Nephrology Dialysis Transplantation最新文献

{"title":"Big databases and biobanks for studying the links between CKD, cognitive impairment, and dementia.","authors":"Carmine Zoccali, Francesca Mallamaci, Kerry Rosenberg, Robert Unwin, Pedro Imenez Silva, Maria Adelina Simeoni, Gaye Hafez, Giovambattista Capasso, Dorothea Nitsch","doi":"10.1093/ndt/gfae255","DOIUrl":"10.1093/ndt/gfae255","url":null,"abstract":"<p><p>Research on cognitive function in individuals with chronic kidney disease (CKD) is critical due to the significant public health challenge posed by both CKD and cognitive impairment. CKD affects approximately 10-15% of the adult population, with higher prevalence in the elderly, who are already at increased risk for cognitive decline. Cognitive impairment is notably higher in CKD patients, particularly those with severe stages of the disease, and progresses more rapidly in those on dialysis. This review explores how data from large biobank studies such as the Alzheimer's Disease Neuroimaging Initiative, UK Biobank, and others could be used to enhance understanding the progression and interplay between CKD and cognitive decline. Each of these data sources has specific strengths and limitations. Strengths include large sample sizes and longitudinal data across different groups, and in different settings. Addressing limitations leads to challenges in dealing with heterogeneous data collection methods, and addressing missing data, which requires the use of sophisticated statistical techniques. Combining data from multiple databases can mitigate individual study limitations, particularly via the 'epidemiological triangulation' concept. Using such data appropriately holds immense potential to better understand the pathobiology underlying CKD and cognitive impairment. Addressing the inherent challenges with a clear strategy is crucial for advancing our understanding and improving the lives of those affected by both CKD and cognitive impairment.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii37-ii45"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625226","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":"The role of the intestinal microbiome in cognitive decline in patients with kidney disease.","authors":"Carsten A Wagner, Isabelle Frey-Wagner, Alberto Ortiz, Robert Unwin, Sophie Liabeuf, Yoko Suzumoto, Anna Iervolino, Alessandra Stasi, Vincenzo Di Marzo, Loreto Gesualdo, Ziad A Massy","doi":"10.1093/ndt/gfae253","DOIUrl":"10.1093/ndt/gfae253","url":null,"abstract":"<p><p>Cognitive decline is frequently seen in patients with chronic kidney disease (CKD). The causes of cognitive decline in these patients are likely to be multifactorial, including vascular disease, uraemic toxins, blood-brain barrier leakage, and metabolic and endocrine changes. Gut dysbiosis is common in patients with CKD and contributes to the increase in uraemic toxins. However, the gut microbiome modulates local and systemic levels of several metabolites such as short-chain fatty acids or derivatives of tryptophan metabolism, neurotransmitters, endocannabinoid-like mediators, bile acids, hormones such as glucagon-like peptide 1 (GLP1) or cholecystokinin (CCK). These factors can affect gut function, immunity, autonomic nervous system activity and various aspects of brain function. Key areas include blood-brain barrier integrity, nerve myelination and survival/proliferation, appetite, metabolism and thermoregulation, mood, anxiety and depression, stress and local inflammation. Alterations in the composition of the gut microbiota and the production of biologically active metabolites in patients with CKD are well documented and are favoured by low-fiber diets, elevated urea levels, sedentary lifestyles, slow stool transit times and polypharmacy. In turn, dysbiosis can modulate brain function and cognitive processes, as discussed in this review. Thus, the gut microbiome may contribute to alterations in cognition in patients with CKD and may be a target for therapeutic interventions using diet, prebiotics and probiotics.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii4-ii17"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625297","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":"CONNECT: what has been done and what needs to be done.","authors":"Giovambattista Capasso, Robert J Unwin","doi":"10.1093/ndt/gfae248","DOIUrl":"10.1093/ndt/gfae248","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii1-ii3"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625275","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":"Care pathways for patients with cognitive impairment and chronic kidney disease.","authors":"Marion Pépin, Konstantinos Giannakou, Hélène Levassort, Ana Farinha, Mickaël Bobot, Vincenzina Lo Re, Aleksandra Golenia, Jolanta Małyszko, Francesco Mattace-Raso, Aleksandra Klimkowcz-Mrowiec, Liliana Garneata, Evgueniy Vazelov, Elena Stepan, Giovanna Capolongo, Ziad Massy, Andrzej