bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL cholesterol and C-reactive protein levels
Authors: Ryan Dan , Moss Arthur , McCarthy Jeanette , Goldenberg Ilan , Zareba Wojciech , Sparks Charles , Corsetti James 
Published: October 2011

SummaryFew studies are available in human populations investigating involvement of vascular inflammation and oxidative stress-related dysfunctional transformation of high-density lipoprotein (HDL) in establishing cardiovascular disease (CVD) risk. To this end, the current work investigated a subgroup of post-infarction patients at high-risk for recurrent events defined by high levels of HDL cholesterol (HDL-C) and concurrently high levels of C-reactive protein (CRP). Thrombospondin-4 (TSP-4), a matricellular protein of vessel walls associated with inflammation, was investigated in terms of CVD risk using multivariable modelling with a well-characterised functional genetic polymorphism of THBS4 (A387P, rs1866389) along with previously demonstrated risk-related functional genetic polymorphisms of CYBA (C242T, rs4673) and CETP (TaqIB, rs708272), and a set of blood markers. Results revealed risk-association for the gain-of-function P-allele of the THBS4 polymorphism (hazard ratio 2.00, 95% confidence interval 1.10–3.65, p=0.024). Additionally, von Willebrand factor was associated with D-dimer levels in the higher-risk P allele patients suggestive of a connection between endothelial dysfunction and thrombogenesis. In conclusion, TSP-4, a matricellular protein involved in regulating vascular inflammation, plays a role in establishing recurrent coronary risk in postinfarction patients with high levels of HDL-C and CRP. Further studies should focus on additional effects of vascular inflammatory processes on anti-atherogenic functionality of HDL particles.
Pathogens and atherosclerosis: Update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis
Authors: Ann Campbell Lee , Rosenfeld Michael 
Published: October 2011

SummaryIt is currently unclear what causes the chronic inflammation within atherosclerotic plaques. One emerging paradigm suggests that infection with bacteria and/or viruses can contribute to the pathogenesis of atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at non-vascular sites. This paradigm has been supported by multiple epidemiological studies that have established positive associations between the risk of cardiovascular disease morbidity and mortality and markers of infection. It has also been supported by experimental studies showing an acceleration of the development of atherosclerosis following infection of hyperlipidaemic animal models. There are now a large number of different infectious agents that have been linked with an increased risk of cardiovascular disease. These include: Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. However, there are significant differences in the strength of the data supporting their association with cardiovascular disease pathogenesis. In some cases, the infectious agents are found within the plaques and viable organisms can be isolated suggesting a direct effect. In other cases, the association is entirely based on biomarkers. In the following review, we evaluate the strength of the data for individual or groups of pathogens with regard to atherosclerosis pathogenesis and their potential contribution by direct or indirect mechanisms and discuss whether the established associations are supportive of the infectious disease paradigm. We also discuss the failure of antibiotic trials and the question of persistent infection.
Venous thromboembolism in patients with symptomatic atherosclerosis
Authors: Goldhaber Samuel , Lessard Darleen , Goldberg Robert , Emery Catherine , Spencer Frederick , Piazza Gregory 
Published: October 2011

SummaryPatients with atherosclerosis have an increased risk of venous thromboembolism (VTE). We studied patients in the population-based Worcester VTE Study of 1,822 consecutive patients with validated VTE to compare clinical characteristics, prophylaxis, treatment, and outcomes of VTE in patients with and without symptomatic atherosclerotic cardiovascular disease, defined as history of ischaemic heart disease, history of positive cardiac catheterisation, percutaneous coronary intervention, or coronary artery bypass graft surgery, or history of peripheral artery disease. Of the 1,818 patients with VTE, 473 (26%) had a history of symptomatic atherosclerosis. Patients with atherosclerosis were significantly older (mean age 71.9 years vs. 61.6 years) and were more likely to have immobility (57.2% vs. 46.7%), prior heart failure (36.9% vs. 10.7%), chronic lung disease (26.4% vs. 15.5%), cerebrovascular disease (18.1% vs. 9.8%), and chronic kidney disease (4.9% vs. 1.9%) (all p<0.001) compared with non-atherosclerosis patients. Thromboprophylaxis was omitted in more than one-third of atherosclerosis patients who had been hospitalised for non-VTE-related illness or had undergone major surgery within the three months prior to VTE. Patients with atherosclerosis were significantly more likely to suffer in-hospital major bleeding (7.6% vs. 3.8%, p=0.0008). In conclusion, patients with atherosclerosis and VTE are more likely to suffer a complicated hospital course. Despite a high frequency of comorbid conditions contributing to the risk of VTE, we observed a low rate of thromboprophylaxis in patients with symptomatic atherosclerosis.
Neutrophilic granulocytes – promiscuous accelerators of atherosclerosis
Authors: Döring Yvonne , Megens Remco , Soehnlein Oliver , Drechsler Maik 
Published: October 2011

