bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescriber responsibility, predictors for initiation, and 20-year trends in use of non-aspirin non-steroidal anti-inflammatory drugs in patients with cardiovascular contraindications: a nationwide cohort study
Authors: Schmidt Morten , Pottegård Anton 
Published: June 2020

Abstract

Aims
To examine whether prescription patterns complied with recommendations not to use non-steroidal anti-inflammatory drugs (NSAIDs) in patients with cardiovascular contraindications. Moreover, we examined predictors for initiation and prescriber responsibility.

Methods and results
We used Danish medical databases to identify all patients with first-time cardiovascular disease during 1996–2017 (n = 628 834). We assessed standardized prevalence proportions, predictors from logistic regression, and prescriber identifiers. One-year prevalence of NSAID initiation increased 3.4% from 1996 (19.4%) to 2001 (22.7%) and declined by 2.7% thereafter until 2017 (13.5%). Trends were independent of age, sex, and disease subtype, although larger annual declines occurred for heart failure (3.9%) and ischaemic heart disease (3.5%) since 2002. One-year prevalence remained highest among patients with venous thromboembolism (16.6%) and angina (13.8%), and lowest for ST-segment elevation myocardial infarction (7.0%) and heart failure (8.8%). Initiators were predominantly prescribed ibuprofen (59%), diclofenac (23%), and etodolac (6%). Diclofenac and coxib use declined, while ibuprofen and naproxen use increased. Median prescribed pill dose of ibuprofen declined after 2008 from moderate/high (600 mg) to low (400 mg). Treatment duration declined for all NSAIDs, except celecoxib. Rheumatic, obesity, and pain-related conditions predicted NSAID initiation. General practitioners issued 86–91% of all NSAID prescriptions, followed by hospital prescribers (7.3–12%).

Conclusions
Initiation of NSAIDs in patients with cardiovascular disease declined since 2002. Shorter treatment duration, declining COX-2 inhibition, and increasing use of naproxen and low-dose ibuprofen suggest adherence to guidelines when NSAIDs cannot be avoided. Still, NSAID use remained prevalent despite cardiovascular contraindications, warranting awareness of appropriateness of use among general practitioners in particular.
Macrophage Depletion in CCR2−/− Mice Delays Bacterial Clearance and Enhances Neutrophil Infiltration in an Acute Otitis Media Model
Authors: Hur Dong Gu , Kurabi Arwa , Lim Hyun Woo , Spriggs Meghan , Pak Kwang , Ryan Allen F 
Published: June 2020

Abstract

Background
Otitis media (OM) is a common and potentially serious disease of childhood. Although OM is multifactorial on origin, bacterial infection is a unifying component. Many studies have established a critical role for innate immunity in bacterial clearance and OM resolution. A key component of innate immunity is the recruitment of immune and inflammatory cells, including macrophages.

Methods
To explore the role of macrophages in OM, we evaluated the expression of genes related to macrophage function during a complete episode of acute OM in the mouse caused by middle ear (ME) inoculation with Haemophilus influenzae. We also combined CCR2 deficiency with chlodronate liposome toxicity to deplete macrophages during OM.

Results
Macrophage genes were robustly regulated during OM. Moreover, macrophage depletion enhanced and prolonged the infiltration of neutrophils into the infected ME and increased the persistence of bacterial infection.

Conclusions
The results illustrate the critical role played by macrophages in OM resolution.
The Polysemy of Security Community-Building: Toward a “People-Centered” Association of Southeast Asian Nations (ASEAN)?
Authors: Martel Stéphanie 
Published: June 2020

