bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Darunavir/Ritonavir and Rifabutin Coadministered in HIV-Negative Healthy Volunteers
Authors: Sekar Vanitha , Lavreys Ludo , Van de Casteele Tom , Berckmans Cindy , Spinosa-Guzman Sabrina , Vangeneugden Tony , De Pauw Martine , Hoetelmans Richard 
Published: July 2010

ABSTRACT

The drug-drug interaction between rifabutin (RFB) and darunavir/ritonavir (DRV/r) was examined in a randomized, three-way crossover study of HIV-negative healthy volunteers who received DRV/r 600/100 mg twice a day (BID) (treatment A), RFB 300 mg once a day (QD) (treatment B), and DRV/r 600/100 mg BID plus RFB 150 mg every other day (QOD) (treatment C). The sequence of treatments was randomized, and each treatment period lasted 12 days. Full pharmacokinetic profiles were determined for DRV, ritonavir, and RFB and its active metabolite, 25-
O
-desacetylrifabutin (desRFB), on day 13. The DRV and ritonavir areas under the plasma concentration-time curve from zero to 12 h (AUC
12h
) increased by 57% and 66%, respectively, in the presence of RFB. The RFB exposure was comparable between treatment with RFB QD alone (treatment B) and treatment with DRV/r plus RFB QOD (treatment C); however, based on least-square means ratios, the minimum plasma concentration (
C
min
) increased by 64% and the maximum plasma concentration (
C
max
) decreased by 28%, respectively. The exposure (AUC within the dosage interval and at steady state [AUC
τ
]) to desRFB was considerably increased (by 881%) following treatment with DRV/r/RFB. The exposure to the parent drug plus the metabolite increased 1.6-fold in the presence of DRV/r. Adverse events (AEs) were more commonly reported during combined treatment (83% versus 44% for RFB and 28% for DRV/r); similarly, grade 3-4 AEs occurred in 17% versus 11% and 0%, respectively, of volunteers. Eighteen of 27 volunteers (66.7%) prematurely discontinued the trial; all volunteers discontinuing for safety reasons (
n
= 9) did so during RFB treatment phases. These results suggest that DRV/r may be coadministered with RFB with a dose adjustment of RFB to 150 mg QOD and increased monitoring for RFB-related AEs. Based on the overall safety profile of DRV/r, no dose adjustment of DRV/r is considered to be warranted. Given the safety profile seen with the combination of RFB with a boosted protease inhibitor in this and other studies, it is not recommended to conduct further studies with this combination in healthy volunteers.
How a service-oriented architecture may change the software development process
Authors: Haines Marc N. , Rothenberger Marcus A. 
Published: July 2010

Introduction

Software development practices have evolved substantially during the past decade. As so called "agile" approaches have gained more acceptance and applications have become progressively more distributed in terms of their physical execution and the development of components, the service-oriented approach to IT architecture has become an important alternative to traditional software development. Another impetus for the trend to a Service-Oriented Architecture (SOA) is provided by enterprise system vendors as they are incorporating the service-oriented paradigm into their products. Substantial efforts related to open standards (such as Web service standards) and open source products (such as open source enterprise service bus, development tools) are further driving a service-oriented approach for information systems.
A key question is whether SOA adopters are going to be ready for this change and whether they can provide a technical and an organizational environment in which SOA-related technologies can be leveraged to their full potential. There is some indication that currently this may not be the case. In fact, some organizations that have embarked on SOA-related projects early have experienced disappointments. As with other technology waves, the important question is not whether SOA is inherently a good or a bad idea, but rather how it can be done right in a given context. This article tries to answer this question with respect to the software development process.
While much of the literature, both in academia and industry, has focused on business implications of SOA, technological realization, architectural issues, and implementation guidelines, few publications have addressed the impact of SOA on the software development process and its methodology. As with any organizational change, modifications to software development processes or practices entail switching cost. Therefore, individuals as well as organizations are inclined to stay with "proven" methodologies, although adjustments based on task requirements and technology characteristics should be key drivers for the methodology choice and are needed to help adopters leverage the full potential of SOA.
This article examines the differences and discusses which parts of development process and methodology may require adjustments to effectively leverage a SOA. It presents the results of a field study suggesting changes to software development practices that are necessary to accommodate the unique properties of the service-oriented approach.
Historicism as a Cultural Pattern: Practising a Mode of Thought
Authors: Fulda Daniel 
Published: July 2010

