bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bleeding Classification in Clinical Trials: Observer Variability and Clinical Relevance
Authors: Graafsma Yvonne P , Prins Martin H , Lensing Anthonie W A , de Haan Rob J , Huisman Menno V , Büller Harry R 
Published: July 2018

SummaryTo evaluate the bleeding classification in a recent trial on venous thrombosis treatment, a selection of reported bleeding episodes was adjudicated twice by an independent committee and graded by the treating physician and independent clinical experts on the clinical severity and impact on the patient’s life.The kappa values for the dichotomy major bleeding versus minor or no bleeding were 0.79 (95% CI, 0.57-1.0) for the agreement between the two members of the adjudication committee and 0.77 (95% CI, 0.52-1.0) for the agreement between both adjudication sessions. The kappa values for the dichotomy major or minor bleeding versus no bleeding were 0.42 and 0.44. The weighted kappa values for the agreement between the treating physician and the independent experts were 0.76 for the Clinical severity and 0.79 for the impact on the patient’s life (95% CI, 0.63-0.88 and 0.70-0.89). The association between the adjudication result expressed as major bleeding or minor or no bleeding and the Clinical grading by the treating physician resulted in an ROC curve with an area under the curve of 0.98 for the Clinical severity and 0.99 for the impact on the patient’s life. The dichotomy major or minor bleeding versus no bleeding resulted in areas under the curve of 0.70 and 0.66.In conCIusion, the applied criteria for major bleeding are reproducible and Clinically relevant. The criteria for minor bleeding are not reproducible and are less associated with the observed Clinical relevance.
Ultrasensitive Fluorogenic Substrates for Serine Proteases
Authors: Butenas Saulius , DiLorenzo Maria E , Mann Kenneth G 
Published: July 2018

SummarySelective, sensitive assays for the quantitation of serine proteases involved in coagulation and fibrinolysis have been developed employing fluorogenic substrates containing a 6-amino-1-naphthalenesulfonamide leaving group (PNS-substrates). Over one hundred substrates were evaluated for hydrolysis by the serine proteases of blood coagulation and fibrinolysis, and substrate structure-efficiency correlations were examined. PNS-substrates which contain Lys in the P1 position are specific for Lys-plasmin and are either not hydrolyzed or hydrolyzed at a relatively low rate by factor Xa, thrombin, or urokinase-type plasminogen activator (uPA). These substrates allow quantitation of Lys-plasmin at concentrations as low as 1 pM. Eighteen of over 90 substrates tested for factor XIa are hydrolyzed by this enzyme at a relatively high rate reaching a kcat value of 170 s-1 and allowing quantitation of factor XIa at 10 fM. Eighteen of almost 90 PNS-substrates tested display high specificity for thrombin, some exceeding that for factor Xa by > 10,000-fold and > 100-fold for activated protein C (APC). Seven of these substrates have a over 100 s-1 and three of them have a KM below 1 μM. They allow the quantitation of thrombin at concentrations as low as 20 fM. For APC, uPA and the factor Vila/tissue factor complex, quantitation is feasible at 1 pM concentration. For factor Xa and factor VIIa the limits are 0.4 pM and 40 pM respectively. The PNS-substrates presented in this study may be employed for the development of direct and sensitive serine protease assays.
Effects of Plasma Kallikrein Specific Inhibitor and Active-site Blocked Factor VIIa on the Pulmonary Vascular Injury Induced by Endotoxin in Rats
Authors: Uchiba Mitsuhiro , Okajima Kenji , Murakami Kazunori , Okabe Hiroaki , Okamoto Shosuke , Okada Yoshio 
Published: July 2018

SummaryThe acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. To evaluate the role of the coagulation system in the pathogenesis of ARDS in sepsis, we examined the effects of the administration of a synthetic plasma kallikrein specific inhibitor (PKSI) and of active-site blocked factor VIIa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PKSI prevented the pulmonary vascular injury induced by ET as well as pulmonary histological changes in animals administered ET, but it did not affect the intravascular coagulation. The opposite effect was seen with DEGR-VIIa, which prevented the intravascular coagulation but not the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutrophils.Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neutrophils. The intrinsic pathway of coagulation may be more important than the extrinsic pathway in the pulmonary vascular injury produced byET.
A Fast and Robust Dual-label Nonradioactive Oligonucleotide Ligation Assay for Detection of Factor V Leiden
Authors: Chakravarty Anders , Hansen Torben Stiig , Hørder Mogens , Kristensen Søren Risom 
Published: July 2018

