bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrinolytic status in acute coronary syndromes: Evidence of differences in relation to clinical features and pathophysiological pathways
Authors: Shantsila Eduard , Montoro-Garcia Silvia , Tapp Luke , Apostolakis Stavros , Wrigley Benjamin , Lip Gregory 
Published: April 2012

SummaryLimited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p<0.001) while PAI-1 activity was higher in STEMI (p<0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p<0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p<0.05). In STEMI, TAFI levels peaked at day 7 (p<0.05) and dropped significantly by day 30 (p<0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p<0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyteplatelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
Thirty-Day Mortality After Ischemic Stroke and Intracranial Hemorrhage in Patients With Atrial Fibrillation On and Off Anticoagulants
Authors: Fang Margaret C. , Go Alan S. , Chang Yuchiao , Borowsky Leila H. , Pomernacki Niela K. , Udaltsova Natalia , Singer Daniel E. 
Published: April 2012

Background and Purpose—
Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation.

Methods—
We followed 13 559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors.

Results—
We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45–0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88–2.98). Therapeutic international normalized ratios (2–3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20–0.70), whereas international normalized ratios >3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21–5.86).

Conclusions—
Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.
Association Between Changes in Lipid Profiles and Progression of Symptomatic Intracranial Atherosclerotic Stenosis
Authors: Kim Dong-Eog , Kim Jeong-Yeon , Jeong Sang-Wuk , Cho Yong-Jin , Park Jong-Moo , Lee Ju-Hun , Kang Dong-Wha , Yu Kyung-Ho , Bae Hee-Joon , Hong Keun-Sik , Koo Ja-Seong , Lee Seung-Hoon , Lee Byung-Chul , Han Moon-Ku , Rha Joung-Ho , Lee Yong-Seok , Kim Gyeong-Moon , Chae Seok-Lae , Kim Jong S. , Kwon Sun U. 
Published: April 2012

Background and Purpose—
Predictors of progression of intracranial atherosclerotic stenosis have not been clearly identified. We investigated whether poststroke changes in lipid profiles would affect the prognosis of symptomatic intracranial atherosclerotic stenosis.

Methods—
This is a substudy of Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). From 10 centers we enrolled 230 subjects with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or basilar artery. At baseline and 7 months after stroke, subjects underwent MR angiogram and assessment of cardiovascular risk factors including lipoprotein levels. Progression of intracranial atherosclerotic stenosis was determined by comparing stenosis on the baseline and follow-up MR angiograms.

Results—
Cilostazol treatment was more frequently seen in the nonprogression group (109 of 198 [55.1%]) than in the progression group (11 of 32 [34.4%]). At 7 months after stroke when compared with baseline, low-density lipoprotein cholesterol and total cholesterol levels decreased in both groups. However, only nonprogressors showed increase in high-density lipoprotein cholesterol levels between baseline and follow-up. Changes in apolipoprotein B/apolipoprotein A-I levels were not different between the groups, although apolipoprotein B/A-I at 7 months was higher in progressors than in nonprogressors. Remnant lipoprotein cholesterol levels decreased in nonprogressors, whereas they did not change in progressors. In multivariable analyses, after adjusting for cilostazol treatment and remnant lipoprotein cholesterol reduction or apolipoprotein B/A-I at 7 months, high-density lipoprotein cholesterol elevation remained as a significant predictor for the nonprogression.

Conclusions—
This is the first prospective multicenter study to demonstrate that high-density lipoprotein cholesterol elevation, along with remnant lipoprotein cholesterol reduction and low apolipoprotein B/A-I, is associated with prevention of angiographic progression of symptomatic intracranial atherosclerotic stenosis.

