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The development of paliperidone nanocrystals for the treatment of schizophrenia. 开发用于治疗精神分裂症的帕利哌酮纳米晶体。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-20 DOI: 10.1088/2516-1091/ad8fe7
Phattalapol Lhaglham, Luksika Jiramonai, Xing-Jie Liang, Bingchuan Liu, Fangzhou Li

Schizophrenia is a complex and chronic psychiatric disorder that significantly impacts patients' quality of life. Ranking 12th among 310 diseases and injuries that result in disability, the number of patients suffering from schizophrenia continues to rise, emphasizing the urgent need for developing effective treatments. Despite the availability of effective antipsychotic drugs, over 80% of patients taking oral antipsychotics experience relapses, primarily caused by non-adherence as the high dosing frequency is required. In this review, we discuss about schizophrenia, its incidence, pathological causes, influencing factors, and the challenges of the current medications. Specifically, we explore nanocrystal technology and its application to paliperidone, making it one of the most successful long-acting antipsychotic drugs introduced to the market. We highlight the clinical advantages of paliperidone nanocrystals, including improved adherence, efficacy, long-term outcomes, patient satisfaction, safety, and cost-effectiveness. Additionally, we address the physicochemical factors influencing the drug's half-life, which crucially contribute to long-acting medications. Further studies on nanocrystal-based long-acting medications are crucial for enhancing their effectiveness and reliability. The successful development of paliperidone nanocrystals holds great promise as a significant approach for drug development, with potential applications for other chronic disease management.

精神分裂症是一种复杂的慢性精神疾病,严重影响患者的生活质量。在导致残疾的310种疾病和伤害中,精神分裂症患者的人数继续增加,排在第12位,这强调了开发有效治疗方法的迫切需要。尽管有有效的抗精神病药物,但超过80%服用口服抗精神病药物的患者出现复发,主要是由于需要高剂量频率而不依从性所致。在这篇综述中,我们讨论了精神分裂症,其发病率,病理原因,影响因素,以及当前药物的挑战。具体来说,我们探索纳米晶体技术及其在帕利哌酮中的应用,使其成为市场上最成功的长效抗精神病药物之一。我们强调了帕利哌酮纳米晶体的临床优势,包括改善依从性、疗效、长期结局、患者满意度、安全性和成本效益。此外,我们解决了影响药物半衰期的物理化学因素,这对长效药物至关重要。进一步研究纳米晶体长效药物对于提高其有效性和可靠性至关重要。帕利哌酮纳米晶体的成功开发作为一种重要的药物开发方法具有很大的前景,并具有潜在的应用于其他慢性疾病的治疗。
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引用次数: 0
Harms associated with retinal implantation of a stimulating electrode array to treat outer-retinal degeneration: a systematic review and meta-analysis of safety. 视网膜植入刺激电极阵列治疗视网膜外变性的危害:安全性的系统回顾和荟萃分析。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-11 DOI: 10.1088/2516-1091/ad811e
Luke E Hallum, Shaun L Cloherty

Retinal implantation of an electrode array is an emerging treatment for vision loss caused by outer-retinal degeneration. This article collects and analyses harms associated with the treatment reported in the peer-reviewed literature, thus enabling informed decision-making by patients, clinicians, researchers, engineers, and policymakers. We searched MEDLINE, Embase, and clinical trials registries for peer-reviewed journal articles reporting harms outcomes. We extracted data from articles including study design, definitions of 'serious adverse event', and timing of adverse events. We applied the McMaster tool to these articles to assess the risk of bias in harms assessment and reporting. Our searches returned 585 abstracts. We reviewed the full text of 59 articles describing 11 different devices. McMaster scores ranged from 3 to 12 (maximum 15; higher scores indicate less risk). We compiled a comprehensive list of all serious and non-serious adverse events associated with retinal implantation. Several harms were common across devices. Our meta-analysis showed that serious adverse events are log-uniformly distributed throughout follow-up. Improved reporting and further clinical studies are needed to develop a reliable safety profile of retinal implantation. Our findings will help guide the design, conduct, and reporting of future clinical trials of retinal implantation and other emerging treatments for vision loss. (PROSPERO registration: CRD42022308123.).