AbstractThis article contributes to ongoing debates on security community-building in international relations (IR) by focusing on the productive role of discursive contestation in this process. It builds on recent work associated with the “practice” turn, discourse theory, and the study of security communities in the Global South to propose a new understanding of how the diversification of security governance impacts security community-building. The article develops an original discourse-based approach that conceptualizes security community-building as a polysemic, omnidirectional, and contested process in which social agents debate the meaning of security and the boundaries of community. It applies this approach to the case of Association of Southeast Asian Nations (ASEAN) to show how contestation over the organization's identity as a security community “in the making” takes place along two dimensions. First, different (and potentially incompatible) versions of the community compete for dominance. Second, contestation also unfolds “internally,” among social agents who agree on which version ought to prevail. I illustrate this part of the argument through an examination of the debate over ASEAN's identity as a “people-centered” community. The demonstration is supported by the analysis of “texts” enacted in the discursive field where the security community is talked into existence, as well as interviews with practitioners.
Molecular and biochemical insights into the in vivo evolution of AmpC-mediated resistance to ceftolozane/tazobactam during treatment of an MDR Pseudomonas aeruginosa infection
Authors: Arca-Suárez Jorge , Vázquez-Ucha Juan Carlos , Fraile-Ribot Pablo Arturo , Lence Emilio , Cabot Gabriel , Martínez-Guitián Marta , Lasarte-Monterrubio Cristina , Rodríguez-Iglesias Manuel , Beceiro Alejandro , González-Bello Concepción , Galán-Sánchez Fátima , Oliver Antonio , Bou Germán 
Published: June 2020

AbstractBackgroundPseudomonas aeruginosa may develop resistance to novel cephalosporin/β-lactamase inhibitor combinations during therapy through the acquisition of structural mutations in AmpC.ObjectivesTo describe the molecular and biochemical mechanisms involved in the development of resistance to ceftolozane/tazobactam in vivo through the selection and overproduction of a novel AmpC variant, designated PDC-315.MethodsPaired susceptible/resistant isolates obtained before and during ceftolozane/tazobactam treatment were evaluated. MICs were determined by broth microdilution. Mutational changes were investigated through WGS. Characterization of the novel PDC-315 variant was performed through genotypic and biochemical studies. The effects at the molecular level of the Asp245Asn change were analysed by molecular dynamics simulations using Amber.ResultsWGS identified mutations leading to modification (Asp245Asn) and overproduction of AmpC. Susceptibility testing revealed that PAOΔC producing PDC-315 displayed increased MICs of ceftolozane/tazobactam, decreased MICs of piperacillin/tazobactam and imipenem and similar susceptibility to ceftazidime/avibactam compared with WT PDCs. The catalytic efficiency of PDC-315 for ceftolozane was 10-fold higher in relation to the WT PDCs, but 3.5- and 5-fold lower for piperacillin and imipenem. IC50 values indicated strong inhibition of PDC-315 by avibactam, but resistance to cloxacillin inhibition. Analysis at the atomic level explained that the particular behaviour of PDC-315 is linked to conformational changes in the H10 helix that favour the approximation of key catalytic residues to the active site.ConclusionsWe deciphered the precise mechanisms that led to the in vivo emergence of resistance to ceftolozane/tazobactam in P. aeruginosa through the selection of the novel PDC-315 enzyme. The characterization of this new variant expands our knowledge about AmpC-mediated resistance to cephalosporin/β-lactamase inhibitors in P. aeruginosa.
First-Line Toxicological Screening with Fully Automated Extraction
Authors: Robin Tiphaine , El Balkhi Souleiman , Dulaurent Sylvain , Marquet Pierre , Saint-Marcoux Franck 
Published: June 2020

Abstract
In clinical toxicology, laboratories need screening methods allowing unambiguous identification of the compounds in a short turnaround time to either confirm or exclude the hypothesis of drug overdose or poisoning with a toxicant. We developed a fully automated screening procedure designed to identify and quantify in a single run 245 compounds of interest in clinical toxicology. Sample extraction was carried out by a programmable liquid handler directly coupled to a liquid chromatography–tandem mass spectrometry (LC–MS-MS) system. Data acquisition was performed in the positive and negative ionization modes with up to 15 multiple reaction monitoring (MRM) transitions per compound, each with optimized collision energy to enable both qualitative library searching and quantitation. The method was validated according to the ISO 15189 requirements and was applied to real patient samples (n = 127). The 15 MRM transitions per compound provided higher confidence for the identification of all the compounds. The quantitative method was fully validated with satisfactory intra- and inter-assay imprecision and inaccuracy with CV% lower than 20%. For only nine molecules, imprecision and inaccuracy were relatively high but never exceeded 31.7%. Comparison with dedicated quantitative methods using conventional MRM monitoring performed using 127 patient samples (n = 175 pairs of measured concentrations) showed excellent correlation (R2 = 0.96). A robustness study showed that calibration curves prepared for up to 1 month yielded uncertainty &lt; 20%. Retention times ranged from 0.89 min for metformin to 9.72 min for difenacoum. The automated sample preparation required 8 min and was followed by 10 min chromatographic separation. This first-line screening procedure yields high confidence in compound detection and should be useful in core labs facing clinical toxicology situations where rapid and reliable results are needed.
The dust and cold gas content of local star-forming galaxies
Authors: Popesso P , Concas A , Morselli L , Rodighiero G , Enia A , Quai S 
Published: June 2020

