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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** Department of cancer epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China Metabolic epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight changecancer(HR_(cancer)=1.12,95%CI:1.03-1.21,P=0.009),and heart disease(HR_(Heart diseases)=1.21,95%CI:1.11-1.31,Pcancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,Pcancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality cancer Stroke Heart diseases Body mass index

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Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

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Chinese Medical Journal 2024年第8期137卷 980-989页

作者： Zhiyuan Fan Jing Zhou Yuan Tian Yu Qin Zhaojun Liu Liankun Gu Sanford M.Dawsey Wenqiang Wei Dajun Deng national Central cancer Registry 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(MOE/Beijing) Division of EtiologyPeking University Cancer Hospital and InstituteBeijing 100142China division of cancer epidemiology and genetics National Cancer InstituteBethesdaMDUSA Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell ***,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is *** study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)***:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to *** DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy *** cumulative regression and progression rates of ESCdys were evaluated using competing risk ***:A total of 205 patients with baseline m/M ESCdys were *** proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A ***2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable ***:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

关键词： Somatic copy number variations Esophageal squamous cell carcinoma Esophageal neoplasms Squamous intraepithelial lesions DNA copy number variations Prognosis Prospective study

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EZH2 is a prognostic factor associated with tumor stemness and immune infiltration in skull base chordoma

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Genes & Diseases 2024年第5期11卷 85-87页

作者： Qian Liu Mingxuan Li Yujia Xiong Yutao Shen Tianshun Ma Tianhao Zhang Xiaohong R.Yang Yazhuo Zhang Jiwei Bai Beijing Neurosurgical institute Capital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China division of cancer epidemiology and genetics National Cancer InstituteNIHDHHSBethesdaMD 20892USA

Enhancer of zeste homolog 2(EZH2),an epigenetic regulator that inhibits transcription primarily through trimethylation of Lys-27 in histone 3(H3K27me3),has been reported to play an important role in the regulation of cell cycle,autophagy,and apoptosis,and DNA damage repair.1 EZH2 is highly expressed in a variety of cancers including prostate cancer,breast cancer,and renal clear cell carcinoma,and is associated with adverse prognosis.1 Moreover,it has been reported that EZH2 might increase tumor stemness and metastasis capacity and inhibit antitumor immunity by affecting T cells,NK cells,macrophages,and immune checkpoints.2,3 However,the prognostic value and the mechanism of EZH2 have not been investigated in *** this study,RNA sequencing and whole genome sequencing data based on 48 skull base chordomas as well as immunohistochemistry of paraffin sections were analyzed to elucidate the role of EZH2 in skull base *** found copy number gain mediated high EZH2 expression is associated with tumor stemness,M2 macrophage infiltration,and adverse prognosis in ***,we demonstrated that EZH2 promotes the proliferation,migration,and invasion of chordoma cells in in vitro cell experiments.

关键词： EZH2 immunity invasion

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of cancer Biology and genetics and Comprehensive cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

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贫困所致传染病(英文) 2024年第3期13卷 1-15页

作者： Mohan Malu Thangaraj Jeromie W. V. Pandey Sumit Priya G. Sri Lakshmi Arunachalam Sivavallinathan Sharma Rahul Shewade Hemant Deepak Aishwarya B. Afeeq K. Khatoon Afsana Gokulvijay B. Sireesha Gude Chandra Kavita Nandhakumar S. Samuel Prince Viswanathan C. Nanditha Shanmugasundaram Devika Rao Raghuram Murhekar Manoj V. Jeyashree Kathiresan Indian Council of Medical Research-national institute of epidemiology R-127 TNHB Ayapakkam Chennai Tamil Nadu India TB Support Network WHO Country Office for India New Delhi India Central Tuberculosis division Government of India New Delhi India

Background Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY *** We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the national Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical *** Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and *** The optimal utilization of NPY is enabled by strong political commitment and

关键词： national Tuberculosis Elimination Programme Nutritional status Direct benefit transfer Ni-kshay Poshan Yojana Implementation Cash transfer scheme Grounded theory India

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Structure of a histone hexamer bound by the chaperone domains of SPT16 and MCM2

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Science China(Life Sciences) 2024年第6期67卷 1305-1307页

作者： Songlin Gan Wen-Si Yang Liting Wei Zhiguo Zhang Rui-Ming Xu Key Laboratory of Epigenetic Regulation and Intervention Institute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Life Sciences University of Chinese Academy of SciencesBeijing 100049China institute for cancer genetics Department of Pediatrics and Department of Genetics and DevelopmentColumbia University Irving Medical CenterNew York 10032USA School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin ***... 详细信息

关键词： structure nucleosome passage

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Unveiling the distinctive traits of functional rye centromeres:minisatellites, retrotransposons, and R-loop formation

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Science China Life Sciences 2024年第9期67卷 1989-2002页

作者： Chang Liu Shulan Fu Congyang Yi Yang Liu Yuhong Huang Xianrui Guo Kaibiao Zhang Qian Liu James A.Birchler Fangpu Han State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Plant genetics and Breeding Sichuan Agricultural University division of Biological Science University of Missouri

Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments. Despite their conserved functionality, centromeric DNA sequences exhibit rapid evolution, presenting diverse sizes and compositions across species. The functional significance of rye centromeric DNA sequences, particularly in centromere identity, remains unclear. In this study, we comprehensively characterized the sequence composition and organization of rye centromeres. Our findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs) and interspersed minisatellites. We systematically classified LTR-RTs into five categories, highlighting the prevalence of younger CRS1, CRS2, and CRS3 of CRSs(centromeric retrotransposons of Secale cereale) were primarily located in the core centromeres and exhibited a higher association with CENH3 nucleosomes. The minisatellites, mainly derived from retrotransposons, along with CRSs, played a pivotal role in establishing functional centromeres in rye. Additionally, we observed the formation of R-loops at specific regions of CRS1, CRS2, and CRS3, with both rye pericentromeres and centromeres exhibiting enrichment in R-loops. Notably, these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres, suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere specification. Our work provides insights into the DNA sequence composition, distribution, and potential function of R-loops in rye centromeres. This knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres, offering implications for the development of synthetic centromeres in future plant modifications and beyond.

关键词： centromere LTR-RTs minisatellite rye R-loop

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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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