bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes of HIV‐infected patients with Kaposi's sarcoma receiving nonnucleoside reverse transcriptase inhibitor‐based antiretroviral therapy in Uganda
Authors: Asiimwe FM , Moore DM , Were W , Nakityo R , Campbell J , Barasa A , Mermin J , Kaharuza F 
Published: November 2011

BackgroundClinical outcomes for patients with Kaposi's sarcoma (KS) using nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based highly active antiretroviral therapy (HAART) in resource‐limited settings have not previously been described.MethodsWe evaluated HIV‐infected patients aged ≥ 18 years, who initiated HAART in the Home‐Based AIDS Care (HBAC) project in Tororo, Uganda, between May 2003 and February 2008 and were diagnosed with KS at baseline or during follow‐up. We examined independent risk factors for having either prevalent or incident KS and risk factors for death among patients with KS.ResultsOf 1121 study subjects, 17 (1.5%) were diagnosed with prevalent KS and 18 (1.6%) with incident KS over a median of 56.1 months of follow‐up. KS was associated with male sex [adjusted odds ratio (AOR) 2.41; 95% confidence interval (CI) 1.20–4.86] and baseline CD4 cell count < 50 cells/μL (AOR 3.25; 95% CI 1.03–10.3). Eleven (65%) of 17 patients with prevalent KS and 13 (72%) of 18 patients with incident KS experienced complete regression (P = 0.137). Eighteen (64%) of 28 patients who remained on NNRTI‐based HAART experienced regression of their KS and six (86%) of seven patients who were switched to protease inhibitor‐containing HAART regimens had regression of their KS (P = 0.23). Mortality among those with KS was significantly associated with visceral disease (hazard ratio 19.22; 95% CI 2.42–152).ConclusionPrevalent or incident KS was associated with 30% mortality. The resolution of KS lesions among individuals who initiated HAART with NNRTI‐based regimens was similar to that found in studies using only protease inhibitor‐based HAART.
Use of L1, metalanguage, and discourse markers: L2 learners' regulation during individual task performance
Authors: Gánem‐Gutiérrez Gabriela Adela , Roehr Karen 
Published: November 2011

This study reports on an investigation into the use of L1, discourse markers, and metalanguage for regulatory purposes during individual task performance. The study involved nine L1 English university‐level learners of L2 Spanish. Drawing on thinkaloud protocols, the extent to which the participants used the three linguistic tools while completing a form‐focused task was investigated. The analysis reveals the importance of L1 and metalanguage as problem‐solving tools, while discourse markers appear to be valuable devices to structure and organize thought. The findings support the Vygotskian view regarding the social origins of individual cognition and provide further evidence of the pedagogical value of metalanguage and use of L1 to enable L2 learners to explore form‐meaning relationships and overcome specific language difficulties during task performance.El presente estudio informa sobre una investigación acerca del uso de la lengua materna (L1), los marcadores del discurso y el metalenguaje como herramientas lingüísticas de regulación durante la ejecución de tareas individuales. Nueve estudiantes de español como lengua extranjera (L1 inglés) a nivel universitario participaron en la investigación. Con el fin de obtener información acerca del uso de dichas herramientas lingüísticas se les pidió a los participantes que expresaran sus pensamientos verbalmente mientras completaban una tarea gramatical. El análisis revela la importancia del L1 y el metalenguaje como instrumentos para la resolución de problemas relacionados con la segunda lengua, mientras que los marcadores del discurso parecen ser de gran utilidad en términos cognitivos, por ejemplo para ayudar a organizar y estructurar el pensamiento. Los resultados apoyan el pensamiento de Vygotsky quien adjudicó orígenes sociales al desarrollo cognitivo. Nuestra investigación también demuestra el valor pedagógico del metalenguaje y del uso del L1 como herramientas que facilitan el descubrimiento de la interacción entre forma y significado en términos lingüísticos.
Cell–Cell Communication in the Kidney Microcirculation
Authors: SORENSEN CHARLOTTE MEHLIN , HOLSTEIN‐RATHLOU NIELS‐HENRIK 
Published: November 2011

