bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Concussion a Risk Factor for Epilepsy?
Authors: Wennberg Richard , Hiploylee Carmen , Tai Peter , Tator Charles H. 
Published: March 2018

AbstractBackground:Epidemiologic studies have suggested that concussion, or mild traumatic brain injury (mTBI), is associated with a twofold or greater increase in relative risk for the development of post-traumatic epilepsy. To assess the clinical validity of these findings, we analyzed the incidence of epilepsy in a large cohort of post-concussion patients in whom concussion was strictly defined according to international guidelines.Methods:A retrospective cohort study of 330 consecutive post-concussion patients followed by a single concussion specialist. Exclusion criteria: abnormal brain CT/MRI, Glasgow Coma Scale<13 more than 1-hour post-injury, hospitalization >48 hours. Independent variable: concussion. Outcome measure: epilepsy incidence (dependent variable).Results:The mean number of concussions/patient was 3.3 (±2.5), mean age at first clinic visit 28 years (±14.7), and mean follow-up after first concussion 7.6 years (±10.8). Eight patients were identified whose medical records included mention of seizures or convulsions or epilepsy. Upon review by an epileptologist none met criteria for a definite diagnosis of epilepsy: four had episodic symptoms incompatible with epileptic seizures (e.g., multifocal paraesthesiae, multimodality hallucinations, classic migraine) and normal EEG/MRI investigations; four had syncopal (n=2) or concussive (n=2) convulsions. Compared with annual incidence (0.5/1000 individuals) in the general population, there was no difference in this post-concussion cohort (p=0.49).Conclusion:In this large cohort of post-concussion patients we found no increased incidence of epilepsy. For at least the first 5-10 years post-injury, concussion/mTBI should not be considered a significant risk factor for epilepsy. In patients with epilepsy and a past history of concussion, the epilepsy should not be presumed to be post-traumatic.
Source Finding in the Era of the SKA (Precursors): Aegean 2.0
Authors: Hancock Paul J. , Trott Cathryn M. , Hurley-Walker Natasha 
Published: March 2018

AbstractIn the era of the SKA precursors, telescopes are producing deeper, larger images of the sky on increasingly small time-scales. The greater size and volume of images place an increased demand on the software that we use to create catalogues, and so our source finding algorithms need to evolve accordingly. In this paper, we discuss some of the logistical and technical challenges that result from the increased size and volume of images that are to be analysed, and demonstrate how the Aegean source finding package has evolved to address these challenges. In particular, we address the issues of source finding on spatially correlated data, and on images in which the background, noise, and point spread function vary across the sky. We also introduce the concept of forced or prioritised fitting.
Autistic traits in a sample of adult patients with schizophrenia: prevalence and correlates
Authors: Barlati S. , Deste G. , Gregorelli M. , Vita A. 
Published: March 2018

AbstractBackgroundSchizophrenia and autism spectrum disorder (ASD) are currently conceptualized as distinct disorders. However, the relationship between these two disorders has been revisited in recent years due to evidence that they share phenotypic and genotypic expressions. This study aimed to identify ASD traits in patients with schizophrenia, and to define their demographic, psychopathological, cognitive and functional correlates.MethodSeventy-five schizophrenia patients (20 females, mean age 42 ± 12) were evaluated with the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). Participants were also assessed with clinical, neuropsychological, and psychosocial functioning measures.ResultsOf the 75 patients, 47 were negative to all the autism scales administered (ADOS-TOT-NEG), 21 patients were positive to the ADOS Language sub-domain (ADOS-L-POS), 21 patients were positive to the ADOS Reciprocal Social Interaction (RSI) sub-domain (ADOS-RSI-POS), 14 patients were positive to the ADOS Total scale (ADOS-TOT-POS), and nine patients were positive to the ADI-R scale (ADI-R-POS). Demographic (duration of illness), psychopathological (negative symptoms and general psychopathology), and cognitive (working memory and processing speed) differences emerged between schizophrenic patients with and without ASD traits, while no differences in psychosocial functioning were detected. Results of this study indicate the existence, in a sample of patients with a diagnosis of schizophrenia, of a distinct group of subjects with ASD features, characterized by specific symptomatological and cognitive profile.ConclusionsThese findings may contribute to better characterize patients with schizophrenia in order to develop new procedures and therapeutic tools in a more personalized perspective.
Is Welfare Retrenchment Inevitable? Scope and Drivers of Healthcare Reforms in Five Spanish Regions During the Crisis
Authors: DEL PINO ELOÍSA , RAMOS JUAN A. 
Published: March 2018

