Clinica Chimica Acta最新文献

{"title":"Targeted exonic sequencing identifies novel variants in a cerebral small vessel disease cohort.","authors":"Paul J Dunn, Neven Maksemous, Robert A Smith, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths","doi":"10.1016/j.cca.2024.120120","DOIUrl":"10.1016/j.cca.2024.120120","url":null,"abstract":"<p><strong>Background and aims: </strong>Cerebral small vessel diseases (CSVDs) are a set of conditions that affect the small blood vessels in the brain and can cause severe neurological pathologies such as stroke and vascular dementia. The most common monogenic CSVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which is caused by mutations in NOTCH3. However, only 15-20% of CADASIL cases referred for genetic testing have pathogenic mutations in NOTCH3. We hypothesise that other monogenic causes of CSVD may be causing a CADASIL-like CSVD phenotype.</p><p><strong>Methods: </strong>To test this, we performed whole exome sequencing for 50 individuals suspected of having CADASIL, but did not exhibit a disease-causing mutation in NOTCH3, and applied targeted analysis of all monogenic forms of CSVD.</p><p><strong>Results: </strong>This analysis identified three mutations affecting the Collagen type IV genes in three individuals likely to be causative of CSVD.</p><p><strong>Conclusions: </strong>This suggests that screening for all monogenic forms of CSVD when one monogenic form is clinically suspected may improve diagnosis in clinically suspected monogenic CSVD. However, despite these findings, the majority of NOTCH3 negative CSVD cases did not have candidate mutations in known CSVD genes, suggesting that additional genetic factors contributing to the disease are yet to be identified.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120120"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosensing for rapid detection of MDR, XDR and PDR bacteria.","authors":"Samad Rastmanesh, Ilghar Zeinaly, Vahid Alivirdiloo, Ahmad Mobed, Mohammad Darvishi","doi":"10.1016/j.cca.2024.120121","DOIUrl":"10.1016/j.cca.2024.120121","url":null,"abstract":"<p><p>The emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria poses a significant threat to global public health, complicating the management of infectious diseases and increasing morbidity and mortality rates. Rapid and sensitive detection of these resistant pathogens is crucial for effective treatment and infection control. This manuscript provides a comprehensive overview of various biosensor technologies developed for the rapid identification and quantification of MDR and XDR bacteria. We discuss the principles of operation, sensitivity, specificity, and practical applications of different biosensing platforms, including electrochemical, optical, and piezoelectric sensors. Additionally, we explore recent advancements in nanomaterials and microfluidics that enhance biosensor performance and enable point-of-care testing. The manuscript also addresses the challenges faced in the implementation of these technologies in clinical settings, such as regulatory hurdles and the need for standardization. A systematic literature review was conducted to identify relevant studies. Databases utilized include PubMed and Scopus, covering the time frame from 2015 to 2024. The literature screening criteria focused on the inclusion of only clinically validated studies to ensure the reliability and applicability of the findings. By highlighting the potential of biosensors to revolutionize the detection of drug-resistant bacteria, this work aims to inform researchers, clinicians, and policymakers about the critical role of innovative diagnostic tools in combating antibiotic resistance and improving patient outcomes.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120121"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological characteristics of patients with low titer anti-phospholipase A2 receptor antibodies verified by indirect immunofluorescence assay.","authors":"Hao-Yuan Cui, Chao Li, Yu-Bing Wen, Wei Ye, Wen-Ling Ye, Hang Li, Li-Meng Chen","doi":"10.1016/j.cca.2024.120070","DOIUrl":"10.1016/j.cca.2024.120070","url":null,"abstract":"<p><strong>Objective: </strong>Laboratory extensively applied enzyme-linked immunosorbent assay (ELISA) to measure anti-phospholipase A2 receptor antibodies (PLA2R-abs) since its diagnostic significance on PLA2R related primary membranous nephropathy (PLA2R-related pMN) was discovered. However, PLA2R-abs determined by ELISA (PLA2R-ELISA) could infrequently yield inconclusive results, specifically a grey-zone defined as PLA2R-abs ranging from 2 to 20 RU/mL. Recently, researchers suggested that double-check grey-zone PLA2R-abs by indirect immunofluorescence (IIF) could improve diagnostic accuracy. We evaluated the diagnostic performance of PLA2R-IIF in assessing PLA2R-related pMN and summarized clinicopathological characteristics of grey-zone population to provide more evidence for clinical practice.