Please cite this paper as: Sorensen CM, Holstein‐Rathlou N‐H. Cell–cell communication in the kidney microcirculation. Microcirculation 19: 451–460, 2012.AbstractIn the renal vasculature of humans, rats, and mice, at least four isoforms of Cx, Cxs 37, 40, 43, and 45 are expressed. In the ECs, Cx40 is the predominantly expressed Cx, whereas Cx45 is suggested to be expressed in the VSMCs. The preglomerular vasculature has a higher expression of Cxs than the postglomerular vasculature. Cxs form gap junctions between neighboring cells, and as in other organ systems, the major function of Cxs in the kidney appears to be mediation of intercellular communication. Cxs may also form hemichannels that allow cellular secretion of signaling molecules like ATP, and thereby mediate paracrine signaling. Renal Cxs facilitate vascular conduction, juxtaglomerlar apparatus calcium signaling, and enable ECs and VSMCs to communicate. Thus, current research suggests multiple roles for Cxs in important regulatory mechanisms within the kidney, including the renin‐angiotensin system, TGF, and salt and water homeostasis. Interestingly, changes in the activity of the renin‐angiotensin system or changes in blood pressure seem to affect the expression of the renal vascular Cxs. At the systemic level, renal Cxs may be involved in blood pressure regulation, and possibly in the pathogenesis of hypertension and diabetes.
Comparison of Plaque- and Enzyme-Linked Immunospot-Based Assays To Measure the Neutralizing Activities of Monoclonal Antibodies Specific to Domain III of Dengue Virus Envelope Protein
Authors: Liu Lidong , Wen Kun , Li Jie , Hu Dongmei , Huang Yanfen , Qiu Liwen , Cai Jianpiao , Che Xiaoyan 
Published: November 2011

ABSTRACTThe plaque reduction neutralization test (PRNT) is used widely to measure the neutralization activity of anti-dengue virus (DENV) antibodies, but it is time-consuming and labor-intensive and has low sample throughput. For fast and convenient measurement of neutralizing antibodies, especially in evaluating the efficiency of the DENV vaccines on a large scale, a new method is needed to replace PRNT. In recent decades, several microneutralization assays have been developed to overcome the limitations of PRNT. In the present study, we evaluated one of these, the enzyme-linked immunospot microneutralization test (ELISPOT-MNT), in comparison with PRNT. ELISPOT-MNT is performed in 96-well format, and the plaques are developed after 2 to 4 days using an ELISA to transform them into spots, which are detected automatically with an ELISPOT instrument. The assay is faster than PRNT, has a high throughput, and is more objective. We used 10 monoclonal antibodies (MAbs) against domain III of the DENV envelope protein (EDIII) to evaluate the two assays; all of these MAbs cross-react with all four serotypes of DENV as measured by immunofluorescence assay. The two neutralization assays were performed simultaneously to measure the 50% inhibitory concentration (IC50) of these MAbs. Using PRNT as the reference and treating IC50values higher than 50 μg/ml of MAbs as negative, ELISPOT-MNT showed a sensitivity of 95.6% and specificity of 88.24% when 10 MAbs were tested against four DENV serotype strains. A good correlation (R2= 0.672;P= 0.000) was observed between the two assays, making ELISPOT-MNT a potentially valuable method for measure of neutralizing antibodies against DENV.
Primary and Probable Secondary Dengue Virus (DV) Infection Rates in Relation to Age among DV IgM-Positive Patients Residing in the United States Mainland Versus the Caribbean Islands
Authors: Prince Harry E. , Yeh Cindy , Lapé-Nixon Mary 
Published: November 2011

