Allergology International最新文献

{"title":"Human T follicular helper cells and their impact on IgE and IgG4 production across allergy, malignancy, and IgG4-related disease","authors":"Mitsuhiro Akiyama,&nbsp;Waleed Alshehri,&nbsp;Sho Ishigaki,&nbsp;Koichi Saito,&nbsp;Yuko Kaneko","doi":"10.1016/j.alit.2024.07.005","DOIUrl":"10.1016/j.alit.2024.07.005","url":null,"abstract":"<div><div>Human T follicular helper (Tfh) cells play a crucial role in orchestrating B cell differentiation, maturation, and immunoglobulin class switching. Recent studies have underscored the presence of Bcl-6 + Tfh cells not only in secondary lymphoid organs but also within tertiary lymphoid structures at inflammatory sites, emphasizing their pivotal role in disease pathogenesis. Furthermore, Tfh cells have been found to transit between lesion sites, lymph nodes, and peripheral blood, as revealed by T cell receptor repertoire analysis. Among Tfh subsets, Tfh2 cells have emerged as central orchestrators in driving the production of IgE and IgG4 from B cells. Their critical role in diseases such as allergy, malignancy, and IgG4-related disease highlights their profound impact on balancing inflammation and immune tolerance. Our current review provides the molecular characteristics of human Tfh cells, the differentiation pathways of Tfh subsets, mechanisms by which Tfh subsets induce IgE and IgG4 production, and their clinical implications in allergy, malignancy, and IgG4-related disease.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 25-32"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the IgE response by T follicular regulatory cells","authors":"Alexander L. Dent","doi":"10.1016/j.alit.2024.08.004","DOIUrl":"10.1016/j.alit.2024.08.004","url":null,"abstract":"<div><div>Allergen-specific IgE is a major mediator of allergic responses and contributes greatly to allergic disease in the human population. Therapies that inhibit the production of IgE would be useful for lessening the burden of allergic disease. A great deal of research has focused on how IgE responses are regulated, and several factors that promote the production of allergic IgE have been characterized. T follicular helper (TFH) cells expressing IL-4 are required for the development of IgE expressing B cells in the germinal center (GC). Ig somatic hypermutation and B cell selection in the GC leads to the development of high affinity allergen-specific IgE that promotes anaphylaxis, a severe form of allergic response. T follicular regulatory (TFR) cells are also found in the GC response and act with TFH cells in the selection of high affinity IgE + B cells. This review examines the current literature on IgE responses and TFR cells. In mouse studies, TFR cells have a suppressive role on IgE responses in allergic airway disease, however TFR cells also play a helper role in the IgE response in food allergy. In human studies, TFR cells correlate with a decreased allergic response but evidence for a direct suppressive role of TFR cells on IgE <em>in vivo</em> is lacking. TFR cells may represent a new target for allergy therapies, but caution must be exercised to promote the suppressor activity of TFR cells and not the helper activity of TFR cells on IgE responses.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 20-24"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quaternary ammoniums activate human dendritic cells and induce a specific T-cell response in vitro","authors":"Marine Peyneau ,&nbsp;Mathilde Zeller ,&nbsp;Virginie Paulet ,&nbsp;Benoît Noël ,&nbsp;Marie-Hélène Damiens ,&nbsp;Natacha Szely ,&nbsp;Andreas Natsch ,&nbsp;Marc Pallardy ,&nbsp;Sylvie Chollet-Martin ,&nbsp;Luc de Chaisemartin ,&nbsp;Saadia Kerdine-Römer","doi":"10.1016/j.alit.2024.07.003","DOIUrl":"10.1016/j.alit.2024.07.003","url":null,"abstract":"<div><h3>Background</h3><div>In many countries, neuro-muscular blocking agents (NMBAs) are the first cause of perioperative anaphylaxis. Epidemiological studies identified pholcodine, a quaternary ammonium-containing opiate as one of the sensitization sources. However, NMBA anaphylaxis exists in countries where pholcodine was unavailable, prompting the hypothesis of other sensitizing molecules, most likely quaternary ammonium compounds (QACs).</div><div>Indeed, QACs are commonly used as disinfectants, antiseptics, preservatives, and detergents. Occupational exposure to QACs has been reported as a risk factor for NMBA anaphylaxis, but little is known about the sensitization mechanism and the capacity of these molecules to elicit an immune response. We aimed to establish the immunogenicity of QACs representative of the main existing chemical structures.