Joshua J Strohl, Joseph T Gallagher, Pedro N Gómez, Joshua M Glynn, Patricio T Huerta
{"title":"Framework for automated sorting of neural spikes from Neuralynx-acquired tetrode recordings in freely-moving mice.","authors":"Joshua J Strohl, Joseph T Gallagher, Pedro N Gómez, Joshua M Glynn, Patricio T Huerta","doi":"10.1186/s42234-021-00079-3","DOIUrl":"10.1186/s42234-021-00079-3","url":null,"abstract":"<p><strong>Background: </strong>Extracellular recording represents a crucial electrophysiological technique in neuroscience for studying the activity of single neurons and neuronal populations. The electrodes capture voltage traces that, with the help of analytical tools, reveal action potentials ('spikes') as well as local field potentials. The process of spike sorting is used for the extraction of action potentials generated by individual neurons. Until recently, spike sorting was performed with manual techniques, which are laborious and unreliable due to inherent operator bias. As neuroscientists add multiple electrodes to their probes, the high-density devices can record hundreds to thousands of neurons simultaneously, making the manual spike sorting process increasingly difficult. The advent of automated spike sorting software has offered a compelling solution to this issue and, in this study, we present a simple-to-execute framework for running an automated spike sorter.</p><p><strong>Methods: </strong>Tetrode recordings of freely-moving mice are obtained from the CA1 region of the hippocampus as they navigate a linear track. Tetrode recordings are also acquired from the prelimbic cortex, a region of the medial prefrontal cortex, while the mice are tested in a T maze. All animals are implanted with custom-designed, 3D-printed microdrives that carry 16 electrodes, which are bundled in a 4-tetrode geometry.</p><p><strong>Results: </strong>We provide an overview of a framework for analyzing single-unit data in which we have concatenated the acquisition system (Cheetah, Neuralynx) with analytical software (MATLAB) and an automated spike sorting pipeline (MountainSort). We give precise instructions on how to implement the different steps of the framework, as well as explanations of our design logic. We validate this framework by comparing manually-sorted spikes against automatically-sorted spikes, using neural recordings of the hippocampus and prelimbic cortex in freely-moving mice.</p><p><strong>Conclusions: </strong>We have efficiently integrated the MountainSort spike sorter with Neuralynx-acquired neural recordings. Our framework is easy to implement and provides a high-throughput solution. We predict that within the broad field of bioelectronic medicine, those teams that incorporate high-density neural recording devices to their armamentarium might find our framework quite valuable as they expand their analytical footprint.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39759922","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":"Motor improvements enabled by spinal cord stimulation combined with physical training after spinal cord injury: review of experimental evidence in animals and humans.","authors":"Ismael Seáñez, Marco Capogrosso","doi":"10.1186/s42234-021-00077-5","DOIUrl":"https://doi.org/10.1186/s42234-021-00077-5","url":null,"abstract":"<p><p>Electrical spinal cord stimulation (SCS) has been gaining momentum as a potential therapy for motor paralysis in consequence of spinal cord injury (SCI). Specifically, recent studies combining SCS with activity-based training have reported unprecedented improvements in motor function in people with chronic SCI that persist even without stimulation. In this work, we first provide an overview of the critical scientific advancements that have led to the current uses of SCS in neurorehabilitation: e.g. the understanding that SCS activates dormant spinal circuits below the lesion by recruiting large-to-medium diameter sensory afferents within the posterior roots. We discuss how this led to the standardization of implant position which resulted in consistent observations by independent clinical studies that SCS in combination with physical training promotes improvements in motor performance and neurorecovery. While all reported participants were able to move previously paralyzed limbs from day 1, recovery of more complex motor functions was gradual, and the timeframe for first observations was proportional to the task complexity. Interestingly, individuals with SCI classified as AIS B and C regained motor function in paralyzed joints even without stimulation, but not individuals with motor and sensory complete SCI (AIS A). Experiments in animal models of SCI investigating the potential mechanisms underpinning this neurorecovery suggest a synaptic reorganization of cortico-reticulo-spinal circuits that correlate with improvements in voluntary motor control. Future experiments in humans and animal models of paralysis will be critical to understand the potential and limits for functional improvements in people with different types, levels, timeframes, and severities of SCI.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39563782","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}
Steven Schulte, Manuela Gries, Anne Christmann, Karl-Herbert Schäfer
