bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and clinical significance of esophageal abnormalities in children with celiac disease
Authors: Smolander Meri , Nurminen Samuli , Repo Marleena , Kivelä Laura , Kivistö Juho E , Hiltunen Pauliina , Huhtala Heini , Pauniaho Satu-Liisa , Kurppa Kalle 
Published: May 2020

SummaryVariable endoscopic and histological findings of esophageal lining are often detected in celiac disease, with unknown significance. We investigated the frequency and significance of such abnormalities in children. Macroscopic esophageal findings as reported by endoscopist and histological results by pathologist were compared between 316 celiac disease patients and 378 disease controls who had undergone upper gastrointestinal endoscopy with systematic esophageal biopsy sampling. Association between esophageal abnormalities and other clinical and histological characteristics of the disease was evaluated in celiac disease patients. Endoscopic esophageal findings were reported least often (3.8%) of all diseases in celiac disease, whereas histopathologic abnormalities were frequent (16.8%, n = 53). Children with celiac disease and esophageal histopathology reported more reflux than those with normal esophagus (5.7 vs. 0.8%, P = 0.032), whereas the groups were comparable in the frequency and severity of other symptoms, demographic data, prevalence of celiac disease-associated and other coexisting chronic conditions, family history of celiac disease, anthropometric and laboratory parameters, and degree of villous atrophy. Only 2 (3.7%) out of the 53 children with histologic findings had esophageal symptoms at diagnosis, and altogether seven were treated with acid blockers. Four children had increased number (≥15 eosinophils per high-power field) of esophageal eosinophils, but none of them had definite eosinophilic esophagitis. The remaining 45 children had only unspecific inflammation in the esophagus and reported no esophageal problems during a median of 6.9 years follow-up. To conclude, although relatively common, histopathological esophageal findings in celiac disease are mostly unspecific and without major clinical significance even in a long-term follow-up.
Stroke in acute type A aortic dissection: the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD)
Authors: Chemtob Raphaelle A , Fuglsang Simon , Geirsson Arnar , Ahlsson Anders , Olsson Christian , Gunn Jarmo , Ahmad Khalil , Hansson Emma C , Pan Emily , Arnadottir Linda O , Mennander Ari , Nozohoor Shahab , Wickbom Anders , Zindovic Igor , Pivodic Aldina , Jeppsson Anders , Hjortdal Vibeke , Gudbjartsson Tomas 
Published: May 2020

Abstract

OBJECTIVES
Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients.

METHODS
The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014.

RESULTS
Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P &lt; 0.001), syncope (30.6% vs 17.6%, P &lt; 0.001), cardiogenic shock (33.1% vs 20.7%, P &lt; 0.001) and pericardial tamponade (25.9% vs 14.7%, P &lt; 0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P = 0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34–3.05; P &lt; 0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27–2.23; P &lt; 0.001).

CONCLUSIONS
Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
Initial and long-term antithrombotic therapy after left atrial appendage closure with the WATCHMAN
Authors: Ledwoch Jakob , Sievert Kolja , Boersma Lucas V A , Bergmann Martin W , Ince Hüseyin , Kische Stephan , Pokushalov Evgeny , Schmitz Thomas , Schmidt Boris , Gori Tommaso , Meincke Felix , Protopopov Alexey Vladimir , Betts Timothy R , Mazzone Patrizio , Foley David , Grygier Marek , De Potter Tom , Sievert Horst ,   for the EWOLUTION Investigators
Published: May 2020

Abstract

Aims
Evidence regarding post-procedural antithrombotic regimen other than used in randomized trials assessing percutaneous left atrial appendage (LAA) closure is limited. The present work aimed to compare different antithrombotic strategies applied in the real-world EWOLUTION study.

