bluuebunny/crossref_metadata_2025_split huggingface dataset:
Budget impact of intravenous iron therapy with ferric carboxymaltose in patients with chronic heart failure and iron deficiency in Germany
Authors: Theidel Ulrike , Väätäinen Saku , Martikainen Janne , Soini Erkki , Hardt Thomas , Doehner Wolfram 
Published: July 2017

AbstractAimsTreatment of iron deficiency (ID) in patients with heart failure (HF) with intravenous iron substitution [ferric carboxymaltose (FCM)] has previously shown significant improvements in exercise capacity, New York Heart Association (NYHA) functional class, quality of life, and reduction of hospitalization. The aim of this study was to estimate the budget impact of FCM treatment for patients with HF and ID.Methods and resultsIndividual patient data from four double‐blind randomized controlled trials were pooled for this analysis. Expected outcomes were modelled for a treatment period of 1 year, using multivariate statistical methods. Associated unit costs were derived from claims data. Budget impact was calculated from the perspective of the Statutory Health Insurance. Multiple deterministic sensitivity analyses were performed. The annual budget impact for therapy with FCM vs. no‐iron therapy was €2 735 505 and €2 695 474 for 1000 patients, respectively, resulting in additional annual costs of €40.03 for each treated patient. Main costs drivers are the FCM treatment cost and cost of hospitalizations due to HF worsening. FCM therapy compared with no‐iron therapy resulted in reduced cost per 1000 patients: for reduced hospitalization due to HF worsening (52 vs. 129 hospitalizations amounting to €230 591 vs. €597 078), for reduced other medication (€1 611 007 vs. €1 679 908), fewer outpatient visits (€332 523 vs. €378 019), and home visits (€29 627 vs. €40 469). Sensitivity analyses showed robustness of the results.ConclusionsTherapy with FCM has a minimal budget impact of €40 031 per 1000 patients per year. This budget impact translates into reduced and shorter hospitalizations and improved symptomatic status of the patients.
Curtailed T‐cell activation curbs effector differentiation and generates CD8+ T cells with a naturally‐occurring memory stem cell phenotype
Authors: Zanon Veronica , Pilipow Karolina , Scamardella Eloise , De Paoli Federica , De Simone Gabriele , Price David A. , Martinez Usatorre Amaia , Romero Pedro , Mavilio Domenico , Roberto Alessandra , Lugli Enrico 
Published: July 2017

AbstractHuman T memory stem (TSCM) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long‐lived T‐cell memory and are thus considered an attractive population to be used in adoptive transfer‐based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T‐cell receptor stimulation curbs human effector CD8+ T‐cell differentiation and allows the generation of CD45RO–CD45RA+CCR7+CD27+CD95+ ‐phenotype cells from highly purified naïve T‐cell precursors, resembling naturally‐occurring human TSCM. These cells proliferate extensively in vitro and in vivo, express low amounts of effector‐associated genes and transcription factors and undergo considerable self‐renewal in response to IL‐15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly‐activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long‐lived memory T cells with potential application in adoptive cell transfer immunotherapy.
The development and impact of primary health care in China from 1949 to 2015: A focused review
Authors: Li Huazhang , Liu Kun , Gu Jianjun , Zhang Yimin , Qiao Yun , Sun Xiaoming 
Published: July 2017

SummaryHigh‐quality primary health care (PHC) services are associated with better health outcomes and positive health equity. Providing PHC services to all inhabitants is one of the Chinese government's health care objectives. However, an imbalance between people's increasing health needs and effective health service utilization exists in China. The objective of this review is to identify evidence for PHC development in China and to summarize the challenges as a reference for the future improvement of China's PHC system. Literature searches related to China's PHC were performed in PubMed, Web of Science, China National Knowledge Infrastructure, and Wan‐fang databases. Related data were collected from the China Statistical Yearbook on Health and Family Planning 2003–2016, the China National Health Accounts Report 2015, and An Analysis Report of National Health Services Survey in China, 2013. The PHC network and the population's health have improved in China in recent years, with general practitioners as “gatekeepers” who have gradually taken the initiative to offer health services to residents. The limitation of input and shortages of resources and skilled health care providers may restrict the sustainable development of China's PHC system. Therefore, policy support from the government is necessary.
Guiding cellular activity with polarized light
Authors: Constant Colin , Bergano Andrea , Sugaya Kiminobu , Dogariu Aristide 
Published: July 2017

