SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Applying the Fuzzy BWM to Determine the Cryptocurrency Trading System under Uncertain Decision Process

The crypto and digital assets ecosystems have attracted investment, regulators, and speculators to their environment. As the blockchain-based framework can reduce transaction costs, generate distributed trust, and enable decentralized platforms, it has become a potential new base for decentralized business models. Previous studies have highlighted the advantages and drawbacks of each platform, such as interest rates, cost concerns, transparency issues, hacking issues, and hazards. Consequently, it is challenging for investors to evaluate the cryptocurrency trading system which determines the optimum exchanges and crucial aspects. Therefore, in order to rank the optimal digital token trading system, this paper develops an evaluation architecture to determine the various token trading systems. The developed architecture integrates fuzzy theory and the best-worst method (BWM) into the decision-making process to assess decision behaviors regarding preference for digital token trading systems in investors in Taiwan. First, this work establishes the views and parameters by modifying the Delphi method based on a literature review and survey. Second, the fuzzy-BWM is applied to obtain the fuzzy weights of the views and parameters. Then, defuzzification and BWM are used to rank the optimal alternatives of the digital token trading systems for investors. The results indicate that the optimal digital token trading system is the decentralized platform, and the critical parameters are gas fees, interest rates, and the mechanism of savings under fuzzy uncertain scenarios. This means that when considering the uncertain and ambiguous characteristics of the expert decision process in digital token trading systems, the evaluation is decentralized and the gas fees are the most important parameter in the digital token investment platform. Academically, the fuzzy BWM-based decision-making architecture can provide corporations and investors with valuable guidance to rank the optimal digital token trading systems based on fuzzy uncertain scenarios. Commercially, the proposed architecture could provide corporations and investors with a useful model to measure the optimal digital token trading system

Expression of Axl in Lung Adenocarcinoma and Correlation with Tumor Progression

We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001) and the patient's clinical stage (P < .0001). Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer