Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Thrombocytosis and bleeding in myeloproliferative neoplasms: exploring clinical diversity and risk of acquired von Willebrand syndrome—insights from a UK center","authors":"Giulia Simini ,&nbsp;Andrew Innes ,&nbsp;Saravanan Vinayagam ,&nbsp;Golzar Mobayen ,&nbsp;Nilanthi Karawitage ,&nbsp;Simone Claudiani ,&nbsp;Zain Odho ,&nbsp;Mike Laffan ,&nbsp;Deepa J. Arachchillage","doi":"10.1016/j.rpth.2025.102954","DOIUrl":"10.1016/j.rpth.2025.102954","url":null,"abstract":"<div><h3>Background</h3><div>Myeloproliferative neoplasms (MPNs) represent a group of blood disorders characterized by myeloid cell proliferation and an associated increased risk of thrombosis and bleeding. Platelet count may have a direct link to these complications.</div></div><div><h3>Objectives</h3><div>To share our MPN clinic’s experience with hemostatic testing and bleeding outcomes in patients with platelets ≥ 800 × 10⁹/L.</div></div><div><h3>Methods</h3><div>This was a single-center retrospective study from May 2022 to September 2024. Clinical characteristics, treatments, and bleeding events of patients with MPN or chronic myeloid leukemia were recorded. Laboratory assessments included full blood count, renal function, coagulation profiles, platelet function test, and von Willebrand factor (VWF) assays.</div></div><div><h3>Results</h3><div>A total of 39 patients were included, majority of whom received aspirin for thrombosis prevention (76%). The study found that bleeding complications occurred in 33% of patients, with mucocutaneous bleeding being the most common. There was a trend toward bleeding in patients on aspirin (<em>P</em> = .07). However, platelet count alone did not predict bleeding risk. While some patients showed abnormal VWF function, low VWF levels were not consistently associated with increased bleeding. Interestingly, we found moderate negative correlation between baseline VWF ristocetin/antigen and activated partial thromboplastin time (<em>P</em> = .02; <em>r</em> = −.37) and prothrombin time (<em>P</em> = .009, <em>r</em> = −.45), suggesting other potential coagulation imbalances associated with bleeding diathesis in MPNs. Post cytoreduction, there was a significant increase in mean VWF ristocetin/antigen ratio (<em>P</em> = .0009).</div></div><div><h3>Conclusion</h3><div>The study illustrates the limitations of relying solely on platelet counts to estimate bleeding risk in MPN patients. Assessment of VWF activity and careful selection of antithrombotic therapy were highlighted as important considerations.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102954"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium binding by γ-carboxyglutamic acid: it takes two to tether","authors":"Hans Ippel,&nbsp;Sem J. Peijnenborgh,&nbsp;Tilman M. Hackeng,&nbsp;Stijn M. Agten","doi":"10.1016/j.rpth.2025.102964","DOIUrl":"10.1016/j.rpth.2025.102964","url":null,"abstract":"<div><h3>Background</h3><div>The small family of vitamin K-dependent proteins are characterized by posttranslational modification of specific glutamic acid residues to yield γ-carboxyglutamic acid (Gla). Gla residues give these proteins calcium ion-binding properties, which are essential for a number of coagulation factors and mineralization processes. Biophysical characteristics of Gla are, however, incomplete, hindering molecular dynamics simulations and protein structure predictions.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate the general biophysical characteristics (p<em>K</em>_a and <em>K</em>_D) of calcium binding to γ-carboxyglutamic acid in a protein environment and determine how positioning of γ-carboxyglutamic acid influences cooperative calcium binding and protein structure.</div></div><div><h3>Methods</h3><div>Residue-based p<em>K</em>_a of Gla carboxyl groups in model peptides was individually determined by measuring ¹H and ¹³C nuclear magnetic resonance chemical shift changes as a function of pH. In addition, residue-based <em>K</em>_D values of Ca²⁺ binding were determined using Ca²⁺ nuclear magnetic resonance titrations. Secondary structure of peptides and proteins was assessed using circular dichroism and nuclear magnetic resonance.