bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Review and Meta-Analysis of the Tolerability and Hepatotoxicity of Antifungals in Empirical and Definitive Therapy for Invasive Fungal Infection
Authors: Wang Jiun-Ling , Chang Chia-Hsuin , Young-Xu Yinong , Chan K. Arnold 
Published: March 2010

ABSTRACTTo evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.
Telbivudine Exhibits No Inhibitory Activity against HIV-1 Clinical Isolates
In Vitro
Authors: Lin Kai , Karwowska Sylwia , Lam Eric , Limoli Kay , Evans Thomas G. , Avila Claudio 
Published: March 2010

ABSTRACT

Most approved drugs with activity against hepatitis B virus (HBV) have activity against human immunodeficiency virus type 1 (HIV-1), which precludes their use in patients who are coinfected with HBV and HIV-1 and who are not receiving antiretroviral therapy due to the risk of inducing resistance. The activity of telbivudine, a highly selective HBV inhibitor, against temporally and geographically distinct wild-type and multidrug-resistant HIV-1 clinical isolates was evaluated
in vitro
. No inhibition was observed with up to 600 μM drug, which supports further exploration of telbivudine as a therapeutic option for the treatment of HBV infections in patients coinfected with HIV-1.
Effects of Inoculum, pH, and Cations on the
In Vitro
Activity of Fidaxomicin (OPT-80, PAR-101) against
Clostridium difficile
Authors: Babakhani F. , Seddon J. , Robert N. , Shue Y.-K. , Sears P. 
Published: March 2010

ABSTRACT

The effects of the inoculum, pH, cation concentrations, and different lots of commercial media on the
in vitro
susceptibility of
Clostridium difficile
to fidaxomicin were examined. Of the factors evaluated, only pH alterations influenced the activity of fidaxomicin against
C. difficile
, noticeably reducing its activity at higher pH (≥7.9).
Type IV Secretion Machinery Promotes Ton-Independent Intracellular Survival of
Neisseria gonorrhoeae
within Cervical Epithelial Cells
Authors: Zola Tracey A. , Strange Heather R. , Dominguez Nadia M. , Dillard Joseph P. , Cornelissen Cynthia N. 
Published: March 2010

ABSTRACT

Survival of
Neisseria gonorrhoeae
within host epithelial cells is expected to be important in the pathogenesis of gonococcal disease. We previously demonstrated that strain FA1090 derives iron from a host cell in a process that requires the Ton complex and a putative TonB-dependent transporter, TdfF. FA1090, however, lacks the gonococcal genetic island (GGI) that is present in the majority of strains. The GGI in strain MS11 has been partially characterized, and it encodes a type IV secretion system (T4SS) involved in DNA release. In this study we investigated the role of iron acquisition and GGI-encoded gene products in gonococcal survival within cervical epithelial cells. We demonstrated that intracellular survival of MS11 was dependent on acquisition of iron from the host cell, but unlike the findings for FA1090, expression of the Ton complex was not required. Survival was not dependent on a putative TonB-like protein encoded in the GGI but instead was directly linked to T4SS structural components in a manner independent of the ability to release or internalize DNA. These data suggest that expression of selected GGI-encoded open reading frames confers an advantage during cervical cell infection. This study provides the first link between expression of the T4SS apparatus and intracellular survival of gonococci.
AdpC Is aPrevotella intermedia17 Leucine-Rich Repeat Internalin-Like Protein
Authors: Iyer Divya , Anaya-Bergman Cecilia , Jones Kevin , Yanamandra Sai , Sengupta Dipanwita , Miyazaki Hiroshi , Lewis Janina P. 
Published: March 2010

ABSTRACTThe oral bacteriumPrevotella intermediaattaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with theTreponema pallidumLRR (LRRTP) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strainEscherichia coliBL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than controlE. coliBL21 cells expressing a shamP. intermedia17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein ofP. intermedia17.
Functional Characterization of the IlpA Protein of
Vibrio vulnificus
as an Adhesin and Its Role in Bacterial Pathogenesis
Authors: Lee Kyung-Jo , Lee Na Yeon , Han Yang-Soo , Kim Juri , Lee Kyu-Ho , Park Soon-Jung 
Published: March 2010

