bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endostatin sensitizes p53‐deficient non‐small‐cell lung cancer to genotoxic chemotherapy by targeting DNA‐dependent protein kinase catalytic subunit
Authors: Jia Lin , Lu Xin‐an , Liu Guanghua , Wang Shan , Xu Min , Tian Yang , Zhang Shaosen , Fu Yan , Luo Yongzhang 
Published: August 2017

AbstractEndostatin was discovered as an endogenous angiogenesis inhibitor with broad‐spectrum antitumour activities. Although clinical efficacy was observed when endostatin was combined with standard chemotherapy for non‐small cell lung cancer (NSCLC), as well as other cancer types, the specific mechanisms underlying the benefit of endostatin are not completely understood. Extensive investigations suggest that endostatin is a multifunctional protein possessing more than anti‐angiogenic activity. Here, we found that endostatin exerts a direct chemosensitizing effect on p53‐deficient tumour cells. Concomitant treatment with endostatin and genotoxic drugs resulted in therapeutic synergy in both cellular and animal models of p53‐deficient NSCLC. Mechanistically, endostatin specifically interacts with DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) in tumour cells and suppresses its DNA repair activity. Using isogenic NSCLC cells with different p53 statuses, we discovered that p53‐deficient tumour cells show chemoresistance to genotoxic drugs, creating a synthetic dependence on DNA‐PKcs‐mediated DNA repair. In this setting, endostatin exerted inhibitory effects on DNA‐PKcs activity, leading to accumulation of DNA lesions and promotion of the therapeutic effect of genotoxic chemotherapy. In contrast, p53‐proficient tumour cells were more sensitive to genotoxic drugs so that DNA‐PKcs could be cleaved by drug‐activated caspase‐3, making DNA‐PKcs inhibition less effective during this ongoing apoptotic process. Therefore, our data demonstrate a novel mechanism for endostatin as a DNA‐PKcs suppressor, and indicate that combination therapy of endostatin with genotoxic drugs could be a promising treatment strategy for cancer patients with p53‐deficient tumours. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Comprehensive T‐cell immunophenotyping and next‐generation sequencing of human papillomavirus (HPV)‐positive and HPV‐negative head and neck squamous cell carcinomas
Authors: Poropatich Kate , Fontanarosa Joel , Swaminathan Suchitra , Dittmann Dave , Chen Siqi , Samant Sandeep , Zhang Bin 
Published: August 2017

AbstractThe success of programmed cell death 1 (PD‐1) inhibition in achieving a clinical response in a subset of head and neck squamous cell carcinoma (HNSCC) patients emphasizes the need to better understand the immunobiology of HNSCC. Immunophenotyping was performed for 30 HCSCC patients [16 human papillomavirus (HPV)‐positive; 14 HPV‐negative] on matched tissue from the primary tumour site, locally metastatic cervical lymph nodes (LNs), uninvolved local cervical LNs, and peripheral blood. CD4+ and CD8+ T‐cell lymphocytes obtained from tissue were analysed for expression levels of the inhibitory receptors PD‐1, TIM‐3 and CTLA‐4. Next‐generation sequencing of the T‐cell receptor (TCR) β chain was performed on patients (n = 9) to determine receptor repertoire diversity and for clonality analysis. HPV‐negative HNSCC patients, particularly those with stage IV disease, had significantly higher proportions of CD8+ T cells expressing CTLA‐4 in tumour tissue (P = 0.0013) and in peripheral blood (P = 0.0344) than HPV‐positive patients, as well as higher expression levels of TIM‐3+PD‐1+ CD8+ T cells (P = 0.0072) than controls. For all patients, PD‐1 expression on CD8+ T cells – particularly in HPV‐negative HNSCC cases – strongly correlated (r = 0.63, P = 0.013) with tumour size at the primary site. The top CD8+ TCR clones from tumour tissue significantly overlapped with circulating peripheral blood TCR clones (r = 0.946), and HPV‐positive patients had frequently expanded TCR clones that were more hydrophobic – and potentially more immunogenic – than those from HPV‐negative patients. Collectively, our findings demonstrate, for the first time, that high‐stage HPV‐negative HNSCC patients with primary tumours at different sites in the head and neck have elevated peripheral CTLA‐4+CD8+ T‐cell levels, that tumour‐familiar CD8+ T cells are detectable in peripheral blood from HNSCC patients, and that TCRs from HPV‐positive HNSCC patients potentially recognize distinctly immunogenic cognate antigens. However, our findings are preliminary, and need to be further confirmed in a larger patient cohort; also, how these factors affect patient response to immunotherapy needs to be determined. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Impact of clinical evidence communications and drug regulation changes concerning rosiglitazone on prescribing patterns of antidiabetic therapies
Authors: Noh Yoojin , Kang Dae Ryong , Kim Dae Jung , Lee Kwang Jae , Lee Sukhyang , Shin Sooyoung 
Published: August 2017

AbstractPurposeCardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs).MethodsPatient data were extracted from the Korean health insurance claims database for 2007 to 2015. Linear regression and interrupted time series analyses were performed to examine drug utilization trends and the impact of 5 milestone events regarding rosiglitazone safety on AD utilization.ResultsA steady growth was observed in the AD consumption, with metformin preserving its dominant market share throughout the period. Pioglitazone use has increased since 2008 in response to safety issues surrounding rosiglitazone. A significant decline in rosiglitazone use was observed after Nissen's meta‐analysis and safety warnings (2007) and after restriction/suspension of access to rosiglitazone (2010), associated with a drop in prevalence by 29.5%/year and 99.5%/year, respectively. The most common AD newly started among users who discontinued rosiglitazone in 2010 was pioglitazone, followed by dipeptidyl peptidase‐4 (DPP‐4) inhibitors. Our concomitancy analysis showed that DPP‐4 inhibitors have overtaken sulfonylureas since 2014 as the most common add‐on to metformin.ConclusionsThe most frequently added AD in diabetes patients who had switched off rosiglitazone in 2010 was pioglitazone, followed by DPP‐4 inhibitors. Despite new evidence from a long‐term clinical trial and the Food and Drug Administration's subsequent decision to eliminate access restrictions on rosiglitazone in 2013, domestic regulations were left intact; hence, its use remained negligible in Korea.
Metamizole use during first trimester—A prospective observational cohort study on pregnancy outcome
Authors: Dathe Katarina , Padberg Stephanie , Hultzsch Stefanie , Meixner Katja , Tissen‐Diabaté Tatjana , Meister Reinhard , Beck Evelin , Schaefer Christof 
Published: August 2017

AbstractIntroductionThe analgesic metamizole (dipyrone) is not recommended during pregnancy due to limited experience. In several countries, metamizole has no market authorization because of agranulocytosis as a rare but severe adverse effect. However, in others, metamizole is available and widely used as a pain reliever, and its use occurs also during pregnancy, often followed by fears of potential teratogenic risk.MethodsThis prospective observational cohort study compared pregnancy outcomes of 446 women exposed with metamizole in the first trimester with a randomly selected control cohort comprising 887 women not exposed to metamizole. Relevant data were obtained via structured questionnaires applied during the first trimester and 2 months after the expected date of birth between January 2000 and December 2015.ResultsThe rate of major birth defects (7/373, 1.9%) was not increased in the metamizole cohort (OR adjusted 1.15, 95% CI 0.4‐3.5). The cumulative incidences for spontaneous abortions did not reveal a significant difference between the exposed (12.2%, 32/446) and comparison cohort (19.4%, 77/887) (HR adjusted 0.72, 95% CI 0.5‐1.1). Elective terminations of pregnancy (ETOP), mostly for “social” reasons, were more frequent in the metamizole (12.5%, 45/446) than in the comparison cohort (9.4%, 50/887; HR adjusted 1.48, 95% CI 0.98‐2.2).ConclusionsMetamizole exposure in the first trimester does not seem to bear a substantial teratogenic risk. Our study results support reassurance in those instances where metamizole has been used during an unrecognized pregnancy or where its use appears indispensable.
Helium permeation as a fast quality indicator for barrier properties of solar cell encapsulates
Authors: Schulze Stefan‐H. , Ehrich Christian , Meitzner Rico , Pander Matthias 
Published: August 2017

