bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐dose dobutamine stress steady‐state free precession (SSFP) cine MRI at 3T with patient adaptive local radiofrequency (RF) shimming using dual‐source RF transmission
Authors: Berger Alexander , Schnackenburg Bernhard , Schneeweis Christopher , Kelle Sebastian , Klein Christoph , Kouwenhoven Marc , Fleck Eckart , Gebker Rolf
Published: February 2015

Purpose

To prospectively assess the feasibility, image quality, and diagnostic accuracy of high‐dose dobutamine stress magnetic resonance imaging (DSMR) using steady‐state free precession (SSFP) cine imaging at 3T applying a dual‐source radiofrequency (RF) excitation magnetic resonance imaging (MRI) system with parallel transmission and patient adaptive local RF shimming.

Materials and Methods

DSMR using SSFP cine imaging was performed in 44 patients at 3T scheduled for a clinically indicated coronary angiography. The effect of conventional versus dual‐source RF transmission was assessed regarding homogeneity of the B1 field, contrast‐to‐noise ratios (CNRs) at rest, image quality, and diagnostic accuracy of DSMR using long and short axis.

Results

The mean percentage of the intended flip angle within the heart increased from 88 ± 9.1% with single‐source to 103 ± 5.6% (P < 0.001) dual‐source RF transmission. CNR increased for dual‐source particularly at the apex (63.4 ± 24.2 vs. 36.5 ± 16.5, P < 0.001) but also at the base of the left ventricle (LV) (50.1 ± 14.8 vs. 39.3 ± 15.8, P < 0.001). Image quality of dual‐source was higher both at rest (2.8 ± 0.5 vs. 2.6 ± 0.7, P < 0.001) and stress (2.5 ± 0.7 vs. 2.0 ± 1.0, P < 0.001). The number of segments with severe artifacts or nondiagnostic image quality at stress was lower with dual‐source RF transmission (8% vs. 27%, P < 0.001). The diagnostic accuracy of DSMR in coronary territories using dual‐source RF transmission was significantly higher (77% vs. 65%, P = 0.04).

Conclusion

Patient adaptive local RF shimming using dual‐source RF transmission provided significantly improved image quality and higher diagnostic accuracy of SSFP during DSMR at 3T compared to conventional RF transmission. J. Magn. Reson. Imaging 2015;42:746–753.
Grape skin extracts from winemaking by‐products as a source of trapping agents for reactive carbonyl species
Authors: Sri Harsha Pedapati SC , Mesias Marta , Lavelli Vera , Morales Francisco J
Published: February 2015

BACKGROUND

Clinical evidence supports the relationship between carbonyl stress and type II diabetes and its related pathologies. Methylglyoxal (MGO) is the major dicarbonyl compound involved in carbonyl stress. Efforts are therefore being made to find dietary compounds from natural sources that could exert an MGO trapping response.

RESULTS

The in vitro MGO trapping capacity of six red and seven white grape skin extracts (GSE) obtained from winemaking by‐products was investigated. Methanolic GSE exhibited a promising MGO trapping capacity that was higher in red GSE (IC50 2.8 mg mL−1) when compared with white GSE (IC50 3.2 mg mL−1). The trapping ability for red GSE correlated significantly with total phenolic content and antioxidant capacity. However, no correlations were observed for white GSE, which suggests that other compounds were involved in the trapping activity.

CONCLUSION

GSE may be considered a natural source of carbonyl stress inhibitors, thus opening up its possible utilization as a nutraceutical ingredient. Further investigations are required to understand the mechanism involved in the carbonyl trapping ability of red and white grape skin samples and their relationship with glycation. © 2015 Society of Chemical Industry
Berry ripening, pre‐processing and thermal treatments affect the phenolic composition and antioxidant capacity of grape (Vitis vinifera L.) juice
Authors: Genova Giuseppe , Tosetti Roberta , Tonutti Pietro
Published: February 2015

BACKGROUND

Grape juice is an important dietary source of health‐promoting antioxidant molecules. Different factors may affect juice composition and nutraceutical properties. The effects of some of these factors (harvest time, pre‐processing ethylene treatment of grapes and juice thermal pasteurization) were here evaluated, considering in particular the phenolic composition and antioxidant capacity.

RESULTS

Grapes (Vitis vinifera L., red‐skinned variety Sangiovese) were collected twice in relation to the technological harvest (TH) and 12 days before TH (early harvest, EH) and treated with gaseous ethylene (1000 ppm) or air for 48 h. Fresh and pasteurized (78 °C for 30 min) juices were produced using a water bath. Three‐way analysis of variance showed that the harvest date had the strongest impact on total polyphenols, hydroxycinnamates, flavonols, and especially on total flavonoids. Pre‐processing ethylene treatment significantly increased the proanthocyanidin, anthocyanin and flavan‐3‐ol content in the juices. Pasteurization induced a significant increase in anthocyanin concentration. Antioxidant capacity was enhanced by ethylene treatment and pasteurization in juices from both TH and EH grapes.

CONCLUSION

These results suggest that an appropriate management of grape harvesting date, postharvest and processing may lead to an improvement in nutraceutical quality of juices. Further research is needed to study the effect of the investigated factors on juice organoleptic properties. © 2015 Society of Chemical Industry
Identification and molecular characterization of 48 kDa calcium binding protein as calreticulin from finger millet (Eleusine coracana) using peptide mass fingerprinting and transcript profiling
Authors: Singh Manoj , Metwal Mamta , Kumar Vandana A , Kumar Anil
Published: February 2015

BACKGROUND

Attempts were made to identify and characterize the calcium binding proteins (CaBPs) in grain filling stages of finger millet using proteomics, bioinformatics and molecular approaches.

