bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of psychological factors and healthcare use with the discrepancy between subjective and objective respiratory-health complaints in the general population
Authors: Selinheimo Sanna , Vasankari Tuula , Jokela Markus , Kanervisto Merja , Pirkola Sami , Suvisaari Jaana , Paunio Tiina
Published: March 2018

Background

We examined the prevalence of self-perceived respiratory symptoms (SRS) in the absence of any objective findings of respiratory pathology, and the association of such prevalence with psychological factors and healthcare use in the general population.

Methods

The study was conducted among a nationally representative sample of Finnish adults (BRIF8901). Respiratory functioning was measured by a spirometry test. Structured questionnaires were used to measure SRS, physician visits and psychological factors of alexithymia, sense of coherence, illness worry and common mental disorders. Individuals with a diagnosed respiratory disease or a severe psychiatric disorder, determined in a diagnostic interview, were excluded, giving a sample comprising 4544 participants.

Results

Twenty-six per cent of the general population and 36% of those with no diagnosed severe psychiatric disorder or respiratory disease experienced SRS despite a normal spirometry result. Psychological factors were associated with SRS (0.0001 < p < 0.032), and on the number of physician visit explaining 42.7% of the difference in visits between individuals with and without SRS, respectively. Illness worry was associated most strongly with SRS [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.19–1.41, p < 0.0001] and higher numbers of physician visits (OR 1.35, CI 1.32–1.38, p < 0.00001), even after several adjustments.

Conclusions

Respiratory symptoms without objective findings are common in the general population. The study results underline the role of psychological factors in the reporting of respiratory symptoms and the associated medical burden, thereby indicating the functional nature of the symptomatology.
Vilnius: The GAIDA Festival, October-November 2017
Authors: McGinn Claire
Published: March 2018

Elliott Carter's quotable 80s slur – ‘about one minute of minimalism is a lot, because it is all the same’ – was happily not applicable at this year's GAIDA festival in Vilnius. The 2017 programme of the biggest contemporary music festival in the Baltic States displayed many diverse faces of repetitive music and more besides, with a particular focus on eclectic post-minimalist David Lang (who pointedly denounced -isms and post-s in his programmed talk).
Plasmons in N-doped graphene nanostructures tuned by Au/Ag films: a time-dependent density functional theory study
Authors: Shu Xiaoqin , Cheng Xinlu , Zhang Hong
Published: March 2018

The energy resonance point of the prominent peak of the absorption spectrum of nitrogen-doped graphene is in the ultraviolet region.
The chemistry of PET imaging with zirconium-89
Authors: Dilworth Jonathan R. , Pascu Sofia I.
Published: March 2018

This review describes the coordination chemistry that underpins PET imaging with zirconium-89 and discusses the biological data obtainable from the radiolabelled complexes.
A leap forward in iridium–NHC catalysis: new horizons and mechanistic insights
Authors: Iglesias Manuel , Oro Luis A.
Published: March 2018

Ir–NHC catalysts have been crucial to the advance of an ever-growing diversity of processes thanks to their prolific reactivity and mechanistic flexibility.
Cobalt phosphide/carbon dots composite as an efficient electrocatalyst for oxygen evolution reaction
Authors: Zhu Mengmeng , Zhou Yunjie , Sun Yue , Zhu Cheng , Hu Lulu , Gao Jin , Huang Hui , Liu Yang , Kang Zhenhui
Published: March 2018

Cobalt phosphide/carbon dots composite exhibits good electrocatalytic activity and stability towards the oxygen evolution reaction.
Core–shell structured MnSiO3 supported with CNTs as a high capacity anode for lithium-ion batteries
Authors: Feng Jing , Li Qin , Wang Huijun , Zhang Min , Yang Xia , Yuan Ruo , Chai Yaqin
Published: March 2018

Benefiting from a one-dimensional tube structure and carbon nanotubes to accelerate Li+ transfer and improve conductivity, core–shell structured MnSiO3 supported with CNTs (CNT@MnSiO3) exhibits a higher performance than other metal silicates as a lithium-ion battery anode.
Two-phase systems developed with hydrophilic and hydrophobic deep eutectic solvents for simultaneously extracting various bioactive compounds with different polarities
Authors: Cao Jun , Chen Luyao , Li Mohan , Cao Fuliang , Zhao Linguo , Su Erzheng
Published: March 2018

Two-phase systems developed with hydrophilic deep eutectic solvents (DESs) and hydrophobic DESs were prepared in this study for the first time.
High internal phase water/oil and oil/water gel emulsions formed using a glucose-based low-molecular-weight gelator
Authors: Ono Fumiyasu , Shinkai Seiji , Watanabe Hisayuki
Published: March 2018

High internal phase silicone-oil-containing water/oil and oil/water emulsions were prepared using low loadings of a glucose-based low-molecular-weight gelator.
Solar light driven photocatalytic degradation of levofloxacin using TiO2/carbon-dot nanocomposites
Authors: Sharma Shelja , Umar Ahmad , Mehta Surinder Kumar , Ibhadon Alex O. , Kansal Sushil Kumar
Published: March 2018

