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Engineered Regeneration 2024年第2期5卷 255-268页

作者： Hadi Hajiali jane McLaren Cristina Gonzalez-García Salah Abdelrazig Dong-Hyun Kim Matthew j.Dalby Manuel Salmerón-Sánchez Felicity R.A.j.rose School of Pharmacy Nottingham Biodiscovery InstituteUniversity of NottinghamNottinghamUK Healthcare Technologies Institute School of Chemical EngineeringUniversity of BirminghamBirminghamUK Centre for the Cellular Microenvironment University of GlasgowGlasgowUK Centre for Analytical Bioscience Advanced Materials&Healthcare Technologies DivisionSchool of PharmacyUniversity of NottinghamNottinghamUK Marine Microbiomics Program in BiologyDivision of Science and MathematicsNew York University Abu Dhabi(NYUAD)P.O.Box 129188Abu DhabiUnited Arab Emirates

Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe ***,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor *** study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone *** study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive *** into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways *** gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC *** adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic *** study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone *** adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.

关键词： Adenosine release Osteogenic signalling pathways Human mesenchymal stromal cells Bone regeneration

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Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee j Dufault Katherine M Adler David O Carpenter steven G Gilbert Raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their *** may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics *** To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food *** The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ***-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)*** test group participated in the six-week online nutritional epigenetics tutorial,while the control group did *** efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention *** intake scores were derived for both ultra-processed and whole/organic *** sample t-tests were conducted to determine any differences in mean diet scores within each *** There was a significant difference in the diet scores of the test group between the pre-and post-intervention *** parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

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A glycine-rich nuclear effector VdCE51 of Verticillium dahliae suppresses plant immune responses by inhibiting the accumulation of GhTRXH2

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The Crop journal 2024年第4期12卷 1137-1149页

作者： Chi Li Yingqi Huang Wenjing Shang jieyin Chen steven j.Klosterman Krishna V.Subbarao jun Qin Xiaoping Hu State Key Laboratory of Crop Stress Resistance and High-Efficiency Production Key Laboratory of Plant Protection Resources and Pest Management of Ministry of EducationKey Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural AffairsCollege of Plant ProtectionNorthwest A&F UniversityYangling 712100ShaanxiChina State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Western Agricultural Research Center Chinese Academy of Agricultural SciencesChangji 831100XinjiangChina Agricultural Research Service United States Department of AgricultureSalinasCA 93905USA Department of Plant Pathology University of CaliforniaDavisc/o United States Agricultural Research StationSalinasCA 93905USA

Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash *** of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A glycine-rich nuclear effector,VdCE51,was able to suppress immune responses in tobacco against Botrytis cinerea and Sclerotinia *** effector was a required factor for full virulence of ***,and its nuclear localization was a requisite for suppressing plant *** thioredoxin GhTRXH2,identified as a positive regulator of plant immunity,was a host target of *** findings show a virulence regulating mechanism whereby the secreted nuclear effector VdCE51 interferes with the transcription of PR genes,and the SA signaling pathway by inhibiting the accumulation of GhTRXH2,thus suppressing plant immunity.

关键词： Verticillium dahliae Plant immunity Effector Thioredoxin

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Constraints on what controls millennial-scale basin-wide denudation across mountain belts, Asia

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Science China Earth Sciences 2024年

作者： Ye YANG steven A.BINNIE Sheng XU Cong-Qiang LIU Tibor j.DUNAI Institute of Surface-Earth System Science School of Earth System Science Tianjin University Institute of Geology and Mineralogy University of Cologne

The terrestrial cosmogenic nuclide dataset consisting of 123310Be measurements of fluvial sediment samples across the Asian mountain belts is used to constrain the influence of climate,tectonics and topography on Earth-surface denudation processes.10Be-derived basin-wide denudation rates were recalculated using a Monte Carlo simulation approach that relied on pixel-by-pixel production *** rates derived span four orders of magnitude,from 7.4±0.7 mm kyr-1（1σ;Central Tibetan Plateau） to 9,646+777744mm kyr-1（1σ;Southern Tibetan Plateau）,with a median of 186 mm *** our results with the traditional basin-wide production rate scaling model using a centroid coordinate and mean elevation,suggests that 96.6%of production rates will be underestimated using the latter method,especially for basins with a large *** bias between both methods reaches as large as 40%,caused by basin hypsometry and the nonlinear scaling of production rate with elevation and *** of the correlations between uniformly recalculated denudation rates and tectonics,climate,topography,and rock lithology will facilitate the extrapolation of denudation rates in unknown basins using available *** the perspective of local scales,precipitation coupled with neotectonics-driven landslides is likely the most influential factor in subtropical Taiwan Island,while topography primarily constrains surface denudation rates in the eastern Tibetan Plateau within a narrow range of *** highland regions with glacier coverage,such as the Pamir,central and southern Tibetan Plateau,high denudation rates are affected by glaciation,whereas lower precipitation and high erosion base level may limit river incision and evolving relief in the Central Tibetan *** contrast to local-scale findings highlighting a dominant factor constraining denudation rate,our large-scale quantitative analyses across the Asian mountain belts finds that （1） topographic metrics including

