cord-001525-b7kbyp3s	2015	The aim of the current study was to assess the overall in vitro bactericidal activity of nine newly synthesized diamides in dependence on time and concentration against clinical isolates of MRSA as representatives of multidrug-resistant bacteria. The MBC was defined as the lowest concentration of substance, which produced ≥99.9% killing Table 1 : Chemical structures and in vitro MIC and MBC [ g/mL] values of tested 5-and 4-chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides (bactericidal effect of individual compounds against particular strains marked in bold). In the present study the series of nine newly synthesized diamides was evaluated as prospective bactericidal agents against representatives of multidrugresistant bacteria, three clinical isolates of MRSA, and Staphylococcus aureus ATCC 29213 (methicillin-susceptible) as the reference and quality control strain. It is of note that based on time-kill assays in the present study, all tested diamides (particularly compound 1f exhibiting rapid bactericidal concentration-dependent effect even at 2x MIC) were most effective against isolate MRSA 63718, which is the strain with elevated vancomycin MIC of 2 g/mL.
cord-001532-kz3b01wq	2015	Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. The mechanisms by which NFV acts on tumor cells are multifactorial and include inhibition of cellular proteases, Akt activation, and NF -B signaling, as well as induction of the endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and autophagy [11, 16, 17] . The Akt inhibitor LY294002 completely suppressed Akt phosphorylation in HSV-1 infected cells, but NFV did not reduce the levels of phosphorylated Akt even at drug concentrations that potently block virus production ( Figure 3 ). Interestingly, although endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and autophagy are well known effects of NFV [16, [26] [27] [28] [29] , neither ER dilation nor the abundance of double-membrane bound vesicles consistent with autophagosomes appeared consistently different between NVF-treated and untreated HSV-1-infected cells.
cord-001541-5d64esp4	2015	We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) .
cord-001546-ndz3oarf	2015	Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice.
cord-001605-8p06bpt1	2015	title: The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type. marneffei MCO participates in conidial DHN-melanin synthesis, we combined 55 fungal MCO sequences and performed alignments using CLUSTALW (http://www.genome.jp/ tools/clustalw/). marneffei PbrB, this clade comprises of characterized laccases functioning in conidial DHN-melanin synthesis. Talaromyces (Penicillium) marneffei pbrB Gene Cytoplasmic protein extracts from the wild type and ΔpbrB mutant cultured in brain heart infusion broth at 37°C for 3 days were capable of catalyzing L-DOPA (data not shown).
cord-001639-p9mbmfaq	2015	title: Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. Hence, to conduct molecular epidemiology studies, including sequence analysis for both genomic segments, is an important step to explain the links between emergence, spreading and maintenance of the vvIBDV strains around the world. The demographic history of the segment B of the IBDV genome for non-vvIBDV lineage, showed a trend toward a decrease in genetic diversity, possibly generated by the introduction of effective vaccination programs against classical and low virulent strains from early stages of the discovery of the disease [67, 68] .
cord-001655-uqw74ra0	2015	The sets of viral genotypes ranged from that which would be expected for a straightforward co-infection by 2 virus strains in snake #45, to more complex combinations such as that in snake #33, which contained the sequences of 1 S and 10 distinct L segments. We applied homogenates from samples to cultures of boa constrictor-derived JK cells and monitored levels of virus RNA by qRT-PCR using genotype-discriminating primers. Thus, sequences of multiple viral genotypes Recombinant genome segments with unusual organizations. Virus populations replicate as stable ensembles in culture: (A) Liver homogenate from snake #38 was applied to cultures of JK cells and replication was monitored by measuring supernatant viral RNA levels using qRT-PCR and genotype-specific primers. Although we detected many instances of snake tissues containing multiple viral genotypes, our results do not prove that individual cells in these animals were multiply infected.
cord-001658-algzczs8	2015	title: Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus from a Novel Outbreak in Belgium, January 2015 Here, we report the complete genome sequence (28,028 nt) of a PEDV strain isolated during a novel outbreak in Belgium. Therefore, the complete genome of this novel isolate, BEL/15V010/2015, was unraveled by next-generation sequencing, in order to assess its genetic relation to other PEDV isolates circulating around the globe. Complete genome sequence of a highly prevalent isolate of porcine epidemic diarrhea virus in South China Complete genome sequence of a novel porcine epidemic diarrhea virus in south China Complete genome sequence of porcine epidemic diarrhea virus strain USA/Colorado/2013 from the United States Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States
cord-001674-tp4o7fxx	2015	An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. This intramembrane proteolysis by SPP is thought to be important for the clearance of the ER membrane by removing small protein remnants anchored at FIGURE 1 | Classical and alternative pathways for MHC class I presentation. Furin-processed antigens targeted to the secretory route were presented by MHC class I at the cell surface and could elicit functional CD8 T-cell responses in vivo in a TAP-independent fashion (75, 81) . Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins
cord-001676-68y733y3	2015	After filtering transcripts for minimally confident variation (we required at least one time-matched, infected condition compared with mock-infected absolute fold change 2 and a false discovery rate [FDR]-adjusted P-value < 0.01), the log 2 of the normalized intensity of the retained transcripts (16, 063) for all 167 samples were then clustered by using the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm [18] . Data corresponding to macrophage signatures in different cellular states are colored red (see S3 Table for Within the inflammation-associated modules (N1 and N2), the H5N1 virus induced the earliest gene expression changes and the highest peak expression levels, corroborating previous observations that H5N1 viruses are strong inducers of inflammatory and IFN response signaling in vivo [10, 24, 25] . We infected mice with 10 3 PFU of the H5N1 virus (a 100-fold reduced dose compared with that used in the experiments to fit the model), determined lung virus titers at the same time points used for the initial experiment (S3 Fig), and then evaluated the segmented linear model''s ability to predict cytokine-associated gene expression.
cord-001677-p6ikd8ns	2015	To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. In this study, we explored different sites in HVRs 7, 8 and 9 of hAd5 hexon for the insertion of a peptide corresponding to the porcine reproductive and respiratory syndrome virus (PRRSV) main neutralizing epitope B [19] of the GP5 protein. In the current study, we find a new site in HVR7 for incorporation of foreign peptide into hAd5 hexon, and determine that the peptide was also exposed on the virion surface making it readily accessible for antibody binding and be potentially useful for vaccination. Herein, we report a novel adenovirus vector (Ad5HVR7epB) with the insertion of the PRRSV main neutralizing epitope B in 3 different HVR regions of the major capsid protein hexon.
cord-001700-c6elsnag	2015	Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. To generate MARV GP-specific mAbs, BALB/c mice were immunized with GPΔmuc antigens from either MARV strain Ci67, Musoke, Angola, or Ravn ( Fig 1A) . To characterize the binding of mAbs, we performed enzyme-linked immunosorbent assays (ELISAs) with recombinant GPs from four MARV strains, and determined EC50 values for binding with different forms of MARV Ravn GP: GP, GPΔmuc, GPcl (Fig 2A) . Two of the highly cross-reactive MARV antibodies, mAbs 40G1 and 2D8, also exhibit binding to Ebola, Sudan, Bundibugyo and Reston virus mucin-deleted GPs by ELISA (Fig 5A) .
cord-001704-pdxm0iiw	2015	hmPA6 injection before or after LeTx administration protected all rats from developing anthrax (Fig. 6C) . In the present study, we developed four murine mAbs that could well neutralize LeTx in vitro, and one clone was selected to form a human/mouse chimeric antibody known as hmPA6. In the in vivo test in the present study, irrespective of whether LF was injected before or after hmPA6, the antibody protected the rats from death provided that it was administered before or simultaneously with PA. In summary, we reported a human/murine chimeric IgG, namely, hmPA6, which can specifically identify PA with high affinity, neutralize LeTx, and protect macrophages and F344 rats from anthrax-related death. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity An anthrax lethal factor-neutralizing monoclonal antibody protects rats before and after challenge with anthrax toxin
cord-001712-a1sbdhhn	2015	title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. In this study, we demonstrated additional contributions of inflammation to the progression of lung cancer metastasis and a novel molecular target of EGCG, human neutrophil elastase, which induces lung cancer cell migration. 14 demonstrated that the natural polyphenol product curcumin inhibits tumor proliferation induced by neutrophil elastase via the upregulation of AAT in lung cancer. These results indicated that treatment with EGCG at a concentration between 10 and 20 μ M induces a substantial anti-migratory effect without affecting the proliferation of A549 cells exposed to neutrophil elastase. Our results showed that the neutrophil elastase-induced decrease in IRS-1 expression was significantly inhibited by EGCG in A549 cells.
cord-001734-bbeznd3r	2015	Taken together, CD and NMR results define the 172-residue NS3pro domain to be an intrinsically disordered protein which is lacking of both stable secondary and tertiary structures in the absence of the NS2B cofactor [22, [31] [32] [33] [34] [35] [36] . On the other hand, only a small set of broad peaks could be detected in its HSQC spectrum (Fig 4B) , indicating that the NS3B (1-130) in the LMPC micelle undergoes significant conformational exchanges on μs-ms time scale, or/and dynamic aggregation, which thus prevents from further high-resolution NMR studies. Interestingly, although NMR characterization deciphers that the NS3pro domains have different dynamics on the μs-ms time scale in the contexts of being complexed with NS (48-100) in buffer and with NS2B (1-130) in the LMPC micelle, they have very similar enzymatic activities.
cord-001740-1px4aq89	2015	title: GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders CONCLUSIONS: In children and adults with severe GM-CSF negative PAP a close cooperation between pneumologists and hemato-oncologists is needed to diagnose the underlying diseases, some of which are caused by mutations of transcription factor GATA2. Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the progressive accumulation of surfactant in the alveoli of the lungs, leading to hypoxemic respiratory failure and, in severe cases, to death [1]. PAP is caused by (i) genetic diseases which result in dysfunction of surfactant or surfactant production (SFTPC, SFTPB, ABCA3, TTF1 deficiency) mainly presenting during infancy, by (ii) disruption of GM-CSF signaling from mutations in the receptor (GM-CSFRa, GM-CSFRb) or from acquired autoantibodies against GM-CSF, and by (iii) disorders that presumably impair surfactant clearance because of abnormal numbers or defective phagocytic functions of alveolar macrophages [2] .
cord-001746-pbahviaz	2015	Although there is evidence that adult patients with underlying cardiac or pulmonary disease are more likely to develop influenza-associated pneumonia than those without underlying medical conditions [6, 7] , much of the data describing factors associated with influenzaassociated pneumonia among adults comes from case series conducted at single sites and during a limited number of seasons. The following data were collected on patients: demographics, results of laboratory tests for influenza, influenza vaccination status for the current season, underlying medical conditions, bacterial coinfections, CXR data, antiviral treatment, clinical outcomes, and discharge diagnoses. Patients with pneumonia were significantly more likely than patients without pneumonia to reside in a nursing home prior to hospital admission, to have received influenza vaccine, and to have the following underlying medical conditions: chronic lung disease, cardiovascular disease, and immunosuppression.
cord-001762-dtvzwin8	2015	title: Development of a Rapid Detection Method for Potato virus X by Reverse Transcription Loop-Mediated Isothermal Amplification Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been used to detect viral RNA molecules because of its simplicity and high sensitivity for a number of viruses. RT-LAMP for the detection of Potato virus X (PVX) was developed and compared with conventional reverse transcription polymerase chain reaction (RT-PCR) to demonstrate its advantages over RT-PCR. This study showed similar results in that the RT-LAMP assay included two loop primers and took only 15 min for detection of PVX. Simple and rapid detection of Potato leafroll virus (PLRV) by reverse transcription loop-mediated isothermal amplification (RT-LAMP) Reverse transcription loop-mediated isothermal amplification of DNA for detection of Potato virus Y Rapid detection and differentiation of Dengue virus serotypes by a real-time reverse transcription-loop-mediated isothermal amplification assay Development of loop-mediated isothermal amplification assay for specific and rapid detection of camelpox virus in clinical samples
cord-001765-7wv4cb37	2015	One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. The studies described here are the first to demonstrate protection of guinea pigs and macaques with a single dose of highly attenuated rVSV expressing EBOVGP, and we believe that the N4CT1-EBOVGP1 vector has the essential safety and efficacy characteristics for use in a vaccine to prevent EBOV infection in humans and the great apes.
cord-001781-afg1nmib	2015	We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. The results presented here highlight three main findings: 1) when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor; but in peri-urban landscapes emergence factors converge, including higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture; 2) high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks; as are 3) landscapes where intensive and extensive forms of poultry production are co-located. Hence diseases associated with rice production are likely to peak in peri-urban areas given other risk factors such as land-use diversity, CTI, and distance to infrastructure.
cord-001823-v60vv99o	2015	By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. The objective of this paper is to assess the effect of all possible intervention strategies (isolation, media impact, safe burial, and vaccination) on controlling the spread of Ebola virus in Guinea, Sierra Leone, Liberia. Using the model, we evaluate the potential effect of increasing the fraction of latent individuals prior to symptoms onset, shortening the duration between symptoms onset and isolation, improving media coverage, following restrict burial procedures, and administrating timely vaccine on the epidemic of Ebola infection. If the effectiveness of isolation increases to 80%, i.e., the relative transmissibility  of isolated individuals decreases to 20% (magenta lines in Fig. 5 ), then about 35%, 65%, 60% of pre-symptomatic patients need to be detected in Guinea, Sierra Leone and Liberia to control the disease.
cord-001831-3aonqyub	2015	Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Research over recent decades has identified a group of virus-encoded proteins able to mediate the passage of ions and solutes across cellular membranes, termed viroporins [1, 2] . Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1, 2] . This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of these small DNA tumor viruses.
cord-001843-ceatyj3o	2015	PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. The duplex UNDP-PCR assay is suitable for simultaneous detection of RNA and DNA viruses in early viral infection, providing an effective approach for diagnosis of swine diseases. The duplex UNDP-PCR assay developed in this study provided a useful tool for simultaneous detection of RNA (TGEV) and DNA viruses (PCV2) without the need for viral nucleic acid extraction, purification and reverse transcription.
cord-001848-idmj2d7p	2015	We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Previously, we showed that transient transfection of an expression construct that generates IFN-l4 protein induced interferon signaling, with activation of interferon-stimulated genes (ISGs) and generation of antiviral response in HepG2, a human hepatoma cell line (Prokunina-Olsson and others 2013). The stable HepG2-ISRE-Luc cells were transfected with corresponding constructs in 96-well plates; untransfected cells were treated with human recombinant interferons-IFNa (2 ng/mL; PBL Assay Science) or custom IFN-l3 (10 ng/ mL). Previously, by performing Western blot analysis, we were unable to detect IFN-l4 in culture media of HepG2 cells transiently transfected with an IFN-l4-producing construct, even though this transfection resulted in strong activation of interferon signaling (Prokunina-Olsson and others 2013). IFN-l4 was detectable in culture media of IFNL4-transfected PHHs and HepG2 cells, but not in corresponding Halo-transfected cells (Fig. 2B) .
cord-001859-d62iuk72	2015	Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis.
cord-001863-sd391n5w	2015	
cord-001866-s5otdtwq	2015	Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications. All well-defined protein spots that were at least twofold (Mann-Whitney test, < 0.05) differentially expressed between the sham and retinal detachment vitreous groups were selected for identification with nanoliquid chromatographyelectrospray ionization tandem mass spectrometry (LC-MS/MS). This proteomic investigation of the rabbit vitreous has identified a set of proteins that assist our understanding of the pathogenesis of rhegmatogenous retinal detachment and its Journal of Ophthalmology 7 complications.
cord-001875-ulq1xqma	2015	Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. Previously, data have indicated that environmental factors affect the prevalence of H5N1 and H7N9, with the infection and spread of the two viruses being closely correlated with bird habitats, migration, and local climate factors (e.g., temperature and relative humidity) 17 . We collected the H5N1 and H7N9 influenza data reported on the Chinese mainland from The climate dataset contained the air temperature, ground surface temperature, relative humidity, wind speed, and atmospheric pressure of all meteorological stations in the reported provinces at the reported dates for each record. Environmental factors influencing the spread of the highly pathogenic avian influenza H5N1 virus in wild birds in
cord-001890-kbiwze0z	2015	
cord-001891-5op0yss9	2015	RESULTS: An air-cleaning device powered by electrokinetic propulsion has been adapted to provide a universal method for collecting samples of the aerobiome. For 23 common fungal species by quantitative polymerase chain reaction (qPCR), there was 100 % sensitivity and apparent specificity of 87 %, with the reference filter taken as "gold standard." Further, bacterial analysis of 16S RNA by amplicon sequencing showed equivalent community structure captured by the electrokinetic device and the reference filter. CONCLUSIONS: This work introduces a very simple plug-and-play device that can sample air at a high-volume flow rate with no moving parts and collect particles down to the sub-micron range. The performance of the device is substantially equivalent to capture by pumping through a filter for microbiome analysis by quantitative PCR and amplicon sequencing. We demonstrate the application of ionic propulsion technology to capture a wider range of particle sizes than with traditional air filter sampling, with no significant bias in fungal and bacterial community recovery.
cord-002129-3xg5guk4	2015	title: How unclogging a sink can be lethal: case report of an accidental methyl bromide poisoning leading to a multiple organ failure We present here a case report of acute accidental methyl bromide poisoning, responsible for a severe multiple organ failure (MOF). A few hours later, the patient presented an acute coronary syndrome, complicated by severe arrhythmias, namely ventricular fibrillation, responsible for a cardiogenic shock with a left ventricular ejection fraction (LVEF) at 30%. Several authors have studied methyl bromide''s neurotoxicity and reported similar brain MRI results. Given the fact that the patient was highly unstable, presented acute renal failure, and in the hypothesis of a septic shock, we decided not to perform an angiocoronarography immediately. A case of chronic methyl bromide intoxication showing symmetrical lesions in the basal ganglia and brain stem on magnetic resonance imaging Peripheral neuropathy induced by acute methyl bromide skin exposure: a case report
cord-002372-ody77u5n	2015	Ginseng polysaccharides (GPs) are the responsible ingredient of ginseng in immunomodulation, and are classified as acidic and neutral GPs. Although GPs participate in various immune reactions including the stimulation of immune cells and production of cytokines, the precise function of GPs together with its potential receptor(s) and their signal transduction pathways have remained largely unknown. quinquefolius are mediated by PS with a molecular weight higher than 100 kDa. It was reported that acidic GPs promoted the production of cytotoxic cells against tumors and stimulated macrophages to produce helper types 1 and 2 (Th1 and Th2) cytokines [26, 27] . Because GPs were reported to significantly increase the viability of peritoneal macrophage cells [8] and ginseng was shown to inhibit degradation of long-lived proteins and to stimulate protein synthesis similar to polypeptide growth factors [41] , it was suggested that maintaining the cell viability under the condition of viral infection-induced stress might be an another alternative mechanism for the protective effects of GP.
cord-003342-wmmbkmrg	2015	In this study, a set of LAMP primers were designed targeting the prfA gene sequence of Listeria monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were employed to increase the sensitivity and specificity of the LAMP reactions. The results indicate that the detection limit of this novel LAMP assay with the newly designed primers and additives was 10 fg per reaction, which is ten-fold more sensitive than a commercial Isothermal Amplification Kit and hundred-fold more sensitive than previously reported LAMP assays. This highly sensitive LAMP assay has been shown to detect 11 strains of Listeria monocytogenes, and does not detect other Listeria species (including Listeria innocua and Listeria invanovii), providing some advantages in specificity over commercial Isothermal Amplification Kits and previously reported LAMP assay. Loop-mediated isothermal amplification, developed and reported by Notomi et al., in 2000 [1] , can specifically, sensitively and rapidly amplify nucleic acids with two pairs of primers recognizing 6 independent sequences of a target gene under isothermal conditions.
cord-005010-xg2bv9gy	2015	title: Mechanism of Preferential Packaging of Negative Sense Genomic RNA by Viral Nucleoproteins in Crimean-Congo Hemorrhagic Fever Virus In the present work, by analyzing genomic sequences of RNA viruses either with negative or positive sense, performing different docking experiments and carrying out molecular dynamic (MD) simulations, we undertook to study the mechanism conferring different affinities to CCHFV nucleoprotein for negative and positive sense RNAs''. Figure 1 , also, shows that irrespective of their senses, long RNAs have comparatively higher affinities to nucleoprotein than short RNAs. Based on the results of aforementioned docking experiments, we then selected CCHFV nucleoproteins-RNA complexes of maximum binding energies for positive and negative sense RNAs (both short and long) to carry out MD simulations.
cord-005041-1d95mz2f	2015	2005 wurde dieses Konzept infrage gestellt, da Evidenz dafür vorlag, dass Thoraxkompressionen von bis zu 180 s vor einer Defibrillation das Überleben verbessern können, wenn der Rettungsdienst erst nach mehr als 4−5 min eintrifft [196, 197] . Der ERC empfiehlt, dass CPR fortgeführt werden soll, während ein Defibrillator oder AED gebracht und angelegt wird, aber dann soll die Defibrillation nicht weiter verzögert werden. Conventional and chest-compression-only cardiopulmonary resuscitation by bystanders for children who have out-of-hospital cardiac arrests: a prospective, nationwide, populationbased cohort study Impact of dispatcher-assisted bystander cardiopulmonary resuscitation on neurological outcomes in children with out-of-hospital cardiac arrests: a prospective, nationwide, population-based cohort study Public access defibrillation improved the outcome after out-of-hospital cardiac arrest in schoolage children: a nationwide, population-based, Utstein registry study in Japan Defibrillation or cardiopulmonary resuscitation first for patients with out-of-hospital cardiac arrests found by paramedics to be in ventricular fibrillation?
cord-005111-en9d79bj	2015	Auch jenseits der Ebola-Epidemie stellt sich beispielsweise für Infektionskrankheiten, zu deren Bekämpfung bereits Impfstoffe oder antivirale Arzneimittel entwickelt wurden, zum einen die Frage, in welchem Umfang diese Gegenmittel präventiv bevorratet werden. Als weiteres Gut von Verfassungsrang, das auf ebenso hoher Ebene angesiedelt werden muss wie das Leben, ist die Funktionsfähigkeit des Rechtsstaats an sich zu nennen. Die Argumentationslinie gegen die Maximierungsformel ist zu entkräften, indem man sich dem Problem mit einem praktischen Blick nähert: Stellt der Staat eine Priorisierung für den Zugang zu Impfstoffen auf, wird damit festgelegt, welche Gruppen eine Begünstigung erhalten und damit aus dem gleichsam natürlichen Lauf der pandemischen Situation herausgehoben werden. Die Unterschiede zwischen beiden Gruppen sind wie gezeigt erheblich, sodass eine Abwägung zwischen den Gruppenunterschieden und der Intensität der Ungleichbehandlung vor dem Hintergrund des Art. 3 Abs. 1 GG im Ergebnis zur Rechtfertigung dieser Ungleichbehandlung führen muss.
