bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of the additional benefit of population screening for dementia beyond a passive case‐finding approach
Authors: Mate Karen E. , Magin Parker J. , Brodaty Henry , Stocks Nigel P. , Gunn Jane , Disler Peter B. , Marley John E. , Pond C. Dimity 
Published: March 2016

AbstractObjectiveGeneral practitioners (GPs) fail to identify more than 50% of dementia cases using the existing passive case‐finding approach. Using data from the “Ageing in General Practice” study, we sought to establish the additional benefit of screening all patients over the age of 75 for dementia beyond those patients already identified by passive case‐finding.MethodPatients were classified as “case‐finding” (n = 425) or “screening” (n = 1006) based on their answers to four subjective memory related questions or their GP's clinical judgement of their dementia status. Cognitive status of each patient was formally assessed by a research nurse using the Cambridge Cognition Examination (CAMCOG‐R). Patients then attended their usual GP for administration of the GP assessment of Cognition (GPCOG) dementia screening instrument, and follow‐up care and/or referral as necessary in light of the outcome.ResultsThe prevalence of dementia was significantly higher in the case‐finding group (13.6%) compared to the screening group (4.6%; p < 0.01). The GPCOG had a positive predictive value (PPV) of 61% in the case‐finding group and 39% in the screening group; negative predictive value was >95% in both groups. GPs and their patients both found the GPCOG to be an acceptable cognitive assessment tool. The dementia cases missed via case‐finding were younger (p = 0.024) and less cognitively impaired (p = 0.020) than those detected.ConclusionThere is a very limited benefit of screening for dementia, as most people with dementia could be detected using a case‐finding approach, and considerable potential for social and economic harm because of the low PPV associated with screening.
Effects of healthcare reform on health resource allocation and service utilization in 1110 Chinese county hospitals: data from 2006 to 2012
Authors: Fang Pengqian , Hu Ruirong , Han Qiuxia 
Published: March 2016

SummaryThe central government of China launched a large‐scale, expensive health reform in April 2009 because of the serious health‐related problems in the country. This reform aims to re‐establish a universal healthcare system, which is expected to provide affordable basic healthcare. Independent two‐sample t‐test, one‐way ANOVA and chi‐squared test were conducted to analyze the effect of the health reform on health resource allocation and service utilization in Chinese county hospitals. First, we described the hospitals' financial performance in terms of funding sources, balances and fiscal compensations (for personnel expenditure). Second, we discussed the total number of health personnel as well as the structure (number of medical personnel per thousand population and ratio of doctors and nurses) and quality of the health personnel. Lastly, we investigated the county hospitals' health resource utilization, bed occupancy and average medical expense per visit. Then, we probed different reasons and provided multiple approaches to existing problems. Copyright © 2016 John Wiley & Sons, Ltd.
Different mechanisms of action of 2, 2’, 4, 4’‐tetrabromodiphenyl ether (BDE‐47) and its metabolites (5‐OH‐BDE‐47 and 6‐OH‐BDE‐47) on cell proliferation in OVCAR‐3 ovarian cancer cells and MCF‐7 breast cancer cells
Authors: Karpeta Anna , Maniecka Anna , Gregoraszczuk Ewa Łucja 
Published: March 2016

AbstractData concerning the possible action of polybrominated diphenyl ethers (PBDEs) in hormone‐dependent cancer are scarce. Some data showed that PBDEs may directly affect breast cancer cells formation and only one research showed increased proliferation of the OVCAR‐3 cells, but the results are ambiguous and the mechanisms are not clear. There is growing evidence that not only parent compounds but also its metabolites may be involved in cancer development. The present study was, therefore, designed to determine the effect of BDE‐47 and its metabolites (2.5 to 50 ng ml–1) on proliferation (BrdU), cell‐cycle genes (real‐time PCR) and protein expression (Western blot), protein expression of oestrogen receptors (α β), extracellular signal‐regulated kinases 1 and 2 (ERK1/2) and protein kinase Cα (PKCα) in OVCAR‐3 ovarian and MCF‐7 breast cancer cells. In OVCAR‐3 cells, the parent compound stimulated cell proliferation by activating CDK1, CDK7, E2F1 and E2F2. Independent of time of exposure, BDE‐47 had no effect on ERα and ERβ protein expression and ERK1/2 and PKCα phosphorylation. Metabolites had no effect on cell proliferation but increased both ERs protein expression and ERK1/2 and PKCα phosphorylation. In MCF‐7 cells, the parent compound displayed no effect on cell proliferation but decreased ERα and increased ERβ protein expression with concomitant induction of PKCα phosphorylation. Both metabolites increased MCF‐7 cell proliferation, ERK1/2 and PKCα phosphorylation and decreased ERα and ERβ protein expression.We suggest that studies concerning PBDEs with fewer bromine atoms should be continued to understand environmental links to different hormone‐dependent cancers. Copyright © 2016 John Wiley & Sons, Ltd.
Detection of Circulating Tumor Cells Using a Novel Immunomagnetic Bead Method in Lung Cancer Patients
Authors: Ji Jin‐Ling , Jiang Yu‐Zhang , Tang Qian‐Qiu , He Xiao‐Dong , Shen Zuo‐Jun , Zhang Bai‐Yin 
Published: March 2016