Methods and results
A total of 998 patients with successful WATCHMAN implantation were available for the present analysis. The composite ischaemic endpoint of stroke, transitory ischaemic attack, systemic embolism and device thrombus, and the bleeding endpoint defined as at least major bleeding were assessed during an initial period (from implant until first medication change) and long-term period (from first change up to 2 years). The antithrombotic medication chosen in the initial phase was dual antiplatelet therapy (DAPT) in 60%, oral anticoagulation (OAC) in 27%, single antiplatelet therapy (SAPT) in 7%, and no medication in 6%. In the second long-term phase, SAPT was used in 65%, DAPT in 23%, no therapy in 8%, and OAC in 4%. No significant differences were found between the groups regarding the ischaemic endpoint both in the initial period (Kaplan–Meier estimated rate 2.9% for DAPT vs. 4.3% for OAC vs. 3.9% for SAPT or no therapy) and in the second period (4.2% for SAPT vs. 1.8% for DAPT vs. 3.5% for no therapy). With respect to bleeding events, the only difference was found in the initial phase with a higher incidence in patients under SAPT or no therapy.

Conclusions
Tailored antithrombotic treatment using even very reduced strategies such as SAPT or no therapy showed no significant differences regarding ischaemic complications after LAA closure.
Predictors of recurrence of atrial fibrillation within the first 3 months after ablation
Authors: Zink Matthias Daniel , Chua Winnie , Zeemering Stef , di Biase Luigi , Antoni Bayes de Luna , David Callans , Hindricks Gerhard , Haeusler Karl Georg , Al-Khalidi Hussein R , Piccini Jonathan P , Mont Lluís , Nielsen Jens Cosedis , Escobar Luis Alberto , de Bono Joseph , Van Gelder Isabelle C , de Potter Tom , Scherr Daniel , Themistoclakis Sakis , Todd Derick , Kirchhof Paulus , Schotten Ulrich 
Published: May 2020

Abstract

Aims
Freedom from atrial fibrillation (AF) at 1 year can be achieved in 50–70% of patients undergoing catheter ablation. Recurrent AF early after ablation most commonly terminates spontaneously without further interventional treatment but is associated with later recurrent AF. The aim of this investigation is to identify clinical and procedural factors associated with recurrence of AF early after ablation.

Methods and results
We retrospectively analysed data for recurrence of AF within the first 3 months after catheter ablation from the randomized controlled AXAFA–AFNET 5 trial, which demonstrated that continuous anticoagulation with apixaban is as safe and as effective compared to vitamin K antagonists in 678 patients undergoing first AF ablation. The primary outcome of first recurrent AF within 90 days was observed in 163 (28%) patients, in which 78 (48%) patients experienced an event within the first 14 days post-ablation. After multivariable adjustment, a history of stroke/transient ischaemic attack [hazard ratio (HR) 1.54, 95% confidence interval (CI) 0.93–2.6; P = 0.11], coronary artery disease (HR 1.85, 95% CI 1.20–2.86; P = 0.005), cardioversion during ablation (HR 1.78, 95% CI 1.26–2.49; P = 0.001), and an age:sex interaction for older women (HR 1.01, 95% CI 1.00–1.01; P = 0.04) were associated with recurrent AF. The P-wave duration at follow-up was significantly longer for patients with AF recurrence (129 ± 31 ms vs. 122 ± 22 ms in patients without AF, P = 0.03).

Conclusion
Half of all early AF recurrences within the first 3 months post-ablation occurred within the first 14 days post-ablation. Vascular disease and cardioversion during the procedure are strong predictors of recurrent AF. P-wave duration at follow-up was longer in patients with recurrent AF.

Trial registration
Clinicaltrials.gov identifier NCT02227550
The hidden layers of microbial community structure: extracting the concealed diversity dimensions from our sequencing data
Authors: Fasolo Andrea , Treu Laura , Stevanato Piergiorgio , Concheri Giuseppe , Campanaro Stefano , Squartini Andrea 
Published: May 2020

