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Interactive effects of reproductive assets and ambient predation risk on the threat-sensitive decisions of Trinidadian guppies

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Current Zoology 2016年第3期62卷 221-226页

作者： Jemma KATWAROO-ANDERSEN chris K. ELVIDGE Indar RAMNARINE Grant E. bROWN Department of biology Concordia University 7141 Sherbrooke St. West Montreal QC H4B 1R6 Canada Department of Life Sciences University of the West Indies St. Augustine Trinidad and Tobago

Threat-sensitive behavioral trade-offs allow prey animals to balance the conflicting demands of successful predator detection and avoidance and a suite of fitness-related activities such as forag- ing, mating, and territorial defense. Here, we test the hypothesis that background predation level and reproductive status interact to determine the form and intensity of threat-sensitive behavioral decisions of wild-caught female Trinidadian guppies Poecilia reticulata. Gravid and nongravid gup- pies collected from high- and low-predation pressure populations were exposed to serial dilutions of conspecific chemical alarm cues. Our results demonstrate that there was ＇no effect of reproduct- ive status on the response of females originating from a low-predation population, with both gravid and nongravid guppies exhibiting strong anti-predator responses to the lowest concentration of alarm cues tested. Increasing cue concentrations did not result in increases in response intensity. Conversely, we found a significant effect of reproductive status among guppies from a high- predation population. Nongravid females from the high-predation population exhibited a strong graded （proportional） response to increasing concentrations of alarm cue. Gravid females from the same high-predation population, however, shifted to a nongraded response. Together, these re- sults demonstrate that accrued reproductive assets influence the threat-sensitive behavioral deci- sions of prey, but only under conditions of high-ambient predation risk.

关键词： asset protection antipredator behavior fitness trade-offs ecological uncertainty chemical alarm cues.

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Study of disorder in pulsed laser deposited double perovskite oxides by first-principle structure prediction

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npj Computational Materials 2021年第1期7卷 826-833页

作者： Edoardo Fertitta Sujit Das Debalina banerjee Farbod Ebrahimi Clément barraud Kai Du He Tian chris J.Pickard Cedric Weber Ramamoorthy Ramesh Peter Littlewood David Dubbink Happy Electron Ltd. LondonUnited Kingdom Department of Materials Science and Engineering University of CaliforniaBerkeleyCAUSA Department of Physics King’s College LondonLondonUnited Kingdom laboratoire Matériaux et Phénomènes Quantiques UMR 7162Universitéde ParisCNRSParisFrance Center of Electron Microscopy School of Materials Science and EngineeringZhejiang UniversityHangzhouChina Department of Materials Science and Metallurgy CambridgeUnited Kingdom Advanced Institute for Materials Research Tohoku UniversitySendaiJapan Department of Physics James Franck InstituteUniversity of ChicagoChicagoILUSA

Double perovskite oxides,with generalized formula A_(2)bb'O_(6),attract wide interest due to their multiferroic and charge transfer *** offer a wide range of potential applications such as spintronics and electrically tunable ***,great practical limitations are encountered,since a spontaneous order of the b-site cations is notoriously hard to *** this joint experimental-theoretical work,we focused on the characterization of double perovskites la2TiFeO6 and la_(2)VCuO_(6) films grown by pulsed laser deposition and interpretation of the observed b-site disorder and partial charge transfer between the b-site ions.A random structure sampling method was used to show that several phases compete due to their corresponding configurational *** order to capture a representative picture of the most relevant competing microstates in realistic experimental conditions,this search included the potential formation of non-stoichiometric phases as well,which could also be directly related to the observed partial charge *** optimized the information encapsulated in the potential energy landscape,captured via structure sampling,by evaluating both enthalpic and entropic *** terms were employed as a metric for the competition of different *** approach,applied herein specifically to la_(2)TiFeO_(6),highlights the presence of highly entropic phases above the ground state which can explain the disorder observed frequently in the broader class of double perovskite oxides.

