bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory Diagnostics in Thrombophilia
Authors: Hart Christina , Linnemann Birgit 
Published: January 2019

AbstractA thrombophilic disorder is a hereditary or acquired condition that increases the risk of thrombosis. The most common hereditary thrombophilias that predispose to venous thrombosis in the Caucasian population are the heterozygous forms of the factor V Leiden and prothrombin G20210A mutation that are generally detected by direct DNA genotyping. Immunologic antigen assays and chromogenic or clot-based activity assays are used to identify deficiencies in the natural coagulation inhibitors antithrombin, protein C and protein S. Because pre-analytical errors and acquired causes of low antithrombin, protein C or protein S levels are considerably more common than hereditary deficiencies, all potential conditions that may lower activity levels of the natural coagulation inhibitors (e.g. concomitant liver disease, pregnancy, anticoagulant therapy) must be considered and excluded before the diagnosis of an inhibitor deficiency can be made. To avoid misclassification, the diagnosis should not be made based on a single abnormal test result. Thus, repetitive testing when the patient is not on anticoagulant therapy is mandatory to confirm the diagnosis. Screening for antiphospholipid syndrome (APS) comprises testing for lupus anticoagulants (LAs) and the presence of IgG or IgM antibodies directed against phospholipids and phospholipid-binding proteins such as β-2-glycoprotein-I. A combination of clot-based assays has been recommended to demonstrate LA activity, whereas solid-phase immunoassays allow the detection of anti-cardiolipin and anti-β-2-glycoprotein-I antibodies. The diagnosis of APS requires the persistence of antiphospholipid antibodies for at least 12 weeks together with thrombotic and/or obstetric features of APS.
Perinatal Factors Affecting Coagulation Parameters at Birth in Preterm and Term Neonates: A Retrospective Cohort Study
Authors: Go Hayato , Ohto Hitoshi , Nollet Kenneth E. , Kashiwabara Nozomi , Ogasawara Kei , Chishiki Mina , Miyazaki Kyohei , Sato Kenichi , Sato Maki , Kawasaki Yukihiko , Momoi Nobuo , Hosoya Mitsuaki 
Published: January 2019

AbstractTo date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time–international normalized ratio correlated with intraventricular hemorrhage (p = 0.000; β = 0.180) and placental abruption (PA; p = 0.000; β = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p = 0.000; β =  − 0.217), gestational age (GA; p = 0.000; β =  − 0.282), and PA (p = 0.000; β = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome (p = 0.007; β =  − 0.114), pregnancy-induced hypertension (p = 0.000; β =  − 0.141), and Apgar score at 1 minute (p = 0.043; β = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes (p = 0.049). Finally, antithrombin III levels positively correlated with GA (p = 0.000) and BW (p = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates.
Management of Patients with Asymptomatic and Symptomatic Carotid Artery Disease: Update on Anti-Thrombotic Therapy
Authors: Pastori Daniele , Eikelboom John , Anand Sonia , Patel Manesh , Tanguay Jean-Francois , Ricco Jean-Baptiste , Debus Eike , Mazzolai Lucia , Bauersachs Rupert , Verhamme Peter , Bosch Jackie , Nikol Sigrid , Nehler Mark , Aboyans Victor , Violi Francesco 
Published: January 2019

AbstractThe most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (< 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60% the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily at the exception of patient at very high bleeding risk. For patients with symptomatic CAAD ≥50%, the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily is recommended. New perspectives for anti-thrombotic therapy for the treatment of patients with CAAD come from the novel dual pathway strategy combining a low-dose anticoagulant (i.e. rivaroxaban) and aspirin that may help reduce long-term ischaemic complications in patients with CAAD. This review summarizes current evidence and recommendations for the anti-thrombotic management of patients with symptomatic or asymptomatic CAAD or those undergoing carotid revascularization.
Thermodynamically reversible paths of the first fusion intermediate reveal an important role for membrane anchors of fusion proteins
Authors: Smirnova Yuliya G. , Risselada Herre Jelger , Müller Marcus 
Published: January 2019