ABSTRACT
Microbial metabarcoding is the standard approach to assess communities’ diversity. However reports are often limited to simple OTU abundances for each phylum, giving rather one-dimensional views of microbial assemblages, overlooking other accessible aspects. The first is masked by databases incompleteness; OTU picking involves clustering at 97% (near-species) sequence identity, but different OTUs regularly end up under a same taxon name. When expressing diversity as number of obtained taxonomical names, a large portion of the real diversity lying within the data remains underestimated. Using the 16S sequencing results of an environmental transect across a gradient of 17 coastal habitats we first extracted the number of OTUs hidden under the same name. Further, we observed which was the deepest rank yielded by annotation, revealing for which microbial groups are we missing most knowledge. Data were then used to infer an evolutionary aspect: what is, in each phylum the success of the present time individuals (abundances for each OTU) in relation to their prior evolutionary success in differentiation (number of OTUs). This information reveals whether the past speciation/diversification force is matched by the present competitiveness in reproduction/persistence. The final layer explored is functional diversity, i.e. abundances of groups involved in specific environmental processes.
parSMURF, a high-performance computing tool for the genome-wide detection of pathogenic variants
Authors: Petrini Alessandro , Mesiti Marco , Schubach Max , Frasca Marco , Danis Daniel , Re Matteo , Grossi Giuliano , Cappelletti Luca , Castrignanò Tiziana , Robinson Peter N , Valentini Giorgio 
Published: May 2020

Abstract

Background
Several prediction problems in computational biology and genomic medicine are characterized by both big data as well as a high imbalance between examples to be learned, whereby positive examples can represent a tiny minority with respect to negative examples. For instance, deleterious or pathogenic variants are overwhelmed by the sea of neutral variants in the non-coding regions of the genome: thus, the prediction of deleterious variants is a challenging, highly imbalanced classification problem, and classical prediction tools fail to detect the rare pathogenic examples among the huge amount of neutral variants or undergo severe restrictions in managing big genomic data.

Results
To overcome these limitations we propose parSMURF, a method that adopts a hyper-ensemble approach and oversampling and undersampling techniques to deal with imbalanced data, and parallel computational techniques to both manage big genomic data and substantially speed up the computation. The synergy between Bayesian optimization techniques and the parallel nature of parSMURF enables efficient and user-friendly automatic tuning of the hyper-parameters of the algorithm, and allows specific learning problems in genomic medicine to be easily fit. Moreover, by using MPI parallel and machine learning ensemble techniques, parSMURF can manage big data by partitioning them across the nodes of a high-performance computing cluster. Results with synthetic data and with single-nucleotide variants associated with Mendelian diseases and with genome-wide association study hits in the non-coding regions of the human genome, involhing millions of examples, show that parSMURF achieves state-of-the-art results and an 80-fold speed-up with respect to the sequential version.

Conclusions
parSMURF is a parallel machine learning tool that can be trained to learn different genomic problems, and its multiple levels of parallelization and high scalability allow us to efficiently fit problems characterized by big and imbalanced genomic data. The C++ OpenMP multi-core version tailored to a single workstation and the C++ MPI/OpenMP hybrid multi-core and multi-node parSMURF version tailored to a High Performance Computing cluster are both available at https://github.com/AnacletoLAB/parSMURF.
Giant Gaussian process models of geomagnetic palaeosecular variation: a directional outlook
Authors: Brandt Daniele , Constable Catherine , Ernesto Marcia 
Published: May 2020

