Thrombosis and haemostasis最新文献

{"title":"Ticagrelor Therapy Modifications after Acute Coronary Syndrome: An Ever-Evolving Issue.","authors":"Felice Gragnano, Dominick J Angiolillo","doi":"10.1055/a-2448-7029","DOIUrl":"10.1055/a-2448-7029","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"607-609"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508515","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":"Treatment Modifications in Acute Coronary Syndrome Patients Treated with Ticagrelor: Insights from the FORCE-ACS Registry.","authors":"Niels M R van der Sangen, Jaouad Azzahhafi, Dean R P P Chan Pin Yin, Lucas J G Zaaijer, Wout W A van den Broek, Ronald J Walhout, Melvyn Tjon Joe Gin, Ron Pisters, Deborah M Nicastia, Jorina Langerveld, Georgios J Vlachojannis, Rutger J van Bommel, Yolande Appelman, José P S Henriques, Wouter J Kikkert, Jurriën M Ten Berg","doi":"10.1055/a-2421-8866","DOIUrl":"10.1055/a-2421-8866","url":null,"abstract":"<p><p>Patients presenting with acute coronary syndrome (ACS) are frequently treated with the P2Y₁₂-inhibitor ticagrelor. Some patients prematurely discontinue ticagrelor, but the incidence of reasons for and clinical implications of treatment modification are relatively unknown.Data from 4,278 ACS patients (mean age: 63.6 years, 26.1% women) who were discharged on ticagrelor and enrolled in the FORCE-ACS registry between 2015 and 2020 were used. Treatment modifications were categorized as physician-recommended discontinuation, alteration, interruption, or disruption and occurred in 26.7, 20.1, 2.8, and 3.1% of patients within 12 months of follow-up (VISUAL SUMMARY: ). Underlying reasons for treatment modification differed per type of modification. Overall, the rate of ischemic events defined as all-cause death, myocardial infarction, or stroke was 6.6% at 12 months of follow-up. Cox regression analysis using time-updated modification variables as independent variables showed that treatment interruption (adjusted hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.48-5.79, <i>p</i> < 0.01) and disruption (adjusted HR: 2.33, 95% CI: 1.07-5.07, <i>p</i> = 0.03) were associated with an increased risk of ischemic events even after adjustment for relevant confounders. Discontinuation and alteration were not associated with increased ischemic risk.In clinical practice, treatment modifications in ACS patients discharged on ticagrelor are common, although type and reasons for modification are heterogeneous. Treatment interruption and disruption are associated with excess cardiovascular risk.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"597-606"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between Screening-Detected Atrial Fibrillation and Blood Pressure Levels in Elderly Hypertensive Patients: The OMRON Heart Study.","authors":"Keitaro Senoo, Mitsuko Nakata, Arito Yukawa, Kohei Kawai, Jun Munakata, Masahiro Makino, Nobunari Tomura, Hibiki Iwakoshi, Tetsuro Nishimura, Satoshi Shimoo, Hirokazu Shiraishi, Satoshi Teramukai, Satoaki Matoba","doi":"10.1055/a-2484-0641","DOIUrl":"10.1055/a-2484-0641","url":null,"abstract":"<p><p>Hypertension is a well-known risk factor for atrial fibrillation (AF) and strokes, but studies assessing screening-detected AF in hypertensive populations and its relationship to the blood pressure (BP) are scarce.We prospectively recruited hypertensive patients (aged ≥60 years) from all over Japan in a decentralized clinical trial. Participants were asked to measure their electrocardiogram (ECG) and BP at home for 3 months with a BP monitor equipped with ECG.Between April 2022 and July 2023, 4,078 hypertensive patients from across the country participated in this study. The mean age was 66.3 ± 5.5 years, and the male proportion was 80.3%. After excluding those with no measurement data (<i>n</i> = 258), AF detection was 5.8% (<i>n</i> = 220/3,820), and the time to AF detection was 3 to 109 days (median 28 days). The mean BP at baseline was 133 ± 14/85 ± 9 mmHg in the morning and 125 ± 14/79 ± 9 mmHg in the evening. AF detection did not significantly differ between the baseline BP categories (log rank test, <i>p</i> = 0.54), with hazard ratios (95% confidence interval) of 0.83 (0.57-1.19), 0.79 (0.55-1.14), and 0.99 (0.59-1.68) for systolic BP (SBP) 135 to 144 and/or diastolic BP (DBP) 85 to 89, SBP 145 to 159 and/or DBP 90 to 99, and SBP ≥ 160 and/or DBP ≥ 100, respectively (SBP ≤ 134 and DBP ≤ 84 as a reference). The results did not change when taking into account the impact of the measurement rates and antihypertensive drugs on AF detection during the observation period.Detection of undiagnosed AF was 5.8% in elderly hypertensives, with no significant differences between the baseline BP categories and no effect of the measurement rate or antihypertensive drugs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"545-552"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Loss in Women of Childbearing Potential Taking Oral Anticoagulants for Venous Thromboembolism (The BLEED Study).","authors":"Elvira Grandone, Mario Mastroianno, Gabriella Pacilli, Donatella Colaizzo, Alessandra Margaglione, Behnood Bikdeli, Gregory Piazza","doi":"10.1055/a-2461-6822","DOIUrl":"10.1055/a-2461-6822","url":null,"abstract":"<p><p>Oral anticoagulants (OAC) may exacerbate menstrual bleeding in women of childbearing age; however, the existing literature