ImmunityPub Date : 2024-09-30DOI: 10.1016/j.immuni.2024.08.018
Alexander Lercher, Jin-Gyu Cheong, Michael J. Bale, Chenyang Jiang, Hans-Heinrich Hoffmann, Alison W. Ashbrook, Tyler Lewy, Yue S. Yin, Corrine Quirk, Emma J. DeGrace, Luis Chiriboga, Brad R. Rosenberg, Steven Z. Josefowicz, Charles M. Rice
{"title":"Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease","authors":"Alexander Lercher, Jin-Gyu Cheong, Michael J. Bale, Chenyang Jiang, Hans-Heinrich Hoffmann, Alison W. Ashbrook, Tyler Lewy, Yue S. Yin, Corrine Quirk, Emma J. DeGrace, Luis Chiriboga, Brad R. Rosenberg, Steven Z. Josefowicz, Charles M. Rice","doi":"10.1016/j.immuni.2024.08.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.018","url":null,"abstract":"Pathogen encounter can result in epigenetic remodeling that shapes disease caused by heterologous pathogens. Here, we examined innate immune memory in the context of commonly circulating respiratory viruses. Single-cell analyses of airway-resident immune cells in a disease-relevant murine model of SARS-CoV-2 recovery revealed epigenetic reprogramming in alveolar macrophages following infection. Post-COVID-19 human monocytes exhibited similar epigenetic signatures. In airway-resident macrophages, past SARS-CoV-2 infection increased activity of type I interferon (IFN-I)-related transcription factors and epigenetic poising of antiviral genes. Viral pattern recognition and canonical IFN-I signaling were required for the establishment of this innate immune memory and augmented secondary antiviral responses. Antiviral innate immune memory mounted by airway-resident macrophages post-SARS-CoV-2 was necessary and sufficient to ameliorate secondary disease caused by influenza A virus and curtailed hyperinflammatory dysregulation and mortality. Our findings provide insights into antiviral innate immune memory in the airway that may facilitate the development of broadly effective therapeutic strategies.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"23 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-30DOI: 10.1016/j.immuni.2024.09.002
Ye Liu, Yifang Chen, Uyanga Batzorig, Jingting Li, Celia Fernández-Méndez, Samiksha Mahapatra, Fengwu Li, Shebin Sam, Tatsuya Dokoshi, Seung-Phil Hong, Teruaki Nakatsuji, Richard L. Gallo, George L. Sen
{"title":"The transcription regulators ZNF750 and LSD1/KDM1A dampen inflammation on the skin’s surface by silencing pattern recognition receptors","authors":"Ye Liu, Yifang Chen, Uyanga Batzorig, Jingting Li, Celia Fernández-Méndez, Samiksha Mahapatra, Fengwu Li, Shebin Sam, Tatsuya Dokoshi, Seung-Phil Hong, Teruaki Nakatsuji, Richard L. Gallo, George L. Sen","doi":"10.1016/j.immuni.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.002","url":null,"abstract":"The surface of the skin is continually exposed to pro-inflammatory stimuli; however, it is unclear why it is not constantly inflamed due to this exposure. Here, we showed undifferentiated keratinocytes residing in the deep epidermis could trigger a strong inflammatory response due to their high expression of pattern recognition receptors (PRRs) that detect damage or pathogens. As keratinocytes differentiated, they migrated outward toward the surface of the skin and decreased their PRR expression, which led to dampened immune responses. ZNF750, a transcription factor expressed only in differentiated keratinocytes, recruited the histone demethylase KDM1A/LSD1 to silence genes coding for PRRs (<em>TLR3</em>, <em>IFIH1</em>/MDA5, and <em>DDX58</em>/RIG1). Loss of ZNF750 or KDM1A in human keratinocytes or mice resulted in sustained and excessive inflammation resembling psoriatic skin, which could be restored to homeostatic conditions upon silencing of <em>TLR3</em>. Our findings explain how the skin’s surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"18 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interleukin-34-orchestrated tumor-associated macrophage reprogramming is required for tumor immune escape driven by p53 inactivation","authors":"Zhigang Nian, Yingchao Dou, Yiqing Shen, Jintang Liu, Xianghui Du, Yong Jiang, Yonggang Zhou, Binqing Fu, Rui Sun, Xiaohu Zheng, Zhigang Tian, Haiming Wei","doi":"10.1016/j.immuni.2024.08.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.015","url":null,"abstract":"As the most frequent genetic alteration in cancer, more than half of human cancers have p53 mutations that cause transcriptional inactivation. However, how p53 modulates the immune landscape to create a niche for immune escape remains elusive. We found that cancer stem cells (CSCs) established an interleukin-34 (IL-34)-orchestrated niche to promote tumorigenesis in p53-inactivated liver cancer. Mechanistically, we discovered that <em>Il34</em> is a gene transcriptionally repressed by p53, and p53 loss resulted in IL-34 secretion by CSCs. IL-34 induced CD36-mediated elevations in fatty acid oxidative metabolism to drive M2-like polarization of foam-like tumor-associated macrophages (TAMs). These IL-34-orchestrated TAMs suppressed CD8<sup>+</sup> T cell-mediated antitumor immunity to promote immune escape. Blockade of the IL-34-CD36 axis elicited antitumor immunity and synergized with anti-PD-1 immunotherapy, leading to a complete response. Our findings reveal the underlying mechanism of p53 modulation of the tumor immune microenvironment and provide a potential target for immunotherapy of cancer with p53 inactivation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"34 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-24DOI: 10.1016/j.immuni.2024.08.019