ABSTRACT

Vibrio vulnificus
is a Gram-negative bacterium that causes a fatal septicemia. One of its virulence factors is a membrane-bound lipoprotein, IlpA, which can induce cytokine production in human immune cells. In the present study, the role of IlpA as an adhesion molecule was investigated. An
ilpA
-deleted
V. vulnificus
mutant showed significantly decreased adherence to INT-407 human intestinal epithelial cells, which in turn resulted in reduced cytotoxicity. The
ΔilpA
mutant recovered the adherence ability of the wild type by complementation in
trans
with the intact
ilpA
gene. In addition, pretreatment of
V. vulnificus
with anti-IlpA polyclonal antibodies resulted in a significant reduction of bacterial adherence. To localize the domain of IlpA required for cytoadherence, three truncated recombinant IlpA polypeptides were constructed and tested for the ability to adhere to human cells by a ligand-binding immunoblot assay and fluorescence microscopy. The polypeptide containing the carboxy (C)-terminal hydrophilic domain exhibited direct binding to INT-407 cells. Therefore, the C-terminal domain of IlpA allows this protein to be an adhesion molecule of
V. vulnificus
.
STOCHASTIC AUTOMATA NETWORKS FOR MODELLING SCHEDULING SCHEME IN WiMAX NETWORKS
Authors: MOKDAD LYNDA , BEN-OTHMAN JALEL 
Published: March 2010

WiMAX (Worldwide Interpretability for Microwave Access) is one of the leader standards of broadband Wireless Access (BWA). This standard becomes a competitor of 4G or LTE (Long Terme Evolution) with the introduction of different class of service flow (UGS, rtPS, nrtPS, BE). Each service class has its own QoS requirements. Even if the standard specify the transmission policy of each service class, it recommends the implementation of an admission control (AC) without any specification. This task is let to the operator. In this paper, we propose an implementation of an AC algorithm mechanism for IEEE 802.16. The performance evaluation of these networks by analytical models is not easy due to the state space explosion, thus we use the Stochastic Automata Networks (SAN) formalism to model our proposed AC mechanism. With the SAN we calculate the rewards of the proposed AC and we show that the proposed solution is efficient.
The Influence of Tropical Deforestation on the Northern Hemisphere Climate by Atmospheric Teleconnections
Authors: Snyder Peter K. 
Published: March 2010

AbstractNumerous studies have identified the regional-scale climate response to tropical deforestation through changes to water, energy, and momentum fluxes between the land surface and the atmosphere. There has been little research, however, on the role of tropical deforestation on the global climate. Previous studies have focused on the climate response in the extratropics with little analysis of the mechanisms responsible for propagating the signal out of the tropics. A climate modeling study is presented of the physical processes that are important in transmitting a deforestation signal out of the tropics to the Northern Hemisphere extratropics in boreal winter. Using the Community Climate System Model, version 3 Integrated Biosphere Simulator (CCM3–IBIS) climate model and by imposing an exaggerated land surface forcing of complete tropical forest removal, the thermodynamic and dynamical atmospheric response is evaluated regionally within the tropics, globally as the climate signal propagates to the Northern Hemisphere, and then regionally in Eurasia where land–atmosphere feedbacks contribute to amplifying the climate signal and warming the surface and lower troposphere by 1–4 K. Model results indicate that removal of the tropical forests causes weakening of deep tropical convection that excites a Rossby wave train emanating northeastward away from the South American continent. Changes in European storm-track activity cause an intensification and northward shift in the Ferrel cell that leads to anomalous adiabatic warming over a broad region of Eurasia. Regional-scale land–atmosphere feedbacks are found to amplify the warming. While hypothetical, this approach illustrates the atmospheric mechanisms linking the tropics with Eurasia that may otherwise not be detectable with more realistic land-use change simulations.
Dynamical Mechanism for the Increase in Tropical Upwelling in the Lowermost Tropical Stratosphere during Warm ENSO Events
Authors: Calvo N. , Garcia R. R. , Randel W. J. , Marsh D. R. 
Published: March 2010

Abstract
The Brewer–Dobson circulation strengthens in the lowermost tropical stratosphere during warm El Niño–Southern Oscillation (ENSO) events. Dynamical analyses using the most recent version of the Whole Atmosphere Community Climate Model show that this is due mainly to anomalous forcing by orographic gravity waves, which maximizes in the Northern Hemisphere subtropics between 18 and 22 km, especially during the strongest warm ENSO episodes. Anomalies in the meridional gradient of temperature in the upper troposphere and lower stratosphere (UTLS) are produced during warm ENSO events, accompanied by anomalies in the location and intensity of the subtropical jets. This anomalous wind pattern alters the propagation and dissipation of the parameterized gravity waves, which ultimately force increases in tropical upwelling in the lowermost stratosphere. During cold ENSO events a similar signal, but of opposite sign, is present in the model simulations. The signals in ozone and water vapor produced by ENSO events in the UTLS are also investigated.
Was the North Pacific Wintertime Climate Less Stormy during the Mid-Holocene?
Authors: Chiang John C. H. , Fang Yue 
Published: March 2010

