Blood Vessels, Thrombosis & Hemostasis最新文献

{"title":"In vivo neuroprotection in ischemic stroke by activated protein C requires β-arrestin 2","authors":"Biao Xiang ∗ ,&nbsp;Yaoming Wang ∗ ,&nbsp;Ruslan Rust ,&nbsp;Kassandra Kisler ,&nbsp;William J. Mack ,&nbsp;José A. Fernández ,&nbsp;Berislav V. Zlokovic † ,&nbsp;John H. Griffin †","doi":"10.1016/j.bvth.2024.100037","DOIUrl":"10.1016/j.bvth.2024.100037","url":null,"abstract":"<div><h3>Abstract</h3><div>The protease activated protein C (APC) and its variants provide neuroprotection for murine ischemic stroke and mortality reduction for murine sepsis. For these actions, APC’s in vivo mechanism of action, similar to in vitro studies using cultured cells, involves protease activated receptor 1 (PAR1)–mediated biased signaling. APC/PAR1 signaling in vitro requires β-arrestin 2, an intracellular scaffold protein, and β-arrestin 2–initiated signaling can alter diverse intracellular signaling pathways. This study used a proximal transient middle cerebral artery occlusion model to study the neuroprotective actions of the signaling-selective APC variant, 3K3A-APC, in β-arrestin 2–deficient (<em>Arrb2</em>^–/–) mice. Based on quantitation of brain injuries, 3K3A-APC significantly limited brain injury in control mice to relatively small, localized areas, whereas 3K3A-APC’s protection was lost in <em>Arrb2</em>^–/– mice. Thus, the major in vitro mechanism of action that requires β-arrestin 2 for APC/PAR1 biased signaling is central to the in vivo mechanism of action for APC’s neuroprotection.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 1","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093755","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":"Low incidence of thromboembolism with Fiix-monitored warfarin compared to conventional warfarin and DOACs in patients with AF","authors":"Arnar B. Ingason ,&nbsp;Brynja R. Gudmundsdottir ,&nbsp;Ragnar Palsson ,&nbsp;Johann P. Hreinsson ,&nbsp;Sigrun H. Lund ,&nbsp;Loic R. Letertre ,&nbsp;Edward Rumba ,&nbsp;Arnar S. Agustsson ,&nbsp;Einar S. Bjornsson ,&nbsp;Pall T. Onundarson","doi":"10.1016/j.bvth.2025.100056","DOIUrl":"10.1016/j.bvth.2025.100056","url":null,"abstract":"<div><h3>Abstract</h3><div>Mixed population studies suggest that monitoring only coagulation factors II and X (Fiix) instead of conventional prothrombin time improves clinical outcomes in patients on warfarin. We hypothesized that Fiix-monitored warfarin (Fiix-warfarin) provides better real-world clinical outcomes than PT based international normalized ratio (PT-INR) monitored warfarin (PT-warfarin), apixaban, dabigatran, and rivaroxaban in non-valvular atrial fibrillation (AF) patients. We performed a retrospective population cohort study over a 5-year period including all long-term orally anticoagulated adult AF patients in the Greater Reykjavik area. Baseline characteristics differences were adjusted using inverse probability of treatment weighting. Principal outcomes were rates of total thromboembolism (TE), all-cause death, and major bleeding. Outcomes with Fiix-warfarin were used as reference. The study population consisted of 6417 patients anticoagulated long-term for 12 914 person-years (py), ie, Fiix-warfarin (n = 1257/py = 2514), PT-warfarin (n = 1904/py = 3998), apixaban (n = 1171/py = 1639), rivaroxaban (n = 1536/py = 3226) or dabigatran (n = 549/py = 1537). PT-warfarin (1.9% per py; hazard ratio (HR) 1.86 [<em>P</em> =.007]), apixaban (1.9% ppy; HR 1.94 [<em>P</em> = .02]), and dabigatran (2.2% ppy; HR 2.19 [<em>P</em> = .01]) had higher TE rates of than Fiix-warfarin (1.1% ppy). Similarly, rivaroxaban trended towards higher TE rates (1.6% ppy; HR 1.58; [<em>P</em> = .07]). Rivaroxaban had significantly higher all-cause mortality rate than Fiix-warfarin (3.0% vs 2.0% ppy; HR 1.48; [<em>P</em> =.04]). Major bleeding rates were similar. Warfarin anticoagulation variability was lower with Fiix-monitoring than with PT-monitoring. We conclude that Fiix-monitored warfarin could be the most effective long-term oral anticoagulant for patients with AF.