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                  <text>Dominio científico: Coronavirus</text>
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                <text>Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak</text>
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                <text>Chang-Hwan Lee, Moran Ki</text>
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                <text>The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.</text>
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                <text>2015</text>
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                <text>Middle East respiratory syndrome, coronavirus infections, Epidemiologic investigation, infectious diseases, Korea, Outbreak</text>
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                <text>DOI: 10.4178/epih/e2015040</text>
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                <text>Epidemiology and Health</text>
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                <text>Korean Society of Epidemiology</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Mechanism of nucleic acid unwinding by SARS-CoV helicase.</text>
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                <text>Adeyemi O. Adedeji, Bruno Marchand, Aartjan J. W. te Velthuis, Eric J. Snijder, Susan Weiss, Robert L. Eoff, Kamalendra Singh, Stefan G. Sarafianos</text>
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                <text>The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5' → 3' polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ~280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis.</text>
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                <text>DOI: 10.1371/journal.pone.0036521</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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            <description>A name given to the resource</description>
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                <text>Mild Encephalitis with a Reversible Splenial Lesion (MERS) Accompanied by Myelitis: A Case Report</text>
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                <text>Ju-Young Lee, Min Woo Lee, Chaeyoung Lee, Jinhyuk Yoo, Jong Seok Bae, Hong  Ki Song</text>
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            <description>An account of the resource</description>
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                <text>Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) can present with various manifestations of central nervous system (CNS) dysfunction. However, MERS with myelitis has rarely been reported. We reported a case of MERS with concomitant myelitis. Case Report: A 35-year-old male was admitted to our department because of decreased mentality. Before admission, he complained of headache, fever over 38.0oC and urinary retention. Brain MRI showed a lesion on the splenium and spine MRI revealed diffuse lesions in the cervicothoracic segments. He was treated with an IV steroid pulse regimen for 5 days. Remarkably, he recovered from his neurological symptoms after 1 month of symptom onset. Conclusion: This is the first report on MERS with concomitant myelitis in Korea. While the etiology is unknown, certain trophisms of infectious pathogens to the CNS structure may have a role in this syndrome.</text>
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                <text>2015</text>
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                <text>encephalitis, Myelitis, Corpus Callosum, Urinary retention, Ataxia of gait</text>
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                <text>DOI: 10.18700/jnc.2015.8.2.118</text>
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                <text>Journal of Neurocritical Care</text>
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                <text>The Korean Neurocritical Care Society</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Neurology. Diseases of the nervous system</text>
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            <description>A language of the resource</description>
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                <text>EN, KO</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Systematic artifacts in support vector regression-based compound potency prediction revealed by statistical and activity landscape analysis.</text>
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                <text>Jenny Balfer, Jürgen Bajorath</text>
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                <text>Support vector machines are a popular machine learning method for many classification tasks in biology and chemistry. In addition, the support vector regression (SVR) variant is widely used for numerical property predictions. In chemoinformatics and pharmaceutical research, SVR has become the probably most popular approach for modeling of non-linear structure-activity relationships (SARs) and predicting compound potency values. Herein, we have systematically generated and analyzed SVR prediction models for a variety of compound data sets with different SAR characteristics. Although these SVR models were accurate on the basis of global prediction statistics and not prone to overfitting, they were found to consistently mispredict highly potent compounds. Hence, in regions of local SAR discontinuity, SVR prediction models displayed clear limitations. Compared to observed activity landscapes of compound data sets, landscapes generated on the basis of SVR potency predictions were partly flattened and activity cliff information was lost. Taken together, these findings have implications for practical SVR applications. In particular, prospective SVR-based potency predictions should be considered with caution because artificially low predictions are very likely for highly potent candidate compounds, the most important prediction targets.</text>
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                <text>2015</text>
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                <text>DOI: 10.1371/journal.pone.0119301</text>
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                <text>PLoS ONE</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>The nucleocapsid protein of human coronavirus NL63.</text>
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                <text>Kaja Zuwala, Anna Gołda, Wojciech Kabala, Michał Burmistrz, Michal Zdzalik, Paulina Nowak, Sylwia Kedracka-Krok, Mirosław Zarębski, Jerzy Dobrucki, Dominik Florek, Slawomir Zeglen, Jacek Wojarski, Jan Potempa, Grzegorz Dubin, Krzysztof Pyrc</text>