Abstract
Model evidence is presented to make the case that the midlatitude North Pacific wintertime transient eddy activity may have been significantly weaker during the mid-Holocene (∼6000 yr BP). A simulation of the mid-Holocene climate in an atmospheric general circulation model coupled to a reduced gravity ocean model showed significant reduction to transient eddy activity, up to 30% in the main storm-track region. The reduced baroclinic eddy activity is associated with basinwide climate changes over the northern and tropical Pacific, including a deepening of the Aleutian low, colder SSTs in the western and central North Pacific, a strengthening and southward shift of the subtropical jet, and a strengthened South Pacific convergence zone. These associated climate changes are consistently simulated across a range of Paleoclimate Modeling Intercomparison Project Phase II (PMIP2) coupled models forced with mid-Holocene climate forcings, suggesting they are a robust response to mid-Holocene orbital forcing. The authors link the mid-Holocene climate changes to two related modern-day analogs: (i) interannual variations in wintertime North Pacific storminess and (ii) the phenomenon of midwinter suppression whereby North Pacific transient eddy activity in today’s climate is reduced in midwinter. In both instances, the associated North Pacific climate conditions resemble those seen in the mid-Holocene simulations. While it remains to be seen which analog is dynamically more appropriate, the latter link—midwinter suppression—offers the simple physical interpretation that the mid-Holocene reduction in storminess is a consequence of a “more winterlike” climate resulting from the mid-Holocene precessional forcing.
Is Appropriate Management of Atrial Fibrillation in Primary Care a Utopia?
Authors: Lygidakis Charilaos , Argyriadou Stella , Lygera Anastasia 
Published: March 2010

Objective: The authors aimed at reporting on whether or not primary care doctors follow atrial fibrillation (AF) treatment protocols, and on the mental distress of such patients. Methods: A total of 138 patients with first detected or recurrent AF were examined in a health center. Demographic data were collected and their lifestyle and medical history for rhythm-related pathologies and chronic medication were investigated. Physical examination, electrocardiogram (EKG), and in selected cases, lab analysis were carried-out. CHADS2 index was used for assessing the stroke risk in patients with AF, while the General Health Questionnaire-12 (GHQ-12) for personal health perception was performed in all patients. Results: According to CHADS2 the majority of the patients had at least 1 risk factor and half of those receiving oral vitamin K antagonists presented an out-of-range international normalized ratio (INR). In 24 cases, patients used both aspirin and oral anticoagulants, while in 41 cases, medication was corrected according to index. GHQ-12 seemed to be significantly worse in paroxysmal and persistent cases, as well as in women with recurrent AF. Many paroxysmal AF patients under 75 years continued caffeine intake, whereas an extensive use of benzodiazepines was noticed in the majority of patients. Conclusions: Shortages and limitations of the peripheral or rural units and health centers and inadequate knowledge and application of the guidelines, seemed to be major factors responsible for mismanaging AF patients. More education in prehospital cardiology may contribute in improving management of arrhythmias in primary care.
c-Myc controls the development of CD8αα TCRαβ intestinal intraepithelial lymphocytes from thymic precursors by regulating IL-15–dependent survival
Authors: Jiang Wei , Ferrero Isabel , Laurenti Elisa , Trumpp Andreas , MacDonald H. Robson 
Published: March 2010

AbstractThe murine gut epithelium contains a large population of thymus-derived intraepithelial lymphocytes (IELs), including both conventional CD4+ and CD8αβ+ T cells (expressing T-cell receptor αβ [TCRαβ]) and unconventional CD8αα+ T cells (expressing either TCRαβ or TCRγδ). Whereas conventional IELs are widely accepted to arise from recirculation of activated CD4+ and CD8αβ+ T cells from the secondary lymphoid organs to the gut, the origin and developmental pathway of unconventional CD8αα IELs remain controversial. We show here that CD4-Cre-mediated inactivation of c-Myc, a broadly expressed transcription factor with a wide range of biologic activities, selectively impairs the development of CD8αα TCRαβ IELs. In the absence of c-Myc, CD4− CD8− TCRαβ+ thymic precursors of CD8αα TCRαβ IELs are present but fail to develop on adoptive transfer in immunoincompetent hosts. Residual c-Myc–deficient CD8αα TCRαβ IEL display reduced proliferation and increased apoptosis, which correlate with significantly decreased expression of interleukin-15 receptor subunits and lower levels of the antiapoptotic protein Bcl-2. Transgenic overexpression of human BCL-2 resulted in a pronounced rescue of CD8αα TCRαβ IEL in c-Myc–deficient mice. Taken together, our data support a model in which c-Myc controls the development of CD8αα TCRαβ IELs from thymic precursors by regulating interleukin-15 receptor expression and consequently Bcl-2–dependent survival.
Identification during the follow-up of time-dependent prognostic factors for the competing risks of death and blast phase in primary myelofibrosis: a study of 172 patients
Authors: Morel Pierre , Duhamel Alain , Hivert Benedicte , Stalniekiewicz Laure , Demory Jean-Loup , Dupriez Brigitte 
Published: March 2010