AbstractThe advent of flexible electronic devices and flexible thin‐film photovoltaic modules increases the need for transparent and flexible high‐barrier films. Conventional methods for measuring the barrier properties of such films are costly and time consuming. In our work, we present a method where we correlate water vapor and helium transmission rate measurements on strained barrier films with thin‐film solar module performance. We show that the detected properties correlate well with the performance of a CIGS mini module exposed to damp‐heat environment. The critical strain limit for a substantial decrease in barrier properties was identified for an ETFE‐based barrier film incorporating an inorganic barrier layer. It was found that the detection of the helium transmission rate provides a fast and reliable way to identify damage to barrier films and is therefore suitable as means for quality control or incoming goods inspection.
Divergent Proteome Patterns of Egg Albumen from Domestic Chicken, Duck, Goose, Turkey, Quail and Pigeon
Authors: Sun Congjiao , Liu Junnian , Li Wenbo , Xu Guiyun , Yang Ning 
Published: August 2017

AbstractTo uncover a diversity of genetic and biological unknowns, a comprehensive and comparative proteomic analysis is performed on egg albumen of domestic chicken, duck, goose, turkey, quail, and pigeon with tandem mass tags quantification technology. In this study, a total of 148, 138, 150, 162, 183, and 179 proteins are identified in egg albumen of the above six species, respectively. Venn plots, PCA, and cluster analysis all reveal the highest similarity of protein composition between duck and goose (≈75%). Additionally, the six species have 52 proteins detected in common in the egg albumen. As revealed by GO and pathway analyses, the plausible functions of these highly conserved proteins are to provide a secure environment and prevent the early death of embryonic cells. Species‐specific proteins such as haptoglobin in pigeon, serpin‐like protein HMSD in duck, and ovodefensin in chicken are also screened and are likely associated with species‐dependent biological processes. Furthermore, Enzyme Code analysis indicated egg albumen have abundant enzyme activity, with hydrolases accounting for more than half of the total enzymes. This study is the first to provide the proteome profiles of egg albumen for the major poultry species, which will be instructive for the understanding of species‐specific biological problems with egg albumen.
Cyclopropyllithium aggaregation and199Hg NMR as a tool for exchange studies with organo‐mercury compounds
Authors: Fox Thomas , Günther Harald 
Published: August 2017

AbstractLow‐temperature NMR studies revealed aggregate formation in cyclopropyllithium compounds. For C3H5Li (1), a static tetramer [1J(6Li,13C) = 6.5 Hz] was found in diethylether (DEE), while in tetrahydrofuran (THF) a dimer and a fluxional tetramer [1J(6Li,13C) = 9.3 and 4.7 Hz, respectively] were detected.Trans‐2,3‐dimethyl‐1 (2) yielded in DEE/THF (1:1) diastereomeric dimers [1J(6Li,13C) = 9.3 Hz] and 2,2,3,3‐tetramethyl‐1 (3) formed dimers in DEE and DEE/THF [1J(6Li,13C) = 10.0 and 9.6 Hz, respectively]. For bis‐(trans‐2,3‐dimethylcyclopropyl)‐mercury (7), ligand exchange could be detected by the isotopic fingerprint method with199Hg NMR at room temperature.199Hg NMR in connection with specific deuteration may thus be used for ligand exchange studies in the field of organomercury compounds.
Interrupter technique in infancy: Higher airway resistance and lower short‐term variability in preterm versus term infants
Authors: Usemann Jakob , Demann Désirée , Anagnostopoulou Pinelopi , Korten Insa , Gorlanova Olga , Schulzke Sven , Frey Urs , Latzin Philipp 
Published: August 2017

