bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the modified Glasgow Prognostic Score (mGPS) have a prognostic role in esophageal cancer?
Authors: Walsh Siun M. , Casey Sarah , Kennedy Raymond , Ravi Narayanasamy , Reynolds John V. 
Published: March 2016

BackgroundThe modified Glasgow Prognostic Score (mGPS), which combines indices of decreased plasma albumin and elevated CRP, has reported independent prognostic significance in colorectal cancer, but its value in upper gastrointestinal cancer is unclear. The aim of this study was to assess the prognostic significance of mGPS in patients with operable esophageal malignancy.MethodsPatients undergoing resection with curative intent between January 2008 and June 2013 were included. The mGPS was scored as 0, 1, or 2 based on CRP(>10 mg/L) and albumin(<35g/L). The mGPS score (0 vs. 1/2 combined) was correlated with patient and tumor characteristics, and operative and oncologic outcomes.ResultsTwo hundred and twenty‐three patients were included. Median (range) follow‐up was 21(12–70) months. The mGPS was 0 in 174 patients(78%). mGPS was significantly associated with positive nodal status(P = 0.008) and stage ≥III (P = 0.017). There was a significant improvement in overall survival in patients with mGPS = 0 (47.8 vs. 37.5 months, P = 0.014) but in multivariate analysis, only TNM‐stage and nodal status were found to be independent prognostic indicators.ConclusionsmGPS is associated with advanced stage but has no independent prognostic significance and does not impact on operative outcomes. Consequently, this data does not support its routine application in patient selection or prognostication. J. Surg. Oncol. 2016;113:732–737. © 2016 Wiley Periodicals, Inc.
Soyasaponin Bb inhibits the recruitment of toll‐like receptor 4 (TLR4) into lipid rafts and its signaling pathway by suppressing the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase‐dependent generation of reactive oxygen species
Authors: Zhang Yajie , Chen Fengping , Chen Jiading , Huang Suqun , Chen Junbin , Huang Jian , Li Nan , Sun Suxia , Chu Xinwei , Zha Longying 
Published: March 2016

ScopeWe and others recently showed that soyasaponin Bb (SSBb) inhibited lipopolysaccharide (LPS)‐induced inflammation in macrophages. Since the recruitment of toll‐like receptor 4 (TLR4) into lipid rafts is vital for LPS‐initiated signaling, we investigated whether this process would be modulated by SSBb.Methods and resultsBy using sucrose gradient ultracentrifuge, we found that pretreatment of macrophages with SSBb inhibited LPS‐induced recruitments of TLR4, myeloid differentiation primary response protein 88 (MyD88) and Toll/IL‐1 receptor domain‐containing adaptor inducing interferon‐β (TRIF) into fractions enriched with lipid rafts marker flotillin‐1. We also found SSBb decreased co‐localization of TLR4 and lipid rafts by utilizing confocal immunofluorescence microscopy. Additionally, we observed that SSBb suppressed LPS‐induced formation of TLR4/MyD88 and TLR4/TRIF complexes, production of pro‐inflammatory molecules, and activation of nuclear factor kappa B (NF‐κB). Furthermore, we found that these inhibitory effects of SSBb were associated with reduced reactive oxygen species (ROS) because pretreating cells with N‐acetyl‐L‐cysteine and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited LPS‐induced TLR4 recruitment into lipid rafts and NF‐κB activation. SSBb also inhibited NADPH oxidase activation by blocking interaction between gp91phox and p47phox similarly as DPI.ConclusionSSBb can inhibit TLR4 recruitment into lipid rafts and its signaling by suppressing the NADPH oxidase‐dependent ROS generation.
Combined geometric and algebraic solutions for removal of bSSFP banding artifacts with performance comparisons
Authors: Hoff Michael N. , Andre Jalal B. , Xiang Qing‐San 
Published: March 2016

