The Japanese journal of physiology最新文献

{"title":"Measuring blood flow through intrapulmonary and intracardiac shunts: a technical labyrinth","authors":"G. Foster","doi":"10.1113/JP278820","DOIUrl":"https://doi.org/10.1113/JP278820","url":null,"abstract":"Intracardiac and intrapulmonary pathways permitting the right-to-left shunting of venous blood can impair pulmonary gas exchange efficiency and provide passageways for the arterialization of venous blood clots. Intrapulmonary arteriovenous anastomoses (IPAVAs) are recruited with increasing exercise intensity, acute hypoxia, and when cardiac output is increased by physiological or pharmacological stress. Whether IPAVA recruitment is sufficient in magnitude to impair pulmonary gas exchange efficiency has been a matter of great debate. As with most fields of research, settling this debate probably requires the development of novel methodology. In this case, methodology is needed to permit the accurate measurement of blood flow and gas exchange through shunt pathways that may be susceptible to pre-capillary gas exchange. This is a void remaining to be filled; yet, several tools have been used separately to approximate blood flow through IPAVAs or gas exchange deficits due to shunt. Measuring blood flow through either pathway is technically challenging and typically relies on the lung’s ability to filter blood. It is reasoned that if particles larger in diameter than the pulmonary capillaries are injected into a peripheral vein and subsequently observed in the systemic arterial circulation, they must have travelled by way of cardiac or pulmonary shunt. In animal models, solid 25-μm-diameter microspheres can be injected into a peripheral vein and physically collected in the arterial circulation. Anatomical shunt fraction can be calculated using the fraction of microspheres collected and measures of cardiac output. In humans, shunt fraction can be assessed by injecting radiolabelled macroaggregates and using nuclear medicine to count the particles that have bypassed the lung. Agitated saline contrast echocardiography, another approach, uses a mixture of small air bubbles injected into a peripheral vein; detection of saline contrast in the left ventricle is a sure sign of intracardiac or intrapulmonary shunt. Saline contrast is more feasible, and, therefore, frequently used in humans, but it provides little detail with respect to the magnitude of shunted blood owing to methodological limitations (Hackett et al. 2016; Boulet et al. 2017). Finally, the multiple inert gas elimination technique (MIGET) provides an assessment of gas exchange through the infusion of six inert gases of varying blood solubilities. Measurements of gas retained in the blood and excreted from the lung are mathematically modelled to approximate the lung’s ventilation– perfusion distribution, including an estimated shunt fraction. MIGET is a highly complex technique successfully used by just a few worldwide. In this issue of The Journal of Physiology, Stickland et al (2019) conducted a highly technical study involving the combination of three techniques for measuring intracardiac/intrapulmonary shunt in anaesthetized canines. Measurements were made at rest, with dopamine and dobutami","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76653949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New molecular motif contributes to NKCC2 trafficking","authors":"Keyona N King-Medina, Cesar A Romero","doi":"10.1113/JP278896","DOIUrl":"https://doi.org/10.1113/JP278896","url":null,"abstract":"One of the most important functions of the kidney is the formation of urine and the maintenance of electrolyte and water homeostasis. The Na+–K+–2Cl− cotransporter (NKCC2) is a major contributor to this process by actively reabsorbing Na+, K+ and Cl− in the kidney’s loop of Henle. The properties of this transporter are the subject of a recent article in The Journal of Physiology by Marcoux et al. (2019) in which they report that variants of this protein alter trafficking of NKCC2, which ultimately influences the reabsorption of sodium chloride (NaCl) along the thick ascending limb of the loop of Henle (TAL). The TAL is one segment of the nephron and is of particular interest since approximately 25% of the Na+ in the glomerular filtrate is reabsorbed from it back into the circulation (Castrop & Schnermann, 2008; Ares et al. 2011; Marcoux et al. 2019). The magnitude of the reabsorption implies that this segment (and NKCC2) is important in the control of blood pressure and total body sodium homeostasis. In humans, NKCC2 is the major determinant of ion movement from the lumen of the TAL, across the tubular epithelium and back into the blood. NKCC2 is a membrane protein that has 12 transmembrane (TM) domains and a large intracellular loop near the middle of the molecule, a structure that is similar to other related membrane ion transporters","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88068977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From atoms to physiology: what it takes to really understand inflammasomes","authors":"F. Schmidt","doi":"10.1113/JP277027","DOIUrl":"https://doi.org/10.1113/JP277027","url":null,"abstract":"Rapid inflammatory responses to cytosolic threats are mediated by inflammasomes – large macromolecular signalling complexes that control the activation of the pro‐inflammatory cytokines interleukin (IL)‐1β and IL‐18, as well as cell death by pyroptosis. Different inflammasome sensors are activated by diverse direct and indirect signals, and subsequently nucleate the polymerization of the adaptor molecule ASC to form signalling platforms macroscopically observed as ASC specks. Caspase‐1 is autocatalytically activated at these sites and subsequently matures pro‐inflammatory cytokines and the pore‐forming effector molecule gasdermin D. While most molecules and basic assembly principles have been deduced from reductionist experimental systems, we still lack fundamental information on the structure and regulation of these complexes in their physiological environment and in the interplay with other signalling pathways. In this review, novel experimental approaches are proposed, including some that rely on nanobodies and single domain antibodies, to understand inflammasome assembly and regulation in the context of the relevant tissues or cells.