Clinical Trial Registration Information—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00130039.
Ascending and Descending VPs in English
Authors: Janke Vikki , Neeleman Ad 
Published: April 2012

AbstractWe argue that English allows both rightward-descending VP shell structures and more traditional rightward-ascending VPs. The choice between these depends on case theory and economy. Case theory triggers VP shell formation whenever the verb is merged with a DP object after it has been merged with some other category. The reason is that VP shell formation allows verb and object to surface in adjacent positions, a prerequisite for case licensing in English. Economy has the effect that in all other circumstances, VP shell formation is blocked. Our argument is based on a range of intricate data, many of which involve the distribution of object-oriented floating quantifiers. We end with a discussion of the binding data that are often taken to support a uniformly descending structure—incorrectly, in our view.
The Italian Left Periphery: A View from Locality
Authors: Abels Klaus 
Published: April 2012

AbstractIn this article, I discuss the interaction of locality phenomena with the left periphery in Italian as elaborated in Rizzi 1997, 2001a, 2004b. It turns out that long-distance crossing possibilities fully predict the local orderings entailed by Rizzi’s left-peripheral template. In fact, both descriptive gains (in terms of topic positions) and explanatory gains (regarding the position and behavior of topics and of Rizzi’s (2001a) Int) can be made if local ordering is reduced to locality. This suggests that the left-peripheral template should be derived from some appropriate theory of locality and should not be taken as a theoretical primitive.
On the Relationship of Object Agreement and Accusative Case: Evidence from Amharic
Authors: Baker Mark C. 
Published: April 2012

AbstractThis article shows that accusative case and object agreement are not closely related in Amharic, a language in which both are morphologically overt. This suggests that it is wrong to generalize Chomsky’s claim that agreement and case are both manifestations of the same Agree relation from subjects to objects across the board. I show that object agreements in Amharic are the true manifestations of Agree (not pronominal clitics), whereas accusative case is assigned independently, to the lower of two nominals in the same domain. The relationship between case and agreement can thus vary parametrically.
On Raising out of Control
Authors: Ndayiragije Juvénal 
Published: April 2012

AbstractHornstein (1999) put forward two thought-provoking ideas that generated a stimulating debate on control: (a) A-movement out of CP complements of control verbs is a design feature of Universal Grammar as first suggested by Kuno (1976), and (b) obligatory control (OC) is an instance of A-movement. This article presents new evidence from Kirundi (Bantu) that supports (a) but defies (b), a paradox that is only apparent. Four sets of facts are discussed: antilocality in promise-constructions, control obviation in inverse OC constructions, passivization in transitive expletive OC constructions, and OC in long-distance inversion constructions. These facts are shown to challenge the movement account of OC while supporting (a) and the PRO-based account.
Determination of mercury, cadmium and lead in human milk in Iran
Authors: Goudarzi MA , Parsaei P , Nayebpour F , Rahimi E 
Published: April 2012

Breast milk contains both essential and nonessential trace elements. Mercury, cadmium and lead are nonessential, potentially toxic heavy metals with hematotoxic, neurotoxic and nephrotoxic properties even at very low concentrations. The objectives of this study were to determine the concentrations of mercury, cadmium and lead in the breast milk of healthy lactating women who were living in Isfahan, Iran. Concentrations of mercury, cadmium and lead were determined by graphite furnace atomic absorption spectrometry in 37 milk samples from healthy lactating women collected on first to sixth postpartum week. Accuracy of the analysis was checked by various methods including the use of reference material. The mean ± SD of the concentrations of mercury, cadmium and lead in human milk were 0.92 ± 0.54 μg/L (range 0.0–2.07 μg/L), 1.92 ± 1.04 μg/L (range 0.45–5.87 μg/L) and 7.11 ± 3.96 μg/L (range 3.06–19.47 μg/L), respectively. The results of this study showed that the concentrations of mercury, lead and cadmium in the milk samples from lactating women in Isfahan were high, which makes a major public health hazard for the inhabitants, especially neonatal and children, of the industrial locations. The results of the present study indicate a need for establishing safe intake values of heavy metals in human milk.
Histamine is a modulator of metamorphic competence in Strongylocentrotus purpuratus(Echinodermata: Echinoidea)
Authors: Sutherby Josh , Giardini Jamie-Lee , Nguyen Julia , Wessel Gary , Leguia Mariana , Heyland Andreas 
Published: April 2012

