Bioelectronic medicine最新文献

{"title":"Harnessing metamaterials for efficient wireless power transfer for implantable medical devices.","authors":"Sultan Mahmud, Ali Nezaratizadeh, Alfredo Bayu Satriya, Yong-Kyu Yoon, John S Ho, Adam Khalifa","doi":"10.1186/s42234-023-00136-z","DOIUrl":"10.1186/s42234-023-00136-z","url":null,"abstract":"<p><p>Wireless power transfer (WPT) within the human body can enable long-lasting medical devices but poses notable challenges, including absorption by biological tissues and weak coupling between the transmitter (Tx) and receiver (Rx). In pursuit of more robust and efficient wireless power, various innovative strategies have emerged to optimize power transfer efficiency (PTE). One such groundbreaking approach stems from the incorporation of metamaterials, which have shown the potential to enhance the capabilities of conventional WPT systems. In this review, we delve into recent studies focusing on WPT systems that leverage metamaterials to achieve increased efficiency for implantable medical devices (IMDs) in the electromagnetic paradigm. Alongside a comparative analysis, we also outline current challenges and envision potential avenues for future advancements.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic compartmentalization of rat vagal afferent neurons to model gut-brain axis.","authors":"Gregory Girardi, Danielle Zumpano, Helen Raybould, Erkin Seker","doi":"10.1186/s42234-023-00140-3","DOIUrl":"10.1186/s42234-023-00140-3","url":null,"abstract":"<p><strong>Background: </strong>Vagal afferent neurons represent the key neurosensory branch of the gut-brain axis, which describes the bidirectional communication between the gastrointestinal system and the brain. These neurons are important for detecting and relaying sensory information from the periphery to the central nervous system to modulate feeding behavior, metabolism, and inflammation. Confounding variables complicate the process of isolating the role of the vagal afferents in mediating these physiological processes. Therefore, we developed a microfluidic model of the sensory branch of the gut-brain axis. We show that this microfluidic model successfully compartmentalizes the cell body and neurite terminals of the neurons, thereby simulates the anatomical layout of these neurons to more accurately study physiologically-relevant processes.</p><p><strong>Methods: </strong>We implemented a primary rat vagal afferent neuron culture into a microfluidic platform consisting of two concentric chambers interconnected with radial microchannels. The microfluidic platform separated cell bodies from neurite terminals of vagal afferent neurons. We then introduced physiologically-relevant gastrointestinal effector molecules at the nerve terminals and assessed their retrograde transport along the neurite or capacity to elicit an electrophysiological response using live cell calcium imaging.</p><p><strong>Results: </strong>The angle of microchannel outlets dictated the probability of neurites growing into a chamber versus tracking along chamber walls. When the neurite terminals were exposed to fluorescently-labeled cholera toxin subunit B, the proteins were taken up and retrogradely transported along the neurites over the course of 24 h. Additionally, mechanical perturbation (e.g., rinsing) of the neurite terminals significantly increased intracellular calcium concentration in the distal soma. Finally, membrane-displayed receptor for capsaicin was expressed and trafficked along newly projected neurites, as revealed by confocal microscopy.</p><p><strong>Conclusions: </strong>In this work, we developed a microfluidic device that can recapitulate the anatomical layout of vagal afferent neurons in vitro. We demonstrated two physiologically-relevant applications of the platforms: retrograde transport and electrophysiological response. We expect this tool to enable controlled studies on the role of vagal afferent neurons in the gut-brain axis.