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Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 649-661页

作者： Zheng Wang Guihu Zhao Bin Li Zhenghuan Fang Qian Chen Xiaomeng Wang Tengfei Luo Yijing Wang Qiao Zhou Kuokuo Li Lu Xia Yi Zhang Xun Zhou Hongxu pan Yuwen Zhao Yige Wang Lin Wang Jifeng Guo Beisha Tang Kun Xia Jinchen Li National Clinical Research centre for Geriatric Disorders Department of GeriatricsXiangya HospitalCentral South UniversityChangsha 410008China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China centre for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Reproductive Medicine Center Xiangya HospitalCentral South UniversityChangsha 410008China

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification ***,an increasing number of computational methods are developed to predict the effects of variants in human non-coding ***,it is difficult for inexperienced users to select appropriate computational methods from dozens of available *** solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different ***,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better ***,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.

关键词： Non-coding variant Pathogenicity estimation Functional prediction Performance assessment Prediction model

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The hypoxia adaptation of small mammals to plateau and underground burrow conditions

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Animal Models and Experimental Medicine 2021年第4期4卷 319-328页

作者： Mengke Li Dan pan Hong Sun Lei Zhang Han Cheng Tian Shao Zhenlong Wang School of Life Sciences Zhengzhou UniversityZhengzhouP.R.China centre for Nutritional Ecology Zhengzhou UniversityZhengzhouP.R.China

Oxygen is one of the important substances for the survival of most life systems on the earth,and plateau and underground burrow systems are two typical hypoxic *** mammals living in hypoxic environments have evolved different adaptation strategies,which include increased oxygen delivery,metabolic regulation of physiological responses and other physiological responses that change tissue oxygen *** predictions have also shown that these animals have evolved different adaptations to extreme *** particular,vascular endothelial growth factor(VEGF)and erythropoietin(EPO),which have specific functions in the control of O_(2) delivery,have evolved adaptively in small mammals in hypoxic *** mole-rats and blind mole-rats are typical hypoxic model animals as they have some resistance to *** review primarily summarizes the main living environment of hypoxia tolerant small mammals,as well as the changes of phenotype,physiochemical characteristics and gene expression mode of their long-term living in hypoxia environment.

关键词： hypoxia adaptation multi-omics plateau small mammals underground burrow systems

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Anti-Angiogenic and Anti-Metastatic Effects of Biogenic Silver Nanoparticles Synthesized Using Azadirachta indica

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Advances in Bioscience and Biotechnology 2022年第4期13卷 188-206页

作者： Shedrack Reuben Kitimu Peter Kirira Ahmed A. Abdille Judith Sokei Dominic Ochwang’i Peter Mwitari Andrew Makanya Naomi Maina Department of Molecular Biology and Biotechnology Pan-African University Nairobi Kenya Department of Veterinary Physiology Biochemistry and Pharmacology Sokoine University of Agriculture Morogoro Tanzania Department of Physical Sciences Mount Kenya University Kiambu Kenya Department of Veterinary Anatomy and Physiology University of Nairobi Nairobi Kenya centre for Traditional Medicine and Drug Research Kenya Medical Research Institute Nairobi Kenya Department of Biochemistry Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya

Background: Nanotechnology symbolizes a broad discipline with enormous potential in cancer treatment bridging one of the bottlenecks of traditional approaches in cancer therapy which is an inability to deliver adequate quantities of anti-cancer drugs to the tumor area. Studies on nanoparticles indicate their importance in cancer angiogenesis and metastasis. Aim: The present study assessed anti-angiogenesis and anti-metastatic effects of biogenic silver nanoparticles (AgNPs) synthesized from neem plant (Azadirachta indica). Methods: Chicken chorioallantoic membrane (CAM) and two-dimensional (2D) wound healing assays were used to study anti-angiogenic and anti-metastatic effects of the AgNPs respectively. Twenty-four fertilized eggs were divided into four groups: two biogenic AgNPs treatments at 100 μg/ml and 200 μg/ml;negative control (1% DMSO) and positive control (cyclophosphamide). On day 8 of incubation, filter discs impregnated with different concentration levels of the treatments were placed on the CAM. On day 12 of incubation, the CAMs were imaged using a stereomicroscope, scaled using ImageJ, and different morphometric and spatial parameters computed using AngioTool software. Vessel area, vessel percent area, total number of junctions, total vessel length, average vessel length, mean lacunarity, and junction density were measured. The crown-rump length (CRL) and fetal weight were also recorded on day 16 of incubation. In order to determine relative gene expression profiles of iNOS and VEGF, total RNA was extracted from the CAM, and qRT-PCR was performed with β-Actin as a reference gene. For the 2D wound healing assay, DU145 human prostate cells were grown in Dulbecco’s Modified Eagle’s Medium supplemented with 10% Fetal Bovine Serum. Results: Biogenic AgNPs demonstrated anti-angiogenic effects in a dose-dependent manner in the parameters generated from the CAM images. Also, qRT-PCR revealed down-regulation of iNOS and VEGF genes. The 2-dimensional wound heali

关键词： Biogenic AgNPs cancer Angiogenesis Metastasis CAM

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Implications of apoptosis in cancer immunotherapy

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Advances in Bioscience and Biotechnology 2012年第6期3卷 679-685页

作者： Gregory Lee Bixia Ge UBC centre for Reproductive Health University of British Columbia Vancouver Canada

Inhibitions or blockages of ligand-receptor interactions on cancer cell surfaces by exogenous competetors or antibodies often result in apoptosis or “programmed cell death.” The underlying mechanisms of action for cellular apoptosis depend greatly on the molecular nature of specific ligand-receptor interactions and the signal transduction pathways involved. Two such unrelated systems which are potentially involved in apoptosis of cancer cells are described in this review. They are, respectively, gonadotropinreleasing hormone (GnRH) receptor and cancerous immunoglobulins, or CA215, both of which are widely expressed on the surface of cancer cells from diversified tissue origins. Bindings of GnRH or its decapeptide analogs as ligands to GnRH receptor were known to induce apoptosis of several extrapituitary cell types in gonadal tissues, as well as different cancer cells. Monoclonal antibodies against the GnRH receptor of cancer cells were shown to induce apoptosis, similar to the action of GnRH analogs. In contrast, RP215 monoclonal antibody reacts specifically with the carbohydrate-associated epitope of cancerous immunoglobulins and is known to induce apoptosis of cancer cells in vitro. It also causes growth inhibition of tumor cells in nude mouse experimental models. Elucidations of the specific mechanisms of apoptosis in cancer cells of these two molecular interaction systems will not only lead to a better understanding of cancer biology but also benefit patients in cancer monitoring and therapy.

关键词： Apoptosis GHR106 RP215 CA215 pan-cancer Biomarker GnRH Receptor

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Predilection site and risk factor of second primary cancer:A pancancer analysis based on the SEER database

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Chinese Medical Journal 2023年第12期136卷 1500-1502页

作者： Shan Xiong Hengrui Liang Peng Liang Xiuyu Cai Caichen Li Ran Zhong Jianfu Li Bo Cheng Feng Zhu Limin Ou Zisheng Chen Yi Zhao Hongsheng Deng Zhuxing Chen Zhichao Liu Zhanhong Xie Feng Li Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouGuangdong 510120China Department of General Internal Medicine Sun Yat-sen University Cancer CentreState Key Laboratory of Oncology in South ChinaCollaborative Innovation Centre for Cancer MedicineGuangzhouGuangdong 510160China Department of General Internal Medicine Detroit Médica Center Sinai-Grace HospitalDetroit MI 48235USA Department of Oncology The First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510660China Department of Respiratory Medicine The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalQingyuanGuangdong 511518China Department of Thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China

To the Editor:Over the past few years,the number of cancer survivors has continued to increase,primarily driven by the growing and aging population and the improvements in cancer detection and *** than 16.9 million Americans with prior cancers were alive on January 1,2019,and the number of cancer survivors was estimated to reach>22.1 million by January 1,2030.[1]The lifetime risk of individual second primary cancer(SPC)has been confirmed when confronted with such a large amount of cancer survivors.[2]Definition of specific site is shown in supplementary material,http://***/CM9/B616.