Wiecek","doi":"10.1093/ndt/gfae264","DOIUrl":"10.1093/ndt/gfae264","url":null,"abstract":"<p><p>Various epidemiological datasets and pathophysiological hypotheses have highlighted a significant link between chronic kidney disease (CKD) and cognitive impairment (CI); each condition can potentially exacerbate the other. Here, we review the mutual consequences of CKD and CI on health outcomes and care pathways and highlight the complexities due to the involvement of different specialists. Our narrative review covers (i) the burden of CI among patients with CKD, (ii) the impact of CI on kidney health, (iii) access to kidney replacement therapy for people with CI, (iv) resources in cognitive care and (v) potential models for integrated 'nephro-cognitive' care. CI (ranging from mild CI to dementia) has a significant impact on older adults, with a high prevalence and a strong association with CKD. Furthermore, CI complicates the management of CKD and leads to a higher mortality rate, poorer quality of life and higher healthcare costs. Due to difficulties in symptom description and poor adherence to medical guidelines, the presence of CI can delay the treatment of CKD. Access to care for patients with both CKD and CI is hindered by physical, cognitive and systemic barriers, resulting in less intensive, less timely care. Multidisciplinary approaches involving nephrologists, geriatricians, neurologists and other specialists are crucial. Integrated care models focused on person-centred approaches, shared decision-making and continuous co-management may improve outcomes. Future research should focus on the putative beneficial effects of these various strategies on both clinical and patient-reported outcomes.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii28-ii36"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625234","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":"Genetic and circulating biomarkers of cognitive dysfunction and dementia in CKD.","authors":"Carmine Zoccali, Francesca Mallamaci, Carsten A Wagner, Robert Unwin, Maiken Nedergaard, Gaye Hafez, Jolanta Malyszko, Marion Pepin, Ziad Massy, Giuseppe Paolisso, Giuseppe Remuzzi, Giovambattista B Capasso","doi":"10.1093/ndt/gfae259","DOIUrl":"10.1093/ndt/gfae259","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is commonly accompanied by cognitive dysfunction and dementia, which, in turn, increase the risk of hospitalization, cardiovascular events and death. Over the last 30 years, only four studies focused on genetic markers of cognitive impairment in CKD and kidney failure (KF), indicating a significant gap in research. These studies suggest potential genetic predispositions to cognitive decline in CKD patients but also underscore the necessity for more comprehensive studies. Seventeen reports have established connections between cognitive function and kidney disease markers such as estimated glomerular filtration rate (eGFR), Cystatin C and albuminuria. A rapid eGFR decline has been associated with cognitive deterioration and vascular dementia, and mild to moderate eGFR reductions with diminished executive function in elderly men. Various biomarkers have been associated to Alzheimer's disease or dementia in CKD and KF. These include amyloid beta and phosphorylated tau proteins, uremic toxins, gut microbiota, metabolic indicators, hypertension, endothelial dysfunction, vitamins and inflammation. However, the causal relevance of these associations remains unclear. Overall, the available evidence points to a complex interplay between the different biomarkers and cognitive health in CKD patients, underscoring the need for more research to elucidate these relationships.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii64-ii75"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625279","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":"Cognitive impairment in kidney transplanted patients.","authors":"Jolanta Malyszko, Aleksandra Golenia, Michele Farisco, Vincenzina Lo Re, Aleksandra Klimkowicz-Mrowiec, Giovambattista Capasso, Dimitris Goumenos, Merita Rroji, Andreja Figurek, Gaye Hafez","doi":"10.1093/ndt/gfae250","DOIUrl":"10.1093/ndt/gfae250","url":null,"abstract":"<p><p>Chronic kidney disease affects almost all of the organs. Recently, more attention has been paid to the kidney and the central nervous system connections. In patients on kidney replacement therapy, including kidney transplantation, there is an increased prevalence of cognitive impairment, and depression and other neurological complications, such as cerebrovascular disorders and movement disorders. Kidney transplant recipients need an assessment for the risk factors and the pattern of cognitive impairment (memory, attention and executive function decline). This enables an accurate diagnosis to be made at an earlier stage. Partial post-transplant cognitive impairment recovery is also important. Finally, doctors and patients alike face numerous