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Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDnA

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Cancer Biology & Medicine 2021年第3期18卷 875-887页

作者： Anjie Zhu Peng Yuan nanlin Hu Mingzhou Li Wenmiao Wang Xue Wang Jian Yue Jiayu Wang Yang Luo Fei Ma Pin Zhang Qing Li Binghe Xu Shanbo Cao Giuseppe Lippi Yoichi naito Mohammed A.Osman gustavo n.marta Gianluca Franceschini Armando Orlandi Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of BreastOncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of VIP Medical Services National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Acorn Med Biotechnology Co. Ltd.Beijing 101102China Section of Clinical Biochemistry University Hospital of VeronaVeronaVerona 37100Italy Department of Breast and Medical Oncology National Cancer Center Hospital EastKashiwa 277-8577Japan Clinical Oncology General Organization for Teaching HospitalsCairo 11435Egypt Department of Radiation Oncology Hospital Sírio-LibanêsSao Paulo 01308-050Brazil Multidisciplinary Breast Center Fondazione Policlinico Universitario A.Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00176Italy Unit of Medical Oncology Fondazione Policlinico Universitario A.Gemelli IRCCSRoma 00176Italy

Objective:Apatinib is an oral TKI targeting ***-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m *** vinorelbine also holds promise as a treatment of choice in patients with m *** study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m *** addition,we detected gene variants in ct DnA to explore the therapeutic ***:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/*** were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was *** secondary endpoints were ORR,CBR,OS,and *** eligible for ct DnA detection were evaluated before and during ***:Forty patients were *** median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and *** 20 patients,ct DnA was detected at baseline and during treatment.A significant difference was found in PFS for undetected *** baseline ct DnA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity *** with no gene variant detected and lower variant allele frequencies in ct DnA at baseline showed longer PFS.

关键词： Metastatic breast cancer apatinib oral vinorelbine ct DnA

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Insights into adsorbent tortuosity across aqueous adsorption systems

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Particuology 2024年第5期88卷 71-88页

作者： Ackmez Mudhoo marta Otero Khim Hoong Chu Department of Chemical and Environmental Engineering Faculty of EngineeringUniversity of MauritiusRéduit 80837Mauritius Department of Applied Chemistry and Physics Universidad de LeónCampus de Vegazana 24071 LeónSpain Department of Chemical Engineering Faculty of EngineeringUniversity of MalayaKuala Lumpur 50603Malaysia

Pore network,pore connectivity,and the resulting effective adsorbate pore diffusivity within an adsorbent are critical physical considerations in mass transport modeling of aqueous *** to these three adsorbent features are the adsorbent tortuosity and tortuosity factor *** concepts encompass the collective hindrance to intra-adsorbent adsorbate transport arising because of a disorderly adsorbent porous *** is crucial for materials scientists,chemists,chemical engineers,and water treatment specialists to understand the complex and variable connections among adsorbate chemistry,adsorbent chemistry,adsorbent porosity,pore shape,size,and tortuosity,pore wall effect,adsorbate-adsorbent interactions,and adsorbate-adsorbate interactions in competitively contaminated aqueous *** tortuosity has been sporadically studied in aqueous adsorption *** the small population of these studies,insightful observations and inferences have been ***,as it appears,no review has been published to compile,compare,and contrast these ***,this review concisely brings up those observations and interpretations around adsorbent tortuosity for aqueous adsorption *** notion of an adsorbent's tortuosity being single-valued is argued to be ***,perspectives are aired on possible research and development directions for elucidating the dynamic attributes of adsorbent tortuosity and applying them in real-scale adsorption-oriented water *** data acquired by filling in these research gaps can enable the design of adsorbents more adapted for real-scale water purification.

