bluuebunny/crossref_metadata_2025_split huggingface dataset:
ensembldb: an R package to create and use Ensembl-based annotation resources
Authors: Rainer Johannes , Gatto Laurent , Weichenberger Christian X 
Published: January 2019

Abstract

Summary
Bioinformatics research frequently involves handling gene-centric data such as exons, transcripts, proteins and their positions relative to a reference coordinate system. The ensembldb Bioconductor package retrieves and stores Ensembl-based genetic annotations and positional information, and furthermore offers identifier conversion and coordinates mappings for gene-associated data. In support of reproducible research, data are tied to Ensembl releases and are kept separately from the software. Premade data packages are available for a variety of genomes and Ensembl releases. Three examples demonstrate typical use cases of this software.

Availability and implementation
ensembldb is part of Bioconductor (https://bioconductor.org/packages/ensembldb).

Supplementary information
Supplementary data are available at Bioinformatics online.
Haplotype assembly of autotetraploid potato using integer linear programing
Authors: Siragusa Enrico , Haiminen Niina , Finkers Richard , Visser Richard , Parida Laxmi 
Published: January 2019

Abstract

Summary
Haplotype assembly of polyploids is an open issue in plant genomics. Recent experimental studies on highly heterozygous autotetraploid potato have shown that available methods do not deliver satisfying results in practice. We propose an optimal method to assemble haplotypes of highly heterozygous polyploids from Illumina short-sequencing reads. Our method is based on a generalization of the existing minimum fragment removal model to the polyploid case and on new integer linear programs to reconstruct optimal haplotypes. We validate our methods experimentally by means of a combined evaluation on simulated and experimental data based on 83 previously sequenced autotetraploid potato cultivars. Results on simulated data show that our methods produce highly accurate haplotype assemblies, while results on experimental data confirm a sensible improvement over the state of the art.

Availability and implementation
Executables for Linux at http://github.com/Computational Genomics/HaplotypeAssembler.

Supplementary information
Supplementary data are available at Bioinformatics online.
Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells
Authors: Muniraj Nethaji , Siddharth Sumit , Nagalingam Arumugam , Walker Alyssa , Woo Juhyung , Győrffy Balázs , Gabrielson Ed , Saxena Neeraj K , Sharma Dipali 
Published: January 2019

Abstract
Withaferin A (WFA), a steroidal lactone, negatively regulates breast cancer growth however, its mechanisms of action remain largely elusive. We found that WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells. WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion. Autolysosomes display the characteristics of acidic compartments in WFA-treated cells; however, the protein degradation activity of lysosomes is inhibited. Blockade of autophagic flux reduces the recycling of cellular fuels leading to insufficient substrates for tricarboxylic acid (TCA) cycle and impaired oxidative phosphorylation. WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation. AMPK inhibition abrogates while AMPK activation potentiates WFA’s effect. WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells. Genetic knockout of BECN1 and ATG7 fails to rescue cells from WFA treatment; in contrast, addition of methyl pyruvate to supplement TCA cycle protects WFA-treated cells. Together, these results implicate that WFA is a potent lysosomal inhibitor; energetic impairment is required for WFA-induced apoptosis and growth inhibition and combining WFA and 2-DG is a promising therapeutic strategy for breast cancer.
Transfinite fractal dimension of trees and hierarchical scale-free graphs
Authors: Komjáthy Júlia , Molontay Roland , Simon Károly 
Published: January 2019

Abstract
In this article, we introduce a new concept: the transfinite fractal dimension of graph sequences motivated by the notion of fractality of complex networks proposed by Song et al. We show that the definition of fractality cannot be applied to networks with ‘tree-like’ structure and exponential growth rate of neighbourhoods. However, we show that the definition of fractal dimension could be modified in a way that takes into account the exponential growth, and with the modified definition, the fractal dimension becomes a proper parameter of graph sequences. We find that this parameter is related to the growth rate of trees. We also generalize the concept of box dimension further and introduce the transfinite Cesaro fractal dimension. Using rigorous proofs, we determine the optimal box-covering and transfinite fractal dimension of various models: the hierarchical graph sequence model introduced by Komjáthy and Simon, Song–Havlin–Makse model, spherically symmetric trees and supercritical Galton–Watson trees.
Tallage-at-Will in Later Medieval England
Authors: Bailey Mark 
Published: January 2019