ABSTRACT
We use dust masses (Mdust) derived from far-infrared data and molecular gas masses (Mmol) based on CO luminosity to calibrate proxies based on a combination of the galaxy Balmer decrement, disc inclination, and gas metallicity. We use such proxies to estimate Mdust and Mmol in the local SDSS sample of star-forming galaxies (SFGs). We study the distribution of Mdust and Mmol along and across the main sequence (MS) of SFGs. We find that Mdust and Mmol increase rapidly along the MS with increasing stellar mass (M*), and more marginally across the MS with increasing SFR (or distance from the relation). The dependence on M* is sub-linear for both Mdust and Mmol. Thus, the fraction of dust (fdust) and molecular gas mass (fmol) decreases monotonically towards large M*. The star formation efficiency (SFE, inverse of the molecular gas depletion time) depends strongly on the distance from the MS and it is constant along the MS. As nearly all galaxies in the sample are central galaxies, we estimate the dependence of fdust and fgas on the host halo mass and find a tight anticorrelation. As the region where the MS is bending is numerically dominated by massive haloes, we conclude that the bending of the MS is due to a lower availability of molecular gas mass in massive haloes rather than a lower efficiency in forming stars.
An expanded catalogue of low surface brightness galaxies in the Coma cluster using Subaru/Suprime-Cam
Authors: Alabi Adebusola B , Romanowsky Aaron J , Forbes Duncan A , Brodie Jean P , Okabe Nobuhiro 
Published: June 2020

ABSTRACT
We present a catalogue of low surface brightness (LSB) galaxies in the Coma cluster obtained from deep Subaru/Suprime-Cam V- and R-band imaging data within a region of $\mathord {\sim }4$ deg2. We increase the number of LSB galaxies presented in Yagi et al. (2016) by a factor of $\mathord {\sim }3$ and report the discovery of 29 new ultradiffuse galaxies (UDGs). We compile the largest sample of UDGs with colours and structural parameters in the Coma cluster. While most UDGs lie along the red-sequence relation of the colour–magnitude diagram, $\mathord {\sim }16$ per cent are outside (bluer or redder) the red-sequence region of Coma cluster galaxies. Our analyses show that there is no special distinction in the basic photometric parameters between UDGs and other LSB galaxies. We investigate the clustercentric colour distribution and find a remarkable transition at a projected radius of $\mathord {\sim }0.6$ Mpc. Within this cluster core region and relative to the red-sequence of galaxies, LSB galaxies are on average redder than co-spatial higher surface brightness galaxies at the 2σ level, highlighting how vulnerable LSB galaxies are to the physical processes at play in the dense central region of the cluster. The position of the transition radius agrees with expectations from recent cosmological simulation of massive galaxy clusters within which ancient infalls are predicted to dominate the LSB galaxy population.
Forbidden line diagnostics of photoevaporative disc winds
Authors: Ballabio G , Alexander R D , Clarke C J 
Published: June 2020