This paper reports the synthesis of TiO2 quantum dots, carbon dots (C-dots), and TiO2/C-dots using facile sol–gel and hydrothermal methods.
Silica aerogel films via ambient pressure drying for broadband reflectors
Authors: Wang Xiaobo , Zhang Yue , Luo Jieya , Wang Dong , Gao Hong , Zhang Jingjing , Xing Yan , Yang Zhou , Cao Hui , He Wanli
Published: March 2018

This manuscript demonstrates the advantages of silica aerogel films over nanoparticles in broadening the reflection bandwidth of cholesteric liquid crystals.
Reversible switching of PEDOT:PSS conductivity in the dielectric–conductive range through the redistribution of light-governing polymers
Authors: Kalachyova Y. , Guselnikova O. , Postnikov P. , Fitl P. , Lapcak L. , Svorcik V. , Lyutakov O.
Published: March 2018

Chemical modification of PEDOT:PSS allows grafting light-switchable moieties to PSS chains and light induced reversible tuning of materials conductivity in dielectric-semimetal range.
The influence of isolated and penta-hydrated Zn2+ on some of the intramolecular proton-transfer processes of thymine: a quantum chemical study
Authors: Li Dejie , Han Ying , Li Huijuan , Zhang Ping , Kang Qi , Li Zhihua , Shen Dazhong
Published: March 2018

The influence of isolated and penta-hydrated Zn2+ on some of the intramolecular proton-transfer processes of thymine is investigated by DFT modeling.
Recent advances in nanoparticle-based lateral flow immunoassay as a point-of-care diagnostic tool for infectious agents and diseases
Authors: Banerjee Ruptanu , Jaiswal Amit
Published: March 2018

Recent advances in lateral flow immunoassay-based devices as a point-of-care analytical tool for the detection of infectious diseases are reviewed.
One-step synthesis of cobalt-doped MoS2 nanosheets as bifunctional electrocatalysts for overall water splitting under both acidic and alkaline conditions
Authors: Xiong Qizhong , Zhang Xian , Wang Haojie , Liu Guoqiang , Wang Guozhong , Zhang Haimin , Zhao Huijun
Published: March 2018

Cobalt covalent doping in MoS2 effectively regulates its electronic structure to decrease the hydrogen adsorption free energy for high HER and simultaneously contributes additional catalytic active sites for the OER.
Preparation of an ultrathin Pt electrocatalyst via a galvanic replacement reaction of electrodeposited CuCl for the oxidation of methanol in an alkaline medium
Authors: Chao Long , Liu Nian , Xiong Xiujuan , He Fang , Huang Ting , Xie Qingji , Yao Shouzhuo
Published: March 2018

An ultrathin and high-efficiency Pt electrocatalyst is prepared by the galvanic replacement reaction between electrodeposited CuCl and K2PtCl4 for alkaline methanol oxidation.
A benzoic acid terpyridine-based cyclometalated iridium(iii) complex as a two-photon fluorescence probe for imaging nuclear histidine
Authors: Zhang Qiong , Lu Xin , Wang Hui , Tian Xiaohe , Wang Aidong , Zhou Hongping , Wu Jieying , Tian Yupeng
Published: March 2018

A series of two-photon active cyclometalated iridium(iii) complexes (Ir1, Ir2 and Ir3) were designed.
Cyanotrifluoromethylthiolation of unactivated dialkyl-substituted alkynesviacyano migration: synthesis of trifluoromethylthiolated acrylonitriles
Authors: Ji Meishan , Yu Jiajia , Zhu Chen
Published: March 2018

Herein a novel, elusive cyanotrifluoromethylthiolation of unactivated dialkyl-substituted alkynes by means of intramolecular distal cyano migration is reported.
Polysulfide-triggered fluorescent indicator suitable for super-resolution microscopy and application in imaging
Authors: A. Anila Hoskere , Sreedharan Sreejesh , Ali Firoj , Smythe Carl G. , Thomas Jim A. , Das Amitava
Published: March 2018

A new physiologically benign and cell membrane permeable BODIPY based molecular probe, MB-Sn, specifically senses intracellular hydrogen polysulfides (H2Sn, n > 1) localized in the endoplasmic reticulum.
Integration of Au nanoparticles with a g-C3N4 based heterostructure: switching charge transfer from type-II to Z-scheme for enhanced visible light photocatalysis
Authors: Shi Li , Li Zhao , Marcus Kyle , Wang Guanzhi , Liang Kun , Niu Wenhan , Yang Yang
Published: March 2018

A switch from type-II to Z-scheme charge transfer by introducing Au and g-C3N4 in a hybrid photocatalyst.
Effective formation of stable and versatile double-stranded β-sheets templated by a hydrogen-bonded duplex
Authors: Shi You-Di , Tang Quan , Jiang Ya-Fei , Pei Qiang , Tan Hong-Wei , Lu Zhong-Lin , Gong Bing
Published: March 2018

