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Simulating the Evolution of Signaling Signatures During CART-Cell and Tumor Cell Interactions. 模拟 CART 细胞与肿瘤细胞相互作用过程中信号特征的演变
Viren Shah, Justin Womack, Anthony E Zamora, Scott S Terhune, Ranjan K Dash

Immunotherapies have been proven to have significant therapeutic efficacy in the treatment of cancer. The last decade has seen adoptive cell therapies, such as chimeric antigen receptor T-cell (CART-cell) therapy, gain FDA approval against specific cancers. Additionally, there are numerous clinical trials ongoing investigating additional designs and targets. Nevertheless, despite the excitement and promising potential of CART-cell therapy, response rates to therapy vary greatly between studies, patients, and cancers. There remains an unmet need to develop computational frameworks that more accurately predict CART-cell function and clinical efficacy. Here we present a coarse-grained model simulated with logical rules that demonstrates the evolution of signaling signatures following the interaction between CART-cells and tumor cells and allows for in silico based prediction of CART-cell functionality prior to experimentation.Clinical Relevance- Analysis of CART-cell signaling signatures can inform future CAR receptor design and combination therapy approaches aimed at improving therapy response.

免疫疗法已被证明在治疗癌症方面具有显著疗效。过去十年中,嵌合抗原受体 T 细胞(CART-细胞)疗法等采用性细胞疗法获得了美国食品及药物管理局(FDA)针对特定癌症的批准。此外,还有许多临床试验正在研究更多的设计和靶点。然而,尽管 CART 细胞疗法令人兴奋,潜力巨大,但不同的研究、患者和癌症对疗法的反应率却大相径庭。开发能更准确预测 CART 细胞功能和临床疗效的计算框架的需求仍未得到满足。在这里,我们提出了一个用逻辑规则模拟的粗粒度模型,该模型展示了 CART 细胞与肿瘤细胞相互作用后信号特征的演变,并允许在实验前对 CART 细胞的功能进行基于硅的预测。临床相关性--对 CART 细胞信号特征的分析可以为未来的 CAR 受体设计和旨在改善治疗反应的联合治疗方法提供信息。
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引用次数: 0
An Open Expandable Data Protocol for Multipolar Stimulation in Cochlear Implants. 人工耳蜗多极刺激的开放式可扩展数据协议
Abraham Akinin, Razi-Ul Haque

Cochlear implants (CI) have restored hearing to many deaf patients. It is the most successful neuroprosthetic in the field. However, in past decades technical improvements have plateaued and the market has solidified among 3 manufacturers. Proprietary software, and know-how are some of the barriers to innovation and disruption in CIs. In this paper we propose an open data communication protocol for cochlear implants that supports multipolar stimulation, accommodates an expandable number of channels, and minimizes the transmission of redundant information. We also present a method for implementing multipolar stimulation in single supply stimulators with a bridge-type switch matrix through pulse-polarity modulation. This combines the advantages of lower voltage (lower power) operation with more targeted stimulation.Clinical Relevance- In addition to enabling the development of new tools for research and clinical deployment, the presented data communication protocol will promote clinical research in more advanced auditory coding strategies.

人工耳蜗(CI)使许多耳聋患者恢复了听力。它是该领域最成功的神经假体。然而,在过去的几十年里,技术的进步已趋于平稳,市场已被 3 家制造商所垄断。专有软件和专有技术是阻碍人工耳蜗创新和颠覆的一些障碍。在本文中,我们提出了一种用于人工耳蜗的开放式数据通信协议,该协议支持多极刺激,可扩展通道数量,并最大限度地减少冗余信息的传输。我们还提出了一种通过脉冲极性调制在带有桥式开关矩阵的单电源刺激器中实现多极刺激的方法。临床意义--除了能为研究和临床应用开发新工具外,所介绍的数据通信协议还将促进更先进的听觉编码策略的临床研究。
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引用次数: 0
An Enhanced Synthetic Cystoscopic Environment for Use in Monocular Depth Estimation. 用于单眼深度估计的增强型合成膀胱镜环境
Peter Somers, Mario Deutschmann, Simon Holdenried-Krafft, Samuel Tovey, Johannes Schule, Carina Veil, Valese Aslani, Oliver Sawodny, Hendrik P A Lensch, Cristina Tarin

