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3D Coaxial Bioprinting: Process Mechanisms, Bioinks and Applications. 三维同轴生物打印:工艺机制、生物墨水和应用。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-04-01 Epub Date: 2022-04-20 DOI: 10.1088/2516-1091/ac631c
Tarun Shyam Mohan, Pallab Datta, Sepehr Nesaei, Veli Ozbolat, Ibrahim T Ozbolat

In the last decade, bioprinting has emerged as a facile technique for fabricating tissues constructs mimicking the architectural complexity and compositional heterogeneity of native tissues. Amongst different bioprinting modalities, extrusion-based bioprinting (EBB) is the most widely used technique. Coaxial bioprinting, a type of EBB, enables fabrication of concentric cell-material layers and enlarges the scope of EBB to mimic several key aspects of native tissues. Over the period of development of bioprinting, tissue constructs integrated with vascular networks, have been one of the major achievements made possible largely by coaxial bioprinting. In this review, current advancements in biofabrication of constructs with coaxial bioprinting are discussed with a focus on different bioinks that are particularly suitable for this modality. This review also expounds the properties of different bioinks suitable for coaxial bioprinting and then analyses the key achievements made by the application of coaxial bioprinting in tissue engineering, drug delivery and in-vitro disease modelling. The major limitations and future perspectives on the critical factors that will determine the ultimate clinical translation of the versatile technique are also presented to the reader.

在过去的十年中,生物打印技术已成为模仿原生组织的结构复杂性和成分异质性制造组织构建体的一种简便技术。在各种生物打印模式中,挤压式生物打印(EBB)是应用最广泛的技术。同轴生物打印是 EBB 的一种,可制造同心的细胞-材料层,并扩大了 EBB 的范围,使其能够模仿原生组织的几个关键方面。在生物打印技术的发展过程中,与血管网络相结合的组织构建物是主要通过同轴生物打印技术实现的重大成就之一。在这篇综述中,我们讨论了目前利用同轴生物打印技术进行生物制造的进展,重点是特别适用于这种模式的不同生物墨水。本综述还阐述了适合同轴生物打印的不同生物墨水的特性,然后分析了在组织工程、药物输送和体外疾病建模中应用同轴生物打印所取得的主要成就。此外,还向读者介绍了决定这一多功能技术最终临床应用的关键因素的主要局限性和未来展望。
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引用次数: 0
Recent progress in bioactive gas delivery for cancer immunotherapy 癌症免疫治疗中生物活性气体输送的最新进展
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-01-18 DOI: 10.1088/2516-1091/ac4c43
Yang Liu, Tiandong Chen, N. Gu, Fang Yang
Tumors with high mortality rates are still a major threat to human survival and health worldwide. In recent years, cancer immunotherapy has made rapid clinical progress in eliminating cancers by activating the host’s own immune system. Particularly, the use of physiological bioactive gas molecules such as nitric oxide, carbon monoxide and hydrogen sulfide have been developed as novel immunotherapeutic strategies. In this review, we have summarized the current strategies for antitumor immunotherapy via bioactive gas molecules, targeting delivery to the tumor microenvironment. We summarize the biofunctions of bioactive gases to the immune system, then gas delivery nanocarriers for antitumor immunotherapy and the current status of the platform are presented. Furthermore, since gas could specifically respond to the ultrasound, ultrasound-assisted gas delivery is generalized as a promising potential pathway for enhanced immunotherapy. Finally, we have discussed the challenges and opportunities for bioactive gas delivery and the effects of acoustic enhanced immunotherapy in future developments and possible clinical applications.