ethical concerns and challenges regarding the transplantation of kidneys and other solid organs. In this review, we examined some key issues regarding cognitive impairment in kidney transplant patients. We focused on the mechanism of cognitive impairment in kidney transplant recipients, patterns of cognitive impairment; evaluation of patients with cognitive impairment for kidney transplantation, the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, non-pharmacological interventions and unmet medical needs, psychological and ethical issues in kidney transplantation, and unmet needs. As cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem, screening for cognitive function before and after kidney transplantation would be worth considering in standard routine practice.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii46-ii53"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625290","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":"Cognitive impairment in chronic kidney disease: role of brain imaging, functional imaging, electroencephalography, cerebrospinal fluid biomarkers and sensors.","authors":"Alexandre Andrade, Maie Bachmann, Mickaël Bobot, Annette Bruchfeld, Ivo Fridolin, Laila-Yasmin Mani, Hong Xu","doi":"10.1093/ndt/gfae256","DOIUrl":"10.1093/ndt/gfae256","url":null,"abstract":"<p><p>Chronic kidney disease is associated with cognitive impairment although the underlying mechanisms are still not fully understood. Characterization and efficient monitoring of the cognitive impact of kidney disease and ensuing therapies are critical for the accurate clinical management of patients. A vast array of imaging modalities, biomarkers, and sensors have shown relevance for the assessment of cognitive impairment. Knowing the potential and limitations of these paraclinical techniques is a necessary condition to improve the understanding of this phenomenon and to design monitoring protocols and guidelines applicable to this clinical population. The goal of this review is to provide an overview of current imaging modalities and biomarker sources available to the community, for the benefit of the research and clinical community.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":"40 Supplement_2","pages":"ii18-ii27"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625254","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":"Comparison of estimated glomerular filtration rate equations on prediction of mortality, kidney failure, and acute kidney injury.","authors":"Denise M J Veltkamp, Maarten B Rookmaaker, Mark C H de Groot, Marianne C Verhaar, Wouter W van Solinge, Saskia Haitjema, Robin W M Vernooij","doi":"10.1093/ndt/gfaf054","DOIUrl":"https://doi.org/10.1093/ndt/gfaf054","url":null,"abstract":"<p><strong>Background: </strong>The CKD-EPIASR-NB2009 estimated glomerular filtration rate (eGFR) equation has shown substantial overestimation of GFR in Europeans, hence new equations have been developed. We examined the effect of introducing the European Kidney Function Consortium (EKFC) or Lund-Malmö revised (LMR) eGFR equations on KDIGO eGFR-category classification in a large cohort. We compared the EKFC and LMR equations with the CKD-EPIASR-NB2009 formula in view of discriminative ability of all-cause mortality, kidney failure with replacement therapy (KFRT), and acute kidney injury (AKI) risks across eGFR-categories.</p><p><strong>Methods: </strong>Individuals ≥18y with a SCr measurement (December 2006-July 2024) at University Medical Center Utrecht, were included. Hazard ratios (HRs) were analysed for all outcomes per eGFR-category, per equation. Harrell's Concordance index (C-index) was used to assess the ability of risk discrimination across eGFR-categories. Whether reclassification between eGFR-categories was justified by the occurrence of events, was assessed with net reclassification improvement analysis.</p><p><strong>Results: </strong>In total, 285,686 individuals were included. Compared with the CKD-EPIASR-NB2009 equation, the EKFC and LMR estimated GFR lower (mean -6.3(SD5.3) and -10.7(SD6.5)ml/min/1.732, respectively). The number of individuals with eGFR <60ml/min/1.73m2 increased 29.0%(EKFC) and 36.4%(LMR). The EKFC predominantly reclassified older individuals, and the LMR older men, to worse eGFR-categories. HRs of reclassified individuals to worse eGFR-categories were mainly higher compared with the non-reclassified. The EKFC and LMR equations showed equal/improved C-index for mortality (EKFC 0.584/LMR 0.588/CKD-EPIASR-NB2009 0.570), KFRT (0.895/0.900/0.897), and AKI (0.606/0.609/0.599). The LMR equation reclassified more individuals without an event to worse eGFR-categories.</p><p><strong>Conclusion: </strong>eGFR-category classification was substantially different when using the EKFC or LMR equation compared with the CKD-EPIASR-NB2009 formula. Both equations showed equal to improved ability of risk stratification across eGFR-categories. Shifts in eGFR-category classification might significantly impact clinical decisions. Given that we have identified variation between equations, a careful consideration of the advantages and disadvantages of different eGFR equations is essential.