Journal of Huntington's disease最新文献

{"title":"Lack of Evidence for Kynurenine Pathway Dysfunction in Huntington's Disease: CSF and Plasma Analyses from the HDClarity Study.","authors":"Vinod Khetarpal, Todd Herbst, Celia Dominguez, Ignacio Munoz-Sanjuan, Cristina Sampaio, Bryan Marks, Dennis L Miller, James Farnham, Aaron Ledvina, Hannah Anglehart, Imran Rehmani, Amber LaFayette, Natasha Spridco, Douglas Langbehn, Edward J Wild, Robert Pacifici","doi":"10.1177/18796397241301761","DOIUrl":"10.1177/18796397241301761","url":null,"abstract":"<p><strong>Background: </strong>Evidence from animal studies and post-mortem studies of brains from people with Huntington's disease (PwHD) has suggested that the kynurenine pathway (KP) may be dysregulated in Huntington's disease (HD).</p><p><strong>Objective: </strong>To determine whether there are differences in KP metabolites in the CSF and plasma of PwHD versus healthy controls enrolled in the HDClarity study.</p><p><strong>Methods: </strong>CSF and plasma samples from 141 PwHD with mild and moderate manifest disease and 75 healthy controls were analyzed for 3-hydroxykynurenine (3-OH-KYN), quinolinic acid, kynurenine, anthranilic acid, kynurenic acid, and tryptophan concentrations using validated high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. The primary and secondary endpoints compared metabolite concentrations between groups, and an exploratory analysis (PwHD only) evaluated the association between the metabolite levels and severity of disease.</p><p><strong>Results: </strong>No significant differences in CSF or plasma concentrations of any of the six KP metabolites were observed between PwHD and controls, and there were no strong associations between the concentration of any KP metabolite and disease severity. A principal component analysis of the combined CSF and plasma measures showed a substantial positive correlation among all metabolites except for tryptophan in plasma.</p><p><strong>Conclusions: </strong>We found no evidence to support the hypothesis of dysregulation of KP metabolites in HD based on CSF and plasma metabolite levels. The monitoring of KP metabolites in CSF or plasma is unlikely to serve as a pharmacodynamic biomarker for disease progression or therapeutic intervention in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"85-92"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of neurofilament light chain in Huntington's disease like 2 and Huntington's disease.","authors":"David G Anderson, Aline Ferreira-Correia, Filipe B Rodrigues, Lauren M Byrne, Edward J Wild, Amanda Krause","doi":"10.1177/18796397241300141","DOIUrl":"10.1177/18796397241300141","url":null,"abstract":"<p><p>Huntington's disease-like 2 (HDL2) closely resembles Huntington's disease (HD) in clinical and pathological features. Neurofilament light chain (NfL) is an important biomarker in HD research and holds potential in HDL2. To evaluate NfL's utility in HDL2, a comparative analysis among HDL2 (n = 12), HD (n = 9), and unaffected controls (n = 9) was conducted. Employing a cross-sectional design, NfL levels were assessed in blood plasma. Concentrations were notably elevated in both HD and HDL2 groups compared to controls. HD patients displayed higher NfL levels than HDL2, possibly reflecting disease duration differences. NfL effectively distinguished HDL2 from controls, highlighting its promise as a possible biomarker in HDL2 research.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"103-108"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458211","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":"Acceptance and commitment therapy with Huntington's disease: A narrative review and case report of a caregiver-assisted intervention.","authors":"Simone H Schriger, Chelsi N Nurse, C Virginia O'Hayer","doi":"10.1177/18796397251315162","DOIUrl":"10.1177/18796397251315162","url":null,"abstract":"<p><p>Acceptance and commitment therapy (ACT) is an experiential, action-oriented talk therapy that emphasizes acceptance of painful inner experience through increased psychological flexibility. In this narrative review and case report, we first review the extant literature on applications of ACT to patients with a variety of mental and physical health challenges, including neurodegenerative disorders, and their caregivers. We then discuss applications of ACT to Huntington's disease (HD). We provide a case report of a 52-year-old man living with HD who, accompanied by his caregiver, received a virtually-delivered 6-session ACT intervention. We measured the patient's self-reported symptoms of depression (PHQ-9) and anxiety (GAD-7) as well as his health-related quality of life (HDQoL) and level of cognitive fusion (i.e., being attached to his thoughts; CFQ-13) at baseline and following the intervention. At follow-up, the patient had a clinically significant reduction in depressive symptoms (from moderate to mild symptomatology) and cognitive fusion. Further, the patient had improvements in quality of life across the domains of physical functioning, mood, and worries. The promising outcomes of this case, as well as extant literature on the effectiveness of ACT in supporting individuals with similar neurodegenerative disorders, suggests that ACT may hold promise as a scalable and impactful intervention for individuals living with HD and their caregivers. We conclude with a call for further study of ACT with this population to build a more robust evidence base that can be used to benefit individuals living with HD and their caregivers.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"3-15"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458301","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":"Are people living with Huntington's disease experiencing person-centered integrated care?","authors":"Sandra Bartolomeu Pires, Dorit Kunkel, Nicholas Goodwin, Sally Dace, David Culliford, Christopher Kipps, Mari Carmen Portillo","doi":"10.1177/18796397241288449","DOIUrl":"https://doi.org/10.1177/18796397241288449","url":null,"abstract":"<p><p><b>Background:</b> Huntington's disease (HD) is among the most complex long-term neurological conditions, necessitating care and management from multiple partners within and beyond the health sector. However, there is a paucity of evidence describing how individuals receive this multifaceted care and whether current care provision adequately meets their needs. <b>Objective:</b> To understand if current care provision is meeting the complex needs of people living with HD in England and assess their perceived need for integrated care. <b>Methods:</b> A cross-sectional survey was co-designed with patient and public representatives, as part of a mixed-methods study to explore what integrated care means for people living with HD. The survey was distributed online and via charities, collecting quantitative and qualitative data. Descriptive statistics and content analysis were performed. <b>Results:</b> A total of 153 people, from 45 counties in England, participated in the survey. When assessing person-centered coordinated care, 65% of respondents rated their care as very poor, poor, or expressed a neutral opinion; carers reported the lowest scores. Although 58% of the participants said it was extremely important to have a care coordinator, only 19% of people reported having one, with these coordinators being identified in only 40% of the counties. Nevertheless, people with access to a care coordinator reported markedly improved care experiences. <b>Conclusions:</b> People living with HD commonly report fragmented care, geographical inequalities in care access, and unmet complex needs. Future research should focus on developing an HD integrated care model tailored to address these complex needs, including an evaluation of the cost-effectiveness of an HD care coordinator.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"535-546"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458149","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":"Sleep-wake cycle and 24-h motor activity in early-mid Huntington's disease patients: An actigraphy-based study.","authors":"Cesa Scaglione, Maria Vitiello, Lorenzo Tonetti, Sara Giovagnoli, Giorgio Barletta, Giovanna Calandra-Buonaura, Pietro Guaraldi, Felice Di Laudo, Vincenzo Natale, Federica Provini","doi":"10.1177/18796397241287227","DOIUrl":"https://doi.org/10.1177/18796397241287227","url":null,"abstract":"<p><p><b>Background:</b> Disrupted 24-h sleep-wake and rest-activity cycles are known common features in Huntington's disease (HD) patients; however, critical periods during the 24-h cycle have been less studied. <b>Objective:</b> To analyze the differences between early-mid stage HD patients and healthy controls (HC) in sleep patterns and 24-h motor activity by using actigraphic monitoring. <b>Methods:</b> Twenty HD patients (13 females; mean age ± SD 56.45 ± 16.94) at early-mid stage of the disease and 20 HC were actigraphically monitored for a week. We applied the Functional Linear Modeling (FLM) to analyze motor activity from the actigraphic data. We analyzed parameters regarding both the time spent in bed and out of bed; get-up time (GUT); time in bed (TIB); midpoint of sleep (MS); sleep motor activity (SMA); sleep onset latency (SOL); total sleep time (TST); wake after sleep onset (WASO); sleep efficiency (SE); number and duration of awakenings (AWK); diurnal motor activity (DMA) and diurnal total sleep time (DTST). <b>Results:</b> Ten patients were in Stage I, 6 in Stage II and 4 in Stage III. HD patients presented lower SE and higher TIB, SOL, WASO, AWK and AWK > 5 min in comparison to HC. Moreover, higher motor activity was observed in patients with HD, in particular between 2:15 and 4:00 am, from around 40 min prior to bedtime until 20 min after bedtime, and from around 20 min prior to get-up time until 50 min after get-up time. <b>Conclusions:</b> Actigraphy documented a specific 24-h motor pattern in HD, potentially constituting a disease signature.