bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD
Authors: Hartjes Floor J. , Vonk Judith M. , Faiz Alen , Hiemstra Pieter S. , Lapperre Thérèse S. , Kerstjens Huib A.M. , Postma Dirkje S. , van den Berge Maarten ,   and the Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) Study Group
Published: April 2018

ABSTRACTBackground and objectiveInflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers for clinical response to inhaled corticosteroids (ICS).MethodsIn total, 114 steroid‐naïve COPD patients of the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study using ICS or placebo during 30‐month follow‐up were included. Cell counts in blood, sputum, biopsies and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV1), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated.ResultsCross‐sectional analyses at baseline showed that higher blood eosinophils were significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV1 changes. Higher baseline biopsy eosinophils were associated with an increase in symptoms during 6‐ and 30‐month ICS treatment. In addition, higher biopsy neutrophils were associated with a more marked reduction in hyperinflation during 6‐month ICS treatment compared with placebo.ConclusionOur findings indicate that blood eosinophils reflect eosinophils in other compartments, in contrast to neutrophils, in ICS‐naïve COPD patients. Both baseline eosinophils and neutrophils do not predict ICS‐induced lung function changes over a period of 6–30 months. The associations of biopsy eosinophils with worsening respiratory symptoms and biopsy neutrophils with improvement in hyperinflation during ICS treatment deserve further investigation.
Perspectival Disagreement
Authors: Rast Erich H. 
Published: April 2018

AbstractA phenomenon called perspectival disagreement is laid out and modelled on the basis of modifications to known consensus measures for qualitative representations of preferences and transitive values by binary relations. Cases of perspectival disagreement are of general philosophical interest, because they allow for the possibility that two or more agents judge the value positions of other agents differently even when their assessments are based on the same evidence. Various examples of perspectival disagreement are given, generalizations are discussed, and it is argued that any representation by cardinal utilities also gives rise to some form of perspectivity. Although the examples strongly suggest that this phenomenon occurs in real life, it is concluded in the end that it does not pose any fundamental threat to representations of preferences and values as binary relations. Instead, position‐sensitive measures of disagreement ought to be taken as a modelling option for cases in which the relative importance of preference changes matters to an agent.
Influence of class IV laser therapy on the outcomes of tibial plateau leveling osteotomy in dogs
Authors: Renwick S. Michelle , Renwick Alasdair I. , Brodbelt David C. , Ferguson John , Abreu Humberto 
Published: April 2018

AbstractObjectiveTo determine the effects of low‐level laser therapy (LLLT) on clinical outcomes in dogs with cranial cruciate ligament disease treated with tibial plateau leveling osteotomy (TPLO).Study designRandomized, placebo‐controlled clinical trial. Owners and surgeons (care providers and assessors) were masked.AnimalsNinety‐five dogs were admitted for TPLO and assigned to 1 of 2 groups, laser group (LG; n = 51) or placebo group (PG; n = 44).MethodsThree treatments (laser or placebo) were administered within a 4‐day perioperative period. A fourth treatment was recommended and was accepted in 28.4% of cases (LG, n = 14; PG, n = 13). Dogs in the LG group received laser at wavelengths 660 nm red (100 mW) and at 800, 905 and 970 nm infrared (maximum 15 W continuous wave, 20 W peak pulsed wave), administered simultaneously. Dogs in the PG group received placebo laser (660 nm, 4 mW). Other treatments were identical. Outcomes were measured by difference in clinical metrology instruments (Liverpool Osteoarthritis in Dogs and adjusted Canine Orthopedic Index [COI]), osteotomy healing on a radiographic scale, time to cessation of nonsteroidal anti‐inflammatory drug administration, and wound healing by owner questionnaire.ResultsThe only difference detected between groups consisted of a greater improvement in the gait section of the adjusted COI (ACOI) in the LG group (median [interquartile range; IQR] = 6 [4‐7.5]) compared with the PG group (median [IQR] = 4 [2‐6]; P < .05).ConclusionThe laser protocol used in this study was associated with a greater improvement in ACOI gait in dogs treated with TPLO but did not improve any other clinical metrology instrument scores or bone healing.Clinical significanceThis study provides some evidence that LLLT may improve the gait of dogs recovering from a TPLO, as assessed by owners.
The Artemisinin Derivative Artemisone Is a Potent Inhibitor of Human Cytomegalovirus Replication
Authors: Oiknine-Djian E. , Weisblum Y. , Panet A. , Wong H. N. , Haynes R. K. , Wolf D. G. 
Published: April 2018

