Experimental hematology最新文献

{"title":"\"Beyond the Genetic Blueprint: Disrupting the Epitranscriptomic Code in Myeloproliferative Neoplasms\".","authors":"Hamed Soleymani, Shamim Khoshnevisan, Sepideh Gholamian, Parsa Sheybani","doi":"10.1016/j.exphem.2026.105942","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105942","url":null,"abstract":"<p><p>Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are driven by canonical JAK2, CALR, or MPL mutations that constitutively activate JAK-STAT signaling. Yet, the clinical reality reveals a sobering paradox: JAK inhibitors modify symptoms but fail to eradicate the malignant clone, reduce mutant allele burden, or reverse fibrosis. This therapeutic ceiling suggests that oncogenic signaling alone cannot explain disease persistence, progression, or transformation to secondary acute myeloid leukemia. Emerging evidence iMPLicates epitranscriptomics, the dynamic chemical modification of RNA, as an underexplored but fundamentally critical layer of regulatory control in MPN pathobiology. RNA modifications, particularly N6-methyladenosine (m⁶A), are orchestrated by specialized \"writers\" (METTL3/METTL14), \"erasers\" (FTO/ALKBH5), and \"readers\" (YTHDF/IGF2BP proteins) that collectively govern transcript stability, translation, splicing, and localization. In MPNs, this machinery is transcriptionally dysregulated rather than mutated, creating a feed-forward oncogenic loop wherein JAK-STAT signaling upregulates m⁶A writers, which in turn stabilize and translate key oncogenes (MYC, BCL2, JAK2 itself) while suppressing tumor suppressors. Moreover, metabolic shifts during disease progression, particularly IDH1/2 mutations that generate the oncometabolite 2-hydroxyglutarate, may alter α-ketoglutarate-dependent RNA demethylase activity and thereby provide a plausible link between metabolic remodeling and epitranscriptomic dysregulation during leukemic transformation. This review synthesizes the biological rationale, mechanistic evidence, and emerging therapeutic strategies targeting epitranscriptomic regulators in MPNs. We propose that epitranscriptomic remodeling represents both a driver of clonal fitness and a therapeutic vulnerability, positioning RNA modification pathways as promising frontiers for disease-modifying intervention in these recalcitrant malignancies.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105942"},"PeriodicalIF":2.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206797","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":"The nuclear oncoprotein SET is necessary for MLL/KMT2A mediated transcriptional activation.","authors":"Maria-Paz Garcia-Cuellar, Robert K Slany","doi":"10.1016/j.exphem.2026.105941","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105941","url":null,"abstract":"<p><p>The nuclear oncoprotein SET (patient \"SE\" translocation) has been implicated in the etiology of MLL (KMT2A) induced leukemia. Here we examine the details of this dependency in murine, primary hematopoietic cells. ChIP, RNAseq and immunoprecipitations demonstrated Set as downstream target of HoxA9 and confirmed a direct interaction with Mll. Set and Mll globally co-localized to promoter regions. Impairing Set expression phenocopied a knockdown of select Mll fusion targets with Set driving a pro-proliferative gene expression program that contained features indicative for Mll involvement. Molecularly, Set depletion caused dissociation of Mll from chromatin accompanied by a selective loss of RNA PolymeraseII Ser2-P. Concomitant with a function of Set as inhibitor of protein phosphatase 2A (PP2A), specific recruitment of PP2A to the Meis1 promoter, a known Mll target, inhibited transcription in reporter assays and in the natural chromatin environment. We identified Mitogen and stress induced kinase 1 (Msk1) as potential substrate protected by Set from dephosphorylation. Phosphorylated Msk1-P colocalized with Mll and disappeared from chromatin upon Set depletion. Biochemically, Msk-1 bound directly to Mll as well as to menin, a known Mll tethering factor. Loss of Set/Mll/Msk1 selectively affected H3K14 acetylation at promoters and this could be partially attributed to the reduced presence of the histone acetyltransferase Moz (Kat6a). Finally, we show that kinase inhibitors augment menin inhibitor activity in MLL leukemia cells, indicating a connection between cellular signaling and MLL-function.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105941"},"PeriodicalIF":2.