bluuebunny/crossref_metadata_2025_split huggingface dataset:
A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic‐resistant Pseudomonas aeruginosa; a preliminary report of efficacy
Authors: Wright A. , Hawkins C.H. , Änggård E.E. , Harper D.R. 
Published: July 2009

Objectives:  To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage‐PA) targeting antibiotic‐resistant Pseudomonas aeruginosa in chronic otitis.Design:  Randomised, double‐blind, placebo‐controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process.Setting:  A single specialist university hospital.Participants:  24 patients with chronic otitis with a duration of several years (2–58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic‐resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage‐PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage‐PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured.Main outcome measures:  Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow‐up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only.Results:  Relative to day 0, pooled patient‐ and physician‐reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported.Conclusion:  The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo‐resistant P. aeruginosa.
Post‐cholecystectomy cystic duct stump leak: a preventable morbidity
Authors: SHAIKH Irshad Ahammed A. , THOMAS Harun , JOGA Kishore , AMIN A. Ibrahim , DANIEL Thomas 
Published: July 2009

OBJECTIVE: While major bile duct injury is the most serious complication following laparoscopic cholecystectomy, bile leak from the cystic duct stump remains the commonest morbidity. This is a retrospective assessment of all patients who had a cholecystectomy over a 5‐year period from April 2003 to March 2008.METHODS: Data related to bile leakage were obtained from the Unisoft endoscopic retrograde cholangio‐pancreatography (ERCP) database.RESULTS: Overall 2011 cholecystectomies were performed, of which 488 were done as emergency procedures. Thirteen patients had significant bile leakage, three of which were from accessory ducts, in one the source could not be identified and nine had a cystic duct stump leak (CDSL), which formed the basis of this study. Eight of the nine CDSL patients had successful ERCP and stenting. One had a percutaneous trans‐hepatic cholangiography and stenting. CDSL following emergency laparoscopic cholecystectomy was up to threefold higher than after elective procedures.CONCLUSION: The CDSL of 0.44% was comparable to the reported incidence in the literature. Endoscopic management remains the treatment of choice. Emergency cholecystectomies seem to have a higher incidence of CDSL.
Baseline study of the leaf‐litter ant fauna in a French Guianese forest
Authors: GROC SARAH , ORIVEL JÉRÔME , DEJEAN ALAIN , MARTIN JEAN‐MICHEL , ETIENNE MARIE‐PIERRE , CORBARA BRUNO , DELABIE JACQUES H. C. 
Published: July 2009

Abstract. 1. Leaf‐litter ants represent a major component of biodiversity and are excellent bioindicators reflecting the health of terrestrial ecosystems. This study, conducted in an unspoiled forest near the Nouragues Research Station, represents the first inventory of leaf‐litter ant diversity conducted in French Guiana, and so can be considered as the baseline dataset for ants in this country.2. Ants were extracted from the leaf‐litter using the Ants of the Leaf Litter Protocol, along an altitudinal gradient at four forest sites, including an inselberg.3. A total of 196 ant species representing 46 genera distributed over eight subfamilies were collected. Four distinct communities spread over a gradient of diversity were thus identified: the liana forest was the most species‐rich (140 species) followed by the forested plateau (102 species), the transition forest (87 species) and the forest at the top of the inselberg (71 species).4. The discovery of species new to science plus several species recorded for the first time in French Guiana, coupled with the particular context of this area, suggests that the Nouragues Research Station might represent a centre of endemism. Once completed, this leaf‐litter ant dataset will contribute greatly to the knowledge of ant biodiversity in French Guiana, and has the potential to progressively become an indispensable tool for country‐wide conservation planning programmes.
A Live AttenuatedBordetella pertussisCandidate Vaccine Does Not Cause Disseminating Infection in Gamma Interferon Receptor Knockout Mice
Authors: Skerry Ciaran M. , Cassidy Joseph P. , English Karen , Feunou-Feunou Pascal , Locht Camille , Mahon Bernard P. 
Published: July 2009

