Journal of Gastroenterology最新文献

{"title":"Alpha-fetoprotein combined with initial tumor shape irregularity in predicting the survival of patients with advanced hepatocellular carcinoma treated with immune-checkpoint inhibitors: a retrospective multi-center cohort study.","authors":"Feng Zhang, Yong-Shuai Wang, Shao-Peng Li, Bin Zhao, Nan Huang, Rui-Peng Song, Fan-Zheng Meng, Zhi-Wen Feng, Shen-Yu Zhang, Hua-Chuan Song, Xiao-Peng Chen, Lian-Xin Liu, Ji-Zhou Wang","doi":"10.1007/s00535-024-02202-y","DOIUrl":"https://doi.org/10.1007/s00535-024-02202-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are playing a significant role in the treatment of hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of alpha-fetoprotein (AFP) and initial tumor shape irregularity in patients treated with ICIs.</p><p><strong>Methods: </strong>In this retrospective, multi-center study, 296 HCC patients were randomly divided into the training set and the validation set in a 3:2 ratio. The training set was used to evaluate prognostic factors and to develop an easily applicable ATSI (AFP and Tumor Shape Irregularity) score, which was verified in the validation set.</p><p><strong>Results: </strong>The ATSI score was developed from two independent prognostic risk factors: baseline AFP ≥ 400 ng/ml (HR 1.73, 95% CI 1.01-2.96, P = 0.046) and initial tumor shape irregularity (HR 1.94, 95% CI 1.03-3.65, P = 0.041). The median overall survival (OS) was not reached (95% CI 28.20-NA) in patients who met no criteria (0 points), 25.8 months (95% CI 14.17-NA) in patients who met one criterion (1 point), and 17.03 months (95% CI 11.73-23.83) in patients who met two criteria (2 points) (P = 0.001). The median progression-free survival (PFS) was 10.83 months (95% CI 9.27-14.33) for 0 points, 8.03 months (95% CI 6.77-10.57) for 1 point, and 5.03 months (95% CI 3.83-9.67) for 2 points (P < 0.001). The validation set effectively verified these results (median OS, 37.43/24.27/14.03 months for 0/1/2 points, P = 0.028; median PFS, 13.93/8.30/4.90 months for 0/1/2 points, P < 0.001).</p><p><strong>Conclusions: </strong>The ATSI score can effectively predict prognosis in HCC patients receiving ICIs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Novel subharmonic-aided pressure estimation for identifying high-risk esophagogastric varices.","authors":"Hidekatsu Kuroda, Tamami Abe, Naohisa Kamiyama, Takuma Oguri, Asami Ito, Ippeki Nakaya, Takuya Watanabe, Hiroaki Abe, Kenji Yusa, Yudai Fujiwara, Hiroki Sato, Akiko Suzuki, Kei Endo, Yuichi Yoshida, Takayoshi Oikawa, Keisuke Kakisaka, Kei Sawara, Akio Miyasaka, Takayuki Matsumoto","doi":"10.1007/s00535-024-02194-9","DOIUrl":"https://doi.org/10.1007/s00535-024-02194-9","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Severe ulcerative colitis: diagnostic criteria and therapy\".","authors":"Makoto Naganuma","doi":"10.1007/s00535-024-02200-0","DOIUrl":"https://doi.org/10.1007/s00535-024-02200-0","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse.","authors":"Kei Nishioka, Haruei Ogino, Eikichi Ihara, Takatoshi Chinen, Yusuke Kimura, Mitsuru Esaki, Xiaopeng Bai, Yosuke Minoda, Yoshimasa Tanaka, Masafumi Wada, Yoshitaka Hata, Yoko M Ambrosini, Yoshihiro Ogawa","doi":"10.1007/s00535-024-02199-4","DOIUrl":"https://doi.org/10.1007/s00535-024-02199-4","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors.</p><p><strong>Methods: </strong>In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively.</p><p><strong>Results: </strong>In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions.</p><p><strong>Conclusion: </strong>The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum.","authors":"Rex Devasahayam Arokia Balaya, Partho Sen, Caroline W Grant, Roman Zenka, Marimuthu Sappani, Jeyaseelan Lakshmanan, Arjun P Athreya, Richard K Kandasamy, Akhilesh Pandey, Seul Kee Byeon","doi":"10.1007/s00535-024-02197-6","DOIUrl":"https://doi.org/10.1007/s00535-024-02197-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC.</p><p><strong>Methods: </strong>We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC.</p><p><strong>Results: </strong>We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites.</p><p><strong>Conclusions: </strong>Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Mac2-binding protein glycosylated isomer (M2BPGi) as a prognostic biomarker in pancreatic ductal adenocarcinoma: iCAFs-derived M2BPGi drives tumor invasion.","authors":"Naotaka Kugiyama, Katsuya Nagaoka, Rin Yamada, Takehisa Watanabe, Hajime Yamazaki, Shinya Ushijima, Fumiya Otsuka, Yukiko Uramoto, Hajime Iwasaki, Motohiro Yoshinari, Shunpei Hashigo, Hiromitsu Hayashi, Takatsugu Ishimoto, Yoshihiro Komohara, Yasuhito Tanaka","doi":"10.1007/s00535-024-02195-8","DOIUrl":"https://doi.org/10.1007/s00535-024-02195-8","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Mac2-binding protein glycosylated isomer (M2BPGi), a known biomarker for liver fibrosis, is also elevated in other fibrotic tissues. However, its role in PDAC remains unexplored. This study investigates the potential of M2BPGi as a prognostic biomarker for PDAC and elucidates its role in cancer progression.</p><p><strong>Methods: </strong>We analyzed serum M2BPGi levels in 83 PDAC patients and 60 healthy controls, examining the relationship with clinical outcomes. Tissue immunostaining and in vitro experiments were conducted to investigate M2BPGi-secreting cells and its role.</p><p><strong>Results: </strong>Serum M2BPGi levels were significantly higher in PDAC patients than in controls (0.98 vs. 0.59, p < 0.0001). Notably, elevated serum M2BPGi was associated with worse progression-free survival (144 days vs. 260 days, p = 0.017) and overall survival (OS) (245 days vs. 541 days, p < 0.001) following chemotherapy. Multivariable Cox regression analysis further confirmed that a high serum M2BPGi level is an independent risk factor for OS (HR: 2.44, 95% CI 1.26-4.74, p = 0.008). Immunostaining revealed that M2BPGi is secreted by both cancer cells and cancer-associated fibroblasts (CAFs), with high M2BP expression in CAFs correlating with poor prognosis. Furthermore, M2BPGi-secreting CAFs exhibited characteristics of inflammatory CAFs. M2BPGi directly activated mTOR signaling and epithelial-mesenchymal transition in PDAC cells, enhancing their invasive and migratory capabilities.</p><p><strong>Conclusions: </strong>Our findings identify M2BPGi as a promising prognostic biomarker for PDAC. Moreover, we demonstrate that inflammatory CAFs promote tumor invasion and contribute to poor outcomes by secreting M2BPGi, revealing a novel mechanism of PDAC progression.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe ulcerative colitis: diagnostic criteria and therapy.","authors":"Mitsuro Chiba","doi":"10.1007/s00535-024-02198-5","DOIUrl":"10.1007/s00535-024-02198-5","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of preceding treatment for head and neck squamous cell carcinoma on synchronous superficial esophageal squamous cell carcinoma.","authors":"Tomoya Ueda, Ryu Ishihara, Yasuhiro Tani, Yoshiaki Ando, Gentaro Tanabe, Yuta Fujimoto, Noriaki Ito, Nobutoshi Tsukuda, Kazuki Matsuyama, Muneshin Morita, Minoru Kato, Shunsuke Yoshii, Satoki Shichijo, Takashi Kanesaka, Sachiko Yamamoto, Koji Higashino, Noriya Uedo, Tomoki Michida, Takashi Fujii","doi":"10.1007/s00535-024-02201-z","DOIUrl":"https://doi.org/10.1007/s00535-024-02201-z","url":null,"abstract":"<p><strong>Background: </strong>Patients with esophageal squamous cell carcinoma (ESCC) frequently develop synchronous head and neck squamous cell carcinoma (HNSCC). With advances in endoscopic technology and widespread screening of synchronous cancers, the detection of synchronous HNSCC and superficial ESCC (SESCC) is increasing. We aimed to evaluate the impact of preceding HNSCC treatment on synchronous SESCC.</p><p><strong>Methods: </strong>This single-center retrospective study enrolled patients with synchronous HNSCC and SESCC who were treated between January 2010 and December 2023. Tumor size and depth of SESCC before and after HNSCC treatment were evaluated. The factors associated with SESCC progression were investigated.</p><p><strong>Results: </strong>Of the 299 patients with synchronous HNSCC and SESCC, 134 who underwent preceding HNSCC treatment with follow-up esophagogastroduodenoscopy (EGD) for SESCC were evaluated. Chemoradiotherapy was the most common treatment for HNSCC (56.0%), followed by surgery (17.2%), radiotherapy (14.9%), local resection (7.5%), and chemotherapy (4.5%). The tumor size of SESCC increased after HNSCC treatment in 18 patients (13.4%). Multivariate analysis revealed that an EGD interval of ≥ 120 days was significantly associated with increased tumor size in SESCC (odds ratio, 6.64; 95% confidence interval, 1.91-23.1). Tumor regrowth was observed in 70.6% of SESCCs that shrank with HNSCC treatment, mostly within six months. Tumor depth aggravation was rare (2.2%), but progression to advanced ESCC was observed in two patients.