Psychiatry and Clinical Neurosciences最新文献

{"title":"Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.","authors":"Xin Yang, Shuping Fang, Wenqi Lyu, Yongbo Hu, Huifang Xu, Xiao Jiang, Yurou Zhao, Yuwei Zhang, Jin Li, Weihong Kuang","doi":"10.1111/pcn.13709","DOIUrl":"10.1111/pcn.13709","url":null,"abstract":"<p><strong>Aim: </strong>Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap.</p><p><strong>Methods: </strong>We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).</p><p><strong>Results: </strong>The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.</p><p><strong>Conclusions: </strong>Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of disease-modifying therapies against Alzheimer's disease.","authors":"Takeshi Iwatsubo","doi":"10.1111/pcn.13681","DOIUrl":"10.1111/pcn.13681","url":null,"abstract":"<p><p>To successfully develop disease-modifying therapies (DMT) against Alzheimer's disease (AD), it is important to target the mild stage of the disease, before the pathological changes progress and dementia symptoms are fully manifested. To this end, the AD Neuroimaging Initiative (ADNI), a large-scale observational study, was initiated in the U.S. with the goal of development of DMT that are effective in the early stages of mild cognitive impairment (MCI) by utilizing imaging and biomarkers. In Japan, J-ADNI enrolled and followed up 537 patients, mainly with MCI, and established a platform for evaluation including amyloid PET, and demonstrated a high similarity in the clinical course of amyloid-positive MCI (prodromal AD) in Japan and the U.S. In 2023, the anti-Aβ antibody lecanemab successfully completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also, phase III trial of donanemab was completed successful. The J-TRC study was initiated in Japan as a \"trial ready cohort (TRC)\" consisting of participants who met the eligibility criteria for participation in preclinical and prodromal AD trials. Based on such a platform, the development of DMT for AD will progress more rapidly in the future.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergism of ApoE4 and systemic infectious burden is mediated by the APOE-NLRP3 axis in Alzheimer's disease.","authors":"Xue-Ting Liu, Xiu Chen, Na Zhao, Fan Geng, Meng-Meng Zhu, Qing-Guo Ren","doi":"10.1111/pcn.13704","DOIUrl":"10.1111/pcn.13704","url":null,"abstract":"<p><strong>Background: </strong>Systemic infections are associated with the development of AD, especially in individuals carrying the APOE4 genotype. However, the detailed mechanism through which APOE4 affects microglia inflammatory response remains unclear.</p><p><strong>Methods: </strong>We obtained human snRNA-seq data from the Synapse AD Knowledge Portal and assessed the DEGs between APOE3 and APOE4 isoforms in microglia. To verify the interaction between ApoE and infectious products, we used ApoE to stimulate in vitro and in vivo models in the presence or absence of LPS (or ATP). The NLRP3 gene knockout experiment was performed to demonstrate whether the APOE-NLRP3 axis was indispensable for microglia to regulate inflammation and mitochondrial autophagy. Results were evaluated by biochemical analyses and fluorescence imaging.</p><p><strong>Results: </strong>Compared with APOE3, up-regulated genes in APOE4 gene carriers were involved in pro-inflammatory responses. ApoE4-stimulation significantly increased the levels of NLRP3 inflammasomes and ROS in microglia. Moreover, compared with ApoE4 alone, the co-incubation of ApoE4 with LPS (or ATP) markedly promoted pyroptosis. Both NF-κB activation and mitochondrial autophagy dysfunction were contributed by the increased level of NLRP3 inflammasomes induced by ApoE4. Furthermore, the pathological impairment induced by ApoE4 could be reversed by NLRP3 KO.</p><p><strong>Conclusions: </strong>Our study highlights the importance of NLRP3 inflammasomes in linking ApoE4 with microglia innate immune function. These findings not only provide a molecular basis for APOE4-mediated neuroinflammatory but also reveal the potential reason for the increased risk of AD in APOE4 gene carriers after contracting infectious diseases.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.","authors":"Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi, Taisuke Yatomi, Kengo Yonezawa, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Sotaro Moriyama, Shinichiro Nakajima, Takashige Yamada, Hiroshi Morisaki, Yu Iwabuchi, Masahiro Jinzaki, Kimio Yoshimura, Tsuyoshi Eiro, Sakiko Tsugawa, Sadamitsu Ichijo, Yu Fujimoto, Tomoyuki Miyazaki, Takuya Takahashi, Hiroyuki Uchida","doi":"10.1111/pcn.13734","DOIUrl":"https://doi.org/10.1111/pcn.13734","url":null,"abstract":"<p><strong>Aim: </strong>Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.</p><p><strong>Methods: </strong>In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score.</p><p><strong>Results: </strong>Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score.