An effective approach to construct stable and versatile double-stranded β-sheets composed of tetra- and penta-peptides through a hydrogen-bonded duplex template has been explored.
Probing the temperature-dependent changes of the interfacial hydration and viscosity of Tween20 : cholesterol (1 : 1) niosome membrane using fisetin as a fluorescent molecular probe
Authors: Mishra Jhili , Swain Jitendriya , Mishra Ashok Kumar
Published: March 2018

Location of fisetin molecules in TW20 : cholesterol (1 : 1) niosome membrane.
The influence of a hydrophobic carrier, reactant and product during H2O adsorption on Pd surface for the oxidative esterification of methacrolein to methyl methacrylate
Authors: Ma Jing , Yang Xueqing , Nie Yan , Wang Baohe
Published: March 2018

Taking the one-step oxidative esterification of MAL to MMA as a model reaction, the effects of the hydrophobic carrier SDB copolymer, the reactant CH3OH and the product MMA during the adsorption of H2O on a Pd surface were investigated.
A theoretical perspective of the enhanced photocatalytic properties achieved by forming tetragonal ZnS/ZnSe hetero-bilayer
Authors: Zhou Jia , Zhen Xiaofeng
Published: March 2018

The t-ZnS/ZnSe BL demonstrates good electron–hole separation by allocation of photo-induced electrons and holes in different layers.
Structural transformation of h-BN overlayers on Pt(111) in oxidative atmospheres
Authors: Meng Caixia , Li Yifan , Wu Hao , Wei Wei , Ning Yanxiao , Cui Yi , Fu Qiang , Bao Xinhe
Published: March 2018

Controlled structural transformation of h-BN overlayers on Pt(111) in oxidative atmospheres including oxygen intercalation, formation of boron oxide, and oxygen etching.
A unified model of Grignard reagent formation
Authors: Shao Yunqi , Liu Zhen , Huang Pan , Liu Boping
Published: March 2018

Understanding the selectivity and kinetics: a unified ionic model of Grignard reagent formation.
Can 2,2,2-trifluoroethanol be an efficient protein denaturant than methanol and ethanol under thermal stress?
Authors: Mohanta Dayanidhi , Jana Madhurima
Published: March 2018

We report the heterogeneous unfolding phenomenon of a small protein Chymotrypsin Inhibitor 2 in various concentrations of methanol, ethanol and TFE solutions by performing atomistic molecular dynamics simulation studies. Our study reveals that the unfolding phenomenon of CI2 under thermal stress majorly depends on the concentration and the nature of the alcohol.
Spectrum of hydrodynamic volumes and sizes of macromolecules of linear polyelectrolytes versus their charge density in salt-free aqueous solutions
Authors: Pavlov Georges M. , Dommes Olga A. , Okatova Olga V. , Gavrilova Irina I. , Panarin Evgenii F.
Published: March 2018

Viscous flow was studied in salt-free solutions of random N-methyl-N-vinylacetamide copolymers that varied in the average number of charged units. The ranges are determined where the effect of the average charge density manifests itself in different ways.
Theoretical studies on the synergistic extraction of Am3+ and Eu3+ with CMPO–HDEHP and CMPO–HEH[EHP] systems
Authors: Huang Pin-Wen , Wang Cong-Zhi , Wu Qun-Yan , Lan Jian-Hui , Song Gang , Chai Zhi-Fang , Shi Wei-Qun
Published: March 2018

Synergistic extraction and separation of Eu3+/Am3+ with CMPO–HDEHP and CMPO–HEH[EHP] systems have been theoretically investigated.
A valence balanced rule for discovery of 18-electron half-Heuslers with defects
Authors: Anand Shashwat , Xia Kaiyang , I. Hegde Vinay , Aydemir Umut , Kocevski Vancho , Zhu Tiejun , Wolverton Chris , Snyder G. Jeffrey
Published: March 2018

Thermodynamically stable ground state half-Heusler structures are valence balanced irrespective of electron count or stoichiometry.
Towards the systematic crystallisation of molecular ionic cocrystals: insights from computed crystal form landscapes
Authors: Mohamed Sharmarke , Alwan Ahmad A. , Friščić Tomislav , Morris Andrew J. , Arhangelskis Mihails
Published: March 2018

The underlying molecular and crystal properties affecting the crystallisation of organic molecular ionic cocrystals (ICCs) are investigated.
Cage-like Ta@Bqn complexes (n = 23–28, q = −1–+ 3) in 18-electron configurations with the highest coordination number of twenty-eight
Authors: Li Hai-Ru , Liu Hui , Lu Xiao-Qin , Zan Wen-Yan , Tian Xin-Xin , Lu Hai-Gang , Wu Yan-Bo , Mu Yue-Wen , Li Si-Dian
Published: March 2018

First-principles investigations predict the possibility of endohedral cage-like Ta@Bqn complexes (n = 23–28, q = −1–+ 3) in 18-electron configurations with the highest coordination number of twenty-eight in spherical environments.
A robust and stretchable superhydrophobic PDMS/PVDF@KNFs membrane for oil/water separation and flame retardancy
Authors: Li Deke , Gou Xuelian , Wu Daheng , Guo Zhiguang
Published: March 2018

