{"title":"The significance of antigen-antibody-binding avidity in clinical diagnosis.","authors":"Yaxin Li, He S Yang, P J Klasse, Zhen Zhao","doi":"10.1080/10408363.2024.2379286","DOIUrl":"https://doi.org/10.1080/10408363.2024.2379286","url":null,"abstract":"<p><p>Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-15"},"PeriodicalIF":6.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747618","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":"Transthyretin mutagenesis: impact on amyloidogenesis and disease.","authors":"Zaida L Almeida, Daniela C Vaz, Rui M M Brito","doi":"10.1080/10408363.2024.2350379","DOIUrl":"https://doi.org/10.1080/10408363.2024.2350379","url":null,"abstract":"<p><p>Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. \"Hot spot\" mutation regions are mainly assigned to β-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various <i>in vitro</i> TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-25"},"PeriodicalIF":10.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287861","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":"Circulating tumor DNA (ctDNA): can it be used as a pan-cancer early detection test?","authors":"Michael J Duffy, John Crown","doi":"10.1080/10408363.2023.2275150","DOIUrl":"10.1080/10408363.2023.2275150","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting possibilities is as a relatively noninvasive pan-cancer screening test. Preliminary findings with ctDNA tests such as Galleri or CancerSEEK suggest that they have high specificity (> 99.0%) for malignancy. Their sensitivity varies depending on the type of cancer and stage of disease but it is generally low in patients with stage I disease. A major advantage of ctDNA over existing screening strategies is the potential ability to detect multiple cancer types in a single test. A limitation of most studies published to-date is that they are predominantly case-control investigations that were carried out in patients with a previous diagnosis of malignancy and that used apparently healthy subjects as controls. Consequently, the reported sensitivities, specificities and positive predictive values might be lower if the tests are used for screening in asymptomatic populations, that is, in the population where these tests are likely be employed. To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"241-253"},"PeriodicalIF":10.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479091","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":"Development of next-generation reference interval models to establish reference intervals based on medical data: current status, algorithms and future consideration.","authors":"Chaochao Ma, Zheng Yu, Ling Qiu","doi":"10.1080/10408363.2023.2291379","DOIUrl":"10.1080/10408363.2023.2291379","url":null,"abstract":"<p><p>Evidence derived from laboratory medicine plays a pivotal role in the diagnosis, treatment monitoring, and prognosis of various diseases. Reference intervals (RIs) are indispensable tools for assessing test results. The accuracy of clinical decision-making relies directly on the appropriateness of RIs. With the increase in real-world studies and advances in computational power, there has been increased interest in establishing RIs using big data. This approach has demonstrated cost-effectiveness and applicability across diverse scenarios, thereby enhancing the overall suitability of the RI to a certain extent. However, challenges persist when tests results are influenced by age and sex. Reliance on a single RI or a grouping of RIs based on age and sex can lead to erroneous interpretation of results with significant implications for clinical decision-making. To address this issue, the development of next generation of reference interval models has arisen at an historic moment. Such models establish a curve relationship to derive continuously changing reference intervals for test results across different age and sex categories. By automatically selecting appropriate RIs based on the age and sex of patients during result interpretation, this approach facilitates clinical decision-making and enhances disease diagnosis/treatment as well as health management practices. Development of next-generation reference interval models use direct or indirect sampling techniques to select reference individuals and then employed curve fitting methods such as splines, polynomial regression and others to establish continuous models. In light of these studies, several observations can be made: Firstly, to date, limited interest has been shown in developing next-generation reference interval models, with only a few models currently available. Secondly, there are a wide range of methods and algorithms for constructing such models, and their diversity may lead to confusion. Thirdly, the process of constructing next-generation reference interval models can be complex, particularly when employing indirect sampling techniques. At present, normative documents pertaining to the development of next-generation reference interval models are lacking. In summary, this review aims to provide an overview of the current state of development of next-generation reference interval models by defining them, highlighting inherent advantages, and addressing existing challenges. It also describes the process, advanced algorithms for model building, the tools required and the diagnosis and validation of models. Additionally, a discussion on the prospects of utilizing big data for developing next-generation reference interval models is presented. The ultimate objective is to equip clinical laboratories with the theoretical framework and practical tools necessary for developing and optimizing next-generation reference interval models to establish next-generation reference intervals while ","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"298-316"},"PeriodicalIF":10.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037509","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}
