bluuebunny/crossref_metadata_2025 huggingface dataset:
The Critical Role of Dynamin‐Related Protein 1 in Hypoxia‐Induced Pulmonary Vascular Angiogenesis
Authors: Shen Tingting , Wang Na , Yu Xiufeng , Shi Jiucheng , Li Qian , Zhang Chen , Fu Li , Wang Shuang , Xing Yan , Zheng Xiaodong , Yu Lei , Zhu Daling
Published: March 2015

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by pulmonary vascular obstruction due in part to excessive pulmonary artery endothelial cells (PAECs) migration and proliferation. The mitochondrial fission protein dynamin‐related protein‐1 (DRP1) has important influence on pulmonary vascular remodeling. However, whether DRP1 participates in the development and progression of pulmonary vascular angiogenesis has not been reported previously. To test the hypothesis that DRP1 promotes the angiogenesis via promoting the proliferation, stimulating migration, and inhibiting the apoptosis of PAECs in mitochondrial Ca2+‐dependent manner, we performed following studies. Using hemodynamic analysis and morphometric assay, we found that DRP1 mediated the elevation of right ventricular systemic pressure (RVSP), right heart hypertrophy, and increase of pulmonary microvessels induced by hypoxia. DRP1 inhibition reversed tube network formation in vitro stimulated by hypoxia. The mitochondrial Ca2+ inhibited by hypoxia was recovered by DRP1 silencing. Moreover, pulmonary vascular angiogenesis promoted by DRP1 was reversed by the specific mitochondrial Ca2+ uniporter inhibitor Ru360. In addition, DRP1 promoted the proliferation and migration of PAECs in mitochondrial Ca2+‐dependent manner. Besides, DRP1 decreased mitochondrial membrane potential, reduced the DNA fragmentation, and inhibited the caspase‐3 activation, which were all aggravated by Ru360. Therefore, these results indicate that the mitochondrial fission machinery promotes migration, facilitates proliferation, and prevents from apoptosis via mitochondrial Ca2+‐dependent pathway in endothelial cells leading to pulmonary angiogenesis. J. Cell. Biochem. 116: 1993–2007, 2015. © 2015 Wiley Periodicals, Inc.
Oral squamous cancer cell exploits hnRNP A1 to regulate cell cycle and proliferation
Authors: Yu Cheng , Guo Jihua , Liu Yu , Jia Jun , Jia Rong , Fan Mingwen
Published: March 2015

Oral squamous cell carcinoma (OSCC) is a common human malignant tumor with high mortality. So far, the molecular pathogenesis of OSCC remains largely unclear. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an important multi‐function splicing factor and closely related to tumorigenesis. hnRNP A1 is overexpressed in various tumors, and promotes aerobic glycolysis and elongation of telomere, but the function of hnRNP A1 in cell cycle and proliferation remains unclear. We found that hnRNP A1 was overexpressed in OSCC tissues, and was required for the growth of OSCC cells. Moreover, hnRNP A1 was highly expressed in the G2/M cell cycle phase. Knockdown of hnRNP A1 induced G2/M arrest. DNA microarray assay result showed that hnRNP A1 regulated the expression of a number of target genes associated with G2/M phase. Moreover, hnRNP A1 controlled the alternative splicing of CDK2 exon 5. These findings suggested that hnRNP A1 plays key roles in the regulation of cell cycle progression and pathogenesis of OSCC. J. Cell. Physiol. 230: 2252–2261, 2015. © 2015 Wiley Periodicals, Inc.
β‐Arrestin2 Contributes to Cell Viability and Proliferation via the Down‐Regulation of FOXO1 in Castration‐Resistant Prostate Cancer
Authors: Duan Xiaolu , Kong Zhenzhen , Liu Yang , Zeng Zhiwen , Li Shujue , Wu Wenqi , Ji Weidong , Yang Bicheng , Zhao Zhijian , Zeng Guohua
Published: March 2015

β‐Arrestin2 has been identified to act as a corepressor of androgen receptor (AR) signaling by binding to AR and serving as a scaffold to affect the activity and expression of AR in androgen‐dependent prostate cancer cells; however, little is known regarding its role in castration‐resistant prostate cancer (CRPC) progression. Here, our data demonstrated that β‐arrestin2 contributes to the cell viability and proliferation of CRPC via the downregulation of FOXO1 activity and expression. Mechanistically, in addition to its requirement for FOXO1 phosphorylation induced by IGF‐1, β‐arrestin2 could inhibit FOXO1 activity in an Akt‐independent manner and delay FOXO1 dephosphorylation through the inhibition of PP2A phosphatase activity and the attenuation of the interaction between FOXO1 and PP2A. Furthermore, β‐arrestin2 could downregulate FOXO1 expression via ubiquitylation and proteasomal degradation. Together, our results identified a novel role for β‐arrestin2 in the modulation of the CRPC progress through FOXO1. Thus, the characterization of β‐arrestin2 may represent an alternative therapeutic target for CRPC treatment. J. Cell. Physiol. 230: 2371–2381, 2015. © 2015 Wiley Periodicals, Inc.
Cross‐Talk Between VEGF and BMP‐6 Pathways Accelerates Osteogenic Differentiation of Human Adipose‐Derived Stem Cells
Authors: Li Ching‐Ju , Madhu Vedavathi , Balian Gary , Dighe Abhijit S. , Cui Quanjun
Published: March 2015

