bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transposable Elements Contribute to Genome Dynamics and Gene Expression Variation in the Fungal Plant PathogenVerticillium dahliae
Authors: Torres David E , Thomma Bart P H J , Seidl Michael F 
Published: June 2021

AbstractTransposable elements (TEs) are a major source of genetic and regulatory variation in their host genome and are consequently thought to play important roles in evolution. Many fungal and oomycete plant pathogens have evolved dynamic and TE-rich genomic regions containing genes that are implicated in host colonization and adaptation. TEs embedded in these regions have typically been thought to accelerate the evolution of these genomic compartments, but little is known about their dynamics in strains that harbor them. Here, we used whole-genome sequencing data of 42 strains of the fungal plant pathogen Verticillium dahliae to systematically identify polymorphic TEs that may be implicated in genomic as well as in gene expression variation. We identified 2,523 TE polymorphisms and characterize a subset of 8% of the TEs as polymorphic elements that are evolutionary younger, less methylated, and more highly expressed when compared with the remaining 92% of the total TE complement. As expected, the polyrmorphic TEs are enriched in the adaptive genomic regions. Besides, we observed an association of polymorphic TEs with pathogenicity-related genes that localize nearby and that display high expression levels. Collectively, our analyses demonstrate that TE dynamics in V. dahliae contributes to genomic variation, correlates with expression of pathogenicity-related genes, and potentially impacts the evolution of adaptive genomic regions.
Damages and Recovery of Profits in Intellectual Property Litigation before Italian Courts
Authors: Ricolfi Marco 
Published: June 2021

Abstract
The purpose of the article is twofold. At a more general level, it aims to illustrate how the changes in intellectual property litigation adopted in Italy since 2005, particularly in connection with the setting of damages suffered by rights holders and the recovery of profits obtained by infringers, have been remarkably successful in increasing the overall efficacy of the protection system. At the same time, it focuses on one particular feature of the system, the newly introduced recovery of profits from innocent infringers, arguing that the adoption of this second limb of recovery is questionable from a policy viewpoint and introduces a number of difficulties in the enforcement process, several of which transpire to be intractable. Some other aspects of the actions, both with regard to damages and recovery of profits, adopted in the recent Italian legislation are examined against the background of the EU enforcement directive and of TRIPS, with a view to highlighting both the strong points and the incongruities of the rules.
‘The Implementation of the Directive on Copyright and Related Rights in the Digital Single Market’ ‒ Conference Report on the Sixth Binational Seminar of the Technische Universität Dresden and Charles University in Prague, 1 December 2020
Authors: Linke David , Žikovská Petra 
Published: June 2021

Abstract
‘It’s drafting time!’, but we are not talking about Patrick Mahomes, Alexis Lafrenière or Stephen Curry,1 rather about the implementation proposals for the Digital Single Market (DSM) Directive. This Directive caused a certain media stir in the run-up to it, and now the national legislatures need to implement the provisions of the Directive into the respective national laws. The Member States have until June 2021 to make the relevant transpositions. It will become apparent that very different approaches are being pursued in this respect, but that there are also similarities. For that reason, the sixth binational seminar has taken this as an opportunity to examine on 1 December 2020 the implementation efforts made by Germany and the Czech Republic in a comparative legal analysis under the topic: ‘The Implementation of the Directive on Copyright and related rights in the Digital Single Market’.
Primary mental health care for older persons in India: how age-inclusive are public policies?
Authors: Kafczyk Tom , Hämel Kerstin 
Published: June 2021

