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Fingolimod Real World Experience: Efficacy and Safety in Clinical Practice 芬戈莫德真实世界经验:临床实践的有效性和安全性
Pub Date : 2015-11-26 DOI: 10.1155/2015/389360
J. Fonseca
Fingolimod is a multiple sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence, and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using, as source of information, abstracts, posters, and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long-term experience no new safety signals were observed.
Fingolimod是一种多发性硬化症治疗药物,于2011年在欧洲获得许可。其疗效已在三个大型III期试验中得到证明,并在世界各地的监管提交中使用。与往常一样,在这些试验中,纳入和排除标准的设计是为了获得一个均匀的人群,在不同的治疗组中具有可互换的特征。虽然这是获得调查问题的可靠答案的最佳策略,但它并不能保证临床实践中的治疗效果,因为在现实世界中存在伴随治疗、合并症、依从性和持久性挑战。但是,为了对现实生活中的病人做出明智的治疗决定,我们需要有治疗效果的证据,也就是所谓的治疗效果。这项工作的目的是审查fingolimod的有效性,使用,作为信息来源,摘要,海报和手稿。这一非正统策略的发展是因为超过一半的芬戈莫德的出版经验仍然在摘要和海报上。被审查的研究中只有一小部分已经发表在同行评议的期刊上。芬戈莫似乎至少和临床试验时一样有效和安全,而且长期使用后没有观察到新的安全信号。
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引用次数: 22
Do Three Different Passive Assessments of Quadriceps Spasticity Relate to the Functional Activity of Walking for Children Diagnosed with Cerebral Palsy? 脑性麻痹儿童四头肌痉挛的三种不同被动评估与行走功能活动有关吗?
Pub Date : 2015-10-20 DOI: 10.1155/2015/872015
H. White, T. Uhl, S. Augsburger
A stiff-knee gait pattern is frequently associated with several impairments including quadriceps spasticity in children diagnosed with cerebral palsy (CP). The relationship of clinical measures of quadriceps spasticity and the stiff-knee gait pattern in children diagnosed with CP has not been well established. Therefore, the purpose of this study was to determine the ability of clinical measures of quadriceps spasticity (modified Ashworth scale [MAS], Ely tests, and pendulum test) to categorize a stiff-knee gait pattern in children with CP. Children were categorized as having a stiff-knee gait pattern based on kinematic and EMG gait data. Results of a logistic regression model revealed that the only significant measure was A1 of the pendulum test. Discriminant analysis functions were used to predict group membership (stiff-knee, not stiff-knee gait pattern) for each measure. The A1 of the pendulum test demonstrated the highest classification accuracy and the highest sensitivity compared to the other measures. Therefore, a negative pendulum test (indicated by an A1 value of 45 degrees or more) is more useful for ruling out a stiff-knee gait pattern compared to the other clinical measures.
在诊断为脑瘫(CP)的儿童中,硬膝步态模式通常与几种损伤相关,包括股四头肌痉挛。四头肌痉挛的临床测量与诊断为CP的儿童的硬膝步态模式的关系尚未得到很好的确定。因此,本研究的目的是确定股四头肌痉挛的临床测量(改良Ashworth量表[MAS]、Ely测试和钟摆测试)对CP患儿僵硬-膝关节步态模式进行分类的能力。基于运动学和肌电图步态数据,将患儿分为僵硬-膝关节步态模式。逻辑回归模型的结果显示,唯一显著的测量是摆试验的A1。判别分析函数用于预测每个测量的群体成员(硬膝,而不是硬膝步态模式)。与其他方法相比,摆试验的A1表现出最高的分类精度和最高的灵敏度。因此,与其他临床测量相比,负摆试验(由45度或更高的A1值表示)对于排除僵硬的膝关节步态模式更有用。
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引用次数: 6
Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning. 性别差异及慢性压力与恢复对器乐学习的影响。
Pub Date : 2015-01-01 Epub Date: 2015-04-16 DOI: 10.1155/2015/697659
Angela L McDowell, Kathryn M H Fransen, Kevin S Elliott, Alhasan Elghouche, Polina V Kostylev, Pamela K O'Dea, Preston E Garraghty

We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern.

