bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis
Authors: Ford John A , Shyangdan Deepson , Uthman Olalekan A , Lois Noemi , Waugh Norman 
Published: July 2014

ObjectiveTo indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA).DesignNMA.Data sourcesThe following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science.Eligibility criteria for selecting studiesOnly randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions.ResultsSeven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections.ConclusionsWe found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections.Systematic review registrationNot registered.
The first 1000 days of life: prenatal and postnatal risk factors for morbidity and growth in a birth cohort in southern India
Authors: Kattula Deepthi , Sarkar Rajiv , Sivarathinaswamy Prabhu , Velusamy Vasanthakumar , Venugopal Srinivasan , Naumova Elena N , Muliyil Jayaprakash , Ward Honorine , Kang Gagandeep 
Published: July 2014

ObjectiveTo estimate the burden and assess prenatal and postnatal determinants of illnesses experienced by children residing in a semiurban slum, during the first 1000 days of life.DesignCommunity-based birth cohortSettingSouthern IndiaParticipantsFour hundred and ninety-seven children of 561 pregnant women recruited and followed for 2 years with surveillance and anthropometry.Main outcome measureIncidence rates of illness; rates of clinic visits and hospitalisations; factors associated with low birth weight, various illnesses and growth.ResultsData on 10 377.7 child-months of follow-up estimated an average rate of 14.8 illnesses/child-year. Gastrointestinal and respiratory illnesses were 20.6% and 47.8% of the total disease burden, respectively. The hospitalisation rate reduced from 46/100 child-years during infancy to 19/100 child-years in the second year. Anaemia during pregnancy (OR=2.3, 95% CI=1.08 to 5.18), less than four antenatal visits (OR=6.8, 95% CI=2.1 to 22.5) and preterm birth (OR=3.3, 95% CI=1.1 to 9.7) were independent prenatal risk factors for low birth weight. Female gender (HR=0.88, 95% CI=0.79 to 0.99) and 6 months of exclusive breast feeding (HR=0.76, 95% CI=0.66 to 0.88) offered protection against all morbidity. Average monthly height and weight gain were lower in female child and children exclusively breast fed for 6 months.ConclusionsThe high morbidity in Indian slum children in the first 1000 days of life was mainly due to prenatal factors and gastrointestinal and respiratory illness. Policymakers need disease prevalence and pathways to target high-risk groups with appropriate interventions in the community.
Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)
Authors: Quint Jennifer K , Müllerova Hana , DiSantostefano Rachael L , Forbes Harriet , Eaton Susan , Hurst John R , Davis Kourtney , Smeeth Liam 
Published: July 2014

ObjectivesThe optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.Setting951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.Primary outcome measureThe primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.Results951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%).ConclusionsPatients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.
RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification: RAPID study protocol
Authors: Almeida Osvaldo P , MacLeod Colin , Flicker Leon , Ford Andrew , Grafton Ben , Etherton-Beer Christopher 
Published: July 2014

IntroductionDepressive symptoms are common and undermine the quality of life of people with Alzheimer's disease (AD). Cholinesterase inhibitors and antidepressants have all but no effect on the mood of patients, and their use increases adverse events. Cognitive bias modification (CBM) targets attentional and interpretative biases associated with anxiety, dysphoria and depression and may be useful to treat depression in AD (DAD). This trial aims to determine the effect of CBM on depression scores and the quality of life of people with DAD.Methods and analysisRandomised, double-blind, parallel, controlled trial of CBM (1:1 allocation ratio). Participants will be 80 adults with probable AD living in the Western Australian community who score 8 or more on the Cornell Scale for Depression in Dementia (CSDD). They will have mild to moderate dementia (Mini-Mental State Examination—MMSE score ≥15) and will be free of severe sensory impairment or suicidal intent. The intervention will consist of 10 40 min sessions of CBM delivered over 2 weeks using a high-resolution monitor using a local computer station at the Western Australian Centre for Health and Ageing. The primary outcomes of interest are the 2-week change, from baseline, in the severity of CSDD scores and the Quality of Life AD (QoL-AD) scores. Secondary outcomes include changes in the CSDD, QoL-AD after 12 weeks, and changes in MMSE scores, negative attentional and interpretative bias and the proportion of participants with CSDD <8 after 2 and 12 weeks.Ethics and disseminationThe study will comply with the principles of the Declaration of Helsinki and participants will provide written informed consent. The Ethics Committee of the Royal Perth Hospital will approve and oversee the study (REG14-036). The results of this trial will provide level 2 evidence of efficacy for CBM as a treatment of DAD.Trial registration numberAustralian and New Zealand Clinical Trials Registry number ACTRN12614000420640, date registered 06/04/2014.
Estimating population prevalence of potential airflow obstruction using different spirometric criteria: a pooled cross-sectional analysis of persons aged 40–95 years in England and Wales
Authors: Scholes Shaun , Moody Alison , Mindell Jennifer S 
Published: July 2014