AbstractActin, cytoskeleton protein forming microfilaments, play a crucial role in cellular motility. Here we show that exposure to very low levels of polarized light guide their orientation in‐vivo within the live cell. Using a simple model to describe the role of actin‐filament orientation in directional cellular motion, we demonstrate that the actin polymerization/depolymerization mechanism develops primarily along this direction and, under certain conditions, can lead to guidance of the cell movement. Our results also show a dose dependent increase in actin activity in direct correspondence to the level of laser irradiance. We found that total expression of Tau protein, which stabilize microtubules, was decreased by the irradiance, indicating that exposure to the light may change the activity of kinase, leading to increased cell activity.magnified image
Hepatocytes of Wistar and Sprague Dawley rats differ significantly in their central metabolism
Authors: Garg Richa , Heinzle Elmar , Noor Fozia 
Published: July 2017

AbstractWistar and Sprague‐Dawley (SD) rats are most commonly used experimental rats. They have similar genetic background and are therefore, not discriminated in practical research. In this study, we compared metabolic profiles of Wistar and SD rat hepatocytes from middle (6 months) and old (23 months) age groups. Principle component analysis (PCA) on the specific uptake and production rates of amino acids, glucose, lactate and urea indicated clear differences between Wistar and SD rat hepatocytes. SD rat hepatocytes showed higher uptake rates of various essential and non‐essential amino acids, particularly in early culture phases (0‐12 h) compared to later phases (12‐24 h). SD hepatocytes seem to be more sensitive to isolation procedure and in vitro culture requiring more amino acids for cellular maintenance and repair. Major differences between Wistar and SD rat hepatocytes were observed for glucose and branched chain amino acid metabolism. We conclude that the observed differences in the central carbon metabolism of isolated hepatocytes from these two rats should be considered when using one or the other rat type in studies on metabolic effects or diseases such as diabetes or obesity.
Navigating Inclusion in Transitions from Conflict: The Formalised Political Unsettlement
Authors: Bell Christine , Pospisil Jan 
Published: July 2017

AbstractThe project of ensuring that political settlements are inclusive is key to attempts to navigate transitions from conflict over the last quarter of a century or so. Examining such transitions, we point to the emergence of the ‘formalised political unsettlement’ as a persistent outcome. The formalised political unsettlement translates the disagreement at the heart of the conflict into a set of political and legal institutions for continuing negotiation. As the conditions of its emergence are unlikely to change and the formalised political unsettlement may be here to stay, we point to the opportunities for navigating between elite inclusion and broader societal inclusion that it offers. Copyright © 2017 John Wiley & Sons, Ltd.
Transcriptional profiling of articular cartilage in a porcine model of early post‐traumatic osteoarthritis
Authors: Sieker Jakob T. , Proffen Benedikt L. , Waller Kimberly A. , Chin Kaitlyn E. , Karamchedu Naga Padmini , Akelman Matthew R. , Perrone Gabriel S. , Kiapour Ata M. , Konrad Johannes , Murray Martha M. , Fleming Braden C. 
Published: July 2017

