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Reemergence of Oropouche virus between 2023 and 2024 in Brazil 2023 至 2024 年间奥罗普切病毒在巴西再次出现
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.27.24310296
BSc Gabriel C. Scachetti, BSc Julia Forato, PhD Ingra M. Claro, Xinyi Hua, DrPH, PhD Bárbara B. Salgado, MSc Aline Vieira, BSc Camila L. Simeoni, PhD Aguyda R C. Barbosa, BSc Italo L. Rosa, PhD Gabriela F. de Souza, Luana C. N. Fernandes BSc, Ana Carla, BSc H. de Sena, BSc Stephanne C. Oliveira, PhD Carolina M. L. Singh, PhD Shirlene T. de Lima, PhD Ronaldo de Jesus, PhD Mariana A. Costa, PhD Rodrigo B Kato, BSc Josilene F. Rocha, BSc Leandro C. Santos, PhD Janete T. Rodrigues, PhD Marielton P. Cunha, MD PhD Ester C. Sabino, PhD Nuno R. Faria, PhD Scott C Weaver, PhD Camila M. Romano, Dr rer nat Pritesh Lalwani, PhD José Luiz Proença-Módena, PhD William M. de Souza
Background: Oropouche virus (OROV; species Orthobunyavirus oropoucheense) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024. Methods: In this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along with in vitro and in vivo characterization. Molecular screening data included 234 patients with febrile illness or central nervous system (CNS) manifestations between December 2023 and May 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024. Findings: In 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness and 2.1% (3 of 141) of patients with CNS manifestations between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype. Interpretation: These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity.
背景:奥罗普切病毒(OROV;Orthobunyavirus oropoucheense的一种)是一种节肢动物传播的病毒,自20世纪50年代以来曾在中美洲和南美洲爆发过奥罗普切热。本研究调查了导致 2023 年至 2024 年巴西再次出现奥罗普切热的病毒学因素。研究方法在这项研究中,我们结合了 2015 年 1 月 1 日至 2024 年 6 月 29 日期间巴西的 OROV 基因组、分子和血清学数据,以及体外和体内特征描述。分子筛查数据包括亚马孙州2023年12月至2024年5月期间234名发热疾病或中枢神经系统(CNS)表现的患者。基因组数据包括患者的两个基因组 OROV 序列。血清学数据来自中和抗体测试,比较了原型 OROV 菌株 BeAn 19991 和 2024 年流行的菌株。流行病学数据包括2014年1月1日至2024年6月29日向巴西卫生部报告的病例总数。研究结果2024 年,巴西所有五个大区都在以前未流行的地区发现了自体 OROV 感染病例。27个联邦单位中有19个报告了病例,83.2%的感染病例(8,284例中的6,895例)发生在北巴西,与过去十年报告的病例相比,发病率增加了近200倍。2023年12月至2024年5月期间,我们在亚马孙地区10.8%的发热病人(93人中有10人)和2.1%的中枢神经系统表现病人(141人中有3人)中检测到了OROV RNA。我们证明,2023-2024 年的疫情是由新型 OROV 重变种引起的,与原型菌株相比,它在哺乳动物细胞中的复制滴度高出约 100 倍。与原型菌株相比,2023-2024 年的 OROV 重变种比原型菌株更早出现斑块,产生的斑块数量是原型菌株的 1.7 倍,斑块大小也比原型菌株大 2.5 倍。此外,2016年从以前感染过OROV的人身上采集的血清显示,与原型相比,对重配株的中和能力至少降低了32倍。解读:这些发现全面评估了巴西的奥罗波切热,有助于更好地了解2023-2024年奥罗波切热再次爆发的情况。最近发病率的上升可能与一种新的重配病毒复制效率较高有关,这种病毒也能逃避以前的免疫。
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引用次数: 0
Association between cardiometabolic phenotypes with atherogenic index of plasma: a cross-sectional study from the Azar Cohort Study 心脏代谢表型与血浆致动脉粥样硬化指数之间的关系:一项来自阿扎尔队列研究的横断面研究
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.24311169
S. Soheilifard, R. Mahdavi, E. Faramarzi
Background: This study was conducted to determine the relationship between cardiometabolic phenotypes and atherogenic index of plasma in the Azar cohort population. Methods: This cross sectional study included 9,515 participants aged 35 to 55, using data from the Azar Cohort Study. Metabolic syndrome was defined based on ATP III criteria. Participants were then classified into four cardiometabolic phenotypes by considering BMI and metabolic syndrome components: metabolically healthy normal weight (MHNW, BMI <25 kg/m2), metabolically unhealthy normal weight (MUHNW, BMI <25 kg/m2), metabolically healthy obese (MHO, BMI >25 kg/m2), and metabolically unhealthy obese (MUHO, BMI>25 kg/m2). AIP was calculated. Result :Among the subjects, 4,801 (50.5%) were metabolically healthy obese (MHO) and 2,680 (28.2%) were metabolically unhealthy obese (MUHO). High-risk AIP levels (>0.21) differed significantly across cardiometabolic phenotypes, with MUHNW (79.6%) and MUHO (64.6%) showing the highest proportions compared to MHNW (13.5%) and MHO (18.6%). After adjusting for confounders, multinomial logistic regression analysis showed individuals in the third tertial of AIP were 103.46 times more likely to be MUHNW (OR = 103.46, 95% CI: 52.82to202.64), 55.77 times more likely to be MUHO (OR = 55.77, 95% CI: 45.65to68.12), and 2.22 times more likely to be MHO (OR = 2.22, 95% CI: 1.91to2.64) compared to the MHNW phenotype (p < 0.001 for all). Conclusion: The study demonstrates significant variation in high risk AIP levels across cardiometabolic phenotypes, emphasizing the need for detailed metabolic health assessments beyond BMI to better predict cardiovascular risk. Keywords: cardiometabolic phenotypes, atherogenic index of plasma, BMI, metabolic health.
