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Classification of Children's Heart Sounds With Noise Reduction Based on Variational Modal Decomposition 基于变分模态分解的儿童心音降噪分类
Pub Date : 2022-05-26 DOI: 10.3389/fmedt.2022.854382
Anqi Zhang, Jiaming Wang, Fei Qu, Zhaoming He
Purpose Children's heart sounds were denoised to improve the performance of the intelligent diagnosis. Methods A combined noise reduction method based on variational modal decomposition (VMD) and wavelet soft threshold algorithm (WST) was proposed, and used to denoise 103 phonocardiogram samples. Features were extracted after denoising and employed for an intelligent diagnosis model to verify the effect of the denoising method. Results The noise in children's phonocardiograms, especially crying noise, was suppressed. The signal-to-noise ratio obtained by the method for normal heart sounds was 14.69 dB at 5 dB Gaussian noise, which was higher than that obtained by WST only and the other VMD denoising method. Intelligent classification showed that the accuracy, sensitivity and specificity of the classification system for congenital heart diseases were 92.23, 92.42, and 91.89%, respectively and better than those with WST only. Conclusion The proposed noise reduction method effectively eliminates noise in children's phonocardiograms and improves the performance of intelligent screening for the children with congenital heart diseases.
目的对儿童心音进行降噪处理,提高智能诊断的效果。方法提出一种基于变分模态分解(VMD)和小波软阈值算法(WST)的组合降噪方法,并对103份心音图样本进行降噪处理。去噪后提取特征,并用于智能诊断模型,验证去噪方法的效果。结果患儿心音图噪声,尤其是哭闹噪声均得到抑制。在5 dB高斯噪声下,该方法获得的正常心音信噪比为14.69 dB,高于单纯WST和其他VMD去噪方法。智能分类表明,该分类系统对先天性心脏病的准确率、灵敏度和特异性分别为92.23%、92.42%和91.89%,均优于单纯WST分类。结论所提出的降噪方法有效地消除了儿童心音图中的噪声,提高了先天性心脏病儿童智能筛查的效果。
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引用次数: 3
Guidance for the Interpretation of Continual Cuffless Blood Pressure Data for the Diagnosis and Management of Hypertension 连续无袖带血压数据用于高血压诊断和治疗的解释指南
Pub Date : 2022-05-17 DOI: 10.3389/fmedt.2022.899143
J. Solà, M. Cortés, David Perruchoud, B. De Marco, M. Lobo, C. Pellaton, G. Wuerzner, N. Fisher, Jay A. Shah
Hypertension remains the leading risk factor for death worldwide. Despite its prevalence, success of blood pressure (BP) management efforts remains elusive, and part of the difficulty lies in the tool still used to diagnose, measure, and treat hypertension: the sphygmomanometer introduced by Samuel Siegfried Karl von Basch in 1867. In recent years, there has been an explosion of devices attempting to provide estimates of BP without a cuff, overcoming many limitations of cuff-based BP monitors. Unfortunately, the differences in underlying technologies between traditional BP cuffs and newer cuffless devices, as well as hesitancy of changing a well-implemented standard, still generate understandable skepticism about and reluctance to adopt cuffless BP monitors in clinical practice. This guidance document aims to navigate the scientific and medical communities through the types of cuffless devices and present examples of robust BP data collection which are better representations of a person's true BP. It highlights the differences between data collected by cuffless and traditional cuff-based devices and provides an initial framework of interpretation of the new cuffless datasets using, as an example, a CE-marked continual cuffless BP device (Aktiia BP Monitor, Aktiia, Switzerland). Demonstration of novel BP metrics, which have the potential to change the paradigm of hypertension diagnosis and treatment, are now possible for the first time with cuffless BP monitors that provide continual readings over long periods. Widespread adoption of continual cuffless BP monitors in healthcare will require a collaborative and thoughtful process, acknowledging that the transition from a legacy to a novel medical technology will be slow. Finally, this guidance concludes with a call to action to international scientific and expert associations to include cuffless BP monitors in original scientific research and in future versions of guidelines and standards.