视网膜植入电极阵列是一种新兴的治疗视网膜外变性引起的视力丧失的方法。本文收集并分析了同行评议文献中报道的与治疗相关的危害,从而使患者、临床医生、研究人员、工程师和政策制定者能够做出明智的决策。我们检索了MEDLINE、Embase和临床试验注册库,查找同行评议的报告危害结果的期刊文章。我们从文章中提取数据,包括研究设计、“严重不良事件”的定义和不良事件发生的时间。我们将麦克马斯特工具应用于这些文章,以评估危害评估和报告中的偏倚风险。我们检索了585篇摘要。我们回顾了59篇文章的全文,这些文章描述了11种不同的设备。麦克马斯特得分范围从3到12(最多15分;得分越高,风险越小)。我们编制了一份与视网膜植入术相关的所有严重和非严重不良事件的综合清单。有几种危害是跨设备常见的。我们的荟萃分析显示,严重不良事件在随访期间呈对数均匀分布。完善的报告和进一步的临床研究需要建立一个可靠的安全性的视网膜植入术。我们的研究结果将有助于指导未来视网膜植入和其他新兴视力丧失治疗的临床试验的设计、实施和报告。(普洛斯彼罗注册号:CRD42022308123)。
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引用次数: 0
6G networks for the operating room of the future. 未来手术室的 6G 网络。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-21 DOI: 10.1088/2516-1091/ad819c
Franziska Jurosch, Nicolai Kröger, Sven Kolb, Fidan Mehmeti, Eimo Martens, Stefanie Speidel, Wolfgang Kellerer, Dirk Wilhelm, Jonas Fuchtmann

Technical setups in today's operating rooms (ORs) are becoming increasingly complex, especially with the integration of applications which rely on the fusion of multiple information sources. While manufacturers have already started to make use of such approaches, the quest for fully integrated ORs becoming standard is still ongoing. We describe a variety of state-of-the-art projects that envision an OR of the future in order to identify missing building blocks. While these initial implementations of sensor fused ORs have shown to be promising, all current proposals lack a scalable networking backbone that serves the needs of future applications. We therefore discuss how the coming 6G standard's envisioned advancements can provide a flexible and intelligent platform to enable the fully integrated OR of the future.

当今手术室(or)的技术设置正变得越来越复杂,特别是依赖于多个信息源融合的应用集成。虽然制造商已经开始使用这些方法,但对完全集成的ORs成为标准的追求仍在进行中。我们描述了各种最先进的项目,这些项目设想了未来的OR,以确定缺失的构建模块。虽然这些传感器融合的ORs的初步实现已经显示出很有希望,但目前所有的建议都缺乏一个可扩展的网络骨干来满足未来应用的需求。因此,我们将讨论即将到来的6G标准的设想进展如何提供一个灵活和智能的平台,以实现未来的完全集成或。
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引用次数: 0
Systematic review of experimental paradigms and deep neural networks for electroencephalography-based cognitive workload detection. 基于脑电图的认知工作量检测的实验范例和深度神经网络的系统回顾。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-21 DOI: 10.1088/2516-1091/ad8530
Vishnu K N, Cota Navin Gupta

This article summarizes a systematic literature review of deep neural network-based cognitive workload (CWL) estimation from electroencephalographic (EEG) signals. The focus of this article can be delineated into two main elements: first is the identification of experimental paradigms prevalently employed for CWL induction, and second, is an inquiry about the data structure and input formulations commonly utilized in deep neural networks (DNN)-based CWL detection. The survey revealed several experimental paradigms that can reliably induce either graded levels of CWL or a desired cognitive state due to sustained induction of CWL. This article has characterized them with respect to the number of distinct CWL levels, cognitive states, experimental environment, and agents in focus. Further, this literature analysis found that DNNs can successfully detect distinct levels of CWL despite the inter-subject and inter-session variability typically observed in EEG signals. Several methodologies were found using EEG signals in its native representation of a two-dimensional matrix as input to the classification algorithm, bypassing traditional feature selection steps. More often than not, researchers used DNNs as black-box type models, and only a few studies employed interpretable or explainable DNNs for CWL detection. However, these algorithms were mostly post hoc data analysis and classification schemes, and only a few studies adopted real-time CWL estimation methodologies. Further, it has been suggested that using interpretable deep learning methodologies may shed light on EEG correlates of CWL, but this remains mostly an unexplored area. This systematic review suggests using networks sensitive to temporal dependencies and appropriate input formulations for each type of DNN architecture to achieve robust classification performance. An additional suggestion is to utilize transfer learning methods to achieve high generalizability across tasks (task-independent classifiers), while simple cross-subject data pooling may achieve the same for subject-independent classifiers.