高死亡率的肿瘤仍然是全世界人类生存和健康的主要威胁。近年来,癌症免疫疗法通过激活宿主自身的免疫系统,在消除癌症方面取得了快速的临床进展。特别是,生理活性气体分子如一氧化氮、一氧化碳和硫化氢的使用已被开发为新的免疫治疗策略。在这篇综述中,我们总结了目前通过生物活性气体分子靶向递送到肿瘤微环境的抗肿瘤免疫治疗策略。我们总结了生物活性气体对免疫系统的生物功能,然后介绍了用于抗肿瘤免疫治疗的气体递送纳米载体和该平台的现状。此外,由于气体可以对超声产生特异性反应,超声辅助气体输送被认为是增强免疫治疗的一种有前途的潜在途径。最后,我们讨论了生物活性气体输送的挑战和机遇,以及声学增强免疫疗法在未来发展和可能的临床应用中的作用。
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引用次数: 0
Spike sorting: new trends and challenges of the era of high-density probes 尖峰分选:高密度探针时代的新趋势和挑战
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-01-07 DOI: 10.1088/2516-1091/ac6b96
A. P. Buccino, Samuel Garcia, P. Yger
Recording from a large neuronal population of neurons is a crucial challenge to unravel how information is processed by the brain. In this review, we highlight the recent advances made in the field of ‘spike sorting’, which is arguably a very essential processing step to extract neuronal activity from extracellular recordings. More specifically, we target the challenges faced by newly manufactured high-density multi-electrode array devices (HD-MEA), e.g. Neuropixels probes. Among them, we cover in depth the prominent problem of drifts (movements of the neurons with respect to the recording devices) and the current solutions to circumscribe it. In addition, we also review recent contributions making use of deep learning approaches for spike sorting, highlighting their advantages and disadvantages. Next, we highlight efforts and advances in unifying, validating, and benchmarking spike sorting tools. Finally, we discuss the spike sorting field in terms of its open and unsolved challenges, specifically regarding scalability and reproducibility. We conclude by providing our personal view on the future of spike sorting, calling for a community-based development and validation of spike sorting algorithms and fully automated, cloud-based spike sorting solutions for the neuroscience community.
从大量神经元群体中进行记录是解开大脑如何处理信息的关键挑战。在这篇综述中,我们强调了“尖峰分选”领域的最新进展,这可以说是从细胞外记录中提取神经元活动的一个非常重要的处理步骤。更具体地说,我们针对新制造的高密度多电极阵列器件(HD-MEA)所面临的挑战,例如Neuropixels探针。其中,我们深入讨论了漂移(神经元相对于记录设备的运动)的突出问题以及目前限制漂移的解决方案。此外,我们还回顾了最近利用深度学习方法进行尖峰排序的贡献,强调了它们的优缺点。接下来,我们将重点介绍在统一、验证和基准测试尖峰排序工具方面所做的努力和取得的进展。最后,我们讨论了尖峰排序领域的开放性和未解决的挑战,特别是在可扩展性和可再现性方面。最后,我们对尖峰排序的未来提出了个人观点,呼吁以社区为基础开发和验证尖峰排序算法,并为神经科学社区提供全自动、基于云的尖峰排序解决方案。
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引用次数: 15
Protein Based Biomaterials for Therapeutic and Diagnostic Applications. 用于治疗和诊断的蛋白质生物材料。
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-01-01 Epub Date: 2021-10-26 DOI: 10.1088/2516-1091/ac2841
Stanley Chu, Andrew L Wang, Aparajita Bhattacharya, Jin Kim Montclare

Proteins are some of the most versatile and studied macromolecules with extensive biomedical applications. The natural and biological origin of proteins offer such materials several advantages over their synthetic counterparts, such as innate bioactivity, recognition by cells and reduced immunogenic potential. Furthermore, proteins can be easily functionalized by altering their primary amino acid sequence and can often be further self-assembled into higher order structures either spontaneously or under specific environmental conditions. This review will feature the recent advances in protein-based biomaterials in the delivery of therapeutic cargo such as small molecules, genetic material, proteins, and cells. First, we will discuss the ways in which secondary structural motifs, the building blocks of more complex proteins, have unique properties that enable them to be useful for therapeutic delivery. Next, supramolecular assemblies, such as fibers, nanoparticles, and hydrogels, made from these building blocks that are engineered to behave in a cohesive manner, are discussed. Finally, we will cover additional modifications to protein materials that impart environmental responsiveness to materials. This includes the emerging field of protein molecular robots, and relatedly, protein-based theranostic materials that combine therapeutic potential with modern imaging modalities, including near-infrared fluorescence spectroscopy (NIRF), single-photo emission computed tomography/computed tomography (SPECT/CT), positron emission tomography (PET), magnetic resonance imaging (MRI), and ultrasound/photoacoustic imaging (US/PAI).

