bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases
Authors: Arendt Wiebke , Hebecker Stefanie , Jäger Sonja , Nimtz Manfred , Moser Jürgen 
Published: January 2012

ABSTRACTThe specific aminoacylation of the phospholipid phosphatidylglycerol (PG) with alanine or with lysine catalyzed by aminoacyl-phosphatidylglycerol synthases (aaPGS) was shown to render various organisms less susceptible to antibacterial agents. This study makes use ofPseudomonas aeruginosachimeric mutant strains producing lysyl-phosphatidylglycerol (L-PG) instead of the naturally occurring alanyl-phosphatidylglycerol (A-PG) to study the resulting impact on bacterial resistance. Consequences of such artificial phospholipid composition were studied in the presence of an overall of seven antimicrobials (β-lactams, a lipopeptide antibiotic, cationic antimicrobial peptides [CAMPs]) to quantitatively assess the effect of A-PG substitution (with L-PG, L-PG and A-PG, increased A-PG levels). For the employed Gram-negativeP. aeruginosamodel system, an exclusive charge repulsion mechanism does not explain the attenuated antimicrobial susceptibility due to PG modification. Additionally, the specificity of nine orthologous aaPGS enzymes was experimentally determined. The newly characterized protein sequences allowed for the establishment of a significant group of A-PG synthase sequences which were bioinformatically compared to the related group of L-PG synthesizing enzymes. The analysis revealed a diverse origin for the evolution of A-PG and L-PG synthases, as the specificity of an individual enzyme is not reflected in terms of a characteristic sequence motif. This finding is relevant for future development of potential aaPGS inhibitors.
Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial
Authors: Lötvall J , Bakke P S , Bjermer L , Steinshamn S , Scott-Wilson C , Crim C , Sanford L , Haumann B 
Published: January 2012

BackgroundFluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β2agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma.Trial designA multicentre, randomised, double-blind, parallel-group, placebo-controlled study.MethodsParticipants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0–4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23–24 h postdose; day 29) and wm FEV1(0–4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment.Results60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0–4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI −3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1(mean difference 183 ml) and 0–4 h postdose wm FEV1(mean difference 236 ml).ConclusionFF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.Trial registration numberclinical trials.gov—NCT00731822.
Design and rationale of the tobacco, exercise and diet messages (TEXT ME) trial of a text message-based intervention for ongoing prevention of cardiovascular disease in people with coronary disease: a randomised controlled trial protocol: Figure 1
Authors: Chow C K , Redfern J , Thiagalingam A , Jan S , Whittaker R , Hackett M , Graves N , Mooney J , Hillis G S 
Published: January 2012

BackgroundAlthough supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease, providing access to such interventions is a major challenge. This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk.Methods and analysisRandomised controlled trial with 6 months of follow-up to evaluate the feasibility, acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care. A total of 720 patients with coronary artery disease will be randomised to either standard care or the TEXT ME intervention. The intervention group will receive multiple weekly text messages that provide information, motivation, support to quit smoking (if relevant) and recommendations for healthy diets and exercise. The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months. Secondary end points include a change in systolic blood pressure, smoking status, quality of life, medication adherence, waist circumference, physical activity levels, nutritional status and mood at 6 months. Process outcomes related to acceptability and feasibility of TEXT ME will also be collected.Ethics and disseminationPrimary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee—Westmead. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences.Clinical trials registration numberACTRN12611000161921.
A clinical approach to paediatric acid–base disorders
Authors: Carmody J Bryan , Norwood Victoria F 
Published: January 2012

AbstractAcid–base disorders are common in pediatric patients. We present a simple methodology for assessing both simple and complex acid–base disorders that is applicable to patients of all ages, and focus specifically on the usefulness of this approach in the pediatric patient. The application of four simple rules in sequence will define even the most complicated acid–base disturbance. However, because acid–base disorders are manifestations of systemic disorders, the primary value of characterizing them is that each generates a unique differential diagnosis. For each of the cardinal acid base disorders, the common and clinically-relevant causes in pediatric patients are explored. Additional diagnostic tools (including the serum anion gap, the delta–delta, the alveolar-arterial gradient, urine anion gap, and urine chloride), certain easily-recalled mnemonics, and empiric rules of thumb are also useful in specific situations. The treatment of acid–base disturbances is also considered, though treatment is generally best directed at the underlying disorder.
CK2 Inhibitor CX-4945 Suppresses DNA Repair Response Triggered by DNA-Targeted Anticancer Drugs and Augments Efficacy: Mechanistic Rationale for Drug Combination Therapy
Authors: Siddiqui-Jain Adam , Bliesath Joshua , Macalino Diwata , Omori Mayuko , Huser Nanni , Streiner Nicole , Ho Caroline B. , Anderes Kenna , Proffitt Chris , O'Brien Sean E. , Lim John K. C. , Von Hoff Daniel D. , Ryckman David M. , Rice William G. , Drygin Denis 
Published: January 2012