研究背景本研究旨在确定阿扎尔队列人群的心脏代谢表型与血浆致动脉粥样硬化指数之间的关系。研究方法这项横断面研究利用阿扎尔队列研究的数据,纳入了 9,515 名 35 至 55 岁的参与者。代谢综合征是根据 ATP III 标准定义的。然后,根据体重指数和代谢综合征成分将参与者分为四种心脏代谢表型:代谢健康正常体重(MHNW,体重指数 25 kg/m2)和代谢不健康肥胖(MUHO,体重指数>25 kg/m2)。计算出 AIP。结果 :受试者中有 4 801 人(50.5%)属于代谢健康型肥胖(MHO),2 680 人(28.2%)属于代谢不健康型肥胖(MUHO)。不同心脏代谢表型的高危 AIP 水平(>0.21)差异显著,其中 MUHNW(79.6%)和 MUHO(64.6%)与 MHNW(13.5%)和 MHO(18.6%)相比比例最高。在对混杂因素进行调整后,多项式逻辑回归分析表明,AIP 第三序列中的个体成为 MUHNW 的可能性是 MUHO 的 103.46 倍(OR = 103.46,95% CI:52.82to202.64),成为 MUHO 的可能性是 MHNW 表型的 55.77 倍(OR = 55.77,95% CI:45.65 至 68.12),成为 MHO 的可能性是 MHNW 表型的 2.22 倍(OR = 2.22,95% CI:1.91 至 2.64)(P < 0.001)。结论该研究表明,不同心血管代谢表型的高风险 AIP 水平存在显著差异,这强调了除体重指数外,还需要进行详细的代谢健康评估,以更好地预测心血管风险。关键词:心脏代谢表型、血浆致动脉粥样硬化指数、体重指数、代谢健康。
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引用次数: 0
Hot Spring Residency and Disease Association: a Crossover Gene-Environment Interaction (GxE) Study in Taiwan 温泉居住地与疾病的关系:台湾的一项基因与环境交互作用 (GxE) 交叉研究
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.24311167
H.-Y. Wu, K.-J. Chang, W. Chiu, C.-Y. Wang, Y.-T. Hsu, Y.-C. Wen, P.-H. Chiang, Y.-H. Chen, H.-J. Dai, C.-H. Lu, Y.-C. Chen, H.-Y. Tsai, C.-H. Hsu, A.-R. Hsieh, S.-H. Chiou, Y.-P. Yang, C.-C. Hsu
Background The advent of genetic biobanking has powered gene-environment interaction (GxE) studies in various disease contexts. Therefore, we aimed to discover novel GxE effects that address hot spring residency as a risk to inconspicuous disease association. Methods A complete genetic and demographic registry comprising 129,451 individuals was obtained from Taiwan Biobank (TWB). Geographical disease prevalence was analyzed to identify putative disease association with hot-spring residency, multivariable regression and logistic regression were rechecked to exclude socioeconomic confounders in geographical-disease association. Genome-wide association study (GWAS), gene ontology (GO), and protein-protein interaction (PPI) analysis identified predisposing genetic factors among hotspring-associated diseases. Lastly, a polygenic risk score (PRS) model was formulated to stratify environmental susceptibility in accord to their genetic predisposition. Results After socioeconomic covariate adjustment, prevalence of dry eye disease (DED) and valvular heart disease (VHD) was significantly associated with hot spring distribution. Through single nucleotide polymorphisms (SNPs) discovery and subsequent PPI pathway aggregation, CDKL2 and BMPR2 kinase pathways were significantly enriched in hot-spring specific DED and VHD functional SNPs. Notably, PRS predicted disease well in hot spring regions (PRSDED: AUC=0.9168; PRSVHD AUC=0.8163). Hot spring and discovered SNPs contributed to crossover GxE effect on both DED (relative risk (RR)G+E-=0.99; RRG+E+=0.35; RRG+E+=2.04) and VHD (RRG+E-=0.99; RRG+E+=0.49; RRG+E+=2.01). Conclusion We identified hot-spring exposure as a modifiable risk in the PRS predicted GxE context of DED and VHD.
