BMJ oncology最新文献

{"title":"Sintilimab plus bevacizumab followed by resection in intermediate-stage hepatocellular carcinoma: a phase Ib clinical trial with biomarker analysis.","authors":"Hui-Chuan Sun, Xiao-Dong Zhu, Zi-Yi Wang, Qiang Gao, Yuan Ji, Ying-Hong Shi, Xiao-Ying Wang, Shuang-Jian Qiu, Cheng Huang, Ying-Hao Shen, Jian Zhou, Jia Fan","doi":"10.1136/bmjonc-2024-000578","DOIUrl":"10.1136/bmjonc-2024-000578","url":null,"abstract":"<p><strong>Objective: </strong>This phase Ib trial aimed to assess the safety and efficacy of sintilimab plus bevacizumab (sintilimab/bev), followed by resection in patients with potentially resectable intermediate-stage hepatocellular carcinoma (HCC) and explore the clinical implications of circulating tumour DNA (ctDNA) and T cell receptor (TCR) repertoire.</p><p><strong>Methods and analysis: </strong>Eligible patients with intermediate-stage HCC received sintilimab/bev treatment. Patients with partial response or stable disease for at least two consecutive evaluations and technically resectable received hepatectomy. Postoperatively patients continued to receive sintilimab/bev until tumour recurrence or intolerable toxicities for up to 12 months. The primary endpoints were treatment safety and event-free survival (EFS). Plasma ctDNA measurements and TCR repertoire were analysed.</p><p><strong>Results: </strong>30 patients were enrolled. 17 (56.7%) patients received liver resection. Grade 3 treatment-related adverse events occurred in seven patients (23.3%). No grade 4/5 AE or postoperative mortality was observed. The median EFS of the 30 patients was 16.3 months (95% CI 13.4 to 19.2). The 12-month and 24-month survival rates were 93.2% and 82.0%, respectively. Of the 17 patients who received hepatectomy, the median recurrence-free survival was 14.1 months (95% CI 8.9 to 19.4). A lower ctDNA measurement and higher TCR repertoire were associated with better tumour response or patients' survival.</p><p><strong>Conclusions: </strong>The study suggested systemic therapy with sintilimab/bev was safe and effective in patients with intermediate-stage HCC, and resection in selected patients was associated with improved survival. ctDNA measurement and TCR repertoire may help identify patients who may benefit from sintilimab/bev treatment and patients with a higher risk of tumour recurrence.</p><p><strong>Trial registration number: </strong>NCT04843943.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000578"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569049","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":"Six-year performance of risk-based selection for lung cancer screening in the Manchester Lung Health Check cohort.","authors":"Patrick Goodley, Haval Balata, Hilary A Robbins, Richard Booton, Matthew Sperrin, Philip A J Crosbie","doi":"10.1136/bmjonc-2024-000560","DOIUrl":"10.1136/bmjonc-2024-000560","url":null,"abstract":"<p><strong>Objective: </strong>Risk prediction models are used to determine eligibility for targeted lung cancer screening. However, prospective data regarding model performance in this setting are limited. Here we report the performance of the PLCO_m2012 risk model, which calculates 6 year lung cancer risk, in a cohort invited for lung cancer screening in a socioeconomically deprived area.</p><p><strong>Methods and analysis: </strong>Calibration (expected/observed (E/O) lung cancer diagnoses over 6 years) and discrimination (area under the receiver operating characteristic curve) of PLCO_m2012 and other models was performed in Manchester Lung Health Check (M-LHC) participants, where PLCO_m2012 ≥1.51% was used prospectively to determine screening eligibility. Lung cancers diagnosed by any route were captured within 6 years of risk assessment, for both screened and non-screened participants. Performance of a range of models was evaluated.</p><p><strong>Results: </strong>Out of 2541 attendees, 56% were high-risk (n=1430/2541) and offered screening; 44% were low-risk (n=1111/2541) and not screened. Over 6 years, 7.3% (n=105/1430) and 0.9% (n=10/1111) were diagnosed with lung cancer in the high and low-risk cohorts, respectively (p<0.0001). Risk was underestimated in both high-risk, screened (E/O 0.68 (0.57-0.82)) and low-risk, unscreened groups (E/O 0.61 (0.33-1.14)). Most other models also underestimated risk.</p><p><strong>Conclusion: </strong>Risk-based eligibility using PLCO_m2012 successfully classified most eventual lung cancer cases in the high-risk, screened group. Prediction models generally underestimated risk in this socioeconomically deprived cohort, irrespective of screening status. The effect of screening on increasing the probability of lung cancer diagnosis should be considered when interpreting measures of prediction model performance.