ObjectivesConsistent estimation of the burden of chronic obstructive pulmonary disease (COPD) has been hindered by differences in methods, including different spirometric cut-offs for impaired lung function. The impact of different definitions on the prevalence of potential airflow obstruction, and its associations with key risk factors, is evaluated using cross-sectional data from two nationally representative population surveys.DesignPooled cross-sectional analysis of Wave 2 of the UK Household Longitudinal Survey and the Health Survey for England 2010, including 7879 participants, aged 40–95 years, who lived in England and Wales, without diagnosed asthma and with good-quality spirometry data. Potential airflow obstruction was defined using self-reported physician-diagnosed COPD; a fixed threshold (FT) forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 and an age-specific, sex-specific, height-specific and ethnic-specific lower limit of normal (LLN). Standardised questions elicited self-reported information on demography, smoking history, ethnicity, occupation, respiratory symptoms and cardiovascular disease.ResultsConsistent across definitions, participants classed with obstructed airflow were more likely to be older, currently smoke, have higher pack-years of smoking and be engaged in routine occupations. The prevalence of airflow obstruction was 2.8% (95% CI 2.3% to 3.2%), 22.2% (21.2% to 23.2%) and 13.1% (12.2% to 13.9%) according to diagnosed COPD, FT and LLN, respectively. The gap in prevalence between FT and LLN increased in older age groups. Sex differences in the risk of obstruction, after adjustment for key risk factors, was sensitive to the choice of spirometric cut-off, being significantly higher in men when using FT, compared with no significant difference using LLN.ConclusionsApplying FT or LLN spirometric cut-offs gives a different picture of the size and distribution of the disease burden. Longitudinal studies examining differences in unscheduled hospital admissions and risk of death between FT and LLN may inform the choice as to the best way to include spirometry in assessments of airflow obstruction.
Shortened Lung Clearance Index is a repeatable and sensitive test in children and adults with cystic fibrosis
Authors: Hannon David , Bradley Judy M , Bradbury Ian , Bell Nicholas , Elborn J Stuart , O'Neill Katherine 
Published: July 2014