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80089007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The organization of the sympathetic nervous system: shining new light on historic views","authors":"A. Incognito, N. Jendzjowsky","doi":"10.1113/JP278898","DOIUrl":"https://doi.org/10.1113/JP278898","url":null,"abstract":"The organization and spatial distribution of neurons within the sympathetic nervous system (SNS) have been long-standing questions in autonomic neuroscience, particularly concerning the functional innervation of target organs. First understood as an ‘alarm reaction’ system turned on en masse, advancements in nerve recording techniques have revealed sympathetic outflow to be differentially controlled to distinct functional subunits within (DiBona 2000; Incognito et al. 2019) and between (Rundqvist et al. 1997) organ systems. Our modern understanding of sympathetic control is now regionand function-specific, governed by an intricate topography within central autonomic nuclei (e.g. rostral ventrolateral medulla; RVLM). Despite intensive efforts to elucidate the regulation of sympathetic outflow, a consensus amongst investigators regarding how topographic arrangements mediate unique activation patterns remains to be reached. Expanding the organizational framework of the SNS is crucial for understanding pathophysiological manifestations. Specifically, cardiovascular disease states present with hallmark sympathetic overactivation, predictive of disease severity (Rundqvist et al. 1997), and with characteristic region-specific alterations in sympathetic outflow to morphologically distinct target organs (e.g. heart, kidney, muscle; Rundqvist et al. 1997). Thus, investigating how the central autonomic circuitry mediates sympathoexcitatory patterns may elucidate cardiovascular (or other) disease mechanisms of neurogenic origin. In a recent article in The Journal of Physiology, Farmer & colleagues (2019) used viral vector tracing and optogenetic manipulation, in vivo, of spinally projecting RVLM neurons to test if these neurons possess the anatomical chassis and functional capacity to elicit sympathoexcitation to regionally and morphologically distinct target organs. The primary objectives were to (1) identify RVLM neurons synapsing at both rostral and caudal thoracic spine regions (i.e. axon collaterals at T2 and T10 spinal segments) and (2) identify if selective stimulation of RVLM neurons with known projections to the caudal thoracic spine (i.e. T12) elicits parallel activation of post-ganglionic nerves in regionally (i.e. rostral thoracic spine) and/or morphologically (i.e. non-vascular) distinct target organs. The authors suggest that evidence of RVLM neurons with functioning axon collaterals would revive older views of generalized/global SNS activation properties, adding an intriguing supplement to the well-established modern view of differential control. Using healthy Sprague–Dawley rats, the first objective was to define the anatomical organization of RVLM projections using retrograde viral tracing. Investigators performed bilateral pressure injections of recombinant herpes simplex retrograde viral vectors into the interomediolateral column (IML) at T2 and T10. Differences in fluorescent tags enabled neurons projecting from the two sites of injection","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85192681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving beyond an empiric trial to using combined physiology and anatomy to predict success of oral appliances in obstructive sleep apnoea","authors":"D. Rapoport","doi":"10.1113/JP278922","DOIUrl":"https://doi.org/10.1113/JP278922","url":null,"abstract":"Both diagnosis and severity of obstructive sleep apnoea (OSA) have traditionally been assessed through the apnoea–hypopnoea index, a simple count of how often obstruction occurs. However, it is now widely accepted that this metric performs poorly in predicting the success of various non-continuous positive airway pressure (CPAP) therapies; the rate of obstructive events appears to be insensitive to the cause(s) of obstruction in a particular patient. This failure has led several groups to propose that an interaction of multiple pathophysiological factors underlie OSA and that specific therapies may work best in a subset of patients. The ‘holy grail’ has been to define such subsets using this ‘phenotypic’ approach. The problem is exemplified by response to oral appliances, as there is a substantial failure rate in unselected patients. As the time to titration is often prolonged and cost of an empiric therapeutic trial is non-trivial because of needing multiple titration visits and sleep studies, it would be advantageous to be able to select patients with a higher than average success rate. The simplest, but so far