EJC paediatric oncology最新文献

{"title":"Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline","authors":"Miguel Vieira Martins ,&nbsp;Anna Sofie Buhl Rasmussen ,&nbsp;Jesper Heldrup ,&nbsp;Linea Natalie Toksvang ,&nbsp;Marianne Ifversen ,&nbsp;Stine Nygaard Nielsen ,&nbsp;Kjeld Schmiegelow ,&nbsp;Inge Margriet van der Sluis","doi":"10.1016/j.ejcped.2025.100225","DOIUrl":"10.1016/j.ejcped.2025.100225","url":null,"abstract":"<div><div>Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the <em>ALLTogether1</em>. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100225"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548379","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":"Screening for childhood cancer: Several devils in the details","authors":"Logan G. Spector,&nbsp;Erin L. Marcotte","doi":"10.1016/j.ejcped.2025.100224","DOIUrl":"10.1016/j.ejcped.2025.100224","url":null,"abstract":"","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100224"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548378","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":"IGH rearrangements in Down syndrome acute lymphoblastic leukemia","authors":"Naomi Michels ,&nbsp;Jade Admiraal ,&nbsp;Aurélie Boeree ,&nbsp;Edwin Sonneveld ,&nbsp;Anthony V. Moorman ,&nbsp;Gabriele Escherich ,&nbsp;Rosemary Sutton ,&nbsp;H. Berna Beverloo ,&nbsp;Rob Pieters ,&nbsp;C. Michel Zwaan ,&nbsp;Monique L. den Boer ,&nbsp;Judith M. Boer","doi":"10.1016/j.ejcped.2025.100223","DOIUrl":"10.1016/j.ejcped.2025.100223","url":null,"abstract":"<div><h3>Background</h3><div>The <em>IGH</em> locus is susceptible to translocations or insertions that contribute to B-cell precursor acute lymphoblastic leukemia (ALL) by ectopic or enhanced expression of a gene relocated to the <em>IGH</em> enhancer. The frequency of <em>IGH</em> rearrangements is relatively high in Down syndrome (DS) ALL. <em>IGH</em> rearrangements can be cryptic and might not be detected as a chimeric transcript, hence, their frequency, partner genes and prognostic value are largely unknown.</div></div><div><h3>Methods</h3><div>We performed RNA-sequencing and <em>IGH</em> break-apart fluorescent in-situ hybridization (FISH) to determine the genetic and clinical characteristics of <em>IGH</em> rearrangements in 50 DS ALL patients.</div></div><div><h3>Results</h3><div>We identified 10 patients with a chimeric <em>IGH</em> transcript and another 22 <em>IGH-</em>rearranged patients solely by FISH. The <em>IGH</em> rearrangement was clonal (≥ 50 % of leukemic cells) in 11 cases and subclonal (10–50 % of cells) in 21 cases. Almost one-third of the subclonal <em>IGH</em> rearrangements co-occurred with known oncogenic driver aberration. The partner gene was identified in 16 cases and the most frequent partners were <em>CEBPD</em> (n = 6) and <em>CRLF2</em> (n = 4). A trend towards a worse event-free survival was seen for DS ALL patients with a clonal <em>IGH</em> rearrangement (clonal: HR 3.34, p = 0.053; subclonal: HR 1.80, p = 0.31) compared with DS ALL patients without an <em>IGH</em> rearrangement.</div></div><div><h3>Conclusion</h3><div>By combining RNA-sequencing and FISH, we identified <em>IGH</em> rearrangements in 64 % (n = 32) of DS ALL. A clonal <em>IGH</em> rearrangement (22 %) may point to an unfavorable outcome in DS ALL.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548380","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":"Non-invasive wearable devices in paediatric cancer care: Advancing personalized medicine, addressing challenges and shaping the future","authors":"Christa Koenig ,&nbsp;Roland A. Ammann ,&nbsp;Eva Brack","doi":"10.1016/j.ejcped.2025.100220","DOIUrl":"10.1016/j.ejcped.2025.100220","url":null,"abstract":"<div><div>Wearable devices (WDs) are capable of collecting large volumes of objective and clinically relevant patient data that is not yet routinely captured. This ability to collect continuous, real-time data offers a unique opportunity to gather health information in new and insightful ways. In paediatric oncology, advancement in treatment have led to significant improvements in survival rates. However, aggressive therapies often result in a range of distressing side effects, which can severely impact quality of life, and even can become life-threatening themselves. Supportive care plays a crucial role in mitigating these symptoms, aiming to prevent and manage side effects. Patient-reported outcomes should be used to guide initiation and choice of supportive care treatment whenever possible. In this context, continuous monitoring of vital signs, physical activity and other health parameters using WDs could add individual, patient specific information regarding a patient’s current condition. In this article we discuss the requirements of non-invasive WDs for their use in paediatric oncology, give an overview on possible areas of application in children with cancer and discusses challenges that must be addressed. Also we identify key research gaps and speculate on future perspectives.