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61.
Asif Ali Nigel Balfour Jamieson Ishaq N Khan David Chang Elisa Giovannetti Nicola Funel Adam E Frampton Jennifer Morton Owen Sansom Thomas R Jeffry Evans Fraser Duthie Colin J McKay Jas Samra Anthony J Gill Andrew Biankin Karin A Oien 《American journal of cancer research》2022,12(12):5668
Despite progress in genomic characterization, no single prognostic marker that can be evaluated using an easy-to-perform and relatively inexpensive method is available for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs, which are stable, tumor- and tissue-specific molecules, are potentially ideal biomarkers, and we established an inter-laboratory validated method to investigate miR-21 as a prognostic biomarker in PDAC. The study samples of PDAC patients were recruited from a test cohort of Glasgow (n = 189) and three validation cohorts of Pisa (n = 69), Sydney (n = 249), and International Cancer Genome Consortium (ICGC) (n = 249). Tissue microarrays were used for miR-21 staining by chromogenic in situ hybridization (CISH). The patients were subdivided into no/low and high miR-21 staining groups using a specific histoscore. Furthermore, miR-21 staining was evaluated against clinicopathological variables and follow-up data by Fisher/log-rank test and Cox proportional models. The prognostic variables found to be significant in univariate analysis (P value < 0.10) were included in multivariate analysis in a backward-stepwise fashion. MiR-21 expression was cytoplasmic, with more consistent staining in the malignant ductal epithelium than in the stroma. The expression of miR-21 was significantly associated with tumor size and lymph node metastasis, whereas no association was observed with other clinicopathological variables. High miR-21 staining (histoscore ≥ 45 [median score]) was an independent predictor of survival in the Glasgow test cohort (HR 2.37, 95% CI: 1.42-3.96, P < 0.0001) and three validation cohorts (Pisa, HR 2.03, 95% CI: 1.21-3.39, P = 0.007; Sydney, HR 2.58, 95% CI (1.21-3.39), P < 0.0001; and ICGC, HR 3.34, 95% CI: 2.07-5.84, P = 0.002) when adjusted for clinical variables in a multivariate model. In comparison to the patients with low miR-21, the patients with high miR-21 expression had significant increase in OS as they benefit from gemcitabine-based adjuvant chemotherapy (Glasgow 16.5 months [with chemotherapy] vs 10.5 months [without chemotherapy]); Sydney 25.0 vs 10.6; ICGC 25.2 vs 11.9. These results indicated that miR-21 is a predictor of survival, prompting prospective trials. Evaluation of miR-21 offers new opportunities for the stratification of patients with PDAC and might facilitate the implementation of clinical management and therapeutic interventions for this devastating disease. 相似文献
62.
Femmy M Bijnsdorp Allard J van der Beek Marjolein I Broese van Groenou Karin I Proper Swenneke G van den Heuvel Ccile RL Boot 《Scandinavian journal of work, environment & health》2022,48(3):190
ObjectivesThis study aims to provide insight into (i) how the combination of paid work and family care is longitudinally associated with gender-related differences in depressive symptoms and (ii) the role of work characteristics in this association.MethodsData were derived from STREAM, a Dutch prospective cohort study of older workers aged 45–64 years. Respondents were included if they were employed in at least one measurement between 2015 and 2017 (N=12 447). Mixed-models were applied to disentangle between-person (BP) and within-person (WP) effects of family caregiving on depressive symptoms. Analyses were stratified by gender. Work characteristics (social support, autonomy, emotional and mental workload) were separately added to the multivariable models.ResultsFor older employees, family caregiving was positively associated with depressive symptoms between and within persons for both women [BP B=0.80, 95% confidence interval (CI) 0.52–1.08; WP B=0.32, 95% CI 0.08–0.56] and men (BP B=0.75, 95% CI 0.45–1.05; WP B=0.25, 95% CI 0.01–0.48). Social support at work reduced the adverse effect of family care on depressive symptoms for women (BP) and men (BP and WP). Emotional workload partly explained the effect of family care for both women and men (BP).ConclusionsThe longitudinal association between family care and mental health was similar for male and female employees. Resources at work (ie, social support) could protect caregiving employees against depressive symptoms. More research is needed regarding the relative impact of the care context compared to the work context of working family caregivers. 相似文献
63.
Katia Keglberg Hrvig Kajsa Ugelvig Petersen Karin Srig Hougaard Christian Lindh Cecilia Hst Ramlau-Hansen Gunnar Toft Aleksander Giwercman Birgit Bjerre Hyer Esben Meulengracht Flachs Jens Peter Bonde Sandra Sgaard Tttenborg 《Environmental health perspectives》2022,130(10)
Background: Concerns remain about the human reproductive toxicity of the widespread per- and polyfluoroalkyl substances (PFAS) during early stages of development.Objectives: We examined associations between maternal plasma PFAS levels during early pregnancy and male offspring reproductive function in adulthood.Methods: The study included 864 young men (age range:18.9–21.2 y) from the Fetal Programming of Semen Quality (FEPOS) cohort established between 2017 and 2019. Plasma samples from their mothers, primarily from the first trimester, were retrieved from the Danish National Biobank and levels of 15 PFAS were measured. Seven PFAS had detectable levels above the limit of detection in of the samples and were included in analyses. Semen quality, testicular volume, and levels of reproductive hormones and PFAS were assessed in the young men. We used weighted quantile sum (WQS) regression to estimate the associations between combined exposure to maternal PFAS and reproductive function, and negative binomial regression to estimate the associations of single substances, while adjusting for a range of a priori–defined fetal and postnatal risk factors.Results: By a 1-unit increase in the WQS index, combined maternal PFAS exposure was associated with lower sperm concentration (; 95% CI: , ), total sperm count (; 95% CI: , ), and a higher proportion of nonprogressive and immotile sperm (5%; 95% CI: 1%, 8%) in the young men. Different PFAS contributed to the associations with varying strengths; however, perfluoroheptanoic acid was identified as the main contributor in the analyses of all three outcomes despite the low concentration. We saw no clear association between exposure to maternal PFAS and testicular volume or reproductive hormones.Discussion: In a sample of young men from the general Danish population, we observed consistent inverse associations between exposure to maternal PFAS and semen quality. The study needs to be replicated in other populations, taking combined exposure, as well as emerging short-chain PFAS, into consideration. https://doi.org/10.1289/ EHP10285相似文献
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65.
Günther Vogel Fritz Lauterbach Sybille Buchheim Manfred Kölzer Waltraud Kröger Dorothea Nitz Karin Prescher Gerlind Rott 《Naunyn-Schmiedeberg's archives of pharmacology》1963,244(4):334-350
Ohne Zusammenfassung 相似文献
66.
67.
Sanne Jensen Davíð R.M.A. Højgaard Katja A. Hybel Erik Lykke Mortensen Gudmundur Skarphedinsson Karin Melin Tord Ivarsson Judith Becker Nissen Bernhard Weidle Robert Valderhaug Nor Christian Torp Kitty Dahl Scott Compton Per Hove Thomsen 《Journal of child psychology and psychiatry, and allied disciplines》2020,61(9):969-978
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69.
Philip J. Lupo Ruth E. Luna-Gierke Tiffany M. Chambers Björn Tavelin Michael E. Scheurer Beatrice Melin Karin Papworth 《International journal of cancer. Journal international du cancer》2020,146(3):791-802
Perinatal factors have been associated with soft tissue sarcomas (STS) in case-control studies. However, (i) the contributions of factors including fetal growth remain unknown, ( ii ) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973–2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23–2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25–6.71) in recent years (2000–2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05–3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08–2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS. 相似文献
70.