Scandinavian Journal of Clinical & Laboratory Investigation最新文献

{"title":"Extending the Lund-Malmö creatinine-based GFR equation to cystatin C - validation results from the European Kidney Function Consortium (EKFC) cohort of children and adults.","authors":"Jonas Björk, Ulf Nyman, Ulla Berg, Arend Bökenkamp, Etienne Cavalier, Natalie Ebert, Björn O Eriksen, Laurence Derain Dubourg, Karolien Goffin, Anders Grubb, Magnus Hansson, Anders Larsson, Sandrine Lemoine, Karin Littmann, Christophe Mariat, Toralf Melsom, Elke Schaeffner, Per-Ola Sundin, Kajsa Åsling-Monemi, Pierre Delanaye, Hans Pottel","doi":"10.1080/00365513.2024.2441280","DOIUrl":"10.1080/00365513.2024.2441280","url":null,"abstract":"<p><p>The aim of the present study was to extend the creatinine-based Lund-Malmö GFR equation for use with rescaled cystatin C (r-LMR_Cys) and validate it against measured GFR (mGFR) in the EKFC cystatin C cohort of children (<i>n</i> = 2,293) and adults (<i>n</i> = 7,727). Rescaling was obtained by dividing each biomarker by a Q-value, representing the population-specific median biomarker level among healthy individuals. Validation included median bias/precision/accuracy (percent estimates within ±30% of mGFR, P₃₀). Performance was compared with the EKFC-equation (EKFC_Cys), the CAPA cystatin C equation, the corresponding equations based on rescaled creatinine (r-LMR_Cr and EKFC_Cr) and the arithmetic mean of r-LMR_Cr and CAPA (r-LMR_Cr+CAPA), r-LMR_Cr and r-LMR_Cys (r-LMR_Mean), and EKFC_Cr and EKFC_Cys (EKFC_Mean). The overall P₃₀ of r-LMR_Cys in adults was 86.2% (95% CI 85.4%-86.9%), which was 6.6 percentage points (pp; 95% CI 5.8-7.4 pp) higher than for CAPA and similar to r-LMR_Cr (P₃₀ 87.4%, 95% CI 86.6%-88.1%). r-LMR_Cys and EKFC_Cys exhibited similar performance both overall and across subgroups of age, sex, GFR and BMI and in children. All three arithmetic mean equations had similar P₃₀-accuracy and generally performed better than the corresponding single-marker equations. Our results show that the Lund-Malmö GFR equation can be adapted for use with rescaled cystatin C with performance that is similar to the best-performing equations based on rescaled creatinine. The generality of the applied biomarker rescaling principle implies that the future demand for population- and biomarker-specific GFR estimating equations can be expected to decrease substantially.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"577-583"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954228","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":"FlowDiff: a simple, flow cytometry-based approach for performing a leukocyte differential count.","authors":"Konstantinos Dimopoulos, Delphine Bonneau, Jens Hannibal","doi":"10.1080/00365513.2024.2426140","DOIUrl":"10.1080/00365513.2024.2426140","url":null,"abstract":"<p><p>To overcome the challenges of a manual leukocyte differential count, we have developed FlowDiff, an 8-colour, single tube flow cytometry panel, and investigated whether it could potentially replace the manual differential in our laboratory. The instrument was set up in accordance with the EuroFlow settings, and the protocol comprised a stain-lyse no wash process, taking approximately 30 min of working time, without the addition of a toxic lysis reagent. We found a very good correlation for all leukocyte populations between FlowDiff and the Sysmex XN analyzer in 80 normal, non-flagged samples. In addition, FlowDiff showed a very good correlation with manual differential in 168 abnormal samples, as well as a high diagnostic accuracy. FlowDiff correctly identified all samples with acute leukemia (<i>N</i> = 13) and differentiated all B-lymphomas (<i>N</i> = 49) in samples with lymphocytosis. Moreover, FlowDiff detected an additional five samples with B-lymphocytosis without any prior hematological malignancy, which turned out to be a B-lymphoma. Our data suggest that FlowDiff, our 8-colour flow cytometry-based differential, is comparable to, and can successfully substitute the manual differential.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"493-501"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644715","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":"Sentinel testing, analytical sigma metrics and a risk management approach as part of a simplified method verification/validation process.","authors":"Claudio Ilardo, Chèhine Lamarti, Batricia Al Muhanna, Michel Bastelica, Nathalie Benaily","doi":"10.1080/00365513.2024.2442512","DOIUrl":"10.1080/00365513.2024.2442512","url":null,"abstract":"<p><strong>Introduction: </strong>Verification and validation of analytical methods are crucial aspects of quality assurance in a laboratory. This study aimed to develop a risk analysis and assessment tool to streamline the process of identifying so-called 'sentinel' tests.