RESULTS

A distinctly observed blue color band of 48 kDa stained by Stains‐all was eluted and analyzed as calreticulin (CRT) using nano liquid chromatography–tandem mass spectrometry (nano LC‐MS). Based on the top hits of peptide mass fingerprinting results, conserved primers were designed for isolation of the CRT gene from finger millet using calreticulin sequences of different cereals. The deduced nucleotide sequence analysis of 600 bp amplicon showed up to 91% similarity with CRT gene(s) of rice and other plant species and designated as EcCRT1. Transcript profiling of EcCRT1 showed different levels of relative expression at different stages of developing spikes. The higher expression of EcCRT1 transcripts and protein were observed in later stages of developing spikes which might be due to greater translational synthesis of EcCRT1 protein during seed maturation in finger millet.

CONCLUSIONS

Preferentially higher synthesis of this CaBP during later stages of grain filling may be responsible for the sequestration of calcium in endoplasmic reticulum of finger millet grains. © 2015 Society of Chemical Industry
Environmental Factors Governing Soil Water Repellency Dynamics in a Pinus Pinaster Plantation in NW Spain
Authors: Benito Rueda Elena , Rodríguez‐Alleres María , Varela Teijeiro Eufemia
Published: February 2015

Soil water repellency (SWR) is a dynamic property that changes throughout the year. The objective of this work was to identify the environmental factors governing the temporal patterns in SWR in a pine plantation in northwest Spain with a view of predicting its occurrence and persistence. For this purpose, 24 samples were collected from the soil surface (0–5 cm) at 25 different times over a 1‐year period and analysed for SWR by using water drop penetration time test and soil moisture measurements. Temporal variations in SWR exhibited a well‐defined seasonal pattern. The soil surface was largely wettable from late autumn to early spring and extremely water repellent during summer and early autumn. Repellency persistence was rather variable during spring. There was highly significant correlation between SWR and soil moisture content. The moisture range defining the presence or absence of repellency under field conditions was 22–57%. There were also significant correlations with the target variables (maximum temperature, minimum temperature, precipitation and water balance during variably long antecedent periods), with coefficients that increased with increasing length of the antecedent period considered. The moisture content of soil at the time of sampling and the average maximum temperature for the 28 days before sampling are the best predictors of occurrence of SWR and its persistence in different seasons. Copyright © 2015 John Wiley & Sons, Ltd.
Kinetic and Molecular Weight Modeling of Miniemulsion Polymerization Initiated by Oil‐Soluble Initiators
Authors: Shang Yue , Shan Guorong , Pan Pengju
Published: February 2015

A mathematical model for the miniemulsion polymerization initiated by oil‐soluble initiators is described in detail with comparisons to experiment results. The desorption of primary radicals and particle population balance are introduced to illustrate the distribution of radical per particles. The effects of different variable factors including the particle size, surfactant layer, initiator, and aqueous phase inhibitor are considered, and the model predictions coincide well with experiment results under different above‐mentioned conditions. The model is found to be useful in explaining the ongoing debate about the origin of effective radical in miniemulsion polymerization initiated by oil‐soluble initiators. It is found that the effective radicals are originated from the primary radicals desorbed from the particles, and the contribution of the small amount of initiator dissolved in the aqueous phase can be ignored.

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Polyethylene‐Assisted Exfoliation of Hexagonal Boron Nitride in Composite Fibers: A Combined Experimental and Computational Study
Authors: Meng Jiangsha , Tajaddod Navid , Cranford Steven W. , Minus Marilyn L.
Published: February 2015

A joint experimental and computational approach is used to explore the exfoliation mechanism for hexagonal boron nitride (h‐BN) in polyethylene (PE)/h‐BN composite fibers during hot‐drawing. A shear‐flow gel‐spinning apparatus is utilized to fabricate PE/h‐BN composite fibers with 11 wt% h‐BN loading. Different exfoliation states of the h‐BN platelets before and after hot‐drawing are experimentally examined using wide‐angle X‐ray diffraction and Raman spectroscopy. Compared with the undrawn (as‐spun) fibers, both analyses show that the intensity of the major h‐BN peaks attributed to interlayer interaction significantly decreased for the drawn fibers, suggesting exfoliation of the h‐BN. A full atomistic steered molecular dynamics approach is used to obtain baseline force and work required for h‐BN layer separation, as well as to simulate the h‐BN exfoliation behavior as a result of the PE matrix shearing effect in the composite. Computational results indicate that a large interactive area between the polymer and the fillers is required to induce enough stress transfer to exceed the h‐BN exfoliation force/energy threshold. Once this threshold is achieved, complete exfoliation of the platelets to monolayer h‐BN is demonstrated. By understanding the relationship between interfacial area and interaction strength between polymer matrix and fillers, this work provides new insight toward use of polymers for producing mono‐ and few‐layered h‐BN.