ABSTRACTTo identify the molecular pathophysiology present in early post‐traumatic osteoarthritis (PTOA), the transcriptional profile of articular cartilage and its response to surgical PTOA induction were determined. Thirty six Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Cartilage was harvested at 1 and 4 weeks post‐operatively and histology and RNA‐sequencing were performed and compared to controls. Microscopic cartilage scores significantly worsened at 1 (p = 0.028) and 4 weeks (p = 0.001) post‐surgery relative to controls, but did not differ between untreated, reconstruction or repair groups. Gene expression after ACL reconstruction and ACL transection were similar, with only 0.03% (includingSERPINB7andCR2) and 0.2% of transcripts (includingINHBA) differentially expressed at 1 and 4 weeks respectively.COL2A1,COMP,SPARC,CHAD, andEF1ALPHAwere the most highly expressed non ribosomal, non mitochondrial genes in the controls and remained abundant after surgery. A total of 1,275 genes were differentially expressed between 1 and 4 weeks post‐surgery. With the treatment groups pooled, 682 genes were differentially expressed at both time‐points, with the most significant changes observed inMMP1,COCH,POSTN,CYTL1, andPTGFR. This study confirmed the development of a microscopic PTOA stage after ACL surgery in the porcine model. Upregulation of multiple proteases (includingMMP1andADAMTS4) were found; however, the level of expression remained orders of magnitude below that of extracellular matrix protein‐coding genes (includingCOL2A1andACAN). In summary, genes with established roles in PTOA as well as novel targets for specific intervention were identified. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:318–329, 2018.
Water status and must composition in grapevine cv. Chardonnay with different soils and topography and a mini meta‐analysis of the δ13C/water potentials correlation
Authors: Brillante Luca , Mathieu Olivier , Lévêque Jean , van Leeuwen Cornelis , Bois Benjamin 
Published: July 2017

AbstractBACKGROUNDThe measurement of carbon isotopic discrimination in grape sugars at harvest (δ13C) is an integrated assessment of water status during ripening. It is an efficient alternative to assess variability in the field and discriminate between management zones in precision viticulture, but further work is needed to completely understand the signal.RESULTSThis work, spanning over 3 years, performed in a hillslope toposequence in Burgundy, delineates the relationships between main soil properties (gravel amount, slope, texture) and the grapevine water status assessed by δ13C. The highest δ13C, indicating most severe water deficit, was recorded in gravelly soils on steep slopes. The amount of sugars and malic and tartaric acids was also related to δ13C. The relationship between δ13C and predawn leaf water potentials (Ψpd) was also investigated, because the absolute values of measured δ13C were lower than the values currently found in the literature.CONCLUSIONSA mini‐meta‐analysis was performed, which showed that the slope of the relationships between minimum Ψpd and δ13C was stable across studies (a change of 1‰ in δ13C corresponded to a change of −0.2 MPa in the minimum Ψpd), while the intercept of the comparison δ13C/Ψpd changed, probably because of genetic variations between varieties, or environmental differences. © 2017 Society of Chemical Industry
Toxicity of zearalenone on the intestines of pregnant sows and their offspring and alleviation with modified halloysite nanotubes
Authors: Liu Min , Zhu Dandan , Guo Tao , Zhang Yuanyuan , Shi Baoming , Shan Anshan , Chen Zhihui 
Published: July 2017

AbstractBACKGROUNDThe objective of this study was to examine the effects of maternal exposure to zearalenone (ZEN) on the intestines of pregnant sows and offspring on postnatal days (PD) 1, 21 and 188. Eighteen pregnant sows (six per treatment) were fed a control diet (ZEN, 0.03 mg kg−1), ZEN diet (ZEN, 2.77 mg kg−1) and ZEN + 1% modified halloysite nanotube (MHNT) diet (ZEN, 2.76 mg kg−1) respectively from gestation days (GD) 35 to 70. At the end of the experiment, three sows of each group on GD70 and the offspring on PD1, PD21 and PD188 were killed to analyze the changes of intestines.RESULTSThe results showed that ZEN caused oxidative stress, an inflammatory response, changes in the structure of jejunum and alterations of the bacterial numbers in cecal digesta in pregnant sows and PD1 and PD21 piglets. On PD188, bacterial numbers were also altered. MHNTs supplementation reduced the amount of ZEN in the intestine and reversed to a large extent the effects induced by ZEN on the intestines of pregnant sows and offspring.CONCLUSIONThe results obtained from this study indicated that MHNTs treatment was beneficial for the adsorption of ZEN in the intestine of sows. © 2017 Society of Chemical Industry
Modelling the demand for inbound medical tourism: The case of Malaysia
Authors: Tang Chor Foon , Lau Evan 
Published: July 2017

