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                  <text>Dominio científico: Coronavirus</text>
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                <text>Middle East respiratory syndrome coronavirus (MERS Cov) outbreak so far exempted Sub Saharan Africa; is it good news or call for action?</text>
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                <text>Ballah Akawu Denue</text>
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                <text>The reported cases of MERS Cov in Arabian Peninsula and sporadic caseselsewhere except in sub Saharan Africa at present is disquieting considering itsinitial clinical feature that mimic flu like symptoms caused by other viruses.However MERS Cov is associated with organ dysfunction and high mortality.Although the mode of transmission is still unclear, it is postulated that itspreads through close contact, possibly via respiratory route. High similaritiesof MERS CoV carried by humans and camels may suggest that the diseases arezoonotic. Furthermore, airborne nosocomial transmission can occur in theroom shared by the patients in the hospitals. There is still the confusion oftransmission through body fluids or clinical samples, including stools and across transmission with medical devices or hands. Currently, all known casescan be directly or indirectly linked to Middle East from where it derives its name. Cases reported outside the Middle East first developed infection in the Middle East and then were exported outside the region. Several hospital-acquired outbreaks that resulted in upsurge of MERS Cov cases in Jeddah revealed lack of systematic implementation of infection prevention and control measures to effectively control emerging infectious diseases. The causative agent is detected and identified using Enzyme Linked Immuunosorbent Assay (ELISA) and real-time polymerase chain reaction (RT-PCR) that is expensive and not readily available in hospitals located in resource poor settings such as sub Saharan Africa. Although, so far no case of MERS Cov has been reported from sub Saharan Africa, the devastating consequences of MERS epidemic will be more catastrophic if it emerges in developing nations especially in sub Saharan Africa where there are no up to date facilities for investigations and management of such cases. Against this backdrop, we review this hazardous and incurable disease believing that it would create the necessary awareness among stakeholders to prepare for ‘alien’diseases like MERS Cov.Pilgrims all over the world visit Saudi Arabia for religious obligation (Hajj). This is a potential way this virus could be transmitted across the globe within a short span especially if an epidemic occurs during or towards the end of the hajj exercise.</text>
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                <text>2015</text>
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                <text>DOI: </text>
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                <text>Global Journal of Medicine and Public Health</text>
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                <text>Makhdoomi Printers</text>
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                <text>Medicine</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Identification and mapping of linear antibody epitopes in human serum albumin using high-density Peptide arrays.</text>
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                <text>Lajla Bruntse Hansen, Søren Buus, Claus Schafer-Nielsen</text>
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                <text>We have recently developed a high-density photolithographic, peptide array technology with a theoretical upper limit of 2 million different peptides per array of 2 cm(2). Here, we have used this to perform complete and exhaustive analyses of linear B cell epitopes of a medium sized protein target using human serum albumin (HSA) as an example. All possible overlapping 15-mers from HSA were synthesized and probed with a commercially available polyclonal rabbit anti-HSA antibody preparation. To allow for identification of even the weakest epitopes and at the same time perform a detailed characterization of key residues involved in antibody binding, the array also included complete single substitution scans (i.e. including each of the 20 common amino acids) at each position of each 15-mer peptide. As specificity controls, all possible 15-mer peptides from bovine serum albumin (BSA) and from rabbit serum albumin (RSA) were included as well. The resulting layout contained more than 200.000 peptide fields and could be synthesized in a single array on a microscope slide. More than 20 linear epitope candidates were identified and characterized at high resolution i.e. identifying which amino acids in which positions were needed, or not needed, for antibody interaction. As expected, moderate cross-reaction with some peptides in BSA was identified whereas no cross-reaction was observed with peptides from RSA. We conclude that high-density peptide microarrays are a very powerful methodology to identify and characterize linear antibody epitopes, and should advance detailed description of individual specificities at the single antibody level as well as serologic analysis at the proteome-wide level.</text>
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                <text>2013</text>
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                <text>DOI: 10.1371/journal.pone.0068902</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>Dominio científico: Coronavirus</text>
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                <text>Non-esterified fatty acids generate distinct low-molecular weight amyloid-β (Aβ42) oligomers along pathway different from fibril formation.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Amit Kumar, Rebekah L Bullard, Pritesh Patel, Lea C Paslay, Dipti Singh, Ewa A. Bienkiewicz, Sarah E. Morgan, Vijayaraghavan Rangachari</text>
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            <description>An account of the resource</description>
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                <text>Amyloid-β (Aβ) peptide aggregation is known to play a central role in the etiology of Alzheimer's disease (AD). Among various aggregates, low-molecular weight soluble oligomers of Aβ are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the Aβ aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on Aβ42 aggregation. NEFAs uniquely affected Aβ42 aggregation rates that depended on both the ratio of Aβ:NEFA as well the critical micelle concentration (CMC) of the NEFAs. More importantly, irrespective of the kind of NEFA used, we observed that two distinct oligomers, 12-18 mers and 4-5 mers were formed via different pathway of aggregation under specific experimental conditions: (i) 12-18 mers were generated near the CMC in which NEFAs augment the rate of Aβ42 aggregation towards fibril formation, and, (ii) 4-5 mers were formed above the CMC, where NEFAs inhibit fibril formation. The data indicated that both 12-18 mers and 4-5 mers are formed along an alternate pathway called 'off-pathway' that did not result in fibril formation and yet have subtle structural and morphological differences that distinguish their bulk molecular behavior. These observations, (i) reflect the possible mechanism of Aβ aggregation in physiological lipid-rich environments, and (ii) reiterate the fact that all oligomeric forms of Aβ need not be obligatory intermediates of the fibril formation pathway.</text>
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                <text>2011</text>
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                <text>DOI: 10.1371/journal.pone.0018759</text>
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                <text>PLoS ONE</text>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Lennart Michel Reinke, Martin Spiegel, Teresa Plegge, Anika Hartleib, Inga Nehlmeier, Stefanie Gierer, Markus Hoffmann, Heike Hofmann-Winkler, Michael Winkler, Stefan Pöhlmann</text>
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                <text>The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.</text>
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                <text>2017</text>
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                <text>DOI: 10.1371/journal.pone.0179177</text>
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                <text>PLoS ONE</text>
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                <text>Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia.</text>
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                <text>Ines Brini, Aida Guerrero, Naila Hannachi, Jihene Bouguila, Dorothea Orth-Höller, Amira Bouhlel, Lamia Boughamoura, Benjamin Hetzer, Wegene Borena, Britta Schiela, Dorothee von Laer, Jalel Boukadida, Heribert Stoiber</text>
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                <text>This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1-3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient's demographic situation and clinical manifestations (p</text>
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                <text>DOI: 10.1371/journal.pone.0188325</text>
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                <text>PLoS ONE</text>
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                  <text>Dominio científico: Coronavirus</text>
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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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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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            <description>A language of the resource</description>
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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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                <text>Public Library of Science (PLoS)</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>DOI: 10.1371/journal.pone.0112060</text>
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                <text>PLoS ONE</text>
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                  <text>Dominio científico: Coronavirus</text>
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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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                <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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                <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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                <text>DOI: 10.1371/journal.pone.0112602</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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        <src>https://www.socictopen.socict.org/files/original/6940d5c4dc3d12f3e24bfdf3fa3d2d7c.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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                <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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                <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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            <name>Coverage</name>
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                <text>Science, Medicine</text>
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                <text>EN</text>
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