高血压仍然是世界范围内死亡的主要危险因素。尽管血压(BP)普遍存在,但成功的血压管理工作仍然难以捉摸,部分困难在于仍然用于诊断、测量和治疗高血压的工具:1867年由塞缪尔·齐格弗里德·卡尔·冯·巴什(Samuel Siegfried Karl von Basch)引入的血压计。近年来,出现了大量尝试提供不带袖带的血压估计的设备,克服了基于袖带的血压监测仪的许多局限性。不幸的是,传统的血压袖带和新型无袖带设备之间的基础技术差异,以及改变一个实施良好的标准的犹豫,仍然产生了可以理解的怀疑,不愿意在临床实践中采用无袖带血压监测仪。本指导文件旨在通过无袖带设备的类型引导科学界和医学界,并提供可靠的血压数据收集示例,这些数据更好地代表了一个人的真实血压。它强调了无袖带和传统袖带设备收集的数据之间的差异,并提供了一个解释新无袖带数据集的初步框架,以ce标记的连续无袖带BP设备为例(Aktiia BP Monitor, Aktiia, Switzerland)。有可能改变高血压诊断和治疗模式的新型血压指标的演示,现在首次有可能使用无套管的血压监测仪,提供长时间的连续读数。在医疗保健领域广泛采用连续无套管BP监测仪将需要一个协作和深思熟虑的过程,承认从传统到新型医疗技术的过渡将是缓慢的。最后,本指南呼吁国际科学和专家协会采取行动,将无袖BP监测仪纳入原始科学研究和未来版本的指南和标准中。
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引用次数: 9
Near-Infrared Photobiomodulation of Living Cells, Tubulin, and Microtubules In Vitro 活细胞、微管蛋白和微管的近红外光生物调节
Pub Date : 2022-05-04 DOI: 10.3389/fmedt.2022.871196
M. Staelens, E. Di Gregorio, A. Kalra, H. T. Le, N. Hosseinkhah, M. Karimpoor, L. Lim, J. Tuszynski
We report the results of experimental investigations involving photobiomodulation (PBM) of living cells, tubulin, and microtubules in buffer solutions exposed to near-infrared (NIR) light emitted from an 810 nm LED with a power density of 25 mW/cm2 pulsed at a frequency of 10 Hz. In the first group of experiments, we measured changes in the alternating current (AC) ionic conductivity in the 50–100 kHz range of HeLa and U251 cancer cell lines as living cells exposed to PBM for 60 min, and an increased resistance compared to the control cells was observed. In the second group of experiments, we investigated the stability and polymerization of microtubules under exposure to PBM. The protein buffer solution used was a mixture of Britton-Robinson buffer (BRB aka PEM) and microtubule cushion buffer. Exposure of Taxol-stabilized microtubules (~2 μM tubulin) to the LED for 120 min resulted in gradual disassembly of microtubules observed in fluorescence microscopy images. These results were compared to controls where microtubules remained stable. In the third group of experiments, we performed turbidity measurements throughout the tubulin polymerization process to quantify the rate and amount of polymerization for PBM-exposed tubulin vs. unexposed tubulin samples, using tubulin resuspended to final concentrations of ~ 22.7 μM and ~ 45.5 μM in the same buffer solution as before. Compared to the unexposed control samples, absorbance measurement results demonstrated a slower rate and reduced overall amount of polymerization in the less concentrated tubulin samples exposed to PBM for 30 min with the parameters mentioned above. Paradoxically, the opposite effect was observed in the 45.5 μM tubulin samples, demonstrating a remarkable increase in the polymerization rates and total polymer mass achieved after exposure to PBM. These results on the effects of PBM on living cells, tubulin, and microtubules are novel, further validating the modulating effects of PBM and contributing to designing more effective PBM parameters. Finally, potential consequences for the use of PBM in the context of neurodegenerative diseases are discussed.