cord-005379-5x4deimg	2015	title: Dietary Selenium Status Regulates the Transcriptions of Selenoproteome and Activities of Selenoenzymes in Chicken Kidney at Low or Super-nutritional Levels To determine dietary selenium (Se) status regulates the transcriptions of selenoproteome and activities of selenoenzymes in chicken kidney, 1-day-old chickens received low Se (0.028 mg Se per kg of diet) or super-nutritional Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. Low Se significantly reduced total antioxidant capability (T-AOC), glutathione (GSH) content, but malondialdehyde (MDA) content in the kidney increased and decreased glutathione peroxidase (Gpx) and thioredoxin reductase (TrxR) activity with changes in their mRNA levels. Se could protect the renal antioxidant function from oxidative damage [14] , and Se deficiency or excess causes a lot of selenoprotein resultant metabolic disorders in pig kidney [15] .
cord-005491-di58oqe3	2015	Given that COPD exacerbations are a significant contributor to morbidity and mortality associated with this disease, and cause substantial financial costs, mainly due to hospitalization, it is crucial to better understand the factors leading to COPD exacerbations to be able to develop effective measures to prevent and/or treat these exacerbations. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease-A systematic review Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: A metaanalysis Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: A 2 year follow up study
cord-006035-9y504uyf	2015	In fact, the Government of India is short of technical advice on many issues pertaining to outbreak investigations and usually depends on multiple agencies -some of their own and some from outsides -for solving the mystery and instituting preventive measures, which ultimately do not go beyond recommending mass vaccination against Japanese encephalitis in affected areas [2] . For example, in an outbreak of AES amongst children in Andhra Pradesh, India in 2003, the virology group concluded it to be an outbreak of acute encephalitis caused by Chandipura virus [4] and the neurology team claimed the outbreak was caused by a neurovascular stroke called as "epidemic brain attack", not by any encephalitis [5] . Since the case fatality rate in children with severe dengue infection is high, pediatricians have a very important role to play to reduce the disease burden, and the minimum we can do is to update the health care personnel and community at various forums, about the various atypical manifestations of dengue for prompt recognition and management.
cord-006100-zvb7bxix	2015	The paper also serves to identify that although contingencies management for epidemiological issues require technical and scientific considerations to feature in governance arrangements, equally there are key "wicked problems" in the context public policy that pervade the health security sector. There are studies which consider crisis management, resilience and risk in the context of UK public policy (e.g. McConnell, 2003; Drennan and McConnell, 2006; Brassett et al., 2013) , however, there are very few case-based research studies which illustrate crisis and disaster governance challenges from the perspective of those institutions and policy actors that are responsible for managing such "wicked problems" from a macro-level policy position. The wicked problem of UK territorial governance UK policy actors (i.e. in Scottish and UK governments) in the area of health security have highlighted the domestic state-level challenges of managing planning for pandemic disease within UK borders and the political dimensions to this process.
cord-006104-f9000hjy	2015	
cord-006137-nrw6zztp	2015	It is now widely accepted that mutations in the gene encoding PfCRT, a digestive vacuole (DV) transporter located in the DV membrane is the primary factor in CQ resistance in Plasmodium falciparum, albeit that other proteins probably also contribute to the level of resistance [6] . In the last few months two studies have investigated the physiological role of PfCRT and mechanism of PfKelch13-based artemisinin resistance, respectively. In the case of CQ-sensitive PfCRT 3D7 , a wide range of naturally occurring cationic species, including among others amino acids, peptides derived from hemoglobin degradation and glutathione, exerted a cis-inhibition of TEA transport into the liposomes. The inactive analog, deoxyartemisinin caused no such effect so that PI3P formation occurred uninhibited and SS-EEA1-mCherry remained "The problem of artemisinin resistance represents a serious risk to the future success of the malaria control and elimination program." Artemisinin resistance in Plasmodium falciparum malaria A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
cord-006204-grjrf1n5	2015	We describe how a collaboration between the NPHIs of England and South Africa built a mutually beneficial professional relationship to help implement the WHO International Health Regulations, build capacity for health protection, and promote the exchange of information, advice, and expertise. NPHIs generally lead disease surveillance and outbreak investigations, provide reference laboratory services (specialist diagnostic services for rare organisms and confirmatory tests requiring specialised infrastructure and resources), and advise their governments on development and evaluation of interventions in public health. • executing specific epidemiology projects, • building epidemiological capacity at NICD, • supporting short-term HPA/PHE secondees visiting each institute, • providing, by the senior HPA/PHE epidemiologist, public health leadership within NICD, 3. Management expertise advanced when senior members of NICD staff spent shorter periods (1-2 weeks) with HPA/PHE counterparts in the UK exchanging ideas on management approaches in specific areas of work and exploring ideas for collaborative projects.
cord-006541-ror7z8h7	2015	title: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). The DC-SIGNR level in the serum of patients with lung cancer (14.9434 ± 0.3152 mg/ml) was significantly lower than that in healthy controls (3.4696 ± 0.2471 mg/ml) (P = 0.0003; Fig. 1a) . Serum concentrations of DC-SIGNR correlated significantly with lung cancer patients who have brain metastasis Our study demonstrated that serum levels of DC-SIGNR in lung cancer patients were significantly lower than those in healthy individuals. Furthermore, we found that the serum DC-SIGNR levels correlated significantly with brain metastasis and serum NK cells percentage in lung cancer patients. In the present study, we detected a significantly negative correlation between serum levels of DC-SIGNR and serum percentage of NK cells in lung cancer patients.
cord-007101-m0fs2f2a	2015	Due to the high degree of similarity in anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa) is considered a clinically relevant model to study factors influencing human gastrointestinal, immune, and brain development. Thus, the HMA pig model has the potential to be a valuable model for investigating how the gut microbiota composition changes in response to environmental factors, such as age, diet, vaccination, antibiotic use and infection. While differences between mother-fed or FF neonates of both species can be appreciated, marked differences in the gut microbiota Table 1 Advantages of the swine model • Omnivorousnutritional requirement and physiology similar to human • High genome and protein sequence similarities with human • Immune system more closely resembles human • Brain growth and development patterns similar to human ○ The major brain growth spurt similar to human ○ Gross anatomical features of the brain are comparable to that of human infants • Body sizeallowing various surgical manipulation and collection of adequate quantity of samples.
cord-007367-e31zhty6	2015	
cord-007404-s2qnhswe	2015	The existing studies have provided different theoretical predictions for epidemic threshold of the susceptible-infected-recovered (SIR) model on complex networks, while the numerical verification of these theoretical predictions is still lacking. To understand the effectiveness of the variability measure, the distribution of outbreaks sizes is investigated near the epidemic threshold on random regular networks. Considering that the existing theories more or less have some limitations (e.g., the HMF theory neglects the quenched structure of the network; QMF theory ignores dynamical correlations 14 ) , some numerical methods such as the finite-size scaling analysis, 15 susceptibility, 16 and lifetime measure 17 have been proposed to check the accuracies of different theoretical predictions for the SIS model. In this work, we perform extensive numerical simulations of the SIR model on networks with finite size, and present a numerical identification method by analyzing the peak of the epidemic variability 24,25 (i.e., the maximal value of the epidemic variability) to identify the epidemic threshold.
cord-007571-xzm36og6	2015	To prevent the spread of infection and injury, emergency nurses must be well prepared to appropriately select and use personal protective equipment (PPE). 5 Recently the CDC issued revised standards for EVD precautions, which include detailed guidance on the types of PPE required during patient care and strategies for ensuring safe practice. 6 Because of the complex and detailed nature of the guidance on caring for a patient with known or suspected EVD, emergency nurses should seek information about precautions and PPE standards directly from the CDC Web page at http://www.cdc.gov/vhf/ebola/hcp/index.html. Examples of strategies that can be used to prevent injury include strict adherence to infection control precautions, hands-on and in situ training, and staffing that supports safe care. 7 The CDC recommends that health care providers receive repeated training and demonstrate competency in performing all Ebola-related infection control practices and procedures, including donning and doffing proper PPE before engaging in patient care activities.
cord-007869-22qxdgrq	2015	5 In addition to drawing attention to the role of lung transplantation to improve survival and functional status in these patients, we hope our report''s fi ndings can motivate timely implementation of the necessary effective measures to reduce dust exposures and provide a healthful working environment for our country''s coal miners. Bafadhel and colleagues 1 report in a recent issue of CHEST (June 2011) that serum procalcitonin levels are high in patients admitted to hospital with pneumonia but not in those admitted with exacerbations of asthma or COPD. We examined the usefulness of serum procalcitonin in patients with moderate to severe exacerbations of asthma due to infections. We recruited 25 patients (11 men) with confi rmed diagnosis of asthma during what was considered an infective exacerbation (increased symptoms as measured by a seven-point Likert scale, increased sputum volume and purulence) that was not severe enough to require hospitalization.
cord-009636-5kddituy	2015	
cord-009655-ekc2p7k9	2015	Building dampness and indoor mould growth are recognized risk factors for respiratory health, including asthma, rhinitis and asthmatic symptoms [1] . Environmental Relative Moldiness Index has been used in epidemiological studies, and higher ERMI levels have been found in home dust among children with asthma as compared to controls without asthma [31] [32] [33] . [39] have extended the use of the ERMI-index and other microbial markers in the home environment to study exacerbation of asthma, measured as decreased FEV1% among non-smoking adult asthmatics in Scotland. Moreover, respiratory effects of different types of indoor biological contaminants, including fungal DNA measured by mould-specific quantitative PCR and calculation of the ERMI-index, should be extended from the home environment to other indoor environments such as day care centres, schools, hospitals and offices. Higher environmental relative moldiness index (ERMI) Values measured in homes of asthmatic children in Boston
cord-009862-37ki2pd8	2015	Here, we report many of these plant growth‐promoting processes related to nitrogen fixing species already described in Acetobacteraceae family, especially Gluconacetobacter diazotrophicus and their importance to agriculture. To date, among all Acetobacteraceae genera only some representatives of the genera Gluconacetobacter, Acetobacter, Komagataeibacter, Swaminathania, Asaia, and Acetobacter are reported as nitrogen fixing bacteria and the strategies used in order to obtain these new species are described in Table 1 [3, 47, [51] [52] [53] [54] [55] 59] . They succeed to isolate from sugarcane plants a group of acid-tolerant bacteria able to fix nitrogen even at pH below 3.5 using a minimal medium based on LG medium [64] , named LGI-P medium, that presents 10% of raw sugar as carbon source and pH around 5.5. It is a nitrogen-fixing bacterium originally classified as Acetobacter diazotrophicus but later renamed to the genus Gluconacetobacter based on the 16S rDNA sequence and the predominant type of ubiquinone [18, 19] .
cord-010027-r0tl01kq	2015	Further profiling of other T cell populations may help to further understand this expression which may act as a biomarker or provide a therapeutic target Biomarkers that are able to distinguish stage II and III colon cancer patients at high risk of developing disease recurrence, who may benefit from adjuvant chemotherapy, are still lacking. *AM supported by the NIHR and the Academy of Medical Sciences ABSTRACTS S·17 Assessment of HER2 Status on Needle Core Biopsy of Breast Cancer: Impact of Histopathological Concordance P M Pigera; AHS Lee; IO Ellis; EA Rakha; Z Hodi Nottingham City Hospital, Nottingham, UK One of the key recommendations introduced in the ASCO/CAP update guideline recommendation on HER2 testing is the novel concept of "histopathological concordance." It is proposed that certain tumour morphological features such as histologic type and grade should trigger repeating a molecular test in cases of "discordance".
cord-010130-28bt3x25	2015	RESULTS: After a median follow‐up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [CI] 59–81) at 100 days and 77% (95% CI 67–87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus‐virus‐associated cystitis was 19% (13/70). In the present analysis, we described infectious complications after unmanipulated, T-cell replete haplo-HSCT using post-transplant Cy in 70 consecutive patients and found, aside from a high incidence of viral infections/reactivations, especially in the early posttransplant period, a quite low incidence of late bacterial infections, together with a very low incidence of IFIs after day +180 (2 events in the overall 11 observed). In conclusion, the present single-center data on 70 consecutive patients receiving T-cell replete haplo-HSCT with post-transplant Cy confirm a high rate of viral infections before day +100 and a lower incidence of infections afterward, suggesting a satisfactory although non-optimal immune reconstitution after this type of transplantation.
cord-012136-9sx61tso	2015	As health research has been predominantly quantitative, 6 the low proportion of qualitative studies published in obesity journals may not relate to poor quality, but to a lack of understanding, making it difficult for editors and reviewers to judge the value and quality of qualitative reports. 7 In our experience leading qualitative, obesity-related research with clinical and health services foci, we have gained some experience in addressing potential challenges with publication. Using checklists to explain methodological and reporting details of qualitative studies may also benefit from a halo effect as it is consistent with many journal requirements for quantitative research. Finally, the inclusion of explicit instructions within authorship guidelines for obesity journals can highlight the range of research considered for publication, which can include requiring applicable reporting checklists and be accompanied by the inclusion of scientists, clinicians, and administrators at all stages of the peer-review process who possess methodological expertise in both quantitative and qualitative research.
cord-012329-rquefe2l	2015	Berardi points to the fact that cognitive or immaterial labor, far from gaining more and more autonomy with respect to capital, is becoming increasingly captured and controlled inside the digital networks, through the generalized implementation of what he calls technical and financial automatisms operating exclusively according to the logic of competition and surplus extraction and engendering more and more psychological and social automatisms (ibid., 88; Berardi 2009b, 7) . Instead of fixed capital migrating to living labor (the immaterial means of production increasingly residing in the brains of cognitive laborers), thereby granting it more autonomy as Hardt and Negri claim, Stiegler states that through generalized automation as exteriorization and short-circuiting of psychic and cognitive functions in the DNT, we cannot but admit that the multitude''s collective intelligence is becoming increasingly proletarianized (ibid., 45).
cord-012335-4io15ho0	2015	title: The Art of Living with NZT and ICT: Dialectics of an Artistic Case Study The dialectical relationship between vulnerability and technology constitutes the core of Hegel''s Master and Slave (the primal scene of contemporary philosophy). Building on a movie/novel (Limitless) devoted to vulnerability coping and living with ICT, I challenge the claim that modern heroism entails overcoming vulnerability with the help of enhancement and computers. Gradually, however, due to the tools and technologies he develops and puts to use, the Slave becomes increasingly powerful and autonomous, and the Master increasingly vulnerable and dependent. Building on a recent action movie, featuring a typical modern hero struggling in a world of ICT, I will argue that this is not the case. So far, the movie/novel seems in complete agreement with Coeckelbergh''s verdict that modern heroes, notably in contemporary action films, are very powerful and have limited vulnerability.
cord-012511-fl5llkoj	2015	We were tasked to evaluate the 6 following interventions: invasive mechanical ventilators, influenza antiviral drugs for treatment (but not large-scale prophylaxis), influenza vaccines, respiratory protective devices for healthcare workers and surgical face masks for patients, school closings to reduce transmission, and airport-based screening to identify those ill with novel influenza virus entering the United States. To allow easy comparison between results (a specification), we standardized a risk space defined by using ranges of transmission and clinical severity from a previously published influenza severity assessment framework ( Figure 1 ) [5] . Standardized epidemiological curves-contact matrix: To model the 4 epidemic curves (Figure 2 ), we built a simple, nonprobabilistic (ie, deterministic) model in which we divided the population into 4 age groups (0-10, 11-20, 21-60, ≥61 years).
cord-014527-nvzfpntu	2015	A negative outcome was associated with higher fecal S100A12 concentrations in CE dogs, but the response to different forms of treatment and fecal S100A12 has not been reported, and this information will be important to further evaluate the utility of fecal S100A12 as a biomarker for gastrointestinal disease. Statistical analysis was performed using non-parametric 2-or multiple-group comparisons, the likelihood ratio to evaluate the association between groups of dogs and response to treatment, and a receiver operating characteristic curve to calculate sensitivity and specificity at the optimum cut-off concentration. The objectives of this study were to describe pulmonary transit time and myocardial perfusion normalized to heart rate (nPTT and nMP, respectively), evaluated by means of contrast echocardiography, in dogs with stable stage C ACVIM myxomatous mitral valve disease (MMVD), and to assess short-term effects of pimobendan on these parameters.
cord-016880-q44623s8	2015	
cord-017258-5mzr5s22	2015	
cord-017520-r786yd6i	2015	Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic proand anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. The steps of an inflammatory reaction to trauma involve fluid phase mediators (cytokines, chemokines, coagulation-and complement activation products, oxygen radicals, eicosanoids, and nitric oxide (NO)) and cellular effectors (neutrophils, monocytes/macrophages, and endothelial cells) that translate the trauma-induced signals into cellular responses.
cord-017894-8iahlshj	2015	title: A Multiplex Polymerase Chain Reaction for Differential Detection of Turkey Coronavirus from Chicken Infectious Bronchitis Virus and Bovine Coronavirus A multiplex polymerase chain reaction (PCR) method for differential detection of turkey coronavirus (TCoV), infectious bronchitis virus (IBV), and bovine coronavirus (BCoV) is presented in this chapter. Primers are designed from the conserved or variable regions of nucleocapsid (N) or spike (S) protein genes of TCoV, IBV, and BCoV and used in the same PCR reaction. There is a close antigenic and genomic relationship between TCoV and infectious bronchitis virus (IBV) according to studies of immunofl uorescent antibody assay ( IFA ), enzyme-linked immunosorbent assay ( ELISA ), and sequence analysis in our and other laboratories [ 3 -8 ] . Nucleocapsid protein gene sequence analysis reveals close genomic relationship between turkey coronavirus and avian infectious bronchitis virus Differential detection of turkey coronavirus, infectious bronchitis virus, and bovine coronavirus by a multiplex polymerase chain reaction
cord-018111-5qx8tolv	2015	• Bradycardia-most common pre-arrest rhythm in children with hypotension, hypoxemia and acidosis (Fig. 3 ) -Sinus bradycardia • Maybe non-pathologic in case of well conditioned individuals like athletes • Causes include: hypothermia, hypoglycemia, hypoxia, hypothyroidism, electrolyte imbalance, toxic ingestion, head injury with raised ICP • Treatment-identify cause and treating that condition • HR < 60 bpm in a child who is a well-ventilated patient, but showing poor perfusion, chest compression should be initiated • If HR remains below 60 despite adequate ventilation and oxygenation, then epinephrine or atropine (0.02 mg/kg-0.1 mg min and 0.5 mg max) should be given • Symptomatic bradycardia unchanged by above may require pacing • AV mode blocks -First degree-prolonged PR interval • Generally asymptomatic -Second degree-2 types
cord-018469-3ip6566z	2015	However, whether such a carbohydrate moiety preserves a B cell epitope or a potent antigenic determinant must be determined immunologically, including at least demonstration of its antibody-binding specificity and capacity in eliciting immune responses in vivo (Wang et al. Methods currently in use include non-covalent binding of underivatized carbohydrate antigens by passive adsorption on a chip, such as nitrocellulose-coated glass slides (Wang et al. For example, the method of nitrocellulose-based immobilization of carbohydratecontaining macromolecules, including polysaccharides, glycoproteins, and glycolipids, is suitable for the high-throughput construction of carbohydrate antigen microarrays (Wang et al. A high-precision robot designed to produce cDNA microarrays is utilized to spot carbohydrate antigens of various structural configurations onto a nitrocellulose-coated glass slide. Given the structural diversity of carbohydrate antigens, examining each antigen preparation to determine the efficacy of its immobilization in a given type of substrate and the surface display of the desired glyco-epitopes in a microarray assay is essential.
cord-018639-0g1ov96t	2015	
cord-018746-s9knxdne	2015	
cord-018846-gmujrso2	2015	The routine use of tonsillectomy as a treatment option for recurrent tonsillitis and peritonsillar abscess has decreased over the last decade and clearer indications for surgery have emerged. Furthermore, with a few rare exceptions (e.g. Arcanobacterium haemolyticum , Neisseria gonorrhoeae and Fusobacterium spp.) anti-microbial treatment is not benefi cial for bacterial causes of tonsillitis except GABHS given that there is not a signifi cant reduction in the rate of complications or in duration of clinical symptoms [ 7 ] . The Infectious Disease Society of America (IDSA) recommends testing for GABHS unless a patient presents with symptoms strongly suggestive of a viral etiology; examples of such symptoms include cough, coryza, rhinorrhea, stomatitis or hoarseness. Children that do not meet these criteria but have multiple antibiotic allergies or intolerances or suffer from periodic fevers, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome) or with a history of peritonsillar abscesses may also be considered candidates for tonsillectomy.
cord-018969-0zrnfaad	2015	
cord-021248-ui1di3qa	2015	Through a systematic review methodology from 111 previous studies about RFID technology for public sector, we found six key areas of RFID applications: defense and security, identification, environmental applications, transportation, healthcare and welfare, and agriculture-livestock. We also suggest that the diffusion and applications of RFID can involve unexpected disadvantages including technological deficiency, uncertain benefits, dubious transparency, uncomfortable privacy issue, and unequal distribution of digital power and literacy. Rigorous research is required to explore what factors are critical to adopt and implement new RFID applications in terms of technology governance and digital literacy. Consequently, 49 literatures were publishedbetween 2006 and 2008 and it forms almost 45 % of our collected studies For this study, we categorized governments'' way of using RFID technology in 6 areas; Agriculture and Livestock, Defense and Security, Environmental Applications, Healthcare and Welfare, Identification, and Transportation.
