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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

Volatile organic compounds emitted by Megaplatypus mutatus associated fungi: chemical identification and temperature-modulated responses by the ambrosial beetle

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ecological Processes 2024年第2期 3-15页

作者： esteban D.Ceriani-Nakamurakare Mariel Slodowicz Cecilia Carmarán Paola Gonzalez-Audino Instituto de Micología y Botánica (INMi Bo) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Departamento de Ingeniería Agrícola y Uso de la Tierra Facultad de Agronomía Universidad de Buenos Aires (UBA) Centro de Investigaciones de Plagas e Insecticidas (CIPeIN) Unidad de Investigación y Desarrollo Estratégico Para la Defensa (UNIDEF) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Departamento de Biodiversidad y Biología experimental (DBBe) Facultad de Ciencias Exactas y Naturales (FCEy N) Universidad de Buenos Aires (UBA)

Background In ambrosia and bark beetles–fungi interaction, volatile organic compounds(VOCs) play a central role in mediating various aspects of community dynamics of beetles and/or fungi. These functions include facilitating beetle habitat location, mate identification, and fungal partner differentiation. However, the understanding on this context remains limited, especially in the globally distributed subfamily Platypodinae, which comprises predomi-nantly ambrosia beetles. There is a lack of chemical data on ambrosia fungi from native South American species. This study addresses this gap by characterizing VOCs from twelve fungal species associated with Megaplatypus mutatus and assessing species-specific behavioral responses during *** Fungal VOCs were collected by gas chromatography–mass spectrometry combined with solid-phase microextraction and Y-olfactometry assays of males and females were performed at dispersal stage. Statistical analyses involved: non-metric multidimensional scaling multivariate plot and PeRMANOVA test, a cluster analysis through unweighted pair group method with Jaccard index, and finally, a chi-square goodness-of-fit test for beetle behavioral *** We identified 72 VOCs from the fungal species isolated from M. mutatus galleries, exocuticle, and gut. The olfactory behavior of M. mutatus demonstrated its capacity to discriminate between volatile profiles, showing a pref-erence for either the fungus or the control source. Our results also enhance the understanding in a chemotaxonomic context and in the behavioral responses of M. mutatus revealing the beetle's remarkable low temperature toler-ance and its capability to maintain mobility and orientation toward volatile sources even after zero-degree Celsius *** This study presents a comprehensive insight into fungal VOC profiles, emphasizing the sources of isola-tion within pest associated fungi, as well as its symbiotic species from the Raffaelea genus. In

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Photosynthetic Gas exchange and Nitrogen Assimilation in Green Bean Plants Supplied with Two Sources of Silicon

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Phyton-International Journal of experimental Botany 2024年第5期93卷 963-980页

作者： Julio C.Anchondo-Páez esteban Sánchez Carlos A.Ramírez-estrada Alondra Salcido-Martínez erick H.Ochoa-Chaparro Department of Plant Physiology Centro de Investigación en Alimentación y DesarrolloCiudad Delicias33089México

Beans contain a wide range of vitamins,proteins,calcium,and zinc which make them an important food source for many *** meet the demand for bean production worldwide,large amounts of fertilizers and pesticides are ***,the cost of production and environmental impact *** produce food sustainably,the use of beneficial nutrients such as silicon as a biostimulant has been ***,information about the effect of different sources of silicon on the metabolism of bean plants is *** plants *** were grown in pots for 60 days and the effect of foliar application of silicon nanoparticles and the silicon-based biostimulant Codasilat 4 concentrations(0,1,2,and 4 mM)on total biomass,yield,photosynthetic pigment concentration,photosynthetic activity,stomatal conductance,transpiration rate,chlorophyll fluorescence,and nitrogen assimilation were *** results obtained showed that the supply of silicon at a dose of 1 mM functioned as a biostimulant,favoring gas exchange and nitrogen assimilation within the plant,which stimulated growth and *** results of this research work allowed a better comprehension of the effects of silicon application through silicon nanoparticles and the biostimulant Codasilon the physiology of green bean plants.

关键词： Nanoparticles silicon Phaseolus vulgaris L.

