Journal of immunological methods最新文献

{"title":"Defining positivity in the lymphocyte transformation test with cytokine read-out: What is the best of bad choices?","authors":"Bernhardt Sachs ,&nbsp;Leonie Weinhold ,&nbsp;Caspar A. Heubach ,&nbsp;Diana Dubrall ,&nbsp;Philipp Deck ,&nbsp;Günther Weindl ,&nbsp;Markus Nöthen ,&nbsp;Per Hoffmann ,&nbsp;Stefanie Röseler ,&nbsp;Gerda Wurpts ,&nbsp;Amir S. Yazdi ,&nbsp;Andreas Glässner","doi":"10.1016/j.jim.2026.114035","DOIUrl":"10.1016/j.jim.2026.114035","url":null,"abstract":"<div><h3>Background</h3><div>Various approaches have been published to define a positive result in the lymphocyte transformation test (LTT) with interferon-γ (IFN-γ) read-out using ELISA. While statistical analyses cannot improve data quality, they may impact on defining a positive result. The objective of this study was thus to explore different statistical approaches for the optimal discrimination of drug-allergic patients and controls based on the IFN-γ concentrations of their drug-stimulated and unstimulated peripheral blood mononuclear cells in the LTT.</div></div><div><h3>Methods</h3><div>The IFN-γ concentrations of 59 LTTs with drug-allergic patients (39 immediate-type, 20 delayed-type) and corresponding controls obtained in a case-control study design were applied in seven different statistical approaches. The performance parameter was the area under the curve (AUC) of the receiver operating characteristics (ROC) analysis, integrating sensitivity and specificity. Subgroup analyses were performed for delayed and immediate-type reactions and different drug groups.</div></div><div><h3>Results</h3><div>Although there were numerical differences between the AUCs of the different approaches, these differences were marginal, and no approach demonstrated clear superiority. Numerically, the statistical approach with an added constant yielded the highest AUC (0.679; 95% CI 0.581–0.776; sensitivity: 69.0%; specificity: 63.8%). The performance indicators for this approach were higher in the subgroup of delayed-type reactions (AUC 0.791; 95% CI 0.643–0.939; sensitivity: 78.9%; specificity: 75.0%). If the individual best approach was selected, numerical differences of the AUCs between the drug classes were observed.</div></div><div><h3>Conclusion</h3><div>We encourage researchers working with the LTT with IFN-γ or another cytokine read-out to test different statistical approaches on their raw data to explore how the different approaches perform.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"547 ","pages":"Article 114035"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948939","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":"Development, validation and stability study of an ELISA method to quantify the major allergen Jun a 1 in Juniperus ashei extracts","authors":"M. Angeles López-Matas,&nbsp;Javier Álvarez,&nbsp;Tamara Aranda,&nbsp;Jerónimo Carnés","doi":"10.1016/j.jim.2026.114039","DOIUrl":"10.1016/j.jim.2026.114039","url":null,"abstract":"<div><div>A functional allergen quantification kit requires two key components: a pair of monoclonal antibodies (mAbs) that do not interfere with each other at the protein binding site, and a reference standard with sufficient purity and stability. Despite the clinical relevance of Jun a 1 in patients with Cupressaceae pollinosis, no commercial kits are currently available for its quantification in allergenic extracts. The aim of this study was to develop and validate a sandwich ELISA kit for the quantification of Jun a 1 in <em>Juniperus ashei</em> extracts, using appropriately selected mAbs and a stable standard. To this end, Jun a 1 was purified to &gt;95% purity, as confirmed by SDS-PAGE, Western blot, and mass spectrometry analysis. Its stability was demonstrated after 48 months of storage. The linear B-cell epitopes recognized by the mAbs were identified and mapped onto the Jun a 1 structure, confirming that they are non-overlapping. Following validation, the ELISA method proved to be specific, linear, accurate, and precise. In conclusion, we successfully developed and validated an ELISA assay for the quantification of Jun a 1 in <em>J. ashei</em> extracts, supported by the generation of suitable monoclonal antibodies and a stable reference standard.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"547 ","pages":"Article 114039"},"PeriodicalIF":1.