cord-021872-rhi7hi9m	2015	
cord-021933-5082epvg	2015	In an effort to better identify and track potential outbreaks related to infectious diseases, both naturally occurring and those related to biowarfare and terrorism, public health practitioners developed surveillance systems designed to analyze routinely collected health information. They define PHEP as the capability of the public health and health care systems, communities, and individuals, to prevent, protect against, quickly Second highest priority agents include those that are moderately easy to disseminate, result in moderate morbidity rates and low mortality rates, and require specific enhancements of the CDC''s diagnostic capacity and enhanced disease surveillance. The information provided by surveillance systems, used in conjunction with clinical data, will ultimately help public health practitioners identify an etiologic agent. As preparedness strategies become more standardized and evidence based, our ability to respond to public health emergencies, including biological attacks, will improve. Real-time public health surveillance for emergency preparedness
cord-022173-kb6mez61	2015	
cord-022501-9wnmdvg5	2015	Methods: Using published data on (1) the prevalence of MRSA and other bacterial pathogens causing cSSSI in the US, (2) the in-vitro susceptibility rates of commonly used regimens in cSSSI in the US in relation to the most pervasive pathogens identified above, and (3) estimated costs of failure of initial, empiric treatment from a recent study of a large US multi-hospital database, we developed a model to predict the expected clinical and economic impact of increasing prevalence of MRSA. Small outbreaks of VEB-1 ESBL producing Acinetobacter baumannii in Belgian nursing homes and hospitals through cross-border transfer of patients from northern France Methods: From 01/04 to 03/05, all Belgian acute hospitals were invited to report cases of nosocomial infections/colonisations due to MDR Ab isolates presenting a resistance profile similar to the French epidemic strain (resistance to all agents except carbapenems and colistin) and to send such isolates to the reference laboratory for phenotypic confirmation and for genotypic characterization (PCR of VEB-1 and class 1 Integron, PFGE typing).
cord-022736-38q8jbcl	2015	• Incorporating long-term risk reduction and preparedness measures in normal development planning and programs, including support for specific mitigation measures where required; • Assisting in the planning and implementation of post-disaster rehabilitation and reconstruction, including defining new development strategies that incorporate risk-reduction measures relevant to the affected area; • Reviewing the impact of large settlements of refugees or displaced persons on development, and seeking ways to incorporate the refugees and displaced persons in development strategies; • Providing technical assistance to the authorities managing major emergency assistance operations of extended duration (especially in relation to displaced persons and the possibilities for achieving durable solutions in such cases).
cord-023890-z346hh2c	2015	However, at present, the issue of lipid therapy in ALI/ARDS is still controversial due, at least in part, to inconclusive or contradicting results in several recent clinical trials using n-3 PUFAs. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory diseases whose clinical severity depends on the grade of inflammatory response. The first RCT showed the ability of an enteral formula with a high n-3/n-6 PUFA ratio (1:1) to reduce pulmonary inflammation and improve clinical outcomes, i.e., better oxygenation, shorter requirement for mechanical ventilation, shorter ICU-LOS, and less incidence of new organ failure; however, no difference in mortality was observed in ARDS patients (Gadek et al. The first RCT analyzed the effect of an enteral n-3 PUFA-enriched diet in septic patients with ALI or ARDS showing that the administration of the study formula, compared to a control formula with less lipids than in the previous three studies, was associated to a shorter ICU-LOS but not to an improvement in gas exchange or in a lower incidence of novel organ failures (Grau-Carmona et al.
cord-030374-p66vzmpg	2015	This method is preferred to using the transit times at the lower stress states to directly determine the shock pressure from an inferred wave velocity because of the complicated compressive response of fused silica below ~25 GPa. The variation in strain for the material involved in this style of compression is significant, however, the volume fraction is less than 10%. SESAME 7592 and 7386 equations of state were used for the GDP ablator and fused silica, respectively 6 considering the same drive conditions were used) and within the uncertainty of the VISAR derived stress value of 33.6 ± 5.0 GPa. No preferred orientation corrections in GSAS were required to provide a match of (110), (101), (111) and (210) peak intensities to previously published powder data found in the crystallographic information file (cif) 8 .
cord-102738-e5zojanb	2015	Among statistical predictors for retention and in-game high scores, the data from our first year suggest that people recruited based on real-world physics interest and via real-world events, but only with an intermediate science education, are more likely to become engaged and skilled contributors. Recruitment activities in-world and online, an engaging in-game core loop, a structural gameplay to frame, structure and motivate the player''s continual progression through the levels, as well as an active community where participants get a sense of continually contributing to science, are all central components of the strategy laid out to hopefully realizing the scientific goals of Quantum Moves. While Quantum Moves is unique compared to other citizen science games in having an engaging and challenging core game loop that by itself lives up to prominent definitions of (casual) games (Juul, 2005; Salen & Zimmerman, 2004) , we also expect that a well-designed structural gameplay (sometimes called metagame) is central to frame, structure and motivate the play experience, both helping and goading players to move from level to level along appropriate learning curves balanced between boredom and anxiety.
cord-157259-eozvlu4z	2015	This paper is concerned with stochastic SIR and SEIR epidemic models on random networks in which individuals may rewire away from infected neighbors at some rate $omega$ (and reconnect to susceptible individuals with probability $alpha$ or else simply drop the edge if $alpha=0$), so-called preventive rewiring. The models are denoted SIR-$omega$ and SEIR-$omega$, and we focus attention on the early stages of an outbreak, where we derive expression for the basic reproduction number $R_0$ and the expected degree of the infectious nodes $E(D_I)$ using two different approximation approaches. This paper aims mainly at comparing the predictions from both modelling methodologies (pairwise/stochastic) for the initial phase of Susceptible-Infectious-Recovered (SIR) and Susceptible-Exposed-Infectious-Recovered (SEIR) epidemics with preventive rewiring among individuals (so, with an interplay between the spread of the disease and the rewiring process, that is, between disease''s dynamics and network dynamics).
cord-252143-mfl6ey0y	2015	Included are a review of the potential applications of IgY in the control of enteric infections of either bacterial or viral origin such as enterotoxigenic Escherichia coli, Salmonella spp., rotavirus, porcine transmissible gastroenteritis virus, and porcine epidemic diarrhea virus. A major challenge currently facing the swine industry is to develop alternative means for controlling diarrhea in young pigs (particularly neonatal and early-weaned piglets) that are not only cost effective, but also allow for sustainable pork production. Oral administration of specific IgY antibodies has been shown to be highly effective against a variety of intestinal pathogens which cause diarrhea in animals and human such as enterotoxigenic Escherichia coli (ETEC), Salmonella spp., bovine and human rotaviruses, bovine coronavirus, porcine transmissible gastroenteritis virus (TGEV), and porcine epidemic diarrhea virus (PEDV) [14, 16] . In addition to reducing the incidence and severity of piglet diarrhea, several studies have shown that IgY has growth promoting effects in early-weaned pigs, similar to spray-dried animal plasma and spray-dried porcine plasma [36] [37] [38] [39] .
cord-252485-cxi3cr15	2015	We and other groups have recently reported that recombinant viruses of Sendai virus (SeV), a prototype of the family Paramyxoviridae, in which the C proteins are knocked-out or mutated, generate dsRNA in infected cells at levels similar to the production of IFN-β (Takeuchi et al., 2008; Irie et al., 2010) . These unusual RNAs exhibited distinct properties in infected cells in terms of encapsidation with the viral N protein and subcellular distribution with SG marker proteins and RLRs. Our results suggest that RNA-typedependent mechanisms recognize and accumulate virus-derived, IFN-β-inducible, unusual RNAs into specific compartment to trigger the production of IFN-β, and that SeV may evade detection by the host innate immune system by preventing the production of these RNA species. Since the naked cbDI genomes have been reported readily to form an ideal structure as the RIG-I ligands of 5 -triphosphated, blunt-ended dsRNA (Kolakofsky, 1976) , these results indicated that the major IFN-β-inducing viral RNA species produced in the cells infected with CNT was encapsidated cbDI genomes, whereas those for SeV-4C(-) and NDV were not.
cord-254713-ghcwfcx2	2015	RESULTS: From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Studies which aimed to identify potential reservoirs of emerging human CoVs have revealed that the Betacoronavirus SARS-CoV was closely related to CoVs detected in bats, specifically members of the genus (Rhinolophus), which brought the hypothesis of a spillover of this virus to several animal species (including civet cats and raccoons) sold in Chinese markets as bushmeat for human consumption [9] [10] [11] . A total of 351 bats belonging to 3 endemic bat species of the family Pteropodidae were captured and sampled: Rousettus madagascariensis (n = 179), Pteropus rufus (n = 76) and Eidolon dupreanum (n = 96) ( Table 1) . In the context of this study, we detected 14 coronaviruses forming nine genetically distinct strains in two endemic Malagasy frugivorous bat species.
cord-255141-55ho9av4	2015	A QX-like strain was analysed by high-throughput Illumina sequencing and genetic variation across the entire viral genome was explored at the sub-consensus level by single nucleotide polymorphism (SNP) analysis. The E and 3b protein products play key roles in coronavirus virulence, and RNA folding demonstrated that the mutations in the 5′UTR did not alter the predicted secondary structure. Coronavirus accessory proteins are generally dispensable for virus replication, but they play vital roles in virulence and pathogenesis by affecting host innate immune responses, encoding pro-or anti-apoptotic activities, or by effecting other signalling pathways that influence disease outcomes (Susan & Julian, 2011) . Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus Analysis of a QX-like avian infectious bronchitis virus genome identified recombination in the region containing the ORF 5a, ORF 5b, and nucleocapsid protein gene sequences
cord-255158-cxt824rp	2015	In a modified SAON rabbit model, we found destructive repair at subchondral region of femoral head, i.e. a dominate old bone resorption without adequate new bone formation to maintain normal bone homeostasis; and knockdown of Src expression by Src specific siRNA could enhance osteoblast differentiation, promote osteogenesis and inhibit the function of osteoclasts [14] . In this study, we investigated corticosteroid-associated bone loss at metaphysis of femoral head using an established SAON rabbit model [14] and potential effects of Src siRNA for prevention of SAOP. This study investigated the bone loss induced by pulsed LPS and MPS using an established SAON rabbit model and tested the therapeutic potential of Src siRNA, a bone anabolic and anti-resorption agent for prevention of corticosteroid associated osteoporosis (SAOP). The loss of trabecular bone at metaphysis of femoral head after pulsed LPS and MPS treatment was reversed by Src siRNA administration in the present study, with significantly better micro-CT indices, including BMD, BV/TV, Tb. Th and Conn.
cord-255350-dmbl4emn	2015	CEACAM7 is a human cellular adhesion protein that is expressed on the surface of colon and rectum epithelial cells and is downregulated in colorectal cancers. The overall fold of CEACAM7 is similar to those of CEACAM1 and CEACAM5; however, there are differences, the most notable of which is an insertion that causes the C′′ strand to buckle, leading to the creation of a hydrogen bond in the dimerization interface. The dimer interface is formed from the second -sheet, A 0 GFCC 0 C 00 , specifically the GFCC 0 C 00 strands and the CC 0 , C 0 C 00 and FG loops (Fig. 1c) . The dimerization constant of CEACAM7 was estimated by sedimentation-equilibrium analysis using analytical ultrain 50 mM Tris-HCl, 50 mM sodium chloride pH 7.5 with rotor speeds of 29 000, 32 000 and 35 000 rev min À1 (blue, red and green curves, respectively).
cord-255536-x1z2o9gs	2015	The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. In the Epstein-Barr herpes virus (EBV), G-quadruplexes modulate EBV nuclear antigen 1 (EBNA1) activity and translation (Murat et al., 2014) ; in particular, BRACO-19 inhibited EBNA1-dependent stimulation of viral DNA replication http://dx.doi.org/10.1016/j.antiviral.2015.03.016 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. We demonstrate that treatment with the G-quadruplex ligand BRACO-19 greatly stabilizes these sequences resulting in decrease of infectious viral particles, reduction of late viral transcripts, inhibition of Taq polymerase processing at the HSV-1 genome, specifically affecting viral DNA replication at G-quadruplex regions.
cord-256201-vjzfzshh	2015	Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis. Finally, we found that the mutation rate reduction afforded by the twenty GATC motifs was fully reverted at 42 C and in the presence of the base analog 5-fluorouracil (5-FU), two stress factors that promote overexpression of repair-associated error prone polymerases (Layton and Foster 2005; Malkova and Haber 2012) , thus suggesting that addition of GATC motifs renders the phage sensitive to stress-induced mutagenesis. We have shown that introduction of GATC sites in the /X174 genome can reduce the spontaneous mutation rate of the phage by up to fiftyfold, indicating that phage DNA can undergo MMR if the required sequence motifs are present.
cord-256550-72i1x02f	2015	Concern over escape from a laboratory of a deadly human-contagious virus (e.g., influenza, severe acute respiratory syndrome [SARS] , and Middle East respiratory syndrome [MERS] viruses) prompted the U.S. Government to hold back funding for this research "until a robust and broad deliberative process (2) is completed that results in the adoption of a new USG gain-of-function research policy." This discussion is now under way in the United States and is to be completed in 2016. Defending the safety of his work in the first letter (3), Dr. Fouchier calculated that it would likely take more than a million years for an escape from his lab through a laboratory-acquired infection (LAI). If P 1 is really as low as Fouchier suggests, we would need to wait 670 years to reach a 1% chance of escape, an elapsed time that would appear to make the research enterprise safe in some researchers'' thinking, but risk equals likelihood times consequences, and consequences such as fatalities could be very high for a human-contagious influenza virus with a high case fatality rate.
cord-256583-z3pd339v	2015	Whereas historically, Ebola epidemics spread via person-to-person transmission, the current outbreak in West Africa has seen unexpectedly extensive spread of nosocomial disease, despite HCWs'' reliance on previously effective infection control procedures such as patient isolation, barrier nursing procedures, and required personal protective equipment (PPE) [1] . In our view, the most concerning examples include Dr Khan [3] , a Sierra Leonean virologist who contracted Ebola despite his extensive experience and careful adherence to procedures; Dr Spencer [4] , a Médecins Sans Frontières physician who became symptomatic upon returning to New York despite working in well-designed isolation units built specifically to protect HCWs from EVD infection; and Dr Sacra, an obstetrician who contracted Ebola without having knowingly cared for any EVD patients [5] . Realizing the threat of nosocomial infection, the Taiwan Centers for Disease Control responded by implementing traffic control bundling (TCB), which included triage and diversion of patients before they enter the hospital; clear delineation of zones of risk between contaminated and clean zones; and gloves-on hand disinfection at checkpoints between zones of risk ( Figure 1 ) [11] .
cord-256635-zz58w3ro	2015	In 1995, in agreement with the German Federal Ministry of Health, the Robert Koch Institute established a public health microbiology system consisting of national reference centers (NRCs) and consultant laboratories (CLs). As part of this concept, the RKI implemented a weekly epidemiological bulletin, formed the Committee for Infectious Disease Epidemiology, trained epidemiologists for surveillance and outbreak investigation and set up a system of national reference laboratories: national reference centers (NRCs) and consultant laboratories (CLs) (Petersen et al., 2000) . In the next step, the Advisory Board for Public Health Microbiology (formerly called the Committee for Infectious Disease Epidemiology) assesses the proposal and provides the RKI with a recommendation on whether to set up a new laboratory. At the end of each appointment period, an evaluation of the laboratories is performed by the RKI in cooperation with the Advisory Board for Public Health Microbiology, which again consults national and international professional societies and experts.
cord-256779-e9wz0qb3	2015	Further, CNTs surface engineered with folic acid and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) showed tumor targeted delivery of DOX with improved cytotoxicity toward cancer cells and enhanced cellular uptake speculated to be mediated by endocytosis and tiny nano-needle mechanism [2, 8] . Fig. 3 presents the different conjugates based on CNTs employed in the delivery of anticancer bioactives varying from pristine CNTs to drug loaded CNTs. From the aforesaid account it may be concluded that the surface engineered CNTs could have promising potential in cancer therapy. Biotinylated amphiphile-single walled carbon nanotubes conjugate for target-specific delivery to cancer cells Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes Polymer functionalized single walled carbon nanotubes mediated drug delivery of gliotoxin in cancer cells
cord-256849-8w2avwo2	2015	title: Identify-Isolate-Inform: A Tool for Initial Detection and Management of Measles Patients in the Emergency Department The "Identify-Isolate-Inform" tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases. Following a brief review of measles, this paper describes the novel 3I tool, initially developed for Ebola virus disease, 4 as adapted for use in the initial detection and management of measles patients in the emergency department (ED). During a measles outbreak, after donning appropriate respiratory protection, emergency physicians (EP) should carefully assess the oropharynx in patients presenting with non-specific viral syndromes and assess for the presence of Koplik spots. 12 Conversely, patients with signs and symptoms of measles (prodrome of fever, cough/coryza/conjunctivitis, Koplik spots followed by rash), should be immediately masked and isolated using airborne precautions.
cord-256852-lrz17bdx	2015	15 The U.S. Institute of Medicine (IOM) has published a report "Countering the Problem of Falsified and Substandard Drugs." 16 The IOM recommendations to "stem the global trade" in such products are laudable in advising that the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology, and other U.S. and international pharmaceutical and financing agencies be more actively involved in setting standards and financing improvements; yet this report falls far short of making a strong call for standardized, agreed-upon quality assessment technologies; an international law convention; and a more activist, internationally recognized lead organization, all three of which are essential for stopping the many health threats of fake drugs.
cord-256995-itiz6mqv	2015	C-reactive protein levels were raised in 14 cases of the 19 cases, histological findings either supported or were a decisive factor for the classification of microbiologically related cause of death in 14 cases. In a retrospective study including 42 autopsies performed at our Institute, where microbiological test had been applied, analyses were made with regard to: type of microbiological tests performed, microorganisms found, histological findings, antemortem information, C-reactive protein measurement and cause of death. In a retrospective study including 42 autopsies performed at our Institute, where microbiological test had been applied, analyses were made with regard to: type of microbiological tests performed, microorganisms found, histological findings, antemortem information, C-reactive protein measurement and cause of death. Microbiological sampling remains an important part of the autopsy yielding the cause of death in 42.8% of the cases in which it was performed.
cord-258049-l55mx4lp	2015	We performed a prospective, multicenter, multiyear study [10] [11] [12] to examine the typical inpatient clinical course of and to develop hospital discharge guidelines for children age <2 years hospitalized with bronchiolitis. A child was considered clinically improved on the earliest date he/she met all of the following criteria: (1) none or mild retractions and improved or stable retractions compared with the previous inpatient day; (2) daily estimated average respiratory rate (RR) <60 breaths per minute for age <6 months, <55 breaths/minute for age 6 to 11 months, and <45 breaths/minute for age 12 months with a decreasing or stable trend over the course of the current day; (3) daily estimated average RAO2 saturation 90%, lowest RAO2 saturation 88% 21 ; and (4) not receiving intravenous (IV) fluids or for children receiving IV fluids a clinician report of the child maintaining oral hydration.
cord-258173-dftwz6l4	2015	The aim of the study was to study and to compare simple infections and viral coinfections of respiratory syncytial virus (RSV) in hospitalized children. In addition, children with RSV infections are also exposed to a variety of other respiratory viruses with a similar seasonal pattern, mainly during winter months, such as influenza, rhinovirus (RV), human metapneumovirus (hMPV), and human bocavirus (HBoV). 1 Despite the fact that numerous studies have revealed that an important number of ARI pediatric patients become simultaneously infected with multiple respiratory viruses, there are few studies focused on analyzing viral coinfections. We aimed to compare, in a prospective study, clinical characteristics and severity of single versus viral coinfections, defined as simultaneous detection of RSV with RV, hMPV, or HBoV, in a large cohort of hospitalized children.
cord-260107-gqbtkf0x	2015	
cord-261118-rzdxdzp5	2015	title: Drug hypersensitivity causing organizing eosinophilic pneumonia in a pediatric patient The presentation is typically rapid over the course of 1e5 days, and generally involves fever, myalgias, pleuritic chest pain, crackles on lung exam, plus or minus peripheral eosinophilia as was the case in our patient. Bronchoalveolar lavage is the diagnostic study of choice to diagnose an eosinophilic lung disease as it may be the only clue revealing a high eosinophil count (typically >25% when the normal in BAL fluid is <1%). 4 There have been very few reported cases of organizing eosinophilic pneumonia being associated with pulmonary embolism or a pneumomediastinum. Eosinophilic pneumonia has no obvious association with pulmonary embolism but still could be the possible etiology. 5 At 8 weeks of life the patient had a lung biopsy which showed the eosinophilic pneumonia. If corticosteroids fail to improve the patient''s condition, other treatment options could include IVIG, and cyclosporine A.
cord-261421-k1s5iy3u	2015	To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1–2 month intervals from 2 independent groups of animals during April 2013–May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Furthermore, MERS-CoV infection in dromedary camels was definitively proven by the detection of virus and virus sequences in respiratory specimens, feces, and milk collected from camels in Qatar (9, 13) , Oman (14) , Saudi Arabia (5, 15, 16) , and Egypt (17) . To address these limitations and to clarify the dynamics of MERS-CoV infection in these animals, we conducted a year-round study in which we collected a large number of specimens from the upper respiratory tracts of live dromedary camels and from the lungs of dromedary camel carcasses. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia
cord-263239-andje0wu	2015	Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. To corroborate that PI4KA activity is required for the step of viral genome replication, we performed a time-of-addition experiment in which AL-9 was added to the cells at different time points after infection with RLuc-EMCV. The Picornavirus EMCV Converges on the Host Lipid Pathway Used by HCV localized throughout the cytoplasm and at the Golgi, OSBP was mainly found at ROs in infected cells, where it largely colocalized with 3AB ( Fig 6D, Pearson''s correlation coefficient = 0.71). Finally, data are presented suggesting that the OSBP-mediated exchange of PI4P and cholesterol at RO-MCSs is critical for EMCV genome replication and the global organization of ROs. Membrane alterations in the cytoplasm of cardiovirus-infected cells were already observed decades ago by electron microscopy [37, 38, 63] .
cord-263489-i4tkdgy4	2015	title: Phage display for identifying peptides that bind the spike protein of transmissible gastroenteritis virus and possess diagnostic potential Herein, we use similar technology and advance previous work by using the rS-AD as an immobilizing target to select phages from a peptide display library, with diagnostic potential for TGEV. Our results indicate that phages bearing peptide ligands that bind rS-AD can be used to develop a phage-mediated ELISA with high sensitivity and specificity to distinguish TGEV from other common swine viruses. To compare the sensitivities of phage-mediated ELISA to antibody-mediated ELISA, TGEV serially diluted in 0.1 M NaHCO 3 (pH 8.6) was coated onto duplicate ELISA plates overnight at 4°C followed by blocking with 5 % skim milk for 3 h at rt. Predicted amino acid sequences were generated for ten selected phages In summary, we identified peptides that specifically bind to TGEV and can form the basis of new diagnostic tests where the sensitivity of phTGEV-SAD15 was 0.1 lg of TGEV.