本文综述了基于深度神经网络的脑电信号认知负荷估计的相关文献。本文的重点可以概括为两个主要元素:首先是识别普遍用于CWL归纳的实验范式,其次是对基于深度神经网络(DNN)的CWL检测中常用的数据结构和输入公式的研究。该研究揭示了几种实验范式,它们可以可靠地诱导CWL的分级水平或由于持续诱导CWL而达到期望的认知状态。本文从不同CWL水平的数量、认知状态、实验环境和关注的主体等方面对它们进行了描述。此外,本文献分析发现,尽管在EEG信号中通常观察到主体间和会话间的变化,但dnn可以成功检测到不同水平的CWL。我们找到了几种方法,使用二维矩阵的原生表示的脑电图信号作为分类算法的输入,绕过传统的特征选择步骤。通常情况下,研究人员使用dnn作为黑盒型模型,只有少数研究使用可解释或可解释的dnn进行CWL检测。然而,这些算法大多是事后数据分析和分类方案,只有少数研究采用了实时CWL估计方法。此外,有人建议使用可解释的深度学习方法可以阐明脑电图与CWL的相关性,但这仍然是一个未开发的领域。该系统综述建议使用对时间依赖性敏感的网络和针对每种DNN架构的适当输入公式来实现稳健的分类性能。另一个建议是利用迁移学习方法来实现跨任务(任务独立分类器)的高泛化性,而简单的跨主题数据池可以实现相同的主题独立分类器。
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引用次数: 0
Enhancing mammography: a comprehensive review of computer methods for improving image quality. 增强乳腺 X 射线摄影:全面回顾提高图像质量的计算机方法。
IF 5 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-26 DOI: 10.1088/2516-1091/ad776b
Joana Cristo Santos, Miriam Seoane Santos, Pedro Henriques Abreu

Mammography imaging remains the gold standard for breast cancer detection and diagnosis, but challenges in image quality can lead to misdiagnosis, increased radiation exposure, and higher healthcare costs. This comprehensive review evaluates traditional and machine learning-based techniques for improving mammography image quality, aiming to benefit clinicians and enhance diagnostic accuracy. Our literature search, spanning 2015 - 2024, identified 115 articles focusing on contrast enhancement and noise reduction methods, including histogram equalization, filtering, unsharp masking, fuzzy logic, transform-based techniques, and advanced machine learning approaches. Machine learning, particularly architectures integrating denoising autoencoders with convolutional neural networks, emerged as highly effective in enhancing image quality without compromising detail. The discussion highlights the success of these techniques in improving mammography images' visual quality. However, challenges such as high noise ratios, inconsistent evaluation metrics, and limited open-source datasets persist. Addressing these issues offers opportunities for future research to further advance mammography image enhancement methodologies.