关键词： laser double structure

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Establishment of Geomagnetic Observatories in Pakistan and Repeat Station Results from Northern Part of Pakistan

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Journal of Earth Science and Engineering 2013年第1期3卷 42-49页

作者： Madeeha Ashfaque Ghulam Murtaza Jean Rasson chris Turbitt Pakistan Space and Upper Atmosphere Research Commission Karachi 75270 Pakistan Royal Meteorological Institute of belgium Dorbes B-5670 Belgium british Geological Survey Edinburgh EH9 3LA UK

A geomagnetic observatory was established at Karachi （geog coord： 24.95°N, 167.14° E）, Pakistan in 1983 which comprised of AMOS-Ⅲ （Automatic Magnetic Observatory System）. In 2006 SUPARCO （Space and Upper Atmosphere Research Commission） planned to upgrade the old observatory of Karachi in order to qualify it as an IMO （Intermagnet Magnetic Observatory）. Dr. Jean Rasson agreed to give support and assist us in the upgradation. bGS （british Geological Survey） provided a complete observatory instrument setup. Due to perturbations traceable to the increased urbanization, the observatory has been shifted to a site ＂Sonmiani＂, 80 km north-west of Karachi, where long term protection from cultural noise is offered. This site in a sparsely built research complex was selected after a magnetic survey. A new observatory has also been established at Islamabad （geog cord： 33.75° N, 72.87° E） which is mountainous region. SUPARCO purchased new equipment for the establishment of new observatories. Plan of upgradation of observatory at Quetta is also under consideration in order to improve the monitoring of geomagnetic field on the western part of Pakistan. Repeat station work has been done for the northern part of Pakistan with the collaboration of IRM, belgium. The obtained results also compared with the global geomagnetic model （IGRF）.

关键词： Pakistan geomagnetic observatory Karachi repeat station survey.

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Carbon and Nitrogen Mineralisation of a Lixisol in South Sudan Zone of burkina Faso

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Agricultural Sciences 2023年第11期14卷 1547-1560页

作者： Abdramane Sanon Alain P. K. Gomgnimbou Kalifa Coulibaly Fidele K. Zongo Tièro-Wè chris Julius Dabire Wilfiried Sanou Hassan b. Nacro Centre National de la Recherche Scientifique et Technologique (CNRST) Institut de l’Environnement et de Recherche Agricole (INERA) Laboratoire Sol-Eau-Plante (SEP) Station de Farako-Ba Bobo-Dioulasso Burkina Faso laboratoire d’étude et de recherche sur la fertilité du sol (LERF) Institut du Développement Rural (IDR) Université Nazi Boni Bobo-Dioulasso Burkina Faso Centre universitaire de Tenkodogo Université Thomas Sankara Ouagadougou Burkina Faso Unité de Formation et de Recherches en Sciences de la Vie et de laTerre Université Joseph KI-Zerbo Ouagadougou Burkina Faso

In today’s environment where agriculture needs to produce sustainably, local fertilizer resources must be encouraged to achieve multiple crop performance and environmental goals. The purpose of this study was to investigate the effects of combined inputs of biowaste and inorganic fertilisers on the mineralization of carbon and nitrogen of a Lixisol under continuous upland rice growing conditions. To this end, agronomic trials were set up in 2018 and 2019, using a Fisher randomized complete block design with 6 treatments and four replications at Farako-ba research station. The treatments were: T1 (Control), T2 (NPK + Urea), T3 (7500 kgha of Chicken droppings);T4 (7500 kg/ha of chicken droppings + 100 kg/ha of urea);T5 (7500 kg/ha of chicken droppings + 500 kg/ha of burkina Phosphate);T6 (7500 kg/ha of chicken droppings + 500 kg/ha of burkina Phosphate + 100 kg/ha of urea). Highest respirometry was observed in treatments T3, T4 and T6 and treatment T4 significantly increased the mineralization coefficient by 15% after 21 days of incubation. T4 and T6 resulted in increases in ammonium ion of 74.15% and 100%, respectively, compared to the control. Likewise, treatments T4 and T6 resulted in a significant increase in nitrate ion of 104.83 and 103.25%, respectively. biowaste combined with inorganic fertilizers may have a capacity to improve the availability of leachate nutrients under upland rice conditions.

关键词： bio-Waste Rice Carbone Nitrogen and Mineralisation

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Therapeutic Routes of a Group of Heart Failure Patients Followed in a Cameroonian Urban Setting

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World Journal of Cardiovascular Diseases 2023年第10期13卷 686-700页