AbstractWhat is the basis for the enormous success of Historicism? In my paper I attempt to answer this question by deploying the concept of the cultural pattern. A ‘cultural pattern’ may be defined as the connection of concepts and practices which have gained a relative perpetuity through cultural habitualization. Cultural patterns include a combination of interpretative schemes according to which the world can be categorized, structured and interpreted with individual or social practices which either develop out of, or follow these schemes. Because they combine concepts and practices in a significant manner they gain a contour which enables the creation of communicative addressability, practical appropriation and discursive analysis and hence the creation of a long-term exemplary status. A cultural pattern according to this definition has a relative stability and an observable effect over a long period of time, but which is simultaneously liable to permanent actualization and adaption. Historicism has been considered to be a basic thought-pattern of modernity since Troeltsch, Meinecke and Koselleck; defining Historicism as a cultural pattern can help to explain its long-term effectiveness and its continuing productivity to the present day.
Two Kinds of Historicism: Resurrection and Restoration in French Historical Painting
Authors: Bann Stephen 
Published: July 2010

AbstractThe historicist approach is rarely challenged by art historians, who draw a clear distinction between art history and the present-centred pursuit of art criticism. The notion of the ‘period eye’ offers a relevant methodology. Bearing this in mind, I examine the nineteenth-century phase in the development of history painting, when artists started to take trouble over the accuracy of historical detail, instead of repeating conventions for portraying classical and biblical subjects. This created an unprecedented situation at the Paris Salon, where such representations of history could be experienced as a collective ‘dream-work’, in Freud’s sense. In France, this new pictorial language dates back to the aftermath of the Revolution, and the activities of the ‘Lyon School’. Two artists, Richard and Révoil, were its leading proponents. However their initial closeness has obscured the differences in their approach to the past. Substituting for Freud’s ‘condensation’ and ‘displacement’ the concepts of ‘Resurrection’ and ‘Restoration’, I analyse the pictorial language of the two painters, taking two works as examples. The conclusion is that Révoil, also a collector, was a precursor of the historical museum, which convinces through accumulating objects. Richard, however, employs technical and rhetorical devices to evoke empathetic reactions, and anticipates the illusionism of cinema.
Mechanisms underlying γδ T-cell subset perturbations in SIV-infected Asian rhesus macaques
Authors: Harris Levelle D. , Klatt Nichole R. , Vinton Carol , Briant Judith A. , Tabb Brian , Ladell Kristin , Lifson Jeffrey , Estes Jacob D. , Price David A. , Hirsch Vanessa M. , Brenchley Jason M. 
Published: July 2010

AbstractT cells that express the γδ T-cell receptor, which recognize microbial or stress-induced antigens, represent a minority of blood T cells but constitute a major proportion of intraepithelial lymphocytes in the gastrointestinal mucosa. As microbial products have been shown to translocate from the gastrointestinal tract into circulation in chronically HIV/Simian immunodeficiency virus (SIV)–infected individuals, we conducted a study of Vδ1 and Vδ2 T-cell frequency, phenotype, and function in blood, spleen, lymph nodes, gastrointestinal mucosa, and bronchoalveolar lavage of uninfected and chronically SIVsmE543-infected rhesus macaques (RMs). We found: (1) SIV-associated inversion of Vδ1/Vδ2 T cells occurs in blood and in several tissues; (2) γδ T cells are not infected by SIV in vivo; (3) the Vδ1/Vδ2 inversion involves expansion of Vδ1 T cells; (4) expanded Vδ1 T cells are phenotypically and functionally different from Vδ1 T cells from uninfected RMs; and (5) the stimulus underlying expansion of Vδ1 T cells appears to be microbial translocation. These data highlight the importance of microbial translocation–induced immune activation in chronically infected individuals and provide new insights into an immune dysregulation phenomenon that is a hallmark of HIV/SIV infection. These findings may lead to novel therapeutic interventions that improve the immune responses against microbial antigens, and thus, decrease microbial translocation–induced im-mune activation.
Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo
Authors: Seiffert Martina , Schulz Angela , Ohl Sibylle , Döhner Hartmut , Stilgenbauer Stephan , Lichter Peter 
Published: July 2010