{"title":"Using multielectrode arrays to investigate neurodegenerative effects of the amyloid-beta peptide.","authors":"Steven Schulte, Manuela Gries, Anne Christmann, Karl-Herbert Schäfer","doi":"10.1186/s42234-021-00078-4","DOIUrl":"10.1186/s42234-021-00078-4","url":null,"abstract":"<p><strong>Background: </strong>Multielectrode arrays are widely used to analyze the effects of potentially toxic compounds, as well as to evaluate neuroprotective agents upon the activity of neural networks in short- and long-term cultures. Multielectrode arrays provide a way of non-destructive analysis of spontaneous and evoked neuronal activity, allowing to model neurodegenerative diseases in vitro. Here, we provide an overview on how these devices are currently used in research on the amyloid-β peptide and its role in Alzheimer's disease, the most common neurodegenerative disorder.</p><p><strong>Main body: </strong>Most of the studies analysed here indicate fast responses of neuronal cultures towards aggregated forms of amyloid-β, leading to increases of spike frequency and impairments of long-term potentiation. This in turn suggests that this peptide might play a crucial role in causing the typical neuronal dysfunction observed in patients with Alzheimer's disease.</p><p><strong>Conclusions: </strong>Although the number of studies using multielectrode arrays to examine the effect of the amyloid-β peptide onto neural cultures or whole compartments is currently limited, they still show how this technique can be used to not only investigate the interneuronal communication in neural networks, but also making it possible to examine the effects onto synaptic currents. This makes multielectrode arrays a powerful tool in future research on neurodegenerative diseases.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39838119","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}
Santosh Chandrasekaran, Matthew Fifer, Stephan Bickel, Luke Osborn, Jose Herrero, Breanne Christie, Junqian Xu, Rory K J Murphy, Sandeep Singh, Matthew F Glasser, Jennifer L Collinger, Robert Gaunt, Ashesh D Mehta, Andrew Schwartz, Chad E Bouton
{"title":"Historical perspectives, challenges, and future directions of implantable brain-computer interfaces for sensorimotor applications.","authors":"Santosh Chandrasekaran, Matthew Fifer, Stephan Bickel, Luke Osborn, Jose Herrero, Breanne Christie, Junqian Xu, Rory K J Murphy, Sandeep Singh, Matthew F Glasser, Jennifer L Collinger, Robert Gaunt, Ashesh D Mehta, Andrew Schwartz, Chad E Bouton","doi":"10.1186/s42234-021-00076-6","DOIUrl":"10.1186/s42234-021-00076-6","url":null,"abstract":"<p><p>Almost 100 years ago experiments involving electrically stimulating and recording from the brain and the body launched new discoveries and debates on how electricity, movement, and thoughts are related. Decades later the development of brain-computer interface technology began, which now targets a wide range of applications. Potential uses include augmentative communication for locked-in patients and restoring sensorimotor function in those who are battling disease or have suffered traumatic injury. Technical and surgical challenges still surround the development of brain-computer technology, however, before it can be widely deployed. In this review we explore these challenges, historical perspectives, and the remarkable achievements of clinical study participants who have bravely forged new paths for future beneficiaries.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2021-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39437486","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}
Shubham Debnath, Todd J Levy, Mayer Bellehsen, Rebecca M Schwartz, Douglas P Barnaby, Stavros Zanos, Bruce T Volpe, Theodoros P Zanos
{"title":"A method to quantify autonomic nervous system function in healthy, able-bodied individuals.","authors":"Shubham Debnath, Todd J Levy, Mayer Bellehsen, Rebecca M Schwartz, Douglas P Barnaby, Stavros Zanos, Bruce T Volpe, Theodoros P Zanos","doi":"10.1186/s42234-021-00075-7","DOIUrl":"10.1186/s42234-021-00075-7","url":null,"abstract":"<p><strong>Background: </strong>The autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses.</p><p><strong>Methods: </strong>Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population.</p><p><strong>Results: </strong>A significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions.</p><p><strong>Conclusions: </strong>These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.</p><p><strong>Trial registration: </strong>This study registered with Clinicaltrials.gov , identifier NCT04100486 . Registered September 24, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04100486 .</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39370254","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}
Andrew Perley, Mehrdad Roustaei, Marcelo Aguilar-Rivera, David C Kunkel, Tzung K Hsiai, Todd P Coleman, Parinaz Abiri
{"title":"Miniaturized wireless gastric pacing via inductive power transfer with non-invasive monitoring using cutaneous Electrogastrography.","authors":"Andrew Perley, Mehrdad Roustaei, Marcelo Aguilar-Rivera, David C Kunkel, Tzung K Hsiai, Todd P Coleman, Parinaz Abiri","doi":"10.1186/s42234-021-00074-8","DOIUrl":"https://doi.org/10.1186/s42234-021-00074-8","url":null,"abstract":"<p><strong>Background: </strong>Gastroparesis is a debilitating disease that is often refractory to pharmacotherapy. While gastric electrical stimulation has been studied as a potential treatment, current devices are limited by surgical complications and an incomplete understanding of the mechanism by which electrical stimulation affects physiology.</p><p><strong>Methods: </strong>A leadless inductively-powered pacemaker was implanted on the gastric serosa in an anesthetized pig. Wireless pacing was performed at transmitter-to-receiver distances up to 20 mm, frequency of 0.05 Hz, and pulse width of 400 ms. Electrogastrogram (EGG) recordings using cutaneous and serosal electrode arrays were analyzed to compute spectral and spatial statistical parameters associated with the slow wave.</p><p><strong>Results: </strong>Our data demonstrated evident change in EGG signal patterns upon initiation of pacing. A buffer period was noted before a pattern of entrainment appeared with consistent and low variability in slow wave direction. A spectral power increase in the EGG frequency band during entrainment also suggested that pacing increased strength of the slow wave.