cord-265292-yyh1kikb	2015	
cord-265472-b1s4stvz	2015	In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. We can infer that a similar response may be associated with different safety in relation to the development of autoimmune reactions to vaccines, particularly in the patients with genetic predisposition to an enhanced response to vaccine inoculation [85] . HSP was associated with seasonal influenza, influenza A (H1N1), pneumococcal and meningococcal disease, hepatitis A virus (HAV), HBV, anti-human papilloma virus (HPV) vaccines, and following multiple combinations of vaccines, such as typhoid, cholera and yellow fever [139, [171] [172] [173] . Hepatitis B vaccination and undifferentiated connective tissue disease: another brick in the wall of the autoimmune/inflammatory syndrome induced by adjuvants (Asia)
cord-267003-k7eo2c26	2015	7 The human body is usually capable of eliminating respiratory viral infections with no sequelae; however, in some cases, viruses bypass the immune response of the airways, causing conceivable severe respiratory diseases. 49, 50 virus effect on the immune system Post-viral sustained desensitization of lung sentinel cells to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with viral infection. Hendaus et al human-alveolar basal-epithelial cells) during a respiratory viral infection by increasing the expression of ICAM-1. It has been recommended that treatment or prevention of a viral disease may be a superior method for diminishing 62 It has also been published that live attenuated influenza vaccine is effective in reducing the incidence of all-cause AOM [86] [87] [88] and pneumonia 89 compared to placebo in children. Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells
cord-267360-pemva816	2015	OBJECTIVES: The aim of our research was to test the efficiency of PO(2)/FiO(2) and CAP severity scores in predicting mortality and intensive care unit (ICU) admission with influenza pneumonia patients. In this study, we want to test the efficiency of PO 2 / FiO 2 and CAP severity scores in predicting mortality and ICU admission with influenza pneumonia patients. So, we finally used eight severity scores or indices (PSI, CURB-65, CRB-65, SMART-COP, LIS, PO 2 /FiO 2 , lymphocyte count and PaO 2 /FiO 2 combined lymphocyte count) to compare AUCs for mortality prediction in hospitalized patients with influenza pneumonia ( Table 4 ). This study demonstrated that PO 2 /FiO 2 combined lymphocyte count is simple and reliable severity predictor of hospitalized patients with influenza pneumonia, which is significantly better than current CAP Commons and Denholm (28) investigated 105 patients of H1N1 influenza infection and found that the common used CAP severity scores (PSI and CURB-65) had insufficient predictive ability to lowrisk patients in ICU admission.
cord-268593-rvxxv1dn	2015	
cord-268902-npug5c8p	2015	In agreement with the findings in mosquitoes, a recent study has identified a C-type lectin in the shrimp Marsupenaeus japonicus that interacts with an envelope protein of White spot syndrome virus (WSSV) and consequently associates with a cell-surface calreticulin, which serves as a membrane receptor that facilitates viral entry in a cholesterol-dependent manner [128] . The interaction between lectins and viral glycoproteins may lead to the three following consequences: (1) lectins, such as MBL and SPs, function as pattern recognition molecules that bind a repertoire of viruses and activate antiviral immune responses; (2) lectins are employed as attachment factors that recruit viral particles to the cell membrane to enhance viral entry, e.g., some mammalian lectins (DC-SIGN, L-SIGN, MR and MPRs) or their homologs in arthropods (mosGCTLs); and (3) some intracellular lectins, such as calnexin and ERGIC-53, function as susceptibility factors associated with virus-encoded proteins to facilitate viral replication or assembly (please refer to Figures 1 and 4) .
cord-269194-b1wlr3t7	2015	Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats. With the development and administration of newer drugs that target specific biological processes of HIV, routine and clinical monitoring of viral loads using a real-time quantitative PCR assay continues to be critical to predict treatment failure and early emergence of drug resistance mutations, within a timeframe that would increase subsequent treatment success.
cord-269652-t7ghng17	2015	The AAP Committee on Fetus and Newborn have published a clinical report on the evaluation of asymptomatic infants (<37 and !37 week gestation) with risk factors for sepsis. 7 CRP has been used in the algorithm-based guideline from the AAP Committee on Fetus and Newborn for the evaluation of asymptomatic term and preterm infants with a risk factor for sepsis. It is recommended to discuss complicated cases, such as multidrug resistant organisms and infants not improving while on therapy or those requiring unconventional dosing regimens and antimicrobial agents, with pediatric infectious disease specialists. Suggested durations of antiviral therapy, prophylaxis, and suppressive regimen for congenital and perinatal or postnatally acquired viral infections adapted from 2014 Nelson''s Pediatric Antimicrobial Therapy 32 and the AAP Committee on Infectious Diseases and the Committee on Fetus and Newborn 41 are shown in Table 3 .
cord-270772-zshjrc87	2015	The emergence of the pandemic influenza virus A(H1N1)pdm09 in 2009 and avian influenza virus A(H7N9) in 2013 provided unique opportunities for assessing genetic predispositions to severe disease because many patients did not have any underlying risk factor or neutralizing antibody against these agents, in contrast to seasonal influenza viruses. Integration of knowledge from genetic and phenotypic studies is essential to identify important gene targets for treatment and prevention of influenza virus infection. Specific amino acid changes in the viral proteins have been associated with increased disease severity in humans or adaptation of avian influenza viruses in humans [13] . High-throughput screening platforms have allowed researchers to systematically screen a large number of genes associated with influenza virus infection in vitro, in animals or in humans. 9 Host genetic determinants of influenza virus disease severity identified in humans. Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection This study incorporated in vitro, animal and human data to prioritize genes for future research on genetic susceptibility to severe influenza
cord-273136-hrgtaunt	2015	The aim of this chapter is to describe the animal models generated by transgenic technology for the functional analysis of the protective axis of the renin–angiotensin system, consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin (Ang)-(1-7), and Mas. Transgenic overexpression of the components of this axis in general led to an ameliorated cardiac and vascular damage in disease states and to an improved metabolic profile. 1, 2 The aim of this chapter is to describe the animal models generated by transgenic technology for the functional analysis of the protective axis of the RAS, consisting of angiotensin-converting enzyme 2 (ACE2), Ang-(1-7), and Mas. In biomedical research, the use of rats and mice has become a major tool, considering the easiness of breeding, growth, and maintenance and the similarity with human organisms in most cardiovascular and metabolic systems. Our group and others have developed several transgenic and KO rat and mouse models with genetic deletion and/or overexpression of components of the ACE2/Ang-(1-7)/Mas axis.
cord-273372-69rlh9or	2015	In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. We have found that indeed there is much prior knowledge regarding small molecules that have been shown to be active against the Ebola virus in vitro or in animal models 10-13 , including a number of FDA-approved drugs 14-16 . Medicinal chemistry analysis of small molecules active against the Ebola virus We have recently described an expert''s medicinal chemistry 26 analysis of the over 320 NIH probe compounds using public and commercial sources of chemical structures and the issues related to doing this type of analysis 27 . By organizing the data on small molecules tested against the Ebola virus similarly in a central database and using machine learning models based on public data may help identify additional compounds for testing.
cord-274129-vaygaqe5	2015	We describe an impedimetric cell-based biosensor constructed from poly-l-lysine (PLL)-modified screen-printed carbon electrode for real-time monitoring of dengue virus (DENV) infection of surface-immobilized baby hamster kidney (BHK-21) fibroblast cells. Cytopathic effects (CPE) induced by DENV-2 New Guinea C strain (including degenerative morphological changes, detachment, membrane degradation and death of host cells), were reflected by drastic decrease in impedance signal response detected as early as ~30 hours post-infection (hpi). In comparison to conventional inspection methods such as microscopy and plaque assay that rely on observable changes in the morphology and surface coverage of cells, the EIS technique offers a more promising platform for studying virus-host interactions based on the real-time measurement of CPE-induced impedance response (Cho et al., 2007) . Here we report an impedimetric cell-based biosensor constructed from poly-L-lysine (PLL)-modified screen-printed carbon electrode (SPCE) for real-time monitoring of DENV infection of surface-immobilized baby hamster kidney (BHK-21) fibroblast cells.
cord-274377-57zy6unz	2015	To this end we re-examined the anti-viral properties of CQ, and show here that it inhibited the pH-dependent endosomal entry of a pseudotyped virus (PV) bearing EBOV glycoproteins, in the same way as did the potent and specific vacuolar-ATPase (vATPase) inhibitor bafilyomycin A1 (BafA1) (a non-medical laboratory compound). We also show that licensed and widely used proton pump inhibitors (PPIs) for treatment of gastric acid reflux, omeprazole (OM) and esomeprazole (ESOM), inhibited PV EBOV entry, likely by their off-target inhibitory activity on endosomal vATPase. In this instance, a ''fusion inhibitor'' could target the host cell machinery preventing acidification of the endosome, working to inhibit virus entry of several different viruses. Given the volume of research suggesting these off target effects depend on an ability to affect intracellular pH, we hypothesised that these drugs would, like CQ and BafA1, inhibit EBOV, MARV and influenza virus pH dependent entry.
cord-274557-2071770h	2015	i.e., cold-ethanol or ion-exchange chromatography, contaminants, route of application, i.e., intra muscular (IMIG), intravenous (IVIG), or subcutaneous (SCIG), the rate of increase of the exogenous IgG in the circulation of the recipient over time and, last but not least an eventually existing risk factor from patients'' side ( Figure 1 ) as well as incorrect handling of the concentrate are factors having a role in inducing non-infectious AEs related to administration of IgG concentrates ( Table 1) . The complement-mediated AEs were considered to be caused by aggregates in the product ("spontaneous complement activation" or anti-complementary activity or ACA) or by in vivo formation of immune complexes (ICs, patient''s condition related; e.g., subclinical infections or the unnoticed presence of anti-IgA antibodies) and therefore only IgG concentrates with low or absent ACA is accepted by authorities for human use.
cord-274569-jh0dyyz7	2015	These routes require maturation of the EE into recycling endosomes or multivesicular bodies (MVBs), which can either fuse with lysosomes (L) to generate endolysosomes (EL) or with the plasma membrane to release intraluminal vesicles to the milieu as exosomes. These routes require maturation of the EE into recycling endosomes or multivesicular bodies (MVBs), which can either fuse with lysosomes (L) to generate endolysosomes (EL) or with the plasma membrane to release intraluminal vesicles to the milieu as exosomes. This mechanism was recently reported for HCV [113] , where exosomes derived from infected human hepatoma cells containing full-length viral RNA, along with core and envelope proteins [115] , were shown to be infectious and a major route of transmission. demonstrated that B lymphocytes infected with Epstein-Barr virus (EBV), a human gammaherpesvirus associated with a variety of lymphoblastoid and epithelial cancers, released exosomes containing MHC II molecules, and that these vesicles were capable of activating specific CD4 + T cell clones in vitro [122] .
cord-274791-1fmouoal	2015	A recent study comparing a cohort of pregnant women between 13 to 35 weeks gestation and non-pregnant women showed no differences in respiratory rate, oxygen saturation and transcutaneous carbon dioxide levels in pregnant compared with non-pregnant subjects wearing the N95 FFR during exercise and sedentary activities for over a 1-hour period [17] . Our study was performed to address the limited data on N95-mask usage in pregnancy with the aim of investigating the effects of breathing through the N95 mask materials on respiratory functions at rest, during low intensity work, and recovery thereafter in pregnant healthcare workers. Prior to the N95 cycle, an additional 15-minute conditioning period was allowed to enable patient to adapt Fig. 1 Determination of average work intensity of Health care workers: In phase I pregnant subjects performed simulated patient care activities while breathing through a tight fitting mask with a pneumotachometer.
cord-275307-d7htyfcl	2015	Development of a novel bioinformatics pipeline to detect highconfidence SOX cleavage sites across the transcriptome following PARE Prior analyses of individual mRNAs indicated that the KSHV RNase SOX cuts at specific locations within the RNA, in a manner dependent on the sequence surrounding the cleavage site [5] . This example shows the expected distribution for a cut site followed by exonucleolytic degradation due PARE libraries from two replicates of SOX-expressing or GFP control cells and extracted the 5'' end of each mapped read, which represents the cleavage site (S1 Table) . Indeed, the sequences flanking the set of reproducible SOX cut sites (identified with a confidence level of 99.99%) were a closer match to the motif compared to those surrounding GFP-specific fragment ends, as shown by the distribution of the log likelihood scores (Fig 6A) .
cord-275443-9ib77yws	2015	Considering that mAb D7 resulted in a significant reduction in viral titers in the lungs of mice infected with three different virus strains at 6 dpi, we chose that time point to determine the viral RNA loads in different tissues and fecal samples. To compare the above results with pathological findings in mice infected with three different virus strains, and treated with mAb D7 and irrelevant mAb IgG, we chose the heart, brain and lung from different treatment groups at 6 dpi to perform histopathological and immunohistochemical analysis. To gain a better understanding of the effect of CIV on the innate immune response and to ascertain whether passive immunization with monoclonal antibody affected the levels of cytokines, we examined the levels of IFN-γ and TNF-α in the lungs of mice in the virus-infected and mAb D7 groups.
cord-275621-wy48jhsb	2015	We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. ACS is currently defined as a new pulmonary infiltrate on chest X-ray consistent with alveolar consolidation but not atelectasis, in conjunction with at least one of the following clinical findings: fever (>38.5°C), reduced oxygen saturation or PaO 2 (<60 mmHg), tachypnea, intercostal retractions, nasal flaring or accessory muscle use, chest pain, cough, wheeze or rales [11, 12] . Abbreviations ACS: Acute chest syndrome; Hb: Hemoglobin; SCD: Sickle cell disease; SSA: Sub-Saharan Africa; VOC: Vaso-occlusive crisis. Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease Associated factors of acute chest syndrome in children with sickle cell disease in French Guiana Morphine is associated with acute chest syndrome in children hospitalized with sickle cell disease
cord-275635-d50bxe7c	2015	To explore the possibility of developing a vaccine against transmissible gastroenteritis virus (TGEV) infection, a recombinant swinepox virus (rSPV-SA) expressing a TGEV protective antigen has been constructed. Results from the passive immunity protection test of new born piglets demonstrated that the recombinant live-vector vaccine, rSPV-SA, could 100% protect piglets from the SPV infection, and there was no significant clinical symptom in the rSPV-SA treatment group during this experiment. Eight one-month-old swine (Large White) were randomly divided into four groups (2 pigs per group) and were immunized twice at 0 and 28 days with infectious rSPV-SA (1 × 10 8 PFU/ml in 2 ml of PBS), inactivated-TGEV (1 × 10 8 PFU/ml in 2 ml of PBS), wtSPV (1 × 10 8 PFU/ml in 2 ml of PBS) or PBS, each time via three routes: oral, nasal, and intraperitoneal. To explore whether mice or swine generated TGEV neutralizing antibodies, serum from the PBS, wtSPV, inactivated-TGEV and rSPV-SA treated mice and pig were collected at 0, 14, 21, 35, 42 days post-primary immunization (1:100-1:12,800 dilution in a 100 l volume).
cord-276850-tnlyk0wz	2015	
cord-276876-acr04xkz	2015	After transitioning the cat to a higher sodium diet and instituting several enrichment changes to the cat''s environment, average water consumption and urine output levels decreased to almost normal levels and USG increased from 1.006 to 1.022. 1, 2 Once PU/PD is confirmed to exist, the diagnostic approach should include a thorough history, physical examination and minimum database, including a complete blood count (CBC), serum chemistry profile, thyroxine (T4) concentration, urinalysis (UA) and urine culture to rule out more common causes of PU/PD such as diabetes mellitus, renal disease, hepatic insufficiency, hyperthyroidism and pyometra. Although these findings provide further evidence for the diagnosis of PP in this cat, we realize that without advanced imaging of intracranial structures and constant monitoring of plasma AVP levels to determine a threshold for release a distinction between dipsogenic diabetes insipidus and psychogenic polydipsia cannot be made in the case presented here.
cord-277337-ij0dn77h	2015	In healthcare facilities, an enhanced infection prevention and control (IPC) strategy against MERS has been implemented for case isolation, the management of hospitalized patients, and the monitoring of exposed healthcare personnel. Close contacts with confirmed or suspected cases are quarantined at home or at health facilities and monitored actively twice a day by phone call, checking for fever or any new symptoms for 14 days from the last-exposure date. Casual contacts with confirmed or suspected cases are monitored actively twice a day by telephone for fever or new-symptom development for 14 days from the last-contact date. The Ministry of Health and Welfare will make full efforts for the early identification of cases, the quarantine/isolation and monitoring of all contacts and suspected cases, the full implementation of IPC measures, and risk communication to the public and national and international partners [4] . Intensified public health measures help control MERS-CoV outbreak in the Republic of Korea
cord-277364-vy2yirek	2015	PCV2 is recognized as one of the most important viruses causing severe economic impact in the swine industry worldwide and it has been described to cause different conditions depending on the virus, host immunity, Veterinary Microbiology 176 (2015) Intestinal disorders in growing and finishing pigs have been associated with several infectious agents, including Porcine circovirus type 2 (PCV2). The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. Animal selection criteria included the following four features: (a) older than four weeks of age (nursery, growing and finishing pigs), (b) clinical digestive signs, (c) availability of intestinal and lymphoid tissues to assess histopathological lesions and to detect PCV2 DNA by in situ hybridization (ISH) and (d) presence of microscopic lesions in the intestine.
cord-277802-f8pyn3rx	2015	Aminomethylated derivatives of hydroxycarbazoles have been also mentioned in a different study [60] , which described the synthesis of a small series of phenolic Mannich bases 47 (Fig. 8 ) obtained from 5-substituted 2-hydroxy-5H-benzo[b]carbazole-6,11-diones along with their in vitro anticancer evaluation at National Cancer Institute (NCI) using an in-house developed screening panel of approximately 60 cell lines derived from nine different types of cancer. Recently, Mannich bases 132 ( Fig. 24 ) obtained using Schiff bases derived from 5-fluoroisatin and 4-arylideneaminoanilines as substrates and ciprofloxacin as amine reagent were shown to be generally less potent antibacterials than reference drug ciprofloxacin, although some candidates had MIC values comparable to those of ciprofloxacin against the investigated bacteria [164] . Both types of Mannich bases 133l and 134l, featuring a 1,2,4-triazole moiety at position 5 of the triazolethione scaffold, showed good antibacterial activity, but compounds 134l were generally more potent than 133l, and two of candidates 134l actually had MIC values comparable to those of reference drug ciprofloxacin [177] .
cord-278554-rg92gcc6	2015	To estimate the proportion of healthcare workers (HCWs) willing to work during an influenza pandemic and identify associated risk factors, we undertook a systematic review and meta-analysis compliant with PRISMA guidance. Meta-analyses of specific factors showed that male HCWs, physicians and nurses, full-time employment, perceived personal safety, awareness of pandemic risk and clinical knowledge of influenza pandemics, role-specific knowledge, pandemic response training, and confidence in personal skills were statistically significantly associated with increased willingness. Data extraction was performed by a single researcher (YA) using a piloted form collecting details of study characteristics {title, author, publication year, place, study period, study design, participants, subject [pandemic of avian influenza origin/influenza A(H1N1)pdm09/non-specified, hypothetical influenza pandemic]}; definition of outcome measures; questionnaire type; validation; statistical analysis and any stated limitations; percentage of willingness to work; and risk factors association with willingness.
cord-278833-wlhmcdcn	2015	FINDINGS: The hot start effect was investigated in a one-step real-time RT-PCR assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV). CONCLUSIONS: The study demonstrates the potential of aptamer-dependent hot start RT for the improvement of diagnostic real-time RT-PCR assays. In the present study, the aptamer was analyzed in a one-step real-time RT-PCR assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) to investigate the potential of a hot start RT for improved real-time RT-PCR performance. The one-step real-time RT-PCR was performed in a 25-μL reaction mix containing 10 μL of RNA template, 1x PCR reaction buffer (altona Diagnostics GmbH), 2.4 mM MgCl 2 (Sigma-Aldrich), 240 μg/μL BSA (Roche), 1 U of Platinum® Taq DNA Polymerase high fidelity (Invitrogen), 156 U of SuperScript® III Reverse Transcriptase (Invitrogen). The analytic sensitivity was determined by analyzing a half-logarithmic serial dilution Table 1 Hit rate of 25 μM aptamer and without aptamer in real-time RT-PCR MERS-CoV assay.
cord-279551-py2awuav	2015	title: Clinical and molecular investigation of a canine distemper outbreak and vector-borne infections in a group of rescue dogs imported from Hungary to Switzerland In the present study, we describe a distemper outbreak in 15 rescue dogs that were imported from Hungary to Switzerland by an animal welfare organisation. Canine distemper virus (CDV) is one of the most important viral pathogens in domestic dogs and causes high morbidity and mortality worldwide, particularly in unvaccinated dogs or dogs with incomplete vaccination [1] . The study provides data on vaccination, medical history, clinical examinations and diagnostic imaging of the dogs and CDV testing, testing for canine parvovirus (CPV) and vector-borne infections. The vaccine-specific real-time reverse transcription (RT)quantitative (q)PCR was negative for all ten dogs that were tested, which supports the finding of infection with a wild-type CDV strain.
cord-279638-jr1mbh7s	2015	Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Update on the mechanism of action and on clinical efficacy of extracorporeal photopheresis in the treatment of acute and chronic graft versus host disease in children Extracorporeal photopheresis (photochemotherapy) in the treatment of acute and chronic graft versus host disease: immunological mechanisms and the results from clinical studies Role of extracorporeal photopheresis (ECP) in treatment of steroid-refractory acute graft-versus-host disease Extracorporeal Photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: best practice recommendations from an Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and Italian Group for Bone Marrow Transplantation (GITMO) consensus process Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report Extracorporeal photochemotherapy in graft-versus-host disease: a longitudinal study on factors influencing the response and survival in pediatric patients
cord-280386-a8qr7nl6	2015	The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. To identify and prioritize targeted interventions to reduce the public health impact of foodborne diseases, public health policy makers and other stakeholders need aetiology-specific regional and global estimates of the incidence and mortality of diarrhoeal diseases caused by pathogens that are commonly transmitted through foods. While approach 1 analysed national incidence and mortality of disease by pathogens commonly transmitted through foods estimated primarily by correcting surveillance data to account for underreporting and under-diagnosis, approach 2 relied on systematic reviews of studies identifying causative agents in patients with diarrhoea.
cord-281061-uoszpnst	2015	A biotinylated anti-hemagglutinin antibody that bound a broad range of group 1 influenza A viruses and latex-conjugated α2,3 (blue) and α2,6 (red) sialylglycopolymers were used in an immunochromatographic strip test, with avidin and lectin immobilized on a nitrocellulose membrane at test and control lines, respectively. The strip test could detect the receptor binding specificity of a wide range of influenza viruses, as well as small increases in the binding affinity of variant H5N1 viruses to α2,6 sialylglycans at viral titers >128 hemagglutination units. In conclusion, the immunochromatographic strip test developed in this study should be useful for monitoring potential changes in the receptor binding specificity of group 1 influenza A viruses in the field. In this study, we developed a new easy-to-use immunochoromatographic strip test to detect the emergence of AI viruses with increased human-type receptor specificity and confirmed the applicability of this test using AI viruses isolated in several different geographic areas.
