• 【人类脱落乳牙干细胞的生物库: 巴西的应用和发展概述。】 复制标题 收藏 收藏
    DOI:10.1159/000506677 复制DOI
    作者列表:Zalaf BR,Bringel M,Jorge PK,de Oliveira B,Tanabe K,Santos CF,Oliveira RC,Rios D,Cruvinel T,Lourenço Neto N,Oliveira TM,Machado MAAM
    BACKGROUND & AIMS: :A biobank is an organized collection of biological human material and its associated information stored for research according to regulations under institutional responsibility, without commercial purposes, being a mandatory and strategical activity for research, regenerative medicine, and innovation. Stem cells have largely been employed in research and frequently stored in biobanks, which have been used as an essential source of biological materials. Stem cells of human exfoliated deciduous teeth (SHED) are stem cells which have a high multipotency and can be easily obtained. Besides, this extremely accessible tissue has advantages with respect to storage, as the SHED obtained in childhood can be used in later life, which implies the necessity for the creation and regulation of biobanks. The proper planning for the creation of a biobank includes knowledge of the material types to be stored, requirements regarding handling and storage conditions, storage time, and room for the number of samples. Thus, this study aimed to establish an overview of the development of a SHED biobank. Ethical and legal standardization, current applications, specific orientations, and challenges for the implementation of a SHED biobank were discussed. Through this overview, we hope to encourage further studies to use SHED biobanks.
    背景与目标: : 生物库是根据机构责任下的法规为研究而存储的生物人类材料及其相关信息的有组织的集合,没有商业目的,是研究,再生医学和创新的强制性和战略性活动。干细胞已广泛用于研究,并经常存储在生物库中,这些生物库已被用作生物材料的重要来源。人脱落的乳牙 (SHED) 的干细胞是具有高多能性且易于获得的干细胞。此外,这种极易接近的组织在存储方面具有优势,因为在童年时期获得的棚子可以在以后的生活中使用,这意味着创建和调节生物库的必要性。创建生物库的适当计划包括要存储的材料类型的知识,有关处理和存储条件的要求,存储时间以及样品数量的空间。因此,本研究旨在概述棚屋生物库的发展。讨论了道德和法律标准化,当前的应用,特定的方向以及实施棚屋生物库的挑战。通过此概述,我们希望鼓励进一步的研究使用棚子生物银行。
  • 【英国生物库社区队列中预测新型冠状病毒肺炎和死亡率的既往合并症。】 复制标题 收藏 收藏
    DOI:10.1093/gerona/glaa183 复制DOI
    作者列表:Atkins JL,Masoli JAH,Delgado J,Pilling LC,Kuo CL,Kuchel GA,Melzer D
    BACKGROUND & AIMS: BACKGROUND:Hospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes, or coronary heart disease, but whether these comorbidities are true risk factors (ie, more common than in the general older population) is unclear. We estimated associations between preexisting diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort. METHODS:UK Biobank (England) participants with baseline assessment 2006-2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and preexisting common diagnoses association tested with hospitalized laboratory-confirmed COVID-19 (March 16 to April 26, 2020), alone or with mortality, in logistic models. RESULTS:Of 269 070 participants aged older than 65, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common comorbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (21.5%), type 2 diabetes (type 2, 19. 9%), and asthma (17.6%). However, in models adjusted for comorbidities, age group, sex, ethnicity, and education, preexisting diagnoses of dementia, type 2 diabetes, chronic obstructive pulmonary disease, pneumonia, depression, atrial fibrillation, and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first 5 remaining statistically significant for related mortality. Chronic kidney disease and asthma were risk factors for COVID-19 hospitalization in women but not men. CONCLUSIONS:There are specific high-risk preexisting comorbidities for COVID-19 hospitalization and related deaths in community-based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.
