{"title":"Shaping of the nephron - a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney.","authors":"Will W Minuth","doi":"10.1186/s40348-020-0094-9","DOIUrl":"https://doi.org/10.1186/s40348-020-0094-9","url":null,"abstract":"<p><strong>Background: </strong>The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weight babies resulting in oligonephropathy. For the fetal human kidney, there was no negative effect reported on the early stages of nephron anlage such as the niche, pretubular aggregate, renal vesicle, or comma-shaped body. In contrast, pathological alterations were identified on subsequently developing S-shaped bodies and glomeruli. While the atypical glomeruli were closely analyzed, the S-shaped bodies and the pre-stages received little attention even though passing the process of nephron shaping. Since micrographs and an explanation about this substantial developmental period were missing, the shaping of the nephron in the fetal human kidney during the phase of late gestation was recorded from a microanatomical point of view.</p><p><strong>Results: </strong>The nephron shaping starts with the primitive renal vesicle, which is still part of the pretubular aggregate at this point. Then, during extension of the renal vesicle, a complex separation is observed. The medial part of its distal pole is fixed on the collecting duct ampulla, while the lateral part remains connected with the pretubular aggregate via a progenitor cell strand. A final separation occurs, when the extended renal vesicle develops into the comma-shaped body. Henceforth, internal epithelial folding generates the tubule and glomerulus anlagen. Arising clefts at the medial and lateral aspect indicate an asymmetrical expansion of the S-shaped body. This leads to development of the glomerulus at the proximal pole, whereas in the center and at the distal pole, it results in elongation of the tubule segments.</p><p><strong>Conclusions: </strong>The present investigation deals with the shaping of the nephron in the fetal human kidney. In this important developmental phase, the positioning, orientation, and folding of the nephron occur. The demonstration of previously unknown morphological details supports the search for traces left by the impairment of nephrogenesis, enables to refine the assessment in molecular pathology, and provides input for the design of therapeutic concepts prolonging nephrogenesis.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-020-0094-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37565420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Hegge, Ferry Niepel, A. Lange, A. Vogelgesang, M. Heckmann, J. Ruhnau
{"title":"Functional analysis of granulocyte and monocyte subpopulations in neonates","authors":"I. Hegge, Ferry Niepel, A. Lange, A. Vogelgesang, M. Heckmann, J. Ruhnau","doi":"10.1186/s40348-019-0092-y","DOIUrl":"https://doi.org/10.1186/s40348-019-0092-y","url":null,"abstract":"","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-019-0092-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41608547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silvia Rudloff, Christoph Bührer, Frank Jochum, Thomas Kauth, Mathilde Kersting, Antje Körner, Berthold Koletzko, Walter Mihatsch, Christine Prell, Thomas Reinehr, Klaus-Peter Zimmer
{"title":"Vegetarian diets in childhood and adolescence : Position paper of the nutrition committee, German Society for Paediatric and Adolescent Medicine (DGKJ).","authors":"Silvia Rudloff, Christoph Bührer, Frank Jochum, Thomas Kauth, Mathilde Kersting, Antje Körner, Berthold Koletzko, Walter Mihatsch, Christine Prell, Thomas Reinehr, Klaus-Peter Zimmer","doi":"10.1186/s40348-019-0091-z","DOIUrl":"10.1186/s40348-019-0091-z","url":null,"abstract":"<p><p>In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met through a balanced, vegetable-based diet; however, due to their higher nutrient requirements per kilogramme of body weight, vegetarian children have a higher risk for developing nutrient deficiencies than adults. With a vegetarian diet, the mean intakes of some nutrients, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are lower than in omnivores or those eating fish. For other nutrients, such as iron and zinc, the bioavailability from vegetable foodstuffs is reduced when the intake of phytates and fibre is high; thus, the prevalence of iron deficiency can be increased despite high vitamin C intake. In addition, vitamin B12 is only found in animal-source foods. Vitamin B12 should be supplemented in people of all age groups who follow a strict vegan diet without consuming animal products. A vegetarian diet in childhood and adolescence requires good information and supervision by a paediatrician, if necessary, in cooperation with an appropriately trained dietary specialist.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2019-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47991263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Reinehr, Dirk Schnabel, Martin Wabitsch, Susanne Bechtold-Dalla Pozza, Christoph Bührer, Bettina Heidtmann, Frank Jochum, Thomas Kauth, Antje Körner, Walter Mihatsch, Christine Prell, Silvia Rudloff, Bettina Tittel, Joachim Woelfle, Klaus-Peter Zimmer, Berthold Koletzko