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"501-509"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458184","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":"Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington's Disease: Data from the TRACK and ENROLL HD Cohorts.","authors":"Sarah M Gray, Jing Dai, Anne C Smith, Jacob T Beckley, Negah Rahmati, Michael C Lewis, Michael C Quirk","doi":"10.3233/JHD-240030","DOIUrl":"10.3233/JHD-240030","url":null,"abstract":"<p><strong>Background: </strong>There is evidence for dysregulated cholesterol homeostasis in Huntington's disease (HD). The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-OHC) is decreased in manifest HD. 24(S)-OHC is an endogenous positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor, suggesting lower 24(S)-OHC may contribute to NMDA receptor hypofunction in HD. We hypothesized changes in 24(S)-OHC would be associated with cognitive impairment in early HD.</p><p><strong>Objective: </strong>To determine the interactions between oxysterols (24(S)-OHC, 25-OHC, and 27-OHC) at the NMDA receptor, the plasma levels of these oxysterols, and how these levels relate to cognitive performance.</p><p><strong>Methods: </strong>An <i>in vitro</i> competition assay was used to evaluate interactions at the NMDA receptor, liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) was used to measure plasma 24(S)-OHC, 25-OHC, and 27-OHC levels, and correlation analyses investigated their relationship to performance on cognitive endpoints in TRACK and ENROLL-HD (NCT01574053).</p><p><strong>Results: </strong><i>In vitro</i>, 25-OHC and 27-OHC attenuated the PAM activity of 24(S)-OHC on the NMDA receptor. Lower plasma 24(S)-OHC levels and 24(S)/25-OHC ratios were detected in participants with early HD. Moderate and consistent associations were detected between plasma 24(S)/25-OHC ratio and performance on Stroop color naming, symbol digit modality, Trails A/B, and emotion recognition. Little association was observed between the ratio and psychiatric or motor endpoints, suggesting specificity for the relationship to cognitive performance.</p><p><strong>Conclusions: </strong>Our findings support growing evidence for dysregulated CNS cholesterol homeostasis in HD, demonstrate a relationship between changes in oxysterols and cognitive performance in HD, and propose that NMDA receptor hypofunction may contribute to cognitive impairment in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"449-465"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289159","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":"Mortality trends and disparities in adults with Huntington's disease in the United States.","authors":"Humza Saeed, Abdullah, Hira Hameed, Hafiz Mohammad Maaz, Abdul Wasay, Zubair Amin, Muhammad Khubaib Arshad, Hritvik Jain, Aman Goyal","doi":"10.1177/18796397241287399","DOIUrl":"https://doi.org/10.1177/18796397241287399","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD), an autosomal dominant disorder, is characterized by progressive neurodegeneration, psychiatric issues, dementia, and worsening chorea over time. Its prevalence varies by ethnicity and region.</p><p><strong>Objective: </strong>This study aims to analyze mortality trends and disparities in adults with HD in the United States (US).</p><p><strong>Methods: </strong>This study analyzed death certificates from 1999 to 2020 for deaths due to HD (ICD-10 code G10) in individuals aged 25 and older. Age-adjusted mortality rates (AAMRs) and annual percent change (APC) were calculated by year, gender, age groups, race/ethnicity, geographics and urbanization status.</p><p><strong>Results: </strong>Between 1999 and 2020, there were 24,121 reported deaths among patients with HD. During this period, the AAMR increased from 4.3 to 6.0 per 1,000,000 population, with a notable surge from 2018 to 2020 (APC: 9.88; 95% CI: 5.45 to 13.20). Older adults exhibited the highest AAMRs at 10.4 per 1,000,000 when analyzed by age-group. Men and women had comparable AAMRs (5.2 vs. 5.0). By race, non-Hispanic (NH) Whites had the highest AAMRs (6.0), followed by NH African Americans (3.3) and Hispanics (2.8). Additionally, non-metropolitan areas experienced higher AAMRs compared to metropolitan areas (6.6 vs. 4.8).