我们报告了一项实验研究的结果,该实验涉及到缓冲溶液中活细胞、微管蛋白和微管的光生物调节(PBM),该缓冲溶液暴露于810 nm LED发出的近红外(NIR)光下,其功率密度为25 mW/cm2,脉冲频率为10 Hz。在第一组实验中,我们测量了HeLa和U251癌细胞在50-100 kHz范围内的交流电(AC)离子电导率的变化,这些活细胞暴露在PBM中60分钟,与对照细胞相比,观察到它们的电阻增加。在第二组实验中,我们研究了暴露于PBM下微管的稳定性和聚合。所使用的蛋白质缓冲溶液是布里顿-罗宾逊缓冲液(BRB又名PEM)和微管缓冲液的混合物。紫杉醇稳定的微管(~2 μM微管)在LED下暴露120分钟,荧光显微镜图像显示微管逐渐解体。这些结果与微管保持稳定的对照组进行了比较。在第三组实验中,我们在整个微管蛋白聚合过程中进行了浊度测量,以量化pbm暴露的微管蛋白与未暴露的微管蛋白样品的聚合速率和聚合量,在相同的缓冲溶液中,将微管蛋白重悬至最终浓度为~ 22.7 μM和~ 45.5 μM。与未暴露的对照样品相比,吸光度测量结果表明,浓度较低的微管蛋白样品在PBM中暴露30分钟后,聚合速度较慢,聚合总量减少。相反,在45.5 μM微管蛋白样品中观察到相反的效果,表明暴露于PBM后聚合速率和聚合物总质量显著增加。这些关于PBM对活细胞、微管蛋白和微管影响的结果是新颖的,进一步验证了PBM的调节作用,并有助于设计更有效的PBM参数。最后,讨论了在神经退行性疾病中使用PBM的潜在后果。
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引用次数: 8
Porous Scaffold-Hydrogel Composites Spatially Regulate 3D Cellular Mechanosensing 多孔支架-水凝胶复合材料空间调节三维细胞力学传感
Pub Date : 2022-05-02 DOI: 10.3389/fmedt.2022.884314
M. DiCerbo, M. M. Benmassaoud, Sebastián L. Vega
Cells encapsulated in 3D hydrogels exhibit differences in cellular mechanosensing based on their ability to remodel their surrounding hydrogel environment. Although cells in tissue interfaces feature a range of mechanosensitive states, it is challenging to recreate this in 3D biomaterials. Human mesenchymal stem cells (MSCs) encapsulated in methacrylated gelatin (GelMe) hydrogels remodel their local hydrogel environment in a time-dependent manner, with a significant increase in cell volume and nuclear Yes-associated protein (YAP) localization between 3 and 5 days in culture. A finite element analysis model of compression showed spatial differences in hydrogel stress of compressed GelMe hydrogels, and MSC-laden GelMe hydrogels were compressed (0–50%) for 3 days to evaluate the role of spatial differences in hydrogel stress on 3D cellular mechanosensing. MSCs in the edge (high stress) were significantly larger, less round, and had increased nuclear YAP in comparison to MSCs in the center (low stress) of 25% compressed GelMe hydrogels. At 50% compression, GelMe hydrogels were under high stress throughout, and this resulted in a consistent increase in MSC volume and nuclear YAP across the entire hydrogel. To recreate heterogeneous mechanical signals present in tissue interfaces, porous polycaprolactone (PCL) scaffolds were perfused with an MSC-laden GelMe hydrogel solution. MSCs in different pore diameter (~280–430 μm) constructs showed an increased range in morphology and nuclear YAP with increasing pore size. Hydrogel stress influences MSC mechanosensing, and porous scaffold-hydrogel composites that expose MSCs to diverse mechanical signals are a unique biomaterial for studying and designing tissue interfaces.
被包裹在三维水凝胶中的细胞表现出不同的细胞力学感知能力,这是基于它们重塑周围水凝胶环境的能力。尽管组织界面中的细胞具有一系列机械敏感状态,但在3D生物材料中重建这一状态具有挑战性。包裹在甲基丙烯酸明胶(GelMe)水凝胶中的人间充质干细胞(MSCs)以一种时间依赖性的方式重塑其局部水凝胶环境,在培养3至5天期间,细胞体积和细胞核yes相关蛋白(YAP)定位显著增加。压缩有限元分析模型显示了压缩GelMe水凝胶的水凝胶应力的空间差异,并将msc负载的GelMe水凝胶压缩(0-50%)3天,以评估水凝胶应力的空间差异对三维细胞力学传感的作用。与25%压缩GelMe水凝胶的中心(低应力)MSCs相比,边缘(高应力)MSCs明显更大,更少圆形,并且核YAP增加。在50%的压缩下,GelMe水凝胶始终处于高应力状态,这导致整个水凝胶中MSC体积和核YAP的持续增加。为了重现存在于组织界面中的异质机械信号,我们将载msc的凝胶溶液灌注到多孔聚己内酯(PCL)支架中。不同孔径(~280 ~ 430 μm)构建的MSCs,随着孔径的增大,形貌和细胞核YAP的变化幅度增大。水凝胶应力影响间充质干细胞的力学传感,多孔支架-水凝胶复合材料使间充质干细胞暴露于不同的机械信号中,是研究和设计组织界面的独特生物材料。
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引用次数: 2
Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines 内皮细胞粘附分子-纳米药物(无法)达到的目标
Pub Date : 2022-04-07 DOI: 10.3389/fmedt.2022.846065
N. Milosevic, M. Rütter, A. David
Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.