Deficiency in vascular endothelial growth factor (VEGF) or bone morphogenetic proteins (BMPs) results in fracture non‐unions. Therefore, it is indispensable to comprehend the combined effect of VEGF and BMPs on the osteogenic differentiation of osteoprogenitor mesenchymal stem cells (MSCs) that are either naturally occurring at the fracture repair site or exogenously added to enhance the bone repair. We found that the combination of VEGF and BMP‐6 enhanced COL1A2 expression, which correlated with upregulated expression of osterix, Dlx5, and Msx2 in human adipose‐derived stem cells (hADSCs). Cross‐talk between VEGF and BMP‐6 pathways upregulated activation of p38 mitogen‐activated kinase (p38 MAPK) and inhibited activation of protein kinase B (PKB, also known as Akt), whereas phosphorylation of “mothers against decapentaplegic” homologs 1/5/8 (Smads 1/5/8) and extracellular signal‐regulated kinases 1 and 2 (ERK 1/2) was not affected. Consistent with these findings, p38 inhibitor SB203580, or siRNA knockdown of osterix, abrogated crosstalk between the VEGF and BMP‐6 pathways and significantly reduced the observed upregulation of COL1A2. Nuclear translocation of the phosphorylated form of osterix was also inhibited by SB203580. Although crosstalk between the VEGF‐BMP‐6 pathways did not show an effect on the extent of mineralization, inhibition of any one of the three components that were upregulated through the cross‐talk, i.e., osterix, Dlx5, and p38 activation, led to a complete inhibition of mineralization. Inhibition of PKB/Akt activation, which is attenuated through the cross‐talk, significantly enhanced ALP gene expression. These observations imply that crosstalk between the VEGF and BMP‐6 signaling pathways enhances osteogenic differentiation of MSCs. J. Cell. Physiol. 9999: 2671–2682, 2015. © 2015 Wiley Periodicals, Inc.
Stepping toward discharge: Level of ambulation in hospitalized patients
Authors: Sallis Robert , Roddy‐Sturm Yvonne , Chijioke Eziaku , Litman Kerry , Kanter Michael H. , Huang Brian Z. , Shen Ernest , Nguyen Huong Q.
Published: March 2015

Little information is available on how active adult patients are during their hospitalization. The purpose of this study is to describe the level of ambulation in hospitalized patients. This was a cohort study of ambulatory patients from 3 hospital medical‐surgical units conducted March 2014 through July 2014. Patients wore an accelerometer upon admission to the unit until discharge to home. Sensor placement and data review were performed as part of routine care. Step counts were merged with administrative and clinical data for analysis. Data were available on 777 patients who had at least 24 hours of monitoring prior to discharge. The sample included 57% females, and 55% were nonwhite. The median total step count over 24 hours was 1158 (interquartile range: 636–2238). Patients who were older accrued fewer steps compared to younger patients (962 vs 1294, P < 0.0001). For patients who had at least 48 hours of monitoring (n = 378), there was an increase from 811 steps in the first 24 hours to 1188 steps in the final 24 hours prior to discharge. More frequent documentation was associated with higher step counts (P ≤ 0.001). We found that a diverse sample of hospitalized adult patients accrued over 1000 steps in the 24 hours prior to discharge home. Journal of Hospital Medicine 2015;10:384–389. © 2015 Society of Hospital Medicine
MRI phenotype of breast cancer: Kinetic assessment for molecular subtypes
Authors: Blaschke Eric , Abe Hiroyuki
Published: March 2015

Purpose

To evaluate the dynamic contrast‐enhanced magnetic resonance imaging (MRI) kinetic characteristics of newly diagnosed breast cancer molecular subtypes.

Materials and Methods

Breast MRI examinations of 112 patients with newly diagnosed breast cancer were reviewed. Cases of newly diagnosed invasive ductal carcinoma were sorted by molecular subtype (28 TN, 11 HER2 +, 73 Lum A/B) and MRI field strength, with lesion segmentation and kinetic analyses performed on a dedicated workstation. For kinetic assessment, 50% and 100% thresholds were employed for display of medium and rapid uptake. Kinetic profiles in terms of percent volume for six kinetic types (medium‐persistent, medium‐plateau, medium‐washout, fast‐persistent, fast‐plateau, fast‐washout) relative to the whole volume of the lesion were obtained. Statistical analysis of the kinetic profiles was performed using Welch's t‐test.

Results

Percent volume of HER2‐positive lesions with >100% uptake at early phase on 3T strength MRI exams was significantly greater compared with luminal A/B (93.8 ± 0.92 vs. 77.3 ± 7.2; P < 0.01) and triple negative (93.8 ± 0.92 vs. 81.3 ± 8.2; P < 0.05) subtypes. The >50% early phase uptake for HER2+ lesions was also higher than Lum A/B (99.1 ± 0.73 vs. 93.6 ± 3.05; P < 0.01) at 3T. In the 1.5T subgroup the percent volume of HER2+ tumors with >50% and >100% early phase uptake trended higher than Lum A/B lesions without reaching significance.