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K jacobs steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy j Kendall David A Dorward jonathan A Fallowfield Peter C Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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亚洲高山流域千年尺度地表剥蚀的制约因素

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中国科学:地球科学 2024年

作者：杨业 steven A.BINNIE 徐胜刘丛强 Tibor j.DUNAI 天津大学地球系统科学学院表层地球系统科学研究院 Institute of Geology and Mineralogy University of Cologne

本研究利用前人1233个亚洲高山流域沉积物宇宙成因核素10Be数据统一计算了地表剥蚀速率,以约束构造、气候和地形如何影响和控制地表剥蚀过程.基于高程数据逐个像元的核素产率,使用蒙特卡洛模拟方法重新计算了10Be流域剥蚀速率.剥蚀速率... 详细信息

本研究利用前人1233个亚洲高山流域沉积物宇宙成因核素10Be数据统一计算了地表剥蚀速率,以约束构造、气候和地形如何影响和控制地表剥蚀过程.基于高程数据逐个像元的核素产率,使用蒙特卡洛模拟方法重新计算了10Be流域剥蚀速率.剥蚀速率变化范围从（7.4±0.7）mm ka-1（1σ;青藏高原内部）到(9,646744+777)mm ka-1（1σ;青藏高原南部）跨四个数量级,中位数为186mm ka-1.逐个像元计算的核素产率与传统模型使用质心坐标和平均高程计算的核素产率相比,后者96.6%核素产率被低估,其中高程差越大越被低估.两种方法计算的产率偏差可达40%,究其原因可能是流域高程分布不均和核素产率随海拔和纬度呈非线性变化.通过量化地表剥蚀速率与构造、气候、地形和岩性之间的相关性将有助于推演未知流域的剥蚀速率.从局部小尺度分析,亚热带台湾岛地区剥蚀速率可能主要受降水和新构造驱动的山体滑坡影响,而降水变化范围较窄的青藏高原东部的剥蚀速率主要受控于地形;冰川覆盖的高原地区剥蚀速率受冰川作用影响,如帕米尔、青藏高原内部和南部地区;青藏高原内部剥蚀速率较低是因为较低的降水和较高的侵蚀基准面,从而限制了河流的下切和地表起伏度演化.与局部小尺度强调单一主控因素不同,本研究对亚洲高山流域宏观大尺度进行量化分析发现:（1）地形指标（包括坡度、地形起伏度和河道陡峭指数）与剥蚀速率在千年尺度呈现一致的幂函数关系,而非简单线性;（2）剥蚀速率与气候（包括与海拔相关的降水、温度和植被覆盖度）和新构造活动（地震核密度分布）呈近似幂函数关系,为次要控制因素;（3）岩性与剥蚀速率没有明显的相关性,可能受限于流域复杂的岩性混合和低分辨率的可侵蚀指数数据.

关键词： Be剥蚀速率气候变化构造抬升地形梯度亚洲高山流域

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Clathrin light chains negatively regulate plant immunity by hijacking the autophagy pathway

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Plant Communications 2024年第8期5卷 172-188页

作者： Hu-jiao Lan jie Ran Wen-Xu Wang Lei Zhang Ni-Ni Wu Ya-Ting Zhao Min-jun Huang Min Ni Fen Liu Ninghui Cheng Paul A.Nakata jianwei Pan steven A.Whitham Barbara j.Baker jian-Zhong Liu Zhejiang Provincial Key Laboratory of Biotechnology on Specialty Economic Plants Zhejiang Normal UniversityJinhua 321004China Institute of Plant Genetics and Developmental Biology College of Chemistry and Life SciencesZhejiang Normal UniversityJinhua 321004China College of Life Sciences Lanzhou UniversityLanzhou 730000China Department of Plant Pathology and Microbiology Iowa State UniversityAmesIA 50011USA Department of Plant and Microbial Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA Plant Gene Expression Center U.S.Department of Agriculture-Agricultural Research ServiceAlbanyCA 94706USA Lushan Botanical Garden Chinese Academy of SciencesJiujiang 332000China U.S.Department of Agriculture-Agricultural Research Service Children’s Nutrition Research CenterDepartment of PediatricsBaylor College of MedicineHoustonTX 77030USA

