MD – Peter Schlenke, PhD – Peter Bugert, MD Beate Mayer, MD Axel Pruß, MD Franz F. Wagner, MD Patrick Wuchter, PhD – Jason Acker, MD Gregor Bein, MD – Reinhard Burger, Robert Koch, PhD Toni Cathomen, PhD Jens Dreier, MD Hermann Eichler, MD – Andreas Humpe, MD Harald Klüter, MD – Jens Meier, MD – Rainer Moog, German Red, PhD – Bristol Andrew D. Mumford, CardioVascular, PhD – Thierry Peyrard, MD – Erwin Strasser, PhD – Pieter F. van der Meer, MD – Mark H. Yazer, E. Strasser, J. Piñeyroa, J. Cid, M. Lozano, P. Schlenke, von Heymann, Berlin Lier, H. Cologne, C. Rosenthal, L. Kaufner, Berlin, P.F.W. Strengers, Amsterdam, J. Cottrell, A. Al Sanani, I. Ogu, D. Chaffin, WV Huntington, D’Alessandro, P. A. Bugert, Research Articles, Meta-Analysis Qin, X. G. Han
{"title":"Contents Vol. 50, 2023","authors":"MD – Peter Schlenke, PhD – Peter Bugert, MD Beate Mayer, MD Axel Pruß, MD Franz F. Wagner, MD Patrick Wuchter, PhD – Jason Acker, MD Gregor Bein, MD – Reinhard Burger, Robert Koch, PhD Toni Cathomen, PhD Jens Dreier, MD Hermann Eichler, MD – Andreas Humpe, MD Harald Klüter, MD – Jens Meier, MD – Rainer Moog, German Red, PhD – Bristol Andrew D. Mumford, CardioVascular, PhD – Thierry Peyrard, MD – Erwin Strasser, PhD – Pieter F. van der Meer, MD – Mark H. Yazer, E. Strasser, J. Piñeyroa, J. Cid, M. Lozano, P. Schlenke, von Heymann, Berlin Lier, H. Cologne, C. Rosenthal, L. Kaufner, Berlin, P.F.W. Strengers, Amsterdam, J. Cottrell, A. Al Sanani, I. Ogu, D. Chaffin, WV Huntington, D’Alessandro, P. A. Bugert, Research Articles, Meta-Analysis Qin, X. G. Han","doi":"10.1159/000535411","DOIUrl":"https://doi.org/10.1159/000535411","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139012756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Frietsch, Maria B. Rondinelli, Jerrold H. Levy
{"title":"Congratulation, Appraisal, and Comment on the 25 Years Anniversary of Serious Hazards of Blood Transfusion","authors":"Thomas Frietsch, Maria B. Rondinelli, Jerrold H. Levy","doi":"10.1159/000532049","DOIUrl":"https://doi.org/10.1159/000532049","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139233540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vitro Hemostatic Functions of Cold-Stored Platelets","authors":"J. Kirschall, G. Uzun, T. Bakchoul, I. Marini","doi":"10.1159/000533735","DOIUrl":"https://doi.org/10.1159/000533735","url":null,"abstract":"Background: Transfusion of platelets is a life-saving medical strategy used worldwide to treat patients with thrombocytopenia as well as platelet function disorders. Summary: Until the end of 1960s, platelets were stored in the cold because of their superior hemostatic functionality. Cold storage of platelets was then abandoned due to better posttransfusion recovery and survival of room temperature (RT)-stored platelets, demonstrated by radioactive labeling studies. Based on these findings, RT became the standard condition to store platelets for clinical applications. Evidence shows that RT storage increases the risk of septic transfusion reactions associated with bacterial contamination. Therefore, the storage time is currently limited to 4–7 days, according to the national guidelines, causing a constant challenge to cover the clinical request. Despite the enormous efforts made to optimize storage conditions of platelets, the quality and efficacy of platelets still decrease during the short storage time at RT. In this context, during the last years, cold storage has seen a renaissance due to the better hemostatic functionality, reduced risk of bacterial contamination, and potentially longer storage time. Key Messages: In this review, we will focus on the impact of cold storage on the in vitro platelet functions as promising alternative storage temperature for future medical applications.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139267885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaxuan Yang, Aijing Li, Minghao Li, Shulin Ruan, Luyi Ye