AbstractThe need to improve the primary mental healthcare system in India has gained increasing public health attention. Concomitantly, efforts to frame and develop appropriate public mental health care through legislation and related strategies and programmes have been undertaken. Because older people in India are particularly prone to mental health problems, this study explores the inclusiveness of Indian public policies in addressing the primary mental health care needs of older people from a cross-policy perspective. The basis of this thematic document analysis is 41 key national strategic documents (1999–2018) from different thematically grouped policy fields. In the context of population ageing, socio-economic challenges for older people and changing family norms, the policies delineate a pronounced interest in old-age-inclusive primary mental health care, whereas international policies are regarded as important reference points. While some of the policies address older persons as a vulnerable group in general, others delineate a more differentiated picture of the older population. Moreover, as new rights with implications for old-age mental health care, including community-based access to mental health care, have emerged, an integrated old-age mental healthcare policy spanning across sectors remains absent. Although old-age-inclusive primary mental health care is an emerging trend in India, its development as a cross-cutting policy issue remains in its infancy. Accordingly, unambiguous integrated policy approaches are needed to address the complex mental healthcare needs of older persons, and further research should be undertaken to focus on mental healthcare strategies and approaches at the primary care level.
Evidence of the impact of a national anti-tobacco prevention campaign across demographic subgroups
Authors: Vallone Donna M , Perks Siobhan N , Pitzer Lindsay , Liu Michael , Kreslake Jennifer M , Rath Jessica M , Hair Elizabeth C 
Published: June 2021

Abstract
Mass media campaigns are an effective population-level intervention for preventing tobacco use. However, little evidence exists for whether these campaigns similarly influence demographic subgroups. This study examined the effects of the truth® campaign to reduce tobacco use among demographic subgroups. We used data from a national, continuous, cross-sectional tracking survey of 15–24-year-olds (n = 32 331). We used a measure of weekly aggregated campaign exposure to assess whether cigarette smoking intentions and current cigarette use varied by race/ethnicity, financial situation and population density subgroups, controlling for factors known to be associated with tobacco use. Examining estimates across subgroup categories in light of the overall model estimates revealed that the effects of week-level campaign exposure on cigarette smoking intentions and current cigarette use were similar across subgroups. Wald tests of equality across estimates in each subgroup suggested that the estimates did not differ from one another in any given instance. The truth campaign does not differ significantly in its capacity to prompt declines in tobacco use across a broad spectrum of US youth and young adults. Mass media tobacco prevention campaigns can be an effective and critical component of a comprehensive tobacco control program, particularly with respect to reducing tobacco-related disparities among demographic subgroups.
Assessing the impact of alcohol consumption on the genetic contribution to mean corpuscular volume
Authors: Thompson Andrew , King Katharine , Morris Andrew P , Pirmohamed Munir 
Published: June 2021

Abstract
The relationship between the genetic loci that influence mean corpuscular volume (MCV) and those associated with excess alcohol drinking is unknown. We used white British participants from the UK Biobank (n = 362 595) to assess the association between alcohol consumption and MCV, and whether this was modulated by genetic factors. Multivariable regression was applied to identify predictors of MCV. GWAS, with and without stratification for alcohol consumption, determined how genetic variants influence MCV. SNPs in ADH1B, ADH1C and ALDH1B were used to construct a genetic score to test the assumption that acetaldehyde formation is an important determinant of MCV. Additional investigations using Mendelian randomization and phenome­wide association analysis were conducted. Increasing alcohol consumption by 40 g/week resulted in a 0.30% [95% confidence interval CI: 0.30–0.31%] increase in MCV (P &lt; 1.0 × 10−320). Unstratified (irrespective of alcohol intake) GWAS identified 212 loci associated with MCV, of which 108 were novel. There was no heterogeneity of allelic effects by drinking status. No association was found between MCV and the genetic score generated from alcohol metabolizing genes. Mendelian randomization demonstrated a causal effect for alcohol on MCV. Seventy-one SNP-outcome pairs reached statistical significance in phenome­wide association analysis, with evidence of shared genetic architecture for MCV and thyroid dysfunction, and mineral metabolism disorders. MCV increases linearly with alcohol intake in a causal manner. Many genetic loci influence MCV, with new loci identified in this analysis that provide novel biological insights. However, there was no interaction between alcohol consumption and the allelic variants associated with MCV.
Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise
Authors: Danese Silvio , Peyrin-Biroulet Laurent 
Published: June 2021

