The role of influenza virus gene constellation and viral morphology on cytokine induction, pathogenesis, and viral virulence.

Key Messages 1. H5N1 viruses that cause severe disease in humans are potent inducers of proinflammatory cytokines in contrast to seasonal influenza viruses, and this may play a role in the mechanism of H5N1 pathogenesis. 2. H5N1 viruses are predominantly spherical in morphology. Virus morphology does not influence the ability to induce proinflammatory cytokines. 3. The NS1 viral protein may play a role in the potency of proinflammatory induction. 4. The H5N1 haemagglutinin and neuraminidase do not appear to transfer the high cytokine phenotype. 5. The ability to induce cytokines is a polygenic trait, involving a combination of different viral genes.published_or_final_versio

Occult respiratory viral infections in coronial autopsies: a pilot project.

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Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

<p>Abstract</p> <p>Background</p> <p>The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20^thcentury. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.</p> <p>Results</p> <p>Relative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through <it>in toto </it>transfer of an avian influenza virus.</p> <p>Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.</p> <p>Conclusions</p> <p>Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.</p

Heterologous influenza vRNA segments with identical non-coding sequences stimulate viral RNA replication in trans

The initiation of transcription and replication of influenza A virus requires the 5' and 3' ends of vRNA. Here, the role of segment-specific non-coding sequences of influenza A virus on viral RNA synthesis was studied. Recombinant viruses, with the nonstructural protein (NS) segment-specific non-coding sequences replaced by the corresponding sequences of the neuraminidase (NA) segment, were characterized. The NS and NA vRNA levels in cells infected with these mutants were much higher than those of the wild type, whereas the NS and NA mRNA levels of the mutants were comparable to the wild-type levels. By contrast, the PB2 vRNA and mRNA levels of all the tested viruses were similar, indicating that vRNA with heterologous segment-specific non-coding sequences was not affected by the mutations. The observations suggested that, with the cooperation between the homologous 5' and 3'segment-specific sequences, the introduced mutations could specifically enhance the replication of NA and NS vRNA

In-Flight Transmission of SARS-CoV-2.

Four persons with severe acute respiratory syndrome coronavirus 2 infection had traveled on the same flight from Boston, Massachusetts, USA, to Hong Kong, China. Their virus genetic sequences are identical, unique, and belong to a clade not previously identified in Hong Kong, which strongly suggests that the virus can be transmitted during air travel

Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Event Monitoring System to Classify Unexpected Events for Production Planning

[EN] Production planning prepares companies to a future production scenario. The decision process followed to obtain the production plan considers real data and estimated data of this future scenario. However, these plans can be affected by unexpected events that alter the planned scenario and in consequence, the production planning. This is especially critical when the production planning is ongoing. Thus providing information about these events can be critical to reconsider the production planning. We herein propose an event monitoring system to identify events and to classify them into different impact levels. The information obtained from this system helps to build a risk matrix, which determines the significance of the risk from the impact level and the likelihood. A prototype has been built following this proposal.This research has been carried out in the framework of the project GV/2014/010 funded by the Generalitat Valenciana (Identificacion de la informacion proporcionada por los nuevos sistemas de deteccion accesibles mediante internet en el ambito de las "sensing enterprises" para la mejora de la toma de decisiones en la planificacion de la produccion).Boza, A.; Alarcón Valero, F.; Alemany Díaz, MDM.; Cuenca, L. (2017). Event Monitoring System to Classify Unexpected Events for Production Planning. Lecture Notes in Business Information Processing. 291:140-154. https://doi.org/10.1007/978-3-319-62386-3_7S140154291Barták, R.: On the boundary of planning and scheduling: a study (1999)Buzacott, J.A., Corsten, H., Gössinger, R., Schneider, H.M.: Production Planning and Control: Basics and Concepts. Oldenbourg Wissenschaftsverlag, München (2012)Özdamar, L., Bozyel, M.A., Birbil, S.I.: A hierarchical decision support system for production planning (with case study). Eur. J. Oper. Res. 104(3), 403–422 (1998)Van Wezel, W., Van Donk, D.P., Gaalman, G.: The planning flexibility bottleneck in food processing industries. J. Oper. Manag. 24(3), 287–300 (2006)Shamsuzzoha, A.H., Rintala, S., Cunha, P.F., Ferreira, P.S., Kankaanpää, T., Maia Carneiro, L.: Event monitoring and management process in a non-hierarchical business network. In: Intelligent Non-hierarchical Manufacturing Networks, pp. 349–374. Wiley, Hoboken (2013)Sacala, I.S., Moisescu, M.A., Repta, D.: Towards the development of the future internet based enterprise in the context of cyber-physical systems. In: 19th International Conference on Control Systems and Computer Science, CSCS 2013, pp. 405–412 (2013)Chen, K.C.: Decision support system for tourism development: system dynamics approach. J. Comput. Inf. 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Appl. 38(5), 4829–4838 (2011)SAP AG: SAP AG 2014. Next-Generation Business and the Internet of Things. Studio SAP | 27484enUS (14/03) (2014)Carneiro, L.M., Cunha, P., Ferreira, P.S., Shamsuzzoha, A.: Conceptual framework for non-hierarchical business networks for complex products design and manufacturing. Procedia CIRP 7, 61–66 (2013)Vargas, A., Cuenca, L., Boza, A., Sacala, I., Moisescu, M.: Towards the development of the framework for inter sensing enterprise architecture. J. Intell. Manuf. 26, 55–72 (2016)Barash, G., Bartolini, C., Wu, L.: Measuring and improving the performance of an IT support organization in managing service incidents, pp. 11–18 (2007)Liu, R., Kumar, A., van der Aalst, W.: A formal modeling approach for supply chain event management. Decis. Support Syst. 43(3), 761–778 (2007)Söderholm, A.: Project management of unexpected events. Int. J. Proj. Manag. 26(1), 80–86 (2008)Bearzotti, L.A., Salomone, E., Chiotti, O.J.: An autonomous multi-agent approach to supply chain event management. Int. J. Prod. Econ. 135(1), 468–478 (2012)Baron, M.M., Pate-Cornell, M.E.: Designing risk-management strategies for critical engineering systems. IEEE Trans. Eng. Manag. 46(1), 87–100 (1999)Bartolini, C., Stefanelli, C., Tortonesi, M.: SYMIAN: analysis and performance improvement of the IT incident management process. IEEE Trans. Netw. Serv. Manag. 7(3), 132–144 (2010)Cox Jr., L.A.: What’s wrong with risk matrices? Risk Anal. Int. J. 28(2), 497–512 (2008)Shim, J.P., Warkentin, M., Courtney, J.F., Power, D.J., Sharda, R., Carlsson, C.: Past, present, and future of decision support technology. Decis. 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DNA intercalator stimulates influenza transcription and virus replication

Influenza A virus uses its host transcription machinery to facilitate viral RNA synthesis, an event that is associated with cellular RNA polymerase II (RNAPII). In this study, various RNAPII transcription inhibitors were used to investigate the effect of RNAPII phosphorylation status on viral RNA transcription. A low concentration of DNA intercalators, such as actinomycin D (ActD), was found to stimulate viral polymerase activity and virus replication. This effect was not observed in cells treated with RNAPII kinase inhibitors. In addition, the loss of RNAPIIa in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPIIa) to hyperphosphorylated RNAPII (RNAPIIo)