BackgroundCirculating tumor cells (CTCs) are detectable in peripheral blood of metastatic lung cancer patients. In this article, we evaluate a new CTC separation method based on a combination of anti‐EpCAM and immunomagnetic beads with the aim to detect CTCs more conveniently and specifically.MethodsLung cancer cells were magnetically labeled by anti‐EpCAM magnetic beads, and subsequently captured by magnetic separation using our novel device. Isolated lung cancer cells were identified by pathomorphological by hematoxylin–eosin staining protocol. The system was used to detect CTCs in 2 ml blood. Blood samples of healthy donors spiked with lung cancer cell line A549 cells were used to determine the sensitivity and specificity of the method. Prevalence of CTCs was examined in samples from 56 patients with lung cancer.ResultsRegression analysis of number of recovered versus spiked A549 cells yielded a coefficient of determination of R2 = 0.996 (P < 0.001). The average recovery was 68% or more at each spiking level. The coefficient of variation increased as the number of spiked cells decreased, ranging from 6.4% (1,000‐cell spike) to 18.4% (50‐cell spike). Forty‐nine of the fifty‐six patients (87.5%) were found to have CTCs in peripheral blood. None of the 2 ml peripheral blood samples of the 20 healthy subjects analyzed were found to have CTCs.ConclusionsThis novel turbulence device provides a new tool allowing for feasible and specific detection of CTCs in lung cancer patients. It is likely clinically useful in diagnosis and monitoring of lung cancer and may have a role in clinical decision making.
Proteomic analysis of Rhodotorula mucilaginosa: dealing with the issues of a non‐conventional yeast
Authors: Addis Maria Filippa , Tanca Alessandro , Landolfo Sara , Abbondio Marcello , Cutzu Raffaela , Biosa Grazia , Pagnozzi Daniela , Uzzau Sergio , Mannazzu Ilaria 
Published: March 2016

AbstractRed yeasts ascribed to the species Rhodotorula mucilaginosa are gaining increasing attention, due to their numerous biotechnological applications, spanning carotenoid production, liquid bioremediation, heavy metal biotransformation and antifungal and plant growth‐promoting actions, but also for their role as opportunistic pathogens. Nevertheless, their characterization at the 'omic' level is still scarce. Here, we applied different proteomic workflows to R. mucilaginosa with the aim of assessing their potential in generating information on proteins and functions of biotechnological interest, with a particular focus on the carotenogenic pathway. After optimization of protein extraction, we tested several gel‐based (including 2D‐DIGE) and gel‐free sample preparation techniques, followed by tandem mass spectrometry analysis. Contextually, we evaluated different bioinformatic strategies for protein identification and interpretation of the biological significance of the dataset. When 2D‐DIGE analysis was applied, not all spots returned a unambiguous identification and no carotenogenic enzymes were identified, even upon the application of different database search strategies. Then, the application of shotgun proteomic workflows with varying levels of sensitivity provided a picture of the information depth that can be reached with different analytical resources, and resulted in a plethora of information on R. mucilaginosa metabolism. However, also in these cases no proteins related to the carotenogenic pathway were identified, thus indicating that further improvements in sequence databases and functional annotations are strictly needed for increasing the outcome of proteomic analysis of this and other non‐conventional yeasts. Copyright © 2016 John Wiley & Sons, Ltd.
Net Fluorescein Flux Across Corneal Endothelium Strongly Suggests Fluid Transport is due to Electro-osmosis
Authors: Sanchez J. M. , Cacace V. , Kusnier C. F. , Nelson R. , Rubashkin A. A. , Iserovich P. , Fischbarg J. 
Published: March 2016