背景 基因生物库的出现为各种疾病背景下的基因-环境相互作用(GxE)研究提供了动力。因此,我们旨在发现新的 GxE 效应,以解决温泉居住与不明显疾病相关的风险问题。方法 我们从台湾生物库(TWB)获得了一份完整的遗传和人口登记表,其中包括 129,451 人。分析了地理疾病流行率,以确定疾病与温泉居住地的潜在关联,并重新检查了多变量回归和逻辑回归,以排除地理-疾病关联中的社会经济混杂因素。全基因组关联研究(GWAS)、基因本体论(GO)和蛋白质相互作用(PPI)分析确定了温泉相关疾病的易感遗传因素。最后,建立了多基因风险评分(PRS)模型,根据遗传易感性对环境易感性进行分层。结果 经社会经济协变量调整后,干眼病(DED)和瓣膜性心脏病(VHD)的患病率与温泉分布有显著相关性。通过单核苷酸多态性(SNPs)的发现和随后的PPI通路聚合,CDKL2和BMPR2激酶通路在温泉特异性DED和VHD功能性SNPs中明显富集。值得注意的是,PRS能很好地预测温泉地区的疾病(PRSDED:AUC=0.9168;PRSVHD AUC=0.8163)。温泉和发现的 SNPs 对 DED(相对风险 (RR)G+E-=0.99; RRG+E+=0.35; RRG+E+=2.04) 和 VHD(RRG+E-=0.99; RRG+E+=0.49; RRG+E+=2.01)都有交叉 GxE 效应。结论 我们发现,在 PRS 预测 DED 和 VHD 的 GxE 背景下,温泉暴露是一种可改变的风险。
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引用次数: 0
Dual exposure-by-polygenic score interactions highlight disparities across social groups in the proportion needed to benefit 双重暴露与多基因得分之间的相互作用凸显了不同社会群体在获益所需比例上的差异
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.24311065
S. Nagpal, G. Gibson
The transferability of polygenic scores across population groups is a major concern with respect to the equitable clinical implementation of genomic medicine. Since genetic associations are identified relative to the population mean, inevitably differences in disease or trait prevalence among social strata influence the relationship between PGS and risk. Here we quantify the magnitude of PGS-by-Exposure (PGSxE) interactions for seven human diseases (coronary artery disease, type 2 diabetes, obesity thresholded to body mass index and to waist-to-hip ratio, inflammatory bowel disease, chronic kidney disease, and asthma) and pairs of 75 exposures in the White-British subset of the UK Biobank study (n=408,801). Across 24,198 PGSxE models, 746 (3.1%) were significant by two criteria, at least three-fold more than expected by chance under each criterion. Predictive accuracy is significantly improved in the high-risk exposures and by including interaction terms with effects as large as those documented for low transferability of PGS across ancestries. The predominant mechanism for PGSxE interactions is shown to be amplification of genetic effects in the presence of adverse exposures such as low polyunsaturated fatty acids, mediators of obesity, and social determinants of ill health. We introduce the notion of the proportion needed to benefit (PNB) which is the cumulative number needed to treat across the range of the PGS and show that typically this is halved in the 70th to 80th percentile. These findings emphasize how individuals experiencing adverse exposures stand to preferentially benefit from interventions that may reduce risk, and highlight the need for more comprehensive sampling across socioeconomic groups in the performance of genome-wide association studies.
多基因评分在不同人群中的可转移性是基因组医学公平临床应用的一个主要问题。由于遗传关联是相对于人群平均值确定的,因此不同社会阶层的疾病或性状流行率的差异不可避免地会影响 PGS 与风险之间的关系。在此,我们量化了英国生物库研究的白种英国人子集(n=408,801)中七种人类疾病(冠心病、2 型糖尿病、以体重指数和腰臀比为阈值的肥胖症、炎症性肠病、慢性肾病和哮喘)和 75 对暴露的 PGS-by-Exposure (PGSxE) 相互作用的程度。在 24198 个 PGSxE 模型中,有 746 个模型(3.1%)在两个标准下具有显著性,比每个标准下的偶然性预期至少高出三倍。预测准确性在高风险暴露中得到了显著提高,并且通过加入交互项,其效应与记录的 PGS 跨血统低转移性的效应一样大。PGSxE 相互作用的主要机制被证明是在低多不饱和脂肪酸、肥胖介质和健康不良的社会决定因素等不利暴露条件下遗传效应的放大。我们引入了 "获益所需比例"(PNB)的概念,即在整个 PGS 范围内需要治疗的累积人数,并表明通常在第 70 到 80 百分位数时,获益所需比例会减半。这些发现强调了经历不利暴露的个体如何从可能降低风险的干预措施中优先受益,并突出了在进行全基因组关联研究时对社会经济群体进行更全面采样的必要性。
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引用次数: 0
Towards Personalized Breast Cancer Risk Management: A Thai Cohort Study on Polygenic Risk Scores 实现个性化乳腺癌风险管理:泰国多基因风险评分队列研究
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.28.24311135
Vorthunju Nakhonsri, Manop Pithukpakorn, J. Eu-ahsunthornwattana, C. Ngamphiw, Rujipat Wasitthankasem, Alisa Wilantho, Pongsakorn Wangkumhang, Manon Boonbangyang, S. Tongsima