作者： chris Nadège Nganou-Gnindjio bâ Hamadou Melissa Djuidje Djampouop Marie Ntep Gwet Félicité Kamdem Pierre Mintom Juliette Valerie Ndobo Siddikatou Djibrilla Guillaume Ebene Manon Joel Noutackdie Tochie Samuel Kingue Faculty of Medicine and biomedical Sciences University of Yaoundé 1 Yaoundé Cameroon Institut Supérieur des Sciences de la Santé Université des Montagnes Bangangte Cameroon Faculty of Medicine and Pharmaceuticals Sciences University of Douala Douala Cameroon Faculty of Health Sciences University of Buea Buea Cameroon

background: Heart failure (HF) is a rising global health problem. Patients with HF tend to use several therapies obtained via different treatment routes to relieve their symptoms. It is rampant in sub-Saharan Africa (SSA), leading to poor health-seeking behaviours and worsened HF health outcomes. We aimed to describe the different therapeutic routes of HF patients from the onset of their first symptom until treatment in a specialised cardiology centre to identify and rebuke harmful therapeutic routes. Materials and Methods: This was a cross-sectional study at the Yaoundé Central Hospital in Cameroon between December 2018 to July 2019. Patients were recruited by consecutive convenient sampling. Adult patients aged above 18 years with confirmed HF were included using the Framingham criteria. Variables relating to socio-demographic and clinical data and the health-seeking behaviours of HF patients were studied. Results: We included 132 patients with a mean age of 62.90 years (62.88% women). Very few patients (0.90%) followed an ideal route;60.71% of subjects had a pseudo-ideal route, 19.64% accessed a specialised facility directly, and 21.42% used an erratic route. At the arrival time in a cardiology unit, 49.24% and 35.61% of our subjects were in NYHA stage III and IV HF compared to 15.15% for stage II. None of them was in Stage I. Conclusion: Most heart failure patients in Cameroon have resorted to non-specialised care, which worsens their clinical presentation. There is an urgent need for health education of HF patients in our context.

关键词： Heart Failure Therapeutic Care Route Cameroon

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Converting antimicrobial into targeting peptides reveals key features governing protein import into mitochondria and chloroplasts

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Plant Communications 2023年第4期4卷 99-116页

作者： Oliver D.Caspari Clotilde Garrido chris Olaw Yves Choquet Francis-Andre´Wollman Ingrid lafontaine UMR7141(CNRS/Sorbonne Universite´) Institut de Biologie Physico-Chimique13 Rue Pierre et Marie Curie75005 ParisFrance Centre for Microscopy and Cellular Imaging Biology Department Loyola Campus of Concordia University7141 Sherbrooke W.Montre´alQC H4B 1R6Canada Present address:Department of Microbiology Institut Pasteur28 Rue Docteur Roux75015 ParisFrance Present address:UMR7238(CNRS/Sorbonne Universite´) Institut de Biologie Paris-SeineSorbonne Jussieu 7-9 quai Saint Bernard75005 ParisFrance

We asked what peptide features govern targeting to the mitochondria versus the chloroplast,using antimicrobial peptides as a starting *** approach was inspired by the endosymbiotic hypothesis that organelle-targeting peptides derive from antimicrobial amphipathic peptides delivered by the host cell,to which organelle progenitors became *** explore the molecular changes required to convert antimicrobial into targeting peptides,we expressed a set of 13 antimicrobial peptides in Chlamydomonas *** were systematically modified to test distinctive features of mitochondrion-and chloroplast-targeting peptides,and we assessed their targeting potential by following the intracellular localization and maturation of a Venus fluorescent reporter used as a cargo *** targeting can be achieved by some unmodified antimicrobial peptide *** to both organelles is improved by replacing lysines with *** targeting is enabled by the presence of flanking unstructured sequences,additional constraints consistent with chloroplast endosymbiosis having occurred in a cell that already contained *** indeed targeting peptides evolved from antimicrobial peptides,then required modifications imply a temporal evolutionary scenario with an early exchange of cationic residues and a late acquisition of chloroplast-specific motifs.

关键词： antimicrobial peptide Chlamydomonas reinhardtii endosymbiotic organellogenesis presequence targeting peptide transit peptide

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Recent advances and applications of deep learning methods in materials science

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npj Computational Materials 2022年第1期8卷 548-573页