AbstractAccumulation of leukemic cells in patients with chronic lymphocytic leukemia (CLL) is due to prolonged cell survival rather than increased proliferation. Survival of CLL cells depends on microenvironmental factors. Even though long-lived in vivo, CLL cells rapidly die by spontaneous apoptosis in vitro unless cocultured with stromal cells or their conditioned medium. In the present study, we show that survival of CLL cells is maintained in high cell density cultures, where the main prosurvival activity is delivered by monocytes. Cytokine array and enzyme-linked immunosorbent assay studies revealed increased expression of soluble CD14 by monocytes in the presence of CLL cells. The addition of recombinant soluble CD14 to primary CLL cells resulted in significantly increased cell survival rates, which were associated with higher activity nuclear factor κB. Quantification of serum levels of soluble CD14 revealed abnormally high levels of this protein in CLL patients, indicating a potential role of soluble CD14 in vivo. In summary, the presented data show that monocytes help in the survival of CLL cells by secreting soluble CD14, which induces nuclear factor κB activation in these cells, and that CLL cells actively shape their microenvironment by inducing CD14 secretion in accessory monocytes.
Price regulation, new entry, and information shock on pharmaceutical market in Taiwan: a nationwide data-based study from 2001 to 2004
Authors: Hsiao Fei-Yuan , Tsai Yi-Wen , Huang Weng-Foung 
Published: July 2010

Abstract

Background
Using non-steroidal anti-inflammatory drugs (NSAIDs) as a case, we used Taiwan's National Health Insurance (NHI) database, to empirically explore the association between policy interventions (price regulation, new drug entry, and an information shock) and drug expenditures, utilization, and market structure between 2001 and 2004.

Methods
All NSAIDs prescribed in ambulatory visits in the NHI system during our study period were included and aggregated quarterly. Segmented regression analysis for interrupted time series was used to examine the associations between two price regulations, two new drug entries (cyclooxygennase-2 inhibitors) and the rofecoxib safety signal and expenditures and utilization of all NSAIDs. Herfindahl index (HHI) was applied to further examine the association between these interventions and market structure of NSAIDs.

Results
New entry was the only variable that was significantly correlated with changes of expenditures (positive change, p = 0.02) and market structure of the NSAIDs market in the NHI system. The correlation between price regulation (first price regulation, p = 0.62; second price regulation, p = 0.26) and information shock (p = 0.31) and drug expenditure were not statistically significant. There was no significant change in the prescribing volume of NSAIDs per rheumatoid arthritis (RA) or osteoarthritis (OA) ambulatory visit during the observational period. The market share of NSAIDs had also been largely substituted by these new drugs up to 50%, in a three-year period and resulted in a more concentrated market structure (HHI 0.17).

Conclusions
Our empirical study found that new drug entry was the main driving force behind escalating drug spending, especially by altering the market share.
Increased expression of cardiac IL-17 after burn
Authors: Oppeltz Richard F , Zhang Qiong , Rani Meenakshi , Sasaki Jennifer R , Schwacha Martin G 
Published: July 2010

Abstract

Background
Cardiac dysfunction is a common complication associated with major burns. While recent findings have linked the Th-17 T-cell response to the development of autoimmune myocarditis, the role of IL-17 and the Th-17 T-cell response in the development of post-burn cardiac dysfunction remains unknown.