我们之前的研究表明,21天的慢性约束压力会影响工具学习,但总体而言,很少有研究考察压力对学习影响的性别差异。我们进一步研究了性别差异对乐器学习42天慢性应激的反应,以及从慢性应激中恢复的情况。大鼠在有或没有先前的食欲经验的厌恶训练任务中进行测试,并收集每日体重数据作为压力指数。与对照组相比,雄鼠在应激期的第22 ~ 42天保持体重减轻,雌鼠则相反。应激男性在食欲习得和厌恶学习中反应速度加快,学习效率降低。男性总体上表现出较慢的逃逸成形时间和更多的电击暴露。相比之下,应激雌性在获取和维持转移动物和维持厌恶动物期间表现出较慢的食欲反应速度和较高的食欲和厌恶效率,但总体上降低了回避率。这些任务揭示了压力对目标导向行为影响的重要细微差别,并进一步强调了性差异对食欲动机和厌恶动机的影响。此外,这些数据强调,系统是暂时的影响慢性压力在性别差异模式。
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引用次数: 7
Evaluation of Motor Neuron Excitability by CMAP Scanning with Electric Modulated Current. 调制电流CMAP扫描对运动神经元兴奋性的评价。
Pub Date : 2015-01-01 Epub Date: 2015-08-26 DOI: 10.1155/2015/360648
Tiago Araújo, Rui Candeias, Neuza Nunes, Hugo Gamboa

Introduction. Compound Muscle Action Potential (CMAP) scan is a noninvasive promissory technique for neurodegenerative pathologies diagnosis. In this work new CMAP scan protocols were implemented to study the influence of electrical pulse waveform on peripheral nerve excitability. Methods. A total of 13 healthy subjects were tested. Stimulation was performed with an increasing intensities range from 4 to 30 mA. The procedure was repeated 4 times per subject, using a different single pulse stimulation waveform: monophasic square and triangular and quadratic and biphasic square. Results. Different waveforms elicit different intensity-response amplitude curves. The square pulse needs less current to generate the same response amplitude regarding the other waves and this effect is gradually decreasing for the triangular, quadratic, and biphasic pulse, respectively. Conclusion. The stimulation waveform has a direct influence on the stimulus-response slope and consequently on the motoneurons excitability. This can be a new prognostic parameter for neurodegenerative disorders.

介绍。复合肌动作电位(CMAP)扫描是一种无创的神经退行性病理诊断技术。本文采用新的CMAP扫描方案来研究电脉冲波形对周围神经兴奋性的影响。方法。共对13名健康受试者进行了测试。刺激强度从4到30 mA不等。每个受试者重复4次,使用不同的单脉冲刺激波形:单相方形、三角形、二次和双相方形。结果。不同的波形产生不同的强度-响应振幅曲线。对于其他波,方形脉冲产生相同的响应幅值所需的电流更少,而对于三角形脉冲、二次脉冲和双相脉冲,这种影响分别逐渐减小。结论。刺激波形直接影响刺激-反应斜率,从而影响运动神经元的兴奋性。这可能是神经退行性疾病的一个新的预后参数。
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引用次数: 4
Change in Motor and Nonmotor Symptoms Severity in a "Real-Life" Cohort of Subjects with Parkinson's Disease. 帕金森病患者“现实生活”队列中运动和非运动症状严重程度的变化
Pub Date : 2015-01-01 Epub Date: 2015-08-20 DOI: 10.1155/2015/368989
Adib Jorge de Saráchaga, Amin Cervantes-Arriaga, Rodrigo Llorens-Arenas, Humberto Calderón-Fajardo, Mayela Rodríguez-Violante

Background. Parkinson's disease (PD) is a chronic and progressive disorder. Rates of change in motor symptoms have been more studied compared to nonmotor symptoms. The objective was to describe these changes in a real-life cohort of subjects with PD. Methods. A cohort study was carried out from 2011 to 2013. Consecutive patients with PD were recruited from a movement disorders clinic. MDS-UPDRS, PDQ-8, and NMSS were applied to all subjects at an initial evaluation and a subsequent visit (21 ± 3 months). Disease severity was categorized using a recent classification of MDS-UPDRS severity. Results. The MDS-UPDRS Part III showed a significant decrease of 7.2 ± 2.31 points (p = 0.001) between evaluations. A mean increase of 0.9 ± 0.6 points (p = 0.015) in the MDS-UPDRS Part IV was observed. An increase of 14.3 ± 11.4 points (p = 0.043) in the NMSS total score was found; when assessed individually, the difference was statistically significant only for the perceptual problems/hallucinations item. Quality of life remained unchanged. Conclusion. Motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization. Nonmotor symptoms worsened as a whole. The overall effect in the quality of life was negligible.