As technology advances and sensing devices improve, it is becoming more and more pertinent to ensure accurate positioning of these devices, especially within the human body. This task remains particularly difficult during manual, minimally invasive surgeries such as cystoscopies where only a monocular, endoscopic camera image is available and driven by hand. Tracking relies on optical localization methods, however, existing classical options do not function well in such a dynamic, non-rigid environment. This work builds on recent works using neural networks to learn a supervised depth estimation from synthetically generated images and, in a second training step, use adversarial training to then apply the network on real images. The improvements made to a synthetic cystoscopic environment are done in such a way to reduce the domain gap between the synthetic images and the real ones. Training with the proposed enhanced environment shows distinct improvements over previously published work when applied to real test images.

随着技术的进步和传感设备的改进,确保这些设备的精确定位变得越来越重要,尤其是在人体内部。这项任务在人工微创手术(如膀胱镜检查)中尤其困难,因为在这种手术中,只能使用单目内窥镜摄像机图像,并由人工驱动。跟踪依赖于光学定位方法,然而,现有的经典方法在这种动态、非刚性环境中并不能很好地发挥作用。这项工作建立在近期工作的基础上,利用神经网络从合成生成的图像中学习有监督的深度估计,并在第二步训练中使用对抗训练,然后将网络应用于真实图像。对合成膀胱镜环境的改进是为了缩小合成图像与真实图像之间的域差距。在应用于真实测试图像时,使用建议的增强型环境进行训练的效果明显优于之前发表的研究成果。
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引用次数: 0
An Evaluation of Hybrid Deep Learning Models for Classifying Multiple Lower Limb Actions. 评估混合深度学习模型对多种下肢动作的分类。
Zilu Wang, Ian Daly, Junhua Li

Brain-computer Interfaces (BCIs) interpret electroencephalography (EEG) signals and translate them into control commands for operating external devices. The motor imagery (MI) paradigm is popular in this context. Recent research has demonstrated that deep learning models, such as convolutional neural network (CNN) and long short-term memory (LSTM), are successful in a wide range of classification applications. This is because CNN has the property of spatial invariance, and LSTM can capture temporal associations among features. A combination of CNN and LSTM could enhance the classification performance of EEG signals due to the complementation of their strengths. Such a combination has been applied to MI classification based on EEG. However, most studies focused on either the upper limbs or treated both lower limbs as a single class, with only limited research performed on separate lower limbs. We, therefore, explored hybrid models (different combinations of CNN and LSTM) and evaluated them in the case of individual lower limbs. In addition, we classified multiple actions: MI, real movements and movement observations using four typical hybrid models and aimed to identify which model was the most suitable. The comparison results demonstrated that no model was significantly better than the others in terms of classification accuracy, but all of them were better than the chance level. Our study informs the possibility of the use of multiple actions in BCI systems and provides useful information for further research into the classification of separate lower limb actions.

脑机接口(BCI)可解释脑电图(EEG)信号,并将其转化为操作外部设备的控制指令。运动图像(MI)范例在这方面很受欢迎。最近的研究表明,卷积神经网络(CNN)和长短期记忆(LSTM)等深度学习模型在广泛的分类应用中取得了成功。这是因为卷积神经网络具有空间不变性,而 LSTM 可以捕捉特征之间的时间关联。由于 CNN 和 LSTM 的优势互补,两者的结合可以提高脑电信号的分类性能。这种组合已被应用于基于脑电图的 MI 分类。然而,大多数研究都集中在上肢,或将两个下肢作为一个类别,对单独下肢的研究非常有限。因此,我们探索了混合模型(CNN 和 LSTM 的不同组合),并在单个下肢的情况下对其进行了评估。此外,我们还对多种动作进行了分类:我们使用四种典型的混合模型对多种动作进行了分类:MI、真实动作和动作观察,并旨在确定哪种模型最合适。比较结果表明,就分类准确性而言,没有哪个模型明显优于其他模型,但所有模型都优于偶然水平。我们的研究为在 BCI 系统中使用多种动作的可能性提供了信息,并为下肢单独动作分类的进一步研究提供了有用信息。
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引用次数: 0
An Image Classification Approach to Pre-Determine Extent of Development of Post-Operative Necrosis in Skin Flaps. 预判皮瓣术后坏死发展程度的图像分类方法
G Spacagna, T Fevens, J Barralet