Significance
The isolated transmembrane domains (TMDs) of fusion proteins such as SNARE molecules drastically lower the free energy of both the stalk barrier and metastable stalk, which is not trivially explained by molecular shape arguments. The here-demonstrated methodology may have far-reaching applications in the fields of medicine and pharmacology because it enables screening and rational design of novel fusion inhibitors and accelerators.
Transparency and reflection
Authors: Boyle Matthew 
Published: January 2019

AbstractMuch recent work on self-knowledge has been inspired by the idea that the ‘transparency’ of questions about our own mental states to questions about the non-mental world holds the key to understanding how privileged self-knowledge is possible. I critically discuss some prominent recent accounts of such transparency, and argue for a Sartrean interpretation of the phenomenon, on which this knowledge is explained by our capacity to transform an implicit or ‘non-positional’ self-awareness into reflective, ‘positional’ self-knowledge.
Numerical simulation for homogeneous–heterogeneous reactions and Newtonian heating in the silver-water nanofluid flow past a nonlinear stretched cylinder
Authors: Suleman Muhammad , Ramzan Muhammad , Ahmad Shafiq , Lu Dianchen 
Published: January 2019

Abstract
The present exploration aims to deliberate silver-water nanofluid flow with homogeneous–heterogeneous reactions and magnetic field impacts past a nonlinear stretched cylinder. The novelty of the presented work is enhanced with the addition of Newtonian heating, heat generation/absorption, viscous dissipation, nonlinear thermal radiation and joule heating effects. The numerical solution is established via Shooting technique for the system of ordinary differential equations with high nonlinearity. The influences of miscellaneous parameters including nanoparticles volume fraction

0.0
≤
ϕ
≤
0.3

,

magnetic parameter

1.0
≤
Μ
≤
4.0

,

nonlinearity exponent

1.0
≤
n
≤
5.0

,

curvature parameter

0.0
≤
γ
≤
0.4

,

conjugate parameter

0.4
≤
λ
≤
0.7

,

heat generation/absorption parameter

(
0.2
≤

E

c

≤
0.8
)
,

radiation parameter

0.7
≤
K
*

≤
1.0

,

Eckert number

(
0.1
≤

E

c

≤
0.7
)
,

strength of homogeneous reaction

0.1
≤

κ

1

≤
1.8

,

strength of heterogeneous reaction

0.1
≤

κ

2

≤
1.8

and Schmidt number

(
3.0
≤

S

c

≤
4.5
)

on axial velocity, temperature profile, local Nusselt number, and skin friction coefficient are discussed via graphical illustrations and numerically erected tabulated values. It is examined that the velocity field diminishes while the temperature profile enhances for mounting values of the magnetic parameter. An excellent concurrence is achieved when our obtained numerical calculations are compared with an already published paper in limiting case; hence dependable results are being presented.
On the Treatment of Heteroscedasticity in Crop Yield Data
Authors: Ker Alan P , Tolhurst Tor N 
Published: January 2019

AbstractIn empirical applications with crop yield data, conditioning for heteroscedasticity is both important and challenging. It is important because the scale of the distribution can markedly influence the results, and challenging because statistical tests for the common heteroscedasticity assumptions (constant or proportional variance) often lead to ambiguous conclusions. Alternatively, Harri et al. (2011) proposed a methodology that estimates the degree of heteroscedasticity, removing the need to make a specific assumption. Such approaches assume that volatility changes are symmetric (identical) across tails of the yield distribution. We propose a generalization to the Harri et al. (2011) methodology, which allows asymmetry between the tails, akin to the generalization of GARCH to AGARCH. Using U.S. county level yield data from 1951–2017, we find evidence of asymmetry in corn and soybean, but not wheat. Moreover, the asymmetry takes a particular form—increasing volatility in the lower tail. To investigate economic significance, we consider the effect of imposing symmetric heteroscedasticity in rating crop insurance contracts, as currently done by the USDA's Risk Management Agency in rating their Area Risk Protection products. We find that relaxing the symmetry assumption leads to economically and statistically significant rents. Our results suggest that the Risk Management Agency and others should consider the possibly asymmetric nature of heteroscedasticity in crop yield data.
PROSSTT: probabilistic simulation of single-cell RNA-seq data for complex differentiation processes
Authors: Papadopoulos Nikolaos , Gonzalo Parra R , Söding Johannes 
Published: January 2019

