Brain tumor research and treatment最新文献

{"title":"Excessively Delayed Radiation Changes After Proton Beam Therapy for Brain Tumors: Report of Two Cases.","authors":"Jeongmin Han, Seong Wook Lee, Na Young Han, Ho-Shin Gwak","doi":"10.14791/btrt.2024.0017","DOIUrl":"10.14791/btrt.2024.0017","url":null,"abstract":"<p><p>Delayed cerebral necrosis is a well-known complication of radiation therapy (RT). Because of its irreversible nature, it should be avoided if possible, but avoidance occurs at the expense of potentially compromised tumor control, despite the use of the modern advanced technique of conformal RT that minimizes radiation to normal brain tissue. Risk factors for radiation-induced cerebral necrosis include a higher dose per fraction, larger treatment volume, higher cumulative dose, and shorter time interval (for re-irradiation). The same principle can be applied to proton beam therapy (PBT) to avoid delayed cerebral necrosis. However, conversion of PBT radiation energy into conventional RT is still short of clinical support, compared to conventional RT. Herein, we describe two patients with excessively delayed cerebral necrosis after PBT, in whom follow-up MRI showed no RT-induced changes prior to 3 years after treatment. One patient developed radiation necrosis at 4 years after PBT to the resection cavity of an astroblastoma, and the other developed brainstem necrosis that became symptomatic 6 months after its first appearance on the 3-year follow-up brain MRI. We also discuss possible differences between radiation changes after PBT versus conventional RT.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 2","pages":"141-147"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917517","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":"Spontaneous Regression of a Large Vestibular Schwannoma: Is Nonoperative Management Reasonable?","authors":"Kok Ann Colin Teo, Rachit Agrwal, Pin Lin Kei, Su Lone Lim, Siyang Ira Sun, Shiong Wen Low","doi":"10.14791/btrt.2024.0008","DOIUrl":"10.14791/btrt.2024.0008","url":null,"abstract":"<p><p>Vestibular schwannomas (VSs) are the most common cerebellopontine tumors. The natural history of smaller-sized VSs (<30 mm) has been well-studied, leading to the recommendation of a \"watch and wait\" approach. However, large VSs (>30 mm) have not been extensively studied, mainly because of their rarity. As such, most patients are conventionally offered surgery which carries a significant risk of neurological morbidity. Here, we report a case of a giant VS (>40 mm) in a 30-year-old man who regressed spontaneously. He was lost to follow-up for 18 years and, upon re-presentation, the symptomatology drastically improved and repeat imaging demonstrated a marked reduction in tumor size. Referring to similar cases in other studies, we postulate that most large and giant VSs undergo a phase of growth and stasis, followed by regression due to shifts in the balance between tumorigenic and regressive factors. Taken together with emerging molecular data, further studies are required to better understand the history of large and giant VSs to shape more personalized treatment options. This potentially includes non-operative management as a tenable option.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 2","pages":"125-131"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917547","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":"Application of a Standardized Treatment Paradigm as a Strategy to Achieve Optimal Onco-Functional Balance in Glioma Surgery.","authors":"Chin Hong Ngai, Colin Teo, Jen Yinn Foo, Sheng Lim, Jia Qian Sophie Koh, Hui-Minn Chan, Ne-Hooi Will Loh, Kejia Teo","doi":"10.14791/btrt.2024.0011","DOIUrl":"10.14791/btrt.2024.0011","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, characterized by their invasive persistence and tendency to affect critical brain regions, pose a challenge in surgical resection due to the risk of neurological deficits. This study focuses on a personalized approach to achieving an optimal onco-functional balance in glioma resections, emphasizing maximal tumor removal while preserving the quality of life.</p><p><strong>Methods: </strong>A retrospective analysis of 57 awake surgical resections of gliomas at the National University Hospital, Singapore, was conducted. The inclusion criteria were based on diagnosis, functional boundaries determined by direct electrical stimulation, preoperative Karnofsky Performance Status score, and absence of multifocal disease on MRI. The treatment approach included comprehensive neuropsychological evaluation, determination of suitability for awake surgery, and standard asleep-awake-asleep anesthesia protocol. Tumor resection techniques and postoperative care were systematically followed.</p><p><strong>Results: </strong>The study included 53 patients (55.5% male, average age 39 years), predominantly right-handed. Over half reported seizures as their chief complaint. Tumors were mostly low-grade gliomas. Positive mapping of the primary motor cortex was conducted in all cases, with awake surgery completed in 77.2% of cases. New neurological deficits were observed in 26.3% of patients at 1 month after operation; most showed significant improvement at 6 months.</p><p><strong>Conclusion: </strong>The standardized treatment paradigm effectively achieved an optimal onco-functional balance in glioma patients. While some patients experienced neurological deficits postoperatively, the majority recovered to their preoperative baseline within 3 months. The approach prioritizes patient empowerment and customized utilization of functional mapping techniques, considering the challenge of preserving diverse languages in a multilingual patient population.