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Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo

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世界胃肠病理生理学杂志:英文版(电子版) 2023年第4期14卷 71-85页

作者： christopher K murphy michelle m O’Donnell James W Hegarty Sarah Schulz Colin Hill R Paul Ross mary C Rea Ronald Farquhar Laurent Chesnel Research and Development Adiso Therapeutics Inc.ConcordMA 01742United States APC microbiome Ireland University College CorkCork T12 K8AFIreland Teagasc Food Research Centre Moorepark FermoyCork P61 C996Ireland Executive Leadership Team Adiso Therapeutics Inc.ConcordMA 01742United States

BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(***)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly *** recently reported the isolation of ADS024,a Bacillus velezensis(***)strain,which demonstrated direct in vitro bactericidal activity against ***,with minimal collateral impact on other members of the gut *** this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse *** To investigate the in vivo efficacy of *** ADS024 in protecting against CDI challenge in mouse *** To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with *** the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown *** single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of *** ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar *** the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by miSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on *** studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical mani

关键词： Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model microbiota

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非ST段抬高急性冠脉综合征患者随机应用依诺肝素或普通肝素抗凝治疗的疗效和出血并发症：系统综述

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美国医学会杂志（中文版） 2005年第4期24卷 209-216页

作者： John L. Petersen Kenneth W. mahaffey Vic Hasselblad Elliott m. Antman marc Cohen Shaun G. Goodman Anatoly Langer michael A. Blazing Anne Le-moigne-Amrani James A. de Lemos christopher C. Nessel Robert A. Harrington James J. Ferguson Eugene Braunwald Robert m. Califf 徐成斌（译） Duke Clinical Research Institute Durham NC Cardiovascular Division Department of Medicine Brigham and Women＇s Hospital Boston Mass Division of Cardiology Newark Beth Israel Medical Center. Newark. NJ Canadian Heart Research Centre and Terrence Donnelly Heart Centre Division of Cardiology St Michael＇s Hospital University of TorontoToronto Ontario Division of Cardiology University of Texas Southwestem Dallas Aventis Inc BridgewaterNJ St Luke＇s-Episcopal Hospital Texas Heart InstituteHouston

背景：抗凝疗法已成为急性冠脉综合征（acute coronary syndrome，ACS）治疗指南推荐的标准疗法。但是，最近某些试验在ACS患者中对依诺肝素（enoxaparin）与普通肝素（unfractionated heparin）的应用进行了比较，发现这些抗凝疗法的... 详细信息

背景：抗凝疗法已成为急性冠脉综合征（acute coronary syndrome，ACS）治疗指南推荐的标准疗法。但是，最近某些试验在ACS患者中对依诺肝素（enoxaparin）与普通肝素（unfractionated heparin）的应用进行了比较，发现这些抗凝疗法的疗效及安全性并不及既往试验结果。目的：有6项随机对照试验对依诺肝素与普通肝素治疗ACS患者进行了比较，对其终点（即全因死亡及非致死性心肌梗死）、输血与大出血进行系统评估。资料来源：从杜克临床研究所（Duke Clinical Research Institute）获取ESSENCE、A to Z及SYNERGY试验的原始数据。由TImI 11B、ACUTEⅡ及INTERACT研究的主要研究人员提供各自的基线特征和事件发生频率。研究选取：在非ST段抬高ACS患者中比较依诺肝素与普通肝素的6项随机对照试验均人选进行分析。数据提取：从全部试验人群和随机分组前未接受抗凝治疗的亚人群中获取疗效终点和安全性终点。数据综合：应用随机效应经验性贝叶斯模型（random—effects empirical Bayes model），系统评估21946例患者的结果。依诺肝素与普通肝素30天死亡率无显著差异（3．0％比3．0％，优势比[odds ratio，OR]，1．00；95％可信区间[confidence interval，CI]，0．85～1．17）。在所有试验人群中，依诺肝素与普通肝素相比，30天死亡或非致死性心肌梗死（myocardial infarction，mI）联合终点显著下降，具有统计学差异（10．1％比11．0％；OR，0．91；95％CI，0．83～0．99；所需治疗例数107）。随机分组前未接受抗凝治疗的依诺肝素组患者30天死亡或mI联合终点亦显著下降，具有统计学差异（8．0％比9．4％；OR，0．81；95％CI，0．70～0．94；所需治疗例数72）。随机分组后第7天，总体安全人群或者随机分组前未接受抗凝治疗的人群输血（OR，1．01；95％CI，0．89～1．14）或大出血的发生率（OR，1．04；95％CI，0．83～1．30）无显著差异。结论：对近22000例各类ACS患者进行系统回顾发现，在预防死亡或mI联合终点方面依诺肝素较普通肝素更有效。

关键词：非ST段抬高急性冠脉综合征随机对照试验依诺肝素普通肝素抗凝治疗出血并发症患者系统综述疗效

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Common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma

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Cancer Biology & medicine 2018年第S1期15卷 10-11页

