bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathways: Dysregulated Glutamatergic Signaling Pathways in Cancer
Authors: Prickett Todd D. , Samuels Yardena 
Published: May 2012

Abstract
The neurotransmitter glutamate interacts with glutamate receptor proteins, leading to the activation of multiple signaling pathways. Dysfunction in the glutamatergic signaling pathway is well established as a frequent player in diseases such as schizophrenia, Alzheimer disease, and brain tumors (gliomas). Recently, aberrant functioning of this pathway has also been shown in melanoma. In both glioma and melanoma, glutamate secretion stimulates tumor growth, proliferation, and survival through activation of the mitogen-activated protein kinase and phosphoinositide 3-kinase/Akt pathways. In the future, extracellular glutamate levels and glutamatergic signaling may serve as biological markers for tumorigenicity and facilitate targeted therapy for melanoma. Clin Cancer Res; 18(16); 4240–6. ©2012 AACR.
Novel Single-Chain Antibody-Targeted Microbubbles for Molecular Ultrasound Imaging of Thrombosis
Authors: Wang Xiaowei , Hagemeyer Christoph E. , Hohmann Jan David , Leitner Ephraem , Armstrong Paul C. , Jia Fu , Olschewski Manfred , Needles Andrew , Peter Karlheinz , Ahrens Ingo 
Published: May 2012

Background—
Molecular imaging is a fast emerging technology allowing noninvasive detection of vascular pathologies. However, imaging modalities offering high resolution currently do not allow real-time imaging. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) selectively targeted to activated platelets would offer high-resolution, real-time molecular imaging of evolving and dissolving arterial thrombi.

Methods and Results—

Lipid-shell based gas-filled MBs were conjugated to either a single-chain antibody specific for activated glycoprotein IIb/IIIa via binding to a Ligand-Induced Binding Site (LIBS-MBs) or a nonspecific single-chain antibody (control MBs). Successful conjugation was assessed in flow cytometry and immunofluorescence double staining. LIBS-MBs but not control MBs strongly adhered to both immobilized activated platelets and microthrombi under flow. Thrombi induced in carotid arteries of C57Bl6 mice in vivo by ferric chloride injury were then assessed with ultrasound before and 20 minutes after MB injection through the use of gray-scale area intensity measurement. Gray-scale units converted to decibels demonstrated a significant increase after LIBS-MB but not after control MB injection (9.55±1.7 versus 1.46±1.3 dB;
P
<0.01). Furthermore, after thrombolysis with urokinase, LIBS-MB ultrasound imaging allows monitoring of the reduction of thrombus size (
P
<0.001).

Conclusion—
We demonstrate that glycoprotein IIb/IIIa–targeted MBs specifically bind to activated platelets in vitro and allow real-time molecular imaging of acute arterial thrombosis and monitoring of the success or failure of pharmacological thrombolysis in vivo.
U.S. Diurnal Temperature Range Variability and Regional Causal Mechanisms, 1901–2002
Authors: Lauritsen Ryan G. , Rogers Jeffrey C. 
Published: May 2012

Abstract
Long-term (1901–2002) diurnal temperature range (DTR) data are evaluated to examine their spatial and temporal variability across the United States; the early century origin of the DTR declines; and the relative regional contributions to DTR variability among cloud cover, precipitation, soil moisture, and atmosphere/ocean teleconnections. Rotated principal component analysis (RPCA) of the Climatic Research Unit (CRU) Time Series (TS) 2.1 dataset identifies five regions of unique spatial U.S. DTR variability. RPCA creates regional orthogonal indices of cloud cover, soil moisture, precipitation, and the teleconnections used subsequently in stepwise multiple linear regression to examine their regional impact on DTR, maximum temperature (Tmax), and minimum temperature (Tmin).
The southwestern United States has the smallest DTR and cloud cover trends as both Tmax and Tmin increase over the century. The Tmin increases are the primary influence on DTR trend in other regions, except in the south-central United States, where downward Tmax trend largely affects its DTR decline. The Tmax and DTR tend to both exhibit simultaneous decadal variations during unusually wet and dry periods in response to cloud cover, soil moisture, and precipitation variability. The widely reported post-1950 DTR decline began regionally at various times ranging from around 1910 to the 1950s. Cloud cover alone accounts for up to 63.2% of regional annual DTR variability, with cloud cover trends driving DTR in northern states. Cloud cover, soil moisture, precipitation, and atmospheric/oceanic teleconnection indices account for up to 80.0% of regional variance over 1901–2002 (75.4% in detrended data), although the latter only account for small portions of this variability.
Polyazomethine with vinylene and phenantridine moieties in the main chain: Synthesis, characterization, opto(electrical) properties and theoretical calculations
Authors: Iwan Agnieszka , Guimarães Jeconias Rocha , Santos Maria Cristina dos , Schab-Balcerzak Ewa , Krompiec Michal , Palewicz Marcin , Sikora Andrzej 
Published: May 2012