AbstractTo what extent, in the context of severe economic crisis, do governments of the right and the left have room for manoeuvre to choose their fiscal consolidation paths? To what degree might this margin be broader in multilevel systems? The severity of the crisis suffered by Spain since 2007, combined with the significant scope of the powers and related expenditure capacities of the Autonomous Communities, make the Spanish regions a highly suitable case for controlled comparisons of fiscal adjustment policies and welfare reforms. Specifically examining healthcare retrenchment in the regions, we find that although the regional governments were all subjected to considerable budget constraints and were forced to cut social policies, they were also able to ensure a certain degree of leeway in selecting their individual healthcare retrenchment policies, in part by strategically utilising the multilevel institutions provided by the Spanish Autonomic State.
Updating the epidemiological transition model
Authors: Mercer A. J. 
Published: March 2018

AbstractThe main feature of the epidemiological transition is a shift in the recorded causes of death from infectious diseases to other morbid conditions. This paper outlines modifications made to Omran's original model and stages of transition, and suggests that without a focus on aetiology and morbidity, these have been basically descriptive rather than explanatory, and potentially misleading because infections have been confirmed as causes of various chronic diseases. Common infections and related immune responses or inflammatory processes contribute to the multifactorial aetiology of morbid conditions that together make a substantial contribution to overall mortality, and infectious causation is suspected for many others because of strong evidence of association. Investigation into possible infectious causes of conditions frequently recorded as the underlying cause of death can be integrated into a framework for comparative research on patterns of disease and mortality in support of public health and prevention. A theory of epidemiological transition aimed at understanding changes in disease patterns can encompass the role in different conditions and chronic diseases of infections contracted over the life course, and their contribution to disability, morbidity and mortality relative to other causes and determinants.
Genetic Regulation of Plasma Levels of Vitamin K-dependent Proteins Involved in Hemostasis
Authors: Almasy Laura , Blangero John , Stone William , Borrell Montse , Urrutia Teresa , Mateo José , Fontcuberta Jordi , Souto Juan Carlos 
Published: March 2018

SummaryVitamin K-dependent proteins play a critical role in hemostasis. We have analysed the genetic and environmental correlations between measures of several vitamin K-dependent proteins in 21 Spanish extended families, including 397 individuals. Plasma functional levels of factors II, VII, IX, X, protein C and functional protein S were assayed in an automated coagulometer. Antigenic levels of total and free protein S were measured using an ELISA method. A maximum likelihood-based covariance decomposition analysis was used to assess the heritability of each trait and the genetic and environmental correlations between all possible pairs. All of the plasma levels had a significant genetic component (heritability) ranging from 22% to 52% of the phenotypic variance. Among the 28 possible pairs of genetic correlations, 18 were significant at a level of p <0.05 and six exhibited a p-value between 0.05 and 0.10. Positive environmental correlation was observed for 25 of the pairs (p <0.05). We conclude that genetic effects account for a large proportion of the observed phenotypic variation in vitamin K-dependent proteins. Some of the genes appear to pleiotropically influence all of these traits, since most pairs of phenotypes exhibit significant genetic correlation. However, since these phenotypes show a high degree of environmental correlation, it is also likely that the same environmental factors influence them co-jointly.
Exogenous Factors from Animal Sources that Induce Platelet Aggregation
Authors: Chow Geraldine , Kini R. Manjunatha 
Published: March 2018

