American Journal of Pathology最新文献

{"title":"Recent Advances in Chronic Traumatic Encephalopathy.","authors":"Katharine J Babcock, Bobak Abdolmohammadi, Ann C McKee","doi":"10.1016/j.ajpath.2025.07.008","DOIUrl":"10.1016/j.ajpath.2025.07.008","url":null,"abstract":"<p><p>Exposure to repeated head impacts (RHIs), such as those experienced in contact sports or military service, can lead to the development of chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. CTE cannot be diagnosed during life, only by post-mortem neuropathologic examination. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau as neurofibrillary tangles and dotlike neurites, preferentially at the depths of cortical sulci. The biomechanics of RHI involve acceleration, deceleration, and rotational forces that distort brain tissue and strain fragile structures, such as blood vessels and axons, especially in the crevices of the brain, where these forces are localized. CTE is unique from other tauopathies in its molecular structure, pattern, and regional distribution of tau. Studies in American football, rugby, and ice hockey players demonstrate a dose-response relationship between years of exposure to sport and increased CTE risk and severity. The clinical symptoms associated with CTE are classified as traumatic encephalopathy syndrome. Exposure to RHI also increases the deposition of other pathologic proteins, including β-amyloid, α-synuclein, and transactive response DNA-binding protein (TDP-43), raising the risk for other neurodegenerations, such as Alzheimer disease, Lewy body disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815577","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":"The Long Noncoding RNA TUG1 Is Down-Regulated in Osteonecrosis of the Femoral Head and Enhances the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Stimulating the Wnt/β-Catenin Pathway","authors":"Xudong Duan,&nbsp;Jiewen Zhang,&nbsp;Yiwei Zhao,&nbsp;Guanzhi Liu,&nbsp;Zixuan Wu,&nbsp;Zidong Wu,&nbsp;Yutian Lei,&nbsp;Fangze Xing,&nbsp;Ruomu Cao,&nbsp;Heng Li,&nbsp;Ning Kong,&nbsp;Chengyan Liu,&nbsp;Yiyang Li,&nbsp;Run Tian,&nbsp;Kunzheng Wang,&nbsp;Pei Yang","doi":"10.1016/j.ajpath.2025.04.020","DOIUrl":"10.1016/j.ajpath.2025.04.020","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) is an orthopaedic disease with multifaceted pathogenesis. The role of long noncoding RNA (lncRNA) taurine-up-regulated gene 1 (<em>TUG1</em>) in ONFH remains unexplored. Thus, lncRNA expression profiles in subchondral bone from patients with ONFH and healthy controls were analyzed using microarray analysis, RT-qPCR, and bioinformatics. To evaluate the effect of <em>TUG1</em> on osteogenic differentiation, <em>TUG1</em> was overexpressed or knocked down in human bone marrow mesenchymal stem cells (hBMSCs), assessed via quantitative RT-PCR, Western blot analysis, and staining assays. <em>In vivo</em>, <em>TUG1</em> was knocked down using adeno-associated viruses in a rat ONFH model. Micro–computed tomography, histology, enzyme-linked immunosorbent assay, quantitative RT-PCR, and immunohistochemistry were used to assess bone mass and osteogenic markers. <em>TUG1</em> was significantly down-regulated in ONFH subchondral bone. Overexpression of <em>TUG1</em> in hBMSCs up-regulated osteogenesis-related genes and proteins (runt-related transcription factor 2, osteopontin, osteocalcin, collagen type I alpha 1 chain, bone morphogenetic protein 2, and β-catenin), enhanced alkaline phosphatase activity, and increased mineralization. Conversely, <em>TUG1</em> knockdown reduced these markers. <em>In vivo</em>, <em>TUG1</em> knockdown disrupted bone microstructure and decreased osteogenic marker expression in the femoral head. This study revealed that <em>TUG1</em> is down-regulated in ONFH subchondral bone, leading to osteogenic dysfunction through the Wnt/β-catenin pathway. It provided a better understanding of lncRNA's regulatory role in local osteonecrosis and offered new insights into ONFH pathogenesis. This study provides a reference for future research and treatment strategies.