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Kinetic Investigations of Cu‐Mediated ATRP in Aqueous Solution
Authors: Smolne Sebastian , Buback Michael
Published: February 2015

Cu‐mediated atom‐transfer radical polymerization (ATRP) is studied via on‐line vis/NIR spectroscopy in an aqueous solution of a monomer‐free model system, with CuBr/2,2′‐bipyridine acting as the catalyst, and 2‐hydroxyethyl 2‐bromoisobutyrate as the initiator, at a pressure of up to 2000 bar. Excess NaBr is added to avoid the water‐assisted dissociation of the Br–Cu(II)/L bond. The activation–deactivation equilibrium constant, Kmodel, is measured at different compositions of the water–poly(ethylene glycol) dimethylether (PEO) solvent mixture, in which PEO mimics a water‐soluble monomer. Kmodel increases by about three orders of magnitude in passing from a PEO to a water environment. The change in Kmodel is essentially due to the effect on the activation rate coefficient. Kinetic analysis of the model system upon variation of NaBr concentration in conjunction with predici simulations shows that the NaBr content has no significant impact on the activation and deactivation rate coefficients and thus on Kmodel, but on dispersity and on the degree of chain‐end functionality.

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Condensed Mode Cooling for Ethylene Polymerization: Part I. The Effect of Different Induced Condensing Agents on Polymerization Rate
Authors: Alizadeh Arash , Namkajorn Montree , Somsook Ekasith , McKenna Timothy F. L.
Published: February 2015

The effect of commonly used induced condensing agents (ICAs) on the rate of polymerization of ethylene on a supported Ziegler–Natta catalyst in a gas‐phase process is investigated. It is observed that the instantaneous rate of ethylene polymerization is promoted in presence of all ICAs studied. This is attributed to the effect of the heavy ICAs in enhancing the local concentration of ethylene at the active polymerization sites that are dispersed within the growing polymer particles. It is found that the higher the solubility of ICA in the polymer, the greater the observed effect. It is also observed that the enhancement due to the presence of an ICA is greater during the initial phase of the polymerization.

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Novel Hyperbranched Polysiloxanes Containing Acetoacetyl Groups Synthesized Through Transesterification Reaction
Authors: Niu Song , Yan Hongxia
Published: February 2015

Development of an innovative strategy to prepare hyperbranched polysiloxanes (HBPS) is highly desirable due to the significant shortcomings of conventional fabrication approaches: the precursors need pre‐synthesis, the hydrosilylation reaction is conducted using costly catalysts, and hydrolysis of organosiloxanes easily results in gelation. Here, novel HBPS containing acetoacetyl groups (HBPS‐Ac) are synthesized through a cost‐efficient and easily controllable transesterification reaction. It is shown by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), 1H NMR, and gas chromatography (GC) measurements that the polymerization process is a straightforward technique to prepare new HBPS. The polymers are capable to remove formaldehyde due to the highly efficient reaction of the active methylene in the acetoacetyl group with formaldehyde at room temperature. Notably, coatings incorporating 4 wt% of the polymers allow for formaldehyde absorption, while integrated performances are kept almost unaffected. Therefore, HBPS‐Ac are promising as scavengers for formaldehyde.

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ARVCF expression is significantly correlated with the malignant phenotype of non‐small cell lung cancer
Authors: Zhang Di , Tang Na , Liu Yang , Wang En‐Hua
Published: February 2015

Armadillo repeat gene deleted in velo‐cardio‐facial syndrome (ARVCF) is a member of the p120 catenin (p120ctn) family; it contains nine central Armadillo repeats and binds to the juxtamembrane domain of E‐cadherin. We used immunohistochemistry to measure ARVCF expression in 121 patients with NSCLC and western blotting to examine differences in ARVCF expression between lung cancer and adjacent normal lung tissues. We interfered with ARVCF expression in two lung cancer cell lines and measured its effects on invasion and proliferation. ARVCF expression correlated with the malignant phenotype and poor prognosis. We also observed ARVCF‐dependent changes in small GTPase (mainly RhoA) activity in lung cancer cells. We confirmed that ARVCF plays an important role in the malignant phenotype. © 2015 Wiley Periodicals, Inc.
Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing
Authors: Ammar‐Khodja Fatima , Bonnet Crystel , Dahmani Malika , Ouhab Sofiane , Lefèvre Gaelle M. , Ibrahim Hassina , Hardelin Jean‐Pierre , Weil Dominique , Louha Malek , Petit Christine
Published: February 2015

The genetic heterogeneity of congenital hearing disorders makes molecular diagnosis expensive and time‐consuming using conventional techniques such as Sanger sequencing of DNA. In order to design an appropriate strategy of molecular diagnosis in the Algerian population, we explored the diversity of the involved mutations by studying 65 families affected by autosomal recessive forms of nonsyndromic hearing impairment (DFNB forms), which are the most prevalent early onset forms. We first carried out a systematic screening for mutations in GJB2 and the recurrent p.(Arg34*) mutation in TMC1, which were found in 31 (47.7%) families and 1 (1.5%) family, respectively. We then performed whole exome sequencing in nine of the remaining families, and identified the causative mutations in all the patients analyzed, either in the homozygous state (eight families) or in the compound heterozygous state (one family): (c.709C>T: p.(Arg237*)) and (c.2122C>T: p.(Arg708*)) in OTOF, (c.1334T>G: p.(Leu445Trp)) in SLC26A4, (c.764T>A: p.(Met255Lys)) in GIPC3, (c.518T>A: p.(Cys173Ser)) in LHFPL5, (c.5336T>C: p.(Leu1779Pro)) in MYO15A, (c.1807G>T: p.(Val603Phe)) in OTOA, (c.6080dup: p.(Asn2027Lys*9)) in PTPRQ, and (c.6017del: p.(Gly2006Alafs*13); c.7188_7189ins14: p.(Val2397Leufs*2)) in GPR98. Notably, 7 of these 10 mutations affecting 8 different genes had not been reported previously. These results highlight for the first time the genetic heterogeneity of the early onset forms of nonsyndromic deafness in Algerian families.
Accelerating 4D flow MRI by exploiting vector field divergence regularization
Authors: Santelli Claudio , Loecher Michael , Busch Julia , Wieben Oliver , Schaeffter Tobias , Kozerke Sebastian
Published: February 2015

Purpose

To improve velocity vector field reconstruction from undersampled four‐dimensional (4D) flow MRI by penalizing divergence of the measured flow field.