作者： Kamal Choudhary brian DeCost Chi Chen Anubhav Jain Francesca Tavazza Ryan Cohn Cheol Woo Park Alok Choudhary Ankit Agrawal Simon J.L.billinge Elizabeth Holm Shyue Ping Ong chris Wolverton Materials Science and Engineering Division National Institute of Standards and TechnologyGaithersburgMD20899USA Theiss Research La JollaCA92037USA DeepMaterials LLC Silver SpringMD20906USA Material Measurement Science Division National Institute of Standards and TechnologyGaithersburgMD20899USA Department of NanoEngineering University of California San DiegoSan DiegoCA92093USA Energy Technologies Area Lawrence Berkeley National LaboratoryBerkeleyCAUSA Department of Materials Science and Engineering Carnegie Mellon UniversityPittsburghPA15213USA Department of Materials Science and Engineering Northwestern UniversityEvanstonIL60208USA Department of Electrical and Computer Engineering Northwestern UniversityEvanstonIL60208USA Department of Applied Physics and Applied Mathematics and the Data Science Institute Fu Foundation School of Engineering and Applied SciencesColumbia UniversityNew YorkNY10027USA

Deep learning(DL)is one of the fastest-growing topics in materials data science,with rapidly emerging applications spanning atomistic,image-based,spectral,and textual data *** allows analysis of unstructured data and automated identification of *** recent development of large materials databases has fueled the application of DL methods in atomistic prediction in *** contrast,advances in image and spectral data have largely leveraged synthetic data enabled by high-quality forward models as well as by generative unsupervised DL *** this article,we present a high-level overview of deep learning methods followed by a detailed discussion of recent developments of deep learning in atomistic simulation,materials imaging,spectral analysis,and natural language *** each modality we discuss applications involving both theoretical and experimental data,typical modeling approaches with their strengths and limitations,and relevant publicly available software and *** conclude the review with a discussion of recent cross-cutting work related to uncertainty quantification in this field and a brief perspective on limitations,challenges,and potential growth areas for DL methods in materials science.

关键词： learning limitations textual

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FAIR Principles:Interpretations and Implementation Considerations

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Data Intelligence 2020年第1期2卷 10-29,293-302,322页

作者： Annika Jacobsen Ricardo de Miranda Azevedo Nick Juty Dominique batista Simon Coles Ronald Cornet Melanie Courtot Merce Crosas Michel Dumontier chris T.Evelo Carole Goble Giancarlo Guizzardi Karsten Kryger Hansen Ali Hasnain Kristina Hettne Jaap Heringa Rob W.W.Hooft Melanie Imming Keith G.Jeffery Rajaram Kaliyaperumal Martijn GKersloot christine R.Kirkpatrick Tobias Kuhn Ignasi labastida barbara Magagna PeterMcQuilton Natalie Meyers Annalisa Montesanti Mirjam van Reisen Philippe Rocca-Serra Robert Pergl Susanna-Assunta Sansone Luiz Olavo bonino da Silva Santos Juliane Schneider George Strawn Mark Thompson Andra Waagmeester Tobias Weigel Mark D.Wilkinson Egon L.Willighagen Peter Wittenburg Marco Roos barend Mons Erik Schultes Leiden University Medical Center Leiden2333 ZAThe Netherlands Institute of Data Science Maastricht UniversityUniversiteitssingel 60Maastricht 6229 ERThe Netherlands Department of Computer Science The University of ManchesterOxford RoadManchester M139PLUK Oxford e-Research Centre Department of Engineering SciencesUniversity of OxfordOxford OX13PJUK School of Chemistry Faculty of Engineering and Physical SciencesUniversity of SouthamptonSO171BJUK Amsterdam UMC University of AmsterdamAmsterdam 1000 GGThe Netherlands European bioinformatics Institute(EMbL-EbI) HinxtonCambridgeCB101SDUK Harvard University CambridgeMassachusetts 02138USA Department of bioinformatics–biGCaT NUTRIMMaastricht UniversityMaastricht 6229 ERThe Netherlands Conceptual and Cognitive Modeling Research Group(CORE) Free University of Bozen-BolzanoBolzano 39100Italy Aalborg University Aalborg DK-9220Denmark Insight Centre for Data Analytics National University of Ireland GalwayH91 TK33Ireland Centre for Digital Scholarship Leiden University LibrariesLeiden2333 ZAThe Netherlands Department of Computer Science Vrije Universiteit AmsterdamDe Boelelaan 11051081 HV AmsterdamThe Netherlands Dutch Techcentre for Life Sciences(DTL) UtrechtThe Netherlands SURF Utrecht 3511 EPThe Netherlands Keith G Jeffery Consultants FaringdonUK Castor EDC Paasheuvelweg 25Wing 5D1105 BPAmsterdamThe Netherlands San Diego Supercomputer Center University of California San DiegoLa JollaCalifornia 92093USA Learning and Research Resources Centre(CRAI) Universitat de Barcelona08007 BarcelonaSpain Environment Agency Austria A-1090 ViennaAustria University of Notre Dame 75004 ParisFrance Health Research board(HRb) Dublin 2DO2 H638Ireland Liacs Institute of Advanced Computer Science Leiden University2311 GJ LeidenThe Netherlands Czech Technical University in Prague Faculty of Information Technology(FIT CTU)16000 Prague 6Czech Republic GO FAIR International Support&Coordination Office(GFISCO) LeidenThe Netherlands Harvard Catalys

The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in *** intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital *** has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR ***,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible ***,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-*** introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR *** self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the ***,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.