    背景与目标:
  • 3 Biobank governance: trends and perspectives. 复制标题 收藏 收藏

    【生物库治理: 趋势和前景。】 复制标题 收藏 收藏
    DOI:10.1159/000104446 复制DOI
    作者列表:Gottweis H,Zatloukal K
    BACKGROUND & AIMS: :Biobanks are a challenge and topic for governance. Today, biobanks are identified as a biomedical scientific/infrastructural development that warrants a political/legal/ethical reaction with the goal to integrate biobanks into the preexisting fabric of regulation, medicine, law and society. Biobank governance is always a response to sociocultural challenges and requires the building of trust, acceptance, and careful political negotiation. Biobanks are regulated in networks of governance in which the state is one actor next to others, and the ordering and structuring of the interaction between biobanks, society, and politics operates through a variety of actors, on different levels and along particular rationalities. Such networks of governance reflect, to some extent, a postregulatory state in which governance has become a complicated architecture and field of action involving a multitude of forces and rationalities. Biobank governance is still a relatively new field of political-legal intervention and it will be crucial for the future of biobanks to establish governance regimes that appropriately link research with society and politics.
    背景与目标: : 生物库是治理的挑战和话题。如今,生物库被确定为生物医学科学/基础设施发展,需要政治/法律/伦理反应,其目标是将生物库整合到监管,医学,法律和社会的现有结构中。生物银行治理始终是对社会文化挑战的回应,需要建立信任,接受和认真的政治谈判。生物库在治理网络中受到监管,在该网络中,国家是与其他人相邻的一个行为者,生物库,社会和政治之间相互作用的排序和结构通过各种行为者在不同的层次上以及特定的理性运作。这种治理网络在某种程度上反映了一种后监管状态,在这种状态下,治理已成为涉及多种力量和合理性的复杂体系结构和行动领域。生物银行治理仍然是政治法律干预的一个相对较新的领域,对于生物银行的未来而言,建立将研究与社会和政治适当联系起来的治理制度至关重要。
  • 【挪威母婴队列研究的生物库: 未来100年的资源。】 复制标题 收藏 收藏
    DOI:10.1007/s10654-006-9041-x 复制DOI
    作者列表:Rønningen KS,Paltiel L,Meltzer HM,Nordhagen R,Lie KK,Hovengen R,Haugen M,Nystad W,Magnus P,Hoppin JA
    BACKGROUND & AIMS: INTRODUCTION:Long-term storage of biological materials is a critical component of any epidemiological study. In designing specimen repositories, efforts need to balance future needs for samples with logistical constraints necessary to process and store samples in a timely fashion. OBJECTIVES:In the Norwegian Mother and Child Cohort Study (MoBa), the Biobank was charged with long-term storage of more than 380,000 biological samples from pregnant women, their partners and their children for up to 100 years. METHODS:Biological specimens include whole blood, plasma, DNA and urine; samples are collected at 50 hospitals in Norway. All samples are sent via ordinary mail to the Biobank in Oslo where the samples are registered, aliquoted and DNA extracted. DNA is stored at -20 degrees C while whole blood, urine and plasma are stored at -80 degrees C. RESULTS:As of July 2006, over 227,000 sample sets have been collected, processed and stored at the Biobank. Currently 250-300 sets are received daily. An important part of the Biobank is the quality control program. CONCLUSION:With the unique combination of biological specimens and questionnaire data, the MoBa Study will constitute a resource for many future investigations of the separate and combined effects of genetic, environmental factors on pregnancy outcome and on human morbidity, mortality and health in general.
