bluuebunny/crossref_metadata_2025 huggingface dataset:
Association study of polymorphism in the serotonin transporter gene promoter, methylation profiles, and expression in patients with major depressive disorder
Authors: Iga Jun‐ichi , Watanabe Shin‐ya , Numata Shusuke , Umehara Hidehiro , Nishi Akira , Kinoshita Makoto , Inoshita Masatoshi , Shimodera Shinji , Fujita Hirokazu , Ohmori Tetsuro
Published: March 2016

The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT‐linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r = 0.40, p = 0.035, controls: p = 0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 ± 0.24, controls: 4.70 ± 0.19, unpaired t‐test, p = 0.04). 5HTT expression using real‐time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright © 2016 John Wiley & Sons, Ltd.
The challenge of predicting problematic chemicals using a decision analysis tool: Triclosan as a case study
Authors: Perez Angela L , Gauthier Alison M , Ferracini Tyler , Cowan Dallas M , Kingsbury Tony , Panko Julie
Published: March 2016

Manufacturers lack a reliable means for determining whether a chemical will be targeted for deselection from their supply chain. In this analysis, 3 methods for determining whether a specific chemical (triclosan) would meet the criteria necessary for being targeted for deselection are presented. The methods included a list-based approach, use of a commercially available chemical assessment software tool run in 2 modes, and a public interest evaluation. Our results indicated that triclosan was included on only 6 of the lists reviewed, none of which were particularly influential in chemical selection decisions. The results from the chemical assessment tool evaluations indicated that human and ecological toxicity for triclosan is low and received scores indicating that the chemical would be considered of low concern. However, triclosan's peak public interest tracked several years in advance of increased regulatory scrutiny of this chemical suggesting that public pressure may have been influential in deselection decisions. Key data gaps and toxicity endpoints not yet regulated such as endocrine disruption potential or phototoxicity, but that are important to estimate the trajectory for deselection of a chemical, are discussed. Integr Environ Assess Manag 2017;13:198–207. © 2016 SETAC

Key Points

Triclosan appears on 6 out of 122 or 5% of state, federal, and international regulatory and authoritative chemicals lists. The pros and cons of chemical analysis software to predict deselection are discussed. Despite receiving a “green” score of 93% using chemical analysis software, triclosan was marked for deselection based on possible human endocrine effects and aquatic toxicity. Several examples and case studies are presented for other chemicals where “green” grades were computed including 2 other widely used microbiocide chemicals that scored significantly lower than triclosan in their “Green Grade” with scores of 77% and 78%.
Effect of hyaluronic acid in bone formation and its applications in dentistry
Authors: Zhao Ningbo , Wang Xin , Qin Lei , Zhai Min , Yuan Jing , Chen Ji , Li Dehua
Published: March 2016

Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory‐based experiments and clinical applications will be achieved in the next few years. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560–1569, 2016.
Malaria sporozoite protein expression enhances baculovirus‐mediated gene transfer to hepatocytes
Authors: Tamura Takahiko , Kawabata Chiaki , Matsushita Shunsuke , Sakaguchi Miako , Yoshida Shigeto
Published: March 2016

Background

Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte‐specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin‐related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity.

Methods

BVs displaying an ectodomain consisting of three different CSP variants (full‐length, N‐terminal and C‐terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated.

Results

We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus.

Conclusions

BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte‐specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.
An Old Man and The “Sea of Leadership”
Authors: Andersen Jon Aarum
Published: March 2016

Leadership has been a scientific discipline for over 100 years. The magnitude of research has increased tremendously. Many different objects of study related to leadership have been investigated with the ambition to solve a variety of problems that appear to be more or less relevant for those in leadership positions. In the current article, the author provides one person's description of eight specific areas of leadership scholarship throughout all these years and how he has reflected upon these theories in light of this fundamental question: what has leadership research really accomplished? These considerations on leadership theories are a product of a lifetime spent on leadership research.
Rediscovering Deep Time: Sustainability and the Need to Re‐Engage With Multiple Dimensions of Time in Leadership Studies
Authors: Satterwhite Rian , Sheridan Kate , Miller Whitney McIntyre
Published: March 2016