ABSTRACT

Human cytomegalovirus (HCMV) is a major cause of disease in immunocompromised individuals and the most common cause of congenital infection and neurosensorial disease. The expanding target populations for HCMV antiviral treatment along with the limitations of the currently available HCMV DNA polymerase inhibitors underscore the need for new antiviral agents with alternative modes of action. The antimalarial artemisinin derivative artesunate was shown to inhibit HCMV
in vitro
yet has demonstrated limited antiviral efficacy
in vivo
, prompting our search for more potent anti-HCMV artemisinin derivatives. Here we show that the innovative artemisinin derivative artemisone, which has been screened for its activity against malaria parasites in human clinical studies, is a potent and noncytotoxic inhibitor of HCMV. Artemisone exhibited an antiviral efficacy comparable to that of ganciclovir (50% effective concentration, 1.20 ± 0.46 μM) in human foreskin fibroblasts, with enhanced relative potency in lung fibroblasts and epithelial cells. Significantly, the antiviral efficacy of artemisone was consistently ≥10-fold superior to that of artesunate in all cells. Artemisone effectively inhibited both laboratory-adapted and low-passage-number clinical strains, as well as drug-resistant HCMV strains. By using quantitative viral kinetics and gene expression studies, we show that artemisone is a reversible inhibitor targeting an earlier phase of the viral replication cycle than ganciclovir. Importantly, artemisone most effectively inhibited HCMV infection
ex vivo
in a clinically relevant multicellular model of integral human placental tissues maintained in organ culture. Our promising findings encourage preclinical and clinical studies of artemisone as a new inhibitor against HCMV.
Autoregulation of SafA Assembly through Recruitment of a Protein Cross-Linking Enzyme
Authors: Fernandes Catarina G. , Moran Charles P. , Henriques Adriano O. 
Published: April 2018

ABSTRACT

The coat of
Bacillus subtilis
spores is a multiprotein protective structure that also arbitrates many of the environmental interactions of the spore. The coat assembles around the cortex peptidoglycan layer and is differentiated into an inner and an outer layer and a crust. SafA governs assembly of the inner coat, whereas CotE drives outer coat assembly. SafA localizes to the cortex-coat interface. Both SafA and its short form C30 are substrates for Tgl, a coat-associated transglutaminase that cross-links proteins through ε-(γ-glutamyl)lysyl isopeptide bonds. We show that SafA and C30 are distributed between the coat and cortex layers. The deletion of
tgl
increases the extractability of SafA, mainly from the cortex. Tgl itself is mostly located in the inner coat and cortex. The localization of Tgl-cyan fluorescent protein (Tgl-CFP) is strongly, but not exclusively, dependent on
safA
. However, the association of Tgl with the cortex requires
safA
. Together, our results suggest an assembly pathway in which Tgl is first recruited to the forming spore in a manner that is only partially dependent on SafA and then is drafted to the cortex by SafA. Tgl, in turn, promotes the conversion of coat- and cortex-associated SafA into forms that resist extraction, possibly by catalyzing the cross-linking of SafA to other coat proteins, to the cortex, and/or to cortex-associated proteins. Therefore, the final assembly state of SafA relies on an autoregulatory pathway that requires the subcellular localization of a protein cross-linking enzyme. Tgl most likely exerts a “spotwelding” activity, cross-linking preformed complexes in the cortex and inner coat layers of spores.