Polygenic Risk Scores (PRS) are now playing an important role in predicting overall risk of breast cancer risk by means of adding contribution factors across independent genetic variants influencing the disease. However, PRS models may work better in some ethnic populations compared to others, thus requiring populaion specific validation. This study evaluates the performance of 140 previously published PRS models in a Thai population, an underrepresented ethnic group. To rigorously evaluate the performance of 140 breast PRS models, we employed generalized linear models (GLM) combined with a robust evaluation strategy, including Five fold cross validation and bootstrap analysis in which each model was tested across 1,000 bootstrap iterations to ensure the robustness of our findings and to identify models with consistently strong predictive ability. Among the 140 models evaluated, 38 demonstrated robust predictive ability, identified through > 163 bootstrap iterations (95% CI: 163.88). PGS004688 exhibited the highest performance, achieving an AUROC of 0.5930 (95% CI: 0.5903,0.5957) and a McFadden's pseudo R squared of 0.0146 (95% CI: 0.0139,0.0153). Women in the 90th percentile of PRS had a 1.83 fold increased risk of breast cancer compared to those within the 30th to 70th percentiles (95% CI: 1.04,3.18). This study highlights the importance of local validation for PRS models derived from diverse populations, demonstrating their potential for personalized breast cancer risk assessment. Model PGS004688, with its robust performance and significant risk stratification, warrants further investigation for clinical implementation in breast cancer screening and prevention strategies. Our findings emphasize the need for adapting and utilizing PRS in diverse populations to provide more accessible public health solutions.
多基因风险评分(PRS)通过增加影响该疾病的独立基因变异的贡献因子,目前在预测乳腺癌的总体风险方面发挥着重要作用。然而,PRS 模型在某些种族人群中可能比在其他种族人群中效果更好,因此需要针对特定人群进行验证。本研究评估了之前发表的 140 个 PRS 模型在泰国人群(一个代表性不足的种族群体)中的表现。为了严格评估 140 个乳腺 PRS 模型的性能,我们采用了广义线性模型(GLM),并结合稳健的评估策略,包括五倍交叉验证和自举分析,其中每个模型都要经过 1000 次自举迭代测试,以确保我们的研究结果的稳健性,并找出具有持续强大预测能力的模型。在所评估的 140 个模型中,有 38 个模型通过 > 163 次引导迭代(95% CI:163.88)证明了其稳健的预测能力。PGS004688 的性能最高,AUROC 为 0.5930(95% CI:0.5903,0.5957),McFadden's 伪 R 平方为 0.0146(95% CI:0.0139,0.0153)。与 30% 至 70% 百分位数的妇女相比,PRS 第 90 百分位数的妇女罹患乳腺癌的风险增加了 1.83 倍(95% CI:1.04,3.18)。这项研究强调了对来自不同人群的 PRS 模型进行局部验证的重要性,证明了这些模型在个性化乳腺癌风险评估中的潜力。模型 PGS004688 性能可靠,风险分层显著,值得进一步研究,以便在临床上用于乳腺癌筛查和预防策略。我们的研究结果强调了在不同人群中调整和利用 PRS 的必要性,以提供更方便的公共卫生解决方案。
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引用次数: 0
Representational drawing ability is associated with the syntactic language comprehension phenotype in autistic individuals 表象绘画能力与自闭症患者的句法语言理解表型有关
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.26.24310995
A. Vyshedskiy, R. Venkatesh, E. Khokhlovich
The relationship between symbolic thinking and language abilities is a topic of intense debate. We have recently discovered three distinct phenotypes of language comprehension, which we defined as command, modifier and syntactic phenotypes (Vyshedskiy et al., 2024). Individuals in the command phenotype were limited to comprehension of simple commands, while those in the modifier phenotype showed additional comprehension of color, size, and number modifiers. Finally, individuals in the most-advanced syntactic phenotype added comprehension of spatial prepositions, verb tenses, flexible syntax, possessive pronouns, complex explanations, and fairytales. In this report we analyzed how these three language phenotypes differed in their symbolic thinking as exhibited through their drawing abilities. In a cohort of 39,654 autistic individuals 4- to 21-years-of-age, parents reported that 'drawing, coloring and art' was manifested by 36.0% of participants. Among these individuals, representational drawing was manifested by 54.1% of individuals with syntactic-, 27.7% of those with modifier-, and 10.1% of those with command-phenotype (all pairwise differences between the phenotypes were statistically significant, p < 0.0001). The ability to draw a novel image per parent's description (e.g. a three-headed horse) was reported by 34.6% of individuals with syntactic-, 7.9% of those with modifier-, and 1.9% of individuals with command-phenotype (all pairwise differences between the phenotypes were statistically significant, p < 0.0001). These results show strong association between the representational drawing ability and the syntactic-language-comprehension-phenotype, suggesting a potential benefit of drawing interventions in language therapy.
