Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT- based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro

Moments : an unfolding journey of self-discovery through photographic art

Tässä opinnäytetyössä tutkitaan itsensä löytämisen prosessia valokuvataiteen kautta, keskittyen siihen, miten kymmenen vuoden katukuvauksen kokemus on muokannut visuaalista kieltä ja lähestymistapaa tulevaisuuden käytännöille. Taiteellista tutkimusmenetelmää hyödynnetään yhdistämällä autoetnografiaa ja itsereflektiota, jotta voidaan tarkastella ulkoisia motiiveja ja sisäisiä tuntemuksia, ohjaten intuitiolla ja nykyhetken tietoisuudella. Tutkimus perustuu teoreettiseen viitekehykseen, joka analysoi erilaisten valokuvaajien pohdintoja ja filosofioita, mukaan lukien esimerkiksi käsitteet ratkaiseva hetki, zen-filosofia ja mindfulness, sekä introspektiiviset teemat, jotka ovat syvästi juurtuneita teokseen. Matkalta kertyneitä oivalluksia sovelletaan uuteen taiteelliseen projektiin, joka keskittyy sisäiseen ohjaukseen naisten kuvaamisessa luonnollisissa ympäristöissä. On päätelty, että valokuvaus, kun sitä lähestytään tietoisesti ja nykyhetkeen uppoutuen, toimii arvokkaana työkaluna itsensä löytämisessä, muuttaen esteet luovan inspiraation lähteiksi ja edistäen syvempää sitoutumista sekä aiheisiin että taiteilijan omaan matkaan. Tämä työ esittää valokuvauksen ei pelkästään maailman dokumentointina, vaan reflektiivisenä välineenä, joka paljastaa henkilökohtaisia ja universaaleja totuuksia.This thesis explores the self-discovery process through photographic art, focusing on how a decade of street photography has shaped visual language and approach for future practice. An artistic research methodology is employed, integrating autoethnography and self-reflection to examine outward motivations and inward sensations, guided by intuition and present-moment awareness. The research is grounded in a theoretical framework that analyzes various photographers’ reflections and philosophies, including concepts like the decisive moment, Zen philosophy, and mindfulness, along with introspective themes embedded in the work. Insights gained from this journey are applied to a new artistic project focused on inner guidance when photographing women in natural settings. It is concluded that photography, when approached mindfully and immersed in the present, serves as a valuable tool for self-discovery, transforming obstacles into sources of creative inspiration and fostering deeper engagement with both subjects and the artist’s journey. Ultimately, this work presents photography not merely as a documentation of the world but as a reflective medium that reveals personal and universal truths

Cyber-bullying from a socio-ecological perspective: a review of evidence from cross-national data

Background: Involvement in bullying has been shown to result from a complex interplay between individuals and their wider social environment. Using Bronfenbrenner's classic ecological theory as a starting point the current paper reviews findings on cyber-bullying from the cross-national survey data of the EU Kids Online project; a representative sample of 25,142 internet-using European children aged 9-16 years. Methods: Research outputs on cyber-bullying using the EU Kids Online data were accumulated. With the child at the centre, factors associated with cyberbullying were considered at different levels of the socio-ecological system: a) the individual level (e.g., socio-demographic, psychological and internet use characteristics of the child), b) the immediate social environment (e.g., awareness, mediation and support sought of parents, teachers and peers), and c) the more distal environment (e.g., policy regulations, national statistics and cultural norms at the country level).The results for each level were reviewed and synthesised using a qualitative approach. Findings: Risk and protective factors associated with the experience of cyber-bullying were identified on the level of the individual (e.g., psychological difficulties increased risk), the social environment (e.g., peer support increased coping), the country (e.g., higher national crime rates increased risk) and their interactions (e.g., online activities were related to cyber-bullying dependent on countries’ mobile phone penetration). Discussion: An evidence-based framework with regards to the experience of cyber-bullying among young people from a socio-ecological perspective is presented. Implications for prevention and intervention efforts to consider different levels of the socio-ecological system as well as their interactions are pointed out

Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11

For 21 putative BRCA1 and BRCA2 splice site variants, the concordance between mRNA analysis and predictions by in silico programs was evaluated. Aberrant splicing was confirmed for 12 alterations. In silico prediction tools were helpful to determine for which variants cDNA analysis is warranted, however, predictions for variants in the Cartegni consensus region but outside the canonical sites, were less reliable. Learning algorithms like Adaboost and Random Forest outperformed the classical tools. Further validations are warranted prior to implementation of these novel tools in clinical settings. Additionally, we report here for the first time activated cryptic donor sites in the large exon 11 of BRCA2 by evaluating the effect at the cDNA level of a novel tandem duplication (5 breakpoint in intron 4; 3 breakpoint in exon 11) and of a variant disrupting the splice donor site of exon 11 (c.6841+1G>C). Additional sites were predicted, but not activated. These sites warrant further research to increase our knowledge on cis and trans acting factors involved in the conservation of correct transcription of this large exon. This may contribute to adequate design of ASOs (antisense oligonucleotides), an emerging therapy to render cancer cells sensitive to PARP inhibitor and platinum therapies

Predicting Online and Offline Civic Participation among Young Czech Roma: The Roles of Resources, Community Perceptions and Social Norms

Roma in the Czech Republic represent a large ethnic minority that faces intolerance and social exclusion. This study aims to describe factors that boost civic participation among Roma adolescents and emerging adults. Specifically, it asks whether different factors apply to Roma and members of the majority, and whether different factors boost offline and online participation. Survey data were analysed from Roma (n = 157) and majority (n = 573) participants between the ages of 15 and 28. Hierarchical regression models suggested that certain factors (a sense of collective influence and peer participatory norm) predict all forms of civic participation, regardless of ethnicity. For Roma youth, in contrast with the majority, offline participation was associated with a perceived lack of opportunities and unmet needs in their communities, which suggests that their offline civic participation might be a reaction to perceived communal problems. Finally, a lack of education was identified as a major explanation for lower rates of online participation among Roma

Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study

Aim To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). Patients and methods Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin ® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin ® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation. Results A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients). Conclusions Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected

Cyberbullying in Europe: a review of evidence from cross-national data

Chapter - No abstract available

EU Kids Online 2020: technical report

This report describes in detail the methodology used for the EU Kids Online IV project (see the description of the four phases of the project in the next section). Within this project, a large-scale survey of children aged 9–17 from 19 European countries was conducted. The data were collected between autumn 2017 and summer 2019 from 25,101 children by national teams from the EU Kids Online network. This report provides information about the nature of the project, how the questionnaire was developed, sampling and data collection, ethical issues, data management and weighting. The information in this report should enable dataset users to understand the logic and nature of the survey. For dataset users, we also recommend using the ‘Data Dictionary’ (available at eukidsonline.net), a related document that systematically maps all the information related to the data in the dataset. Moreover, Annex 2 of this report provides concise key guidelines for dataset users. We highly recommend using these short guidelines during work with the EU Kids Online 2020 dataset. Annex 3 contains a description of the key variables. Full questionnaires and their national forms are available at eukidsonline.net