Abstract
Patients diagnosed with germline mutations in MMR genes (Lynch Syndrome, LS) have up to 70-80% lifetime risk of colorectal cancer. Therefore, this high-risk population has the potential to ...benefit from effective chemopreventive strategies. Naproxen is an NSAID widely used for pain treatment with an excellent safety profile that has demonstrated to be more efficacious preventing colorectal cancer compared to aspirin in vivo using an intestinal tissue-specific mouse model of LS (VC-Msh2-LoxP). The ‘Naproxen trial' was designed to evaluate the modulation of PGE2 levels in colorectal mucosa, evaluate safety and tolerability, and discover novel molecular pathways involved in the chemopreventive activity of naproxen in LS patients. Methods: Participants were randomized to naproxen 440 mg (HD), 220 mg (LD) and placebo by mouth daily for 6 months. Modulation of prostaglandin levels, number of adverse events (AEs) observed in each treatment arm and gene expression profiles by next-generation sequencing (mRNAseq) in normal colorectal mucosa of LS patients after 6 months of intervention were examined. Results: Eighty participants diagnosed with LS were randomized, 25 participants to HD, 27 to LD, and 28 to placebo. From these patients, 54 were considered evaluable per-protocol analysis: 16 in the HD group, 15 in the LD and 23 in placebo. The level of prostaglandin E2 in the colorectal mucosa decreased significantly after treatment with both LD and HD naproxen when compared to placebo (-91.2%±14.1, -93.6%±7.9, and 23.8%±108.4, P-value<0.001, respectively). Moreover, levels of PGE2 urinary metabolite (PGE-M) were significantly changed in both treatment groups when compared to placebo (-47.7%±56.9, -41.1%±40.5, 7.6%±94.3, P-Value<0.018). The intervention was well tolerated, no severe AEs related to treatment were reported, and the total number of AEs was not different across treatment arms. LD and HD naproxen promoted the activity of the immune system by activating different immune cell types without any effect on lymphoid cellularity and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Conclusions: Naproxen is a promising strategy for immune interception in LS that induces immune-modulation coupled with changes in the dynamics of the intestinal crypt. We have also discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity.
Citation Format: Laura Reyes Uribe, Wenhui Wu, Ozkan Gelincik, Prashant V. Bommi, Alejandro Francisco-Cruz, Luisa M. Solis, Patrick M. Lynch, Ramona Lim, Elena Stoffel, Priyanka Kanth, N. Jewel Samadder, Maureen E. Mork, Melissa W. Taggart, Ginger L. Milne, Lawrence J. Marnett, Lana Vornik, Diane D. Liu, Maria Revuelta, Kyle Chang, Y. Nancy You, Levy Kopelovich, Ignacio I. Wistuba, J. Jack Lee, Shizuko Sei, Robert H. Shoemaker, Eva Szabo, Ellen Richmond, Asad Umar, Marjorie Perloff, Powell H. Brown, Steven M. Lipkin, Eduardo Vilar. Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa abstract. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT111.
The educational integration of Information and Communication Technologies (ICT) has been put to the test because of the need to implement «emergency remote education» as a result of COVID-19. Within ...this context of uncertainty («viral modernity»), flexible education is an option to promote a more just, equitable, accessible and creative educational system. In order to properly interpret the effects of this unique educational circumstance, it is essential to study the previous situation in terms of the use of digital technologies in teaching practices. The objective of the study is to describe the educational integration of ICT and the teacher education model to obtain evidence that contributes to understanding the phenomenon. To this end, a questionnaire consisting of two self-reporting tools and a scale on the description of teaching practice with ICT was applied. The sample is made up of teachers from public primary and secondary schools (N = 251). Data collection was carried out in the months prior to the closure of schools due to the Covid-19 pandemic. A univariate analysis of the variables and contrast tests of non-parametric hypotheses was carried out, along with calculation of the reliability and construction validity of the measuring instruments. The results reveal the most frequent types of teaching practice with ICT and the spaces where digital technologies are commonly used. Various weaknesses can be identified in digital competence among teachers, as well as in the initial/continuing training model, which contribute to the understanding of the difficulties encountered during "emergency remote education". Participation in ICT didactic innovation projects and the performance of ICT Coordination are associated with more experiential training. Flexible education requires a redefinition of the teacher training model that encourages learning anywhere, anytime.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This systematic literature review aimed to discover how the concept of digital teaching competence (DTC) has been developed, how its dimensions have been defined, and how educational development ...models and models that evaluate teachers’ digital teaching competence have been constructed. Concurrently, this review aimed to draw conclusions on the implementation processes of digital teaching competence in order to uncover its strengths and limitations, and to propose future lines of research to develop it further in initial teacher training programmes. A systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was proposed in order to achieve these aims. We chose the time frame of 2015 to the end of 2021 in an attempt to cover the appearance of the first scientific articles dealing with the subject, up until the present day. Thus, the inclusion criteria covered scientific research articles from the Web of Science (WoS) and Scopus databases, in English or Spanish, that focused on samples of teachers in primary education, secondary education, baccalaureates, and initial teacher training. The database searches, which will be detailed in depth later, initially provided a corpus of 127 articles, which was reduced to 26 articles after screening for duplicity and applying the inclusion criteria.