Abstract
Conventional systemic and biologic agents are the mainstay of inflammatory bowel disease (IBD) management; however, many of these agents are associated with loss of clinical response, highlighting the need for effective, novel targeted therapies. Janus kinase (JAK) 1-3 and tyrosine kinase 2 (TYK2) mediate signal transduction events downstream of multiple cytokine receptors that regulate targeted gene transcription, including the interleukin-12, interleukin-23, and type I interferon receptors for TYK2. This review summarizes the role of TYK2 signaling in IBD pathogenesis, the differential selectivity of TYK2 inhibitors, and the potential clinical implications of TYK2 inhibition in IBD. A PubMed literature review was conducted to identify studies of JAK1-3 and TYK2 inhibitors in IBD and other immune-mediated inflammatory diseases. Key efficacy and safety information was extracted and summarized. Pan-JAK inhibitors provide inconsistent efficacy in patients with IBD and are associated with toxicities resulting from a lack of selectivity at therapeutic dosages. Selective inhibition of TYK2 signaling via an allosteric mechanism, with an agent that binds to the regulatory (pseudokinase) domain, may reduce potential toxicities typically associated with JAK1-3 inhibitors. Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases. Allosteric TYK2 inhibition is more selective than JAK1-3 inhibition and has the potential to limit toxicities typically associated with JAK1-3 inhibitors. Future studies will be important in establishing the role of selective, allosteric TYK2 inhibition in the management of IBD.
PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer
Authors: Rugo Hope S , Loi Sherene , Adams Sylvia , Schmid Peter , Schneeweiss Andreas , Barrios Carlos H , Iwata Hiroji , Diéras Véronique , Winer Eric P , Kockx Mark M , Peeters Dieter , Chui Stephen Y , Lin Jennifer C , Nguyen-Duc Anh , Viale Giuseppe , Molinero Luciana , Emens Leisha A 
Published: June 2021

Abstract

Background
In the phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced or metastatic triple-negative breast cancer patients who were programmed death-ligand 1 (PD-L1)+ (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry assay. Here we evaluate 2 other PD-L1 assays for analytical concordance with SP142 and patient-associated clinical outcomes.

Methods
Samples from 614 patients (68.1% of intention-to-treat population) were centrally evaluated by immunohistochemistry for PD-L1 status on IC (VENTANA SP142, SP263, Dako 22C3) or as a combined positive score (CPS; 22C3).

Results
Using SP142, SP263, and 22C3 assays, PD-L1 IC ≥1% prevalence was 46.4% (95% confidence interval [CI] = 42.5% to 50.4%), 74.9% (95% CI = 71.5% to 78.3%), and 73.1% (95% CI = 69.6% to 76.6%), respectively; 80.9% were 22C3 CPS ≥1. At IC ≥1% (+), the analytical concordance between SP142 and SP263 and 22C3 was 69.2% and 68.7%, respectively. Almost all SP142+ cases were captured by other assays (double positive), but several SP263+ (29.6%) or 22C3+ (29.0%) cases were SP142– (single positive). A+nP clinical activity vs placebo+nP in SP263+ and 22C3+ patients (progression-free survival [PFS] hazard ratios [HRs] = 0.64 to 0.68; overall survival [OS] HRs = 0.75 to 0.79) was driven by double-positive cases (PFS HRs = 0.60 to 0.61; OS HRs = 0.71 to 0.75) rather than single-positive cases (PFS HRs = 0.68 to 0.81; OS HRs = 0.87 to 0.95). Concordance for harmonized cutoffs for SP263 (IC ≥4%) and 22C3 (CPS ≥10) to SP142 (IC ≥1%) was subpar (approximately 75%).

Conclusions
22C3 and SP263 assays identified more patients as PD-L1+ (IC ≥1%) than SP142. No inter-assay analytical equivalency was observed. Consistent improved A+nP efficacy was captured by the SP142 PD-L1 IC ≥1% subgroup nested within 22C3 and SP263 PD-L1+ (IC ≥1%) populations.
Perforated Meckel’s diverticulitis secondary to a corn kernel obstruction of lumen in an elderly patient
Authors: De la Cruz Garcia Isidora , Tan Kimberley , Riddell Andrew 
Published: June 2021

