Critical reviews in oncology/hematology最新文献

{"title":"Metabolic cross-talk between glioblastoma and glioblastoma-associated microglia/macrophages: From basic insights to therapeutic strategies","authors":"Yuan Gao ,&nbsp;Mengxia Zhang ,&nbsp;Guihua Wang ,&nbsp;Weiwei Lai ,&nbsp;Shuxian Liao ,&nbsp;Yao Chen ,&nbsp;Qian Ning ,&nbsp;Shengsong Tang","doi":"10.1016/j.critrevonc.2025.104649","DOIUrl":"10.1016/j.critrevonc.2025.104649","url":null,"abstract":"<div><div>Glioblastoma (GBM), a highly malignant “cold” tumor of the central nervous system, is characterized by its ability to remodel the GBM immune microenvironment (GME), leading to significant resistance to immunotherapy. GBM-associated microglia/macrophages (GAMs) are essential components of the GME. Targeting GAMs has emerged as a promising strategy against GBM. However, their highly immunosuppressive nature contributes to GBM progression and drug resistance, significantly impeding anti-GBM immunotherapy. Accumulating evidence suggests that metabolic reprogramming accompanies GBM progression and GAM polarization, which are in turn driven by specific metabolic abnormalities and altered cellular signaling pathways. Importantly, metabolic crosstalk between GBM and GAMs further promotes tumor progression. Clarifying and disrupting this metabolic crosstalk is expected to enhance the antitumor phenotype of GAMs and inhibit GBM malignant progression. This review explores metabolism-based interregulation between GBM and GAMs and summarizes recent therapeutic strategies targeting this crosstalk, offering new insights into GBM immunotherapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104649"},"PeriodicalIF":5.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373021","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 microRNAs: A remarkable opportunity as non-invasive biomarkers from adult to pediatric brain tumor patients","authors":"Federica D’Antonio ,&nbsp;Zaira Spinello ,&nbsp;Lavinia Bargiacchi ,&nbsp;Elena Splendiani ,&nbsp;Sabrina Rossi ,&nbsp;Laura Masuelli ,&nbsp;Angela Mastronuzzi ,&nbsp;Franco Locatelli ,&nbsp;Elisabetta Ferretti ,&nbsp;Giuseppina Catanzaro","doi":"10.1016/j.critrevonc.2025.104650","DOIUrl":"10.1016/j.critrevonc.2025.104650","url":null,"abstract":"<div><div>Central nervous system (CNS) tumors represent the most frequent solid tumors among adolescents and children, and the leading cause of cancer-related death in men &lt; 40 and women &lt; 20 years of age. Brain tumors are challenging to diagnose, monitor, and treat. The current diagnostic approach involves magnetic resonance imaging (MRI), tumor histology, molecular characterization and cytologic analysis of cerebrospinal fluid (CSF). However, surgical procedures pose potential risks to the patient's health, not achieving good accuracy. For these reasons, it is crucial to identify new non-invasive disease biomarkers to improve patients’ stratification at diagnosis and during follow-up and prognosis. MicroRNAs (miRNAs) are a class of short RNA molecules that have been demonstrated in numerous studies to be dysregulated in brain tumor patients. As a result, they may be used as biomarkers of brain tumors. Additionally, miRNAs can be analyzed in liquid biopsy samples, such as blood and CSF, providing a non-invasive source of biomolecular data on patients' disease status. This review aims to highlight the role of miRNAs in liquid biopsy, also known as circulating miRNAs, as potential non-invasive cancer biomarkers in both adult and pediatric populations and to suggest their potential impact on clinical trials.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104650"},"PeriodicalIF":5.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348336","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":"Recent insights and applications of nanocarriers-based drug delivery systems for colonic drug delivery and cancer therapy: An updated review","authors":"Sobia Noreen ,&nbsp;Irsah Maqbool ,&nbsp;Anum Saleem ,&nbsp;Hassan Mahmood ,&nbsp;Nadia Rai","doi":"10.1016/j.critrevonc.2025.104646","DOIUrl":"10.1016/j.critrevonc.2025.104646","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most prevalent malignant tumor globally and is associated with high morbidity and mortality rates. The advancement of novel nanocarrier-based drug delivery systems has revolutionized therapeutic strategies for colonic drug delivery and cancer treatment. This review provides updated insights into various nanocarrier technologies, including quantum dots (QDs), polymeric nanoparticles (PNPs), magnetic