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100220"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471467","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":"Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome","authors":"Daniela Di Carlo ,&nbsp;Lisa Lyngsie Hjalgrim ,&nbsp;Beatrice Coppadoro ,&nbsp;Michela Casanova ,&nbsp;Andrea Ferrari ,&nbsp;Véronique Minard-Colin ,&nbsp;Hans Merks ,&nbsp;Gianni Bisogno","doi":"10.1016/j.ejcped.2025.100221","DOIUrl":"10.1016/j.ejcped.2025.100221","url":null,"abstract":"<div><h3>Introduction</h3><div>In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown that adding MC to 9 blocks of standard chemotherapy and surgery/radiotherapy improved overall survival. Following these results, MC has been incorporated into the standard of care for high-risk RMS patients. Drug doses were empirically titrated to avoid severe myelosuppression.</div><div>Aspects like treatment adherence and drug doses effectively administered may have an important impact on the survival results and deserve to be studied.</div></div><div><h3>Methods</h3><div>We analyzed 171 patients included in the RMS2005 protocol who received MC to quantify the deviation from the indications in terms of duration of maintenance and received doses and study its impact on survival.</div></div><div><h3>Results</h3><div>Considering both drugs, 101/169 (60 %) of patients received a delivered cumulative dose (DCD) of at least 80 % of the planned cumulative dose, with a median DCD of 83 % (IQR 71–96).</div><div>The median VNL and CPM relative dose intensity (RDI) was 0.88 (IQR 0.68–1).</div><div>When the DCD or RDI for VNL, CPM and VNL plus CPM are included in the univariate and multivariate Cox model, as continuous or categorical variables, the effect is not significant both on the risk of developing events or death.</div></div><div><h3>Conclusion</h3><div>The presented data about maintenance therapy suggested that dose modifications (as we registered them) did not affect event-free and overall survival.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508548","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":"European clinical practice recommendations for the diagnosis and treatment of paediatric pineal tumours","authors":"Sarita Depani ,&nbsp;Alexandre Vasiljevic ,&nbsp;Martin Mynarek ,&nbsp;Christelle Dufour ,&nbsp;Elke Pfaff ,&nbsp;Ata Ur Maaz ,&nbsp;Léa Guerrini-Rousseau ,&nbsp;Francois Doz ,&nbsp;Martin Hasselblatt ,&nbsp;Thankamma Ajithkumar ,&nbsp;Kristian Aquilina ,&nbsp;Martin U. Schuhmann ,&nbsp;Eelco Hoving ,&nbsp;Anna Tietze ,&nbsp;Ulrike Löbel ,&nbsp;Barry Pizer ,&nbsp;Katja von Hoff ,&nbsp;On behalf of the SIOP-Europe Rare Embryonal and Sarcomatous Tumours (REST) group","doi":"10.1016/j.ejcped.2025.100217","DOIUrl":"10.1016/j.ejcped.2025.100217","url":null,"abstract":"<div><div>Paediatric tumours of the pineal region are rare CNS tumours accounting for 3% of brain tumours in children and adolescents; the majority of which are germ cell tumours. This review focuses on pineal parenchymal tumours (pineoblastoma, pineal parenchymal tumour of intermediate differentiation, pineocytoma) and those specifically arising in the pineal region (papillary tumours of the pineal region, desmoplastic myxoid tumour of the pineal region, SMARCB1-mutant and pineal cyst), which together account for up to a third of pineal tumours. In recent years, the diagnostic classification of these specific tumour-types has been refined by the integration of molecular pathology. Given the differences in grade, tumour biology and clinical behaviour, an accurate integrated neuropathological diagnosis is essential in deciding an appropriate treatment strategy which can range from surgery only to intensive multi-modal therapies. The most common of these tumours in children is WHO Grade 4 pineoblastoma, where specific molecular subgroups occurring in very young patients are difficult to treat successfully. Further challenges include the anatomical position and associated surgical risk together with a lack of molecularly annotated clinical data and consequent limited evidence to guide the therapeutic approach due to their rarity. These guidelines aim to provide a framework for diagnosis, prognostication and management based on current literature and expert opinion.