Abstract

Summary
Cellular lineage trees can be derived from single-cell RNA sequencing snapshots of differentiating cells. Currently, only datasets with simple topologies are available. To test and further develop tools for lineage tree reconstruction, we need test datasets with known complex topologies. PROSSTT can simulate scRNA-seq datasets for differentiation processes with lineage trees of any desired complexity, noise level, noise model and size. PROSSTT also provides scripts to quantify the quality of predicted lineage trees.

Availability and implementation
https://github.com/soedinglab/prosstt.

Supplementary information
Supplementary data are available at Bioinformatics online.
ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection
Authors: Morel Maryan , Bacry Emmanuel , Gaïffas Stéphane , Guilloux Agathe , Leroy Fanny 
Published: January 2019

Summary
With the increased availability of large electronic health records databases comes the chance of enhancing health risks screening. Most post-marketing detection of adverse drug reaction (ADR) relies on physicians’ spontaneous reports, leading to under-reporting. To take up this challenge, we develop a scalable model to estimate the effect of multiple longitudinal features (drug exposures) on a rare longitudinal outcome. Our procedure is based on a conditional Poisson regression model also known as self-controlled case series (SCCS). To overcome the need of precise risk periods specification, we model the intensity of outcomes using a convolution between exposures and step functions, which are penalized using a combination of group-Lasso and total-variation. Up to our knowledge, this is the first SCCS model with flexible intensity able to handle multiple longitudinal features in a single model. We show that this approach improves the state-of-the-art in terms of mean absolute error and computation time for the estimation of relative risks on simulated data. We apply this method on an ADR detection problem, using a cohort of diabetic patients extracted from the large French national health insurance database (SNIIRAM), a claims database containing medical reimbursements of more than 53 million people. This work has been done in the context of a research partnership between Ecole Polytechnique and CNAMTS (in charge of SNIIRAM).
Clinical and Microbiologic Variables Predictive of Orthopedic Complications Following Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children
Authors: McNeil J Chase , Vallejo Jesus G , Kok Eric Y , Sommer Lauren M , Hultén Kristina G , Kaplan Sheldon L 
Published: January 2019

Abstract

Background
Staphylococcus aureus is the most common cause of acute hematogenous osteoarticular infections (AHOAIs) in children. The risk factors for the development of orthopedic complications (OC) after AHOAI are poorly understood. We sought to describe clinical and microbiologic variables present on the index admission that may predict OC in S. aureus AHOAI.

Methods
Staphylococcus aureus AHOAI cases were identified from 2011–2017 at Texas Children’s Hospital and reviewed for the development of OC. OC included chronic osteomyelitis, growth arrest, avascular necrosis, chronic dislocation, and pathologic fracture. All S. aureus isolates were characterized by pulsed-field gel electrophoresis and agr group.

Results
A total of 286 cases were examined of which 27 patients (9.4%) developed OC. Patients who developed OC more often had infection with an agr group III organism (P = .04), bacteremia (P = .04), delayed source control (P &lt; .001), ≥2 surgical procedures (P &lt; .001), intensive care unit admission (P = .09), and fever &gt;4 days after admission (P = .008). There was no association with OC and patient age, methicillin resistance, or choice/route of antibiotics. In multivariable analyses of OC, infection with agr group III S. aureus, prolonged fever, and delayed source control remained statistically significant.