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 2","pages":"100-108"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917512","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":"Awake Surgery for Angiocentric Glioma in the Eloquent Area in an Adolescent: A Case Report.","authors":"Yuma Yano, Ryosuke Matsuda, Fumi Okada, Maiko Takeda, Ryosuke Maeoka, Ichiro Nakgawa","doi":"10.14791/btrt.2023.0044","DOIUrl":"10.14791/btrt.2023.0044","url":null,"abstract":"<p><p>Angiocentric glioma (AG) is an extremely rare tumor that often develops in adolescents. Awake surgery for AG occurring in the eloquent area has not been reported to date. We report a case involving a right-handed 15-year-old boy with AG. He presented with a first-time generalized tonic-clonic seizure and was rushed to the local hospital. CT of the head indicated a left frontal low-density mass with no calcification. He was subsequently referred to our hospital. Comparison with a CT scan obtained two years prior due to mild head trauma indicated that the lesion showed a trend toward enlargement. The lesion was located in the anterior and lateral portions of the primary motor cortex, and MRI showed homogenous hypointensity on T1-weighted and hyperintensity on T2-weighted images. Contrast-enhanced MRI showed a linear contrast effect. The patient underwent awake surgery with successful intraoperative brain mapping and total resection, and brain function was preserved. Pathological analysis revealed AG. He returned to his normal life and has shown no recurrence without additional treatment for 2 years. Thus, awake surgery for complete tumor resection while preserving brain function is effective and safe even in adolescents with AGs.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"75-79"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693660","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":"Lynch Syndrome-Associated Glioblastoma Treated With Concomitant Chemoradiotherapy and Immune Checkpoint Inhibitors: Case Report and Review of Literature.","authors":"Kenta Nakase, Ryosuke Matsuda, Shoh Sasaki, Ichiro Nakagawa","doi":"10.14791/btrt.2023.0042","DOIUrl":"10.14791/btrt.2023.0042","url":null,"abstract":"<p><p>Lynch syndrome (LS) is an autosomal dominant disorder caused by mutations in mismatch repair (MMR) genes and is also known to be associated with glioblastomas. The efficacy of immunotherapy for LS-associated glioblastomas remains unknown. Herein, we report a rare case of LS-associated glioblastoma, treated with chemotherapy using immune checkpoint inhibitors (ICI). A 41-year-old female patient presented with headaches and sensory disturbances in the right upper limb for 6 weeks. She had been treated for rectal cancer and had a family history of LS. MRI revealed two ring-enhancing lesions in the left precentral gyrus. She underwent subtotal resection, leading to a pathological diagnosis of isocitrate dehydrogenase wild-type glioblastoma. She received daily administration of (temozolomide, 75 mg/m²) and concurrent radiotherapy (60 Gy) postoperatively. However, the tumor recurred 1 year after the initial treatment. A molecular genetic study showed high microsatellite instability (MSI), and she was treated with pembrolizumab therapy. Disease progression occurred despite six cycles of pembrolizumab therapy and radiotherapy at the dose of 40 Gy. She died due to glioblastoma progression 19 months after the initial treatment. The present case demonstrates that some LS-associated glioblastomas may be resistant to ICI despite high MSI, possibly because of intratumor heterogeneity related to MMR deficiency.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"70-74"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693666","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":"Comprehensive Molecular Genetic Analysis in Glioma Patients by Next Generation Sequencing.","authors":"Taeeun Kim, Ahwon Lee, Stephan Ahn, Jae Sung Park, Sin Soo Jeun, Youn Soo Lee","doi":"10.14791/btrt.2023.0036","DOIUrl":"10.14791/btrt.2023.0036","url":null,"abstract":"<p><strong>Background: </strong>Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies.</p><p><strong>Methods: </strong>We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools.</p><p><strong>Results: </strong>A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials.</p><p><strong>Conclusion: </strong>We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"23-39"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693664","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":"Temporal Analysis of Postoperative Outcomes With or Without Intraoperative Motor Evoked Potentials and Somatosensory Evoked Potentials Monitoring for Intracranial Meningioma Surgery.","authors":"Na Il Shin, Hye Jin Hong, Young Il Kim, Il Sup Kim, Jae Hoon Sung, Sang Won Lee, Seung Ho Yang","doi":"10.14791/btrt.2023.0050","DOIUrl":"10.14791/btrt.2023.0050","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution.</p><p><strong>Methods: </strong>Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups.</p><p><strong>Results: </strong>In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality.</p><p><strong>Conclusion: </strong>Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"50-57"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693579","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":"Suggestion of Follow-Up Period in Nonfunctioning Pituitary Incidentaloma Based on MRI Characteristics.","authors":"Hyunchul Jung, Seung-Yeob Yang, Keun-Tae Cho","doi":"10.14791/btrt.2023.0046","DOIUrl":"10.14791/btrt.2023.0046","url":null,"abstract":"<p><strong>Background: </strong>For patients diagnosed with asymptomatic, non-functional pituitary incidentaloma (PI), periodic follow-up is generally proposed. However, the recommended follow-up period differs among existing guidelines and consensus is lacking. Thus, this study aimed to suggest follow-up periods for PI based on MRI characteristics.