Pub Date : 2023-12-08DOI: 10.1038/s41435-023-00223-w
François Ghiringhelli, Marion Thibaudin
Checkpoint blockade immunotherapy is a therapeutic revolution in cancer treatment. However, only 5% of patients with metastatic colorectal cancer benefit from these therapies, and these tumors genetically harbored microsatellite instability status. In contrast, tumors with stable microsatellites are considered resistant to immunotherapy, and standard treatment with chemotherapies is standard of care, with few chances of curative intent. In a recent clinical trial, we demonstrated that the combination of two chemotherapies with two immunotherapies promotes the recruitment and activation of the adaptive immune system at the tumor level, resulting in clinical benefit in a significant number of patients. In parallel, a biological study revealed biomarkers of response, including CTLA-4 expression and induction of a tumor-specific immune response.
{"title":"Targeting CTLA-4: a possible solution for microsatellite-stable colorectal cancer","authors":"François Ghiringhelli, Marion Thibaudin","doi":"10.1038/s41435-023-00223-w","DOIUrl":"10.1038/s41435-023-00223-w","url":null,"abstract":"Checkpoint blockade immunotherapy is a therapeutic revolution in cancer treatment. However, only 5% of patients with metastatic colorectal cancer benefit from these therapies, and these tumors genetically harbored microsatellite instability status. In contrast, tumors with stable microsatellites are considered resistant to immunotherapy, and standard treatment with chemotherapies is standard of care, with few chances of curative intent. In a recent clinical trial, we demonstrated that the combination of two chemotherapies with two immunotherapies promotes the recruitment and activation of the adaptive immune system at the tumor level, resulting in clinical benefit in a significant number of patients. In parallel, a biological study revealed biomarkers of response, including CTLA-4 expression and induction of a tumor-specific immune response.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138574196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-08DOI: 10.1038/s41435-023-00231-w
Abi G. Yates, Annie Khamhoung, Cameron S. McAlpine
{"title":"Interleukin-3 gets a fresh start in the brain","authors":"Abi G. Yates, Annie Khamhoung, Cameron S. McAlpine","doi":"10.1038/s41435-023-00231-w","DOIUrl":"10.1038/s41435-023-00231-w","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138568082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-08DOI: 10.1038/s41435-023-00226-7
Jonathan H. Lam, Nicole Baumgarth
{"title":"To whom B cells toll extrafollicular responses","authors":"Jonathan H. Lam, Nicole Baumgarth","doi":"10.1038/s41435-023-00226-7","DOIUrl":"10.1038/s41435-023-00226-7","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138568483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-20DOI: 10.1038/s41435-023-00228-5
Cuong Thi Pham, Laurie Rangan, Susan Schlenner
{"title":"RNA modifications—a regulatory dimension yet to be deciphered in immunity","authors":"Cuong Thi Pham, Laurie Rangan, Susan Schlenner","doi":"10.1038/s41435-023-00228-5","DOIUrl":"10.1038/s41435-023-00228-5","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00228-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-17DOI: 10.1038/s41435-023-00229-4
Frédéric Fumeron, Gilberto Velho, Fawaz Alzaid, Ray El Boustany, Claire Vandiedonck, Amélie Bonnefond, Philippe Froguel, Louis Potier, Michel Marre, Beverley Balkau, Ronan Roussel, Nicolas Venteclef
Inflammation has been associated with renal diseases. The Interferon Regulatory Factor (IRF)-5 is a key transcription factor in the pro-inflammatory polarization of M1-like macrophages. GWAS have reported that the IRF5 locus is associated with autoimmune diseases and with the estimated glomerular filtration rate (eGFR). We study whether allelic variations in IRF5 are associated with the incidence of chronic kidney disease (CKD) in a general population. We genotyped eleven IRF5 SNPs in the French D.E.S.I.R. cohort from the general population (n = 4820). Associations of SNPs with baseline renal parameters were assessed. Data were analyzed for three endpoints during a 9-year follow-up, incidence of:at least stage 3 CKD, the KDIGO criterion “certain drop in eGFR”, and incidence of micro/macro albuminuria. In the cross-sectional analysis, rs10954213 and rs10954214 were associated with eGFR and rs1874328 with urinary albumin/creatinine ratio (ACR). Rs3807306, rs11761199, rs78658945, rs1874328, rs10954213 and rs11770589 were associated with the incidence of stage 3 CKD in multi-adjusted models. Rs4731532, rs3807306, and rs11761199 were associated with the incidence of CKD defined by the KDIGO. Rs4731532, rs3807306, rs11761199 and rs79288514 were associated with the incidence of micro/macro albuminuria. Our results support the hypothesis of the importance of IRF5 mediated macrophage polarization in the etiology of CKD.
