bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective
Authors: Corso Simona , Giordano Silvia 
Published: July 2013

Abstract
Targeted therapies have opened new perspectives in clinical oncology. However, clinicians have observed a lack of response in a relevant percentage of patients and frequent relapse in patients who initially respond. Therefore, a compelling challenge is to identify mechanisms underlying resistance and strategies to circumvent these hurdles. A growing body of evidence indicates that MET, the tyrosine kinase receptor for hepatocyte growth factor (HGF), is frequently implicated in resistance to targeted therapies. In this review, we highlight cell-autonomous and non–cell-autonomous mechanisms through which MET drives resistance, and we discuss some unsolved issues related to the selection of patients who could benefit from combined therapies.
Significance: Resistance is, at present, the major limitation to the efficacy of targeted therapies. Inappropriate MET activation is very frequently implicated in the onset of primary and secondary resistance to these therapies. Deciphering the role of the HGF/MET axis in resistance to different drugs could guide the design of new clinical trials based on combinatorial therapies, and it might help to overcome, or possibly prevent, the onset of resistance. Cancer Discov; 3(9); 978–92. ©2013 AACR.
Incidence and Clinical Impact of Stroke Complicating Percutaneous Coronary Intervention
Authors: Werner Nicolas , Bauer Timm , Hochadel Matthias , Zahn Ralf , Weidinger Franz , Marco Jean , Hamm Christian , Gitt Anselm K. , Zeymer Uwe 
Published: July 2013

Background—
Stroke is a rare but serious complication of percutaneous coronary interventions (PCIs). So far, scant information is available about the incidence and outcome of patients developing stroke after PCI for stable angina or acute coronary syndrome (ACS) in daily clinical practice in Europe today.

Methods and Results—
Between 2005 and 2008, 46 888 patients undergoing PCI were enrolled into the PCI Registry of the Euro Heart Survey Programme (176 centers in 33 European countries) to document patient’s characteristics, PCI details, and hospital complications in different PCI indications. Stroke was observed in 0.4% of the procedures in the total population, in 0.3% of PCIs in elective patients, and in 0.6% in PCIs performed for ACS. The overall in-hospital mortality was 19.2% for patients who developed stroke (elective PCIs, 10.0%; PCI for ACS, 23.2%) compared with 1.3% for those without stroke (elective PCIs, 0.2%; PCI for ACS, 2.3%). In multivariate analysis hemodynamic instability, age ≥75 years, history of stroke, and congestive heart failure were found to be independent predictors for periprocedural stroke in ACS, whereas only PCI of a bypass graft and renal failure could be identified as independent predictors for stroke in elective patients.

Conclusions—
Stroke as complication of PCI occurs rarely (0.4%) in clinical practice in Europe today. However, peri-interventional stroke is still associated with an exceedingly high in-hospital mortality rate. Most predictors for periprocedural stroke are not modifiable and cannot be diminished before PCI. Therefore, treatment of patients with stroke after PCI needs further research.
Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes
Authors: Steg P. Gabriel , Harrington Robert A. , Emanuelsson Håkan , Katus Hugo A. , Mahaffey Kenneth W. , Meier Bernhard , Storey Robert F. , Wojdyla Daniel M. , Lewis Basil S. , Maurer Gerald , Wallentin Lars , James Stefan K. 
Published: July 2013

Background—
We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial.

Methods and Results—

Of 18 624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50–0.90;
P
=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59–0.95;
P
=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62–0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24–0.96) and subacute (4 hours–30 days; HR, 0.60; 95% CI, 0.39–0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43–2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment ≥80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48–0.88).