Deep optics preconditioner for modulation-free pyramid wavefront sensing

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Photonics Research 2024年第2期12卷 301-312页

作者： FeLIPe GUZMÁN JORGe TAPIA CAMILO WeINBeRGeR NICOLÁS HeRNÁNDeZ JORGe BACCA BeNOIT NeICHeL esteban VeRA School of electrical engineering Pontificia Universidad Católica de Valparaı´soValparaı´soChile Department of Systems engineering Universidad Industrial de SantanderBucaramangaColombia Laboratoire d’Astrophysique de Marseille MarseilleFrance

The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).However,its exquisite sensitivity has a limited linear range of operation,or dynamic range,although it can be extended through the use of beam modulation—despite sacrificing sensitivity and requiring additional optical *** by artificial intelligence techniques,this work proposes to train an optical layer—comprising a passive diffractive element placed at a conjugated Fourier plane of the pyramid prism—to boost the linear response of the pyramid sensor without the need for cumbersome *** develop an end-2-end simulation to train the diffractive element,which acts as an optical preconditioner to the traditional least-square modal phase estimation *** results with a large range of turbulence conditions show a noticeable improvement in the aberration estimation performance equivalent to over 3λ∕D of modulation when using the optically preconditioned deep PWFS(DPWFS).experimental results validate the advantages of using the designed optical layer,where the DPWFS can pair the performance of a traditional PWFS with 2λ∕D of *** and adding an optical preconditioner to the PWFS is just the tip of the iceberg,since the proposed deep optics methodology can be used for the design of a completely new generation of wavefront sensors that can better fit the demands of sophisticated adaptive optics applications such as ground-to-space and underwater optical communications and imaging through scattering media.

关键词： process optics pyramid

Disparate outcomes in Hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: Large cohort study

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World Journal of Diabetes 2024年第5期15卷 886-897页

作者： Joseph Matthew Gosnell George Golovko esteban Arroyave Akshata Moghe Michael L Kueht Omar AbdulSaldarriaga Kevin H McKinney Heather L Stevenson Monique R Ferguson Department of Pathology University of Texas Medical BranchGalvestonTX 77555United States Department of Pharmacology&Toxicology University of Texas Medical BranchGalvestonTX 77555United States Department of Medicine University of Texas Health Science Center at HoustonHoustonTX 77030United States Department of Surgery University of Texas Medical BranchGalvestonTX 77555United States Center for Tropical Diseases Department of Internal MedicineUniversity of Texas Medical BranchGalvestonTX 77555United States Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient ***,these conditions seem to have disparate rates and outcomes between different ethnic *** combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South *** To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic *** This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations *** cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast *** This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino *** mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB *** This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Hispanic Diabetes mellitus TriNetX Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatotic liver disease Hepatocellular carcinoma

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent e.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CReB3L1(rs72910057-T,P=5.40e−09)and GCM1(rs1491489378-T,P=3.16e−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35e−13)and FTO(P=2.11e−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45e−03).Novel MRI-PDFF genetic signals(CReB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

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Journal of Sport and Health Science 2024年第2期13卷 133-144页

作者： María Rodriguez-Ayllon Patricio Solis-Urra Cristina Arroyo-ávila Miriam álvarez-Ortega Pablo Molina-García Cristina Molina-Hidalgo Manuel Gómez-Río Belinda Brown Kirk I.erickson Irene.esteban-Cornejo Department of epidemiology Erasmus University Medical Center RotterdamRotterdamGD 3015the Netherlands Department of Physical education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18071Spain Faculty of education and Social Sciences Universidad Andres BelloVina del Mar 2531015Chile Department of Nuclear Medicine Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Physical Medicine and Rehabilitation Service Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Department of Psychology University of PittsburghPittsburghPA 15260USA Centre for Healthy Ageing Health Futures InstituteMurdoch UniversityMurdochWA 6150Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Advent Health Research Institute Neuroscience Institute OrlandoOrlandoFL 32803USA Physiopathology of Obesity and Nutrition Research Center(CIBeRobn) Institute of Health Carlos Ⅲ(ISCⅢ)Madrid 28029Spain