cord-281665-6n7aq4k9	2015	This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. This study describes the economic burden on patients with tuberculosis, identifies related factors by comparing two areas with different management models, and provides a policy recommendation for the tuberculosis control system in China. Significant factors related to the total out-of-pocket costs were study setting (t = -3.10, P = 0.002), age (t = -4.04, P < 0.001), number of clinical visits (t = 4.46, P < 0.001), residence (t = 3.19, P = 0.002), diagnosis delay (t = 3.47, P = 0.001), hospitalization (t = 15.04, P < 0.001), intake of liver protective drugs (t = 2.78, P = 0.006) and intake of second-line drugs (t = 2.87, P = 0.004) ( Table 5) .
cord-282151-mai4eggf	2015	METHODS: During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). 6 Many studies have been published on the clinical manifestations of A(H1N1) pneumonia during the acute phase of illness, [7] [8] [9] [10] [11] [12] [13] [14] [15] but no information has been reported on symptoms and radiographic and lung function changes in convalescence. Information recorded included demographic data, underlying medical conditions, symptoms, signs, laboratory and chest radiograph fi ndings before therapy and during follow-up, and the clinical course, treatment, and adverse events during hospital stay.
cord-282558-u977bqca	2015	Abstract The presence of antibodies to feline coronavirus (FCoV) and feline immunodeficiency virus (FIV), together with feline leukemia virus (FeLV) antigen was investigated in 169 ill household and stray cats attending a veterinary surgery in Istanbul in 2009–14. Symptoms typically associated with wet feline infectious peritonitis (FIP) including ascites, abdominal distention or pleural effusion, coupled in many cases with non-antibiotic responsive fever, were observed in 19% (32/169) of cats, and 75% (24/32) of these cats were FCoV seropositive. Worldwide the prevalence of FCoV infections may be up to 90% in multi-cat environments and 10-60% in household cats (Herrewegh et al., 1997; Pedersen et al., 2004; Bell et al., 2006; Addie et al., 2009; Sharif et al., 2009; Taharaguchi et al., 2012) . Several risk factors have been reported to be associated with FCoV infection and with FIP development, including age, breed, gender, multi-cat environment and stress (Bell et al., 2006; Pesteanu-Somogyi et al., 2006; Addie et al., 2009; Sharif et al., 2009; Worthing et al., 2012) .
cord-283641-2u16otbf	2015	For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient''s specimens or investigation of specific antibody response in serum specimens. Glossary EIA Enzyme immunoassays are methods used to estimate virus-specific IgG and IgM antibodies or virus antigens by enzyme-labeled conjugates. Nucleic acid testing has become the main approach for the demonstration of the presence of virus while cultivation is used by fewer specialized laboratories and antigen detection methods have moved to the point of care. Diagnostic applications of the measurement of the avidity of IgG antibodies against specific antigens have been developed to help distinguish serological responses due to acute infections from those of chronic or past infections. In immunofluorescence tests, cells from a clinical specimen are fixed on a glass slide and viral antigens present in the cells are detected by fluorescein-labeled virus-specific antibodies.
cord-285180-32bxx94u	2015	Time-course Western blot analysis revealed that the PK-PDCoV-N cells stably express and accumulate robust levels of a ∼45 kDa recombinant N protein, larger than its predicted molecular weight of approximately 38 kDa possibly due to post-translational modifications and the presence of C-terminal myc and histidine tags (Fig. 1C ). To identify the differentially expressed cellular protein spots in PK-PDCoV-N cells at different time points, 10 protein spots with a statistically significant alteration, including 8 up-regulated and 2 down-regulated protein spots (Fig. 4B) , were selected and manually excised from the stained gels. These proteins showing altered expression were associated with various cellular functions including intracellular transport, metabolic processes, gene regulation, the stress response, protein synthesis, cytoskeleton networks, and cell division. Coronavirus infection of cultured cells is known to cause ER stress and to induce the UPR, which then crosstalks with various cellular signaling pathways, including mitogen-activated protein kinase cascades, autophagy, apoptosis, and innate immune responses, indicating the involvement of UPR activation in virus-host interactions and viral pathogenesis .
cord-286228-0666mbr7	2015	5 In 1996, the CDC replaced the term ''universal precautions'' with ''standard precautions'', which aimed to prevent nosocomial infection in patients as well as HCWs, and concerned other micro-organisms as well as BBVs. 6 The CDC updated the definition of standard precautions in 2007 2 to include new elements of respiratory hygiene as a consequence of lessons learned in the outbreak of severe acute respiratory syndrome, and safe injection practices as a result of the multiple outbreaks involving BBVs and other organisms that occurred principally from the re-use of needles and contaminated multi-dose vials. 1 Standard infection control precautions published by Health Protection Scotland include both a policy and independent supplementary literature reviews to provide evidence for their required actions, similar to, but not overlapping with, the CDC model. 4 The epic3 account lacks some of the basics of the CDC''s standard precautions, but includes critical information on several high-infection-risk deviceassociated procedures.
cord-288701-nx9fg4yn	2015	The aim of the present study was to develop a multiplex real-time RT-PCR assay, based on the TaqMan technology, for the rapid and unambiguous characterisation of all bovine pestiviruses, including the emerging HoBi-like strains. Analysis of field samples tested positive for BVDV-1, BVDV-2 or HoBi-like virus by a nested PCR protocol revealed that the developed TaqMan assay had equal or higher sensitivity and was able to discriminate correctly the viral species in all tested samples, whereas a real-time RT-PCR assay previously developed for HoBi-like pestivirus detection showed cross-reactivity with few high-titre BVDV-2 samples. To overcome these limitations, we have developed a multiplex real-time RT-PCR assay for simultaneous detection of the different species of bovine pestiviruses, including the emerging HoBi-like group, allowing a rapid, sensitive and specific diagnosis of pestivirus infection and characterisation of the viral species.
cord-289690-af6lsj1g	2015	BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic celland B-lymphopenia, irrespective of severity of the clinical phenotype. Defects of transcription factor GATA-2 have recently been identified in a few overlapping phenotypes associated with myeloid malignancies: dendritic cell, monocyte, B-and NK-cell deficiency; MonoMAC syndrome (monocytopenia with Mycobacterium avium complex infections); Emberger syndrome (early onset primary lymphedema, multiple warts, sensorineural deafness, dysmorphism); and familial MDS/AML with no additional known phenotype. We present an adolescent male with GATA-2 deficiency and early manifestation of diffuse parenchymal lung disease (DPLD) as well as an atypical course of Epstein-Barr virus (EBV) infection.
cord-291961-usl8z6ep	2015	METHODS: The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. CONCLUSIONS: The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR. Previous studies have indicated that a number of HPyVs are associated with human diseases, such as progressive multifocal leukoencephalopathy (JCPyV), hemorrhagic cystitis (BKPyV), Merkel cell carcinoma (MCPyV), and trichodysplasia spinulosa (TSPyV) [3, 7, 9, [17] [18] [19] . Because initial infections with most HPyVs occur in infancy, the prevalence of HPyV6 in NPAs from children was detected with real-time PCR. The detection rate for HPyV6 by real-time PCR assay was 1.7 % in 887 NPA samples collected from hospitalized children with RTI.
cord-292092-o6s5nw49	2015	title: Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015 The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. 5 The laboratory diagnosis of MERS-CoV infection is mainly performed using real-time reverse transcription PCR (RT-PCR) to detect viral RNA in specimens. This study was performed to analyze recent viral genomic nucleic acid sequences and to discuss the efficacy of the RT-PCR protocols for the molecular diagnosis of MERS-CoV infections. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission Table 1 Conservation of the primer and probe region sequences of the WHO-recommended assays for the molecular diagnosis of MERS-CoV
cord-292853-xihpfidg	2015	A social-ecological framework is used to differentiate the impact of exposure to traumatic stressors and the development of (or resistance to) PTSD, based on the individual''s or group''s (i) personal, unique physical characteristics, including skin color, racial background, gender, and sexual orientation; and (ii) family, ethnocultural, and community membership, including majority or minority group status, religious beliefs and practices, socioeconomic resources, and political and civic affiliations. Depending on Social, cultural, and other diversity issues in the traumatic stress field 505 their cultural background and its traditions and beliefs, individuals may also have "multiple vulnerability status"-that is, to be members of more than one group or to have characteristic that cause them to be even more susceptible to discrimination or victimization (i.e., adolescent black male in the United States; a baby born with physical or developmental disabilities in a culture that endorses selective resources to the ablebodied; a gay man or lesbian woman of color in a highly homophobic and racist society).
cord-292963-8wzyfb2j	2015	Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). CONCLUSION: The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The clinical, radiological and pathological data of 19 cases with severe pneumonia caused by human infected avian influenza (H7N9) from December 18, 2013 to April 18, 2014 in Shenzhen Third People''s Hospital, China, were collected. Onset from middle lobe and lower lobe of lungs, the lesions in the cases of human infected avian influenza A (H7N9) are mainly displayed as ground-glass opacities and lung consolidation, which change rapidly and are absorbed slowly, too [2, 6, 11] , with a mortality rate of about 36%. Generally, severe pneumonia caused by human infected avian influenza A (H7N9) is demonstrated with ground-glass opacities and lung consolidation by chest CT scan.
cord-293857-o8rlqsq5	2015	Also, we will outline successful designs of organic carbamates, including a variety of cyclic ether-derived carbamates, as suitable amide bond surrogates leading to a wide range of novel organic carbamates as potent HIV-1 protease, βsecretase, serine protease, and cysteine protease inhibitors. 172−174 A number of FDA-approved HIV protease inhibitor drugs contain an important carbamate functionality. 179, 230 Further development of carbamate-derived novel HIV-1 protease inhibitors is shown in Figure 12 . This backbone binding strategy to combat drug resistance led to the development of a series of very potent carbamate-derived protease inhibitors. Carbamate derivative 281 (Figure 24 ), a diphenyl phosphonate ester containing a Cbz group and bearing a single amino acid side chain, showed very good inhibitory activity against human plasma kallikrein, useful for the treatment of hereditary angioedema. Design and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity studies and biological evaluation
cord-294945-hcf7gsv8	2015	The objectives of this study were to identify the proteins that were differentially regulated and the physiological changes that occurred during different time periods in ''H41'', ''H69'', and ''H71'' when responding to treatments of flooding, 40 °C, and both stresses combined. By the comparative proteomic analysis, 85 protein peaks that were differentially expressed in response to combination treatments at 0, 6, and 24 h, 69 (33 in ''H41'', 29 in ''H69'', and 9 in ''H71'') were identified, of which were cultivar specific. Compared to NFC treatment at 0 h, NFH treatment for 6 h showed that the abundances of peaks 271 (phosphoserine aminotransferase), 272 (imidazole glycerol phosphate synthase subunit hisF), Table 6 Identification of differentially expressed proteins found in cauliflower ''H71'' plants by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in comparison to combination treatments for 0 and 6 h.
cord-295187-konm26x5	2015	However, two distinct features were observed in the CCoV-I genome: (i) the presence of an additional ORF between the spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is more closely related to that of feline coronavirus type I and presents a furin cleavage site. Canine coronavirus (CCoV) is usually responsible for mild enteritis in young dogs Buonavoglia, 2008, 2011) , although fatal disease has been associated to a pantropic variant of the virus (Decaro et al., , 2010a Marinaro et al., 2010; Zicola et al., 2012; Ntafis et al., 2012) . Alignment of complete genome sequences of CCoV-I strain 23/03 and reference alphacoronaviruses showed the closest genetic relatedness with CCoV-IIa isolates (83.82-84.98% nt identity), followed by TGEV (82.81%) and . Molecular characterization of a canine coronavirus NA/09 strain detected in a dog''s organs
cord-296028-hqrd1e8p	2015	Ultimately, the purpose of summarizing and critiquing some of the arguments within the GOF/PPP debate is to emphasize the many epistemic and ethical value judgments inherent to RBA and to provide evidence for prior claims that a consensus-building quantitative assessment is unlikely (1). As summarized here, many of the disagreements within the GOF/PPP debate involve epistemic and ethical value judgments that suggest that definitive quantitative risk-benefit analysis is not possible. Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion mBio addresses the pause in gain-offunction (GOF) experiments involving pathogens with pandemic potential (PPP) Conducting risk and benefit analysis on gain-of-function research involving pathogens with pandemic potential An epistemological perspective on the value of gain-of-function experiments involving pathogens with pandemic potential Vagueness and costs of the pause on gain-of-function (GOF) experiments on pathogens with pandemic potential, including influenza virus
cord-296129-rkadl46r	2015	Finally, a distributed food supply network supported with diverse agricultural products can increase resilience by providing access to diversified markets for producers and improved food access to consumers with more food choices, while expanding the need for skilled jobs supporting the regionally based food industry. As the two models below, North Carolina Central Piedmont Network and the South Carolina Food Hub demonstrate, decentralized models that link producers to consumers provide opportunities for farmers that utilize high-yield, low input techniques such as biointensive and other agroecological techniques a convenient and reasonable access to markets. Using biological and agricultural diversity to expand locally based, sustainable farming systems, foster new farmers and food entrepreneurs, and build distributed aggregation, processing and marketing networks that focus on triple bottom line benefits-environmental, social, and economic-have the potential to strengthen our food security and our communities, providing resilience to both acute and long-term stress.
cord-296326-8oes5g6k	2015	30 Here we report the use of MWCNT/Tyr for the improved synthesis of lipophilic hydroxytyrosol and dihydrocaffeoyl catechols, and their antiviral activity against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), Coxsackie virus type B3 (Cox B3), Adenovirus type 2 and type 5, and Cytomegalovirus (CMV). The activity of native Tyr (81.2 U/mg) was determined by the dopachrome assay following the oxidation of L-tyrosine at 475 nm (the enzyme unit is defined as the increase in absorbance of 10 À3 unit/min at 25°C in 0.1 M phosphate buffer, pH 7.0). In particular, compound 3b was added at different times on VERO cells infected with 0.1 MOI of HSV-1, to determine the inhibition of the virus yield during specific periods in the virus life-cycle.
cord-297045-6snl1jfx	2015	title: Use and Interpretation of a Rapid Respiratory Syncytial Virus Antigen Detection Test Among Infants Hospitalized in a Neonatal Intensive Care Unit — Wisconsin, March 2015 On March 25, 2015, the Wisconsin Division of Public Health was notified of a possible respiratory syncytial virus (RSV) infection outbreak among infants hospitalized in a neonatal intensive care unit (NICU). On March 25, 2015, the Wisconsin Division of Public Health was notified of a possible respiratory syncytial virus (RSV) infection outbreak among infants hospitalized in a neonatal intensive care unit (NICU). A nasopharyngeal swab specimen collected from neonate A was tested using a single-manufacturer rapid RSV antigen detection test (RRADT) at the hospital laboratory; the result was positive. A nasopharyngeal swab specimen collected from neonate A was tested using a single-manufacturer rapid RSV antigen detection test (RRADT) at the hospital laboratory; the result was positive.
cord-297257-lzybfwc2	2015	The quest for clinical candidates to counteract immune activation has become a "hot topic" in AIDS research, because HIV infection is characterized by malignant immune hyperactivation which correlates with disease progression and poor response to antiretroviral therapy (ART) [1] [2] [3] [4] [5] . We here provide a state of the art of the studies investigating the use of chloroquine/hydroxychloroquine as a therapeutic tool for HIV/AIDS and suggest the possible biological grounds for the clinical results obtained. This view is supported by another recent study which shows that chloroquine sensitizes to apoptosis the latently infected cells upon viral reactivation, likely by removing the anti-apoptotic effect of the virus structural gag gene products [50] . Published clinical studies evaluating the effects of chloroquine/hydroxychloroquine administration, alone or in combination with other drugs, in HIV infected subjects.
cord-297290-jglk8f8d	2015	title: Clinical features of human metapneumovirus genotypes in children with acute lower respiratory tract infection in Changsha, China Reverse transcription polymerase chain reaction (RT‐PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 2613 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to February 2011 (a period of 3.5 years). To further explore the epidemiological and clinical features of various genotypes of hMPV, we summarized the data on the hMPV positive patients hospitalized for acute lower respiratory tract infections in Hunan Province over a period of 3.5 years (Sep. 2007 -Feb. 2011 ) The present study revealed that the hMPV positive rate was 5.2%, in hospitalized children with acute lower respiratory tract infections in Hunan Province, that was similar to Beijing [Zhu et al., 2011; Lu et al., 2013] , higher than Southern China (2.6%) [Cai et al., 2014] , and lower than Chongqing (10.2%) [Zhang et al., 2012] and Taiwan (23%) [Wei et al., 2013] .
cord-297325-fbilhauu	2015	Nevertheless, despite sustained demyelination and CNS inflammation, the SR T cell response declined during viral persistence, suggesting that chronic JHMV infection establishes an environment which supports ongoing clinical improvement and regulates autoimmune responses. This is supported by activation of JHMV-specific T cells within the CLN [34] and detection of myelin antigens in MS patients and rodents with experimental autoimmune encephalomyelitis (EAE) [35] [36] [37] , as well as following demyelination induced by oligodendrocyte death [38] . To determine whether CNSinfiltrating myeloid cells, comprising macrophages and dendritic cells, and/or microglia are capable of processing and presenting self-Ag within the CNS following infection, both potential APC populations were purified based on differential CD45 expression [44, 45] at distinct times p.i. and tested for the ability to support SR T cell activation in the absence of exogenously added Ag. Infiltrating myeloid cells at day 7 p.i.
cord-297326-n0fpu8s3	2015	Here, we develop a model that explains the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in Hong Kong in 2003. These equations involve three stocks (SUSCEPTIBLE, LATENT, INFECTED), three auxiliary variables (prevalence, contagion rate, recovery rate) and three parameters (incubation period, case fatality, disease duration). The simulation output for the variable ''sick per day'' fit the data reported by the Hong Kong authorities (Fig. 4a) , suggesting that the model was able to reproduce the epidemic curve. These results are consistent with a previous report showing the basic reproductive numbers for different SARS epidemic curves, which supports the notion that our model is able to largely replicate the disease outbreak in Hong Kong [31] . Under these conditions, the model output fits the epidemic curve observed in the Hong Kong SARS-CoV outbreak (Fig. 4) .
cord-297682-knd6avhu	2015	As a result, infection control practices, including strict hand hygiene, viral testing of patient samples, and use of isolation precautions, quarantine rooms, and personal protective equipment, were mandated for routine use with all patients who sought treatment at emergency departments (EDs) with respiratory symptoms and fever (7, 8) . First, we aimed to determine the association between the use of viral testing and subsequent hospital resource utilization (antibiotic/antiviral drugs prescribed; radiology studies conducted; cultures and bronchoscopies performed), including the duration of isolation precautions. Table 2 describes likelihood of deaths, ICU admission, length of stay, and use of isolation precautions in the study cohort and among hospitalizations in which the patient had a positive or negative NP swab sample. In this study, viral testing of respiratory samples during hospitalization was not associated with a significant reduction in odds of patient deaths or length of hospital stay after adjustment for critical clinical confounding factors.
cord-298503-l60cdllh	2015	Newly synthesized proteins and lipids leave the endoplasmic reticulum (ER) at specialized transitional regions called ER exit sites (ERES) (Jamieson and Palade, 1967; Sesso et al., 1994; Bannykh et al., 1996; Hammond and Glick, 2000; Tang et al., 2005) and enter the intermediate compartment (IC) that has been shown to operate as an obligatory a post-ER sorting station in the early biosynthetic-secretory trafficking of mammalian cells. Electron microscopic (EM) studies using a temperature-sensitive mutant of Semliki Forest virus (SFV ts-1) to synchronize the transport of viral membrane glycoproteins from ER to the plasma membrane (PM) showed that when the cells are shifted from 39 1C to 15 1C the proteins exit the ER, but accumulate in vacuoles/saccules (up to 0.5 mm in diameter), tubules, and vesicles in the cis-Golgi region and more peripheral locations (Saraste and Kuismanen, 1984) . ERGIC-53, a membrane protein of the endoplasmic reticulum-Golgi intermediate compartment, is identical to MR60, an intracellular mannose-specific lectin of myelomonocytic cells
cord-298922-k568hlf4	2015	Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection. In our current study, we used a quantitative proteomics approach based on an iTRAQ tandem mass spectrometry (MS/MS) technique to identify proteins differentially expressed between PEDV-infected and mock-infected Vero E6 cells. To verify the differential expression of the selected DEPs, equivalent volumes of the cell lysate replicates from the PEDV-infected (V1-V3) and mock-infected (C1-C3) Vero E6 cells were pooled into the V and C samples, respectively, and western blotting was performed as described above, with the following exceptions: a 1:1000 dilution of the polyclonal antibodies anti-␤ tubulin, anti-integrin-␤3, anti-cystatin-C, anti-protein S100-A2, anti-apolipoprotein E4, and anti-centrin from rabbit (Beijing Biosynthesis Biotechnology, Beijing, China) was used as the primary antibody, and a 1:5000 dilution of the HRP-conjugated goat anti-rabbit IgG (Sigma-Aldrich, St. Louis, USA) was used as the secondary antibody.
cord-299352-9pcb2enl	2015	• Strategies to consider include development of a more precise system to risk stratify geographic settings susceptible to disease outbreaks, reconsideration of the 2005 International Health Regulations Criteria to allow for earlier responses to localized epidemics before they reach epidemic proportions, increasing the flexibility of the World Health Organization director general to characterize epidemics with more granularity, development of guidelines for best practices to promote partnership with local stakeholders and identify locally acceptable response strategies, and, most importantly, making good on international commitments to establish a fund for public health emergency preparedness and response. An International Health Systems fund, through a sustained investment by global partners, would provide much needed preparedness in future cases of outbreaks in LMICs, where local resources are not capable of controlling epidemics [22] .
cord-299549-bjqwwzam	2015	When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host''s immune system to recover. In most patients, Ebola viral burden elevates by time and triggers an extremely strong immune attack-a phenomenon called ''cytokine storm'' (Sullivan et al., 2003) , during which monocytes and/or macrophages produce a massive amount of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukins (ILs), and The virus burden, inflammatory response, and specific antibodies are the main contributors to different outcomes: mortality, survival, or symptomless infection (Fig. 2) , suggesting that the appropriate intervention strategy in each stage would accordingly be able to control the Ebola virus. Nonetheless, this phenomenon does give clues to the treatment against Ebola virus disease (EVD)-early activated innate immune responses may prevent the viral infection.