Conclusion—
Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872.
Under-Reporting of Socioeconomic Status of Patients in Stroke Trials
Authors: Magin Parker , Victoire Anousha , Zhen Xi May , Furler John , Pirotta Marie , Lasserson Daniel S. , Levi Christopher , Tapley Amanda , van Driel Mieke 
Published: July 2013

Background and Purpose—
The 2001 Revised Consolidated Standards of Reporting of Trials (CONSORT) statement requires reporting of Randomized Controlled Trials (RCTs) to include participants’ baseline demographics. This enables comparison of intervention and control groups on potential confounding variables as well as assessment of study generalizability. Socioeconomic status (SES) is associated with access to care and outcomes (mortality, functional outcome, recurrent stroke, and hospital readmission) poststroke. We aimed to document the reporting of baseline SES in reports of RCTs of stroke and transient ischemic attack.

Methods—
Measures of SES were extracted from studies reporting trials of stroke or transient ischemic attack published in 12 major journals in the disciplines of general medicine, general neurology, cerebrovascular disease, and rehabilitation subsequent to revised CONSORT. Percentages of studies reporting SES measures were calculated. Differences in reporting between journal categories, and temporal trends in reporting, were tested.

Results—
Only 12% of studies reported any SES measure. Journal categories did not differ in rate of SES reporting. SES reporting did not increase over time.

Conclusions—
Improving reporting of SES could enhance clinicians’ ability to evaluate RCT findings and apply them to their patients.
Incidence and Risks of Subarachnoid Hemorrhage in China
Authors: Zhang Jingfen , Liu Guorong , Arima Hisatomi , Li Yuechun , Cheng Guojuan , Shiue Ivy , Lv Lin , Wang Huiling , Zhang Chunyang , Zhao Jianchun , Anderson Craig S. 
Published: July 2013

Background and Purpose—
To determine incidence and risks of subarachnoid hemorrhage in China.

Methods—
A prospective, population-based, 1:2 matched case–control study in Baotou, Inner Mongolia (≈2 million population) in 2009–2011. Multiple variable models used to determine relative risk and population-attributable risks for exposures.

Results—
For a total of 226 patients (mean age, 59 years; 65% women; 434 controls), crude annual incidence (per 100 000) of subarachnoid hemorrhage was 6.2 (95% confidence intervals, 5.4–7.0); 4.3 (3.3–5.2) for men and 8.2 (6.9–9.6) for women. Compared with nonsmokers, adjusted relative risk of subarachnoid hemorrhage in current smokers was 2.31 (95% confidence interval, 1.31–4.09) but was 4.00 (1.62–9.89) in women. Population-attributable risk for smoking, hypertension, and low income were 18%, 36% and 59%, respectively.

Conclusions—
The incidence of subarachnoid hemorrhage in China is slightly lower than in Western countries and is related to smoking, hypertension, and poor socioeconomic status.
Influence of MODIS-Derived Dynamic Vegetation on VIC-Simulated Soil Moisture in Oklahoma
Authors: Ford Trent W. , Quiring Steven M. 
Published: July 2013

Abstract
Soil moisture–vegetation interactions are an important component of land–atmosphere coupling, especially in semiarid regions such as the North American Great Plains. However, many land surface models parameterize vegetation using an interannually invariant leaf area index (LAI). This study quantifies how utilizing a dynamic vegetation parameter in the variability infiltration capacity (VIC) hydrologic model influences model-simulated soil moisture. Accuracy is assessed using in situ soil moisture observations from 20 stations from the Oklahoma Mesonet. Results show that VIC simulations generated with an interannually variant LAI parameter are not consistently more accurate than those generated with the invariant (static) LAI parameter. However, the static LAI parameter tends to overestimate LAI during anomalously dry periods. This has the greatest influence on the accuracy of the soil moisture simulations in the deeper soil layers. Soil moisture drought, as simulated with the static LAI parameter, tends to be more severe and persist for considerably longer than drought simulated using the interannually variant LAI parameter. Dynamic vegetation parameters can represent interannual variations in vegetation health and growing season length. Therefore, simulations with a dynamic LAI parameter better capture the intensity and duration of drought conditions and are recommended for use in drought monitoring.
Visualizing Uncertainty
Authors: Kirschenbaum Susan S. , Trafton J. Gregory , Schunn Christian D. , Trickett Susan B. 
Published: July 2013