Methods
Male C57BL/6 mice were subjected to a major burn (3rd degree, 25% TBSA) or sham treatment. Three hours after injury plasma and tissue (i.e., heart, lung, liver, small intestine) samples were collected and analyzed for the expression of Th-17 cytokine (i.e., IL-6, IL-17, IL-22, IL-23, TGF-β) levels by ELISA.

Results
Cardiac tissue levels of the Th-17 cytokines, IL-6, IL-17 and IL-22 were significantly elevated at 3 hrs after burn as compared to sham levels. IL-17 was analyzed 1, 3 and 7 days after burn and showed a return to baseline levels and without a difference in the burn group. Burn-induced alterations in the level of these cytokines in plasma or other tissues were not evident. The cardiac Th-17 cytokine response after burn injury was specific, as cardiac levels of Th-1 (IFN-γ) and Th-2 (IL-10) cytokines were not significantly affected after injury. The cardiac Th-17 response correlated with a significant increase in Troponin levels at 3 hr. after burn.

Conclusion
These findings indicate that early after burn, cardiac tissue is associated with significantly elevated levels of Th-17 cytokines. The early Th-17 response after burn appears to be specific for cardiac tissue and may promote myocardial inflammation and dysfunction associated with this form of trauma.
Novel O-palmitolylated beta-E1 subunit of pyruvate dehydrogenase is phosphorylated during ischemia/reperfusion injury
Authors: Folmes Clifford DL , Sawicki Grzegorz , Cadete Virgilio JJ , Masson Grant , Barr Amy J , Lopaschuk Gary D 
Published: July 2010

Abstract

Background
During and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized.

Results
2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls. Of the five proteins with the greatest change in abundance, two were increased (long chain acyl-coenzyme A dehydrogenase (48 ± 1 versus 39 ± 3 arbitrary units, n = 3, P < 0.05) and α subunit of ATP synthase (189 ± 15 versus 113 ± 23 arbitrary units, n = 3, P < 0.05)), while two were decreased (24 kDa subunit of NADH-ubiquinone oxidoreductase (94 ± 7 versus 127 ± 9 arbitrary units, n = 3, P < 0.05) and D subunit of ATP synthase (230 ± 11 versus 368 ± 47 arbitrary units, n = 3, P < 05)). Two forms of pyruvate dehydrogenase βE1 subunit, the rate-limiting enzyme for glucose oxidation, were also identified. The protein level of the more acidic form of pyruvate dehydrogenase was reduced during reperfusion (37 ± 4 versus 56 ± 7 arbitrary units, n = 3, P < 05), while the more basic form remained unchanged. The more acidic isoform was found to be O-palmitoylated, while both isoforms exhibited ischemia/reperfusion-induced phosphorylation. In silico analysis identified the putative kinases as the insulin receptor kinase for the more basic form and protein kinase Cζ or protein kinase A for the more acidic form. These modifications of pyruvate dehydrogenase are associated with a 35% decrease in glucose oxidation during reperfusion.

Conclusions
Cardiac ischemia/reperfusion induces significant changes to a number of metabolic proteins of the mitochondrial proteome. In particular, ischemia/reperfusion induced the post-translational modification of pyruvate dehydrogenase, the rate-limiting step of glucose oxidation, which is associated with a 35% decrease in glucose oxidation during reperfusion. Therefore these post-translational modifications may have important implications in the regulation of myocardial energy metabolism.
Circumvention of multi-drug resistance of cancer cells by Chinese herbal medicines
Authors: Chai Stella , To Kenneth KW , Lin Ge 
Published: July 2010

Abstract
Multi-drug resistance (MDR) of cancer cells severely limits therapeutic outcomes. A proposed mechanism for MDR involves the efflux of anti-cancer drugs from cancer cells, primarily mediated by ATP-binding cassette (ABC) membrane transporters including P-glycoprotein. This article reviews the recent progress of using active ingredients, extracts and formulae from Chinese medicine (CM) in circumventing ABC transporters-mediated MDR. Among the ABC transporters, Pgp is the most extensively studied for its role in MDR reversal effects. While other MDR reversal mechanisms remain unclear, Pgp inhibition is a criterion for further mechanistic study. More mechanistic studies are needed to fully establish the pharmacological effects of potential MDR reversing agents.
Post-coital intra-cerebral venous hemorrhage in a 78-year-old man with jugular valve incompetence: a case report
Authors: Albano Beatrice , Gandolfo Carlo , Del Sette Massimo 
Published: July 2010

Abstract

Introduction
Spontaneous intra-cerebral hemorrhage can occur in patients with venous disease due to obstructed venous outflow.

