bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral-Bacterial Interactions and Risk of Acute Otitis Media Complicating Upper Respiratory Tract Infection
Authors: Pettigrew Melinda M. , Gent Janneane F. , Pyles Richard B. , Miller Aaron L. , Nokso-Koivisto Johanna , Chonmaitree Tasnee 
Published: September 2011

ABSTRACT

Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus,
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
were significantly associated with AOM (
P
< 0.05 by χ
2
test). Children with high respiratory syncytial virus loads (≥3.16 × 10
7
copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with
Streptococcus pneumoniae
(odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and
Haemophilus influenzae
(OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and
H. influenzae
together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.
Containment of an Outbreak of KPC-3-Producing Klebsiella pneumoniae in Italy
Authors: Agodi Antonella , Voulgari Evangelia , Barchitta Martina , Politi Leda , Koumaki Vasiliki , Spanakis Nicholas , Giaquinta Loredana , Valenti Giovanna , Romeo Maria Antonietta , Tsakris Athanassios 
Published: September 2011

ABSTRACT

From March 2009 to May 2009, 24 carbapenem-resistant
Klebsiella pneumoniae
isolates were recovered from 16 patients hospitalized in an Italian intensive care unit (ICU). All isolates contained KPC-3 carbapenemase and belonged to a single pulsed-field gel electrophoresis (PFGE) clone of multilocus sequence type 258 (designated as ST258). A multimodal infection control program was put into effect, and the spread of the KPC-3-producing
K. pneumoniae
clone was ultimately controlled without closing the ICU to new admissions. Reinforced infection control measures and strict monitoring of the staff adherence were necessary for the control of the outbreak.
Cellular Human CLE/C14orf166 Protein Interacts with Influenza Virus Polymerase and Is Required for Viral Replication
Authors: Rodriguez Ariel , Pérez-González Alicia , Nieto Amelia 
Published: September 2011

ABSTRACT
The influenza A virus polymerase associates with a number of cellular transcription-related factors, including RNA polymerase II. We previously described the interaction of influenza virus polymerase subunit PA with human CLE/C14orf166 protein (hCLE), a positive modulator of this cellular RNA polymerase. Here, we show that hCLE also interacts with the influenza virus polymerase complex and colocalizes with viral ribonucleoproteins. Silencing of hCLE causes reduction of viral polymerase activity, viral RNA transcription and replication, virus titer, and viral particle production. Altogether, these findings indicate that the cellular transcription factor hCLE is an important protein for influenza virus replication.
Transmission of Clonal Hepatitis C Virus Genomes Reveals the Dominant but Transitory Role of CD8+T Cells in Early Viral Evolution
Authors: Callendret Benoît , Bukh Jens , Eccleston Heather B. , Heksch Ryan , Hasselschwert Dana L. , Purcell Robert H. , Hughes Austin L. , Walker Christopher M. 
Published: September 2011

ABSTRACTThe RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8+T cells is a dominant force driving early amino acid replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8+T cell responses combined with sequencing of recovered virus at frequent intervals revealed that most acute-phase nonsynonymous mutations were clustered in class I epitopes and appeared much earlier than those in the remainder of the HCV genome. Moreover, the ratio of nonsynonymous to synonymous mutations, a measure of positive selection pressure, was increased 50-fold in class I epitopes compared with the rest of the HCV genome. Finally, some mutation of the clonal H77C genome toward a genotype 1a consensus sequence considered most fit for replication was observed during the acute phase of infection, but the majority of these amino acid substitutions occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8+T cells. This influence of immune pressure on viral evolution appears to subside as chronic infection is established and genetic drift becomes the dominant evolutionary force.
RelA Ser276 Phosphorylation-Coupled Lys310 Acetylation Controls Transcriptional Elongation of Inflammatory Cytokines in Respiratory Syncytial Virus Infection
Authors: Brasier Allan R. , Tian B. , Jamaluddin M. , Kalita Mridul K. , Garofalo Roberto P. , Lu Muping 
Published: September 2011