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167504","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":"Prominin-1 (CD133) is essential for the determination of the phenotype of Philadelphia chromosome-positive leukemia.","authors":"Anna Metodieva, Jana Karbanová, Claudia Chiriches, Afsar Ali Mian, Peter Carmeliet, Marc Tjwa, Denis Corbeil, Martin Ruthardt","doi":"10.1016/j.exphem.2026.105918","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105918","url":null,"abstract":"<p><p>The human PROMININ-1 (PROM-1, CD133), detected by its AC133 epitope, is expressed on the surface of leukemia-initiating cells of Philadelphia chromosome-positive (Ph+) leukemia cells. Ninety-five percent of chronic myeloid leukemia (CML) cases are Ph+. Ph+ acute lymphoblastic leukemia (ALL) accounts for twenty-five to thirty percent of adult ALL and is considered a high-risk ALL subgroup. Targeting the t(9;22)-fusion protein BCR::ABL1 with ABL1-directed kinase inhibitors (TKIs) is a proven therapeutic concept for CML and Ph+ ALL. Resistance against TKI comprises mutations in BCR::ABL1, but many patients exhibit a primary resistance with unknown mechanisms. Here, we investigated the impact of PROM-1 on the leukemogenesis and the therapy response of Ph+ leukemias. We applied flow cytometry, co-immunoprecipitation, immunoblotting, stem cell assays, and leukemia induction in vivo to cell lines, syngeneic mouse models, and human Ph+ long-term cultures. We found a direct relationship between BCR::ABL1 and PROM-1, a shift from CML towards ALL upon the loss of Prom-1, as well as a link between the response to TKIs and the PROM-1 expression. In contrast to solid tumors, resistance was accompanied by a progressive loss of PROM-1. Our data suggest that PROM-1 plays an essential role in both cell fate decision and induction of the BCR::ABL1-related leukemic phenotype, highlighting its impact on the drug response of Ph+ leukemias. Teaser abstract The Philadelphia chromosome (Ph) is the product of the t(9;22), which fuses the BCR gene on chromosome 22 to the ABL1 gene on chromosome 9. The result is the BCR::ABL1 oncogene, which is responsible for the induction of chronic myeloid leukemia (CML) and for about a third of acute lymphoblastic leukemia (Ph+ ALL). Only little is known about how t(9;22) induces either CML or ALL, and why there is a difference between the two diseases regarding their response to inhibitors that can inactivate BCR::ABL1. Here, we show that a gene called PROMININ-1 is involved in both processes: determining whether BCR::ABL1 induces CML or ALL, and explaining the weaker response of Ph+ ALL compared to CML to inhibitors of BCR::ABL1. We found that the reduction of PROMININ-1 increased the proportion of ALL induced by BCR::ABL1 in the mouse. We could not reproduce these findings in humans but distinguish CML from Ph+ ALL by the expression of PROMININ-1. Also resistance to BCR::ABL1 inhibitors was associated with low expression of PROMININ-1 in Ph+ ALL. These findings are in contrast to observations in solid tumors where a higher level of PROMININ-1 is accompanied by therapy resistance. Our findings contribute to a better understanding of the different types of Ph+ leukemia and their response to therapy, which will help patients better manage these diseases.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105918"},"PeriodicalIF":2.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105987","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":"The Role of Aldehyde Dehydrogenase 2 in Hematopoiesis is Stress-Severity Dependent.","authors":"Liangliang Wu, Xingmin Feng, Felix A Dingler, Zhijie Wu, Shouguo Gao, Jichun Chen, Ketan J Patel, Neal S Young","doi":"10.1016/j.exphem.2026.105940","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105940","url":null,"abstract":"<p><p>Aldehyde dehydrogenase 2 (ALDH2) is a key mitochondrial enzyme that detoxifies reactive aldehydes including formaldehyde, thereby mitigating their genotoxic effects. While ALDH2 deficiency exacerbates bone marrow (BM) failure in Fanconi anemia models, its role under exogenous genotoxic stress is less clear. In this study, we used Aldh2^-/- mice to investigate how ALDH2 deficiency impacts hematopoiesis following treatment with busulfan (BSF), sublethal total body irradiation (TBI), or a combined (BSF+TBI) regimen. Under BSF or TBI monotherapy, Aldh2^-/- mice exhibited moderate increases in DNA damage, measured by γH2AX expression in hematopoietic stem and progenitor cells (HSPCs), with a mild decline in BM cell engraftment, compared to Aldh2^+/+ controls. However, BSF+TBI treatment triggered more severe HSPC DNA damage confirmed by concordant γH2AX and 53BP1 elevation, and a sharper decline in mature hematopoietic cells. Notably, this dual stress significantly upregulated DNA repair and metabolic adaptation genes, including Ccno, Pold4, Taf1c, Npr2, and Aldh18a1. These