Abstract
Meckel’s diverticulum (MD) is the most common congenital malformation of the gastrointestinal tract. The most frequent complications are bleeding, intestinal obstruction, intussusception and neoplasm. Perforation because of diverticulitis is very rare and usually associated to foreign bodies. We report a case of an elderly man who presented with right iliac fossa pain, raised inflammatory markers and a computer tomography (CT) scan suggestive of Meckel’s diverticulitis. He underwent a laparoscopic converted to open small bowel resection and primary anastomosis for perforated MD, which revealed a corn kernel at its base in the absence of ectopic gastric or pancreatic tissue. Symptomatic and perforated MD secondary to a phytobezoar is extremely rare in elderly patients, hence the importance of clinical suspicion in patients with abdominal pain, independent from their age, to avoid delay in diagnosis, which can lead to increased morbidity and mortality in this demographic.
eBASCS: Disentangling overlapping astronomical sources II, using spatial, spectral, and temporal information
Authors: Meyer Antoine D , van Dyk David A , Kashyap Vinay L , Campos Luis F , Jones David E , Siemiginowska Aneta , Zezas Andreas 
Published: June 2021

ABSTRACT
The analysis of individual X-ray sources that appear in a crowded field can easily be compromised by the misallocation of recorded events to their originating sources. Even with a small number of sources, which none the less have overlapping point spread functions, the allocation of events to sources is a complex task that is subject to uncertainty. We develop a Bayesian method designed to sift high-energy photon events from multiple sources with overlapping point spread functions, leveraging the differences in their spatial, spectral, and temporal signatures. The method probabilistically assigns each event to a given source. Such a disentanglement allows more detailed spectral or temporal analysis to focus on the individual component in isolation, free of contamination from other sources or the background. We are also able to compute source parameters of interest like their locations, relative brightness, and background contamination, while accounting for the uncertainty in event assignments. Simulation studies that include event arrival time information demonstrate that the temporal component improves event disambiguation beyond using only spatial and spectral information. The proposed methods correctly allocate up to 65${{\ \rm per\ cent}}$ more events than the corresponding algorithms that ignore event arrival time information. We apply our methods to two stellar X-ray binaries, UV Cet and HBC 515 A, observed with Chandra. We demonstrate that our methods are capable of removing the contamination due to a strong flare on UV Cet B in its companion ≈40× weaker during that event, and that evidence for spectral variability at times-scales of a few ks can be determined in HBC 515 Aa and HBC 515 Ab.
Modelling of SN 2013dx associated with the low-redshift GRB130702A points to diversity in GRB/SN properties
Authors: Mazzali P A , Pian E , Bufano F , Ashall C 
Published: June 2021

ABSTRACT
The properties of the broad-lined Type Ic supernova (SN) 2013dx, associated with the long gamma-ray burst GRB 130702A at a redshift z = 0.145, are derived via spectral modelling. SN 2013dx was similar in luminosity to other GRB/SNe, with a derived value of the mass of 56Ni ejected in the explosion of ≈0.4 M⊙. However, its spectral properties suggest a smaller explosion kinetic energy. Radiation transport models were used to derive a plausible mass and density distribution of the SN ejecta in a one-dimensional approximation. While the mass ejected in the explosion that is obtained from the modelling (Mej ≈ 9 M⊙) is similar to that of all other well-studied GRB/SNe, the kinetic energy is significantly smaller (EK ∼ 1052 erg). This leads to a smaller EK/Mej ratio, ≈1051 erg/M⊙, which is reflected in the narrower appearance of the spectral lines. While the low EK does not represent a problem for the scenario in which magnetar energy aids powering the explosion and the nucleosynthesis, it is nevertheless highly unusual. SNe Ic with similar EK have never been seen in coincidence with a GRB, and no well-observed GRB/SN has shown similarly low EK and EK/Mej.
Measuring time delays – I. Using a flux time series that is a linear combination of time-shifted light curves
Authors: Springer Ofer M , Ofek Eran O 
Published: June 2021