{"title":"CRISPR/Cas9-Editing K562 Cell Line as a Potential Tool in Transfusion Applications: Knockout of Vel Antigen Gene","authors":"Jiaxuan Yang, Aijing Li, Minghao Li, Shulin Ruan, Luyi Ye","doi":"10.1159/000534012","DOIUrl":"https://doi.org/10.1159/000534012","url":null,"abstract":"<b><i>Introduction:</i></b> The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. <b><i>Methods:</i></b> To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. <b><i>Results:</i></b> The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. <b><i>Conclusion:</i></b> In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135876462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Meybohm, Lotta Hof, Suma Choorapoikayil, Kai Zacharowski
{"title":"Patient Blood Management: We Still Have Work to Do","authors":"Patrick Meybohm, Lotta Hof, Suma Choorapoikayil, Kai Zacharowski","doi":"10.1159/000534087","DOIUrl":"https://doi.org/10.1159/000534087","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134973216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eungjun Yoon, Tae Yeul Kim, Hyungsuk Kim, Duck Cho
{"title":"Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing","authors":"Eungjun Yoon, Tae Yeul Kim, Hyungsuk Kim, Duck Cho","doi":"10.1159/000534273","DOIUrl":"https://doi.org/10.1159/000534273","url":null,"abstract":"<b><i>Introduction:</i></b> Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. <b><i>Methods:</i></b> Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jk<sup>a</sup>) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fy<sup>b</sup> and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. <b><i>Results:</i></b> Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. <b><i>Discussion:</i></b> Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135219224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes-Moritz von Behren, Jan Wesche, Andreas Greinacher, Konstanze Aurich
{"title":"Indocyanine Green-Labeled Platelets for Survival and Recovery Studies","authors":"Johannes-Moritz von Behren, Jan Wesche, Andreas Greinacher, Konstanze Aurich","doi":"10.1159/000533623","DOIUrl":"https://doi.org/10.1159/000533623","url":null,"abstract":"<b><i>Introduction:</i></b> Before being implemented in daily clinical routine, new production strategies for platelet concentrates (PCs) must be validated for their efficacy. Besides in vitro testing, the establishment of new methods requires the labeling of platelets for in vivo studies of platelets’ survival and recovery. Indocyanine green (ICG) is a Food and Drug Administration-approved near-infrared (NIR) fluorescent dye for diagnostic use in vivo, suitable for non-radioactive direct cell labeling of platelets. <b><i>Methods:</i></b> Platelets from PCs in storage solutions with different plasma concentrations were labeled with ICG up to concentrations of 200 μ<sc>m</sc>. Whole blood (WB) was used as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. The impact of labeling processes was assessed by the quantification of CD62P expression and PAC-1 binding as platelet function markers. Platelet aggregation was analyzed by light transmission aggregometry. ICG-labeling efficiency and stability of platelets were determined by flow cytometry. <b><i>Results:</i></b> Platelets from PCs could be successfully labeled with 10 μ<sc>m</sc> ICG after 1 and 4 days of storage. The best labeling efficiency of 99.8% ± 0.1% (immediately after labeling) and 81% ± 6.2% (after 24 h incubation with WB) was achieved by plasma replacement by 100% platelet additive solution for the labeling process. Since the washing process slightly impaired platelet function, ICG labeling itself did not affect platelets. Immediately after the ICG-labeling process, plasma was re-added, resulting in a recovered platelet function. <b><i>Conclusion:</i></b> We developed a Good Manufacturing Practice compatible protocol for ICG fluorescent platelet labeling suitable for survival and recovery studies in vivo as a non-radioactive labeling alternative.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Max Bittrich, Katharina Kriegsmann, Carola Tietze-Stolley, Kamram Movassaghi, Matthias Grube, Vladan Vucinic, Daniela Wehler, Andreas Burchert, Martin Schmidt-Hieber, Andreas Rank, Heinz A. Dürk, Bernd Metzner, Christoph Kimmich, Marcus Hentrich, Christian Kunz, Frank Hartmann, Cyrus Khandanpour, Maike de Wit, Udo Holtick, Michael Kiehl, Andrea Stoltefuß, Alexander Kiani, Ralph Naumann, Christian W. Scholz, Hans-Joachim Tischler, Martin Görner, Franziska Brand, Martin Ehmer, Nicolaus Kröger