Purpose - Clinicians and care workers currently cannot determine the final extent of necrosis once it begins. If the area is relatively small, it may heal like a normal wound, whereas re-operation may be the only option if it spreads. This paper represents work toward a predictive algorithm using full-thickness random rat skin flap photographs to determine whether the tissue will develop irretrievable necrosis.Methods - Using post-surgery images taken over a series of days of ischemic flaps, features were extracted, selected, and input into a classification algorithm to see if it could provide information on the future condition of the flaps. We split our data into two groups: flaps that underwent normal healing and slow healing. When consulting with a specialist, it was observed that the resulting dermal damage was not severe when a flap had ≤ 40% necrosis over its length on the final day. Three classifiers were implemented: K-Nearest Neighbor (KNN), Random Forest, and Support Vector Machine (SVM).Results - The trained KNN was able to correctly determine whether a flap developed a necrotic area larger or less than 40% of its length with an accuracy of 91% using only images one day post-surgery. Under leave-one-out cross-validation, the Random Forest and SVM achieved accuracies of 82% and 79.5%, respectively, using images spanning ten days post-surgery.Conclusion - We have shown that a classifier can accurately determine whether ischemic skin flaps will develop severe necrotic tissue.Clinical Relevance- An algorithm that assesses early timepoint images and predicts necrosis spread is not only a vital tool for patients and clinicians but is also an extremely important tool to accelerate research into necrosis reduction strategies that ultimately may find application for more life-threatening necrosis-related conditions.

目的 - 目前,临床医生和护理人员无法确定坏死开始后的最终范围。如果坏死面积相对较小,可能会像正常伤口一样愈合,而如果坏死范围扩大,重新手术可能是唯一的选择。方法--利用缺血皮瓣手术后几天内拍摄的一系列图像,提取、选择特征并输入分类算法,看它能否提供有关皮瓣未来状况的信息。我们将数据分为两组:正常愈合的皮瓣和缓慢愈合的皮瓣。在向专家咨询时,我们发现,当皮瓣在最后一天的长度上坏死≤40%时,所造成的真皮损伤并不严重。使用了三种分类器:结果 - 仅使用手术后一天的图像,训练有素的 KNN 能够正确判断皮瓣坏死面积是否大于或小于其长度的 40%,准确率为 91%。结论 - 我们已经证明,分类器可以准确判断缺血皮瓣是否会出现严重的坏死组织。临床相关性--评估早期时间点图像并预测坏死扩散的算法不仅是患者和临床医生的重要工具,也是加速研究减少坏死策略的极其重要的工具,这些策略最终可能会应用于更多危及生命的坏死相关病症。
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引用次数: 0
An Instrument for High-throughput Testing of Heart Tissue In Vitro. 体外心脏组织高通量测试仪器
Emily J Lam Po Tang, Toan Pham, Jordyn Chan, Kenneth Tran, June-Chiew Han, Khoon Lim, Poul M F Nielsen, Andrew J Taberner

Cardiac trabeculae are small samples of heart muscle tissue that can be dissected and studied in vitro to better understand the underlying physiology of cardiac muscle. However, instruments for such experimentation often (1) involve delicate mounting of the muscle, (2) constrain investigations to one muscle at a time and, thus, (3) cannot retain the muscle in the same experimental configuration for post-experimental assessment including imaging analysis. Here, we present a novel device that allows trabeculae to be secured by a visible-light photo-initiated hydrogel, manipulated via a force sensor, and stimulated while being imaged. We use our robust, accurate image registration techniques to measure cantilever and gel deformation during trabecula contraction and thereby provide a measure of trabecula force production during twitches. A variety of experiments can then be conducted, with the potential for the trabecula to be fixed in place using hydrogel for further post-experiment analysis, as well as longitudinal evaluation. The device has multiple wells making it amenable to high-throughput testing.Clinical Relevance- These methods may allow longitudinal and high-throughput studies of cardiac tissue samples in health and disease.

