Experimental and molecular pathology最新文献

{"title":"The multifunctional protein CCN1/CYR61: Bridging physiology and disease","authors":"Racha Kerek,&nbsp;Joe Sawma Awad ,&nbsp;Mariam Bassam ,&nbsp;Carla Hajjar ,&nbsp;Fouad Ghantous,&nbsp;Karelle Rizk,&nbsp;Mohamad Rima","doi":"10.1016/j.yexmp.2025.104969","DOIUrl":"10.1016/j.yexmp.2025.104969","url":null,"abstract":"<div><div>The matricellular protein CYR61/CCN1 is a member of the CCN protein family that plays significant roles in a broad range of physiological processes, including development, tissue repair, and inflammation, among others. CCN1 is also implicated in pathological conditions such as cancer and fibrosis. The diverse functions of CCN1 arise from its ability to bind different receptors located on many cell types, thereby activating diverse signaling pathways. The diverse, yet contradictory, functions mediated by CCN1 makes it a compelling target for investigation, as it offers the prospect of understanding fundamental cellular topics and their possible implications in various diseases. Recently, new cellular functions were attributed to CCN1, including senescence, pro-/anti- fibrosis, and rejuvenation. In this review, we discuss all these new findings along with the basic knowledge about CCN1 to provide an overall understanding of its conflicting roles and their potential corresponding mechanisms of action.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104969"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868283","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":"Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu","authors":"Darab Ghadimi ,&nbsp;Regina Fölster-Holst ,&nbsp;Sophia Blömer ,&nbsp;Michael Ebsen ,&nbsp;Christoph Röcken ,&nbsp;Jumpei Uchiyama ,&nbsp;Shigenobu Matsuzaki ,&nbsp;Wilhelm Bockelmann","doi":"10.1016/j.yexmp.2025.104967","DOIUrl":"10.1016/j.yexmp.2025.104967","url":null,"abstract":"<div><div>Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive <em>Bifidobacterium bifidum</em> (<em>B. bifidum</em>) and Gram-negative <em>Pseudomonas aeruginosa</em> PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-<em>N</em>-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and <em>B. bifidum</em><strong>.</strong> In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104967"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868282","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":"Morphological characteristics, extracellular vesicle structure and stem-like specificity of human follicular fluid cell subpopulation during osteodifferentiation","authors":"Wiesława Kranc ,&nbsp;Mariusz Kaczmarek ,&nbsp;Katarzyna Kowalska ,&nbsp;Wojciech Pieńkowski ,&nbsp;Sylwia Ciesiółka ,&nbsp;Aneta Konwerska ,&nbsp;Paul Mozdziak ,&nbsp;Maciej Brązert ,&nbsp;Michal Jeseta ,&nbsp;Robert Z. Spaczyński ,&nbsp;Leszek Pawelczyk ,&nbsp;Bartosz Kempisty","doi":"10.1016/j.yexmp.2025.104965","DOIUrl":"10.1016/j.yexmp.2025.104965","url":null,"abstract":"<div><div>Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed <em>via</em> Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104965"},"PeriodicalIF":2.8,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850570","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":"The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways","authors":"Garth Wentley ,&nbsp;Russel J. Reiter ,&nbsp;Yong-Xiao Wang ,&nbsp;Gerald Maarman","doi":"10.1016/j.yexmp.2025.104966","DOIUrl":"10.1016/j.yexmp.2025.104966","url":null,"abstract":"<div><div>Previous research has demonstrated that melatonin protects against muscle damage while also improving the performance of injured muscle. However, its impact on healthy skeletal muscle remains largely unexplored. We exposed differentiated C2C12 myotubes to two melatonin concentrations (10 nM or 50 nM). The 10 nM concentration did not affect any of the mitochondrial respiration parameters. Whereas 50 nM concentration reduced mitochondrial complex II-linked oxidative phosphorylation (OXPHOS), electron transfer system (ETS) capacity, the contribution of complex II to ETS, and residual oxygen consumption (ROX). Neither concentration influenced the mitochondrial coupling control ratios, nor the coupling control efficiency ratios. Furthermore, neither concentration affected ATP production but reduced superoxide dismutase activity. The 50 nM increased catalase activity without affecting autophagy or citrate synthase activity. Moreover, 50 nM reduced activated JAK2 and STAT3 protein expression, while 10 nM reduced JAK2 without affecting STAT3. Th 50 nM increased activated AKT and ERK1/2 expression with no effect on p38 or PGC1-α expression. Our data suggests that melatonin (50 nM) triggers an oxygen-sparing effect on mitochondrial respiration, which is mediated via its antioxidant actions and its ability to enhance pro-survival pathways. Therefore, melatonin intake may have ergogenic effects on healthy muscles, in the absence of pathology, e.g., consumption before sporting events or physical exercise may aid in the reduction of oxidative stress often associated with such activities. However, this is an in vitro study, and therefore, the clinical relevance of the data should be considered with caution.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104966"},"PeriodicalIF":2.