{"title":"A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation","authors":"Max Bittrich, Katharina Kriegsmann, Carola Tietze-Stolley, Kamram Movassaghi, Matthias Grube, Vladan Vucinic, Daniela Wehler, Andreas Burchert, Martin Schmidt-Hieber, Andreas Rank, Heinz A. Dürk, Bernd Metzner, Christoph Kimmich, Marcus Hentrich, Christian Kunz, Frank Hartmann, Cyrus Khandanpour, Maike de Wit, Udo Holtick, Michael Kiehl, Andrea Stoltefuß, Alexander Kiani, Ralph Naumann, Christian W. Scholz, Hans-Joachim Tischler, Martin Görner, Franziska Brand, Martin Ehmer, Nicolaus Kröger","doi":"10.1159/000531935","DOIUrl":"https://doi.org/10.1159/000531935","url":null,"abstract":"<b><i>Introduction:</i></b> In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34<sup>+</sup> precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., &gt;10/µL) CD34<sup>+</sup> cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34<sup>+</sup> cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34<sup>+</sup> mobilization in PM patients. <b><i>Methods:</i></b> The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34<sup>+</sup> cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34<sup>+</sup> count in peripheral blood. <b><i>Results:</i></b> 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40–78 years old, slightly more often male (<i>n</i> = 97, 58%), mostly newly diagnosed (<i>n</i> = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (<i>n</i> = 155) underwent apheresis, 78% of them (<i>n</i> = 117) achieved &gt;2.0 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM−PLX patients (62%). <b><i>Conclusion:</i></b> The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136079073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Challenges for Plasma-Derived Medicinal Products","authors":"Rainer Moog, Teija Dehmer-Laitinen, Uwe Taborski","doi":"10.1159/000533736","DOIUrl":"https://doi.org/10.1159/000533736","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136062715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ozone Improves Oxygenation and Offers Organ Protection after Autologous Blood Transfusion in a Simulated Carbon Dioxide Pneumoperitoneal Environment in a Rabbit Hemorrhagic Shock Model","authors":"Yu Gan, Xue Tian, Han Yao, Fei Huo, Yi Feng","doi":"10.1159/000527934","DOIUrl":"https://doi.org/10.1159/000527934","url":null,"abstract":"<b><i>Objectives:</i></b> Autologous blood transfusion techniques are well applied in surgery, but the red blood cells (RBCs) collected during laparoscopic surgery may forfeit their ability to oxygenate. O<sub>3</sub> is a potent oxidation gas. This study investigates whether O<sub>3</sub> could improve the oxygen-carrying capacity of RBCs, reduce inflammatory reactions, and offer organ protection. <b><i>Methods:</i></b> We established a hemorrhagic shock model in rabbits, and simulated CO<sub>2</sub> pneumoperitoneum and O<sub>3</sub> were applied before autologous blood transfusion. Perioperative mean arterial pressure and arterial blood gas were recorded, blood gas and RBC morphology of collected blood were analyzed, plasma IL-6, ALT, AST, CRE, and lung histopathology POD0 and POD3 were tested, as well as postoperative survival quality. <b><i>Results:</i></b> Autologous blood that underwent simulated CO<sub>2</sub> pneumoperitoneum had a lower pH and SaO<sub>2</sub> and a higher PaCO<sub>2</sub> than the control group. After O<sub>3</sub> treatment, PaO<sub>2</sub> and SaO<sub>2</sub> increased significantly, with unchanged pH values and PaCO<sub>2</sub>. RBCs in autologous blood were drastically deformed after CO<sub>2</sub> conditioning and then reversed to normal by O<sub>3</sub> treatment. Rabbits that received CO<sub>2</sub>-conditioned autologous blood had a compromised survival quality after surgery, higher plasma IL-6 levels, higher lung injury scores on POD0, higher ALT and AST levels on POD3, and O<sub>3</sub> treatment alleviated these adverse outcomes. <b><i>Conclusion:</i></b> O<sub>3</sub> can restore RBC function, significantly improve blood oxygenation under simulated CO<sub>2</sub> pneumoperitoneum, offer organ protection, and improve the postoperative survival quality in the rabbit hemorrhage shock model.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135579483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}