Influence of unrecorded alcohol consumption on liver cirrhosis mortality

Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans(e.g.,cosmetics containing alcohol).The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality.Compounds besides ethanol have been hypothesized as being responsible for this observation.On the other hand,chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds.However,illegally produced spirits regularly contain higher percentages of alcohol(above 45%by volume),but for considerably less costs compared with licit beverages,potentially causing more problematic patterns of drinking.In this review,it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates.Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking.It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits(e.g.,higher levels of certain contaminants in home-produced products)and liver toxicity on a population scale.Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine,which were reported to be consumed as surrogate alcohol in Russia,leading to an outbreak of acute cholestatic liver injury,histologically different from conventional alcoholic liver disease.

Challenges in microRNAs’ targetome prediction and validation

MicroRNAs(miRNAs)are small RNA molecules with important roles in post-transcriptional regulation of gene expression.In recent years,the predicted number of miRNAs has skyrocketed,largely as a consequence of high-throughput sequencing technologies becoming ubiquitous.This dramatic increase in miRNA candidates poses multiple challenges in terms of data deposition,curation,and validation.Although multiple databases containing miRNA annotations and targets have been developed,ensuring data quality by validating miRNA-target interactions requires the efforts of the research community.In order to generate databases containing biologically active miRNAs,it is imperative to overcome a multitude of hurdles,including restricted miRNA expression patterns,distinct miRNA biogenesis machineries,and divergent miRNA-mRNA interaction dynamics.In the present review,we discuss recent advances and limitations in miRNA prediction,identification,and validation.Lastly,we focus on the most enriched neuronal miRNA,miR-124,and its gene regulatory network in human neurons,which has been revealed using a combined computational and experimental approach.

High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay

Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors(HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference(HT-RNAi) screens has led to the identification of several key factors involved in the viral lifecycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested(such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase Ⅲα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HTRNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.

Between evidence and new perspectives on the current state of the multimodal approach to gastric cancer:Is there still a role for radiation therapy?

In patients affected by gastric cancer(GC), especially those in advanced stage, the multidisciplinary app-roach of treatment is fundamental to obtain a good disease control and quality of life. Although many chemotherapeutics in combination to radiotherapy are adopted in the peri- or postoperative setting, the most optimal timing, regimens and doses remains con-troversial. In the era of radical surgery performed with D2-lymphadenectomy, the role of radiation therapy remains to be better defined. Categories of patients, who could benefit more from an intensified local trea-tment rather than more toxic systemic therapy, are still under investigation. Evidence and recent updates of the randomized trials, meta-analysis and prospective trials show that the postoperative radiotherapy plays a fundamental role in reducing the loco-regional recurrence and in turn the disease-free survival in operable advanced GC patients, also after a well performed D2 surgery. Therapeutic decisions should be taken considering the individual patients, but the multimodal approach is necessary to guarantee a longer survival and a good quality of life. Ongoing randomized trials could better define the timing and the combination of radiotherapy and systemic therapy.

Two-dimensional organic cathode materials for alkali-metal-ion batteries

With the increasing demand for large-scale battery systems in electric vehicles（EVs） and smart renewable energy grids, organic materials including small molecules and polymers utilized as electrodes in rechargeable batteries have received increasing attraction. In recent years, two-dimensional（2D） organic materials possessing planar layered architecture exhibit optional chemical modification, high specific surface area as well as unique electrical/magnetic properties, which have been emerging as the promising functional materials for wide applications in optoelectronics, catalysis, sensing, etc. Integrating with high-density redox-active sites and hierarchical porous structure, significant achievements in 2D organic materials as cathode materials for alkali-metal-ion batteries have been witnessed. In this review, the recent progress in synthetic approaches, structure analyses, electrochemical characterizations of 2D organic materials as well as their application in alkali-metal-ion batteries containing lithium ion battery（LIB）, lithium sulfur battery（LSB）, lithium air battery（LAB） and sodium ion battery（SIB） are summarized systematically,and their current challenges including cycling stability and electron conductivity for cathode materials in battery fields are also discussed.

Influence of PAN-Fiber Stretching during Thermal Treatment on the Stabilization Reactions

The stabilization of PAN-fibers without additional co-monomers was investigated with thermo-gravimetry and evolved gas analysis (FTIR-spectroscopy and MS-spectrometry). One fiber type had been drawn after spinning, while the other was used as-spun. During the thermal treatment, fiber shrinkage was either restricted or unrestricted. Investigations of influencing chemical and physical reactions regarding this restriction were conducted. Differences in the mass loss and gas emissions were observed, depending on the strained or unstrained state of the fibers. The change of crystallinity and molecular orientation of the fiber as reason of the measured variations was discussed. The emission of ammonia and other nitrogen containing gases (supposedly nitriles/ isocyanates) could be attributed to different aspects of the stabilization process. The length restriction resulted in a change in ammonia emission, associated with the cyclization reaction of poly acrylonitrile. The onset and amount of side reactions were influenced as well.

Performance demonstration of the PENELOPE main amplifier HEPA I using broadband nanosecond pulses

We report on the energetic and beam quality performance of the second to the last main amplifier section HEPA I of the PENELOPE laser project. A polarization coupled double-12-pass scheme to verify the full amplification capacity of the last two amplifiers HEPA I and II was used. The small signal gain for a narrow-band continuous wave laser was 900 and 527 for a broadband nanosecond pulse, demonstrating 12.6 J of output pulse energy. Those pulses, being spectrally wide enough to support equivalent 150 fs long ultrashort pulses, are shown with an excellent spatial beam quality. A first active correction of the wavefront using a deformable mirror resulted in a Strehl ratio of 76% in the single-12-pass configuration for HEPA I.

Contribution of Fluid Dynamics to Woodwind Instruments Investigations of Timbre and Pitch of Bassoon Bocals

The discussed topic of isolating certain parameters which describe the timbre in connection with bocals of bassoons is of major interest for manufacturers and artist likewise since a reduction in the overall shear stress of these kinds of technical diffusors is very helpful but not sufficient. The timbre seen from the side of the musician has to be the same. Up to now two criteria have been isolated which have a deep influence on the easier blowing of the bassoon and on the comparable timbre due to geometrical reasons. If the geometrical outer contour is designed carefully, it is possible to modify the shape and preserve the timbre.