cord-299790-vciposnk	2015	Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. For instance, one study showed that 15.3% of ambulatory patients with influenza-like illness had two viruses detected, 6 and another found that in 28.2% of children with community-acquired pneumonia, the illness was due to mixed viral-bacterial infections. 7 Others also previously described respiratory viral 8, 9 and bacterial co-infections 10, 11 in various settings, although most focus on specific pathogen combinations, especially of the synergism between influenza and Streptococcus pneumoniae (S. Mean proportion for dual infections with nasal symptoms lay in between at 0.748, statistically different from both viral (P = 0.002) and bacterial (P < 0.001) mono-pathogen levels.
cord-300123-fzijbney	2015	RESULTS: We collected 337 rectal swabs from 307 diarrheic foals in the Hidaka district of Hokkaido, the largest thoroughbred horse breeding region in Japan, between 2012 and 2014. [10] reported that approximately 30 % of healthy and diarrheic thoroughbred foals in central Kentucky in the United States were infected with ECoV, using a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Therefore, we investigated ECoV using molecular diagnostic methods on rectal swabs collected from thoroughbred foals in the Hidaka district Open Access *Correspondence: nemoto_manabu@equinst.go.jp 1 Epizootic Research Center, Equine Research Institute, Japan Racing Association, 1400-4 Shiba, Shimotsuke, Tochigi 329-0412, Japan Full list of author information is available at the end of the article of Hokkaido, which is the largest thoroughbred horse breeding region in Japan. Compared with central Kentucky, ECoV is not prevalent among thoroughbred foals in Hidaka district of Hokkaido, but some outbreaks have occurred in draft racehorses.
cord-300808-fgdyzzty	2015	In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. Plasma from adults (n = 557) living in a malaria-endemic region in Kilifi, Kenya, were initially tested in pools of five (Fig. 1b) and then individually for their capacity to agglutinate mixtures of erythrocytes infected with three culture-adapted Kenyan parasite isolates, each stained with a different DNA dye. The binding of the LAIR-1-containing antibodies to specific RIFINs was confirmed by the finding that MGD21 stained CHO cells transfected with the candidate antigens (PF3D7_1400600 and PF3D7_1040300), but not with irrelevant RIFINs that were similarly expressed (PF3D7_0100400 and PF3D7_0100200) or not detected (PF3D7_1100500) in 3D7-MGD21 + and 3D7-MGD21ghosts (Fig. 4c ).
cord-301064-ex6qb6zj	2015	Although genetic diversity is an essential part of virus biology, classical approaches to virus control often ignore evolutionary processes and focus on understanding in great detail the molecular bases of pathogenesis, virus-host interaction, and drug-virus interference. Although many studies appear in evolutionary biology journals, particularly those on viral experimental evolution, mathematical modeling, molecular evolution, and phylogenetics, a large proportion are submitted to journals that focus on virology and pathogenesis. We have established the journal Virus Evolution with this aim in mind, and we hope that it will grow into a successful and dynamic inter-disciplinary community of researchers interested in understanding why and how viruses have and continue to evolve. The Board has expertise in animal, plant, and bacterial viruses and in a wide range of techniques, including experimental evolutionary biology, molecular epidemiology, metagenomics, structural biology, population genetics, ecology, and molecular virology.
cord-301563-s0ypy2hf	2015	For example, human immunodeficiency virus 1 (HIV-1) prevents antiviral interferon response via Vpr-and Vif-directed, ubiquitin-mediated proteosomal degradation of interferon regulatory factor 3 (IRF-3) (Okumura et al., 2008) ; the papain-like protease (PLpro) domains of many coronaviruses, such as severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), and mouse hepatitis virus A59 (MHV-A59), have deubiquitinating (DUB) activity that blocks type I interferons (IFNs) induction (Barretto et al., 2005; Chen et al., 2007b; Clementz et al., 2010; Devaraj et al., 2007; Frieman et al., 2009; Lindner et al., 2005; Zheng et al., 2008) ; the leader proteinase (L pro ) of Foot-and-mouth virus (FMDV) acts as a deubiquitinase that cleaves ubiquitin chains from retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor associated factor 6 (TRAF6), and TRAF3, thereby inhibiting the activation of type I IFN signaling ; the N-terminal protease (Npro) of bovine viral diarrhea virus interacts with IRF-3 and promotes its polyubiquitination and subsequent degradation through the proteasome (Chen et al., 2007a) ; the latency associated protein ORF73 of murid herpesvirus-4 (MuHV-4) associates with the host ubiquitin-ligase complex to promote poly-ubiquitination and subsequent proteasomal degradation of p65/RelA, which inhibits the activity of nuclear factor B (NF-B) to facilitate the establishment of MuHV-4 latency (Rodrigues et al., 2009) .
cord-302268-dmb0293x	2015	Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Vaccines made from live-attenuated or inactivated pathogens can elicit robust protective immune responses because those vaccines contain naturally occurring adjuvants. A benefit of using AS04 adjuvant in human vaccines is the effective induction of robust Th1-type immune responses by promoting IL-2 and IFN-γ production, which cannot be achieved by using alum alone. Thus, flagellin fusion proteins are suitable adjuvants for the development of vaccines to induce robust antigen-specific immune responses. Main benefits of these adjuvants are induction of high and long-lasting antibody titer, induction of balanced Th1 and Th2 type immunity, and induction of CMI including cytotoxic T cell response (42) .
cord-302543-ipaoge55	2015	In this chapter we analyze the binding and dissociation kinetics (if applicable) of (1) IFN-gamma as a function of aptamer variants and inclusion of spacer in addition to spacer (Tuleuova et al., 2010) , (2) GST-N protein in PBS and GST-N protein in 10-fold diluted serum to an LPSCF fiber-optic biosensor (Huang et al., 2009) , (3) cytochrome c mutant to a superoxide biosensor (Wegerich et al., 2009) , (4) CA-II to an ABS ligand on an SPR biosensor surface (Williams et al., 2009 ), (5) glycerol secretion from differentiated (murine 3T3-L1) adipocytes to a microfluidic platform for fluorescence-based assay (Clark et al., 2010) , and (6) different concentrations of CRP in solution to a sandwich-type assay using a label-free detection method, reflectometric interference spectroscopy (Albrecht et al., 2010) .
cord-302836-wy36ac6y	2015	Our study revealed that the spectrum and production of ten compounds, under investigation, were higher in organized tissue than the undifferentiated mass, however, aerial portions of the in vitro raised plants (leaf and stem) were found to be devoid of therapeutically relevant triterpenoid, glycyrrhizin. Here we are reporting the simultaneous assessment of ten compounds-eight flavonoids (butin, quercetin, isoliquiritigenin, formononetin, glabridin, 4 0 -O-methylglabridine, hispaglabridin A and hispaglabridin B) and two terpenoids (glycyrrhizin and 18a-glycyrritinic acid) in the licorice root and in vitro raised callus, organ culture and plantlets of G. As most of the terpenoids and flavonoids were found in the licorice roots, the role of basal media composition and PGR effect on root tissue differentiation and secondary metabolite production was investigated in in vitro raised cultures of G.
cord-303055-rttaoiwt	2015	Full-scale experiments and CFD simulations were performed to study potential inter-cubicle airborne transmissions through a shared anteroom due to the hinged door opening. When the dirty cubicle door remains fully open, temperature difference and concentration gradient across the doorway induce the two-way buoyancy-driven flow and transport of airborne agents across the doorway. The longer the dirty cubicle door remains fully open (10 s, 30 s or 60 s) or the smaller the air change rate (34–8.5 ACH for each cubicle), the more airborne pathogens are being transported into the ''clean'' cubicle and the longer time it takes to remove them after the door is closed. Small-scale experiments and theoretical models [7, 8] confirmed that the opening and closing motion of hinged doors can induce transient airflows and turbulence close to the doorway, followed by air exchange and the transport of airborne particles into the anteroom through the doorway.
cord-303189-ktl4jw8v	2015	Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. In these cells, the HCV-induced miR-21 has been recently reported to be involved in evasion of IFN-I production and stimulation of HCV replication, upon suppression of MyD88 and IRAK1 expression, that is required for the TLR7-mediated sensing of the virus [100] . Amongst RNA viruses that, as HCV, can establish a persistent infection, HIV-1, a lentivirus from the Retroviridae family, represents a paradigm for its ability to prevent or circumvent the innate immune response mediated by IFN-I. Overall, viruses as HCV and HIV-1 have evolved nifty strategies to dampen the host innate response in cells where a productive infection may take place, while they induce infection-independent mechanisms in non-permissive cells to facilitate the viral life cycle and promote a chronic inflammation.
cord-303884-ogu3f3o5	2015	Antiviral agents targeting the entry of enveloped viruses are of major interest since they inhibit an early step in the viral life cycle which minimizes the cell damage caused by intracellular viral replication. Small interfering RNA (siRNA) sequences targeting CHIKV nsP3 and E1 genes were reported to signifi cantly reduce CHIKV titers at 24 h post-infection in transfected Vero cells [ 14 ] . In a highthroughput screening for CHIKV nsP2 inhibitors that target the nsP2-mediated transcriptional shut off, a natural compound derivative (ID1452-2) was shown to partially block the nsP2 activity resulting in inhibition of CHIKV replication in cell culture [ 29 ] . When designing/developing antivirals against the Chikungunya virus it may be important to develop classes of compounds that have pan-alphavirus activity and that could thus also be used for the treatment of alphaviruses other than CHIKV. Inhibition of Chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression
cord-303935-qdehf6rb	2015	title: Changes in Clinical Presentation and Epidemiology of Respiratory Pathogens Associated With Acute Respiratory Illness in Military Trainees After Reintroduction of Adenovirus Vaccine The Center for Advanced Molecular Detection at Joint Base San Antonio-Lackland prospectively collects demographic, clinical, and polymerase chain reaction data from respiratory specimens (throat swab and nasal wash) among Air Force trainees presenting for care of ARI. Acute respiratory illness in military trainees post-VI is associated with decreased severity of systemic symptoms and reduced fever and heart rate. The purpose of this study was to evaluate (1) changes in clinical presentations of ARI pre-and post-VI, and (2) reductions in proportions of disease due to Ad. We also sought to further evaluate for evidence of nonvaccine type serotype shift and to determine whether the frequencies of common non-Ad respiratory pathogens have changed after VI, in trainees presenting for care of ARI, which have not previously been described in the published literature.
cord-304251-dohglrm1	2015	Thus recent decades have seen a most dramatic change with the emergence globally also of new viral infections – notably human immunodeficiency viruses (HIV) – and the appearance of some other dangerous and sometimes lethal infections formerly seen mainly in, and reported from, resource‐poor areas especially in parts of Asia, Latin America and Africa. Gradually, however, the unexpected consequences of some oral viral infections have emerged and been recognised, not without some surprise (Scully, 1983) especially the oncogenicity of some herpesviruses (Eglin et al, 1983) and human papillomaviruses (HPVs) which we (Eglin et al, 1983; Maitland et al, 1987; Cox et al, 1993 ) and many others (e.g. Lind et al, 1986) have explored, culminating in the appreciation of unanticipated transmission routes for some cancers, such as sexual (Scully, 2002) . The recent several decades have also seen a most dramatic change with the emergence globally of new viral infectionsnotably human immunodeficiency viruses (HIV)and the appearance also in resource-rich countries, of some other dangerous and sometimes lethal infections hitherto latent, unrecognised or unappreciated in resource-poor areas.
cord-304585-dfh3b9ln	2015	The purpose of the study is to investigate the relationships of recreancy, perceived risk of infection, and political partisanship in the public''s vaccine hesitancy during the H1N1 epidemic of 2009-2010. They are recreancy theory, which emphasizes the role of institutional trust at both the national and local level in health behavior decision-making; the health belief model, which brings together both the rational process of decision-making in health agency and the affective elements of things such as fear and worry; and the political partisanship perspective, which argues that all health care matters are inherently political, become differentially embedded in the philosophies of political parties, and form the responses of party members to specific matters. Our second hypothesis is that those individuals who trust in the ability of local hospitals and health agencies to deal with the H1N1 outbreak were more likely to be willing to be vaccinated than those lacking such trust.
cord-309359-85xiqz2w	2015	Continuous emergence of multiple mutant strains from several regions has aggravated porcine epidemic diarrhea endemic conditions and highlighted the need for new vaccines based on the current circulating PEDV. Genetic variabil ity and phylogeny of current Chinese porcine epidemic diarrhea virus strains based on spike, ORF3, and mem brane genes Molecular characteriza tion and phylogenetic analysis of membrane protein genes of porcine epidemic diarrhea virus isolates in China Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States Molecular epidemiology and phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) field isolates in Korea Cell culture isolation and sequence analysis of genetically diverse US porcine epi demic diarrhea virus strains including a novel strain with a large deletion in the spike gene Genetic characterization of porcine epidemic diarrhea vi rus (PEDV) isolates from southern Vietnam during 2009 2010 outbreaks
cord-310110-haukpwtf	2015	title: Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro Our findings suggest that MBL, the host innate molecule, has differential interference effects with human and avian influenza virus and limited antiviral effect against H7N9 virus. Different concentrations of rhMBL were diluted in HBSS containing Ca 2þ and mixed with influenza virus in a total volume of 100 mL and preincubated at 37 C for 1 h, and then transferred to wells precoated with fetuin (Sigma, USA) and incubated at 37 C for 4 h, After washing, 100 mL of HRP-labeled peanut lectin (3 mg/mL) was added and after 1 h at room temperature, the wells were washed and o-phenylenediamine dihydrochloride in citrate buffer was added, reaction was stopped by 2 M H 2 SO 4 , and the OD at 492 nm was measured. Therefore, the strong MBL-H7N9 virus interaction whereas limited effects on viral HA-receptor binding or NA-mediated releasing, might amplify immune dysfunctions in vivo and confer clinical severity of H7N9 infection via activating complement pathway and further investigates are needed. Human mannan-binding lectin inhibits the infection of influenza A virus without complement
cord-310268-8q4tk6fd	2015	Nucleic acid aptamers are RNA and single-stranded (ss) DNA oligonucleotides with lengths typically ranging from 15 to 70 mers, which have the same level of target-binding affinity as monoclonal antibodies (the dissociation constant (K d ) usually ranges from 0.1 to 50 nM) [5, 6] . This SELEX is able to generate DNA aptamers that recognize the cell-surface or intracellular target protein in their native conformation, which shows great potential in cell-specific therapeutics and diagnostic applications [26] [27] [28] . Recently, modified cell-SELEX methods have been developed to select aptamers targeting specific cells like disease state cells and metastatic cells. In the era of personalized medicine, DNA aptamer-based therapeutics and diagnostics are believed to have great potential for extensive application because of their flexibility to specifically bind to any molecule targets.
cord-311293-do7m1090	2015	In this study, we investigated the effects of supplementing sows'' gestation and lactation feed with 15% oat (prebiotic source) on the levels of probiotic population in milk. Furthermore bifidobacteria within the sow milk samples were further evaluated for probiotic potential based on aggregating properties, and acidand bile-tolerance after exposure to hydrochloric acid (pH 2.5) and bile salts (0%, 0.25%, 0.50%, 1.0% and 2.0%). Together our results suggest that inclusion of oat in feeding systems could have the potential to improve the intestinal health of piglets by increasing the population of bifidobacteria. Each bacterial isolate was inoculated (1%, v/v) in MRS broth supplemented with different concentrations of antibiotics (ampicillin at 3 and 4 mg/L, chloramphenicol at 4 and 6 mg/L, erythromycin at 1 and 2 mg/L, and gentamicin at 65 and 66 mg/L) and growth was examined after 24 h incubation at 37 °C using a 96-well microplate reader. In this study, we isolated potential probiotic bifidobacteria from sow milk.
cord-312307-0hqqheho	2015	Specimens positive for enteroviruses were further confirmed using standard molecular approaches that involved amplification and sequencing of the human enterovirus VP4/VP2 gene using primers described previously. Based on previously described EV-D68 classification, 11 the newly sequenced strains from Malaysia were found within clade A (MY-Cluster-1) and clade B (MY-Cluster-2). Phylogenetic analysis of the P1 region indicated that 91.7% (11/12) of the Malaysian EV-D68 formed clusters, suggesting the transient EV-D68 outbreaks were most likely caused by at least two viral lineages ( Figure 1) . Such observation suggests an ongoing ''''clade shift'''' or lineage replacement of circulating EV-D68 in causing new outbreak, as observed in other enterovirus-associated outbreaks. Our data suggest that the recent EV-D68 strains associated with unprecedented severe respiratory outbreaks in the USA in 2014 were probably descended from the recent EV-D68 lineages circulating in Thailand and Malaysia. Seven strains of enterovirus D68 detected in the United States during the 2014 severe respiratory disease outbreak
cord-313737-cob5hf5q	2015	1 The conference opened with Professor Tawfik Khoja outlining the challenges to infection prevention and control in the Middle East. Among the challenges he covered were public reporting and external scrutiny, hand hygiene, antibiotic resistance, the healthcare environment, surveillance and outbreaks, an increasingly elderly population, new threats [such as Ebola and Middle East respiratory syndrome coronavirus (MERS-CoV)], meticillinresistant Staphylococcus aureus (MRSA), C. Dr Phin highlighted a useful CDC toolkit providing advice on respiratory protection for healthcare workers, and also a recent BMJ review concluding that facemasks may help to prevent the spread of respiratory viruses in the community. As to which interventions we should use for each organism, this depends on organism and setting, although screening, isolation, stewardship, hand hygiene, and cleaning/ disinfection are the pillars of infection control. Dr Muhammad Halwani then gave an overview of infection control in the Middle East, focusing on acinetobacter and pseudomonas.
cord-315234-pqn7qhm8	2015	title: An Unexpected Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in the Republic of Korea, 2015 This report includes a summary of a current outbreak of the Middle East Respiratory Syndrome Coronavirus infection in the Republic of Korea as of June 23, 2015. Between May and June 2015, there was an outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection with a considerable number of cases in the Republic of Korea. As of June 23, a cluster of 38 persons including 4 healthcare workers with confirmed MERS-CoV are known to have had direct or indirect contact with the index patient. By June 23, 81 persons with confirmed MERS-CoV are known to have had direct or indirect contact with patient 14. However, there still is no sound evidence of community transmission; the MERS-CoV infection in the Republic of Korea is healthcare-associated, accelerated by inter-hospital spread. Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV)
cord-315304-pge45105	2015	Viral infection is associated with both direct (invasive disease) and indirect (immune modulation) effects affecting susceptibility to other infections and promoting allograft rejection. The risk for viral infection is a function of the intensity of exposure and virulence of the specific virus, the intensity of immune suppression used to prevent graft rejection or graft-versus-host disease, underlying immune deficits, and factors affecting host susceptibility. Multiple factors contribute to viral reactivation after transplantation, including graft rejection and therapy, immune suppression (especially reduction of T-cell mediated, cytotoxic immunity), inflammation, and tissue injury. The clinical presentation of CMV (HHV-5) can range from a ''CMV syndrome'' including fever, malaise, leukopenia, to a ''flu-like'' illness with myalgias and fatigue, to a more significant end-organ disease with pneumonitis, colitis, encephalitis, hepatitis, or chorioretinitis. The treatment of viral infections in the renal transplantation recipient includes: the reduction of immunosuppression, antiviral therapy, diagnosis and treatment of co-infections (such as CMV, EBV, HHV-6, or À7), and use of adjunctive therapies such as immunoglobulins or colony stimulating factors.
cord-315339-dcui85lw	2015	Although neutralizing antibodies directed against the HA globular head are highly efficient at preventing and clearing influenza virus infection, they can also FIGURE 3 In the memory phase, migratory lung DCs capture viral antigen retained on follicular DCs (FDCs) in tertiary lymphoid organs and present it to specific T cells in the respiratory draining lymph nodes. This explains why passively transferred IgG is effective at preventing severe disease from respiratory infections in experimental animals and why serum IgG antibodies are the main correlate of protection for parentally administered inactivated influenza vaccines in humans (Section Respiratory Virus Vaccines). Nasal administration of influenza vaccine with type I IFN was effective at inducing serum antigen-specific IgG2a and mucosal IgA antibody responses and at providing full protection against influenza virus challenge (Proietti et al., 2002) .
cord-316245-n6tmn4ph	2015	METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV) by multiplex real-time PCR. Multiplex real-time PCR was performed using Roche, Lightcycler 480 II (Roche Diagnostics, Penzberg, Germany) to identify the following 14 respiratory viruses: influenza A (FluA), influenza B (FluB), respiratory syncytial viruses A and B (RSV), human coronaviruses 229E, OC43, HKU1 and NL63 (hCoV), human metapneumoviruses A and B (hMPV), human parainfluenza virus types 1, 2 , 3, and 4 (PIV1, PIV2, PIV3, and PIV4), human rhinoviruses A, B, and C (HRV), human enteroviruses (EV), human adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV).
cord-316434-mz4y5am2	2015	In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. Co-administration with vectors encoding papillomavirus L1 or L2 significantly enhances the antigen-specific CD8 + T cell immune responses generated by CRT/E7 or OVA DNA vaccination In order to characterize the antigen-specific CD8 + T cell immune responses generated by vaccination with CRT/ E7 or OVA DNA in combination with vectors containing codon-optimized BPV1 L1 or L2 DNA, C57BL/6 mice (five per group) were vaccinated intradermally via gene gun with CRT/E7 or OVA DNA with or without BPV1 L1 or L2 DNA twice at 1-week intervals.
cord-316676-4fxvzj01	2015	In 2007, HUGO Pan-Asia SNP Consortium (PASNP 1.0) was set up with 93 researchers from 40 institutions in 11 Asian countries to map human genetic diversity in Asia. Despite the achievements that Asian countries and consortiums have made, they still face formidable challenges in terms of funding, regulation, collaboration, and the ethical, legal, and social issues (ELSI) of genomics in Asia. As we show in the next section, the development of human genomics in Asia faces not only similar issues as do other national and transnational endeavors, such as funding, standardization of data and samples, harmonization of ELSI practices and regulations, and gaining public trust, but also some Asia-specific issues and local concerns in the practice of Asian science and collaboration. Building regional collaborative genomics networks, such as ACC and PASNP 1.0 and 2.0, is the first and vital step toward better science, medicine, and health in Asia.
