical features of branching points, plays an essential role in diagnosing eye diseases. However, existing methods used for this purpose often are coarse-level and lack fine-grained analysis for efficient annotation. To mitigate these issues, this paper proposes a novel method for detecting retinal branching angles using a self-configured image processing technique. Additionally, we offer an open-source annotation tool and a benchmark dataset comprising 40 images annotated with retinal branching angles. Our methodology for retinal branching angle detection and calculation is detailed, followed by a benchmark analysis comparing our method with previous approaches. The results indicate that our method is robust under various conditions with high accuracy and efficiency, which offers a valuable instrument for ophthalmic research and clinical applications. The dataset and source codes are available at https://github.com/Retinal-Research/RBAD.

视网膜图像的检测分析,特别是分支点的几何特征,在眼科疾病的诊断中起着至关重要的作用。然而,用于此目的的现有方法通常是粗级别的,并且缺乏用于有效注释的细粒度分析。为了解决这些问题,本文提出了一种利用自配置图像处理技术检测视网膜分支角度的新方法。此外,我们还提供了一个开源的注释工具和一个包含40张带有视网膜分支角度注释的图像的基准数据集。我们的视网膜分支角检测和计算的方法是详细的,其次是基准分析比较我们的方法与以前的方法。结果表明,该方法在各种条件下均具有良好的鲁棒性,具有较高的准确度和效率,为眼科研究和临床应用提供了有价值的工具。数据集和源代码可在https://github.com/Retinal-Research/RBAD上获得。
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引用次数: 0
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
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... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics
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