ABSTRACT
Dengue virus (DV) primary infection and probable secondary infection rates in relation to patient age (years) were determined for DV IgM-positive U.S. mainland residents (presumed travelers to areas of DV endemicity) and Caribbean island (area of DV endemicity) residents by evaluating IgG status and IgG avidity. Regardless of place of residence, most patients ≤20 years old exhibited primary infection and most patients >60 years old exhibited probable secondary infection. Among patients 21 to 60 years old, the primary infection rate was markedly higher in U.S. residents.
Factor VII–Activating Protease Promotes the Proteolysis and Inhibition of Tissue Factor Pathway Inhibitor
Authors: Kanse Sandip M. , Declerck Paul J. , Ruf Wolfram , Broze George , Etscheid Michael 
Published: November 2011

Objective—
Factor VII–activating protease (FSAP) activates both factor VII and pro-urokinase and inhibits platelet-derived growth factor-BB, thus regulating hemostasis- and remodeling-associated processes in the vasculature. A genetic variant of FSAP (Marburg I polymorphism) results in low enzymatic activity and is associated with an enhanced risk of carotid stenosis and stroke. We postulate that there are additional substrates for FSAP that will help to explain its role in vascular biology and have searched for such a substrate.

Methods and Results—
Using screening procedures to determine the influence of FSAP on various hemostasis-related processes on endothelial cells, we discovered that FSAP inhibited tissue factor pathway inhibitor (TFPI), a major anticoagulant secreted by these cells. Proteolytic degradation of TFPI by FSAP could also be demonstrated by Western blotting, and the exact cleavage sites were determined by N-terminal sequencing. The Marburg I variant of FSAP had a diminished ability to inhibit TFPI. A monoclonal antibody to FSAP that specifically inhibited FSAP binding to TFPI reversed the inhibitory effect of FSAP on TFPI.

Conclusion—
The identification of TFPI as a sensitive substrate for FSAP increases our understanding of its role in regulating hemostasis and proliferative remodeling events in the vasculature.
Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria
Authors: Francischetti Ivo M.B. , Oliveira Carlo J. , Ostera Graciela R. , Yager Stephanie B. , Debierre-Grockiego Françoise , Carregaro Vanessa , Jaramillo-Gutierrez Giovanna , Hume Jen C.C. , Jiang Lubin , Moretz Samuel E. , Lin Christina K. , Ribeiro José M.C. , Long Carole A. , Vickers Brandi K. , Schwarz Ralph T. , Seydel Karl B. , Iacobelli Massimo , Ackerman Hans C. , Srinivasan Prakash , Gomes Regis B. , Wang Xunde , Monteiro Robson Q. , Kotsyfakis Michail , Sá-Nunes Anderson , Waisberg Michael 
Published: November 2011

Objective—
The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria.

Methods and Results—

DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (
Pf
-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-γ levels, and ameliorated clinical score (day 5) with a trend for increased survival.

Conclusion—
Therapeutic use of DF in malaria is proposed.
Fatty Acid-Induced Nuclear Translocation of Heparanase Uncouples Glucose Metabolism in Endothelial Cells
Authors: Wang Fang , Wang Ying , Zhang Dahai , Puthanveetil Prasanth , Johnson James D. , Rodrigues Brian 
Published: November 2011

Objective—
Heparanase is an endoglycosidase that specifically cleaves carbohydrate chains of heparan sulfate. We have recently reported that high fatty acid increased the nuclear content of endothelial heparanase. Here, we examined the mechanism and the consequences behind this nuclear translocation of heparanase.

Methods and Results—
Bovine coronary artery endothelial cells were grown to confluence and incubated with palmitic acid. Palmitic acid induced rapid nuclear accumulation of heparanase that was dependent on Bax activation and lysosome permeabilization. Heat shock protein 90 was an important mediator of palmitic acid-induced shuttling of heparanase to the nucleus. Nuclear heparanase promoted cleavage of heparan sulfate, a potent inhibitor of histone acetyltransferase activity and gene transcription. A TaqMan gene expression assay revealed an increase in genes related to glucose metabolism and inflammation. In addition, glycolysis was uncoupled from glucose oxidation, resulting in accumulation of lactate.