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels *** aimed to explore the relationship between physical activity and Aβin middle-aged and older ***:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,*** were eligible if they included physical activity and Aβdata in adults aged 45 years or ***-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ***:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and *** physical activity was positively associated with Aβonly in the CSF(estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older ***,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included *** observational studies,higher levels of physical activity were positively associated with Aβonly in ***,further research is needed t

关键词： Aging Cognitive impairment Dementia exercise PeT

Understanding the Link:emotional Attention in Italian Families and Children’s Social Development

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International Journal of Mental Health Promotion 2024年第9期26卷 709-718页

作者： Catalda Corvasce Juan Pedro Martínez-Ramón Francisco Manuel Morales-Rodríguez Lidia Pellicer-García Inmaculada Méndez Cecilia Ruiz-esteban Liceo Statale“Carlo Cafiero” Barletta(BT)76121Italy Department of Developmental Psychology and education University of MurciaMurcia30100Spain Department of Developmental Psychology and education University of GranadaCampus of La CartujaGranadaCP 18071Spain Department of Spanish Language and General Linguistics University of MurciaCampus of La MercedMurciaCP 30001Spain

Background:emotional attention refers to the capacity to recognize and properly respond to one’s and others’emotional *** another note,family is a primary source of socialization that influences the development of various social *** another line,adolescence is a complex stage that has been associated with emotional difficulties that could be related to competences such as prosociability and *** is inferred that through the family context and the attention that is processed,a series of competencies are transmitted to the youngsters,but this relationship is still *** this reason,the study’s purpose was to examine the relationship between the emotional attention of mothers and fathers and the social and prosocial competencies of their ***:To accomplish this,a cross-sectional study and ex post facto design were *** Trait-Meta Mood Scale(TMMS-24)-to assess emotional attention-,the Strengths and Difficulties Questionnaire(SDQ)-to determine the prosociality dimension-,and the Test on Passing Developmental Tasks in Adolescence(TCS-A)-to measure social inclusionwere *** participants were N=228 families composed of n=114 mothers/fathers(67.5%females)and n=114 daughters/sons(38.5%females)selected through non-probabilistic sampling using a convenience sample in the Bari region of Italy.A descriptive and inferential analysis-Student’s test and Pearson’s correlation-was performed with the statistic package SPSS version 28(significance level pesults:The findings showed that the families possessed an adequate background in emotional attention and that their daughters and sons were also generally well-adjusted in social inclusion and *** also found certain signs that the prosocial competence of the children could be related to the behavior of their mothers and ***:In conclusion,social inclusion is related to prosocial behavior,and maybe primarily cultivated within families where paren

关键词： educational style coping strategies stress social inclusion emotional attention prosociality

Simplified seismic scenario analysis of existing masonry buildings accounting for local site effects

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Frontiers of Structural and Civil engineering 2024年第2期18卷 309-318页

作者： Ayşe e.ÖZSOYÖZBAY Işıl SANRI KARAPINAR Zehra N.KUTLU İsmail e.KILIÇ Department of Civil engineering Maltepe UniversityIstanbul 34857Turkey School of engineering and Construction Oryx Universal CollegeDoha 12253Qatar

This study discusses the effects of local sites and hazard amplification on the seismic vulnerability assessment of existing masonry *** this context,a rapid seismic evaluation procedure was implemented on an old masonry building stock in the historical center Galata,located inİstanbul,to determine the seismic risk priority of the built *** scenarios were generated for all soil classes,different moment magnitudes,and source-to-site distances to obtain more accurate results for the seismic vulnerability assessment of the studied building ***,damage distributions estimated under nine different scenarios with/without site effects were compared and illustrated in maps to discuss changes in vulnerability owing to amplification *** this study,by re-examining the rapid seismic evaluation procedure by including geo-hazard-based assessment,the importance of site effects on the vulnerability and risk assessment of built heritage was *** proposed framework integrating field data and local site effects is believed to advance the current applications for vulnerability assessment of masonry buildings and provide an improvement in the application of rapid seismic assessment procedures with more reliable results.

关键词： masonry buildings seismic vulnerability assessment cultural heritage local site effect