蛋白质是一些用途最广泛、研究最深入的大分子,具有广泛的生物医学应用。蛋白质的天然和生物来源为这些材料提供了比合成材料更大的优势,如天生的生物活性、细胞的识别能力和降低的免疫原性潜力。此外,蛋白质可以通过改变其伯氨基酸序列而容易地功能化,并且通常可以自发地或在特定的环境条件下进一步自组装成更高阶的结构。这篇综述将介绍基于蛋白质的生物材料在递送小分子、遗传物质、蛋白质和细胞等治疗货物方面的最新进展。首先,我们将讨论二级结构基序(更复杂蛋白质的构建块)具有独特特性的方式,使其能够用于治疗递送。接下来,讨论了由这些构建块制成的超分子组装体,如纤维、纳米颗粒和水凝胶,这些构建块被设计成以内聚的方式表现。最后,我们将介绍对蛋白质材料的额外修饰,这些修饰赋予材料环境响应性。这包括蛋白质分子机器人的新兴领域,以及将治疗潜力与现代成像模式相结合的基于蛋白质的治疗材料,包括近红外荧光光谱(NIRF)、单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)、正电子发射断层扫描(PET)、磁共振成像(MRI),以及超声/光声成像(US/PAI)。
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引用次数: 6
Wave-based optical coherence elastography: The 10-year perspective. 基于波的光学相干弹性成像:十年展望。
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2022-01-01 DOI: 10.1088/2516-1091/ac4512
Fernando Zvietcovich, Kirill V Larin

After 10 years of progress and innovation, optical coherence elastography (OCE) based on the propagation of mechanical waves has become one of the major and the most studied OCE branches, producing a fundamental impact in the quantitative and nondestructive biomechanical characterization of tissues. Preceding previous progress made in ultrasound and magnetic resonance elastography; wave-based OCE has pushed to the limit the advance of three major pillars: (1) implementation of novel wave excitation methods in tissues, (2) understanding new types of mechanical waves in complex boundary conditions by proposing advance analytical and numerical models, and (3) the development of novel estimators capable of retrieving quantitative 2D/3D biomechanical information of tissues. This remarkable progress promoted a major advance in answering basic science questions and the improvement of medical disease diagnosis and treatment monitoring in several types of tissues leading, ultimately, to the first attempts of clinical trials and translational research aiming to have wave-based OCE working in clinical environments. This paper summarizes the fundamental up-to-date principles and categories of wave-based OCE, revises the timeline and the state-of-the-art techniques and applications lying in those categories, and concludes with a discussion on the current challenges and future directions, including clinical translation research.