Abstract
Tallage-at-will was a seigniorial tax on unfree tenants and hereditary serfs in medieval England, and one of the two main tests of villeinage under the common law. Contemporary lawyers argued that it was compulsory and uncertain, which has led many historians to portray it as a variable, exorbitant and arbitrary component of villein rent, but this article offers the first comprehensive survey of its form, operation and significance. It reveals that by c.1300 the frequency and level of tallage had become codified and largely fixed, it existed in various forms, it was not found on many manors, and methods of determining individual contributions varied. Thus the example of tallage-at-will serves to reinforce the heterogeneity of villeinage in England and, by extension, the unevenness of its experience on the ground. The absence of tallage-at-will from a sizeable minority of manors c.1300, and its rapid decline and disappearance after 1348–9 from many more, raises questions about its significance as one of the two key tests of villeinage in the common law. Finally, the differences between villein tallage and free aid are explored, and found to be less clear-cut than medieval lawyers would have us believe.
Can complex mitral valve repair be performed with robotics? An institution’s experience utilizing a dedicated team approach in 500 patients†
Authors: Loulmet Didier F , Ranganath Neel K , Neuburger Peter J , Nampiaparampil Robert G , Galloway Aubrey C , Grossi Eugene A 
Published: January 2019

AbstractOBJECTIVESThe full potential of robotics has not been achieved in terms of addressing the most challenging mitral valve (MV) cases. We outline our technique and report our early results with totally endoscopic robotic MV repair in a wide range of pathologies.METHODSFrom May 2011 to August 2017, a dedicated team attempted totally endoscopic robotic MV repair in 500 MV regurgitation patients. Repair complexity was scored in 3 categories. We analysed our sequential case experience by quartiles.RESULTSPatient mean age was 60.8 years (range 18–88). Aetiologies included: degenerative 382 (76.4%), functional 37 (7.4%), inflammatory 22 (4.4%) and others 59 (11.8%). Mitral annular calcification was present in 64 (12.8%) cases. Simple MV repair (annuloplasty alone or with 1 leaflet segment repair) was performed in 240 (48%) patients, complex (repair involving more than 1 segment on the same leaflet) in 140 (28%) patients and most complex (bileaflet repair or mitral annular calcification excision with atrioventricular groove repair) in 120 (24%) patients. Concomitant procedures included: left appendage closure (94.8%), patent foramen ovale/atrial septal defect (PFO/ASD) closure (19.6%), cryoablation (19.4%), tricuspid repair (6.2%) or hybrid percutaneous coronary revascularization (7.8%). The overall repair rate was 99.4%, with 0.6% early mortality and 1.2% stroke rate (0.2% permanent neurological deficit). Case complexity increased with our experience. Despite an increase in aortic occlusion and perfusion times (median 86.5 and 125 min) and a slight decrease in operating room extubation rate (overall 64%), length of hospital stay (median 4 days) and 30-day readmission rate (overall 3.6%) were not affected by the progressive inclusion of more complex cases.CONCLUSIONSTotally endoscopic robotic MV repair performed by a dedicated team allows one to address the entire spectrum of pathological complexity and provides consistent results.
Mechanical haemolytic anaemia assessed with four-dimensional flow cardiac magnetic resonance
Authors: Uchida Wataru , Tokuda Yoshiyuki , Takehara Yasuo , Usui Akihiko 
Published: January 2019

Abstract
A 66-year-old woman developed marked haemolytic anaemia 2 years after total aortic arch replacement using a branched Dacron graft. Echocardiography confirmed bicuspid aortic valve stenosis. A four-dimensional flow magnetic resonance imaging revealed a jet flow arising from the aortic valve along with the vortex and turbulent flow inside the kinked prosthetic graft at the ascending aorta. She underwent a reoperation to replace the aortic valve and correct the kinking. The estimated energy loss after intervention was relieved to 2.9 mJ/cardiac cycle from 4.3 mJ/cardiac cycle before intervention. The patient’s anaemia resolved immediately after the reoperation.
Variability of repairable bicuspid aortic valve phenotypes: towards an anatomical and repair-oriented classification†
Authors: de Kerchove Laurent , Mastrobuoni Stefano , Froede Lennart , Tamer Saadallah , Boodhwani Munir , van Dyck Michel , el Khoury Gebrine , Schäfers Hans-Joachim 
Published: January 2019