Theory and Methods

Iterative image reconstruction in which magnitude and phase are regularized separately in alternating iterations was implemented. The approach allows incorporating prior knowledge of the flow field being imaged. In the present work, velocity data were regularized to reduce divergence, using either divergence‐free wavelets (DFW) or a finite difference (FD) method using the ℓ1‐norm of divergence and curl. The reconstruction methods were tested on a numerical phantom and in vivo data. Results of the DFW and FD approaches were compared with data obtained with standard compressed sensing (CS) reconstruction.

Results

Relative to standard CS, directional errors of vector fields and divergence were reduced by 55–60% and 38–48% for three‐ and six‐fold undersampled data with the DFW and FD methods. Velocity vector displays of the numerical phantom and in vivo data were found to be improved upon DFW or FD reconstruction.

Conclusion

Regularization of vector field divergence in image reconstruction from undersampled 4D flow data is a valuable approach to improve reconstruction accuracy of velocity vector fields. Magn Reson Med 75:115–125, 2016. © 2015 Wiley Periodicals, Inc.
Polarized multichannel transmit MRI to reduce shading near metal implants
Authors: Bachschmidt Theresa J. , Köhler Michael , Nistler Jürgen , Geppert Christian , Jakob Peter M. , Nittka Mathias
Published: February 2015

Purpose

To investigate the benefit of a two‐channel transmit system on shading close to total hip replacements and other elongated metal structures in parallel to the magnet bore.

Methods

An analytical model comprising a water cylinder and a metal rod is introduced to describe the B1 effects close to elongated metal structures and it is verified. The dependence of the optimal polarization, which induces minimum shading, on the position of the metal is analyzed. Furthermore, the optimal polarization for two patients is determined both on the basis of the model and experimentally and its benefit compared with circular polarization is investigated.

Results

The cylindrical model approximates the modification of the B1 field due to the metal well, and the optimal polarization strongly depends on the position of the rod. In vivo, shading can be ameliorated by the use of the optimal polarization; for total hip replacements with shafts of titanium, this polarization can be determined on the basis of both the analytical model and the experimental data.

Conclusion

Parallel transmission offers the possibility of a substantial reduction of shading close to long metal structures in parallel to the magnet bore. Magn Reson Med 75:217–226, 2016. © 2015 Wiley Periodicals, Inc.
Trends, Victims, and Injuries in Injurious Patient Assaults on Adult, Geriatric, and Child/Adolescent Psychiatric Units in US Hospitals, 2007–2013
Authors: Staggs Vincent S.
Published: February 2015

While rates of other nurse‐sensitive adverse outcomes have declined in recent years, little is known about trends in rates of assault by psychiatric inpatients. The primary purpose of this study was to examine recent trends in injurious assault rates against patients and staff on adult, geriatric, and child/adolescent psychiatric units, using data from a nationwide sample of hospitals. A secondary aim was to assess the frequency with which patients and various types of hospital staff were reported as the most severely injured victim. National Database of Nursing Quality Indicators® data from 2007 to 2013 were extracted. The sample comprised 345 hospitals (324 general, 5 pediatric, 16 psychiatric), 438 adult, 75 geriatric, and 105 child/adolescent units, each with assault rate data from at least three of the seven study years. All but four states in the United States were represented. Spearman's rank coefficients were used to test for time trends. In 16.3 million patient days, nearly three‐quarters of the 14,877 injurious assaults by patients involved injury only to hospital staff, whereas one‐fifth resulted in injury only to patients. A registered nurse was named most frequently as the most severely injured victim (32.1% of assaults), and nursing staff of all types accounted for 64.9% of the most severely injured. Assault rates did not change significantly over time. Unlike several other nursing‐sensitive adverse outcomes that have been the focus of policymakers, assault rates have not declined in recent years and remain a problem in need of more focused attention. © 2015 Wiley Periodicals, Inc.
Oral leukoplakia in patients with Fanconi anaemia without hematopoietic stem cell transplantation
Authors: Grein Cavalcanti Laura , Lyko Karine Fátima , Araújo Renata Lins Fuentes , Amenábar José Miguel , Bonfim Carmem , Torres‐Pereira Cassius Carvalho
Published: February 2015

Background

Fanconi anaemia is a genetic disease characterized by congenital abnormalities, progressive bone marrow failure, and a higher predisposition of oral squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of oral mucosa lesions in patients with Fanconi anaemia without hematopoietic stem cell transplantation (HSCT).

Procedure

Patients with Fanconi anaemia who had not undergone HSCT was cross‐sectional evaluated for the presence of oral lesions.