The opto(electrical) properties and theoretical calculations of polyazomethine with vinylene and phenantridine moieties in the main chain were investigated in the present study. 2,5-Bis(hexyloxy)-1,4-bis[(2,5-bis(hexyloxy)-4-formyl-phenylenevinylene]benzene was polymerized in solution with 3,8-diamino-6-phenylphenanthridine (PAZ-PV-Ph). The temperatures of 5% weight loss ( T5%) of the polyazomethine was observed at 356 °C in nitrogen. Electrochemical properties of thin film of the polymer were studied by differential pulse voltammetry. The HOMO level of the PAZ-PV-Ph was at −4.97 eV. The energy band gap ( Eg) was detected of approximately ∼1.9 eV. Energy band gap ( Egopt) was additionally calculated from absorption spectrum and absorption coefficient α. The absorption UV-vis spectra of polyazomethine recorded in solution showed a blue shift in comparison with the solid state. HOMO-LUMO levels and Eg were additionally calculated theoretically by density functional theory and molecular simulations of PAZ-PV-Ph are presented. Current density–voltage ( J– U) measurements were performed on ITO/PAZ-PV-Ph/Al, ITO/TiO2/PAZ-PV-Ph/Al and ITO/PEDOT/PAZ-PV-Ph:TiO2/Al devices in the dark and during irradiation with light (under illumination of 1000 W m−2). The polymer was tested using AFM technique and roughness ( Ra, Rms) along with skew and kurtosis are presented.
Almost partial generalized Jordan derivations: a fixed point approach
Authors: Gordji Madjid Eshaghi , Park Choonkil , Lee Jung Rye 
Published: May 2012

Abstract
Using fixed point method, we investigate the Hyers-Ulam stability and the superstability of partial generalized Jordan derivations on Banach modules related to Jensen type functional equations.

Mathematics Subject Classification 2010: Primary, 39B52; 47H10; 47B47; 13N15; 39B72; 17C50; 39B82; 17C65.
Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium
Authors: Hayoz Sébastien , Jia Cuihong , Hegg CC 
Published: May 2012

Abstract

Background
ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s) by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices.

Results
Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP) and a G protein-coupled P2Y receptor agonist (UTP). Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone.

Conclusions
The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP release following injury could lead to progenitor cell proliferation, differentiation and regeneration. Thus, understanding mechanisms of ATP release is of paramount importance to improve our knowledge about tissue homeostasis and post-injury neuroregeneration. It will lead to development of treatments to restore loss of smell and, when transposed to the central nervous system, improve recovery following central nervous system injury.
Association between human cartilage glycoprotein 39 (YKL-40) and arterial stiffness in essential hypertension
Authors: Ma Wei-hong , Wang Xiu-ling , Du Yi-meng , Wang Yi-biao , Zhang Yan , Wei De-e , Guo Lin-lin , Bu Pei-Li 
Published: May 2012

Abstract

Background
YKL-40, a proposed marker of inflammation and endothelial dysfunction, is associated with atherosclerosis and an increased cardiovascular mortality in the general population. However, the relationship between YKL-40 and arterial stiffness in hypertensive patients has not been adequately assessed.

Methods
The relationship between serum levels of YKL-40 and arterial stiffness was evaluated in 93 essential hypertensive subjects and 80 normal subjects. Essential hypertensive subjects were divided into two groups based upon urinary albumin-to-creatinine ratio (ACR): nonmicroalbuminuric group, (ACR <30 mg/g, n = 50) and microalbuminuric group (ACR ≥30 mg/g, n = 43). Large artery wall stiffness was assessed by measuring femoral arterial stiffness and carotid-femoral pulse wave velocity (cf-PWV). Serum levels of YKL-40 were determined by enzyme-linked immunosorbent assay (ELISA).

Results
The study demonstrated that YKL-40,cf-PWV and femoral arterial stiffness were increased significantly (P<0.05) in the hypertensive group compared with normal controls. These measurements were also increased significantly ( P<0.05) in the microalbuminuric group compared with the nonmicroalbuminuric group. YKL-40 was positively correlated with cf-PWV( r = 0.44, P = 0.000) and femoral arterial stiffness ( r = 0.42, P =0.001). Multiple linear stepwise regression analysis showed that YKL-40 was the impact factor of arterial stiffness ( P<0.05).