乳房x线摄影成像仍然是乳腺癌检测和诊断的金标准,但图像质量的挑战可能导致误诊,增加辐射暴露和更高的医疗保健费用。这篇全面的综述评估了传统和基于机器学习的技术,以提高乳房x光检查图像质量,旨在使临床医生受益并提高诊断准确性。我们从2015年到2024年的文献检索中发现了115篇关于对比度增强和降噪方法的文章,包括直方图均衡化、滤波、非锐利掩蔽、模糊逻辑、基于变换的技术和先进的机器学习方法。机器学习,特别是集成去噪自动编码器和卷积神经网络的架构,在不影响细节的情况下提高图像质量方面非常有效。讨论强调了这些技术在提高乳房x线摄影图像视觉质量方面的成功。然而,诸如高噪声比、不一致的评估指标和有限的开源数据集等挑战仍然存在。解决这些问题为进一步推进乳房x光图像增强方法的未来研究提供了机会。
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引用次数: 0
Lifetime engineering of bioelectronic implants with mechanically reliable thin film encapsulations 具有机械可靠薄膜封装的生物电子植入物的寿命工程
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-11-09 DOI: 10.1088/2516-1091/ad0b19
Martin Niemiec, Kyungjin Kim
Abstract While the importance of thin form factor and mechanical tissue biocompatibility has been made clear for next generation bioelectronic implants, material systems meeting these criteria still have not demonstrated sufficient long-term durability. This review provides an update on the materials used in modern bioelectronic implants as substrates and protective encapsulations, with a particular focus on flexible and conformable devices. We review how thin film encapsulations are known to fail due to mechanical stresses and environmental surroundings under processing and operating conditions. This information is then reflected in recommending state-of-the-art encapsulation strategies for designing mechanically reliable thin film bioelectronic interfaces. Finally, we assess the methods used to evaluate novel bioelectronic implant devices and the current state of their longevity based on encapsulation and substrate materials. We also provide insights for future testing to engineer long-lived bioelectronic implants more effectively and to make implantable bioelectronics a viable option for chronic diseases in accordance with each patient’s therapeutical timescale.
虽然薄的外形因素和机械组织生物相容性对于下一代生物电子植入物的重要性已经明确,但满足这些标准的材料系统仍然没有证明足够的长期耐用性。本综述提供了现代生物电子植入物中用作基板和保护封装的材料的最新情况,特别关注柔性和可适应的设备。我们回顾了在加工和操作条件下,薄膜封装是如何由于机械应力和环境环境而失效的。这些信息随后反映在推荐最先进的封装策略中,用于设计机械可靠的薄膜生物电子界面。最后,我们评估了用于评估新型生物电子植入装置的方法以及基于封装和衬底材料的寿命现状。我们还为未来的测试提供了见解,以更有效地设计长寿命的生物电子植入物,并根据每个患者的治疗时间表使植入式生物电子成为慢性病的可行选择。
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引用次数: 0
The stochastic digital human is now enrolling for in silico imaging trials – Methods and tools for generating digital cohorts 随机数字人现在正在参加计算机成像试验——生成数字队列的方法和工具
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-10-18 DOI: 10.1088/2516-1091/ad04c0
Aldo Badano, MIguel Lago, Elena Sizikova, Jana Delfino, Shuyue Guan, Mark A Anastasio, Berkman Sahiner
Abstract Randomized clinical trials, while often viewed as the highest evidentiary bar by which to judge the quality of a medical intervention, are far from perfect. In silico imaging trials are computational studies that seek to ascertain the performance of a medical device by collecting this information entirely via computer simulations. The benefits of in silico trials for evaluating new technology include significant resource and time savings, minimization of subject risk, the ability to study devices that are not achievable in the physical world, allow for the rapid and effective investigation of new technologies and ensure representation from all relevant subgroups. To conduct in silico trials, digital representations of humans are needed. We review the latest developments in methods and tools for obtaining digital humans for in silico imaging studies. First, we introduce terminology and a classification of digital human models. Second, we survey available methodologies for generating digital humans with healthy status and for generating diseased cases and discuss briefly the role of augmentation methods. Finally, we discuss approaches for sampling digital cohorts and understanding the trade-offs and potential for study bias associated with selecting specific patient distributions.
随机临床试验通常被视为判断医疗干预质量的最高证据标准,但它远非完美。计算机成像试验是一种计算机研究,旨在通过完全通过计算机模拟收集这些信息来确定医疗设备的性能。评估新技术的硅片试验的好处包括节省大量资源和时间,将受试者风险降至最低,能够研究在物理世界中无法实现的设备,允许对新技术进行快速有效的调查,并确保来自所有相关子群体的代表。为了进行计算机试验,需要人类的数字表示。我们回顾了获取数字人体用于计算机成像研究的方法和工具的最新发展。首先,我们介绍了数字人体模型的术语和分类。其次,我们调查了产生健康状态的数字人类和产生疾病病例的可用方法,并简要讨论了增强方法的作用。最后,我们讨论了采样数字队列的方法,并了解与选择特定患者分布相关的权衡和潜在的研究偏差。
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引用次数: 2
Updates on polyurethane and its multifunctional applications in biomedical engineering 聚氨酯及其在生物医学工程中的多功能应用进展
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-08-11 DOI: 10.1088/2516-1091/acef84
Z. Miri, S. Faré, Qianli Ma, H. Haugen
Polyurethanes (PUs) have properties that make them promising in biomedical applications. PU is recognized as one of the main families of blood and biocompatible materials. PU plays a vital role in the design of medical devices in various medical fields. The structure of PU contains two segments: soft and hard. Its elastomeric feature is due to its soft segment, and its excellent and high mechanical property is because of its hard segment. It is possible to achieve specific desirable and targeted properties by changing the soft and hard chemical structures and the ratio between them. The many properties of PU each draw the attention of different medical fields. This work reviews PU highlighted properties, such as biodegradability, biostability, shape memory, and improved antibacterial activity. Also, because PU has a variety of applications, this review restricts its focus to PU’s prominent applications in tissue engineering, cardiovascular medicine, drug delivery, and wound healing. In addition, it contains a brief review of PU’s applications in biosensors and oral administration.
聚氨酯(pu)的特性使其在生物医学领域的应用前景广阔。聚氨酯是公认的血液和生物相容性材料的主要家族之一。聚氨酯在各个医疗领域的医疗器械设计中起着至关重要的作用。PU的结构分为软、硬两部分。其弹性体特性是由于其软段,其优异和高的机械性能是由于其硬段。通过改变软硬化学结构和它们之间的比例,可以实现特定的理想和目标性能。聚氨酯的许多特性都引起了不同医学领域的关注。本文综述了聚氨酯的主要特性,如生物降解性、生物稳定性、形状记忆和提高的抗菌活性。此外,由于聚氨酯具有多种用途,本文将重点介绍聚氨酯在组织工程、心血管医学、药物输送和伤口愈合等方面的突出应用。此外,还简要介绍了聚氨酯在生物传感器和口服给药方面的应用。
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引用次数: 2
Wearable facial electromyography: in the face of new opportunities 佩戴式面部肌电图:面对新机遇
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-07-06 DOI: 10.1088/2516-1091/ace508
B. Levit, Shira Klorfeld-Auslender, Y. Hanein
Facial muscles play an important role in a vast range of physiological functions, ranging from mastication to communication. Any disruption in their normal function may lead to serious negative effects on human well-being. A very wide range of medical disorders and conditions in psychology, neurology, psychiatry, and cosmetic surgery are related to facial muscles, and scientific explorations spanning over decades exposed many fascinating phenomena. For example, expansive evidence implicates facial muscle activation with the expression of emotions. Yet, the exact manner by which emotions are expressed is still debated: whether facial expressions are universal, how gender and cultural differences shape facial expressions and if and how facial muscle activation shape the internal emotional state. Surface electromyography (EMG) is one of the best tools for direct investigation of facial muscle activity and can be applied for medical and research purposes. The use of surface EMG has been so far restricted, owing to limited resolution and cumbersome setups. Current technologies are inconvenient, interfere with the subject normal behavior, and require know-how in proper electrode placement. High density electrode arrays based on soft skin technology is a recent development in the realm of surface EMG. It opens the door to perform facial EMG (fEMG) with high signal quality, while maintaining significantly more natural environmental conditions and higher data resolution. Signal analysis of multi-electrode recordings can also reduce crosstalk to achieve single muscle resolution. This perspective paper presents and discusses new opportunities in mapping facial muscle activation, brought about by this technological advancement. The paper briefly reviews some of the main applications of fEMG and presents how these applications can benefit from a more precise and less intrusive technology.
面部肌肉在从咀嚼到交流等一系列生理功能中发挥着重要作用。对其正常功能的任何破坏都可能导致对人类福祉的严重负面影响。在心理学、神经病学、精神病学和整容外科中,广泛的医学疾病和状况都与面部肌肉有关,几十年来的科学探索揭示了许多迷人的现象。例如,大量证据表明面部肌肉的激活与情绪的表达有关。然而,情绪表达的确切方式仍然存在争议:面部表情是否普遍,性别和文化差异如何影响面部表情,面部肌肉激活是否以及如何影响内部情绪状态。表面肌电图(EMG)是直接观察面部肌肉活动的最佳工具之一,可用于医学和研究目的。由于分辨率有限和设置繁琐,表面肌电图的使用迄今为止一直受到限制。目前的技术不方便,干扰受试者的正常行为,并且需要知道如何正确放置电极。基于软皮技术的高密度电极阵列是表面肌电领域的最新发展。它为高信号质量的面部肌电信号(fEMG)打开了大门,同时保持了更自然的环境条件和更高的数据分辨率。多电极记录的信号分析也可以减少串扰,达到单肌肉分辨率。这篇前瞻性的文章提出并讨论了这一技术进步所带来的面部肌肉激活映射的新机遇。本文简要回顾了fEMG的一些主要应用,并介绍了这些应用如何从更精确、更少干扰的技术中受益。
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引用次数: 0
A systematic review of cardiac in-silico clinical trials. 心脏计算机临床试验的系统综述。
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2023-07-01 DOI: 10.1088/2516-1091/acdc71
Cristobal Rodero, Tiffany M G Baptiste, Rosie K Barrows, Hamed Keramati, Charles P Sillett, Marina Strocchi, Pablo Lamata, Steven A Niederer