SummaryActivated protein C resistance is in almost all cases caused by the factor V Leiden mutation (FV:R506Q). Due to the high prevalence and clinical significance of the mutation reliable methods suited for processing large sets of samples are in demand. We here present the oligonucleotide ligation assay (OLA) with lanthanide labeled oligonucleotides for the detection of FV Leiden. The assay is based on time resolved fluorescence measurement of lanthanide labeled oligonucleotides (DELFIA: Delayed Enhanced Lanthanide Fluorescence Immuno Assay) and on the specificity of T-4 DNA Ligase to join two adjacent oligonucleotides only when the two are complementary to the PCR template at the ligation junction. The Europium/Samarium fluorescence pattern is specific for each of the three genotypes (G/G, G/A, A/A) and clearly separates the three genotypes. By using a wildtype probe (Samarium labeled) and a mutant-specific probe (Europium labeled) simultaneously an internal control of the assay is included in each reaction. The assay is simple to perform, can be partly automated and is ideal for processing large sets of samples.
The Regulation of Platelet Aggregation In Vitro by Interleukin-1 β and Tumor Necrosis Factor-α: Changes in Pregnancy and in Pre-eclampsia
Authors: Bar J , Zosmer A , Hod M , Elder M G , Sullivan M H F 
Published: July 2018

SummaryPlatelet activation occurs in early pregnancy in women at risk of developing pre-eclampsia. Cytokines have been implicated in the pathogenesis of pre-eclampsia, so we determined the effects of interleukin- 1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the in vitro aggregation of human platelets. IL-1β increased aggregation of platelets from non-pregnant and pre-eclamptic women, and inhibited the aggregation of platelets from normal pregnant women. This latter effect was linked to a diminished P-selectin expression on ADP-stimulated whole blood platelets in normal pregnant women (p = 0.011). Platelet aggregation in response to ADP was found to be inhibited after preincubation with TNF-α in non-pregnant (38%, p = 0.01) and in normal pregnant women (54%, p = 0.001) and not affected in pre-eclamptic women. The inhibitory effects of TNF-α were mediated through the P75 receptor for TNF-α.
Sensitive Measurement of Thrombopoietin by a Monoclonal Antibody Based Sandwich Enzyme-linked Immunosorbent Assay
Authors: Folman Claudia C , von dem Borne Albert E G K , Rensink Irma H J A M , Gerritsen Winald , van der Schoot C Ellen , de Haas Masja , Aarden Lucien 
Published: July 2018

SummaryIn this report a sensitive enzyme-linked immunosorbent assay (ELISA) for the measurement of plasma thrombopoietin (Tpo) is described that is solely based on monoclonal antibodies (MoAbs).The assay has an intra and inter-assay variance of 5-7% and 7-13%, respectively. Native and recombinant human Tpo (rhTpo) were recognized equally well, no cross reactivity with other cytokines was found and rhTpo added to plasma and serum was completely recovered. With the ELISA, Tpo concentrations in EDTA-anticoagulated plasma of all controls (n = 193) could be determined, since the limit of detection (2 ± 0.8 A.U./ml, mean ± sd) was lower than the concentration found in controls (11 ± 8 A.U./ml, mean ± sd; 2.5th-97.5th percentile: 4-32 A.U./ml). Tpo levels in serum were on average 3.4 times higher than in plasma.We showed in vivo that Tpo is bound by platelets, as in thrombocytopenic patients (n = 5) a platelet transfusion immediately led to a drop in plasma Tpo level, whereas in patients receiving chemotherapy the induced thrombocytopenia was followed by a rise in plasma Tpo levels.In summary, these results indicate that this ELISA is a reliable tool for Tpo measurements and is applicable for large scale studies.
The Importance of Enzyme Inhibition Kinetics for the Effect of Thrombin Inhibitors in a Rat Model of Arterial Thrombosis
Authors: Elg Margareta , Gustafsson David , Deinum Johanna 
Published: July 2018