ABSTRACT
Several phenomena in astrophysics generate light curves with time delays. Among these are reverberation mapping and lensed quasars. In these systems, the measurement of the time delay is complicated by the fact that the delayed components are unresolved and that the light curves are generated from a stochastic process. We derive the likelihood function of the observations given a model of either a combination of time-delayed light curves or a single light curve. This likelihood function is different from the auto-correlation-function-based investigated by previous studies. We demonstrate that given a single-band light curve that is a linear combination of two (or more) time-shifted copies of an original light curve, generated from a probability distribution with some roughly known power spectrum, it is possible to test if the total-flux light curve is a composition of time-delayed copies or, alternatively, is consistent with being a single copy of the original light curve. Furthermore, it is possible to measure the time delays between these components even when the flux ratio is about 1/10. In the era of synoptic sky surveys, this method is useful for identifying lensed quasars and simultaneously measuring their time delays, and also for estimating the reverberation time scales of active galactic nuclei. In a companion paper, we derive another method that uses the centre-of-light astrometric position (e.g. of a lensed quasar) along with the combined flux. We also present the proper likelihood function for fitting a power-law model to a power spectrum. We test the new method on simulations and provide python and matlab implementations.
BEDE: Bayesian estimates of dust evolution for nearby galaxies
Authors: De Vis P , Maddox S J , Gomez H L , Jones A P , Dunne L 
Published: June 2021

ABSTRACT
We build a rigorous statistical framework to provide constraints on the chemical and dust evolution parameters for nearby late-type galaxies with a wide range of gas fractions ($3{{\ \rm per\ cent}}\lt f_g\lt 94{{\ \rm per\ cent}}$). A Bayesian Monte Carlo Markov Chain framework provides statistical constraints on the parameters used in chemical evolution models. Nearly a million one-zone chemical and dust evolution models were compared to 340 galaxies. Relative probabilities were calculated from the χ2 between data and models, marginalized over the different time-steps, galaxy masses, and star formation histories. We applied this method to find ‘best-fitting’ model parameters related to metallicity, and subsequently fix these metal parameters to study the dust parameters. For the metal parameters, a degeneracy was found between the choice of initial mass function, supernova metal yield tables, and outflow prescription. For the dust parameters, the uncertainties on the best-fitting values are often large except for the fraction of metals available for grain growth, which is well constrained. We find a number of degeneracies between the dust parameters, limiting our ability to discriminate between chemical models using observations only. For example, we show that the low dust content of low-metallicity galaxies can be resolved by either reducing the supernova dust yields and/or including photofragmentation. We also show that supernova dust dominates the dust mass for low-metallicity galaxies and grain growth dominates for high-metallicity galaxies. The transition occurs around 12 + log (O/H) = 7.75, which is lower than found in most studies in the literature.
Thermal instability and multiphase gas in the simulated interstellar medium with conduction, viscosity, and magnetic fields
Authors: Jennings R Michael , Li Yuan 
Published: June 2021

ABSTRACT
Thermal instability plays a crucial role in the formation of multiphase structures and their dynamics in the interstellar medium, and is a leading theory for cold cloud creation in various astrophysical environments. In this paper, we use 2D simulations to investigate thermal instability under the influence of various initial conditions and physical processes. We experiment with Gaussian random field (GRF) density perturbations of different initial power spectra. We also enrol thermal conduction and physical viscosity in isotropic hydrodynamic and anisotropic magnetohydrodynamic (MHD) simulations. We find that the initial GRF spectral index α has a dramatic impact on the pure hydrodynamic development of thermal instability, influencing the size, number, and motions of clouds. Cloud fragmentation happens due to two mechanisms: tearing and contraction rebound. In the runs with isotropic conduction and viscosity, the structures and dynamics of the clouds are dominated by evaporation and condensation flows in the non-linear regime, and the flow speed is regulated by viscosity. Cloud disruptions happen as a result of the Darrieus–Landau instability. However, at very late times, all individual clouds merge into one cold structure in all hydrodynamic runs. In the MHD case, the cloud structure is determined by both the initial perturbations and the initial magnetic field strength. In high-β runs, anisotropic conduction causes dense filaments to align with the local magnetic fields and the field direction can become reoriented. Strong magnetic fields suppress cross-field contraction and cold filaments can form along or perpendicular to the initial fields.