Conclusion
YKL-40 levels are elevated in essential hypertension subjects with an independent association between increasing YKL-40 levels and increasing arterial stiffness. The study suggests it played a positive role of YKL-40 in the progressing vascular complications in patients with essential hypertension.
Coping with multimorbidity in old age – a qualitative study
Authors: Löffler Christin , Kaduszkiewicz Hanna , Stolzenbach Carl-Otto , Streich Waldemar , Fuchs Angela , van den Bussche Hendrik , Stolper Friederike , Altiner Attila 
Published: May 2012

Abstract

Background
Comparatively few studies address the problems related to multimorbidity. This is surprising, since multimorbidity is a particular challenge for both general practitioners and patients. This study focuses on the latter, analyzing the way patients aged 65–85 cope with multimorbidity.

Methods
19 narrative in-depth interviews with multimorbid patients were conducted. The data was analysed using grounded theory. Of the 19 interviewed patients 13 were female and 6 male. Mean age was 75 years. Participating patients showed a relatively homogeneous socio-economic status. Patients were recruited from the German city of Hamburg and the state of North Rhine-Westphalia.

Results
Despite suffering from multimorbidity, interviewees held positive attitudes towards life: At the social level, patients tried to preserve their autonomy to the most possible extent. At the emotional level, interviewees oscillated between anxiety and strength - having, however, a positive approach to life. At the practical level, patients aimed at keeping their diseases under control. The patients tended to be critical in regards to medication.

Conclusions
These findings might have implications for the treatment of multimorbid patients in primary care and further research: The generally presumed passivity of older individuals towards medical treatment, which can be found in literature, is not evident among our sample of older patients. In future, treatment of these patients might take their potential for pro-active cooperation more strongly into account than it is currently the case.
The effect of taping versus semi-rigid bracing on patient outcome and satisfaction in ankle sprains: a prospective, randomized controlled trial
Authors: Lardenoye Sacha , Theunissen Ed , Cleffken Berry , Brink Peter RG , de Bie Rob A , Poeze Martijn 
Published: May 2012

Abstract
Background
Functional treatment is a widely used and generally accepted treatment for ankle sprain. A meta-analysis comparing the different functional treatment options could not make definitive conclusions regarding the effectiveness, and until now, little was known about patient satisfaction in relation to the outcome.

Methods
Patients with acute ankle sprain received rest, ice, compression and elevation with an compressive bandage at the emergency department. After 5-7 days, 100 patients with grade II and III sprains were randomized into two groups: one group was treated with tape and the other with a semi-rigid ankle brace, both for 4 weeks. Post-injury physical and proprioceptive training was standardized. As primary outcome parameter patient satisfaction and skin complications were evaluated using a predefined questionnaire and numeric rating scale. As secondary outcome parameter the ankle joint function was assessed using the Karlsson scoring scale and range of motion.

Results
Patient-reported comfort and satisfaction during treatment with a semi-rigid brace was significantly increased. The rate of skin complication in this group was significantly lower compared to the tape group (14.6% versus 59.1%, P < 0.0001). Functional outcome of the ankle joint was similar between the two treatment groups, as well as reported pain.

Conclusion
Treatment of acute ankle sprain with semi-rigid brace leads to significantly higher patient comfort and satisfaction, both with similar good outcome.
Therapeutic effects of radix dipsaci, pyrola herb, and cynomorium songaricum on bone metabolism of ovariectomized rats
Authors: Liu Meijie , Xiao Gary Guishan , Rong Peijing , Zhang Zhiguo , Dong Jiazi , Zhao Hongyan , Li Honghong , Li Yan , Pan Jinghua , Liu Hong , Wang Wenlai , Zha Qinglin , Ju Dahong 
Published: May 2012

Abstract

Background
The objective of this study was to evaluate the effects of herbal medicines, such as Radix Dipsaci (RDD), Pyrola Herb (PHD), and Cynomorium songaricum decoction (CSD), on osteoporotic rats induced by ovariectomy (OVX).

Methods
OVX or sham operations were performed on 69 virgin Wistar rats that were divided into six groups: sham (sham, n = 12), OVX control group (OVX, n = 12), and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n = 11, and CSD, n = 11). Non-surgical rats served as normal control (NC, n = 12). The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass and bone turnover were analyzed by histomorphometry. Levels of protein expression and mRNA of OPG and RANKL in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization.

Results
Compared to NC and sham rats, trabecular bone formation was significantly reduced in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD enhanced trabecular bone formation remarkably. No significant change of bone formation was observed in CSD-treated rats. OPG expression of protein and mRNA was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of protein and mRNA was increased significantly in OB and bMSC of OVX control rats. These effects were substantially reversed (increased in OPG and decreased in RANKL) by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No significant changes in either OPG or RANKL expression were observed in OB and bMSC of OVX rats treated with CSD.