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000560"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568954","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":"Cancer incidence and competing mortality risk following 15 presenting symptoms in primary care: a population-based cohort study using electronic healthcare records.","authors":"Matthew E Barclay, Cristina Renzi, Hannah Harrison, Ana Torralbo, Becky White, Samantha Hiu Yan Ip, Juliet Usher-Smith, Jane Lange, Nora Pashayan, Spiros Denaxas, Angela M Wood, Antonis Antoniou, Georgios Lyratzopoulos","doi":"10.1136/bmjonc-2024-000500","DOIUrl":"10.1136/bmjonc-2024-000500","url":null,"abstract":"<p><strong>Objectives: </strong>Assessment of age, sex and smoking-specific risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms.</p><p><strong>Methods and analysis: </strong>Data on patients aged 30-99 in 2007-2017 were extracted from a UK primary care database (CPRD Gold), comprising a randomly selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump and post-menopausal bleed).Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality and to estimate cumulative incidence up to 12 months following index consultation.</p><p><strong>Results: </strong>Data included 1 622 419 patients, of whom 36 802 had a cancer diagnosis and 28 857 died without a cancer diagnosis within 12 months of the index.The risk of specific cancers exceeded the UK urgent referral risk threshold of 3% from a relatively young age for patients with red flag symptoms. For non-organ-specific symptoms, the risk of cancer at individual sites either did not reach the threshold at any age or reached it only in older patients.</p><p><strong>Conclusion: </strong>Patients with new-onset symptoms in primary care often have comparable risks of cancer diagnosis and non-cancer mortality. Non-organ-specific symptoms, in particular, are associated with elevated risk of cancer at multiple different sites. Management of symptomatic patients in primary care should be informed by the risk of different cancer types alongside mortality risk.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000500"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069493","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":"Which patients with symptoms should be referred urgently for investigation of suspected cancer?","authors":"Sarah F Moore","doi":"10.1136/bmjonc-2024-000640","DOIUrl":"10.1136/bmjonc-2024-000640","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000640"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070008","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":"Enhanced immune responses are accompanied by increased MAGEA expression in osteosarcoma metastases.","authors":"Debora M Meijer, Siddh van Oost, Jessica P Roelands, Dina Ruano, I H Briaire-de Bruijn, B E van den Akker, A B Kruisselbrink, P M Wijers-Koster, Manon van der Ploeg, Marieke Ijsselsteijn, S W Lam, Arnoud H de Ru, R T N Tjokrodirijo, M A J van de Sande, Hans Gelderblom, Peter A Van Veelen, M L Kuijjer, Noel de Miranda, Judith V M G Bovee","doi":"10.1136/bmjonc-2024-000472","DOIUrl":"10.1136/bmjonc-2024-000472","url":null,"abstract":"<p><strong>Objective: </strong>Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20%-30%. T cell checkpoint blockade immunotherapies have revolutionised cancer treatment in the last decade, but their impact remains limited in osteosarcoma.</p><p><strong>Methods and analysis: </strong>In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterisation of a unique sample set comprising 30 osteosarcoma samples from seven patients, collected throughout disease progression. We performed RNA-sequencing and imaging mass cytometry analysis on these samples to reveal the immunological landscape during osteosarcoma progression.</p><p><strong>Results: </strong>Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anticancer immunity were enriched in metastatic lesions as compared with primary tumours. Spatial analysis showed T cells infiltrating central regions of osteosarcoma metastases, indicating the absence of an immune excluded environment. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly melanoma antigen family A (MAGEA)-related antigens, in osteosarcoma metastases, which was validated in an independent cohort (N=91). In addition, we demonstrated the presentation of MAGE-derived peptides in three out of four osteosarcoma cell lines.