经过10年的发展和创新,基于机械波传播的光学相干弹性成像(OCE)已成为研究最多的主要分支之一,对组织的定量和无损生物力学表征产生了根本性的影响。超声和磁共振弹性成像的先前进展;基于波的OCE已经推动了三个主要支柱的进步:(1)在组织中实施新的波激发方法,(2)通过提出先进的分析和数值模型来理解复杂边界条件下的新型机械波,以及(3)开发能够检索定量的二维/三维组织生物力学信息的新型估计器。这一显著进展促进了在回答基础科学问题方面的重大进展,并改善了几种类型组织的医学疾病诊断和治疗监测,最终导致了临床试验和转化研究的首次尝试,旨在使基于波的OCE在临床环境中工作。本文总结了基于波浪的OCE的最新基本原理和类别,修订了时间表以及这些类别中最先进的技术和应用,最后讨论了当前的挑战和未来的方向,包括临床翻译研究。
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引用次数: 27
Ethical and social aspects of neural prosthetics 神经修复术的伦理和社会方面
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-10-26 DOI: 10.1088/2516-1091/ac23e6
W. Glannon
Neural prosthetics are devices or systems that bypass, modulate, supplement, or replace regions of the brain and its connections to the body that are damaged and dysfunctional from congenital abnormalities, brain and spinal cord injuries, limb loss, and neuropsychiatric disorders. Some prosthetics are implanted in the brain. Others consist of implants and systems outside the brain to which they are connected. Still others are completely external to the brain. But they all send inputs to and receive outputs from neural networks to modulate or improve connections between the brain and body. As artificial systems, neural prosthetics can improve but not completely restore natural sensory, motor and cognitive functions. This review examines the main ethical and social issues generated by experimental and therapeutic uses of seven types of neural prosthetics: auditory and visual prosthetics for deafness and blindness; deep brain stimulation for prolonged disorders of consciousness; brain-computer and brain-to-brain interfaces to restore movement and communication; memory prosthetics to encode and retrieve information; and optogenetics to modulate or restore neural function. The review analyzes and discusses how recipients of neural prosthetics can benefit from them in restoring autonomous agency, how they can be harmed by trying and failing to use or adapt to them, how these systems affect their identities, how to protect people with prosthetics from external interference, and how to ensure fair access to them. The review concludes by emphasizing the control these systems provide for people and a brief exploration of the future of neural prosthetics.
神经修复术是一种绕过、调节、补充或替代大脑及其与身体连接的区域的装置或系统,这些区域因先天性异常、脑和脊髓损伤、肢体丧失和神经精神障碍而受损和功能失调。一些假肢被植入大脑。其他包括植入物和大脑外的系统,它们与之相连。还有一些完全在大脑之外。但它们都向神经网络发送输入并从神经网络接收输出,以调节或改善大脑和身体之间的连接。作为人工系统,神经假肢可以改善但不能完全恢复自然的感觉、运动和认知功能。这篇综述审查了七种神经假肢的实验和治疗用途所产生的主要伦理和社会问题:耳聋和失明的听觉和视觉假肢;脑深部刺激治疗长期意识障碍;脑-计算机和脑-脑接口,以恢复运动和通信;记忆修复术,用于编码和检索信息;以及调节或恢复神经功能的光遗传学。该综述分析和讨论了神经假肢的接受者如何在恢复自主能动性方面从中受益,他们如何因尝试和不使用或适应神经假肢而受到伤害,这些系统如何影响他们的身份,如何保护使用假肢的人免受外部干扰,以及如何确保公平使用假肢。综述最后强调了这些系统为人们提供的控制,并对神经修复术的未来进行了简要探索。
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引用次数: 1
Magnetic nanomaterials-mediated cancer diagnosis and therapy 磁性纳米材料介导的癌症诊断与治疗
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-10-19 DOI: 10.1088/2516-1091/ac3111
Xiaoli Liu, Huan Zhang, Tingbin Zhang, Yanyun Wang, W. Jiao, Xiaofeng Lu, Xiao Gao, Mengmeng Xie, Qingfeng Shan, Nana Wen, Chen Liu, Wee Siang Vincent Lee, Haiming Fan
Magnetic nanomaterials have been widely used in various biomedical applications, which have seen accelerating interest since the breakthrough in the chemical synthesis of monodispersed iron oxide nanoparticles. Magnetic iron oxide nanoparticles (MIONs) possess excellent biocompatibility, and they can produce multiple physicochemical effects when exposed to magnetic fields. Due to this rapid development in MIONs for cancer diagnosis and therapy, it becomes necessary to present a comprehensive review paper from the biomedical engineering perspective. This review will present an overview of the recent synthesis methods used in the preparation of magnetic nanomaterials. We will then focus on the application of magnetic nanomaterials in imaging and therapy technology, and we will also evaluate their biosafety in vitro, in vivo, and clinical aspects. The therapeutic effects of magnetic theranostics, magnetocatalytic therapy, magnetically targeted therapy, and magnetothermal therapy under the guidance of imaging diagnosis will also be discussed in this review. Finally, we will briefly analyze the challenges of implementing magnetic nanomaterials as a nano-platform for imaging diagnosis and treatment, and we will also offer suggestions for future research in this field.