符号思维与语言能力之间的关系是一个争论不休的话题。我们最近发现了三种不同的语言理解表型,我们将其定义为命令表型、修饰表型和句法表型(Vyshedskiy et al.)命令表型的个体仅限于理解简单的命令,而修饰语表型的个体则对颜色、大小和数字修饰语有额外的理解能力。最后,处于最高级句法表型的个体增加了对空间介词、动词时态、灵活句法、物主代词、复杂解释和童话的理解。在本报告中,我们分析了这三种语言表型在通过绘画能力表现出的符号思维方面有何不同。在 39654 名 4 至 21 岁的自闭症患者中,有 36.0% 的患者家长表示他们有 "绘画、涂色和艺术 "表现。在这些人中,54.1%的句法型自闭症患者、27.7%的修饰型自闭症患者和 10.1%的命令型自闭症患者表现出表象绘画(表型之间的配对差异均有统计学意义,P < 0.0001)。34.6%的句法表型个体、7.9%的修饰表型个体和 1.9%的命令表型个体能够根据父母的描述绘制新奇的图像(如三头马)(表型之间的配对差异均有统计学意义,P < 0.0001)。这些结果表明,表象绘画能力与句法-语言-理解表型之间存在密切联系,表明绘画干预在语言治疗中具有潜在的益处。
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引用次数: 0
Methods for joint modelling of longitudinal omics data and time-to-event outcomes: Applications to lysophosphatidylcholines in connection to aging and mortality in the Long Life Family Study 纵向 omics 数据和时间到事件结果的联合建模方法:长寿家庭研究中溶血磷脂酰胆碱与衰老和死亡率的关系
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.24311176
K. Arbeev, Olivia Bagley, S. Ukraintseva, A. Kulminski, Eric Stallard, Michaela Schwaiger-Haber, Gary Patti, Yian Gu, A. Yashin, Michael A. Province, G. H. S. Center
Studying relationships between longitudinal changes in omics variables and risks of events requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process models [SPM]) to longitudinal metabolomics data from the Long Life Family Study focusing on understudied associations of longitudinal changes in lysophosphatidylcholines (LPC) with mortality and aging-related outcomes (23 LPC species, 5,790 measurements of each in 4,011 participants, 1,431 of whom died during follow-up). JM analyses found that higher levels of the majority of LPC species were associated with lower mortality risks, with the largest effect size observed for LPC 15:0/0:0 (hazard ratio: 0.715, 95% CI (0.649, 0.788)). SPM applications to LPC 15:0/0:0 revealed how the association found in JM reflects underlying aging-related processes: decline in robustness to deviations from optimal LPC levels, better ability of males' organisms to return to equilibrium LPC levels (which are higher in females), and increasing gaps between the optimum and equilibrium levels leading to increased mortality risks with age. Our results support LPC as a biomarker of aging and related decline in robustness/resilience, and call for further exploration of factors underlying age-dynamics of LPC in relation to mortality and diseases.
研究 omics 变量的纵向变化与事件风险之间的关系需要采用特定的方法对纵向结果和时间到事件结果进行联合分析。我们将两种此类方法(联合模型 [JM]、随机过程模型 [SPM])应用于长寿家庭研究(Long Life Family Study)的纵向代谢组学数据,重点研究未被充分研究的溶血磷脂酰胆碱(LPC)纵向变化与死亡率和衰老相关结果之间的关系(23 种 LPC,每种 LPC 在 4011 名参与者中进行了 5790 次测量,其中 1431 人在随访期间死亡)。JM 分析发现,大多数 LPC 种类的水平越高,死亡风险越低,其中 LPC 15:0/0:0 的效应最大(危险比:0.715,95% CI (0.649, 0.788))。将 SPM 应用于 LPC 15:0/0:0,揭示了在 JM 中发现的关联如何反映了与衰老相关的潜在过程:对偏离最佳 LPC 水平的稳健性下降、雄性生物体恢复到平衡 LPC 水平的能力更强(雌性更高)、最佳水平与平衡水平之间的差距增大,从而导致死亡风险随着年龄的增长而增加。我们的研究结果支持将 LPC 作为衰老和相关健壮性/复原力下降的生物标志物,并呼吁进一步探索 LPC 与死亡率和疾病相关的年龄动力学因素。
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引用次数: 0
Residential Methamphetamine Contamination in Boulder Colorado: Incidence and Implications 科罗拉多州博尔德的住宅甲基苯丙胺污染:发生率和影响
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.28.24311138
J. E. Dennison, N. Minick
The manufacture and use of methamphetamine (meth) is a significant problem, in part because it can lead to the contamination of properties where it occurs. Meth contamination can lead to health issues for occupants as well as very high remediation costs for property owners. But even in a state like Colorado, where meth testing and remediation are highly regulated, the number of residences or other types of property that are contaminated in excess of health standards is unknown. Generally, testing for meth contamination occurs only after a property is identified as a likely site for meth use or manufacture, whether by law enforcement, the property owner, or a potential buyer. For this paper, a unique random data set based on a real estate broker's meth screening program was used to determine the incidence of contaminated residences in general. Brokerage clients put 303 residential properties under contract between 2013 and 2022, of which 288 (95%) were screened for meth contamination. Meth was detected in 45 of the 288 screening tests (16%), many at trace levels, while 84% contained no detectable meth. Comprehensive testing was subsequently performed on 35 of these 45 properties and ten of the original 288 (3.47%) screened properties contained meth contamination above state health standards. While the sample size of this analysis was modest, it provides a first real estimate of the incidence of meth-contaminated residential property and an indication of the environmental health significance of this issue.