cord-316719-uej7d5zf	2015	In der aufsuchenden Virusdiagnostik nutzt man dazu eine Reihe von Zelllinien in der Hoffnung, dass sich wenigstens eine davon für die Vermehrung des noch unbekannten Virus als geeignet erweist. Nach ihrer ersten Beschreibung in den 1970er-Jahren sind Mitglieder des Genus Hantavirus zunächst in Asien und Europa als Erreger zoonotischer Erkrankungen identifiziert worden. Mit der so entstandenen "Pan-Hanta-PCR" wurden 2006 die ersten afrikanischen Proben getestet und zwei neuartige, natürlich vorkommende Hantaviren im westafrikanischen Guinea gefunden [7, 8] . Zurzeit wird darüber diskutiert, ob Hantaviren, die als nicht von Insekten übertragene Viren eine Ausnahme innerhalb der Familie der Bunyaviren bilden, im Laufe ihrer Evolution einen Wirtswechsel von Insekten in insektenfressende Fledermäuse vollzogen haben [12] . Das PCR-gestützte Auffinden der verschiedenen Viren in den natürlichen Reservoiren ist wiederum die Voraussetzung dafür, ihre Rolle als mögliche Krankheitserreger des Menschen zu untersuchen.
cord-317061-0bx704ao	2015	The nsp5 of the newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as 3CLpro and its canonical cleavage sites (between nsps) were predicted based on sequence alignment, but the cleavability of these cleavage sites remains to be experimentally confirmed and putative non-canonical cleavage sites (inside one nsp) within the pp1a/1ab awaits further analysis. Some cleavage sites have been identified and confirmed by previous studies, including three cleavage sites of PLpros of human coronavirus 229E (HCoV 229E), mouse hepatitis virus (MHV), SARS-CoV, MERS-CoV and infectious bronchitis virus (IBV), whose cleavages release the first 3 non-structural proteins (Bonilla et al., 1995; Kilianski et al., 2013; Lim and Liu, 1998; Ziebuhr et al., 2007) . In order to set up a more moderate and balanced criteria for protease cleavage site identification, we compared six scanning conditions with different stringency to systematically predict the 3CLpro cleavage sites on pp1a/1ab of five coronaviruses including MERS-CoV. To rapidly evaluate the proteolysis activity of MERS-CoV 3CLpro toward the predicted cleavage sites of different substrates, a sensitive luciferase-based biosensor assay was adopted.
cord-317347-by8albr9	2015	The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. Therefore, the ability of SPF chickens of different age to induce an IBV-specific antibody response and protect against challenge with an IBV field strain was measured. In order to measure IgG (IgY), IgA and IgM antibody levels in plasma and tears of chicken, an IBV-specific enzyme-linked immunosorbent assay (ELISA) was developed as previously described [20] . These data are consistent with a delay in the IgA plasma response to IBV in birds vaccinated at a younger age and a non-significant decline in mean IgA titers in the 1-day-old group. This would be consistent with a drop of presumably natural maternal IBV-specific IgM antibodies in these SPF chickens in the day 7 control age group.
cord-318448-3bkp1mtj	2015	title: An Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in South Korea, 2015 Between May and July 2015, there was an unexpected outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in South Korea. Several super-spreading events, which happened within hospitals from patients 1, 14, 16, and 76, contributed to 80% of all subsequent cases. This large and complex outbreak, which arose in crowded hospitals within metropolitan cities, exposed several problems with the Korean healthcare system, including emergency preparedness and response systems by the government, as well as infection prevention and control measures in hospitals. An Unexpected Outbreak of Middle East Respiratory Syndrome Coronavirus Infection in the Republic of Korea Middle East respiratory syndrome coronavirus (MERS-CoV)-Republic of Korea WHO recommends continuation of strong disease control measures to bring MERS-CoV outbreak in Republic of Korea to an end: for News Release
cord-319746-6bccxgbd	2015	title: Production and Characterization of Human Monoclonal Antibodies from the Cells of A(H1N1)pdm2009 Influenza Virus Infected Indian Donors Abstract Analysis of human monoclonal antibodies (mAbs) developed from influenza infected donors have enormously contributed to the identification of neutralization sensitive epitopes of influenza virus. In this study, we generated strongly neutralizing novel human monoclonal antibodies that were selected from the immune repertoire of influenza infected seropositive patients. Monoclonal antibody 2D8 showed the maximum binding in the in vitro assays and neutralized the human isolate of the pandemic strain as well as the reference strain at lowest concentrations when compared to the 2F12 antibody. The antibodies however, showed comparative neutralization and HAI activity between the laboratory isolates of the pandemic virus and the reference strain A/Cal/07/2009(H1N1). To, the best of our knowledge, these antibodies are the first fully human monoclonal antibodies generated from the immune repertoire of Indian patients infected with A(H1N1)pdm09 virus.
cord-319999-cpdpsg3i	2015	Testing for 23S rRNA mutations conferring macrolide resistance was performed on original specimens by real-time PCR melt curve analysis (6) and confirmed by DNA sequencing at the Lurie Children''s Hospital (Chicago). We found a 23S rRNA point mutation A2063G known to confer macrolide resistance in 10 (10.9%) of 91 specimens by direct real-time PCR with melting curve analysis. Our finding of high-level macrolide resistance in 13.2% of specimens from all 6 centers throughout a broad geographic area in the United States proves this problem has emerged in all regions of the nation and might increase over time, as it has in other countries. Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis Detection of macrolide resistance in Mycoplasma pneumoniae by real-time PCR and high-resolution melt analysis Investigations of Mycoplasma pneumoniae infections in the United States: trends in molecular typing and macrolide resistance from 2006 to 2013
cord-320806-vzqof0nj	2015	3 However, there is relatively little data on other factors (e.g. detection of bacteria with viruses) associated with LOS in hospital in an at-risk population (e.g., Indigenous children who have more severe bronchiolitis) 4 and future bronchiectasis. In the absence of any data from Indigenous children, we combined data from three prospective studies that included 232 Indigenous infants hospitalized with a clinical diagnosis of bronchiolitis, to examine factors (clinical and microbiological) on admission that were associated with (i) prolonged LOS (Aim-1); (ii) presence of persistent symptoms 3 weeks after hospital discharge (Aim-2); (iii) whether presence of cough at 3 weeks was associated with bronchiectasis up to $24 months posthospitalisation (Aim-3); and (iv) re-hospitalization within 6 months for a respiratory illness (Aim-4). In the first prospective study of Indigenous infants hospitalized with bronchiolitis with post-hospitalization data at 3 weeks and 6 months, we found that the severity score on admission, particularly accessory muscle use, was the sole factor associated with prolonged LOS once other factors (clinical and microbiological) were accounted for.
cord-320851-zhf8jdcl	2015	title: Phosphonooxymethyl Prodrug of Triptolide: Synthesis, Physicochemical Characterization, and Efficacy in Human Colon Adenocarcinoma and Ovarian Cancer Xenografts In a mouse model of human colon adenocarcinoma (HT-29), the prodrug administered intraperitoneally was effective in reducing or eliminating xenograft tumors at dose levels as low as 0.3 mg/kg when given daily and at 0.9 mg/kg when given less frequently. A nontoxic, water-soluble, chemically stable, and patentable prodrug approach would be a viable option to overcome some of the physicochemical limitations of triptolide for the clinical development of this natural product. Therefore, the prerequisites for a novel prodrug strategy of triptolide were three-fold: enhanced aqueous solubility, chemical stability, and fast, complete bioconversion in vivo. 46−49 We are now describing an improved synthesis for 4, its physicochemical characterization, and its pharmacodynamic evaluation in human colon adenocarcinoma and ovarian cancer xenografts via intraperitoneal and oral routes and using less frequent dosing schedules than employed in previous studies.
cord-321131-f8qeytxc	2015	Abstract In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. Cell culture studies demonstrated that endosomal cysteine proteases, in particular cathepsin B (CTSB) and/or L (CTSL), can activate the glycoproteins of filoviruses, SARS-CoV, other coronaviruses, and NiV and Hendra (HeV) viruses to facilitate entry into certain cell lines. The notion that coronaviruses, including SARS-CoV, use both a cathepsin-dependent endosomal pathway and a direct cell-surface serine protease-mediated pathway for entry (Simmons et al., 2013) is supported by our finding that the combination of K11777 and camostat was superior to either compound alone.
cord-321393-ffulkqrf	2015	Since 2008, all patients undergo a dedicated pulmonary screening consisting of pulmonary function test (PFT), chest high-resolution computed tomography (HRCT), and bronchial alveolar lavage (BAL) before HCT. Pre-HCT screening with the combination of 3 modalities, reflecting different domains of respiratory status (function, structure, and microbial colonization), reveals important abnormalities in a substantial number of patients. In 2008, we implemented extensive pre-HCT lung screening, which includes pulmonary function test (PFT), chest high-resolution computed tomography (HRCT), and bronchial alveolar lavage (BAL) in all patients. Patient characteristics (age, gender, underlying disease), clinical symptoms, results of pulmonary screening tests, and occurrence of symptomatic lung disease after HCT was registered. Standard pre-HCT pulmonary screening is performed in the week before transplantation and consists of a PFT, HRCT scan, and BAL. Our study in 142 pediatric patients shows that pulmonary screening before HCT with PFT, HRCT, and BAL is feasible.
cord-321762-7kiahjyy	2015	We presented our scheme at the First Indo-US Workshop on Mathematical Chemistry in Shantiniketan, West Bengal, India in 1998 [10] where we reported, as stated in the abstract, that "Geometrisation of macromolecular sequences in the form of a graphical representation provides one … technique where the nucleotides in a gene sequence can be viewed as objects in a 4-dimensional space; the method can be extended, in principle, to include, say proteins, in a 20-dimensional space. This review is a brief introduction to the readers of this new and exciting field of research on graphical representation and numerical characterization (GRANCH) of bio-molecular sequences, based on the talk I presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia, in July 2010 [13] .
cord-321992-lk2ao6m8	2015	In the present study, we investigated the innate immune responses such as cytokine and NK cell activity as well as changes in frequencies of T cells to examine if differences coincide with the higher disease severity of suckling versus weaned pigs. The infected weaned pigs also had significantly higher NK cell frequencies in blood and ileum at PID 5 (P < 0.05) compared to infected suckling pigs ( Fig. 2A and B) . In infected suckling and weaned groups, peak IFN␣, IL-12 and TNF␣ levels coincided with onset of diarrhea and fecal PEDV RNA shedding and peak serum PEDV RNA titers (PIDs 1 and 3, respectively); and (4) Frequencies of CD3+CD4+ T cells were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in frequency of CD3+CD8+ T cells.
cord-322827-h33su548	2015	BACKGROUND: In 2005, China implemented a demonstration program known as "686" to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. This program has contributed to improving care for patients with severe mental disorders, including schizophrenia, psychosis, bipolar disorder and schizoaffective disorder, through increasing access to treatment and integrating hospital and community services designed to provide continuity of evidence-based care and to address patients'' rights. Patients with severe mental disorders were followed-up about their medication adherence, mental health status, social functioning and family burden in 2009 and 2012 to investigate the changes over time following the unlocking efforts. The finding that more than 92% of those unlocked and entered into continuous treatment by the 686 Program remained free of restraints by 2012 demonstrates the feasibility of improving the human rights of persons with severe mental illness by increasing access to mental health care in the community [22] , even with limited societal resources.
cord-325120-jlrievxl	2015	title: Diagnostics-in-a-Suitcase: Development of a portable and rapid assay for the detection of the emerging avian influenza A (H7N9) virus STUDY DESIGN: A suitcase laboratory "Diagnostics-in-a-Suitcase" (56 cm × 45.5 cm × 26.5 cm) containing all reagents and devices necessary for performing a reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed. Several real-time RT-PCRs were developed for sensitive detection of avian influenza (H7N9) virus [15, 16, 19] . Development of real time RT-PCR assays for detection of type A influenza virus and for subtyping of avian H5 and H7 hemagglutinin subtypes Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step real-time RT-PCR assay Development of a reverse transcription loop-mediated isothermal amplification assay for the rapid diagnosis of avian influenza A (H7N9) virus infection Rapid and sensitive detection of H7N9 avian influenza virus by use of reverse transcription-loop-mediated isothermal amplification
cord-325148-oe3yv69y	2015	Greater attention must be paid to animal and environmental biosecurity to prevent introduction of diseases into the herd and to digestive disorders such as diarrhea, internal parasites and appropriate vaccination programs for the calves. Continual video monitoring of the herd, modern thermal infrared imaging of the dry cows and calves body parts to identify early symptoms, and overall animal health and biosecurity risk analysis could achieve a sustainable and efficient replacement management practice in cattle industry. Focusing on improving health management of replacements will yield tremendous returns through decreased losses of animals with the greatest genetic potential on the dairy, decreased costs of medication, improved growth rates, improved feed efficiency and earlier entry into the milking herd. Focusing on improving health management of replacements will yield tremendous returns through decreased losses of animals with the greatest genetic potential on the dairy, decreased costs of medication, improved growth rates, improved feed efficiency and earlier entry into the milking herd.
cord-325555-be78qely	2015	We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. The results suggest that the constant overexpression of BiP in the JEV persistently infected cells somehow holds back CHOP expression, resulting in the prevention of virus-induced apoptosis. In conclusion, BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, a key chaperone involved in ER stress.
cord-326799-bb27iydc	2015	title: Promoting public health legal preparedness for emergencies: review of current trends and their relevance in light of the Ebola crisis OBJECTIVE: This paper examines recent trends regarding public health legal preparedness for emergencies and discusses its role in the recent Ebola outbreak. Amid LMICs, it mostly refers to application of international regulations, whereas in developed states, it focuses on independent legislation and creation of conditions optimal to promoting an effective emergency management. Among developed countries, the United States'' utilisation of health legal preparedness is the most advanced, including the creation of a model comprising four elements: law, competencies, information, and coordination. Review of application of PHLP during the current Ebola crisis Keywords used to extract relevant articles were Ebola, public health, legal preparedness, and emergency. In certain countries, such as the United States, laws regarding infectious diseases provide the legal framework for health system operations in routine situations as well as during emergencies (81) .
cord-326908-l9wrrapv	2015	We test the power of this approach using simulated data and find that the method is sensitive to bias in the estimates of branch lengths, which tends to occur when using underparameterized clock models. 2001) ; uncorrelated beta-distributed rate variation among lineages; misleading node-age priors (i.e., node calibrations that differ considerably from the true node ages); and when data were generated under a strict clock but analyzed with an underparameterized substitution model ( fig. The substitution model was identified as inadequate for the coronavirus data set by the multinomial test statistic estimated using posterior predictive data sets from a clock analysis (P < 0.05); however, it was identified as adequate when using a clock-free method (P = 0.20). In addition, our metric of uncertainty in posterior predictive branch lengths is sensitive to some cases of misspecification of clock models and node-age priors, but not to substitution model misspecification, as shown for our analyses of the coronavirus data set.
cord-326960-9phlylce	2015	This combination of features and product approvals has previously attracted interest from academic researchers, and more recently from industry leaders, to utilize BEVS to develop next generation vaccines, vectors for gene therapy, and other biopharmaceutical complex proteins. expresSF+ cells are used to manufacture three licensed products: Flublok ® influenza vaccine (Protein Sciences Corporation), Glybera ® gene therapy for the treatment of familial lipoprotein lipase deficiency (uniQure), and Ingelvac CircoFLEX ® veterinary vaccine to protect against porcine circovirus type 2 (Boehringer Ingelheim Vetmedica). Recombinant AAV-based gene therapies have been in development and shown promise for some time; however, a major limitation to their implementation had been the inability to scale up the manufacturing process to produce sufficient quantities of rAAVs. The original rAAV vectors were produced in mammalian tissue culture using adherent cells such as HEK293 cells, which required about 5000 175-cm 2 flasks to produce enough material for a large animal study or human clinical trial (~10 15 rAAV particles) [55] .
cord-328501-mbwgi56x	2015	title: Risk factors for febrile respiratory illness and mono-viral infections in a semi-closed military environment: a case-control study CONCLUSION: Increasing age, smoker, recruit-camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military environment. Previous documented risk factors of FRI in other countries included body mass index equal or greater than 25 kg/m 2 , previous respiratory tract infections [30] , overcrowding and closed units [29, [31] [32] [33] , presence of sand and dust storms, extreme temperature changes [34, 35] , smoking [36] , female, Navy service, poor latrine facilities, increasing age and higher rank [37] . Increasing age, smokers, recruit camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military setting. Outbreak of febrile respiratory illness associated with adenovirus 11a infection in a Singapore military training cAMP
cord-329857-pcsuu597	2015	The binding affinity of antibodies to viruses can directly impact the efficacy of mAbs [4] , suggesting that target-specific mechanisms likely account for much of the efficacy of therapeutic mAbs. However, many studies have also highlighted the contribution of Fc-mediated immune effector functions in modulating the efficacy of these mAbs [5] . FcgRs have been shown to be important in modulating the efficacy of therapeutic mAbs [5] due to their involvement in FcgRmediated phagocytosis, cytokine production, ADCC and complement-dependent cytotoxicity (CDC) that aids in virus neutralization (FIGURE 1). Given the importance of FcgRs in mediating virus neutralization and Fc effector functions, a better understanding of how therapeutic antibodies neutralize virus infections in FcgRbearing cells will impact implementation of dosing regiments and allow development of improved therapeutic antibodies against infectious diseases. Given the importance of Fc-FcgR interaction in antibodymediated effector functions, Fc modification could lead to the development of therapeutic antibodies with improved interaction to activating FcgRs. This could enhance FcgR-mediated uptake, cytokine production, antigen presentation, ADCC and CDC.
cord-330218-l5q3n3ri	2015	Neutralization of viruses by antibodies is predicted to depend on high-affinity binding to specific epitopes of surface-exposed viral proteins that are required for binding to target cell receptors (4) . These effector functions are induced upon binding of antibody-virus immune complexes to classical Fc c receptors (FccRs) expressed on the surface of hematopoietic cells such as natural killer (NK) cells, macrophages, and dendritic cells, which results in clearance and induction of T-cell responses (8) . Low antibody-virus stoichiometry may also result in inefficient FccR-mediated effector functions by immune cells as efficient phagocytosis requires the formation of immune complexes and cross-binding to cell-surface FccRs. In addition, as TRIM21 also engages IgM and IgA, it is likely to contribute to early protection, and at the gate of entry of most viral pathogens, the mucosal barrier.
cord-330318-2v2exya7	2015	title: The effectiveness of a shared conference experience in improving undergraduate medical and nursing students'' attitudes towards inter-professional education in an Asian country: a before and after study METHODS: This study evaluated the effectiveness of the 9th SMEC 2013 as a shared conference experience in improving the attitudes of undergraduate medical and nursing students in Singapore towards inter-professional education (IPE). Results obtained for all 3 RIPLS subscales showed overall significant improvements in scores, indicating that the 9 th SMEC 2013 was effective in improving the attitudes of Singaporean healthcare students towards IPE. As the 9 th SMEC 2013 was one of the few healthcare conferences that are organised for students, by students, the results of this study suggest that student-run initiatives can be highly effective in improving attitudes towards IPE. Our study found that participation in a student-led jointly-organised conference event was effective in improving medical and nursing students'' improve attitudes towards IPE.
cord-330502-exmk6gmu	2015	title: A nurse-delivered brief health education intervention to improve pneumococcal vaccination rate among older patients with chronic diseases: A cluster randomized controlled trial Objective The aim of this study was to determine if an additional multi-component health education intervention increases the uptake rate of the pneumococcal vaccination among older patients with chronic diseases. Discussion: A nurse-delivered brief health education intervention was effective in increasing uptake of pneumococcal vaccination among older patients with chronic diseases. Discussion: A nurse-delivered brief health education intervention was effective in increasing uptake of pneumococcal vaccination among older patients with chronic diseases. This large cluster randomized controlled trial, therefore, was conducted to test the effectiveness of a nursedelivered multiple component health education intervention on the uptake rate of PPV and awareness of PPV at 3month follow up among older patients with chronic diseases in Hong Kong.
cord-330647-w1bpeqzg	2015	The largest outbreak of Ebola virus disease (EVD) in history has renewed interest in filoviruses and has provided an unprecedented impetus to the development of new therapeutics and vaccines for this highly lethal infection. Nucleic acid amplification is the diagnostic test of choice because of its high sensitivity (especially in the early phase of illness); its ability to differentiate between different agents of viral hemorrhagic fever; and its relatively lower biohazard, if the viruses are appropriately inactivated; and because antigen and antibody assays are often unavailable in laboratories in nonendemic countries. 119e123 Animal studies also demonstrate the efficacy of favipiravir in the treatment of Junín virus, arenavirus, and EBOV hemorrhagic fevers, and the drug was used to treat human EVD in the 2014 West African epidemic.
cord-331237-t3z1hbox	2015	helvum samples and previously reported sequences, revealed that 12 of the fragments grouped with Leptospira borgpetersenii and Leptospira kirschneri; however, the remaining 58 flaB fragments appeared not to be associated with any reported species. Additionally, the 16S ribosomal RNA gene (rrs) amplified from 27 randomly chosen flaB-positive samples was compared with previously reported sequences, including bat-derived Leptospira spp. A nested PCR based on the flagellin B gene (flaB) sequence was used to amplify the extracted DNA samples (n = 529) to detect the flaB gene of pathogenic Leptospira spp. Six flaB fragments (ZFB08-62, ZFB09-25, ZFB09-32, ZFB12-05, ZFB12-107 and ZFB12-110) in the FC5 cluster were related to the corresponding gene sequences, all of which were identical to Leptospira borgpetersenii strains including Jules, De 10, Arborea, Poi, and Veldrat Batavia 46. The phylogenetic analyses of flaB and rrs infer that genes from potentially pathogenic Leptospira spp.
cord-331361-pd9lt4n2	2015	Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Strikingly, heparin was also active when applied after contact with the virus, and both pretreatment and posttreatment with heparin were effective in inhibiting human PBL-mediated trans-infection of either NiV or HeV (Fig. 2B ). Heparin treatment modestly, but significantly, reduced the percentage of infected cells from both cell lines, indicating that this molecule may also directly inhibit or delay the binding of NiV to its entry receptors EFN-B2 and -B3. Nipah virus (isolate UMMC1; Gen-Bank accession number AY029767) (42), recombinant NiV expressing enhanced green fluorescent protein (45) , and Hendra virus (Australia/ horse/1994) obtained from Porton Down Laboratory, United Kingdom, were prepared on Vero-E6 cells as described previously (46) , and infection virus was used in the INSERM Jean Mérieux BSL4 laboratory in Lyon, France.