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A soft, scalable and adaptable multi-contact cuff electrode for targeted peripheral nerve modulation.","authors":"Valentina Paggi, Florian Fallegger, Ludovic Serex, Olivier Rizzo, Katia Galan, Alice Giannotti, Ivan Furfaro, Ciro Zinno, Fabio Bernini, Silvestro Micera, Stéphanie P Lacour","doi":"10.1186/s42234-023-00137-y","DOIUrl":"10.1186/s42234-023-00137-y","url":null,"abstract":"<p><strong>Background: </strong>Cuff electrodes target various nerves throughout the body, providing neuromodulation therapies for motor, sensory, or autonomic disorders. However, when using standard, thick silicone cuffs, fabricated in discrete circular sizes, complications may arise, namely cuff displacement or nerve compression, due to a poor adaptability to variable nerve shapes and sizes encountered in vivo. Improvements in cuff design, materials, closing mechanism and surgical approach are necessary to overcome these issues.</p><p><strong>Methods: </strong>In this work, we propose a microfabricated multi-channel silicone-based soft cuff electrode with a novel easy-to-implant and size-adaptable design and evaluate a number of essential features such as nerve-cuff contact, nerve compression, cuff locking stability, long-term integration and stimulation selectivity. We also compared performance to that of standard fixed-size cuffs.</p><p><strong>Results: </strong>The belt-like cuff made of 150 μm thick silicone membranes provides a stable and pressure-free conformal contact, independently of nerve size variability, combined with a straightforward implantation procedure. The adaptable design and use of soft materials lead to limited scarring and demyelination after 6-week implantation. In addition, multi-contact designs, ranging from 6 to 16 electrodes, allow for selective stimulation in models of rat and pig sciatic nerve, achieving targeted activation of up to 5 hindlimb muscles.</p><p><strong>Conclusion: </strong>These results suggest a promising alternative to classic fixed-diameter cuffs and may facilitate the adoption of soft, adaptable cuffs in clinical settings.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a standalone ear-EEG device for focal-onset seizure detection.","authors":"McGregor Joyner, Sheng-Hsiou Hsu, Stephanie Martin, Jennifer Dwyer, Denise Fay Chen, Reza Sameni, Samuel H Waters, Konstantin Borodin, Gari D Clifford, Allan I Levey, John Hixson, Daniel Winkel, Jonathan Berent","doi":"10.1186/s42234-023-00135-0","DOIUrl":"10.1186/s42234-023-00135-0","url":null,"abstract":"<p><strong>Background: </strong>Seizure detection is challenging outside the clinical environment due to the lack of comfortable, reliable, and practical long-term neurophysiological monitoring devices. We developed a novel, discreet, unobstructive in-ear sensing system that enables long-term electroencephalography (EEG) recording. This is the first study we are aware of that systematically compares the seizure detection utility of in-ear EEG with that of simultaneously recorded intracranial EEG. In addition, we present a similar comparison between simultaneously recorded in-ear EEG and scalp EEG.</p><p><strong>Methods: </strong>In this foundational research, we conducted a clinical feasibility study and validated the ability of the ear-EEG system to capture focal-onset seizures against 1255 hrs of simultaneous ear-EEG data along with scalp or intracranial EEG in 20 patients with refractory focal epilepsy (11 with scalp EEG, 8 with intracranial EEG, and 1 with both).</p><p><strong>Results: </strong>In a blinded, independent review of the ear-EEG signals, two epileptologists were able to detect 86.4% of the seizures that were subsequently identified using the clinical gold standard EEG modalities, with a false detection rate of 0.1 per day, well below what has been reported for ambulatory monitoring. The few seizures not detected on the ear-EEG signals emanated from deep within the mesial temporal lobe or extra-temporally and remained very focal, without significant propagation. Following multiple sessions of recording for a median continuous wear time of 13 hrs, patients reported a high degree of tolerance for the device, with only minor adverse events reported by the scalp EEG cohort.</p><p><strong>Conclusions: </strong>These preliminary results demonstrate the potential of using ear-EEG to enable routine collection of complementary, prolonged, and remote neurophysiological evidence, which may permit real-time detection of paroxysmal events such as seizures and epileptiform discharges. This study suggests that the ear-EEG device may assist clinicians in making an epilepsy diagnosis, assessing treatment efficacy, and optimizing medication titration.