关键词： Adsorbent Tortuosity Porosity Pore diffusion models Aqueous systems

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High CO_(2)permeation using a new Ce_(0.85)Gd_(0.15)O_(2-δ)-LaniO_(3)composite ceramic–carbonate dual-phase membrane

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Journal of Environmental Sciences 2024年第6期140卷 219-229页

作者： Daniela González-Varela JFrancisco Gómez-García gustavo Tavizon Heriberto Pfeiffer Instituto de Investigaciones en Materiales Universidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico Departamento de Física y Química Teórica Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico 不详

This work shows the synthesis,characterization and evaluation of dense-ceramic membranes made of Ce_(0.85)Gd_(0.15)O_(2-δ)-LaniO_(3)(CG-Ln)composites,where the fluorite-perovskite ratio(CG:Ln)was varied as follows:75:25,80:20 and 85:15 wt.%.Supports were initially characterized by XRD,SEM and electrical conductivity(using vacuum and oxygen atmospheres),to determine the composition,microstructural and ionic-electronic conductivity ***,supports were infiltrated with an eutectic carbonates mixture,producing the corresponding dense dual-phase membranes,in which CO_(2)permeation tests were ***,CO_(2)permeation experiments were performed from 900 to 700℃,in the presence and absence of oxygen(flowed in the sweep membrane side).Results showed that these composites possess high CO_(2)permeation properties,where the O_(2)addition significantly improves the ionic conduction on the sweep membrane ***,the GC80-Ln20 composition presented the best results due to the following physicochemical characteristics:high electronic and ionic conductivity,appropriate porosity,interconnected porous channels,as well as thermal and chemical stabilities between the composite support and carbonate phases.

关键词： CO_(2)permeation Doped CeO_(2) LaniO_(3) Impedance Ceramic carbonate membrane

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Annual variation of adult survival of a south-temperate House Wren population in Argentina

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Avian Research 2024年第2期15卷 229-237页

作者： gustavo J.Fernandez Mariana E.Carro Paulo E.Llambías Grupo de Investigacion en Ecofisiología de Fauna Silvestre INIBIOMA-CONICETAsentamiento Universitario San Martín de los Andes(AUSMA)Universidad Nacional Del ComahuePasaje de la Paz 235(8370)San Martín de los AndesNeuquenArgentina Grupo de Investigacion de Biología de Aves IADIZA CCT-MendozaUniversidad Nacional de CuyoAvenida RuizLeal s/n Parque General San Martin5500MendozaArgentina

Identifying factors affecting the survival of individuals is essential for understanding the evolution of life-history traits and population *** numerous studies on this subject in north-temperate environments,there is a lack of equivalent studies at similar latitudes in the ***,we used a 14-year dataset of capture,banding,and resighting to estimate the annual variation in the apparent adult survival probability of a south-temperate population of House Wrens(Troglodytes aedon bonariae).We evaluated temporal variation in sur-vival and the effect of environmental(climatic)and demographic variables(adult abundance,total number of fledglings produced during each breeding season)on survival *** found that the probability of adult survival decreased as the abundance of breeding adults *** density-dependent effect could be related to the resident lifestyle of southern House Wrens,which could determine an intense competition for territories and resources that ultimately would affect their survival.

关键词： Annual variation CJS Density-dependence Survival Troglodytes aedon bonariae

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Seasonal variation and host sex affect bat–bat fly interaction networks in the Amazonian savannahs

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Integrative Zoology 2024年第3期19卷 400-416页

作者： Paulo MEJIA gustavo Lima URBIETA Bruna da Silva XAVIER IsaíJorge de CASTRO JoséJúlio DE TOLEDO gustavo GRACIOLLI Lucio AndréVIAnA DIAS William Douglas CARVALHO Programa de Pós-Graduação em Biodiversidade Tropical Universidade Federal do Amapá(UNIFAP)MacapáAPBrazil Programa de Pós-Graduação em Ecologia Instituto de BiologiaCentro de Ciências da SaúdeUniversidade Federal do Rio de Janeiro(UFRJ)Rio de JaneiroRJBrazil Laboratório de Mamíferos Instituto de Pesquisas Científicas e Tecnológicas do Estado do Amapá(IEPA)MacapáAPBrazil Programa de Pós-Graduação em Biologia Animal Laboratório de SistemáticaEcologia e Evolução(LSEE)Instituto de BiociênciasUniversidade Federal de Mato Grosso do Sul(UFMS)Campo GrandeMTBrazil Terrestrial Ecology Group(TEG-UAM) Departamento de EcologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Centro de Investigación en Biodiversidad y Cambio Global(CIBC-UAM) Universidad Autónoma de MadridMadridSpain