关键词： lifetime continued primarily

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Pre-coronavirus disease 2019 brain structure might be associated with social anxiety alterations during the pandemic

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Chinese Medical Journal 2023年第13期136卷 1621-1623页

作者： Xun Zhang Qingyuan Li Xun Yang Nanfang pan Xueling Suo Min He Song Wang Graham JKemp Qiyong Gong Huaxi Magnetic Resonance Research Center(HMRRC) Department of RadiologyWest China Hospital of Sichuan UniversityChengduSichuan 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province West China Hospital of Sichuan UniversityChengduSichuan 610041China Research Unit of Psychoradiology Chinese Academy of Medical SciencesChengduSichuan 610041China Department of Interventional Therapy Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Cancer CenterNational Clinical Research Center for CancerBeijing 100021China School of Public Affairs Chongqing UniversityChongqing 400044China Liverpool Magnetic Resonance Imaging centre(LiMRIC)and Institute of Life Course and Medical Sciences University of LiverpoolLiverpool L693BXUK Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamenFujian 361000China

To the Editor:As the novel coronavirus disease 2019(COVID-19)pandemic rapidly spreads around the world,it has resulted in unprecedented economic loss,social turmoil,and detrimental effects on public mental *** particular,the implementation of disease control measures such as nationwide lockdowns,social distancing,school closures,and home quarantine has given rise to a wide range of social anxiety(SA)around the world,from nonclinical manifestations to clinical social anxiety disorder(SAD).[1]Given the potentially severe impairments from SA and the limited mental health care resources,it is vital to identify whether there are vulnerability/risk neuropsychological factors contributing to the progression of SA during the pandemic.

关键词： alterations nationwide closure

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The Quantification of Intra-Fractional Tumour Motion Errors in Lung Stereotactic Ablative Radiotherapy Patients

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2017年第2期6卷 105-110页

作者： Ibrahem H. Kanbayti Qamar Ghafoor Gareth Webster Saddig Jastaniah Diagnostic Radiology Department King Abdulaziz University Jeddah KSA Queen Elizabieth Hospital Oncology Center Birmingham UK Batterjee Medical College Jeddah KSA

This work aims at quantifying intra-fractional motion errors and evaluating the appropriateness of a Planning Target Volume (PTV) margin for Queen Elizabeth (QE) Hospital’s patients. Intra-fractional motion errors were quantified for 29 patients who underwent lung Stereotactic Ablative Radiotherapy (SABR) treatment at the cancer centre of QE Hospital. One hundred thirty post-Cone Beam Computed Tomography (CBCT) scans were collected to calculate these errors. In terms of the adequacy of a PTV margin, the intra-fractional motion errors that were calculated are combined with other geometric errors which were taken from historical audit studies. Then, the combined outcome was compared with the common PTV margin that is delineated by most United Kingdom (UK) oncology centres. The findings of this study showed that the systematic component of intra-fractional motion error is equal to 0.08, 0.08 and 0.08 cm in right/left, superior/anterior and anterior/posterior directions, respectively, While the random component of this error is equal to 0.11, 0.13 and 0.14 cm. In addition to that, a PTV margin of 0.5 cm is the appropriate margin for QE Hospital’s patients and this volume is compatible with the common PTV margin that is delineated by the most UK oncology centres. This work concluded that A PTV margin of 0.5 cm is the suitable volume for lung SABR patients at QE Hospital.