Abstract
The median survival of patients with primary myelofibrosis ranges from 3.5 to 5.5 years, and most patients die from cause related to the disease, including blast phase (BP, in 5%-30% of cases). Because identification of high-risk patients might use information collected during the clinical course, we assessed the prognostic value of time-dependent covariates for 2 competing risks (death and BP) in a series of 172 patients. Significant (P < .01) adverse time-dependent prognostic factors for the risk of death were the time to onset of anemia (hemoglobin < 100 g/L [10 g/dL]), leukocytosis (leukocyte count > 30 × 109/L), thrombocytopenia (platelet count < 150 × 109/L), presence of circulating blasts, intermediate-high or high International Working Group for Myelofibrosis Research and Treatment score, and time to splenectomy. The first 3 dependent covariates and the time to chemotherapy initiation (P = .05) were prognostic factors for the risk of BP. The prognostic effect of onset of leukocytosis was significantly more pronounced for BP than for death. Thus, occurrence during the follow-up of characteristics associated with an adverse prognostic value at diagnosis also influenced the risks of death and BP. Patients with leukocytosis should be closely monitored. These data might efficiently help to evaluate the severity of the disease before treatment decision during the clinical course.
Protein engineering of conger eel galectins by tracing of molecular evolution using probable ancestral mutants
Authors: Konno Ayumu , Yonemaru Shintarou , Kitagawa Atsushi , Muramoto Koji , Shirai Tsuyoshi , Ogawa Tomohisa 
Published: March 2010

AbstractBackgroundConger eel galectins, congerin I (ConI) and congerin II (ConII), show the different molecular characteristics resulting from accelerating evolution. We recently reconstructed a probable ancestral form of congerins, Con-anc. It showed properties similar to those of ConII in terms of thermostability and carbohydrate recognition specificity, although it shares a higher sequence similarity with ConI than ConII.ResultsIn this study, we have focused on the different amino acid residues between Con-anc and ConI, and have performed the protein engineering of Con-anc through site-directed mutagenesis, followed by the molecular evolution analysis of the mutants. This approach revealed the functional importance of loop structures of congerins: (1) N- and C-terminal and loop 5 regions that are involved in conferring a high thermostability to ConI; (2) loops 3, 5, and 6 that are responsible for stronger binding of ConI to most sugars; and (3) loops 5 and 6, and Thr38 residue in loop 3 contribute the specificity of ConI toward lacto-N-fucopentaose-containing sugars.ConclusionsThus, this methodology, with tracing of the molecular evolution using ancestral mutants, is a powerful tool for the analysis of not only the molecular evolutionary process, but also the structural elements of a protein responsible for its various functions.
Orchestrated transcription of biological processes in the marine picoeukaryote Ostreococcus exposed to light/dark cycles
Authors: Monnier Annabelle , Liverani Silvia , Bouvet Régis , Jesson Béline , Smith Jim Q , Mosser Jean , Corellou Florence , Bouget François-Yves 
Published: March 2010

Abstract

Background
Picoeukaryotes represent an important, yet poorly characterized component of marine phytoplankton. The recent genome availability for two species of Ostreococcus and Micromonas has led to the emergence of picophytoplankton comparative genomics. Sequencing has revealed many unexpected features about genome structure and led to several hypotheses on Ostreococcus biology and physiology. Despite the accumulation of genomic data, little is known about gene expression in eukaryotic picophytoplankton.

Results
We have conducted a genome-wide analysis of gene expression in Ostreococcus tauri cells exposed to light/dark cycles (L/D). A Bayesian Fourier Clustering method was implemented to cluster rhythmic genes according to their expression waveform. In a single L/D condition nearly all expressed genes displayed rhythmic patterns of expression. Clusters of genes were associated with the main biological processes such as transcription in the nucleus and the organelles, photosynthesis, DNA replication and mitosis.

Conclusions
Light/Dark time-dependent transcription of the genes involved in the main steps leading to protein synthesis (transcription basic machinery, ribosome biogenesis, translation and aminoacid synthesis) was observed, to an unprecedented extent in eukaryotes, suggesting a major input of transcriptional regulations in Ostreococcus. We propose that the diurnal co-regulation of genes involved in photoprotection, defence against oxidative stress and DNA repair might be an efficient mechanism, which protects cells against photo-damage thereby, contributing to the ability of O. tauri to grow under a wide range of light intensities.