A robust superhydrophobic PDMS/PVDF@KNFs membrane with excellent properties of deformation, stretchability, flame retardation, oil/water separation and oil absorption.
Shape and structure controlling of calcium oxalate crystals by a combination of additives in the process of biomineralization
Authors: Liu Nian , Xie Hao , Ping Hang , Wang Lin , Liu Zewen , Tao Fei , Guo Junhui , Su Bao-Lian
Published: March 2018

Combination of casein and small molecules regulates morphogenesis of calcium oxalate crystals.
Deep eutectic solvent-catalyzed arylation of benzoxazoles with aromatic aldehydes
Authors: Tran Phuong Hoang , Thi Hang Anh-Hung
Published: March 2018

A green and efficient synthesis of 2-arylbenzoxazoles using deep eutectic solvent as a homogeneous catalyst has been developed for the first time.
Quercetin spectrofluorometric quantification in aqueous media using different surfactants as fluorescence promoters
Authors: Alva-Ensastegui J. C. , Palomar-Pardavé M. , Romero-Romo M. , Ramírez-Silva M. T.
Published: March 2018

Quercetin spectrofluorometric quantification was carried out in aqueous media using micelles of surfactants, namely: CTAB, SDS and TX100 as promoters of quercetin fluorescence and stability.
Oxygen self-sufficient fluorinated polypeptide nanoparticles for NIR imaging-guided enhanced photodynamic therapy
Authors: Yuan Pan , Ruan Zheng , Jiang Wei , Liu Le , Dou Jiaxiang , Li Tuanwei , Yan Lifeng
Published: March 2018

Oxygen self-sufficient fluorinated polypeptide nanoparticles have been synthesized via the loading of a NIR photosensitizer (BODIPY-Br2) into a water-dispersible drug delivery system for high efficiency PDT.
Power-efficient and solution-processed red phosphorescent organic light-emitting diodes by choosing combinations of small molecular materials to form a well-dispersed exciplex co-host
Authors: Yao Bing , Lin Xingdong , Zhang Baohua , Wang Hailong , Liu Xuejing , Xie Zhiyuan
Published: March 2018

Intrinsic compatibility of exciplex couple determines the EL performance of the resultant solution-processed phosphorescent OLEDs, particularly driving voltage behaviours.
Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease
Authors: Addinsall Alex B. , Wright Craig R. , Andrikopoulos Sof , van der Poel Chris , Stupka Nicole
Published: March 2018

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.
Identification of long non-coding RNA ZFAS1 as a novel biomarker for diagnosis of HCC
Authors: Luo Ping , Liang Chunzi , Zhang Xianwei , Liu Xuefang , Wang Yingchao , Wu Mengmeng , Feng Xiaobo , Tu Jiancheng
Published: March 2018

Hepatocellular carcinoma (HCC) is the third major cause of cancer-related deaths. Abundant research show that long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of HCC and may serve as diagnostic markers for HCC. In the present study, six lncRNAs were chosen as candidate genes on the basis of previous literature to evaluate their diagnostic value on HCC by qRT-PCR. Experiment was first carried out in 22 pairs of tissues from HCC and then those were differently expressed in tissues were further tested in plasma from 20 HCC patients and 20 control cases. At last, ZFAS1 was chosen to be further analyzed in another 214 plasma samples including 79 control cases, 75 hepatitis B and cirrhosis patients, and 60 HCC patients. The levels of plasma ZFAS1 in HCC were significantly higher than those in healthy controls (P<0.001), and in patients with cirrhosis and hepatitis B (P<0.001), and was positively associated with serum α-fetoprotein (AFP). Meanwhile, the area under the receiver operating characteristic curve (AUC) of ZFAS1 was 0.801 to diagnose HCC from healthy controls, while AFP was 0.798 and the combined AUC of ZFAS1 and AFP was 0.891 (95% CI: 0.829–0.953), slightly higher than ZFAS1 alone. In conclusion, our results indicated that ZFAS1 could serve as a biomarker for diagnosing HCC.
Overexpression of miR-202 resensitizes imatinib resistant chronic myeloid leukemia cells through targetting Hexokinase 2
Authors: Deng Yingjun , Li Xin , Feng Jinxin , Zhang Xiangliang
Published: March 2018