{"title":"Genetic variants of interferon-response factor 5 are associated with the incidence of chronic kidney disease: the D.E.S.I.R. study","authors":"Frédéric Fumeron, Gilberto Velho, Fawaz Alzaid, Ray El Boustany, Claire Vandiedonck, Amélie Bonnefond, Philippe Froguel, Louis Potier, Michel Marre, Beverley Balkau, Ronan Roussel, Nicolas Venteclef","doi":"10.1038/s41435-023-00229-4","DOIUrl":"10.1038/s41435-023-00229-4","url":null,"abstract":"Inflammation has been associated with renal diseases. The Interferon Regulatory Factor (IRF)-5 is a key transcription factor in the pro-inflammatory polarization of M1-like macrophages. GWAS have reported that the IRF5 locus is associated with autoimmune diseases and with the estimated glomerular filtration rate (eGFR). We study whether allelic variations in IRF5 are associated with the incidence of chronic kidney disease (CKD) in a general population. We genotyped eleven IRF5 SNPs in the French D.E.S.I.R. cohort from the general population (n = 4820). Associations of SNPs with baseline renal parameters were assessed. Data were analyzed for three endpoints during a 9-year follow-up, incidence of:at least stage 3 CKD, the KDIGO criterion “certain drop in eGFR”, and incidence of micro/macro albuminuria. In the cross-sectional analysis, rs10954213 and rs10954214 were associated with eGFR and rs1874328 with urinary albumin/creatinine ratio (ACR). Rs3807306, rs11761199, rs78658945, rs1874328, rs10954213 and rs11770589 were associated with the incidence of stage 3 CKD in multi-adjusted models. Rs4731532, rs3807306, and rs11761199 were associated with the incidence of CKD defined by the KDIGO. Rs4731532, rs3807306, rs11761199 and rs79288514 were associated with the incidence of micro/macro albuminuria. Our results support the hypothesis of the importance of IRF5 mediated macrophage polarization in the etiology of CKD.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-04DOI: 10.1038/s41435-023-00225-8
Aroosha Raja, Jonas J. W. Kuiper
Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.
{"title":"Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2)","authors":"Aroosha Raja, Jonas J. W. Kuiper","doi":"10.1038/s41435-023-00225-8","DOIUrl":"10.1038/s41435-023-00225-8","url":null,"abstract":"Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71480723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-27DOI: 10.1038/s41435-023-00220-z
Yentl Lambrechts, Abhishek D. Garg, Giuseppe Floris, Kevin Punie, Patrick Neven, Ines Nevelsteen, Jannes Govaerts, François Richard, Annouschka Laenen, Christine Desmedt, Hans Wildiers, Sigrid Hatse
There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof of concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.
{"title":"Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer","authors":"Yentl Lambrechts, Abhishek D. Garg, Giuseppe Floris, Kevin Punie, Patrick Neven, Ines Nevelsteen, Jannes Govaerts, François Richard, Annouschka Laenen, Christine Desmedt, Hans Wildiers, Sigrid Hatse","doi":"10.1038/s41435-023-00220-z","DOIUrl":"10.1038/s41435-023-00220-z","url":null,"abstract":"There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof of concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41117550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-23DOI: 10.1038/s41435-023-00221-y
Valentina Lykhopiy, Vanshika Malviya, Stephanie Humblet-Baron, Susan M. Schlenner
FOXP3+ regulatory T cells (Treg) are indispensable for immune homoeostasis and for the prevention of autoimmune diseases. Interleukin-2 (IL-2) signalling is critical in all aspects of Treg biology. Consequences of defective IL-2 signalling are insufficient numbers or dysfunction of Treg and hence autoimmune disorders in human and mouse. The restoration and maintenance of immune homoeostasis remain central therapeutic aims in the field of autoimmunity. Historically, broadly immunosuppressive drugs with serious side-effects have been used for the treatment of autoimmune diseases or prevention of organ-transplant rejection. More recently, ex vivo expanded or in vivo stimulated Treg have been shown to induce effective tolerance in clinical trials supporting the clinical benefit of targeting natural immunosuppressive mechanisms. Given the central role of exogenous IL-2 in Treg homoeostasis, a new and promising focus in drug development are IL-2-based approaches for in vivo targeted expansion of Treg or for enhancement of their suppressive activity. In this review, we summarise the role of IL-2 in Treg biology and consequences of dysfunctional IL-2 signalling pathways. We then examine evidence of efficacy of IL-2-based biological drugs targeting Treg with specific focus on therapeutic candidates in clinical trials and discuss their limitations.