Abstract
Drug combination therapies are commonly used for the treatment of cancers to increase therapeutic efficacy, reduce toxicity, and decrease the incidence of drug resistance. Although drug combination therapies were originally devised primarily by empirical methods, the increased understanding of drug mechanisms and the pathways they modulate provides a unique opportunity to design combinations that are based on mechanistic rationale. We have identified protein kinase CK2 as a promising therapeutic target for combination therapy, because CK2 regulates not just one but many oncogenic pathways and processes that play important roles in drug resistance, including DNA repair, epidermal growth factor receptor signaling, PI3K/AKT/mTOR signaling, Hsp90 machinery activity, hypoxia, and interleukin-6 expression. In this article, we show that CX-4945, a clinical stage selective small molecule inhibitor of CK2, blocks the DNA repair response induced by gemcitabine and cisplatin and synergizes with these agents in models of ovarian cancer. Mechanistic studies show that the enhanced activity is a result of inactivation of XRCC1 and MDC1, two mediator/adaptor proteins that are essential for DNA repair and that require phosphorylation by CK2 for their function. These data position CK2 as a valid pharmacologic target for intelligent drug combinations and support the evaluation of CX-4945 in combination with gemcitabine and platinum-based chemotherapeutics in the clinical setting. Mol Cancer Ther; 11(4); 994–1005. ©2012 AACR.
Statistical Analysis of Chinese Phonemic Contrast
Authors: Yu Shuiyuan , Xu Chunshan , Liu Haitao , Chen Yudong 
Published: January 2012

Abstract
Two phonemes that may induce minimal pairs constitute a phonemic contrast. Some phonemic contrasts may disappear for various reasons, which, nevertheless, does not seem to seriously impede linguistic communication. Does it mean that the disappeared phonemic contrasts are unimportant? In our study, we calculated the proportions (here termed degree of contrast) of minimal pairs to the words in which the two contrastive phonemes occur and explored the role of phonemic contrasts in the phonemic combinations. The degree of contrast of phonemes reflects the relation between phonemes. Our results indicate that (1) the average degree of contrast of Chinese phonemes declines exponentially with the increase in the number of syllables, rapidly approaching zero; (2) the average degree of contrast of Chinese consonants that differ from each other in only one distinctive feature and of the consonants that are absent in some Chinese dialects is significantly higher than that of other consonants; (3) the degree of contrast of Chinese consonants that differ from each other in only one distinctive feature is not significantly different from that of the consonants absent in some Chinese dialects; (4) Chinese phonemic combinations exhibit high degree of sparsity, which increases exponentially with the number of syllables and rapidly approaches 1. All these results show that the high degree of sparsity and the low degree of contrast of human languages not only leave enough room for new words, new dialects and new languages to appear but also contribute to effective and reliable communication, because a few phonemic mistakes are not likely to cause wrong decoding (sound recognition) and failed communication.
Relationship between Speech Rate Perceived and Produced by the Listener
Authors: Schwab Sandra 
Published: January 2012

Abstract
The present research examines the impact of listeners’ own rate of speech production on their perception of speech rate. We recorded 28 native French speakers reading a passage at normal, fast and slow rates. The same speakers then assessed the rate of production of these samples by all speakers and at all rates (normal, fast and slow), using a magnitude estimation task. We show that there is an inverse relationship between listeners’ own rate of production and their judgment of rate, so that listeners with slower rates tend to overestimate sample rates relative to faster speakers. This effect of listeners’ own rate was present in the magnitude estimation results at slow and normal rates, but not at fast rates. Furthermore, listeners with a slow rate are more sensitive to rate differences within a given rate category (normal, fast and slow). The listener’s own rate should therefore be considered as a critical factor in speech rate perception.
Long Pentraxin 3/Tumor Necrosis Factor-Stimulated Gene-6 Interaction
Authors: Leali Daria , Inforzato Antonio , Ronca Roberto , Bianchi Roberta , Belleri Mirella , Coltrini Daniela , Di Salle Emanuela , Sironi Marina , Norata Giuseppe Danilo , Bottazzi Barbara , Garlanda Cecilia , Day Anthony J. , Presta Marco 
Published: January 2012

Objective—
Angiogenesis is regulated by the balance between pro- and antiangiogenic factors and by extracellular matrix protein interactions. Fibroblast growth factor 2 (FGF2) is a major proangiogenic inducer inhibited by the interaction with the soluble pattern recognition receptor long pentraxin 3 (PTX3). PTX3 is locally coexpressed with its ligand tumor necrosis factor-stimulated gene-6 (TSG-6), a secreted glycoprotein that cooperates with PTX3 in extracellular matrix assembly. Here, we characterized the effect of TSG-6 on PTX3/FGF2 interaction and FGF2-mediated angiogenesis.