SummaryThe relation between the antithrombotic effect in vivo, and the inhibition constant (K
i) and the association rate constant (k
on) in vitro was investigated for eight different thrombin inhibitors. The carotid arteries of anaesthetized rats were exposed to FeCl3 for 1 h, and the thrombus size was determined from the amount of incorporated 125I- fibrinogen. The thrombin inhibitors were given intravenously, and complete concentration- and/or dose-response curves were constructed. Despite a 50,000-fold difference between the k
i-values comparable plasma concentrations of hirudin and melagatran were needed (0.14 and 0.12 μmol 1-1, respectively) to obtain a 50% antithrombotic effect (IC50) in vivo. In contrast, there was a comparable in vitro (k
i-value) and in vivo (IC50) potency ratio for melagatran and inogatran, respectively. These results can be explained by the concentration of thrombin in the thrombus and improved inhibition by the low-molecular-weight compounds. For all eight thrombin inhibitors tested, there was an inverse relationship between k
on-values in vitro and the slope of the dose response curves in vivo. Inhibitors with k
on-values of <1 X 107 M-1 s-1 gave steep dose response curves with a Hill coefficient >1. The association time for inhibition of thrombin for slow-binding inhibitors will be too long to give effective antithrombotic effects at low plasma concentrations, but at increasing concentrations the association time will decrease, resulting in a steeper dose-response curve and thereby a more narrow therapeutic interval.
Free Protein S Deficiency Is a Risk Factor for Venous Thrombosis
Authors: Faioni Elena M , Valsecchi Carla , Palla Alessandra , Taioli Emanuela , Razzari Cristina , Mannucci Pier Mannuccio 
Published: July 2018

SummaryA recent study suggests that protein S deficiency is not a risk factor for venous thrombosis. Since this unexpected finding would have important clinical implications if confirmed, we performed a case-control study with the aim to determine the prevalence of protein S deficiency in patients with thrombosis and in healthy individuals taken from the general population and the relative risk of thrombosis in protein S-deficient patients. Free protein S concentration was measured in 327 consecutive patients with at least one venous thrombotic episode and in 317 age- and sex-matched control individuals. Different normal reference ranges were obtained and adopted for men and women. Protein S deficiency was found in 3.1% (95% Cl: 1.5-5.2) of patients and in 1.3% of controls (95% Cl: 0.3-2.8). Ten patients and 4 control subjects had protein S deficiency, which determined a relative risk of thrombosis (sex- and age-adjusted odds ratio) of 2.4 (95% Cl: 0.8-7.9). When men and women were analyzed separately, the risk was 5.0 (95% CI: 0.6-43.6) and 1.6 (95% Cl: 0.4-6.7) respectively. PS-deficient men had more thrombotic episodes than women and later in life. Multivariate analysis established that sex was an independent determinant of the number of episodes, as was age, while PS deficiency was not. However sex and PS deficiency status were both determinants of age at first thrombotic episode.
Prevalence of the Prothrombin Gene Variant (nt20210A) in Venous Thrombosis and Arterial Disease
Authors: Arruda Valder R , Annichino-Bizzacchi Joyce M , Gonçalves Marilda S , Costa Fernando F 
Published: July 2018

SummaryThe prothrombin gene variant resulting form a G→A transition at position 20210 has been described as a common genetic risk factor for venous thrombosis. However, the risk for developing arterial disease is unknown. In this investigation, we studied 116 patients with venous thrombosis and 71 with arterial disease, all of whom were compared with 295 controls. Additionally, we also investigated the distribution of the prothrombin alleles among African descendents and Amazonian Indians from Brazil. The prevalence of 0.7% for 20210A allele in the control group increased to 4.3% (P = 0.021) among patients with venous thrombosis. There was also a high prevalence of the mutated allele in a selected arterial disease group (5.7%) without hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to the controls (P = 0.013). Heterozygotes for the allele 20210A were common among individuals of African descent (2%) and rare among Indians. These data support the hypothesis that the prothrombin variant is a risk factor for venous thrombosis and suggest that it may also be a risk factor for arterial disease.
Electrospray Ionisation Mass Spectrometry Facilitates Detection of Fibrinogen (Bβ 14 Arg → Cys) Mutation in a Family with Thrombosis
Authors: Brennan Stephen O , Hammonds Bruce , Spearing Ruth , George Peter M 
Published: July 2018