SummaryNeutrophils, as part of the innate immune system, are classically described to be main actors during the onset of inflammation enforcing rapid neutralisation and clearance of pathogens. Besides their wellstudied role in acute inflammatory processes, recent advances strongly indicate a so far underappreciated importance of neutrophils in initiation and development of atherosclerosis. This review focuses on current findings on the role of neutrophils in atherosclerosis. As pro-inflammatory mechanisms of neutrophils have primarily been studied in the microvascular environment; we here aim at translating these into the context of macrovascular inflammation in atherosclerosis. Since much of the pro-inflammatory activities of neutrophils stem from instructing neighbouring cell types, we highlight the promiscuous interplay between neutrophils and platelets, monocytes, T lymphocytes, and dendritic cells and its possible relevance to atherosclerosis.
Risk factors for symptomatic venous thromboembolism in Thai hospitalised medical patients
Authors: Uaprasert Noppacharn , Vajragupta Laddawan , Numkarunarunrote Numphung , Tanpowpong Nathaporn , Sutcharitchan Pranee , Rojnuckarin Ponlapat 
Published: October 2011

SummaryThromboprophylaxis for venous thromboembolism (VTE) failed to reduce overall mortality in hospitalised medical patients. As a VTE prediction model for Asians is still lacking, this study aimed to identify very high risk patients who would be the main target for prevention. In 2009, medical patients admitted to King Chulalongkorn Memorial hospital, a tertiary care centre, were prospectively evaluated for risk factors. The high-risk cohort was monitored for symptomatic VTE until six weeks after discharge. No heparin prophylaxis was given. Of 1,290 high-risk patients, 27 (2.1%, 95% confidence interval [CI] 1.3–2.9) developed proven VTE, 25.9% of which were diagnosed after discharge. Cases with VTE stayed longer in the hospital (median 18 vs. 11 days, p < 0.001). The significant risk factors in a multivariate analysis were autoimmune disease, solid tumours, family history of VTE, varicose vein and oestrogen with the relative risks of 11.8, 4.7, 120.3, 40.1 and 17.1 (p < 0.001, 0.001, 0.001, 0.002 and 0.038), respectively. Either autoimmune disease or solid tumours were found in 63% of VTE with the relative risk of 4.5 (95% CI 2.1–9.7, p < 0.001). In contrast, previously reported VTE scores in western patients could not stratify the VTE risks, but all the scores predicted higher mortality. In conclusion, VTE is common in Asian hospitalised medical patients. Patients with autoimmune disease and those with solid tumours are highly susceptible to VTE. A prophylactic strategy in these groups is required.
Platelets in atherosclerosis
Authors: Hundelshausen Philipp von , Lievens Dirk 
Published: October 2011

SummaryBeyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.
Partial Compensation for Altered Auditory Feedback: A Tradeoff with Somatosensory Feedback?
Authors: Katseff Shira , Houde John , Johnson Keith 
Published: October 2011

Talkers are known to compensate only partially for experimentally-induced changes to their auditory feedback. In a typical experiment, talkers might hear their F1 feedback shifted higher (so that /ε/ sounds like /æ/, for example), and compensate by lowering F1 in their subsequent speech by about a quarter of that distance. Here, we sought to characterize and understand partial compensation by examining how talkers respond to each step on a staircase of increasing shifts in auditory feedback. Subjects wore an apparatus which altered their real time auditory feedback. They were asked to repeat visually-presented hVd stimulus words while feedback was altered stepwise over the course of 360 trials. We used a novel analysis method to calculate each subject’s compensation at each compensation step relative to their baseline. Results demonstrated that subjects compensated more for small feedback shifts than for larger shifts. We suggest that this pattern is consistent with vowel targets that incorporate auditory and somatosensory information, and a speech motor control system that is driven by differential weighting of auditory and somatosensory feedback.
Prediction of one-layer woven fabrics air permeability using porosity parameters
Authors: Zupin Živa , Hladnik Aleš , Dimitrovski Krste 
Published: October 2011

