Futures Studies in the Interactive Society

This book consists of papers which were prepared within the framework of the research project (No. T 048539) entitled Futures Studies in the Interactive Society (project leader: Éva Hideg) and funded by the Hungarian Scientific Research Fund (OTKA) between 2005 and 2009. Some discuss the theoretical and methodological questions of futures studies and foresight; others present new approaches to or procedures of certain questions which are very important and topical from the perspective of forecast and foresight practice. Each study was conducted in pursuit of improvement in futures fields

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFβ2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone

Evaluierung von Gesundheitsinterventionen bei ein- bis sechsjährigen Kindern

Die Arbeit handelt von Gesundheitsinterventionen bei ein- bis sechsjährigen Kindern, wobei nationale und internationale Projekte analysiert werden

Enantioseparation on Riboflavin Derivatives Chemically Bonded to Silica Gel as Chiral Stationary Phases for HPLC

International audienceAcetylated and/or 3,5-dimethylphenylcarbamated riboflavins were prepared and the resulting riboflavin derivatives as well as natural riboflavin were regioselectively immobilized on silica gel through chemical bonding at the 5’-O- or 3-N-position of the riboflavin to develop novel chiral stationary phases (CSPs) for enantioseparation by high-performance liquid chromatography (HPLC). The chiral recognition abilities of the obtained CSPs were significantly dependent on the structures of the riboflavin derivatives, the position of the chemical bonding on the silica gel, and the structures of the racemic compounds. The CSPs bonded at the 5’-O-position on the silica gel tended to well separate helicene derivatives, while the CSPs bonded at the 3-N-position composed of acetylated and 3,5-dimethylphenylcarbamated riboflavins showed a better resolving ability toward helicene derivatives and bulky aromatic racemic alcohols, respectively, and some of them were completely separated into the enantiomers. The observed difference in the chiral recognition abilities of these riboflavin-based CSPs is discussed based on the difference in their structures, including the substituents of riboflavin and the positions immobilized on the silica gel

A Third Way to the Selected Effect/Causal Role Distinction in the Great Encode Debate

Since the ENCODE project published its final results in a series of articles in 2012, there is no consensus on what its implications are. ENCODE’s central and most controversial claim was that there is essentially no junk DNA: most sections of the human genome believed to be «junk» are functional. This claim was met with many reservations. If researchers disagree about whether there is junk DNA, they have first to agree on a concept of function and how function, given a particular definition, can be discovered. The ENCODE debate centered on a notion of function that assumes a strong dichotomy between evolutionary and non-evolutionary function and causes, prevalent in the Modern Evolutionary Synthesis. In contrast to how the debate is typically portrayed, both sides share a commitment to this distinction. This distinction is, however, much debated in alternative approaches to evolutionary theory, such as the EES. We show that because the ENCODE debate is grounded in a particular notion of function, it is unclear how it connects to broader debates about what is the correct evolutionary frame- work. Furthermore, we show how arguments brought forward in the controversy, particularly arguments from mathematical population genetics, are deeply embedded in their particular disciplinary contexts, and reflect substantive assumptions about the evolution of genomes. With this article, we aim to provide an anatomy of the ENCODE debate that offers a new perspective on the notions of function both sides employed, as well as to situate the ENCODE debate within wider debates regarding the forces operating in evolution

Genomic insights into cancer-associated aberrant CpG island hypermethylation

Carcinogenesis is thought to occur through a combination of mutational and epimutational events that disrupt key pathways regulating cellular growth and division. The DNA methylomes of cancer cells can exhibit two striking differences from normal cells; a global reduction of DNA methylation levels and the aberrant hypermethylation of some sequences, particularly CpG islands (CGIs). This aberrant hypermethylation is often invoked as a mechanism causing the transcriptional inactivation of tumour suppressor genes that directly drives the carcinogenic process. Here, we review our current understanding of this phenomenon, focusing on how global analysis of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development. We also discuss how genome-scale analyses of both normal and cancer cells have refined our understanding of the elusive mechanism(s) that may underpin aberrant CGI hypermethylation

Tailored Basic Life Support Training for Specific Layperson Populations-A Scoping Review.

Background: Basic life support (BLS) is a life-saving link in the out-of-hospital cardiac arrest chain of survival. Most members of the public are capable of providing BLS but are more likely to do so confidently and effectively if they undertake BLS training. Lay members of the public comprise diverse and specific populations and may benefit from tailored BLS training. Data on this topic are scarce, and it is completely unknown if there are any benefits arising from tailored courses or for whom course adaptations should be developed. Methods: The primary objective of this scoping review was to identify and describe differences in patient, clinical, and educational outcomes when comparing tailored versus standard BLS courses for specific layperson populations. This review was undertaken as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation. Results: A primary search identified 1307 studies and after title, abstract, and full-text screening, we included eight publications reporting on tailored courses for specific populations. There were no studies reporting direct comparisons between tailored and standardized training. Seven (88%) studies investigated courses tailored for individuals with a disability, and only one study covered another specific population group (refugees). Overall, the quality of evidence was low as the studies did not compare tailored vs. non-tailored approaches or consisted of observational or pre-post-designed investigations. Conclusions: Tailored BLS education for specific populations is likely feasible and can include such groups into the pool of potential bystander resuscitation providers. Research into comparing tailored vs. standard courses, their cost-to-benefit ratio, how to best adapt courses, and how to involve members of the respective communities should be conducted. Additionally, tailored courses for first responders with and without a duty to respond could be explored