on this issue has several limitations.This study investigates abnormal uterine bleeding in women of childbearing age taking OAC-vitamin K antagonists or direct oral anticoagulants-for venous thromboembolism through a retrospective analysis of prospectively collected data. Uterine bleeding was assessed using the Pictorial Blood Assessment Chart (PBAC) and hemoglobin (Hb) values during anticoagulation compared with prior therapy. The number of unplanned medical visits for bleeding complications was also calculated.From June 2014 to November 2023, 110 women were recruited (median age, 36 years). PBAC scores correlated with Hb values at baseline and during therapy (analysis of variance [ANOVA], <i>p</i> < 0.01), with a significant difference in Hb values before and during anticoagulant therapy (delta Hb) among groups (ANOVA, p.0.034). Seventeen women (15.5%) reported uterine fibroids, experiencing a greater reduction in Hb values during anticoagulant administration than women without uterine fibroids (delta 0.3, interquartile range [IQR]: 0.8, 2.9 vs. 0.5, IQR 1.2, 0.3; p.0.012). Women with selfreported uterine fibroids required more frequent unplanned medical consultations for bleeding (mean visits 5 vs. 4, respectively; Poisson regression, <i>p</i> < 0.05). Among women with uterine fibroids, those taking apixaban showed smaller Hb changes than those on other oral anticoagulants (ANOVA, p.0.047). This difference persisted even after adjusting for potential confounders (multiple ANOVA, p.0.004).Women of childbearing age taking OAC frequently experience changes in Hb values and PBAC scores during treatment, with uterine fibroids playing a significant role.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"523-532"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591167","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":"Unraveling the Molecular Pathogenesis of Protein C Deficiency-Associated VTE: Insights from Protein C Mutations C238G and R189W in Thai Patients.","authors":"Pansakorn Tanratana, Karnsasin Seanoon, Panwajee Payongsri, Praguywan Kadegasem, Ampaiwan Chuansumrit, Nongnuch Sirachainan","doi":"10.1055/a-2408-9529","DOIUrl":"10.1055/a-2408-9529","url":null,"abstract":"<p><p>Protein C (PC) deficiency is a well-established risk factor for thromboembolism (TE), commonly manifesting in pediatric patients. This study aimed to elucidate the pathogenic mechanisms of two novel PC mutations, C238G and R189W, identified in Thai children with both venous and arterial TE.The effects of wild-type (WT), C238G, and R189W PC variants were investigated through transient transfection of HEK293T cells. PC secretion levels were measured, and immunofluorescence analysis was performed to assess intracellular localization. ER stress-related gene expression and UPR activation were evaluated. Structural analysis was conducted to explore the significance of the C238 and R189W residue in PC functionality.The C238G mutation led to a severe 95% reduction in PC secretion, while R189W showed a 30% decrease compared with WT. Immunofluorescence revealed that C238G-PC was predominantly retained in the ER, indicating protein misfolding. C238G-expressing cells exhibited significant upregulation of ER stress-related genes and UPR activation. In contrast, R189W resulted in only a modest increase in UPR gene expression, suggesting a less pronounced impact on protein folding and secretion. Structural analysis demonstrated the critical role of the C238 residue in maintaining PC's disulfide bond and overall conformation.This study reveals distinct molecular mechanisms by which the C238G and R189W mutations contribute to PC deficiency and increased thrombotic risk. The findings emphasize the essential role of the C238 residue in preserving PC structure and secretion, enhancing the understanding of PC deficiency-associated TE in pediatric patients.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"533-544"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Plasma Proteome and Risk of Future Venous Thromboembolism-Results from the HUNT Study.","authors":"Sigrid K Brækkan, Asbjørn L Onsaker, Therese H Nøst, Weihong Tang, Kristian D Hindberg, Vania M Morelli, Weihua Guan, Christian Jonasson, Aaron R Folsom, Kristian Hveem, John-Bjarne Hansen","doi":"10.1055/a-2484-0836","DOIUrl":"10.1055/a-2484-0836","url":null,"abstract":"<p><p>This study aimed to identify novel plasma proteins associated with first-lifetime venous thromboembolism (VTE) and molecular pathways involved in VTE pathogenesis.A case-cohort comprising incident VTE cases (<i>n</i> = 294) and a randomly sampled age- and sex-weighted subcohort (<i>n</i> = 1,066) was derived from the Trøndelag Health Study (HUNT3, n = 50,800). Blood samples were collected and stored at cohort inclusion (2006-2008), and participants were followed up to 5 years. Proteome-wide analyses was performed using the 7k SomaScan® proteomics platform, and weighted Cox-regression models adjusted for age, sex, and sample batch were conducted, with the Bonferroni method applied to account for multiple testing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied on the top-ranked 200 proteins associated with VTE.Out of 7,288 human proteins, 7 proteins were significantly associated with higher VTE risk with <i>p</i>-value <6.9 × 10^-6 (hazard ratios per 1 standard deviation increase in protein levels ranging from 1.39 to 1.86). Except for coagulation factor VIII and tumor necrosis factor soluble receptor II, these proteins were novel associations and included collagen alpha-3(VI):BPTI/Kunitz inhibitor, histo-blood group ABO system transferase, peroxidasin, human epididymis protein 4, and regulator of G protein signaling 3. KEGG analyses of the top-ranked 200 proteins revealed significant pathway enrichment of nine proteins in the complement (mainly lectin pathway) and coagulation (mainly intrinsic pathway) cascades.Our proteome-wide analysis led to discovery of five novel protein candidates associated with 5-year risk of future VTE. KEGG analyses supported an interplay between the complement and coagulation pathways in the pathogenesis of VTE.