心肌小梁是心肌组织的小样本,可以对其进行解剖和体外研究,以更好地了解心肌的基本生理结构。然而,用于此类实验的仪器通常(1)需要对肌肉进行精细安装,(2)每次只能对一块肌肉进行研究,因此(3)无法将肌肉保持在相同的实验结构中进行实验后评估,包括成像分析。在这里,我们提出了一种新型装置,可通过可见光光引发的水凝胶固定小梁,通过力传感器进行操作,并在成像的同时刺激小梁。我们利用稳健、精确的图像配准技术测量小梁收缩时的悬臂和凝胶变形,从而提供小梁抽动时产生的力的测量值。然后就可以进行各种实验,并有可能使用水凝胶将小梁固定到位,以进行进一步的实验后分析和纵向评估。临床意义--这些方法可以对健康和疾病的心脏组织样本进行纵向和高通量研究。
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引用次数: 0
Single Image based Super Resolution Ultrasound Imaging Using Residual Learning of Wavelet Features. 利用小波特征的残差学习实现基于单个图像的超分辨率超声成像
Adithya Sineesh, Manish Rangarajan Shankar, Abhilash Hareendranathan, Mahesh Raveendranatha Panicker, P Palanisamy

The generation of super resolution ultrasound images from the low-resolution (LR) brightness mode (B-mode) images acquired by the portable point of care ultrasound systems has been of sufficient interest in the recent past. With the advancements in deep learning, there have been numerous attempts in this direction. However, all the approaches have been concentrated on employing the direct image as the input to the neural network. In this work, a stationary wavelet (SWT) decomposition is employed to extract the features from the input LR image which is passed through a modified residual network and the learned features are combined using the inverse SWT to reconstruct the high resolution (HR) image at a 4× scale factor. The proposed approach when compared to the state-of-the art approaches, results in an improved high resolution reconstruction.Clinical relevance- The proposed approach will enable the generation of high-resolution images from portable ultrasound systems, allowing for easier interpretation and faster diagnostics in primary care settings.

从便携式医疗点超声系统获取的低分辨率(LR)亮度模式(B-mode)图像生成超分辨率超声图像的问题近年来一直备受关注。随着深度学习技术的进步,人们在这方面进行了大量尝试。然而,所有方法都集中在采用直接图像作为神经网络的输入。在这项工作中,采用了静态小波(SWT)分解从输入的 LR 图像中提取特征,然后通过修改后的残差网络,利用反向 SWT 将学习到的特征进行组合,以 4 倍比例系数重建高分辨率(HR)图像。与最先进的方法相比,所提出的方法改进了高分辨率重建。临床相关性--所提出的方法将使便携式超声系统生成高分辨率图像成为可能,从而使基层医疗机构的解释和诊断更加简便快捷。
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引用次数: 0
Analysis of Heart Rate Variability during the Performance of the Wim Hof Method in Healthy Subjects. 健康受试者执行维姆-霍夫方法时的心率变异性分析
Beatriz F Giraldo Giraldo, David Ferre Lopez, Jordi Sola-Soler