关键词： SABR Geometric Errors Lung cancer

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An endoplasmic reticulum-targeted organic photothermal agent for enhanced cancer therapy

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Chinese Chemical Letters 2022年第2期33卷 793-797页

作者： Kaiye Wang Yanan Xiang Wei pan Hongyu Wang Na Li Bo Tang College of Chemistry Chemical Engineering and Materials ScienceKey Laboratory of Molecular and Nano ProbesMinistry of EducationCollaborative Innovation Centre of Functionalized Probes for Chemical Imaging in Universities of ShandongInstitute of Molecular and Nano ScienceShandong Normal UniversityJi’nan 250014China

Developing selectively targeted photothermal agents to reduce side effects in photothermal therapy remains a great challenge. Inspired by the key role of endoplasmic reticulum in the protein synthesis and intracellular signal transduction, particularly for the immunogenic cell death induced by endoplasmic reticulum stress, we developed an endoplasmic reticulum-targeted organic photothermal agent(Ts-PTRGD) for enhancing photothermal therapy of tumor. The photothermal agent was covalently attached with 4-methylbenzenesulfonamide and cyclic Arg-Gly-Asp(c RGD) peptide for realizing the targeting of endoplasmic reticulum and tumor cell. Owing to its amphiphilic properties, it readily self-assembles in water to form nanoparticles. The photothermal agent possesses excellent photophysical properties and biological compatibility. In vitro and in vivo experiments demonstrate that it can actively target endoplasmic reticulum and effectively ablate tumor with near-infrared laser.

关键词： Photothermal therapy Endoplasmic reticulum Dual-targeting delivery Organic photothermal agents Therapeutic agents

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癌症一级预防的环境与职业干预：一个跨部门的政策框架

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环境与职业医学 2013年第10期30卷 806-810页

作者： Carolina Espina Miquel Porta Joachim Schüz Ildefonso Hernández Aguado Robert V.Percival Carlos Dora Terry Slevin Julietta Rodriguez Guzman Tim Meredith Philip J.Landrigan Maria Neira 汪源何蓉金泰廙 Department of Public Health and Environment World Health Organization(WHO)GenevaSwitzerland Section of Environment and Radiation International Agency for Research on Cancer(IARC)LyonFrance Hospital del Mar Institute of Medical Research(IMIM-Hospital del Marprbb) BarcelonaSpain Networking centre of Biomedical Research in Epidemiology and Public Health(CIBERESP) Spain Universidad Autónoma de Barcelona(UAB) BarcelonaSpain Department of Public Health Facultad de MedicinaUniversidad Miguel HernándezSan Juan de AlicanteSpain Environmental Law Program University of Maryland Carey School of LawBaltimoreMarylandUSA cancer Council Western Australia PerthWestern AustraliaAustralia Occupational Health Program El Bosque UniversityBogotaColombia Department of Sustainable Development and Environment Pan-American Health Organization/WHOWashington DCUSA Department of Preventive Medicine Mount Sinai School of MedicineNew YorkNew YorkUSA

[背景]每年,全球新发癌症近1300万例,癌症死亡760万例;63%的癌症死亡病例发生在中、低收入国家。有相当比例的癌症是由环境和工作场所中致癌物暴露所致。[目的]为环境和职业性癌症的一级预防制定基于循证的全球愿景和战略。[方法]通过在... 详细信息

[背景]每年,全球新发癌症近1300万例,癌症死亡760万例;63%的癌症死亡病例发生在中、低收入国家。有相当比例的癌症是由环境和工作场所中致癌物暴露所致。[目的]为环境和职业性癌症的一级预防制定基于循证的全球愿景和战略。[方法]通过在PubMed中组合使用"环境的"、"职业的"、"暴露"、"癌症"、"一级预防"和"干预"这些搜索词,确定相关研究。为补充文献综述,于2011年3月17—18日在西班牙阿斯图里斯亚召开了"癌症的环境与职业决定因素:一级预防干预"国际会议,该会议由世界卫生组织主办。[讨论]很多由环境和职业引起的癌症都是可以预防的。一级预防政策通过减少或消除非自愿暴露于确认或潜在致癌物质,可最有效地实现预防目的。根据现有的知识,这些策略直接且经济有效,还具有附带效益,即通过减少共同风险因素的暴露,协同降低其他非传染性疾病的风险。[结论]通过整合环境和职业性致癌物初级干预来重振全球癌症控制政策是可能的。

关键词：癌症环境卫生职业的政策一级预防公共卫生

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The SUPER reporting guideline suggested for reporting of surgical technique