</div></div><div><h3>Results</h3><div>Carboxylic acid groups present on Gla residues have 2 different p<em>K</em>_a values of 2.62 ± 0.07 and 5.02 ± 0.05. In presence of calcium ions, p<em>K</em>_a values drop to 2.54 ± 0.02 and 4.55 ± 0.04. Affinity of a single Gla residue for calcium is low (∼15 mM); 2 Gla residues show cooperativity, resulting in a 25-fold increased affinity for calcium ions (0.6 mM). Finally, cooperative calcium ion binding led to increased α-helical content in model proteins.</div></div><div><h3>Conclusion</h3><div>Vitamin K-dependent proteins present Gla residues in a different manner but benefit from cooperative calcium ion binding. Experimentally determined p<em>K</em>_a and <em>K</em>_D values can be used for interpretation of binding interactions or for molecular dynamics simulations of Gla domains with unknown structure.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102964"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association and linkage analysis of histidine-rich glycoprotein identifies common variants associated with plasma histidine-rich glycoprotein concentrations","authors":"Mary I. Underwood ,&nbsp;Ayse Bilge Ozel ,&nbsp;Tanay Deepak ,&nbsp;Beth McGee ,&nbsp;Dave Siemieniak ,&nbsp;Rida A. Malik ,&nbsp;Cherie Teney ,&nbsp;Colin A. Kretz ,&nbsp;Jeffery Weitz ,&nbsp;Karl C. Desch","doi":"10.1016/j.rpth.2025.102955","DOIUrl":"10.1016/j.rpth.2025.102955","url":null,"abstract":"<div><h3>Background</h3><div>The plasma protein histidine-rich glycoprotein (HRG) interacts with multiple plasma ligands with various roles in coagulation, immunity, and angiogenesis. Through its inhibition of factor XIIa, HRG regulates the contact pathway of blood coagulation. Plasma HRG concentrations are highly heritable and vary widely, which may impact HRG function.</div></div><div><h3>Objectives</h3><div>To determine the genetic factors contributing to HRG variability.</div></div><div><h3>Methods</h3><div>Plasma HRG concentrations were measured in a healthy sibling cohort of 1152 subjects and a second healthy cohort of 2304 individuals of Irish descent. We performed genome-wide association study and meta-analysis on the European subset of these cohorts. Using the sibling subset of the 2 cohorts (<em>n</em> = 934 in 460 sibships), we explored linkage patterns to identify additional signals associated with variation in HRG concentrations that may be driven by rare variants. Two HRG missense variants associated with decreased HRG concentrations were expressed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Narrow-sense heritability was estimated at 69%. Meta-analysis identified an association between HRG concentrations and 2 independent signals at the <em>HRG</em> locus. Variants at these chromosome 3 loci collectively explained 45% of the variation in HRG concentrations. <em>In vitro</em> expression of 2 <em>HRG</em> variants associated with decreased HRG concentrations had no impact on HRG secretion. Linkage analysis of HRG concentrations identified 3 further regions contributing to differences in HRG concentrations.</div></div><div><h3>Conclusion</h3><div>The results of this genome-wide association study, investigating HRG concentration variation in a healthy population, provide new insights into the genetic control of circulating HRG concentrations and generate data for colocalization and Mendelian randomization studies.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102955"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cautious use of activated prothrombin complex concentrate in patients receiving emicizumab: new evidence and clinical considerations","authors":"Cedric Hermans","doi":"10.1016/j.rpth.2025.102983","DOIUrl":"10.1016/j.rpth.2025.102983","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102983"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired von Willebrand syndrome in young children with congenital heart defects: focus on patent ductus arteriosus and ventricular septal defect","authors":"Oksana Trębacz ,&nbsp;Katarzyna Szafarz ,&nbsp;Joanna Zdziarska ,&nbsp;Jacek Podlewski ,&nbsp;Piotr Weryński ,&nbsp;Wojciech Tarała ,&nbsp;Teresa Iwaniec","doi":"10.1016/j.rpth.2025.102995","DOIUrl":"10.1016/j.rpth.2025.102995","url":null,"abstract":"<div><h3>Background</h3><div>Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder due to a deficiency of von Willebrand factor (VWF). High shear stress causes stretching and rupture of VWF multimers, leading to functional loss and increased proteolysis. This occurs in cardiovascular diseases, reducing high-molecular-weight multimers (HMWMs). Patent ductus arteriosus (PDA) and ventricular septal defect (VSD) cause blood shunting between systemic and pulmonary circulation, increasing shear stress, and may contribute to AVWS.