LeukemiaPub Date : 2025-09-15DOI: 10.1038/s41375-025-02745-w
E. Onur Karakaslar, Eva M. Argiro, Nadine E. Struckman, Ramin Shirali HZ, Jeppe F. Severens, M. Willy Honders, Susan L. Kloet, Hendrik Veelken, Marcel JT Reinders, Marieke Griffioen, Erik B. van den Akker
{"title":"Resolving inter- and intra-patient heterogeneity in NPM1-mutated AML at single-cell resolution","authors":"E. Onur Karakaslar, Eva M. Argiro, Nadine E. Struckman, Ramin Shirali HZ, Jeppe F. Severens, M. Willy Honders, Susan L. Kloet, Hendrik Veelken, Marcel JT Reinders, Marieke Griffioen, Erik B. van den Akker","doi":"10.1038/s41375-025-02745-w","DOIUrl":"https://doi.org/10.1038/s41375-025-02745-w","url":null,"abstract":"<p><i>NPM1-</i>mutated AML is one of the largest entities in international classification systems of myeloid neoplasms, which are based on integrating morphologic and clinical data with genomic data. Previous research, however, indicates that bulk transcriptomics-based subtyping may improve prognostication and therapy guidance. Here, we characterized the heterogeneity in <i>NPM1</i>-mutated AML by performing single-cell RNA-sequencing and spectral flow cytometry on 16 AML belonging to three distinct subtypes previously identified by bulk transcriptomics. Using single-cell expression profiling we generated a comprehensive atlas of <i>NPM1</i>-mutated AML, collectively reconstituting complete myelopoiesis. The three <i>NPM1</i>-mutated transcriptional subtypes showed consistent differences in the proportions of myeloid cell clusters with distinct patterns in lineage commitment and maturational arrest. In all samples, leukemic cells were detected across different myeloid cell clusters, indicating that <i>NPM1-</i>mutated AML are heavily skewed but not fully arrested in myelopoiesis. Same-sample multi-color spectral flow cytometry recapitulated these skewing patterns, indicating that the three <i>NPM1</i>-mutated subtypes can be consistently identified across platforms. Moreover, our analyses highlighted differences in the abundance of rare hematopoietic stem cells suggesting that skewing occurs early in myelopoiesis. To conclude, by harnessing single-cell RNA-sequencing and spectral flow cytometry, we provide a detailed description of three distinct and reproducible patterns in lineage skewing in <i>NPM1</i>-mutated AML that may have potential relevance for prognosis and treatment of patients with <i>NPM1</i>-mutated AML.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"63 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059610","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}
LeukemiaPub Date : 2025-09-12DOI: 10.1038/s41375-025-02758-5
Jack Bakewell, Anthony V. Moorman, Sarra L. Ryan
{"title":"DUX4-rearranged B-ALL: deciphering a biological and clinical conundrum","authors":"Jack Bakewell, Anthony V. Moorman, Sarra L. Ryan","doi":"10.1038/s41375-025-02758-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02758-5","url":null,"abstract":"<p>The <i>DUX4</i> gene, located within repetitive subtelomeric arrays on chromosomes 4 and 10, plays a critical role in early embryogenesis and has been implicated in several human diseases, including facioscapulohumeral muscular dystrophy (FSHD) and cancer. In B-cell acute lymphoblastic leukemia (B-ALL), <i>DUX4</i> rearrangements (<i>DUX4</i>-r) define a distinct genomic subtype affecting 5–10% of cases, which is more frequent among older children and teenagers. These rearrangements produce truncated DUX4 proteins with neomorphic transcriptional activity, resulting in aberrant gene expression programs and alternative splicing that disrupt normal B-cell precursor development. Patients with <i>DUX4</i>-r B-ALL often present with poor initial treatment responses, though they typically achieve excellent long-term survival rates with intensive chemotherapy regimens. The cryptic nature of <i>DUX4</i> rearrangements has historically posed significant challenges to accurate detection, but recent advancements in next-generation sequencing technologies, including RNA and long-read sequencing, and improved immunophenotyping strategies—such as the use of CD371 as a surrogate marker—are enhancing diagnostic accuracy. This review explores the genetic and biological features of <i>DUX4</i> and its rearrangements, shedding light on their role in leukemogenesis and associated clinical outcomes. Additionally, we highlight emerging technologies that enable the detection of <i>DUX4</i>-r and discuss their implications for clinical use and research. An improved understanding of <i>DUX4</i> biology and its oncogenic potential may pave the way for novel treatment strategies, ultimately improving outcomes for patients with <i>DUX4</i>-r B-ALL.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"33 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035224","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}
