BACKGROUND & AIMS: Background:Treatment of freezing of gait (FOG) is always challenging because of its unpredictable nature and multifactorial physiopathology. Intestinal levodopa infusion has been proposed in recent years as a valuable option for its improvement. FOG in Parkinson's disease (PD) can appear after deep brain stimulation in patients who never had gait symptoms. Objective:To study the effects of intestinal levodopa/carbidopa infusion in unresponsive-FOG that appears in PD patients treated with subthalamic nucleus deep brain stimulation. Methods:We retrospectively collected and analyzed demographic, clinical, and therapeutic data from five PD patients treated with subthalamic nucleus stimulation who developed unresponsive-FOG and received intestinal levodopa/carbidopa infusion as an alternative therapy. FOG was measured based on scores in item 14 of the Unified Parkinson's Disease Rating Scale before and after intestinal levodopa infusion. Results:Administration of intestinal levodopa caused improvement of FOG in the "ON" state in four patients (80%) by 2 or more points in item 14 of the Unified Parkinson's Disease Rating Scale. The improvement was maintained for at least 12 months. Conclusions:Intestinal levodopa infusion may be a valuable therapeutic option for unresponsive-FOG developed after subthalamic nucleus deep brain stimulation.

背景与目标：

BACKGROUND & AIMS: :Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely replaced by DBS of the subthalamic nucleus or internal pallidal segment. These procedures are not only effective in the treatment of parkinsonism, but also in the treatment of hyperkinetic conditions (such as chorea or dystonia) which result from pathophysiologic changes different from those underlying Parkinson's disease. Thus, these interventions probably do not counteract specific aspects of the pathophysiology of movement disorders, but non-specifically remove the influence of the different types of disruptive basal ganglia output from the relatively intact portions of the motor circuitry downstream from the basal ganglia. Knowledge gained from studies in NHPs remains critical for our understanding of the pathophysiology of movement disorders, of the effects of DBS on brain network activity, and the development of better treatments for patients with movement disorders and other neurologic or psychiatric conditions.

背景与目标： : 对非人类灵长类动物 (NHPs) 的研究在我们对基底节的功能以及运动不足性疾病 (如帕金森氏病) 和运动亢进性疾病 (如舞蹈病和肌张力障碍) 的病理生理机制的理解方面取得了重大进展。由于NHPs的大脑在解剖学上与人类的大脑非常接近，因此与其他物种相比，疾病状态以及医学和外科手术方法 (例如深部脑刺激 (DBS)) 的影响可以在NHPs中更忠实地建模。根据受NHPs研究强烈影响的当前基底神经节回路模型，基底神经节被视为分离网络的组成部分，这些网络来自特定的皮质区域，穿过基底神经节和腹侧丘脑，然后返回额叶皮层。根据所涉及的不同皮质区域的假定功能域，这些网络被指定为 “运动”，“眼动”，“关联” 和 “边缘” 电路。这些网络的功能受到纹状体中多巴胺释放的强烈调节。纹状体多巴胺的释放会改变纹状体投射神经元的活性，进而影响 (抑制性) 基底神经节的输出。在帕金森氏病中，纹状体多巴胺的丧失导致基底神经节输出神经元放电的振荡爆发模式的出现，相邻基底神经节神经元放电的同步性增加以及基底神经节输出的总体增加。在帕金森氏症的NHP模型中，在丘脑底核 (基底神经节的主要组成部分之一) 水平上的运动回路失活的抗帕金森氏效应的证明了这些发现的相关性。这一发现也有力地促进了手术干预治疗帕金森氏病患者的复兴。虽然消融程序最初是为此目的使用的，但现在已被丘脑下核或苍白球内部节段的DBS所取代。这些程序不仅可有效治疗帕金森氏症，而且可有效治疗多动性疾病 (例如舞蹈病或肌张力障碍)，这些疾病是由与帕金森氏病不同的病理生理变化引起的。因此，这些干预措施可能不会抵消运动障碍的病理生理学的特定方面，而是非特异性地消除了基底神经节下游运动电路相对完整部分中不同类型的破坏性基底神经节输出的影响。从NHPs研究中获得的知识对于我们了解运动障碍的病理生理学，DBS对脑网络活动的影响以及为运动障碍和其他神经或精神疾病患者开发更好的治疗方法仍然至关重要。

