Journal of Immunotoxicology最新文献

{"title":"Systemic and immunotoxicity induced by topical application of perfluoroheptane sulfonic acid (PFHpS) or perfluorooctane sulfonic acid (PFOS) in a murine model.","authors":"Lisa M Weatherly, Hillary L Shane, Laurel G Jackson, Ewa Lukomska, Rachel Baur, Madison P Cooper, Stacey E Anderson","doi":"10.1080/1547691X.2024.2371868","DOIUrl":"10.1080/1547691X.2024.2371868","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125-2.5% or 7.82-62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b⁺ monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 1","pages":"2371868"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps.","authors":"Drake W Phelps, Ashley M Connors, Giuliano Ferrero, Jamie C DeWitt, Jeffrey A Yoder","doi":"10.1080/1547691X.2024.2343362","DOIUrl":"10.1080/1547691X.2024.2343362","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 1","pages":"2343362"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consideration of the EXiLE test for predicting anaphylaxis after diclofenac etalhyaluronate administration.","authors":"Haruyo Akiyama, Chisato Kurisaka, Dai Muramatsu, Shuhei Takada, Kei Toyama, Keiji Yoshioka, Ryosuke Nakamura","doi":"10.1080/1547691X.2024.2417758","DOIUrl":"10.1080/1547691X.2024.2417758","url":null,"abstract":"<p><p>Diclofenac etalhyaluronate, an active pharmaceutical ingredient in JOYCLU^® (JCL), serves as a joint function improvement agent in knee and hip osteoarthritis patients. However, frequent cases of anaphylaxis induced by JCL administration have been reported. Recent clinical research suggests the potential utility of the basophil activation test (BAT) in predicting JCL-induced anaphylaxis. Nonetheless, the BAT is deemed impractical for routine diagnostic testing due to complex procedures involving whole blood stimulation and flow cytometry-based analyses. In the study reported here, an IgE crosslinking-induced luciferase expression (EXiLE) test which uses patient sera without complicated procedures, was performed with patients who had received JCL, with or without subsequent anaphylactic symptoms. The results of this test were then compared with those of the BAT reported in a clinical research study. Of the six BAT-positive JCL-induced anaphylaxis-experienced patients, four were positive in the EXiLE test and all non-experienced patients were negative in both the BAT and EXiLE tests, thus illustrating a high concordance rate of 92.3%. Further validation of testing conditions is expected to improve these rates. Notably, complement inactivation treatment led to a positive EXiLE result in a BAT-negative patient. In conclusion, it appears that the EXiLE test exhibits promise as an alternative to BAT for predicting JCL-induced anaphylaxis, and in so doing offers a simpler diagnostic approach.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 1","pages":"2417758"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Codon optimized influenza H1 HA sequence but not CTLA-4 targeting of HA antigen to enhance the efficacy of DNA vaccines in an animal model.","authors":"Dito Anurogo, Chia-Yuan Chen, Chu-Chi Lin, Jeanne Adiwinata Pawitan, Daniel W Qiu, J Timothy Qiu","doi":"10.1080/1547691X.2024.2400624","DOIUrl":"10.1080/1547691X.2024.2400624","url":null,"abstract":"<p><p>Infections caused by the influenza virus lead to both epidemic and pandemic outbreaks in humans and animals. Owing to their rapid production, safety, and stability, DNA vaccines represent a promising avenue for eliciting immunity and thwarting viral infections. While DNA vaccines have demonstrated substantial efficacy in murine models, their effectiveness in larger animals remains subdued. This limitation may be addressed by augmenting the immunogenicity of DNA-based vaccines. In the investigation here, protein expression was enhanced <i>via</i> codon optimization and then mouse cytotoxic T-lymphocyte antigen 4 (CTLA-4) was harnessed as a modulatory adjunct to bind directly to antigen-presenting cells. Further, the study evaluated the immunogenicity of two variants of the hemagglutinin (HA) antigen, i.e. the full-length and the C-terminal deletion versions. The study findings revealed that the codon-optimized HA gene (pcHA) led to increased protein synthesis, as evidenced by elevated mRNA levels. Codon optimization also significantly bolstered both cellular and humoral immune responses. In cytokine assays, all plasmid constructs, particularly pCTLA4-cHA, induced robust interferon (IFN)-γ production, while interleukin (IL)-4 levels remained uniformly non-significant. Mice immunized with pcHA displayed an augmented presence of IFNγ⁺ T-cells, underscoring the enhanced potency of the codon-optimized HA vaccine. Contrarily, CTLA-4-fused DNA vaccines did not significantly amplify the immune response.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 1","pages":"2400624"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 responses determine skin rash during recombinant interleukin-2 therapy.","authors":"Charline Sommer, Vanessa Neuhaus, Patricia Gogesch, Thierry Flandre, Susann Dehmel, Katherina Sewald","doi":"10.1080/1547691X.2024.2343359","DOIUrl":"10.1080/1547691X.2024.2343359","url":null,"abstract":"<p><p>The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy. Skin rashes and other side effects, together with poor efficacy led to a drawback of the therapeutic, but modified recIL-2 molecules are on the rise to treat both cancer and inflammatory diseases such as autoimmunity. Still, pathophysiological mechanisms of recIL-2-induced skin rashes are not understood. In the study reported here, a hypothetical literature-based immune-related adverse outcome pathway (irAOP) was developed to identify possible key cells and molecules in recIL-2-induced skin rash. Using this approach, a hypothesis was formed that the induced immune response predominantly is Type 2-driven by T-helper and innate lymphoid cells, leading to the occurrence of cutaneous side effects during recIL-2 therapy. This paper further discusses mechanisms beyond the proposed irAOP which might add to the pathology but currently are less-studied. Together, this hypothetic irAOP forms a basis to clarify possible cellular and molecular interactions leading to recIL-2-induced skin rash. This might be used to adapt existing or develop new test systems to help predict and prevent cutaneous side effects in future IL-2-based or similar therapies.