and metallic nanoparticles, solid lipid nanoparticles (SLNs), and self-microemulsifying and self-nanoemulsifying drug delivery systems (SMEDDS/SNEDDS). These nanocarriers offer enhanced drug stability, controlled release, and targeted delivery, particularly for CRC treatment, resulting in up to 70 % improved therapeutic efficacy and a significant reduction in systemic toxicity as reported in preclinical studies. The review comprehensively discusses the structural composition, mechanisms of action, therapeutic potential, and imaging capabilities of these systems, with a focus on their applications in theranostics and targeted CRC therapy. For instance, polymeric nanoparticles have demonstrated a 50 % increase in bioavailability compared to conventional formulations, while QDs have enabled real-time imaging with high precision for tumor localization. Additionally, the toxicity profiles and challenges associated with these nanocarriers are critically evaluated. Despite significant progress in preclinical and clinical studies, the review highlights the need for optimizing biocompatibility, scalability, and regulatory standards to facilitate the clinical translation of these promising technologies. Emerging formulations such as graphene quantum dots and PEGylated nanoparticles have shown potential for achieving dual therapeutic and diagnostic applications with fewer adverse effects. Overall, nanocarrier-based systems hold great potential for personalized and more effective treatments in colon-targeted therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104646"},"PeriodicalIF":5.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349280","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":"Gynecomastia and its potential progression to male breast cancer: Mechanisms, genetic factors, and hormonal interactions","authors":"Dingyi Fu ,&nbsp;Haoquan Miao ,&nbsp;Zhonglin Wang ,&nbsp;Chuang Yang","doi":"10.1016/j.critrevonc.2025.104651","DOIUrl":"10.1016/j.critrevonc.2025.104651","url":null,"abstract":"<div><div>Gynecomastia is the most common breast condition in men, while male breast cancer remains relatively rare. This review explores the potential relationship between gynecomastia and male breast cancer, with a focus on the roles of hormonal imbalances, genetic factors, and molecular mechanisms in the progression of these conditions. While it remains controversial whether gynecomastia is a precancerous lesion for male breast cancer, this review summarizes the roles of estrogen and androgen receptors, the regulation of aromatase expression, and mutations in key genes such as BRCA1/2. These insights point to possible pathways by which gynecomastia could transition into male breast cancer. Additionally, hormones such as prolactin, insulin-like growth factor-1, and leptin may play significant roles in this progression. We provide an overview of the current understanding and identify key areas for further research, emphasizing the need for large-scale prospective studies to determine the causal relationship between gynecomastia and male breast cancer.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104651"},"PeriodicalIF":5.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143221209","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":"A comprehensive review and meta-analysis of CTC isolation methods in breast cancer","authors":"Alexey S. Rzhevskiy ,&nbsp;Guzel R. Sagitova ,&nbsp;Tamilla A. Karashaeva ,&nbsp;Andrey O. Morozov ,&nbsp;Anastasia S. Fatyanova ,&nbsp;Vlada V. Kazantseva ,&nbsp;Simon A. Joosse ,&nbsp;Andrei V. Zvyagin ,&nbsp;Majid Ebrahimi Warkini","doi":"10.1016/j.critrevonc.2024.104579","DOIUrl":"10.1016/j.critrevonc.2024.104579","url":null,"abstract":"<div><div>The application of circulating tumor cells (CTCs) as diagnostic and prognostic markers in oncology is gaining increasing importance in clinical practice. Currently, various methods exist for detecting CTCs in patients' biological fluids. This systematic review aimed to compare the efficacy of different techniques for isolating and detecting CTCs from blood, against the FDA-cleared CellSearch® technology, in breast cancer patients. We performed a systematic literature search using two databases (PubMed and the Cochrane Library) with the following terms: (\"Circulating tumor cells\" OR CTC) AND \"breast cancer\", covering the period from 2004 to April 2023. The primary outcome measured was the sensitivity, specificity, and overall accuracy of various CTC enrichment methods in comparison with the CellSearch® System. Secondary outcomes included the prognostic value of CTCs in evaluating response to treatment based on survival rates. Generally, a high level of agreement between CellSearch and other methods was observed in isolating CTCs from patients' blood with both metastatic and early-stage disease. Studies asserting the superiority of new methods over CellSearch frequently used clinically unvalidated cut-off thresholds for their patient cohorts. Additionally, these studies sometimes included different nonoverlapping patient cohorts and lacked a standardized chemotherapy treatment protocol, which could affect the quantitative changes in CTC. It is evident that methods simultaneously composed of physical and immunomagnetic approaches for CTC isolation significantly surpass CellSearch, which relies solely on the expression of specific markers on the CTCs’ surface. The count of CTCs has been established as a predictive marker in terms of clinically important parameters namely progression-free survival (PFS) and overall survival (OS). The CTC-count value was significantly correlated with PFS and OS rates.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104579"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775279","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":"Innovations in cancer immunotherapy: A comprehensive overview of recent breakthroughs and future directions","authors":"Chou-Yi Hsu ,&nbsp;Harikumar Pallathadka ,&nbsp;Saade Abdalkareem Jasim ,&nbsp;Jasur Rizaev ,&nbsp;Dmitry Olegovich Bokov ,&nbsp;Ahmed Hjazi ,&nbsp;Shriya Mahajan ,&nbsp;Yasser Fakri Mustafa ,&nbsp;Beneen Husseen ,&nbsp;Mohammed Abed Jawad","doi":"10.1016/j.critrevonc.2024.104588","DOIUrl":"10.1016/j.critrevonc.2024.104588","url":null,"abstract":"<div><div>A major advance in cancer treatment has been the development and refinement of cancer immunotherapy. The discovery of immunotherapies for a wide range of cancers has revolutionized cancer treatment paradigms. Despite relapse or refractory disease, immunotherapy approaches can prolong the life expectancy of metastatic cancer patients. Multiple therapeutic approaches and agents are currently being developed to manipulate various aspects of the immune system. Oncolytic viruses, cancer vaccines, adoptive cell therapies, monoclonal antibodies, cytokine therapies, and inhibitors of immune checkpoints have all proven successful in clinical trials. There are several types of immunotherapeutic approaches available for treating cancer, and others are being tested in preclinical and clinical settings. Immunotherapy has proven successful, and many agents and strategies have been developed to improve its effectiveness. The purpose of this article is to present a comprehensive overview of current immunotherapy approaches used to treat cancer. Cancer immunotherapy advancements, emerging patterns, constraints, and potential future breakthroughs are also discussed.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104588"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820272","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":"Navigating management of localized prostate cancer in the geriatric population","authors":"Kamil Malshy ,&nbsp;Borivoj Golijanin ,&nbsp;Sari Khaleel ,&nbsp;Katherine Danaher ,&nbsp;Jilienne Widener ,&nbsp;Stephen Schmit ,&nbsp;Galina Lagos ,&nbsp;Benedito Carneiro ,&nbsp;Ali Amin ,&nbsp;Liang Cheng ,&nbsp;Gyan Pareek ,&nbsp;Anthony Mega ,&nbsp;Dragan Golijanin ,&nbsp;Elias Hyams","doi":"10.1016/j.critrevonc.2024.104600","DOIUrl":"10.1016/j.critrevonc.2024.104600","url":null,"abstract":"<div><div>Prostate cancer (PCa) is highly prevalent among aging men and a significant contributor to global mortality. Balancing early detection and treatment of “clinically significant” disease with avoiding over-detection and overtreatment of slow-growing tumors is challenging, especially for elderly patients with competing health risks and potentially aggressive disease phenotypes. This review emphasizes the importance of individualized approaches for diagnosing and treating PCa in geriatric patients. Active surveillance and watchful waiting are common strategies, while surgical interventions are less frequent but considered based on comorbidities, disease risk, and patient preferences. Radiotherapy, often combined with androgen deprivation therapy, is typical for higher-risk cases, and focal therapy is emerging to reduce morbidity. An inclusive approach combining advanced diagnostics, life expectancy considerations, and minimally invasive interventions can improve decision-making. Integrating multidisciplinary strategies with better risk stratification and less invasive options can significantly enhance care and outcomes for elderly patients with significant PCa.