Neuro-oncology最新文献

{"title":"Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.","authors":"Na Luo, Wenjun Zhu, Xiaoyu Li, Min Fu, Yuanyuan Zhang, Feng Yang, Yiling Zhang, Ziqi Chen, Qiang Zhang, Bi Peng, Qianxia Li, Xin Chen, Yuanhui Liu, Guangyuan Hu, Xiaohong Peng","doi":"10.1093/neuonc/noae153","DOIUrl":"10.1093/neuonc/noae153","url":null,"abstract":"<p><strong>Background: </strong>Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI.</p><p><strong>Methods: </strong>We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier (BBB) and normal central nervous system cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using a senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence.</p><p><strong>Results: </strong>Our findings indicated that radiation-induced pericyte senescence plays a key role in BBB dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributed to the growth and invasion of glioma cells. We further demonstrated that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin could reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction.</p><p><strong>Conclusions: </strong>Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2288-2304"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.","authors":"Hyery Kim, Hee Mang Yoon, Eun Key Kim, Young Shin Ra, Hyo-Won Kim, Mi-Sun Yum, Min-Jee Kim, Jae Suk Baek, Yu Sub Sung, Sang Min Lee, Hyeong-Seok Lim, Byung Joo Lee, Hyun Taek Lim, Dohyung Kim, Jihee Yoon, Hyunwoo Bae, Soojin Hwang, Yun-Ha Choi, Kyung Ah Kim, In Hee Choi, Seung Won Lee, Su-Jung Park, Beom Hee Lee","doi":"10.1093/neuonc/noae121","DOIUrl":"10.1093/neuonc/noae121","url":null,"abstract":"<p><strong>Background: </strong>The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown.</p><p><strong>Methods: </strong>This open-label, phase II trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.</p><p><strong>Results: </strong>Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22 ± 5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P < .05). Prepubertal patients showed increases in height score and growth velocity (P < .05). Café-au-lait spot intensity decreased significantly (P < .05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation.</p><p><strong>Conclusions: </strong>Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.</p><p><strong>Trial registration: </strong>Cris.nih.go.kr Identifier (KCT0003700).</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2352-2363"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal obesogenic diet operates at the tumor cell of origin to increase incidence and decrease latency of neurofibromatosis type 1 optic pathway glioma.","authors":"Ambrose Chan, Kailong Zhang, Gemma Martin, Sabiha Bano, Jit Chatterjee, Sarvika Mahto, Avery Wang, David H Gutmann, Nicole M Brossier","doi":"10.1093/neuonc/noae136","DOIUrl":"10.1093/neuonc/noae136","url":null,"abstract":"<p><strong>Background: </strong>Pediatric low-grade glioma incidence has been rising in the United States, mirroring the rising rates of pediatric and maternal obesity. Recently, children of obese mothers were demonstrated to develop brain tumors at higher rates. Importantly, obesity in the United States is largely driven by diet, given the prevalence of high-fat and high-sugar (HFHS) food choices. Since high-fat diet exposure can increase embryonic neuroglial progenitor cell (NPC) proliferation, the potential cells of origin for a low-grade glioma, we hypothesized that in utero exposure to an obesogenic diet would modify pediatric brain penetrance and latency by affecting the tumor cell of origin.</p><p><strong>Methods: </strong>We employed several murine models of the neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, in which optic pathway gliomas (Nf1-OPGs) arise from neuroglial progenitor cells in the embryonic third ventricular zone (TVZ). We exposed dams and offspring to an obesogenic HFHS diet or control chow and analyzed fetal neurodevelopment at E19.5 and tumor formation at 6 weeks-3 months.</p><p><strong>Results: </strong>Progeny from HFHS diet-exposed dams demonstrated increased TVZ NPC proliferation and glial differentiation. Dietary switch cohorts confirmed that these effects were dependent upon maternal diet, rather than maternal weight. Obesogenic diet (Ob) similarly accelerated glioma formation in a high-penetrance Nf1-OPG strain and increased glioma penetrance in 2 low-penetrance Nf1-OPG strains. In contrast, Ob exposure in the postnatal period alone did not recapitulate these effects.</p><p><strong>Conclusions: </strong>These findings establish maternal obesogenic diet as a risk factor for murine Nf1-OPG formation, acting in part through in utero effects on the tumor cell of origin.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2339-2351"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MGMT promoter methylation and survival following chemotherapy for WHO grade 4 IDH-mutant astrocytoma.","authors":"Mary Jane Lim-Fat, Patrick Y Wen, Mehdi Touat, Vinay K Puduvalli, J Bryan Iorgulescu","doi":"10.1093/neuonc/noae157","DOIUrl":"10.1093/neuonc/noae157","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2388-2390"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMScope: A scoping review to chart the evolving clinical study landscape in brain and leptomeningeal metastasis.","authors":"Vinton W T Cheng, Richard Heywood, Rasheed Zakaria, Rebecca Burger, Kieran Zucker, Siddarth Kannan, Muhammad Alifian Remifta Putra, Amanda Fitzpatrick, Gary Doherty, Paul Sanghera, Michael D Jenkinson, Carlo Palmieri","doi":"10.1093/neuonc/noae140","DOIUrl":"10.1093/neuonc/noae140","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have challenged the notion that patients with brain metastasis (BM) or leptomeningeal metastasis (LM) should be excluded from systemic therapy clinical trials. This scoping study summarizes the BM/LM clinical studies published between 2010 and 2023.