The current article makes the case that increasing our comfort with and responsiveness to extended timescales—both the far future and past—is essential to leadership against the backdrop of wicked challenges that shape the current and future leadership landscape. We offer a loose structure of four dimensions of time—present, near, distant, and deep time—to help advance this work. We frequently fail in thinking about the broader impact of our leadership work for generations to come and to ground that work in our extended, collective history. In order to think about lasting leadership, and particularly when utilizing a framework of sustainability and peace, it is essential that we critically examine our relationship with time and better incorporate it into our leadership theory, practice, development, and education. We need to further develop our ability to relate to and make sound decisions based on an informed consideration of the futures we wish to create and the deep histories that have led us to where we are now.
Climate Change Leadership as Sustainability Leadership: From the C‐Suite to the Conference of the Parties
Authors: Gallagher Deborah R.
Published: March 2016

Corporate leaders are increasingly called to enact roles as climate change leaders because of escalating risks to production and operations from man‐made climate change. An examination of corporate leaders’ roles within a United Nations Global Compact initiative, Carbon Pricing Champions, shows that three core practices were critical in advancing climate change leadership efforts: securing and maintaining top leader support, embedding the work within the organizational culture, and collaborating with like‐minded companies.
Myocardial extracellular volume fraction measurement in chronic total coronary occlusion: Association with myocardial injury, angiographic collateral flow, and functional recovery
Authors: Chen Yin‐yin , Ren Dao‐yuan , Zeng Meng‐su , Yang Shan , Yun Hong , Fu Cai‐xia , Ge Jun‐bo , Jin Hang , Qian Ju‐ying , Zhang Wei‐guo
Published: March 2016

Purpose

To investigate whether myocardial extracellular volume fraction (ECV) measurement by cardiac MR is indicative of myocardial injury, angiographic collateral flow, and functional recovery in patients with chronic total coronary occlusion (CTO).

Materials and Methods

A total of 50 CTO patients undergoing 1.5 Tesla MR were prospectively enrolled, and 28 underwent a second MR 6 months after revascularization. T1‐mapping based indices, including pre‐ and postcontrast T1 values and ECV, were obtained from infarcted and non‐infarcted myocardium, myocardial segments, and coronary territory. The severity of myocardial injury was rated by transmurality extent of infarction (TEI) and regional wall motion abnormalities (RWMA) score. Angiographic collateral flow was evaluated using Rentrop classification. Improvement in segmental wall motion at 6 months was also assessed.

Results

ECV and postcontrast T1 value significantly outperformed precontrast T1 value for identifying myocardial infarction (area under the receiver operating characteristic curve [AUC]: 0.998 and 0.953 versus 0.824, all P < 0.02). Myocardial ECV was strongly correlated with TEI (P = 0.000), RWMA score (P = 0.000), and collateral classification (P = 0.007 for left anterior descending artery [LAD] territory, P = 0.001 for non‐LAD territory). Furthermore, the likelihood of functional recovery was better predicted by ECV than by late gadolinium enhancement (LGE) (AUC: 0.76 versus 0.68, P < 0.02).

Conclusion

Myocardial ECV may be a useful surrogate to assess myocardial injury and angiographic collateral flow in CTO, and ECV provides incremental value to LGE in assessing functional recovery after revascularization. J. MAGN. RESON. IMAGING 2016;44:972–982.
Variability and bias assessment in breast ADC measurement across multiple systems
Authors: Keenan Kathryn E. , Peskin Adele P. , Wilmes Lisa J. , Aliu Sheye O. , Jones Ella F. , Li Wen , Kornak John , Newitt David C. , Hylton Nola M.
Published: March 2016

Purpose

To assess the ability of a recent, anatomically designed breast phantom incorporating T1 and diffusion elements to serve as a quality control device for quantitative comparison of apparent diffusion coefficient (ADC) measurements calculated from diffusion‐weighted MRI (DWI) within and across MRI systems.

Materials and Methods

A bilateral breast phantom incorporating multiple T1 and diffusion tissue mimics and a geometric distortion array was imaged with DWI on 1.5 Tesla (T) and 3.0T scanners from two different manufacturers, using three different breast coils (three configurations total). Multiple measurements were acquired to assess the bias and variability of different diffusion weighted single‐shot echo‐planar imaging sequences on the scanner‐coil systems.