AbstractOBJECTIVESThe bicuspid aortic valve (BAV) exists in a wide variety of valve phenotypes. The aim of this study was to assess the anatomical characteristics of the different phenotypes and develop a classification system to aid surgical repair.METHODSIn 178 consecutive patients operated on for aortic insufficiency or aortic dilatation in 2 centres, 11 anatomical parameters of BAV were measured by echocardiography and intraoperatively. All BAV judged potentially repairable were included in the study.RESULTSCommissural orientation correlated positively with fusion length (R2 = 0.6, P < 0.001) and negatively with non-functional commissure height (R2 = 0.45, P < 0.001). The cohort was divided into 3 groups according to their commissural orientation (type A: symmetrical, 160–180°, n = 73; type B: asymmetrical, 140–159°, n = 74; and type C: very asymmetrical, 120–139°, n = 31). The patterns of cusp fusion, annulus and aortic size were similar among the groups. Fusion length and the geometric height of the cusps decreased from type A to C; non-functional commissure height increased from type A to C (P < 0.05). Patient age increased from type A to type C. Isolated aortic dilatation was more frequent in type A, and severe aortic insufficiency was more frequent in types B and C (P < 0.05). Valve repair techniques and management of commissural orientation varied among the 3 groups (P < 0.05). Aortic valve replacement and residual aortic insufficiency after repair were more frequent in type C (P < 0.05).CONCLUSIONSThe BAV phenotypes follow a continuous spectrum that extends from symmetrical to very asymmetrical BAV. We describe the main anatomical parameters (including commissure orientation, length of fusion and non-functional commissure height) and their variation across this spectrum. We propose a new repair-oriented classification system based on those parameters that can be used to predict valve repair techniques. This classification needs further validation with regards to surgical techniques and long-term outcomes.
Deep learning for cardiovascular medicine: a practical primer
Authors: Krittanawong Chayakrit , Johnson Kipp W , Rosenson Robert S , Wang Zhen , Aydar Mehmet , Baber Usman , Min James K , Tang W H Wilson , Halperin Jonathan L , Narayan Sanjiv M 
Published: January 2019

Abstract
Deep learning (DL) is a branch of machine learning (ML) showing increasing promise in medicine, to assist in data classification, novel disease phenotyping and complex decision making. Deep learning is a form of ML typically implemented via multi-layered neural networks. Deep learning has accelerated by recent advances in computer hardware and algorithms and is increasingly applied in e-commerce, finance, and voice and image recognition to learn and classify complex datasets. The current medical literature shows both strengths and limitations of DL. Strengths of DL include its ability to automate medical image interpretation, enhance clinical decision-making, identify novel phenotypes, and select better treatment pathways in complex diseases. Deep learning may be well-suited to cardiovascular medicine in which haemodynamic and electrophysiological indices are increasingly captured on a continuous basis by wearable devices as well as image segmentation in cardiac imaging. However, DL also has significant weaknesses including difficulties in interpreting its models (the ‘black-box’ criticism), its need for extensive adjudicated (‘labelled’) data in training, lack of standardization in design, lack of data-efficiency in training, limited applicability to clinical trials, and other factors. Thus, the optimal clinical application of DL requires careful formulation of solvable problems, selection of most appropriate DL algorithms and data, and balanced interpretation of results. This review synthesizes the current state of DL for cardiovascular clinicians and investigators, and provides technical context to appreciate the promise, pitfalls, near-term challenges, and opportunities for this exciting new area.
Assessment of developmental risk information on medicines for inclusion on the WHO’s Essential Medicines List
Authors: Polifka Janine E , J. Boroje Isabella , Ferdosi Hamid , Lamm Steven H 
Published: January 2019

AbstractBackgroundThe WHO develops biannually an Essential Medicines List (EML) of medications proposed for national formularies to be safe, effective and cost-effective. This satisfies the priority healthcare needs of most adult populations, but it does not consider the unique toxicological risks that occur from exposures during pregnancy.MethodsDevelopmental toxicity risk information for the 451 specific agents on the 2017 EML were identified from four well-recognized compendia of teratological assessments. On this basis, each agent was classified as having known, suggested, or little to no developmental risk, or as having insufficient information.ResultsThirteen (3%) EML agents posed known developmental risks, and 115 (25%) had evidence suggesting risk. For 170 (38%) agents, there was little or no evidence of such risk. Thus, risk classification could be determined for 66% of the agents. For an additional 153 (34%) agents, the information was insufficient for classification.ConclusionIt is feasible to expand the classification of most of the EML agents to include the risks from exposure during pregnancy.
Taking the Pulse of Environmental and Fisheries Law: The Common Fisheries Policy, the Habitats Directive, and Brexit
Authors: Appleby Thomas , Harrison James 
Published: January 2019