results suggest that BSF+TBI treatment drives advanced DNA damage and compensatory gene expression shifts in the absence of ALDH2. We conclude that the impact of ALDH2 deficiency on hematopoiesis is dependent on the severity of exogenous stress. TEASER ABSTRACT: The ALDH2 rs671 loss-of-function polymorphism is carried by 30-40% of East Asian individuals, yet its hematopoietic consequences under clinical genotoxic stress remain poorly understood. Using Aldh2^-/- mice, we demonstrate that ALDH2 deficiency increases DNA damage in hematopoietic stem and progenitor cells (HSPCs) following busulfan (BSF) or total body irradiation (TBI) monotherapy, without altering mature hematopoietic cell populations or long-term repopulating capacity. However, combined BSF+TBI treatment unmasks a clear, stress-severity-dependent phenotype: Aldh2^-/- mice exhibit significantly greater HSPC apoptosis and DNA damage confirmed by concordant γH2AX and 53BP1 elevation, and more severe peripheral blood cytopenias. Transcriptomic analysis reveals compensatory upregulation of DNA repair pathways and Aldh18a1, suggesting a metabolic adaptation to mitigate genotoxic burden. These findings establish ALDH2 deficiency as a latent hematopoietic risk factor with direct implications for personalizing conditioning regimens in ALDH2 rs671 carriers undergoing hematopoietic stem cell transplantation.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105940"},"PeriodicalIF":2.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105976","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":"IFC Editorial Board","authors":"","doi":"10.1016/S0301-472X(26)00542-4","DOIUrl":"10.1016/S0301-472X(26)00542-4","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"162 ","pages":"Article 105909"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149155032","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":"Effect of the dominant-negative Ikaros isoform 6 (IK6) on cell function and drug sensitivity in Ph-positive acute lymphoblastic leukemia cell lines.","authors":"Juan Feng, Qishan Hao, Meizhen Xu, Yannan Jia, Qiuyun Fang, Zheng Tian, Min Wang, Jianxiang Wang, Yan Li, Yingchang Mi","doi":"10.1016/j.exphem.2026.105871","DOIUrl":"10.1016/j.exphem.2026.105871","url":null,"abstract":"<p><p>Ikaros family zinc finger 1 (IKZF1) deletions occur commonly in patients with B-cell acute lymphoblastic leukemia (B-ALL) and predict poor outcomes. Ikaros isoform 6 (IK6) is a functionally defective splicing isoform of IKZF1. We aimed to explore the effect of IK6 on the biological functions of acute lymphoblastic leukemia (ALL) cells and its mechanism. We constructed SUP-B15 (human acute lymphoblastic leukemia cell line) cells (Ph-positive) with IK6 knocked down. Western blot was used to detect the expression of IK6 protein. Cell Counting Kit-8 (CCK-8) was used to detect cell proliferation and drug sensitivity. The propidium iodide (PI) assay method was used to detect the cell cycle. The Annexin V-PI assay method was used to detect cell apoptosis. The target cells were cocultured with human stromal cells, and cell migration ability was detected using the Transwell method. RNA sequencing results of SUP-B15 cells interfering with IK6 were analyzed using gene set enrichment analysis (GSEA) software. SUP-B15 cells with IK6 knockdown lost their proliferation advantage and exhibited a decreased proportion in the G0/G1 phase and an increased proportion in the S phase, with downregulation of CDK4, P27, and BCL-2. The sensitivity to dexamethasone increased, but there was no significant change in susceptibility to imatinib and dasatinib. The migration ability of SUP-B15 cells with IK6 knockdown significantly decreased when cocultured with human stromal cells. gene set enrichment analysis (GSEA) in IK6 knockdown SUP-B15 cells showed several signaling pathways altered, which are involved in cell adhesion and migration-related pathways, such as the leukocyte transendothelial migration signaling pathway, the vascular endothelial growth factor (VEGF) signaling pathway, the cell function-related mitogen-activated protein kinase (MAPK) signaling pathway, and so on. IK6 expression affects the biological characteristics of ALL cells and may change the sensitivity of cells to dexamethasone. These alterations may relate to some signaling pathways (such as the MAPK pathway).