TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: After decades of low personal risk for contracting lethal diseases, physicians are suddenly facing the possibility of a substantial increase in occupational risk during an influenza pandemic. If they are not confronted before the onset of an influenza pandemic, feelings of unease and fear or ignorance about physicians' professional obligations could profoundly hinder individual physicians in fulfilling their professional duties. Such feelings could therefore undermine institutional and societal preparations. In their review published in Critical Care, Anantham and coworkers outline the ethical framework that forms the basis of the professional obligations of physicians who respond to health care emergencies, such as an influenza pandemic.

SOLUTION: Pandemic influenza: are we prepared to face our obligations?

PROBLEM: Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates. Fields et al., 2014). Details about the data used for the different species are provided in Table S1 . Sequence data were processed as follows: predicted CDS from the fully sequenced genomes of C. gigas (release 9) and P. fucata were retrieved from http://oysterdb.cn and http://marinegenomics.oist.jp/pinctada fucata, respectively. De novo transcriptome assemblies were performed for all the other 62 bivalve species with the CLC Genomics Workbench (v.7.5, CLC Bio, Aarhus, Denmark) using the de novo assembly tool with "automatic word size" and "automatic bubble size" parameters selected, and setting the minimum allowed contig length to 300 bp. In all transcriptomes, ORFs (Open Reading Frames) longer than 100 codons were predicted with TransDecoder (http://transdecoder.sourceforge.net). We selected the predicted CDS of C. gigas, and of one representative species for the Imparidentia (R. decussatus), Protobranchia (S. velum) and Palaeoheterodonta (P. grandis) lineages to identify a subset of evolutionarily conserved protein-coding genes with a 1:1 orthology ratio across Bivalvia. This was achieved by performing reciprocal tBLASTx searches (the e-value threshold was set a 1 × 10 −10 and only hits displaying sequence identity >50% were considered). This procedure resulted in a selection of 2,846 conserved protein-coding genes, whose orthologous sequences were retrieved in the remaining 60 species. Due to the heterogeneous tissue and developmental stage origin, the different sequencing platforms and depth applied, several of these evolutionarily conserved sequences could not be identified or were fragmented in some transcriptomes. In order to ensure a minimum quality criteria, all the selected species had to display at least 25% of the sequences included in the dataset of evolutionarily conserved genes, with an average length >500 nucleotides.

SOLUTION: Distributed under Creative Commons CC-BY 4.0 Analysis of synonymous codon usage patterns in sixty-four different bivalve species

PROBLEM: Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV-positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence. Genetic, environmental, and viral factors have been incriminated in the etiology of NPC and Epstein-Barr virus (EBV) is strongly associated with the occurrence of NPC. EBV is a member of the gamma herpesviruses, with a 172 kb double-stranded DNA genome. The life cycle of EBV includes latency and lytic replication. Eleven gene products, EBNAs 1~6, LMPs 1, 2A, and 2B, and small RNAs EBER 1 and 2, are expressed during latent infection [6] . Upon induction by chemicals or stress, EBV is activated and enters the lytic cycle, known as reactivation. Three subsets of lytic genes, immediate-early, early, and late genes, are expressed sequentially and, subsequently, viral particles are packaged and released [7, 8] . Through years of study, EBV latent infection has been considered to play an important role in NPC carcinogenesis. In recent years, accumulating evidence has suggested that EBV lytic infection also contributes to the tumorigenesis of NPC. Sero-epidemiological surveys indicate that patients with elevated antibody titers against EBV lytic proteins, such as viral capsid antigen (VCA), DNase, DNA polymerase, and early antigen (EA), have a high risk of NPC [9] [10] [11] [12] [13] [14] [15] . Several EBV lytic products have been detected in the NPC biopsies [16] [17] [18] . In addition, EBV lytic proteins, including BARF1, BHRF1, BRLF1, BALF3, BGLF4, and DNase, have been shown to have various tumorigenic functions [16, [19] [20] [21] [22] . In our previous study, we found that EBV reactivated by chemicals promotes cellular genome instability and tumor growth [23, 24] . Collectively, these reports suggest that inhibition of EBV reactivation might be useful for NPC prevention and therapy. Accordingly, for safety and convenience, we have screened several dietary compounds for anti-EBV activity. We reported that the flavonoids have activity against EBV reactivation and through the inhibition of EBV, NPC tumorigenesis has been repressed [25] [26] [27] . Here, we report that the phytochemical emodin has the potential ability to inhibit EBV reactivation. Emodin, a common traditional Chinese medicine, is an anthraquinone derivative present in the roots or rhizomes of rhubarb. Emodin has various medical applications, including anti-cancer, anti-oxidation, anti-inflammation or allergy, anti-diabetes, and anti-viral or bacterial activities [28] . For its anti-viral effect, emodin has the ability to inhibit the SARS coronavirus [29] , and block the replication of HBV [30], Coxsackievirus [31], zika virus [32], and influenza A virus [33] . Moreover, emodin has been suggested to inhibit the replication of herpesviruses [34] [35] [36] . However, the detailed mechanism is not well elucidated. In this study, based on our screening, we show that emodin inhibits EBV reactivation in epithelial cells, through the mechanism of repressing SP1 expression to inhibit the Zta and Rta promoter activities. Moreover, through its anti-EBV activity, NPC tumorigenesis could be relieved, suggesting emodin is a potential agent for therapy of EBV-associated cancer. Results Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone, Figure 1a ) has been shown to be cytotoxic to human cell lines. Before investigating the anti-EBV effect of emodin, two EBV-positive NPC cell lines, NA and HA, and their parental cells TW01 and HONE-1, were assessed for susceptibility to the cytotoxicity of emodin. The cells were seeded into 96-well plates 24 h prior to treatment; then, emodin was added for 48 h to determine its cytotoxic effect on the NPC cell lines NA and HA. Emodin has significant toxicity to TW01 cells, while the derivative NA cells showed little resistance to the compound (Figure 1b) . A similar effect was seen on HONE-1 and HA cells (Figure 1b) . Furthermore, to evaluate these results more precisely, half maximum of cytotoxicity concentrations 50 (CC50) were calculated and are shown in the top panels of Figure 1b . The CC50 values of TW01 and the derivative NA cell lines were 31 and 79 µM, while the values for HONE-1 and HA were 58 and 65 µM, respectively (Figure 1b) , implying that the cells harboring EBV seemed to be more resistant to emodin (TW01 vs.

SOLUTION:
Emodin Inhibits EBV Reactivation and Represses NPC Tumorigenesis