SUMMARY
Assessment of long-term palaeosecular variation (PSV) of the geomagnetic field is frequently based on simplified versions of a class of statistical models known as giant Gaussian processes (GGP) used to represent temporal variations in spherical harmonic descriptions of the field. Here we propose a new type of analysis to assess the shape and dispersion of the directional distributions caused by PSV. The quantities analysed in this study are equal-area coordinates of rotated distributions of palaeomagnetic directions, ${x_E}$ (east−west) and ${x_N}\ $(north−south) and their standard deviations (${\sigma _E}$ and ${\sigma _N}$). These are easy to determine, and can readily be numerically predicted for any GGP model, avoiding the need for the numerous simulations generally used to determine the scatter and/or elongation of directional distributions. Mean predictions of $\overline {{x_N}} $ for a simplified GGP model are different from the expected geocentric axial dipole (GAD) directions, in agreement with inclination differences noted in previous studies. The best estimates for palaeomagnetic inclination are the expected directions from the mean of virtual geomagnetic poles (VGPs) calculated using an iterative angular cut-off process. Predictions of ${\sigma _{\rm E}}$ and ${\sigma _{\rm N}}$ vary with latitude and are symmetric about the Equator. The N–S direction (${\sigma _{\rm N}}$) is always larger than E–W (${\sigma _{\rm E}}$), but the difference decreases from a maximum at the Equator to the poles, where ${\sigma _{\rm N}} = \ {\sigma _{\rm E}}$. A simplified GGP model is used to show that the parameter α (affecting variances in all Gauss coefficients) is positively correlated with ${\sigma _{\rm E}}$ and ${\sigma _{\rm N}}\ $ while the β parameter, the ratio of dipole to quadrupole family standard deviations, modifies the latitudinal dependence of ${\sigma _{\rm E}}$ and ${\sigma _{\rm N}}$. Experimental error in ${\sigma _{\rm E}}$ and ${\sigma _{\rm N}}$ can be accommodated using the common statistical parameters found in palaeomagnetic data sets, as ${\alpha _{95}}$ from site-mean directions. Predictions of simplified GGP models are compared with both numerical simulations and real data spanning the last 10 Ma. The latitudinal dependence of the proposed measures of PSV (${\sigma _{\rm E}}$ and ${\sigma _N}$) provide useful diagnostics for testing the validity of a GGP model. For the past 10 Ma the best-fitting GGP model with a mean GAD field set to $g_1^0 = \ - 18\ \mu T$ has α = 6.7 µT and β = 4.2. These new directional diagnostics will be used to investigate changes in overall geomagnetic field behaviour over other geological time intervals.
Enhanced magnetic fields within a stratified layer
Authors: Hardy Colin M , Livermore Philip W , Niesen Jitse 
Published: May 2020

SUMMARY
Mounting evidence from both seismology and numerical experiments on core composition suggests the existence of a layer of stably stratified fluid at the top of Earth’s outer core. In such a layer, a magnetostrophic force balance and suppressed radial motion lead to stringent constraints on the magnetic field, named Malkus constraints, which are a much more restrictive extension of the well known Taylor constraints. Here, we explore the consequences of such constraints for the structure of the core’s internal magnetic field. We provide a new simple derivation of these Malkus constraints, and show solutions exist which can be matched to any external potential field with arbitrary depth of stratified layer. From considerations of these magnetostatic Malkus constraints alone, it is therefore not possible to uniquely infer the depth of the stratified layer from external geomagnetic observations. We examine two models of the geomagnetic field defined within a spherical core, which obey the Taylor constraints in an inner convective region and the Malkus constraints in an outer stratified layer. When matched to a single-epoch geomagnetic potential field model, both models show that the toroidal magnetic field within the outer layer is about 100 times stronger compared to that in the inner region, taking a maximum value of 8 mT at a depth of 70 km. The dynamic regime of such a layer, modulated by suppressed radial motion but also a locally enhanced magnetic field, may therefore be quite distinct from that of any interior dynamo.
Methodology to identify the reference rock sites in regions of medium-to-high seismicity: an application in Central Italy
Authors: Lanzano Giovanni , Felicetta Chiara , Pacor Francesca , Spallarossa Daniele , Traversa Paola 
Published: May 2020