BackgroundLung clearance index (LCI) derived from sulfur hexafluoride (SF6) multiple breath washout (MBW) is a sensitive measure of lung disease in people with cystic fibrosis (CF). However, it can be time-consuming, limiting its use clinically.AimTo compare the repeatability, sensitivity and test duration of LCI derived from washout to 1/30th (LCI1/30), 1/20th (LCI1/20) and 1/10th (LCI1/10) to ‘standard’ LCI derived from washout to 1/40th initial concentration (LCI1/40).MethodsTriplicate MBW test results from 30 clinically stable people with CF and 30 healthy controls were analysed retrospectively. MBW tests were performed using 0.2% SF6and a modified Innocor device. All LCI end points were calculated using SimpleWashout software. Repeatability was assessed using coefficient of variation (CV%). The proportion of people with CF with and without abnormal LCI and forced expiratory volume in 1 s (FEV1) % predicted was compared. Receiver operating characteristic (ROC) curve statistics were calculated. Test duration of all LCI end points was compared using paired t tests.ResultsIn people with CF, LCI1/40CV% (p=0.16), LCI1/30CV%,(p=0.53), LCI1/20CV% (p=0.14) and LCI1/10CV% (p=0.25) was not significantly different to controls. The sensitivity of LCI1/40, LCI1/30and LCI1/20to the presence of CF was equal (67%). The sensitivity of LCI1/10and FEV1% predicted was lower (53% and 47% respectively). Area under the ROC curve (95% CI) for LCI1/40, LCI1/30, LCI1/20, LCI1/10and FEV1% predicted was 0.89 (0.80 to 0.97), 0.87 (0.77 to 0.96), 0.87 (0.78 to 0.96), 0.83 (0.72 to 0.94) and 0.73 (0.60 to 0.86), respectively. Test duration of LCI1/30, LCI1/20and LCI1/10was significantly shorter compared with the test duration of LCI1/40in people with CF (p<0.0001) equating to a 5%, 9% and 15% time saving, respectively.ConclusionsIn this study, LCI1/20was a repeatable and sensitive measure with equal diagnostic performance to LCI1/40. LCI1/20was shorter, potentially offering a more feasible research and clinical measure.
Ubiquitin-like Protein FAT10 Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Modifying β-Catenin Degradation
Authors: Yuan Rongfa , Wang Kai , Hu Junwen , Yan Chen , Li Ming , Yu Xin , Liu Xiuxia , Lei Jun , Guo Wuhua , Wu Linquan , Hong Kui , Shao Jianghua 
Published: July 2014

Abstract
The ubiquitin-like protein FAT10 and the homeobox protein HOXB9 each promote metastatic progression in hepatocellular carcinoma (HCC). In this study, we investigated the clinicopathologic significance of FAT10 and HOXB9 in HCC and investigated a mechanistic role for FAT10 in HOXB9-mediated invasiveness and metastasis. Relative to adjacent normal tissues, FAT10 and HOXB9 were markedly overexpressed in HCC, where a positive correlation in their expression and associated malignant characteristics were found. RNAi-mediated silencing of FAT10 decreased HOXB9 expression and inhibited HCC invasion and metastasis in vitro and in vivo. The effects of FAT10 silencing were reversed by HOXB9 overexpression, whereas RNAi-mediated silencing of HOXB9 decreased HCC invasion and metastasis driven by FAT10 overexpression. Mechanistically, FAT10 regulated HOXB9 expression by modulating the β-catenin/TCF4 pathway, directly binding to β-catenin and preventing its ubiquitination and degradation. Together, our results identified a novel HCC regulatory circuit involving FAT10, β-catenin/TCF4, and HOXB9, the dysfunction of which drives invasive and metastatic character in HCC. Cancer Res; 74(18); 5287–300. ©2014 AACR.
The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF
Authors: Watson Ian R. , Li Liren , Cabeceiras Peter K. , Mahdavi Mozhdeh , Gutschner Tony , Genovese Giannicola , Wang Guocan , Fang Zhuangna , Tepper James M. , Stemke-Hale Katherine , Tsai Kenneth Y. , Davies Michael A. , Mills Gordon B. , Chin Lynda 
Published: July 2014

Abstract
Following mutations in BRAF and NRAS, the RAC1 c.85C&gt;T single-nucleotide variant (SNV) encoding P29S amino acid change represents the next most frequently observed protein-coding hotspot mutation in melanoma. However, the biologic and clinical significance of the RAC1 P29S somatic mutation in approximately 4% to 9% of patients remains unclear. Here, we demonstrate that melanoma cell lines possessing the RAC1 hotspot variant are resistant to RAF inhibitors (vemurafenib and dabrafenib). Enforced expression of RAC1 P29S in sensitive BRAF-mutant melanoma cell lines confers resistance manifested by increased viability, decreased apoptosis, and enhanced tumor growth in vivo upon treatment with RAF inhibitors. Conversely, RNAi-mediated silencing of endogenous RAC1 P29S in a melanoma cell line with a co-occurring BRAF V600 mutation increased sensitivity to vemurafenib and dabrafenib. Our results suggest RAC1 P29S status may offer a predictive biomarker for RAF inhibitor resistance in melanoma patients, where it should be evaluated clinically. Cancer Res; 74(17); 4845–52. ©2014 AACR.
High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation
Authors: Holy Erik , Besler Christian , Reiner Martin , Camici Giovanni , Manz Jasmin , Beer Jürg , Lüscher Thomas , Landmesser Ulf , Tanner Felix 
Published: July 2014

