Bita Fakhri, Victoria Wang, Gabriela Perez-Burbano, Anna Wall, Sumithra Mandrekar, Sameer A Parikh, Jennifer Woyach, Tait Shanafelt
{"title":"Pericardial events associated with ibrutinib-based therapies for chronic lymphocytic leukaemia in two landmark trials.","authors":"Bita Fakhri, Victoria Wang, Gabriela Perez-Burbano, Anna Wall, Sumithra Mandrekar, Sameer A Parikh, Jennifer Woyach, Tait Shanafelt","doi":"10.1111/bjh.19710","DOIUrl":"10.1111/bjh.19710","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.
{"title":"Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.","authors":"Chhedi Lal Gupta, Nagaraj Jaganathasamy, Manisha Madkaikar","doi":"10.1111/bjh.19736","DOIUrl":"https://doi.org/10.1111/bjh.19736","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyu Lin, Clare E Anderson, Micaela R Scobie, Thomas D Rodgers, Michael J Kelley, Daphne R Friedman
{"title":"Outcomes of Bruton tyrosine kinase inhibitors for chronic lymphocytic leukaemia in US veterans with severe renal dysfunction.","authors":"Chenyu Lin, Clare E Anderson, Micaela R Scobie, Thomas D Rodgers, Michael J Kelley, Daphne R Friedman","doi":"10.1111/bjh.19737","DOIUrl":"https://doi.org/10.1111/bjh.19737","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta García-Culebras, Patricia Alcalde, Francisco J Márquez-Malaver, Estrella Carrillo, Elena Soria, Concepción Prats, Rosario Morales, María T Vargas, Jose Antonio Pérez-Simón, Jose F Falantes
Addition of molecular data to prognostic models has improved risk stratification of myelodysplastic neoplasms (MDS). However, the role of molecular lesions, particularly in the group of low-risk disease (LR-MDS), is uncertain. We evaluated a set of 227 patients with LR-MDS. Overall survival (OS) and probability of leukaemic progression were the main endpoints. RUNX1 was associated with lower OS and SF3B1 with a reduced risk of death (HR: 1.7, 95% CI, 1.1-2.9; p = 0.05; and HR: 0.23, 95% CI 0.1-0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covariates for the probability of leukaemic progression (p < 0.001). Blast percentage, neither analysed as categorical (<5% vs. 5%-9%; HR: 1.3, 95% CI, 0.7-2.9; p = 0.2) nor as a continuous variable (HR: 1.07, 95% CI, 0.9-1.1; p = 0.07), had impact on survival or probability of progression (sHR: 1.05, 95% CI, 0.9-1.1; p = 0.2). These results retained statistical significance when analysis was restricted to the definition of LR-MDS according to the WHO 2022 and ICC classifications (<5% blasts). Thus, with the incorporation of molecular data, blast percentage happens to lose clinical significance both for survival and probability of progression in the group of patients with LR-MDS.
{"title":"Incorporation mutational profile might reduce the importance of blast count in prognostication of low-risk myelodysplastic syndromes.","authors":"Marta García-Culebras, Patricia Alcalde, Francisco J Márquez-Malaver, Estrella Carrillo, Elena Soria, Concepción Prats, Rosario Morales, María T Vargas, Jose Antonio Pérez-Simón, Jose F Falantes","doi":"10.1111/bjh.19714","DOIUrl":"https://doi.org/10.1111/bjh.19714","url":null,"abstract":"<p><p>Addition of molecular data to prognostic models has improved risk stratification of myelodysplastic neoplasms (MDS). However, the role of molecular lesions, particularly in the group of low-risk disease (LR-MDS), is uncertain. We evaluated a set of 227 patients with LR-MDS. Overall survival (OS) and probability of leukaemic progression were the main endpoints. RUNX1 was associated with lower OS and SF3B1 with a reduced risk of death (HR: 1.7, 95% CI, 1.1-2.9; p = 0.05; and HR: 0.23, 95% CI 0.1-0.5; p < 0.001; respectively). TP53 and RUNX1 mutations were predictive covariates for the probability of leukaemic progression (p < 0.001). Blast percentage, neither analysed as categorical (<5% vs. 5%-9%; HR: 1.3, 95% CI, 0.7-2.9; p = 0.2) nor as a continuous variable (HR: 1.07, 95% CI, 0.9-1.1; p = 0.07), had impact on survival or probability of progression (sHR: 1.05, 95% CI, 0.9-1.1; p = 0.2). These results retained statistical significance when analysis was restricted to the definition of LR-MDS according to the WHO 2022 and ICC classifications (<5% blasts). Thus, with the incorporation of molecular data, blast percentage happens to lose clinical significance both for survival and probability of progression in the group of patients with LR-MDS.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA-seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA-L (Long) and NFYA-S (Short), differing in exon 3 inclusion. Patients with lower NFYA-L but higher NFYA-S expression, termed NFYA-S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA-L but lower NFYA-S expression, termed NFYA-L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA-S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA-L predominant cases, as observed in KMT2A-rearranged leukaemia, were associated with relative chemoresistance. NFYA-S overexpression in OCI-AML3 cells promoted cell proliferation, S-phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML.
