Critical reviews in clinical laboratory sciences最新文献

{"title":"Progress in understanding primary glomerular disease: insights from urinary proteomics and in-depth analyses of potential biomarkers based on bioinformatics.","authors":"Lili Ge,&nbsp;Jianhua Liu,&nbsp;Baoxu Lin,&nbsp;Xiaosong Qin","doi":"10.1080/10408363.2023.2178378","DOIUrl":"https://doi.org/10.1080/10408363.2023.2178378","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) has become a global public health challenge. While primary glomerular disease (PGD) is one of the leading causes of CKD, the specific pathogenesis of PGD is still unclear. Accurate diagnosis relies largely on invasive renal biopsy, which carries risks of bleeding, pain, infection and kidney vein thrombosis. Problems with the biopsy procedure include lack of glomeruli in the tissue obtained, and the sampling site not being reflective of the overall lesion in the kidney. Repeated renal biopsies to monitor disease progression cannot be performed because of the significant risks of bleeding and kidney vein thrombosis. On the other hand, urine collection, a noninvasive method, can be performed repeatedly, and urinary proteins can reflect pathological changes in the urinary system. Advancements in proteomics technologies, especially mass spectrometry, have facilitated the identification of candidate biomarkers in different pathological types of PGD. Such biomarkers not only provide insights into the pathogenesis of PGD but also are important for diagnosis, monitoring treatment, and prognosis. In this review, we summarize the findings from studies that have used urinary proteomics, among other omics screens, to identify potential biomarkers for different types of PGD. Moreover, we performed an in-depth bioinformatic analysis to gain a deeper understanding of the biological processes and protein-protein interaction networks in which these candidate biomarkers may participate. This review, including a description of an integrated analysis method, is intended to provide insights into the pathogenesis, noninvasive diagnosis, and personalized treatment efforts of PGD and other associated diseases.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 5","pages":"346-365"},"PeriodicalIF":10.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833018","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":"Molecular effects of ozone on amino acids and proteins, especially human hemoglobin and albumin, and the need to personalize ozone concentration in major ozone autohemotherapy.","authors":"Fouad Mehraban,&nbsp;Arefeh Seyedarabi","doi":"10.1080/10408363.2023.2185765","DOIUrl":"https://doi.org/10.1080/10408363.2023.2185765","url":null,"abstract":"<p><p>Major ozonated autohemotherapy is a complementary therapy that is widely used to treat various diseases. In the ozonation method, ozone that is dissolved in the plasma immediately reacts with biomolecules and produces H₂O₂ and lipid oxidation products (LOPs), which serve as ozone messengers/signaling molecules and result in the biological and therapeutic effects from ozonation. These signaling molecules affect hemoglobin and albumin, the most abundant proteins in red blood cells and plasma, respectively. Because hemoglobin and albumin perform important physiological functions, structural changes due to complementary therapeutic procedures and interventions such as major ozonated autohemotherapy at incorrect concentrations can lead to disruption of their functions. Oxidation reactions in hemoglobin and albumin can lead to unfavorable high molecular weight species, which can be prevented through personalized and correct use of ozone concentrations. In this review, we describe the molecular aspects of the effects of ozone on hemoglobin and albumin at inappropriate concentrations, which cause oxidation reactions that result in destructive effects; discuss the potential risks when ozonated blood is re-infused into the patient's blood stream in the process of major ozonated autohemotherapy; and emphasize the need for personalization of ozone concentrations.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 5","pages":"382-397"},"PeriodicalIF":10.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824143","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":"Histone deacetylase inhibitors as a potential new treatment for psoriatic disease and other inflammatory conditions.","authors":"Jehan Mohammad Nazri,&nbsp;Katerina Oikonomopoulou,&nbsp;Elvin D de Araujo,&nbsp;Dziyana Kraskouskaya,&nbsp;Patrick T Gunning,&nbsp;Vinod Chandran","doi":"10.1080/10408363.2023.2177251","DOIUrl":"https://doi.org/10.1080/10408363.2023.2177251","url":null,"abstract":"<p><p>Collectively known as psoriatic disease, psoriasis and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases in which patients present with cutaneous and musculoskeletal inflammation. Affecting roughly 2-3% of the world's total population, there remains unmet therapeutic needs in both psoriasis and PsA despite the availability of current immunomodulatory treatments. As a result, patients with psoriatic