IMPORTANCE
In this work, we show how two proteins work together to determine their subcellular location within the coat of bacterial endospores.
Bacillus subtilis
endospores are surrounded by a multilayer protein coat composed of over 80 proteins, which surrounds an underlying peptidoglycan layer (the spore cortex) protecting it from lytic enzymes. How specific coat proteins are targeted to specific layers of the coat is not well understood. We found that the protein SafA recruits a protein-cross-linking enzyme (a transglutaminase) to the cortex and inner layers of the coat, where both are cemented, by cross-linking, into macromolecular complexes.
Global prevalence of visual impairment associated with myopic macular degeneration and temporal trends from 2000 through 2050: systematic review, meta-analysis and modelling
Authors: Fricke Timothy R , Jong Monica , Naidoo Kovin S , Sankaridurg Padmaja , Naduvilath Thomas J , Ho Suit May , Wong Tien Yin , Resnikoff Serge 
Published: April 2018

PurposeWe used systematic review and meta-analysis to identify and assimilate evidence quantifying blindness and visual impairment (VI) associated with myopic macular degeneration (MMD), then derived models to predict global patterns. The models were used to estimate the global prevalence of blindness and VI associated with MMD from 2000 to 2050.MethodsThe systematic review identified 17 papers with prevalence data for MMD VI fitting our inclusion criteria. Data from six papers with age-specific data were scaled to relative age-dependent risk and meta-analysed at VI and blindness levels. We analysed variance in all MMD VI and blindness data as a proportion of high myopia against variables from the place and year of data collection, with a model based on health expenditure providing the best correlation. We used this model to estimate the prevalence and number of people with MMD VI in each country in each decade.ResultsWe included data from 17 studies comprising 137 514 participants. We estimated 10.0 million people had VI from MMD in 2015 (prevalence 0.13%, 95% CI 5.5 to 23.7 million, 0.07% to 0.34%), 3.3 million of whom were blind (0.04%, 1.8 to 7.8 million, 0.03% to 0.10%). We estimate that by 2050, without changing current interventions, VI from MMD will grow to 55.7 million people (0.57%, 29.0 to 119.7 million, 0.33% to 1.11%), 18.5 million of whom will be blind (0.19%, 9.6 to 39.7 million, 0.11% to 0.37%).ConclusionThe burden of MMD blindness and VI will rise significantly without efforts to reduce the development and progression of myopia and improve the management of MMD.
Structural, morphological and magnetic properties of divalent copper-substituted Co–Zn Nanoferrites
Authors: Vara Prasad B. B. V. S. , Ramesh K. V. , Srinivas Adiraj 
Published: April 2018

Nanocrystalline Co[Formula: see text]Zn[Formula: see text]Cu[Formula: see text]Fe2O4 spinel ferrites were prepared by autocombustion method with citric acid as fuel. Paramagnetic divalent copper ions substituted in place of ferromagnetic cobalt ions resulted in the modifications of structural and magnetic properties of the system. All samples were characterized with X-ray diffraction technique for structure determination. Crystallite sizes were calculated using Williamson–Hall plot and size–strain plots. Cation distribution and all other structural parameters were presented. Transmission electron microscopy measurements were done for x = 0 and x = 0.15 and they showed well-developed spherical particles with average sizes of 35 nm and 48 nm. Morphological studies were performed and grain growth was observed to be increased with copper concentration. EDAX measurements revealed the stoichiometric proportions of the samples as per the chemical composition. Mid-IR spectroscopy was used to characterize the spinel phase and displayed two characteristic absorption bands in all samples with a slight shift. M–H loops were recorded using vibrating sample magnetometer at room-temperature and highest saturation magnetization was observed to be 50.2 emu/g for the base (x = 0) sample. Magnetocrystalline anisotropy was discussed with the help of magnetocrystalline anisotropy constant K1.
Inference of gene networks from gene expression time series using recurrent neural networks and sparse MAP estimation
Authors: Chen Chi-Kan 
Published: April 2018