Results

The repeatability of ADC measurements was mixed: the standard deviation relative to baseline across scanner‐coil‐sequences ranged from low variability (0.47, 95% confidence interval [CI]: 0.22–1.00) to high variability (1.69, 95% CI: 0.17–17.26), depending on material, with the lowest and highest variability from the same scanner‐coil‐sequence. Assessment of image distortion showed that right/left measurements of the geometric distortion array were 1 to 16% larger on the left coil side compared with the right coil side independent of scanner‐coil systems, diffusion weighting, and phase‐encoding direction.

Conclusion

This breast phantom can be used to measure scanner‐coil‐sequence bias and variability for DWI. When establishing a multisystem study, this breast phantom may be used to minimize protocol differences (e.g., due to available sequences or shimming technique), to correct for bias that cannot be minimized, and to weigh results from each system depending on respective variability. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:846–855.
Perirenal lymphatic systems: Evaluation using spectral presaturation with inversion recovery T2‐weighted MR images with 3D volume isotropic turbo spin‐echo acquisition at 3.0T
Authors: Matsumoto Shunro , Mori Hiromu , Kiyonaga Maki , Yamada Yasunari , Takaji Ryo , Sato Fuminori , Mimata Hiromitsu , Hijiya Naoki , Moriyama Masatsugu , Tanoue Rika , Tomonari Kenichiro , Matsumoto Tomohiro , Hasebe Terumitsu
Published: March 2016

Purpose

To evaluate the normal anatomy of the perirenal lymphatics using spectral presaturation with inversion recovery (SPIR) T2‐weighted magnetic resonance imaging (MRI) with 3D volume isotropic turbo spin‐echo acquisition (VISTA) at 3.0T.

Materials and Methods

This retrospective study was approved by the two Institutional Review Boards and informed consent was waived. Thin‐collimated axial images obtained using SPIR T2‐weighted MR imaging sequences with 3D VISTA at 3.0T from 50 patients (100 kidneys) with normal renal function were retrospectively reviewed. The perirenal lymphatic vessels were defined as fluid signal intensity structures on this MRI sequence. Two readers independently assessed the degree of visualization of the perirenal lymphatics using a 4‐point scale in four anatomical regions, including the renal hilar, capsular, communicating pericapsular, and subfascial lymphatics, and interobserver agreement was evaluated with weighted kappa statics. The detectability of each lymphatic system was calculated for each reader using confidence level ratings of grades 1 and 2 as positive and grades 3 and 4 as negative.

Results

Interobserver agreement for the visualization grades was almost perfect (kappa value = 0.9). The renal hilar lymphatics along the renal vein were clearly identified in all patients. The detectability of other perirenal lymphatics was 44% for the capsular lymphatics, 39% for communicating pericapsular lymphatics, and 22% for the subfascial lymphatics. There was no laterality regarding the detectability of the perirenal lymphatics.

Conclusion

The findings of this study support the feasibility of SPIR T2‐weighted MR images with 3D‐VISTA at 3.0T for evaluating the perirenal lymphatic systems. J. MAGN. RESON. IMAGING 2016;44:897–905.
Genetic diversity among human parainfluenza virus type 2 isolated in Croatia between 2011 and 2014
Authors: Šantak Maja , Slović Anamarija , Ljubin‐Sternak Sunčanica , Mlinarić Galinović Gordana , Forčić Dubravko
Published: March 2016

The dynamics and evolution of the human parainfluenza virus type 2 (HPIV2) in Croatia, and also globally, are largely unknown. Most HPIV2 infections are treated symptomatically outside the hospital setting. Thus, the diagnosis is missing making it difficult to follow the genetic variation and evolution of the HPIV2. This study explores hospitalized HPIV2 cases in Croatia during 4‐year period (2011–2014). Most cases in this period were reported in October or November (68.75%) and most of patients were under 2 years of age (81.25%). For molecular analyses, we used the F and HN gene sequences and showed that although both regions are equally suitable for phylogenetic analyses it would be advantageous to use regions longer than 2 kb for HPIV2 analyses of isolates which are spatially and temporally closely related. We show here that the dominant cluster in this area was cluster G3 while only one strain isolated in this period was positioned in the distant cluster G1a. Further monitoring of the HPIV2 will determine whether cluster G3 will remain dominant or it will be overruled by cluster G1a. This will be important for the surveillance of virus circulation in population and significance of the viral infection. J. Med. Virol. 88:1733–1741, 2016. © 2016 Wiley Periodicals, Inc.
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

Background

The 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.