ABSTRACT
Respiratory syncytial virus (RSV) is a negative-sense single-stranded RNA virus responsible for lower respiratory tract infections (LRTIs) in humans. In experimental models of RSV LRTI, the actions of the nuclear factor κB (NF-κB) transcription factor mediate inflammation and pathology. We have shown that RSV replication induces a mitogen-and-stress-related kinase 1 (MSK-1) pathway that activates NF-κB RelA transcriptional activity by a process involving serine phosphorylation at serine (Ser) residue 276. In this study, we examined the mechanism by which phospho-Ser276 RelA mediates expression of the NF-κB-dependent gene network. RelA-deficient mouse embryonic fibroblasts (MEFs) complemented with the RelA Ser276Ala mutant are deficient in CXCL2/Groβ, KC, and interleukin-6 (IL-6) expression, but NFKBIA/IκBα is preserved. We show that RSV-induced RelA Ser276 phosphorylation is required for acetylation at Lys310, an event required for transcriptional activity and stable association of RelA with the activated positive transcriptional elongation factor (PTEF-b) complex proteins, bromodomain 4 (Brd4), and cyclin-dependent kinase 9 (CDK9). In contrast to gene loading pattern of PTEF-b proteins produced by tumor necrosis factor (TNF) stimulation, RSV induces their initial clearance followed by partial reaccumulation coincident with RelA recruitment. The RSV-induced binding patterns of the CDK9 substrate, phospho-Ser2 RNA polymerase (Pol) II, follows a similar pattern of clearance and downstream gene reaccumulation. The functional role of CDK9 was examined using CDK9 small interfering RNA (siRNA) and CDK inhibitors, where RSV-induced NF-κB-dependent gene expression was significantly inhibited. Finally, although RSV induces a transition from short transcripts to fully spliced mRNA in wild-type RelA (RelA WT)-expressing cells, this transition is not seen in cells expressing RelA Ser276Ala. We conclude that RelA Ser276 phosphorylation mediates RelA acetylation, Brd4/CDK9 association, and activation of downstream inflammatory genes by transcriptional elongation in RSV infection.
Increased mortality in parents bereaved in the first year of their child's life
Authors: Harper Mairi , O'Connor Rory C , O'Carroll Ronan E 
Published: September 2011

ObjectiveTo identify the relative risk (RR) of mortality in bereaved parents compared with non-bereaved counterparts.DesignRetrospective data linkage study.SettingUnited Kingdom, 1971–2006.ParticipantsA random sample from death registrations (5%) of parents who had a live birth where the infant lived beyond its first year of life (non-bereaved parents) and parents who had experienced a stillbirth or the death of a child in its first year of life (bereaved parents) between 1971 and 2006.Main outcome measuresDeath or widowhood of the parent.ResultsBereaved parents in Scotland (n=738) were more than twice as likely to die in the first 15 years after their child's death than non-bereaved parents (n=50 132), p<0.005. Bereaved mothers in England and Wales (n=481) were more than four times as likely to die in the first 15 years after their child's birth than non-bereaved parents (n=30 956), p<0.001. The mortality risk for bereaved mothers compared with non-bereaved mothers, followed up for 25 years after death, was 1.5 (bereaved n=745, non-bereaved n=36 434), p<0.005. When followed up for 35 years, the risk of mortality for bereaved mothers (n=1120) was 1.2 times that of non-bereaved mothers (n=36 062), p<0.005.ConclusionsBereaved parents who experience stillbirth or infant death have markedly increased mortality compared with non-bereaved parents, up to 25 years (mean) after the death of their child. However, the RR reduces over time.
Comparison of techniques for stent assisted coil embolization of aneurysms
Authors: Spiotta Alejandro M , Wheeler Anne Marie , Smithason Saksith , Hui Ferdinand , Moskowitz Shaye 
Published: September 2011