    背景与目标:
  • 【英国生物库中的表达数量性状基因座衍生分数和白质微结构: 一种整合遗传学和神经影像学的新方法。】 复制标题 收藏 收藏
    DOI:10.1038/s41398-020-0724-y 复制DOI
    作者列表:Barbu MC,Spiliopoulou A,Colombo M,McKeigue P,Clarke TK,Howard DM,Adams MJ,Shen X,Lawrie SM,McIntosh AM,Whalley HC
    BACKGROUND & AIMS: :Expression quantitative trait loci (eQTL) are genetic variants associated with gene expression. Using genome-wide genotype data, it is now possible to impute gene expression using eQTL mapping efforts. This approach can be used to analyse previously unexplored relationships between gene expression and heritable in vivo measures of human brain structural connectivity. Using large-scale eQTL mapping studies, we computed 6457 gene expression scores (eQTL scores) using genome-wide genotype data in UK Biobank, where each score represents a genetic proxy measure of gene expression. These scores were then tested for associations with two diffusion tensor imaging measures, fractional anisotropy (NFA = 14,518) and mean diffusivity (NMD = 14,485), representing white matter structural integrity. We found FDR-corrected significant associations between 8 eQTL scores and structural connectivity phenotypes, including global and regional measures (βabsolute FA = 0.0339-0.0453; MD = 0.0308-0.0381) and individual tracts (βabsolute FA = 0.0320-0.0561; MD = 0.0295-0.0480). The loci within these eQTL scores have been reported to regulate expression of genes involved in various brain-related processes and disorders, such as neurite outgrowth and Parkinson's disease (DCAKD, SLC35A4, SEC14L4, SRA1, NMT1, CPNE1, PLEKHM1, UBE3C). Our findings indicate that eQTL scores are associated with measures of in vivo brain connectivity and provide novel information not previously found by conventional genome-wide association studies. Although the role of expression of these genes regarding white matter microstructural integrity is not yet clear, these results suggest it may be possible, in future, to map potential trait- and disease-associated eQTL to in vivo brain connectivity and better understand the mechanisms of psychiatric disorders and brain traits, and their associated imaging findings.
    背景与目标: : 表达数量性状基因座 (eQTL) 是与基因表达相关的遗传变异。使用全基因组基因型数据,现在可以使用eQTL作图来估算基因表达。这种方法可用于分析基因表达与人类大脑结构连接的可遗传体内测量之间以前未探索的关系。使用大规模eQTL作图研究,我们使用英国生物库中的全基因组基因型数据计算了6457基因表达分数 (eQTL分数),其中每个分数代表基因表达的遗传代理度量。然后测试这些分数与两个扩散张量成像测量的相关性,即分数各向异性 (nfa   =   14,518) 和平均扩散率 (nmd   =   14,485),代表白质结构完整性。我们发现FDR校正了8个eQTL评分与结构连接表型之间的显着关联,包括全局和区域度量 (β 绝对fa   =   0.0339-0.0453; MD  =   0.0308-0.0381) 和单个区域 (β 绝对fa   =   0.0320-0.0561; MD  =   0.0295-0.0480)。据报道,这些eQTL评分中的基因座可以调节与各种脑相关过程和疾病有关的基因的表达,例如神经突生长和帕金森氏病 (DCAKD,SLC35A4,SEC14L4,SRA1,NMT1,CPNE1,PLEKHM1,UBE3C)。我们的研究结果表明,eQTL评分与体内大脑连通性的测量相关,并提供了传统的全基因组关联研究以前未发现的新信息。尽管这些基因的表达对白质微结构完整性的作用尚不清楚,但这些结果表明,将来有可能将潜在的性状和疾病相关的eQTL与体内大脑连接作图,并更好地了解其机制精神疾病和大脑特征,以及他们相关的影像学发现。
  • 【英国生物银行中风险因素关联与具有常规反应率的代表性,基于一般人群的研究的比较: 前瞻性队列研究和个体参与者荟萃分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2020-02-12
    来源期刊:BMJ
    DOI:10.1136/bmj.m131 复制DOI
    作者列表:Batty GD,Gale CR,Kivimäki M,Deary IJ,Bell S
    BACKGROUND & AIMS: OBJECTIVE:To compare established associations between risk factors and mortality in UK Biobank, a study with an exceptionally low rate of response to its baseline survey, against those from representative studies that have conventional response rates. DESIGN:Prospective cohort study alongside individual participant meta-analysis of other cohort studies. SETTING:United Kingdom. PARTICIPANTS:Analytical sample of 499 701 people (response rate 5.5%) in analyses in UK Biobank; pooled data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), including 18 studies and 89 895 people (mean response rate 68%). Both study populations were linked to the same nationwide mortality registries, and the baseline age range was aligned at 40-69 years. MAIN OUTCOME MEASURE:Death from cardiovascular disease, selected malignancies, and suicide. To quantify the difference between hazard ratios in the two studies, a ratio of the hazard ratios was used with HSE-SHS as the referent. RESULTS:Risk factor levels and mortality rates were typically more favourable in UK Biobank participants relative to the HSE-SHS consortium. For the associations between risk factors and mortality endpoints, however, close agreement was seen between studies. Based on 14 288 deaths during an average of 7.0 years of follow-up in UK Biobank and 7861 deaths over 10 years of mortality surveillance in HSE-SHS, for cardiovascular disease mortality, for instance, the age and sex adjusted hazard ratio for ever having smoked cigarettes (versus never) was 2.04 (95% confidence interval 1.87 to 2.24) in UK Biobank and 1.99 (1.78 to 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88 to 1.19). The overall pattern of agreement between studies was essentially unchanged when results were compared separately by sex and when baseline years and censoring dates were aligned. CONCLUSION:Despite a very low response rate, risk factor associations in the UK Biobank seem to be generalisable.