背景。帕金森病(PD)是一种慢性进行性疾病。与非运动症状相比,运动症状的变化率研究得更多。目的是描述现实生活中PD患者队列的这些变化。方法。2011年至2013年进行了一项队列研究。连续从运动障碍诊所招募PD患者。MDS-UPDRS、PDQ-8和NMSS分别应用于所有受试者的初次评估和随后的随访(21±3个月)。疾病严重程度采用最近的MDS-UPDRS严重程度分类进行分类。结果。MDS-UPDRS第三部分在两次评估之间显著下降了7.2±2.31分(p = 0.001)。MDS-UPDRS第四部分平均升高0.9±0.6分(p = 0.015)。NMSS总分提高14.3±11.4分(p = 0.043);当单独评估时,只有知觉问题/幻觉项的差异有统计学意义。生活质量保持不变。结论。观察到运动改善伴有运动并发症的增加,这可能是治疗优化的结果。非运动症状整体恶化。对生活质量的总体影响可以忽略不计。
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引用次数: 1
Motorcycle-Related Traumatic Brain Injuries: Helmet Use and Treatment Outcome. 摩托车相关的创伤性脑损伤:头盔的使用和治疗结果。
Pub Date : 2015-01-01 Epub Date: 2015-03-23 DOI: 10.1155/2015/696787
Mathias Ogbonna Nnanna Nnadi, Olufemi Babatola Bankole, Beleudanyo Gbalipre Fente

Summary. With increasing use of motorcycle as means of transport in developing countries, traumatic brain injuries from motorcycle crashes have been increasing. The only single gadget that protects riders from traumatic brain injury is crash helmet. Objective. The objectives were to determine the treatment outcome among traumatic brain injury patients from motorcycle crashes and the rate of helmet use among them. Methods. It was a prospective, cross-sectional study of motorcycle-related traumatic brain injury patients managed in our center from 2010 to 2014. Patients were managed using our unit protocol for traumatic brain injuries. Data for the study were collected in accident and emergency, intensive care unit, wards, and outpatient clinic. The data were analyzed using Environmental Performance Index (EPI) info 7 software. Results. Ninety-six patients were studied. There were 87 males. Drivers were 65. Only one patient wore helmet. Majority of them were between 20 and 40 years. Fifty-three patients had mild head injuries. Favorable outcome among them was 84.35% while mortality was 12.5%. Severity of the injury affected the outcome significantly. Conclusion. Our study showed that the helmet use by motorcycle riders was close to zero despite the existing laws making its use compulsory in Nigeria. The outcome was related to severity of injuries.

总结。随着发展中国家越来越多地使用摩托车作为交通工具,摩托车碰撞造成的创伤性脑损伤一直在增加。唯一能保护车手免受创伤性脑损伤的装置是头盔。目标。目的是确定摩托车碰撞造成的创伤性脑损伤患者的治疗结果和头盔使用率。方法。本研究是对2010 - 2014年我中心摩托车相关创伤性脑损伤患者进行前瞻性横断面研究。患者使用我们的创伤性脑损伤单元方案进行管理。本研究的资料收集于急症室、加护病房、病房及门诊。采用环境绩效指数(EPI) info 7软件对数据进行分析。结果。对96名患者进行了研究。男性87人。司机年龄为65岁。只有一名患者戴了头盔。他们中的大多数年龄在20到40岁之间。53名患者头部轻度受伤。预后良好率为84.35%,死亡率为12.5%。损伤的严重程度对结果有显著影响。结论。我们的研究表明,尽管尼日利亚现行法律规定摩托车骑手必须戴头盔,但头盔的使用几乎为零。结果与损伤的严重程度有关。
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引用次数: 11
Age- and Sex-Dependent Changes in Androgen Receptor Expression in the Developing Mouse Cortex and Hippocampus. 发育中的小鼠皮质和海马中雄激素受体表达的年龄和性别依赖性变化。
Pub Date : 2015-01-01 Epub Date: 2015-02-03 DOI: 10.1155/2015/525369
Houng-Wei Tsai, Saori Taniguchi, Jason Samoza, Aaron Ridder

During the perinatal period, male mice are exposed to higher levels of testosterone (T) than females, which promotes sexual dimorphism in their brain structures and behaviors. In addition to acting via estrogen receptors after being locally converted into estradiol by aromatase, T also acts directly through androgen receptor (AR) in the brain. Therefore, we hypothesized that AR expression in the developing mouse cortex and hippocampus was sexually dimorphic. To test our hypothesis, we measured and determined AR mRNA and protein levels in mouse cortex/hippocampus collected on the day of birth (PN0) and 7 (PN7), 14 (PN14), and 21 (PN21) days after birth. We demonstrated that, as age advanced, AR mRNA levels increased in the cortex/hippocampus of both sexes but showed no sex difference. Two AR proteins, the full-length (110 kDa) and a smaller isoform (70 kDa), were detected in the developing mouse cortex/hippocampus with an age-dependent increase in protein levels of both AR isoforms at PN21 and a transient masculine increase in expression of the full-length AR protein on PN7. Thus, we conclude that the postnatal age and sex differences in AR protein expression in combination with the sex differences in circulating T may cause sexual differentiation of the mouse cortex/hippocampus.