Bats are the second-most diverse group of mammals in the world,and bat flies are their main ***,significant knowledge gaps remain regarding these antagonistic interactions,especially since diverse factors such as seasonality and host sex can affect their network ***,we explore the influence of such factors by comparing species richness and composition of bat flies on host bats,as well as specialization and modularity of bat–bat fly interaction networks between seasons and adult host *** captured bats and collected their ectoparasitic flies at 10 sampling sites in the savannahs of AmapáState,northeastern region of the Brazilian *** female bats being more parasitized and recording greater bat fly species richness in the wet season,neither relationship was statistically *** pooled network could be divided into 15 compartments with 54 links,and all subnetworks comprised>12 *** total number of links ranged from 27 to 48(for the dry and wet seasons,respectively),and female and male subnetworks had 44 and 41 links,*** values were very low for the pooled network and for all *** results revealed higher bat fly species richness and abundance in the wet season,whereas specialization and modularity were higher in the dry ***,the subnetwork for female bats displayed higher specialization and modularity than the male ***,both seasonality and host sex contribute in different ways to bat–bat fly network *** studies should consider these factors when evaluating bat–bat fly interaction networks.

关键词： Amapá Amazon biome bat flies bats interaction networks

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neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CnRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine n-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRnAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRnAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRnA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DnA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRnAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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neural Regeneration Research 2024年第3期19卷 542-547页

作者： María norte-Muñoz David García-Bernal Diego García-Ayuso Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical *** stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and *** studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional ***,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous ***,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura nadal marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i neurobiologia(UHneurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75nTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene navarro-Lobato Mariam Masmudi-Martín Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-Romero marta Carretero-Rey Sinforiano Posadas María E.Quiros-Ortega Zafar U.Khan Laboratory of neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de Enfermedades neurodegenerativas(CIBERnED) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for *** till now,all potential drug candidates have failed to produce satisfa ctory ***,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of *** this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s ***,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDnF).A knockdown of BDnF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM *** findings suggest that BDnF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s ***,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

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A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors(PPARCS)

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Journal of Sport and Health Science 2024年第1期13卷 81-89页

作者： Sarah J.Hardcastle Chloe Maxwell-Smith Vinicius Cavalheri Terry Boyle marta Leyton Román Cameron Platell Michael Levitt Christobel Saunders Frank Sardelic Sophie nightingale Jacob McCormick Craig Lynch Paul A.Cohen Max Bulsara Dana Hince Sport and Physical Activity Research Centre Sheffield Hallam UniversitySheffieldS102BPUK Institute for Health Research The University of Notre DameFremantleWA 6959Australia Curtin School of Population Health Curtin UniversityPerthWA 6845Australia Curtin School of Allied Health Curtin UniversityPerthWA 6845Australia Allied Health South Metropolitan Health ServiceMurdochWA 6150Australia Australian Centre for Precision Health University of South AustraliaAdelaideSA 5001Australia Department of Didactics of Musical Plastic and Body ExpressionUniversity of ExtremaduraCaceres 10071Spain St.John of God Subiaco Hospital PerthWA 6008Australia Department of Surgery University of MelbourneMelbourneVIC 3010Australia Tamara Private Hospital TamworthNSW 2340Australia Peter MacCallum Cancer Centre MelbourneVIC 3000Australia College of Health and Medicine Australian National UniversityCanberraACT 2600Australia Division of Obstetrics and Gynaecology Medical SchoolUniversity of Western AustraliaPerthWA 6009Australia

Background:Physical activity(PA)is important for cancer *** of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer *** objective of this study was to ascertain whether wearable technology,coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in ***:Cancer survivors from 5 states were randomized to intervention and control *** participants were given a Fitbit Charge 2TMand received up to 6 telephone health coaching *** participants received PA print *** assessments at baseline and 12 weeks measured moderate-to-vigorous PA(MVPA),light PA,and sedentary ***:Eighty-seven participants were recruited(age=63±11 years;74(85%)female).There was a significant net improvement in MVPA of 49.8 min/week,favoring the intervention group(95%confidence interval(95%CI):13.6-86.1,p=0.007).There was also a net increase in MVPA bouts of 39.5 min/week(95%CI:11.9-67.1,p=0.005),favoring the intervention *** groups improved light PA and sedentary behavior,but there were no between-group ***:This’s the first study to demonstrate that,when compared to standard practice(i.e.,PA education),a wearable technology intervention coupled with distance-based health coaching,improves MVPA in non-metropolitan cancer *** results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

关键词： Behavior change Exercise Health disparities Oncology Wearable technology

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