Computational models of the heart are now being used to assess the effectiveness and feasibility of interventions through in-silico clinical trials (ISCTs). As the adoption and acceptance of ISCTs increases, best practices for reporting the methodology and analysing the results will emerge. Focusing in the area of cardiology, we aim to evaluate the types of ISCTs, their analysis methods and their reporting standards. To this end, we conducted a systematic review of cardiac ISCTs over the period of 1 January 2012-1 January 2022, following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). We considered cardiac ISCTs of human patient cohorts, and excluded studies of single individuals and those in which models were used to guide a procedure without comparing against a control group. We identified 36 publications that described cardiac ISCTs, with most of the studies coming from the US and the UK. In 75% of the studies, a validation step was performed, although the specific type of validation varied between the studies. ANSYS FLUENT was the most commonly used software in 19% of ISCTs. The specific software used was not reported in 14% of the studies. Unlike clinical trials, we found a lack of consistent reporting of patient demographics, with 28% of the studies not reporting them. Uncertainty quantification was limited, with sensitivity analysis performed in only 19% of the studies. In 97% of the ISCTs, no link was provided to provide easy access to the data or models used in the study. There was no consistent naming of study types with a wide range of studies that could potentially be considered ISCTs. There is a clear need for community agreement on minimal reporting standards on patient demographics, accepted standards for ISCT cohort quality control, uncertainty quantification, and increased model and data sharing.

