Background: Application of game-based learning in clinical practice has shown potential advantages in

The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Although irreversible EGFR TKIs, such as afatinib or dacomitinib, have been introduced to overcome the acquired resistance, they showed a limited efficacy in NSCLC with T790M. Herein, we identified the novel de novo resistance mechanism to irreversible EGFR TKIs in H1975 and PC9-GR cells, which are NSCLC cells with EGFR T790M. Afatinib activated interleukin-6 receptor (IL-6R)/JAK1/STAT3 signaling via autocrine IL-6 secretion in both cells. Inhibition of IL-6R/JAK1/STAT3 signaling pathway increased the sensitivity to afatinib. Cancer cells showed stronger STAT3 activation and enhanced resistance to afatinib in the presence of MRC5 lung fibroblasts. Blockade of IL-6R/JAK1 significantly increased the sensitivity to afatinib through inhibition of afatinib-induced STAT3 activation augmented by the interaction with fibroblasts, suggesting a critical role of paracrine IL-6R/JAK1/STAT3 loop between fibroblasts and cancer cells in the development of drug resistance.

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Energy dissipation at surfaces and interfaces is mediated by excitation of elementary processes, including phonons and electronic excitation, once external energy is deposited to the surface during exothermic chemical processes. Nonadiabatic electronic excitation in exothermic catalytic reactions results in the flow of energetic electrons with an energy of 1-3 eV when chemical energy is converted to electron flow on a short (femtosecond) time scale before atomic vibration adiabatically dissipates the energy (in picoseconds). These energetic electrons that are not in thermal equilibrium with the metal atoms are called "hot electrons". The detection of hot electron flow under atomic or molecular processes and understanding its role in chemical reactions have been major topics in surface chemistry. Recent studies have demonstrated electronic excitation produced during atomic or molecular processes on surfaces, and the influence of hot electrons on atomic and molecular processes. We outline research efforts aimed at identification of the intrinsic relation between the flow of hot electrons and catalytic reactions. We show various strategies for detection and use of hot electrons generated by the energy dissipation processes in surface chemical reactions and photon absorption. A Schottky barrier localized at the metal-oxide interface of either catalytic nanodiodes or hybrid nanocatalysts allows hot electrons to irreversibly transport through the interface. We show that the chemicurrent, composed of hot electrons excited by the surface reaction of CO oxidation or hydrogen oxidation, correlates well with the turnover rate measured separately by gas chromatography. Furthermore, we show that hot electron flows generated on a gold thin film by photon absorption (or internal photoemission) can be amplified by localized surface plasmon resonance. The influence of hot charge carriers on the chemistry at the metal-oxide interface are discussed for the cases of Au, Ag, and Pt nanoparticles on oxide supports and Pt-CdSe-Pt nanodumbbells. We show that the accumulation or depletion of hot electrons on metal nanoparticles, in turn, can also influence catalytic reactions. Mechanisms suggested for hot-electron-induced chemical reactions on a photoexcited plasmonic metal are discussed. We propose that the manipulation of the flow of hot electrons by changing the electrical characteristics of metal-oxide and metal-semiconductor interfaces can give rise to the intriguing capability of tuning the catalytic activity of hybrid nanocatalysts.

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The purpose of the current study was to evaluate possible overlapping substance abuse and internet addiction in a large, uniformly sampled population, ranging in age from 13 to 18 years. Participants (N=73,238) in the current study were drawn from the 6th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) for students from 400 middle schools and 400 high schools in 16 cities within South Korea. Of adolescent internet users, 85.2% were general users (GU), 11.9% were users with potential risk for internet addiction (PR), and 3.0% were users with high risk for internet addiction (HR). There was a difference in the number of students with alcohol drinking among the GU, PR, and HR groups (20.8% vs 23.1% vs 27.4%). There was a difference in the number of students who smoked among the GS, PR, and HR groups (11.7% vs 13.5% vs 20.4%). There was a difference in the number of students with drug use among the GU, PR, and HR groups (1.7% vs 2.0% vs 6.5%). After adjusting for sex, age, stress, depressed mood, and suicidal ideation, smoking may predict a high risk for internet addiction (OR=1.203, p=0.004). In addition, drug use may predict a high risk for internet addiction (OR=2.591, p<0.001). Because students with a high risk for internet addiction have vulnerability for addictive behaviors, co-morbid substance abuse should be evaluated and, if found, treated in adolescents with internet addiction.

After breast conservation therapy in women 50 years or younger, the addition of MRI to annual mammography screening improves detection of early-stage but biologically aggressive breast cancers at acceptable specificity. Results from this study can inform patient decision making on screening methods after breast conservation therapy.