关键词： FAIR guiding principles FAIR implementation FAIR convergence FAIR communities choices and challenges

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Apple whole genome sequences:recent advances and new prospects

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Horticulture Research 2019年第1期6卷 1247-1270页

作者： Cameron P.Peace Luca bianco Michela Troggio Eric van de Weg Nicholas P.Howard Amandine Cornille Charles-Eric Durel Sean Myles ZoëMigicovsky Robert J.Schaffer Evelyne Costes Gennaro Fazio Hisayo Yamane Steve van Nocker chris Gottschalk Fabrizio Costa David Chagné Xinzhong Zhang Andrea Patocchi Susan E.Gardiner Craig Hardner Satish Kumar Francois laurens Etienne bucher Dorrie Main Sook Jung Stijn Vanderzande Department of Horticulture Washington State UniversityPullmanWA 99164USA Computational biology Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Department of Genomics and biology of Fruit Crops Fondazione Edmund MachSan Michele all’AdigeTN 38010Italy Plant breeding Wageningen University and ResearchWageningen 6708PBThe Netherlands Department of Horticultural Science University of MinnesotaSt.PaulMN 55108USA Institut für biologie und Umweltwissenschaften Carl von Ossietzky Universität26129 OldenburgGermany GQE-Le Moulon Institut National de la Recherche AgronomiqueUniversity of Paris-SudCNRSAgroParisTechUniversitéParis-Saclay91190 Gif-sur-YvetteFrance Institut National de la Recherche Agronomique Institut de Recherche en Horticulture et SemencesUMR 134549071 BeaucouzéFrance Department of Plant Food and Environmental SciencesFaculty of AgricultureDalhousie UniversityTruroNS B2N 5E3Canada The New Zealand Institute for Plant and Food Research Ltd Motueka 7198New Zealand School of biological Sciences University of AucklandAuckland 1142New Zealand AGAP INRACIRADMontpellier SupAgroUniversity of MontpellierMontpellierFrance Plant Genetic Resources Unit USDA ARSGenevaNY 14456USA laboratory of Pomology Graduate School of AgricultureKyoto UniversityKyoto 606-8502Japan Department of Horticulture Michigan State UniversityEast LansingMI 48824USA The New Zealand Institute for Plant and Food Research Ltd(Plant&Food Research) Palmerston North Research CentrePalmerston North 4474New Zealand College of Horticulture China Agricultural University100193 BeijingChina Agroscope 8820 WädenswilSwitzerland Queensland Alliance of Agriculture and Food Innovation University of QueenslandSt Lucia 4072Australia New Cultivar Innovation Plant and Food ResearchHavelock North 4130New Zealand Agroscope 1260 ChanginsSwitzerland

In 2010,a major scientific milestone was achieved for tree fruit crops:publication of the first draft whole genome sequence(WGS)for apple(Malus domestica).This WGS,v1.0,was valuable as the initial reference for sequence information,fine mapping,gene discovery,variant discovery,and tool development.A new,high quality apple WGS,GDDH13 v1.1,was released in 2017 and now serves as the reference genome for *** the past decade,these apple WGSs have had an enormous impact on our understanding of apple biological functioning,trait physiology and inheritance,leading to practical applications for improving this highly valued *** gene identities for phenotypes of fundamental and practical interest can today be discovered much more ***-wide polymorphisms at high genetic resolution are screened efficiently over hundreds to thousands of individuals with new insights into genetic relationships and ***-density genetic maps are constructed efficiently and quantitative trait loci for valuable traits are readily associated with positional candidate genes and/or converted into diagnostic tests for *** understand the species,geographical,and genomic origins of domesticated apple more precisely,as well as its relationship to wild *** WGS has turbo-charged application of these classical research steps to crop improvement and drives innovative methods to achieve more durable,environmentally sound,productive,and consumer-desirable apple *** review includes examples of basic and practical breakthroughs and challenges in using the apple *** for“what’s next”focus on necessary upgrades to the genome sequence data pool,as well as for use of the data,to reach new frontiers in genomics-based scientific understanding of apple.