Methods

Patients 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.

Results

Two 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.

Conclusions

mGPS 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.
Separation and identification of phenolic compounds in Bidens pilosa L. by ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry
Authors: Liang Xianrui , Xu Qiao
Published: March 2016

A validated method based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was established to separate and identify phenolic compounds in Bidens pilosa L. Mass spectrometry experiments were performed both in positive and negative ion modes. A total of 35 compounds were detected, and 26 phenolic compounds were unequivocally identified or tentatively assigned based on retention time, maximum UV absorption, molecular formula, and fragments. The ultra high performance liquid chromatography method was validated and showed good linearity (R2 ≧ 0.9996) over the test range. The limits of detection and quantification were above 0.072 and 0.162 μg/mL, respectively. The relative standard deviations of intraday and interday precision were below 0.3 and 1.6%, respectively.
Enrichment and determination of polybrominated diphenyl ethers in environmental water samples by magnetic solid‐phase extraction with core–shell magnetic carbon microspheres before gas chromatography with mass spectrometry
Authors: Zhou Jia‐Bin , She Xiao‐Kun , Xing Han‐Zhu , Wang Xia , Zhao Ru‐Song
Published: March 2016

Core–shell magnetic carbon microspheres were synthesized by a simple hydrothermal method and used as a novel magnetic solid‐phase extraction adsorbent for the sensitive determination of polybrominated diphenyl ethers in environmental water samples. Gas chromatography with negative chemical ionization mass spectrometry was adopted for the detection. Box–Behnken design was used to investigate and optimize important magnetic solid‐phase extraction parameters through response surface methodology. Under the optimal conditions, low limits of detection (0.07–0.17 ng·L−1), a wide linear range (1–1000 ng·L−1), and good repeatability (0.80–4.58%) were achieved. The developed method was validated with several real water samples, and satisfactory results were obtained in the range of 72.8–97.9%. These results indicated that core–shell magnetic carbon microspheres have great potential as an adsorbent for the magnetic solid‐phase extraction of polybrominated diphenyl ethers at trace levels from environmental water samples.
PolyGuanine methacrylate cryogels for ribonucleic acid purification
Authors: Köse Kazım , Uzun Lokman
Published: March 2016

The isolation and purification of ribonucleic acid have attracted attention recently for the understanding of the functions in detail because of the necessity for the treatment of genetic diseases. In this study, guanine‐incorporated polymeric cryogels were developed to obtain highly purified ribonucleic acid. The satisfactory purification performance was achieved with the guanine‐incorporated poly (2‐hydroxyethyl methacrylate‐guanine methacrylate) cryogels. The most crucial advantages to use guanine as a functional monomer are to obtain a real natural interaction between guanine on the polymeric material and cytosine on the ribonucleic acid. Moreover, using cryogel with a highly porous structure and high swelling ratio provide advantages of getting more water within the structure to get more analyte to interact. The characterization of cryogels has proved the success of the synthesis and the perfect natural interaction to be taken place between the ligand (guanine methacrylate) and the cytosine in the ribonucleic acid molecules. Although the pores within the structure of cryogels are small, they provide efficient and fast adsorption. The chromatographic separation performance was investigated for different conditions (pH, temperature etc.). The desorption ratio and reusability were also analyzed at the end of the five adsorption–desorption cycles with no significant changes.
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

Scope

We 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 results

By 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.

Conclusion

SSBb 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

Purpose

Balanced 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 Methods

An 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.

Results

The 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.

Conclusion

The 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

Purpose

Clinically, 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.

Methods

EV 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.

Results

As 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.