内皮细胞粘附分子长期以来被认为是许多病理的有希望的靶点。尽管有很好的临床前数据,但开发抗细胞粘附分子(CAMs)的小分子抑制剂或单克隆抗体(mab)的一些努力以临床阶段失败告终。与此同时,近年来也报道了许多经过验证的纳米药物靶向cam的方法。广泛的潜在应用已经在各种临床前研究中得到证明,从药物输送到肿瘤血管,炎症内皮的成像,或阻断免疫细胞浸润。然而,没有任何NM候选药物进一步进入临床开发。在这篇综述中,我们将总结针对cam的最先进的NMs的例子,并将它们与已知的针对cam的传统药物并列,试图找出重要的转化障碍。最重要的是,我们将总结提出的策略,以增强内皮CAM靶向NMs,试图提供一个工具目录,以进一步发展。
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引用次数: 4
In silico Effects of Synaptic Connections in the Visual Thalamocortical Pathway 视觉丘脑皮质通路突触连接的计算机效应
Pub Date : 2022-04-05 DOI: 10.3389/fmedt.2022.856412
Swapna Sasi, Basabdatta Sen Bhattacharya
We have studied brain connectivity using a biologically inspired in silico model of the visual pathway consisting of the lateral geniculate nucleus (LGN) of the thalamus, and layers 4 and 6 of the primary visual cortex. The connectivity parameters in the model are informed by the existing anatomical parameters from mammals and rodents. In the base state, the LGN and layer 6 populations in the model oscillate with dominant alpha frequency, while the layer 4 oscillates in the theta band. By changing intra-cortical hyperparameters, specifically inhibition from layer 6 to layer 4, we demonstrate a transition to alpha mode for all the populations. Furthermore, by increasing the feedforward connectivities in the thalamo-cortico-thalamic loop, we could transition into the beta band for all the populations. On looking closely, we observed that the origin of this beta band is in the layer 6 (infragranular layers); lesioning the thalamic feedback from layer 6 removed the beta from the LGN and the layer 4. This agrees with existing physiological studies where it is shown that beta rhythm is generated in the infragranular layers. Lastly, we present a case study to demonstrate a neurological condition in the model. By changing connectivities in the network, we could simulate the condition of significant (P < 0.001) decrease in beta band power and a simultaneous increase in the theta band power, similar to that observed in Schizophrenia patients. Overall, we have shown that the connectivity changes in a simple visual thalamocortical in silico model can simulate state changes in the brain corresponding to both health and disease conditions.