磁性纳米材料已被广泛应用于各种生物医学应用,自单分散氧化铁纳米颗粒的化学合成取得突破以来,人们对磁性纳米材料的兴趣与日俱增。磁性氧化铁纳米颗粒具有良好的生物相容性,在磁场中可以产生多种物理化学效应。鉴于癌症诊断和治疗的MION的快速发展,有必要从生物医学工程的角度提出一篇全面的综述。这篇综述将概述最近用于制备磁性纳米材料的合成方法。然后,我们将重点关注磁性纳米材料在成像和治疗技术中的应用,我们还将评估其在体外、体内和临床方面的生物安全性。本文还将在影像学诊断的指导下讨论磁治疗、磁催化治疗、磁靶向治疗和磁热疗的治疗效果。最后,我们将简要分析将磁性纳米材料作为成像诊断和治疗的纳米平台所面临的挑战,并为该领域的未来研究提供建议。
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引用次数: 14
Hybrid computational modeling methods for systems biology 系统生物学的混合计算建模方法
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-10-05 DOI: 10.1088/2516-1091/ac2cdf
Daniel A Cruz, Melissa L. Kemp
Systems biology models are typically considered across a spectrum from mechanistic to abstracted description; however, the lines between these forms of modeling are increasingly blurred. Ever-increasing computational power is providing novel opportunities for bridging time and length scales. Furthermore, despite biological mechanisms or network topology often ill-defined, the acquisition of high-throughput data leaves modelers with the desire to leverage available measurements. This review surveys modeling tools in which two or more mathematical forms are blended to describe time-dependent processes in a multivariate system. While most commonly manifested as continuous/discrete description, other forms such as mechanistic/inference or deterministic/stochastic hybrid models can be generated. Recent innovations in hybrid modeling methodologies and new applications illustrate advantages for combining model formats to gaining biological systems level insight.
系统生物学模型通常被认为是从机械描述到抽象描述的一个范围;然而,这些建模形式之间的界限越来越模糊。不断增长的计算能力为桥接时间和长度尺度提供了新的机会。此外,尽管生物学机制或网络拓扑结构往往定义不清,但高通量数据的获取使建模人员希望利用可用的测量结果。这篇综述综述了建模工具,其中两种或两种以上的数学形式被混合来描述多元系统中的时间依赖过程。虽然最常见的表现为连续/离散描述,但也可以生成其他形式,如机械/推理或确定性/随机混合模型。混合建模方法和新应用的最新创新说明了将模型格式结合起来以获得生物系统级洞察力的优势。
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引用次数: 6
Synthetic hydrogels as blood clot mimicking wound healing materials. 合成水凝胶作为模拟血凝块的伤口愈合材料。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-10-01 Epub Date: 2021-09-30 DOI: 10.1088/2516-1091/ac23a4
Manuel K Rausch, Sapun H Parekh, Berkin Dortdivanlioglu, Adrianne M Rosales

Excessive bleeding-or hemorrhage-causes millions of civilian and non-civilian casualties every year. Additionally, wound sequelae, such as infections, are a significant source of chronic morbidity, even if the initial bleeding is successfully stopped. To treat acute and chronic wounds, numerous wound healing materials have been identified, tested, and adopted. Among them are topical dressings, such as gauzes, as well as natural and biomimetic materials. However, none of these materials successfully mimic the complex and dynamic properties of the body's own wound healing material: the blood clot. Specifically, blood clots exhibit complex mechanical and biochemical properties that vary across spatial and temporal scales to guide the wound healing response, which make them the ideal wound healing material. In this manuscript, we review blood clots' complex mechanical and biochemical properties, review current wound healing materials, and identify opportunities where new materials can provide additional functionality, with a specific focus on hydrogels. We highlight recent developments in synthetic hydrogels that make them capable of mimicking a larger subset of blood clot features: as plugs and as stimuli for tissue repair. We conclude that future hydrogel materials designed to mimic blood clot biochemistry, mechanics, and architecture can be combined with exciting platelet-like particles to serve as hemostats that also promote the biological wound healing response. Thus, we believe synthetic hydrogels are ideal candidates to address the clear need for better wound healing materials.