    背景与目标:
  • 【英国生物库中镶嵌染色体Y丢失的预测因素及其与死亡率的关联。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-018-30759-1 复制DOI
    作者列表:Loftfield E,Zhou W,Graubard BI,Yeager M,Chanock SJ,Freedman ND,Machiela MJ
    BACKGROUND & AIMS: :Mosaic loss of the Y chromosome (mLOY) is the most commonly reported large structural somatic event. Previous studies have indicated age and cigarette smoking increase the risk of mLOY, but the relationship of other exposures with mLOY and mLOY with disease has not been adequately investigated. We characterized mLOY in a large cohort of 223,338 men from the UK Biobank by scanning for deviations in genotyping array median log2 intensity ratios (mLRR) of the Y chromosome using a standard algorithm. A total of 3,789 (1.7%) men showed evidence for mLOY (mLRR < -0.15). In multivariable-adjusted logistic regression models, we found that mLOY increases exponentially with age (overall P-value < 4.9 × 10-324; p-value for the quadratic term = 2.1 × 10-7), and observed a strong association with current smoking (P-value = 7.8 × 10-184). We observed less mLOY in men of African ancestry (0.4%) compared to men of European ancestry (1.8%, P-value = 0.003). Although mLOY was not associated with prevalent cancer (P-value = 0.61), associations were observed for diabetes (P-value = 0.003) and cardiovascular disease (P-value = 0.01). Using Cox proportional hazards regression models, mLOY was associated with all-cause mortality among men with a high proportion of cells affected (mLRR < -0.40; HR = 1.35, 95% CI = 1.08-1.70, P-value = 0.009). In conclusion, mLOY was associated with several health-related factors as well as with all-cause mortality. Further functional studies are warranted to understand how and in what way mLOY could influence adult male health.
    背景与目标: : Y染色体的镶嵌丢失 (mLOY) 是最常报道的大型结构体细胞事件。先前的研究表明,年龄和吸烟会增加mLOY的风险,但是尚未充分研究其他与mLOY和mLOY的接触与疾病的关系。我们通过使用标准算法扫描Y染色体的基因分型阵列中值log2强度比 (mLRR) 的偏差,在来自英国生物库的223,338名男性的大型队列中表征了mLOY。共有3,789 (1.7%) 名男性显示出mLOY证据 (mlrr  < -0.15)。在多变量调整logistic回归模型中,我们发现mLOY随年龄呈指数增长 (总体p值  <  4.9  ×   10-324; 二次项的p值   =   2.1  ×   10-7),并观察到与当前吸烟有很强的关联 (p值   =   7.8  ×   10-184)。与欧洲血统的男性相比,我们观察到非洲血统的男性 (0.4%) 的mLOY较少 (1.8%,p值   =   0.003)。尽管mLOY与流行的癌症无关 (p值   =   0.61),但观察到糖尿病 (p值   =   0.003) 和心血管疾病 (p值   =   0.01) 的相关性。使用Cox比例风险回归模型,mLOY与受影响细胞比例高的男性的全因死亡率相关 (mlrr  < -0.40; Hr   =   1.35,95% ci   =   1.08-1.70,p值   =   0.009)。总之,mLOY与多种健康相关因素以及全因死亡率相关。有必要进行进一步的功能研究,以了解mLOY如何以及以何种方式影响成年男性健康。
  • 【更正: 通过一项多中心纵向前瞻性队列研究推进头颈部癌症的跨学科研究: 荷兰生活质量和生物医学队列 (NET-QUBIC) 数据仓库和生物库。】 复制标题 收藏 收藏
    DOI:10.1186/s12885-019-6223-y 复制DOI
    作者列表:Verdonck-de Leeuw IM,Jansen F,Brakenhoff RH,Langendijk JA,Takes R,Terhaard CHJ,Baatenburg de Jong RJ,Smit JH,Leemans CR
    BACKGROUND & AIMS: :Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article.