SummaryPlatelets clump together by two different processes: agglutination and aggregation. Agglutination is a passive process, independent of the metabolic status of the platelets. It is a physical phenomenon of binding of a protein or glycoprotein, which has two or more binding domains. In contrast, platelet aggregation is a metabolically active, transmembrane process that requires “live” platelets. It involves activation, shape change, secretion and adhesion. Following the change in light transmission in turbidometric aggregometers, one can monitor both the processes. Only agglutination can be induced in formaldehyde-fixed platelets, but not aggregation. PGE1 inhibits aggregation, but not agglutination. Metabolic inhibitors, such as antimycin A and 2-deoxy-D-glucose, are also used to distinguish aggregation and agglutination. Some exogenous factors isolated from animal sources induce platelet agglutination, whereas others induce aggregation. In this inventory, when possible, we will distinguish between these effects. Some of these factors exhibit phospholipase A2 (PLA2) and proteinase activities, whereas others lack enzymatic activity. Aggregation inducers are divided into three main groups: factors that directly act on platelets (Group I); factors that require a plasma component (Group II); and heterogeneous and partially characterized factors with unknown mechanisms (Group III).
The Mechanism of Action of Angiostatin: Can You Teach an Old Dog New Tricks?
Authors: Stack M. , Wahl Miriam , Pizzo Salvatore , Moser Tammy 
Published: March 2018

SummaryWhat is angiostatin? In 1994, Folkman and colleagues published a landmark paper describing anti-tumor effects in mice with a purified fragment of plasminogen they named angiostatin (1). Although many papers have been published describing activities of cryptic polypeptides derived from plasminogen fragments, this was the first report which associated plasminogen kringles 1–4 as a suppressor of metastasis development. This review will describe what is known about the mechanism of action of angiostatin from the current literature.
Procoagulant Activity of T Lymphoblastoid Cells due to Exposure of Negatively Charged Phospholipid
Authors: Fábregas P. , Jardi M. , Cancelas J. , Rabaneda M. , Felez J. , Barrowcliffe T.W. 
Published: March 2018

SummaryWe have characterised the Procoagulant activity (PCA) of six well-established cell lines by assays of tissue factor (TF), thrombin and FXa generation, flow cytometry using Annexin V, and by binding studies with Factors VIII and IXa.The monocytic (THP-1 & U937) and promyelocytic (NB4) cells expressed high concentrations of TF antigen and activity, whereas TF in the lymphocytic cells (Molt 4, Jurkat & Nalm 6) was very low or absent. However the T-lymphoblastoid cells (Molt 4 & Jurkat) promoted the generation of large amounts of thrombin despite their low TF content, and these cells were also the most active in supporting Factor Xa generation. Molt 4 cells bound Factors VIII and IXa with high capacity and their activity was inhibited by Annexin V. These results indicate that the PCA of T-lymphoblastoid lines is due to expression of negatively charged phospholipids. Flow cytometry studies showed Annexin V binding to the major population of nonapoptotic Molt 4 cells and the PCA of Molt 4 was not increased when apoptosis was induced by staurosporine, indicating that PCA is independent of apoptotic status.
Proline-rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Involved in Different Phases of Platelet Activation by vWF
Authors: Canobbio Ilaria , Lova Paolo , Sinigaglia Fabiola , Balduini Cesare , Torti Mauro 
Published: March 2018