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S48-S59"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways.","authors":"Alexander Mazein, Muhammad Shoaib, Miriam Alb, Christina Sakellariou, Charline Sommer, Katherina Sewald, Kristin Reiche, Patricia Gogesch, Luise A Roser, Samira Ortega Iannazzo, Sapna Sheth, Susanne Schiffmann, Zoe Waibler, Vanessa Neuhaus, Susann Dehmel, Venkata Satagopam, Reinhard Schneider, Marek Ostaszewski, Wei Gu","doi":"10.1080/1547691X.2024.2345154","DOIUrl":"https://doi.org/10.1080/1547691X.2024.2345154","url":null,"abstract":"<p><p>This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case. To this end, the linear adverse outcome pathway (AOP) is expanded into a molecular interaction model in standard systems biology formats. Then it is shown how knowledge related to immunotoxic events can be integrated, encoded, managed, and explored to benefit the research community. The map is accessible online at https://imsavar.elixir-luxembourg.org <i>via</i> the MINERVA Platform for browsing, commenting, and data visualization. Our work transforms a graphical illustration of an AOP into a digitally structured and standardized form, featuring precise and controlled vocabulary and supporting reproducible computational analyses. Because of annotations to source literature and databases, the map can be further expanded to match the evolving knowledge and research questions.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S5-S12"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using irAOP for non-clinical safety evaluation of biotechnology-derived pharmaceuticals and ATMPs: a paradigm shift into a systematic and holistic framework.","authors":"Armin Braun, Susann Dehmel","doi":"10.1080/1547691X.2024.2390920","DOIUrl":"10.1080/1547691X.2024.2390920","url":null,"abstract":"<p><p>The chances and opportunities in modern biology inspired devising new therapeutics are mind blowing. The promises reach from successfully treating so-far incurable diseases like cancer and certain infections, to modulating and fine tuning the immune response to prolong the lifespan by inhibiting aging. However, as underlying therapies become more and more complex and sophisticated, it becomes increasingly difficult to find ways to ensure and predict the safety of these new therapeutics. The ICH guideline S6 (R1) from June 2011 EMA/CHMP/ICH/731268/ 1998 Committee for Medicinal Products for Human Use (CHMP) already stated \"Conventional approaches to toxicity testing of pharmaceuticals may not be appropriate for biopharmaceuticals due to the unique and diverse structural and biological properties of the latter that may include species specificity, immunogenicity, and unpredicted pleiotropic activities\" and is committed to a \"flexible, case-by-case, science-based approach to preclinical safety evaluation\". Initial approaches to this are described in the OECD Test Guidelines for new approach methods (NAM) with the newest update released in 2023 and alternative non-animal test guidelines (https://www.icapo.org/test-guidelines) provided from the International Council on Animal Protection in OECD Programmes (ICAPO; https://www.icapo.org). Beyond that, the European Union-funded innovative medicine initiative project Immune Safety Avatar (imSAVAR) decided to develop a systematic and holistic framework for non-clinical safety assessment of biopharmaceuticals and Advanced Therapy Medicinal Products (ATMP); thereby, the consortium focuses on immuno-regulatory therapeutics. Science-based approaches, such as the mechanistic description of adverse outcomes would be essential to demonstrate the safety of a particular new immuno-therapeutic agent. Here, we re-use the concept of adverse outcome pathways (AOP) to capture immune-related adverse outcomes (irAO), which are aimed to guide us to the use of relevant test systems and experiments. Thus, the focus within imSAVAR is on the use and (further) develop-ment of human and alternative models.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S96-S98"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of immune safety avatar: mimicking the effects of immunomodulatory therapies on the immune system.","authors":"Vanessa Neuhaus, Laure-Alix Clerbaux, Katherina Sewald","doi":"10.1080/1547691X.2024.2354213","DOIUrl":"https://doi.org/10.1080/1547691X.2024.2354213","url":null,"abstract":"<p><p>Innovative therapeutics like biologicals that modulate the immune system are on the rise. However, their immune-modulating characteristics can also lead sometimes to the induction of adverse effects, by triggering unintended immune reactions. Due to the complexity and target-specificity of such therapeutics, these drug-induced adverse events could remain undetected during non-clinical development, if the test systems are, for example, animal-based, and only emerge in clinical development when tested in humans and subsequently lead to discontinuance of otherwise promising drug candidates. To identify adverse effects on the human immune system at an early stage, new