ABSTRACT
Photoevaporation driven by high-energy radiation from the central star plays an important role in the evolution of protoplanetary discs. Photoevaporative winds have been unambiguously detected through blue-shifted emission lines, but their detailed properties remain uncertain. Here we present a new empirical approach to make observational predictions of these thermal winds, seeking to fill the gap between theory and observations. We use a self-similar model of an isothermal wind to compute line profiles of several characteristic emission lines (in particular the [Ne ii] line at 12.81 μm, and optical forbidden lines such as [O i] 6300 Å and [S ii] 4068/4076 Å), studying how the lines are affected by parameters such as the gas temperature, disc inclinations, and density profile. Our model successfully reproduces blue-shifted lines with $v_{\rm peak} \lesssim 10$ km s−1, which decrease with increasing disc inclination. The line widths increase with increasing disc inclinations and range from $\Delta v\sim 15\text{ to }30$ km s−1. The predicted blue-shifts are mostly sensitive to the gas sound speed (and therefore the temperature). The observed [Ne ii] line profiles are consistent with a thermal wind and point towards a relatively high sound speed, as expected for extreme-UV photoevaporation. However, the observed [O i] line profiles require lower temperatures, as expected in X-ray photoevaporation, and show a wider scatter that is difficult to reconcile with a single wind model; it seems likely that these lines trace different components of a multiphase wind. We also note that the spectral resolution of current observations remains an important limiting factor in these studies, and that higher resolution spectra are required if emission lines are to further our understanding of protoplanetary disc winds.
ModelTeller: Model Selection for Optimal Phylogenetic Reconstruction Using Machine Learning
Authors: Abadi Shiran , Avram Oren , Rosset Saharon , Pupko Tal , Mayrose Itay 
Published: June 2020

AbstractStatistical criteria have long been the standard for selecting the best model for phylogenetic reconstruction and downstream statistical inference. Although model selection is regarded as a fundamental step in phylogenetics, existing methods for this task consume computational resources for long processing time, they are not always feasible, and sometimes depend on preliminary assumptions which do not hold for sequence data. Moreover, although these methods are dedicated to revealing the processes that underlie the sequence data, they do not always produce the most accurate trees. Notably, phylogeny reconstruction consists of two related tasks, topology reconstruction and branch-length estimation. It was previously shown that in many cases the most complex model, GTR+I+G, leads to topologies that are as accurate as using existing model selection criteria, but overestimates branch lengths. Here, we present ModelTeller, a computational methodology for phylogenetic model selection, devised within the machine-learning framework, optimized to predict the most accurate nucleotide substitution model for branch-length estimation. We demonstrate that ModelTeller leads to more accurate branch-length inference than current model selection criteria on data sets simulated under realistic processes. ModelTeller relies on a readily implemented machine-learning model and thus the prediction according to features extracted from the sequence data results in a substantial decrease in running time compared with existing strategies. By harnessing the machine-learning framework, we distinguish between features that mostly contribute to branch-length optimization, concerning the extent of sequence divergence, and features that are related to estimates of the model parameters that are important for the selection made by current criteria.
Cholesterol-modifying drugs in COVID-19
Authors: Schmidt Nathalie M , Wing Peter A C , McKeating Jane A , Maini Mala K 
Published: June 2020

Abstract
Infection with severe acute respiratory syndrom coronavirus 2 (SARS-CoV-2) is more likely to lead to poor outcomes in the elderly and those with cardiovascular disease, obesity or metabolic syndrome. Here, we consider mechanisms by which dyslipidaemia and the use of cholesterol-modifying drugs could influence the virus–host relationship. Cholesterol is essential for the assembly, replication and infectivity of enveloped virus particles; we highlight several cholesterol-modifying drugs with the potential to alter the SARS-CoV-2 life cycle that could be tested in in vitro and in vivo models. Although cholesterol is an essential component of immune cell membranes, excess levels can dysregulate protective immunity and promote exaggerated pulmonary and systemic inflammatory responses. Statins block the production of multiple sterols, oxysterols and isoprenoids, resulting in a pleiotropic range of context-dependent effects on virus infectivity, immunity and inflammation. We highlight antiviral, immunomodulatory and anti-inflammatory effects of cholesterol-modifying drugs that merit further consideration in the management of SARS-CoV-2 infection.
Economic interventions to ameliorate the impact of COVID-19 on the economy and health: an international comparison
Authors: Danielli Shaun , Patria Raman , Donnelly Patrice , Ashrafian Hutan , Darzi Ara 
Published: June 2020

Abstract

Background
The COVID-19 pandemic continues to challenge governments and policymakers worldwide. They have rightfully prioritised reducing the spread of the virus through social distancing interventions. However, shuttered business and widespread restrictions on travel and mobility have led to an economic collapse with increasing uncertainty of how quickly recovery will be achieved.

Methods
The authors carried out a review of publicly available information on the economic intervention’s countries have put in place to ameliorate the impact of COVID-19.

Results
The strategies and scale of economic interventions have been broad, ranging from 2.5% to a reported 50% of Gross Domestic Product.