</p><p><strong>Conclusion: </strong>Our preliminary in vivo study using wireless pacing and concurrent EGG recording established the foundations for a minimally invasive approach to understand and optimize the effect of pacing on gastric motor activity as a means to treat conditions of gastric dysmotility.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2021-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39337678","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":"Low frequency conduction block: a promising new technique to advance bioelectronic medicines.","authors":"Silvia V Conde","doi":"10.1186/s42234-021-00073-9","DOIUrl":"https://doi.org/10.1186/s42234-021-00073-9","url":null,"abstract":"<p><p>Nerve conduction block is an appealing way to selective target the nervous system for treating pathological conditions. Several modalities were described in the past, with the kilohertz frequency stimulation generating an enormous interest and tested successfully in clinical settings. Some shortcomings associated with different modalities of nerve blocking can limit its clinical use, as the \"onset response\", the high demand of energy supply, among others. A recent study by Muzquiz and colleagues describes the efficacy and reversibility of low frequency alternating currents in blocking the cervical vagus in the pig, in the absence of an onset effect and apparent lack of neuronal damage.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42234-021-00073-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39218747","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":"Closed-loop neuromodulation will increase the utility of mouse models in Bioelectronic Medicine.","authors":"Timir Datta-Chaudhuri","doi":"10.1186/s42234-021-00071-x","DOIUrl":"https://doi.org/10.1186/s42234-021-00071-x","url":null,"abstract":"<p><p>Mouse models have been of tremendous benefit to medical science for the better part of a century, yet bioelectronic medicine research using mice has been limited to mostly acute studies because of a lack of tools for chronic stimulation and sensing. A wireless neuromodulation platform small enough for implantation in mice will significantly increase the utility of mouse models in bioelectronic medicine. This perspective examines the necessary functionality of such a system and the technical challenges needed to be overcome for its development. Recent progress is examined and the outlook for the future of implantable devices for mice is discussed.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42234-021-00071-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39125083","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}
Maria Ivette Muzquiz, Lindsay Richardson, Christian Vetter, Macallister Smolik, Awadh Alhawwash, Adam Goodwill, Rizwan Bashirullah, Michael Carr, Ken Yoshida
{"title":"In-vivo application of low frequency alternating currents on porcine cervical vagus nerve evokes reversible nerve conduction block.","authors":"Maria Ivette Muzquiz, Lindsay Richardson, Christian Vetter, Macallister Smolik, Awadh Alhawwash, Adam Goodwill, Rizwan Bashirullah, Michael Carr, Ken Yoshida","doi":"10.1186/s42234-021-00072-w","DOIUrl":"https://doi.org/10.1186/s42234-021-00072-w","url":null,"abstract":"<p><strong>Background: </strong>This paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5).</p><p><strong>Methods: </strong>Two bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone.</p><p><strong>Results: </strong>LFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mA<sub>p</sub> (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP.</p><p><strong>Conclusion: </strong>These novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"7 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42234-021-00072-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9938736","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":"Overview of therapeutic applications of non-invasive vagus nerve stimulation: a motivation for novel treatments for systemic lupus erythematosus.","authors":"Charrise M Ramkissoon, Amparo Güemes, Josep Vehi","doi":"10.1186/s42234-021-00069-5","DOIUrl":"10.1186/s42234-021-00069-5","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder that commonly affects the skin, joints, kidneys, and central nervous system. Although great progress has been made over the years, patients still experience unfavorable secondary effects from medications, increased economic burden, and higher mortality rates compared to the general population. To alleviate these current problems, non-invasive, non-pharmacological interventions are being increasingly investigated. One such intervention is non-invasive vagus nerve stimulation, which promotes the upregulation of the cholinergic anti-inflammatory pathway that reduces the activation and production of pro-inflammatory cytokines and reactive oxygen species, culpable processes in autoimmune diseases such as SLE. This review first provides a background on the important contribution of the autonomic nervous system to the pathogenesis of SLE. The gross and structural anatomy of the vagus nerve and its contribution to the inflammatory response are described afterwards to provide a general understanding of the impact of stimulating the vagus nerve. Finally, an overview of current clinical applications of invasive and non-invasive vagus nerve stimulation for a variety of diseases, including those with similar symptoms to the ones in SLE, is presented and discussed. Overall, the review presents neuromodulation as a promising strategy to alleviate SLE symptoms and potentially reverse the disease.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":" ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2021-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s42234-021-00069-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38944972","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}