</p><p><strong>Methods: </strong>MEDLINE, CINAHL, CAB Abstracts, PsycINFO, Cochrane Library, HINARI, International Pharmaceutical Abstracts, PubMed, Scopus, Web of Science, and EMBASE electronic databases were searched on June 21, 2021. An updated search was performed on February 21, 2023. Eligible studies investigated a therapeutic intervention in solid tumor patients with BM and/or LM and reported a patient outcome. Extracted study-level data, including study type, publication date, geographical location, number of BM/LM patients in the study, primary tumor type, and type of therapeutic intervention, were collected.</p><p><strong>Results: </strong>4921 unique studies were eligible for analysis. The key finding is that BM/LM clinical research is expanding globally, both in observational studies and clinical trials. Despite the shift over time toward a higher proportion of systemic therapy trials, the majority still do not include patients with symptomatic disease and lack reporting of BM/LM-specific endpoints. Globally, there has been a trend to more international collaboration in BM/LM clinical studies.</p><p><strong>Conclusions: </strong>Our analysis of the BM/LM literature charts the evolving landscape of studies involving this previously excluded population. Given the increasing clinical research activity, particularly involving late-stage systemic therapy trials, it is imperative that due consideration is given to the intracranial activity of new investigational agents. Wider adoption of standardized reporting of intracranial-specific endpoints will facilitate the evaluation of relative intracranial efficacy.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2193-2207"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma.","authors":"Megan Montoya, Sara A Collins, Pavlina Chuntova, Trishna S Patel, Takahide Nejo, Akane Yamamichi, Noriyuki Kasahara, Hideho Okada","doi":"10.1093/neuonc/noae149","DOIUrl":"10.1093/neuonc/noae149","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could \"reprogram\" intratumoral MDSCs into antigen-presenting cells and thereby restore T-cell responses.</p><p><strong>Methods: </strong>Effects of RRV-IRF8 on survival and tumor growth kinetics were examined in the SB28 murine GBM model. The immunophenotype was analyzed by flow cytometry and gene expression assays. We assayed functional immunosuppression and antigen presentation by ex vivo T-cell-myeloid co-culture.</p><p><strong>Results: </strong>Intratumoral injection of RRV-IRF8 in mice bearing intracerebral SB28 glioma significantly suppressed tumor growth and prolonged survival. RRV-IRF8 treated tumors exhibited significant enrichment of cDC1s and CD8+ T-cells. Additionally, myeloid cells derived from RRV-IRF8 tumors showed decreased expression of the immunosuppressive markers Arg1 and IDO1 and demonstrated reduced suppression of naïve T-cell proliferation in ex vivo co-culture, compared to controls. Furthermore, DCs from RRV-IRF8 tumors showed increased antigen presentation compared to those from control tumors. In vivo treatment with azidothymidine (AZT), a viral replication inhibitor, showed that IRF8 transduction in both tumor and non-tumor cells is necessary for survival benefit, associated with a reprogrammed, cDC1- and CD8 T-cell-enriched TIME.</p><p><strong>Conclusions: </strong>Our results indicate that reprogramming of glioma-infiltrating myeloid cells by in vivo expression of IRF8 may reduce immunosuppression and enhance antigen presentation, achieving improved tumor control.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2272-2287"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.","authors":"Anthony P Y Liu, Bryan K Li, Alexandre Vasiljevic, Michael C Dewan, Benita Tamrazi, Birgit Ertl-Wagner, Jordan R Hansford, Elke Pfaff, Martin Mynarek, Ho-Keung Ng, Derek S Tsang, Nicholas G Gottardo, Amar Gajjar, Eric Bouffet, Christelle Dufour, Barry Pizer, David Schiff, Michael D Jenkinson, Giuseppe Lombardi, Patrick Y Wen, Martin J van den Bent, Annie Huang","doi":"10.1093/neuonc/noae128","DOIUrl":"10.1093/neuonc/noae128","url":null,"abstract":"<p><p>Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2159-2173"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?","authors":"","doi":"10.1093/neuonc/noae185","DOIUrl":"10.1093/neuonc/noae185","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2397"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to the letter by Wang et al.: Selumetinib for plexiform neurofibroma: Advances and ongoing challenges.","authors":"Beom Hee Lee, Hyery Kim, Hee Mang Yoon","doi":"10.1093/neuonc/noae181","DOIUrl":"10.1093/neuonc/noae181","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2394"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing prognostication and treatment response evaluation in primary CNS lymphoma with 18F-FDG-PET/CT.","authors":"Minyoung Oh, Hyungwoo Cho, Ji Eun Park, Ho Sung Kim, Heounjeong Go, Chan-Sik Park, Sang-Wook Lee, Sang Woo Song, Young-Hoon Kim, Young Hyun Cho, Seok Ho Hong, Jeong Hoon Kim, Dong Yun Lee, Jin-Sook Ryu, Dok Hyun Yoon, Jae Seung Kim","doi":"10.1093/neuonc/noae146","DOIUrl":"10.1093/neuonc/noae146","url":null,"abstract":"<p><strong>Background: </strong>The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG).</p><p><strong>Results: </strong>The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% CI: 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI: 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥ 17.0 cm3 had significantly shorter OS (12.5 vs 74.0 months, P = .011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs 46.0 months, P = .001) and OS (median: 21.0 vs 62.0 months, P = .002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (P = .130) or OS (P = .540).</p><p><strong>Conclusion: </strong>Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2377-2387"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}