Conclusions

A 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

Purpose

Longer 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.

Methods

A 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.

Results

After 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.

Conclusions

Although 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.
Processed stigmas of Crocus sativus L. imaged by MALDI‐based MS
Authors: Pittenauer Ernst , Rados Edita , Koulakiotis Nikolaos‐Stavros , Tsarbopoulos Anthony , Allmaier Günter
Published: March 2016

The processed, i.e. dried under certain conditions, stigmas of Crocus sativus L. are one of the most expensive plant parts used commercially. For the color, aroma and biological activity a very complex mixture of glycolipids termed crocins are responsible. Therefore studying structural composition and distribution in the commercial plant material is of great interest. We showed successfully the application of a MALDI‐based mass spectrometric imaging (MSI) approach for stigmas towards different crocin species. MSI opens up the investigation of processed plant materials in various fields allowing studying the processing in detail as well as adulteration attempts (which are quite frequent due to the price of the material). Furthermore, we could demonstrate that a similar number of crocins present in stigmas could be detected by MALDI MSI compared to the classical approach of analyzing the solvent‐extract of stigmas by MALDI‐MS.
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

Hydroxysteroid 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

The 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.
A New Ba0.6Sr0.4TiO3–Silicon Hybrid Metamaterial Device in Terahertz Regime
Authors: Wu Liang , Du Ting , Xu Ningning , Ding Chunfeng , Li Hui , Sheng Quan , Liu Ming , Yao Jianquan , Wang Zhiyong , Lou Xiaojie , Zhang Weili
Published: March 2016

Metamaterials, offering unprecedented functionalities to manipulate electromagnetic waves, have become a research hotspot in recent years. Through the incorporation of active media, the exotic electromagnetic behavior of metamaterials can be dramatically empowered by dynamic control. Many ferroelectric materials such as BaSrTiO3 (abbreviated as BST), exhibiting strong response to external electric field, hold great promise in both microwave and terahertz tunable devices. A new active Ba0.6Sr0.4TiO3–silicon hybrid metamaterial device, namely, a SRR (square split‐ring resonator)–BaSrTiO3 thin film‐silicon three‐layer structure is fabricated and intensively studied. The active Ba0.6Sr0.4TiO3 thin film hybrid metamaterial, with nanoscale thickness, delivers a transmission contrast up to ≈79% due to electrically enabled carrier transport between the ferroelectric thin film and silicon substrate. This work has significantly increased the low modulation rate of ferroelectric based devices in terahertz range, a major problem in this field remaining unresolved for many years. The proposed BST metamaterial is promising in developing high‐performance real world photonic devices for terahertz technology.
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

This 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.1402

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Measurement of relative line intensities for L‐shell X‐rays from selected elements between Z = 68 (Er) and Z = 79 (Au)
Authors: Ganly Brianna , Van Haarlem Yves , Tickner James
Published: March 2016

Relative line intensities of L1, L2 and L3 sub‐shell X‐rays were measured for Er, Tm, Yb, Hf, Ta, W, Pt and Au. The L‐shell X‐ray spectra were recorded by exciting pure element samples (eight cases) and oxide samples (two cases) with approximately 17‐keV exciting radiation from a filtered X‐ray tube source, and measuring the fluorescence spectra with a silicon drift detector. The spectra were carefully fitted to determine line energies and intensities, accounting for Lorentzian line broadening, incomplete charge collection and escape effects. A Monte Carlo approach was used to calculate attenuation and detector efficiency corrections. We report up to 15 line intensity ratios for each element and compare these to Scofield's theoretical predictions and Elam's extrapolated experimental database. Our measured relative line intensities agree best with Elam's data, but overall we find significant discrepancies with previously reported results. For the element Ta, we also find significant errors in the accepted L‐shell line energies in the widely used National Institute of Standard and Technology (NIST) database. Our results highlight the need for an experimental and theoretical re‐evaluation of L‐shell intensity databases to support high‐accuracy X‐ray analysis methods such as X‐ray fluorescence and particle‐induced X‐ray emission. Copyright © 2016 John Wiley & Sons, Ltd.
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

Haloxylon 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

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

Comparative 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.