BACKGROUND & AIMS: :L-shell ionisation and subsequent Coulomb explosion of fully deuterated methyl iodide, CD3I, irradiated with hard X-rays has been examined by a time-of-flight multi-ion coincidence technique. The core vacancies relax efficiently by Auger cascades, leading to charge states up to 16+. The dynamics of the Coulomb explosion process are investigated by calculating the ions' flight times numerically based on a geometric model of the experimental apparatus, for comparison with the experimental data. A parametric model of the explosion, previously introduced for multi-photon induced Coulomb explosion, is applied in numerical simulations, giving good agreement with the experimental results for medium charge states. Deviations for higher charges suggest the need to include nuclear motion in a putatively more complete model. Detection efficiency corrections from the simulations are used to determine the true distributions of molecular charge states produced by initial L1, L2 and L3 ionisation.

背景与目标： : 已通过飞行时间多离子重合技术检查了用硬x射线辐照的全氘代甲基碘CD3I的L壳电离和随后的库仑爆炸。螺旋钻级联有效地放松了核心空位，导致充电状态高达16 +。通过基于实验设备的几何模型数值计算离子的飞行时间，研究了库仑爆炸过程的动力学，以与实验数据进行比较。在数值模拟中应用了先前针对多光子引起的库仑爆炸引入的爆炸参数模型，与中等电荷状态的实验结果非常吻合。较高电荷的偏差表明需要将核运动包括在一个更完整的模型中。来自模拟的检测效率校正用于确定由初始L1，L2和L3电离产生的分子电荷态的真实分布。

BACKGROUND & AIMS: :Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. PERSPECTIVES: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.

背景与目标： : 缓慢深呼吸 (SDB) 通常用于治疗疼痛，但潜在的机制仍然模棱两可。本研究旨在研究指示呼吸方式对实验性热痛的影响，并探索可能的作用机制。在受试者内部的实验设计中，健康志愿者 (n   =   48) 进行了4种呼吸模式: 1) 无节奏呼吸，2) 以参与者的自发呼吸频率进行有节奏的呼吸 (PB)，3) SDB，每分钟6次呼吸，具有高吸气/呼气比 (sdb-h)，和4) SDB，每分钟6次呼吸，具有低吸气/呼气比 (sdb-l)。在呈现每种呼吸模式期间，参与者接受了3种不同温度的疼痛性热刺激，并根据疼痛强度对每种刺激进行了评分。记录呼吸，心率和血压。与无节奏呼吸相比，参与者在3种指示的呼吸模式中的每一种都报告了较少的剧烈疼痛。在指示的呼吸模式中，PB和sdb-h之间的疼痛没有差异，sdb-l减轻的疼痛比PB和sdb-h模式更大。后者的作用与sdb-l期间更大的血压变异性和压力反射有效性指数平行。心血管变化不能介导观察到的呼吸模式对疼痛的影响。观点: 当呼吸以缓慢的节律起搏，相对于吸气而言，呼气时间较长时，SDB更有效地减轻疼痛，但潜在的机制仍有待阐明。