作者： Jittiporn Chaisaingmongkol Anuradha Budhu Hien Dang Siritida Rabibhadana Benjarath Pupacdi So mee Kwon marshonna Forgues Yotsawat Pomyen Vajarabhongsa Bhudhisawasdi Nirush Lertprasertsuke Anon Chotirosniramit Chawalit Pairojkul Chirayu UAuewarakul Thaniya Sricharunrat Kannika Phornphutkul Suleeporn Sangrajrang maggie Cam Ping He Stephen m.Hewitt Kris Ylaya Xiaolin Wu Jesper B.Andersen Snorri S.Thorgeirsson Joshua J.Waterfall Yuelin J.Zhu Jennifer Walling Holly S.Stevenson Daniel Edelman Paul S.meltzer christopher A.Loffredo Natsuko Hama Tatsuhiro Shibata Robert H.Wiltrout Curtis C.Harris Chulabhorn mahidol mathuros Ruchirawat Xinwei Wang Laboratory of Human Carcinogenesis Center for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA Laboratory of Chemical Carcinogenesis Chulabhorn Research InstituteBangkokThailand Center of Excellence on Environmental Health and Toxicology Office of Higher Education CommissionMinistry of EducationBangkokThailand Faculty of medicine Khon Kaen UniversityKhon KaenThailand Faculty of medicine Chiang Mai UniversityChiang MaiThailand HRH Princess Chulabhorn College of medical Science BangkokThailand Chulabhorn Hospital BangkokThailand Rajavej Hospital Chiang MaiThailand National Cancer Institute BangkokThailand Center for Cancer Research National Cancer InstituteBethesdaMarylandUSA FDA Silver SpringMarylandUSA Laboratory of Pathology Center for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA Frederick National Laboratory for Cancer Research FrederickMarylandUSA Biotech Research and Innovation Center(BRIC) Department of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark Genetics Branch Center for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA Georgetown University medical Center WashingtonDCUSA Division of Cancer Genomics National Cancer Center Research InstituteThe University of TokyoTokyoJapan Laboratory of molecular medicine Human Genome CenterThe Institute of Medical ScienceThe University of TokyoTokyoJapan Cancer Inflammation Program Center for Cancer ResearchNational Cancer InstituteBethesdaMarylandUSA

Objective:Intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma(HCC)are clinically disparate primary liver cancers with etiological and biological *** Thailand,both cancer types represent the primary cause ... 详细信息

关键词： Common molecular subtypes

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AAA—01北极地区显生宙古地理演化（三）：一套新的北极地质图

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海洋地质 2008年第3期24卷 49-50页

作者： christopher Harrison marc St - Onge Sergey Strelnikov Boris Lopatin Frederick Wilson Stefan Bergman Arne Solli Hans Jepsen 孙桂华（译）邱燕（校对）加拿大地质调查局俄罗斯地质研究所俄罗斯世界海洋地质和矿产资源研究所美国地质调查局瑞典地质调查局挪威地质调查局丹麦和格陵兰地质调查局不详

作为国际极地年活动的一部分和世界地质图委员会的有关目标，环北极国家合作编制了一份1：500万的基岩地质图和相应的数据库。立体图件覆盖到60°N的陆地和近海，印刷版直径1．3m，每个图幅附有图例。

关键词：北极地区地质图古地理演化显生宙 AAA 委员会部分和数据库

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Impact of marijuana on Response Inhibition: An fmRI Study in Young Adults

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Journal of Behavioral and Brain Science（行为与脑科学期刊） 2011年第3期

作者： Andra m. Smith Rocío A. López Zunini christopher D. Anderson Carmelinda A. Longo Ian Cameron matthew J. Hogan Peter A. Fried

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Phosphorylated low-density lipoprotein receptor-related protein 6 is prevalent in hippocampal progenitor cells and circuits of aged human hippocampus

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Advances in Alzheimer's Disease（阿尔茨海默氏病研究进展） 2013年第4期

作者： christopher P.Sullivan Rosemary Elliott-Bryant Anish Kanesa-Thasan Ann C.mcKee Richard E.Fine John m.Wells Peter J.morin GeriatricResearchEducationandClinicalCenterBedfordVAHospital DepartmentofNeurologyBostonUniversitySchoolofmedicine DepartmentofPathologyBostonUniversitySchoolofmedicineBoston!USA DepartmentofBiochemistryBostonUniversitySchoolofmedicine

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老年择期关节置换术患者术后谵妄的认知和功能预测因子及其后遗症

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麻醉与镇痛 2013年第6期9卷 13-22页

作者： christopher J. Jankowski, mD max R. Trenerry, PhD David J. Cook, mD Shonie L. Buenvenida, m'q Susanna R. Stevens, mS Darrell R. Schroeder, mS David O. Warner, mD 张文奇(译) 刘晓(译) 郭曲练(校) Departments of Anesthesiology Psychology and Biostatistics and Department of Anesthesiology Anesthesiology Clinical Research Unit Mayo Clinic Rochester Minnesota 不详