disease often experience reduced quality of life. Recently, a class of small molecules, commonly investigated as anti-cancer agents, called histone deacetylase (HDAC) inhibitors, have been proposed as a new promising anti-inflammatory treatment for immune- and inflammatory-related diseases. In inflammatory diseases, current evidence is derived from studies on diseases like rheumatoid arthritis (RA) and systematic lupus erythematosus (SLE), and while there are some reports studying psoriasis, data on PsA patients are not yet available. In this review, we provide a brief overview of psoriatic disease, psoriasis, and PsA, as well as HDACs, and discuss the rationale behind the potential use of HDAC inhibitors in the management of persistent inflammation to suggest its possible use in psoriatic disease.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 4","pages":"300-320"},"PeriodicalIF":10.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10056075","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":"Focus on the frontier issue: progress in noninvasive prenatal screening for fetal trisomy from clinical perspectives.","authors":"Meng Tian,&nbsp;Lei Feng,&nbsp;Jinming Li,&nbsp;Rui Zhang","doi":"10.1080/10408363.2022.2162843","DOIUrl":"https://doi.org/10.1080/10408363.2022.2162843","url":null,"abstract":"<p><p>The discovery of cell-free fetal DNA (cffDNA) in maternal blood and the rapid development of massively parallel sequencing have revolutionized prenatal testing from invasive to noninvasive. Noninvasive prenatal screening (NIPS) based on cffDNA enables the detection of fetal trisomy through sequencing, comparison, and bioassays. Its accuracy is better than that of traditional screening methods, and it is the most advanced clinical application of high-throughput sequencing technologies. However, the existing sequencing methods are limited by high costs and complex sequencing procedures. These limitations restrict the availability of NIPS for pregnant women. Many amplification methods have been developed to overcome the limitations of sequencing methods. The rapid development of non-sequencing methods has not been accompanied by reviews to summarize them. In this review, we initially describe the detection principles for sequencing-based NIPS. We summarize the rapidly evolving amplification technologies, focusing on the need to reduce costs and simplify the procedures. To ensure that the testing systems are feasible and that the testing processes are reliable, we expand our vision to the clinic. We evaluate the clinical validity of NIPS in terms of sensitivity, specificity, and positive predictive value. Finally, we summarize the application guidelines and discuss the corresponding quality control methods for NIPS. In addition to cffDNA, extracellular vesicle DNA, RNA, protein/peptide, and fetal cells can also be detected as biomarkers of NIPS. With the development of prenatal testing, NIPS has become increasingly important. Notably, NIPS is a screening test instead of a diagnostic test. The testing methods and procedures used in the NIPS process require standardization.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 4","pages":"248-269"},"PeriodicalIF":10.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9685044","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":"Point of care blood glucose devices in the hospital setting.","authors":"Nam K Tran,&nbsp;Clayton LaValley,&nbsp;Berit Bagley,&nbsp;John Rodrigo","doi":"10.1080/10408363.2023.2170316","DOIUrl":"https://doi.org/10.1080/10408363.2023.2170316","url":null,"abstract":"<p><p>Dysglycemia is common among hospitalized patients. Accurate point-of-care (POC) glucose monitoring is necessary for the safe administration of insulin. Unfortunately, POC glucose meters are not all created equal. Interfering factors such as abnormal hematocrit, abnormal oxygen tension, and oxidizing/reducing substances can lead to inaccurate glucose measurements and result in inappropriate insulin dosing. The introduction of autocorrecting glucose meters has changed the POC testing landscape. Autocorrecting glucose meters provide more accurate measurements and have been associated with improved glycemic control in hospitalized patients. Continuous glucose monitoring has also created interest in using these platforms in at-risk inpatient populations. Future glucose monitoring technologies such as artificial intelligence/machine learning, wearable smart devices, and closed-loop insulin management systems are poised to transform glycemic management. The goal of this review is to provide an overview of glucose monitoring technology, summarize the clinical impact of glucose monitoring accuracy, and highlight emerging and future POC glucose monitoring technologies.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 4","pages":"290-299"},"PeriodicalIF":10.