Methods and Results—

Solid phase binding and surface plasmon resonance assays show that TSG-6 and FGF2 bind the PTX3 N-terminal domain with similar affinity. Accordingly, TSG-6 prevents FGF2/PTX3 interaction and suppresses the inhibition exerted by PTX3 on heparan sulfate proteoglycan/FGF2/FGF receptor complex formation and on FGF2-dependent angiogenesis in vitro and in vivo. Also, endogenous PTX3 exerts an inhibitory effect on vascularization induced by FGF2 in a murine subcutaneous Matrigel plug assay, the inhibition being abolished in
Ptx3
-null mice or by TSG-6 treatment in wild-type animals.

Conclusion—
TSG-6 reverts the inhibitory effects exerted by PTX3 on FGF2-mediated angiogenesis through competition of FGF2/PTX3 interaction. This may provide a novel mechanism to control angiogenesis in those pathological settings characterized by the coexpression of TSG-6 and PTX3, in which the relative levels of these proteins may fine-tune the angiogenic activity of FGF2.
C/EBP Homologous Protein-10 (CHOP-10) Limits Postnatal Neovascularization Through Control of Endothelial Nitric Oxide Synthase Gene Expression
Authors: Loinard Céline , Zouggari Yasmine , Rueda Patricia , Ramkhelawon Bhama , Cochain Clément , Vilar José , Récalde Alice , Richart Adéle , Charue Dominique , Duriez Micheline , Mori Masataka , Arenzana-Seisdedos Fernando , Lévy Bernard I. , Heymes Christophe , Silvestre Jean-Sébastien 
Published: January 2012

Background—
C/EBP homologous protein-10 (CHOP-10) is a novel developmentally regulated nuclear protein that emerges as a critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. In the present study, we analyzed the role of CHOP-10 in postnatal neovascularization.

Methods and Results—

Ischemia was induced by right femoral artery ligation in wild-type and CHOP-10
−/−
mice. In capillary structure of skeletal muscle, CHOP-10 mRNA and protein levels were upregulated by ischemia and diabetes mellitus. Angiographic score, capillary density, and foot perfusion were increased in CHOP-10
−/−
mice compared with wild-type mice. This effect was associated with a reduction in apoptosis and an upregulation of endothelial nitric oxide synthase (eNOS) levels in ischemic legs of CHOP-10
−/−
mice compared with wild-type mice. In agreement with these results, eNOS mRNA and protein levels were significantly upregulated in CHOP-10 short interfering RNA–transfected human endothelial cells, whereas overexpression of CHOP-10 inhibited basal transcriptional activation of the eNOS promoter. Using a chromatin immunoprecipitation assay, we also showed that CHOP-10 was bound to the eNOS promoter. Interestingly, enhanced postischemic neovascularization in CHOP-10
−/−
mice was fully blunted in CHOP-10/eNOS double-knockout animals. Finally, we showed that induction of diabetes mellitus is associated with a marked upregulation of CHOP-10 that substantially inhibited postischemic neovascularization.

Conclusions—
This study identifies CHOP-10 as an important transcription factor modulating vessel formation and maturation.
Risk of Recurrent Stroke in Patients With Silent Brain Infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Imaging Substudy
Authors: Weber Ralph , Weimar Christian , Wanke Isabel , Möller-Hartmann Claudia , Gizewski Elke R. , Blatchford Jon , Hermansson Karin , Demchuk Andrew M. , Forsting Michael , Sacco Ralph L. , Saver Jeffrey L. , Warach Steven , Diener Hans Christoph , Diehl Anke ,   for the PRoFESS Imaging Substudy Group
Published: January 2012

Background and Purpose—
Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality.

Methods—
The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression.

Results—

Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79–2.56;
P
=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI.

Conclusions—
The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00153062.
Abnormal Glucose Regulation in Patients With Acute Stroke Across China
Authors: Jia Qian , Zheng Huaguang , Zhao Xingquan , Wang Chunxue , Liu Gaifen , Wang Yilong , Liu Liping , Li Hao , Zhong Liyong , Wang Yongjun 
Published: January 2012

Background and Purpose—
The prevalence of diabetes is high among patients with ischemic stroke. However, the prevalence of abnormal glucose regulation and clinical characteristics among patients with stroke in the Chinese population is uncertain. We investigated the prevalence of prediabetes and diabetes in Chinese patients after stroke onset in a nationwide cohort study and investigated abnormal glucose regulation in patients with acute stroke across China (ACROSS-China).