LeukemiaPub Date : 2025-09-12DOI: 10.1038/s41375-025-02762-9
Lærke Sloth Andersen, Ricardo Berenguer Navarro, Sara Ekberg, Sæmundur Rögnvaldsson, Marína Rós Levy, Ingigerður Sólveig Sverrisdóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri Ólafsson, Brian G. M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jón Löve, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir
{"title":"Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study","authors":"Lærke Sloth Andersen, Ricardo Berenguer Navarro, Sara Ekberg, Sæmundur Rögnvaldsson, Marína Rós Levy, Ingigerður Sólveig Sverrisdóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri Ólafsson, Brian G. M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jón Löve, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir","doi":"10.1038/s41375-025-02762-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02762-9","url":null,"abstract":"<p>Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07–1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01–1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00–1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"66 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035223","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}
LeukemiaPub Date : 2025-09-11DOI: 10.1038/s41375-025-02751-y
Robert Peter Gale, Andreas Hochhaus
{"title":"Are real world data real world data?","authors":"Robert Peter Gale, Andreas Hochhaus","doi":"10.1038/s41375-025-02751-y","DOIUrl":"10.1038/s41375-025-02751-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2311-2312"},"PeriodicalIF":13.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02751-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LeukemiaPub Date : 2025-09-11DOI: 10.1038/s41375-025-02752-x
Farideh Miraki-Moud, Linda Ariza-McNaughton, Thinzar KoKo, Jad Othman, Randal Stronge, Johann de Bono, Nigel Russell, Ian Thomas, Amanda Gilkes, Alan Burnett, Leandro Rodrigues Santiago, Fay Cafferty, Leo Taussig, Allan Thornhill, Simon O’Connor, Dominique Bonnet, David C. Taussig
{"title":"Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival","authors":"Farideh Miraki-Moud, Linda Ariza-McNaughton, Thinzar KoKo, Jad Othman, Randal Stronge, Johann de Bono, Nigel Russell, Ian Thomas, Amanda Gilkes, Alan Burnett, Leandro Rodrigues Santiago, Fay Cafferty, Leo Taussig, Allan Thornhill, Simon O’Connor, Dominique Bonnet, David C. Taussig","doi":"10.1038/s41375-025-02752-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02752-x","url":null,"abstract":"<p>Male sex is associated with worse outcome in acute myeloid leukemia (AML) in many studies. We analyzed the survival of 4281 patients treated with intensive chemotherapy in the AML17 and AML19 trials based on sex. Men had a significantly lower remission rate than women. Men had a higher incidence of adverse cytogenetic features and a lower incidence of the relatively favorable <i>NPM1</i> mutation. However, male sex was an independent risk factor for survival in multi-variate analysis. We hypothesized that androgen signaling in men could worsen outcomes by protecting AML cells from chemotherapy. We demonstrated high levels of androgen receptor (AR) expression in AML across cytogenetic risk groups. We showed the AR expression was induced by IL-6 signaling in vitro and correlates with poor overall survival. Androgens had no effect on survival of primary AML cells in vitro, nor did they impact gene expression. Androgens did not protect AML cells against chemotherapy either in vitro or in vivo. Similar results were observed with estrogen signaling through estrogen receptor in vitro in AML cells. In conclusion, targeting the androgen pathway may not be a promising clinical strategy and sex hormone signaling in AML cells does not explain the poorer outcomes of men.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"13 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032045","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}