SummaryWe report the first direct detection of a fibrinogen mutation by electrospray ionisation mass spectrometry. The propositus, from a family with a history of thrombosis, came to attention after a pulmonary embolism subsequent to a spontaneous abortion. Prolonged thrombin (41 s) and reptilase times (26 s) together with an impairment of fibrinopeptide B release suggested a mutation at the thrombin cleavage site of the Bβ chain. Direct mass analysis of purified fibrin chains from a thrombin induced clot showed that 50% of the Bβ chains remained uncleaved. The measured mass of the mono sialo isoform of this uncleaved chain was 54150 Da, compared to a value of 54198 Da for normal Bp chains. This decrease of 48 Da in the intact protein is indicative of either a Bβ 14 Arg to Cys, or Arg to Leu substitution. Heterozygosity for the Bβ 14 Arg → Cys mutation was verified by PCR amplification and DNA sequence analysis.
Erythropoietin Administration Increases Production and Reactivity of Platelets in Dogs
Authors: Wolf Roman F , Peng Jinpeng , Friese Paul , Gilmore Laura S , Burstein Samuel A , Dale George L 
Published: July 2018

SummaryAdministration of erythropoietin (EPO) to adult dogs resulted in a dramatic increase in the number of thiazole orange-positive (TO+) platelets, also referred to as reticulated platelets. Pre-treatment level of TO+ platelets was 6.2 ± 0.5% (mean ± 1 SE; n = 5); following day 5 of treatment with 500 U EPO/kg/day, the percentage of TO+ platelets peaked at 16.8 ± 2.3% (n = 5; p <0.02). After cessation of the hormone, the number of TO+ platelets fell rapidly to below starting levels. Unexpectedly, there was a significant decline in total platelet count during EPO administration despite an increased level of TO+ platelets. To assess platelet reactivity, total platelets and TO+ platelets from EPO- treated dogs were analyzed for thrombin-responsiveness as quantitated by P-selectin expression on the cell surface; reactivity was expressed as a thrombin EC50, the thrombin concentration required to activate 50% of platelets. Both total and TO+ platelets were hyperreactive during EPO treatment when compared either to pre-treatment values or to control animals. Thrombin EC50 values for total and TO+ platelets on day 5 fell to 66.5 ± 5.4% (mean ± 1 SE; n = 5; p <0.02) and 62.2 ± 8.7% (n = 5; p <0.025), respectively, of pre-treatment levels. These data indicate that EPO not only promotes the synthesis of increased numbers of TO+ platelets in the dog but that these newly produced platelets are hyperreactive when compared to TO+ platelets from control animals.
Peptide-specific Antibodies as Pro\bes of the Topography of the Ca2+-binding Motifs in αIIbβ3
Authors: Niewiarowska Jolanta , Świderska Mariola , Majewski Tadeusz , Cierniewski Czesław S 
Published: July 2018

SummaryAntibodies against synthetic peptides corresponding to four Ca2+- binding motifs of the αIIb subunit have been obtained and used as molecular probes to analyze the topography of the αIIbβ3 complex. The specificity of the antibodies has been characterized by ELISA and Western immunoblotting in terms of binding capacity and affinity to the isolated αIIbβ3 and its αIIb subunit. Our data suggest that: (a) all four Ca2+-binding motifs of the αIIb are partially exposed on the surface of the intact molecule and accessible to antipeptide antibodies. However, they are not in close vicinity to the ligand recognition domain since the antibodies do not produce complete inhibition of platelet aggregation, (b) The conformation of amino acid stretches which form the second Ca2+-binding motif of αIIb is particularly dependent upon the presence of cation, and this region undergoes significant conformational alterations upon Ca2+ expulsion.
Multiword units in machine translation and translation technology
Authors: Monti Johanna , Seretan Violeta , Corpas Pastor Gloria , Mitkov Ruslan 
Published: July 2018

Abstract
The correct interpretation of Multiword Units (MWUs) is crucial to many applications in Natural Language Processing but is a
challenging and complex task. In recent years, the computational treatment of MWUs has received considerable attention but we
believe that there is much more to be done before we can claim that NLP and Machine Translation (MT) systems process MWUs
successfully. In this chapter, we present a survey of the field with particular reference to Machine Translation and
Translation Technology.
A multilingual gold standard for translation spotting of German compounds and their corresponding multiword units
in English, French, Italian and Spanish
Authors: Clematide Simon , Lehner Stéphanie , Graën Johannes , Volk Martin 
Published: July 2018

