| 221. |
- Moore, Steven C., et al.
(författare)
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Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults
- 2016
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Ingår i: JAMA Internal Medicine. - : AMER MEDICAL ASSOC. - 2168-6106 .- 2168-6114. ; 176:6, s. 816-825
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES Incident cancer during follow-up. RESULTS A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.
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| 222. |
- Morimoto, Akihiro, et al.
(författare)
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A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis
- 2012
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 198, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- n yeasts and worms, KASH (Klarsicht/ANC-1/Syne/ homology) domain and SUN (Sad-1/UNC-84) domain nuclear envelope (NE) proteins play a crucial role in meiotic chromosome movement and homologue pair-ing. However, although the vertebrate SUN domain pro-tein SUN1 is involved in these processes, its partner has remained identified. Based on subcellular localiza-tion screening in mouse spermatocytes, we identified a novel germ cell-specific protein, KASH5, that localized exclusively at telomeres from the leptotene to diplotene stages in both spermatocytes and oocytes. KASH5 pos-sesses hitherto unknown KASH-related sequences that directly interacted with SUN1 and mediated telomere loca-lization. Thus, KASH5 is a mammalian meiosis-specific KASH domain protein. We show that meiotic chromo-some movement depended on microtubules and that KASH5 interacted with the microtubule-associated dynein-dynactin complex. These results suggest that KASH5 connects the telomere-associated SUN1 protein to the cytoplasmic force-generating mechanism involved in meiotic chromosome movement. Our study strongly sug-gests that the meiotic homologue-pairing mechanism mediated by the SUN-KASH NE bridge is highly con-served among eukaryotes. © 2012 Morimoto et al.
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| 223. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 224. |
- Nik-Zainal, Serena, et al.
(författare)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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| 225. |
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| 226. |
- Oei, L., et al.
(författare)
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Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
- 2014
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 59, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fracture applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5 x 10(-8). In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 x 10(-8). However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% Cl: 0.98-1.14; p = 0.17), displaying high degree of heterogeneity (I-2= 57%; Q(het)p = 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. (C) 2013 Elsevier Inc. All rights reserved.
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| 227. |
- Oh, Jiyeon, et al.
(författare)
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Hand and Oral Hygiene Practices of South Korean Adolescents Before and During the COVID-19 Pandemic
- 2023
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Importance Only a few studies have examined the long-term trends of hand and oral hygiene, especially among adolescents.Objective To investigate the 15-year trends in frequency of handwashing and toothbrushing and examine the factors associated with hand and oral hygiene, particularly during the COVID-19 pandemic.Design, Setting, and Participants This cross-sectional study, performed from January 1, 2008, to December 31, 2022, used general population-based data from 963 644 individuals in a national representative survey (Korea Youth Risk Behavior Web-based Survey [KYRBS]).Exposure COVID-19 pandemic.Main Outcomes and Measures Trends in hand and oral hygiene practices were measured by how frequently adolescents washed their hands and whether they fulfilled the recommended guidelines for toothbrushing. An interrupted time series analysis using linear and logistic regression models was performed to assess any associations with the COVID-19 pandemic. Hand and oral hygiene behaviors before and during the pandemic in each sociodemographic subgroup were also compared.Results In the 963 644 adolescents (495 697 [51.4%] male; mean [range] age, 15.01 [12-18] years) who participated in the KYRBS from 2008 to 2022, a 73.3% (95% CI, 59.4%-97.4%; P < .001) immediate increase was seen in overall hand hygiene behavior at the onset of the COVID-19 pandemic compared with the prepandemic period, with a sustained decrease thereafter (beta = -0.018; 95% CI, -0.022 to -0.015; P < .001). Meanwhile, no immediate increase was observed in terms of overall oral hygiene behavior (0.1%; 95% CI, -0.9% to 1.1%; P = .82); however, there was a sustained decrease during the pandemic (beta = -0.018; 95% CI, -0.020 to -0.016; P < .001). Older age, female sex, nonsmoking status, alcohol use, low household economic level, and poor school performance were significantly associated with poor hand hygiene during the pandemic.Conclusions and Relevance In this cross-sectional study of South Korean adolescents, an increase in the prevalence of hand hygiene was observed during the early pandemic; however, this prevalence decreased over time. Meanwhile, the decrease in the prevalence of oral hygiene was more pronounced during the pandemic. This study recommends stronger guidelines for adolescent health coaches, such as teachers or public health advisers, regarding hygiene behaviors, even after the COVID-19 pandemic ends.
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| 228. |
- Oh, Min Kyo, et al.
(författare)
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Effect of CaF2 on Phosphorus Refining from Molten Steel by Electric Arc Furnace Slag using Direct Reduced Iron (DRI) as a Raw Material
- 2020
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Ingår i: Metallurgical and materials transactions. B, process metallurgy and materials processing science. - : Springer. - 1073-5615 .- 1543-1916.
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Tidskriftsartikel (refereegranskat)abstract
- The effect of CaF2 addition on dephosphorization reaction between molten steel and electric arc furnace (EAF) slag using direct reduced iron (DRI) at 1823 K (1550 °C) was investigated. Basicity, the thermodynamic parameter affecting the removal capacity of phosphorus (i.e., phosphate capacity), decreased using DRI due to an increased SiO2 concentration in the slag. To minimize slag volume and maximize dephosphorization efficiency, the CaF2 was added to the slag. As CaF2 content increased (0 to 10 mass pct), dephosphorization efficiency also increased. Thermodynamic analysis in conjunction with slag structural studies using Raman spectroscopy were conducted to explain the complicated phenomena. The results exhibited that even 5 to 6 mass pct CaF2 can improve the dephosphorization efficiency when DRI is used as raw material in an EAF process.
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| 229. |
- Orlando, Ludovic, et al.
(författare)
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Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
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| 230. |
- Park, Hyean Yeol, et al.
(författare)
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Fabrication of binder-free pencil-trace electrode for lithium-ion battery : Simplicity and high performance
- 2016
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:18, s. 4415-4423
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Tidskriftsartikel (refereegranskat)abstract
- (Graph Presented) A binder-free and solvent-free pencil-trace electrode with intercalated clay particles (mainly SiO2) is prepared via a simple pencil-drawing process on grinded Cu substrate with rough surface and evaluated as an anode material for lithium-ion battery. The pencil-trace electrode exhibits a high reversible capacity of 672 mA h g-1 at 100 mA g-1 after 100 cycles, which can be attributed to the unique multilayered graphene particles with lateral size of few micrometers and the formation of LixSi alloys generated by interaction between Li+ and an active Si produced in the electrochemical reduction of nano-SiO2 in the clay particles between the multilayered graphene particles. The multilayered graphene obtained by this process consists of 1 up to 20 and occasionally up to 50 sheets and thus can not only help accommodating the volume change and alleviating the structural strain during Li ion insertion and extraction but also allow rapid access of Li ions during charge-discharge cycling. Drawing with a pencil on grinded Cu substrate is not only very simple but also cost-effective and highly scalable, easily establishing graphitic circuitry through a solvent-free and binder-free approach.
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