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605935","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":"Dietary vitamin E and tocopherol isoform intake and the progression of chronic kidney disease.","authors":"Yanjun Zhang, Ziliang Ye, Yuanyuan Zhang, Sisi Yang, Xiaoqin Gan, Yu Huang, Hao Xiang, Yiting Wu, Yiwei Zhang, Xianhui Qin","doi":"10.1093/ndt/gfaf052","DOIUrl":"https://doi.org/10.1093/ndt/gfaf052","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>It is unclear whether dietary vitamin E and tocopherol isoform intake is associated with health outcomes in patients with chronic kidney disease (CKD). We hypothesize that different dietary tocopherol isoforms have different health effects in people with CKD. Therefore, we aimed to investigate the association between dietary vitamin E and tocopherol isoforms and risks of CKD progression and all-cause mortality in patients with CKD.</p><p><strong>Methods: </strong>In this prospective cohort study, 3 791 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) were included. The main exposures included dietary vitamin E and tocopherol isoforms, which were estimated by the validated Diet History Questionnaire at baseline, year 2, and year 4 before the study outcome was diagnosed. The primary outcome was CKD progression, defined as a 50% decline in the estimated glomerular filtration rate from baseline or initiation of kidney replacement therapy. The secondary outcome was all-cause mortality.</p><p><strong>Results: </strong>During a median follow-up of 5.5 years, 1 188 (31.3%) CKD progression events occurred. There was an L-shaped relationship between total vitamin E intake and risks of CKD progression and all-cause mortality. Regarding dietary tocopherol isoforms, there was an L-shaped relationship of dietary beta-tocopherol with risks of CKD progression and all-cause mortality, a reversed J-shaped relationship between dietary gamma-tocopherol and the risk of CKD progression and a U-shaped association between dietary delta-tocopherol and the risk of CKD progression. There was no significant association between dietary alpha-tocopherol and risks of CKD progression and all-cause mortality.</p><p><strong>Conclusions: </strong>There was an L-shaped association between total vitamin E and CKD progression in patients with CKD. Different dietary tocopherol isoforms have different relationships with CKD progression in patients with CKD, which included an L-shaped association for beta-tocopherol, a reversed J-shaped association for gamma-tocopherol, a U-shaped association for delta-tocopherol and a non-significant association for alpha-tocopherol.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575873","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":"SGLT2 Inhibitors in CKD: Are They Really Effective in All Patients?","authors":"Paola Romagnani","doi":"10.1093/ndt/gfaf051","DOIUrl":"https://doi.org/10.1093/ndt/gfaf051","url":null,"abstract":"<p><p>Sodium-glucose cotransporter-2 (SGLT2) inhibitors effectively slow chronic kidney disease (CKD) progression and reduce cardiovascular events. However, their efficacy across all CKD subgroups remains uncertain. Major clinical trials primarily included overweight or obese patients with advanced CKD, where sodium retention, volume expansion, and glomerular hyperfiltration are key disease drivers. In contrast, many underrepresented CKD subgroups, such as Alport syndrome or most immune-mediated glomerular disorders often affect lean individuals whose CKD progression is not linked to these mechanisms. Emerging evidence suggests that the renal benefits of SGLT2 inhibitors may depend on body mass index (BMI), with greater effects observed in patients with higher BMI, while those with BMI < 25 may show minimal/no benefit. This raises concerns about their applicability in lean, non-diabetic CKD patients, whose disease progression may involve alternative pathways, such as inflammation, autoimmunity, or genetic abnormalities. Animal studies further suggest that SGLT2 inhibitors provide limited renal protection in certain genetic and immune-mediated kidney diseases. Additionally, molecular data indicate that SGLT2 expression is predominantly restricted to the proximal tubule, implying a limited role in CKD driven by non-hyperfiltration mechanisms. While SGLT2 inhibitors have revolutionized CKD treatment in diabetes, obesity, and heart failure, their role in lean, non-diabetic patients remains unclear. Dedicated clinical trials are needed to assess their efficacy in underrepresented CKD subgroups and ensure evidence-based, personalized treatment strategies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575912","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}