LeukemiaPub Date : 2025-09-11DOI: 10.1038/s41375-025-02763-8
Marisol Miranda-Galvis, Kellen C. Tjioe, Muhannad Sharara, McKenzie Maloney, Amany R. Keruakous, Anand Jillella, Vamsi Kota, Avirup Guha, Jorge E. Cortes
{"title":"Estimating the burden of chronic stress through allostatic load in patients with chronic myeloid leukemia","authors":"Marisol Miranda-Galvis, Kellen C. Tjioe, Muhannad Sharara, McKenzie Maloney, Amany R. Keruakous, Anand Jillella, Vamsi Kota, Avirup Guha, Jorge E. Cortes","doi":"10.1038/s41375-025-02763-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02763-8","url":null,"abstract":"<p>Despite advances in tyrosine kinase inhibitor (TKI) therapy, outcomes in chronic myeloid leukemia remain (CML) highly variable, underscoring the need to explore determinants beyond conventional clinical indicators. This study examined the relationship between allostatic load (AL), a biomarker-based index of cumulative chronic stress, social determinants of health (SDH), and treatment outcomes. In a retrospective cohort of 194 patients, AL was calculated using 23 biomarkers spanning cardiovascular, metabolic, hematologic, renal, and hepatic systems. Higher AL was associated with adverse SDH and behavioral factors, including greater extreme poverty (p = 0.02), limited transportation access (p = 0.02), reliance on public health coverage (p = 0.03), and physical inactivity (p = 0.05). Each unit increase in AL reduced the odds of achieving optimal molecular response by 18% (p = 0.02). All 11 disease progressions to advanced CML and all 9 deaths occurred in the high AL group, who also had higher rates of composite adverse events, including loss of molecular response, TKI failure, disease progression, and mortality (p = 0.03). These findings position AL as a promising integrative biomarker to identify high-risk patients facing combined physiological stress burden and social disadvantage, enabling oncology practices to refine risk stratification and implement personalized, multidisciplinary interventions.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"53 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032120","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}
LeukemiaPub Date : 2025-09-10DOI: 10.1038/s41375-025-02757-6
Sven Neubert, Umair Munawar, Julia Mersi, Julia Noderer, Silvia Nerreter, Shilpa Kurian, Seungbin Han, Christina Verbruggen, Emma Besant, Nina Rein, Max Köppel, Johanna Lehmann, Tabea Köhler, Hannah Labinsky, Sigrun Häusl, Yoko Tamamushi, Xiang Zhou, Jule Pinter, Anna Laura Herzog, Kai Lopau, Elion Hoxha, Christoph Rummelt, Elena Gerhard-Hartmann, Andreas Rosenwald, Torsten Steinbrunn, Thomas Nerreter, Michael Hudecek, Hermann Einsele, Leo Rasche, K. Martin Kortüm, Johannes M. Waldschmidt
{"title":"Plasmapheresis facilitates soluble BCMA clearance and contributes to reversing primary resistance to anti-BCMA immunotherapy in multiple myeloma","authors":"Sven Neubert, Umair Munawar, Julia Mersi, Julia Noderer, Silvia Nerreter, Shilpa Kurian, Seungbin Han, Christina Verbruggen, Emma Besant, Nina Rein, Max Köppel, Johanna Lehmann, Tabea Köhler, Hannah Labinsky, Sigrun Häusl, Yoko Tamamushi, Xiang Zhou, Jule Pinter, Anna Laura Herzog, Kai Lopau, Elion Hoxha, Christoph Rummelt, Elena Gerhard-Hartmann, Andreas Rosenwald, Torsten Steinbrunn, Thomas Nerreter, Michael Hudecek, Hermann Einsele, Leo Rasche, K. Martin Kortüm, Johannes M. Waldschmidt","doi":"10.1038/s41375-025-02757-6","DOIUrl":"10.1038/s41375-025-02757-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2563-2567"},"PeriodicalIF":13.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02757-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LeukemiaPub Date : 2025-09-10DOI: 10.1038/s41375-025-02739-8
Magdalini Kanari, Iria Jimenez Garcia, Fabio D. Steffen, Lisa A. Krattiger, Charles Bataclan, Wangjie Liu, Benjamin R. Simona, Bart Deplancke, Olaia Naveiras, Martin Ehrbar, Beat Bornhauser, Jean-Pierre Bourquin