Chronic myeloid leukemia (CML) is a myeloproliferative disease which uniquely expresses a constitutively active tyrosine kinase, BCR/ABL. As a specific inhibitor of the BCR-ABL tyrosine kinase, imatinib becomes the first choice for the treatment of CML due to its high efficacy and low toxicity. However, the development of imatinib resistance limits the long-term treatment benefits of it in CML patients. In the present study, we aimed to investigate the roles of miR-202 in the regulation of imatinib sensitivity in CML cell lines and the possible mechanisms involved in this process. We found miR-202 was down-regulated in seven CML cell lines by quantitative reverse-transcription PCR (qRT-PCR) analysis. Overexpression of miR-202 significantly suppressed proliferation rates of CML cells. By establishing imatinib resistant cell lines originating from K562 and KU812 cells, we observed expressions of miR-202 were down-regulated by imatinib treatments and imatinib resistant CML cell lines exhibited lower level of miR-202. On the contrary, imatinib resistant CML cell lines displayed up-regulated glycolysis rate than sensitive cells with the evidence that glucose uptake, lactate production, and key glycolysis enzymes were elevated in imatinib resistant cells. Importantly, the imatinib resistant CML cell lines were more sensitive to glucose starvation and glycolysis inhibitors. In addition, we identified Hexokinase 2 (HK2) as a direct target of miR-202 in CML cell lines. Overexpression of miR-202 sensitized imatinib resistant CML through the miR-202-mediated glycolysis inhibition by targetting HK2. Finally, we provided the clinical relevance that miR-202 was down-regulated in CML patients and patients with lower miR-202 expression displayed higher HK2 expression. The present study will provide new aspects on the miRNA-modulated tyrosine kinase inhibitor (TKI) sensitivity in CML, contributing to the development of new therapeutic anticancer drugs.
Copper-Catalyzed Tandem Multi-Component Approach to 1,3-Oxazines at Room Temperature by Cross-Dehydrogenative Coupling Using Methanol as C1 Feedstock
Authors: Borpatra Paran , Deb Mohit , Baruah Pranjal
Published: March 2018

A copper(II)-catalyzed multi-component one-pot approach for the synthesis of 1,3-oxazines at room temperature is reported here. Methanol is used as the solvent as well as the carbon source. The methylene carbon of the oxazine product comes from methanol via formaldehyde. tert-Butyl hydroperoxide is used as the oxidant. The reaction uses an environmentally benign metal catalyst and oxidant. No inert atmosphere or precaution is required for the reaction. Most importantly, the reaction avoids the use of carcinogenic formaldehyde.
Some Patients with Antiphospholipid Syndrome Express hitherto Undescribed Antibodies to Cardiolipin-binding Proteins
Authors: Rampazzo P. , Biasiolo A. , Garin J. , Rosato A. , Betterle C. , Ruffatti A. , Pengo V.
Published: March 2018

Contrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor β2-Glycoprotein I (β2GPI). While there is a well-documented link between the risk of thrombosis and the presence of β2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-β2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-β2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients.
High Levels of Adhesion Molecules Are Associated with Impaired Endothelium-dependent Vasodilation in Patients with Peripheral Arterial Disease
Authors: Martone Vincenzo , de Cristofaro Tiziana , Corrado Salvatore , Silvestro Antonio , Di Donato Anna Maria , Bucur Roxana , Scopacasa Francesco , Brevetti Gregorio
Published: March 2018

Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 <253 ng/mL (5.6 ± 1.8% vs 9.6 ± 4.2%, p <0.01). Similarly, in the 17 patients with plasma sVCAM-1 >414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 ± 1.9% vs 9.2 ± 4.5%, p <0.05). Additionally, when endothelial dysfunction was defined as FMD ≤5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD >5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.
Functional Properties of Factor V and Factor Va Encoded by the R2-gene
Authors: Hoekema Lico , Castoldi Elisabetta , Tans Guido , Girelli Domenico , Gemmati Donato , Bernardi Francesco , Rosing Jan
Published: March 2018

Carriership of the factor V (FV) gene marked by the R2-haplotype, a series of linked polymorphisms encoding several amino acid changes in FV, is associated with mild resistance to activated protein C (APC) and with an increased risk of thrombosis. We compared the functional properties of normal FV(a) and R2-FV(a) in model systems and in plasma. FV and R2-FV were equally well activated by thrombin and expressed identical cofactor activities in prothrombin activation. Rate constants of APC-catalyzed inactivation of FVa and R2-FVa were similar both with and without protein S. However, significant differences were observed between haemostatic parameters determined in plasma from homozygous carriers of the R2-gene (n = 5) and age-matched non-carriers (n = 19). Plasma from R2-carriers contained significantly lower FV levels and the ratio of the two FV isoforms (FV1 and FV2) was shifted in favor of FV1. The FV2/FV1 ratio was 1.4 (95% CI = 1.3-1.5) in homozygous carriers of R2 and 2.8 (95% CI = 2.5-3.1) in controls (p <0.00001). In an APC resistance test which quantifies the cofactor activity of FV in APC-catalyzed FVIII(a) inactivation, homozygous R2-carriers had significantly lower (p <0.00001) APC sensitivity ratios (APCsr = 1.54, 95% CI = 1.48-1.60) than controls (APCsr = 2.17, 95% CI = 2.05-2.28). This indicates that R2-FV has reduced cofactor activity in APC-catalyzed FVIII(a) inactivation. The changes of the relative amounts of FV1 and FV2 in carriers of the R2-gene will result in increased thrombin formation in the presence of APC and may provide a mechanistic explanation for the increased thrombotic risk associated with the R2-haplotype.
Relationship of Coagulation Test Abnormalities to Tumour Burden and Postoperative DVT in Resected Colorectal Cancer
Authors: Thorlacius-Ussing O. , Iversen L. H.
Published: March 2018