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157408","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":"Application of a novel branched-DNA assay to quantify killer immunoglobulin-like receptor (KIR) mRNA expression identifies tissue compartmentalization in naïve and SIV-infected rhesus macaques","authors":"Karen Terry ,&nbsp;Kyle W. Kroll ,&nbsp;Rhianna A. Jones ,&nbsp;R. Keith Reeves","doi":"10.1016/j.jim.2025.114022","DOIUrl":"10.1016/j.jim.2025.114022","url":null,"abstract":"<div><div>Natural killer and cytotoxic CD8+ T cells are essential effectors of innate systemic antiviral and antitumor immune responses. Their effector functions and target cell recognition are partly regulated by a polymorphic family of activating and inhibitory killer-cell immunoglobulin-like receptors (KIRs) that interact with major histocompatibility complex (MHC) class I molecules. In Rhesus macaques (<em>Macaca mulatta</em>) (RM), a well-established model for studying simian immunodeficiency virus (SIV) infection and cellular immunobiology, the KIR gene family is highly diverse but remains poorly characterized across tissue compartments. In this study, we used a branched DNA, amplification-free assay with high specificity and reproducibility to simultaneously measure mRNA expression of six KIR genes (Mamu-KIR1D, Mamu-KIR3DH5, Mamu-KIR3DL2, Mamu-KIR3DL4, Mamu-KIR3DH, and Mamu-KIR3DL0) in mononuclear cells from peripheral blood, lymph nodes, and spleen of both naïve and chronically lentivirus-infected RM. Our findings reveal tissue-specific expression patterns of KIR genes that are differentially affected by chronic lentivirus infection, emphasizing the importance of compartmentalized KIR regulation in viral pathogenesis. This proof-of-concept study presents a reliable and scalable framework for the detailed characterization of the KIR gene repertoire in non-human primate models, providing a valuable alternative to traditional qPCR for profiling gene expression in complex tissues.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114022"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809891","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":"Evaluation of a rapid flow cytometry assay to assess functional engraftment in CGD patients post-transplant and comparison with molecular chimerism","authors":"Lan Mai ,&nbsp;Caleb Cornaby ,&nbsp;Lee Ann Baxter-Lowe ,&nbsp;Neena Kapoor ,&nbsp;Maurice R. O'Gorman","doi":"10.1016/j.jim.2025.114006","DOIUrl":"10.1016/j.jim.2025.114006","url":null,"abstract":"<div><div>This study explores the value of the Dihydrorhodamine-123 (DHR-123) flow cytometry assay to rapidly measure donor neutrophil engraftment (chimerism) in patients with Chronic Granulomatous Disease (CGD) following hematopoietic stem cell transplant (HSCT). Flow cytometry-based chimerism testing was compared with traditional molecular methods including sequence tandem repeats (STR), Quantitative-PCR DNA fingerprinting, and next-generation sequencing (NGS). Results comparing the two technologies in a cohort of CGD patients and healthy control subjects demonstrated that the DHR-123 based flow cytometry chimerism assay is an accurate, inexpensive, and rapid method for assessing functional donor neutrophil engraftment post-transplant, and which demonstrated significant correlation with the results of the molecular chimerism assays (R² = 0.9965), making it a valuable tool for ongoing chimerism monitoring post-transplant. The flow cytometry-based assay offers a more rapid and inexpensive alternative to traditional molecular chimerism techniques.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114006"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596645","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":"Novel mRNA vaccines targeting epitope-rich regions of avian coronavirus enhance immunogenic efficacy","authors":"Miao Shen ,&nbsp;Jielin Yao ,&nbsp;Shengkui Xu ,&nbsp;Bowen Zhang ,&nbsp;Xiang Li ,&nbsp;Wenke Ruan","doi":"10.1016/j.jim.2025.114008","DOIUrl":"10.1016/j.jim.2025.114008","url":null,"abstract":"<div><div>Avian coronavirus, also known as infectious bronchitis virus (IBV), poses a significant threat to the poultry industry, with the IBV QX variant strain now endemic in multiple countries. Traditional vaccines have demonstrated limited effectiveness in providing robust immune protection against this pathogen. In this study, we developed two IBV QX strain S1-mRNA vaccines based on different antigen domains and evaluated their safety and immune efficacy. The S1A mRNA-LNP and S1B mRNA-LNP vaccines were successfully produced based on epitope prediction of the S1 protein of the IBV QX strain.</div><div>Both developed mRNA vaccines, along with a conventional inactivated vaccine, were capable of stimulating serum antibody production. ELISPOT assay results showed that the mRNA vaccines were more potent in stimulating lymphocytes to secrete interferon-γ (IFN-γ) than the inactivated vaccine. This enhanced immunostimulatory capacity translated into a significant reduction in viral load within the kidneys. Moreover, the S1A mRNA vaccine conferred immune protection earlier than the inactivated vaccine.</div><div>In conclusion, the IBV S1-mRNA vaccines developed in this study can protect against IBV infection by inducing cellular and humoral immune responses. Selecting different S1 regions also affects the immunogenic efficacy of the mRNA vaccine.