</p><p><strong>Conclusion: </strong>Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and circadian disruption in bipolar disorders: From psychopathology to digital phenotyping in clinical practice.","authors":"André C Tonon, Adile Nexha, Mariana Mendonça da Silva, Fabiano A Gomes, Maria Paz Hidalgo, Benicio N Frey","doi":"10.1111/pcn.13729","DOIUrl":"https://doi.org/10.1111/pcn.13729","url":null,"abstract":"<p><p>Sleep and biological rhythms are integral to mood regulation across the lifespan, particularly in bipolar disorder (BD), where alterations in sleep phase, structure, and duration occur in all mood states. These disruptions are linked to poorer quality of life, heightened suicide risk, impaired cognitive function, and increased relapse rates. This review highlights the pathophysiology of sleep disturbances in BD and aims to consolidate understanding and clinical applications of these phenomena. It also summarizes the evolution of sleep and biological rhythms assessment methods, including ecological momentary assessment (EMA) and digital phenotyping. It underscores the importance of recognizing circadian rhythm involvement in mood regulation, suggesting potential therapeutic targets. Future research directions include elucidating circadian clock gene mechanisms, understanding environmental impacts on circadian rhythms, and investigating the bidirectional relationship between sleep disturbances and mood regulation in BD. Standardizing assessment methods and addressing privacy concerns related to EMA technology and digital phenotyping are essential for advancing research. Collaborative efforts are crucial for enhancing clinical applicability and understanding the broader implications of biological rhythms in BD diagnosis and treatment. Overall, recognizing the significance of sleep and biological rhythms in BD offers promise for improved outcomes through targeted interventions and a deeper understanding of the disorder's underlying mechanisms.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between self-reported parasomnias and psychiatric illness in 370,000 patients with sleep disorders.","authors":"Umaer Hanif, Alyssa Cairns, Vincent Mysliwiec, Ruggero G Bettinardi, Maxime Elbaz, Ulysse Gimenez, Emmanuel J M Mignot","doi":"10.1111/pcn.13723","DOIUrl":"https://doi.org/10.1111/pcn.13723","url":null,"abstract":"<p><strong>Aim: </strong>To assess self-reported parasomnias in patients with sleep disorders and explore relationships with psychiatric illness, comorbidities, subjective sleep assessments, and polysomnographic study results.</p><p><strong>Methods: </strong>Results from intake questionnaires and polysomnographic assessments, collected from 240 sleep centers across 30 US states between 2004 and 2019, were analyzed retrospectively. Of 540,000 total patients, 371,889 who answered parasomnia-specific questions were included. Patients responding \"often\" or \"always\" to parasomnia-specific questions were considered \"symptom-positive,\" whereas a \"few times\" or \"never\" were considered \"symptom-negative\" (controls).</p><p><strong>Results: </strong>The study sample was 54.5% male with mean age 54 years (range, 2-107 years). Frequencies for the different parasomnias were 16.0% for any parasomnia, 8.8% for somniloquy, 6.0% for hypnagogic hallucinations, 4.8% for sleep-related eating disorder, 2.1% for sleep paralysis, and 1.7% for somnambulism. Frequent parasomnias were highly associated with diagnosed depression (odds ratio = 2.72). All parasomnias were associated with being younger and female and with symptoms of depression, anxiety, insomnia, restless legs, pain, medical conditions, fatigue, and sleepiness. Associations with objective sleep metrics showed characteristics of consolidated sleep and differentiated weakly between nonrapid eye movement sleep and rapid eye movement sleep parasomnias. Machine learning accurately classified patients with parasomnia versus controls (balanced accuracies between 71% and 79%). Benzodiazepines, antipsychotics, and opioids increased the odds of experiencing parasomnias, while antihistamines and melatonin reduced the odds. Z-drugs were found to increase the likelihood of a sleep-related eating disorder.</p><p><strong>Conclusion: </strong>Our findings suggest that parasomnias may be clinically relevant, yet understudied, symptoms of depression and anxiety. Further investigation is needed to quantify the nature of multimorbidity, including causality and implications for diagnosis and treatment.