</div></div><div><h3>Objectives</h3><div>To investigate whether children with PDA and VSD experience disturbances in platelet-related activity that cause HMWM loss and an AVWS-like phenotype.</div></div><div><h3>Methods</h3><div>The study involved 54 children with PDA and VSD. Patients who met the screening criteria, including a ristocetin cofactor activity to VWF antigen ratio (VWF:RCo/VWF:Ag) and/or collagen binding to VWF:Ag ratio (VWF:CB/VWF:Ag) &lt;0.8, underwent VWF multimer analysis, and the VWF large multimer index (VWF-LMI) was calculated.</div></div><div><h3>Results</h3><div>Of the 54 patients, 26 (48.1%) underwent multimer analysis, and an AVWS-like phenotype was found in 13 (24.1%). These patients had significantly lower percentage of HMWMs and lower VWF-LMI (27.3 ± 2.9% vs 38.8 ± 5.5% and 75.5 ± 7.3 vs 108.1 ± 14.7, respectively, <em>P</em> &lt; .001). A VWF-LMI &lt;0.8 effectively predicted an AVWS-like phenotype with a sensitivity of 1.0 and a specificity of 0.87, followed by the VWF:CB/VWF:Ag ratio, with a sensitivity of 0.57 and specificity of 0.80 at the same threshold.</div></div><div><h3>Conclusion</h3><div>Nearly a quarter (25%) of children with VSD and PDA exhibit an AVWS-like phenotype. In addition to, VWF multimer analysis and VWF-LMI assessment, the VWF: CB/VWF:Ag ratio is suitable for screening in this group.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102995"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral sinus venous thrombosis in a child with Québec platelet disorder with high-resolution intracellular localization of urokinase in platelets","authors":"Alexandra Zabeida ,&nbsp;Natalie Mathews ,&nbsp;Vanessa Bouskill ,&nbsp;Jennifer Vincelli ,&nbsp;Suzan Williams ,&nbsp;Fred G. Pluthero ,&nbsp;Manuel Carcao ,&nbsp;Walter H.A. Kahr","doi":"10.1016/j.rpth.2025.102966","DOIUrl":"10.1016/j.rpth.2025.102966","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102966"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of heavy menstrual bleeding in a multidisciplinary young women’s clinic: a Dutch experience","authors":"Yara Dixon ,&nbsp;Bart Kabboord ,&nbsp;Carla Groenestein-Sondaal ,&nbsp;Marieke J.H.A. Kruip ,&nbsp;Carolien van der Velden ,&nbsp;Greta Mulders ,&nbsp;C. Heleen van Ommen","doi":"10.1016/j.rpth.2025.102959","DOIUrl":"10.1016/j.rpth.2025.102959","url":null,"abstract":"<div><h3>Background</h3><div>Heavy menstrual bleeding (HMB) is common in young women. It may lead to iron deficiency with or without anemia, decreased school, work, sport, and social participation, and may be the first sign of underlying bleeding disorders (BDs).</div></div><div><h3>Objectives</h3><div>To study the prevalence of BDs, initial and effective management of HMB and iron deficiency (anemia) in young women referred to a tertiary multidisciplinary HMB clinic.</div></div><div><h3>Methods</h3><div>This was a retrospective, single-center chart review evaluating patients aged ≤25 years who visited the multidisciplinary HMB clinic between March 2018 and December 2023.</div></div><div><h3>Results</h3><div>In total, 200 patients (median age, 15 years) were included. At first consultation, BD was already diagnosed in 47 (24%) patients, particularly von Willebrand disease (<em>n</em> = 27). In 32 of 153 (21%) remaining patients, a new BD was diagnosed (von Willebrand disease, <em>n</em> = 21; platelet aggregation defect, <em>n</em> = 8). Initial therapy of HMB mainly consisted of tranexamic acid with (<em>n</em> = 52, 26%) or without (<em>n</em> = 50, 30%) combined oral contraceptive pill. In 60 patients (30%), initial therapy was effective. Effective HMB management was mostly achieved with tranexamic acid combined with a combined oral contraceptive pill (<em>n</em> = 75, 38%) after a median of 1 treatment change (range, 0-10). Iron deficiency was present in 52% of patients, with approximately half having anemia. Treatment consisted of oral and/or intravenous iron supplementation in 77 patients and red blood cell transfusion in 9 patients.</div></div><div><h3>Conclusion</h3><div>BDs and iron deficiency (anemia) were common in young women with HMB. Multiple treatment strategies were needed to achieve an acceptable outcome. A multidisciplinary approach may offer complementary expertise in this patient group.