BACKGROUND & AIMS: :Prescribed burning is a common management tool to control fuel loads, ground vegetation, and facilitate desirable game species. We evaluated soil fungal community responses to long-term prescribed fire treatments in a loblolly pine forest on the Piedmont of Georgia and utilized deep Internal Transcribed Spacer Region 1 (ITS1) amplicon sequencing afforded by the recent Ion Torrent Personal Genome Machine (PGM). These deep sequence data (19,000 + reads per sample after subsampling) indicate that frequent fires (3-year fire interval) shift soil fungus communities, whereas infrequent fires (6-year fire interval) permit system resetting to a state similar to that without prescribed fire. Furthermore, in nonmetric multidimensional scaling analyses, primarily ectomycorrhizal taxa were correlated with axes associated with long fire intervals, whereas soil saprobes tended to be correlated with the frequent fire recurrence. We conclude that (1) multiplexed Ion Torrent PGM analyses allow deep cost effective sequencing of fungal communities but may suffer from short read lengths and inconsistent sequence quality adjacent to the sequencing adaptor; (2) frequent prescribed fires elicit a shift in soil fungal communities; and (3) such shifts do not occur when fire intervals are longer. Our results emphasize the general responsiveness of these forests to management, and the importance of fire return intervals in meeting management objectives.

背景与目标： : 规定燃烧是一种常见的管理工具，可控制燃料负荷，地面植被并促进理想的游戏物种。我们评估了佐治亚州皮埃蒙特的火炬松森林中土壤真菌群落对长期规定的火处理的反应，并利用了最近的离子洪流个人基因组机器 (PGM) 提供的深层内部转录间隔区1 (ITS1) 扩增子测序。这些深度序列数据 (子采样后每个样本读取19,000个读数) 表明，频繁的火灾 (3年火灾间隔) 改变了土壤真菌群落，而不频繁的火灾 (6年火灾间隔) 允许系统重置为类似于没有规定的状态火。此外，在非度量多维标度分析中，主要是外生菌根类群与长火灾间隔相关的轴相关，而土壤腐生倾向于与频繁的火灾复发相关。我们得出的结论是 :( 1) 多重离子激流PGM分析允许对真菌群落进行深度经济有效的测序，但可能遭受短的读取长度和与测序适配器相邻的序列质量不一致的困扰; (2) 频繁的规定火灾引起土壤真菌群落的转变; (3) 当火灾间隔较长时，不会发生这种变化。我们的结果强调了这些森林对管理的总体响应能力，以及回火间隔在实现管理目标中的重要性。

BACKGROUND & AIMS: :The oxygenated hypolimnion accounts for a volumetrically significant part of the global freshwater systems. Previous studies have proposed the presence of hypolimnion-specific bacterioplankton lineages that are distinct from those inhabiting the epilimnion. To date, however, no consensus exists regarding their ubiquity and abundance, which is necessary to evaluate their ecological importance. The present study investigated the bacterioplankton community in the oxygenated hypolimnia of 10 deep freshwater lakes. Despite the broad geochemical characteristics of the lakes, 16S rRNA gene sequencing demonstrated that the communities in the oxygenated hypolimnia were distinct from those in the epilimnia and identified several predominant lineages inhabiting multiple lakes. Catalyzed reporter deposition fluorescence in situ hybridization revealed that abundant hypolimnion-specific lineages, CL500-11 (Chloroflexi), CL500-3, CL500-37, CL500-15 (Planctomycetes) and Marine Group I (Thaumarchaeota), together accounted for 1.5-32.9% of all bacterioplankton in the hypolimnion of the lakes. Furthermore, an analysis of single-nucleotide variation in the partial 16S rRNA gene sequence (oligotyping) suggested the presence of different sub-populations between lakes and water layers among the lineages occurring in the entire water layer (for example, acI-B1 and acI-A7). Collectively, these results provide the first comprehensive overview of the bacterioplankton community in the oxygenated hypolimnion of deep freshwater lakes.