PurposeBalanced steady state free precession (bSSFP) imaging suffers from off‐resonance artifacts such as signal modulation and banding. Solutions for removal of bSSFP off‐resonance dependence are described and compared, and an optimal solution is proposed.Theory and MethodsAn Algebraic Solution (AS) that complements a previously described Geometric Solution (GS) is derived from four phase‐cycled bSSFP datasets. A composite Geometric‐Algebraic Solution (GAS) is formed from a noise‐variance‐weighted average of the AS and GS images. Two simulations test the solutions over a range of parameters, and phantom and in vivo experiments are implemented. Image quality and performance of the GS, AS, and GAS are compared with the complex sum and a numerical parameter estimation algorithm.ResultsThe parameter estimation algorithm, GS, AS, and GAS remove most banding and signal modulation in bSSFP imaging. The variable performance of the GS and AS on noisy data justifies generation of the GAS, which consistently provides the highest performance.ConclusionThe GAS is a robust technique for bSSFP signal demodulation that balances the regional efficacy of the GS and AS to remove banding, a feat not possible with prevalent techniques. Magn Reson Med 77:644–654, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance
Authors: Pinheiro Luis , Blake Kevin , Januskiene Justina , Yue Qun‐Ying , Arlett Peter 
Published: March 2016

AbstractPurposeClinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMA's database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities.MethodsEV was queried for reports of respiratory ADRs coded using MedDRA for the period 1994–2014 for all medicinal products. Descriptive statistics and non‐parametric (chi‐square) independence tests were produced to compare reporting of ILD from Japan versus the rest of the world.ResultsAs of 31 December 2014, there were 26 551 case reports of ILD in EV of which 17 526 (66%) originated in Japan. The reporting rate of ILD for Japan has been consistently higher over the period. The odds that a case report from Japan in EV refers to ILD is OR = 20.7, 95% CI 20.2, 21.3 (p < 0.001), compared to OR = 0.60, 95% CI 0.54, 0.67 (p < 0.001) for pulmonary fibrosis.ConclusionsA geographic imbalance between Japan and the rest of the world in reporting respiratory ADRs as ILD is confirmed. Consequently, the PRAC has developed approaches to address this in relation to signals of ILD it assesses to allow for more targeted risk minimisation including updates to the product information in the EU setting. Copyright © 2016 John Wiley & Sons, Ltd.
New depression diagnosis following prescription of codeine, hydrocodone or oxycodone
Authors: Scherrer Jeffrey F. , Salas Joanne , Bucholz Kathleen K. , Schneider F. David , Burroughs Thomas , Copeland Laurel A. , Sullivan Mark D. , Lustman Patrick J. 
Published: March 2016

AbstractPurposeLonger duration of prescription opioid use is associated with risk of major depression after controlling for daily morphine equivalent dose and pain. It is not known if risk of depression varies as a function of the type of opioid prescribed.MethodsA retrospective cohort design was used to model onset of new depression diagnosis among 11 462 Veterans Health Administration (VA) patients who were prescribed only codeine, only hydrocodone or only oxycodone for >30 days. Patients were free of prevalent opioid use and depression at baseline (2000–2001). Follow‐up was 2002–2012. Propensity scores and weighting were used to balance covariates across opioid type. Cox‐proportional hazard models were computed, using weighted data and additional adjustment for morphine equivalent dose (MED), duration of use, and pain after opioid initiation, to estimate the risk of new depression diagnosis among patients prescribed only codeine, only oxycodone vs. those prescribed only hydrocodone.ResultsAfter controlling for confounding, we observed that patients prescribed codeine, compared to hydrocodone, were significantly more likely to have a new depression diagnosis (HR = 1.27; 95%CI: 1.12–1.43). Oxycodone was significantly associated with onset of new depression diagnosis when exposure was modeled as total days exposed in post‐hoc analysis, but not when exposure was duration of incident period of use.ConclusionsAlthough codeine is a less potent opioid, after controlling for MED, chronic use of this agent is associated with nearly a 30% greater risk of depression compared to hydrocodone. Additional research is needed to determine the mechanisms for this association. Copyright © 2016 John Wiley & Sons, Ltd.
Structural and biochemical insights into 7β‐hydroxysteroid dehydrogenase stereoselectivity
Authors: Savino Simone , Ferrandi Erica Elisa , Forneris Federico , Rovida Stefano , Riva Sergio , Monti Daniela , Mattevi Andrea 
Published: March 2016

ABSTRACTHydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo‐ and regio‐selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β‐hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active‐site accessibility, the bases of the specificity for NADP+, and the general architecture of the steroid binding site. Comparison with 7α‐hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C‐terminal extension reshapes the substrate site of the β‐selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859–865. © 2016 Wiley Periodicals, Inc.
Downregulation of the Ca2+‐activated K+ channel KCa3.1 by histone deacetylase inhibition in human breast cancer cells
Authors: Ohya Susumu , Kanatsuka Saki , Hatano Noriyuki , Kito Hiroaki , Matsui Azusa , Fujimoto Mayu , Matsuba Sayo , Niwa Satomi , Zhan Peng , Suzuki Takayoshi , Muraki Katsuhiko 
Published: March 2016

AbstractThe intermediate‐conductance Ca2+‐activated K+ channel KCa3.1 is involved in the promotion of tumor growth and metastasis, and is a potential therapeutic target and biomarker for cancer. Histone deacetylase inhibitors (HDACis) have considerable potential for cancer therapy, however, the effects of HDACis on ion channel expression have not yet been investigated in detail. The results of this study showed a significant decrease in KCa3.1 transcription by HDAC inhibition in the human breast cancer cell line YMB‐1, which functionally expresses KCa3.1. A treatment with the clinically available, class I, II, and IV HDAC inhibitor, vorinostat significantly downregulated KCa3.1 transcription in a concentration‐dependent manner, and the plasmalemmal expression of the KCa3.1 protein and its functional activity were correspondingly decreased. Pharmacological and siRNA‐based HDAC inhibition both revealed the involvement of HDAC2 and HDAC3 in KCa3.1 transcription through the same mechanism. The downregulation of KCa3.1 in YMB‐1 was not due to the upregulation of the repressor element‐1 silencing transcription factor, REST and the insulin‐like growth factor‐binding protein 5, IGFBP5. The significant decrease in KCa3.1 transcription by HDAC inhibition was also observed in the KCa3.1‐expressing human prostate cancer cell line, PC‐3. These results suggest that vorinostat and the selective HDACis for HDAC2 and/or HDAC3 are effective drug candidates for KCa3.1‐overexpressing cancers.
Chemical synthesis and characterization of elastin‐like polypeptides (ELPs) with variable guest residues
Authors: Aladini Firouzeh , Araman Can , Becker Christian F. W. 
Published: March 2016

The properties of elastin‐like polypeptides (ELPs), specifically the fact that they are soluble in aqueous buffers below and aggregate reversibly above a well‐defined transition temperature, are extensively used for protein purification, enzyme recycling, and more recently, for in vivo applications such as drug delivery and tissue engineering. ELPs are artificial but biocompatible polypeptides composed of pentameric repeats (Val‐Pro‐Gly‐Xaa‐Gly) containing different guest residues Xaa, derived from mammalian elastin. The temperature‐dependent aggregation and desaggregation of ELPs is controlled by composition of the pentameric repeats as well as the number of repetitive units within the ELP. External parameters such as ELP concentration, pH, and most importantly, salt effects heavily influence the transition temperature.Here, we explore the chemical synthesis of a series of 51mer peptides consisting of 10 pentameric ELP repeats with hydrophobic as well as charged guest residues such as isoleucine, leucine, alanine, lysine, and/or glutamate all prepared by Boc‐based solid phase peptide synthesis. These guest residues expand the available toolbox of synthetic ELPs and provide ELPs that can be chemically modified and tuned to specific environments. An N‐terminal cysteine is added allowing disulfide‐based crosslinking of ELPs and to link synthetic ELPs to a recombinantly produced protein using native chemical ligation. Transition temperatures of all synthetic ELPs and the fusion construct were determined by measuring turbidity in solution and spanned a large temperature range between 25 and 70 °C, providing synthetically accessible ELPs with transition temperatures suitable for in vitro and in vivo applications. Cycling between their soluble and aggregate state has been observed at least 6 times without significant loss of material for all synthetic ELPs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Experimental investigation of bearing slip in a wind turbine gearbox during a transient grid loss event
Authors: Helsen J. , Guo Y. , Keller J. , Guillaume P. 
Published: March 2016