</div></div><div><h3>Methods</h3><div>We measured the sensitization potential of seven QACs (two polyquaterniums, three alkyl-ammoniums and two aromatic ammoniums) by using two standard dendritic cells (DCs) models (THP-1 cell line and monocyte derived-dendritic cells). The allergenicity of the sensitizing compounds was further tested in heterologous and autologous T-cell-DC co-culture models.</div></div><div><h3>Results</h3><div>Amongst the seven molecules tested, four could modulate activation markers on DCs, and thus can be classified as chemical sensitizers (polyquaterniums-7 and -10, ethylhexadecyldimethylammonium and benzethonium). This activation was accompanied by the secretion of pro-inflammatory and maturation cytokines. Furthermore, activation by polyquaternium-7 could induce T-cell proliferation in heterologous and autologous coculture models, demonstrating that this molecule can induce a specific CD4⁺ T cell response.</div></div><div><h3>Conclusions</h3><div>We provide evidence at the cellular level that some QACs can elicit an immune response, which could be in line with the hypothesis of these molecules' role in NMBA sensitization.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 105-114"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimated prevalence and incidence of hypersensitivity pneumonitis in Japan","authors":"Tsukasa Okamoto ,&nbsp;Mariko Hanafusa ,&nbsp;Taketomo Abe ,&nbsp;Takashi Shimamura ,&nbsp;Masaru Ito ,&nbsp;Yoko Wakai ,&nbsp;Torahiko Jinta ,&nbsp;Katsuyuki Higa ,&nbsp;Yasuhiro Kondoh ,&nbsp;Yasumi Okouchi ,&nbsp;Ryo Okuda ,&nbsp;Masashi Bando ,&nbsp;Takafumi Suda ,&nbsp;Hiromi Tomioka ,&nbsp;Takeo Fujiwara ,&nbsp;Masato Takase ,&nbsp;Shigemi Yoshihara ,&nbsp;Hiroshi Odajima ,&nbsp;Yasunari Miyazaki","doi":"10.1016/j.alit.2024.06.002","DOIUrl":"10.1016/j.alit.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><div>The latest guidelines on hypersensitivity pneumonitis (HP) categorise the disease as either fibrotic or non-fibrotic because of the greater clinical utility of this stratification. However, the prevalence and incidence of fibrotic and non-fibrotic HP are unknown. This study assessed the exact prevalence and incidence of fibrotic and non-fibrotic HP in Japan in 2021.</div></div><div><h3>Methods</h3><div>For adults, the study hospitals were selected by stratified random sampling according to numbers of beds. The sampling rate was set at about 20%. The questionnaire survey was submitted to the target hospitals. For pediatric cases, a survey was distributed to all members of the Japanese Society of Pediatric Pulmonology and Japanese Society of Pediatric Allergy and Clinical Immunology.</div></div><div><h3>Results</h3><div>Regarding adult cases, in total, 575 facilities responded to the survey, resulting in a response rate of 36.4%. The estimated prevalence and incidence of fibrotic HP were 6.3 and 2.5 per 100,000 population, respectively, versus 3.6 and 2.0 per 100,000 population, respectively, for non-fibrotic HP. Both fibrotic and non-fibrotic HP were more prevalent in southern Japan (Kyushu) and less prevalent in northern Japan (Hokkaido). The incidence of non-fibrotic HP was significantly lower in December than in the other months (relative risk ratio = 0.36, p &lt; 0.001). Three cases of fibrotic HP and five cases of non-fibrotic HP were identified in children.</div></div><div><h3>Conclusions</h3><div>This study determined the prevalence and incidence of fibrotic and non-fibrotic HP in Japan for the first time.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 66-71"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T follicular helper and memory B cells in IgE recall responses","authors":"Joshua F.E. Koenig","doi":"10.1016/j.alit.2024.10.003","DOIUrl":"10.1016/j.alit.2024.10.003","url":null,"abstract":"<div><div>IgE antibodies raised against innocuous environmental antigens cause allergic diseases like allergic rhinitis, food allergy, and allergic asthma. While some allergies are often outgrown, others (peanut, shellfish, tree nut) are lifelong in the majority of individuals. Lifelong allergies are the result of persistent production of allergen-specific IgE. However, IgE antibodies and the plasma cells that secrete them tend to be short-lived. Persistent allergen-specific IgE titres are thought to be derived from the continued renewal of IgE plasma cells from memory B cells in response to allergen encounters. The initial generation of allergen-specific IgE is driven by B cell activation by IL-4 producing Tfh cells, but the cellular and molecular mechanisms of the long-term production of IgE are poorly characterized. This review investigates the mechanisms governing IgE production and Tfh activation in the primary and recall responses, towards the objective of identifying molecular targets for therapeutic intervention that durably inactivate the IgE recall response.