Case presentation
We report the case of a 78-year-old Caucasian man with jugular valve incompetence who experienced an intra-cerebral temporo-occipital hemorrhage following sexual intercourse. He had no other risk factors for an intra-cerebral hemorrhage.

Conclusions
To the best of our knowledge, this is the first case of intra-cerebral hemorrhage due to jugular valve incompetence in association with the physical exertion associated with sexual intercourse.
Development and description of GETT: a Genetic testing Evidence Tracking Tool
Authors: Rousseau François , Lindsay Carmen , Charland Marc , Labelle Yves , Bergeron Jean , Blancquaert Ingeborg , Delage Robert , Gilfix Brian , Miron Michel , Mitchell Grant A. , Oligny Luc , Pazzagli Mario , Mamotte Cyril , Payne Deborah 
Published: July 2010

Abstract

Background: The completion of the Human Genome Project has increased the pace of discovery of genetic markers for disease. Despite tremendous efforts in fundamental research, clinical applications still lag behind expectations, partly due to the lack of effective tools to systematically search for and summarize published data relative to the clinical assessment of new diagnostic molecular tests.

Methods: Through a collaborative process using published tools and an expert panel, we developed a detailed checklist of the evidence that needs to be collected or produced to evaluate the potential usefulness of a new molecular diagnostic test. This tool is called GETT, for Genetic testing Evidence Tracking Tool.

Results: GETT allows 1) researchers to summarize the current evidence and to identify knowledge gaps for further research and; 2) stakeholders to collect data related to a given molecular test and improve their decision-making process. GETT comprises 72 clearly defined items/questions, grouped into 10 categories and 26 sub-themes, including an overview of disease epidemiology and genetics, the available diagnostic tools, and their analytical and clinical performances, availability of quality control programs, laboratory and clinical best practice guidelines, clinical utility, and impact on health care and psycho-social, ethical and legal implications. It also includes a summary of the evidence available and attempts to prioritise knowledge gaps related to the testing. We also compare GETT to other existing frameworks.

Conclusions: This systematic evidence-based tracking tool, which is more detailed than existing frameworks and provides clear definition for each item, will help streamline collection of the available evidence to appraise the potential for clinical application of new molecular diagnostic tests and prioritize research to produce the evidence-base relative to the clinical implementation of molecular diagnostic tests.
Clin Chem Lab Med 2010;48:1397–407.
The Effect of Forest Litter Removal Upon the Structure of the Mineral Soil
Authors: Lunt Herbert A. 
Published: July 2010

AbstractThe beneficial effect of forest litter, and the detrimental effect of its removal upon soil structure has been observed by the writer on several occasions. Measurements of the structure by aggregate analysis of soils in lysimeter tanks under red pine where naturally an excellent mull structure exists, have shown that where the soil has been kept bare of litter for a period of three and one‐half years, the amount of aggregates in the first inch has decreased about 40% in comparison with soil retaining its natural litter cover. Between the one and three‐inch depths, the decrease was between eleven and twenty‐four per cent.In the pan lysimeters in which the soils were not disturbed in any way, removal of the litter over a two and one‐half year period reduced the aggregate structure of the first inch by 36% to 58% depending upon the method used, and in 1 to 3‐inch depth by 5% to 23%.In cases where the natural soil structure is less favorable, removal of the litter may or may not be detrimental to soil structure, depending upon the effect of such treatment upon ground cover and lesser vegetation.