Joris R Delanghe, Charlotte Delrue, Reinhart Speeckaert, Marijn M Speeckaert
{"title":"Unlocking the link between haptoglobin polymorphism and noninfectious human diseases: insights and implications.","authors":"Joris R Delanghe, Charlotte Delrue, Reinhart Speeckaert, Marijn M Speeckaert","doi":"10.1080/10408363.2023.2285929","DOIUrl":"10.1080/10408363.2023.2285929","url":null,"abstract":"<p><p>Haptoglobin (Hp) is a polymorphic protein that was initially described as a hemoglobin (Hb)-binding protein. The major functions of Hp are to scavenge Hb, prevent iron loss, and prevent heme-based oxidation. Hp regulates angiogenesis, nitric oxide homeostasis, immune responses, and prostaglandin synthesis. Genetic polymorphisms in the <i>Hp</i> gene give rise to different phenotypes, including Hp 1-1, Hp 2-1, and Hp 2-2. Extensive research has been conducted to investigate the association between Hp polymorphisms and several medical conditions including cardiovascular disease, inflammatory bowel disease, cancer, transplantation, and hemoglobinopathies. Generally, the Hp 2-2 phenotype is associated with increased disease risk and poor outcomes. Over the years, the Hp 2 allele has spread under genetic pressures. Individuals with the Hp 2-2 phenotype generally exhibit lower levels of CD163 expression in macrophages. The decreased expression of CD163 may be associated with the poor antioxidant capacity in the serum of subjects carrying the Hp 2-2 phenotype. However, the Hp 1-1 phenotype may confer protection in some cases. The Hp1 allele has strong antioxidant, anti-inflammatory, and immunomodulatory properties. It is important to note that the benefits of the Hp1 allele may vary depending on genetic and environmental factors as well as the specific disease or condition under consideration. Therefore, the Hp1 allele may not necessarily confer advantages in all situations, and its effects may be context-dependent. This review highlights the current understanding of the role of Hp polymorphisms in cardiovascular disease, inflammatory bowel disease, cancer, transplantation, hemoglobinopathies, and polyuria.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"275-297"},"PeriodicalIF":10.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444203","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}
Peter H J Slootbeek, Sofie H Tolmeijer, Niven Mehra, Jack A Schalken
{"title":"Therapeutic biomarkers in metastatic castration-resistant prostate cancer: does the state matter?","authors":"Peter H J Slootbeek, Sofie H Tolmeijer, Niven Mehra, Jack A Schalken","doi":"10.1080/10408363.2023.2266482","DOIUrl":"10.1080/10408363.2023.2266482","url":null,"abstract":"<p><p>The treatment of metastatic castration-resistant prostate cancer (mCRPC) has been fundamentally transformed by our greater understanding of its complex biological mechanisms and its entrance into the era of precision oncology. A broad aim is to use the extreme heterogeneity of mCRPC by matching already approved or new targeted therapies to the correct tumor genotype. To achieve this, tumor DNA must be obtained, sequenced, and correctly interpreted, with individual aberrations explored for their druggability, taking into account the hierarchy of driving molecular pathways. Although tumor tissue sequencing is the gold standard, tumor tissue can be challenging to obtain, and a biopsy from one metastatic site or primary tumor may not provide an accurate representation of the current genetic underpinning. Sequencing of circulating tumor DNA (ctDNA) might catalyze precision oncology in mCRPC, as it enables real-time observation of genomic changes in tumors and allows for monitoring of treatment response and identification of resistance mechanisms. Moreover, ctDNA can be used to identify mutations that may not be detected in solitary metastatic lesions and can provide a more in-depth understanding of inter- and intra-tumor heterogeneity. Finally, ctDNA abundance can serve as a prognostic biomarker in patients with mCRPC.The androgen receptor (AR)-axis is a well-established therapeutical target for prostate cancer, and through ctDNA sequencing, insights have been obtained in (temporal) resistance mechanisms that develop through castration resistance. New third-generation AR-axis inhibitors are being developed to overcome some of these resistance mechanisms. The druggability of defects in the DNA damage repair machinery has impacted the treatment landscape of mCRPC in recent years. For patients with deleterious gene aberrations in genes linked to homologous recombination, particularly <i>BRCA1</i> or <i>BRCA2</i>, PARP inhibitors have shown efficacy compared to the standard of care armamentarium, but platinum-based chemotherapy may be equally effective. A hierarchy exists in genes associated with homologous recombination, where, besides the canonical genes in this pathway, not every other gene aberration predicts the same likelihood of response. Moreover, evidence is emerging on cross-resistance between therapies such as PARP inhibitors, platinum-based chemotherapy and even radioligand therapy that target this genotype. Mismatch repair-deficient patients can experience a beneficial response to immune checkpoint inhibitors. Activation of other cellular signaling pathways such as PI3K, cell cycle, and MAPK have shown limited success with monotherapy, but there is potential in co-targeting these pathways with combination therapy, either already witnessed or anticipated. This review outlines precision medicine in mCRPC, zooming in on the role of ctDNA, to identify genomic biomarkers that may be used to tailor molecularly targeted therapies. The most com","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"178-204"},"PeriodicalIF":10.