Conclusions
OC develop following S. aureus AHOAI in 9.4% of cases. Although the development of OC is likely multifactorial, agr group III organisms, prolonged fever, and delayed source control are independently associated with OC. Moreover, early aggressive surgical source control may be beneficial in children with S. aureus AHOAI.
Haplotype-phased genome and evolution of phytonutrient pathways of tetraploid blueberry
Authors: Colle Marivi , Leisner Courtney P , Wai Ching Man , Ou Shujun , Bird Kevin A , Wang Jie , Wisecaver Jennifer H , Yocca Alan E , Alger Elizabeth I , Tang Haibao , Xiong Zhiyong , Callow Pete , Ben-Zvi Gil , Brodt Avital , Baruch Kobi , Swale Thomas , Shiue Lily , Song Guo-qing , Childs Kevin L , Schilmiller Anthony , Vorsa Nicholi , Buell C Robin , VanBuren Robert , Jiang Ning , Edger Patrick P 
Published: January 2019

Abstract

Background
Highbush blueberry (Vaccinium corymbosum) has long been consumed for its unique flavor and composition of health-promoting phytonutrients. However, breeding efforts to improve fruit quality in blueberry have been greatly hampered by the lack of adequate genomic resources and a limited understanding of the underlying genetics encoding key traits. The genome of highbush blueberry has been particularly challenging to assemble due, in large part, to its polyploid nature and genome size.

Findings
Here, we present a chromosome-scale and haplotype-phased genome assembly of the cultivar “Draper,” which has the highest antioxidant levels among a diversity panel of 71 cultivars and 13 wild Vaccinium species. We leveraged this genome, combined with gene expression and metabolite data measured across fruit development, to identify candidate genes involved in the biosynthesis of important phytonutrients among other metabolites associated with superior fruit quality. Genome-wide analyses revealed that both polyploidy and tandem gene duplications modified various pathways involved in the biosynthesis of key phytonutrients. Furthermore, gene expression analyses hint at the presence of a spatial-temporal specific dominantly expressed subgenome including during fruit development.

Conclusions
These findings and the reference genome will serve as a valuable resource to guide future genome-enabled breeding of important agronomic traits in highbush blueberry.
Comparing conceptual frameworks for a fish community MSY (FCMSY) using management strategy evaluation—an example from the North Sea
Authors: Thorpe Robert B , De Oliveira José A A 
Published: January 2019

Abstract
Maximum sustainable yield (MSY) is a well-established concept that is mandated by legislation, and has a clear theoretical meaning in terms of a single stock. However, its definition is problematic in a multispecies setting, which makes it more difficult to apply the MSY principle. In this study of the North Sea fish community, we consider several possible MSY candidates, and evaluate them in terms of their ability to produce optimum long-term yield whilst avoiding unacceptable risk of stock impairment. We perform this evaluation with an ensemble of size-structured models using a management strategy evaluation approach, in which harvest control rules (HCRs) are used to determine levels of fishing as a function of the proposed MSY target and stock status, taking account of recruitment and model parameter uncertainties. We find that HCRs of the type considered here are always useful in the scenarios we tested, as they reduce overfishing risk much more than average long-term yield. This is independent of the precise form of the HCR, so it is more important to implement one rigorously than obsess over the rule details. For a lax definition of overfishing, which accepts relatively severe stock depletion (B &lt; 10% B0), and using HCRs, risks are “low” across all strategies, and the Nash equilibrium is the best performing MSY approach considered here. For more stringent definitions of “at risk” (e.g. likelihood of B &lt; 20% of B0), the application of HCRs can allow a range of alternative formulations of MSY. Thus, the definition of MSY may be sensitive to judgements about acceptable levels of risk, and consistent application of a sensible management framework may be more important than developing the best possible theoretical definition of MSY.
STAP-2 positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions
Authors: Kashiwakura Jun-ichi , Yamashita Shinsuke , Yoshihara Mari , Inui Kyosuke , Saitoh Kodai , Sekine Yuichi , Muromoto Ryuta , Kitai Yuichi , Oritani Kenji , Matsuda Tadashi 
Published: January 2019