在围产期,雄性小鼠比雌性小鼠暴露在更高水平的睾酮(T)中,这促进了它们大脑结构和行为的性别二态性。除了经芳香化酶局部转化为雌二醇后通过雌激素受体起作用外,T还直接通过大脑中的雄激素受体(AR)起作用。因此,我们假设AR在发育中的小鼠皮质和海马中的表达是两性二态的。为了验证我们的假设,我们测量并测定了出生当天(PN0)和出生后7 (PN7)、14 (PN14)和21 (PN21)天收集的小鼠皮质/海马中AR mRNA和蛋白水平。我们发现,随着年龄的增长,两性大脑皮层/海马体中的AR mRNA水平增加,但没有性别差异。在发育中的小鼠皮质/海马体中检测到两种AR蛋白,全长(110 kDa)和较小的亚型(70 kDa), PN21上两种AR亚型的蛋白水平均呈年龄依赖性增加,而PN7上全长AR蛋白的表达则呈短暂的阳性增加。因此,我们认为AR蛋白表达的出生年龄和性别差异结合循环T的性别差异可能导致小鼠皮质/海马的性别分化。
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引用次数: 19
Impact of Age and Duration of Symptoms on Surgical Outcome of Single-Level Microscopic Anterior Cervical Discectomy and Fusion in the Patients with Cervical Spondylotic Radiculopathy. 年龄和症状持续时间对神经根型颈椎病患者单节段显微前路椎间盘切除术融合手术疗效的影响
Pub Date : 2014-01-01 Epub Date: 2014-09-30 DOI: 10.1155/2014/808596
Farzad Omidi-Kashani, Ebrahim Ghayem Hasankhani, Reza Ghandehari

We aim to evaluate the impact of age and duration of symptoms on surgical outcome of the patients with cervical spondylotic radiculopathy (CSR) who had been treated by single-level microscopic anterior cervical discectomy and fusion (ACDF). We retrospectively evaluated 68 patients (48 female and 20 male) with a mean age of 41.2 ± 4.3 (ranged from 24 to 72 years old) in our Orthopedic Department, Imam Reza Hospital. They were followed up for 31.25 ± 4.1 months (ranged from 25 to 65 months). Pain and disability were assessed by Visual Analogue Scale (VAS) and Neck Disability Index (NDI) questionnaires in preoperative and last follow-up visits. Functional outcome was eventually evaluated by Odom's criteria. Surgery could significantly improve pain and disability from preoperative 6.2 ± 1.4 and 22.2 ± 6.2 to 3.5 ± 2.0 and 8.7 ± 5.2 (1-21) at the last follow-up visit, respectively. Satisfactory outcomes were observed in 89.7%. Symptom duration of more and less than six months had no effect on surgical outcome, but the results showed a statistically significant difference in NDI improvement in favor of the patients aged more than 45 years (P = 0.032), although pain improvement was similar in the two groups.

我们的目的是评估年龄和症状持续时间对神经根型颈椎病(CSR)患者接受单节段显微前路颈椎椎间盘切除术和融合(ACDF)治疗的手术结果的影响。我们回顾性评估了Imam Reza医院骨科的68例患者(48名女性和20名男性),平均年龄为41.2±4.3岁(年龄范围从24岁到72岁)。随访时间为31.25±4.1个月(25 ~ 65个月)。术前和末次随访时采用视觉模拟量表(VAS)和颈部残疾指数(NDI)问卷对疼痛和残疾进行评估。功能结果最终根据奥多姆的标准进行评估。手术可显著改善疼痛和残疾,分别从术前的6.2±1.4和22.2±6.2提高到末次随访时的3.5±2.0和8.7±5.2(1-21)。89.7%的患者满意。症状持续时间大于和小于6个月对手术结果没有影响,但结果显示,年龄大于45岁的患者在NDI改善方面差异有统计学意义(P = 0.032),尽管两组疼痛改善相似。
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引用次数: 29
Language Development across the Life Span: A Neuropsychological/Neuroimaging Perspective. 终身语言发展:神经心理学/神经影像学的视角。
Pub Date : 2014-01-01 Epub Date: 2014-12-18 DOI: 10.1155/2014/585237
Mónica Rosselli, Alfredo Ardila, Esmeralda Matute, Idaly Vélez-Uribe