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interfering with sleep apnea.","authors":"Nigel Paul Pedersen, Raul Castillo Astorga","doi":"10.1186/s42234-023-00139-w","DOIUrl":"10.1186/s42234-023-00139-w","url":null,"abstract":"<p><p>The effects of electromagnetic interference have been hiding in plain sight for millennia and are now being applied to the non-invasive stimulation of deep tissues. In the article by Missey et al., the effect of non-invasive stimulation of the hypoglossal nerve by an interference envelope of interfering carrier waves is examined in mice and participants with sleep apnea. This stimulation is capable of activating the nerve and reducing apnea-hypopnea events. Temporally interfering electric fields have potential applications far beyond hypoglossal stimulation and may represent a revolutionary new approach to treating illness and understanding the functional organization of the nervous system.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evoked compound action potential (ECAP)-controlled closed-loop spinal cord stimulation in an experimental model of neuropathic pain in rats.","authors":"Eline M Versantvoort, Birte E Dietz, Dave Mugan, Quoc C Vuong, Saimir Luli, Ilona Obara","doi":"10.1186/s42234-023-00134-1","DOIUrl":"10.1186/s42234-023-00134-1","url":null,"abstract":"<p><strong>Background: </strong>Preclinical models of spinal cord stimulation (SCS) are lacking objective measurements to inform translationally applicable SCS parameters. The evoked compound action potential (ECAP) represents a measure of dorsal column fiber activation. This measure approximates the onset of SCS-induced sensations in humans and provides effective analgesia when used with ECAP-controlled closed-loop (CL)-SCS systems. Therefore, ECAPs may provide an objective surrogate for SCS dose in preclinical models that may support better understanding of SCS mechanisms and further translations to the clinics. This study assessed, for the first time, the feasibility of recording ECAPs and applying ECAP-controlled CL-SCS in freely behaving rats subjected to an experimental model of neuropathic pain.</p><p><strong>Methods: </strong>Adult male Sprague-Dawley rats (200-300 g) were subjected to spared nerve injury (SNI). A custom-made six-contact lead was implanted epidurally covering T11-L3, as confirmed by computed tomography or X-ray. A specially designed multi-channel system was used to record ECAPs and to apply ECAP-controlled CL-SCS for 30 min at 50 Hz 200 µs. The responses of dorsal column fibers to SCS were characterized and sensitivity towards mechanical and cold stimuli were assessed to determine analgesic effects from ECAP-controlled CL-SCS. Comparisons between SNI rats and their controls as well as between stimulation parameters were made using omnibus analysis of variance (ANOVA) tests and t-tests.</p><p><strong>Results: </strong>The recorded ECAPs showed the characteristic triphasic morphology and the ECAP amplitude (mV) increased as higher currents (mA) were applied in both SNI animals and controls (SNI SCS-ON and sham SCS-ON). Importantly, the use of ECAP-based SCS dose, implemented in ECAP-controlled CL-SCS, significantly reduced mechanical and cold hypersensitivity in SNI SCS-ON animals through the constant and controlled activation of dorsal column fibers. An analysis of conduction velocities of the evoked signals confirmed the involvement of large, myelinated fibers.</p><p><strong>Conclusions: </strong>The use of ECAP-based SCS dose implemented in ECAP-controlled CL-SCS produced analgesia in animals subjected to an experimental model of neuropathic pain. This approach may offer a better method for translating SCS parameters between species that will improve understanding of the mechanisms of SCS action to further advance future clinical applications.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10777641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond pediatrics: noninvasive spinal neuromodulation improves motor function in an adult with cerebral palsy.","authors":"Rahul Sachdeva, Kristin Girshin, Yousef Shirkhani, Parag Gad","doi":"10.1186/s42234-023-00133-2","DOIUrl":"10.1186/s42234-023-00133-2","url":null,"abstract":"<p><p>Regaining motor function in individuals with cerebral palsy (CP) has been predominantly studied in children, resulting in an underrepresentation of adults in research efforts. We tested the efficacy of noninvasive spinal neuromodulation with neurorehabilitation (Spinal Cord Innovation in Pediatrics; SCiP™ therapy). A 60-year-old CP participant underwent 