Conclusion

The percent volume of HER2‐positive tumors demonstrating rapid early contrast uptake is significantly increased compared to other molecular subtypes. J. Magn. Reson. Imaging 2015;42:920–924.
Subsurface analysis of painted sculptures and plasters using micrometre‐scale spatially offset Raman spectroscopy (micro‐SORS)
Authors: Conti Claudia , Colombo Chiara , Realini Marco , Matousek Pavel
Published: March 2015

A recently developed variant of spatially offset Raman spectroscopy (SORS) for the non‐invasive analysis of thin painted layers, micro‐SORS, has been applied, for the first time, to real objects of Cultural Heritage – namely painted sculptures and plasters. Thin layers of paint originating from multiple restoration processes often applied over many centuries have been analysed non‐destructively using micro‐SORS to depths inaccessible to, or unresolvable into separate layers, by conventional confocal Raman microscopy. The concept has been demonstrated on several artistic artefacts of historical significance originating from Italy and dating from the medieval to the 18th century. The technique extends the depth applicability of Raman spectroscopy and with its inherently high chemical specificity that expands the portfolio of existing non‐destructive analytical tools in Cultural Heritage permitting to avoid cross‐sectional analysis often necessitated with this type of samples with conventional Raman microscopy. Currently, the method is non‐invasive only for artworks that can be placed under Raman microscope although there is a prospect for its use in a mobile system with largely removed restrictions on sample dimensions. © 2015 The Authors Journal of Raman Spectroscopy Published by John Wiley & Sons Ltd.
Novel highly sensitive Cu‐based SERS platforms for biosensing applications
Authors: Kowalska Aneta Aniela , Kaminska Agnieszka , Adamkiewicz Witold , Witkowska Evelin , Tkacz Marek
Published: March 2015

Novel surface enhanced Raman spectroscopy (SERS) platforms have been prepared and used for the bacteria detection. Unlike typical, expensive SERS platforms prepared from gold or silver, the presented platforms are prepared using copper. A new, simple, cost‐efficient and fast high pressure method is used for platform fabrication, through the decomposition of copper hydride. The platform enhancement factors are verified using the malachite green isothiocyanate as a standard. The platforms exhibit extremely high SERS enhancement factors depending on pressure used for their preparation. The calculated enhancement factors have been found in the range between 1.5 × 106 and 4.6 × 107. The SERS spectra reproducibility is established both across a single platform and among different platforms. The average spectral correlation coefficient (Γ) has been calculated to be 0.82. Fully characterized SERS platforms have then been used for detecting Staphylococcus aureus bacteria. These novel platforms have great potential to become excellent tools for biological or medical diagnostics as an alternative to more common silver or gold SERS platforms. Copyright © 2015 John Wiley & Sons, Ltd.
Clonal differences and impact of defoliation on Sauvignon blanc (Vitis vinifera L.) wines: a chemical and sensory investigation
Authors: Šuklje Katja , Antalick Guillaume , Buica Astrid , Langlois Jennifer , Coetzee Zelmari A , Gouot Julia , Schmidtke Leigh M , Deloire Alain
Published: March 2015

BACKGROUND

The aim of this study, performed on Sauvignon blanc clones SB11 and SB316, grafted on the same rootstock 101–14 Mgt (Vitis riparia × V. ruperstris) and grown at two adjacent vineyards, was two‐fold: (1) to study wine chemical and sensory composition of both clones within an unaltered canopy; and (2) to determine the effect of defoliation (e.g. bunch microclimate) on wine chemical and sensory composition.

RESULTS

Orthogonal projection to latent structures discriminate analysis (OPLS‐DA) was applied to the concentration profiles of volatile compounds derived from gas chromatography–mass spectrometry data. The loadings directions inferred that 3‐isobutyl‐2‐methoxypyrazine (IBMP) discriminated control treatments (shaded fruit zone) of both clones from defoliation treatments (exposed fruit zone), whereas 3‐sulfanyl‐hexan‐1‐ol (3SH), 3‐sulfanylhexyl acetate (3SHA), hexanol, hexyl hexanoate and some other esters discriminated defoliated treatments from the controls. The OPLS‐DA indicated the importance of IBMP, higher alcohol acetates and phenylethyl esters, for discrimination of clone SB11 from clone SB316 irrespective of the treatment. Defoliation in the fruit zone significantly decreased perceived greenness in clone SB11 and elevated fruitier aromas, whereas in clone SB316 the effect of defoliation on wine sensory perception was less noticeable regardless the decrease in IBMP concentrations.

CONCLUSION

These findings highlight the importance of clone selection and bunch microclimate to diversify produced wine styles. © 2015 Society of Chemical Industry
High infiltration of tumor‐associated macrophages is associated with a poor response to chemotherapy and poor prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Takiguchi Shuji , Mori Masaki , Doki Yuichiro
Published: March 2015

Background and objective

Tumor‐associated macrophages (TAMs) are well known to have distinct roles in tumor progression and metastasis. However, the role of TAMs in chemoresistance has not been fully investigated. The aim of this study is to examine whether TAMs, especially M2 macrophages, are associated with the tumor response to chemotherapy with esophageal cancers.

Methods

Using 210 tissues from patients with esophageal cancer who underwent surgery, we calculated the number of intratumoral CD68+ macrophages, CD163+ macrophages, and CD8+ lymphocytes using immunohistochemistry. CD68 and CD163 were used as markers for whole macrophages and M2 macrophages, respectively.

Results

Infiltration of CD68+ macrophages and CD163+ macrophages was significantly associated with tumor depth, lymphatic invasion, and venous invasion. High infiltration of CD68+ macrophages and CD163+ macrophages was significantly associated with poor prognosis for patients undergoing neoadjuvant chemotherapy. Regarding the response to chemotherapy, high infiltration of CD68+ and CD163+ macrophages had a significant association with poor response to chemotherapy, both clinically and pathologically (P < 0.001, P < 0.001). Multivariate analysis showed that infiltration of CD163+ macrophages was an independent prognostic factor in patients undergoing neoadjuvant chemotherapy.