IntroductionStent assisted coiling (SAC) of aneurysms has been adopted with potential mechanical, hemodynamic and biologic properties imparting an advantage over coil embolization alone. The purpose of this investigation is to compare the various techniques of SAC at a single institution with regards to clinical, technical and angiographic complications and success.MethodsPatients who underwent SAC between 2003 and 2010 were identified. Clinical charts, procedures, angiographic and non-invasive radiological images were analyzed to determine the anatomical and procedural details and adverse events. Immediate post-procedural angiograms as well as follow-up imaging were studied to assess the degree of aneurysm occlusion.Results260 aneurysms were identified. The ‘coil through’ technique was employed in 37.3%, ‘balloon stent’ in 36.2%, ‘jailing’ in 10.8% and the ‘coil stent’ technique in 7.7%. Overall rate of adverse events was higher with the ‘coil stent’ and ‘jailing’ techniques compared with the ‘balloon stent’ technique. The ‘coil through’ technique was associated with a significantly lower packing density (31.4±20%) than all other techniques (‘coil stent’ 45.4±22%, ‘jailing’ 42.2±20%, ‘balloon stent’ 44.3±22%). Among ‘coil stent’ patients, an initial Raymond class 1 was achieved in 40%, compared with 57% of ‘jailing’, 28% of ‘coil through’ and 63% of ‘balloon stent’ cases.ConclusionBalloon assisted coil embolization followed by adjunctive stent deployment across the aneurysm neck appears to be the superior technique among stent assisted coiling methods at our institution. It combines a lower rate of thrombotic and coil related complications with a high rate of complete occlusion on initial and follow-up imaging.
Long-term effects of antiplatelet drugs on aneurysm occlusion after endovascular treatment
Authors: Platz Johannes , Güresir Erdem , Seifert Volker , Vatter Hartmut , Berkefeld Joachim 
Published: September 2011

BackgroundThe rates of recanalization and reinterventions after endovascular treatment (EVT) of intracranial aneurysms are unknown. Various risk factors have been suggested including the configuration of the aneurysm and the endovascular technique. Recently, an increasing number of patients have received antiplatelet (AP) drugs periprocedurally, possibly inhibiting early thrombus formation.ObjectiveTo assess the impact of AP drugs on the rate of recurrence and reintervention.MethodsPatients treated at our center were entered into a prospectively conducted database. Those with at least one follow-up angiogram 6 months after EVT were selected for the study. The role of AP medication was assessed by statistical analysis.Results292 patients with 314 aneurysms (206 ruptured) were included. The median follow-up time was 18 months. 129 (41%) were treated with APs (70 with acetylsalicylic acid (ASA), 10 with clopidogrel and 48 with both). 107 angiographic aneurysm recurrences were noted and 61 aneurysms were retreated at least once. In a multivariate model only aneurysm size, initially incomplete occlusion and the length of follow-up were significant predictors (p<0.05). No correlation was found between AP administration and recurrences or reinterventions. Interestingly, patients receiving ASA alone were retreated less often (OR 0.187, 95% CI 0.061 to 0.572, p=0.003).ConclusionAP administration is not associated with an increased rate of aneurysm recurrence or reintervention; ASA even seemed to have some beneficial effect. However, confounding factors may include the lack of standardized indications for AP and the small number of patients in the series. A prospectively conducted study is warranted to further clarify the role of AP medication after EVT.
AN ENERGY-CONSERVING DISCONTINUOUS MULTISCALE FINITE ELEMENT METHOD FOR THE WAVE EQUATION IN HETEROGENEOUS MEDIA
Authors: CHUNG ERIC T. , EFENDIEV YALCHIN , GIBSON RICHARD L. 
Published: September 2011