    背景与目标: : 在原始文章 [1] 发布后,作者报告了R.J. Baatenburg de Jong在文章的HTML版本中被错误标记。
  • 【默认模式节点内的子专业化特征在于10,000英国生物库参与者。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1804876115 复制DOI
    作者列表:Kernbach JM,Yeo BTT,Smallwood J,Margulies DS,Thiebaut de Schotten M,Walter H,Sabuncu MR,Holmes AJ,Gramfort A,Varoquaux G,Thirion B,Bzdok D
    BACKGROUND & AIMS: :The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.
    背景与目标: : 人类默认模式网络 (DMN) 与几种独特的心理能力有关。在这项研究中,我们测试了DMN中大脑范围的区域间交流是否可以从固有活动波动,灰质形态和纤维束解剖结构的群体变异性中得出。在10,000个英国生物库参与者的样本中,模式学习算法揭示了DMN中的功能耦合状态,这些状态与其他宏观大脑网络之间的连通性曲线相关联。此外,DMN灰质体积与fornix的白质微观结构共同变化。总的来说,功能和结构模式掩盖了主要DMN节点内可能的分工: 对于皮质网络相互作用最关键的子区域与处理记忆和位置的海马区的最具预测能力的区域相邻。
  • 【前瞻性多发性硬化生物库样本中的爱泼斯坦-巴尔病毒抗体和维生素d。】 复制标题 收藏 收藏
    DOI:10.1177/1352458513483888 复制DOI
    作者列表:Salzer J,Nyström M,Hallmans G,Stenlund H,Wadell G,Sundström P
    BACKGROUND & AIMS: BACKGROUND:The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction between these two factors has been proposed. OBJECTIVES:The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples. METHODS:Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed. RESULTS:The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1(402-502), and domain EBNA-1(385-420); p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found. CONCLUSIONS:We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.
    背景与目标:
  • 【量化客观测量的体力活动对英国生物库死亡率的预测性能。】 复制标题 收藏 收藏
    DOI:10.1093/gerona/glaa250 复制DOI
    作者列表:Leroux A,Xu S,Kundu P,Muschelli J,Smirnova E,Chatterjee N,Crainiceanu C
    BACKGROUND & AIMS: BACKGROUND:Objective measures of physical activity (PA) derived from wrist-worn accelerometers are compared with traditional risk factors in terms of mortality prediction performance in the UK Biobank. METHODS:A subset of participants in the UK Biobank study wore a tri-axial wrist-worn accelerometer in a free-living environment for up to 7 days. A total of 82,304 individuals over the age of 50 (439,707 person-years of follow-up, 1,959 deaths) had both accelerometry data that met specified quality criteria and complete data on a set of traditional mortality risk factors. Predictive performance was assessed using cross-validated Concordance (C) for Cox regression models. Forward selection was used to obtain a set of best predictors of mortality. RESULTS:In univariate Cox regression, age was the best predictor of all-cause mortality (C=0.681) followed by twelve PA predictors, led by minutes of moderate to vigorous PA (C=0.661) and total acceleration (C=0.661). Overall, 16 of the top 20 predictors were objective PA measures (C from 0.578 to 0.661). Using a threshold of 0.001 improvement in Concordance, the Concordance for the best model that did not include PA measures was 0.735 (9 covariates) compared with 0.748 (12 covariates) for the best model with PA variables (p-value<0.001). CONCLUSIONS:Objective measures of PA derived from accelerometry outperform traditional predictors of all-cause mortality in the UK Biobank except age and substantially improve the prediction performance of mortality models based on traditional risk factors. Results confirm and complement previous findings in the National Health and Nutrition Examination Survey (NHANES).