Pavla Bohacova, Marina Terekhova, Petr Tsurinov, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Thomas Francis, Chelsea Mannie, Laura Arthur, Stephen D.R. Harridge, Daniel Kreisel, Philip A. Mudd, Angela M. Taylor, Coleen A. McNamara, Marina Cella, Sidharth V. Puram, Maxim N. Artyomov
{"title":"Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling","authors":"Pavla Bohacova, Marina Terekhova, Petr Tsurinov, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Thomas Francis, Chelsea Mannie, Laura Arthur, Stephen D.R. Harridge, Daniel Kreisel, Philip A. Mudd, Angela M. Taylor, Coleen A. McNamara, Marina Cella, Sidharth V. Puram, Maxim N. Artyomov","doi":"10.1016/j.immuni.2024.08.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.019","url":null,"abstract":"Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38<sup>hi</sup> expression universally identified CD8<sup>+</sup> and CD4<sup>+</sup> RTEs. We further determined the dynamics of RTEs and mature cells in a cohort of 158 individuals, including age-associated transcriptional reprogramming and shifts in cytokine production. Spectral cytometry profiling revealed two axes of aging common to naive CD8<sup>+</sup> and CD4<sup>+</sup> T cells: (1) a decrease in CD38<sup>++</sup> cells (RTEs) and (2) an increase in CXCR3<sup>hi</sup> cells. Identification of RTEs enables direct assessment of thymic health. Furthermore, resolving the dynamics of naive T cell remodeling yields insight into vaccination and infection responsiveness throughout aging.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"21 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease","authors":"Wei Guo, Ziyi Li, Gerasimos Anagnostopoulos, Wan Ting Kong, Shuangyan Zhang, Svetoslav Chakarov, Amanda Shin, Jiawen Qian, Yiwen Zhu, Wenjuan Bai, Olivier Cexus, Bin'en Nie, Jing Wang, Xiaoyu Hu, Camille Blériot, Zhaoyuan Liu, Baiyong Shen, Nicolas Venteclef, Bing Su, Florent Ginhoux","doi":"10.1016/j.immuni.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.016","url":null,"abstract":"The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH. We revealed a crucial role for the Notch-Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) signaling pathway in controlling the monocyte-to-macrophage transition, with <em>Rbpj</em> deficiency blunting inflammatory macrophages and monocyte-derived KC differentiation and conversely promoting the emergence of protective Ly6C<sup>lo</sup> monocytes. Mechanistically, <em>Rbpj</em> deficiency promoted lipid uptake driven by elevated CD36 expression in Ly6C<sup>lo</sup> monocytes, enhancing their protective interactions with endothelial cells. Our findings uncover the crucial role of Notch-RBPJ signaling in monocyte-to-macrophage transition and will aid in the design of therapeutic strategies for MASH treatment.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"12 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-20DOI: 10.1016/j.immuni.2024.08.017
Alexandra R. Dvorscek, Craig I. McKenzie, Vera C. Stäheli, Zhoujie Ding, Jacqueline White, Stewart A. Fabb, Leonard Lim, Kristy O’Donnell, Catherine Pitt, Daniel Christ, Danika L. Hill, Colin W. Pouton, Deborah L. Burnett, Robert Brink, Marcus J. Robinson, David M. Tarlinton, Isaak Quast
{"title":"Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity","authors":"Alexandra R. Dvorscek, Craig I. McKenzie, Vera C. Stäheli, Zhoujie Ding, Jacqueline White, Stewart A. Fabb, Leonard Lim, Kristy O’Donnell, Catherine Pitt, Daniel Christ, Danika L. Hill, Colin W. Pouton, Deborah L. Burnett, Robert Brink, Marcus J. Robinson, David M. Tarlinton, Isaak Quast","doi":"10.1016/j.immuni.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.017","url":null,"abstract":"<p>Existing antibodies (Abs) have varied effects on humoral immunity during subsequent infections. Here, we leveraged <em>in vivo</em> systems that allow precise control of antigen-specific Abs and B cells to examine the impact of Ab dose, affinity, and specificity in directing B cell activation and differentiation. Abs competing with the B cell receptor (BCR) epitope showed affinity-dependent suppression. By contrast, Abs targeting a complementary epitope, not overlapping with the BCR, shifted B cell differentiation toward Ab-secreting cells. Such Abs allowed for potent germinal center (GC) responses to otherwise poorly immunogenic sites by promoting antigen capture and presentation by low-affinity B cells. These mechanisms jointly diversified the B cell repertoire by facilitating the recruitment of high- and low-affinity B cells into Ab-secreting cell, GC, and memory B cell fates. Incorporation of small amounts of monoclonal Abs into protein- or mRNA-based vaccines enhanced immunogenicity and facilitated sustained immune responses, with implications for vaccine design and our understanding of protective immunity.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"196 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-19DOI: 10.1016/j.immuni.2024.09.009