AbstractThis paper empirically examines the macroeconomic determinants for medical tourism demand using time series econometrics methodology. We find that income, price, exchange rate, SARS outbreak, safety, medical quality, manpower, and medical facilities are significantly affecting the long‐run demand behaviour of medical tourism in Malaysia. In order to attract medical tourists, policymakers in Malaysia should (a) reduce the medical prices, (b) reduce the crime rate and improve safety, and (c) continue the improvement of research, medical quality, manpower, and facilities to support the revolution of inbound medical tourism demand in Malaysia. This is to ensure the Malaysia's sustainable economic development.
Laryngectomy and smoking: An analysis of postoperative risk
Authors: Brady Jacob S. , Crippen Meghan M. , Filimonov Andrey , Eloy Jean Anderson , Baredes Soly , Park Richard Chan Woo 
Published: July 2017

ObjectivesTo investigate the impact of smoking on complication rates following total laryngectomy.Study Design and MethodsThe National Surgical Quality Improvement Program database was queried for all total laryngectomies between 2005 and 2014. Patients were identified as smokers (n = 561) or nonsmokers (n = 513) and compared via univariate and multivariate analyses. A nearest‐neighbor propensity score‐generating algorithm was used to build a subpopulation (n = 714) of matched cases and evaluated in a similar manner. Additionally, pack‐year data was available for select cases and analyzed appropriately.ResultsOn multivariate analysis of the unmatched cohort accounting for demographics and confounders, no significant difference in overall medical complications was identified between groups (odds ratio = 0.799, P = 0.495). Propensity matching corrected for all significantly distributed comorbidities, except for alcohol, which remained associated with the smoking group (P = < 0.001). In the matched population, there were no significant differences in complication rates between the two groups. Pack‐year data was available for 340 patients. These cases were subdivided into cohorts with < 50 (n = 204) and 51+ (n = 136) pack‐years. Postoperative pneumonia, ventilation for more than 48 hours, sepsis, and overall medical complications were associated with > 50 pack‐years of smoking. After multivariate regression, sepsis and overall medical complications remained significant for the 51+ pack‐year smoking cohort.ConclusionAfter accounting for confounding comorbidities, smoking is found to play an insignificant role in the development of postoperative complications following total laryngectomy. However, those with 51+ pack‐years are at an increased risk for postoperative sepsis and overall medical complications following these complex procedures.Level of Evidence4. Laryngoscope, 127:2302–2309, 2017
Mandibular condylar hypoplasia in children with isolated unilateral congenital aural atresia
Authors: Halle Tyler R. , Todd N. Wendell , Soares Bruno P. 
Published: July 2017

Objectives/HypothesisWe hypothesized that children with isolated nonsyndromic unilateral congenital aural atresia have subclinical mandibular condylar hypoplasia ipsilateral to the atretic ear, and that the Jahrsdoerfer score is associated with the degree of condylar hypoplasia.Study DesignRetrospective self‐controlled case series.MethodsWe reviewed high‐resolution computed tomography scans of the temporal bones of 68 children with isolated nonsyndromic unilateral congenital aural atresia. Images were viewed in the transverse (axial) plane perpendicular to the axis of the mandibular ramus and scanned from the mandibular notch to the condylar top. The slice where the condyle had the largest cross‐sectional area was measured and checked for correlation with atresia status, age, and sex. The Jahrsdoerfer score of the atretic ear was calculated and correlated with condyle cross‐sectional area, age, and sex.ResultsCross‐sectional area of the condyle ipsilateral to the atretic ear was, on average, 8.41 mm2 smaller than the contralateral condyle (P < .0001). The Jahrsdoerfer score was not associated with the condylar cross‐sectional area, age, or sex.ConclusionIsolated nonsyndromic unilateral congenital aural atresia is associated with mild hypoplasia of the mandibular condyle ipsilateral to the atretic ear. This is consistent with the hypothesis that congenital aural atresia is a variant of craniofacial (hemifacial) microsomia.Level of Evidence4. Laryngoscope, 128:1191–1195, 2018
Uptake of Retinoic Acid‐Modified PMMA Nanoparticles in LX‐2 and Liver Tissue by Raman Imaging and Intravital Microscopy
Authors: Yildirim Turgay , Matthäus Christian , Press Adrian T. , Schubert Stephanie , Bauer Michael , Popp Jürgen , Schubert Ulrich S. 
Published: July 2017