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824350","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":"Gut-lung Axis mediates asthma pathogenesis: Roles of dietary patterns and their impact on the gut microbiota","authors":"Yanbo Liu,&nbsp;Ying Zhou,&nbsp;Haoyue Zhang,&nbsp;Kaixuan Zhao,&nbsp;Dong Yang","doi":"10.1016/j.yexmp.2025.104964","DOIUrl":"10.1016/j.yexmp.2025.104964","url":null,"abstract":"<div><div>The gut-lung axis, a vital signaling network linking the gastrointestinal and pulmonary systems, regulates immune responses and the progression of respiratory diseases. Nutritional components can modulate the gut microbiome and regulate the synthesis of critical intestinal microbial metabolites, which are essential for maintaining immune homeostasis and supporting respiratory health. Conversely, poor dietary habits exacerbate asthma and other respiratory conditions through the modulation of systemic inflammation and immune responses. Dietary interventions, such as the Mediterranean diet, are reported to restore microbial balance and improve respiratory health by increasing the production of anti-inflammatory metabolites, potentiating immune responses, and preserving epithelial barrier integrity. In contrast, Western dietary patterns, which are characterized by high fat and low fiber intake, disrupt microbial diversity, resulting in increased levels of pro-inflammatory metabolites that aggravate airway inflammation and asthma severity. This review aimed to elucidate the mechanisms underlying the regulatory effects of gut microbes and their metabolites on asthma. Additionally, previous findings related to the gut-lung axis have been summarized, providing insights into potential therapeutic strategies for asthma management.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104964"},"PeriodicalIF":2.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785162","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":"Advances in sepsis research: Insights into signaling pathways, organ failure, and emerging intervention strategies","authors":"Yehua Li ,&nbsp;Siying Ren ,&nbsp;Shen’ao Zhou","doi":"10.1016/j.yexmp.2025.104963","DOIUrl":"10.1016/j.yexmp.2025.104963","url":null,"abstract":"<div><div>Sepsis is a complex syndrome resulting from an aberrant host response to infection. A hallmark of sepsis is the failure of the immune system to restore balance, characterized by hyperinflammation or immunosuppression. However, the net effect of immune system imbalance and the clinical manifestations are highly heterogeneous among patients. In recent years, research interest has shifted from focusing on the pathogenicity of microorganisms to the molecular mechanisms of host responses which is also associated with biomarkers that can help early diagnose sepsis and guide treatment decisions. Despite significant advancements in medical science, sepsis remains a major challenge in healthcare, contributing to substantial morbidity and mortality worldwide. Further research is needed to improve our understanding of this condition and develop novel therapies to improve outcomes for patients with sepsis. This review explores the related signal pathways of sepsis and underscores recent advancements in understanding its mechanisms. Exploration of diverse biomarkers and the emerging concept of sepsis endotypes offer promising avenues for precision therapy in the future.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104963"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704181","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":"The role of lactate and lactylation in ischemic cardiomyopathy: Mechanisms and gene expression","authors":"Mei Zhang ,&nbsp;Xue Kong ,&nbsp;Chenlu Wu ,&nbsp;Jiuhong Li ,&nbsp;Hui Yang ,&nbsp;Lingzhi Huang","doi":"10.1016/j.yexmp.2025.104957","DOIUrl":"10.1016/j.yexmp.2025.104957","url":null,"abstract":"<div><div>Ischemic cardiomyopathy (ICM) is a significant global public health issue, with its pathophysiology encompassing atherosclerotic plaque formation, thrombosis, hypoperfusion, ischemic cell death, and left ventricular remodeling. Lactate is not only regarded as an energy metabolite but also acts as a signaling molecule that influences various physiological processes, regulating metabolism and muscle contraction. Lactylation, an emerging epigenetic modification, affects protein functionality and gene expression through the P300 enzyme. In ICM, lactate accumulation leads to pH imbalance and myocardial cell dysfunction, impacting cellular signaling. This paper will analyze the role of lactylation in ICM, focusing on coronary artery disease (ASCVD) and myocardial infarction (MI). It will also explore the differential expression and immunological characteristics of lactylation-related genes in normal and ICM tissues, providing potential targets for future research.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104957"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512150","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":"Dynamic full-field optical coherence tomography for extemporaneous high-resolution imaging of adrenal glands","authors":"Irene A. Spiridon ,&nbsp;Michel Vix ,&nbsp;Didier Mutter ,&nbsp;Barbara Seeliger","doi":"10.1016/j.yexmp.2025.104958","DOIUrl":"10.1016/j.yexmp.2025.104958","url":null,"abstract":"<div><h3>Background</h3><div>There is an interindividual variance in postoperative adrenocortical capacity, and the minimal functional remnant size is unknown. New imaging technologies may allow for improved intraoperative assessment of adrenal tissue morphology, cell activity, and surgery-related changes<em>.</em> The aim of this experimental study was to provide a pilot assessment of adrenal gland architecture with dynamic full-field optical coherence tomography (D-FF-OCT) in comparison to standard hematoxylin-eosin (HE) examination.