SummaryStimulation of human platelets with von Willebrand factor (vWF) induces the rapid tyrosine phosphorylation of several proteins, but very little is known on the tyrosine kinases involved in this process. In the present work, we investigated and compared the activation of two related tyrosine kinases expressed in platelets: the proline-rich tyrosine kinase 2 (Pyk2) and the focal adhesion kinase (FAK). Both kinases were tyrosine phosphorylated upon vWF interaction with glycoprotein Ib-IX-V complex, but with different mechanisms. Tyrosine phosphorylation of FAK was totally dependent on thromboxane A2 production, and was inhibited by the integrin αIIbβ3 antagonist RGDS peptide. Moreover, chelation of intracellular calcium or inhibition of protein kinase C (PKC) totally blocked vWF-induced tyrosine phosphorylation of FAK, indicating that this event is downstream phospholipase A2 and phospholipase C activation. By contrast, tyrosine phosphorylation of Pyk2 was only partially reduced by aspirin and RGDS, and was not affected by either calcium chelation or PKC inhibition, suggesting that activation of this kinase does not require phospholipase-mediated signalling. Both FAK and Pyk2 translocated to the cytoskeleton upon vWF stimulation of human platelets by a mechanism depending on agonist-induced actin polymerisation. Prevention of cytoskeletal relocation of Pyk2 and FAK by cytochalasin D totally blocked vWFinduced tyrosine phosphorylation of both kinases. Finally, phosphorylation of Pyk2 induced by vWF, but not by thrombin, was inhibited by piceatannol, suggesting that this kinase lies downstream Syk. These results demonstrate that both Pyk2 and FAK are involved in platelet stimulation by vWF, but indicate that only Pyk2 may play a role in the early signal transduction events activated by ligand binding to glycoprotein Ib-IX-V.
Purification and Characterization of a Novel Metalloproteinase, Acurhagin, from
Agkistrodon acutus
Venom
Authors: Wang Wen-Jeng , Huang Tur-Fu 
Published: March 2018

SummaryAcurhagin, a high-molecular mass hemorrhagic metalloproteinase, was purified from the crude venom of Agkistrodon acutus using anionexchange and hydrophobic interaction chromatography. Acurhagin is a monomer with a molecular mass of 51.4 kDa under non-reducing conditions on SDS-PAGE and 48,133 Da by mass spectrometry. Partial amino acid sequence of its metalloproteinase domain is homologous to other high-molecular mass metalloproteinases from snake venoms. It preferentially cleaved Aα. chain of fibrinogen, followed by Bβ chain, while γ chains was minimally affected. Monitored by RP-HPLC, it extensively degraded fibrinogen into various peptide fragments. In aqueous solution, acurhagin autoproteolyzed to a 30 kDa fragment at 37° C. The N-terminal sequence of the 30 kDa fragment of acurhagin showed a high homology to those proteins consisting of disintegrinlike and cysteine-rich domains. Caseinolytic assay showed that the proteinase activity of acurhagin was slightly enhanced by Ca2+ and Mg2+, but completely inhibited by Zn2+. When treated with metal chelators, acurhagin was completely inactivated. Furthermore, acurhagin exerts an inhibitory effect on ADP-induced platelet aggregation of plateletrich plasma in an incubation-time dependent manner. It also impairs collagen- and ristocetin-induced platelet aggregation by cleaving collagen and vWF, respectively.
Elimination of a Human T-cell Region in Staphylokinase by T-cell Screening and Computer Modeling
Authors: Plaisance Stéphane , Vanderlick Kristel , Vandervoort Petra , Brepoels Kathleen , Collen Désiré , De Maeyer Marc , Warmerdam Petra 
Published: March 2018

SummaryStaphylokinase is a potent highly fibrin-selective thrombolytic agent, but it induces a humoral immune response in most treated patients. Staphylokinase-specific T-lymphocytes can be found in normal healthy individuals, from whom a large panel of staphylokinasespecific T-cells were cloned. The staphylokinase amino acid sequence 71-87 was widely recognized, as it induced proliferation of T-cell clones isolated from 90% of the donors. Computer modeling of this area, threaded as 11-mer peptides within the peptide-binding groove of the major HLA-DR alleles, indicated two putative partially overlapping binding sequences. The region-(71-87)-specific T-cell clones recognized either one or the other minimal peptide, confirming that both sequences could be functional T-cell epitopes. Furthermore, to guide the mutagenesis to eliminate T-cell reactivity, the contribution of each residue to the HLA-DR-anchoring and T-cell receptor exposure was evaluated for both binding motifs. Computer calculations combined with functional assays resulted in the design of staphylokinasevariants, including 2 to 4 amino acid substitutions in the region 71-87. These variants were no longer recognized by the region-(71-87)specific T-cell clones, and importantly no new staphylokinase-variantspecific cellular immune response could be measured.
Reduced High Shear Platelet Adhesion to the Vascular Media: Defective von Willebrand Factor Binding to the Interstitial Collagen
Authors: Komorowicz Erzsebet , McBane Robert , Charlesworth Jon , Fass David 
Published: March 2018