甲基苯丙胺(冰毒)的制造和使用是一个严重的问题,部分原因是它会导致所在物业受到污染。冰毒污染会导致居住者的健康问题,并给业主带来高昂的修复费用。但是,即使在科罗拉多州这样一个对冰毒检测和修复有严格规定的州,受污染的住宅或其他类型的财产超过健康标准的数量也是未知数。一般来说,只有在执法部门、业主或潜在买家确定某处房产可能是冰毒使用或制造场所后,才会进行冰毒污染检测。本文使用了基于房地产经纪人冰毒筛查计划的独特随机数据集,以确定一般情况下受污染住宅的发生率。经纪人客户在 2013 年至 2022 年期间签订了 303 处住宅物业合同,其中 288 处(95%)进行了冰毒污染筛查。在 288 项筛查测试中,有 45 项(16%)检测到冰毒,其中许多为痕量冰毒,而 84% 的测试未检测到冰毒。随后对这 45 处房产中的 35 处进行了全面检测,在最初筛查的 288 处房产中,有 10 处(3.47%)的冰毒污染超过了州卫生标准。虽然这项分析的样本量不大,但它首次对受冰毒污染的住宅物业的发生率进行了真实的估计,并表明了这一问题对环境健康的重要性。
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引用次数: 0
Evaluation of the diagnostic value of YiDiXie™-SS, YiDiXie™-HS and YiDiXie™-D in renal cancer 评估YiDiXieâ¢-SS、YiDiXieâ¢-HS和YiDiXieâ¢-D对肾癌的诊断价值
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.28.24310613
Y. Wu, Y. Li, H. Zhou, C. Sun, X. Li, Z. Ge, W. Chen, S. Lin, P. Zhang, W. Wang, S. Chen, W. Li, L. Tao, X. Wu, L. Bi, Y. Lai
BACKGROUND: Renal cancer is a serious threat to human health and causes heavy economic burden. Ultrasound is widely used in screening or preliminary diagnosis of renal tumors, and enhanced CT is widely used in the diagnosis of renal tumors. However, false-positive results of ultrasound and enhanced CT will bring unnecessary mental pain, expensive examination costs, physical injuries, and even adverse consequences such as organ removal and loss of function; while false-negative results of enhanced CT bring delayed treatment, and patients will thus have to bear the adverse consequences of poor prognosis, high treatment costs, poor quality of life, and short survival period. There is an urgent need to find convenient, cost-effective and non-invasive diagnostic methods to reduce the false-positive rate of ultrasound and the false-negative and false-positive rates of enhanced CT in renal tumors. The aim of this study was to evaluate the diagnostic value of YiDiXie-SS, YiDiXie-HS and YiDiXie-D in renal tumors. MATERIALS AND METHODS: 298 subjects (malignant group, n=233; benign group, n=65) were finally included in this study. Remaining serum samples from the subjects were collected and tested by applying the YiDiXie all-cancer detection kit to evaluate the sensitivity and specificity of YiDiXie-SS, YiDiXie-HS and YiDiXie-D, respectively. RESULTS: The sensitivity of YiDiXie-SS in renal ultrasound-positive patients was 98.3% (95% CI: 95.7% - 99.3%; 229/233) with a specificity of 66.2% (95% CI: 54.0% - 76.5%; 43/65). Compared to the application of enhanced CT alone, sequential use of YiDiXie-SS and CT had comparable sensitivity, but the false positive rate decreased from 21.5% (95% CI: 13.3% - 33.0%; 14/65) to 6.2% (95% CI: 2.4% - 14.8%; 4/65). This means that the application of YiDiXie-SS reduced the false-positive rate of ultrasound by 66.2% (95% CI: 54.0% - 76.5%; 43/65) and the false-positive rate of enhanced CT by 71.4% with essentially no increase in malignancy leakage.The sensitivity of YiDiXie-HS in patients with a negative enhanced CT was 86.1% (95% CI. 71.3% - 93.9%; 31/36) and specificity was 84.3% (95% CI: 72.0% - 91.8%; 43/51). This means that YiDiXie-HS reduced the false-negative rate of enhanced CT by 86.1% (95% CI: 71.3% - 93.9%; 31/36).YiDiXie-D had a sensitivity of 29.4% (95% CI: 23.5% - 36.2%; 58/197) and a specificity of 92.9% (95% CI: 68.5% - 99.6%) in patients with positive enhanced CT. This means that YiDiXie-D reduces the false positive rate of enhanced CT by 92.9% (95% CI: 68.5% - 99.6%; 13/14). CONCLUSION: YiDiXie-SS dramatically reduces the false-positive rate of ultrasound and enhanced CT with essentially no increase in delayed treatment of malignant tumors. YiDiXie-HS dramatically reduces the false-negative rate of enhanced CT. YiDiXie-D dramatically reduces the false-positive rate of enhanced CT. The YiDiXie test has significant diagnostic value in renal tumors, and is expected to solve the 3 problems of "high false-positive