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 4-12"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab-related eosinophilia in patients with severe asthma: Post-marketing surveillance in Japan","authors":"Makoto Nagata ,&nbsp;Ryo Yamaguchi ,&nbsp;Makiko Usami ,&nbsp;Mami Orimo ,&nbsp;Masato Ishida","doi":"10.1016/j.alit.2024.08.003","DOIUrl":"10.1016/j.alit.2024.08.003","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 1","pages":"Pages 169-171"},"PeriodicalIF":6.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-year prognoses after low-dose oral food challenge for cow's milk.","authors":"Mai Tokunaga, Ken-Ichi Nagakura, Kyohei Takahashi, Sakura Sato, Motohiro Ebisawa, Noriyuki Yanagida","doi":"10.1016/j.alit.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.alit.2024.09.006","url":null,"abstract":"<p><strong>Background: </strong>Low-dose (LD) oral food challenge (OFC) with heated cow's milk (CM; 3 mL) effectively prevents CM elimination in children with CM allergy (CMA). We investigated the long-term prognoses after an LD-OFC for CMA.</p><p><strong>Methods: </strong>Children with immediate CMA symptoms after consuming <25 mL of CM within 2 years of a baseline LD-OFC were retrospectively analyzed. Children who successfully passed the baseline LD-OFC (LD-passing) continued consuming 3 mL of CM at home, whereas those who failed (LD-failing) continued to avoid CM. Dose escalation occurred through stepwise OFCs or gradually at home. CM tolerance was defined as the ability to repeatedly consume ≥100 mL CM without experiencing symptoms; the inability to do so indicated persistent CMA. The prognoses of the LD-passing and LD-failing groups within 3 years of LD-OFC were compared.</p><p><strong>Results: </strong>Among 113 children, the median age at baseline LD-OFC was 2.8 years; 41 % had an anaphylaxis history, with equal distribution between the LD-passing and LD-failing groups. Three years later, 63 % and 5 % of children demonstrated CM tolerance in the LD-passing and LD-failing groups, respectively (p < 0.001). In the LD-passing group, predictors of persistent CMA were older age (adjusted hazard ratio [95 % confidence interval], 1.37 [1.00-1.88]), higher CM-specific IgE level (2.95 [1.30-6.68]) and other food allergies (2.34 [1.12-4.90]).</p><p><strong>Conclusions: </strong>Failure in LD-OFC is associated with persistent CMA, whereas successful LD-OFC outcomes are associated with a favorable prognosis thereafter, irrespective of a history of anaphylaxis.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peach component-specific IgE measurement helps to differentiate between local and systemic reactions in peach-allergic Japanese patients.","authors":"Yusuke Ando, Sakura Sato, Motohiro Ebisawa, Shiro Sugiura, Komei Ito, Mizuho Nagao, Takao Fujisawa, Shigemi Yoshihara","doi":"10.1016/j.alit.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.alit.2024.09.004","url":null,"abstract":"<p><strong>Background: </strong>Component-resolved diagnostics are used to diagnose food allergies. Currently, reports on sensitization profiles using peach-allergen components in a multicenter setting are lacking. In this study, sensitization profiling of peach allergy was performed to evaluate the clinical utility of each component specific-immunoglobulin E antibody (sIgE ab) test.</p><p><strong>Methods: </strong>Sixty-seven patients with peach allergy were enrolled at four Japanese centers and classified into a local reaction group (LR) with only oral or pharyngeal mucosal symptoms in 36 patients and a systemic reaction group (SR) without LR in 31 patients. Serum sIgE ab tests to peach crude, Pru p 1, Pru p 3, Pru p 4, Pru p 7, and tree pollen were conducted.</p><p><strong>Results: </strong>In the receiver operating characteristic curve analysis, Pru p 1 had the highest area under the curve (AUC) for diagnosing LR, followed by Pru p 4, which outperformed peach crude allergen. Pru p 7 had the highest AUC for diagnosing SR, with the other peach allergen components and peach crude allergen showing lower values.