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593277","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":"Parental role in paediatric cancer treatment decision making at Tikur Anbessa Specialized Hospital, Ethiopia: A mixed method study","authors":"Daniel Betemariem ,&nbsp;Leul Deribe ,&nbsp;Aklil Hailu ,&nbsp;Haileyesus Adam ,&nbsp;Nataliya Berbyuk Lindström","doi":"10.1016/j.ejcped.2025.100218","DOIUrl":"10.1016/j.ejcped.2025.100218","url":null,"abstract":"<div><h3>Background</h3><div>Parental preferences for involvement in treatment decision-making (TDM) in pediatric oncology can vary among passive, collaborative, and active roles, influenced by various factors. This study investigates the parental role in TDM for children with cancer in Ethiopia and identifies the key determinants of this role.</div></div><div><h3>Methods</h3><div>This research employs a mixed-methods approach, combining a cross-sectional survey and phenomenological interviews. A total of 167 parents of children with cancer participated in the survey, utilizing the Control Preference Scale for Pediatrics (CPS-P) and the Krantz Health Opinion Survey (KHOS) to assess parental roles in TDM. Additionally, 11 in-depth interviews were conducted with selected parents. Logistic regression and thematic analysis were used to analyze the quantitative and qualitative data, respectively.</div></div><div><h3>Results</h3><div>The findings reveal that Ethiopian parents predominantly prefer a passive role in TDM. Trust in healthcare providers and parental information preferences emerged as statistically significant predictors of this passive involvement. Other factors influencing parental decision-making included the quality of the parent-provider relationship, the child’s clinical condition, parental beliefs about TDM, and knowledge of cancer.</div></div><div><h3>Conclusions</h3><div>This study offers valuable insights into the parental role in TDM within Ethiopian pediatric oncology care, an area previously unexplored. Understanding parents’ preferences in TDM is crucial for Ethiopian healthcare providers to align communication and amplify patient voices. The findings highlight the need to promote more active parental involvement in TDM by facilitating educational sessions, developing parental education guidelines, and providing accessible cancer information across diverse regions of the country.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387453","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":"Differences in care delivery for children and adolescents with cancer in Europe – Results from the SIOPE OCEAN project","authors":"Maria Otth ,&nbsp;Teresa de Rojas ,&nbsp;Kerstin K. Rauwolf ,&nbsp;Miguel Martins ,&nbsp;Uta Dirksen ,&nbsp;Delphine Heenen ,&nbsp;Lejla Kameric ,&nbsp;Pamela Kearns ,&nbsp;Ruth Ladenstein ,&nbsp;Cormac Owens ,&nbsp;Caroline Queiroz ,&nbsp;Richard Sullivan ,&nbsp;Carmelo Rizzari ,&nbsp;Gilles Vassal ,&nbsp;on behalf of the European Society of Pediatric Oncology (SIOPE)","doi":"10.1016/j.ejcped.2025.100219","DOIUrl":"10.1016/j.ejcped.2025.100219","url":null,"abstract":"<div><h3>Background</h3><div>Variations in access to high quality clinical care and research are global issues for children and adolescents with cancer. Therefore, SIOPE launched the OCEAN project (Organisation of Care and rEsearchfor children with cANcer in Europe) to map the landscape for both these domains. Here we present the clinical care part.</div></div><div><h3>Methods</h3><div>We used a mixed methods approach to map epidemiological data and self-reported care aspects. We described cancer incidence in children and adolescents aged 0–24 years. For the qualitative part, we performed a survey covering a broad range of care aspects. We used descriptive statistics to present the results.