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9679733","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":"Laboratory testing for mitochondrial diseases: biomarkers for diagnosis and follow-up.","authors":"Abraham J Paredes-Fuentes,&nbsp;Clara Oliva,&nbsp;Roser Urreizti,&nbsp;Delia Yubero,&nbsp;Rafael Artuch","doi":"10.1080/10408363.2023.2166013","DOIUrl":"https://doi.org/10.1080/10408363.2023.2166013","url":null,"abstract":"<p><p>The currently available biomarkers generally lack the specificity and sensitivity needed for the diagnosis and follow-up of patients with mitochondrial diseases (MDs). In this group of rare genetic disorders (mutations in approximately 350 genes associated with MDs), all clinical presentations, ages of disease onset and inheritance types are possible. Blood, urine, and cerebrospinal fluid surrogates are well-established biomarkers that are used in clinical practice to assess MD. One of the main challenges is validating specific and sensitive biomarkers for the diagnosis of disease and prediction of disease progression. Profiling of lactate, amino acids, organic acids, and acylcarnitine species is routinely conducted to assess MD patients. New biomarkers, including some proteins and circulating cell-free mitochondrial DNA, with increased diagnostic specificity have been identified in the last decade and have been proposed as potentially useful in the assessment of clinical outcomes. Despite these advances, even these new biomarkers are not sufficiently specific and sensitive to assess MD progression, and new biomarkers that indicate MD progression are urgently needed to monitor the success of novel therapeutic strategies. In this report, we review the mitochondrial biomarkers that are currently analyzed in clinical laboratories, new biomarkers, an overview of the most common laboratory diagnostic techniques, and future directions regarding targeted versus untargeted metabolomic and genomic approaches in the clinical laboratory setting. Brief descriptions of the current methodologies are also provided.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 4","pages":"270-289"},"PeriodicalIF":10.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682028","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":"Diagnostic value of soluble biomarkers for parapneumonic pleural effusion.","authors":"Xi-Shan Cao,&nbsp;Wen-Qi Zheng,&nbsp;Zhi-De Hu","doi":"10.1080/10408363.2022.2158779","DOIUrl":"https://doi.org/10.1080/10408363.2022.2158779","url":null,"abstract":"<p><p>Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 3","pages":"233-247"},"PeriodicalIF":10.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696655","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":"Pathogenicity and virulence of human T lymphotropic virus type-1 (HTLV-1) in oncogenesis: adult T-cell leukemia/lymphoma (ATLL).","authors":"Sanaz Ahmadi Ghezeldasht,&nbsp;David J Blackbourn,&nbsp;Arman Mosavat,&nbsp;Seyed Abdolrahim Rezaee","doi":"10.1080/10408363.2022.2157791","DOIUrl":"https://doi.org/10.1080/10408363.2022.2157791","url":null,"abstract":"<p><p>Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4⁺ T lymphocytes caused by human T lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 was brought to the World Health Organization (WHO) and researchers to address its impact on global public health, oncogenicity, and deterioration of the host immune system toward autoimmunity. In a minority of the infected population (3-5%), it can induce inflammatory networks toward HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or hijacking the infected CD4⁺ T lymphocytes into T regulatory subpopulation, stimulating anti-inflammatory signaling networks, and prompting ATLL development. This review critically discusses the complex signaling networks in ATLL pathogenesis during virus-host interactions for better interpretation of oncogenicity and introduces the main candidates in the pathogenesis of ATLL. At least two viral factors, HTLV-1 trans-activator protein (TAX) and HTLV-1 basic leucine zipper factor (HBZ), are implicated in ATLL manifestation, interacting with host responses and deregulating cell signaling in favor of infected cell survival and virus dissemination. Such molecules can be used as potential novel biomarkers for ATLL prognosis or targets for therapy. Moreover, the challenging aspects of HTLV-1 oncogenesis introduced in this review could open new venues for further studies on acute leukemia pathogenesis. These features can aid in the discovery of effective immunotherapies when reversing the gene expression profile toward appropriate immune responses gradually becomes attainable.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 3","pages":"189-211"},"PeriodicalIF":10.