approaches, assays, and technologies are needed. The Innovative Medicine Initiative (IMI) cooperation Immune Safety Avatar (imSAVAR) project aims to develop a tool for integrated non-clinical safety assessment for immune-modulatory new therapeutic drugs and clinical trial applications. To achieve this goal, imSAVAR has relied on the Adverse Outcome Pathway (AOP) framework to gather knowledge in a structured approach and to design, select or develop, when needed, appropriate test systems for prediction of the immune-related adverse outcomes. So far, the imSAVAR consortium has identified the \"mode of action\" for certain classes of drugs that needed improved risk assessment, including chimeric antigen receptor T cells (CAR T cells), immune checkpoint inhibitors (ICIs), and recombinant proteins (e.g. interleukin [IL]-2), has linked those to their immune-related adverse outcomes and has formulated literature-based immune-related AOPs (irAOPs). Models to measure those immune-specific perturbations were selected, adjusted, or newly developed. The imSAVAR work described in this special issue of <i>The Journal of Immunotoxicology</i> supports our understanding of immune-mediated adverse effects and their early discovery during development to improve the safety of innovative biomedicals.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S1-S4"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing IL-2-induced vascular leakage with an irAOP as tool.","authors":"Patricia Gogesch, Samira Ortega Iannazzo, Tamara Zimmermann, Remi Villenave, Katherina Sewald, Zoe Waibler","doi":"10.1080/1547691X.2024.2369123","DOIUrl":"https://doi.org/10.1080/1547691X.2024.2369123","url":null,"abstract":"<p><p>Immune-related adverse outcome pathways (irAOPs) are a toxicological tool for the structuring of complex immunological mechanisms. The EU-funded IMI-project imSAVAR analyses the applicability of irAOPs in pre-clinical safety assessment of immunotherapies. Here, we use immunotherapy with interleukin (IL)-2 as a use case to develop an irAOP for IL-2-mediated vascular leakage (VL). Despite severe side effects observed upon high-dose treatment, IL-2 remains a promising candidate for cancer- and autoimmune therapy. The secondary systemic capillary leakage syndrome is described by a high mortality and a lethality rate of 20 - 30%. However, due to its non-specific symptoms, it remains a serious but under-diagnosed pathology. VL as general phenomenon is associated with several pro-inflammatory scenarios or observed as severe side effect of immunotherapies. In such situations, the physiological condition, in which endothelial cells (ECs) form the semipermeable seal of the vasculature, can escalate into pathological vascular permeability and finally VL. Although EC-biology and mechanisms underlying VL are ongoing subjects of research since many years, exact understanding of VL pathophysiology remains unclear. With this review, we provide an overview of the development of VL from an immunological perspective in the context of high-dose IL-2 immunotherapy. We structured the corresponding knowledge and generated an irAOP for IL-2-mediated VL with the aim to identify gaps and possible biomarkers. Gained insights from this theoretical approach facilitate the identification of relevant scientific questions as a basis for concrete experimental work. Integration of novel experiment-based knowledge into the existing irAOP could close a 'feedback-loop' by enabling irAOP-refinement and the identification of new questions. At the same time this could give rise to important information to improve test systems for IL-2-based immunotherapy safety-assessment and overall the approach to understand, prevent, or predict VL as critical side effect of other clinical conditions.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S79-S88"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revival of recombinant IL-2 therapy - approaches from the past until today.","authors":"Luise A Roser, Charline Sommer, Samira Ortega Iannazzo, Christina Sakellariou, Zoe Waibler, Patricia Gogesch","doi":"10.1080/1547691X.2024.2335219","DOIUrl":"10.1080/1547691X.2024.2335219","url":null,"abstract":"<p><p>Interleukin-2 (IL-2) was one of the first cytokines discovered and its central role in T cell function soon led to the notion that the cytokine could specifically activate immune cells to combat cancer cells. Recombinant human IL-2 (recIL-2) belonged to the first anti-cancer immunotherapeutics that received marketing authorization and while it mediated anti-tumor effects in some cancer entities, treatment was associated with severe and systemic side effects. RecIL-2 holds an exceptional therapeutic potential, which can either lead to stimulation of the immune system - favorable during cancer treatment - or immunosuppression - used for treatment of inflammatory diseases such as autoimmunity. Due to these pleiotropic immune effects, recIL-2 therapy is still a hot topic in research and modified recIL-2 drug candidates show ameliorated efficacy and safety in pre-clinical and clinical studies. The Immune Safety Avatar (imSAVAR) consortium aims to systemically assess mechanisms leading to adverse events provoked by recIL-2 immunotherapy as a use case in order to aid safety evaluation of future recIL-2-based therapies. Here, we summarize the historical use of recIL-2 therapy, associated side effects, and describe the molecular basis of the dual role of IL-2. Finally, an overview of new recIL-2 compounds and delivery systems, which are currently being developed, will be given, highlighting a possible comeback of recIL-2 therapy.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"21 sup1","pages":"S38-S47"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}