Conclusions

Infiltration of TAMs, especially M2 macrophages, is associated with a poor response to chemotherapy and poor prognosis of patients with esophageal cancer. J. Surg. Oncol. 2015 111:752–759. © 2015 Wiley Periodicals, Inc.
Determination of phthalate esters in Chinese spirits using isotope dilution gas chromatography with tandem mass spectrometry
Authors: Wang Jing , Li Xiaomin , Zhang Qinghe , Xiong Jinping , Li Hongmei
Published: March 2015

Phthalate esters are additives used in polyvinylchloride and are found as contaminants in many food products. An isotope dilution mass spectrometry technique has been developed for accurate analysis of 16 phthalate esters in Chinese spirits by adopting the 16 corresponding isotope‐labeled phthalate esters. The ethanol in the spirit sample was first removed by heating with a water bath at 100°C with a stream of nitrogen, after which the residue was extracted with n‐hexane twice. The phthalates collected were identified and quantified by gas chromatography with tandem mass spectrometry in multiple reaction monitoring mode. The spiking recoveries of 16 analytes ranged from 94.3 to 105.3% with relative standard deviation values of <6.5%. The detection limits for 16 analytes were <10.0 ng/g. The expanded relative uncertainties were from 3.0 to 14%. A survey was performed on Chinese spirits from the market. Six of the nine analyzed samples were contaminated by phthalates. Di‐n‐butyl phthalate and di‐2‐ethylhexyl phthalate showed higher detection frequency and concentrations. This isotope dilution gas chromatography with tandem mass spectrometry method is simple, rapid, accurate, and highly sensitive, which qualifies as a candidate reference method for the determination of phthalates in spirits.
Evaluation of plutonium(IV) extraction rate between nitric acid and tri‐n‐butylphosphate solution using a glass chip microchannel
Authors: Yamamoto Masahiko , Taguchi Shigeo , Sato Soichi , Surugaya Naoki
Published: March 2015

Extraction of Pu(IV) with tri‐n‐butylphosphate is performed using a glass chip microchannel to evaluate the extraction rate. Two‐phase flow forms in the microchannel by introducing a solution of Pu(IV) and tri‐n‐butylphosphate with flow rates above 5 μL/min. The Pu(IV) extraction reaction proceeds at the interface between the two phases. To evaluate the extraction rate, the contact time between the two phases is varied from 0.48 to 4.8 s by changing the confluent length of the microchannel and the flow rate. The Pu concentration of each phase collected from the microchannel is measured with an alpha liquid scintillation counter, and the contact time dependence of Pu(IV) extraction is obtained. An extraction model based on diffusion in the microchannel and the reaction at the interface is proposed and applied to determine the extraction rate. The extraction process is assumed to follow pseudo‐first‐order kinetics, and the extraction rate constant of Pu(IV) is determined to be 1.5 × 10−2 cm/s. The investigation demonstrates that a microfluidic device can be a new tool to determine Pu(IV) extraction rates.
Optimization of modified dispersive liquid–liquid microextraction coupled with high‐performance liquid chromatography for the simultaneous preconcentration and determination of nitrazepam and midazolam drugs: An experimental design
Authors: Goudarzi Nasser , Farsimadan Sahar , Chamjangali Mansour Arab , Bagherian Ghadam Ali
Published: March 2015

A simple, sensitive, and rapid microextraction method, namely, ultrasound‐assisted surfactant‐enhanced emulsification microextraction based on the solidification of floating organic droplet method coupled with high‐performance liquid chromatography was developed for the simultaneous preconcentration and determination of nitrazepam and midazolam. The significant parameters affecting the extraction efficiency were considered using Plackett–Burman design as a screening method. To obtain the optimum conditions with consideration of the selected significant variables, a Box–Behnken design was used. The microextraction procedure was performed using 29.1 μL of 1‐undecanol, 1.36% (w/v) of NaCl, 10.0 μL of sodium dodecyl sulfate (25.0 μg mL−1), and 1.0 μL of Tween80 (25.0 μg mL−1) as an emulsifier in an extraction time of 20.0 min at pH 7.88. In order to investigate the validation of the developed method, some validation parameters including the linear dynamic range, repeatability, limit of detection, and recoveries were studied under the optimum conditions. The detection limits of the method were 0.017 and 0.086 ng mL−1 for nitrazepam and midazolam, respectively. The extraction recovery percentages for the drugs studied were above 91.0 with acceptable relative standard deviation. The proposed methodology was successfully applied for the determination of these drugs in a number of human serum samples.
Increasing the Rainfall Kinetic Energy of Spray Nozzles by using Meshes
Authors: Carvalho Sílvia C. P. , de Lima João L. M. P. , de Lima M. Isabel P.
Published: March 2015

Rainfall simulators are an important tool in studying soil erosion, which is a key process contributing to land degradation. The kinetic energy of simulated rain is central to these studies and it is used as an indicator of the raindrops' ability to detach particles from the soil surface. The main purpose of this experimental work was to explore the usefulness of incorporating meshes underneath pressurised nozzles' rain simulators that intercept the drops sprayed out by the nozzles and change the simulated rain characteristics, namely by increasing the rainfall kinetic energy. The laboratory experiments included testing four types of spray nozzles (discharge from 2·3 to 11·9 L min−1), combined with a high‐density polyethylene mesh (square aperture of 20 mm). The effect of the mesh was studied for three vertical distances between the nozzle and the mesh (0·20, 0·40 and 0·60 m). A laser disdrometer was used to measure the diameter and fall speed of the simulated raindrops. For the mesh‐free simulations, the nozzles produced drops having on average a mean equivalent diameter of around 0·6 mm and a mean fall speed of about 1·5 m s−1. The mesh increased the formation of bigger drops (>2·5 mm) and, consequently, increased the rainfall kinetic energy of the simulated rain; the magnitude of this increase varied with the spray produced by the nozzles. Results show that meshes can be useful for increasing the kinetic energy of the rainfall simulated by nozzles within soil erosion studies. Copyright © 2015 John Wiley & Sons, Ltd.
Improved Electrical Performance of Poly(3‐hexylthiophene) Induced by Stable Doping with Polymer Dopants
Authors: Chen Jiayue , Chen Zhaobin , Yang Dalei , Ye Feng , Wang Sisi , Yang Xiaoniu
Published: March 2015