Objective: This work investigated the impact of uncertainty representation on performance in a complex authentic visualization task, submarine localization. Background: Because passive sonar does not provide unique course, speed, and range information on a contact, the submarine operates under significant uncertainty. There are many algorithms designed to address this problem, but all are subject to uncertainty. The extent of this solution uncertainty can be expressed in several ways, including a table of locations (course, speed, range) or a graphical area of uncertainty. Method: To test the hypothesis that the representation of uncertainty that more closely matches the experts’ preferred representation of the problem would better support performance, even for the nonexpert., performance data were collected using displays that were either stripped of the spatial or the tabular representation. Results: Performance was more accurate when uncertainty was displayed spatially. This effect was only significant for the nonexperts for whom the spatial displays supported almost expert-like performance. This effect appears to be due to reduced mental effort. Conclusion: These results suggest that when the representation of uncertainty for this spatial task better matches the expert’s preferred representation of the problem even a nonexpert can show expert-like performance. Application: These results could apply to any domain where performance requires working with highly uncertain information.
Predictors of Symptoms and Site of Death in Pediatric Palliative Patients With Cancer at End of Life
Authors: Schindera Christina , Tomlinson Deborah , Bartels Ute , Gillmeister Biljana , Alli Amanda , Sung Lillian 
Published: July 2013

Objective: To describe how preferences and treatment influence symptoms at end of life and site of death in pediatric cancer. Methods: We included 61 pediatric palliative patients with cancer whose parents previously participated in a study that elicited preferences for aggressive chemotherapy versus supportive care alone and who subsequently died. Main outcomes were severe pain and dyspnea proximal to death and site of death. Results: Choice of aggressive chemotherapy predicted significantly more severe pain (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.0-9.6; P = .049). Intravenous chemotherapy 4 weeks before death predicted severe dyspnea (OR 15.8, 95% CI 3.7-67.5; P < .001) and death outside the home (OR 0.3, 95% CI 0.1-0.9; P = .038). Conclusions: Parental choice of aggressive chemotherapy and more aggressive treatment proximal to death predicted more pain, dyspnea, and death in hospital. Strategies to improve quality of life are needed.
Fibrinogen Level as a Surrogate for the Outcome of Thrombolytic Therapy Using Tissue Plasminogen Activator for Acute Lower Extremity Intravascular Thrombosis
Authors: Skeik Nedaa , Gits Colton C. , Ehrenwald Eduardo , Cragg Andrew H. 
Published: July 2013

Purpose: Monitoring of fibrinogen level is used to predict bleeding during lower extremity tissue plasminogen activator (tPA) infusions for peripheral arterial or venous thrombolysis. This practice is not fully addressed in the literature. Materials and Methods: We retrospectively reviewed fibrinogen levels and studied bleeding rate from charts of patients who underwent lower extremity tPA infusions at a single hospital from January 2010 to May 2012. Results: The rate of thrombolytic success did not correlate with fibrinogen level ( P = .53). The rate of major bleeding was significantly higher for patients with a fibrinogen level at or below 150 mg/dL ( P = .01). Patients whose tPA infusion was terminated within 46 hours had significantly lower rates of major bleeding ( P = .01) and thrombolytic failure ( P < .01). Periprocedural systolic blood pressure above 160 mm Hg was a risk factor for major bleeding ( P = .02). There was no association between concomitant aspirin use ( P = .90, .51) or hourly tPA dose ( P = .71, .62) and thrombolytic success or major bleeding, respectively. Conclusion: Fibrinogen level ≤150 mg/dL is associated with increased risk of major bleeding during tPA infusions. We suggest serial fibrinogen measurement as a viable method to monitor bleeding risk during lower extremity tPA infusions.
Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy
Authors: Hodyl Nicolette A. , Stark Michael J. , Scheil Wendy , Grzeskowiak Luke E. , Clifton Vicki L. 
Published: July 2013

Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect?Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999–2008; n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios.Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose–response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone.Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.
APOMand high-density lipoprotein cholesterol are associated with lung function and per cent emphysema
Authors: Burkart Kristin M. , Manichaikul Ani , Wilk Jemma B. , Ahmed Firas S. , Burke Gregory L. , Enright Paul , Hansel Nadia N. , Haynes Demondes , Heckbert Susan R. , Hoffman Eric A. , Kaufman Joel D. , Kurai Jun , Loehr Laura , London Stephanie J. , Meng Yang , O’Connor George T. , Oelsner Elizabeth , Petrini Marcy , Pottinger Tess D. , Powell Charles A. , Redline Susan , Rotter Jerome I. , Smith Lewis J. , Soler Artigas María , Tobin Martin D. , Tsai Michael Y. , Watson Karol , White Wendy , Young Taylor R. , Rich Stephen S. , Barr R. Graham 
Published: July 2013

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD.We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema.We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10−6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10−7). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL,PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans andAPOMexpression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema.These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.
Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema
Authors: Ishii Takeo , Abboud Raja T. , Wallace Alison M. , English John C. , Coxson Harvey O. , Finley Richard J. , Shumansky Karey , Paré Peter D. , Sandford Andrew J. 
Published: July 2013

Alveolar macrophages play an important role in chronic obstructive pulmonary diseaseviaproduction of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes.Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed.The results showed that basal expression level ofMMP12mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression ofMMP1mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted.We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.
Propofol sedation for flexible bronchoscopy: a randomised, noninferiority trial
Authors: Grendelmeier Peter , Tamm Michael , Pflimlin Eric , Stolz Daiana 
Published: July 2013

Propofol has been established as a reliable method for sedation in flexible bronchoscopy. There are no data comparing propofol administered as intravenous bolusesversuscontinuous infusion.702 consecutive patients undergoing flexible bronchoscopy were randomly allocated to receive intravenous propofol using either an intermittent bolus technique or a continuous infusion. The primary end-point was the number of adverse events assessed at the end of flexible bronchoscopy and at 24 h.The number of any adverse event was similar in both randomised groups (219versus211, p=0.810). There were complications in eight cases (seven major bleedings, one respiratory failure). As compared with the bolus group, the amount of propofol required was significantly higher in the infusion group (226 ±147 mgversus308±204.8 mg, p<0.0001). In a multivariate regression model, this difference remained significant independent of the duration and the interventions performed during the procedure. The duration of bronchoscopy was significantly longer in the infusion group (median 14 (interquartile range 9–24)versus17 (12–27) min, p<0.0001).Propofol continuous infusion is as safe as bolus administration; however, it is associated with higher propofol requirements and a longer duration of the bronchoscopy.
Wave propagation of cortical population activity under urethane anesthesia is state dependent
Authors: Wanger Tim , Takagaki Kentaroh , Lippert Michael T , Goldschmidt Jürgen , Ohl Frank W 
Published: July 2013

Abstract

Background
Propagating waves of excitation have been observed extensively in the neocortex, during both spontaneous and sensory-evoked activity, and they play a critical role in spatially organizing information processing. However, the state-dependence of these spatiotemporal propagation patterns is largely unexplored. In this report, we use voltage-sensitive dye imaging in the rat visual cortex to study the propagation of spontaneous population activity in two discrete cortical states induced by urethane anesthesia.

Results
While laminar current source density patterns of spontaneous population events in these two states indicate a considerable degree of similarity in laminar networks, lateral propagation in the more active desynchronized state is approximately 20% faster than in the slower synchronized state. Furthermore, trajectories of wave propagation exhibit a strong anisotropy, but the preferred direction is different depending on cortical state.

Conclusions
Our results show that horizontal wave propagation of spontaneous neural activity is largely dependent on the global activity states of local cortical circuits.