</p><p><strong>Methods: </strong>Data on demographics, serology and pathology of patients with PLA2R-ELISA grey-zone results and a native kidney biopsy at Peking Union Medical College Hospital from September 2020 to April 2023 were reviewed. Grey-zone samples were analyzed using PLA2R-IIF. Negative results were defined as no fluorescence and positive results were graded according to fluorescence intensity.</p><p><strong>Results: </strong>This study included a total of 52 grey-zone patients divided into pMN group (n = 36, 69 %) and non-pMN group (n = 16, 31 %) according to renal pathology reports. The pMN patients had higher PLA2R-abs and lower serum creatinine compared to the non-pMN patients (P = 0.003, P < 0.001). No statistically significant differences were observed in 24-hour urine protein and albumin between the two groups. Multiple pathological types were identified in the non-pMN group. The sensitivity and specificity of PLA2R-IIF in PLA2R-ELISA grey-zone population were 72 % and 88 %, respectively, with a total consistent rate of 77 % and a positive predictive value of 93 %.</p><p><strong>Conclusion: </strong>Both pMN and non-pMN patients presented grey-zone PLA2R-ELISA results. It was necessary to perform PLA2R-IIF to assist in the diagnosis of patients with PLA2R-ELISA grey-zone results.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120070"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometric detection of neutrophil elastase cleaved corticosteroid binding globulin and its association with Asn347 site glycosylation, in septic shock patients.","authors":"Jessica H Lee, Zeynep Sumer-Bayraktar, Parul Mittal, Leigh Donnellan, Clifford Young, R Louise Rushworth, John G Lewis, Marni Nenke, Wayne Rankin, Manuela Klingler-Hoffman, Peter Hoffmann, Morten Thaysen-Andersen, David J Torpy, Emily J Meyer","doi":"10.1016/j.cca.2024.120108","DOIUrl":"10.1016/j.cca.2024.120108","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroid-binding globulin (CBG) modulates tissue cortisol availability via modification of cortisol:CBG binding affinity in response to multiple factors, including neutrophil elastase (NE) cleavage of the reactive centre loop (RCL), converting high affinity CBG (haCBG) to low affinity CBG (laCBG). In vitro, glycosylation of the RCL at Asn347 affects NE cleavage susceptibility. To date, no direct measurement of laCBG, which would verify NE cleavage, has been reported.</p><p><strong>Objective: </strong>To measure serum laCBG in septic shock patients by mass spectrometry to confirm NE cleavage in vivo, with Asn347 site glycosylation profiling to determine its impact on NE cleavage, and determine effect of %laCBG on septic shock clinical outcome.</p><p><strong>Methods: </strong>Serum from septic shock patients from a tertiary hospital intensive care unit was analysed by mass spectrometry for CBG affinity forms and Asn347 glycosylation profile, following CBG immunoprecipitation. Data was correlated with septic shock clinical outcome.</p><p><strong>Results: </strong>N-terminal peptide of NE cleaved RCL (AVLQLNEEGVDTAGSTGV) was consistently detected in patient serum, although at low concentrations. Mean %laCBG/total CBG was 0.23 % in septic shock (range = 0.07-0.74 %, SD = 0.12 %); in comparison healthy controls mean %laCBG was 0.04 % (range 0.02-0.08 %, SD = 0.03 %). There was a negative correlation between %laCBG and serum concentrations of CBG with triantennary Asn347 glycans; TS3 (r = -0.190, p = 0.040) and TS3F (r = -0.252, p = 0.006).</p><p><strong>Conclusions: </strong>NE cleaved CBG (laCBG) is present in septic shock patient serum, and %laCBG correlates with Asn347 glycosylation occupancy and composition. However, serum %laCBG did not correlate with septic shock clinical outcome.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120108"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical detection of cervical cancer biomarkers.","authors":"Tummala Anusha, Pradeep Kumar Brahman, Bondili Sesharamsingh, Allu Lakshmi, K Sai Bhavani","doi":"10.1016/j.cca.2024.120103","DOIUrl":"10.1016/j.cca.2024.120103","url":null,"abstract":"<p><p>Cervical cancer (CC) is the fourth most common cancer among women worldwide, following breast, colorectal, and lung cancers. Each year, it accounts for approximately 600,000 new cases and 340,000 deaths. Early-stage cervical cancer is treatable with surgery and chemoradiotherapy (CCRT). However, treatment for metastatic cervical cancer is limited, with bevacizumab combined with chemotherapy being one of the few options, though survival rates remain low. Currently, the diagnosis of cervical cancer primarily relies on Pap smears and colposcopy. Although these methods are essential for detection, they are costly, labor-intensive, and require significant resources. Therefore, there is an urgent need to identify effective biomarkers that can detect cervical cancer at an early stage, improving both the accuracy of diagnosis and the efficacy of treatment. Although numerous cervical cancer biomarkers have been identified for the cervical cancer thanks to advances in technology. In recent times, electrochemical methods have proven to be particularly effective in cervical cancer detection. In this paper, we reviewed the important cervical cancer biomarkers and their detection through electrochemical biosensors, which offer advantages such as higher sensitivity, affordability, and ease of analysis. Furthermore, we discussed the limitations and future prospects of electrochemical biosensors in this field.