Annual Review of Biomedical Engineering最新文献

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Low-Field, Low-Cost, Point-of-Care Magnetic Resonance Imaging. 低视野、低成本、护理点磁共振成像。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110122-022903
Anja Samardzija, Kartiga Selvaganesan, Horace Z Zhang, Heng Sun, Chenhao Sun, Yonghyun Ha, Gigi Galiana, R Todd Constable
{"title":"Low-Field, Low-Cost, Point-of-Care Magnetic Resonance Imaging.","authors":"Anja Samardzija, Kartiga Selvaganesan, Horace Z Zhang, Heng Sun, Chenhao Sun, Yonghyun Ha, Gigi Galiana, R Todd Constable","doi":"10.1146/annurev-bioeng-110122-022903","DOIUrl":"10.1146/annurev-bioeng-110122-022903","url":null,"abstract":"<p><p>Low-field magnetic resonance imaging (MRI) has recently experienced a renaissance that is largely attributable to the numerous technological advancements made in MRI, including optimized pulse sequences, parallel receive and compressed sensing, improved calibrations and reconstruction algorithms, and the adoption of machine learning for image postprocessing. This new attention on low-field MRI originates from a lack of accessibility to traditional MRI and the need for affordable imaging. Low-field MRI provides a viable option due to its lack of reliance on radio-frequency shielding rooms, expensive liquid helium, and cryogen quench pipes. Moreover, its relatively small size and weight allow for easy and affordable installation in most settings. Rather than replacing conventional MRI, low-field MRI will provide new opportunities for imaging both in developing and developed countries. This article discusses the history of low-field MRI, low-field MRI hardware and software, current devices on the market, advantages and disadvantages, and low-field MRI's global potential.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"67-91"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liquid Biopsy Based on Cell-Free DNA and RNA. 基于无细胞 DNA 和 RNA 的液体活检技术
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110222-111259
Conor Loy, Lauren Ahmann, Iwijn De Vlaminck, Wei Gu
{"title":"Liquid Biopsy Based on Cell-Free DNA and RNA.","authors":"Conor Loy, Lauren Ahmann, Iwijn De Vlaminck, Wei Gu","doi":"10.1146/annurev-bioeng-110222-111259","DOIUrl":"10.1146/annurev-bioeng-110222-111259","url":null,"abstract":"<p><p>This review delves into the rapidly evolving landscape of liquid biopsy technologies based on cell-free DNA (cfDNA) and cell-free RNA (cfRNA) and their increasingly prominent role in precision medicine. With the advent of high-throughput DNA sequencing, the use of cfDNA and cfRNA has revolutionized noninvasive clinical testing. Here, we explore the physical characteristics of cfDNA and cfRNA, present an overview of the essential engineering tools used by the field, and highlight clinical applications, including noninvasive prenatal testing, cancer testing, organ transplantation surveillance, and infectious disease testing. Finally, we discuss emerging technologies and the broadening scope of liquid biopsies to new areas of diagnostic medicine.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"169-195"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues. 透明质酸的机械生物学:连接肌肉骨骼组织的生物力学和生物活性。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-073123-120541
Deva D Chan, Farshid Guilak, Robert L Sah, Sarah Calve
{"title":"Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues.","authors":"Deva D Chan, Farshid Guilak, Robert L Sah, Sarah Calve","doi":"10.1146/annurev-bioeng-073123-120541","DOIUrl":"10.1146/annurev-bioeng-073123-120541","url":null,"abstract":"<p><p>Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"25-47"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139081097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insertable Biosensors: Combining Implanted Sensing Materials with Wearable Monitors. 可植入生物传感器:将植入式传感材料与可穿戴式监测器相结合。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110222-101045
David Chimene, Kirstie M K Queener, Brian S Ko, Mike McShane, Michael Daniele
{"title":"Insertable Biosensors: Combining Implanted Sensing Materials with Wearable Monitors.","authors":"David Chimene, Kirstie M K Queener, Brian S Ko, Mike McShane, Michael Daniele","doi":"10.1146/annurev-bioeng-110222-101045","DOIUrl":"10.1146/annurev-bioeng-110222-101045","url":null,"abstract":"<p><p>Insertable biosensor systems are medical diagnostic devices with two primary components: an implantable biosensor within the body and a wearable monitor that can remotely interrogate the biosensor from outside the body. Because the biosensor does not require a physical connection to the electronic monitor, insertable biosensor systems promise improved patient comfort, reduced inflammation and infection risk, and extended operational lifetimes relative to established percutaneous biosensor systems. However, the lack of physical connection also presents technical challenges that have necessitated new innovations in developing sensing chemistries, transduction methods, and communication modalities. In this review, we discuss the key developments that have made insertables a promising option for longitudinal biometric monitoring and highlight the essential needs and existing development challenges to realizing the next generation of insertables for extended-use diagnostic and prognostic devices.