8 weeks of SCiP™ therapy, resulting in significant motor recovery measured by 14.2-points increase in gross motor function measure (GMFM-88) score, ~ three times the Minimal Clinically Important Difference (MCID) of 5-points. This represented gains in kneeling, sitting, and walking functions. The improvement in GMFM-88 score was maintained above the MCID at the follow up visit (10.3 points above the baseline), twenty weeks following the last therapy session, indicating a persistent effect of the therapy. Our preliminary findings support the therapeutic promise of SCiP™ therapy for enhancing motor function in CP adults. Broader investigations are needed to establish its wider applicability.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"10 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The brain-liver cholinergic anti-inflammatory pathway and viral infections.","authors":"Samuel Martínez-Meza, Bhavya Singh, Douglas F Nixon, Nicholas Dopkins, Louie Mar A Gangcuangco","doi":"10.1186/s42234-023-00132-3","DOIUrl":"10.1186/s42234-023-00132-3","url":null,"abstract":"<p><p>Efferent cholinergic signaling is a critical and targetable source of immunoregulation. The vagus nerve (VN) is the primary source of cholinergic signaling in the body, and partially innervates hepatic functionality through the liver-brain axis. Virus-induced disruption of cholinergic signaling may promote pathogenesis in hepatotropic and neurotropic viruses. Therefore, restoring VN functionality could be a novel therapeutic strategy to alleviate pathogenic inflammation in hepatotropic and neurotropic viral infections alike. In this minireview, we discuss the physiological importance of cholinergic signaling in maintaining liver-brain axis homeostasis. Next, we explore mechanisms by which the VN is perturbed by viral infections, and how non-invasive restoration of cholinergic signaling pathways with bioelectronic medicine (BEM) might ameliorate hepatic inflammation and neuroinflammation in certain viral infections.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10731847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trigeminal nerve stimulation: a current state-of-the-art review.","authors":"Keren Powell, Kanheng Lin, Willians Tambo, Andrea Palomo Saavedra, Daniel Sciubba, Yousef Al Abed, Chunyan Li","doi":"10.1186/s42234-023-00128-z","DOIUrl":"https://doi.org/10.1186/s42234-023-00128-z","url":null,"abstract":"<p><p>Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS' success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10717521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative solutions for disease management.","authors":"Dafni Carmina, Valentina Benfenati, Claudia Simonelli, Alessia Rotolo, Paola Cardano, Nicoletta Grovale, Lorenza Mangoni di S Stefano, Tiziana de Santo, Roberto Zamboni, Vincenzo Palermo, Michele Muccini, Francesco De Seta","doi":"10.1186/s42234-023-00131-4","DOIUrl":"10.1186/s42234-023-00131-4","url":null,"abstract":"<p><p>The increasing prevalence of chronic diseases is a driver for emerging big data technologies for healthcare including digital platforms for data collection, systems for active patient engagement and education, therapy specific predictive models, optimized patient pathway models. Powerful bioelectronic medicine tools for data collection, analysis and visualization allow for joint processing of large volumes of heterogeneous data, which in turn can produce new insights about patient outcomes and alternative interpretations of clinical patterns that can lead to implementation of optimized clinical decisions and clinical patient pathway by healthcare professionals.With this perspective, we identify innovative solutions for disease management and evaluate their impact on patients, payers and society, by analyzing their impact in terms of clinical outcomes (effectiveness, safety, and quality of life) and economic outcomes (cost-effectiveness, savings, and productivity).As a result, we propose a new approach based on the main pillars of innovation in the disease management area, i.e. progressive patient care models, patient-centric approaches, bioelectronics for precise medicine, and lean management that, combined with an increase in appropriate private-public-citizen-partnership, leads towards Patient-Centric Healthcare.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"9 1","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}