A series of brominated polystyrenes (BPSs) are readily synthesized and blended as polymer dopants with the p‐type semiconducting polymer, poly(3‐hexylthiophene) (P3HT), to improve theirelectrical performance. The obtained P3HT/BPS blend films exhibit increased carrier concentration resulting from doping of P3HT by BPS, which leads to excellent electrical performance, including enhanced hole mobility and conductivity, and the conductivity or mobility increases with the bromination degree of BPS. Compared with conventional small molecular dopants, the polymer dopant, BPS, shows not only excellent doping stability, but also good solution processibility, which makes it a promising materials for fabrication of low cost, flexible, transparent, and high performance solution processable organic electronic devices.

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NlpI‐mediated modulation of outer membrane vesicle production through peptidoglycan dynamics in Escherichia coli
Authors: Schwechheimer Carmen , Rodriguez Daniel L. , Kuehn Meta J.
Published: March 2015

Outer membrane vesicles (OMVs) are ubiquitously secreted from the outer membrane (OM) of Gram‐negative bacteria. These heterogeneous structures are composed of OM filled with periplasmic content from the site of budding. By analyzing mutants that have vesicle production phenotypes, we can gain insight into the mechanism of OMV budding in wild‐type cells, which has thus far remained elusive. In this study, we present data demonstrating that the hypervesiculation phenotype of the nlpI deletion mutant of Escherichia coli correlates with changes in peptidoglycan (PG) dynamics. Our data indicate that in stationary phase cultures the nlpI mutant exhibits increased PG synthesis that is dependent on spr, consistent with a model in which NlpI controls the activity of the PG endopeptidase Spr. In log phase, the nlpI mutation was suppressed by a dacB mutation, suggesting that NlpI regulates penicillin‐binding protein 4 (PBP4) during exponential growth. The data support a model in which NlpI negatively regulates PBP4 activity during log phase, and Spr activity during stationary phase, and that in the absence of NlpI, the cell survives by increasing PG synthesis. Further, the nlpI mutant exhibited a significant decrease in covalent outer membrane (OM‐PG) envelope stabilizing cross‐links, consistent with its high level of OMV production. Based on these results, we propose that one mechanism wild‐type Gram‐negative bacteria can use to modulate vesiculation is by altering PG‐OM cross‐linking via localized modulation of PG degradation and synthesis.
Detection of subnanotesla oscillatory magnetic fields using MRI
Authors: Jiang Xia , Sheng Jingwei , Li Huanjie , Chai Yuhui , Zhou Xin , Wu Bing , Guo Xiaodong , Gao Jia‐Hong
Published: March 2015

Purpose

Direct mapping of neuronal currents using MRI would have fundamental impacts on brain functional imaging. Previous reports indicated that the stimulus‐induced rotary saturation (SIRS) mechanism had the best potential of direct detection of neural oscillations; however, it lacked the high‐sensitivity level needed. In this study, a novel strategy is proposed in an effort to improve the detection sensitivity.

Methods

In our modified SIRS sequence, an external oscillatory magnetic field is used as the excitation pulse in place of the standard 90‐degree excitation pulse. This approach could potentially lead to tens or even hundreds times of enhancement in the detection sensitivity for low field signals. It also helps to lower the physiological noise, allows for shorter pulse repetition time, and is less affected by the blood oxygen level.

Results

We demonstrate that a 100‐Hz oscillatory magnetic field with magnitude as low as 0.25 nanotesla generated in a current loop can be robustly detected using a 3‐Tesla MRI scanner.

Conclusion

The modified SIRS sequence offers higher detection sensitivity as well as several additional advantages. These promising results suggest that the direct detection of neural oscillation might be within the grasp of the current MRI technology. Magn Reson Med 75:519–526, 2016. © 2015 Wiley Periodicals, Inc.
Contact mechanism of a rock fracture subjected to normal loading and its impact on fast closure behavior during initial stage of fluid flow experiment
Authors: Li Bo , Zhao Zhihong , Jiang Yujing , Jing Lanru
Published: March 2015