我们已经研究了大脑连接使用一个生物学启发的视觉通路的计算机模型,该模型由丘脑的外侧膝状核(LGN)和初级视觉皮层的第4层和第6层组成。模型中的连通性参数由哺乳动物和啮齿动物的现有解剖参数提供。在基本状态下,模型中的LGN和第6层种群以α频带为主振荡,而第4层在θ频带振荡。通过改变皮质内高参数,特别是从第6层到第4层的抑制,我们证明了所有种群都向α模式过渡。此外,通过增加丘脑-皮质-丘脑回路的前馈连接,我们可以在所有人群中过渡到β波段。通过仔细观察,我们观察到这个β带的起源在第6层(小颗粒层);从第6层的丘脑反馈中删除了LGN和第4层的β。这与现有的生理学研究一致,研究表明β节律是在小颗粒层中产生的。最后,我们提出了一个案例研究,以证明在模型神经条件。通过改变网络中的连接,我们可以模拟出β波段功率显著(P < 0.001)下降而θ波段功率同时增加的情况,类似于在精神分裂症患者中观察到的情况。总的来说,我们已经证明,在一个简单的视觉丘脑皮质计算机模型中,连接的变化可以模拟大脑中与健康和疾病状况相对应的状态变化。
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引用次数: 0
Preliminary Analysis of Burn Degree Using Non-invasive Microwave Spiral Resonator Sensor for Clinical Applications 无创微波螺旋谐振器传感器在烧伤程度检测中的临床应用初步分析
Pub Date : 2022-04-05 DOI: 10.3389/fmedt.2022.859498
P. Rangaiah, Bappaditya Mandal, E. Avetisyan, A. Chezhian, B. Augustine, M. Pérez, Robin Augustine
The European “Senseburn” project aims to develop a smart, portable, non-invasive microwave early effective diagnostic tool to assess the depth(d) and degree of burn. The objective of the work is to design and develop a convenient non-invasive microwave sensor for the analysis of the burn degree on burnt human skin. The flexible and biocompatible microwave sensor is developed using a magnetically coupled loop probe with a spiral resonator (SR). The sensor is realized with precise knowledge of the lumped element characteristics (resistor (R), an inductor (L), and a capacitor (C) RLC parameters). The estimated electrical equivalent circuit technique relies on a rigorous method enabling a comprehensive characterization of the sensor (loop probe and SR). The microwave resonator sensor with high quality factor (Q) is simulated using a CST studio suite, AWR microwave office, and fabricated on the RO 3003 substrate with a standard thickness of 0.13 mm. The sensor is prepared based on the change in dielectric property variation in the burnt skin. The sensor can detect a range of permittivity variations (εr 3–38). The sensor is showing a good response in changing resonance frequency between 1.5 and 1.71 GHz for (εr 3 to 38). The sensor is encapsulated with PDMS for the biocompatible property. The dimension of the sensor element is length (L) = 39 mm, width (W) = 34 mm, and thickness (T) = 1.4 mm. The software algorithm is prepared to automate the process of burn analysis. The proposed electromagnetic (EM) resonator based sensor provides a non-invasive technique to assess burn degree by monitoring the changes in resonance frequency. Most of the results are based on numerical simulation. We propose the unique circuit set up and the sensor device based on the information generated from the simulation in this article. The clinical validation of the sensor will be in our future work, where we will understand closely the practical functioning of the sensor based on burn degrees. The senseburn system is designed to support doctors to gather vital info of the injuries wirelessly and hence provide efficient treatment for burn victims, thus saving lives.
欧洲“Senseburn”项目旨在开发一种智能、便携、无创的微波早期有效诊断工具,以评估烧伤的深度和程度。本工作的目的是设计和开发一种方便的无创微波传感器,用于分析烧伤人体皮肤的烧伤程度。采用带螺旋谐振器(SR)的磁耦合环探头,研制了柔性的生物相容性微波传感器。该传感器是通过精确了解集总元件特性(电阻(R),电感(L)和电容(C) RLC参数)来实现的。估计等效电路技术依赖于一种严格的方法,能够全面表征传感器(环路探头和SR)。采用CST studio suite, AWR microwave office对具有高品质因子(Q)的微波谐振器传感器进行了仿真,并在标准厚度为0.13 mm的RO 3003衬底上制作。该传感器是根据烧伤皮肤的介电特性变化来制备的。该传感器可检测介电常数变化范围(εr 3-38)。在(εr 3 ~ 38)的1.5 ~ 1.71 GHz范围内,传感器的响应良好。该传感器采用PDMS封装,具有生物相容性。传感器元件的尺寸为长(L) = 39mm,宽(W) = 34mm,厚(T) = 1.4 mm。软件算法是准备自动化过程烧伤分析。所提出的基于电磁谐振器的传感器提供了一种非侵入性技术,通过监测谐振频率的变化来评估烧伤程度。大多数结果是基于数值模拟的。本文根据仿真产生的信息,提出了独特的电路设置和传感器装置。传感器的临床验证将在我们未来的工作中进行,在那里我们将密切了解基于烧伤程度的传感器的实际功能。senseburn系统旨在支持医生无线收集受伤的重要信息,从而为烧伤患者提供有效的治疗,从而挽救生命。
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引用次数: 3
Effect of Patent Expiry on the Performance of Innovator Multinational Pharmaceutical Companies in a Low Middle Income Country 中低收入国家专利到期对创新型跨国制药公司绩效的影响