Abstract
Basophils are an important cell type in the regulation of Th2 immune responses. Recently, we revealed that signal-transducing adaptor protein-2 (STAP-2) negatively regulates mast cell activation via FcεRI. However, the role of STAP-2 in basophil maturation and activation remained unclear. In this study, we demonstrated the normal development of basophils in STAP-2-deficient (STAP-2−/−) mice. We also demonstrated in vitro normal basophil differentiation and FcεRI expression in STAP-2−/− mice, suggesting that STAP-2 is dispensable for basophil maturation. Using bone marrow-derived cultured basophils (BMBs), we showed that degranulation and cytokine production of STAP-2−/− BMBs were lower than those of wild-type (WT) BMBs upon stimulation with IgE/Ag. In accordance with the reduction of degranulation and cytokine production, phosphorylation of several signal molecules such as Lyn, PLC-γ2 and Erk was reduced in STAP-2−/− BMBs after stimulation via FcεRI. Finally, it was observed that IgE-dependent chronic allergic inflammation of STAP-2−/− mice was significantly inhibited compared with WT mice. Taken together, we conclude that STAP-2 is an adaptor molecule that positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions.
An investigation of single-domain and multidomain medication and adverse drug event relation extraction from electronic health record notes using advanced deep learning models
Authors: Li Fei , Yu Hong 
Published: January 2019

Abstract

Objective
We aim to evaluate the effectiveness of advanced deep learning models (eg, capsule network [CapNet], adversarial training [ADV]) for single-domain and multidomain relation extraction from electronic health record (EHR) notes.

Materials and Methods
We built multiple deep learning models with increased complexity, namely a multilayer perceptron (MLP) model and a CapNet model for single-domain relation extraction and fully shared (FS), shared-private (SP), and adversarial training (ADV) modes for multidomain relation extraction. Our models were evaluated in 2 ways: first, we compared our models using our expert-annotated cancer (the MADE1.0 corpus) and cardio corpora; second, we compared our models with the systems in the MADE1.0 and i2b2 challenges.

Results
Multidomain models outperform single-domain models by 0.7%-1.4% in F1 (t test P &lt; .05), but the results of FS, SP, and ADV modes are mixed. Our results show that the MLP model generally outperforms the CapNet model by 0.1%-1.0% in F1. In the comparisons with other systems, the CapNet model achieves the state-of-the-art result (87.2% in F1) in the cancer corpus and the MLP model generally outperforms MedEx in the cancer, cardiovascular diseases, and i2b2 corpora.

Conclusions
Our MLP or CapNet model generally outperforms other state-of-the-art systems in medication and adverse drug event relation extraction. Multidomain models perform better than single-domain models. However, neither the SP nor the ADV mode can always outperform the FS mode significantly. Moreover, the CapNet model is not superior to the MLP model for our corpora.
Automatic white-box testing of first-order logic ontologies
Authors: Álvez Javier , Hermo Montserrat , Lucio Paqui , Rigau German 
Published: January 2019

AbstractFormal ontologies are axiomatizations in a logic-based formalism. The development of formal ontologies is generating considerable research on the use of automated reasoning techniques and tools that help in ontology engineering. One of the main aims is to refine and to improve axiomatizations for enabling automated reasoning tools to efficiently infer reliable information. Defects in the axiomatization cannot only cause wrong inferences, but can also hinder the inference of expected information, either by increasing the computational cost of or even preventing the inference. In this paper, we introduce a novel, fully automatic white-box testing framework for first-order logic (FOL) ontologies. Our methodology is based on the detection of inference-based redundancies in the given axiomatization. The application of the proposed testing method is fully automatic since (i) the automated generation of tests is guided only by the syntax of axioms and (ii) the evaluation of tests is performed by automated theorem provers (ATPs). Our proposal enables the detection of defects and serves to certify the grade of suitability—for reasoning purposes—of every axiom. We formally define the set of tests that are (automatically) generated from any axiom and prove that every test is logically related to redundancies in the axiom from which the test has been generated. We have implemented our method and used this implementation to automatically detect several non-trivial defects that were hidden in various FOL ontologies. Throughout the paper we provide illustrative examples of these defects, explain how they were found and how each proof—given by an ATP—provides useful hints on the nature of each defect. Additionally, by correcting all the detected defects, we have obtained an improved version of one of the tested ontologies: Adimen-SUMO.