unsuccessful, approach to estimating the chance of success has been to use clinical, polysomnographic (PSG) and/or anthropomorphic measures of the patient at baseline. This assumes that anatomy drives OSA and that a relatively linear relation exists between external features, e.g. body mass index, neck size and awake visual assessment of the upper airway, and the causes of obstruction. The lack of success of these predictions in most published trials supports a competing assumption that sleep, airway mechanics and neural reflexes are as important as anatomy, and that their relative contribution is not evident without explicit testing. In this issue of The Journal of Physiology, Marques and colleagues test one such approach (Marques et al. 2019). Previous evidence, quoted by the authors, suggests that tongue position and measurement of collapsibility of the airway may individually modestly predict success of oral appliances, but their combined value has not been explored. In recent years, research techniques have been developed to assess the ‘phenotype’ of a given patient’s OSA. This is variably defined, and a recent trend is to focus on combinations of physiological ‘traits’ to define such a ‘phenotype’. Because the tools to measure the traits that contribute to the pathophysiology of obstruction require methodologies that are difficult and not suited to the clinical PSG environment, surrogates of the major components (anatomy, airway collapsibility or Pcrit, upper airway responsiveness and loop gain) are also being developed and tested for their ability to predict clinical outcomes. In their study Marques and colleagues test the utility of tongue position and Pcrit individually to predict the outcome of oral appliance therapy using state of the art techniques (sleep endoscopy and determination of Pcrit using CPAP drops). More importantl","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85800575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring","authors":"M. Badran, Bisher Abu Yassin, David T. S. Lin, M. Kobor, N. Ayas, I. Laher","doi":"10.1113/JP277936","DOIUrl":"https://doi.org/10.1113/JP277936","url":null,"abstract":"Obstructive sleep apnoea (OSA) is characterized by intermittent hypoxia, which causes oxidative stress and inflammation and increases the risk of cardiovascular disease. OSA during pregnancy causes adverse maternal and fetal outcomes. The effects of pre‐existing OSA in pregnant women on cardiometabolic outcomes in the offspring are unknown. We evaluated basic metabolic parameters, as well as aortic vascular and perivascular adipose tissue (PVAT) function in response to adiponectin, and examined DNA methylation of adiponectin gene promoter in PVAT in 16‐week‐old adult offspring exposed to gestational intermittent hypoxia (GIH). GIH decreased body weights at week 1 in both male and female offspring, and caused subsequent increases in body weight and food consumption in male offspring only. Adult female offspring had normal levels of lipids, glucose and insulin, with no endothelial dysfunction. Adult male offspring exhibited dyslipidaemia, insulin resistance and hyperleptinaemia. Decreased endothelial‐dependent vasodilatation, loss of anti‐contractile activity of PVAT and low circulating PVAT adiponectin levels, as well as increased pro‐inflammatory gene expression and DNA methylation of adiponectin gene promoter, occurred in adult male offspring. Our results suggest that male offspring of women with OSA could be at risk of developing cardiometabolic disease during adulthood.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"215 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74164130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproducibility and data presentation","authors":"I. Forsythe, Sally Howells, K. Barrett","doi":"10.1113/JP277519","DOIUrl":"https://doi.org/10.1113/JP277519","url":null,"abstract":"These are interesting times! We are participating in a revolution of biological knowledge and in the manipulation of medical phenomena. But accompanying these scientific developments, there is also a realization that the pace of change and the pressure to publish may undermine scientific rigour, prompting increased scrutiny and the challenge to find ways to improve reproducibility in scientific data and publication. [Opening paragraph]","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"252 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75840962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty vessels shed tonnes on programmed cardiovascular risk","authors":"D. Giussani","doi":"10.1113/JP278732","DOIUrl":"https://doi.org/10.1113/JP278732","url":null,"abstract":"Cardiovascular disease remains one of the greatest killers in the world today, causing more than a quarter of all deaths in the UK (https://www.bhf.org.uk/for-professionals/ press-centre/facts-and-figures). It is common knowledge that cardiovascular risk is determined by the interaction between our genetic make-up and lifestyle risk factors, such as smoking, obesity and lack of exercise. There is increasing awareness that the gene–environment interaction before birth may be just as, if not more, important in setting a risk of cardiovascular disease, through a process known as developmental programming (Giussani & Davidge, 2013). In humans, the best evidence to support developmental programming comes from studies of obese women who have fallen pregnant before and after having bariatric surgery (Guénard et al. 2013). These studies show that siblings born before the surgery have an increased risk of cardiovascular