背景与目标： : 含氧的低水离子在全球淡水系统中占很大一部分。先前的研究已经提出，存在特定于hypolimnion的浮游细菌谱系，这些谱系与居住在epilimnion的细菌谱系不同。然而，迄今为止，关于它们的普遍性和丰富性尚无共识，这是评估其生态重要性所必需的。本研究调查了10个深淡水湖的含氧低泡中的浮游细菌群落。尽管湖泊具有广泛的地球化学特征，但16S rRNA基因测序表明，含氧的低水草中的群落与上水草中的群落不同，并确定了居住在多个湖泊中的几个主要谱系。催化的报告分子沉积荧光原位杂交显示，丰富的hypolinion特异性谱系，CL500-11 (Chloroflexi)，CL500-3，CL500-37，CL500-15 (planctoycetes) 和海洋I类 (Thaumarchaeota)，占所有浮游细菌的1.5-32.9% 在湖泊的hypolinion中。此外，对部分16 srrna基因序列中的单核苷酸变异的分析 (寡核苷酸分型) 表明，在整个水层中发生的谱系 (例如，acI-B1和acI-A7) 中，湖泊和水层之间存在不同的亚群。总的来说，这些结果首次全面概述了深淡水湖含氧的低水量中的浮游细菌群落。

BACKGROUND & AIMS: OBJECTIVE:Type 2 diabetes (T2D) is a complex disease characterized by pancreatic islet dysfunction, insulin resistance, and disruption of blood glucose levels. Genome-wide association studies (GWAS) have identified > 400 independent signals that encode genetic predisposition. More than 90% of associated single-nucleotide polymorphisms (SNPs) localize to non-coding regions and are enriched in chromatin-defined islet enhancer elements, indicating a strong transcriptional regulatory component to disease susceptibility. Pancreatic islets are a mixture of cell types that express distinct hormonal programs, so each cell type may contribute differentially to the underlying regulatory processes that modulate T2D-associated transcriptional circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity. METHODS:We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). We also developed a deep learning model based on U-Net architecture to accurately predict open chromatin peak calls in rare cell populations. RESULTS:We show that sci-ATAC-seq profiles allow us to deconvolve alpha, beta, and delta cell populations and identify cell-type-specific regulatory signatures underlying T2D. Particularly, T2D GWAS SNPs are significantly enriched in beta cell-specific and across cell-type shared islet open chromatin, but not in alpha or delta cell-specific open chromatin. We also demonstrate, using less abundant delta cells, that deep learning models can improve signal recovery and feature reconstruction of rarer cell populations. Finally, we use co-accessibility measures to nominate the cell-specific target genes at 104 non-coding T2D GWAS signals. CONCLUSIONS:Collectively, we identify the islet cell type of action across genetic signals of T2D predisposition and provide higher-resolution mechanistic insights into genetically encoded risk pathways.

背景与目标：

BACKGROUND & AIMS: :NrS-1 is the first known phage that can infect Epsilonproteobacteria, one of the predominant primary producers in the deep-sea hydrothermal vent ecosystems. NrS-1 polymerase is a multidomain enzyme and is one key component of the phage replisome. The N-terminal Prim/Pol and HBD domains are responsible for DNA polymerization and de novo primer synthesis activities of NrS-1 polymerase. However, the structure and function of the C-terminus (CTR) of NrS-1 polymerase are poorly understood. Here, we report two crystal structures, showing that NrS-1 CTR adopts one unique hexameric ring-shaped conformation. Although the central helicase domain of NrS-1 CTR shares structural similarity with the superfamily III helicases, the folds of the Head and Tail domains are completely novel. Via mutagenesis and in vitro biochemical analysis, we identified many residues important for the helicase and polymerization activities of NrS-1 polymerase. In addition to NrS-1 polymerase, our study may also help us identify and understand the functions of multidomain polymerases expressed by many NrS-1 related phages.