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102959"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why is the uptake of gene therapy in hemophilia less than expected?","authors":"Glenn F. Pierce ,&nbsp;Mark Skinner ,&nbsp;Brian O’Mahony ,&nbsp;Dawn Rotellini ,&nbsp;Radoslaw Kaczmarek","doi":"10.1016/j.rpth.2025.102948","DOIUrl":"10.1016/j.rpth.2025.102948","url":null,"abstract":"<div><div>Gene therapy has held promise to cure hemophilia since factor (F)VIII and FIX were cloned more than 40 years ago. However, scientific understanding of the adeno-associated virus, the predominant vector used in gene therapy, has been insufficient to overcome many of the hurdles encountered, resulting in failed clinical studies, marginal efficacy, unfavorable benefit/risk, or phase 3 studies that do not sufficiently support wide commercial use. However, a functional cure, defined as permanent factor levels of at least 40%, has seen durable success in some FIX gene therapy recipients. Less success has been seen for FVIII gene therapy. Additional reasons for slow commercial uptake include the need to establish complex reimbursement processes for very high-priced drugs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102948"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gynecologic and obstetric complications in women with congenital fibrinogen disorders: insights from the Prospective Rare Bleeding Disorders Database","authors":"Samin Mohsenian ,&nbsp;Roberta Palla ,&nbsp;Marzia Menegatti ,&nbsp;Andrea Cairo ,&nbsp;Simona Maria Siboni ,&nbsp;Marguerite Neerman-Arbez ,&nbsp;Mehran Karimi ,&nbsp;Helen Pargantou ,&nbsp;Rosanna Asselta ,&nbsp;Danijela Mikovic ,&nbsp;Marko Saracevic ,&nbsp;Britta Laros-van Gorkom ,&nbsp;Laura Jacobs ,&nbsp;Amy Shapiro ,&nbsp;Adrianna Williamson ,&nbsp;Michael Makris ,&nbsp;Alessandro Casini ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.102960","DOIUrl":"10.1016/j.rpth.2025.102960","url":null,"abstract":"<div><h3>Background</h3><div>Women and girls with congenital fibrinogen deficiencies (CFDs) face higher hemorrhagic risks during their reproductive years, yet data on gynecologic and obstetric complications remain limited.</div></div><div><h3>Objectives</h3><div>We aimed to rate the prevalence of heavy menstrual bleeding and obstetric complications in women with CFDs and compare our findings with previous reports.</div></div><div><h3>Methods</h3><div>This study analyzed data from the Prospective Rare Bleeding Disorders Database registry, including available fibrinogen activity and antigen levels, as well as clinical phenotype and genotype (2013-2020).</div></div><div><h3>Results</h3><div>A total of 59 women (8 afibrinogenemic, 15 hypofibrinogenemic, and 36 dysfibrinogenemic cases) were investigated, of which 32 patients had 70 pregnancies. The prevalence of heavy menstrual bleeding was comparable between hypofibrinogenemic (27%) and dysfibrinogenemic (36%) cases, with a higher frequency in afibrinogenemic (75%) cases. The rates of postpartum hemorrhage at 36% and miscarriage at 23% were notably higher than those observed in the general population (1%-10% and 10%-20%, respectively). These complications were similarly distributed among patients with dysfibrinogenemia (35% and 37%) and hypofibrinogenemia (36% and 31%). There were only 2 (4%) bleeds during pregnancy, both occurring in dysfibrinogenemic cases. Miscarriage was also observed in 50% of the asymptomatic dysfibrinogenemic patients. No significant difference in miscarriage and postpartum hemorrhage rates was found between dysfibrinogenemic individuals with and without hotspot variants (<em>P</em> = .94).</div></div><div><h3>Conclusion</h3><div>The high rate of obstetric complications in women with CFDs highlights the need for early diagnosis and the potential need for prophylaxis, as pregnancy may also pose risks in asymptomatic cases. Hotspot variants do not appear to increase the risk of obstetric complications.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102960"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brief comparison of human factor XII-Ala188 and factor XII-Pro188","authors":"Aleksandr Shamanaev,&nbsp;David Gailani","doi":"10.1016/j.rpth.2025.102957","DOIUrl":"10.1016/j.rpth.2025.102957","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 5","pages":"Article 102957"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}