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104600"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873638","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":"Emerging therapeutic frontiers in prostate health: Novel molecular targets and classical pathways in comparison with BPH and prostate cancer","authors":"Muhammad Sajjad Hassan ,&nbsp;Hafiz Muhammad Irfan ,&nbsp;Alamgeer ,&nbsp;Muavia Sarwar ,&nbsp;Zeeshan Jabbar ,&nbsp;Shoaib Nawaz","doi":"10.1016/j.critrevonc.2024.104590","DOIUrl":"10.1016/j.critrevonc.2024.104590","url":null,"abstract":"<div><div>Current therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104590"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796674","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":"Targeting clonal mutations with synthetic microbes","authors":"Michael Renteln","doi":"10.1016/j.critrevonc.2024.104572","DOIUrl":"10.1016/j.critrevonc.2024.104572","url":null,"abstract":"<div><div>Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal\" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Certain companies are using immunotherapies to target clonal mutations. I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104572"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755378","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":"Navigating chemotherapy and immunotherapy in early-stage lung cancer. A critical review and statements from INTERACTION group","authors":"Chiara Catania ,&nbsp;Claudia Proto ,&nbsp;Chiara Bennati ,&nbsp;Salvatore Grisanti ,&nbsp;Ida Colantonio ,&nbsp;Francesco Petrella ,&nbsp;Andrea Riccardo Filippi ,&nbsp;Carlo Genova ,&nbsp;Gaia Piperno ,&nbsp;Nazario Teodorani ,&nbsp;Carlo Greco ,&nbsp;Claudia Sangalli ,&nbsp;Vieri Scotti ,&nbsp;Francesco Agustoni ,&nbsp;Emanuela Olmetto ,&nbsp;Marco Russano ,&nbsp;Vincenzo Agbaje ,&nbsp;Angelo Platania ,&nbsp;Marzia Di Pietro Paolo ,&nbsp;Paolo Borghetti ,&nbsp;Alessandro Russo","doi":"10.1016/j.critrevonc.2025.104633","DOIUrl":"10.1016/j.critrevonc.2025.104633","url":null,"abstract":"<div><h3>Introduction</h3><div>During the recent INTERACTION group congress held on February 16–17, 2024, in Milan, Italy, many aspects of early-stage lung cancer treatment were explored. This review delves into perioperative treatment, a rapidly evolving field with an expanding therapeutic arsenal that includes chemotherapy, target therapy, and immunotherapy. The challenge remains in tailoring treatment strategies to individual patients, identifying patients best suited for surgery versus those necessitating trimodal treatment, particularly in distinguishing surgical candidates from those requiring multimodal approaches and not suitable for surgical approach.</div></div><div><h3>Materials and methods</h3><div>We conducted a literature review of phase III trials on immunotherapy and target therapy in early-stage non-small cell lung cancer (NSCLC), searching in MEDLINE, EMBASE and LILACS, adding the latest data from the European Society of Medical Oncology (ESMO) 2023 and 2024, American Society of Clinical Oncology (ASCO) 2024, and the World Conference on Lung Cancer (WCLC) 2024 conferences. A guidance on unresolved and controversial issues from the panel has been reported, also highlighting the remaining limitations that warrant further investigation and refinement in this field.</div></div><div><h3>Results</h3><div>Most recent data on early-stage NSCLC have been critically reviewed. The panel emphasized the importance of distinguishing, from the outset in a multidisciplinary setting, patients who are suitable for surgical treatment from those who are not. In this context, the importance of accurate staging at the time of diagnosis was highlighted. A paradigm shifts regarding the timing of molecular NGS DNA and RNA testing is strongly recommended.</div></div><div><h3>Conclusion</h3><div>Decisions regarding perioperative treatment in early-stage lung cancer demand early consideration, involving a multidisciplinary team and require an upfront NGS analysis. Such an approach ensures personalized care aligned with each patient's unique characteristics, optimizing treatment efficacy and overall well-being.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"208 ","pages":"Article 104633"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124166","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}