The crosstalk between clathrin-mediated endocytosis(CME)and the autophagy pathway has been reported in mammals;however,the interconnection of CME with autophagy has not been established in ***,we report that the Arabidopsis CLATHRIN LIGHT CHAIN(CLC)subunit 2 and 3 double mutant,clc2-1 clc3-1,phenocopies Arabidopsis AUTOPHAGY-RELATED GENE(ATG)mutants in both autoimmunity and nutrient ***,the autophagy pathway is significantly compromised in the clc2-1 clc3-1 ***,multiple assays demonstrate that CLC2 directly interacts with ATG8h/ATG8i in a domain-specific *** expected,both GFP-ATG8h/GFP-ATG8i and CLC2-GFP are subjected to autophagic degradation,and degradation of GFP-ATG8h is significantly reduced in the clc2-1 clc3-1 ***,simultaneous knockout of ATG8h and ATG8i by CRISPR-Cas9 results in enhanced resistance against Golovinomyces cichoracearum,supporting the functional relevance of the CLC2-ATG8h/8i *** conclusion,our results reveal a link between the function of CLCs and the autophagy pathway in Arabidopsis.

关键词： autophagy clathrin light chain immunity clathrin-mediated endocytosis senescence cell death

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MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity,Memory,and Social Behavior

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Neuroscience Bulletin 2024年第7期40卷 887-904页

作者： Xuehui Wang Donghui Lin jie jiang Yuhua Liu Xinyan Dong jianchen Fan Lifen Gong Weida Shen Linghui Zeng Tonghui Xu Kewen jiang steven A.Connor Yicheng Xie School of Life Sciences Nanchang UniversityNanchang330031China Department of Neurology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Biology York University4700 Keele StreetTorontoON M3J 1P3Canada Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China

Synapse organizers are essential for the development,transmission,and plasticity of *** as rare synapse suppressors,the MAM domain containing glycosylphosphatidylinositol anchor(MDGA)proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex.A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with ***,MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory *** the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective *** address this,we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal *** we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature *** deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials,vesicular glutamate transporter 1 intensity,and neuronal *** effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter ***,evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic *** a behavioral level,memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired,consistent with deficits in long-term potentiation in the CA3-CA1 *** affiliation,a behavioral analog of social deficits in autism,was similarly *** results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits,thereby optimizing this network for plasticity,c

关键词： MDGA2 CA1 pyramidal neurons Glutamatergic inputs Synaptic plasticity Memory Social behaviors Autism Synapse organizers

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Discovery and evaluation of a novel 18F-labeled vasopressin 1a receptor PET ligand with peripheral binding specificity

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4014-4027页

作者： junqi Hu Yinlong Li Chenchen Dong Huiyi Wei Kai Liao junjie Wei Chunyu Zhao Ahmad Chaudhary jiahui Chen Hao Xu Ke Zhong steven HLiang Lu Wang Weijian Ye Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine&Key Laboratory of Basic and Translational Research on Radiopharmaceuticalsthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Radiology and Imaging Sciences Emory UniversityAtlant1GA 30322USA Department of Pharmacy Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

The arginine-vasopressin(AVP)hormone plays a pivotal role in regulating various physiological processes,such as hormone secretion,cardiovascular modulation,and social *** studies have highlighted the V1a receptor as a promising therapeutic ***-depth insights into V1a receptor-related pathologies,attained through in vivo imaging and quantification in both peripheral organs and the central nervous system(CNS),could significantly advance the development of effective V1a *** address this need,we develop a novel V1a-targeted positron emission tomography(PET)ligand,[18F]V1A-2303([18F]8),which demonstrates favorable in vitro binding affinity and selectivity for the V1a *** tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies,autoradiography,biodistribution ***,[18F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity,whole-body distribution,and kinetic *** research indicated[18F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs,and as a foundational element for the development of next-generation,brain-penetrant ligands specifically designed for the CNS.

关键词： Vasopressin Autism V1a receptor Positron emission tomography PET imaging Radiolabeling Fluorine 18 Kinetic modeling

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael j.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick steven P.Hooker Humberto Parada jr. john Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

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