Abstract

Background
A metamorphic life-history is present in the majority of animal phyla. This developmental mode is particularly prominent among marine invertebrates with a bentho-planktonic life cycle, where a pelagic larval form transforms into a benthic adult. Metamorphic competence (the stage at which a larva is capable to undergo the metamorphic transformation and settlement) is an important adaptation both ecologically and physiologically. The competence period maintains the larval state until suitable settlement sites are encountered, at which point the larvae settle in response to settlement cues. The mechanistic basis for metamorphosis (the morphogenetic transition from a larva to a juvenile including settlement), i.e. the molecular and cellular processes underlying metamorphosis in marine invertebrate species, is poorly understood. Histamine (HA), a neurotransmitter used for various physiological and developmental functions among animals, has a critical role in sea urchin fertilization and in the induction of metamorphosis. Here we test the premise that HA functions as a developmental modulator of metamorphic competence in the sea urchin Strongylocentrotus purpuratus.

Results
Our results provide strong evidence that HA leads to the acquisition of metamorphic competence in S. purpuratus larvae. Pharmacological analysis of several HA receptor antagonists and an inhibitor of HA synthesis indicates a function of HA in metamorphic competence as well as programmed cell death (PCD) during arm retraction. Furthermore we identified an extensive network of histaminergic neurons in pre-metamorphic and metamorphically competent larvae. Analysis of this network throughout larval development indicates that the maturation of specific neuronal clusters correlates with the acquisition of metamorphic competence. Moreover, histamine receptor antagonist treatment leads to the induction of caspase mediated apoptosis in competent larvae.

Conclusions
We conclude that HA is a modulator of metamorphic competence in S. purpuratus development and hypothesize that HA may have played an important role in the evolution of settlement strategies in echinoids. Our findings provide novel insights into the evolution of HA signalling and its function in one of the most important and widespread life history transitions in the animal kingdom - metamorphosis.
Cooperative interactions in the West Nile virus mutant swarm
Authors: Ciota Alexander T , Ehrbar Dylan J , Van Slyke Greta A , Willsey Graham G , Kramer Laura D 
Published: April 2012

Abstract

Background
RNA viruses including arthropod-borne viruses (arboviruses) exist as highly genetically diverse mutant swarms within individual hosts. A more complete understanding of the phenotypic correlates of these diverse swarms is needed in order to equate RNA swarm breadth and composition to specific adaptive and evolutionary outcomes.

Results
Here, we determined clonal fitness landscapes of mosquito cell-adapted West Nile virus (WNV) and assessed how altering the capacity for interactions among variants affects mutant swarm dynamics and swarm fitness. Our results demonstrate that although there is significant mutational robustness in the WNV swarm, genetic diversity also corresponds to substantial phenotypic diversity in terms of relative fitness in vitro. In addition, our data demonstrate that increasing levels of co-infection can lead to widespread strain complementation, which acts to maintain high levels of phenotypic and genetic diversity and potentially slow selection for individual variants. Lastly, we show that cooperative interactions may lead to swarm fitness levels which exceed the relative fitness levels of any individual genotype.

Conclusions
These studies demonstrate the profound effects variant interactions can have on arbovirus evolution and adaptation, and provide a baseline by which to study the impact of this phenomenon in natural systems.
Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation
Authors: Trejo-Solís Cristina , Jimenez-Farfan Dolores , Rodriguez-Enriquez Sara , Fernandez-Valverde Francisca , Cruz-Salgado Arturo , Ruiz-Azuara Lena , Sotelo Julio 
Published: April 2012

Abstract

Background
Glioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate.

Methods
The in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia), a copper compound, on rat malignant glioma C6 cells was investigated.

Results
Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH2-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK –specific inhibitor SP600125 prevented Cas III-ia-induced cell death.