AbstractA primary amino‐functionalized methyl methacrylate‐based statistical copolymer is covalently coupled with retinoic acid (RA) and a fluorescent dye (DY590) in order to investigate the feasibility of the RA containing polymeric nanoparticles for Raman imaging studies and to study the possible selectivity of RA for hepatic stellate cells via intravital microscopy. Cationic nanoparticles are prepared by utilizing the nanoprecipitation method using modified polymers. Raman studies show that RA functional nanoparticles can be detectable in all tested cells without any need of additional label. Moreover, intravital microscopy indicates that DY590 is eliminated through the hepatobiliary route but not if used as covalently attached tracing molecule for nanoparticles. However, it is a suitable probe for sensitive detection of polymeric nanoparticles.
Functional Cross‐Linked Electrospun Polyvinyl Alcohol Membranes and Their Potential Applications
Authors: Truong Yen Bach , Choi Jonghyun , Mardel James , Gao Yuan , Maisch Sabrina , Musameh Mustafa , Kyratzis Ilias Louis 
Published: July 2017

Polyvinyl alcohol (PVA) is a water soluble polymer that requires further treatment to be stabilized before it can be used in aqueous environments. Electrospun PVA is cross‐linked by incorporating cross‐linking agents directly into the electrospinning solution followed by post‐electrospinning thermal treatments to attain stability in aqueous environments. Previously published works on post‐treatments include glutaraldehyde vapor exposure or soaking in organic solvents such as ethanol. However, these treatments incur lots of difficulties and hazards especially in scale production. In this study, with a view of imminent scale‐up production required, fabricating electrospun cross‐linked PVA is investigated without using catalysts, toxic vapor exposure, or solvent treatment. To produce cross‐linked electrospun PVA membranes, citric acid, maleic acid, and polyacrylic acid are, respectively, added to PVA solution prior to electrospinning. Two potential applications are examined; the first is to use the membranes as produced for metal uptake in aqueous systems. The second application is for ammonia adsorption after decorating the membranes with a metal organic framework, copper benzene‐1,3,5‐tricarboxylate (HKUST‐1).
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Discriminating Agonist from Antagonist Ligands of the Nuclear Receptors Using Different Chemoinformatics Approaches
Authors: Lagarde Nathalie , Delahaye Solenne , Jérémie Aurore , Ben Nasr Nesrine , Guillemain Hélène , Empereur‐mot Charly , Laville Vincent , Labib Taoufik , Réau Manon , Langenfeld Florent , Zagury Jean‐François , Montes Matthieu 
Published: July 2017

AbstractNuclear receptors (NRs) constitute an important class of therapeutic targets. During the last 4 years, we tackled the pharmacological profile assessment of NR ligands for which we constructed the NRLiSt BDB. We evaluated and compared the performance of different virtual screening approaches: mean of molecular descriptor distribution values, molecular docking and 3D pharmacophore models. The simple comparison of the distribution profiles of 4885 molecular descriptors between the agonist and antagonist datasets didn′t provide satisfying results. We obtained an overall good performance with the docking method we used, Surflex‐Dock which was able to discriminate agonist from antagonist ligands. But the availability of PDB structures in the “pharmacological‐profile‐to‐predict‐bound‐state” (agonist‐bound or antagonist‐bound) and the availability of enough ligands of both pharmacological profiles constituted limits to generalize this protocol for all NRs. Finally, the 3D pharmacophore modeling approach, allowed us to generate selective agonist pharmacophores and selective antagonist pharmacophores that covered more than 99 % of the whole NRLiSt BDB. This study allowed a better understanding of the pharmacological modulation of NRs with small molecules and could be extended to other therapeutic classes.