</p><p><strong>Materials and methods: </strong>The Roche Cobas 8000 systems were evaluated to analyze 83 serum analytes, including routine chemistry, immunoassays, and therapeutic drugs. A failure mode and effects analysis were conducted to produce an analytic risk rating. This was achieved by multiplying the scores for Sigma metrics, the score for potential damage extent, and the score for environmental factors. Each test was assigned a typical risk priority number (RPN). Tests with an RPN of ≤9 were rated as low risk and ranked as 'B'. Tests with an RPN of >10 were considered high risk and graded as 'A'.</p><p><strong>Results: </strong>Regarding the Cobas C701/ISE, 17 of 54 methods were rated as 'A' and subject to a systematic method review process. A total of 37 methods were assigned a rank of 'B' and hence were eligible for a selective verification process. Concerning the Cobas E801, 10 out of 29 methods were classified as 'A' and, therefore, require a systematic verification process. A further nineteen methods were assigned a rank of 'B' and hence eligible for a select verification.</p><p><strong>Conclusions: </strong>This study demonstrated the high effectiveness of the risk analysis and assessment model developed to identify sentinel tests in the lean management of the verification/validation process.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"569-576"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855302","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":"A retrospective study on biotinidase deficiency: analysis of the Eastern Anatolia region patient cohort.","authors":"Oğuzhan Yaralı, Sezai Arslan, Özge Beyza Gündoğdu Öğütlü, Mustafa Can Guler, Büşra Nur Akgül","doi":"10.1080/00365513.2024.2420320","DOIUrl":"10.1080/00365513.2024.2420320","url":null,"abstract":"<p><p>ABTRACTThis study retrospectively reviews individuals diagnosed with biotinidase deficiency in Eastern Anatolia to analyze the genetic variants and their relationship with biotinidase activity levels. The research focuses on determining the percentage impact of different variants on enzyme activity. The study included 357 patients who presented to Erzurum City Hospital with symptoms of biotinidase deficiency between 2018 and 2023 and were referred to the medical genetics department. Biotinidase enzyme levels were determined using spectrophotometric and colorimetric techniques, while Sanger sequencing analyzed the four exons and intron boundaries of the BTD gene. In the analysis of 357 patients (181 boys, 176 girls), the most frequent variant was c.1270G > C | p.Asp424His. Biotinidase enzyme activity was above 30% in 97.3% of patients with a homozygous p.D424His mutation. The mutations that caused the most significant decrease in enzyme activity were c.410G > A p.Arg137His, c.38_delinsTCC p.Cys13phefs*36, and c.1535C > T p.Thr512Met. Hearing loss (4 patients) and optic atrophy (1 patient) were mainly observed in patients with the c.38_delinsTCC mutation (homozygous or heterozygous). Most patients were asymptomatic, and mild symptoms were effectively prevented with biotin treatment. This study provides a detailed analysis of genetic diversity and clinical presentation in biotinidase deficiency cases in Eastern Anatolia, demonstrating the efficacy of biotin treatment. It highlights the significant role of genetic variants in phenotypic diversity and the need for personalized treatment, calling for further genetic research to enhance understanding of variant diversity and its impact on enzyme activity.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"470-476"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507041","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":"Significance of myeloperoxidase, pentraxin-3 and soluble urokinase plasminogen activator receptor determination in patients with moderate carotid artery stenosis.","authors":"Ana Ruzanovic, Marija Saric-Matutinovic, Neda Milinkovic, Snezana Jovicic, Andreja Dimic, David Matejevic, Ognjen Kostic, Igor Koncar, Svetlana Ignjatovic","doi":"10.1080/00365513.2024.2422404","DOIUrl":"10.1080/00365513.2024.2422404","url":null,"abstract":"<p><p>We investigated serum concentrations of specific inflammatory parameters in patients with significant carotid artery stenosis (CAS) of 50-99%, with an