Conclusions
Numerous countries are beginning to ease lockdown restrictions and restart economies in different ways. There is therefore evolving, real-world data that should be used dynamically by governments and policymakers. The strategies on restarting the economy must be balanced against the uncertainty of a possible second wave of COVID-19. A nuanced approach to easing restrictions needs to take into account not only immediate risk to life but longer-term risks of widening inequalities and falling life expectancy.
Genericity and Universality for Operator Ideals
Authors: Beanland Kevin , Causey Ryan M 
Published: June 2020

Abstract
A bounded linear operator $U$ between Banach spaces is universal for the complement of some operator ideal $\mathfrak{J}$ if it is a member of the complement and it factors through every element of the complement of $\mathfrak{J}$. In the first part of this paper, we produce new universal operators for the complements of several ideals, and give examples of ideals whose complements do not admit such operators. In the second part of the paper, we use descriptive set theory to study operator ideals. After restricting attention to operators between separable Banach spaces, we call an operator ideal $\mathfrak{J}$ generic if whenever an operator $A$ has the property that every operator in $\mathfrak{J}$ factors through a restriction of $A$, then every operator between separable Banach spaces factors through a restriction of $A$. We prove that many classical operator ideals (such as strictly singular, weakly compact, Banach–Saks) are generic and give a sufficient condition, based on the complexity of the ideal, for when the complement does not admit a universal operator. Another result is a new proof of a theorem of M. Girardi and W. B. Johnson, which states that there is no universal operator for the complement of the ideal of completely continuous operators.
EFFECTS OF LOCAL BUILDING MATERIALS ON INDOOR GAMMA DOSES AND RELATED RADIOLOGICAL HEALTH RISKS, AYVACIK, ÇANAKKALE/TURKEY
Authors: Top Gülcan , Örgün Yüksel , Karahan Gürsel , Horvath Mark , Kampfl Györgyi 
Published: June 2020

AbstractIn situ indoor gamma dose rate measurements were held in 79 dwellings by NaI(Tl) scintillation probe connected portable dose rate meter. For the building materials and impurities (nodules), spectrometric gamma analysis was applied by a high-resolution HpGe detector. For Ahmetçe and Nusratlı villages in Ayvacik/Çanakkale (Turkey), the measured in situ indoor gamma dose rates and related indoor annual effective dose equivalents (AEDEin) were 3 and 3.3 times, and indoor excess lifetime cancer risks (ELCRin) were 4.25 and 4.68 times higher than those of the world averages, respectively. The used local rocks were mostly ignimbrite and dacitic–rhyolitic tuffaceous (Arıklı tuff), and wall plasters were made of local soil. The highest in situ indoor gamma dose rates of the region belonged to Nusratlı village due to the intense impurities (nodules) and hydrothermal alterations in Arıklı tuff. Spectrometric gamma results revealed that 40K has an important effect on the indoor gamma doses.
Corporate Criminal Liability for the Criminal Offences in Lithuania
Authors: Girdenis Tomas , Laurinaitis Marius , Rotomskis Irmantas , Jurka Raimundas 
Published: June 2020

Abstract
Cases, where operations of legal entities entail unfair income through the malpractice of improving financial reports, are quite frequent. Such behaviour is unacceptable and deserves a stern response from the state, not only against persons involved in illegal activities but also against particular legal entities resorting to such behaviour. The purpose of this article is to analyse the elements of corporate criminal liability in the legislation of Lithuania. The article investigates the fundamentals of corporate criminal liability with the major focus on the problems of distinction and applicability of relevant elements of the latter. The analysis emphasizes the assurance of the inevitability of corporate criminal liability. The article also discusses the method of criminalizing the liability of legal entities, chosen by the Lithuanian legislator, according to which criminal liability can arise only for a limited scope of criminal offences. Presumably, the current legal regulation enables an unreasonable avoidance of criminal liability in cases where the criminal offence falls outside the aforementioned limited scope, even though it was committed to gain a material advantage over the affected party. The article also addresses the guilt of legal entities. In this regard, the article criticizes the approach of the Supreme Court of Lithuania for its evident limitation of corporate criminal liability, especially in the context of large corporations owned by many shareholders. As a possible solution, it was proposed to lay criminal responsibility on corporate governance bodies instead of the shareholders.