In a prospective study, coagulation test results were compared in 137 patients with colorectal cancer (CRC) and 39 subjects with benign colorectal diseases. Prothrombin fragment 1+2 (F1+2), thrombinantithrombin complex (TAT), and soluble fibrin (SF) were measured in plasma before and after surgery. CRC patients presented with significantly higher values of F1+2 and TAT than controls. Patients with localised CRC had elevated values of F1+2 and TAT, whereas patients with advanced CRC also had elevated SF values. TAT and SF levels correlated with tumour spread, and normal values virtually excluded advanced cancer. Postoperative deep venous thrombosis (DVT) was diagnosed by phlebography in 20% of the CRC patients. Preoperative values of the markers did not predict postoperative DVT, but postoperative values did.
Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery
Authors: Larson G. , Lindahl T. L. , Andersson C. , Frison L. , Gustafsson D. , Bylock A. , Eriksson B. I. , Wåhlander K.
Published: March 2018

Patients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.
Aberrant Splicing and Premature Termination of Transcription of the FVIII Gene as a Cause of Severe Canine Hemophilia A: Similarities with the Intron 22 Inversion Mutation in Human Hemophilia
Authors: Hough Christine , Kamisue Seiki , Cameron Cherie , Notley Colleen , Tinlin Shawn , Giles Alan , Lillicrap David
Published: March 2018

We have identified the causative mutation in the hemophilia A dog colony at Queen’s University, Canada and have observed a striking similarity with the intron 22 inversion found in ∼45% of severely affected hemophilia A patients. The canine hemophilia A phenotype arises from aberrant splicing and premature termination of transcription of the FVIII gene, resulting in a polyadenylated transcript lacking exons distal to 22 and terminating with a novel sequence element (NSE). In dogs and other species including humans, this NSE is present in low copy number. One copy of these sequences in the canine genome is within intron 22 and reveals differences in the hybridization banding patterns between normal and hemophilic DNA, suggestive of a large genomic rearrangement. The mutation mechanism may not be uncommon, as identical mutant transcripts were isolated from two hemophilia A littermates that are unrelated to the Queen’s colony and from hemophiliac dogs in the colony at Chapel Hill.
Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of Fluvastatin
Authors: Camera Marina , Toschi Vincenzo , Comparato Carmen , Baetta Roberta , Rossi Francesca , Fuortes Michele , Ezekowitz Michael , Paoletti Rodolfo , Tremoli Elena
Published: March 2018

High cholesterol levels are a known risk factor for coronary events. The molecular links between high serum cholesterol and the increased thrombogenicity of the arterial wall are still matter of investigation. In the present study we investigate the relationship between plasma cholesterol, thrombus formation and TF expression in a atherosclerotic rabbit model.

Hypercholesterolemic rabbits showed a pronounced TF staining as well as NF-κB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-κB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IκBa in unstimulated as well as in TNFa-stimulated cells and also impaired the TNF-α-induced Cdc42 prenylation, indicating that fluvastatin interferes with the transcriptional activation of TF gene.

These results indicate that the prothrombotic phenotype of arterial wall, associated with elevated serum cholesterol levels, is mediated by TF overexpression. Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF synthesis.
Laboratory Diagnosis of Lupus Anticoagulants
Authors: Chantarangkul Veena , Clerici Marigrazia , Bressi Caterina , Mannucci Pier , Tripodi Armando
Published: March 2018

Residual platelets in plasma are considered detrimental after freezing-thawing, as phospholipids released from ruptured platelets may quench lupus anticoagulants (LA). We aimed at assessing the effect of residual platelets after freezing-thawing plasmas tested with two procedures for LA. Blood from 52 patients suspected of having LA were centrifuged at 2,500 g. Plasmas were subdivided into 2 aliquots. One was filtered to remove residual platelets and both were frozen and stored at –70° C. Silica clotting time (SCT) at low and high phospholipid concentrations and Staclot® LA with and without Hexagonal phospholipids were performed on thawed plasmas. Plasmas were considered LA-positive when both SCT and Staclot® LA performed on filtered plasmas were diagnostic for LA. Forty-two of 52 plasmas fulfilled the diagnostic criteria and were retained for subsequent analysis. SCT on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) percentage correction recorded after phospholipids addition for filtered plasmas, i. e., 67% (36%-83%) was reduced to 54% (25%-81%) for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 20.9%). Staclot® LA on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) clotting time difference recorded after phospholipid addition for filtered plasmas, i. e., 40.8 (10-103.5) s was reduced to 31.7 (2.8-88.8) s for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 1.7 s). In conclusion, residual platelets do not affect the diagnostic efficacy of SCT and Staclot® LA. However, the fact that the percentage correction for SCT and the clotting time difference for Staclot® LA are reduced by residual platelets, suggests that weak LA may be lost upon freezing-thawing non-filtered plasmas.
Platelet Activation by the apoB/E Receptor-binding Domain of LDL
Authors: Gorter G. , van Rijn J. M. H. , Akkerman N. J.-W. , Relou I. A. M.
Published: March 2018