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9696653","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":"Mapping of audiometric analysis with microbiological findings in patients with chronic suppurative otitis media (CSOM): a neglected clinical manifestation.","authors":"Shefali Dhingra,&nbsp;Dharam Vir,&nbsp;Jaimanti Bakshi,&nbsp;Praveen Rishi","doi":"10.1080/10408363.2022.2158173","DOIUrl":"https://doi.org/10.1080/10408363.2022.2158173","url":null,"abstract":"<p><p>Otitis media (OM) is an umbrella term for a number of conditions associated with middle ear inflammation. Chronic suppurative otitis media (CSOM), a type of OM, is characterized by long-term middle ear infection with perforated ear drum and otorrhea. The most common outcome associated with it is acquired hearing impairment in infected individuals which ultimately affects their cognitive and scholastic developments. Clinically, CSOM is thought to be a sequel of re-occurring episodes of Acute otitis media (AOM). <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> are found to be the predominant pathogenic isolates in these patients. However, with the emergence of antibiotic resistance amongst these pathogens, the adequate evaluation and treatment of this condition has become more problematic. The disease has also been recognized as one of the neglected tropical clinical manifestations with high prevalence in school-age children, especially in poor or underprivileged countries. Moreover, untreated cases have further worsened the situation by contributing to various life-threatening complications. Thus, effective treatment and surgical strategies, as well as strengthening of hearing care algorithms along with the discovery of novel animal models for advanced clinical research, can jointly help to fight this disease. In this regard, mapping of the audiological analysis with microbiological findings in CSOM patients may help elucidate the frequency that favors growth of specific pathogens. Knowledge about this potential correlation can then support timely detection of the infection, which is perceived as one of the emerging approaches for its management. In addition to these strategies, creating a true sense of awareness among people can also help mitigate this pathological condition by facilitating early identification, prevention, and treatment. This review discusses the incidence, pathogenesis, investigations, complications, and available treatment modalities associated with CSOM.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 3","pages":"212-232"},"PeriodicalIF":10.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9346757","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":"Genotype-phenotype correlation in the spectrum of frontotemporal dementia-parkinsonian syndromes and advanced diagnostic approaches.","authors":"Chiara Zecca,&nbsp;Rosanna Tortelli,&nbsp;Paola Carrera,&nbsp;Maria Teresa Dell'Abate,&nbsp;Giancarlo Logroscino,&nbsp;Maurizio Ferrari","doi":"10.1080/10408363.2022.2150833","DOIUrl":"https://doi.org/10.1080/10408363.2022.2150833","url":null,"abstract":"<p><p>The term frontotemporal dementia (FTD) refers to a group of progressive neurodegenerative disorders characterized mainly by atrophy of the frontal and anterior temporal lobes. Based on clinical presentation, three main clinical syndromes have traditionally been described: behavioral variant frontotemporal dementia (bvFTD), non-fluent/agrammatic primary progressive aphasia (nfPPA), and semantic variant PPA (svPPA). However, over the last 20 years, it has been recognized that cognitive phenotypes often overlap with motor phenotypes, either motor neuron diseases or parkinsonian signs and/or syndromes like progressive supranuclear palsy (PSP) and cortico-basal syndrome (CBS). Furthermore, FTD-related genes are characterized by genetic pleiotropy and can cause, even in the same family, pure motor phenotypes, findings that underlie the clinical continuum of the spectrum, which has pure cognitive and pure motor phenotypes as the extremes. The genotype-phenotype correlation of the spectrum, FTD-motor neuron disease, has been well defined and extensively investigated, while the continuum, FTD-parkinsonism, lacks a comprehensive review. In this narrative review, we describe the current knowledge about the genotype-phenotype correlation of the spectrum, FTD-parkinsonism, focusing on the phenotypes that are less frequent than bvFTD, namely nfPPA, svPPA, PSP, CBS, and cognitive-motor overlapping phenotypes (i.e. PPA + PSP). From a pathological point of view, they are characterized mainly by the presence of phosphorylated-tau inclusions, either 4 R or 3 R. The genetic correlate of the spectrum can be heterogeneous, although some variants seem to lead preferentially to specific clinical syndromes. Furthermore, we critically review the contribution of genome-wide association studies (GWAS) and next-generation sequencing (NGS) in disentangling the complex heritability of the FTD-parkinsonism spectrum and in defining the genotype-phenotype correlation of the entire clinical scenario, owing to the ability of these techniques to test multiple genes, and so to allow detailed investigations of the overlapping phenotypes. Finally, we conclude with the importance of a detailed genetic characterization and we offer to patients and families the chance to be included in future randomized clinical trials focused on autosomal dominant forms of FTLD.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":"60 3","pages":"171-188"},"PeriodicalIF":10.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9397719","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}