Abstract
We have presented prior evidence suggesting that fluid transport results from electro-osmosis at the intercellular junctions of the corneal endothelium. Such phenomenon ought to drag other extracellular solutes. We have investigated this using fluorescein-Na2 as an extracellular marker. We measured unidirectional fluxes across layers of cultured human corneal endothelial (HCE) cells. SV-40-transformed HCE layers were grown to confluence on permeable membrane inserts. The medium was DMEM with high glucose and no phenol red. Fluorescein-labeled medium was placed either on the basolateral or the apical side of the inserts; the other side carried unlabeled medium. The inserts were held in a CO2 incubator for 1 h (at 37 °C), after which the entire volume of the unlabeled side was collected. After that, label was placed on the opposite side, and the corresponding paired sample was collected after another hour. Fluorescein counts were determined with a (Photon Technology) DeltaScan fluorometer (excitation 380 nm; emission 550 nm; 2 nm bwth). Samples were read for 60 s. The cells utilized are known to transport fluid from the basolateral to the apical side, just as they do in vivo in several species. We used 4 inserts for influx and efflux (total: 20 1-h periods). We found a net flux of fluorescein from the basolateral to the apical side. The flux ratio was 1.104 ± 0.056. That difference was statistically significant (p = 0.00006, t test, paired samples). The endothelium has a definite restriction at the junctions. Hence, an asymmetry in unidirectional fluxes cannot arise from osmosis, and can only point instead to paracellular solvent drag. We suggest, once more, that such drag is due to electro-osmotic coupling at the paracellular junctions.
Disease-specific clinical trials networks: the example of cystic fibrosis
Authors: De Boeck Kris , Bulteel Veerle , Fajac Isabelle 
Published: March 2016

Abstract
This article describes the steps of the development and the structure of a disease-specific clinical trials network for cystic fibrosis in Europe. Activities such as reviewing study protocols, feasibility assessments, training and standardizing of procedures, and outcome measurements help to bring high-quality clinical trials to the patients. Cooperation with the pharmaceutical industry, other research networks, patient organizations, and regulatory agencies is very important throughout all activities.

Conclusion: The European Cystic Fibrosis Society—Clinical Trials Network facilitates the development of new treatments for a rare disease and could be a prototype for other diseases.

What is Known:• Clinical research has led to the first approved treatments targeting the basic Cystic Fibrosis defect.• For a rare disease like Cystic Fibrosis, multicenter international collaboration is needed to obtain solid evidence when testing possible new treatments.

What is New:• The Clinical Trials Network established by the European Cystic Fibrosis Society has grown to a fully operational network with well-defined structures, procedures and partnerships.• Standardization of outcome parameters, protocol review, feasibility assessment and other activities help to develop high quality, efficient, relevant and feasible clinical trials, with the aim to bring new treatments to the patients.
Association of cytomegalovirus infection with hypertension risk: a meta-analysis
Authors: Hui Jing , Qu Yuan-yuan , Tang Na , Liu Yong-min , Zhong Hua , Wang La-mei , Feng Qian , Li Zhen , He Fang 
Published: March 2016

Summary

Background
Information regarding association between cytomegalovirus (CMV) infection and essential hypertension (EH) risk is not consistent across studies. Therefore, we conducted a meta-analysis to investigate the association in detail.

Methods
We comprehensively searched the published literature from the PubMed and Embase databases for any study analyzing the association between CMV and EH risk. A random-effects model was used to calculate the pooled odds ratio (OR) with 95 % confidence interval (CI).

Results
Three studies involving 9657 patients were included in the meta-analysis, and the results showed a significantly increased risk of EH in patients with CMV infection. Overall, 79.3 % of the hypertension patients were CMV-positive, which was significantly higher than the percentage for controls (OR = 1.39, 95 % CI = 0.95–2.05, P = 0.017). There was significant heterogeneity among the studies included (I2 = 70.5 %). The funnel plot and Egger’s test also indicated no publication bias.

Conclusions
The results showed a significant association between CMV and EH, which indicates that CMV infection is a possible cause of EH.
Phase diagram of a multiple forces model for animal group formation: marches versus circles determined by the relative strength of alignment and cohesion
Authors: Kubo Yuki , Iwasa Yoh 
Published: March 2016