Air permeability is one of the fundamental textile properties influencing the design of comfortable clothes. In particular, it is very important in the field of technical textiles. Air permeability depends mainly on the fabric structure, which can be described by yarn linear density, type of yarn, warp/weft density and weave. The purpose of our study was to identify a small number of parameters that have the strongest influence on air permeability of cotton fabrics and enable its good prediction. Rather than focusing on the constructional parameters, we decided to include a composite parameter known from the theory of fluids, hydraulic diameter of pores, which treats rectangular-shaped pores as circular ones. In addition to the hydraulic diameter of pores, two other parameters were used for the prediction of air permeability: the number of macro pores and the total porosity of woven fabrics. 36 woven fabric samples were produced using nine frequently implemented weave types together with two warp densities (29.3 and 22 ends/cm) and two weft densities (15 and 20 picks/cm), resulting in four different densities of woven fabrics. The yarns had the same linear density and material in warp and weft directions. Air permeability measurements were performed with the Air Permeability tester FX 3300 Labotester III (Textest Instruments) according to the ISO 9237:1995 (E) standard. Principal components analysis revealed that the four investigated plain weave specimens behave differently than the other samples, which might be explained by weave structure. This multivariate statistical method also confirmed the appropriateness of the three selected parameters for air permeability prediction which was done using multiple linear regression. The high adjusted coefficient of determination (R2) value of 0.94 indicates that the model explains variability in the air permeability to a large extent.
Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man
Authors: Antonova Maria , Wienecke Troels , Olesen Jes , Ashina Messoud 
Published: October 2011

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E2, prostaglandin I2 (prostacyclin) and prostaglandin D2 were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F2α (PGF2α) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF2α or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0–90 min) between PGF2α and placebo ( p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo ( p = 0.500 and p = 1.000, respectively). There was no difference in VMCA ( p = 0.776) and in the diameter of the STA ( p = 0.460) or RA ( p = 0.780) between PGF2α and placebo. Conclusion: The present study shows that PGF2α, unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.
Chronic daily cortical spreading depressions suppress spreading depression susceptibility
Authors: Sukhotinsky Inna , Dilekoz Ergin , Wang Yumei , Qin Tao , Eikermann-Haerter Katharina , Waeber Christian , Ayata Cenk 
Published: October 2011

Background: Migraine is a disabling chronic episodic disorder. Attack frequency progressively increases in some patients. Incremental cortical excitability has been implicated as a mechanism underlying progression. Cortical spreading depression (CSD) is the electrophysiological event underlying migraine aura, and a headache trigger. We hypothesized that CSD events during frequent migraine attacks condition the cortex to increase the susceptibility to further attacks. Methods: A single daily CSD was induced for 1 or 2 weeks in mouse frontal cortex; contralateral hemisphere served as sham control. At the end of CSD conditioning, occipital CSD susceptibility was determined by measuring the frequency of CSDs evoked by topical KCl application. Results: Sham hemispheres developed 8.4 ± 0.3 CSDs/hour, and did not significantly differ from naïve controls without prior cranial surgery (9.3 ± 0.4 CSDs/hour). After 2 but not 1 week of daily CSD conditioning, CSD frequency (4.9 ± 0.3 CSDs/hour) as well as the duration and propagation speed were reduced significantly in the conditioned hemispheres. Histopathological examination revealed marked reactive astrocytosis without neuronal injury throughout the conditioned cortex after 2 weeks, temporally associated with CSD susceptibility. Conclusions: These data do not support the hypothesis that frequent migraine attacks predispose the brain to further attacks by enhancing tissue susceptibility to CSD.
Traumatic Patellar Dislocation
Authors: Bitar Alexandre Carneiro , Demange Marco Kawamura , D’Elia Caio Oliveira , Camanho Gilberto Luis 
Published: October 2011

Background: Over the long term, acute patellar dislocations can result in patellar instability, with high recurrence rates after nonoperative treatment. Purpose: To compare the results of operative (reconstruction of the medial patellofemoral ligament [MPFL]) versus nonoperative treatment of primary patellar dislocation. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Thirty-nine patients (41 knees) (mean age, 24.2 years; range, 12-38 years) with acute patellar dislocation were randomized into 2 groups. One group was treated nonoperatively with immobilization and physiotherapy, the other was treated surgically with MPFL reconstruction; both groups were evaluated with minimum follow-up of 2 years. The Kujala questionnaire was applied to assess pain and quality of life, and recurrence was evaluated. Pearson χ2 or Fisher exact test was used in the statistical evaluation. Results: The statistical analysis showed that the mean Kujala score was significantly lower in the nonoperative group (70.8), when compared with the mean value of the surgical group (88.9; P = .001). The surgical group presented a higher percentage of “good/excellent” results (71.43%) on the Kujala score when compared with the nonoperative group (25.0%; P = .003). The nonoperative group presented a large number of recurrences and subluxations (7 patients; 35% of cases), whereas there were no reports of recurrences or subluxations in the surgical group. Conclusion: Treatment with MPFL reconstruction using the patellar tendon produced better results, based on the analyses of posttreatment recurrences and the better final results of the Kujala questionnaire after a minimum follow-up period of 2 years.
Modelling distortion induced in an assembly by the self piercing rivet process
Authors: Masters I , Fan X , Roy R , Williams D 
Published: October 2011