ABSTRACTBordetella pertussisis the cause of whooping cough and responsible for 300,000 infant deaths per annum. Current vaccines require 6 months to confer optimal immunity on infants, the population at highest risk. Recently, an attenuated strain ofB. pertussis(BPZE1) has been developed to be used as a low-cost, live, intranasal, single-dose vaccine for newborns. Preclinical proof of concept has been established; however, it is necessary to evaluate the safety of BPZE1, especially in immunodeficient models, prior to human clinical trials. Here, the preclinical safety of BPZE1 was examined in well-characterized murine models. Immunocompetent and gamma interferon (IFN-γ) receptor knockout mice were challenged by aerosol with either virulentB. pertussisor BPZE1. The two strains colonized the lung at equal levels, but inflammation was associated with carriage of only virulent bacteria. Virulent bacteria disseminated to the liver of IFN-γ receptor-deficient mice, resulting in atypical pathology. In contrast, attenuated BPZE1 did not disseminate in either immunocompetent or immunodeficient mice and did not induce atypical pathology. In neonatal challenge models, virulentB. pertussisinfection resulted in significant mortality of both immunodeficient and immunocompetent mice, whereas no mortality was observed for any neonatal mice challenged with BPZE1. BPZE1 was shown to elicit strong IFN-γ responses in mice, equivalent to those elicited by the virulent streptomycin-resistantB. pertussisTohama I derivative BPSM, also inducing immunoglobulin G2a, a process requiring TH1 cytokines in mice. These data indicate that a live attenuated whooping cough vaccine candidate shows no signs of disseminating infection in preclinical models but rather evokes an immunological profile associated with optimal protection against disease.
Prevalence and Clinical Characterization of a Newly Identified Human Rhinovirus C Species in Children with Acute Respiratory Tract Infections
Authors: Jin Yu , Yuan Xin-Hui , Xie Zhi-Ping , Gao Han-Chun , Song Jing-Rong , Zhang Rong-Fang , Xu Zi-Qian , Zheng Li-Shu , Hou Yun-De , Duan Zhao-Jun 
Published: July 2009

ABSTRACT
Human rhinovirus C (HRV-C) is a newly identified genotype of HRV found in patients with respiratory tract infections (RTIs); however, its epidemiological profile and clinical characteristics are not well understood. In this study, Chinese children with RTIs were screened for HRV-C and their epidemiological and clinical characteristics were analyzed. From December 2006 to November 2007, 406 nasopharyngeal aspirates from children younger than 14 years of age with RTIs were screened for HRV and other common respiratory viruses by PCR or reverse transcription-PCR. Two-hundred twenty-four (55.2%) of the specimens were infected with at least one virus, including 53 patients with HRV (13%). HRV-A, HRV-B, and HRV-C were detected in 22, 12, and 19 specimens, respectively. HRV-C was detected mainly from December 2006 to April 2007 and from October to November 2007, with peaks in December and April (10/19). Acute upper respiratory infection and bronchopneumonia were observed in 53 and 37% of the cases, respectively. The most common symptoms were cough (82%), runny nose (53%), and fever (37%). Wheezing and bronchiolitis were less common in patients infected with HRV-C than in those infected with respiratory syncytial virus (RSV). Partial sequencing of the genes coding for VP4 and VP2 revealed that the HRV-C strains were 56 to 62% identical at the amino acid level to HRV-B and HRV-A reference strains and 80 to 99% identical to HRV-C reference strains. In conclusion, HRV-C is an important cause of RTIs in children, and highly diversified strains of HRV-C are prevalent in China. HRV-C may produce different epidemiological features, and patients infected with HRV-C may exhibit different clinical features from patients infected with RSV or HRV-A/B.
Strain Typing and Antimicrobial Resistance of Fluoroquinolone-ResistantNeisseria gonorrhoeaeCausing a California Infection Outbreak
Authors: Morris Sheldon R. , Moore Douglas F. , Hannah Paul B. , Wang Susan A. , Wolfe Julia , Trees David L. , Bolan Gail , Bauer Heidi M. 
Published: July 2009

ABSTRACTAntimicrobial-resistantNeisseria gonorrhoeaeis an emerging public health problem as a result of the alarming limitation in treatment options. We examined an outbreak in California of fluoroquinolone-resistantNeisseria gonorrhoeae(QRNG) by evaluation of a combination of routine isolates from the Gonococcal Isolate Surveillance Project and isolates collected by expanded surveillance performed between April 2000 and June 2002. QRNG isolates were characterized by two methods: (i) determination of a combination of antibiogram, auxotype, serovar, Lip type, and patterns of amino acid alteration in the quinolone resistance-determining region of GyrA and ParC (ASLGP) and (ii) pulsed-field gel electrophoresis (PFGE). Strain typing was used to describe the QRNG outbreak strains and the associated antimicrobial resistance profiles. Among 79 isolates that were completely characterized, we identified 20 different ASLGP strain types, and 2 of the types were considered to belong to outbreak strains that comprised 65% (51/79) of the isolates. By PFGE typing, there were 24 different strain types, and 4 of these were considered outbreak types and comprised 66% (52/79) of the isolates. The overall agreement between the typing methods in distinguishing outbreak strains and non-outbreak strains was 84% (66/79). The most common QRNG ASLGP strain type had chromosomally mediated resistance to penicillin and tetracycline and an azithromycin MIC of 0.5 μg/ml. The occurrence of an outbreak caused by QRNG strains that could fail to be eradicated by most antibiotic classes reinforces the serious problem with antimicrobial resistance inNeisseria gonorrhoeaethat the public health system faces. Adherence to a regimen with the recommended antibiotics at the appropriate dose is critical, and monitoring for antimicrobial susceptibility needs to be actively maintained to adapt treatment guidelines appropriately.
Evaluation of the Abbott Investigational Use Only RealTi
m
e Hepatitis C Virus (HCV) Assay and Comparison to the Roche TaqMan HCV Analyte-Specific Reagent Assay
Authors: Pyne Michael T. , Konnick Eric Q. , Phansalkar Amit , Hillyard David R. 
Published: July 2009