{"title":"Clinical relevance of NFYA splice variants in patients with acute myeloid leukaemia undergoing intensive chemotherapy.","authors":"Yi-Tsung Yang, Chi-Yuan Yao, Chein-Jun Kao, Po-Ju Chiu, Ming-En Lin, Hsin-An Hou, Chien-Chin Lin, Wen-Chien Chou, Hwei-Fang Tien","doi":"10.1111/bjh.19733","DOIUrl":"https://doi.org/10.1111/bjh.19733","url":null,"abstract":"<p><p>Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA-seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34<sup>+</sup> haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA-L (Long) and NFYA-S (Short), differing in exon 3 inclusion. Patients with lower NFYA-L but higher NFYA-S expression, termed NFYA-S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA-L but lower NFYA-S expression, termed NFYA-L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA-S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA-L predominant cases, as observed in KMT2A-rearranged leukaemia, were associated with relative chemoresistance. NFYA-S overexpression in OCI-AML3 cells promoted cell proliferation, S-phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute thrombocytopenic purpura (TTP) may present at any stage of pregnancy and the puerperium. Without prompt diagnosis and therapy, serious maternal and fetal outcomes may result. ADAMTS13 replacement via plasma exchange and immunosuppression are the mainstay of treatment. There may be a role, however, for newer therapies, including caplacizumab and recombinant ADAMTS13. Differentiation of immune TTP and congenital TTP is vital, particularly to guide the management of subsequent pregnancies.
{"title":"In a nutshell: TTP and pregnancy.","authors":"P Gounder, M Scully","doi":"10.1111/bjh.19723","DOIUrl":"https://doi.org/10.1111/bjh.19723","url":null,"abstract":"<p><p>Acute thrombocytopenic purpura (TTP) may present at any stage of pregnancy and the puerperium. Without prompt diagnosis and therapy, serious maternal and fetal outcomes may result. ADAMTS13 replacement via plasma exchange and immunosuppression are the mainstay of treatment. There may be a role, however, for newer therapies, including caplacizumab and recombinant ADAMTS13. Differentiation of immune TTP and congenital TTP is vital, particularly to guide the management of subsequent pregnancies.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Glasgow prognostic score (GPS) and CAR-HEMATOTOX (CAR-HT) score identify multiple myeloma (MM) patients at high risk for immune-mediated toxicity and early mortality with cellular immunotherapy. However, their association with outcomes in patients receiving T-cell redirecting bispecific antibodies (bsAb) is unclear. This multi-centre retrospective study examines the association of baseline GPS and CAR-HT scores with outcomes in 126 MM patients treated with bsAb. Overall, 19% were identified as GPS high risk but did not experience increased toxicity or mortality. Conversely, high-risk CAR-HT patients had a higher incidence of infections and inferior survival, suggesting a need for aggressive infection mitigation strategies.