AbstractThis work investigates the behaviour of the high‐speed stage of a wind turbine gearbox during a transient grid loss event. Dynamometer testing on a full‐scale wind turbine nacelle is used. A combination of external and internal gearbox measurements are analysed. Particular focus is on the characterization of the high‐speed shaft tapered roller bearing slip behaviour. This slipping behaviour is linked to dynamic events by many researchers and described as a potential bearing failure initiator; however, only limited full‐scale dynamic testing is documented. Strain gauge bridges in grooves along the circumference of the outer ring are used to characterize the bearing behaviour in detail. It is shown that during the transient event the high‐speed shaft experiences a combined torsional and bending deformation. These unfavourable loading conditions induce roller slip in the bearings during the torque reversals, indicating the potential of the applied load case to go beyond the preload of the tapered roller bearing. Copyright © 2016 John Wiley & Sons, Ltd.
Nanoparticles and radiotracers: advances toward radionanomedicine
Authors: Pratt Edwin C. , Shaffer Travis M. , Grimm Jan 
Published: March 2016

In this study, we cover the convergence of radiochemistry for imaging and therapy with advances in nanoparticle (NP) design for biomedical applications. We first explore NP properties relevant for therapy and theranostics and emphasize the need for biocompatibility. We then explore radionuclide‐imaging modalities such as positron emission tomography (PET), single‐photon emission computed tomography (SPECT), and Cerenkov luminescence (CL) with examples utilizing radiolabeled NP for imaging. PET and SPECT have served as diagnostic workhorses in the clinic, while preclinical NP design examples of multimodal imaging with radiotracers show promise in imaging and therapy. CL expands the types of radionuclides beyond PET and SPECT tracers to include high‐energy electrons (β−) for imaging purposes. These advances in radionanomedicine will be discussed, showing the potential for radiolabeled NPs as theranostic agents. WIREs Nanomed Nanobiotechnol 2016, 8:872–890. doi: 10.1002/wnan.1402This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Leaf C:N:P stoichiometrical and morphological traits of Haloxylon ammodendron over plantation age sequences in an oasis‐desert ecotone in North China
Authors: Zhang Ke , Su Yong‐Zhong , Liu Ting‐Na , Wang Ting 
Published: March 2016

AbstractHaloxylon ammodendron, a typical C4 desert shrub, is widely used in vegetation reestablishment programs to stabilize shifting sand dunes and to control shifting sands encroaching into oases in the oasis‐desert ecotones in northwestern China. In this study, we investigated the morphological traits and analyzed leaf carbon (C), nitrogen (N), and phosphorus (P) stoichiometrical characteristics in an age sequence of 2‐, 5‐, 9‐, 13‐, 16‐, 31‐, and 39‐year old H. ammodendron plantations, to assess their growth development and degeneration processes. Results showed that the height, stem diameter, and canopy increased rapidly in the early establishment stage (2–9 years), and thereafter, showed a slower increase from 13 to 39 years. The leaf C and N concentrations and N:P ratio showed a rapid increase from ages 2–5, but C:N exhibited a significant decline. After 5 years, plantation leaf C, N, C:N, and N:P were stable, and leaf P and C:P showed no significant difference among all plantation ages. Leaf C and N concentrations were mainly affected by soil properties. Limiting nutrient factors in soil changed from nitrogen before 2 years to phosphorus after 5 years. The findings suggested that leaf stoichiometrical characteristics combined with morphological traits can be used to reflect the degeneration trend of H. ammodendron. Further research is needed to reveal the processes and mechanisms of H. ammodendron growth development and degeneration, and its adaption to the soil environment.
The red meat allergy syndrome in Sweden
Authors: Apostolovic Danijela , Tran Thi Anh Thu , Starkhammar Maria , Sánchez-Vidaurre Sara , Hamsten Carl , Van Hage Marianne 
Published: March 2016