背景与目标： : NrS-1是第一个可以感染Epsilonproteobacteria的噬菌体，Epsilonproteobacteria是深海热液喷口生态系统的主要初级生产者之一。NrS-1聚合酶是一种多结构域酶，是噬菌体复制体的关键成分之一。N末端Prim/Pol和HBD结构域负责NrS-1聚合酶的DNA聚合和从头引物合成活性。然而，对NrS-1聚合酶的C末端 (CTR) 的结构和功能知之甚少。在这里，我们报告了两种晶体结构，表明NrS-1 CTR采用一种独特的六聚体环形构象。尽管NrS-1 CTR的中央解旋酶结构域与超家族III解旋酶具有结构相似性，但头和尾结构域的褶皱是完全新颖的。通过诱变和体外生化分析，我们确定了许多对NrS-1聚合酶的解旋酶和聚合活性重要的残基。除了NrS-1聚合酶之外，我们的研究还可能帮助我们鉴定和理解许多NrS-1相关噬菌体表达的多域聚合酶的功能。

BACKGROUND & AIMS: Background:Deep brain stimulation is a surgical treatment for Parkinson's disease. Its impacts on motor symptoms are widely reported; however, little is known about the broader impact of deep brain stimulation on the community lives of people with Parkinson's disease. Lifespace is a measure of lived community mobility, providing an indication of community access and participation. Aims:This pilot study explored the feasibility of remotely monitoring the qualitative and quantitative community outcomes related to deep brain stimulation. Methods:A longitudinal mixed methods study with a convergent design was undertaken exploring the lifespace, quality of life, life satisfaction and lived experiences of people with Parkinson's disease before and after deep brain stimulation. Data were collected through questionnaires, semi-structured interviews and a smartphone-based application which collected geolocation data. Results:Quantitative and qualitative data from eight participants living with Parkinson's disease were analysed and integrated. At baseline, participants had a median age of 68 years and a median Hoehn and Yahr score of 2. Measuring a range of community-based outcomes indicated different change trajectories for individuals across outcomes. Key content areas were developed from the qualitative data: participation in occupations and travel and home. This study indicates the potential value of including geolocation data-based lifespace collection in metropolitan and regional areas. Conclusions:Monitoring lifespace in conjunction with subjective measures provides insights into the complex and individually varied experiences. Further research could explore the impacts of deep brain stimulation on occupations and community participation to gain a deeper understanding of the related needs and support clinical approaches.

背景与目标：

BACKGROUND & AIMS: :Deep brain stimulation (DBS) is an effective neurosurgical treatment for patients with advanced Parkinson's disease (PD) suffering from motor complications that are refractory to further medication management. DBS requires an invasive procedure of implanting brain electrodes while awake, followed by implantation of neurostimulators under general anesthesia. The neurostimulator requires battery monitoring and replacement approximately every 3 to 5 years. These two elements of the technology provide numerous decision points about continuing therapies that can involve ethical choices. Although motor function can be improved with subthalamic nucleus (STN) DBS, the long-term risks of living with implanted hardware should be carefully evaluated for patients with diminishing cognitive capacity. We describe two cases where ethical dilemmas occurred postoperatively as a result of cognitive decline and describe salient ethical dimensions that illustrate the need for a proactive postoperative plan for supervision as a prerequisite for surgery to include neuropsychological testing to predict the likelihood of net benefit to the patient and family beyond just motor improvement.

背景与目标： : 深部脑刺激 (DBS) 是一种有效的神经外科治疗方法，用于患有运动并发症的晚期帕金森氏病 (PD) 患者，这些并发症难以进一步治疗药物。DBS需要在清醒时植入脑电极的侵入性程序，然后在全身麻醉下植入神经刺激器。神经刺激器需要大约每3至5年进行一次电池监测和更换。该技术的这两个要素提供了许多有关可能涉及道德选择的持续疗法的决策点。尽管丘脑底核 (STN) DBS可以改善运动功能，但对于认知能力下降的患者，应仔细评估植入硬件的长期风险。我们描述了两种情况，其中由于认知能力下降而在术后发生伦理困境，并描述了突出的伦理维度，这些维度说明了需要积极的术后监督计划作为手术的先决条件，包括神经心理学测试，以预测对患者和家庭的净收益的可能性，而不仅仅是运动改善。