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Hepatobiliary Surgery and Nutrition 2023年第4期12卷 534-544,I0024-I0026页

作者： Kaiping Zhang Yanfang Ma Jinlin Wu Qianling Shi Leandro Cardoso Barchi Marco Scarci Rene Horsleben Petersen Calvin S.H.Ng Steven Hochwald Ryuichi Waseda Fabio Davoli Robert Fruscio Giovanni Battista Levi Sandri Michel Gonzalez Benjamin Wei Guillaume Piessen Jianfei Shen Xianzhuo Zhang panpan Jiao Yulong He Nuria M.Novoa Benedetta Bedetti Sebastien Gilbert Alan D.L.Sihoe Alper Toker Alfonso Fiorelli Marcelo F.Jimenez Toni Lerut Aung Y.Oo Grace S.Li Xueqin Tang Yawen Lu Hussein Elkhayat Tomaz Stupnik Tanel Laisaar Firas Abu Akar Diego Gonzalez-Rivas Zhanhao Su Bin Qiu Stephen D.Wang Yaolong Chen Shugeng Gao Editorial Office AME Publishing CompanyHong KongChina School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina Department of Cardiovascular Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouChina Evidence-based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhouChina Lanzhou University Institute of Health Data Science LanzhouChina Digestive Surgery Division Department of GastroenterologyUniversity of Sao Paulo School of MedicineSão PauloBrazil Department of Cardiothoracic Surgery Imperial College Healthcare NHS TrustLondonUK Department of Cardiothoracic Surgery University Hospital of CopenhagenRigshospitaletCopenhagenDenmark The Chinese University of Hong Kong Prince of Wales HospitalShatinNew TerritoriesHong KongChina Department of Surgical Oncology Roswell Park Cancer InstituteBuffaloNYUSA Department of General Thoracic Breast and Pediatric SurgeryFukuoka UniversityFukuokaJapan Department of Thoracic Surgery AUSL RomagnaS.Maria delle Croci Teaching HospitalRavennaItaly Clinic of Obstetrics and Gynecology University of Milan-BicoccaSan Gerardo HospitalMonzaItaly Division of General Surgery and Liver Transplantation S.Camillo HospitalRomeItaly Service of Thoracic Surgery Lausanne University Hospital(CHUV)LausanneSwitzerland Division of Cardiothoracic Surgery Department of SurgeryUniversity of Alabama BirminghamBirminghamALUSA University of Lille CNRSInsermCHU LilleUMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to TherapiesLilleFrance Department of Cardiothoracic Surgery Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical UniversityLinhaiChina The First School of Clinical Medicine Lanzhou UniversityLanzhouChina Thoracic Surgery Service University Hospital of SalamancaBiomedical Institute of SalamancaSalamancaSpain Department of Thoracic Surgery Helios Clinic Bonn/Rhein SiegBonnGermany Division of Thoracic Surgery Department of SurgeryThe Ottawa

Background:Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical *** Surgical techniqUe rePorting chEcklist and standaRds(SUPER)aims to address this gap by defining reporting standards for surgical *** SUPER guideline intends to apply to articles that encompass surgical technique in any study design,surgical discipline,and stage of surgical ***:Following the EQUATOR(Enhancing the QUAlity and Transparency Of health Research)Network approach,16 surgeons,journal editors,and methodologists reviewed existing reporting guidelines relating to surgical technique,reviewed papers from 15 top journals,and brainstormed to draft initial items for the *** initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and *** final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER ***:The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique *** items are divided into six sections:background,rationale,and objectives(items 1 to 5);preoperative preparations and requirements(items 6 to 9);surgical technique details(items 10 to 15);postoperative considerations and tasks(items 16 to 19);summary and prospect(items 20 and 21);and other information(item 22).Conclusions:The SUPER reporting guideline has the potential to guide detailed,comprehensive,and transparent surgical technique reporting for *** may also assist journal editors,peer reviewers,systematic reviewers,and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique.

关键词： Surgical technique surgical innovation reporting guideline reporting checklist Surgical techniqUe rePorting chEcklist and standaRds(SUPER)

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