Results

The sample was composed of 78 male and 60 female patients, with a median age of 9 years. Of the 138 patients, approximately 45% manifested at least one oral mucosa abnormality: 35 patients (25%) presented with traumatic injuries, and 16 (12%) exhibited leukoplakia. The following lesions were observed in low prevalence: aphthous ulcers, atrophic tongue, petechiae and hematomas, gingival hyperplasia, mucoceles, herpes, hyperpigmentation, haemangioma, non‐neoplastic proliferative lesions, neutropenic ulcers, papilloma, and candidiasis.

Conclusion

There was a high prevalence of oral leukoplakias in patients with Fanconi anaemia who had not undergone HSCT. It highlights the need of regular oral screenings in this cohort of concern for head and neck malignancies and suggests that oral leukoplakias should be further investigated as part of the syndrome phenotype. Pediatr Blood Cancer 2015;62:1024–1026. © 2015 Wiley Periodicals, Inc.
FN1: A novel fusion partner of ALK in an inflammatory myofibroblastic tumor
Authors: Ouchi Kazutaka , Miyachi Mitsuru , Tsuma Yusuke , Tsuchiya Kunihiko , Iehara Tomoko , Konishi Eiichi , Yanagisawa Akio , Hosoi Hajime
Published: February 2015

Inflammatory myofibroblastic tumors (IMTs) are rare tumors characterized as low‐to‐intermediate grade sarcomas. Rearrangements of the anaplastic lymphoma kinase (ALK) gene have been reported in IMT. Here, we describe a novel fusion gene in an IMT tumor specimen. A 12‐year‐old male was admitted to our hospital with a bladder tumor. We identified the fibronectin 1 gene (FN1) as a fusion partner of ALK using 5′RACE. This novel fusion, FN1–ALK, resulted in ALK overexpression in the IMT. This finding should clarify the causes of IMT and facilitate development of novel therapeutics. Pediatr Blood Cancer 2015;62:909–911. © 2015 Wiley Periodicals, Inc.
Psychiatric disorders in 130 survivors of childhood cancer: Preliminary results of a semi‐standardized interview
Authors: Bagur J. , Massoubre C. , Casagranda L. , Faure‐Conter C. , Trombert‐Paviot B. , Berger C.
Published: February 2015

Background

Although psychological sequelae are well known among survivors of childhood cancer, psychiatric sequelae remain inadequately explored. Long‐term psychiatric sequelae and their main risk factors in this population were evaluated.

Procedure

Initially, 483 survivors of childhood cancer, except leukemia, were invited to complete a questionnaire assessing their health and quality of life. Of them, 130 completed the survey, subsequently consulted with a pediatric oncologist and an internist, and met with a psychologist for a semi‐standardized interview based on the Mini International Neuropsychiatric Interview (MINI), which allowed diagnosis of DSM‐IV Axis 1 psychiatric disorders. The collected data were compared with those of the French general population.

Results

Seventy‐three of the 130 survivors (56.2%) who completed the MINI interview reported experiencing at least one psychiatric disorder since cancer diagnosis, mostly anxiety (39.2%), mood (27.7%), or major depressive (24.6%) disorders; 46 reported at least one current disorder (35.4%). Agoraphobia (P = 0.02) and psychotic disorders were more common (P = 0.003) and general anxiety disorder less common (P < 0.001) among survivors than the general population. Most disorders correlated significantly with survivors’ ratings of lower quality of life. Smoking, cancer type, and treatments significantly influenced the prevalence of psychiatric disorders.

Conclusions

Results were consistent between the self‐questionnaire and MINI interview responses, though time may have biased memory. Vulnerability to and high risk for developing DSM‐IV Axis 1 psychiatric disorders of childhood cancer survivors can persist long after diagnosis and treatment. Thus, systematic and general psychological screening of survivors may facilitate long‐term psychological restoration. Pediatr Blood Cancer 2015;62:847–853. © 2015 Wiley Periodicals, Inc.
Point‐of‐care end‐tidal carbon monoxide reflects severity of hemolysis in sickle cell anemia
Authors: Lal Ashutosh , Patterson Lasandra , Goldrich Alisa , Marsh Anne
Published: February 2015

Carbon monoxide (CO) production from heme catabolism is increased with hemolysis. A portable end‐tidal CO (ETCO) monitor was used to analyze breath samples in 16 children with sickle cell anemia (SCA, 5–14 years). Median (range) ETCO for SCA was 4.35 ppm (1.8–9.7) versus 0.80 ppm (0.2–2.3) for controls (P < 0.001). ETCOc >2.1 ppm provided sensitivity and specificity of 93.8% (69.8–99.8%) for detecting SCA. ETCO correlated with reticulocytosis (P = 0.015) and bilirubin (P = 0.009), and was 32% lower in children receiving hydroxyurea (P = 0.09). Point‐of‐care ETCO analysis may prove useful for non‐invasive monitoring of hemolysis and as a screening test for SCA. Pediatr Blood Cancer 2015;62:912–914. © 2015 Wiley Periodicals, Inc.
Training providers on issues of race and racism improve health care equity
Authors: Nelson Stephen C. , Prasad Shailendra , Hackman Heather W.
Published: February 2015