Fast closure of rock fractures has been commonly observed in the initial stage of fluid flow experiments at environmental temperatures under low or moderate normal stresses. To fully understand the mechanisms that drive this fast closure, the evolution of local stresses acting on contacting asperities on the fracture surfaces prior to fluid flow tests needs to be evaluated. In this study, we modeled numerically the asperity deformation and failure processes during initial normal loading, by adopting both elastic and elastic–plastic deformation models for the asperities on a real rock fracture with measured surface topography data, and estimated their impact on initial conditions for fluid flow test performed under laboratory conditions. Compared with the previous models that simulate the normal contact of a fracture as the approach of two rigid surfaces without deformations, our models of deformable asperities yielded smaller contact areas and higher stresses on contacting asperities at a given normal stress or normal displacement. The results show that the calculated local stresses were concentrated on the contacts of a few major asperities, resulting in crushing of asperity tips. With these higher contact stresses, however, the predicted closure rates by pressure solution are still several orders of magnitude lower than that of the experimental measurements at the initial stage of fluid flow test. This indicates that single pressure solution may not likely to be the principal compaction mechanism for this fast closure, and that the damages on contacting asperities that occur during the initial normal loading stage may play an important role. Copyright © 2015 John Wiley & Sons, Ltd.
Use of clean intermittent self‐catheterization in France: A survey of patient and GP perspectives
Authors: Gonzalez Chiappe Solange , Lasserre Andrea , Chartier Kastler Emmanuel , Falchi Alessandra , Blaizeau Fanette , Blanchon Thierry , Hanslik Thomas , Denys Pierre
Published: March 2015

Aims

To estimate the prevalence of GP (general practitioner) patients performing ISC (intermittent self‐catheterization), to describe GP and patient knowledge about ISC and to assess the patients’ quality of life.

Methods

A cross‐sectional study was conducted in metropolitan France between November 2012 and September 2013 with French Sentinelles GPs and their patients (≥18 years) performing ISC. Linear regression models assessed independent associations between quality of life scores (Qualiveen and SF‐12 scores) and patients’ characteristics.

Results

The prevalence of ISC performers was estimated to be 61.7 (95% confidence interval [CI] = 61.0–62.4) of 100,000 inhabitants. Patients were males in 58.8% of cases and 53.8 years of age on average. They performed 4.84 catheterizations per day for 10.5 years. Over 1 year, there were 118 (55.1%) cases of patient‐reported urinary incontinence (UI) and 158 (63.3%) cases of patient‐reported urinary tract infection (UTI). Symptomatic UTIs were treated with antibiotics in 79.7% of cases. The average Qualiveen score was 1.38 (95%CI: 1.23–1.53). The average SF‐12 Physical Component Score (PCS) and Mental Component Score (MCS) were 38.6 (95%CI: 36.8–40.4) and 46.4 (95%CI: 44.3–48.5), respectively. According to multivariate analysis, a poorer Qualiveen score and constipation reduced the PCS and a urinary medication prescription reduced the MCS. A poorer Qualiveen score was also associated with UI and UTI on bivariate analysis.

Conclusions

ISC seems to be significant in French general practice whereas practical skills remain heterogeneous. UI, UTI, and constipation are recurrent issues among ISC performers that significantly decrease their quality of life. Education and adapted guidelines for GP guidance could improve these patients’ conditions. Neurourol. Urodynam. 35:528–534, 2016. © 2015 Wiley Periodicals, Inc.
Beta‐diversity metrics of the upper digestive tract microbiome are associated with body mass index
Authors: Lin Shih‐Wen , Freedman Neal D. , Shi Jianxin , Gail Mitchell H. , Vogtmann Emily , Yu Guoqin , Klepac‐Ceraj Vanja , Paster Bruce J. , Dye Bruce A. , Wang Guo‐Qing , Wei Wen‐Qiang , Fan Jin‐Hu , Qiao You‐Lin , Dawsey Sanford M. , Abnet Christian C.
Published: March 2015

Objective

Studies of the fecal microbiome have implicated the gut microbiota in obesity, but few studies have examined the microbial diversity at other sites. The association between obesity and the upper gastrointestinal (UGI) microbial diversity was explored.

Methods

The UGI microbiome of 659 healthy Chinese adults with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized using the 16S rRNA gene DNA microarray (HOMIM).

Results

In multivariate‐adjusted models, alpha diversity was not associated with BMI. However, beta diversity, assessed by principal coordinate vectors generated from an unweighted UniFrac distance matrix of pairwise comparisons, was associated with BMI (third and fourth vectors, P = 0.01 and P = 0.03, respectively). Moreover, beta diversity, assessed by cluster membership (three clusters), was also associated with BMI; individuals in the first cluster [median BMI 22.35, odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.05‐4.34] and second cluster [median BMI 22.55, OR = 0.26, 95% CI = 0.09‐0.75] were significantly less likely to be obese (BMI ≥ 27.5) than those in the third cluster (median BMI 23.59).

Conclusions

A beta‐diversity metric of the UGI microbiome is associated with a four fold difference in obesity risk in this Asian population. Future studies should address whether the UGI microbiome plays a causal role in obesity.
Self‐Assembled Functionalized Graphene Nanoribbons from Carbon Nanotubes
Authors: Cunha Eunice , Proença Maria Fernanda , Costa Florinda , Fernandes António J. , Ferro Marta A. C. , Lopes Paulo E. , González-Debs Mariam , Melle-Franco Manuel , Deepak Francis Leonard , Paiva Maria C.
Published: March 2015

Graphene nanoribbons (GNR) were generated in ethanol solution by unzipping pyrrolidine‐functionalized carbon nanotubes under mild conditions. Evaporation of the solvent resulted in regular few‐layer stacks of graphene nanoribbons observed by transmission electron microscopy (TEM) and X‐ray diffraction. The experimental interlayer distance (0.49–0.56 nm) was confirmed by computer modelling (0.51 nm). Computer modelling showed that the large interlayer spacing (compared with graphite) is due to the presence of the functional groups and depends on their concentration. Stacked nanoribbons were observed to redissolve upon solvent addition. This preparation method could allow the fine‐tuning of the interlayer distances by controlling the number and/or the nature of the chemical groups in between the graphene layers.
Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin
Authors: Fu Ou , Pukin Aliaksei V. , Quarles van Ufford H. C. , Kemmink Johan , de Mol Nico J. , Pieters Roland J.
Published: March 2015