Pub Date : 2022-04-04 DOI: 10.3389/fmedt.2022.783460
Farrukh Khalil, J. Onyango
Patent expiry or loss of exclusivity exposes innovator pharmaceutical companies to changes in the market dynamics brought about by increased production of generics by rival companies after patent expiration. This current study focused on the effect of generic products manufacturing and competitive market pressures, price changes, and changes in sales volumes and profitability of innovator multinational pharmaceutical companies after patent expiry. The methodology of this study involved a descriptive survey design and utilized both qualitative and quantitative techniques for data collection, analysis, and presentation. Primary data were collected using the key informants' in-depth interviews and survey questionnaires. The top management, including regional managers, general managers, and directors of each of the eight companies participating in this study, were interviewed to gather the qualitative data. Thirty-six respondents comprising of Product Development Managers and Business Supervising Managers responded to a survey questionnaire through purposive sampling. Findings depicted a significant effect of patent expiry on the generic production and subsequent decline in the performance of multinational innovator companies in the pharmaceutical industry. This study recommends that multinational innovator companies operating in low-income countries, such as Kenya, develop strategic policies to tap into the market by leveraging generic production through collaborative manufacturing with generic companies to share revenues.
专利到期或排他性的丧失使创新制药公司面临竞争对手在专利到期后增加仿制药生产所带来的市场动态变化。本研究主要关注仿制药生产和竞争市场压力、价格变化以及创新跨国制药公司在专利到期后销量和盈利能力的变化的影响。本研究的方法包括描述性调查设计,并利用定性和定量技术进行数据收集、分析和呈现。主要数据的收集采用了对关键信息者的深度访谈和调查问卷。对参与本研究的八家公司的高层管理人员,包括区域经理、总经理和董事进行了访谈,以收集定性数据。由产品开发经理和业务监督经理组成的36名受访者通过有目的抽样的方式回答了一份调查问卷。研究结果表明,专利到期对制药行业跨国创新公司的仿制药生产和随后的业绩下降有显著影响。本研究建议,在肯尼亚等低收入国家运营的跨国创新公司制定战略政策,通过与仿制药公司合作制造来利用仿制药生产来分享收入,从而进入市场。
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引用次数: 1
Crossing Total Occlusions Using a Hydraulic Pressure Wave: Development of the Wave Catheter 用液压波穿越全闭塞:波导管的发展
Pub Date : 2022-04-01 DOI: 10.3389/fmedt.2022.851927
A. Sakes, Menno Lageweg, R. van Starkenburg, Saurabh Sontakke, J. Spronck
With the ongoing miniaturization of surgical instruments, the ability to apply large forces on tissues for resection becomes challenging and the risk of buckling becomes more real. In an effort to allow for high force application in slender instruments, in this study, we have investigated using a hydraulic pressure wave (COMSOL model) and developed an innovative 5F cardiac catheter (L = 1,000 mm) that allows for applying high forces up to 9.0 ± 0.2 N on target tissues without buckling. The catheter uses high-speed pressure waves to transfer high-force impulses through a slender flexible shaft consisted of a flat wire coil, a double braid, and a nylon outer coating. The handle allows for single-handed operation of the catheter with easy adjusting of the input impulse characteristic, including frequency (1–10 Hz), time and number of strokes using a solenoid actuator, and easy connection of an off-the-shelf inflator for catheter filling. In a proof-of-principle experiment, we illustrated that the Wave catheter was able to penetrate a phantom model of a coronary Chronic Total Occlusion (CTO) manufactured out of hydroxyapatite and gelatin. It was found that the time until puncture decreased from 80 ± 5.4 s to 7.8 ± 0.4 s, for a stroke frequency of 1–10 Hz, respectively. The number of strikes until puncture was approximately constant at 80 ± 5.4, 76.7 ± 2.6, and 77.7 ± 3.9 for the different stroke frequencies. With the development of the Wave catheter, first steps have been made toward high force application through slender shafts.