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 8","pages":"Pages 1523-1536"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696732","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":"NSUN5 Mediates Resistance to Doxorubicin via Up-regulation of DNA Damage Repair Proteins BRCA2 and BRIP1 in Colorectal Cancer","authors":"Yuanyuan Xu ,&nbsp;Chao Qin ,&nbsp;Mengrou Zhang ,&nbsp;Qi Wu ,&nbsp;Zhun Li ,&nbsp;Hui Mo ,&nbsp;Chaochao Chen ,&nbsp;Aijun Zhou ,&nbsp;Jianming Li ,&nbsp;Wen Ni","doi":"10.1016/j.ajpath.2025.06.013","DOIUrl":"10.1016/j.ajpath.2025.06.013","url":null,"abstract":"<div><div>Despite advancements in diagnosis and therapy, chemotherapy resistance and metastasis remain significant challenges for colorectal cancer (CRC) patients. Addressing resistance to cell death is crucial for improving cancer treatment outcomes. NOP2/Sun RNA methyltransferase 5 (NSUN5) has been implicated in cancers, but its role in chemotherapy resistance in CRC remains unclear. This study revealed that NSUN5 was highly expressed in CRC through bioinformatics analysis and validation with local cohort. High expression of NSUN5 predicted poorer disease-free survival in CRC patients. <em>Nsun5</em>^−/− mice exhibited reduced tumor incidence and malignancy in the AOM/DSS-induced CRC model. Knockdown or knockout of NSUN5 resulted in diminished proliferation and migration in CRC cell lines, effects that were reversed by NSUN5 overexpression or reintroduction. Intriguingly, overexpression of NSUN5 conferred resistance to doxorubicin, an effective chemotherapeutic agent that leads to DNA damage, whereas NSUN5 deficiency increased CRC cells' sensitivity to doxorubicin, both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, NSUN5 up-regulated the expression of BRCA2 and the BRCA1-interacting helicase 1 (BRIP1), and interacted with these proteins to prevent cell death in response to DNA damage. Analysis of the local cohort and public data sets showed positive correlations between NSUN5, BRCA2, and BRIP1 in CRC. These findings demonstrate the role of NSUN5 in CRC from the perspective of chemotherapy resistance, potentially offering innovative insights into clinical therapy and prognosis of CRC.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1921-1935"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717308","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 Insights into Protein Post-Translational Modifications in Chlamydia-Host Interactions","authors":"Xiang Luo ,&nbsp;Xin Wang ,&nbsp;Canming Hu ,&nbsp;Zhe Liu ,&nbsp;Chunxue Lu ,&nbsp;Shenghua Chen ,&nbsp;Qinqin Bai ,&nbsp;Xindian Zeng ,&nbsp;Lili Chen","doi":"10.1016/j.ajpath.2025.06.011","DOIUrl":"10.1016/j.ajpath.2025.06.011","url":null,"abstract":"<div><div><em>Chlamydia</em> species are responsible for significant diseases in both humans and animals, with their infection processes involving complex interactions with host cells. Protein post-translational modifications (PTMs) have emerged as a critical focus in understanding the complex interplay between <em>Chlamydia</em> and its host. PTMs, including phosphorylation, glycosylation, ubiquitination, acetylation, and methylation, play pivotal roles in regulating key processes during <em>Chlamydia</em> infection, such as bacterial invasion, intracellular survival, immune evasion, and manipulation of host signaling pathways. By modulating both bacterial and host proteins, PTMs serve as essential mechanisms that shape the progression and outcome of <em>Chlamydia</em> infections. This growing area of research not only deepens the understanding of <em>Chlamydia</em>'s pathogenic strategies but also opens new avenues for developing targeted therapeutic interventions against these infections.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1766-1775"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717293","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":"miR-204-5p Mitigates Disc Degeneration via SKI-Mediated Modulation of Apoptotic Signaling and Matrix Remodeling in Nucleus Pulposus","authors":"Rui Ran ,&nbsp;Chao-Yang Gong ,&nbsp;Zuo-Long Wu ,&nbsp;Shun-Bai Zhang ,&nbsp;Kai Zhang ,&nbsp;Wen-Ming Zhou ,&nbsp;Wei Song ,&nbsp;Hao Dong ,&nbsp;Yong-Qiang Shi ,&nbsp;Kai-Sheng Zhou ,&nbsp;Hai-Hong Zhang","doi":"10.1016/j.ajpath.2025.07.006","DOIUrl":"10.1016/j.ajpath.2025.07.006","url":null,"abstract":"<div><div>Dysregulation of nucleus pulposus cells (NPCs) is a critical contributor to intervertebral disc degeneration (IDD). One characteristic of degenerated discs is the increased apoptosis of NPCs and the substantial degradation of the extracellular matrix (ECM). This study identified significantly reduced miR-204-5p levels in IDD tissues. Using lipopolysaccharide (LPS)-treated rat NPCs, miR-204-5p overexpression was found to suppress apoptosis, reduce ECM degradation, and enhance ECM synthesis. Mechanistically, <em>SKI</em> was identified as a direct target of miR-204-5p, with its expression markedly elevated in IDD tissues. Functional assays revealed that modulating <em>SKI</em> expression (overexpression or knockdown) influenced LPS-induced apoptosis, ECM synthesis, and degradation in NPCs. Notably, <em>SKI</em> overexpression exacerbated LPS-induced damage and counteracted the protective effects of miR-204-5p. Importantly, intradiscal delivery of agomiR-204-5p effectively alleviated IDD progression <em>in vivo</em>. Overall, these results emphasize the pivotal role of miR-204-5p in mitigating IDD by targeting <em>SKI</em>, thereby regulating NPC apoptosis and ECM homeostasis. The miR-204-5p/<em>SKI</em> axis thus presents a promising therapeutic avenue for treating IDD.