过度出血或大出血每年造成数百万平民和非平民伤亡。此外,即使最初的出血被成功止住,伤口后遗症(如感染)也是慢性发病率的一个重要来源。为了治疗急性和慢性伤口,人们发现、测试并采用了许多伤口愈合材料。其中包括纱布等局部敷料,以及天然材料和仿生物材料。然而,这些材料都无法成功模拟人体自身伤口愈合材料--血凝块--的复杂动态特性。具体来说,血凝块具有复杂的机械和生化特性,这些特性在空间和时间尺度上各不相同,可引导伤口愈合反应,因此是理想的伤口愈合材料。在本手稿中,我们回顾了血凝块复杂的机械和生化特性,评述了当前的伤口愈合材料,并确定了新材料可提供额外功能的机会,特别关注水凝胶。我们重点介绍了合成水凝胶的最新发展,这些水凝胶能够模拟血凝块的更多特性:作为血栓和组织修复的刺激物。我们的结论是,未来模仿血凝块生物化学、力学和结构设计的水凝胶材料可与令人兴奋的血小板样颗粒相结合,用作止血剂,同时促进生物伤口愈合反应。因此,我们相信合成水凝胶是满足对更好的伤口愈合材料的明确需求的理想候选材料。
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引用次数: 0
Human augmentation by wearable supernumerary robotic limbs: review and perspectives 可穿戴多功能机器人肢体的人体增重:回顾与展望
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-09-17 DOI: 10.1088/2516-1091/ac2294
D. Prattichizzo, Maria Pozzi, Tommaso Lisini Baldi, M. Malvezzi, I. Hussain, S. Rossi, G. Salvietti
Supernumerary robotic limbs (SRLs) are wearable robots designed to enhance the sensorimotor abilities of humans. SRLs can be used to compensate for lost functions in patients with motor deficits and, more in general, to augment the sensorimotor capabilities of humans to interact with the environment. The design and control of SRLs present several challenges. SRLs must have high levels of ergonomics and wearability and, depending on the application, they might also require enhanced robustness and strength. Supernumerary robotics differs from collaborative robotics, since SRLs are not collaborative external agents but rather act under the direct command of the operator who, thanks to the use of suitable interfaces, gains the control of some actions of the SRLs. From the control point of view, it is fundamental to find the right trade-off between the degrees of freedom that are under the direct control of the user and the level of robot autonomy. The adoption of feedback interfaces can help the human to better command and use the SRL. In this review, we discuss all these aspects, relating them to the current literature on SRLs. We also present the main applications and the potential of these relatively recent devices, as well as the main neuroscientific questions they rise on the implications of their use on the users’ body schema.
超级机械臂(SRL)是一种可穿戴机器人,旨在增强人类的感觉运动能力。SRL可用于补偿运动缺陷患者的功能损失,更广泛地说,可用于增强人类与环境相互作用的感觉运动能力。SRL的设计和控制带来了一些挑战。SRL必须具有高水平的人体工程学和耐磨性,根据应用情况,它们可能还需要增强的坚固性和强度。超级机器人与协作机器人不同,因为SRL不是协作的外部代理,而是在操作员的直接指挥下行动,由于使用了合适的接口,操作员可以控制SRL的一些动作。从控制的角度来看,在用户直接控制的自由度和机器人自主性水平之间找到正确的权衡是至关重要的。反馈接口的采用可以帮助人类更好地指挥和使用SRL。在这篇综述中,我们讨论了所有这些方面,并将它们与当前关于SRL的文献联系起来。我们还介绍了这些相对较新设备的主要应用和潜力,以及它们在使用对用户身体模式的影响方面提出的主要神经科学问题。
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引用次数: 27
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Progress in biomedical engineering (Bristol, England)
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