</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105871"},"PeriodicalIF":2.7,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963357","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":"Share your research in Experimental Hematology-Announcing exciting new article types!","authors":"","doi":"10.1016/j.exphem.2026.105492","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105492","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"161 ","pages":"105492"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024240","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":"IFC Editorial Board","authors":"","doi":"10.1016/S0301-472X(26)00528-X","DOIUrl":"10.1016/S0301-472X(26)00528-X","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"161 ","pages":"Article 105895"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149004320","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":"Development of receptor and oncogene-responsive luciferase reporter vectors that are activated via kinase signaling to AP-1","authors":"Daniel J.L. Coleman,&nbsp;Luke Ames,&nbsp;Hurooul Aain,&nbsp;Joanna Gamble,&nbsp;Kinga Koscielniak,&nbsp;Zijin Zhang,&nbsp;Cherisse Lau,&nbsp;Abigail Joyce,&nbsp;Peter N. Cockerill","doi":"10.1016/j.exphem.2026.105491","DOIUrl":"10.1016/j.exphem.2026.105491","url":null,"abstract":"&lt;div&gt;&lt;ul&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;AP-1 motifs support mitogen-activated protein kinase (MAPK)-inducible luciferase activity in LEGO lentiviral vectors.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;LEGO-AP1 vectors can track oncogene activity in leukemic cells.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;LEGO-AP1 vectors are suppressed by MAPK inhibitors.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;LEGO-AP1 activity is increased by a chromatin priming element.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;div&gt;The DUSP5 and CSF2 promoters increase LEGO-AP-1 activity in acute myeloid leukemia (AML) cells.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ul&gt;&lt;/div&gt;&lt;div&gt;&lt;div&gt;This study aimed to generate lentiviral vectors carrying an array of AP-1 motifs driving luciferase gene expression as reporters of mitogen-activated protein kinase (MAPK) activity. We created a series of vectors based on LeGO-iG that were used to generate stably transduced leukemia cell lines. A vector termed LEGO-AP1×6-GM55 containing an array of 6 AP-1 sites linked to the minimal CSF2 promoter was sufficient to support high levels of MAPK-inducible luciferase activity in leukemic cell lines that was suppressed by MAPK inhibitors. The inclusion of a putative chromatin priming element encompassing RUNX and ETS motifs increased the activity of these vectors. The additional inclusion of the full-length mouse CSF2 promoter, or the human DUSP5 promoter further increased the MAPK-dependent activity of these vectors in leukemic cells. These vectors support moderate levels of constitutive activity in cells carrying mutations that activate the RAS/RAF/MEK MAPK signaling pathway, and high-level activity after direct activation of MAPK signaling. They also respond to T-cell receptor activation via MAPK and Ca2+ signaling pathways. This resource will now make it easier to track receptor or oncogene-inducible MAPK activity in cultured cells, and potentially in tumors, close to real-time.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;This study aimed to generate lentiviral vectors carrying an array of AP-1 motifs driving luciferase gene expression as reporters of mitogen-activated protein kinase (MAPK) activity. We created a series of vectors based on LeGO-iG that were used to generate stably transduced leukemia cell lines. A vector termed LEGO-AP1×6-GM55 containing an array of 6 AP-1 sites linked to the minimal CSF2 promoter was sufficient to support high levels of MAPK-inducible luciferase activity in leukemic cell lines that was suppressed by MAPK inhibitors. The inclusion of a putative chromatin priming element encompassing RUNX and ETS motifs increased the activity of these vectors. The additional inclusion of the full-length mouse CSF2 promoter, or the human DUSP5 promoter further increased the MAPK-dependent activity of these vectors in leukemic cells. These vectors support moderate levels of constitutive activity in cells carrying mutations that activate the RAS/RAF/MEK MAPK signaling pathway, and high-level activity after direct activatio","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"161 ","pages":"Article 105491"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757837","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":"Share your research in Experimental Hematology—Announcing exciting new article types!","authors":"","doi":"10.1016/j.exphem.2026.105492","DOIUrl":"10.1016/j.exphem.2026.105492","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"161 ","pages":"Article 105492"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725466","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}