ABSTRACT

The accurate and sensitive measurement of hepatitis C virus (HCV) RNA is essential for the clinical management and treatment of infected patients and as a research tool for studying the biology of HCV infection. We evaluated the linearity, reproducibility, precision, limit of detection, and concordance of viral genotype quantitation of the Abbott investigational use only RealTi
m
e HCV (RealTi
m
e) assay using the Abbott
m
2000 platform and compared the results to those of the Roche TaqMan Analyte-Specific Reagent (TaqMan) and Bayer Versant HCV bDNA 3.0 assay. Comparison of 216 samples analyzed by RealTi
m
e and TaqMan assays produced the following Deming regression equation: RealTi
m
e = 0.940 (TaqMan) + 0.175 log
10
HCV RNA IU/ml. The average difference between the assays was 0.143 log
10
RNA IU/ml and was consistent across RealTi
m
e's dynamic range of nearly 7 log
10
HCV RNA IU/ml. There was no significant difference between genotypes among these samples. The limit of detection using eight replicates of the World Health Organization HCV standard was determined to be 7.74 HCV RNA IU/ml by probit analysis. Replicate measurements of commercial genotype panels were significantly higher than TaqMan measurements for most samples and showed that the RealTi
m
e assay is able to detect all genotypes with no bias. Additionally, we showed that the amplicon generated by the widely used Roche COBAS Amplicor Hepatitis C Virus Test, version 2.0, can act as a template in the RealTi
m
e assay, but potential cross-contamination could be mitigated by treatment with uracil-
N
-glycosylase. In conclusion, the RealTi
m
e assay accurately measured HCV viral loads over a broad dynamic range, with no significant genotype bias.
Respiratory Syncytial Virus Nonstructural Proteins Decrease Levels of Multiple Members of the Cellular Interferon Pathways
Authors: Swedan Samer , Musiyenko Alla , Barik Sailen 
Published: July 2009

ABSTRACT

Viruses of the
Paramyxoviridae
family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique
n
on
s
tructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both of the NS proteins affect the steady-state levels of key members of the IFN pathway. We found that both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing signals, although NS1 was more efficient. Only NS1 reduced IKKε, a key protein kinase that specifically phosphorylates and activates IFN regulatory factor 3. Loss of the TRAF3 and IKKε proteins appeared to involve a nonproteasomal mechanism. Interestingly, NS2 modestly increased IKKε levels. In the IFN response pathway, NS2 decreased the levels of STAT2, the essential transcription factor for IFN-inducible antiviral genes. Preliminary mapping revealed that the C-terminal 10 residues of NS1 were essential for reducing IKKε levels and the C-terminal 10 residues of NS2 were essential for increasing and reducing IKKε and STAT2, respectively. In contrast, deletion of up to 20 residues of the C termini of NS1 and NS2 did not diminish their TRAF3-reducing activity. Coimmunoprecipitation studies revealed that NS1 and NS2 form a heterodimer. Clearly, the NS proteins of RSV, working individually and together, regulate key signaling molecules of both the IFN activation and response pathways.
Assembly of Arenavirus Envelope Glycoprotein GPC in Detergent-Soluble Membrane Microdomains
Authors: Agnihothram Sudhakar S. , Dancho Brooke , Grant Kenneth W. , Grimes Mark L. , Lyles Douglas S. , Nunberg Jack H. 
Published: July 2009

ABSTRACT

The family
Arenaviridae
includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. Genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. In the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern. Arenaviruses are enveloped virions that assemble and bud from the plasma membrane. In this study, we have characterized the microdomain organization of the virus envelope glycoprotein (GPC) on the cell surface by using immunogold electron microscopy. We find that Junín virus (JUNV) GPC clusters into discrete microdomains of 120 to 160 nm in diameter and that this property of GPC is independent of its myristoylation and of coexpression with the virus matrix protein Z. In cells infected with the Candid#1 strain of JUNV, and in purified Candid#1 virions, these GPC microdomains are soluble in cold Triton X-100 detergent and are thus distinct from conventional lipid rafts, which are utilized by numerous other viruses for assembly. Virion morphogenesis ultimately requires colocalization of viral components, yet our dual-label immunogold staining studies failed to reveal a spatial association of Z with GPC microdomains. This observation may reflect either rapid Z-dependent budding of virus-like particles upon coassociation or a requirement for additional viral components in the assembly process. Together, these results provide new insight into the molecular basis for arenavirus morphogenesis.
The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B Virus Infection
Authors: Asabe Shinichi , Wieland Stefan F. , Chattopadhyay Pratip K. , Roederer Mario , Engle Ronald E. , Purcell Robert H. , Chisari Francis V. 
Published: July 2009