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705851","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":"Analyzing 6211 unique variants in the upgraded interactive FVIII web database reveals novel insights into hemophilia A","authors":"Emily H. T. Print ,&nbsp;Anna M. Simmons ,&nbsp;Holly J. Spencer ,&nbsp;Christos Efthymiou ,&nbsp;Victoria A. Harris ,&nbsp;Stephen J. Perkins","doi":"10.1016/j.bvth.2025.100053","DOIUrl":"10.1016/j.bvth.2025.100053","url":null,"abstract":"<div><h3>Abstract</h3><div>Hemophilia A is a rare genetic disease that occurs with mild, moderate, or severe phenotypes and involves dysfunctional or reduced amounts of plasma factor VIII (FVIII). Identifying causal genetic variants in the <em>F8</em> gene is vital for patient care. Our original interactive MySQL database for FVIII in 2013 presented clinical data on 2014 unique FVIII variants in 5072 patients. Here, we expand our database almost threefold with a new total of 6211 unique FVIII variants in 10 064 patients, spanning 1529 of the 2351 FVIII residues (65%). We have also developed a new full-length FVIII structural model that incorporates both its crystal structure and its disordered B domain, which is not visible in available experimental structures. This enabled the assessment of these variants on FVIII. Of the 6211 unique <em>F8</em> variants identified, 730 (12%) were associated with mild phenotypes, 526 (8%) with moderate phenotypes, 2509 (39%) with severe phenotypes, 53 (1%) with multiple severities, and 2393 (40%) with unreported phenotypes. Most variants occurred in the disordered B domain (1281 variants), followed by the A1, A2, and A3 domains (1130, 1071, and 923 variants, respectively) and the C1 and C2 domains (442 and 439 variants, respectively). Inhibitors were associated with 451 variants (7%). Our new structural analyses often revealed changes to the residue solvent surface accessibilities caused by many FVIII variants. The FVIII variant analyses are supported by similar observations in the structurally related FV protein. Our web-accessible FVIII database will enable easier and improved clinical analyses of FVIII genetic variants.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of DNases after hematopoietic stem cell transplant","authors":"Azada Ibrahimova ,&nbsp;Nathan Luebbering ,&nbsp;Lucille Langenberg ,&nbsp;Sheyar Abdullah ,&nbsp;Lauren Strecker ,&nbsp;Kelly E. Lake ,&nbsp;Adam Lane ,&nbsp;Aaron Webster ,&nbsp;Kasiani C. Myers ,&nbsp;Sonata Jodele ,&nbsp;Stella M. Davies","doi":"10.1016/j.bvth.2025.100055","DOIUrl":"10.1016/j.bvth.2025.100055","url":null,"abstract":"<div><h3>Abstract</h3><div>The entire hematopoietic system is rapidly lysed over 8 to 10 days during hematopoietic stem cell transplant (HSCT), releasing toxic intracellular molecules such as cell-free DNA (cfDNA) and proteins such as actin into the circulation. Neutrophil extracellular traps released at the time of engraftment also contribute to the cfDNA burden. Clearance of cfDNA is essential for limiting tissue toxicity. We measured levels of cfDNA, DNase I and DNase1L3 in 108 consecutive patients receiving allogeneic HSCT at baseline and on days 0, 7, 14, 30, and 100. cfDNA levels peak at day 14 and are higher in patients with endothelial injury. DNase I levels are depleted on day 7, recovering quickly by day 14, and remain above baseline at day 100. DNase1L3 levels decreased below baseline at day 0, reached a nadir by day 7, but recovered by day 30 remaining above baseline at day 100. Patients with a periengraftment oxygen requirement and those with transplant-associated thrombotic microangiopathy had higher DNase I levels than those without. DNase1L3 levels did not influence any HSCT outcomes. We analyzed DNase I activity using plasmid DNA degradation and showed decreased activity on days 0 and 7, in agreement with reduced protein levels. Further studies are needed to understand the dynamics of DNases in patients undergoing HSCT, to assess their potential role in HSCT toxicities.