背景:肾癌严重威胁人类健康,并造成沉重的经济负担。超声波被广泛应用于肾脏肿瘤的筛查或初步诊断,增强 CT 被广泛应用于肾脏肿瘤的诊断。然而,超声和增强 CT 的假阳性结果会给患者带来不必要的精神痛苦、昂贵的检查费用、身体伤害,甚至切除器官、丧失功能等不良后果;而增强 CT 的假阴性结果则会延误治疗,患者因此不得不承担预后差、治疗费用高、生活质量差、生存期短等不良后果。因此,急需找到方便、经济、无创的诊断方法,以降低肾肿瘤超声的假阳性率和增强 CT 的假阴性率和假阳性率。本研究旨在评估 YiDiXie-SS、YiDiXie-HS 和 YiDiXie-D 对肾肿瘤的诊断价值。材料与方法:本研究最终纳入了 298 名受试者(恶性组,n=233;良性组,n=65)。收集受试者的剩余血清样本,并使用 YiDiXie 全癌检测试剂盒分别检测 YiDiXie-SS、YiDiXie-HS 和 YiDiXie-D 的灵敏度和特异性。结果:YiDiXie-SS对肾脏超声阳性患者的敏感性为98.3%(95% CI:95.7% - 99.3%;229/233),特异性为66.2%(95% CI:54.0% - 76.5%;43/65)。与单独使用增强 CT 相比,连续使用 YiDiXie-SS 和 CT 的灵敏度相当,但假阳性率从 21.5% (95% CI: 13.3% - 33.0%; 14/65) 下降到 6.2% (95% CI: 2.4% - 14.8%; 4/65)。这意味着应用 YiDiXie-SS 后,超声检查的假阳性率降低了 66.2% (95% CI: 54.0% - 76.5%; 43/65),增强 CT 的假阳性率降低了 71.YiDiXie-HS 对增强 CT 阴性患者的敏感性为 86.1% (95% CI. 71.3% - 93.9%; 31/36),特异性为 84.3% (95% CI: 72.0% - 91.8%; 43/51)。在增强 CT 呈阳性的患者中,YiDiXie-D 的灵敏度为 29.4%(95% CI:23.5% - 36.2%;58/197),特异性为 92.9%(95% CI:68.5% - 99.6%)。这意味着 YiDiXie-D 可将增强 CT 的假阳性率降低 92.9% (95% CI: 68.5% - 99.6%; 13/14)。结论:YiDiXie-SS 显著降低了超声波和增强 CT 的假阳性率,但基本上没有增加恶性肿瘤的延迟治疗。YiDiXie-HS 显著降低了增强 CT 的假阴性率。YiDiXie-D 显著降低了增强 CT 的假阳性率。YiDiXie检验对肾脏肿瘤具有重要的诊断价值,有望解决 "超声假阳性率高"、"增强CT假阴性率高 "和 "增强CT假阳性率高 "三大难题。临床研究注册号:ChiCTR2200066840。关键词:肾癌 超声 增强CT 假阳性 假阴性 易迪协-SS 易迪协-HS 易迪协-D
{"title":"Evaluation of the diagnostic value of YiDiXie™-SS, YiDiXie™-HS and YiDiXie™-D in renal cancer","authors":"Y. Wu, Y. Li, H. Zhou, C. Sun, X. Li, Z. Ge, W. Chen, S. Lin, P. Zhang, W. Wang, S. Chen, W. Li, L. Tao, X. Wu, L. Bi, Y. Lai","doi":"10.1101/2024.07.28.24310613","DOIUrl":"https://doi.org/10.1101/2024.07.28.24310613","url":null,"abstract":"BACKGROUND: Renal cancer is a serious threat to human health and causes heavy economic burden. Ultrasound is widely used in screening or preliminary diagnosis of renal tumors, and enhanced CT is widely used in the diagnosis of renal tumors. However, false-positive results of ultrasound and enhanced CT will bring unnecessary mental pain, expensive examination costs, physical injuries, and even adverse consequences such as organ removal and loss of function; while false-negative results of enhanced CT bring delayed treatment, and patients will thus have to bear the adverse consequences of poor prognosis, high treatment costs, poor quality of life, and short survival period. There is an urgent need to find convenient, cost-effective and non-invasive diagnostic methods to reduce the false-positive rate of ultrasound and the false-negative and false-positive rates of enhanced CT in renal tumors. The aim of this study was to evaluate the diagnostic value of YiDiXie-SS, YiDiXie-HS and YiDiXie-D in renal tumors. MATERIALS AND METHODS: 298 subjects (malignant group, n=233; benign group, n=65) were finally included in this study. Remaining serum samples from the subjects were collected and tested by applying the YiDiXie all-cancer detection kit to evaluate the sensitivity and specificity of YiDiXie-SS, YiDiXie-HS and YiDiXie-D, respectively. RESULTS: The sensitivity of YiDiXie-SS in renal ultrasound-positive patients was 98.3% (95% CI: 95.7% - 99.3%; 229/233) with a specificity of 66.2% (95% CI: 54.0% - 76.5%; 43/65). Compared to the application of enhanced CT alone, sequential use of YiDiXie-SS and CT had comparable sensitivity, but the false positive rate decreased from 21.5% (95% CI: 13.3% - 33.0%; 14/65) to 6.2% (95% CI: 