Cardiorespiratory interaction is related to the heart rate variability (HRV) synchronized with respiration. These metrics help to comprehend the autonomic nervous system (ANS) functionality in cardiovascular mechanisms. In this work, we aim to study the HRV in healthy subjects aged 18-24 years during the breathing techniques based on deep breaths followed by apnoeas, developed by Wim Hof (WHM). The attributes of all participates have been treated as a group and therefore, separated by gender. A total of 11 intervals have been distinguished: starting of basal respiration (SRI = 1), controlled deep breaths (CDB = 3), long expiratory apnoea (LEA = 3), short inspiratory apnoea (SIA = 3) and ending with basal respiration again (FRI = 1). To strengthen the HRV knowledge extraction from these scenarios, time and frequency analysis is conducted. In general, breathing and apnoea intervals presented significant statistically differences (p < 0.05), heart rate (HR) mean between SRI and FRI (p < 0.001), RR variability of LEA intervals (p < 0.01), root mean square of RR intervals during CDB (p < 0.05), maximum high frequency (HF) peak amplitude between SRI and FRI (p = 0.016), and low frequency (LF) area for LEA intervals (p < 0.001). When performing the frequency analysis, it has been observed that the sympathetic nervous system (SNS) has a higher contribution in the apnoea intervals. In conclusion, the WHM method implementation seems to involve a decrease in the HR. Specific breathing techniques could help to control the body in different conditions.Clinical Relevance- The WHM seems to imply a decrease on HR. Furthermore, after the implementation of the WHM, women presented higher HRV.

心肺交互作用与心率变异性(HRV)和呼吸同步有关。这些指标有助于理解自律神经系统(ANS)在心血管机制中的功能。在这项工作中,我们旨在研究 18-24 岁健康受试者在使用 Wim Hof(WHM)开发的基于深呼吸和呼吸暂停的呼吸技术时的心率变异。所有参与者的属性都被视为一个群体,因此按性别分开。总共区分了 11 个时间间隔:开始基础呼吸(SRI = 1)、控制深呼吸(CDB = 3)、长呼气暂停(LEA = 3)、短吸气暂停(SIA = 3)和再次基础呼吸结束(FRI = 1)。为了加强从这些情景中提取心率变异知识,进行了时间和频率分析。一般来说,呼吸和呼吸暂停间歇、SRI 和 FRI 之间的心率(HR)平均值(p < 0.001)、LEA 间歇的 RR 变异性(p < 0.01)、CDB 期间 RR 间歇的均方根(p < 0.05)、SRI 和 FRI 之间的最大高频(HF)峰值振幅(p = 0.016)以及 LEA 间歇的低频(LF)面积(p < 0.001)在统计学上存在显著差异。在进行频率分析时,观察到交感神经系统(SNS)在呼吸暂停间期的贡献较大。总之,实施 WHM 方法似乎会降低心率。特定的呼吸技巧有助于在不同情况下控制身体。此外,实施 WHM 法后,女性的心率变异性更高。
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引用次数: 0
SleepSIM: Conditional GAN-based non-REM sleep EEG Signal Generator. SleepSIM:基于条件 GAN 的非快速眼动睡眠脑电图信号发生器。
Sajila D Wickramaratne, Ankit Parekh

Synthetic data generation has become increasingly popular with the increasing use of generative networks. Recently, Generative Adversarial Network (GAN) architectures have produced exceptional results in synthetic image generation. However, time series generation still needs to be studied. This paper proposes a Conditional GAN-based system to generate unique samples of non-REM sleep electroencephalographic (EEG) signals. The CGAN model had a 1-D Convolution Neural Network based architecture. The model was trained using real EEG from healthy controls. The trained model can generate an artificial 30-second epoch of non-REM sleep whose power spectrum is identical to that of a real sleep EEG.Clinical relevance- Sleep EEG simulation can be used to train and enhance the skillset of fellows and technicians in the sleep medicine field. Variations in EEG signals can be highly complex to model mathematically; however, here, we harness the power of deep learning, using generative models such as CGANs to train, model complex data distributions, and generate diverse and artificial but realistic EEG signals during non-REM sleep.