随着手术器械的不断小型化,在组织上施加大的力进行切除的能力变得具有挑战性,屈曲的风险变得更加真实。为了在细长的器械上施加大的力,在这项研究中,我们研究了使用液压波(COMSOL模型)并开发了一种创新的5F心导管(L = 1,000 mm),它允许在目标组织上施加高达9.0±0.2 N的大力而不会弯曲。导管使用高速压力波通过一个细长的柔性轴传递高强度脉冲,该轴由一个扁平的线圈、一个双编织带和一个尼龙外层组成。手柄允许单手操作导管,易于调整输入脉冲特性,包括频率(1-10 Hz),使用电磁致动器的时间和笔划次数,以及易于连接用于导管填充的现成充气机。在一个原理验证实验中,我们证明了Wave导管能够穿透由羟基磷灰石和明胶制成的冠状动脉慢性完全闭塞(CTO)的幻影模型。结果表明,在1 ~ 10 Hz行程频率下,穿刺时间由80±5.4 s缩短至7.8±0.4 s。在不同的冲程频率下,直到穿刺的撞击次数大致恒定在80±5.4,76.7±2.6和77.7±3.9。随着波导管的发展,通过细长轴向高力应用迈出了第一步。
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引用次数: 0
Optimization of Anti-SARS-CoV-2 Neutralizing Antibody Therapies: Roadmap to Improve Clinical Effectiveness and Implementation. 优化抗 SARS-CoV-2 中和抗体疗法:提高临床疗效和实施的路线图。
IF 2.7 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-28 eCollection Date: 2022-01-01 DOI: 10.3389/fmedt.2022.867982
Karlijn van der Straten, Marit J van Gils, Steven W de Taeye, Godelieve J de Bree

One of the major breakthroughs to combat the current Coronavirus Disease 2019 (COVID-19) pandemic has been the development of highly effective vaccines against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Still, alternatives are needed for individuals who are at high risk of developing severe COVID-19 and are not protected by vaccination. Monoclonal antibodies against the spike protein of SARS-CoV-2 have been shown to be effective as prophylaxis and treatment against COVID-19. However, the emergence of variants of concern (VOCs) challenges the efficacy of antibody therapies. This review describes the neutralization resistance of the clinically-approved monoclonal antibody therapies against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2), and the Omicron (B.1.1.529) variants. To guide the development of monoclonal antibody therapies and to anticipate on the continuous evolution of SARS-CoV-2, we highlight different strategies to broaden the antibody activity by targeting more conserved epitopes and/or simultaneously targeting multiple sites of vulnerability of the virus. This review further describes the contribution of antibody Fc effector functions to optimize the antibody efficacy. In addition, the main route of SARS-CoV-2 antibody administration is currently intravenously and dictates a monthly injection when used as prophylactic. Therefore, we discusses the concept of long-acting antibodies (LAABs) and non-intravenously routes of antibody administration in order to broaden the clinical applicability of antibody therapies.

在应对当前的冠状病毒病 2019(COVID-19)大流行方面取得的重大突破之一是开发出了针对严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)的高效疫苗。然而,对于罹患严重 COVID-19 的高风险人群和无法通过接种疫苗获得保护的人群来说,仍然需要替代疫苗。针对 SARS-CoV-2 尖峰蛋白的单克隆抗体已被证明可有效预防和治疗 COVID-19。然而,令人担忧的变异体(VOCs)的出现对抗体疗法的疗效提出了挑战。本综述介绍了临床批准的单克隆抗体疗法对 Alpha (B.1.1.7)、Beta (B.1.351)、Gamma (P1)、Delta (B.1.617.2) 和 Omicron (B.1.1.529) 变种的中和抗性。为了指导单克隆抗体疗法的开发并预测 SARS-CoV-2 的不断演变,我们重点介绍了通过靶向更多保守表位和/或同时靶向病毒的多个易感位点来扩大抗体活性的不同策略。本综述进一步介绍了抗体 Fc 效应器功能对优化抗体功效的贡献。此外,SARS-CoV-2 抗体目前的主要给药途径是静脉注射,在预防性使用时需要每月注射一次。因此,我们讨论了长效抗体(LAABs)的概念和非静脉注射的抗体给药途径,以扩大抗体疗法的临床适用性。
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Frontiers in medical technology
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