背景术后谵妄（postoperativedelirium，POD）在老年患者中很常见，且与不良预后相关。在行择期手术的患者中，POD的认知和功能性后遗症尚且未知。我们试图研究：①在老年手术患者中，敏感性神经认知测试的较低评分能否作为POD的独立风... 详细信息

背景术后谵妄（postoperativedelirium，POD）在老年患者中很常见，且与不良预后相关。在行择期手术的患者中，POD的认知和功能性后遗症尚且未知。我们试图研究：①在老年手术患者中，敏感性神经认知测试的较低评分能否作为POD的独立风险因子；@POD能否预测手术3个月后的认知和功能下降。方法我们对年龄I〉65岁的全髋关节或全膝关节置换术患者进行了一项前瞻性队列研究。参与者接受术前的神经认知和功能测试。使用混乱评估法诊断POD。出现POD的患者组与对照组在手术后3个月接受重复的神经认知和功能测试。结果418例患者符合入选标准，有42例出现POD。各组之间在基础细微精神状态检查评分、酗酒、抑郁和语言智力等方面没有差别。POD的独立预测因子包括年龄、精神疾病史、功能状态的下降和语言记忆的下降。对于所有测试，POD患者组和匹配的对照组之／＇^-J在术前和术后3个月的变化相似。结论术前神经认知和功能状态的轻微下降可以预测POD。然而在出现POD的小群体中，没有手术后3个月出现认知和功能下降的证据。POD与术前认知功能的降低有关，但在择期手术的老年患者中，可能不存在手术后3个月有害的认知或功能后遗症。

关键词：独立预测因子全膝关节置换术老年患者神经认知择期手术术后谵妄后遗症精神状态检查

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What Is Required to Prevent a Second major Outbreak of SARS-CoV-2 upon Lifting Quarantine in Wuhan City,China

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The Innovation 2020年第1期1卷 152-157页

作者： Lei Zhang mingwang Shen Xiaomeng ma Shu Su Wenfeng Gong Jing Wang Yusha Tao Zhuoru Zou Rui Zhao Joseph T.F.Lau Wei Li Feng Liu Kai Ye Youfa Wang Guihua Zhuang christopher K.Fairley China-Australia Joint Research Center for Infectious Diseases School of Public HealthXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061PR China melbourne Sexual Health Centre Alfred HealthMelbourneAustralia Central Clinical School Faculty of MedicineNursing and Health SciencesMonash UniversityMelbourneVICAustralia Department of Epidemiology and Biostatistics College of Public HealthZhengzhou UniversityZhengzhou 450001 HenanChina Institute of Health Policy management and Evaluation University of TorontoTorontoONCanada School of Public Health and Preventive medicine Faculty of MedicineMonash UniversityMelbourneAustralia Centre for Research Behaviors Centre for Health Behaviours ResearchSchool of Public Health and Primary CareThe Chinese University of Hong KongHong KongHong Kong Bill and melinda Gates Foundation SeattleWAUSA Department of Epidemiology and Health Statistics School of Public HealthSoutheast UniversityNanjing210009 JiangsuChina Shaanxi Provincial Center for Disease Control and Prevention Xi’an710054 ShaanxiChina mOE Key Lab for Intelligent Networks&Networks Security Faculty of Electronics and Information EngineeringXi’an Jiaotong UniversityXi’an 710049 China School of Automation Science and Engineering Faculty of Electronics and Information EngineeringXi’an Jiaotong UniversityXi’an 710049 China Genome Institute the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061 China The School of Life Science and Technology Xi’an Jiaotong UniversityXi’an 710049 China Global Health Institute Department of Epidemiology and BiostatisticsSchool of Public HealthXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China

BACKGROUND The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus *** of this quarantine is *** modelled the effects of two key hea... 详细信息

关键词： Wuhan break major

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen maria Teresa Landi mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le marchand Olle melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist mikael Johansson Neil Caporaso Penella Woll Philip Lazarus matthew BSchabath melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu christopher IAmos Hongxia ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of medicine Carmel Medical CenterHaifa 3448516Israel markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of molecular and Clinical Cancer medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Correction: Strawberry sweetness and consumer preference are enhanced by specific volatile compounds

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Horticulture Research 2021年第1期8卷 3067-3067页

作者： Zhen Fan Tomas Hasing Timothy S.Johnson Drake m.Garner michael L.Schwieterman christopher R.Barbey Thomas A.Colquhoun Charles A.Sims marcio F.R.Resende Vance m.Whitaker Horticultural Sciences Department University of Florida IFAS Gulf Coast Research and Education Center Wimauma FL USA Elo Life Systems Durham NC USA Department of Environmental Horticulture and Plant Innovation Center Institute of Food and Agricultural Sciences University of Florida Gainesville FL USA Plenty Unlimited Inc. South San Francisco CA 94080 USA Food Science and Human Nutrition Department University of Florida Gainesville FL USA Horticultural Sciences Department University of Florida Gainesville FL USA

Since the publication of this article 1,the corresponding author discovered that an additional researcher contributed data and should be included as an *** ***(Plenty Unlimited,Inc.,South San Francisco,CA 94080,US)has... 详细信息

关键词： volatile specific compounds

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