additional focus on patients with moderate stenosis (50-69%), in terms of both symptomatic status and plaque morphology, to determine whether there are certain parameters that can be associated with plaque instability before the progression of CAS to a high degree. The study included 119 CAS patients, 29 of whom had moderate stenosis, and 46 controls. Ultrasonography of the carotid arteries was performed using color flow Doppler and B-mode duplex ultrasound, and serum inflammatory parameters were measured using commercially available enzyme immunoassays. When comparing patients with 50-99% stenosis, only serum amyloid A (SAA) was higher in symptomatic patients, while in the group of patients with 50-69% stenosis, myeloperoxidase (MPO) was higher and pentraxin-3 (PTX-3) was lower in symptomatic compared to asymptomatic patients, and soluble urokinase plasminogen activator receptor (suPAR) was higher in patients with carotid plaque of unstable compared to stable morphology. Our results suggest that the importance of different inflammatory parameters in patients with moderate CAS is not the same as in CAS patients in general, and therefore their separate investigation in patients with high and moderate stenosis may be beneficial. SAA has the potential to be further considered in research to predict CAS symptom risk. There is a possibility that MPO and PTX-3 play a role in the development of CAS symptoms originating from less stenotic plaques and that suPAR is involved in the destabilisation of such plaques.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"486-492"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the clinical, biochemical, and molecular spectrum of Cobalamin C (CblC) defect in 33 patients from Pakistan.","authors":"Sibtain Ahmed, Ling Cai, Fizza Akbar, Ayra Siddiqui, Ralph J DeBerardinis, Min Ni, Hieu Vu, Bushra Afroze","doi":"10.1080/00365513.2024.2394983","DOIUrl":"10.1080/00365513.2024.2394983","url":null,"abstract":"<p><strong>Background: </strong>Cobalamin C is the most common inborn error of intracellular cobalamin metabolism caused by biallelic pathogenic variants in the MMACHC gene, leading to impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Biochemical hallmarks are elevated plasma total homocysteine (HCYs) and low methionine accompanied by methylmalonic aciduria. This study aimed to evaluate the clinical, biochemical, and molecular analysis of Pakistani patients with CblC defect.</p><p><strong>Methods: </strong>Medical charts, urine organic acid (UOA) chromatograms, plasma amino acid levels, plasma tHcy and <i>MMACHC</i> gene results of patients presenting at the Biochemical Genetics Clinic, AKUH from 2013-2021 were reviewed. Details were collected on a pre-structured questionnaire. SPSS 22 was used for data analysis.</p><p><strong>Results: </strong>CblC was found in 33 cases (Male:Female 19:14). The median age of symptoms onset and diagnosis were 300 (IQR:135-1800) and 1380 (IQR: 240-2730) days. The most common clinical features were cognitive impairment (<i>n</i> = 29), seizures (<i>n</i> = 23), motor developmental delay (<i>n</i> = 20), hypotonia (<i>n</i> = 17), and sparse/hypopigmented scalp hair (<i>n</i> = 16). The <i>MMACHC</i> gene sequencing revealed homozygous pathogenic variant c.394C > T, (p.Arg132*) in 32 patients, whereas c.609G > A, (p.TRP203*) in one patient whose ancestors had settled in Pakistan from China decades ago. The median age of treatment initiation was 1530 (IQR: 240-2790). The median pre-treatment HCYs levels were 134 (IQR:87.2-155.5) compared to post-treatment levels of 33.3 (IQR: 27.3-44.95) umol/L.</p><p><strong>Conclusions: </strong>Thirty-three cases of CblC defect from a single center underscores a significant number of the disorder within Pakistan. Late diagnosis emphasizes the need for increased clinical awareness and adequate diagnostic facilities.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"391-397"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120494","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":"Establishment of tumor marker reference intervals for different age and gender groups in the healthy population of South China.","authors":"Yue Meng, Xinwei Li, Huixian Li, Bing Gu","doi":"10.1080/00365513.2024.2400653","DOIUrl":"10.1080/00365513.2024.2400653","url":null,"abstract":"<p><p>To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (<i>p</i> < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"398-404"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294389","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":"Red