BACKGROUND & AIMS: BACKGROUND:MicroRNAs (miRNAs) play important roles in a variety of biological processes by regulating gene expression at the post-transcriptional level. So, the discovery of new miRNAs has become a popular task in biological research. Since the experimental identification of miRNAs is time-consuming, many computational tools have been developed to identify miRNA precursor (pre-miRNA). Most of these computation methods are based on traditional machine learning methods and their performance depends heavily on the selected features which are usually determined by domain experts. To develop easily implemented methods with better performance, we investigated different deep learning architectures for the pre-miRNAs identification. RESULTS:In this work, we applied convolution neural networks (CNN) and recurrent neural networks (RNN) to predict human pre-miRNAs. We combined the sequences with the predicted secondary structures of pre-miRNAs as input features of our models, avoiding the feature extraction and selection process by hand. The models were easily trained on the training dataset with low generalization error, and therefore had satisfactory performance on the test dataset. The prediction results on the same benchmark dataset showed that our models outperformed or were highly comparable to other state-of-the-art methods in this area. Furthermore, our CNN model trained on human dataset had high prediction accuracy on data from other species. CONCLUSIONS:Deep neural networks (DNN) could be utilized for the human pre-miRNAs detection with high performance. Complex features of RNA sequences could be automatically extracted by CNN and RNN, which were used for the pre-miRNAs prediction. Through proper regularization, our deep learning models, although trained on comparatively small dataset, had strong generalization ability.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To compare the efficacy of postoperative adjuvant treatment (gonadotropin-releasing hormone agonists [GnRHas] and oral contraceptives [OCs]) and expectant treatment in preventing recurrent dysmenorrhea following conservative laparoscopic surgery for deep infiltrating endometriosis (DIE) with dysmenorrhea. METHODS:A prospective cohort study was conducted in Shanghai, China. In total, 147 patients with dysmenorrhea who underwent conservative laparoscopic surgery for DIE were enrolled. Following surgery, patients received either postoperative adjuvant therapy (GnRHa or OCs) for 6 months or expectant treatment according to a shared medical decision-making approach. The primary outcome was the postoperative recurrence of dysmenorrhea. The secondary outcomes included reproductive outcomes and drug-induced side effects. RESULTS:The generalized estimating equation analysis illustrated that the visual analog scale for dysmenorrhea was significantly higher in the adjuvant treatment group than in the expectant treatment group. Kaplan-Meier analysis and the log-rank test demonstrated that the cumulative recurrence rate was higher in the expectant treatment group than in the adjuvant treatment group, but no difference was noted between the two hormonal treatments. Similar cumulative 24-month clinical pregnancy rates were observed among the three groups. CONCLUSIONS:Compared with expectant management, postoperative medical treatment more effectively relieved symptoms and prevented the recurrence of dysmenorrhea.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Deep Brain Stimulation (DBS) of thalamus in essential tremor (ET) is effective for the treatment of contralateral tremors. Bilateral DBS controls tremors on both sides but is associated with increased morbidity and risks. We evaluated if unilateral surgery had ipsilateral benefits on tremors and thus could be a potentially safer alternative to bilateral DBS. METHODS:Medication refractory ET patients undergoing unilateral thalamic DBS were included and longitudinally followed. Tremor rating scale was used to record total motor, arm tremor and activities of daily living (ADL) scores at baseline, six months and at last visit (three or more years after surgery). Postoperative scores were recorded with DBS turned OFF and ON. RESULTS:Twenty-two patients with a mean follow-up 3.4 ± 0.14 years were enrolled. When baseline scores were compared to scores with the DBS turned ON, significant improvements were noted in total tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the contralateral side at six months and at the last visit of follow-up (all p < 0.05). Ipsilateral arm tremor (∼56%) improvements were milder compared to the contralateral side (∼73%) tremors. CONCLUSION:Unilateral thalamic DBS in ET demonstrates significant long-term benefits for ipsilateral arm tremors and can be offered to higher risk and to select patients.