SUMMARYTo evaluate the site response using both empirical approaches (e.g. standard spectral ratio, ground motion models (GMMs), generalized inversion techniques, etc.) and numerical 1-D/2-D analyses, the definition of the reference motion, that is the ground motion recorded at stations unaffected by site-effects due to topographic, stratigraphic or basin effects, is needed. The main objective of this work is to define a robust strategy to identify the seismic stations that can be considered as reference rock sites, using six proxies for the site response: three proxies are related to the analysis of geophysical and seismological data (the repeatable site term from the residual analysis, the resonance frequencies from horizontal-to-vertical spectral ratios on noise or earthquake signals, the average shear wave velocity in the first 30 m); the remaining ones concern geomorphological and installation features (outcropping rocks or stiff soils, flat topography and absence of interaction with structures). We introduce a weighting scheme to take into account the availability and the quality of the site information, as well as the fulfillment of the criterion associated to each proxy. We also introduce a hierarchical index, to take into account the relevance of the proposed proxies in the description of the site effects, and an acceptance threshold for reference rock sites identification. The procedure is applied on a very large data set, composed by accelerometric and velocimetric waveforms, recorded in Central Italy in the period 2008–2018. This data set is composed by more than 30 000 waveforms relative to 450 earthquakes in the magnitude range 3.2–6.5 and recorded by more than 450 stations. A total of 36 out of 133 candidate stations are identified as reference sites: the majority of them are installed on rock with flat topography, but this condition is not sufficient to guarantee the absence of amplifications, especially at high frequencies. Seismological analyses are necessary to exclude stations affected by resonances. We test the impact of using these sites by calibrating a GMMs. The results show that for reference rock sites the median predictions are reduced down to about 45 per cent at short periods in comparison to the generic rock motions.
Products, Patents, Proportionality – How German Patent Law Responds to 21st Century Challenges
Authors: Schönbohm Julia , Ackermann-Blome Natalie 
Published: May 2020

Abstract
German patent law faces challenges in trying to accommodate a changing technological and economic reality. As a result, recent legislative initiatives have been dominated by discussions about adjusting the German Patent Act, especially with regard to the claim for an injunction. This article gives a brief overview of these new challenges as well as the legal background of injunctions in German patent law and the underlying case law. It also evaluates the proposed amendment of the provision on injunctions in the discussion draft of the Federal Ministry of Justice and Consumer Protection (BMJV) on the modernisation of patent law of 14 January 2020.
MicroRNA Signature of Epithelial-Mesenchymal Transition in Group B Streptococcal Infection of the Placental Chorioamniotic Membranes
Authors: Weed Samantha , Armistead Blair , Coleman Michelle , Liggit H Denny , Johnson Brian , Tsai Jesse , Beyer Richard P , Bammler Theodor K , Kretzer Nicole M , Parker Ed , Vanderhoeven Jeroen P , Bierle Craig J , Rajagopal Lakshmi , Adams Waldorf Kristina M 
Published: May 2020

AbstractBackgroundInfection-induced preterm birth is a major cause of neonatal mortality and morbidity and leads to preterm premature rupture of placental chorioamniotic membranes. The loss of amniotic epithelial cells and tensile strength preceding membrane rupture is poorly understood. We hypothesized that intrauterine bacterial infection induces changes in microRNA (miRNA) expression, leading to amniotic epithelial cell loss and membrane weakening.MethodsTen pregnant pigtail macaques received choriodecidual inoculation of either group B Streptococcus (GBS) or saline (n = 5/group). Placental chorioamniotic membranes were studied using RNA microarray and immunohistochemistry. Chorioamniotic membranes from women with preterm premature rupture of membranes (pPROM) and normal term pregnancies were studied using transmission electron microscopy.ResultsIn our model, an experimental GBS infection was associated with changes in the miRNA profile in the chorioamniotic membranes consistent with epithelial to mesenchymal transition (EMT) with loss of epithelial (E-cadherin) and gain of mesenchymal (vimentin) markers. Similarly, loss of desmosomes (intercellular junctions) was seen in placental tissues from women with pPROM.ConclusionsWe describe EMT as a novel mechanism for infection-associated chorioamniotic membrane weakening, which may be a common pathway for many etiologies of pPROM. Therapy based on anti-miRNA targeting of EMT may prevent pPROM due to perinatal infection.
Paying Participants in COVID-19 Trials
Authors: Largent Emily A , Lynch Holly Fernandez 
Published: May 2020

Abstract
Trials are in development and underway to examine potential interventions for treatment and prophylaxis of coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances. Here, we review 3 functions of research payment—reimbursement, compensation, and incentive—and identify heightened and novel ethical concerns in the context of a global pandemic. We argue that COVID-19 trial participants should usually be offered reimbursement for research-related expenses, and compensation for their time and effort, as for other types of research under usual circumstances. Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Where essential, however, incentives can be ethically permissible, so long as reasonable efforts are made to minimize the possibility of undue influence.