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114008"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667898","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":"Identifying immunoglobulin abnormalities in the presence of variable polyclonal background","authors":"Jonathan D. Coker,&nbsp;Mindy C. Kohlhagen,&nbsp;Maria A.V. Willrich,&nbsp;David L. Murray","doi":"10.1016/j.jim.2025.114011","DOIUrl":"10.1016/j.jim.2025.114011","url":null,"abstract":"<div><div>Modern mass spectrometry-based methods for the isotyping and quantitation of monoclonal proteins (M-proteins) are now supplanting traditional gel-based methods such as serum protein electrophoresis (SPEP). The resultant improvement in resolution poses new signal processing challenges in the separation of M-protein from normal variations in polyclonal immunoglobulin background. We model normal variations in this background by means of a singular value decomposition and apply a coupled alternating-projection algorithm to separate normal and abnormal spectral components, both of which are variable. Ion simulation results guide our algorithm details and highlight limitations that can exist when testing M-proteins of high concentration. We show experimental quantitation results on clinical submitted sera with acceptable results. Finally, we outline enhancements to the fundamental method which have resulted in an enhanced analytical measuring range for clinical care of patients with plasma cell disorders.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114011"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677910","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":"Effects of culture conditions on cell morphology and differentiation responses to PMA in THP-1 cells","authors":"Alexander Launa,&nbsp;Qiuyue Peng","doi":"10.1016/j.jim.2025.114020","DOIUrl":"10.1016/j.jim.2025.114020","url":null,"abstract":"<div><div>The THP-1 monocyte cell line can be differentiated into macrophage-like cells upon stimulation with phorbol 12-myristate 13-acetate (PMA) and therefore widely used in inflammatory research. However, there is a lack of evidence-based protocols for cell culture and differentiation. In this study, we highlight how culture conditions influence THP-1 cells and their response to PMA stimulation. After thawing, THP-1 cells were cultured for up to 4 weeks and monitored by phase-contrast microscopy. Stressed cells (&gt;1 × 10⁶ cells/mL for 72 h without medium replenishment) were assessed for CD80 and MHC-II expression and the subset distribution by flow cytometry. For PMA stimulation (10 μg/mL), standard cells under normal nutrient conditions (5 × 10⁵ cells/mL), low (2 × 10⁵ cells/mL), and high (1 × 10⁶ cells/mL) cell densities, along with stressed cells at 1 × 10⁶ cells/mL density, were seeded and observed at 24 and 48 h. Cells formed aggregates containing more than 10 cells during the first week in suspension but gradually transitioned to single cells with continuous culture. Metabolically stressed cells developed protrusions, showed increased adherence, and expressed higher levels of MHC-II compared to standard cells (<em>p</em> = 0.02). These cells also displayed signs of partial differentiation, with fewer MHC-II⁻CD80⁻ cells (<em>p</em> &lt; 0.001) and more MHC-II⁺CD80⁻ cells (<em>p</em> &lt; 0.001) than non-stressed cells. Optimal and uniform differentiation was observed after 3–4 weeks of recovery, at seeding densities below 1 × 10⁶ cells/mL, and under non-stressed conditions. These findings show that THP-1 culture conditions, including recovery time post-thawing, stress status and seeding density, have a major impact on their responsiveness to PMA.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114020"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734852","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":"Development of an optimized E0-based indirect ELISA for serological detection of bovine viral diarrhea virus","authors":"Chenjun Jiang ,&nbsp;Wei Sheng ,&nbsp;Zhuoma Gesang ,&nbsp;Yanan Zhong ,&nbsp;Da Qiong ,&nbsp;Jiayan Huang ,&nbsp;Hongbo Zhou ,&nbsp;Sizhu Suolang","doi":"10.1016/j.jim.2025.114021","DOIUrl":"10.1016/j.jim.2025.114021","url":null,"abstract":"<div><div>Bovine viral diarrhea virus (BVDV), a globally prevalent immunosuppressive pathogen, continues to challenge the cattle industry, prompting the search for more effective diagnostic and immunogenic targets. The envelope glycoprotein E2, once the central focus of vaccine and diagnostic research, is now considered suboptimal because of its pronounced sequence variability, which limits cross-subtype efficacy. In contrast, the E0 protein, a more conserved outer membrane glycoprotein, has emerged as a promising alternative owing to its immunogenicity and cross-subtype stability. In this study, the E0 gene of BVDV 1b (XZ02) was engineered by removing its membrane anchor region and incorporating heterologous signal peptides (SPs) to enhance secretion efficiency in an HEK293 suspension cell system. Among the evaluated SPs, the tissue plasminogen activator signal peptide yielded the highest level of secreted E0 protein (up to 2.4 mg/mL after purification). Based on the optimized recombinant E0 antigen, an indirect ELISA was developed to detect BVDV-specific antibodies. The assay demonstrated high sensitivity, specificity, and reproducibility, with a diagnostic agreement rate of 96.53 % (κ = 0.9110), when compared with the commercial IDEXX BVDV Total Antibody kit. These results support the potential of the engineered E0 protein as a reliable, scalable antigen for the serological diagnosis of BVDV.