Seismic data are routinely used to infer in situ properties of earth materials on many scales, ranging from global studies to investigations of surficial geological formations. While inversion and imaging algorithms utilizing these data have improved steadily, there are remaining challenges that make detailed measurements of the properties of some geologic materials very difficult. For example, the determination of the concentration and orientation of fracture systems is prohibitively expensive to simulate on the fine grid and, thus, some type of coarse-grid simulations are needed. In this paper, we describe a new multiscale finite element algorithm for simulating seismic wave propagation in heterogeneous media. This method solves the wave equation on a coarse grid using multiscale basis functions and a global coupling mechanism to relate information between fine and coarse grids. Using a mixed formulation of the wave equation and staggered discontinuous basis functions, the proposed multiscale methods have the following properties. • The total wave energy is conserved. • Mass matrix is diagonal on a coarse grid and explicit energy-preserving time discretization does not require solving a linear system at each time step. • Multiscale basis functions can accurately capture the subgrid variations of the solution and the time stepping is performed on a coarse grid. We discuss various subgrid capturing mechanisms and present some preliminary numerical results.
Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Plasma Metabolomics and Lipid Profiling
Authors: Patterson Andrew D. , Maurhofer Olivier , Beyoğlu Diren , Lanz Christian , Krausz Kristopher W. , Pabst Thomas , Gonzalez Frank J. , Dufour Jean-François , Idle Jeffrey R. 
Published: September 2011

Abstract
There has been limited analysis of the effects of hepatocellular carcinoma (HCC) on liver metabolism and circulating endogenous metabolites. Here, we report the findings of a plasma metabolomic investigation of HCC patients by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), random forests machine learning algorithm, and multivariate data analysis. Control subjects included healthy individuals as well as patients with liver cirrhosis or acute myeloid leukemia. We found that HCC was associated with increased plasma levels of glycodeoxycholate, deoxycholate 3-sulfate, and bilirubin. Accurate mass measurement also indicated upregulation of biliverdin and the fetal bile acids 7α-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochol-4,6-dien-24-oic acid in HCC patients. A quantitative lipid profiling of patient plasma was also conducted by ultraperformance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-TQMS). By this method, we found that HCC was also associated with reduced levels of lysophosphocholines and in 4 of 20 patients with increased levels of lysophosphatidic acid [LPA(16:0)], where it correlated with plasma α-fetoprotein levels. Interestingly, when fatty acids were quantitatively profiled by gas chromatography-mass spectrometry (GC-MS), we found that lignoceric acid (24:0) and nervonic acid (24:1) were virtually absent from HCC plasma. Overall, this investigation illustrates the power of the new discovery technologies represented in the UPLC-ESI-QTOFMS platform combined with the targeted, quantitative platforms of UPLC-ESI-TQMS and GC-MS for conducting metabolomic investigations that can engender new insights into cancer pathobiology. Cancer Res; 71(21); 6590–600. ©2011 AACR.
ARID1A, a Factor That Promotes Formation of SWI/SNF-Mediated Chromatin Remodeling, Is a Tumor Suppressor in Gynecologic Cancers
Authors: Guan Bin , Wang Tian-Li , Shih Ie-Ming 
Published: September 2011

Abstract
ARID1A (BAF250A) promotes the formation of SWI/SNF chromatin remodeling complexes containing BRG1 or BRM. It has emerged as a candidate tumor suppressor based on its frequent mutations in ovarian clear cell and endometrioid cancers and in uterine endometrioid carcinomas. Here, we report that restoring wild-type ARID1A expression in ovarian cancer cells that harbor ARID1A mutations is sufficient to suppress cell proliferation and tumor growth in mice, whereas RNA interference–mediated silencing of ARID1A in nontransformed epithelial cells is sufficient to enhance cellular proliferation and tumorigenicity. Gene expression analysis identified several downstream targets of ARID1A including CDKN1A and SMAD3, which are well-known p53 target genes. In support of the likelihood that p53 mediates the effects of ARID1A on these genes, we showed that p53 was required and sufficient for their regulation by ARID1A. Furthermore, we showed that CDKN1A (encoding p21) acted in part to mediate growth suppression by ARID1A. Finally, we obtained evidence that the ARID1A/BRG1 complex interacted directly with p53 and that mutations in the ARID1A and TP53 genes were mutually exclusive in tumor specimens examined. Our results provide functional evidence in support of the hypothesis that ARID1A is a bona fide tumor suppressor that collaborates with p53 to regulate CDKN1A and SMAD3 transcription and tumor growth in gynecologic cancers. Cancer Res; 71(21); 6718–27. ©2011 AACR.
The Impact of Common Genetic Variations in Genes of the Sex Hormone Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer Aggressiveness
Authors: Sun Tong , Oh William K. , Jacobus Susanna , Regan Meredith , Pomerantz Mark , Freedman Matthew L. , Lee Gwo-Shu Mary , Kantoff Philip W. 
Published: September 2011