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"574-584"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717178","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":"Risk of Recurrent Venous Thromboembolism in Patients with Cancer: An Individual Patient Data Meta-analysis and Development of a Prediction Model.","authors":"Vincent R Lanting, Toshihiko Takada, Floris T M Bosch, Andrea Marshall, Michael A Grosso, Annie M Young, Agnes Y Y Lee, Marcello Di Nisio, Gary E Raskob, Pieter W Kamphuisen, Harry R Büller, Nick van Es","doi":"10.1055/a-2418-3960","DOIUrl":"10.1055/a-2418-3960","url":null,"abstract":"<p><p>About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions.To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT.For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot.After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies.The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"589-596"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Plasma Proteome and Risk of Future Venous Thromboembolism-Results from the HUNT Study in Thrombosis and Haemostasis.","authors":"Drew A Birrenkott, Christopher Kabrhel","doi":"10.1055/a-2575-3388","DOIUrl":"10.1055/a-2575-3388","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"585-588"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998735","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":"Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.","authors":"Tim A C de Vries, Imaad U Mallick, Vinai C Bhagirath, John W Eikelboom, Calvin Gomes, Qilong Yi, Sean McGrath, Jack Hirsh, Noel C Chan","doi":"10.1055/a-2446-1348","DOIUrl":"10.1055/a-2446-1348","url":null,"abstract":"<p><p>Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations.This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF. We used random effects models and the quantile estimation method to estimate the median and a usual on-therapy range (10^th and 90^th percentiles).Of 4,822 unique publications, 53 studies met eligibility (29,266 trough and 12,103 peak levels). Usual on-therapy ranges for trough levels were 38 to 155 and 58 to 206 ng/mL for apixaban 2.5 and 5 mg twice daily; 35 to 138 and 33 to 151 ng/mL for dabigatran 110 and 150 mg twice daily; 8 to 54 and 13 to 66 ng/mL for edoxaban 30 and 60 mg daily; and 16 to 74 and 19 to 72 ng/mL for rivaroxaban 15 and 20 mg daily. The corresponding range for peak levels were 96 to 251 and 132 to 343; 65 to 223 and 76 to 285; 57 to 219 and 127 to 407; 131 to 384, and 169 to 313 ng/mL, respectively.This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"563-573"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thromboembolic Risk among Patients on Dual Antiplatelet Therapy with or without Heparin Thromboprophylaxis.","authors":"Jonas Gmeiner, Rainer Kaiser, Julius Fischer, Angelina Krächan, Lisa Wasner, Thomas Marchant Seiter, Ludwig Weckbach, Konstantin Stark, Jörg Hausleiter, Steffen Massberg, Clemens Scherer","doi":"10.1055/a-2615-4785","DOIUrl":"10.1055/a-2615-4785","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) is a common complication among hospitalized patients. Low-molecular-weight heparin (LMWH) is recommended for thromboprophylaxis, but its benefits in non-surgical patients, particularly those receiving dual antiplatelet therapy (DAPT), remain unclear. Currently, evidence on the risks and benefits of LMWH thromboprophylaxis in patients on DAPT is lacking.This retrospective cohort study included patients hospitalized in the cardiology departments of two hospitals of LMU University Munich between May 2015 and April 2025. Patients receiving DAPT, defined as treatment with aspirin and a P2Y12 inhibitor, were analyzed. The study population was divided into two groups: those who received LMWH prophylaxis and those who did not. The primary endpoint was the incidence of VTE during hospitalization, confirmed through imaging techniques. Secondary endpoints included the need for erythrocyte transfusion.A total of 8,619 patients receiving DAPT were included, of which 2,378 were receiving LMWH prophylaxis. The incidence of VTE was very low and did not differ between the LMWH and non-LMWH groups (0.04% versus 0%, <i>p</i> = 0.28). Subgroup analysis revealed higher bleeding rates as mirrored by more erythrocyte transfusions in the LMWH group (9.4 versus 5.1%, <i>p</i> = 0.004).In patients receiving DAPT, LMWH thromboprophylaxis was associated with a comparably low incidence of VTE but a higher rate of erythrocyte transfusions in subgroup analysis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102626","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}