SummaryFibrillar collagen serves as a thrombogenic surface for platelet adhesion mediated by von Willebrand factor (vWf) at high shear. Although abundant throughout the arterial wall, vWf-dependent platelet deposition to artery cross-sections from perfused citrated blood is localized to the adventitia of the vessel wall. Here we describe a similarly skewed distribution of vWf-binding sites in artery cross-sections. Binding of vWf-coated fluorescent beads, as well as detection of plasma vWf bound to artery cross-section at 3350 s−1 shear rate with indirect particle-immunofluorescence or immunoelectron microscopy demonstrate vWf binding sites in the adventitia, but not in the media. A monoclonal anti-vWf antibody that interferes with vWf-binding to collagen in a microplate ELISA inhibits vWf-binding to both the adventitia and sections of collagen fibrils. Our data suggest that the media, despite its fibrillar collagen content, evidenced by electron microscopy, is defective for vWf-binding, which may explain its thromboresistant nature at high shear rates.
Prothrombotic Genotypes Are not Associated with Pre-eclampsia and Gestational Hypertension: Results from a Large Population-based Study and Systematic Review
Authors: Morrison E. R. , Campbell D. M. , Haites N. E. , Wilson B. J. , Watson M. S. , Greaves M. , Vickers M. A. , Miedzybrodzka Z. H. 
Published: March 2018

SummaryDNA samples collected as part of a large population-based casecontrol study were genotyped to examine the associations of five prothrombotic gene polymorphisms with pre-eclampsia (PE) and gestational hypertension (GH). The polymorphisms studied were: G1691A in Factor V (Factor V Leiden; FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, plasminogen activator inhibitor-1 4G/5G and the platelet collagen receptor α2β1 C807T. A group of 404 women who developed PE were retrospectively compared with 303 women with GH and 164 control women. The frequency of genotypes did not differ significantly between cases of PE or GH and controls for any of the five polymorphisms studied. We conclude that these prothrombotic genotypes are not associated with the development of PE or GH in our population. The systematic review supports our conclusion, for all but cases of severe disease, which appear to be associated with FVL and, to a lesser extent, MTHFR C677T. There is little value in antenatal screening for prothrombotic polymorphisms to predict the development of pre-eclampsia or gestational hypertension.
Increased Superoxide Anion Production by Platelets in Hypercholesterolemic Patients
Authors: Sanguigni Valerio , Pignatelli Pasquale , Caccese Daniela , Pulcinelli Fabio , Lenti Luisa , Magnaterra Roberta , Martini Francesca , Lauro Renato , Violi Francesco 
Published: March 2018

SummaryThe purpose of this study was to investigate the relationship between hypercholesterolemia and superoxide anion production.Experimental studies demonstrated that hypercholesterolemia is associated with enhanced cellular superoxide anion (O2
−) production. Aim of the study was to assess whether the same phenomenon occurs in humans.Lipid profile and platelet O2
− production were measured in 28 patients with hypercholesterolemia, compared with 25 age- and sexmatched healthy subjects, and in 21 out of the 28 patients after 8-week treatment with 10 mg/day atorvastatin (a HMGCoA reductase inhibitor). In order to assess the mechanism by which LDL cholesterol interferes with platelet production of O2
−, human platelets were incubated with LDL cholesterol in the presence of either an inhibitor of the phospholipaseA2 enzyme, AACOCF3, or an inhibitor of NADH/NADPH oxidases, DPI.O2
− platelet generation was significantly higher (p <0.001) and significantly related to LDL cholesterol (p < 0.001 ) in patients as compared to controls. 8-week treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O2
− platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O2
− production, while no significant change in LDL-cholesterol levels was observed. Platelets incubated with LDL cholesterol showed O2
− release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could be responsible for the antioxidant activity of the drug.