心脏的计算模型现在被用于通过计算机临床试验(isct)评估干预措施的有效性和可行性。随着isct的采用和接受程度的提高,将出现报告方法和分析结果的最佳做法。在心脏病学领域,我们的目标是评估isct的类型,他们的分析方法和报告标准。为此,我们对2012年1月1日至2022年1月1日期间的心脏isct进行了系统回顾,遵循系统回顾和荟萃分析(PRISMA)的首选报告项目。我们考虑了人类患者队列的心脏isct,并排除了单个个体的研究和那些在没有与对照组进行比较的情况下使用模型指导手术的研究。我们确定了36篇描述心脏isct的出版物,其中大多数研究来自美国和英国。在75%的研究中,进行了验证步骤,尽管具体的验证类型在研究之间有所不同。ANSYS FLUENT是19%的isct中最常用的软件。14%的研究没有报告具体使用的软件。与临床试验不同,我们发现缺乏一致的患者人口统计报告,28%的研究没有报告。不确定度量化是有限的,只有19%的研究进行了敏感性分析。在97%的isct中,没有提供链接以方便访问研究中使用的数据或模型。研究类型没有一致的命名,广泛的研究可能被认为是isct。显然,需要就患者人口统计学的最低报告标准、ISCT队列质量控制的公认标准、不确定性量化以及增加模型和数据共享达成社区协议。
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引用次数: 1
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Progress in biomedical engineering (Bristol, England)
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