{"title":"Immune prognostic score predicts the risk of infection and survival outcomes in patients with relapsed multiple myeloma treated with bispecific antibodies.","authors":"Othman Salim Akhtar, Aniko Szabo, Vineel Bhatlapenumarthi, Mark Forsberg, Metodi Balev, Anannya Patwari, Heloise Cheruvalath, Divaya Bhutani, Sharmilan Thanendrarajan, Binod Dhakal, Maurizio Zangari, Tanvi Patel, Asis Shrestha, Samer Al-Hadidi, Dennis Cooper, Suzanne Lentzsch, Frits van Rhee, Mansi R Shah, Aishee Bag, Anita D'Souza, Carolina Schinke, Rajshekhar Chakraborty, Nishi Shah, Meera Mohan","doi":"10.1111/bjh.19700","DOIUrl":"https://doi.org/10.1111/bjh.19700","url":null,"abstract":"<p><p>The Glasgow prognostic score (GPS) and CAR-HEMATOTOX (CAR-HT) score identify multiple myeloma (MM) patients at high risk for immune-mediated toxicity and early mortality with cellular immunotherapy. However, their association with outcomes in patients receiving T-cell redirecting bispecific antibodies (bsAb) is unclear. This multi-centre retrospective study examines the association of baseline GPS and CAR-HT scores with outcomes in 126 MM patients treated with bsAb. Overall, 19% were identified as GPS high risk but did not experience increased toxicity or mortality. Conversely, high-risk CAR-HT patients had a higher incidence of infections and inferior survival, suggesting a need for aggressive infection mitigation strategies.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiří Štika, Michaela Pešová, Kateřina Staňo Kozubík, Magdalena Skalníková, Lenka Dostálová, Tomáš Loja, Lenka Radová, Veronika Palušová, Kamila Réblová, Zuzana Vrzalová, Ivona Blaháková, Jakub Trizuljak, Stjepan Uldrijan, Jan Blatný, Michal Šmída, Šárka Pospíšilová, Michael Doubek
The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia-4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR/Cas9-mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG-01). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other CYCS variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies.
{"title":"A novel thrombocytopenia-4-causing CYCS gene variant decreases caspase activity: Three-generation study.","authors":"Jiří Štika, Michaela Pešová, Kateřina Staňo Kozubík, Magdalena Skalníková, Lenka Dostálová, Tomáš Loja, Lenka Radová, Veronika Palušová, Kamila Réblová, Zuzana Vrzalová, Ivona Blaháková, Jakub Trizuljak, Stjepan Uldrijan, Jan Blatný, Michal Šmída, Šárka Pospíšilová, Michael Doubek","doi":"10.1111/bjh.19694","DOIUrl":"https://doi.org/10.1111/bjh.19694","url":null,"abstract":"<p><p>The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia-4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR/Cas9-mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG-01). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other CYCS variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In their paper, Klaassen et al. present their findings on the revised Kids ITP Tools (KIT). This important work provides an update to the validated measure for evaluating health-related quality of life (HRQoL) in children with immune thrombocytopenia (ITP). ITP, an acquired autoimmune disorder, results in thrombocytopenia and places children at risk for significant bleeding. Thankfully, the majority of children with ITP will have a brief disease course and no or mild bleeding symptoms. The rarity of severe bleeding events or the development of chronic disease provides a challenge with regard to clinical trial design, making alternative measures of pharmacological efficacy extremely important. Commentary on: Dhir et al. Quality of life in childhood immune thrombocytopenia: Revision of the Kids' ITP Tools (KIT). Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19662.
{"title":"Lightening the load for paediatric ITP: The importance of health-related quality of life.","authors":"Cindy E Neunert, Michele P Lambert","doi":"10.1111/bjh.19719","DOIUrl":"https://doi.org/10.1111/bjh.19719","url":null,"abstract":"<p><p>In their paper, Klaassen et al. present their findings on the revised Kids ITP Tools (KIT). This important work provides an update to the validated measure for evaluating health-related quality of life (HRQoL) in children with immune thrombocytopenia (ITP). ITP, an acquired autoimmune disorder, results in thrombocytopenia and places children at risk for significant bleeding. Thankfully, the majority of children with ITP will have a brief disease course and no or mild bleeding symptoms. The rarity of severe bleeding events or the development of chronic disease provides a challenge with regard to clinical trial design, making alternative measures of pharmacological efficacy extremely important. Commentary on: Dhir et al. Quality of life in childhood immune thrombocytopenia: Revision of the Kids' ITP Tools (KIT). Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19662.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}