Low density lipoprotein (LDL) increases the sensitivity of human platelets for agonists by activating p38MAPK. Antibody 4G3 disturbs apoB100 binding to the classical apoB/E receptor and inhibits LDLinduced p38MAPK activation, whereas an antibody against a distal domain on apoB100 has no effect. Peptide RLTRKRGLKLA mimics the binding domain of apoB100 called the B-site and activates platelet p38MAPK. Activation by B-site peptide is dose-dependent, transient and followed by desensitization, in accordance with receptor-mediated signalling. A scrambled peptide and a partially homologous peptide RKLRKRLLRDA mimicking the apoB/E receptor binding site of apoE in high density lipoprotein (HDL) also activate p38MAPK albeit 40% weaker, but an uncharged peptide lacks p38MAPK activating capacity. LDL and B-site peptide bind to the same binding sites and initiate similar signalling to p38MAPK and cytosolic phospholipase A2. Thus, LDL and to a lesser extent HDL activate platelets via specific domains in the protein moiety that recognize receptors of the LDL receptor family.
Pharmacokinetics of New Synthetic Heparin Mimetics
Authors: Hérault J. P. , Bernat A. , Roye F. , Michaux C. , Schaeffer P. , Bono F. , Petitou M. , Herbert J. M.
Published: March 2018

Pharmacokinetics of oligosaccharides displaying various affinities for antithrombin (AT) allowed us to show that there was a close relationship between the plasma half-life of these antithrombotic oligosaccharides and their affinity for AT. Recently, we have described new heparin mimetics comprising an AT binding domain and a thrombin binding domain separated by a neutral methylated saccharide sequence. These compounds displayed strong anti-Xa and anti-IIA activities and, in contrast to heparin, escaped neutralisation by platelet factor 4. The aim of this work was to compare the pharmacokinetics of several of these heparin mimetics in rats. These compounds differed by their length, charge and affinity for AT (AT-binding domain). The results obtained indicate that the prolongation of the AT binding domain did not modify significantly their affinities for AT. However, an increase in the number of charges leads to a decrease in the half-life. When a methylated spacer was added in order to minimise the non-specific interactions to other proteins, half-lives of the heparin mimetic were in the same range than that of the pentasaccharide used as an AT binding domain.

In conclusion, this study shows the influence of the charge of the oligosaccharides on their pharmacokinetics and underlines the importance of minimising their non-specific binding to plasma proteins in order to obtain compounds with predictive pharmacokinetics.
Local tissue factor pathway inhibitor release in the human forearm
Authors: Burggraaf Jacobus , Schoemaker Rik , Cohen Adam , Kluft Cornelis , Chia Stanley , Webb David , Newby David , Kemme Michiel
Published: March 2018

Nineteen healthy men received unilateral brachial artery infusions of either unfractioned heparin (0.3-100 IU/min), saline or the endothelium-dependent vasodilators substance P (2-8 pmol/min) and bradykinin (100-1000 pmol/min), and the endothelium-independent vasodilator sodium nitroprusside (2-8 µg/min). Heparin caused a dose-dependent increase in plasma TFPI concentrations in both arms (ANOVA, p <0.0001). Estimated net forearm TFPI release was 7 ± 16, 29 ± 20 and 138 ± 72 ng/100 mL tissue/min during 10, 30 and 100 IU/min of heparin respectively (ANOVA, p <0.0001). Compared to the systemic circulation, the forearm sensitivity to heparin induced TFPI release was 3.6-fold lower (166 ± 67 ng/IU vs. 596 ± 252 ng/IU: t-test, p = 0.004). Substance P, bradykinin and sodium nitroprusside all caused substantial dose-dependent increases in blood flow (ANOVA, p <0.001 for all) without affecting plasma TFPI concentrations. There are important regional differences in endothelial TFPI release, with the forearm circulation being relatively insensitive to heparin.
Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk
Authors: Mira Yolanda , Mateo Jose , Falco Cristina , Villa Piedad , Estelles Amparo , Corella Dolores , Fontcuberta Jordi , Aznar Justo , Vayá Amparo
Published: March 2018