Conclusion—
The results presented in this study demonstrate that fatty acid can provoke lysosomal release of heparanase, its nuclear translocation, activation of genes controlling glucose metabolism, and accumulation of lactate. Given that lactate and inflammation have been implicated in the progression of atherosclerosis, our data may serve to reduce the associated cardiovascular complications seen during diabetes.
Brain Natriuretic Peptide Predicts Functional Outcome in Ischemic Stroke
Authors: Rost Natalia S. , Biffi Alessandro , Cloonan Lisa , Chorba John , Kelly Peter , Greer David , Ellinor Patrick , Furie Karen L. 
Published: November 2011

Background and Purpose—
Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic stroke and increased poststroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke.

Methods—
We measured BNP in consecutive patients aged ≥18 years admitted to our stroke unit between 2002 to 2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using Trial of ORG 10172 in Acute Stroke Treatment criteria. Outcomes were measured as 6-month modified Rankin Scale score (“good outcome”=0–2 versus “poor”) as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared with clinical model alone was assessed by comparing receiver operating characteristic curves.

Results—

Of 569 patients with ischemic stroke, 46% were female; mean age was 67.9±15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (
P
<0.0001) and left atrial dilatation (
P
<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR, 0.64; 95% CI, 0.41–0.98) and increased the odds of death (OR, 1.75; 95% CI, 1.36–2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (
P
=0.013) and mortality (
P
<0.03) after cardioembolic stroke.

Conclusions—
Serum BNP levels are strongly associated with cardioembolic stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with cardioembolic stroke.
Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes
Authors: Madhusudhan Thati , Wang Hongjie , Straub Beate K. , Gröne Elisabeth , Zhou Qianxing , Shahzad Khurrum , Müller-Krebs Sandra , Schwenger Vedat , Gerlitz Bruce , Grinnell Brian W. , Griffin John H. , Reiser Jochen , Gröne Hermann-Josef , Esmon Charles T. , Nawroth Peter P. , Isermann Berend 
Published: November 2011

AbstractThe cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a protease-activated receptor-1 (PAR-1) and endothelial protein C receptor-dependent mechanism. Conversely, the signaling mechanism through which aPC protects podocytes remains unknown. While exploring the latter, we identified a novel aPC/PAR-dependent cytoprotective signaling mechanism. In podocytes, aPC inhibits apoptosis through proteolytic activation of PAR-3 independent of endothelial protein C receptor. PAR-3 is not signaling competent itself as it requires aPCinduced heterodimerization with PAR-2 (human podocytes) or PAR-1 (mouse podocytes). This cytoprotective signaling mechanism depends on caveolin-1 dephosphorylation. In vivo aPC protects against lipopolysaccharide-induced podocyte injury and proteinuria. Genetic deletion of PAR-3 impairs the nephroprotective effect of aPC, demonstrating the crucial role of PAR-3 for aPC-dependent podocyte protection. This novel, aPC-mediated interaction of PARs demonstrates the plasticity and cell-specificity of cytoprotective aPC signaling. The evidence of specific, dynamic signaling complexes underlying aPC-mediated cytoprotection may allow the design of cell type specific targeted therapies.
The effect of walking on falls in older people: the 'Easy Steps to Health' randomized controlled trial study protocol
Authors: Voukelatos Alexander , Merom Dafna , Rissel Chris , Sherrington Cathie , Watson Wendy , Waller Karen 
Published: November 2011

Abstract

Background
Falls in older people continue to be a major public health issue in industrialized countries. Extensive research into falls prevention has identified exercise as a proven fall prevention strategy. However, despite over a decade of promoting physical activity, hospitalisation rates due to falls injuries in older people are still increasing. This could be because efforts to increase physical activity amongst older people have been unsuccessful, or the physical activity that older people engage in is insufficient and/or inappropriate. The majority of older people choose walking as their predominant form of exercise. While walking has been shown to lower the risk of many chronic diseases its role in falls prevention remains unclear. This paper outlines the methodology of a study whose aims are to determine: if a home-based walking intervention will reduce the falls rate among healthy but inactive community-dwelling older adults (65 + years) compared to no intervention (usual activity) and; whether such an intervention can improve risk factors for falls, such as balance, strength and reaction time.