Abstract
This article describes a new word alignment gold standard for German nominal compounds and their multiword translation
equivalents in English, French, Italian, and Spanish. The gold standard contains alignments for each of the ten
language pairs, resulting in a total of 8,229 bidirectional alignments. It covers 362 occurrences of 137 different
German compounds randomly selected from the corpus of European Parliament plenary sessions, sampled according to the
criteria of frequency and morphological complexity. The standard serves for the evaluation and optimisation of
automatic word alignments in the context of spotting translations of German compounds. The study also shows that in
this text genre, around 80% of German noun types are morphological compounds indicating potential multiword units in
their parallel equivalents.
Dutch compound splitting for bilingual terminology extraction
Authors: Macken Lieve , Tezcan Arda 
Published: July 2018

Abstract
As compounds pose a problem for applications that rely on precise word alignments, we developed a state-of-the-art
compound splitter for Dutch that makes use of corpus frequency information and linguistic knowledge. Domain-adaptation
techniques are used to combine large out-of-domain and dynamically compiled in-domain frequency lists.
As compounds are not always translated compositionally, we developed a novel methodology for word alignment. We train
the word alignment models twice: a first time on the original data set and a second time on the data set in which the
compounds are split into their component parts.
Experiments show that the compound splitter combined with the novel word alignment technique considerably improves
bilingual terminology extraction results.
A flexible framework for collocation retrieval and translation from parallel and comparable corpora
Authors: Mendoza Rivera Oscar , Mitkov Ruslan , Corpas Pastor Gloria 
Published: July 2018

Abstract
This paper outlines a methodology and a system for collocation retrieval and translation from parallel and comparable
corpora, developed with translators and language learners in mind. It is based on a phraseology framework, applies
statistical techniques, and employs source tools and online resources. The collocation retrieval and translation has
proved successful for English and Spanish and can be easily adapted to other languages. The evaluation results are
promising and future goals are proposed. Furthermore, conclusions are drawn on the nature of comparable corpora and
how they can be better exploited to suit particular needs of target users.
On identification of bilingual lexical bundles for translation purposes
Authors: Grabowski Łukasz 
Published: July 2018

Abstract
Grounded in phraseology and corpus linguistics, this paper aims to explore the use of bilingual lexical bundles to
improve the degree of naturalness and textual fit of translated texts. More specifically, this study attempts to
identify lexical bundles, that is, recurrent sequences of 3–7 words with similar discursive functions in a
purpose-designed comparable corpus of English and Polish patient information leaflets, with 100 text samples in each
language. Because of cross-linguistic differences, we additionally apply a number of formal criteria in order to
filter out the bundles in each subcorpus. The results show that bilingual lexical bundles with overlapping discourse
functions in texts and extracted from comparable corpora hold unexplored potential for machine translation,
computer-assisted translation and bilingual lexicography.
The quest for croatian idioms as multiword units
Authors: Kocijan Kristina , Librenjak Sara 
Published: July 2018

Abstract
Idiomatic expressions are types of MWUs in which the meaning of the unit does not equal the cummulative meaning of its
parts. They are culturally dependent, so the translation cannot be inferred from the expression itself. Croatian
language has a very rich idiomatic structure. A few such expressions can be understood in direct translation but most
are different from the literal translations. As the idioms are rooted in the tradition of the language and society
from which they hail, they need special treatment in computational linguistics. Using NooJ as an NLP tool, we describe
different types of Croatian idioms that will help us recognize them in texts. Idioms recognition should be given
special treatment, being the major task in translation.
Anaphora resolution, collocations and translation
Authors: Wehrli Eric , Nerima Luka 
Published: July 2018

Abstract
Collocation identification and anaphora resolution are widely recognised as major issues for natural language
processing, and particularly for machine translation. This paper focuses on their intersection domain, that is
verb-object collocations in which the object has been pronominalised. To handle such cases, an anaphora resolution
procedure must link the direct object pronoun to its antecedent. The identification of a collocation can then be made
on the basis of the verb and its object or its antecedent. Results obtained from the translation of a large corpus
will be discussed, as well as an evaluation of the precision of the anaphora resolution procedure for this specific
task.