Background: The inference of genetic regulatory networks (GRNs) provides insight into the cellular responses to signals. A class of recurrent neural networks (RNNs) capturing the dynamics of GRN has been used as a basis for inferring small-scale GRNs from gene expression time series. The Bayesian framework facilitates incorporating the hypothesis of GRN into the model estimation to improve the accuracy of GRN inference. Results: We present new methods for inferring small-scale GRNs based on RNNs. The weights of wires of RNN represent the strengths of gene-to-gene regulatory interactions. We use a class of automatic relevance determination (ARD) priors to enforce the sparsity in the maximum a posteriori (MAP) estimates of wire weights of RNN. A particle swarm optimization (PSO) is integrated as an optimization engine into the MAP estimation process. Likely networks of genes generated based on estimated wire weights are combined using the majority rule to determine a final estimated GRN. As an alternative, a class of [Formula: see text]-norm ([Formula: see text]) priors is used for attaining the sparse MAP estimates of wire weights of RNN. We also infer the GRN using the maximum likelihood (ML) estimates of wire weights of RNN. The RNN-based GRN inference algorithms, ARD-RNN, [Formula: see text]-RNN, and ML-RNN are tested on simulated and experimental E. coli and yeast time series containing 6–11 genes and 7–19 data points. Published GRN inference algorithms based on regressions and mutual information networks are performed on the benchmark datasets to compare performances. Conclusion: ARD and [Formula: see text]-norm priors are used for the estimation of wire weights of RNN. Results of GRN inference experiments show that ARD-RNN, [Formula: see text]-RNN have similar best accuracies on the simulated time series. The ARD-RNN is more accurate than [Formula: see text]-RNN, ML-RNN, and mostly more accurate than the reference algorithms on the experimental time series. The effectiveness of ARD-RNN for inferring small-scale GRNs using gene expression time series of limited length is empirically verified.
Trabalho e ação sindical em Redes Globais de Produção
Authors: Ramalho José Ricardo , Dos Santos Rodrigo Salles Pereira 
Published: April 2018

O artigo pretende fazer um balanço da incorporação do trabalho e da ação coletiva sindical à abordagem das redes globais de produção (RGPs) e de seus limites e potencial para o desenvolvimento de uma concepção sociológica multiagente e multiescalar do mundo do trabalho. Partindo da organização em rede das estratégias corporativas e seus impactos sobre as condições e relações de trabalho, a intenção é aprofundar o entendimento: (1) da conformação de redes laborais dispersas geograficamente, embora funcionalmente integradas; (2) do impacto destas sobre as formas de agência individual de trabalhadores, em suas variadas segmentações etária, étnica, de gênero e geográfica; e (3) das restrições e oportunidades à emergência de formas de ação e poder coletivo transnacionais condicionantes da agência econômica e política e influentes sobre a forma concreta dessas redes.
O desmonte dos direitos, as novas configurações do trabalho e o esvaziamento da ação coletiva: consequências da reforma trabalhista
Authors: Krein José Dari 
Published: April 2018

O presente artigo procura analisar a reforma trabalhista sancionada recentemente no Brasil. Para isso, são destacados os seus efeitos sobre a configuração dos elementos centrais da relação de emprego (formas de contratação, jornada, remuneração e proteção social) e sobre a organização sindical. Parte-se da hipótese que a reforma trabalhista em questão ajusta a regulação do trabalho às características do capitalismo contemporâneo, predominando a visão do trabalho como “labor” e não como “opus”. A reforma amplia a liberdade dos empregadores em determinar as condições de contratação, o uso da força de trabalho e a remuneração dos trabalhadores. Ou seja, busca-se imputar o processo de definição das regras da relação de emprego às empresas, restringindo a participação das organizações dos trabalhadores e do Estado. Esse processo acarreta, primeiramente, o aumento da insegurança dos trabalhadores e a perda de direitos, bem como a diminuição da proteção social. A reforma também busca esvaziar as organizações sindicais na qualidade de organizações de classe, visto que passa a prevalecer a visão de organizações mais descentralizadas e articuladas com os interesses das empresas.
Ventricular Electrical Delay Measured From Body Surface ECGs Is Associated With Cardiac Resynchronization Therapy Response in Left Bundle Branch Block Patients From the MADIT-CRT Trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy)
Authors: Plesinger Filip , Jurak Pavel , Halamek Josef , Nejedly Petr , Leinveber Pavel , Viscor Ivo , Vondra Vlastimil , McNitt Scott , Polonsky Bronislava , Moss Arthur J. , Zareba Wojciech , Couderc Jean-Philippe 
Published: April 2018

Background:
Although cardiac resynchronization therapy (CRT) is beneficial in heart failure patients with left bundle branch block, 30% of these patients do not respond to the therapy. Identifying these patients before implantation of the device is one of the current challenges in clinical cardiology.