    背景与目标:
  • 【通过次最大运动测试对全因死亡率评估的心肺健康的预后相关性: 英国生物库前瞻性研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.mayocp.2019.12.030 复制DOI
    作者列表:Laukkanen JA,Kunutsor SK,Yates T,Willeit P,Kujala UM,Khan H,Zaccardi F
    BACKGROUND & AIMS: OBJECTIVE:To investigate whether the inverse associations of cardiorespiratory fitness (CRF) with all-cause and cardiovascular mortality in the general population vary among individuals who are at different levels of pretest risk. PATIENTS AND METHODS:Cardiorespiratory fitness was assessed through submaximal bicycle tests in 58,892 participants aged 40 to 69 years who completed baseline questionnaires between January 1, 2006, and December 31, 2010, in the UK Biobank Prospective Study. Participants were categorized into risk categories, which determined allocation to an individualized bicycle protocol. The groups at minimal risk (category 1), small risk (category 2), and medium risk (category 3) were tested at 50%, 35% of the predicted maximal workload, and constant level, respectively. We investigated associations of CRF with mortality across different levels of pretest risk and determined whether CRF improves risk prediction. RESULTS:During a median follow-up of 5.8 years, 936 deaths occurred. Cardiorespiratory fitness was linearly associated with mortality risk. Comparing extreme fifths of CRF, the multivariable-adjusted hazard ratios (95% CIs) for mortality were 0.63 (0.52-0.77), 0.54 (0.36-0.82), 0.81 (0.46-1.43), and 0.58 (0.48-0.69) in categories 1, 2, and 3 and overall population, respectively. The addition of CRF to a 5-year mortality risk score containing established risk factors was associated with a C-index change (0.0012; P=.49), integrated discrimination improvement (0.0005; P<.001), net reclassification improvement (+0.0361; P=.005), and improved goodness of fit (likelihood ratio test, P<.001). Differences in 5-year survival were more pronounced across levels of age, smoking status, and sex. CONCLUSION:Cardiorespiratory fitness, assessed by submaximal exercise testing, improves mortality risk prediction beyond conventional risk factors and its prognostic relevance varies across cardiovascular risk levels.
    背景与目标:
  • 【英国生物银行中女性的遗传因素、对健康生活方式行为的坚持和浸润性乳腺癌的风险。】 复制标题 收藏 收藏
    DOI:10.1093/jnci/djz241 复制DOI
    作者列表:Arthur RS,Wang T,Xue X,Kamensky V,Rohan TE
    BACKGROUND & AIMS: BACKGROUND:Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. METHODS:Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. RESULTS:Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. CONCLUSION:Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.
