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Introduction: Short telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE). Aim and methods: TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls. Results: Seventy-nine individuals were included (mean age 69.77 ± 0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p

Abstract Background There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. Results After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with q val = 0.029 and q val = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. Conclusions Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

Purpose: In this Report we analyse the place of civic education in the Greek Education system. The integration of civic education into education since 1982 represents a major step forward in the upgrading of general education. However the curricula are mainly characterised by teacher-centred approaches, with a strong emphasis on the achievement of cognitive objectives and little emphasis on the learning process and teaching strategy. Design/methodology/approach: This report is based on an analysis of the place of social studies in the Greek education system. We analysed the aims of the curricula, the role of teachers, the didactic approaches, the educational practices and the assessment. Findings: From our analysis we have detected a gap between the public rhetoric about the role of social sciences and their implementation in the Greek education. Although it seems that the general principles of curricula are permeated by a more democratic and flexible note which encourages critical thinking and participation, they are not implemented in practice and by and large are annulled due to the great emphasis the Greek education system places on knowledge acquisition and exams. The elimination of Social studies in some classes points to a school which is cut off from the current socio-economic reality, thus condemning students to a passive attitude towards social and educational affairs. Research limitations/implications: This article reports on the research conducted on civic education since the 1990's and onwards. The study of all these researches leads us to the conclusion that neither the curricula nor the textbooks of social studies courses have been extensively analysed, and this could be a future field of research. Another area of research is the role of school charters, the didactic approaches and the assessment in this course in the Greek education context. Practical implications: Upheavals in the history of the Greek governmental system and democracy left their indelible mark on citizens' education; changes in the title of the course, the time allotted to its teaching and the content of school knowledge evidence its dependence on the respective socio-political and ideological regime as well as its indoctrinational character. The turning points in civic education which can be pinpointed between 1982 and 2003 were linked with the educational policy of socialist governments and the gradual paradigm shift in social studies.

BackgroundYoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC).MethodsWe pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted.ResultsThe analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women.ConclusionsWe found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

BackgroundEvidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium.MethodsA total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer.ResultsCompared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84).ConclusionOur results indicate a weak inverse association between tea consumption and gastric cancer.

BackgroundThe role of allium vegetables on gastric cancer (GC) risk remains unclear.MethodsWe evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach.ResultsTotal allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata.ConclusionsIn a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

ObjectiveThis study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls.MethodsA two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer.ResultsCompared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only.ConclusionsThese findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

The rapidly changing reality, which has been influenced by the development of technology and the industrial revolution since the nineteenth century, has largely weakened the teaching profession and the form and type of professional certification. This weakening also devaluates the idea of citizenship, which is largely conveyed during the education process. Contemporary education (4.0) is focused on practical education, where the space for shaping attitudes and creating behaviour patterns is marginalised. The relationship between education and industry related to socialisation and culture-forming processes is part of the development of individuals in societies and part of a broader formal development plan for different types of state and national organisations. The processes of systemic changes in education do not always keep up with the changing social, political and economic situation. The authors of this article indicate how the teacher education process looked in the past, through a sociohistorical approach based on the understanding of what teachers think about the meaning of digital learning in everyday school life and work. In order to do this, it was necessary to undertake an investigation from the perspective of the teachers themselves. This was helpful for the analysis of the semantic and ideological imperfection of education 4.0, based on the role of teaching staff in digital citizenship education.

Purpose: In this Report we analyse the place of civic education in the Greek Education system. The integration of civic education into education since 1982 represents a major step forward in the upgrading of general education. However the curricula are mainly characterised by teacher-centred approaches, with a strong emphasis on the achievement of cognitive objectives and little emphasis on the learning process and teaching strategy. Design/methodology/approach: This report is based on an analysis of the place of social studies in the Greek education system. We analysed the aims of the curricula, the role of teachers, the didactic approaches, the educational practices and the assessment. Findings: From our analysis we have detected a gap between the public rhetoric about the role of social sciences and their implementation in the Greek education. Although it seems that the general principles of curricula are permeated by a more democratic and flexible note which encourages critical thinking and participation, they are not implemented in practice and by and large are annulled due to the great emphasis the Greek education system places on knowledge acquisition and exams. The elimination of Social studies in some classes points to a school which is cut off from the current socio-economic reality, thus condemning students to a passive attitude towards social and educational affairs. Research limitations/implications This article reports on the research conducted on civic education since the 1990’s and onwards. The study of all these researches leads us to the conclusion that neither the curricula nor the textbooks of social studies courses have been extensively analysed, and this could be a future field of research. Another area of research is the role of school charters, the didactic approaches and the assessment in this course in the Greek education context. Practical implications Upheavals in the history of the Greek governmental system and democracy left their indelible mark on citizens’ education; changes in the title of the course, the time allotted to its teaching and the content of school knowledge evidence its dependence on the respective socio-political and ideological regime as well as its indoctrinational character. The turning points in civic education which can be pinpointed between 1982 and 2003 were linked with the educational policy of socialist governments and the gradual paradigm shift in social studies.

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

Self-injurious and aggressive behaviors are common in fragile X syndrome (FXS). However, little is known about the persistence of these behaviors and associated risk markers. We established the prevalence and persistence of self-injurious and aggressive behaviors over eight years in males with FXS, and associations with risk markers. Results showed 77% and 69% persistence rates for self-injurious and aggressive behavior, respectively. Baseline levels of repetitive behavior "predicted" persistent self-injurious behavior. Chronological age, impulsivity and overactivity were associated with persistent aggressive behavior but only impulsivity predicted persistence. This is the first study to document the persistence of self-injurious and aggressive behavior in FXS over the medium to long term and to identify behavioral risk markers that might facilitate targeted early intervention.

Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our study was to assess the impact of COVID-19 on early lung cancer patients’ surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor’s size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic [median time 47 days, interquartile rate (IQR): 23–100] vs. [median time 18 days, IQR: 11–23], p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.