</div></div><div><h3>Results</h3><div>The cancer incidence across Europe was 15/100’000 and 26/100’000 in those aged 0–14 and 15–24 years respectively in 2022. Representatives from 37 countries responded to the survey. These countries cover 385 centres treating cancer in children and adolescents, including 18 cancer centres. Highly specialized treatment modalities and care structures are not available in every country. Public health insurances reimburse standard of care treatments in most countries (35/37); however, they do not cover all costs and additional funding is reported to be needed in up to one fifth of countries.</div></div><div><h3>Discussion</h3><div>Differences exist in many aspects of clinical care of the 37 countries, but the key aspects are delivered in all countries. We interpret that highly specialised diagnostic tools and treatment modalities must be concentrated in selected centres. A well-functioning national and international collaboration must be guaranteed to give all children and adolescents with cancer equal access to best clinical care.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100219"},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419439","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":"An assessment of circulating biomarkers and germline genetic variants in predicting chemotherapy associated mucositis in Ewing sarcoma","authors":"Pawan Gulati ,&nbsp;Vickyanne Carruthers ,&nbsp;Claire Hutton ,&nbsp;Chloe Cassidy ,&nbsp;Edward B. Amankwatia ,&nbsp;Séréna Pascual ,&nbsp;Electra Florence ,&nbsp;Tsegay G. Gebru ,&nbsp;Andrea L. Jorgensen ,&nbsp;Alastair Greystoke ,&nbsp;Guy Makin ,&nbsp;Martin G. McCabe ,&nbsp;Daniel B. Hawcutt ,&nbsp;Gareth J. Veal ,&nbsp;David Jamieson","doi":"10.1016/j.ejcped.2025.100216","DOIUrl":"10.1016/j.ejcped.2025.100216","url":null,"abstract":"<div><h3>Background</h3><div>Treatment of Ewing sarcoma is associated with severe toxicities including chemotherapy-induced mucositis. Here we investigated the role of circulating biomarkers and genetic factors in predicting mucositis severity in Ewing sarcoma.</div></div><div><h3>Methods</h3><div>Blood samples were collected from 111 Ewing sarcoma patients during treatment. Circulating total CK18 and FLT3 ligand concentrations were measured in plasma. Germline DNA was used to investigate associations between genetic variants and mucositis severity.</div></div><div><h3>Results</h3><div>An increase in median tCK18 levels was observed during cycle 1, from 189 (86−736) U/L at cycle 1 day 1 pre-chemotherapy to 311 (141–1138) U/L on cycle 1 day 2–5 (p = 0.0001). Patients experiencing a ≥ 1.3-fold increase in tCK18 at 48–120 hours after administration of the first cycle had a higher likelihood of developing grade 3 mucositis in any cycle (p = 0.044). Genetic analysis revealed an association between a gene set associated with chemotherapy induced severe mucositis and differentially expressed genes set for minor salivary gland (p = 4.12 ×10⁻⁴) and esophageal mucosa (p = 1.55 ×10⁻⁵).</div></div><div><h3>Discussion</h3><div>Early increases in circulating CK18 levels correlated with grade 3 mucositis. Genome-wide association analysis highlighted genes that may be associated with mucositis pathology, offering insights into biological mechanisms underlying susceptibility.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100216"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104304","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":"How to use monoclonal antibody-based therapy in ALL","authors":"Erica Brivio ,&nbsp;Sujith Samarasinghe","doi":"10.1016/j.ejcped.2025.100214","DOIUrl":"10.1016/j.ejcped.2025.100214","url":null,"abstract":"<div><div>Acute Lymphoblastic Leukemia (ALL) represents a significant challenge in haematology, particularly due to its aggressive nature, high relapse rates in adults and toxicity of treatment. Over the past decade, monoclonal antibody (MoAb)-based therapies have emerged as a promising approach to target specific antigens on leukemic cells, offering higher specificity, reduced toxicity, and improved response rates. This article provides an in-depth examination of the journey from laboratory research to clinical application, discussing mechanisms of action, key MoAbs used in ALL, their clinical applications, current challenges, and potential future directions in antibody-based therapy.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"5 ","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143171720","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}