{"title":"Daucosterol regulates JAK2-STAT3 signaling pathway to promote megakaryocyte differentiation","authors":"Zhongkang Zhang, Guangbin Shang, Zhen Lu, Jia Hu, Huizhen Liu, Ting Lu, Xiaonan Lu","doi":"10.1016/j.bcmd.2024.102858","DOIUrl":"10.1016/j.bcmd.2024.102858","url":null,"abstract":"<div><p>Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. <em>Sarcandra glabra</em>, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102858"},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032116","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}
Matthew Hudkins , Heather Hamilton , Samantha J. Underwood , Diana E. Kazmierczak , Elizabeth N. Dewey , Steven C. Kazmierczak , William B. Messer , Akram Khan , Martin A. Schreiber , David H. Farrell
{"title":"Extreme γ′ fibrinogen levels in COVID-19 patients","authors":"Matthew Hudkins , Heather Hamilton , Samantha J. Underwood , Diana E. Kazmierczak , Elizabeth N. Dewey , Steven C. Kazmierczak , William B. Messer , Akram Khan , Martin A. Schreiber , David H. Farrell","doi":"10.1016/j.bcmd.2024.102856","DOIUrl":"10.1016/j.bcmd.2024.102856","url":null,"abstract":"<div><p>COVID-19 disease progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"107 ","pages":"Article 102856"},"PeriodicalIF":2.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000342/pdfft?md5=e08897c9e445c8fe9f4eb50cb0df99cd&pid=1-s2.0-S1079979624000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to commentary on “Unmasking the morphological alteration of erythrocytes among women suffering from PCOS”","authors":"Sutithi Dey, Rajen Haldar","doi":"10.1016/j.bcmd.2024.102839","DOIUrl":"10.1016/j.bcmd.2024.102839","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102839"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054478","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}
Daniel Martínez-Carballeira , Alberto Caro , Ángel Bernardo , José Ramón Corte , José Carlos Iglesias , Isabel Asunción Hernández de Castro , Laura Gutiérrez , Inmaculada Soto
{"title":"Rare bleeding disorders: Real-world data from a Spanish tertiary hospital","authors":"Daniel Martínez-Carballeira , Alberto Caro , Ángel Bernardo , José Ramón Corte , José Carlos Iglesias , Isabel Asunción Hernández de Castro , Laura Gutiérrez , Inmaculada Soto","doi":"10.1016/j.bcmd.2024.102837","DOIUrl":"10.1016/j.bcmd.2024.102837","url":null,"abstract":"<div><h3>Introduction</h3><p>Due to their low prevalence, rare bleeding disorders (RBDs) remain poorly characterized.</p></div><div><h3>Aim</h3><p>To gain insight of RBDs through our clinical practice.</p></div><div><h3>Methods</h3><p>Retrospective study of the medical records of RBD patients followed up at the Central University Hospital of Asturias between January 2019 and December 2022.</p></div><div><h3>Results</h3><p>A total of 149 patients were included. Factor (F) VII (44 %) and FXI (40 %) deficiencies were the most common diagnosed coagulopathies. Most of the patients were asymptomatic (60.4 %) and the most frequent type of bleeding were mucocutaneous and after surgery. All replacement treatments were administered on demand and no patient was on a prophylaxis regimen. Currently available products were safe; allergic reactions after administration of plasma were the most frequent complication. Genetic analysis, carried out on 55 patients (37 %), showed that the most frequent mutations in RBDs are of missense type (71.9 %). We identified 11 different novel genetic alterations in affected genes. The c.802C > T (p.Arg268Cys) variant, previously described, was identified in 71 % (15 of 21) of the patients with FXI deficiency genotyped and none were related (probable founder effect).</p></div><div><h3>Conclusion</h3><p>Our study on an unusual large single center cohort of RBD patients portrays location-dependent distinct genetic drives and clinical practice particularities.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102837"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139826106","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":"Platelet activation and blood extracellular vesicles: The influence of venepuncture and short blood storage","authors":"Ivica Marić , Klemen Žiberna , Ana Kolenc , Elvira Maličev","doi":"10.1016/j.bcmd.2024.102842","DOIUrl":"https://doi.org/10.1016/j.bcmd.2024.102842","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) as membrane-bound particles released by various cells are potential tools for diagnosis and treatment. Blood cells, particularly platelets, are the source of circulating EVs.</p></div><div><h3>Material</h3><p>EVs were enriched with gradient ultracentrifugation and measured by nanoparticle tracking assay. A flow cytometric multiplex assay was used for cellular source determination. Activation of platelets was measured as a percentage of CD62p+/CD61+ platelets and correlated with the concentration and size of released EVs.</p></div><div><h3>Results</h3><p>In general there was no statistically significant correlation between EVs` concentration and degree of platelet activation. EVs from different cellular sources were detected. Comparing different needle thicknesses, there was a decrease in the EVs concentration for the 16G needle versus the 21G needle, but no difference was observed for EVs` size and phenotype or platelets activation. During blood storage, platelet activation increased, but there was no effect on the EVs` concentration, size, or phenotype.