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50161025","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":"Analytical performance specifications and quality assurance of point-of-care testing in primary healthcare.","authors":"Anne Stavelin, Sverre Sandberg","doi":"10.1080/10408363.2023.2262029","DOIUrl":"10.1080/10408363.2023.2262029","url":null,"abstract":"<p><p>Point-of-care testing (POCT) is the fastest-growing segment of laboratory medicine. This review focuses on the essential aspects of setting analytical performance specifications (APS) and performing quality assurance for POCT in primary healthcare. In-vitro diagnostic medical devices for POCT are typically small and easy to operate. Users often have little to no laboratory experience and may not necessarily see the value of conducting quality assurance on their devices. Therefore, training, guidance, and motivation should be integral parts of the total quality management system, as they are vital for managing errors and ensuring reliable results. It is common to believe that the analytical quality of POCT should be comparable to that of laboratory testing, and as a result, APS should be the same. This paper challenges this concept. The APS for POCT can often be less stringent compared to those used in a central laboratory because the requester is closer to both the analytical and clinical situation. Point-of-care instruments should be selected based on clinical needs, the required analytical quality and user-friendliness in the intended usage setting.Quality assurance should include both internal quality control (IQC) and external quality assessment (EQA). It is recommended that IQC protocols should be dependent on the complexity of the POCT device. A scoring system to determine how frequent IQC should be analyzed in primary healthcare on different types of POCT devices has been suggested. The main challenge in EQA for POCT involves using suitable control materials that reflect instrument performance on patient samples. Obtaining commutable control materials for POCT is difficult since the matrix often is whole blood. An essential aspect of EQA for POCT is that feedback reports should be easily interpretable. Users should receive advice from the EQA organizer regarding the root causes of deviating results. Quality assurance for POCT is not an easy task and presents numerous challenges. However, there is evidence that quality assurance improves the quality of POCT measurements and, consequently, can enhance patient outcomes.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"164-177"},"PeriodicalIF":10.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106484","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}
Mohammad Samare-Najaf, Seyed Ali Razavinasab, Ali Samareh, Navid Jamali
{"title":"Omics-based novel strategies in the diagnosis of endometriosis.","authors":"Mohammad Samare-Najaf, Seyed Ali Razavinasab, Ali Samareh, Navid Jamali","doi":"10.1080/10408363.2023.2270736","DOIUrl":"10.1080/10408363.2023.2270736","url":null,"abstract":"<p><p>Endometriosis, an enigmatic and chronic disorder, is considered a debilitating condition despite being benign. Globally, this gynecologic disorder affects up to 10% of females of reproductive age, impacting almost 190 million individuals. A variety of genetic and environmental factors are involved in endometriosis development, hence the pathophysiology and etiology of endometriosis remain unclear. The uncertainty of the etiology of the disease and its complexity along with nonspecific symptoms have led to misdiagnosis or lack of diagnosis of affected people. Biopsy and laparoscopy are referred to as the gold standard for endometriosis diagnosis. However, the invasiveness of the procedure, the unnecessary operation in disease-free women, and the dependence of the reliability of diagnosis on experience in this area are considered the most significant limitations. Therefore, continuous studies have attempted to offer a noninvasive and reliable approach. The recent advances in modern technologies have led to the generation of large-scale biological data sets, known as -omics data, resulting in the proceeding of the -omics century in biomedical sciences. Thereby, the present study critically reviews novel and noninvasive biomarkers that are based on -omics approaches from 2020 onward. The findings reveal that biomarkers identified based on genomics, epigenomics, transcriptomics, proteomics, and metabolomics are potentially able to diagnose endometriosis, predict prognosis, and stage patients, and potentially, in the near future, a multi-panel of these biomarkers will generate clinical benefits.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"205-225"},"PeriodicalIF":10.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157259","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":"Artificial intelligence in serum protein electrophoresis: history, state of the art, and perspective.","authors":"He He, Lingfeng Wang, Xia Wang, Mei Zhang","doi":"10.1080/10408363.2023.2274325","DOIUrl":"10.1080/10408363.2023.2274325","url":null,"abstract":"<p><p>Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. The test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPEP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. This review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPEP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"226-240"},"PeriodicalIF":10.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421467","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}
Anaëlle L. Dentand, Morton G. Schubert, Pierre-Alexandre Krayenbuehl
{"title":"Current iron therapy in the light of regulation, intestinal microbiome, and toxicity: are we prescribing too much iron?","authors":"Anaëlle L. Dentand, Morton G. Schubert, Pierre-Alexandre Krayenbuehl","doi":"10.1080/10408363.2024.2331477","DOIUrl":"https://doi.org/10.1080/10408363.2024.2331477","url":null,"abstract":"Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron def...","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"16 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594821","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}