cord-331932-oujdl459	2015	The user‐friendly assay detected and differentiated between four viruses [porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus, porcine circovirus type 2, porcine respiratory corona virus], four bacteria (Mycoplasma hyopneumoniae, Pasteurella multocida, Salmonella enterica serovar Choleraesuis, Streptococcus suis), and further differentiated between type 1 and type 2 PRRSV as well as toxigenic and non‐toxigenic P. Here, a microarray assay with associated multiplex RT-PCRs for detection and differentiation of four viruses and four bacteria involved in PRDC using a novel user-friendly electronic microarray in which capture probe printing, hybridization, washing and reporting are fully integrated and automated is described. Similarly, representative whole-genome sequences, as well as full and partial sequences of homologous genes from related and unrelated non-targets such as TGEV, porcine circovirus type 1 (PCV1), as well as other Salmonella enterica serovars, and Mycoplasma species were downloaded for in silico analysis of probe specificity. The analytical specificity of the viral and bacterial multiplex PCR assays was assessed by amplifying panels of 14 non-target viruses and 21 bacteria, respectively (Table 3) .
cord-332003-67e9fchy	2015	Although challenged later on as detailed in Section 7, this mechanism and the possibility to use such so called cell-penetrating peptides (CPPs) as non-viral delivery vectors for biomolecules, fostered a very large interest. Since the chemical conjugation and purification of negatively charged ONs with the most popular cationic CPPs has turned out to be difficult, most applications have concerned chargeneutral ON analogues such as Peptide Nucleic Acids (PNAs) and PMO (see Section 3). Unexpectedly, in a well-characterized HeLa 705 cell assay with a positive read-out ( Fig. 1) , splicing redirection using PNA or PMO oligomers conjugated to various standard CPPs (Tat, Penetratin or oligo-arginines) was not achieved in our research groups [57] . This led to the development of several arginine-rich peptides as PMO conjugates for use in muscle cells and in vivo mouse models of DMD as outlined in Section 4.
cord-332055-lrpfzsog	2015	National and world organizations define asthma "by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation." 12 The reversibility of airflow obstruction is the hallmark distinguishing asthma from other obstructive respiratory disorders. In contrast, chronic obstructive pulmonary disease (COPD)/ emphysema is defined as "persistent airflow limitation that is usually progressive and associated with enhanced chronic inflammatory responses in the airways and the lungs." 12 These patients also frequently wheeze, but may have a different course of acute and chronic disease. Rapid evaluation by lung-cardiac inferior vena cava (LCI) integrated ultrasound for differentiating heart failure from pulmonary disease as the cause of acute dyspnea in the emergency setting Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes
cord-332075-gxmae2rs	2015	title: Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds. To evaluate whether this genotype VII isolate could be used as a vaccine vector for geese we generated a recombinant virus rmNA-VP3 expressing VP3 protein of GPV after modifying the polybasic F cleavage site of NA-1 to the dibasic motif of LaSota.
cord-332317-wrztpeb8	2015	Nucleocapsid (N) protein of transmissible gastroenteritis virus (TGEV) packages viral RNA genome to form a ribonucleoprotein complex. The present study thus provides protein-related information about interaction of TGEV N protein with host cell that should be useful for understanding host cell response to coronavirus pathogenesis infection and the underlying mechanism of coronavirus replication. Recently, some reports showed that N protein of TGEV play an important role in host cell for virus replication. Three cellular proteins, hnRNP U, ACTN4, and vimentin, were identified both by GST-N pull down and Co-IP in TGEV-infected cells, which should have more biological importance in the context of infection. The interaction between the cellular vimentin and N protein of TGEV was confirmed in TGEV-infected ST cells. Host cell proteins interacting with the 3 end of TGEV coronavirus genome influence virus replication EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication
cord-333351-homxj9uz	2015	Plus d''une soixantaine de virus a été isolée ou détectée chez des chauves-souris qui, selon différentes modalités, se trouvent ainsi impliquées dans la circulation de beaucoup d''entre eux ; c''est le cas, notamment, de Rhabdoviridae du genre Lyssavirus, de Paramyxoviridae comme les virus Nipah et Hendra, de Filoviridae (virus Ebola et Marburg) ou de Coronaviridae comme les agents du syndrome respiratoire aigu sévère (SRAS) et du syndrome respiratoire du Moyen-Orient (MERS). Cependant, même si les contacts entre les Hommes et les chauves-souris sont faibles, la rareté des infections humaines par des Lyssavirus n''appartenant pas au génotype 1 n''est pas clairement expliquée car certains au moins de ces virus sont très largement répandus depuis longtemps ; sans doute leur véritable pathogénicité pour l''Homme est-elle faible (l''observation de cas non mortels et de sujets en bonne santé apparente porteurs d''anticorps semble en témoigner), mais les déterminants de cette pathogénicité demeurent inconnus.
cord-333535-pzjj2wxc	2015	Despite the limited number of enteric diseases in adult cattle that would benefit from antimicrobial therapy, surveys indicate that diarrhea is a relatively common reason for the use of antibiotics. If Salmonella are the main target of antimicrobial therapy in adult cattle with diarrhea, drug selection should ideally be based on the results of susceptibility testing using bacterial strains recovered from that particular dairy or feedlot. Despite this importance, the United States Department of Agriculture Dairy 2007 study shows a preweaned Antimicrobial Decision Making heifer calf mortality rate of 8.7% and reports that only 40% of farms can supply an adequate number of replacements from their own herd. The investigators concluded that amoxicillin had a significant effect on disease by decreasing mortality and number of scouring days; however, treatment success could not be predicted by whether the E coli cultured from rectal swabs was susceptible or resistant to the antimicrobial being used.
cord-335567-ssnvr6nj	2015	In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. In recent years six new human respiratory viruses have been reported including human metapneumovirus (hMPV) [16] , bocavirus and four new human coronaviruses including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), HCoV-HKU1 and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients
cord-336663-fawcn6em	2015	Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. However, because most clinical laboratories do not type the isolates, there is little published information about epidemiologic and clinical features of HAdV infections by type in children with ALRTIs. To identify HAdV types and species in children with ALRTIs in Beijing area and to characterize clinical features and laboratory findings of hospitalized HAdVinfected cases, respiratory specimens were collected from hospital-admitted pediatric patients with ALRTIs and typed HAdV positive samples using PCR and sequencing. This may also suggest that schoolage children are exposed to the most common endemic types of HAdV early in life, thereby establishing a protective immunity resulting only in mild clinical symptoms, such that upper respiratory tract infection does not require care in an emergency department or hospital in this age group.
cord-336727-pvo7hs1x	2015	2, 3 Following missteps in management of the first locally diagnosed case in Dallas, which led to loss of trust in health officials, 3, 4 several state governors initiated quarantines of even symptom-free international aid workers returning from Ebola relief efforts, 5 and there were several high-profile news reports of institutions asking students and employees with spurious connections to the disease to stay home . The U.S. experience with the Ebola epidemic is reminiscent of prior outbreaks, such as avian flu and severe acute respiratory syndrome (SARS), in which public and health professional reactions were poorly matched to communicated risks, 6 ,11 yet factors contributing to these disconnects are not Electronic supplementary material The online version of this article (doi: 10 .1007/s11606-015-3493-1) contains supplementary material, which is available to authorized users. Our primary outcome was level of management intensity, which was defined a priori by responses to two of the clinical vignettes (eSurvey 3-4) evaluating knowledge of transmission methods and incubation period in patients with low likelihood of contagious Ebola virus disease.
cord-337707-xbwilp1w	2015	title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. Based on a bootscan analysis of the complete genome of the 3 HCoV-OC43s belonging to the circulating genotypes B, C, and D, it was assumed that a hot spot was likely located between the nsp12 and S genes, more precisely at the nsp12/nsp13 junction. This study focuses on the sequences of the nsp12, S, and N genes of 15 HCoV-OC43s detected in respiratory specimens sampled from 2001 to 2013. In this study, all HCoV-OC43s including the VR759 prototype strain are associated with three accession numbers in GenBank, for nsp12, S, and N genes ( Table 1 ).
cord-338041-gl65i3s0	2015	Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Based on the data matrix of nucleotide composition, the MD and SVM were applied to predict hosts of coronaviruses. The data matrix with 19 factors as columns and 730 samples as rows was fitted to SVM and MD models, all predictions in leave-one-out cross-validations were listed in Supplementary Table S2 and summarized in Table 1 according to host species. Cross-host evolution research of SARS-CoV in palm civet and humans indicated that the variations in spike genes seemed to be essential for the transition of coronavirus from animal-to-human transmission to human-to-human transmission 25 . The MD correctly predicts bats as the natural hosts of the three viruses, and the SVM indicates that Rs3367 and SL-CoV-WIV1 are harmful to humans.
cord-339386-sxyeuiw1	2015	The virus was quickly identified as a new CoV most closely related to several bat CoVs. 6 This report was followed by a number of other reports identifying a total of 537 infected individuals, all of whom had acute respiratory symptoms, severe in most, and fatal in 145 (as of May 11, 2014) . 6 Between then and May 2014, a total of 537 cases occurred, all infected by this virus, now termed the Middle East respiratory syndrome coronavirus (MERS-CoV). In response to the global spread and associated severe disease, the World Health Organization coordinated a rapid and effective control program that included isolation of cases, careful attention to contact, droplet and airborne infection control procedures, quarantine of exposed persons in some settings, and efforts to control spread between countries through travel advisories and travel alerts.
cord-340905-8nyew5i5	2015	The objective of the present study was to elucidate the relationship between the genotypes and geographic distribution of TCoV isolates from turkey farms in multiple states in the United States by using sequence analysis and comparing the full-length S gene. Three genetic groups, referred to as groups I, II, and III, were observed in North American TCoV isolates ( Fig. 2A) Because of the high degree of variation, most phylogenetic groupings based on the S1a deduced amino acid sequences did not have a bootstrap value over 50 % (Fig. 2B) . Nevertheless, the Texas TCoV isolates of group II and all three TCoV isolates of group III shown in the phylogenetic tree based on the full-length S nucleotide sequences still clustered according to their S1a amino acid sequences containing their HVR. In the present study, similar to previous findings with IBV strains, most of the variations in the S protein sequences among TCoV isolates were observed in the amino-terminal half.
cord-341434-2xrdv92m	2015	Etiology Pasteurella multocida is a Gram-negative nonmotile coccobacillus that causes pasteurellosis, also known as ''snuffles'', the primary respiratory disease affecting domestic rabbits (Deeb and DiGiacomo, 2000; Guo et al., 2012) . Research Complications Pasteurellosis can cause considerable economic losses (El Tayeb et al., 2004; Ferreira et al., 2012; Stahel et al., 2009 ) and has the potential to affect different types of research studies using rabbits due to the multisystemic nature of the disease, and the possibility of high morbidity and mortality. piliforme is a pleomorphic, Gramnegative, spore-forming, motile, obligate intracellular rod-shaped bacterium that causes Tyzzer''s disease and infects various animals including mice, nonhuman primates, gerbils, rats, rabbits, and others (Allen et al., 1965; Ganaway et al., 1971; Pritt et al., 2010) . Research Complications EPEC infection can cause high morbidity and mortality in laboratory rabbit colonies and can affect studies involving intestinal physiology in rabbits.
cord-342996-honeavwj	2015	title: The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis We conducted a systematic review and exploratory meta-analysis to evaluate the clinical effectiveness of convalescent plasma, serum, or hyperimmune immunoglobulin for the treatment of severe acute respiratory infections (SARIs) of viral etiology, to help inform clinical management of MERS-CoV infection. Four observational studies [24, 30, 37, 48] and 1 systematic review [22] reported data on severe cases of influenza A(H1N1)pdm09 infection treated with convalescent plasma (Table 3 and Supplementary Table 3 ). A case-comparison study at moderate risk of bias [30] reported no significant difference in length of hospital stay between treatment and control patients with severe pandemic influenza A (H1N1) infection who required ECMO ( Table 3) .
cord-344610-mqq6fmsp	2015	Usually only four prolyl-specific peptidases are considered: DPPIV (EC 3.4.14.5), fibroblast activation protein α (FAP; EC 3.4.21.B28), and the more recently discovered DPP8 and DPP9 (EC 3.4.14). However, due to similarities in substrate specificity and structural homology, it is more relevant to consider a broader family that also includes prolyl oligopeptidase (PREP; EC 3.4.21.26), dipeptidyl peptidase II (DPPII) (EC 3.4.14.2), and prolyl carboxypeptidase (PRCP; EC 3.4.16.2). Three other studies also found no to low DPPIV expression or activity associated with human monocytes and/or macrophages (82, [136] [137] [138] . Dipeptidyl peptidase 4 is present in low amounts on freshly isolated human NK cells and its expression is only upregulated in a small subpopulation after IL-2 stimulation (158) . Dipeptidyl peptidase 8 and 9 have been found to be abundantly present in the macrophage-rich regions of human atherosclerotic plaques and considering DPP9''s role in macrophage activation, it might potentially be involved in atherogenesis (82). Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells
cord-345011-3rukouk3	2015	In addition to its peptidase activity, DPP4 also possesses noncatalytic function via interactions with a range of ligands including ADA, caveolin-1, fibronectin, coronavirus spike protein, collagen, glypican-3, insulin-like growth factor 2 receptor, fibroblast activation protein, and CXCR4. reported that the increase of circulating DPP4 activity in diabetic patients results in a reduction of plasma GLP-1 (fasting and in response to meals) [50] . reported in a recent meta-analysis including 18 randomized clinical trials and 4,988 patients on DPP4 inhibition therapy and 3,546 patients on control treatment (other diabetic treatments or placebo) and demonstrated that DPP4 inhibitors are safe from a cardiovascular standpoint and have beneficial effects on cardiovascular events compared to other diabetic medications and placebo [3] . Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidly obese patients undergoing biliopancreatic diversion The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1
cord-345254-glm2dxhh	2015	By contrast, unhelped memory CD8 T cells mounted poor recall responses when transferred into CD4 T-cell-sufficient mice and could not be sustained in the CNS, despite efficient virus control. Donor mice were treated with anti-mouse CD4 or control mAb at day À2 and 0 relative to intraperitoneal immunization for comparative analysis of ''unhelped'' versus ''helped'' CD8 T cells. As T cells are the primary mediators of JHMV control in the CNS during the first 14 days p.i. 29, 30 the inability of CD4-depleted mice to reduce viral load suggested impaired CD8 T-cell recruitment or function. 15 We therefore examined potential defects in effector functions of brain-derived unhelped virus-specific CD8 T cells by measurement of ex vivo cytolytic activity and IFN-c expression. To generate unhelped or helped donor memory CD8 T cells, Thy-1.1 mice were either treated with anti-CD4 or control mAb before JHMV immunization.
cord-347577-p0a2rboi	2015	The subsequent viral titer decrease was less rapid, and infectious Ebola virus particles persisted for all 8 days of the test. 17, 18 In response to the EVD epidemic, both the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention advised direct disposal of Ebola-contaminated liquid waste into sewage systems (wastewater collection and treatment systems) and latrines without disinfection. A current Ebola virus outbreak strain from Guinea (Makona-WPGC07) was spiked to two end concentrations (10 2 and 10 6 TCID 50 mL −1 ) into a domestic wastewater (untreated sewage) sample. Microbial activity within wastewater matrices would be expected to contribute to more rapid inactivation of infectious viral particles; 36, 42 however, the true effect of microbial activity on Ebola virus persistence is unknown. 34 Further assessment is necessary to determine Ebola inactivation and dilution within this period and potential human exposure routes, including workers within the sewer system and Ebola virus persistence within wastewater sludges.
cord-348829-87bvym6i	2015	OBJECTIVES: To identify the main respiratory pathogens isolated from calves in Québec dairy herds with a high incidence of BRD, and to determine if there is an association between the presence of these pathogens and clinical signs of pneumonia, lung consolidation, or average daily gain. Therefore, the first objective of this study was to identify the main respiratory pathogens found in preweaned dairy calves from herds with a high prevalence of BRD. The current study focuses on the prevalence of microbial pathogens in cases of BRD in preweaned dairy calves in relatively small herds using an objective measure (lung consolidation) for the definition of cases of BRD in living animals. Mycoplasma bovis was the third most frequently found bacteria in the current study, but it was the only 1 associated with clinical score, lung consolidation, and poor subsequent ADG.
cord-349649-6nrjpwh5	2015	BACKGROUND: Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. To assess any difference in antibody status between OM and CM herds, the prevalences of positive herds at each sampling occasion among OM and CM herds, respectively, were calculated with exact binomial confidence intervals using the package "binom" for R [29] . The incidence risk of newly infected herds, i.e. herds that went from negative to having at least one of four primiparous cows with a positive test result, did not differ statistically between OM and CM herds in any study year, neither for BRSV nor for BoCV (Table 1 ).
cord-350083-kldu8q8x	2015	title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach
cord-350762-rh4zbehk	2015	In this study, we utilize microRNA (miRNA)-expressing constructs (a type of RNA interference) in an attempt to target and knockdown five NDV structural RNAs for nucleoprotein (NP), phosphoprotein (P), matrix (M), fusion (F), and large (L) protein genes. Using pre-miRNA to activate the cellular RNAi pathway, a miRNA can be used to target the messenger RNA of NDV structural proteins, leading to the degradation of the transcripts and inhibiting viral replication [11] . In this study, we attempted to determine if constitutive expression of miRNA sequences targeting the mRNA of five of the structural NDV proteins in chicken embryo fibroblast cells (DF-1) would lead to decreased viral yield after infection, and/or resistance against NDV cytopathic effects. Inhibition of Newcastle disease virus replication by RNA interference targeting the matrix protein gene in chicken embryo fibroblasts
cord-351186-llnlto7p	2015	Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments. Through personal and phone interviews we contacted employees at business facility in Saudi Arabia who may have had contact with Patient #1 during the incubation period; we investigated the places he visited, presence or absence of MERS symptoms in the individuals he contacted, history of visiting medical facilities in the Middle East, and history of consuming camel milk or meat, among other things.
cord-351868-w4d45fue	2015	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. In order to test subcellular localization of the N protein in LLC-MK2 cells, the maxFP-Green-N/NL63-N encoding RNA was prepared based on the original plasmid. For EMSA assay 10 μg of RNA or DNA corresponding in sequence to the N-NL63 gene (prepared in the same manner as for the transfection of eukaryotic cells) was incubated in buffered solution (5 mM Tris, 50 mM NaCl, pH8.0) with 10 μg of the NTD or CTD for 30 minutes at room temperature. The constructs of NTD and CTD used in this study were designed based on literature data, HCoV-NL63 N protein amino acid sequence alignment with known homologs and on the comparative analysis of currently available crystal structures of these homologs.
cord-352664-heoj8ji8	2015	In this study, we developed a robust and rapid ''field pathogenomics'' strategy, using transcriptome sequencing of PST-infected wheat leaves to gain insight into the population structure of an emerging pathogen. To characterize the genotypic diversity of PST at the field level, we collected 219 samples of wheat and triticale infected with PST from 17 different counties across the UK in the spring and summer of 2013 ( Figure 1a ; Table S1 in Additional file 1). To determine the relationship between the 2013 PST field isolates and previously prevalent PST populations, the genomes of 14 UK and 7 French purified PST isolates collected between 1978 and 2011 were sequenced using an Illumina whole-genome shotgun approach Figure 2 Identification of wheat varieties using transcriptome data generated directly from PST-infected field samples. We used multivariate discriminant analysis of principal components (DAPC) with the 34,764 biallelic SNP sites to define the population structure and identify groups of genetically related PST isolates.
cord-353310-19kzb6ag	2015	Compared with VicS-v, the more attenuated VicS-del strain had two non-synonymous changes in the non-structural protein 6 (nsp6), a transmembrane (TM) domain that may participate in autocatalytic release of the 3-chymotrypsin-like protease, a polymorphic difference at the end of the S2 gene, which coincided with the body transcription-regulating sequence (B-TRS) of mRNA 3 and a truncated open reading frame for a peptide encoded by gene 4 (4b). Phylogenetic analysis of the whole genome showed that VicS-v and VicS-del did not cluster with strains from other countries, supporting the hypothesis that Australian IBV strains have been evolving independently for some time, and analyses of individual polymerase peptide and S glycoprotein genes suggested a distant common ancestor with no recent recombination. For VicSdel, the readings were mapped to the genome of VicS-v and the previously determined sequence of the structural protein gene region of VicS-del (GAN JN983807).
cord-353787-24c98ug8	2015	Measurement of immune expression may help define individual heterogeneity in infectious disease susceptibility and transmission and facilitate our understanding of infection dynamics and risk in the natural environment; furthermore, it may provide a means of surveillance that can filter individuals carrying previously unknown acute infections of potential ecological or zoonotic importance. Potentiating much of this is the possibility of combining gene expression profiles with analytical tools derived from ecology and systems biology to reverse engineer interaction networks between immune responses, other organismal traits and the environment (including symbiont exposures), revealing regulatory architecture. Studies in wild field voles, briefly reviewed below, have aimed to identify distributional infection patterns associated with different antipathogen strategies in natural populations and to link these to expression signatures in immune-relevant genes.
cord-354151-psog34u3	2015	METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. [1] [2] [3] [4] A few population-level studies in Europe were based on observations in one respiratory season only (the 2009 H1N1 pandemic) in which the annually recurring influenza epidemic occurred relatively early. Almost all of the included respiratory viruses (influenza A and B virus, RSV, coronavirus) except rhinovirus showed very clear seasonality in their reporting over time. Viruses that showed a shifted trend of reporting during years with early influenza A epidemics were of respiratory nature with clear winter seasonality and with epidemics occurring relatively close in time to influenza A virus epidemics.
cord-355499-5vj3oasa	2015	title: Transmissible Gastroenteritis Virus (TGEV) Infection Alters the Expression of Cellular MicroRNA Species That Affect Transcription of TGEV Gene 7 In this study, we performed microRNA microarray assay and predicted targets of altered miRNAs. The results showed TGEV infection caused the change of miRNAs profile. In conclusion, differentially expressed miR-4331 that is caused by TGEV infection can suppress transcription of TGEV gene 7 via targeting cellular CDCA7. Overall, we observed that TGEV infection caused the change of miRNA profile and miR-4331 suppressed transcription of TGEV gene 7 via directly targeting CDCA7. The major findings in this study are that TGEV infection leads to the change of cellular miRNAs expression profile, and altered miRNAs regulate transcription of TGEV gene 7 through targeting cellular CDCA7. In conclusion, the results of the present study provide evidence that TGEV infection resulted in altered profiles of miRNAs in PK-15 cells and the differentially expressed miR-4331 was involved in regulation of TGEV transcription by targeting cellular CDCA7.