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687950","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":"Hematologists’ comfort and experiences with providing care to transgender youth","authors":"Eric S. Mullins ,&nbsp;Tanya L. Kowalczyk Mullins","doi":"10.1016/j.bvth.2025.100054","DOIUrl":"10.1016/j.bvth.2025.100054","url":null,"abstract":"<div><h3>Abstract</h3><div>Transgender and gender-diverse (TG) people with preexisting risk factors for thrombosis may seek hematologic evaluation before starting gender-affirming hormone therapy (GAHT). Because no formal guidelines on management of thrombosis risk exist, variations in management are likely to occur. We characterized hematologists’ experience and comfort with caring for TG youth and explored experiences with recommending thromboprophylaxis before GAHT. Hematologists caring for youth aged ≤22 years and practicing in the midwestern United States completed semistructured interviews assessing demographics, practice characteristics, comfort with caring for TG people, education in TG clinical care, suggested interventions to improve comfort, and experiences with recommending and/or prescribing thromboprophylaxis before GAHT. Of the 15 hematologists interviewed (12 pediatric, 2 adult, and 1 dual trained), nearly all had cared for TG adolescents (n = 12) or young adults (n = 14). Participants reported variable comfort with asking about name and pronouns and knowledge about the gender transition process. Although most hematologists reported having had some education about TG clinical care, this primarily occurred after formal training was completed. Suggested interventions to increase comfort with caring for TG youth included educating hematologists about gender care, changes in the electronic medical record, and more data on thrombosis risk associated with GAHT. One-third of participants had recommended and started thromboprophylaxis for patients before GAHT. Five additional hematologists had evaluated youths before GAHT but had not recommended thromboprophylaxis. Because hematologists are evaluating patients for potential thromboprophylaxis before GAHT, education about caring for TG people and data about thrombosis risk are needed to improve care for this population.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601656","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":"Cardiovascular risk factors in myeloproliferative neoplasms: associations with survival and thrombotic outcomes","authors":"Joan How ,&nbsp;Orly Leiva ,&nbsp;Robert Redd ,&nbsp;Anna E. Marneth ,&nbsp;Daniel J. DeAngelo ,&nbsp;Christina M. Dieli-Conwright ,&nbsp;Areej El-Jawahri ,&nbsp;Baransal Kamaz ,&nbsp;Chulwoo Kim ,&nbsp;R. Coleman Lindsley ,&nbsp;Marlise Luskin ,&nbsp;Maximilian Stahl ,&nbsp;Mohammed Wazir ,&nbsp;Lachelle D. Weeks ,&nbsp;Gabriela S. Hobbs","doi":"10.1016/j.bvth.2025.100051","DOIUrl":"10.1016/j.bvth.2025.100051","url":null,"abstract":"<div><h3>Abstract</h3><div>Cardiovascular risk factors (CVRFs) are important modifiers of thrombosis in patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). We performed a retrospective cohort analysis evaluating CVRFs in 1005 patients with myeloproliferative neoplasms (MPNs) from the Dana-Farber Cancer Institute Hematologic Malignancies Data Repository from 2014 to 2023. We also included a non-MPN group of 1543 age- and sex-matched controls with no known diagnoses of hematologic malignancies to evaluate whether CVRFs differentially affected outcomes. CVRFs were identified through International Classification of Diseases codes for hypertension, hyperlipidemia, type 2 diabetes mellitus (DM2), current smoking, or body mass index ≥30 before MPN diagnosis. CVRFs occurred in 34% of patients with MPNs. Patients with MPN with ≥1 CVRF had increased risk of death (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.9-3.35) and arterial/venous thrombosis (HR, 3.05; 95% CI 2.39-3.92). Within MPN subtypes, patients with ET, PV, and MF who had CVRFs also demonstrated worse overall survival and thrombotic outcomes. Among CVRFs, only DM2 predicted worse thrombotic outcomes in patients with MPNs. The HR of CVRF on thrombosis was decreased in patients with MPNs compared with non-MPN controls (HR, 0.51; 95% CI, 0.36-0.86). Looking at ET, PV, and MF specifically, the presence of a CVRF also had less of an impact on thrombotic risk in ET compared with controls (HR, 0.35; <em>P</em> = .019); no interactions between MPN diagnosis and CVRFs were seen in patients with PV and MF. Our results underscore both the necessity of managing CVRFs in MPNs to improve patient morbidity and mortality and the need to ameliorate thrombotic risk with measures beyond addressing CVRFs.