</p><p><strong>Conclusions: </strong>Timely endoscopic follow-up, preferably within 120 days, is crucial for managing synchronous SESCC after HNSCC treatment to prevent tumor progression. Tumor regrowth should be monitored when SESCC shrinks with HNSCC treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.","authors":"Genso Notoya, Takahiro Kishikawa, Kengo Yasugi, Takuma Iwata, Takahiro Seimiya, Koji Miyabayashi, Ryota Takahashi, Keisuke Yamamoto, Hideaki Ijichi, Motoyuki Otsuka, Mitsuhiro Fujishiro","doi":"10.1007/s00535-024-02192-x","DOIUrl":"https://doi.org/10.1007/s00535-024-02192-x","url":null,"abstract":"<p><strong>Background: </strong>The proto-oncogene WWP1 is overexpressed in various cancers and contributes to tumor growth and poor prognosis. Recently, WWP1 inhibition was reported to suppress tumor development and cell proliferation by activating the PTEN function. However, the expression profiles and clinical significance of WWP1 in pancreatic ductal adenocarcinoma (PDAC) tissues remain undetermined. Therefore, this study aimed to evaluate the WWP1 expression in PDAC and investigate the therapeutic potential of WWP1 inhibition.</p><p><strong>Methods: </strong>Cellular proliferation assays were performed using a doxycycline-inducible shWWP1 expression system. Transcriptome analyses were conducted to identify the altered pathways in WWP1-depleted cells. PTEN ubiquitination by WWP1 was confirmed using immunoprecipitation assays. In vivo xenograft and drug screening assays were performed to evaluate the clinical significance of WWP1 inhibition.</p><p><strong>Results: </strong>WWP1 was significantly upregulated in PDAC tissues and associated with poor prognosis. WWP1 depletion significantly reduced the proliferation of PDAC cell lines, correlating with the suppression of the PI3K-AKT pathway. Mechanistically, as reported in other cancer types, PTEN is a target of WWP1 in PDAC cells. PTEN silencing abrogated the growth-inhibitory effects in WWP1-depleted cells, suggesting that the anti-tumor effects of WWP1 inhibition are mediated through PTEN activation. In vivo xenograft studies confirmed that WWP1 depletion substantially inhibited tumor growth. Moreover, drug screening assays revealed that WWP1 depletion had an additive effect with the PI3K-AKT pathway inhibitors on hindering tumor growth.</p><p><strong>Conclusion: </strong>WWP1 inhibition enhances the anti-tumor effects of PI3K-AKT pathway inhibitors through PTEN activation. Thus, WWP1 could be a potential therapeutic target in PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the Japanese version of the Esophageal Hypervigilance and Anxiety Scale for esophageal symptoms.","authors":"Akinari Sawada, Yoshimasa Hoshikawa, Hiroko Hosaka, Masahiro Saito, Hirotaka Tsuru, Shunsuke Kato, Eikichi Ihara, Tomoyuki Koike, Toshio Uraoka, Kunio Kasugai, Katsuhiko Iwakiri, Daniel Sifrim, John Erik Pandolfino, Tiffany H Taft, Yasuhiro Fujiwara","doi":"10.1007/s00535-024-02193-w","DOIUrl":"https://doi.org/10.1007/s00535-024-02193-w","url":null,"abstract":"<p><strong>Background: </strong>The Esophageal Hypervigilance and Anxiety Scale (EHAS) is an English questionnaire created in the USA to assess these factors in all patients with esophageal diseases. The aim of this study was to develop and validate the Japanese version of EHAS and investigate the relationship between EHAS scores and symptoms in untreated disorders of esophagogastric junction (EGJ) outflow.</p><p><strong>Methods: </strong>This prospective study recruited patients who underwent high-resolution manometry (HRM) at six tertiary centers in Japan. The EHAS was translated to Japanese using standard forward and backward translation methods. Patients completed the following questionnaires: the Japanese EHAS, Eckardt score, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for assessment of construct validity. Logistic regression analysis identified factors associated with esophageal symptom severity in untreated disorders of EGJ outflow.</p><p><strong>Results: </strong>Overall, we analyzed 432 patients. Their main symptoms were dysphagia and reflux. The most common HRM diagnosis was normal (35.9%), followed by achalasia (29.4%). The Japanese EHAS demonstrated excellent reliability, and construct validity, with two subscales similar to the original EHAS. Total EHAS score moderately correlated to Eckardt score (r = 0.545, p < 0.001). In 113 patients with untreated disorders of EGJ outflow, multivariable analysis demonstrated that younger age, type II achalasia, and higher EHAS score were independently associated with higher Eckardt score.</p><p><strong>Conclusions: </strong>The Japanese EHAS is a reliable and valid questionnaire. Its subscale scores can be used as in the original version with some caution. Future studies are warranted to assess the appropriateness of factor loading.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}