{"title":"A three-dimensional ex vivo model recapitulates in vivo features and drug resistance phenotypes in childhood acute lymphoblastic leukemia","authors":"Magdalini Kanari, Iria Jimenez Garcia, Fabio D. Steffen, Lisa A. Krattiger, Charles Bataclan, Wangjie Liu, Benjamin R. Simona, Bart Deplancke, Olaia Naveiras, Martin Ehrbar, Beat Bornhauser, Jean-Pierre Bourquin","doi":"10.1038/s41375-025-02739-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02739-8","url":null,"abstract":"<p>Acute lymphoblastic leukemia (ALL) preferentially localizes in the bone marrow (BM) and displays recurrent patterns of medullary and extra-medullary involvement. Leukemic cells exploit their niche for propagation and survive selective pressure by chemotherapy in the BM microenvironment, suggesting the existence of protective mechanisms. Here, we established a three-dimensional (3D) BM mimic with human mesenchymal stromal cells and endothelial cells that resemble vasculature-like structures to explore the interdependence of leukemic cells with their microenvironment. This model recapitulates recurrent topologic differences between B-cell and T-cell precursor ALL, whereby B-ALL interacts more closely with the mesenchymal compartment. Migration versatility was found to be associated with subtype, consistent with increased motility observed in T-ALL in vivo. Single-cell RNA signatures revealed similarities to profiles from in vivo patient derived xenografts, suggesting relevant states ex vivo. Furthermore, enhanced migration, adherence and cell cycle heterogeneity was visualized in our co-culture model. Finally, drug response experiments in this 3D model confirm clinically relevant sensitivity and resistance patterns that reflect specific disease phenotypes and may provide a broader dynamic range for drug response testing.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"13 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025304","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}
LeukemiaPub Date : 2025-09-10DOI: 10.1038/s41375-025-02738-9
Alessandra Zaza, Giuseppe Zardo, Cristina Banella, Sara Tucci, Elisabetta de Marinis, Martina Gentile, Serena Travaglini, Mariadomenica Divona, Tiziana Ottone, Germana Castelli, Anna Maria Cerio, Daniela F. Angelini, Isabella Faraoni, Raffaele Palmieri, Paquale Niscola, Emanuele Ammatuna, Adriano Venditti, Clara Nervi, Maria Teresa Voso, Gianfranco Catalano, Nelida Ines Noguera
{"title":"PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias","authors":"Alessandra Zaza, Giuseppe Zardo, Cristina Banella, Sara Tucci, Elisabetta de Marinis, Martina Gentile, Serena Travaglini, Mariadomenica Divona, Tiziana Ottone, Germana Castelli, Anna Maria Cerio, Daniela F. Angelini, Isabella Faraoni, Raffaele Palmieri, Paquale Niscola, Emanuele Ammatuna, Adriano Venditti, Clara Nervi, Maria Teresa Voso, Gianfranco Catalano, Nelida Ines Noguera","doi":"10.1038/s41375-025-02738-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02738-9","url":null,"abstract":"<p>At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell’s growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse. We characterized the metabolic peculiarity and fuel requirement of PML::RARα expressing cells, to identify new targets for tailored therapies in resistant or relapsed APL patients. We analyzed cell metabolism in primary samples from seven APL patients, comparing them with normal CD34+ cells differentiated to promyelocyte and granulocyte, and different PML::RARα expressing cell lines. We show that the PML::RARα oncoprotein inhibits glycolysis, promotes tricarboxylic acid cycle (TCA), and favors long chain fatty acids (LCFA) catabolism. Targeting CD36 function, that promotes the cellular uptake of fatty acids to feed oxidative phosphorylation (OXPHOS), effectively restores sensitivity to ATO in NB4 ATO-resistant clones. Notably, our data demonstrate that glycolytic impairment via AKT inhibition by PML::RARα renders APL cells reliant on OXPHOS. This dependency confers high sensitivity to the VTX-AZA combination, suggesting the therapeutic efficacy of targeted combination treatment in resistant or relapsed APLs.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"24 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025303","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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