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                <text>Human coronavirus (HCoV) NL63 was first described in 2004 and is associated with respiratory tract disease of varying severity. At the genetic and structural level, HCoV-NL63 is similar to other members of the Coronavirinae subfamily, especially human coronavirus 229E (HCoV-229E). Detailed analysis, however, reveals several unique features of the pathogen. The coronaviral nucleocapsid protein is abundantly present in infected cells. It is a multi-domain, multi-functional protein important for viral replication and a number of cellular processes. The aim of the present study was to characterize the HCoV-NL63 nucleocapsid protein. Biochemical analyses revealed that the protein shares characteristics with homologous proteins encoded in other coronaviral genomes, with the N-terminal domain responsible for nucleic acid binding and the C-terminal domain involved in protein oligomerization. Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. Furthermore, no significant alteration in cell cycle progression in cells expressing the protein was observed. This is in stark contrast with results obtained for other coronaviruses, except for the SARS-CoV.</text>
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                <text>DOI: 10.1371/journal.pone.0117833</text>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Mahmoud Aly, Mohamed Elrobh, Maha Al Zayer, Sameera Aljuhani, Hanan Balkhy</text>
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                <text>The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow:</text>
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                <text>2017</text>
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                <text>DOI: 10.1371/journal.pone.0183850</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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                <text>EN</text>
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the Middle East respiratory coronavirus (MERS-CoV) receptor-binding domain as an antigen.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Jiaming Lan, Yao Deng, Hong Chen, Guangwen Lu, Wen Wang, Xiao-juan Guo, Zhuozhuang Lu, George F. Gao, Wen-Jie Tan</text>
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            <description>An account of the resource</description>
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                <text>The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.</text>
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                <text>2014</text>
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            <description>An unambiguous reference to the resource within a given context</description>
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                <text>DOI: 10.1371/journal.pone.0112602</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="3386">
                <text>PLoS ONE</text>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
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              <elementText elementTextId="3387">
                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.</text>
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                <text>Yíngyún Caì, Shuqing Yu, Elena N Postnikova, Steven Mazur, John  G. Bernbaum, Robin Burk, Teng Fei Zhang, Sheli R. Radoshitzky, Marcel A. Müller, Ingo Jordan, Laura Bollinger, Lisa E. Hensley, Peter B. Jahrling, Jens H. Kuhn</text>
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                <text>Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.</text>
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                <text>2014</text>
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                <text>DOI: 10.1371/journal.pone.0112060</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>A multi-method approach to curriculum development for in-service training in China's newly established health emergency response offices.</text>
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                <text>Yadong Wang, Xiangrui Li, Yiwen Yuan, Mahomed S Patel</text>
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            <description>An account of the resource</description>
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                <text>To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings.The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China's policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel.Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills.This study adds to the emerging literature on China's enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively.</text>
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                <text>DOI: 10.1371/journal.pone.0100892</text>
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                <text>PLoS ONE</text>
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            <name>Publisher</name>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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                <text>EN</text>
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        <src>https://www.socictopen.socict.org/files/original/2f47edb06e738af8219561bc49aebc44.pdf</src>
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              <name>Title</name>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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          <element elementId="50">
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                <text>Is there still room for novel viral pathogens in pediatric respiratory tract infections?</text>
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                <text>Blanca Taboada, Marco A Espinoza, Pavel Isa, Fernando E Aponte, María A Arias-Ortiz, Jesús Monge-Martínez, Rubén Rodríguez-Vázquez, Fidel Díaz-Hernández, Fernando Zárate-Vidal, Rosa María Wong-Chew, Verónica Firo-Reyes, Carlos N del Río-Almendárez, Jesús Gaitán-Meza, Alberto Villaseñor-Sierra, Gerardo Martínez-Aguilar, Ma del Carmen Salas-Mier, Daniel E Noyola, Luis F. Pérez-González, Susana López, José I. Santos-Preciado, Carlos Farias</text>
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                <text>Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.</text>
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                <text>2014</text>
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                <text>DOI: 10.1371/journal.pone.0113570</text>
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            <elementTextContainer>
              <elementText elementTextId="3359">
                <text>PLoS ONE</text>
              </elementText>
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            <name>Publisher</name>
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              <elementText elementTextId="3360">
                <text>Public Library of Science (PLoS)</text>
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            <name>Coverage</name>
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                <text>Science, Medicine</text>
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                <text>EN</text>
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