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1905-1920"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717307","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":"Discovery and Mechanistic Insights into Vascular Permeability Factor/Vascular Endothelial Growth Factor through the Work of Harold F. Dvorak and Ann M. Dvorak","authors":"Stephen J. Galli","doi":"10.1016/j.ajpath.2024.08.017","DOIUrl":"10.1016/j.ajpath.2024.08.017","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 8","pages":"Pages 1360-1362"},"PeriodicalIF":4.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696735","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":"Hyperactivation of Transforming Growth Factor-β–Activated Kinase 1 Causes Skeletal Muscle Pathology Reminiscent of Inflammatory Myopathies","authors":"Meiricris Tomaz da Silva ,&nbsp;Anirban Roy ,&nbsp;Ashok Kumar","doi":"10.1016/j.ajpath.2025.07.005","DOIUrl":"10.1016/j.ajpath.2025.07.005","url":null,"abstract":"<div><div>Loss of skeletal muscle mass and strength is a debilitating consequence of various chronic diseases, inflammatory myopathies, and neuromuscular disorders. Inflammation plays a major role in the perpetuation of myopathy in degenerative muscle diseases. Transforming growth factor-β–activated kinase 1 (TAK1) is a major signaling protein that mediates the activation of multiple intracellular signaling pathways in response to inflammatory cytokines and microbial products. Recent studies have demonstrated that TAK1 is essential for the growth and maintenance of skeletal muscle mass in adult mice. However, the effects of overstimulation of TAK1 activity in the regulation of skeletal muscle mass remain unknown. The present study investigated the effects of varying levels of TAK1 activation on skeletal muscle in adult mice. Results showed that although low levels of TAK1 activation improve skeletal muscle mass, sustained hyperactivation of TAK1 causes myopathy in adult mice. Excessive stimulation of TAK1 manifested pathologic features, such as myofiber degeneration and regeneration, cellular infiltration, increased expression of proinflammatory molecules, and interstitial fibrosis. Hyperactivation of TAK1 also up-regulated proteolytic systems and various catabolic signaling pathways in skeletal muscle of adult mice. Altogether, this study demonstrated that physiological levels of activation of TAK1 lead to myofiber hypertrophy, whereas its hyperactivation results in myofiber damage and other pathologic features resembling inflammatory myopathies.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1885-1904"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717295","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":"Enhancement of Tumor Necrosis Factor-α–Mediated Hepatic Apoptosis and Liver Injury by Hepatitis B Virus Surface Antigen","authors":"Wei Liu ,&nbsp;Yan-Ting Lin ,&nbsp;Dong-Ge Han ,&nbsp;Ai-Chao Shi ,&nbsp;Qiang Liu ,&nbsp;Zhen-Tang Jing","doi":"10.1016/j.ajpath.2025.07.003","DOIUrl":"10.1016/j.ajpath.2025.07.003","url":null,"abstract":"<div><div>Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine with a variety of biological functions, such as cell proliferation, metabolic activation, inflammatory response, and cell death. TNF-α can induce a variety of mechanisms to initiate hepatocyte apoptosis, resulting in subsequent liver damage. Hepatitis B virus surface antigen (HBsAg) is the most abundant hepatitis B virus protein in the hepatocyte during chronic virus infection. However, its role in TNF-α–mediated apoptosis of hepatocytes has not been revealed. We report here that HBsAg promotes TNF-α–mediated hepatocyte apoptosis through inhibiting TNF-α–mediated anti-apoptotic complex I–dependent NF-κB activation and enhancing TNF-α–mediated pro-apoptotic complex II assembly. Mechanistically, HBsAg-mediated inhibition of complex I assembly was associated with down-regulation of K63-linked receptor-interacting protein kinase 1 (RIPK1) ubiquitination through repression of cellular inhibitor of apoptosis protein-1 (cIAP1) expression. Secretion-deficient HBsAg variant S204R enhances their pro-apoptotic abilities via further inhibition of RIPK1 ubiquitination. Expression of HBsAg in mice injected with recombinant adenovirus-associated virus 8 promoted D-galactosamine/lipopolysaccharide–induced TNF-α–mediated liver injury and damage by a mouse model. In conclusion, HBsAg may predispose hepatocytes to TNF-α–mediated apoptosis and mice to acute liver injury by switching TNF-α–mediated anti-apoptotic complex I to pro-apoptotic complex II, showing novel insights into the underlying mechanisms of hepatitis B virus–associated liver injury.