Summary
In the last decade, a novel type of food allergy presenting with severe allergic reactions several hours after consumption of red meat has been recognized. The allergic responses are due to IgE antibodies directed against the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) found in mammalian meat. This review presents the red meat allergy syndrome in Sweden, discusses the features of the immune response to carbohydrates, and highlights the presence of heat stable α-Gal-containing proteins in meat.
The number of diagnosed red meat allergy cases in Sweden has increased significantly over the past few years. All patients have been tick bitten. Our recent work has shown that α-Gal is present in the European tick Ixodes ricinus (I. ricinus), thus potentially explaining the strong association between anti-α-Gal IgE and tick bites, with development of red meat allergy as a secondary phenomenon. Further studies using immunoproteomics have identified novel α-Gal-containing meat proteins that bound IgE from red meat allergic patients. Four of these proteins were stable to thermal processing pointing to the fact that the allergenicity of red meat proteins is preserved in cooked meat. In keeping with the fact that the α-Gal epitope is structurally related to the blood group B antigen, a positive association with the B-negative blood groups among our red meat allergic patients was noted. A selective IgE reactivity to the pure carbohydrate moiety was observed when investigating the specificity of the α-Gal immune response. IgE from red meat allergic patients does not recognize the other major mammalian carbohydrate, N-glycolylneuraminic acid (Neu5Gc), also present in high amounts in red meat. Furthermore, neither common cross-reactive carbohydrate determinants (CCDs) from plants nor venoms are targets of the IgE response in these patients.
Taken together, the α-Gal carbohydrate has shown to be a potentially clinically relevant allergen that should be taken into account in the diagnosis of food allergy. Many new findings in the field of red meat allergy have been obtained during the past years, but further efforts to understand the process of digestion, absorption, and delivery of α-Gal-containing molecules to the circulation are needed.
Characteristics of a supersonic elliptic jet
Authors: Aravindh Kumar S.M. , Rathakrishnan E. 
Published: March 2016

ABSTRACTComparative mixing of a Mach 2 elliptical free jet from a convergent-divergent elliptic nozzle with an aspect ratio of 2:1 in the presence of adverse and marginally favourable pressure gradients has been studied experimentally. It is found that the mixing of the elliptical jet is higher than that for the equivalent circular jet at all the levels of expansion. The decay of elliptic jet is significantly higher than the equivalent circular jet in all three zones of the jet field – the core, characteristic decay and fully developed regions. The reason for the faster decay of the elliptic jet is found to be the continuous variation in the size of the mixing-promoting vortices shed from the nozzle exit owing to its azimuthal asymmetry. The evolution of the jet and its axis-switching phenomenon has been studied using iso-pitot pressure contours taken at different axial locations in the plane normal to the jet axis. As expected, the elliptic jet spreads faster along the minor axis plane than the major axis plane, leading to axis-switching at all the levels of expansion studied. The axis-switching of the elliptic jet shifts upstream with increase in nozzle pressure ratio (NPR) from 4 to 5; from 5 to 7, it shifts downstream. But at marginally under-expanded condition of NPR 8, the axis-switching is found to shift slightly upstream. The occurrence of axis-switching in the elliptic jet indicates enhanced near-field mixing, compared to the equivalent circular jet. The shadowgraph pictures of the jet reveal that the waves prevailing in the elliptic jet are significantly weaker than those in the circular jet.
Toolkit for Epidemiologic Response to an Acute Chemical Release
Authors: Duncan Mary Anne , Orr Maureen F. 
Published: March 2016

AbstractWhen a large chemical incident occurs and people are injured, public health agencies need to be able to provide guidance and respond to questions from the public, the media, and public officials. Because of this urgent need for information to support appropriate public health action, the Agency for Toxic Substances and Disease Registry (ATSDR) of the US Department of Health and Human Services has developed the Assessment of Chemical Exposures (ACE) Toolkit. The ACE Toolkit, available on the ATSDR website, offers materials including surveys, consent forms, databases, and training materials that state and local health personnel can use to rapidly conduct an epidemiologic investigation after a large-scale acute chemical release. All materials are readily adaptable to the many different chemical incident scenarios that may occur and the data needs of the responding agency. An expert ACE team is available to provide technical assistance on site or remotely. (Disaster Med Public Health Preparedness. 2016;10:631–632)
Connectedness properties of the set where the iterates of an entire function are unbounded
Authors: OSBORNE J. W. , RIPPON P. J. , STALLARD G. M. 
Published: March 2016

We investigate the connectedness properties of the set$I^{\!+\!}(f)$of points where the iterates of an entire function$f$are unbounded. In particular, we show that$I^{\!+\!}(f)$is connected whenever iterates of the minimum modulus of$f$tend to$\infty$. For a general transcendental entire function $f$, we show that$I^{\!+\!}(f)\cup \{\infty \}$is always connected and that, if$I^{\!+\!}(f)$is disconnected, then it has uncountably many components, infinitely many of which are unbounded.