Abstract
Our previous work suggested that there was no significant association between plasma steroid hormone levels and prostate cancer tumor grade at diagnosis. In this study, we systematically tested the hypothesis that inherited variations in the androgen and estrogen metabolic pathways may be associated with plasma levels of steroid hormones, or prostate cancer aggressiveness at diagnosis. Plasma hormone levels including total testosterone, total estradiol, and sex hormone–binding globulin were measured in a cohort of 508 patients identified with localized prostate cancer. D'Amico risk classification at diagnosis was also determined. A total of 143 single-nucleotide polymorphisms (SNPs) from 30 genes that are involved in androgen and estrogen metabolism were selected for analysis. The global association of genotypes with plasma hormone levels and prostate cancer aggressiveness (D'Amico risk classification) was statistically analyzed. Q values were estimated to account for multiple testing. We observed significant associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151), HSD17B3 (rs9409407), and HSD17B1 (rs12602084), with P values of 0.002, 0.006, and 0.006, respectively. We also observed borderline significant associations between prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005), UGT2B15 (rs2045100; P = 0.007), and HSD17B12 (rs7932905; P = 0.008). No individual SNP was associated with both clinical variables. Genetic variants of genes in hormone metabolic pathways may influence plasma androgen levels or prostate cancer aggressiveness. However, it seems that the inherited variations affecting plasma hormone levels differ from those affecting disease aggressiveness. Cancer Prev Res; 4(12); 2044–50. ©2011 AACR.
Involvement of IRAKs and TRAFs in anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells
Authors: Guo Donglin , Zhou Fang , Chen Dongdong , Xie Hongxiang , Wang Ting , Wang Haibo , Xu Guoying , Wen Haiping , Hong Zhou 
Published: September 2011

SummaryOur previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β2-glycoprotein I/β2-glycoprotein I (anti-β2GPI/β2GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its downstream molecules have not been well explored. In this study, we have established that interleukin-1 receptor-associated kinases (IRAKs) and tumour necrosis factor receptor-associated factors (TRAFs) are crucial downstream molecules of anti-β2GPI/β2GPI-induced TLR4 signaling pathway in THP-1 cells and explored the potential mechanisms of their self-regulation. Treatment of THP-1 cells with anti-β2GPI/β2GPI complex induced IRAKs and TRAFs expression and activation. Anti-β2GPI/β2GPI complex firstly induced expression of IRAK4 and IRAK1, then IRAK1 phosphorylation and last IRAK3 upregulation. In addition, anti-β2GPI/β2GPI complex simultaneously and acutely enhanced mRNA levels of TRAF6, TRAF4 and zinc finger protein A20 (A20), while chronically increased A20 protein level. Moreover, anti-β2GPI/β2GPI complex-induced IRAKs and TRAFs expression and activation were attenuated by knockdown of ANX2 by infection with ANX2-specific RNA interference lentiviruses (LV-RNAi-ANX2) or by treatment with paclitaxel, which inhibits TLR4 as an antagonist of myeloid differentiation protein 2 (MD-2) ligand. Furthermore, both IRAK1/4 inhibitor and a specific proteasome inhibitor MG-132 could attenuate TRAFs expression as well as TF expression induced by anti-β2GPI/β2GPI complex. In conclusion, our results indicate that IRAKs and TRAFs play important roles in anti-β2GPI/β2GPI-stimulated TLR4/TF signaling pathway in THP-1 cells and contribute to the pathological processes of antiphospholipid syndrome (APS).