This study focuses on the issue of school bullying and explores the potential of video games as a tool to prevent and address this problem. To accomplish this, the video game Monité, specifically ...designed for the prevention of school bullying, was utilized, using the paradigm of digital game-based learning as an intervention methodology that emphasizes its educational and recreational potential. This study was conducted using a quasi-experimental approach, employing a pre-test and post-test design with a non-equivalent control group. The sample consisted of 92 boys and girls from fifth and sixth grade in primary education in the province of Cáceres, Spain. Data were collected through questionnaires from the System for the Evaluation of Children and Adolescents (SENA), which allowed for the gathering of information on peer problems, school problems and family issues. The results show that there are significant differences between the intervention group and the control group regarding problems external to individuals. In conclusion, this study investigates the use of the video game Monité as a tool to prevent school bullying and analyzes its impact on students’ perception of external agents such as family, peer group, and school. Our findings support its implementation in educational environments as an effective strategy.
Objective: To design a Computer-aided diagnosis (CAD) system using an optimized methodology over the P3b wave in order to objectively and accurately discriminate between healthy controls (HC) and ...schizophrenic subjects (SZ). Methods: We train, test, analyze, and compare various machine learning classification approaches optimized in terms of the correct classification rate (CCR), the degenerated Youden's index (DYI) and the area under the receiver operating curve (AUC). CAD system comprises five stages: electroencephalography (EEG) preprocessing, feature extraction, seven electrode groupings, discriminant feature selection, and binary classification. Results: With two optimal combinations of electrode grouping, filtering, feature selection algorithm, and classification machine, we get either a mean CCR = 93.42%, specificity = 0.9673, sensitivity = 0.8727, DYI = 0.9188, and AUC = 0.9567 (total-15 Hz-J5-MLP), or a mean CCR = 92.23%, specificity = 0.9499, sensitivity = 0.8838, DYI = 0.9162, and AUC = 0.9807 (right hemisphere-35 Hz-J5-SVM), which to our knowledge are higher than those available to date. Conclusions: We have verified that a more restrictive low-pass filtering achieves higher CCR as compared to others at higher frequencies in the P3b wave. In addition, results validate previous hypothesis about the importance of the parietal-temporal region, associated with memory processing, allowing us to identify powerful {feature,electrode} pairs in the diagnosis of schizophrenia, achieving higher CCR and AUC in classification of both right and left Hemispheres, and parietal-temporal EEG signals, like, for instance, the {PSE, P4} pair (J5 and mutual information feature selection). Significance: Diagnosis of schizophrenia is made thoroughly by psychiatrists but as any human-based decision that has a subjective component. This CAD system provides the human expert with an objective complimentary measure to help him in diagnosing schizophrenia.
The growing relevance of video games in the social landscape requires an in-depth evaluation of the bidirectional influences of these adjacent contexts, among which the educational and cultural ...contexts stand out. This permeability allows the study of the cultural aspects surrounding the production and use of video games as tools for cultural dissemination. Our research enunciates, recognises, analyses and evaluates the impact of these tools with the aim of being taken into consideration by the scientific community and the general population, who most frequently consume, use and socialise through video games around the world. Based on this, a systematic literature review (SLR) was carried out using the Prisma 2020 Protocol, using the WOS and SCOPUS databases as documentary sources, and the selection of research articles that explore the cultural aspects of video games according to pre-established criteria. The final sample (N = 45) was subjected to a study that posed 12 research questions around which this work is structured. As a result, it is evident that video games have a direct impact on the transmission of culture. Patterns and agents of cultural representation, transmission and communication were identified, allowing researchers to evaluate the impact of video games on culture and to approach this object of study from an academic perspective, helping to open up other lines of research related to the influence of video games on the assimilation of culture, the learning of relevant issues related to it or the transmission of specific cultural elements.
Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate ...that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosomes released by injured epithelial cells promote proliferation, α-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-β1 mRNA among other yet to be identified moieties. This study suggests that TGF-β1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis.
Gamification allows for the implementation of experiences that simulate the design of (video) games, giving individuals the opportunity to be the protagonists in them. Its inclusion in the ...educational environment responds to the need to adapt teaching–learning processes to the characteristics of homo videoludens, placing value once again on the role of playful action in the personal development of individuals. The interest that has arisen in studying the implications of gamification processes in the different educational stages, in order to determine their impact and suitability, has led to an increase in scientific publications. With the intention of studying the presence and implications of gamification in teacher training as a methodological principle implemented in the teaching–learning process, both in its initial and permanent stages, this systematic review of the literature identifies those instructional design models applied in the field of gamification, as well as its educational significance. Thus, the need to introduce gamified practices in the field of teacher training is observed, providing an experiential learning that allows teachers to apply this methodology in a relevant way in their professional development, based on their own experience.
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