disease compared to those born after. Therefore, such studies highlight that changes in the environment even within the same womb can programme a differential risk of cardiovascular disease in offspring of the same family. This provides strong evidence in humans that the quality of the environment experienced during critical, early periods of development directly influences long-term cardiovascular health. Unsurprisingly, these concepts have renewed and amplified a focus on prevention rather than treatment to reduce the burden of cardiovascular disease, and for preventative medicine to start as early as possible in the developmental trajectory rather than waiting to treat disease after it has become irreversible. In this issue of The Journal of Physiology, Badran et al. (2019) investigated the effects of obstructive sleep apnoea during pregnancy on cardiometabolic function in the adult offspring using an established mouse model. Obstructive sleep apnoea is characterized by episodes of intermittent hypoxia, which promote oxidative and inflammatory stress, and increase the risk of cardiovascular dysfunction in affected patients (Badran et al. 2019). However, animal models have not addressed the effects of maternal obstructive sleep apnoea during pregnancy on the","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"09 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86047832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCN3 has minimal involvement in the sensation of acute, inflammatory and neuropathic pain","authors":"Mackellar Dewar","doi":"10.1113/JP278770","DOIUrl":"https://doi.org/10.1113/JP278770","url":null,"abstract":"Hyperpolarization-activated cyclical nucleotide-gated (HCN) channels have recently garnered attention as drivers of chronic pain. These channels cause an inward current in response to membrane hyperpolarization, leading to the cyclical generation of action potentials. Of the four channels belonging to the HCN family (HCN1–4), HCN1 HCN2, and HCN3 are the main channels responsible for hyperpolarization-activated current in neurons. Previous research has shown that loss of HCN2 activity can eliminate thermal hyperalgesia in inflammatory pain, as well as both thermal and mechanical hyperalgesia in neuropathic pain. Additionally, HCN1 activity has been shown to regulate cold hypersensitivity and nerve injury-induced pain. Given the involvement of other HCN channels, Lainez et al. (2019) sought to determine the role of HCN3 in chronic pain. They first investigated the expression of HCN3 in sensory neurons by performing immunohistochemistry on cultured lumbar dorsal root ganglion (DRG) neurons. Staining with β3-tubulin and HCN3 antibodies showed that 60% of small (<20 μm diameter) and medium–large (>20 μm diameter) neurons expressed HCN3. Further staining was done to determine the co-localization of HCN3 with subpopulations of DRG neurons; about 35% of small unmyelinated neurons, 86% of large myelinated neurons, and 63% of small and medium neurons with nociceptive function were found to express HCN3. Together, these experiments reveal the abundant expression of HCN3 in DRG neurons of various functions and size classes. While these findings are consistent with a previous study showing widespread expression of HCN3 in rat DRG neurons (Chaplan et al. 2003), they contradict the low HCN3 expression found by a study in mice (Moosmang et al. 2001). Next, the authors investigated whether HCN3 contributes to the hyperpolarization-activated current (Ih). Whole-cell patch clamp experiments showed that 97 of 107 neurons with HCN2 deletion had a significant Ih, providing initial evidence that other isoforms contribute to the current. Previous research has identified HCN1 as predominantly involved in large neurons, whereas HCN3 probably contributes to the Ih in small and medium neurons (Momin et al. 2008). In combination with the low expression of HCN4 in these cells (Moosmang et al. 2001; Chaplan et al. 2003), HCN2 and HCN3 appear to be the major isoforms involved in small and medium neurons. Given this information, Lainez et al. (2019) then studied the relative contribution of HCN2 and HCN3 to Ih. To do so, they measured V1/2 following forskolin-induced cAMP elevation in wild type (WT), HCN2−/− and HCN3−/− neurons. The heightened levels of cAMP led to its binding to the various HCN isoforms; HCN1 and HCN3 are relatively insensitive to this interaction, but binding to HCN2 and HCN4 will cause an increase in V1/2. In small neurons a similar increase in V1/2 was seen in both WT and HCN3−/− groups after forskolin application, whereas no shift was seen in HCN2−/− neuron","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88129932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle nitrate storage – the missing piece of the nitrate supplementation puzzle?","authors":"K. A. Wickham, J. Nyakayiru, D. G. McCarthy, Daniel T. Cervone","doi":"10.1113/JP278785","DOIUrl":"https://doi.org/10.1113/JP278785","url":null,"abstract":"Over the last decade, nitrate (NO3−) supplementation – delivered as beetroot juice (BRJ) or sodium/potassium nitrate – has gained widespread attention for its potential as a therapeutic and ergogenic aid (Jones et al. 2018). Specifically, NO3− supplementation has been shown to reduce blood pressure and improve exercise performance (Jones et al. 2018). These benefits have been attributed to an increase in nitric oxide (NO) bioavailability following exogenous NO3− intake.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89565017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}