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"197-221"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR/Cas Technology: The Unique Synthetic Biology Genome-Editing Tool Shifting the Paradigm in Viral Diagnostics, Defense, and Therapeutics. CRISPR/Cas 技术:独特的合成生物学基因组编辑工具,改变了病毒诊断、防御和治疗的范式。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-081723-013033
Lang Zhou, Aleksandr L Simonian
{"title":"CRISPR/Cas Technology: The Unique Synthetic Biology Genome-Editing Tool Shifting the Paradigm in Viral Diagnostics, Defense, and Therapeutics.","authors":"Lang Zhou, Aleksandr L Simonian","doi":"10.1146/annurev-bioeng-081723-013033","DOIUrl":"10.1146/annurev-bioeng-081723-013033","url":null,"abstract":"<p><p>The emergence of the COVID-19 pandemic has starkly exposed our significantly limited ability to promptly identify and respond to emergent biological threats. Consequently, there is an urgent need to advance biotechnological methods for addressing both known and unforeseen biological hazards. Recently, the CRISPR/Cas system has revolutionized genetic engineering, enabling precise and efficient synthetic biology applications. Therefore, this review aims to provide a comprehensive introduction to the fundamental principles underlying the CRISPR/Cas system and assess the advantages and limitations of various CRISPR/Cas-based techniques applicable to the detection of, defense against, and treatment of viral infections. These techniques include viral diagnostics, the development of antiviral vaccines, B cell engineering for antibody production, viral activation/interference, and epigenetic modifications. Furthermore, this review delves into the challenges and bioethical considerations associated with use of the CRISPR/Cas system. With the continuous evolution of technology, the CRISPR/Cas system holds considerable promise for addressing both existing and unforeseen biological threats.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"247-272"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound. 组织切削术:利用超声波进行机械组织消融的方法。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-073123-022334
Zhen Xu, Tatiana D Khokhlova, Clifford S Cho, Vera A Khokhlova
{"title":"Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound.","authors":"Zhen Xu, Tatiana D Khokhlova, Clifford S Cho, Vera A Khokhlova","doi":"10.1146/annurev-bioeng-073123-022334","DOIUrl":"10.1146/annurev-bioeng-073123-022334","url":null,"abstract":"<p><p>Histotripsy is a relatively new therapeutic ultrasound technology to mechanically liquefy tissue into subcellular debris using high-amplitude focused ultrasound pulses. In contrast to conventional high-intensity focused ultrasound thermal therapy, histotripsy has specific clinical advantages: the capacity for real-time monitoring using ultrasound imaging, diminished heat sink effects resulting in lesions with sharp margins, effective removal of the treated tissue, a tissue-selective feature to preserve crucial structures, and immunostimulation. The technology is being evaluated in small and large animal models for treating cancer, thrombosis, hematomas, abscesses, and biofilms; enhancing tumor-specific immune response; and neurological applications. Histotripsy has been recently approved by the US Food and Drug Administration to treat liver tumors, with clinical trials undertaken for benign prostatic hyperplasia and renal tumors. This review outlines the physical principles of various types of histotripsy; presents major parameters of the technology and corresponding hardware and software, imaging methods, and bioeffects; and discusses the most promising preclinical and clinical applications.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"141-167"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct Electron Transfer-Type Oxidoreductases for Biomedical Applications. 生物医学应用中的直接电子转移型氧化还原酶。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110222-101926
Keisei Sowa, Junko Okuda-Shimazaki, Eole Fukawa, Koji Sode