Race is an independent factor in health disparity. We developed a training module to address race, racism, and health care. A group of 19 physicians participated in our training module. Anonymous survey results before and after the training were compared using a two‐sample t‐test. The awareness of racism and its impact on care increased in all participants. White participants showed a decrease in self‐efficacy in caring for patients of color when compared to white patients. This training was successful in deconstructing white providers' previously held beliefs about race and racism. Pediatr Blood Cancer 2015;62:915–917. © 2015 Wiley Periodicals, Inc.
A Revised Growth Model for Transparent Conducting Ga Doped ZnO Films: Improving Crystallinity by Means of Buffer Layers
Authors: Abduev Aslan , Akmedov Akhmed , Asvarov Abil , Chiolerio Alessandro
Published: February 2015

Ga‐doped ZnO (GZO) thin films are recently raising both scientific and industrial interests, due to the lack of natural resources. Indium is a crucial raw material, due to ITO modern touchscreen market. By doping ZnO with Ga conductive transparent thin films with various concentrations of dopant are prepared by DC magnetron sputtering from ceramic targets. It is shown how the Ga content plays an important role on the growth kinetics on an initial stage of the film formation and hence on the morphologies, microstructure and electrical properties of as‐grown GZO films. A mechanism explaining the role of Ga content on the nucleation process and the structure of growing films is proposed. Based on this mechanism, it is successfully demonstrated that the crystalline quality and hence the conductivity of GZO thin films can be improved by using a GZO buffer layer.
Anti‐inflammatory properties of Lipidosterolic extract of Serenoa repens (Permixon®) in a mouse model of prostate hyperplasia
Authors: Bernichtein Sophie , Pigat Natascha , Camparo Philippe , Latil Alain , Viltard Mélanie , Friedlander Gérard , Goffin Vincent
Published: February 2015

BACKGROUND

Permixon®, the hexanic lipidosterolic extract of saw palmetto Serenoa repens (LSESr), has shown properties that highlight its benefit in the management of benign prostate hyperplasia (BPH). To address its actual anti‐inflammatory potency, we used a unique pro‐inflammatory mouse model of prostate hyperplasia involving prostate‐specific over‐expression of prolactin transgene (Pb‐Prl).

METHODS

Six month‐old Pb‐Prl males were administered with Permixon® per os at the daily dose of 100 mg/kg for 28 days. Body and prostate weights were measured weekly and at sacrifice, respectively. Prostate histology was carefully assessed by a pathologist and detailed quantifications of epithelial and stromal compartments were performed using image analysis software. Luminal cell proliferation index was determined using Ki‐67 immunostaining, and apoptosis using Bax/Bcl2 mRNA ratio. Tissue inflammation and fibrosis were assessed by histological analyses then quantified using CD45 immunostaining and picrosirius staining, respectively. Expression profiling of selected pro‐inflammatory cytokines, chemokines, and chemokine receptors was performed by quantitative RT‐PCR.

RESULTS

In this model, Permixon® significantly decreased tissue weight and proliferation index specifically in the ventral lobe. Although treatment had no noticeable effect on epithelial histology of any lobe, it markedly reduced the histological hallmarks of inflammation in all lobes. This was confirmed by the global down‐regulation of prostate pro‐inflammatory cytokine profile, with significant reduction of CCR7, CXCL6, IL‐6, and IL‐17 expression.

CONCLUSIONS

In this mouse model of prostate hyperplasia, Permixon® exerted potent anti‐inflammatory properties in the whole prostate while anti‐androgenic effects were lobe‐specific, suggesting that distinct LSESr components may be involved in these effects. Our results support the beneficial role of Permixon® treatment for BPH. The relevance of CCR7, CXCL6, IL‐6, and IL‐17 as potential biomarkers to follow up BPH inflammatory status needs to be assessed. Prostate 75:706–722, 2015. © 2015 Wiley Periodicals, Inc.
Prostate cancer screening using risk stratification based on a multi‐state model of genetic variants
Authors: Yen Amy Ming‐Fang , Auvinen Anssi , Schleutker Johanna , Wu Yi‐Ying , Fann Jean Ching‐Yuan , Tammela Teuvo , Chen Sam Li‐Sheng , Chiu Sherry Yueh‐Hsia , Chen Hsiu‐Hsi
Published: February 2015

Background

Risk‐stratified screening for prostate cancer (PCa) with prostate‐specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy.

Methods

Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six‐state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score‐based approach combined with a series of computer simulation models was applied to optimize individual screening policies.

Results

The 10‐year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years‐old, as the reference group, the recommended age beginning screening was approximately 47 years‐old for the top 5% risk group and 55 years‐old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups­.­­

Conclusions

A multi‐state genetic variant‐based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub‐group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four‐year interval after age 55 years). Prostate 75:825–835, 2015. © 2015 Wiley Periodicals, Inc.
Safety of enzalutamide in patients with metastatic castration‐resistant prostate cancer previously treated with docetaxel: Expanded access in North America
Authors: Joshua Anthony M. , Shore Neal D. , Saad Fred , Chi Kim N. , Olsson Carl A. , Emmenegger Urban , Scholz Mark , Berry William , Mukherjee Som D. , Winquist Eric , Haas Naomi B. , Foley Margaret A. , Dmuchowski Carl , Perabo Frank , Hirmand Mohammad , Hasabou Nahla , Rathkopf Dana ,   for The Enzalutamide Expanded Access Study Investigators
Published: February 2015

BACKGROUND

The open‐label, single‐arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration‐resistant prostate cancer (mCRPC) who had previously received docetaxel.

METHODS

Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected.

RESULTS

Median age was 71 years (range 43–97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03–9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%).