Conclusions
Our study showed that RDD and PHD increased bone formation by stimulating overexpression of OPG and downregulation of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as alternative therapeutic agents for postmenopausal osteoporosis.
Impact on learning of an e-learning module on leukaemia: a randomised controlled trial
Authors: Morgulis Yuri , Kumar Rakesh K , Lindeman Robert , Velan Gary M 
Published: May 2012

Abstract

Background
e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources.

Methods
A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period.

Results
Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive.

Conclusions
A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.
Production of 2,3-butanediol in Saccharomyces cerevisiae by in silico aided metabolic engineering
Authors: Ng ChiamYu , Jung Moo-young , Lee Jinwon , Oh Min-Kyu 
Published: May 2012

Abstract

Background
2,3-Butanediol is a chemical compound of increasing interest due to its wide applications. It can be synthesized via mixed acid fermentation of pathogenic bacteria such as Enterobacter aerogenes and Klebsiella oxytoca. The non-pathogenic Saccharomyces cerevisiae possesses three different 2,3-butanediol biosynthetic pathways, but produces minute amount of 2,3-butanediol. Hence, we attempted to engineer S. cerevisiae strain to enhance 2,3-butanediol production.

Results
We first identified gene deletion strategy by performing in silico genome-scale metabolic analysis. Based on the best in silico strategy, in which disruption of alcohol dehydrogenase (ADH) pathway is required, we then constructed gene deletion mutant strains and performed batch cultivation of the strains. Deletion of three ADH genes, ADH1, ADH3 and ADH5, increased 2,3-butanediol production by 55-fold under microaerobic condition. However, overproduction of glycerol was observed in this triple deletion strain. Additional rational design to reduce glycerol production by GPD2 deletion altered the carbon fluxes back to ethanol and significantly reduced 2,3-butanediol production. Deletion of ALD6 reduced acetate production in strains lacking major ADH isozymes, but it did not favor 2,3-butanediol production. Finally, we introduced 2,3-butanediol biosynthetic pathway from Bacillus subtilis and E. aerogenes to the engineered strain and successfully increased titer and yield. Highest 2,3-butanediol titer (2.29 g·l-1) and yield (0.113 g·g-1) were achieved by Δadh1 Δadh3 Δadh5 strain under anaerobic condition.

Conclusions
With the aid of in silico metabolic engineering, we have successfully designed and constructed S. cerevisiae strains with improved 2,3-butanediol production.
Factors explaining the gender disparity in lipid-lowering treatment goal attainment rate in Chinese patients with statin therapy
Authors: Zhang Rui , Zhao Liancheng , Liang Lirong , Xie Gaoqiang , Wu Yangfeng 
Published: May 2012

Abstract

Background
The lipid-lowering treatment goal attainment rate is lower for women than for men among Chinese patients, but the reasons for this disparity have not been fully explored yet.

Objectives
To elucidate the potential factors and the significance of their contributions towards the observed discrepancy in lipid-lowering treatment goal attainment rates between Chinese women and men.

Methods
We used data from 1808 patients from 21 tertiary and 6 secondary hospitals in China who received and maintained statin therapy treatment for at least 2 months. Lipid-lowering treatment goal attainment was defined as low-density lipoprotein cholesterol (LDL- C) reaching the treatment targets recommended by the Chinese Guidelines on Prevention and Control of Dyslipidemia in Adults. Logistic Regression was used to explore possible factors associated with gender disparity in goal attainment rates, and to what extent each factor contributes.

Results
A total of 674 women and 1134 men were enrolled in the study. Women had a significantly lower LDL-C goal attainment rate than that of men (46.0% vs 53.8%, P = 0.002), particularly in high and very high CVD risk groups. Among high and very high risk patients, approximately 35%, 7%, 5%, and 5% of gender disparity in LDL-C goal attainment rate was attributable to the gender difference in baseline LDL-C level, cardiovascular co-morbidities and associated risk factors, socioeconomic status, and the dosage of statin treatment, respectively. Approximately 50% of the gender disparity remained unexplained by these factors.

Conclusions
Although nearly half of the gender disparity in lipid-lowering treatment goal attainment rate can be explained by the gender differences in baseline lipid level, socioeconomic status, cardiovascular co-morbidities and associated risk factors, and the dosage of statin in high and very high CVD risk patients, the other half of the gender disparity remains unexplained and requires further study to fully understand what other factors are at play.