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"567 ","pages":"120103"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Need to consider exact trough time: Comment on \"Daily dosing frequency as a determinant of clozapine concentration-to-dose ratio: Data from a therapeutic drug monitoring service (2019-2022)\".","authors":"Yuki Kikuchi","doi":"10.1016/j.cca.2024.120119","DOIUrl":"10.1016/j.cca.2024.120119","url":null,"abstract":"","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120119"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of current patient-based real-time quality control in clinical chemistry testing.","authors":"Ergin Çam, Deniz I Topcu, Alev Kural","doi":"10.1016/j.cca.2024.120115","DOIUrl":"10.1016/j.cca.2024.120115","url":null,"abstract":"<p><strong>Introduction: </strong>To perform simulation studies on patient-based real-time quality control (PBRTQC) for aspartate aminotransferase (AST), iron (Fe), potassium (K), and thyrotropin (thyroid stimulating hormone, TSH) analytes, focusing on optimizing systematic error detection while minimizing data loss.</p><p><strong>Methods: </strong>Clinical laboratory data for the four analytes were analyzed using various truncation methods. Among these methods, truncation limits corresponding to fixed percentiles (e.g., 1st-99th percentiles), reference change value based on between-individual biological variation (RCVg), and truncation limits derived from ± 3 standard deviations from the mean were included. These exclusion methods were applied using trimming or winsorization techniques, and transformation methods (logarithmic, square root, and Yeo-Johnson transformations) were employed to fit the data to a normal or near-normal distribution. Moving average techniques, such as exponentially weighted moving average (EWMA), were used with various block sizes to evaluate systematic error detection performance.</p><p><strong>Results: </strong>Truncation based on RCVg improved performance for analytes with lower individuality indices-AST, potassium, and TSH-by enabling faster error detection. In contrast, methods either without truncation or with winsorization applied proved to be more effective for Fe. Among the moving average methods, EWMA with smaller block sizes (20 and 30) generally showed superior performance by detecting systematic errors more quickly.</p><p><strong>Conclusion: </strong>RCVg-based truncation improves error detection for analytes with low individuality when combined with PBRTQC methods like EWMA, minimizing data loss. Tailored strategies considering analyte-specific individuality and distribution are essential for optimal error monitoring, warranting further validation in diverse clinical settings.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120115"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of transient elevation of creatinine caused by severe hyperuricemia.","authors":"Qiong Wu, Yumeng Gao, Xinyuan Zhang, Wenbo Cui, Shumin Li, Chunyu Luo, Dianjun Mo, Xinqi Cheng","doi":"10.1016/j.cca.2024.120110","DOIUrl":"10.1016/j.cca.2024.120110","url":null,"abstract":"<p><strong>Background: </strong>To explore the underlying causes of significant fluctuations in creatinine levels within three days due to transient and severe uric acid elevation, and to provide evidence for the interpretation of abnormal test results and clinical diagnosis and management.</p><p><strong>Methods: </strong>The issues were resolved by retesting the samples, comparing results across different detection platforms, and analyzing the reaction curve. We comprehensively reviewed patients' general conditions, imaging examinations, and treatments. Additionally, we compared pre- and post-admission changes in laboratory indices and performed an extensive literature search for comprehensive analysis.</p><p><strong>Results: </strong>At the patient's first visit, the levels of uric acid (UA), creatinine (CR), and urea (UREA) were measured at 891 umol/L, 211 umol/L, and 7.8 mmol/L, respectively using a Roche full-automatic biochemical analyzer and its corresponding reagents. Subsequent testing yielded 917 umol/L, 211 umol/L, and 8.3 mmol/L for UA, CR, and UREA. After retesting with the Beckman automatic biochemical analyzer and its corresponding reagents, the results for UA, CR, and UREA were 1013 umol/L, 221 umol/L, and 7.75 mmol/L, respectively. The results of the two detection systems were in agreement. A supplementary measurement of Cystatin C (CYSC) at 1.69 mg/L indicates renal dysfunction, consistent with the observed increase in CR levels and ruling out false elevation due to assay-related issues. At 48 h post-admission, untreated, the levels of blood UA, CR, and UREA decreased to 567umol/L, 77umol/L, and 5.1 mmol/L, respectively. Through literature review and analysis, it was determined that the transient abnormal increase in the patient's creatinine level may be attributed to a substantial accumulation of uric acid crystals obstructing the renal tubules, leading to an impediment in renal tubular excretion which subsequently resolves spontaneously.