CONCLUSION

In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial. Prostate 75: 836–844, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.
MiR200c targets IRS1 and suppresses prostate cancer cell growth
Authors: Su Wenjing , Xu Miao , Chen Xueqin , Nie Ling , Chen Ni , Gong Jing , Zhang Mengni , Su Zhengzheng , Huang Lei , Zhou Qiao
Published: February 2015

Background

The downregulation of the tumor suppressor miR200c plays important roles in many malignant tumors. This study aims to show that miR200c is a posttranscriptional regulator of insulin receptor substrate 1 (IRS1) and over‐expression of miR200c suppresses prostate cancer cell growth.

Methods

Bioinformatics analysis was used to show potential post‐translational regulation of IRS1 by miR200c. Dual reporter gene assays were chosen to test the binding of miR200c to the potential seed sequences in IRS1 3′UTR. RT‐PCR, Q‐PCR and western blot were applied to determine the regulation effect of miR200c on IRS1. CCK8 assay, soft agar assay, trypan blue exclusion assay and flow cytometric analysis were used to measure the biological effects of miR200c on prostate cancer cell proliferation and apoptosis.

Results

The 449–455 nt, 3061–3067 nt, and 3096–3102 nt of the IRS1 3′‐UTR were identified as three potential seed sequences for miR200c. MiR200c directly binds to IRS1 through the seed sequences in IRS1 3′‐UTR. Artificial overexpression of miR200c significantly downregulated the mRNA and protein levels of IRS1, together with decreased cell proliferation and increased cell death of PC3 and DU145 cells.

Conclusions

Our results suggest that miR200c plays crucial roles in prostate cancer by post‐transcriptional regulation of IRS1. The mir200c/IRS1 pathway may be a potential therapeutic target to prevent prostate cancer cell growth. Prostate 75:855–862, 2015. © 2015 Wiley Periodicals, Inc.
IL‐17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through CD44‐VCAM‐1 interaction
Authors: Chen Chong , Zhang Qiuyang , Liu Sen , Parajuli Keshab R. , Qu Yine , Mei Jiandong , Chen Zhiquan , Zhang Hui , Khismatullin Damir B. , You Zongbing
Published: February 2015

BACKGROUND

Extravasation is a critical step in cancer metastasis, in which adhesion of intravascular cancer cells to the vascular endothelial cells is controlled by cell surface adhesion molecules. The role of interleukin‐17 (IL‐17), insulin, and insulin‐like growth factor 1 (IGF1) in adhesion of prostate cancer cells to the vascular endothelial cells is unknown, which is the subject of the present study.

METHODS

Human umbilical vein endothelial cells (HUVECs) and human prostate cancer cell lines (PC‐3, DU‐145, LNCaP, and C4–2B) were analyzed for expression of vascular cell adhesion molecule 1 (VCAM‐1), integrins, and cluster of differentiation 44 (CD44) using flow cytometry and Western blot analysis. The effects of IL‐17, insulin, and IGF1 on VCAM‐1 expression and adhesion of prostate cancer cells to HUVECs were examined. The interaction of VCAM‐1 and CD44 was assessed using immunoprecipitation assays.

RESULTS

Insulin and IGF1 acted with IL‐17 to increase VCAM‐1 expression in HUVECs. PC‐3, DU‐145, LNCaP, and C4–2B cells expressed β1 integrin but not α4 integrin. CD44 was expressed by PC‐3 and DU‐145 cells but not by LNCaP or C4–2B cells. When HUVECs were treated with IL‐17, insulin or IGF1, particularly with a combination of IL‐17 and insulin (or IGF1), adhesion of PC‐3 and DU‐145 cells to HUVECs was significantly increased. In contrast, adhesion of LNCaP and C4–2B cells to HUVECs was not affected by treatment of HUVECs with IL‐17 and/or insulin/IGF1. CD44 expressed in PC‐3 cells physically bound to VCAM‐1 expressed in HUVECs.

CONCLUSIONS

CD44‐VCAM‐1 interaction mediates the adhesion between prostate cancer cells and HUVECs. IL‐17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through increasing VCAM‐1 expression in the vascular endothelial cells. These findings suggest that IL‐17 may act with insulin/IGF1 to promote prostate cancer metastasis. Prostate 75:883–895, 2015. © 2015 Wiley Periodicals, Inc.
Influence of Ga/(Ga + In) grading on deep‐defect states of Cu(In,Ga)Se2 solar cells
Authors: Kotipalli Ratan , Vermang Bart , Fjällström Viktor , Edoff Marika , Delamare Romain , Flandre Denis
Published: February 2015

The benefits of gallium (Ga) grading on Cu(In,Ga)Se2 (CIGS) solar cell performance are demonstrated by comparing with ungraded CIGS cells. Using drive‐level capacitance profiling (DLCP) and admittance spectroscopy (AS) analyses, we show the influence of Ga grading on the spatial variation of deep defects, free‐carrier densities in the CIGS absorber, and their impact on the cell's open‐circuit voltage Voc. The parameter most constraining the cell's Voc is found to be the deep‐defect density close to the space charge region (SCR). In ungraded devices, high deep‐defect concentrations (4.2 × 1016cm–3) were observed near the SCR, offering a source for Shockley–Read–Hall recombination, reducing the cell's Voc. In graded devices, the deep‐defect densities near the SCR decreased by one order of magnitude (2.5 × 1015 cm–3) for back surface graded devices, and almost two orders of magnitude (8.6 × 1014 cm–3) for double surface graded devices, enhancing the cell's Voc. In compositionally graded devices, the free‐carrier density in the absorber's bulk decreased in tandem with the ratio of gallium to gallium plus indium ratio GGI = Ga/(Ga + In), increasing the activation energy, hindering the ionization of the defect states at room temperature and enhancing their role as recombination centers within the energy band. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Proton dissociation and transfer in hydrated phosphoric acid clusters
Authors: Suwannakham Parichart , Chaiwongwattana Sermsiri , Sagarik Kritsana
Published: February 2015