AbstractMany species of fish, bird, and insect form groups of individuals that move together, called schools, flocks, or swarms, of characteristic shape and speed. Here we study a model that traces movements of many individuals, in which each individual moves at a constant speed, and changes its movement angle in response to its neighbors within a radius of interaction. Outside of a short range of separation (or repulsion), each individual changes moving direction to achieve a similar moving direction as its neighbors (alignment) and to move toward them (cohesion). Between each pair of individuals within an interaction range, both alignment and cohesion are at work simultaneously (multiple forces model). This is different from many other models for animal group formation in which only one of the two forces is at work (single force model), different forces operating in different zones of between‐individual distance. Depending on the relative strength of alignment and cohesion, our model produces groups of two distinct patterns: marches and circles. We showed the phase diagram of group patterns depending on the relative strength of alignment and cohesion. As the strength of alignment relative to cohesion increases, the shapes of groups change gradually in the following order: (1) circles, (2) mixture of circles and marches, (3) short marches, (4) long marches, (5) wide marches. We derived a formula for the spatial size of circles, which explains that the radius of circles does not change with the number of individuals, but it increases with moving speed and decreases with the sensitivity of moving direction to neighbors.
Molecular mode of action of NKP-1339 – a clinically investigated ruthenium-based drug – involves ER- and ROS-related effects in colon carcinoma cell lines
Authors: Flocke Lea S. , Trondl Robert , Jakupec Michael A. , Keppler Bernhard K. 
Published: March 2016

AbstractSodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action.
Biochemical Characterization of Arbequina Extra Virgin Olive Oil Produced in Turkey
Authors: Uluata Sibel , Altuntaş Ümit , Özçelik Beraat 
Published: March 2016

AbstractVarieties of the olive cultivar Arbequina have recently been cultivated in Turkey. The objective of the study is to characterize and evaluate extra‐virgin olive oils (EVOO) produced from Arbequina grown in the Aegean and Mediterranean regions of Turkey. Major and minor components such as carotenoids, squalene, phenolics and tocopherols were studied to assess their effects on product quality and health benefits. The samples, identified as ArbqI and ArbqA, were from the Izmir and Adana provinces, respectively. Samples were analyzed by GC‐FID to determine fatty acid composition, sterol composition, TAG profile and squalene content. Individual phenolic fractions were analyzed by LC–MS/MS and tocopherol isomers were determined by HPLC. According to the results obtained from this study; Total phenolic content (TPC) of the samples were 454.68 and 50.86 mg Gallic acid/kg oil for ArbqI and ArbqA, respectively. Hydroxytyrosol and tyrosol were determined to be the main phenols. The major tocopherol isomer found in ArbqI and ArbqA was α‐tocopherol with levels of 179.55 and 202.5 mg/kg oil, respectively. β‐Carotene levels in both samples were similar at 0.2 mg/kg. Findings of this study were compared with the literature on Arbequina olive oil produced in different countries. It was determined that Arbequina olive oil of high quality can be produced in Turkey, especially in the Aegean region.
Big data analytics in E-commerce: a systematic review and agenda for future research
Authors: Akter Shahriar , Wamba Samuel Fosso 
Published: March 2016

Abstract
There has been an increasing emphasis on big data analytics (BDA) in e-commerce in recent years. However, it remains poorly-explored as a concept, which obstructs its theoretical and practical development. This position paper explores BDA in e-commerce by drawing on a systematic review of the literature. The paper presents an interpretive framework that explores the definitional aspects, distinctive characteristics, types, business value and challenges of BDA in the e-commerce landscape. The paper also triggers broader discussions regarding future research challenges and opportunities in theory and practice. Overall, the findings of the study synthesize diverse BDA concepts (e.g., definition of big data, types, nature, business value and relevant theories) that provide deeper insights along the cross-cutting analytics applications in e-commerce.
Organizational governance of inter-firm resource combinations: The impact of structural embeddedness and vertical resource relatedness
Authors: Kim Sungho , Jin Kyuho 
Published: March 2016

AbstractFirms not only combine resources within firm boundaries but tap into, acquire, or consolidate resources outside firm boundaries. Alliances and mergers and acquisitions (M&A) are distinct vehicles for governing inter-firm resource combinations. Prior studies on the governance choice between them have relied on firm- or dyad-level attributes to explicate the choice firms make about the governance. However, any firm or dyad is a micro-structure embedded in networks that shape the flow of information and resources to the focal firm or dyad. In addition, although alliances and mergers and acquisitions involve either horizontal or vertical resource combinations, the vertical dimension of resource relatedness has been largely neglected in prior research. This study examines the impact of structural embeddedness and vertical resource relatedness on governance choice. We find that structural embeddedness is an important driver of governance choice and that a significant portion of resource combinations occurs along the vertical dimension of relatedness.
Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation
Authors: Mackenzie S. G. , Leinonen I. , Ferguson N. , Kyriazakis I. 
Published: March 2016

AbstractThe objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.