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal dose of vortioxetine: High dose (≥20 mg) is overestimated, lower dose (5-10 mg) may be enough for many.","authors":"Yuki Furukawa","doi":"10.1111/pcn.13732","DOIUrl":"https://doi.org/10.1111/pcn.13732","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practice Guidelines for Bipolar Disorder by the JSMD (Japanese Society of Mood Disorders).","authors":"Tadafumi Kato, Kazuyoshi Ogasawara, Keisuke Motomura, Masaki Kato, Teruaki Tanaka, Yoshikazu Takaesu, Shintaro Nio, Taro Kishi, Mirai So, Kiyotaka Nemoto, Eiji Suzuki, Koichiro Watanabe, Koji Matsuo","doi":"10.1111/pcn.13724","DOIUrl":"https://doi.org/10.1111/pcn.13724","url":null,"abstract":"<p><p>The Japanese Society of Mood Disorders (JSMD) published treatment guidelines of bipolar disorder in 2011. The present guidelines incorporating new findings were developed to comply to the guidelines of the National Academy of Medicine (NAM) by utilizing systematic reviews and meta-analysis and taking patient and family opinions as well as insights from multiple professional fields into account. They support combination therapy using mood stabilizers and second-generation antipsychotics in many aspects. They also have limitations, including the grouping of mood stabilizers and second-generation antipsychotics when meta-analysis was performed despite their distinct properties, due to the scarcity of drug-specific evidence. Despite the limitations, these guidelines provide clinical decision support for psychiatrists in Japan.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homogenization of word relationships in schizophrenia: Topological analysis of cortical semantic representations.","authors":"Ryusuke Hayashi, Shizuo Kaji, Yukiko Matsumoto, Satoshi Nishida, Shinji Nishimoto, Hidehiko Takahashi","doi":"10.1111/pcn.13727","DOIUrl":"https://doi.org/10.1111/pcn.13727","url":null,"abstract":"<p><strong>Aim: </strong>Patients with schizophrenia typically exhibit symptoms of disorganized thought and display concreteness and over-inclusion in verbal reports, depending on the level of abstraction. While concreteness and over-inclusion may appear contradictory, the underlying psychopathology that explains these symptoms remains unclear. In the current study, we used functional magnetic resonance imaging with an encoding modeling approach to examine how concepts of various words, represented as brain activity, are anomalously connected at different levels of abstraction in patients with schizophrenia.</p><p><strong>Methods: </strong>Fourteen individuals diagnosed with schizophrenia and 17 healthy controls underwent functional magnetic resonance imaging to measure brain activity representing concepts of various words. We used a persistent homology (PH) method to analyze the topological structures of word representations in schizophrenia patients, healthy controls, and random data, across different levels of abstraction by varying dissimilarity scales in the representation space.</p><p><strong>Results: </strong>The results revealed that patients with schizophrenia exhibited more homogeneous word relationships across different levels of abstraction compared with healthy controls. Additionally, topological structures exhibited a shift toward a random network structure in patients with schizophrenia compared with controls. The PH method successfully distinguished semantic representations of patients with schizophrenia from those of controls.</p><p><strong>Conclusions: </strong>The current results provide an explanation for the mechanisms underlying the deficits in abstraction ability observed in schizophrenia. The isotopic connection of individual concepts reflects both the reduction of contextual connections at a semantically fine-grained scale and the absence of clear boundaries between related concepts at a coarse scale, which lead to concreteness and over-inclusion, respectively.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial treatment choices for long-term remission of chronic insomnia disorder in adults: a systematic review and network meta-analysis.","authors":"Yuki Furukawa, Masatsugu Sakata, Toshiaki A Furukawa, Orestis Efthimiou, Michael Perlis","doi":"10.1111/pcn.13730","DOIUrl":"https://doi.org/10.1111/pcn.13730","url":null,"abstract":"<p><strong>Background: </strong>We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT-I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder.</p><p><strong>Methods: </strong>We searched multiple databases to December 27, 2023. We included trials in hypnotic-free adults with chronic insomnia comparing at least two of CBT-I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long-term remission. Secondary outcomes included all-cause dropout and self-reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random-effects network meta-analyses (CRD42024505519).</p><p><strong>Findings: </strong>We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT-I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15-2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88-3.30: moderate]) and no clear difference of CBT-I against combination (1.07 [95% CI, 0.63-1.80: moderate]). CBT-I was associated with fewer dropouts than pharmacotherapy. Short-term outcomes favored CBT-I over pharmacotherapy except total sleep time. Given the average long-term remission rate in the pharmacotherapy-initiating arms of 28%, CBT-I resulted in a long-term remission rate of 41% (95% CI, 31%-53%) and combination 40% (95% CI, 25%-56%).</p><p><strong>Interpretation: </strong>The current study found that starting with CBT-I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT-I alone.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}