{"title":"Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.).","authors":"Thomas Reinehr, Dirk Schnabel, Martin Wabitsch, Susanne Bechtold-Dalla Pozza, Christoph Bührer, Bettina Heidtmann, Frank Jochum, Thomas Kauth, Antje Körner, Walter Mihatsch, Christine Prell, Silvia Rudloff, Bettina Tittel, Joachim Woelfle, Klaus-Peter Zimmer, Berthold Koletzko","doi":"10.1186/s40348-019-0090-0","DOIUrl":"https://doi.org/10.1186/s40348-019-0090-0","url":null,"abstract":"<p><strong>Background: </strong>Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below reference values, it is debated whether vitamin D should be supplemented after infancy.</p><p><strong>Methods: </strong>The effects of vitamin D supplementation in children > 2 years of age are analyzed based on a literature review of randomized controlled trials (RCTs).</p><p><strong>Results: </strong>Vitamin D supplementation can potentially reduce the risk for influenza infections and improve asthma bronchiale exacerbation; however, it has no impact on asthma bronchiale severity. Vitamin D supplementation has no relevant effect on attention-deficit/hyperactivity disorders, cardiac failure, hypertension, or incidence of type II diabetes mellitus. Vitamin D supplementation has no effect on the rate of multiple sclerosis relapses, but on the number of new lesions detected by MRI. For other endpoints, RCTs are lacking.</p><p><strong>Conclusion: </strong>Based on currently available studies, routine vitamin D supplementation is not be recommended for children aged > 2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-019-0090-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37394610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Berthold Koletzko, Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Burkhard Lawrenz, Antje Körner, Walter Mihatsch, Silvia Rudloff, Klaus-Peter Zimmer
{"title":"Complementary foods in baby food pouches: position statement from the Nutrition Commission of the German Society for Pediatrics and Adolescent Medicine (DGKJ, e.V.).","authors":"Berthold Koletzko, Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Burkhard Lawrenz, Antje Körner, Walter Mihatsch, Silvia Rudloff, Klaus-Peter Zimmer","doi":"10.1186/s40348-019-0089-6","DOIUrl":"https://doi.org/10.1186/s40348-019-0089-6","url":null,"abstract":"<p><p>Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods marketed in baby food pouches often have a high energy density and are predominantly extremely high in sugar content, with up to almost 90% of the total energy content. Regular consumption bears the risks of imbalanced nutrient provision and increased risks for dental caries and overweight. Complementary foods for infants and young children should have a balanced composition following the recommendations of the German Society of Pediatrics and Adolescent Medicine (DGKJ) and should contain only limited amounts of sugar. We discourage the feeding of pureed complementary foods from baby food pouches.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-019-0089-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37030189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susanne Brandstetter, Antoaneta A Toncheva, Jakob Niggel, Christine Wolff, Silvia Gran, Birgit Seelbach-Göbel, Christian Apfelbacher, Michael Melter, Michael Kabesch
{"title":"KUNO-Kids birth cohort study: rationale, design, and cohort description.","authors":"Susanne Brandstetter, Antoaneta A Toncheva, Jakob Niggel, Christine Wolff, Silvia Gran, Birgit Seelbach-Göbel, Christian Apfelbacher, Michael Melter, Michael Kabesch","doi":"10.1186/s40348-018-0088-z","DOIUrl":"https://doi.org/10.1186/s40348-018-0088-z","url":null,"abstract":"<p><strong>Background: </strong>Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.</p><p><strong>Results: </strong>After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.</p><p><strong>Conclusions: </strong>The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0088-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36850617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin S Antony, Ngadhnjim Latifi, A K M Ashiqul Haque, Andrés Lamsfus-Calle, Alberto Daniel-Moreno, Sebastian Graeter, Praveen Baskaran, Petra Weinmann, Markus Mezger, Rupert Handgretinger, Michael S D Kormann