Abstract
There has long been a tension between environmental regulation and the European Common Fisheries Policy (CFP), which has been addressed over time through progressive reform of the CFP. It is now recognised that Member States may comply with their obligations under EU nature conservation law by taking unilateral non-discriminatory measures within their territorial seas to protect the marine environment from threats posed by fishing. Nevertheless, fundamental uncertainties remain when it comes to the application of these obligations to offshore waters. This article explores the options available to coastal states in this context and the weaknesses of the procedures introduced to the reformed CFP in 2013. It is argued that compliance with nature conservation law in the context of fisheries is not discretionary and that in the absence of measures agreed at the EU level, Member States must comply with their obligations under the Habitats Directive in their capacity as a flag state. Finally, the article addresses the implications of Brexit for the protection of European Marine Sites in UK waters, suggesting that Brexit offers opportunities to strengthen the protection of marine ecosystems by making future access arrangements for foreign fishing vessels conditional upon compliance with nature conservation laws.
Dynamics of mobility-stasis in refugee journeys: Case of resettlement from Turkey to Canada
Authors: Yıldız Uğur , Sert Deniz Ş 
Published: January 2019

Abstract
The refugee Odyssey is often not a linear, straightforward movement from point A to point B, from sending country to receiving one. Rather, it involves multiple paths, gateways, entry and exit points, and territories en route to the country of resettlement. Crucially, the journey involves not only mobility but also immobility and/or periods of stasis—breaks that are, in many cases, a natural part of the journey. Alongside this diversity of paths and movements, the refugee experience—understood in terms of the practices and acts of refugees en route—is also far from homogeneous. Each journey may well have an episodic character, where the course, direction, and periods of waiting for one asylum traveller can differ significantly from those of previous and/or future travellers—even if the departure point and destination are the same. Within this context, this article examines the breaks or periods of stasis that punctuate the refugee Odyssey, which we call mobistasis. We base our empirical findings on research conducted with people en route to resettlement in Canada via Turkey where they initially seek asylum and await resettlement. Drawing on fieldwork in Turkey and Canada between April 2014 and October 2016 and semi-structured interviews conducted with asylum travellers from non-European countries, the article illustrates how Turkey as the country of asylum is more than a space of mere ‘transit’. It rather constitutes a space of mobistasis—stasis within movement—in the asylum voyage towards countries of resettlement.
Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes
Authors: Al-Holou Wajd N , Hodges Tiffany R , Everson Richard G , Freeman Jacob , Zhou Shouhao , Suki Dima , Rao Ganesh , Ferguson Sherise D , Heimberger Amy B , McCutcheon Ian E , Prabhu Sujit S , Lang Frederick F , Weinberg Jeffrey S , Wildrick David M , Sawaya Raymond 
Published: January 2019

Abstract

BACKGROUND
Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data.

OBJECTIVE
To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection.

METHODS
We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression.

RESULTS
Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio = 2.5, 95% confidence interval: 1.8-3.4, P < .001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P < .001) and a lower rate of neurological complications (11% vs 20%, respectively, P = .018) than those who underwent intralesional resection.

CONCLUSION
Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option.
Inequality: traditional drivers and the role of union power
Authors: Jaumotte Florence , Osorio Buitron Carolina 
Published: January 2019

Abstract
We examine the factors explaining the increase in gross and net income inequality in advanced economies since the 1980s. Our results support the view that globalization, technological progress, financial deregulation and lower top marginal tax rates are associated with higher inequality, and we find that the relation between the decline in union density and the rise in top decile income shares—a phenomenon which labour economists have long been discussing—is widespread across advanced economies. The influence of union density on top income shares appears to be causal, as evidenced by our instrumental variable estimates and the inclusion of potentially omitted variables.
Taking Responsibility for Responsibility
Authors: Levy Neil 
Published: January 2019

AbstractGovernments, physicians, media and academics have all called for individuals to bear responsibility for their own health. In this article, I argue that requiring those with adverse health outcomes to bear responsibility for these outcomes is a bad basis for policy. The available evidence strongly suggests that the capacities for responsible choice, and the circumstances in which these capacities are exercised, are distributed alongside the kinds of goods we usually talk about in discussing distributive justice, and this distribution significantly explains why people make bad health choices. These facts suggest that we cannot justifiably hold them responsible for these choices. We do better to hold responsible those who determine the ways in which capacities and circumstances are distributed: they are indirectly responsible for these adverse health outcomes and possess the capacities and resources to take responsibility for these facts.