Methods:
We verified the diagnostic contribution and an optimized computerized approach to measuring ventricular electrical activation delay (VED) from body surface 12-lead ECGs. We applied the method to ECGs acquired before implantation (baseline) in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy). VED values were dichotomized using its quartiles, and we tested the association of VED values with the MADIT-CRT primary end point of heart failure or death. Multivariate Cox proportional models were used to estimate the risk of study end points. In addition, the association between VED values and hemodynamic changes after CRT-D implantation was examined using 1-year follow-up echocardiograms.

RESULTS:

Our results showed that left bundle branch block patients with baseline VED <31.2 ms had a 35% risk of MADIT-CRT end points, whereas patients with VED ≥31.2 ms had a 14% risk (
P
<0.001). The hazard ratio for predicting primary end points in patients with low VED was 2.34 (95% confidence interval, 1.53–3.57;
P
<0.001). Higher VED values were also associated with beneficial hemodynamic changes. These strong VED associations were not found in the right bundle branch block and intraventricular conduction delay cohorts of the MADIT-CRT trial.

Conclusions:
Left bundle branch block patients with a high baseline VED value benefited most from CRT, whereas left bundle branch block patients with low VED did not show CRT benefits.
Benefits of a Legally Non-Binding Agreement: The Case of the 2013 US-Russian Agreement on the Elimination of Syrian Chemical Weapons
Authors: Hayashi Mika 
Published: April 2018

Abstract
The deal struck between the United States and Russia in September 2013, the ‘Framework for Elimination of Syrian Chemical Weapons,’ amounts to a legally non-binding agreement, and not a treaty. The objective of this agreement – namely, that of averting the pending crisis in Syria at that time – highlights what a non-binding agreement, as opposed to a treaty, can do. Somewhat curiously, various actors kept referring to the 2013 agreement even when binding instruments covering the same questions were in place. Thus, this note also explores the distinct benefits of the 2013 agreement even in the presence of the binding instruments. In some cases, the preference for the 2013 agreement can be explained as a search for leverage against Russia. In other cases, the rhetorical preference for the non-binding agreement could indicate a desire to discuss the question of enforcement without addressing institutional requirements of the OPCW or the UN Security Council.
20α- and 20β-dihydrocortisone may interfere in LC-MS/MS determination of cortisol in saliva and urine
Authors: Israelsson Marlen , Brattsand Ralph , Brattsand Göran 
Published: April 2018

Background LC-MS/MS methods offer high selectivity in cortisol determinations. However, endogenous steroid metabolites may still interfere and compromise the results, for example in the diagnosis of Cushing’s syndrome. Erroneously elevated cortisol may, in particular, be misleading at the low concentrations found in salivary samples obtained at late night and after dexamethasone suppression. Methods Interferences in our LC-MS/MS method used for determination of cortisol in saliva and urine were identified by comparing their retention times and mass spectra with those of pure candidate substances. The chromatographic conditions used in our LC-MS/MS method, including column and mobile phase gradient, were varied in order to separate the target compound from the interferences. Results Two interferences, which were co-eluting or eluting close to cortisol in our original method, were successfully separated from cortisol by adjustment of the chromatographic conditions. These interferences were found in both urine and saliva and were identified as the two endogenous cortisol isomers 20α- and 20β-dihydrocortisone. The isomers share molecular mass and mass spectrometric fragmentation pattern with cortisol using electrospray ionization in the positive-ion mode. Both give rise to the transitions m/z 363.1>121.1, 363.1>115.1 and 363.1>97.1. In our original LC-MS/MS setup, the 20β-dihydrocortisone co-eluted with cortisol in the chromatography step resulting in false high determinations. Conclusions Cortisol determination by LC-MS/MS may suffer from erroneously elevated results unless 20α- and 20β-dihydrocortisone are chromatographically separated from cortisol.