{"title":"IL-2 immunotherapy for targeting regulatory T cells in autoimmunity","authors":"Valentina Lykhopiy, Vanshika Malviya, Stephanie Humblet-Baron, Susan M. Schlenner","doi":"10.1038/s41435-023-00221-y","DOIUrl":"10.1038/s41435-023-00221-y","url":null,"abstract":"FOXP3+ regulatory T cells (Treg) are indispensable for immune homoeostasis and for the prevention of autoimmune diseases. Interleukin-2 (IL-2) signalling is critical in all aspects of Treg biology. Consequences of defective IL-2 signalling are insufficient numbers or dysfunction of Treg and hence autoimmune disorders in human and mouse. The restoration and maintenance of immune homoeostasis remain central therapeutic aims in the field of autoimmunity. Historically, broadly immunosuppressive drugs with serious side-effects have been used for the treatment of autoimmune diseases or prevention of organ-transplant rejection. More recently, ex vivo expanded or in vivo stimulated Treg have been shown to induce effective tolerance in clinical trials supporting the clinical benefit of targeting natural immunosuppressive mechanisms. Given the central role of exogenous IL-2 in Treg homoeostasis, a new and promising focus in drug development are IL-2-based approaches for in vivo targeted expansion of Treg or for enhancement of their suppressive activity. In this review, we summarise the role of IL-2 in Treg biology and consequences of dysfunctional IL-2 signalling pathways. We then examine evidence of efficacy of IL-2-based biological drugs targeting Treg with specific focus on therapeutic candidates in clinical trials and discuss their limitations.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, genome-wide association studies (GWAS) have been instrumental in unraveling the genetic architecture of complex diseases, including psoriasis. The application of large-scale GWA studies in psoriasis has illustrated several associated loci that participate in the cutaneous inflammation, however explaining a fraction of the disease heritability. With the advent of high-throughput sequencing technologies and functional genomics approaches, the post-GWAS era aims to unravel the functional mechanisms underlying the inter-individual variability in psoriasis patients. In this review, we present the key advances of psoriasis GWAS in under-represented populations, rare, non-coding and structural variants and epistatic phenomena that orchestrate the interplay between different cell types. We further review the gene-gene and gene-environment interactions contributing to the disease predisposition and development of comorbidities through Mendelian randomization studies and pleiotropic effects of psoriasis-associated loci. We finally examine the holistic approaches conducted in psoriasis through system genetics and state-of-the-art transcriptomic analyses, discussing their potential implication in the expanding field of precision medicine and characterization of comorbidities.
{"title":"Disentangling the complexity of psoriasis in the post-genome-wide association era","authors":"Charalabos Antonatos, Katerina Grafanaki, Sophia Georgiou, Evangelos Evangelou, Yiannis Vasilopoulos","doi":"10.1038/s41435-023-00222-x","DOIUrl":"10.1038/s41435-023-00222-x","url":null,"abstract":"In recent years, genome-wide association studies (GWAS) have been instrumental in unraveling the genetic architecture of complex diseases, including psoriasis. The application of large-scale GWA studies in psoriasis has illustrated several associated loci that participate in the cutaneous inflammation, however explaining a fraction of the disease heritability. With the advent of high-throughput sequencing technologies and functional genomics approaches, the post-GWAS era aims to unravel the functional mechanisms underlying the inter-individual variability in psoriasis patients. In this review, we present the key advances of psoriasis GWAS in under-represented populations, rare, non-coding and structural variants and epistatic phenomena that orchestrate the interplay between different cell types. We further review the gene-gene and gene-environment interactions contributing to the disease predisposition and development of comorbidities through Mendelian randomization studies and pleiotropic effects of psoriasis-associated loci. We finally examine the holistic approaches conducted in psoriasis through system genetics and state-of-the-art transcriptomic analyses, discussing their potential implication in the expanding field of precision medicine and characterization of comorbidities.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10262265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-11DOI: 10.1038/s41435-023-00217-8
Isaure Vanmeerbeek, Stefan Naulaerts, Abhishek D. Garg
Therapeutic testing in animal models has been the cornerstone of translational medicine. However, this trend is starting to change in favour of non-animal alternatives. Considering the high failure rates of forward translation from animal models to human application, the above paradigm shift is definitely welcome. But the enthusiasm toward this progress should not become the basis for completely replacing animal testing because the reliability and representativeness of non-animal alternatives still needs more investigation. And this particularly applies to analyses of the immune system and validation of immunotherapies. In this editorial, we discuss the application of reverse translation as a possible key to robustly connecting human immune data with animal testing to increase the benefit-to-risk ratio of translating immunotherapies toward prospective clinical trials.
{"title":"Reverse translation: the key to increasing the clinical success of immunotherapy?","authors":"Isaure Vanmeerbeek, Stefan Naulaerts, Abhishek D. Garg","doi":"10.1038/s41435-023-00217-8","DOIUrl":"10.1038/s41435-023-00217-8","url":null,"abstract":"Therapeutic testing in animal models has been the cornerstone of translational medicine. However, this trend is starting to change in favour of non-animal alternatives. Considering the high failure rates of forward translation from animal models to human application, the above paradigm shift is definitely welcome. But the enthusiasm toward this progress should not become the basis for completely replacing animal testing because the reliability and representativeness of non-animal alternatives still needs more investigation. And this particularly applies to analyses of the immune system and validation of immunotherapies. In this editorial, we discuss the application of reverse translation as a possible key to robustly connecting human immune data with animal testing to increase the benefit-to-risk ratio of translating immunotherapies toward prospective clinical trials.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00217-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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