</p><p><strong>Conclusions: </strong>Since 1999, mortality from HD has increased, particularly from 2018 to 2020, with higher rates in older adults, men, NH Whites, and non-metropolitan areas. Further research is essential to consolidate data, standardize reporting practices, and address disparities to improve outcomes.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"491-500"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458168","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":"Study protocol for the iMarkHD study in individuals with Huntington's disease.","authors":"Daniel J van Wamelen, Naomi H Martin, Orsolya Makos, James Badenoch, Jose Manuel Valera-Bermejo, Monika Hartmann, Alay Rangel Cristales, Tobias C Wood, Mattia Veronese, Manuela Moretto, Fernando Zelaya, Flavio dell'Acqua, Owen O'Daly, David J Lythgoe, Cedric Ginestet, Federico Turkheimer, Nikki Palasits, Ladislav Mrzljak, John H Warner, Eugenii A Rabiner, Roger Gunn, Sarah J Tabrizi, Cristina Sampaio, Andrew Wood, Steven Cr Williams","doi":"10.1177/18796397241288165","DOIUrl":"https://doi.org/10.1177/18796397241288165","url":null,"abstract":"<p><p><b>Background:</b> Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the <i>huntingtin</i> gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. <b>Objective:</b> In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. <b>Methods:</b> Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. <b>Results:</b> Recruitment is currently active and started in September 2022. <b>Conclusions:</b> By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"479-489"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458215","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":"Exploring relationships among gait, balance, and physical activity in individuals with Huntington's disease.","authors":"Lauren E Tueth, Allison M Haussler, Sidney T Baudendistel, Gammon M Earhart","doi":"10.1177/18796397241285000","DOIUrl":"10.1177/18796397241285000","url":null,"abstract":"<p><strong>Background: </strong>Individuals with Huntington's disease (HD) experience a variety of motor and non-motor symptoms, but little is known about how these symptoms are related to one another. It is important to characterize the deficits present and explore the relationships among these symptoms in order to provide high quality clinical care.</p><p><strong>Objective: </strong>The purpose of this study was to characterize gait, balance, and physical activity level in individuals with HD and explore the relationships among motor and non-motor symptoms.</p><p><strong>Methods: </strong>Individuals completed one lab visit and wore a sensor for seven days to capture physical activity level. During the lab visit, gait, balance, and cognitive status were assessed using validated measures. A 2 × 2 ANOVA (Group×Condition) was used to assess differences in gait between individuals with HD vs. controls, while t-tests were used for other clinical measures. Correlations as well as a mixed effects model explored relationships among clinical measures in the HD group.</p><p><strong>Results: </strong>Individuals with HD walk significantly slower and have significantly worse balance than controls. Gait velocity and balance were significantly correlated with cognitive status in individuals with HD. Additionally, balance performance and balance confidence were not significantly correlated, indicating that there may be a lack of self-awareness of deficits present in individuals with HD. In-lab measures were not significant predictors of physical activity.</p><p><strong>Conclusions: </strong>Motor impairments in individuals with HD are correlated with cognitive impairment. Clinicians should be aware of the impact of cognitive impairment when selecting interventions to address motor symptoms in individuals with HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"557-568"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458162","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":"Huntington's Disease Clinical Trials Update: September 2024.","authors":"Mena Farag, Sarah J Tabrizi, Edward J Wild","doi":"10.1177/18796397241293955","DOIUrl":"https://doi.org/10.1177/18796397241293955","url":null,"abstract":"<p><p>In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"409-418"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458165","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}