Methods/Design
This study uses a randomised controlled trial design.
A total of 484 older people exercising less than 120 minutes per week will be recruited through the community and health care referrals throughout Sydney and neighboring regions. All participants are randomised into either the self-managed walking program group or the health-education waiting list group using a block randomization scheme.
Outcome measures include prospective falls and falls injuries, quality of life, and physical activity levels. A subset of participants (n = 194) will also receive physical performance assessments comprising of tests of dynamic balance, strength, reaction time and lower limb functional status.

Discussion
Certain types of physical activity can reduce the risk of falls. As walking is already the most popular physical activity amongst older people, if walking is shown to reduce falls the public health implications could be enormous. Conversely, if walking does not reduce falls in older people, or even puts older people at greater risk, then health resources targeting falls prevention need to be invested elsewhere.

Trial Registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000380099
The redundancy of NMR restraints can be used to accelerate the unfolding behavior of an SH3 domain during molecular dynamics simulations
Authors: Duclert-Savatier Nathalie , Martínez Leandro , Nilges Michael , Malliavin Thérèse E 
Published: November 2011

1 Abstract

Background
The simulation of protein unfolding usually requires recording long molecular dynamics trajectories. The present work aims to figure out whether NMR restraints data can be used to probe protein conformations in order to accelerate the unfolding simulation. The SH3 domain of nephrocystine (nph SH3) was shown by NMR to be destabilized by point mutations, and was thus chosen to illustrate the proposed method.

Results
The NMR restraints observed on the WT nph SH3 domain were sorted from the least redundant to the most redundant ones. Protein NMR conformations were then calculated with: (i) the set full including all NMR restraints measured on nph SH3, (ii) the set reduced where the least redundant restraints with respect to the set full were removed, (iii) the sets random where randomly picked-up restraints were removed. From each set of conformations, we recorded series of 5-ns MD trajectories. The β barrel architecture of nph SH3 in the trajectories starting from sets (i) and (iii) appears to be stable. On the contrary, on trajectories based on the set (ii), a displacement of the hydrophobic core residues and a variation of the β barrel inner cavity profile were observed. The overall nph SH3 destabilization agrees with previous experimental and simulation observations made on other SH3 domains. The destabilizing effect of mutations was also found to be enhanced by the removal of the least redundant restraints.

Conclusions
We conclude that the NMR restraint redundancy is connected to the instability of the SH3 nph domain. This restraint redundancy generalizes the contact order parameter, which is calculated from the contact map of a folded protein and was shown in the literature to be correlated to the protein folding rate. The relationship between the NMR restraint redundancy and the protein folding is also reminiscent of the previous use of the Gaussian Network Model to predict protein folding parameters.
Main-duct intraductal papillary mucinous adenoma of the pancreas
Authors: Takuma Kensuke , Kamisawa Terumi , Tabata Taku , Kurata Masanao , Honda Goro , Horiguchi Shin-ichiro 
Published: November 2011

Abstract

Background
The prevalence of carcinoma in main-duct intraductal papillary mucinous neoplasm (IPMN) is high, and surgical resection is recommended for all patients with a main-duct IPMN.

Results
A main-duct IPMN with typical imagings including protruding lesions in the dilated main pancreatic duct was resected, but the histology was intraductal papillary mucinous adenoma of the pancreas.

Discussion
It has been reported that the presence of mural nodules and dilatation of MPD are significantly higher in malignant IPMNs. The presented case had protruding lesions in the dilated main pancreatic duct on endoscopic ultrasonography, but the histology was adenoma.

Conclusion
Preoperative distinction between benign and malignant IPMNs is difficult.