</p><p><strong>Conclusions: </strong>Sensitization to Pru p 1 was associated with LRs, while sensitization to Pru p 7 was associated with SRs; approximately one-third of patients in the SR group tested negative for the titer of peach crude sIgE ab, many of whom tested positive for the titer of Pru p 7 sIgE ab. We conclude that measuring Pru p 1, Pru p 4, and Pru p 7 sIgE ab titers is useful to differentiate LRs and SRs in peach-allergic Japanese patients.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of anti-MGL_1304 IgE using the ImmunoCAP system for diagnosis of type I allergy to sweat.","authors":"Shunsuke Takahagi, Masaya Moriwaki, Kaori Ishii, Natsuko Asakura, Michihiro Hide","doi":"10.1016/j.alit.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.alit.2024.11.004","url":null,"abstract":"<p><strong>Background: </strong>Type I allergy to sweat is involved in the pathogenesis of atopic dermatitis (AD) and cholinergic urticaria (CholU), with MGL_1304 from Malassezia globosa being the major causative antigen. Currently, no standard diagnostic test exists for sweat allergy that uses serum.</p><p><strong>Methods: </strong>The ImmunoCAP (iCAP) system to measure antigen-specific IgE was developed using recombinant MGL_1304 (rMGL_1304). Using a positive histamine release test (HRT) against the semi-purified sweat antigen (QR) as a criterion for diagnosing sweat allergy, the diagnostic usefulness of anti-MGL_1304 IgE detected through iCAP was analyzed in comparison with conventional anti-Malassezia antigen m227 IgE (anti-m227 IgE).</p><p><strong>Results: </strong>The iCAP system with rMGL_1304 detected anti-MGL_1304 IgE in serum samples without detection of non-specific reactions. In 93 patients with AD or CholU, of which 58 were HRT-positive, anti-MGL_1304 IgE titers correlated with histamine release levels in HRT against QR better than anti-m227 IgE titers. The cutoff value for sweat allergy diagnosis was 1.55 U_A/mL for anti-m227 IgE (sensitivity: 79.3 %; specificity: 65.7 %) and 0.671 U_A/mL for anti-MGL_1304 IgE (sensitivity: 84.5 %; specificity: 80.0 %). Clinical features of AD and CholU were partially associated with anti-m227 IgE and anti-MGL_1304 IgE titers but not with histamine release in HRT using QR.</p><p><strong>Conclusions: </strong>Anti-MGL_1304 IgE detection using iCAP is simple and can help diagnosis of sweat allergy with better accuracy than conventional anti-Malassezia antigen IgE.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of corneal squamous cell carcinoma antigen-1 in early infancy in predicting atopic dermatitis and food allergy: A prospective study.","authors":"Maki Ozawa, Chika Katagiri, Chieko Okamura, Masashi Miyai, Yukiko Matsunaga, Daichi Murata, Christopher Takaya Knight, Tomoko Onodera, Masayuki Asano, Junko Endo, Ryoko Omori, Toshiya Takahashi, Masatoshi Saito, Takushi Hanita, Shimpei Watanabe, Shinichi Sato, Nobuko Tabata, Osamu Iizawa, Yoshihide Asano, Setsuya Aiba","doi":"10.1016/j.alit.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.alit.2024.11.005","url":null,"abstract":"<p><strong>Background: </strong>Identification of predictive biomarkers is crucial for formulating preventive interventions and halting the progression of atopic march. Although controversial, the use of accessible markers to predict or detect early onset of atopic diseases is highly desirable. Therefore, this study aimed to investigate whether corneal squamous cell carcinoma antigen-1 (SCCA1) collected from infants can predict the development of atopic dermatitis and food allergy.</p><p><strong>Methods: </strong>This prospective study enrolled 117 infants aged 2 months (55 female and 62 male infants). The participants were monitored to evaluate the occurrence of eczematous changes at several time points, and stratum corneum samples were obtained. The association of corneal SCCA1 with the development of atopic dermatitis and food allergy in the first 3 years of life was evaluated using univariate and multivariate logistic regression.</p><p><strong>Results: </strong>The corneal SCCA1 level was significantly higher in children who developed atopic dermatitis than in children who did not (cheek at 2 months: 1653.06 ± 178.48 ng/mg vs. 786.95 ± 101.59 ng/mg, P = 0.0033). The corneal SCCA1 level was also significantly higher in children who developed food allergy than in children who did not (perioral skin at 2 months: 2567.31 ± 408.09 ng/mg vs. 1120.85 ± 188.49 ng/mg, P = 0.0018).</p><p><strong>Conclusions: </strong>The findings suggest that non-invasive measurements of corneal SCCA1 at 2 months of age is useful for predicting atopic dermatitis and food allergy in infants at risk for atopic dermatitis and subsequent food allergy.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}