    背景与目标:
  • 【通过磁共振成像评估的饮酒,心脏形态和功能之间的性别特异性关联: 来自英国生物库人口研究的见解。】 复制标题 收藏 收藏
    DOI:10.1093/ehjci/jeaa242 复制DOI
    作者列表:Simon J,Fung K,Kolossváry M,Sanghvi MM,Aung N,Paiva JM,Lukaschuk E,Carapella V,Merkely B,Bittencourt MS,Karády J,Lee AM,Piechnik SK,Neubauer S,Maurovich-Horvat P,Petersen SE
    BACKGROUND & AIMS: AIMS:Data regarding the effects of regular alcohol consumption on cardiac anatomy and function are scarce. Therefore, we sought to determine the relationship between regular alcohol intake and cardiac structure and function as evaluated with cardiac magnetic resonance imaging. METHODS AND RESULTS:Participants of the UK Biobank who underwent cardiac magnetic resonance were enrolled in our analysis. Data regarding regular alcohol consumption were obtained from questionnaires filled in by the study participants. Exclusion criteria were poor image quality, missing, or incongruent data regarding alcohol drinking habits, prior drinking, presence of heart failure or angina, and prior myocardial infarction or stroke. Overall, 4335 participants (61.5 ± 7.5 years, 47.6% male) were analysed. We used multivariate linear regression models adjusted for age, ethnicity, body mass index, smoking, hypertension, diabetes mellitus, physical activity, cholesterol level, and Townsend deprivation index to examine the relationship between regular alcohol intake and cardiac structure and function. In men, alcohol intake was independently associated with marginally increased left ventricular end-diastolic volume [β = 0.14; 95% confidence interval (CI) = 0.05-0.24; P = 0.004], left ventricular stroke volume (β = 0.08; 95% CI = 0.03-0.14; P = 0.005), and right ventricular stroke volume (β = 0.08; 95% CI = 0.02-0.13; P = 0.006). In women, alcohol consumption was associated with increased left atrium volume (β = 0.14; 95% CI = 0.04-0.23; P = 0.006). CONCLUSION:Alcohol consumption is independently associated with a marginal increase in left and right ventricular volumes in men, but not in women, whereas alcohol intake showed an association with increased left atrium volume in women. Our results suggest that there is only minimal relationship between regular alcohol consumption and cardiac morphology and function in an asymptomatic middle-aged population.
    背景与目标:
  • 【探索电子鼻技术通过呼出挥发性化合物 (VOC) 的非侵入性呼吸筛查识别间质性肺疾病 (ILD) 的能力: 来自欧洲IPF注册中心 (eurIPFreg) 和Biobank的一项试点研究。】 复制标题 收藏 收藏
    DOI:10.3390/jcm8101698 复制DOI
    作者列表:Krauss E,Haberer J,Maurer O,Barreto G,Drakopanagiotakis F,Degen M,Seeger W,Guenther A
    BACKGROUND & AIMS: BACKGROUND:There is an increasing interest in employing electronic nose technology in the diagnosis and monitoring of lung diseases. Interstitial lung diseases (ILD) are challenging in regard to setting an accurate diagnosis in a timely manner. Thus, there is a high unmet need in non-invasive diagnostic tests. This single-center explorative study aimed to evaluate the usefulness of electronic nose (Aeonose®) in the diagnosis of ILDs. METHODS:Exhaled volatile organic compound (VOC) signatures were obtained by Aeonose® in 174 ILD patients, 23 patients with chronic obstructive pulmonary disease (COPD), and 33 healthy controls (HC). RESULTS:By dichotomous comparison of VOC's between ILD, COPD, and HC, a discriminating algorithm was established. In addition, direct analyses between the ILD subgroups, e.g., cryptogenic organizing pneumonia (COP, n = 28), idiopathic pulmonary fibrosis (IPF, n = 51), and connective tissue disease-associated ILD (CTD-ILD, n = 25) were performed. Area under the Curve (AUC) and Matthews's correlation coefficient (MCC) were used to interpret the data. In direct comparison of the different ILD subgroups to HC, the algorithms developed on the basis of the Aeonose® signatures allowed safe separation between IPF vs. HC (AUC of 0.95, MCC of 0.73), COP vs. HC (AUC 0.89, MCC 0.67), and CTD-ILD vs. HC (AUC 0.90, MCC 0.69). Additionally, to a case-control study design, the breath patterns of ILD subgroups were compared to each other. Following this approach, the sensitivity and specificity showed a relevant drop, which results in a poorer performance of the algorithm to separate the different ILD subgroups (IPF vs. COP with MCC 0.49, IPF vs. CTD-ILD with MCC 0.55, and COP vs. CT-ILD with MCC 0.40). CONCLUSIONS:The Aeonose® showed some potential in separating ILD subgroups from HC. Unfortunately, when applying the algorithm to distinguish ILD subgroups from each other, the device showed low specificity. We suggest that artificial intelligence or principle compound analysis-based studies of a much broader data set of patients with ILDs may be much better suited to train these devices.
    背景与目标:

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