Traditionally, prediction of the dimensions of an assembly has concentrated on the variation of the constituent components and fixtures. Although recent methods have accounted for both statistical variation and flexibility of sheet metal components, the impact of the joining process has largely been ignored for riveted and spot-welded assemblies. The self-piercing rivet (SPR) has been used increasingly in the automotive industry for joining lightweight aluminium body structures, but the localized distortion around an SPR has been shown to be greater than that associated with the spot weld commonly used in steel body constructions. Consequently incorporation of such distortion into the simulation process for predicting the overall distortion of assemblies would be useful. This paper presents a simulation method based on a local/global approach where the distortion occurring around a single SPR is projected on to a global assembly at each rivet location. The results for both flat sheet assemblies and a simple top-hat assembly are presented for comparison and show that the method can be valuable in the early design stages by predicting the distortion from the joining process. Some suggestions for improving the method are also discussed.
The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations
Authors: Huang Gang , Zhao Xinghui , Wang Lan , Elf Shannon , Xu Hao , Zhao Xinyang , Sashida Goro , Zhang Yue , Liu Yan , Lee Jennifer , Menendez Silvia , Yang Youyang , Yan Xiaomei , Zhang Pu , Tenen Daniel G. , Osato Motomi , Hsieh James J.-D. , Nimer Stephen D. 
Published: October 2011

AbstractThe mixed-lineage leukemia (MLL) H3K4 methyltransferase protein, and the heterodimeric RUNX1/CBFβ transcription factor complex, are critical for definitive and adult hematopoiesis, and both are frequently targeted in human acute leukemia. We identified a physical and functional interaction between RUNX1 (AML1) and MLL and show that both are required to maintain the histone lysine 4 trimethyl mark (H3K4me3) at 2 critical regulatory regions of the AML1 target gene PU.1. Similar to CBFβ, we show that MLL binds to AML1 abrogating its proteasome-dependent degradation. Furthermore, a subset of previously uncharacterized frame-shift and missense mutations at the N terminus of AML1, found in MDS and AML patients, impairs its interaction with MLL, resulting in loss of the H3K4me3 mark within PU.1 regulatory regions, and decreased PU.1 expression. The interaction between MLL and AML1 provides a mechanism for the sequence-specific binding of MLL to DNA, and identifies RUNX1 target genes as potential effectors of MLL function.
DART: Denoising Algorithm based on Relevance network Topology improves molecular pathway activity inference
Authors: Jiao Yan , Lawler Katherine , Patel Gargi S , Purushotham Arnie , Jones Annette F , Grigoriadis Anita , Tutt Andrew , Ng Tony , Teschendorff Andrew E 
Published: October 2011

Abstract

Background
Inferring molecular pathway activity is an important step towards reducing the complexity of genomic data, understanding the heterogeneity in clinical outcome, and obtaining molecular correlates of cancer imaging traits. Increasingly, approaches towards pathway activity inference combine molecular profiles (e.g gene or protein expression) with independent and highly curated structural interaction data (e.g protein interaction networks) or more generally with prior knowledge pathway databases. However, it is unclear how best to use the pathway knowledge information in the context of molecular profiles of any given study.

Results
We present an algorithm called DART (Denoising Algorithm based on Relevance network Topology) which filters out noise before estimating pathway activity. Using simulated and real multidimensional cancer genomic data and by comparing DART to other algorithms which do not assess the relevance of the prior pathway information, we here demonstrate that substantial improvement in pathway activity predictions can be made if prior pathway information is denoised before predictions are made. We also show that genes encoding hubs in expression correlation networks represent more reliable markers of pathway activity. Using the Netpath resource of signalling pathways in the context of breast cancer gene expression data we further demonstrate that DART leads to more robust inferences about pathway activity correlations. Finally, we show that DART identifies a hypothesized association between oestrogen signalling and mammographic density in ER+ breast cancer.

Conclusions
Evaluating the consistency of prior information of pathway databases in molecular tumour profiles may substantially improve the subsequent inference of pathway activity in clinical tumour specimens. This de-noising strategy should be incorporated in approaches which attempt to infer pathway activity from prior pathway models.