</p></div><div><h3>Conclusions</h3><p>Preanalytical factors like needle thickness and storage time can affect the MVs' properties. Activation of platelets during blood collection or blood storage occurs; however, it is difficult to determine its effect on the physiological properties of EVs since the mechanisms of EVs` biogenesis and especially clearness are not precisely known.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102842"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000202/pdfft?md5=9311cf50b5aae847a6f9869128d371da&pid=1-s2.0-S1079979624000202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on “unmasking the morphological alteration of erythrocytes among women suffering from PCOS”","authors":"Shuwei Fan , Guomei Shi , Kelan Li","doi":"10.1016/j.bcmd.2024.102840","DOIUrl":"10.1016/j.bcmd.2024.102840","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102840"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012134","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}
Auria Godard , Robert Seute , Alexandra Grimaldi , Thomas Granier , Jacques Chiaroni , Wassim El Nemer , Maria De Grandis
{"title":"A comparative study of two routinely used protocols for ex vivo erythroid differentiation","authors":"Auria Godard , Robert Seute , Alexandra Grimaldi , Thomas Granier , Jacques Chiaroni , Wassim El Nemer , Maria De Grandis","doi":"10.1016/j.bcmd.2024.102829","DOIUrl":"10.1016/j.bcmd.2024.102829","url":null,"abstract":"<div><h3>Background</h3><p>Erythropoiesis is a complex developmental process in which a hematopoietic stem cell undergoes serial divisions and differentiates through well-defined stages to give rise to red blood cells. Over the last decades, several protocols have been developed to perform <em>ex vivo</em> erythroid differentiation, allowing investigation into erythropoiesis and red cell production in health and disease.</p></div><div><h3>Results</h3><p>In the current study, we compared the two commonly used protocols by assessing the differentiation kinetics, synchronisation, and cellular yield, using molecular and cellular approaches. Peripheral blood CD34<sup>+</sup> cells were cultured in a two-phase (2P) or a four-phase (4P) liquid culture (LC) and monitored for 20 days. Both protocols could recapitulate all stages of erythropoiesis and generate reticulocytes, although to different extents. Higher proliferation and viability rates were achieved in the 4P-LC, with a higher degree of terminal differentiation and enucleation, associated with higher levels of the erythroid-specific transcription factors GATA-1, KLF-1, and TAL-1. Although the 2P-LC protocol was less efficient regarding terminal erythroid differentiation and maturation, it showed a higher yield of erythroid progenitors in the erythropoietin (EPO)-free expansion phase.</p></div><div><h3>Conclusions</h3><p>We provide data supporting the use of one protocol or the other to study the biological processes occurring in the early or late stages of erythroid differentiation, depending on the physiological process or pathological defect under investigation in a given study.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102829"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S107997962400007X/pdfft?md5=718346331294e764ec71ad08f76c0fc4&pid=1-s2.0-S107997962400007X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Da Costa , Narla Mohandas , Ludivine David-NGuyen , Jessica Platon , Isabelle Marie , Marie Françoise O'Donohue , Thierry Leblanc , Pierre-Emmanuel Gleizes
{"title":"Diamond-Blackfan anemia, the archetype of ribosomopathy: How distinct is it from the other constitutional ribosomopathies?","authors":"L. Da Costa , Narla Mohandas , Ludivine David-NGuyen , Jessica Platon , Isabelle Marie , Marie Françoise O'Donohue , Thierry Leblanc , Pierre-Emmanuel Gleizes","doi":"10.1016/j.bcmd.2024.102838","DOIUrl":"10.1016/j.bcmd.2024.102838","url":null,"abstract":"<div><p>Diamond-Blackfan anemia (DBA) was the first ribosomopathy described in humans. DBA is a congenital hypoplastic anemia, characterized by macrocytic aregenerative anemia, manifesting by differentiation blockage between the BFU-e/CFU-e developmental erythroid progenitor stages. In 50 % of the DBA cases, various malformations are noted. Strikingly, for a hematological disease with a relative erythroid tropism, DBA is due to ribosomal haploinsufficiency in 24 different ribosomal protein (RP) genes. A few other genes have been described in DBA-like disorders, but they do not fit into the classical DBA phenotype (Sankaran et al., 2012; van Dooijeweert et al., 2022; Toki et al., 2018; Kim et al., 2017 [<span>[1]</span>, <span>[2]</span>, <span>[3]</span>, <span>[4]</span>]).</p><p>Haploinsufficiency in a RP gene leads to defective ribosomal RNA (rRNA) maturation, which is a hallmark of DBA. However, the mechanistic understandings of the erythroid tropism defect in DBA are still to be fully defined. Erythroid defect in DBA has been recently been linked in a non-exclusive manner to a number of mechanisms that include: 1) a defect in translation, in particular for the <em>GATA1</em> erythroid gene; 2) a deficit of HSP70, the GATA1 chaperone, and 3) free heme toxicity. In addition, p53 activation in response to ribosomal stress is involved in DBA pathophysiology. The DBA phenotype may thus result from the combined contributions of various actors, which may explain the heterogenous phenotypes observed in DBA patients, even within the same family.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102838"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921039","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}