</p><p><strong>Methods: </strong>Between 2007 and 2023, 245 patients who were diagnosed with PI were retrospectively assessed. Their mean clinical and neuroradiological follow-up periods were 74.2 and 27.3 months, respectively. Their baseline clinical and neuroradiological characteristics were analyzed. These 245 patients were divided into two groups: those with PI size progression and those without PI size progression. Additionally, neuroradiological features of each group were analyzed according to presumptive diagnoses of PI.</p><p><strong>Results: </strong>PI size increased in 33 of 245 patients. For the remaining 212 patients, PI size decreased or stayed unchanged. Of the 33 patients with PI size progression, ten underwent surgery. Stalk deviation (<i>p</i><0.001) and lesion enhancement (<i>p</i>=0.001) were significantly more observed in those with PI size progression than in those without PI size progression. MRI morphological factors were not related to changes in PI size in the presumptive Rathke's cleft cyst group. In the presumptive pituitary adenoma group, absence of tumor enhancement (<i>p</i><0.001) and stalk deviation (<i>p</i><0.001) were significantly associated with tumor reduction and progression, respectively.</p><p><strong>Conclusion: </strong>Our findings support an additional guideline for patients with asymptomatic non-functional PI without stalk deviation and enhancement. For these patients, the clinical and neuroradiological follow-up periods could be reduced.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"40-49"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693668","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":"Clinical Practice Guidelines for Brain Metastasis From Solid Tumors.","authors":"Kyoung Su Sung","doi":"10.14791/btrt.2023.0049","DOIUrl":"10.14791/btrt.2023.0049","url":null,"abstract":"<p><p>With advancements in systemic cancer therapies, the incidence and diagnosis of brain metastases (BMs) have increased, necessitating updated clinical practice guidelines. There also were developments in neurosurgical and radiotherapeutic modalities for intracranial lesions, as well as advances in immune and targeted therapies for BMs of systemic cancers. Recently, the ASCO-SNO-ASTRO and EANO-ESMO have published clinical guidelines for BMs from solid tumors. The ASCO-SNO-ASTRO guidelines, published in 2021, underwent a systematic literature review and critical evaluation by their Expert Panel, addressing the key questions in various therapies such as surgery, radiotherapy, and systemic therapy for the recommendations. Similarly, the EANO-ESMO guidelines, also published in 2021, involved a selection of relevant literature by expert authors, with final references confirmed through consensus, focusing on prevention, diagnosis, therapy, and follow-up. This review aims to provide an overview of the recent clinical practice guidelines for BMs from solid tumors, based on these two recently developed guidelines.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"14-22"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693663","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":"Intracranial Involvement of Systemic Hodgkin Lymphoma: A Case Report and Literature Review.","authors":"Hwanhee Lee, Sangjun Ahn, Seung Heon Cha, Won Ho Cho","doi":"10.14791/btrt.2023.0041","DOIUrl":"10.14791/btrt.2023.0041","url":null,"abstract":"<p><p>A 27-year-old male patient, previously diagnosed with Hodgkin lymphoma (HL), presented with gait disturbance. Brain MRI showed a 4.5 cm mass lesion in the right occipital lobe, suggesting either intracranial involvement of HL or a potential meningioma. Despite high-dose methotrexate and steroid treatment, the patient's symptoms persisted, and imaging showed an enlarging mass, leading to surgical intervention. Histopathological examination confirmed central nervous system (CNS) involvement of HL. Postoperatively, the patient underwent whole-brain radiotherapy and demonstrated marked clinical improvement. Our literature review from 1980 to 2023 identified only 46 cases of intracranial HL (IC-HL), underscoring its rarity. Lymphomas represent 2.2% of brain tumors, with 90%-95% being diffuse large B-cell lymphoma (DLBCL). In contrast, the incidence of CNS-HL patients is a mere 0.02%. Notably, IC-HL and intracranial DLBCL have differences in their typical locations and treatment strategies. Unlike DLBCL, which predominantly appears in the supratentorial region (87%), IC-HL is found there in 61.5% of cases. Additionally, 33.3% of IC-HL cases occur in the cerebellum, with 43.5% associated with posterior circulation regions. Furthermore, while biopsy followed by chemotherapy induction is a common strategy for DLBCL, 81.8% of IC-HL cases underwent surgical resection, and only 18.1% had a biopsy alone. The distinct characteristics of IC-HL tumors, including their larger size, attachment to the dura, and fibrotic nature with clear boundaries, might account for the preference for surgical intervention. The unique features of IC-HL compared to DLBCL highlight the need for distinct considerations in diagnosis and management.</p>","PeriodicalId":72453,"journal":{"name":"Brain tumor research and treatment","volume":"12 1","pages":"63-69"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693665","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}