SummaryThrombus formation is determined by the balance between prothrombotic mediators and anti-thrombotic factors. High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown. In human aortic endothelial cells in culture, HDL (50 μg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 μg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 μmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.
Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing
Authors: Bruges Gustavo , Crespo Gustavo , Salazar Victor , Deglesne Pierre-Antoine , Schneider Heike , Cabrera-Fuentes Hector , Schmitz M. Lienhard , Preissner Klaus , Lopéz Mercedes 
Published: July 2014

SummaryThrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.
Proto-Siraya Phonology: A Reconstruction
Authors: Adelaar Alexander 
Published: July 2014

In this paper I make a phonological comparison of Siraya dialects and reconstruct Proto-Siraya phonology applying the comparative method. Siraya is a dormant language with various dialects once spoken in Southwest Taiwan. The present reconstruction is largely based on 17th century liturgical texts and a wordlist, and to a lesser extent on wordlists of various dialects collected at the turn of the 20th century. An unexpected outcome of this comparison is that Proto-Siraya still had distinct reflexes of Proto-Austronesian *R and *S, although they subsequently merged in a palatal fricative in the individual dialects of Siraya. Dans cet article, nous effectuons une comparaison phonologique des dialectes du siraya, et reconstruisons la phonologie du proto-siraya en appliquant la méthode comparative. Le siraya est une langue ‘en sommeil’ très dialectalisée qui était parlée autrefois au sud-ouest de Taiwan. Notre reconstruction est basée pour l’essentiel sur les textes liturgiques du 17ème siècle, et dans une moindre mesure sur des listes de mots de différents dialectes recueillis au tout début du 20ème siècle. Cette comparaison a permis la découverte inattendue de la préservation par le proto-siraya de la distinction entre les consonnes *R et *S du proto-austronésien, bien qu’elles se soient confondues en une fricative palatale dans les différents dialectes du siraya.
Sensitivity of Modeled Precipitation to Sea Surface Temperature in Regions with Complex Topography and Coastlines: A Case Study for the Mediterranean
Authors: Senatore Alfonso , Mendicino Giuseppe , Knoche Hans Richard , Kunstmann Harald 
Published: July 2014

Abstract
An analysis of the effects of SST representation on precipitation in long-term continuous simulations was carried out for the Mediterranean peninsula of Calabria, Italy, which is characterized by complex coastlines and orography. A parameterization analysis was performed to find an optimal model configuration, using a method where SST fields are directly ingested from NCEP datasets into the Weather Research and Forecasting (WRF) Model lower boundary condition files. The results of the optimal configuration were used for a comparison with recorded precipitation patterns for a very wet period (from November 2008 to January 2009), adopting several interpolation options available in the WRF Preprocessing System. An additional comparison was made against a uniform variation of the original SST fields by ε = ±0.5 K. It was found that the interpolation options mainly affect near-coastline SSTs, where methods requiring fewer source data points have several advantages. Effects of SST representation on precipitation, accumulated over the whole 3-month period, are generally lower than ±2%, but a specific class of events (synoptic situations) with strong differences in precipitation patterns was identified. These events are connected to pressure systems moving from the African coast to the north and approaching the Sicilian and Calabrian coastlines. Two of these events, which occurred on 27–29 December 2008 and 9 January 2009, were analyzed in detail, highlighting that small variations of SST values induce slight shifts in the paths of the weather fronts. These slight shifts are important enough to determine whether or not wet air masses can reach the mountain ranges close to the coast, where rainfall intensity is enhanced by orographic effects.