The role played by a hypercoagulable state, either inherited or acquired, in the pathogenesis of upper-extremity deep vein thrombosis (UEDVT) remains a question of debate. We performed a case-control study including 79 patients with a first objectively confirmed episode of UEDVT, 31 secondary and 48 primary, and 165 healthy controls. Nine patients (11.4%) with UEDVT were carriers of the prothrombin G20210A mutation vs. six (3.7%) in controls; P = 0.025, OR: 3.39 (95% CI 1.16 to 9.88). No statistical difference was observed between cases and controls for the factor V Leiden mutation, AT, protein C or protein S deficiency and anticardiolipin antibodies (ACAs). Thirteen (35.1%) UEDVT patients were oral contraceptive (OC) users vs. 12 (16%) controls; P = 0.020, OR: 2.89 (95% CI 1.16-7.21). When secondary UEDVT patients were compared with controls, no differences were observed in any of the risk factors analysed. On the other hand, when primary UEDVT was considered, six (12.5%) patients were carriers of the prothrombin G20210A mutation vs. six (3.7%) controls; P = 0.031, OR: 3.76 (95% CI 1.15-12.26). Regarding ACAs, a borderline statistical significance was observed when primary UEDVT was compared with controls, P = 0.048; OR: 4.88 (95% CI 1.05-22.61). In primary UEDVT, 52% of the fertile women were OC users vs. 16% of controls; P = 0.001, OR:5.78 (95% CI 2.13-15.67). When the interaction of both factors, i.e. prothrombin G20210A mutation and OC intake, were considered, the risk increased markedly, indicating a synergistic effect as observed with other thrombotic locations. In patients with primary UEDVT screening for antithrombin, protein C and protein S deficiency and APC resistance would not be justified, although it might be reasonable to determine the carrier status of the prothrombin G20210A mutation only in OC users.
A quantitative measure of the efficacy of factor VIII in hemophilia A mice
Authors: Parker Ernest , Lollar Pete
Published: March 2018

We developed a quantitative method to study the efficacy of intravenously delivered human factor VIII in hemophilia A mice. Mortality was assessed after tail transection under conditions in which there were no survivors in untreated hemophilia A mice. Blood loss was significantly greater in untreated hemophilia A mice compared to normal C57BL/6 mice, and in hemophilia A non-survivors that were treated with subtherapeutic doses of factor VIII. The up-and-down method for small samples yielded an estimated dose of factor VIII producing survival in 50% of the mice (ED50) of 58 units/kg (95% confidence interval: 42.4 - 78.5 units/kg). This method should be useful in the evaluation and comparison of novel factor VIII products delivered either parenterally or in a gene therapy setting.
Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers
Authors: Antoniades Charalambos , Tentolouris Costas , Toutouza Marina , Marinou Kyriakoula , Goumas George , Tsioufis Costas , Toutouzas Pavlos , Stefanadis Christodoulos , Tousoulis Dimitris
Published: March 2018

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400IU/day (group B), vitamin C 2g/day plus vitamin E 800IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.
A rapid, automated flow cytometric method to measure activated degranulated platelets by density determination
Authors: Sorette Martin , Hetherington Edward , Zelmanovic David , Kling Gail , Dugailliez Jacques , Pujol-Moix Nuria , Okrongly David , Chapman Sabrinah
Published: March 2018

Platelet activation is reported to correlate with acute coronary syndromes. A platelet analysis method on the ADVIA®120 Hematology System provides rapid analysis of platelet density, reported as mean platelet component (MPC) concentration, utilizes routine hematology specimens, requires no pre-treatment, and thirty seconds to generate results. Sub-populations of platelets separated by density gradients showed excellent correlation with the ADVIA 120 MPC parameter (r = 0.997). Platelet activation induced by thrombin treatment resulted in a shift of platelets into the lowest density fraction (d ≤ 1.068 g/mL) with a corresponding reduction in MPC from 24.7 to 20.6 g/dL, N = 4 subjects (p < 0.004). There was also excellent correlation between expression of CD62P measured by fluorescence flow cytometry and the ADVIA 120 Hematology System MPC values (r = 0.85). These results indicate that the ADVIA 120 MPC parameter may be a useful new test for assessing activated platelets and platelet density.
PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of non-fatal myocardial infarction
Authors: Wiman Björn , Hallqvist Johan , Sten-Linder Margareta , de Faire Ulf , Leander Karin
Published: March 2018

This study examines the relationship between plasma Plasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-1 4G/5G polymorphism, and their association with the risk of myocardial infarction (MI). Furthermore, this study explores whether a high level of PAI-1 or whether the PAI-1 4G/5G polymorphism synergistically interacts with any established environmental risk factor for MI. This case-referent study of subjects aged 45-70 and living in Stockholm includes 851 men and 361 women with first-time MI and 1051 men and 505 women who were randomly chosen as referents from a population register. The adjusted odds ratio (OR) of MI was 1.9 (95% confidence interval [CI] 1.4-2.8) for men with a plasma PAI-1 activity level greater than the 90th percentile value of referents. The corresponding OR for women was 1.5 (95% CI 0.9-2.5). A strong indication of synergistic interaction was found in men for the co-exposure to high plasma PAI-1 activity and current smoking, an adjusted synergy index score of 3.9 (95% CI 1.2-13.2). In women, the 4G allele was associated slightly with an increased risk of MI, OR 1.4 (95% CI 1.0-1.9). This association was not found in men. There were no clear indications of synergistic interaction effects involving the PAI-1 4G/5G polymorphism and the environmental exposures considered (cigarette smoking, physical inactivity, overweight, diabetes mellitus, hypercholesterolaemia, hypertension, high C-reactive protein and hypertriglyceridaemia).