Methods—
The ACROSS-China study consecutively recruited patients hospitalized for acute stroke in 2008 to 2009 and investigated the prevalence of impaired glucose tolerance and diabetes among the patients on day 14 after stroke onset. Oral glucose tolerance test was performed in the diagnosis of abnormal glucose regulation.

Results—
The prevalence of abnormal glucose regulation was 68.7% among all the patients with stroke. Diabetes was identified in 42.3% of all the patients (45.8% for patients with ischemic stroke, 31.2% for patients with intracerebral hemorrhage, and 26.4% for patients with subarachnoid hemorrhage, respectively). Prediabetes (impaired fasting glucose and impaired glucose tolerance) was identified in 26.4% of all the patients with stroke. The prevalence of diabetes and impaired glucose tolerance was the highest in the patients with atherothrombotic infarction (73.4%).

Conclusions—
The prevalence of abnormal glucose regulation was high in Chinese patients with acute stroke, especially in patients with atherothrombotic infarction. Oral glucose tolerance test identified a large percentage of patients with newly diagnosed diabetes or impaired glucose tolerance after stroke onset.
Residual Flow After Cerebral Aneurysm Coil Occlusion
Authors: Lavoie Pascale , Gariépy Jean-Luc , Milot Geneviève , Jodoin Steve , Bédard Fernand , Trottier Francois , Verreault René 
Published: January 2012

Background and Purpose—
The purpose of this study was to estimate the performance measures of MR angiography (MRA) in the diagnosis of aneurysm residual flow after coil occlusion.

Methods—
Patients having at least 1 cerebral aneurysm treated with coil occlusion were prospectively and consecutively enrolled. Time of flight and contrast-enhanced MRA were performed the same day of the DSA follow-up. The degree of aneurysm occlusion and dimensions of the residual flow were evaluated by independent readers at MRA and digital subtraction angiogram. MRA performance measures were estimated in a cross-sectional analysis and repeated in subgroups of aneurysm sizes and locations. MRA predictive values for recurrence were also estimated using a longitudinal design.

Results—

We obtained 167 aneurysm evaluations for each imaging modality. Class 3 residual flow was seen on digital subtraction angiogram follow-up in 27%. The sensitivity and specificity of MRA was 88% (95% CI, 80–94) and 79% (95% CI, 67–88), respectively. The positive predictive value for a Class 3 recurrence was 67% (95% CI, 51–80) and the negative predictive value was 93% (95% CI, 86–97). Time-of-flight MRA underestimated the length of the residual flow (
P
=0.039), whereas contrast-enhanced MRA overestimated its width (
P
<0.0001). MRA sensitivity for a Class 3 residual flow was lower for aneurysms <6 mm (
P
=0.01).

Conclusions—
MRA has sufficient accuracy for screening of aneurysm residual flow after coil occlusion. Due to its lower negative predictive value, recurrent aneurysms should be confirmed with digital subtraction angiogram before planning a retreatment. Routine use of MRA to follow small aneurysms should wait better estimation of its performance in this particular subgroup.
Delirium in Acute Stroke
Authors: Shi Qiyun , Presutti Roseanna , Selchen Daniel , Saposnik Gustavo 
Published: January 2012

Background and Purpose—
Delirium is common in the early stage after hospitalization for an acute stroke. We conducted a systematic review and meta-analysis to evaluate the outcomes of acute stroke patients with delirium.

Methods—
We searched MEDLINE, EMBASE, CINAHL, Cochrane Library databases, and PsychInfo for relevant articles published in English up to September 2011. We included observational studies for review. Two reviewers independently assessed studies to determine eligibility, validity, and quality. The primary outcome was inpatient mortality and secondary outcomes were mortality at 12 months, institutionalization, and length of hospital stay.

Results—
Among 78 eligible studies, 10 studies (n=2004 patients) met the inclusion criteria. Stroke patients with delirium had higher inpatient mortality (OR, 4.71; 95% CI, 1.85–11.96) and mortality at 12 months (OR, 4.91; 95% CI, 3.18–7.6) compared to nondelirious patients. Patients with delirium also tended to stay longer in hospital compared to those who did not have delirium (mean difference, 9.39 days; 95% CI, 6.67–12.11) and were more likely to be discharged to a nursing homes or other institutions (OR, 3.39; 95% CI, 2.21–5.21).

Conclusions—
Stroke patients with development of delirium have unfavorable outcomes, particularly higher mortality, longer hospitalizations, and a greater degree of dependence after discharge. Early recognition and prevention of delirium may improve outcomes in stroke patients.