</div></div><div><h3>Methods</h3><div>D-FF-OCT was performed on freshly resected porcine adrenal glands to simultaneously assess both morphology and metabolic activity in real time, and for comparison with standard histopathology. Left and right adrenal glands were assessed from 8 pigs (1 M, 7 F, mean weight 43.9 ± 8.3 kg).</div></div><div><h3>Results</h3><div>The evaluation with D-FF-OCT proved fast in terms of acquisition time, averaging 32 min/specimen. The technique required a relatively short learning curve and provided morphological details similar to standard microscopy. In the comparative analysis of both methods, D-FF-OCT scans allowed easy identification of normal adrenal morphology and facilitated differentiation of the structural components of the cortical and medullary areas based on architectural and vascular patterns. Furthermore, it was possible to distinguish more accurately between cell subpopulations based on their metabolic activity.</div></div><div><h3>Conclusion</h3><div>While HE examination remains the gold standard for morphological evaluation, time weighs heavy on this ancillary technique. In our study, we prove that D-FF-OCT is effective in achieving a comparable level of morphological details, with added metabolic activity of the cells, a combination which can prove useful in the real-time assessment of various diseases requiring adrenal surgery.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104958"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436986","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":"Diagnostic next-generation sequencing to detect MYD88 L265P in Lymphoplasmacytic lymphoma compared to ddPCR","authors":"Lauren M. Wainman,&nbsp;Guohong Huang,&nbsp;Donald C. Green,&nbsp;Gregory J. Tsongalis,&nbsp;Laura J. Tafe,&nbsp;Wahab A. Khan,&nbsp;Prabhjot Kaur,&nbsp;Parth S. Shah ,&nbsp;Jeremiah X. Karrs","doi":"10.1016/j.yexmp.2025.104956","DOIUrl":"10.1016/j.yexmp.2025.104956","url":null,"abstract":"<div><div>Lymphoplasmacytic lymphoma (LPL) is a B-cell lymphoproliferative disorder typically involving the bone marrow with infiltration by small lymphocytes and plasma cells. Studies have identified MYD88 L265P mutation as a diagnostic marker to distinguish LPL from other small B-cell lymphomas. Detection rates for this mutation have varied depending on the analytic methodology, with previous data suggesting that routine next-generation sequencing (NGS) does not demonstrate the required sensitivity to reliably detect MYD88 L265P. NGS has become part of routine clinical testing because it allows detection of variants across multiple genes. To study the utility of NGS in the detection of MYD88 L265P, we performed droplet digital PCR (ddPCR) and routine NGS on a cohort of 34 cases of lymphoid neoplasms (22 LPL, 4 CLL, 1 MCL, 1 MGUS, 2 plasma cell myeloma, and 4 negative bone marrow cases). We utilized manual review and BAMtools to assess MYD88 L265P in NGS cases. Limit of detection for ddPCR was determined to be 0.4 % variant allele frequency (VAF) with 10 ng DNA input. MYD88 L265P VAF detection by NGS and ddPCR was comparable down to 0.5 % VAF (R² = 0.968). Setting an appropriate threshold for detection based on ddPCR results resulted in zero NGS false positives. We found that low tumor content did not impact the detection of MYD88 L265P by NGS. This study demonstrates that NGS can be a sensitive and reliable method for detection of MYD88 L265P with adequate coverage and specific assessment parameters.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104956"},"PeriodicalIF":2.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419267","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":"Matrix metalloproteinase-3 is a potent prognostic factor associated with cell proliferation and migration in prostate cancer","authors":"Ai Sato ,&nbsp;Kiyoshi Takagi ,&nbsp;Mio Yamaguchi-Tanaka ,&nbsp;Jotaro Okushima ,&nbsp;Yuto Yamazaki ,&nbsp;Akihiro Ito ,&nbsp;Takashi Suzuki","doi":"10.1016/j.yexmp.2025.104954","DOIUrl":"10.1016/j.yexmp.2025.104954","url":null,"abstract":"<div><div>Prostate cancer is a common malignancy in men around the world, and it is crucial to explore novel biomarkers to improve its treatment. Prostate cancer cells typically invade the surrounding stroma, and remodeling of the extracellular matrix (ECM) is a crucial step in the progress of prostate cancer. Matrix metalloproteinase-3 (MMP3) is an enzyme that degrades several ECM components and is implicated in human malignancies. However, the clinical and biological significance of MMP3 has not been well elucidated.</div><div>We therefore immunolocalized MMP3 in prostate cancer tissues (<em>n</em> = 117) and demonstrated that MMP3 immunoreactivity was correlated with aggressive phenotype of prostate cancer, including higher proliferation/invasion ability, and shorter disease-free survival. In addition, subsequent in vitro analysis revealed that overexpression of MMP3 significantly increased the proliferative and migratory abilities of PC-3 and DU-145 prostate cancer cell lines, depending on conditioned media from WMPY-1 prostate stromal cells.</div><div>It was concluded that MMP3 might contribute to prostate cancer progression by modifying the ECM surrounding prostate cancer cells and could serve as a potent prognostic factor in prostate cancer.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104954"},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377986","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}