ABSTRACT

The impact of virus dose on the outcome of infection is poorly understood. In this study we show that, for hepatitis B virus (HBV), the size of the inoculum contributes to the kinetics of viral spread and immunological priming, which then determine the outcome of infection. Adult chimpanzees were infected with a serially diluted monoclonal HBV inoculum. Unexpectedly, despite vastly different viral kinetics, both high-dose inocula (10
10
genome equivalents [GE] per animal) and low-dose inocula (10° GE per animal) primed the CD4 T-cell response after logarithmic spread was detectable, allowing infection of 100% of hepatocytes and requiring prolonged immunopathology before clearance occurred. In contrast, intermediate (10
7
and 10
4
GE) inocula primed the T-cell response before detectable logarithmic spread and were abruptly terminated with minimal immunopathology before 0.1% of hepatocytes were infected. Surprisingly, a dosage of 10
1
GE primed the T-cell response after all hepatocytes were infected and caused either prolonged or persistent infection with severe immunopathology. Finally, CD4 T-cell depletion before inoculation of a normally rapidly controlled inoculum precluded T-cell priming and caused persistent infection with minimal immunopathology. These results suggest that the relationship between the kinetics of viral spread and CD4 T-cell priming determines the outcome of HBV infection.
Systematic Study of the Genetic Response of a Variable Virus to the Introduction of Deleterious Mutations in a Functional Capsid Region
Authors: Luna Eva , Rodríguez-Huete Alicia , Rincón Verónica , Mateo Roberto , Mateu Mauricio G. 
Published: July 2009

ABSTRACTWe have targeted the intersubunit interfaces in the capsid of foot-and-mouth disease virus to investigate the genetic response of a variable virus when individual deleterious mutations are systematically introduced along a functionally defined region of its genome. We had previously found that the individual truncation (by mutation to alanine) of 28 of the 42 amino acid side chains per protomer involved in interactions between capsid pentameric subunits severely impaired infectivity. We have now used viral RNAs individually containing each of those 28 deleterious mutations (or a few others) to carry out a total of 96 transfections of susceptible cells, generally followed by passage(s) of the viral progeny in cell culture. The results revealed a very high frequency of fixation in the capsid of second-site, stereochemically diverse substitutions that compensated for the detrimental effect of primary substitutions at many different positions. Most second-site substitutions occurred at or near the capsid interpentamer interfaces and involved residues that are spatially very close to the originally substituted residue. However, others occurred far from the primary substitution, and even from the interpentamer interfaces. Remarkably, most second-site substitutions involved only a few capsid residues, which acted as “second-site hot spots.” Substitutions at these hot spots compensated for the deleterious effects of many different replacements at diverse positions. The remarkable capacity of the virus to respond to the introduction of deleterious mutations in the capsid with the frequent fixation of diverse second-site mutations, and the existence of second-site hot spots, may have important implications for virus evolution.
APPLICATION OF THE EMPIRICAL MODE DECOMPOSITION TO FIELD TILTMETER DATA FOR HYDRAULIC FRACTURE MAPPING
Authors: CHEN ZUORONG , JEFFREY ROBERT G. 
Published: July 2009

Empirical Mode Decomposition (EMD) is a fully data-driven, adaptive technique for analyzing time series from nonlinear and nonstationary processes. The starting point of EMD is to treat the signal as a superposition of different intrinsic modes of oscillations (fast oscillations superimposed on slow oscillations). The essence of this method is to empirically identify the intrinsic oscillatory modes by their characteristic time scale imbedded in a signal, and then decompose the signal into a collection of a finite and often small number of intrinsic mode functions (IMF) through a so-called sifting process. Each IMF component then represents only one mode of both amplitude and frequency modulated oscillation of the signal at a certain time scale or frequency band, and the sum of all the IMF components as well as a residual produces a perfect reconstruction of the original signal. Partial reconstruction can be achieved by selectively removing fast or slowly varying IMFs, which provides a method to remove unwanted (noise) parts of the signal. In this paper, the EMD is applied to quantitative analysis of field tiltmeter data collected to monitor and map hydraulic fractures. The fracture-related tilt components are extracted by identifying the relevant IMFs that contribute to them, which allows removing the noise and background trend components from the raw data. The extracted tilt data are then inverted to obtain the volume and orientation of the hydraulic fractures. Physically reasonable prediction of the hydraulic fracture volume is used to demonstrate that the application of EMD to field tiltmeter data analyzing can be successfully carried out.