Richard A. Flavell, Esen Sefik
{"title":"Sensing DNA as danger: The discovery of cGAS","authors":"Richard A. Flavell, Esen Sefik","doi":"10.1016/j.immuni.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.009","url":null,"abstract":"<p>Insight into how the immune system recognizes and responds to pathogens had led to landmark advances in biology and medicine in the last decades. This year’s Albert Lasker Award for Basic Medical Research honors Zhijian “James” Chen for the discovery of cGAS, the enzyme that senses foreign and “pathogenic” self-DNA—self-DNA aberrantly located in intracellular compartments. The definition of the cGAS-STING pathway opens new horizons for the understanding and treatment of human disease.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"50 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-18DOI: 10.1016/j.immuni.2024.08.013
Samantha Y. Tse-Kang, Khursheed A. Wani, Nicholas D. Peterson, Amanda Page, Fiachra Humphries, Read Pukkila-Worley
{"title":"Intestinal immunity in C. elegans is activated by pathogen effector-triggered aggregation of the guard protein TIR-1 on lysosome-related organelles","authors":"Samantha Y. Tse-Kang, Khursheed A. Wani, Nicholas D. Peterson, Amanda Page, Fiachra Humphries, Read Pukkila-Worley","doi":"10.1016/j.immuni.2024.08.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.013","url":null,"abstract":"<p>Toll/interleukin-1/resistance (TIR)-domain proteins with enzymatic activity are essential for immunity in plants, animals, and bacteria. However, it is not known how these proteins function in pathogen sensing in animals. We discovered that the lone enzymatic TIR-domain protein in the nematode <em>C. elegans</em> (TIR-1, homolog of mammalian sterile alpha and TIR motif-containing 1 [SARM1]) was strategically expressed on the membranes of a specific intracellular compartment called lysosome-related organelles. The positioning of TIR-1 on lysosome-related organelles enables intestinal epithelial cells in the nematode <em>C. elegans</em> to survey for pathogen effector-triggered host damage. A virulence effector secreted by the bacterial pathogen <em>Pseudomonas aeruginosa</em> alkalinized and condensed lysosome-related organelles. This pathogen-induced morphological change in lysosome-related organelles triggered TIR-1 multimerization, which engaged its intrinsic NAD<sup>+</sup> hydrolase (NADase) activity to activate the p38 innate immune pathway and protect the host against microbial intoxication. Thus, TIR-1 is a guard protein in an effector-triggered immune response, which enables intestinal epithelial cells to survey for pathogen-induced host damage.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"33 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142237023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-13DOI: 10.1016/j.immuni.2024.08.014
Johanna Chiffelle, David Barras, Rémy Pétremand, Angela Orcurto, Sara Bobisse, Marion Arnaud, Aymeric Auger, Blanca Navarro Rodrigo, Eleonora Ghisoni, Christophe Sauvage, Damien Saugy, Alexandra Michel, Baptiste Murgues, Noémie Fahr, Martina Imbimbo, Maria Ochoa de Olza, Sofiya Latifyan, Isaac Crespo, Fabrizio Benedetti, Raphael Genolet, George Coukos
{"title":"Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma","authors":"Johanna Chiffelle, David Barras, Rémy Pétremand, Angela Orcurto, Sara Bobisse, Marion Arnaud, Aymeric Auger, Blanca Navarro Rodrigo, Eleonora Ghisoni, Christophe Sauvage, Damien Saugy, Alexandra Michel, Baptiste Murgues, Noémie Fahr, Martina Imbimbo, Maria Ochoa de Olza, Sofiya Latifyan, Isaac Crespo, Fabrizio Benedetti, Raphael Genolet, George Coukos","doi":"10.1016/j.immuni.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.014","url":null,"abstract":"<p>Adoptive cell therapy (ACT) using <em>in vitro</em> expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon <em>in vitro</em> expansion, yielding products enriched in tumor-specific CD8<sup>+</sup> cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunityPub Date : 2024-09-10DOI: 10.1016/j.immuni.2024.08.012
Giuseppe Giuliani, Jayajit Das
{"title":"Neighbor’s feedback helps macrophages learn tolerance in the gut","authors":"Giuseppe Giuliani, Jayajit Das","doi":"10.1016/j.immuni.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.012","url":null,"abstract":"<p>Intestinal macrophages play a key role in regulating immune tolerance in the gut. In this issue of <em>Immunity</em>, Mertens et al. uncover a mechanism for the establishment of memory in macrophage tolerance in the gut involving a bistable metabolic switch in macrophages and an intercellular positive feedback between macrophages and intestinal epithelial cells (IECs).</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"108 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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