AbstractBackgroundIn preschool children, measurement of airway resistance using interrupter technique (Rint) is feasible to assess the degree of bronchial obstruction. Although some studies measured Rint in infancy, values of Rint and its variability in preterm infants are unknown. In this study, Rint and its variability was measured at infancy and compared between healthy term and preterm infants.MethodsHigh quality Rint measurements in term (n = 50) and preterm (n = 48) infants were obtained at postmenstrual age of 42‐50 weeks in two study centers in Switzerland. Intra‐measurement variability of Rint in one measurement and inter‐measurement variability between two subsequent measurements was assessed by coefficient of variation (CV).ResultsMean Rint in term infants was 4.2 ± (SD; 1.9) kPa · s · L−1and in preterm infants was 5.6 ± (2.8) kPa · s · L−1. Mean CV in term infants was 29.6 ± (14.9)% and in preterm infants was 20.2 ± (8.4)%. Rint was significantly lower (95%CI −2.31 to −0.38;P = 0.007) and CV significantly higher (95%CI 4.53‐14.3;P < 0.001) in term compared to preterm infants. There were no differences in mean Rint and mean CV between the first and the second measurement obtained in a subgroup of term (n = 24, 48%) and preterm (n = 22, 45%) infants.ConclusionsOur results suggest that differences in airway mechanics between term and preterm infants can be assessed with the interrupter technique during early infancy. Before clinical application of Rint measurements in this age group, reasons underlying the variability of measurements should be further investigated.
A new insight into CFTR allele frequency in Brazil through next generation sequencing
Authors: Nunes Luisa M. , Ribeiro Roberto , Niewiadonski Vivian D.T. , Sabino Ester , Yamamoto Guilherme L. , Bertola Débora R. , Gaburo Nelson , da Silva Filho Luiz Vicente R.F. 
Published: August 2017

AbstractBackgroundAs of 2013, fewer than 20% of patients in the Brazilian CF Registry had two CFTR mutations identified. The aim of this study was to sequence the coding region of the CFTR in Brazilian CF patients and determine the frequency of mutations in this cohort.MethodsPatients with CF and those with suspected atypical CF or CFTR‐related disorders were invited to enroll. Total DNA was extracted from blood samples, quantified, and purified. Library preparation was performed using Ion Xpress™ Plus gDNA and Amplicon Library preparation kits (Life Technologies), as well as sequencing using the Ion Torrent platform (Life Technologies).ResultsA total of 141 patients were enrolled, and 45 mutations were identified. Among 126 CF patients, we identified mutations in 97.2% of alleles. The three most common mutations were F508del, G542X, and 3120 + 1G‐>A. Five novel pathogenic mutations were also identified.ConclusionsNext generation sequencing (NGS) allowed the identification of mutations in most CF alleles and confirmed allelic heterogeneity in our population.
The politics of water: a review of hydropolitical frameworks and their application in China
Authors: Rogers Sarah , Crow‐Miller Britt 
Published: August 2017

Academic literature on the politics of water encompasses hydrosocial relations at different scales, the role of technology in hydropolitics, and the various rationalities and discourses behind the governance of water. In this advanced review, we outline the key hydropolitical frameworks, tracing the development of scholarship that examines the relations between power, water, society, and technology. We then synthesize the literature on hydropolitics in China, which boasts both the world's largest dam (by installed capacity) and the world's largest interbasin transfer project. We consider the extent to which different frameworks have been productively applied in a Chinese context, not just to understand big infrastructure, but to question of water pollution, agricultural water use, and water scarcity. In doing so, we find that critical scholarship on hydropolitics in China has a number of significant gaps. These gaps constrain our understanding of the inherent political nature of the many acute water challenges China currently faces and challenges that have impacts well beyond its borders.WIREs Water2017, 4:e1239. doi: 10.1002/wat2.1239This article is categorized under:Engineering Water > Planning WaterHuman Water > Rights to WaterHuman Water > Water Governance
Concurrent metabolism of pentose and hexose sugars by the polyextremophile Alicyclobacillus acidocaldarius
Authors: Lee Brady D , Apel William A , DeVeaux Linda C , Sheridan Peter P 
Published: August 2017

Abstract
Alicyclobacillus acidocaldarius is a thermoacidophilic bacterium capable of growth on sugars from plant biomass. Carbon catabolite repression (CCR) allows bacteria to focus cellular resources on a sugar that provides efficient growth, but also allows sequential, rather than simultaneous use when more than one sugar is present. The A. acidocaldarius genome encodes all components of CCR, but transporters encoded are multifacilitator superfamily and ATP-binding cassette-type transporters, uncommon for CCR. Therefore, global transcriptome analysis of A. acidocaldarius grown on xylose or fructose was performed in chemostats, followed by attempted induction of CCR with glucose or arabinose. Alicyclobacillus acidocaldarius grew while simultaneously metabolizing xylose and glucose, xylose and arabinose, and fructose and glucose, indicating that CCR did not control carbon metabolism. Microarrays showed down-regulation of genes during growth on one sugar compared to two, and occurred primarily in genes encoding: (1) regulators; (2) enzymes for cell wall synthesis; and (3) sugar transporters.
White Bass (Morone chrysops) Preferentially Retain n‐3 PUFA in Ova When Fed Prepared Diets with Varying FA Content
Authors: Fuller S. Adam , Rawles Steven D. , McEntire Matthew E. , Bader Troy J. , Riche Marty , Beck Benjamin H. , Webster Carl D. 
Published: August 2017