背景与目标：

BACKGROUND & AIMS: :OBJECTIVE. The objective of this study was to compare image quality and clinically significant lesion detection on deep learning reconstruction (DLR) and iterative reconstruction (IR) images of submillisievert chest and abdominopelvic CT. MATERIALS AND METHODS. Our prospective multiinstitutional study included 59 adult patients (33 women, 26 men; mean age ± SD, 65 ± 12 years old; mean body mass index [weight in kilograms divided by the square of height in meters] = 27 ± 5) who underwent routine chest (n = 22; 16 women, six men) and abdominopelvic (n = 37; 17 women, 20 men) CT on a 640-MDCT scanner (Aquilion ONE, Canon Medical Systems). All patients gave written informed consent for the acquisition of low-dose (LD) CT (LDCT) after a clinically indicated standard-dose (SD) CT (SDCT). The SDCT series (120 kVp, 164-644 mA) were reconstructed with interactive reconstruction (IR) (adaptive iterative dose reduction [AIDR] 3D, Canon Medical Systems), and the LDCT (100 kVp, 120 kVp; 30-50 mA) were reconstructed with filtered back-projection (FBP), IR (AIDR 3D and forward-projected model-based iterative reconstruction solution [FIRST], Canon Medical Systems), and deep learning reconstruction (DLR) (Advanced Intelligent Clear-IQ Engine [AiCE], Canon Medical Systems). Four subspecialty-trained radiologists first read all LD image sets and then compared them side-by-side with SD AIDR 3D images in an independent, randomized, and blinded fashion. Subspecialty radiologists assessed image quality of LDCT images on a 3-point scale (1 = unacceptable, 2 = suboptimal, 3 = optimal). Descriptive statistics were obtained, and the Wilcoxon sign rank test was performed. RESULTS. Mean volume CT dose index and dose-length product for LDCT (2.1 ± 0.8 mGy, 49 ± 13mGy·cm) were lower than those for SDCT (13 ± 4.4 mGy, 567 ± 249 mGy·cm) (p < 0.0001). All 31 clinically significant abdominal lesions were seen on SD AIDR 3D and LD DLR images. Twenty-five, 18, and seven lesions were detected on LD AIDR 3D, LD FIRST, and LD FBP images, respectively. All 39 pulmonary nodules detected on SD AIDR 3D images were also noted on LD DLR images. LD DLR images were deemed acceptable for interpretation in 97% (35/37) of abdominal and 95-100% (21-22/22) of chest LDCT studies (p = 0.2-0.99). The LD FIRST, LD AIDR 3D, and LD FBP images had inferior image quality compared with SD AIDR 3D images (p < 0.0001). CONCLUSION. At submillisievert chest and abdominopelvic CT doses, DLR enables image quality and lesion detection superior to commercial IR and FBP images.