The dynamics and mechanisms of proton dissociation and transfer in hydrated phosphoric acid (H3PO4) clusters under excess proton conditions were studied based on the concept of presolvation using the H3PO4–H3O+–nH2O complexes (n = 1–3) as the model systems and ab initio calculations and Born–Oppenheimer molecular dynamics (BOMD) simulations at the RIMP2/TZVP level as model calculations. The static results showed that the smallest, most stable intermediate complex for proton dissociation (n = 1) is formed in a low local‐dielectric constant environment (e.g., ε = 1), whereas proton transfer from the first to the second hydration shell is driven by fluctuations in the number of water molecules in a high local‐dielectric constant environment (e.g., ε = 78) through the Zundel complex in a linear H‐bond chain (n = 3). The two‐dimensional potential energy surfaces (2D‐PES) of the intermediate complex (n = 1) suggested three characteristic vibrational and 1H NMR frequencies associated with a proton moving on the oscillatory shuttling and structural diffusion paths, which can be used to monitor the dynamics of proton dissociation in the H‐bond clusters. The BOMD simulations over the temperature range of 298–430 K validated the proposed proton dissociation and transfer mechanisms by showing that good agreement between the theoretical and experimental data can be achieved with the proposed rate‐determining processes. The theoretical results suggest the roles played by the polar solvent and iterate that insights into the dynamics and mechanisms of proton transfer in the protonated H‐bond clusters can be obtained from intermediate complexes provided that an appropriate presolvation model is selected and that all of the important rate‐determining processes are included in the model calculations. © 2015 Wiley Periodicals, Inc.
Resolving the structure of inner ear ribbon synapses with STED microscopy
Authors: Rutherford Mark A.
Published: February 2015

Synapses are diverse in form and function; however, the mechanisms underlying this diversity are poorly understood. To illuminate structure/function relationships, robust analysis of molecular composition and morphology is needed. The molecular‐anatomical components of synapses—vesicles, clusters of voltage‐gated ion channels in presynaptic densities, arrays of transmitter receptors in postsynaptic densities—are only tens to hundreds of nanometers in size. Measuring the topographies of synaptic proteins requires nanoscale resolution of their molecularly specific labels. Super‐resolution light microscopy has emerged to meet this need. Achieving 50 nm resolution in thick tissue, we employed stimulated emission depletion (STED) microscopy to image the functionally and molecularly unique ribbon‐type synapses in the inner ear that connect mechano‐sensory inner hair cells to cochlear nerve fibers. Synaptic ribbons, bassoon protein, voltage‐gated Ca2+ channels, and glutamate receptors are inhomogeneous in their spatial distributions within synapses; the protein clusters assume variations of shapes typical for each protein specifically at cochlear afferent synapses. Heterogeneity of substructure among these synapses may contribute to functional differences among auditory nerve fibers. The morphology of synaptic voltage‐gated Ca2+ channels matures over development in a way that depends upon bassoon protein, which aggregates in similar form. Functional properties of synaptic transmission appear to depend on voltage‐gated Ca2+ channel cluster morphology and position relative to synaptic vesicles. Super‐resolution light microscopy is a group of techniques that complement electron microscopy and conventional light microscopy. Although technical hurdles remain, we are beginning to resolve the details of molecular nanoanatomy that relate mechanistically to synaptic function. Synapse, 69:242–255, 2015. ©2015 Wiley Periodicals, Inc.
Resolving presynaptic structure by electron tomography
Authors: Perkins Guy A. , Jackson Dakota R. , Spirou George A.
Published: February 2015

A key goal in neurobiology is to generate a theoretical framework that merges structural, physiological, and molecular explanations of brain function. These categories of explanation do not advance in synchrony; advances in one category define new experiments in other categories. For example, the synapse was defined physiologically and biochemically before it was visualized using electron microscopy. Indeed, the original descriptions of synapses in the 1950s were lent credence by the presence of spherical vesicles in presynaptic terminals that were considered to be the substrate for quantal neurotransmission. In the last few decades, our understanding of synaptic function has again been driven by physiological and molecular techniques. The key molecular players for synaptic vesicle structure, mobility and fusion were identified and applications of the patch clamp technique permitted physiological estimation of neurotransmitter release and receptor properties. These advances demand higher resolution structural images of synapses. During the 1990s a second renaissance in cell biology driven by EM was fueled by improved techniques for electron tomography (ET) with the ability to compute virtual images with nm resolution between image planes. Over the last 15 years, ET has been applied to the presynaptic terminal with special attention to the active zone and organelles of the nerve terminal. In this review, we first summarize the technical improvements that have led to a resurgence in utilization of ET and then we summarize new insights gained by the application of ET to reveal the high‐resolution structure of the nerve terminal. Synapse, 69:268–282, 2015. © 2015 Wiley Periodicals, Inc.