</p><p><strong>Conclusion: </strong>These findings indicate a concurrent augmentation of cytotoxic antitumour immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation suggests the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000472"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569046","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":"From prediction to practice: mitigating bias and data shift in machine-learning models for chemotherapy-induced organ dysfunction across unseen cancers.","authors":"Matthew Watson, Pinkie Chambers, Luke Steventon, James Harmsworth King, Angelo Ercia, Heather Shaw, Noura Al Moubayed","doi":"10.1136/bmjonc-2024-000430","DOIUrl":"10.1136/bmjonc-2024-000430","url":null,"abstract":"<p><strong>Objectives: </strong>Routine monitoring of renal and hepatic function during chemotherapy ensures that treatment-related organ damage has not occurred and clearance of subsequent treatment is not hindered; however, frequency and timing are not optimal. Model bias and data heterogeneity concerns have hampered the ability of machine learning (ML) to be deployed into clinical practice. This study aims to develop models that could support individualised decisions on the timing of renal and hepatic monitoring while exploring the effect of data shift on model performance.</p><p><strong>Methods and analysis: </strong>We used retrospective data from three UK hospitals to develop and validate ML models predicting unacceptable rises in creatinine/bilirubin post cycle 3 for patients undergoing treatment for the following cancers: breast, colorectal, lung, ovarian and diffuse large B-cell lymphoma.</p><p><strong>Results: </strong>We extracted 3614 patients with no missing blood test data across cycles 1-6 of chemotherapy treatment. We improved on previous work by including predictions post cycle 3. Optimised for sensitivity, we achieve F2 scores of 0.7773 (bilirubin) and 0.6893 (creatinine) on unseen data. Performance is consistent on tumour types unseen during training (F2 bilirubin: 0.7423, F2 creatinine: 0.6820).</p><p><strong>Conclusion: </strong>Our technique highlights the effectiveness of ML in clinical settings, demonstrating the potential to improve the delivery of care. Notably, our ML models can generalise to unseen tumour types. We propose gold-standard bias mitigation steps for ML models: evaluation on multisite data, thorough patient population analysis, and both formalised bias measures and model performance comparisons on patient subgroups. We demonstrate that data aggregation techniques have unintended consequences on model bias.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000430"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069930","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":"Bedside implications of the use of surrogate endpoints in solid and haematological cancers: implications for our reliance on PFS, DFS, ORR, MRD and more.","authors":"Timothée Olivier, Alyson Haslam, Dagney Ochoa, Eduardo Fernandez, Vinay Prasad","doi":"10.1136/bmjonc-2024-000364","DOIUrl":"10.1136/bmjonc-2024-000364","url":null,"abstract":"<p><p>Clinical endpoints, such as overall survival, directly measure relevant outcomes. Surrogate endpoints, in contrast, are intermediate, stand-in measures of various tumour-related metrics and include tumour growth, tumour shrinkage, blood results, etc. Surrogates may be a time point measurement, that is, tumour shrinkage at some point (eg, response rate) or biomarker-assessed disease status, measured at given time points (eg, circulating tumour DNA, ctDNA). They can also be measured over time, as with progression-free survival, which is the time until a patient presents with either disease progression or death. Surrogates are increasingly used in trials supporting the marketing authorisation of novel oncology drugs. Yet, the trial-level correlation between surrogates and clinical endpoints-meaning to which extent an improvement in the surrogate predicts an improvement in the direct endpoint-is often moderate to low. Here, we provide a comprehensive classification of surrogate endpoints: time point measurements and time-to-event endpoints in solid and haematological malignancies. Also, we discuss an overlooked aspect of the use of surrogates: the limitations of surrogates outside trial settings, at the bedside. Surrogates can result in the inappropriate stopping or switching of therapy. Surrogates can be used to usher in new strategies (eg, ctDNA in adjuvant treatment of colon cancer), which may erode patient outcomes. In liquid malignancies, surrogates can mislead us to use novel drugs and replace proven standards of care with costly medications. Surrogates can lead one to intensify treatment without clear improvement and possibly worsening quality of life. Clinicians should be aware of the role of surrogates in the development and regulation of drugs and how their use can carry real-world, bedside implications.