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1854-1868"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717294","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":"Poly (ADP-Ribose) Polymerase 1 and 2 in B-Cell Lymphoma","authors":"Andrea Molina-Alvarez ,&nbsp;Blanca Sanchez-Gonzalez ,&nbsp;Luis Colomo ,&nbsp;José Yélamos","doi":"10.1016/j.ajpath.2025.07.004","DOIUrl":"10.1016/j.ajpath.2025.07.004","url":null,"abstract":"<div><div>B-cell lymphomas represent a heterogeneous group of malignancies characterized by complex genetic, epigenetic, and microenvironmental alterations. Defects in the DNA damage response (DDR) are critical drivers of lymphomagenesis, generating therapeutic vulnerabilities that can be exploited by targeting key DDR regulators, such as poly (ADP-ribose) polymerase-1 (PARP-1) and PARP-2. Preclinical studies demonstrate that DDR-defective B-cell lymphomas are highly sensitive to PARP-1/PARP-2 inhibition, and early-phase clinical trials using nonselective PARP inhibitors, either as monotherapy or in combination with chemotherapy, immunotherapy, or epigenetic agents, have yielded encouraging results. However, emerging evidence reveals that PARP-1 and PARP-2 play distinct roles in B-cell lymphoma pathogenesis: loss of PARP-1 accelerates lymphomagenesis, whereas loss of PARP-2 delays tumor progression. These findings challenge the current paradigm of pan-PARP inhibition and highlight the need for isoform-selective strategies. Although PARP-1–selective inhibitors have entered clinical trials for homologous recombination–deficient tumors, the development of PARP-2–selective inhibitors remains at an early stage. Future research should prioritize the design of PARP-2–targeted therapies, coupled with biomarker-driven patient selection and rational combination strategies that enhance DNA damage and modulate the tumor immune microenvironment. Selectively targeting PARP-2 offers a promising approach to improving outcomes for patients with aggressive, refractory, or relapsed B-cell lymphomas and represents a critical step forward in advancing precision oncology within hematologic malignancies.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1776-1787"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717309","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":"The Importance of Mentorship in Career Development","authors":"Fred Sanfilippo","doi":"10.1016/j.ajpath.2025.07.002","DOIUrl":"10.1016/j.ajpath.2025.07.002","url":null,"abstract":"<div><div>Receiving guidance and help from mentors is an essential component of career development and planning, especially in academic medicine and biomedical research, where the availability of resources and job opportunities are becoming more challenging. Mentors share their wisdom, experience, content expertise, and networks with mentees to provide ideas and feedback, identify and open opportunities, deal with problems and avoid mistakes, and especially to assist in evaluating the many personal and professional factors involved in decision making about career paths and job options. Identifying, engaging, and utilizing mentors appropriately is a key part of career development, and effective mentorship can come from several sources, including personal interactions, passive role models, and artificial intelligence. Providing mentorship is an important responsibility that includes various risks and benefits that should be clearly understood before the role of mentor is undertaken. Moreover, mentors should carefully assess whom to accept as a mentee by considering the time, skills, and interest needed to meet their own expectations along with those of their prospective mentees. With increasing awareness of the value of mentorship, more academic health centers, medical schools, and departments provide programs to help their students, trainees, faculty, and staff better access, understand, and take advantage of mentorship opportunities, as well as offer programs to enhance the skills and abilities of those interested in being effective mentors.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 10","pages":"Pages 1758-1765"},"PeriodicalIF":3.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717311","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}