{"title":"Direct Electron Transfer-Type Oxidoreductases for Biomedical Applications.","authors":"Keisei Sowa, Junko Okuda-Shimazaki, Eole Fukawa, Koji Sode","doi":"10.1146/annurev-bioeng-110222-101926","DOIUrl":"10.1146/annurev-bioeng-110222-101926","url":null,"abstract":"<p><p>Among the various types of enzyme-based biosensors, sensors utilizing enzymes capable of direct electron transfer (DET) are recognized as the most ideal. However, only a limited number of redox enzymes are capable of DET with electrodes, that is, dehydrogenases harboring a subunit or domain that functions specifically to accept electrons from the redox cofactor of the catalytic site and transfer the electrons to the external electron acceptor. Such subunits or domains act as built-in mediators for electron transfer between enzymes and electrodes; consequently, such enzymes enable direct electron transfer to electrodes and are designated as DET-type enzymes. DET-type enzymes fall into several categories, including redox cofactors of catalytic reactions, built-in mediators for DET with electrodes and by their protein hierarchic structures, DET-type oxidoreductases with oligomeric structures harboring electron transfer subunits, and monomeric DET-type oxidoreductases harboring electron transfer domains. In this review, we cover the science of DET-type oxidoreductases and their biomedical applications. First, we introduce the structural biology and current understanding of DET-type enzyme reactions. Next, we describe recent technological developments based on DET-type enzymes for biomedical applications, such as biosensors and biochemical energy harvesting for self-powered medical devices. Finally, after discussing how to further engineer and create DET-type enzymes, we address the future prospects for DET-type enzymes in biomedical engineering.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"357-382"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Kidney Disease Modeling with Organoids and Organs-on-Chips. 利用有机体和芯片器官建立肾脏疾病模型
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-072623-044010
Samira Musah, Rohan Bhattacharya, Jonathan Himmelfarb
{"title":"Kidney Disease Modeling with Organoids and Organs-on-Chips.","authors":"Samira Musah, Rohan Bhattacharya, Jonathan Himmelfarb","doi":"10.1146/annurev-bioeng-072623-044010","DOIUrl":"10.1146/annurev-bioeng-072623-044010","url":null,"abstract":"<p><p>Kidney disease is a global health crisis affecting more than 850 million people worldwide. In the United States, annual Medicare expenditures for kidney disease and organ failure exceed $81 billion. Efforts to develop targeted therapeutics are limited by a poor understanding of the molecular mechanisms underlying human kidney disease onset and progression. Additionally, 90% of drug candidates fail in human clinical trials, often due to toxicity and efficacy not accurately predicted in animal models. The advent of ex vivo kidney models, such as those engineered from induced pluripotent stem (iPS) cells and organ-on-a-chip (organ-chip) systems, has garnered considerable interest owing to their ability to more accurately model tissue development and patient-specific responses and drug toxicity. This review describes recent advances in developing kidney organoids and organ-chips by harnessing iPS cell biology to model human-specific kidney functions and disease states. We also discuss challenges that must be overcome to realize the potential of organoids and organ-chips as dynamic and functional conduits of the human kidney. Achieving these technological advances could revolutionize personalized medicine applications and therapeutic discovery for kidney disease.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"383-414"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets. 肺部气溶胶给药的最新发展:新技术、新载体和新目标。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1146/annurev-bioeng-110122-010848
Ian R Woodward, Catherine A Fromen
{"title":"Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets.","authors":"Ian R Woodward, Catherine A Fromen","doi":"10.1146/annurev-bioeng-110122-010848","DOIUrl":"10.1146/annurev-bioeng-110122-010848","url":null,"abstract":"<p><p>There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":" ","pages":"307-330"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning. 电子皮肤:与机器学习融合的机遇与挑战。
IF 12.8 1区 工程技术
Annual Review of Biomedical Engineering Pub Date : 2024-07-01 DOI: 10.1146/annurev-bioeng-103122-032652
Ja Hoon Koo, Young Joong Lee, Hye Jin Kim, Wojciech Matusik, Dae-Hyeong Kim, Hyoyoung Jeong
{"title":"Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning.","authors":"Ja Hoon Koo, Young Joong Lee, Hye Jin Kim, Wojciech Matusik, Dae-Hyeong Kim, Hyoyoung Jeong","doi":"10.1146/annurev-bioeng-103122-032652","DOIUrl":"https://doi.org/10.1146/annurev-bioeng-103122-032652","url":null,"abstract":"<p><p>Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":"26 1","pages":"331-355"},"PeriodicalIF":12.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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