The bacterial adhesion lectin LecA is an attractive target for interference with the infectivity of its producer P. aeruginosa. Divalent ligands with two terminal galactoside moieties connected by an alternating glucose‐triazole spacer were previously shown to be very potent inhibitors. In this study, we chose to prepare a series of derivatives with various new substituents in the spacer in hopes of further enhancing the LecA inhibitory potency of the molecules. Based on the binding mode, modifications were made to the spacer to enable additional spacer–protein interactions. The introduction of positively charged, negatively charged, and also lipophilic functional groups was successful. The compounds were good LecA ligands, but no improved binding was seen, even though altered thermodynamic parameters were observed by isothermal titration calorimetry (ITC).
The use of zinc dimethacrylate functionalized graphene as a reinforcement in rubber composites
Authors: Lin Yong , Chen Yizhong , Zhang Ying , Jia Deming , Luo Yuangfang , Liu Lan
Published: March 2015

Zinc dimethacrylate functionalized graphene (Z‐GE), as reinforcing nanofiller for natural rubber (NR), was synthesized by liquid‐phase exfoliation and in situ method. The morphology and structure of Z‐GE were characterized to confirm the exfoliation and functionalization of GE. The NR/Z‐GE composites were prepared and investigated by mechanical analysis, crosslinked network analysis and the analysis of thermal conductivity. The results showed that the tensile strength, tear strength and modulus at 300% strain of NR/Z‐GE‐20 composites (contents 1.400 phr GE) were increased by 142%, 76% and 231% as compared with the pure NR, respectively. And the thermal conductivity of NR/Z‐GE‐30 composites is enhanced by 39% as that of the pure NR. This significant improvement is attributed to the formation of covalent crosslinked network and ionic crosslinked network and efficient interfacial interaction between GE and NR matrix. This method provides a new insight into the fabrication of multifunctional GE composites and enlarges its potential applications in high performance GE‐based rubber composites. Copyright © 2015 John Wiley & Sons, Ltd.
Alemtuzumab based reduced intensity transplantation for pediatric severe aplastic anemia
Authors: Ngwube Alexander , Hayashi Robert J. , Murray Lisa , Loechelt Brett , Dalal Jignesh , Jaroscak Jennifer , Shenoy Shalini
Published: March 2015

Background

Hematopoietic cell transplantation (HCT) is curative in patients with severe aplastic anemia (SAA). HCT is considered at presentation when a HLA‐matched related donor (MRD) is available and has a high success rate. Unrelated donor (URD) transplants are typically undertaken if immunosuppressive therapy fails. Increased toxicity and graft rejection are often encountered in this setting.

Procedure

We report a prospective multi‐center trial of HCT in 17 children with SAA following novel reduced intensity conditioning with alemtuzumab, fludarabine and melphalan, and the best available donor. Nine were URD transplants matched at 7–8/8 loci, and performed following failure of immune suppression. Median follow up was 61 months (range 6–128).

Results

All patients engrafted. Estimated 5 year event‐free and overall‐survival was 88% (95%CI 65.7–96.7). Five year overall survival for MRD and URD transplants was 100% and 78% (95%CI 45–93.6) respectively. Median times to neutrophil and platelet engraftment was 14 (range 10–27) and 23.5 (range 11–65) days respectively. Treatment related mortality was 12%. The incidence of grade II–IV and III–IV acute graft‐versus‐host disease was 29% and 18% respectively. At two years, all but one patient discontinued immunosuppression successfully. Laboratory measures of immune reconstitution normalized at one year and infection rates were low in the latter part of the first year.

Conclusions

HCT using this RIC approach was well tolerated and successful in achieving donor engraftment and early immune reconstitution with good quality of life free of immune suppression. Children with SAA can be successfully transplanted using alemtuzumab based conditioning. Pediatr Blood Cancer 2015;62:1270–1276. © 2015 Wiley Periodicals, Inc.
Osteosarcoma in patients younger than 12 years old without metastases have similar prognosis as adolescent and young adults
Authors: Eleutério Sabrina Jeane Prates , Senerchia Andreza Almeida , Almeida Maria Teresa , Costa Cecilia Maria Da , Lustosa Daniel , Calheiros Luiz Mario , Barreto Jose Henrique Silva , Brunetto Algemir Lunardi , Macedo Carla Renata Pacheco Donato , Petrilli Antonio Sergio
Published: March 2015

Background

Childhood cancer is relatively rare and tends to present specific age distribution, as a prognostic factor for some of these diseases. Information on how young age affects prognosis, response to chemotherapy, and local control options in children versus AYA with osteosarcoma (OST) is minimal.

Methods

In order to identify the main differences in clinicalpathologic features, surgical approaches and survival rates of primary high grade OST of the extremity between children (n = 156; <12 years old) and AYA (n = 397; 12–30 years old), the institutional database with 553 patients treated by BOTG studies over 15 years were reviewed.

Results

There were no differences in metastasess at diagnosis, tumor size, and grade of necrosis between the two age groups. The rate of amputation was 30% higher in the children group (P = 0.018). The rate of limb salvage surgery using reconstruction with allograft or autograft was 70% higher in the children group (P = 0.018) while endoprosthesis rate was 40% higher in the AYA group (P = 0.018). The log rank test revealed that survival is similar between the two age groups for non‐metastatic patients (P = 0.424 for OS and P = 0.393 for EFS). Metastatic patients of both ages group had higher risk of dying compared to non‐metastatic (HR 3.283 95% CI 2.581–4.177; P < 0.001). Children with metastases at diagnosis had less OS time (P = 0.049) and EFS time (P = 0.032) than adolescents.