Conclusions
Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS –dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections
Authors: Pillai Dylan R , Lau Rachel , Khairnar Krishna , Lepore Rosalba , Via Allegra , Staines Henry M , Krishna Sanjeev 
Published: April 2012

AbstractBackgroundMonitoring resistance phenotypes forPlasmodium falciparum, usingin vitrogrowth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.MethodsPlasmodium falciparumisolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations inpfatp6andpfmdr1.ResultsResistance to artemetherin vitrowas significantly associated with apfatp6haplotype encoding two amino acid substitutions (pfatp6A623E and S769N; (mean IC50(95% CI) values of 8.2 (5.7 – 10.7) for A623/S769versus623E/769 N 13.5 (9.8 – 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number ofpfmdr1was not itself associated with increased IC50values for artemether, but when interactions between thepfatp6haplotype and increased copy number ofpfmdr1were examined together, a highly significant association was noted with IC50values for artemether (mean IC50(95% CI) values of 8.7 (5.9 – 11.6)versus16.3 (10.7 – 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs inpfmdr1are also associated with differences in sensitivity to some artemisinins.ConclusionsThese findings were further explored in molecular modelling experiments that suggest mutations inpfatp6are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations inpfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed.
A rare giant gastrointestinal stromal tumor of the stomach traversing the upper abdomen: a case report and literature review
Authors: Zhou Lei , Liu Chang , Bai Ji-Gang , Wei Ji-Chao , Qu Kai , Tian Feng , Tai Ming-Hui , Wang Rui-Tao , Meng Fan-Di 
Published: April 2012

Abstract
We present the case of a 66-year-old woman with a huge gastrointestinal stromal tumor of the stomach that traversed her upper abdomen. The predominant abdominal sign was a huge, palpable mass, but there were no other distinctive findings in her physical examination or her routine blood workup, including biochemical markers. It was difficult to judge the origin of the mass upon imaging. Furthermore, radiological findings revealed that the mass had a complex relationship with many major blood vessels. An exploratory laparotomy revealed a huge tumor protruding from the anterior wall of the stomach fundus, on the lesser curvature of the stomach, measuring approximately 21 × 34 × 11 cm in diameter and weighing 5.5 kg. A complete resection was performed and the tumor was characterized on immunohistochemistry as a gastrointestinal stromal tumor of the stomach. Preoperative diagnosis of gastrointestinal stromal tumors can be difficult, and we hope that the presentation of this rare case and literature review will benefit other diagnosing clinicians having similar problems.
Proteolytic activation of proapoptotic kinase protein kinase Cδ by tumor necrosis factor α death receptor signaling in dopaminergic neurons during neuroinflammation
Authors: Gordon Richard , Anantharam Vellareddy , Kanthasamy Anumantha G , Kanthasamy Arthi 
Published: April 2012

Abstract

Background
The mechanisms of progressive dopaminergic neuronal loss in Parkinson’s disease (PD) remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. Several lines of evidence from human studies and experimental models over the last decade have identified neuroinflammation as a potential pathophysiological mechanism contributing to disease progression. Tumor necrosis factor α (TNF) has recently emerged as the primary neuroinflammatory mediator that can elicit dopaminergic cell death in PD. However, the signaling pathways by which TNF mediates dopaminergic cell death have not been completely elucidated.

Methods
In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. Etanercept and neutralizing antibodies to tumor necrosis factor receptor 1 (TNFR1) were used to block TNF signaling. We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS) model of nigral dopaminergic degeneration.

Results
TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ), an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. Both TNFR1 neutralizing antibodies and the soluble TNF receptor Etanercept blocked TNF-induced PKCδ proteolytic activation. Proteolytic activation of PKCδ was accompanied by translocation of the kinase to the nucleus. Notably, inhibition of PKCδ signaling by small interfering (si)RNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. Further, primary dopaminergic neurons obtained from PKCδ knockout (−/−) mice were resistant to TNF toxicity. The proteolytic activation of PKCδ in the mouse substantia nigra in the neuroinflammatory LPS model was also observed.

Conclusions
Collectively, these results identify proteolytic activation of PKCδ proapoptotic signaling as a key downstream effector of dopaminergic cell death induced by TNF. These findings also provide a rationale for therapeutically targeting PKCδ to mitigate progressive dopaminergic degeneration resulting from chronic neuroinflammatory processes.