关键词： breakthrough hundreds frontier

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培美曲塞加铂类联合或不联合帕博利珠单抗对初治转移性非鳞状NSCLC患者的疗效与安全性分析：KEYNOTE-189研究方案指定的最终分析

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中国肺癌杂志 2022年第6期25卷 443-456页

作者：周彩存 Delvys RODRíGUEZ-AbREU S.F.POWELL M.J.HOCHMAIR S.GAD GEEL E.ESTEbAN E.FELIP G.SPERANZA F.De ANGELIS M.DóMINE S.Y.CHENG H.G.bISCHOFF N.PELED M.RECK R.HUI E.b.GARON M.bOYER T.KURATA J.YANG M.C.PIETANZA F.SOUZA M.C.GARASSINO 同济大学附属上海市肺科医院肿瘤科 Medical Oncology Complejo Hospitalario Universitario Insular Materno-Infantil de Gran CanariaUniversidad de Las Palmas de Gran Canaria Oncology Sanford Health 4. Department of Respiratory and Critical Care MedicineKarl Landsteiner Institute of Lung Research and Pulmonary Oncology Thoracic Oncology Karmanos Cancer InstituteWayne State University Department of Medical Oncology Hospital Universitario Central de Asturias Medical Oncology Department Vall d'Hebron UniversityVall d'Hebron Institute of Oncology (VHIO) 8. Centre Integre de Cancerologie de la MontérégieH?pital Charles-Le Moyne 9. Medical Oncology DepartmentHospital Universitario Fundacidn Jiménez DiazIIS-FJD Sunnybrook Health Sciences Centre Thoraxklinik Heidelberg Department of Oncology Shaare Zedek Medical Center LungenClinic Airway Research Center NorthGerman Center for Lung Research Department of Medical Oncology Westmead Hospital and University of Sydney Department of Medicine David Geffen School of Medicine at UCLA Department of Medical Oncology Chris O'Brien Lifehouse Department of Thoracic Oncology Kansai Medical University Hospital Merck & Co. Inc. Fondazione IRCCS Istituto Nazionale dei Tumori University of Chicago Medicine & biological Sciences Knapp Center for Biomedical Discovery

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的总生存期(over... 详细信息

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)。本研究报告了研究方案指定的最终分析的疗效结局,包括从培美曲塞-铂类交叉至帕博利珠单抗治疗的患者,以及完成35个周期(约2年)帕博利珠单抗治疗组的疗效。方法符合条件的患者以2:1随机分配至帕博利珠单抗,每3周一次,200 mg (n=410)或安慰剂(n=206)(共35周期,约2年),加上4个周期的培美曲塞(500 mg/m~2)和由研究者选择的每3周顺铂(75 mg/m~2)或卡铂(曲线下面积5 mg/min/mL)治疗,随后使用培美曲塞直至疾病进展。若符合纳入标准,分配至安慰剂联合培美曲塞加铂类治疗的患者可在疾病进展时转向帕博利珠单抗治疗。主要研究终点为OS和PFS。结果中位随访31.0个月,无论PD-L1的表达水平如何,与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类治疗可使患者的OS[风险比(hazard ratio,HR)为0.56;95%可信区间(confidence interval,CI) 0.46-0.69]和PFS (HR=0.49;95%CI:0.41-0.59)显著获益。接受帕博利珠单抗联合培美曲塞-铂类治疗的患者客观缓解率(objective response rate,ORR)(48.3%vs 19.9%)和第二次/后续无进展生存期(PFS2;HR=0.50;95%CI:0.41-0.61)均得到改善。安慰剂联合培美曲塞-铂类组的84例患者(40.8%)交叉至帕博利珠单抗治疗组。72.1%的接受帕博利珠单抗联合培美曲塞-铂类的患者和66.8%的接受安慰剂联合培美曲塞-铂类的患者发生了3级-5级不良事件。56例患者完成了35个周期(约2年)的帕博利珠单抗治疗;ORR为85.7%,53例(94.6%)患者存活至数据截止时间。结论与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类可持续提高疗效,且安全性可控。该研究结果支持将帕博利珠单抗联合培美曲塞-铂类作为初治转移性非鳞状NSCLC患者的一线治疗方案。

关键词：帕博利珠单抗化疗非鳞状非小细胞肺癌

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