Conclusion

Non‐metastatic OST in preadolescent patients does not appear to be significantly differentfrom those seen in AYA patients, but has local control challenges. Children presenting with metastases should be considered an ultra‐high‐risk group. Pediatr Blood Cancer 2015;62:1209–1213. © 2015 Wiley Periodicals, Inc.
CD19: A multifunctional immunological target molecule and its implications for Blineage acute lymphoblastic leukemia
Authors: Weiland Judith , Elder Alex , Forster Victoria , Heidenreich Olaf , Koschmieder Steffen , Vormoor Josef
Published: March 2015

Over the last 20–30 years CD19 has gained attention as a potential target in the therapy of B‐cell malignancies. In particular, targeting CD19 with the bispecific T‐cell engager (BiTE) antibody Blinatumomab and T‐cells modified by chimeric antigen receptors (CAR) has shown promising efficacy in early phase clinical trials for adults and children with precursor B‐cell ALL (BCP–ALL). This review will discuss the rationale behind targeting CD19 in BCP‐ALL and its potential importance in BCP‐ALL signaling pathways. Pediatr Blood Cancer 2015;62:1144–1148. © 2015 Wiley Periodicals, Inc.
Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T‐cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434
Authors: Winter Stuart S. , Dunsmore Kimberly P. , Devidas Meenakshi , Eisenberg Nancy , Asselin Barbara L. , Wood Brent L. , Leonard RN Marcia S. , Murphy John , Gastier‐Foster Julie M. , Carroll Andrew J. , Heerema Nyla A. , Loh Mignon L. , Raetz Elizabeth A. , Winick Naomi J. , Carroll William L. , Hunger Stephen P.
Published: March 2015

Background

Nelarabine has shown impressive single agent clinical activity in T‐cell acute lymphoblastic leukemia (T‐ALL), but has been associated with significant neurotoxicities in heavily pre‐treated patients. We showed previously that it was safe to add nelarabine to a BFM‐86 chemotherapy backbone (AALL00P2). Children's Oncology Group (COG) AALL0434 is a Phase III study designed to test the safety and efficacy of nelarabine when incorporated into a COG augmented BFM–based regimen, which increases exposure to agents with potential neurotoxicity compared to the historical AALL00P2 regimen.

Procedure

AALL0434 included a safety phase to assess nelarabine toxicity. Patients with high‐risk (HR) T‐ALL were randomized to receive Capizzi‐style escalating methotrexate (MTX) plus pegaspargase or high dose (HD) MTX with/without six five‐days courses of nelarabine. We report results from 94 patients who participated in the initial safety phase of the study.

Results

There were no differences in the incidence of peripheral motor neuropathies, sensory neuropathies or central neurotoxicities among those randomized to the nelarabine (n = 47) and non‐nelarabine arms (n = 47).

Conclusions

The addition of nelarabine to COG‐augmented BFM chemotherapy regimen is safe and feasible. The ongoing AALL0434 Efficacy Phase will determine whether the addition of nelarabine treatment improves outcome for patients with T‐ALL. Pediatr Blood Cancer 2015;62:1176–1183. © 2015 Wiley Periodicals, Inc.
Participation in pediatric oncology research protocols: Racial/ethnic, language and age‐based disparities
Authors: Aristizabal Paula , Singer Jenelle , Cooper Renee , Wells Kristen J. , Nodora Jesse , Milburn Mehrzad , Gahagan Sheila , Schiff Deborah E. , Martinez Maria E.
Published: March 2015

Background

Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio‐demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type, and insurance status.

Procedure

Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children's Hospital.

Results

Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyzes revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non‐Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; P = 0.021) and among children of Spanish‐speaking vs. English‐speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; P = 0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; P < 0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately.

Conclusions

There was significant underrepresentation in protocol participation for Hispanics, children of Spanish‐speaking parents, and patients ages 15–21. Research is needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. Pediatr Blood Cancer 2015;62:1337–1344. © 2015 Wiley Periodicals, Inc.
Lysine methylation modulates the protein–protein interactions of yeast cytochrome C Cyc1p
Authors: Winter Daniel L. , Abeygunawardena Dhanushi , Hart‐Smith Gene , Erce Melissa A. , Wilkins Marc R.
Published: March 2015

In recent years, protein methylation has been established as a major intracellular PTM. It has also been proposed to modulate protein‐protein interactions (PPIs) in the interactome. To investigate the effect of PTMs on PPIs, we recently developed the conditional two‐hybrid (C2H) system. With this, we demonstrated that arginine methylation can modulate PPIs in the yeast interactome. Here, we used the C2H system to investigate the effect of lysine methylation. Specifically, we asked whether Ctm1p‐mediated trimethylation of yeast cytochrome c Cyc1p, on lysine 78, modulates its interactions with Erv1p, Ccp1p, Cyc2p and Cyc3p. We show that the interactions between Cyc1p and Erv1p, and between Cyc1p and Cyc3p, are significantly increased upon trimethylation of lysine 78. This increase of interaction helps explain the reported facilitation of Cyc1p import into the mitochondrial intermembrane space upon methylation. This first application of the C2H system to the study of methyllysine‐modulated interactions further confirms its robustness and flexibility.