</p><p><strong>Conclusion: </strong>Severe hyperuricemia may result in a transient increase in blood CR levels and could potentially lead to the development of acute uric acid nephropathy. When a clinical laboratory encounters test results inconsistent with the clinical manifestations, it is essential to not only address any potential detection issues but also proactively investigate the underlying reasons for abnormal test results through comprehensive literature reviews and other rigorous methodologies.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120110"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid hormone concentrations in dried blood spots: A comparison between capillary and venous blood samples.","authors":"Anouk Olthof, Vera H de Kleijne, Anita Boelen, Annemieke C Heijboer","doi":"10.1016/j.cca.2024.120099","DOIUrl":"10.1016/j.cca.2024.120099","url":null,"abstract":"<p><strong>Background: </strong>An important aspect of the shift towards dried blood spots (DBS) as a sample matrix for laboratory measurements, is the availability of robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that can reliably quantify analyte concentrations in DBS. The development and validation of these LC-MS/MS methods, however, concerns an extensive process, for which large amounts of DBS samples are required. DBS are usually obtained from capillary blood samples, but they can also be prepared from venous (residual) blood samples, which are widely available in clinical laboratories. Therefore, we aimed to determine whether DBS prepared from (residual) venous blood samples, collected in EDTA blood tubes, can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones in DBS.</p><p><strong>Methods: </strong>Capillary DBS and venous blood samples (EDTA tube and tube without additives) were collected from twenty healthy volunteers (12F/8M). From both venous blood samples, DBS were prepared volumetrically. Samples were analyzed using in-house developed LC-MS/MS methods for testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), cortisol, cortisone, corticosterone, and for dehydroepiandrosterone sulfate (DHEA-S).</p><p><strong>Results: </strong>DBS made from venous blood collected in EDTA tubes compared with capillary blood showed a correlation coefficient of ≥ 0.89 for all steroid hormones except corticosterone (0.67). DBS made from venous blood collected in tubes without additives showed a strong correlation with both DBS made from venous blood collected in EDTA tubes (≥0.97 for all steroid hormones) and capillary DBS (>0.90) except corticosterone (0.64).</p><p><strong>Conclusion: </strong>DBS prepared from (residual) venous blood collected in EDTA blood tubes can be used for future development and validation of LC-MS/MS methods to quantify steroid hormones, except for corticosterone, in capillary DBS.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120099"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR integrated biosensors: A new paradigm for cancer detection","authors":"Arzoo Saini ,&nbsp;Neeraj Dilbaghi ,&nbsp;Neelam Yadav","doi":"10.1016/j.cca.2025.120179","DOIUrl":"10.1016/j.cca.2025.120179","url":null,"abstract":"<div><div>Cancer remains one of the leading causes of morbidity and mortality globally, necessitating need for advancements of technologies for early therapeutics. Conventional detection methodologies often lag behind in terms of sensitivity, specificity, and cost-effectiveness, leading to delayed diagnosis and inadequate treatment. The need of advanced diagnostic techniques has considerably increased and led to the development of biosensors. Biosensing technologies offer several advantages over conventional methods hence, overcome limitations and improve diagnostic accuracy. Biosensors, particularly CRISPR-Cas based biosensors have emerged as a revolutionary technology for oncology diagnostics due to their high precision and adaptability. CRISPR-based biosensors provide remarkable precision, sensitivity, multiplexing capabilities, specificity, and rapidness for developing a cost-effective and portable point of care diagnostic device for cancer detection. In this review, we have discussed cancer pathogenicity, assessed the traditional detection techniques, and explored the advancements and advantages of biosensors, particularly CRISPR-based biosensors, in the detection of some major cancer types, namely lung, liver, colorectal, prostate, and cervical cancers. CRISPR-based biosensors represent a significant potential in cancer diagnostics, offering precise, cost-effective, and rapid detection of cancer biomarkers. The integration of CRISPR technology with biosensors holds substantial promise for enhancing early detection and improving patient outcomes in cancer diagnostics.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"569 ","pages":"Article 120179"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}