{"title":"Gene correction of HBB mutations in CD34<sup>+</sup> hematopoietic stem cells using Cas9 mRNA and ssODN donors.","authors":"Justin S Antony, Ngadhnjim Latifi, A K M Ashiqul Haque, Andrés Lamsfus-Calle, Alberto Daniel-Moreno, Sebastian Graeter, Praveen Baskaran, Petra Weinmann, Markus Mezger, Rupert Handgretinger, Michael S D Kormann","doi":"10.1186/s40348-018-0086-1","DOIUrl":"https://doi.org/10.1186/s40348-018-0086-1","url":null,"abstract":"<p><strong>Background: </strong>β-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of β-globin and autologous transplantation is a promising therapeutic approach, the risk of insertional mutagenesis or low transgene expression is apparent. However, targeted gene correction of HBB mutations with programmable nucleases such as CRISPR/Cas9, TALENs, and ZFNs with non-viral repair templates ensures a higher safety profile and endogenous expression control.</p><p><strong>Methods: </strong>We have compared three different gene-editing tools (CRISPR/Cas9, TALENs, and ZFNs) for their targeting efficiency of the HBB gene locus. As a proof of concept, we studied the personalized gene-correction therapy for a common β-thalassemia splicing variant HBB<sup>IVS1-110</sup> using Cas9 mRNA and several optimally designed single-stranded oligonucleotide (ssODN) donors in K562 and CD34<sup>+</sup> hematopoietic stem cells (HSCs).</p><p><strong>Results: </strong>Our results exhibited that indel frequency of CRISPR/Cas9 was superior to TALENs and ZFNs (P < 0.0001). Our designed sgRNA targeting the site of HBB<sup>IVS1-110</sup> mutation showed indels in both K562 cells (up to 77%) and CD34<sup>+</sup> hematopoietic stem cells-HSCs (up to 87%). The absolute quantification by next-generation sequencing showed that up to 8% site-specific insertion of the NheI tag was achieved using Cas9 mRNA and a chemically modified ssODN in CD34<sup>+</sup> HSCs.</p><p><strong>Conclusion: </strong>Our approach provides guidance on non-viral gene correction in CD34<sup>+</sup> HSCs using Cas9 mRNA and chemically modified ssODN. However, further optimization is needed to increase the homology directed repair (HDR) to attain a real clinical benefit for β-thalassemia.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0086-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36678458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemotherapy and the pediatric brain.","authors":"Chrysanthy Ikonomidou","doi":"10.1186/s40348-018-0087-0","DOIUrl":"https://doi.org/10.1186/s40348-018-0087-0","url":null,"abstract":"<p><p>Survival rates of children with cancer are steadily increasing. This urges our attention to neurocognitive and psychiatric outcomes, as these can markedly influence the quality of life of these children. Neurobehavioral morbidity in childhood cancer survivors affects diverse aspects of cognitive function, which can include attention, memory, processing speed, intellect, academic achievement, and emotional health. Reasons for neurobehavioral morbidity are multiple with one major contributor being chemotherapy-induced central nervous system (CNS) toxicity. Clinical studies investigating the effects of chemotherapy on the CNS in children with cancer have reported causative associations with the development of leukoencephalopathies as well as smaller regional grey and white matter volumes, which have been found to correlate with neurocognitive deficits.Preclinical work has provided compelling evidence that chemotherapy drugs are potent neuro- and gliotoxins in vitro and in vivo and can cause brain injury via excitotoxic and apoptotic mechanisms. Furthermore, chemotherapy triggers DNA (deoxyribonucleic acid) damage directly or through increased oxidative stress. It can shorten telomeres and accelerate cell aging, cause cytokine deregulation, inhibit hippocampal neurogenesis, and reduce brain vascularization and blood flow. These mechanisms, when allowed to operate on the developing brain of a child, have high potential to not only cause brain injury, but also alter crucial developmental events, such as myelination, synaptogenesis, neurogenesis, cortical thinning, and formation of neuronal networks.This short review summarizes key publications describing neurotoxicity of chemotherapy in pediatric cancers and potential underlying pathomechanisms.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0087-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36654375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases.","authors":"Dirk Holzinger, Dirk Foell, Christoph Kessel","doi":"10.1186/s40348-018-0085-2","DOIUrl":"https://doi.org/10.1186/s40348-018-0085-2","url":null,"abstract":"<p><p>S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin. Furthermore, S100 levels can be used to monitor disease activity to subclinical level, as their serum concentrations decrease with successful treatment.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0085-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36523453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan E G Burdach, Mike-Andrew Westhoff, Maximilian Felix Steinhauser, Klaus-Michael Debatin
{"title":"Precision medicine in pediatric oncology.","authors":"Stefan E G Burdach, Mike-Andrew Westhoff, Maximilian Felix Steinhauser, Klaus-Michael Debatin","doi":"10.1186/s40348-018-0084-3","DOIUrl":"https://doi.org/10.1186/s40348-018-0084-3","url":null,"abstract":"<p><p>Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0084-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36452918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}