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114021"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756918","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":"Dependence of the amplification factor on the body water deuterium enrichment","authors":"Erdem Şanal ,&nbsp;Julia Drylewicz ,&nbsp;Kiki Tesselaar ,&nbsp;Becca Asquith ,&nbsp;José A.M. Borghans ,&nbsp;Rob J. de Boer","doi":"10.1016/j.jim.2025.114010","DOIUrl":"10.1016/j.jim.2025.114010","url":null,"abstract":"<div><div>Heavy water (<span><math><mrow><msub><mrow><mi>D</mi></mrow><mrow><mn>2</mn></mrow></msub><mi>O</mi></mrow></math></span>) labeling is the state-of-the-art technique to track the dynamics of circulating cells <em>in vivo</em>. <span><math><mrow><msub><mrow><mi>D</mi></mrow><mrow><mn>2</mn></mrow></msub><mi>O</mi></mrow></math></span> labels dividing cells through incorporation of deuterium into newly synthesized DNA, which is measured using GC/MS. The labeling rate depends on (1) the level of body water enrichment, (2) cell kinetics, and (3) an amplification factor quantifying the deoxyribose enrichment relative to the body water enrichment. This amplification factor is typically estimated using a reference population undergoing rapid turnover (such as granulocytes), and is larger than one because deoxyribose contains seven hydrogens that can be replaced by deuterium. In a meta-analysis, we found that individuals differ markedly in this amplification factor. Since the amplification factor also depends on the level of body water enrichment, we use conventional binomial expressions to describe the fractions of deoxyribose incorporating zero, one, two, or more deuterium atoms. We extend this classic binomial model with a new parameter, <span><math><mrow><mn>0</mn><mo>&lt;</mo><mi>γ</mi><mo>&lt;</mo><mn>1</mn></mrow></math></span>, describing the relative contribution of hydrogens from body water during deoxyribose synthesis. While for most studies, our ‘novel Binomial’ model reasonably explains the slope with which the amplification factor declines with the level of body water enrichment, we find that some individual amplification factors differ considerably from their expected values Re-fitting deuterium labeling data of granulocytes with the Binomial model reveals that the actual decrease is steeper than expected. We speculate that this residual variation depends on differences in diet, metabolism, and/or life style, which apparently correlate with daily fluid intake.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114010"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677908","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":"Development and clinical application of component-resolved diagnostic using light-initiated chemiluminescence assay to characterize house dust mite components-specific IgE","authors":"Qinqin Liu ,&nbsp;Yuanmin Sun ,&nbsp;Huiqiang Li ,&nbsp;Xueyan Wang","doi":"10.1016/j.jim.2025.114019","DOIUrl":"10.1016/j.jim.2025.114019","url":null,"abstract":"<div><h3>Objective</h3><div>Developed a rapid, sensitive, and homogeneous immunoassay to characterize specific immunoglobulin E (sIgE) against House Dust Mite (HDM) components.</div></div><div><h3>Methods</h3><div>Initially, the reaction conditions were optimized, and the levels of sIgE to the major HDM components -Der p 1, Der p 2, and Der p 23- were measured using the Light-initiated Chemiluminescence Assay (LiCA) assay. The performance of this assay was evaluated in accordance with established clinical guidelines. Subsequently, the sIgE reactivities to these components were analyzed among 90 children with various allergic diseases.</div></div><div><h3>Results</h3><div>We established an assay for HDM component sIgE using LiCA technology. The coefficient of variation for repeatability ranged from 2.64 % to 9.36 %, while the intermediate precision varied from 5.77 % to 9.89 %. Component-resolved diagnosis (CRD) indicated that Der p 2 was the most frequently recognized component (75.56 %), followed by Der p 1 at 64.44 %. The highest co-sensitization rate was observed for Der p 1 and Der p 2 (35.56 %). Der p 23 sIgE levels were significantly elevated in patients with asthma (<em>P</em> &lt; 0.001). Additionally, a greater complexity in allergic symptoms was associated with an increased positive rate of Der p 23 (<em>P</em> = 0.007).</div></div><div><h3>Conclusion</h3><div>The HDM assay developed here is the first attempt to characterize HDM components sIgE by LiCA. This method is easy to operate, faster and has high detection accuracy. Der p 2 was most frequently recognized among the HDM components. Furthermore, our findings indicate a significant correlation between the complexity of allergic symptoms and elevated levels of Der p 23 sIgE.</div></div>","PeriodicalId":16000,"journal":{"name":"Journal of immunological methods","volume":"546 ","pages":"Article 114019"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683916","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}