AbstractWe evaluated the fatty acid (FA) composition of broodstock white bass ova fed one of six commercial diets with increasing polyunsaturated FA content (n‐6/n‐3 ratio; 0.36, 0.39, 0.46, 0.83, 1.07, 1.12) eight weeks prior to sampling. Fatty acid profiles of ova from brooders fed each of the six diets were significantly altered according to canonical discriminant analysis. Ova FA profiles resulting from the 0.39 diet separated those from the 0.36 diet based on lower 18:2n‐6 (LNA) and higher 20:1n‐9 concentrations from the 0.36 diet. Ova profiles were further separated based on lower concentrations of 22:5n‐3 (DPA) from the 0.46 diet, lower concentrations of 20:5n‐3 (EPA) in the 1.12 and 0.83 diets, and lower concentrations of 22:6n‐3 (DHA) in all other diets relative to the 0.46 diet. Changes in ova FA profile at four and eight weeks were consistent with dietary intake with an approximate 2% increase in any given FA class with increasing time on individual diet. There was no correlation between dietary ARA concentrations (0.7–1.1 mol%), or dietary EPA/ARA ratios (7–15), and the concentrations (1.4–1.7 mol%) or ratios (3.3–4.4) found in the ova by diet. Our results suggest that white bass females have the ability to preferentially incorporate n‐3 PUFA, particularly DHA, suggesting mobilization of this FA from other tissues for ova deposition or preferential dietary incorporation of PUFA into ova. These results will add to the limited FA information available in white bass and enable nutritionists to formulate broodstock diets that maximize reproductive potential in this species.
Application of β‐Sitosterol + γ‐Oryzanol‐Structured Organogel as Migration Barrier in Filled Chocolate Products
Authors: Wendt Alexandra , Abraham Karin , Wernecke Christin , Pfeiffer Julia , Flöter Eckhard 
Published: August 2017

AbstractOil migration in filled pralines is a phenomenon that is highly correlated with the occurrence of chocolate bloom. In this study the potential to suppress or prevent oil migration by incorporation of sterol/sterolster‐structured organogels was evaluated. Different quantities, 2.5 or 14% (w/w), of gel with structurant levels of either 10 or 25% (w/w) were studied in a layered model system. The gel was either a part of the nougat or of the chocolate phase, or as a separate layer. Samples were monitored regularly for a period of 24 weeks at storage temperatures of 10, 18 and 28 °C. The amount of migrated oil was determined via DSC analysis of a surface sample. The results indicate that, despite the additional oil brought into the system via the oleogel, the level of oil found in the chocolate layer is reduced through the presence of the gel. In particular, the three‐layer system and gelled chocolate appear to be promising routes to either suppress oil migration or improve nutritional profiles by incorporation of liquid oils.
Materialism pathways: The processes that create and perpetuate materialism
Authors: Richins Marsha L. 
Published: August 2017

AbstractMaterialism has been examined in many social science disciplines from multiple perspectives. This review synthesizes this extensive literature into two organizing frameworks that describe how materialism develops in children and how materialism is reinforced and perpetuated in adulthood. The major components of the developmental model are the daily event cycle, developmental tasks, cultural influence, and family environment, all of which interact to influence how materialistic a child becomes. The reinforcement model describes how personal qualities that materialists tend to possess make them more vulnerable to threats in daily events, resulting in psychological discomfort. The desire to reduce this discomfort, in conjunction with the transformative powers that materialists ascribe to acquisition, results in actions and outcomes that reinforce materialistic tendencies. Suggestions for furthering the study of materialism are also included.