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 3","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of sickle trait on maternal and perinatal outcomes among pregnant women","authors":"Sarah Sewaralthahab ,&nbsp;Jiling Chou ,&nbsp;Stephen Fernandez ,&nbsp;Nawar Shara ,&nbsp;Hedy P. Smith","doi":"10.1016/j.bvth.2025.100049","DOIUrl":"10.1016/j.bvth.2025.100049","url":null,"abstract":"<div><h3>Abstract</h3><div>The risk of multiple adverse pregnancy outcomes and perinatal outcomes among pregnant women with sickle cell trait (SCT) is not known. Our objective was to compare differences in adverse outcomes, specifically pregnancy-related hypertensive disease (PRHD), pyelonephritis/urinary tract infection (UTI), and low birth weight (LBW), between pregnant women with SCT and healthy controls. This was a retrospective cohort study of women who delivered between 2015 and 2020. We included all women with SCT, that is, hemoglobin electrophoresis AS. Women with SCT were matched in a 1:2 to women without SCT, controlling for age, gravidity, and parity. Our primary outcomes were PRHD, pyelonephritis/UTI, and LBW baby. Multivariable logistic regression modeling examined the associations between patients’ characteristics and the primary outcomes.There were 162 women with SCT, and 324 healthy control women were enrolled. Bivariate analysis revealed that women with SCT had a higher proportion of PRHD (38.9% vs 34.9%; <em>P</em> = .39), pyelonephritis/UTI (11.7% vs 7.1%; <em>P</em> = .09), but a lower proportion of LBW (10.5% vs 16.0%; <em>P</em> = .1). In multivariable analysis, after controlling for confounders, SCT was not an independent predictor of PRHD. However, SCT was an independent predictor of pyelonephritis/UTI (adjusted odds ratio [aOR], 1.98; 95% confidence interval [CI], 1.02-3.85) and of a lower risk of having a LBW baby (aOR, 0.48; 95% CI, 0.25-0.94). SCT is not associated with an increased risk of PRHD. However, SCT is associated with pregnancy outcomes, including higher risk of pyelonephritis/UTI but a lower risk of LBW babies.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601310","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":"A NOTCH4 intron 28 regulatory element controls arterial specification and lymphoid development from hPSCs","authors":"Ho Sun Jung ,&nbsp;Divine Mensah Sedzro ,&nbsp;Peng Liu ,&nbsp;Igor I. Slukvin","doi":"10.1016/j.bvth.2025.100046","DOIUrl":"10.1016/j.bvth.2025.100046","url":null,"abstract":"<div><h3>Abstract</h3><div>NOTCH signaling plays a critical role in arterial specification, and the formation of transient definitive lymphomyeloid progenitors and hematopoietic stem cells from hemogenic endothelium (HE). To investigate NOTCH signaling mechanisms critical for arterial and lymphoid specification, we performed single-cell multiomics analysis of human pluripotent stem cells (hPSCs) at different stages of hematopoietic differentiation. These studies uncovered the activation of NOTCH signaling and the arterial program, along with dynamic changes in related regulons throughout the HE specification and the endothelial-to-hematopoietic transition. We revealed that expression of NOTCH4 in the arterial endothelium is controlled by a <em>cis</em>-regulatory element within intron 28 (<em>NOTCH4in28</em>) through SOX17 binding. Deletion of <em>NOTCH4in28</em> in conventional and conditional iSOX17 hPSCs impaired the formation of the early wave DLL4⁺CXCR4^+/− HE with arterial features, as well as hematopoietic progenitors with T and natural killer lymphoid potential. Collectively, we provide compelling evidence that NOTCH4 and the <em>NOTCH4in28 cis</em>-regulatory element play an important role in arterial specification and lymphoid development in hPSC cultures.</div></div>","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal variation in immune thrombotic thrombocytopenic purpura in New England","authors":"Jorge N. Ruiz Lopez ,&nbsp;Ishan Tatake ,&nbsp;Pavan K. Bendapudi","doi":"10.1016/j.bvth.2025.100050","DOIUrl":"10.1016/j.bvth.2025.100050","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563421","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":"Regression of pathological blood vessels by inhibition of mast cell function","authors":"WonKyung J. Cho ,&nbsp;Sharad K. Mittal ,&nbsp;Aastha Singh ,&nbsp;Elsayed Elbasiony ,&nbsp;Lei Xi ,&nbsp;Olufemi S. Folorunso ,&nbsp;Vinay K. Pulimamidi ,&nbsp;Sunil K. Chauhan","doi":"10.1016/j.bvth.2025.100044","DOIUrl":"10.1016/j.bvth.2025.100044","url":null,"abstract":"","PeriodicalId":100190,"journal":{"name":"Blood Vessels, Thrombosis & Hemostasis","volume":"2 2","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}