2.4% - 14.8%; 4/65). This means that the application of YiDiXie-SS reduced the false-positive rate of ultrasound by 66.2% (95% CI: 54.0% - 76.5%; 43/65) and the false-positive rate of enhanced CT by 71.4% with essentially no increase in malignancy leakage.The sensitivity of YiDiXie-HS in patients with a negative enhanced CT was 86.1% (95% CI. 71.3% - 93.9%; 31/36) and specificity was 84.3% (95% CI: 72.0% - 91.8%; 43/51). This means that YiDiXie-HS reduced the false-negative rate of enhanced CT by 86.1% (95% CI: 71.3% - 93.9%; 31/36).YiDiXie-D had a sensitivity of 29.4% (95% CI: 23.5% - 36.2%; 58/197) and a specificity of 92.9% (95% CI: 68.5% - 99.6%) in patients with positive enhanced CT. This means that YiDiXie-D reduces the false positive rate of enhanced CT by 92.9% (95% CI: 68.5% - 99.6%; 13/14). CONCLUSION: YiDiXie-SS dramatically reduces the false-positive rate of ultrasound and enhanced CT with essentially no increase in delayed treatment of malignant tumors. YiDiXie-HS dramatically reduces the false-negative rate of enhanced CT. YiDiXie-D dramatically reduces the false-positive rate of enhanced CT. The YiDiXie test has significant diagnostic value in renal tumors, and is expected to solve the 3 problems of \"high false-positive ","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141795823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caries incidence in school-based oral health programs 校本口腔保健计划中的龋齿发生率
Pub Date : 2024-07-30 DOI: 10.1101/2024.07.29.24311175
PhD Mph Ryan Richard Ru7
Background: School-based caries prevention can increase access to critical dental services and reduce oral health inequities. However, little is known regarding the incidence of dental caries in children participating in school caries prevention, and caries diagnosis is often interval censored. Methods: In this paper, we used data from a longitudinal, school- based, randomized clinical trial of minimally invasive treatments for dental caries to estimate the per-visit incidence rate and compare the hazard of dental caries in children receiving either silver diamine fluoride or glass ionomer dental sealants. To account for interval censoring, we used semiparametric transformation models for univariate failure time data and imputed the caries incidence using G-imputation. Results: There were 3040 children that met inclusion criteria for analysis, 1516 (49.9%) of which were randomly assigned to receive silver diamine fluoride and 1524 (50.1%) assigned to receive glass ionomer dental sealants. There were no differences in the hazard of caries between treatments (HR = 0.98, 95% CI = 0.73, 1.24), while children with caries at baseline had a significant increase in the hazard of new caries (HR = 2.54, 95% CI = 2.26, 2.83) compared to those that were caries-free. The per-visit caries incidence ranged from 4.8 to 11.1 per 1000 person-years and increased with each successive study observation. Conclusions: School-based caries prevention can positively affect caries incidence, and results can be used to inform future program design and implementation.
背景:校本龋病预防可以增加获得关键牙科服务的机会,减少口腔健康不平等。然而,人们对参与学校龋病预防的儿童的龋齿发病率知之甚少,而且龋病诊断往往是间隔性的。方法:在本文中,我们使用了一项龋齿微创治疗的纵向、基于学校的随机临床试验的数据,以估算每次就诊的发病率,并比较接受二胺氟化银或玻璃离子体牙齿密封剂的儿童的龋齿危险性。为了考虑间隔普查,我们使用半参数转换模型处理单变量失败时间数据,并使用 G-imputation 估算龋齿发病率。结果有 3040 名儿童符合纳入分析的标准,其中 1516 名(49.9%)儿童被随机分配接受二胺氟化银治疗,1524 名(50.1%)儿童被分配接受玻璃离聚体牙齿密封剂治疗。与无龋儿童相比,基线时有龋齿的儿童患新龋的风险显著增加(HR = 2.54,95% CI = 2.26,2.83)。每次就诊的龋病发生率为每千人年 4.8 至 11.1 例,并随着每次研究观察的进行而增加。结论:以学校为基础的龋病预防可对龋病发病率产生积极影响,研究结果可为今后的项目设计和实施提供参考。
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