Fernanda D'Avila da Silva , Maria Eduarda de Andrade Galiciolli , Ana Carolina Irioda , Cláudia Sirlene Oliveira , Bruna Candia Piccoli , Alessandro de Souza Prestes , Bruna Cogo Borin , Andre Passaglia Schuch , Estael Ochoa-Rodríguez , Yanier Nuñez-Figueredo , João Batista Teixeira da Rocha
{"title":"Investigation of the cytotoxicity, genotoxicity and antioxidant prospects of JM-20 on human blood cells: A multi-target compound with potential therapeutic applications","authors":"Fernanda D'Avila da Silva , Maria Eduarda de Andrade Galiciolli , Ana Carolina Irioda , Cláudia Sirlene Oliveira , Bruna Candia Piccoli , Alessandro de Souza Prestes , Bruna Cogo Borin , Andre Passaglia Schuch , Estael Ochoa-Rodríguez , Yanier Nuñez-Figueredo , João Batista Teixeira da Rocha","doi":"10.1016/j.bcmd.2024.102827","DOIUrl":"10.1016/j.bcmd.2024.102827","url":null,"abstract":"<div><p><span><span>JM-20 is a 1,5-benzodiazepine compound fused to a dihydropyridine<span><span> fraction with different pharmacological properties. However, its potential toxic effects on blood cells have not yet been reported. Thus, the present study aimed to investigate, for the first time, the possible cytotoxicity of JM-20 through </span>cell viability<span><span>, cell cycle, morphology changes, reactive species (RS) to DCFH-DA, and lipid peroxidation in human leukocytes, its </span>hemolytic<span> effect on human erythrocytes, and its potential DNA </span></span></span></span>genotoxicity using plasmid DNA </span><em>in vitro</em><span>. Furthermore, the compound's ability to reduce the DPPH radical was also measured. Human blood was obtained from healthy volunteers (30 ± 10 years old), and the leukocytes or erythrocytes were immediately isolated and treated with different concentrations of JM-20. A cytoprotective effect was exhibited by 10 μM JM-20 against 1 mM tert-butyl hydroperoxide (t-but-OOH) in the leukocytes. However, the highest tested concentrations of the compound (20 and 50 μM) changed the morphology and caused a significant decrease in the cell viability of leukocytes (p < 0.05, in comparison with Control). All tested concentrations of JM-20 also resulted in a significant increase in intracellular RS as measured by DCFH-DA in these cells (p < 0.05, in comparison with Control). On the other hand, the results point out a potent antioxidant effect of JM-20, which was similar to the classical antioxidant α-tocopherol. The IC</span><sub>50</sub> value of JM-20 against the lipid peroxidation induced by (FeII) was 1.051 μM ± 0.21, while the IC<sub>50</sub> value of α-tocopherol in this parameter was 1.065 μM ± 0.34. Additionally, 50 and 100 μM JM-20 reduced the DPPH radical in a statistically similar way to the 100 μM α-tocopherol (p < 0.05, in comparison with the control). No significant hemolysis in erythrocytes, no cell cycle changes in leukocytes, and no genotoxic effects in plasmid DNA were induced by JM-20 at any tested concentration. The <span><em>in silico</em></span><span> pharmacokinetic<span> and toxicological properties of JM-20, derivatives, and nifedipine were also studied. Here, our findings demonstrate that JM-20 and its putative metabolites exhibit similar characteristics to nifedipine, and the </span></span><em>in vitro</em> and <em>in silico</em> data support the low toxicity of JM-20 to mammals.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"106 ","pages":"Article 102827"},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510183","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}
Brígida Santos , Catarina Ginete , Elisângela Gonçalves , Mariana Delgadinho , Armandina Miranda , Paula Faustino , Ana Paula Arez , Miguel Brito
{"title":"Characterization of a cohort of Angolan children with sickle cell anemia treated with hydroxyurea","authors":"Brígida Santos , Catarina Ginete , Elisângela Gonçalves , Mariana Delgadinho , Armandina Miranda , Paula Faustino , Ana Paula Arez , Miguel Brito","doi":"10.1016/j.bcmd.2023.102822","DOIUrl":"10.1016/j.bcmd.2023.102822","url":null,"abstract":"<div><h3>Background</h3><p>Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous.</p></div><div><h3>Objectives</h3><p>This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity.</p></div><div><h3>Methods</h3><p>The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months.</p></div><div><h3>Results</h3><p>A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels.</p></div><div><h3>Conclusions</h3><p>the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"105 ","pages":"Article 102822"},"PeriodicalIF":2.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979623000992/pdfft?md5=6ac4fc1b23206523b69ea849bc5368bf&pid=1-s2.0-S1079979623000992-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139094036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}