背景与目标： : 目的。这项研究的目的是比较亚毫西弗胸部和腹盆腔CT的深度学习重建 (DLR) 和迭代重建 (IR) 图像的图像质量和临床上重要的病变检测。材料和方法。我们的前瞻性多机构研究包括59名成年患者 (33名女性，26名男性; 平均年龄 ± SD，65 ± 12岁; 平均体重指数 [体重 (公斤) 除以身高 (米) 的平方] = 27 ± 5)，他们接受了常规胸部 (n = 22; 16名女性，六名男性) 和腹部骨盆 (n = 37; 17名女性，20名男性) 在640-MDCT扫描仪 (Aquilion ONE，佳能医疗系统) 上进行CT。所有患者均在临床指示的标准剂量 (SD) CT (SDCT) 后获得了低剂量 (LD) CT (LDCT) 的书面知情同意书。用交互式重建 (IR) (自适应迭代剂量减少 [AIDR] 3D，佳能医疗系统) 重建SDCT系列 (120 kVp，164-644 mA)，用滤波反投影 (FBP) 重建LDCT (100 kVp，120 kVp; 30-50 mA)，IR (AIDR 3D和基于正向投影模型的迭代重建解决方案 [第一]，佳能医疗系统) 和深度学习重建 (DLR) (高级智能Clear-IQ引擎 [AiCE]，佳能医疗系统)。四位经过专业培训的放射科医生首先读取所有LD图像集，然后以独立，随机和盲的方式将它们与SD AIDR 3D图像并排比较。亚专业放射科医生以3点比例评估LDCT图像的图像质量 (1 = 不可接受，2 = 次优，3 = 最佳)。获得描述性统计，并进行Wilcoxon符号秩检验。结果。LDCT的平均体积CT剂量指数和剂量长度乘积 (2.1 ± 0.8 mGy，49 ± 13mGy·cm) 低于SDCT的平均体积CT剂量指数和剂量长度乘积 (13 ± 4.4 mGy，567 ± 249 mGy·cm) (p <0.0001)。在SD AIDR 3D和LD DLR图像上观察到所有31个具有临床意义的腹部病变。在LD AIDR 3D，LD FIRST和LD FBP图像上分别检测到25、18和7个病变。在SD AIDR 3D图像上检测到的所有39个肺结节也在LD DLR图像上记录。LD DLR图像被认为可用于腹部97% (35/37) 和胸部LDCT研究的95-100% (21-22/22) 的解释 (p = 0.2-0.99)。LD FIRST、LD AIDR 3D和LD FBP图像与SD AIDR 3D图像相比具有较差的图像质量 (p <0.0001)。结论。在超毫西弗胸部和腹部盆腔CT剂量下，DLR使图像质量和病变检测优于商业IR和FBP图像。

BACKGROUND & AIMS: :Epilepsy is a frequent neurological disorder, although onset and progression of seizures remain difficult to predict in affected patients, irrespective of their epileptogenic condition. Previous studies in animal models as well as human epileptic brain tissue revealed a remarkably diverse pattern of gene expression implicating epigenetic changes to contribute to disease progression. Here we mapped for the first time global DNA methylation patterns in chronic epileptic rats and controls. Using methyl-CpG capture associated with massive parallel sequencing (Methyl-Seq) we report the genomic methylation signature of the chronic epileptic state. We observed a predominant increase, rather than loss of DNA methylation in chronic rat epilepsy. Aberrant methylation patterns were inversely correlated with gene expression changes using mRNA sequencing from same animals and tissue specimens. Administration of a ketogenic, high-fat, low-carbohydrate diet attenuated seizure progression and ameliorated DNA methylation mediated changes in gene expression. This is the first report of unsupervised clustering of an epigenetic mark being used in epilepsy research to separate epileptic from non-epileptic animals as well as from animals receiving anti-convulsive dietary treatment. We further discuss the potential impact of epigenetic changes as a pathogenic mechanism of epileptogenesis.

背景与目标： : 癫痫是一种常见的神经系统疾病，尽管无论发病情况如何，癫痫发作的发作和进展仍难以预测。先前在动物模型以及人类癫痫脑组织中的研究揭示了一种非常不同的基因表达模式，这些基因表达涉及表观遗传变化，从而导致疾病进展。在这里，我们首次绘制了慢性癫痫大鼠和对照组的全球DNA甲基化模式。使用与大规模平行测序 (methyl-Seq) 相关的甲基-CpG捕获，我们报告了慢性癫痫状态的基因组甲基化特征。我们观察到慢性大鼠癫痫的主要增加，而不是DNA甲基化的丧失。使用来自相同动物和组织标本的mRNA测序，异常甲基化模式与基因表达变化呈负相关。给予生酮，高脂，低碳水化合物饮食可减轻癫痫发作的进展，并改善DNA甲基化介导的基因表达变化。这是在癫痫研究中使用无监督的表观遗传标记聚类的第一份报告，该遗传标记用于将癫痫与非癫痫动物以及接受抗惊厥饮食治疗的动物分开。我们进一步讨论了表观遗传变化作为癫痫发生的致病机制的潜在影响。