Language development has been correlated with specific changes in brain development. The aim of this paper is to analyze the linguistic-brain associations that occur from birth through senescence. Findings from the neuropsychological and neuroimaging literature are reviewed, and the relationship of language changes observable in human development and the corresponding brain maturation processes across age groups are examined. Two major dimensions of language development are highlighted: naming (considered a major measure of lexical knowledge) and verbal fluency (regarded as a major measure of language production ability). Developmental changes in the brain lateralization of language are discussed, emphasizing that in early life there is an increase in functional brain asymmetry for language, but that this asymmetry changes over time, and that changes in the volume of gray and white matter are age-sensitive. The effects of certain specific variables, such as gender, level of education, and bilingualism are also analyzed. General conclusions are presented and directions for future research are suggested.

语言发展与大脑发育的特定变化有关。本文的目的是分析从出生到衰老发生的语言-大脑联系。本文综述了神经心理学和神经影像学文献的研究成果,并对人类发育过程中可观察到的语言变化与相应的大脑成熟过程之间的关系进行了研究。语言发展的两个主要方面被强调:命名(被认为是词汇知识的主要衡量标准)和语言流畅性(被认为是语言生产能力的主要衡量标准)。讨论了大脑语言侧化的发育变化,强调在生命早期,语言功能的大脑不对称增加,但这种不对称随着时间的推移而改变,灰质和白质体积的变化是年龄敏感的。还分析了某些特定变量的影响,如性别、教育水平和双语能力。总结了本文的研究结论,并提出了今后的研究方向。
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引用次数: 55
Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of Sleep Spindles in Rats. 大鼠失神发作的年龄依赖性增加和睡眠纺锤波的固有频率动态。
Pub Date : 2014-01-01 Epub Date: 2014-06-23 DOI: 10.1155/2014/370764
Evgenia Sitnikova, Alexander E Hramov, Vadim Grubov, Alexey A Koronovsky

The risk of neurological diseases increases with age. In WAG/Rij rat model of absence epilepsy, the incidence of epileptic spike-wave discharges is known to be elevated with age. Considering close relationship between epileptic spike-wave discharges and physiologic sleep spindles, it was assumed that age-dependent increase of epileptic activity may affect time-frequency characteristics of sleep spindles. In order to examine this hypothesis, electroencephalograms (EEG) were recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave discharges and sleep spindles were detected in frontal EEG channel. Sleep spindles were identified automatically using wavelet-based algorithm. Instantaneous (localized in time) frequency of sleep spindles was determined using continuous wavelet transform of EEG signal, and intraspindle frequency dynamics were further examined. It was found that in 5-months-old rats epileptic activity has not fully developed (preclinical stage) and sleep spindles demonstrated an increase of instantaneous frequency from beginning to the end. At the age of 7 and 9 months, when animals developed matured and longer epileptic discharges (symptomatic stage), their sleep spindles did not display changes of intrinsic frequency. The present data suggest that age-dependent increase of epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle frequency.

患神经系统疾病的风险随着年龄的增长而增加。在WAG/Rij缺失癫痫模型中,癫痫尖波放电的发生率随着年龄的增长而升高。考虑到癫痫峰波放电与生理性睡眠纺锤波的密切关系,假设癫痫活动的年龄依赖性增加可能影响睡眠纺锤波的时频特性。为了验证这一假设,我们在5、7、9月龄时分别记录了WAG/Rij大鼠的脑电图。额叶脑电图通道检测到尖峰波放电和睡眠纺锤波。采用基于小波的算法自动识别睡眠纺锤波。对脑电信号进行连续小波变换,确定睡眠纺锤波的瞬时(时间局部)频率,并进一步研究纺锤波内的频率动态。结果发现,5月龄大鼠癫痫活动尚未完全发展(临床前阶段),睡眠纺锤波的瞬时频率从始至终呈增加趋势。在7和9个月大时,当动物发育成熟,癫痫放电时间更长(症状期)时,它们的睡眠纺锤波没有表现出固有频率的变化。目前的数据表明,WAG/Rij大鼠癫痫活动的年龄依赖性增加影响睡眠纺锤波频率的内在动态。
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引用次数: 22
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