blood cell in preeclampsia: attenuated nitric oxide generation and enhanced reactive oxygen species formation and eryptosis.","authors":"Tülay Turan Butun, Nur Özen, Nihal Ozturk, Ahmet Yildirim, Ece Kilavuz, Ceyda Karadag, Burcu Aykan Yuksel, Filiz Basrali, Burak Karadag, Pinar Ulker","doi":"10.1080/00365513.2024.2394982","DOIUrl":"10.1080/00365513.2024.2394982","url":null,"abstract":"<p><p>Preeclampsia (PE) pathogenesis is strongly related to diminished nitric oxide (NO) bioavailability and enhanced oxidative stress. Emerging evidence suggests that red blood cells (RBCs) eNOS enzyme contributes to systemic NO bioavailability by its ability of both NO and ROS generation. We aimed to investigate RBC eNOS enzyme activity, NO and ROS generation capacity, eryptosis index and aggregation levels in preeclamptic and uncomplicated pregnant women. Fifty-eight PE patients and 36 healthy pregnant women were included to the investigation. RBC eNOS enzyme activity, intracellular NO, calcium and ROS concentrations and eryptosis levels were determined <i>via</i> flow cytometric methods. RBC deformability and aggregation were measured <i>via</i> LORRCA. Intracellular NO and phosphorylated RBC eNOS levels decreased in PE group compared to healthy pregnant group (<i>p</i> < 0.05, <i>p</i> < 0.001 respectively). Intracellular ROS and calcium levels, eryptosis values and aggregation indexes in the PE group were significantly higher than healthy pregnant group (<i>p</i> < 0.05, <i>p</i> < 0.01, <i>p</i> < 0.05, <i>p</i> < 0.05 respectively). Our results demonstrate for the first time that RBC produce lower NO and higher ROS under PE conditions. Further, RBC of PE patients were more prone to eryptosis and aggregation compared to control group. Our results suggest that, in addition to endothelial cells, RBC also contribute to decreased plasma NO bioavailability <i>via</i> producing less NO and high ROS in PE. Considering increased tendency to eryptosis and aggregation, RBC seem to play role in haemodynamic changes of PE pathogenesis.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"379-390"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353018","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":"Correction.","authors":"","doi":"10.1080/00365513.2024.2403191","DOIUrl":"10.1080/00365513.2024.2403191","url":null,"abstract":"","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"428"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294388","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":"Diagnosis of lactose intolerance: concordance between 13910-C/T genotype and lactose tolerance test in a Danish population.","authors":"Sumaya Durrani Khan, Henrik L Jørgensen, Nikki H Mitchell","doi":"10.1080/00365513.2024.2417273","DOIUrl":"10.1080/00365513.2024.2417273","url":null,"abstract":"<p><p>The association between the MCM6-13910-C/T polymorphism and lactose intolerance in individuals of European descent is well known. However, the notion that having a single versus a double allelic mutation might influence one's phenotype has been hypothesized. This study investigated whether patients with the three genotypes C/C, C/T, T/T differed in response to a lactose tolerance test (LTT) in a Danish setting. Anonymized data on 603 individuals with results for both genetic test and LTT were investigated. Mean delta glucose values were plotted for the time points of the LTT (0, 15, 30, 45 and 60 min) for the C/C, C/T and T/T genotype, respectively. Further, the agreement between the three genotypes and the diagnostic interpretation of the LTT were examined using a cut-off of > 1.4 mmol/L rise in glucose. In subjects with the C/C genotype, mean glucose delta levels were markedly lower compared to both the C/T and T/T genotypes at all time points. Overall, a difference between mean glucose delta values among the C/T and T/T genotype could not be shown. Using a LTT cut-off of > 1.4 mmol/L, the proportions of lactose intolerant LTT results for each genotype were as follows: 58% among C/C, 5% among C/T, and 7% among T/T. In a Danish healthcare setting, the C/C genotype was on average associated with a smaller glucose response during a LTT when compared to the C/T and T/T genotypes. A marked difference in the LTT response among the C/T and T/T genotype was not observed.</p>","PeriodicalId":21474,"journal":{"name":"Scandinavian Journal of Clinical & Laboratory Investigation","volume":" ","pages":"416-420"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473786","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}