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000364"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069076","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":"Consideration of initial steps to implementation of prostate cancer screening following the EU recommendation.","authors":"Patricia Fitzpatrick","doi":"10.1136/bmjonc-2024-000579","DOIUrl":"10.1136/bmjonc-2024-000579","url":null,"abstract":"","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000579"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069764","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":"Associations between socioeconomic factors and PSA testing in a population-based organised testing programme and routine healthcare: a register-based study of 50-year-old men.","authors":"Emil Järbur, Erik Holmberg, Thomas Björk-Eriksson, Ola Bratt, Rebecka Arnsrud Godtman","doi":"10.1136/bmjonc-2024-000400","DOIUrl":"10.1136/bmjonc-2024-000400","url":null,"abstract":"<p><strong>Objective: </strong>Population-based, organised prostate cancer testing (OPT) programmes were started in Sweden in 2020. The influence of socioeconomic factors on prostate cancer testing in this setting is not known. We examined associations between socioeconomic factors and (1) participation in OPT and (2) unorganised prostate-specific antigen (PSA) testing.</p><p><strong>Methods and analysis: </strong>Region Västra Götaland's OPT programme invited 21 174 men aged 50 years in 2020-2021. Regional data on unorganised testing in 2013-2014 of men aged 50-52 years were retrieved from Western Sweden Study of Opportunistic Prostate Cancer Screening database. Data on income, education, cohabitation and country of birth were collected from Statistic Sweden. Univariable and multivariable Poisson regression was used to calculate incidence rate ratios (IRRs) with CIs for PSA testing by socioeconomic category.</p><p><strong>Results: </strong>Participation in OPT was associated with all investigated socioeconomic factors; multivariable IRRs: low versus non-low income 0.63 (95% CI 0.58 to 0.68), single versus non-single household 0.78 (95% CI 0.75 to 0.81), low versus average education 0.84 (95% CI 0.78 to 0.90) and non-Nordic versus Nordic country of birth 0.88 (95% CI 0.84 to 0.92). Unorganised PSA testing was negatively associated with low income 0.83 (95% CI 0.78 to 0.90) and single household 0.87 (95% CI 0.82 to 0.92), but not with low education 1.00 (95% CI 0.92 to 1.08) or non-Nordic country of birth 0.98 (95% CI 0.91 to 1.06).</p><p><strong>Conclusion: </strong>Socioeconomic factors influenced PSA testing among 50-year-old men, both in an organised testing programme and in unorganised, clinical testing. An active offer of testing is not enough to achieve socioeconomic equality in the early detection of prostate cancer.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000400"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070030","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":"Circulating tumour cell clusters: isolation, biological significance and therapeutic implications.","authors":"Yufan Yang, Guanyin Huang, Jingru Lian, Chunhao Long, Boxi Zhao, Xuefei Liu, Binyu Zhang, Weijian Ye, Junhao Chen, Longxiang Du, Zhuofeng Jiang, Jialing Liu, Jianglin Zhang, Chengzhi Hu, Qingfeng Chen, Xin Hong","doi":"10.1136/bmjonc-2024-000437","DOIUrl":"10.1136/bmjonc-2024-000437","url":null,"abstract":"<p><p>Circulating tumour cells (CTCs) and CTC clusters are considered metastatic precursors due to their ability to seed distant metastasis. However, navigating the bloodstream presents a significant challenge for CTCs, as they must endure fluid shear forces and resist detachment-induced anoikis. Consequently, while a large number of cells from the primary tumour may enter the circulation, only a tiny fraction will result in metastasis. Nevertheless, the metastatic potency dramatically increases when CTCs travel in conjunction with other cell types to form CTC clusters, including neutrophils, myeloid-derived suppressor cells, macrophages, platelets, cancer-associated fibroblasts and red blood cells found in circulation. Such heterotypic CTC clustering events have been identified in a variety of cancer types and may serve as intriguing therapeutic targets and novel biomarkers for liquid biopsy. This review summarises recent advances in microfluidic technologies designed for the isolation of CTC clusters and explores the biological properties of distinct types of CTC clusters within the circulatory system. Investigation of the mechanisms of CTC cluster-blood microenvironment interactions may offer a promising avenue for gaining fresh insights into CTC cluster-mediated metastatic progression and reveal potential opportunities for devising personalised antimetastasis treatments.</p>","PeriodicalId":72436,"journal":{"name":"BMJ oncology","volume":"3 1","pages":"e000437"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069747","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}