随着生成网络的应用日益广泛,合成数据生成也变得越来越流行。最近,生成对抗网络(GAN)架构在合成图像生成方面取得了卓越的成果。然而,时间序列生成仍有待研究。本文提出了一种基于条件 GAN 的系统,用于生成独特的非快速眼动睡眠脑电图(EEG)信号样本。CGAN 模型采用基于一维卷积神经网络的架构。该模型使用健康对照组的真实脑电图进行训练。训练后的模型可生成 30 秒的非快速眼动睡眠人工时程,其功率谱与真实睡眠脑电图相同。临床意义--睡眠脑电图模拟可用于培训和提高睡眠医学领域研究员和技术人员的技能。脑电信号的变化可能是非常复杂的数学模型;但是,在这里,我们利用深度学习的力量,使用 CGANs 等生成模型进行训练,为复杂的数据分布建模,并在非快速眼动睡眠期间生成多样、人工但真实的脑电信号。
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引用次数: 0
Arterial Wave Separation Analysis and Reflection Wave Transit Time Estimation using a Double Rayleigh Flow Rate Model. 使用双瑞利流速模型进行动脉波分离分析和反射波通过时间估算。
Rahul Manoj, Aneesh S, Raj Kiran V, Nabeel P M, Mohanasankar Sivaprakasam, Jayaraj Joseph

Arterial pulse wave separation analysis (WSA) requires simultaneously measured pressure and flow rate waveform from the same arterial site. Modelling approaches to flow rate waveforms offers a methodological and instrumentational advantage. However, current techniques are limited to the aortic site. For non-aortic sites such as carotid artery, modelling methods that were developed for aortic sites are not likely to capture the intrinsic differences in the carotid flow rate. In this work, a double-Rayleigh flow rate model for the carotid artery is developed to separate the forward and backward pressure waves using WSA (DRMWSA). The model parameters are optimally found based on characteristic features - obtained from the pressure waveform. The DRMWSA was validated using a database of 4374 virtual (healthy) subjects, and its performance was compared with actual flow rate based WSA (REFWSA) at the carotid artery. An RMSE < 2 mmHg were obtained for forward and backward pressure waveforms. The reflection quantification indices (ΔPF, ΔPB), (RM, RI) obtained from DRMWSA demonstrated strong and statistically significant correlation (r > 0.96, p < 0.001) and (r > 0.80, p < 0.001) respectively, with insignificant bias (p > 0.05), upon comparing with counterparts in REFWSA. A moderate correlation (r = 0.64, p < 0.001) was obtained for reflection wave transit time between both methods. The proposed method minimises the measurements required for WSA and has the potential to widen the vascular screening procedures incorporating carotid pulse wave dynamics.Clinical Relevance-This methodology quantifies arterial pressure wave reflections in terms of pressure augmentation and reflection transit time. The methodological advantage of using only a single waveform helps easy translation to technological solutions for clinical research.

动脉脉搏波分离分析(WSA)需要同时测量同一动脉部位的压力和流速波形。流速波形建模方法在方法和仪器方面都具有优势。然而,目前的技术仅限于主动脉部位。对于非主动脉部位,如颈动脉,为主动脉部位开发的建模方法不可能捕捉到颈动脉流速的内在差异。在这项工作中,为颈动脉开发了双雷利流率模型,利用 WSA(DRMWSA)将前向和后向压力波分开。模型参数是根据从压力波形中获得的特征值优化确定的。DRMWSA 使用 4374 名虚拟(健康)受试者的数据库进行了验证,并将其性能与颈动脉基于实际流速的 WSA(REFWSA)进行了比较。正向和反向压力波形的 RMSE 均小于 2 mmHg。DRMWSA 获得的反射量化指数(ΔPF、ΔPB)和(RM、RI)分别与 REFWSA 的对应指数相比,显示出很强的统计学意义上的显著相关性(r > 0.96,p < 0.001)和(r > 0.80,p < 0.001),偏差不明显(p > 0.05)。两种方法的反射波通过时间具有中等相关性(r = 0.64,p < 0.001)。该方法最大程度地减少了 WSA 所需的测量,有望拓宽包含颈动脉脉搏波动态的血管筛查程序。只使用单一波形的方法优势有助于轻松转化为临床研究的技术解决方案。
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引用次数: 0
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Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
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