bluuebunny/crossref_metadata_2025 huggingface dataset:
Pegylated granulocyte‐colony stimulating factor versus non‐pegylated granulocyte‐colony stimulating factor for peripheral blood stem cell mobilization: A systematic review and meta‐analysis
Authors: Kuan Jew W. , Su Anselm T. , Leong Chooi F.
Published: May 2017

Granulocyte‐colony stimulating factor (G‐CSF) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood, enabling its harvest by few apheresis procedures. The pegylated G‐CSF has longer half‐life and is given once only, which is more comfortable for patients, whereas the non‐pegylated requires multiple daily injection because of its short half‐life. We summarized results of randomized trials comparing the efficacy and safety of pegylated and non‐pegylated G‐CSF for peripheral blood stem cell mobilization. We searched the Cochrane CENTRAL, MEDLINE, EMBASE, and two conference proceedings. Two authors made the selection, extracted data and evaluated methodological quality using GRADE independently. We used random‐effects model for meta‐analysis. We found 3956 records and retrieved 47 full texts. We included eight randomized trials with a total number of 554 randomized and 532 analyzed subjects. The meta‐analysis included five trials because not all trials reported the same outcomes. Pooling data from two studies shows no evidence for a difference in the successful mobilization rate (CD34+ cell ≥ 2 × 106/kg collected) between pegfilgrastim 6 mg (early administration) and filgrastim 5 µg/kg/day (147 participants; risk ratio (RR) 0.87, 95% confidence interval (95%CI) 0.67‐1.11; P = .26). Pooling data from three studies shows no difference in the incidence of adverse events between pegylated and non‐pegylated G‐CSF (170 participants; RR 0.86, 95%CI 0.34‐2.17; P = .75). No difference found on the quantity of CD34+ cells collected, number of apheresis procedure in successful mobilization, level of peak PB CD34+ cells achieved, and day of neutrophil and platelet engraftment.
Proteinase‐Activated Receptor‐2 Modulates Ve‐Cadherin Expression to Affect Human Vascular Endothelial Barrier Function
Authors: Zhang Rui , Ge Jianjun
Published: May 2017

Published data indicate that the protease‐activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve‐cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function. The transepithelial electric resistance (TER) and permeability to dextran were assessed as indicators of barrier function. The expression of Ve‐cadherin in Huvec cells was assessed by real‐time RT‐PCR, Western blotting, and chromatin immunoprecipitation. The results showed that exposure to tryptase in the culture, the barrier function of the Huvec monolayers, was markedly compromised; the levels of Ve‐cadherin, one of the tight junction proteins, were suppressed as well. This was mimicked by exposing Huvec monolayers to the active PAR2 peptides (PAR2AP). After exposing to PAR2AP, the levels of histone deacetylase (HDAC)11 were increased in the Huvec cells. HDAC11 formed a complex with the transcription factor of Ve‐cadherin to attenuate the Erg gene transcription activities and suppressed the expression of Ve‐cadherin. In conclusion, activation of PAR2 compromises the vascular endothelial barrier function by suppressing the expression of Ve‐cadherin. J. Cell. Biochem. 118: 4587–4593, 2017. © 2017 Wiley Periodicals, Inc.
Mechanistic Principles Behind Molecular Mechanism of Rifampicin Resistance in Mutant RNA Polymerase Beta Subunit of Mycobacterium tuberculosis
Authors: Singh Aditi , Grover Sonam , Sinha Siddharth , Das Mriganko , Somvanshi Pallavi , Grover Abhinav
Published: May 2017

Evolution of drug‐resistant Mycobacterium strains threatens the TB treatment and control programs globally. Rifampicin (RIF) is an important first line antitubercular drug. Resistance to Rifampicin is caused mainly by mutations in its target RNA polymerase beta subunit protein (RpoB). RpoB contains a Rifampicin resistance determining region (RRDR) and has several potent sites for mutations. In this study, we have investigated mutations of a single site (H451) to eight different amino acids, involved in RIF resistance. Long‐term molecular dynamics simulations were performed on wild type (WT) and mutant protein structures and various structural analysis were carried out to elucidate the dynamic behavior of WT and mutant forms. Essential dynamics uncovered the difference in conformational flexibility and collective modes of motions between WT and mutants. MMPBSA calculations and interaction pattern analysis revealed the binding site relocation in some mutants. This study presents an exhaustive analysis of RIF binding to the WT and mutant RpoB and clearly highlights structural mechanism for differences in stable binding of Rifampicin with WT than the mutant targets. J. Cell. Biochem. 118: 4594–4606, 2017. © 2017 Wiley Periodicals, Inc.
miR‐34a Targets HDAC1‐Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells
Authors: Zhao Qingguo , Li Shuqiang , Li Nan , Yang Xiaoling , Ma Shengchao , Yang Anning , Zhang Hui , Yang Songhao , Mao Caiyan , Xu Lingbo , Gao Tingting , Yang Xiaoming , Zhang Huiping , Jiang Yideng
Published: May 2017

Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy‐induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR‐34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE−/− mice fed with high methionine diet, whereas miR‐34a expression was inhibited. Over‐expression of HDAC1 inhibited H3K9ac level and promoted the accumulation of total cholesterol, free cholesterol, and triglycerides in the foam cells. Furthermore, up‐regulation of miR‐34a reduced HDAC1 expression and inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) in the foam cells. These data suggest that HDAC1‐related H3K9ac plays a key role in Hcy‐mediated lipid metabolism disorders, and that miR‐34a may be a novel therapeutic target in Hcy‐related atherosclerosis. J. Cell. Biochem. 118: 4617–4627, 2017. © 2017 Wiley Periodicals, Inc.
Necroptosis Resumes Apoptosis in Hippocampus but Not in Frontal Cortex
Authors: Nikseresht Sara , Khodagholi Fariba , Dargahi Leila , Ahmadiani Abolhassan
Published: May 2017

Cell death subsequent to or concurrent with neuroinflammation results in some damages like neuron loss and spatial memory impairment. In this study, we demonstrated the temporal pattern of neuroinflammation, necroptotic, and apoptotic cell deaths in hippocampus and frontal cortex following intracerebroventricular administration of lipopolysaccharide (LPS). We evaluated receptor interacting protein kinase 1 (RIP1), RIP3, and two related metabolic enzymes including glutamate‐ammonia ligase (GLUL) and glutamate dehydrogenase (GLUD) as necroptosis factors. Apoptosis pathway, antioxidant status and inflammatory cytokines were also assessed. Based on the probable role of these brain regions in working memory performance, spontaneous alternation was evaluated through the Y‐maze apparatus. RIP1, RIP3, and then GLUL and GLUD, as well as apoptosis markers, inflammatory regulators, and antioxidant defense demonstrated different time‐dependent patterns in hippocampus and frontal cortex. Interestingly, in hippocampus but not in frontal cortex, necroptosis resumed apoptosis. Our results in behavioral section revealed that neuroinflammation along with apoptosis and necroptosis pathways could lead to reversible short‐term memory impairment after LPS injection. In conclusion, it can be suggested that there is a region‐specific response of cell deaths regulators activation in hippocampus and frontal cortex. In addition, elucidating the time profile of events in response to neuroinflammation would be of great help in mechanistic studies and understanding of pathways interaction. J. Cell. Biochem. 118: 4628–4638, 2017. © 2017 Wiley Periodicals, Inc.
Shikonin Inhibited Migration and Invasion of Human Lung Cancer Cells via Suppression of c‐Met‐Mediated Epithelial‐to‐Mesenchymal Transition
Authors: Hsieh Yei‐San , Liao Chiung‐Ho , Chen Wan‐Shen , Pai Jih‐Tung , Weng Meng‐Shih
Published: May 2017

Epithelial‐to‐mesenchymal transition (EMT) is a major process to regulate cell migration and invasion. Inhibition of epidermal growth factor receptor (EGFR)‐mediated EMT by tyrosine kinase inhibitors (TKIs) is a strategy to prevent lung cancer invasion. However, drug resistance is emerged and accelerated invasion through other signaling bypassing EGFR after TKIs therapy. c‐Met signaling pathway is highly activated in EGFR‐mutated lung cancer cells. Targeting c‐Met signaling pathway may be a strategy to suppress EGFR‐independent migration and invasion for lung cancer therapy. Therefore, we examined the anti‐migration and anti‐invasion abilities of shikonin, an active compound from Lithospermum erythrorhizon, in highly and ligand‐induced c‐Met activation lung cancer cells. Our results revealed that cell viability and cell cycle progression did not change under 1 μM of shikoinin treatment in highly c‐Met expressive HCC827 lung cancer cells. Endogenous c‐Met activation was dose‐dependently inhibited and the migration and invasion activity of HCC827 cells were suppressed by shikonin treatment. Induction of E‐cadherin expression and inhibition of vimentin, slug, and snail expression by shikonin was through c‐Met‐mediated PI3K/Akt and ERK signaling suppression. Furthermore, hepatocyte growth factor (HGF)‐induced migration, invasion and EMT marker change were reversed by shikonin in low c‐Met expressive A549 lung cancer cells. Inhibition of HGF‐induced c‐Met, PI3K/Akt and MEK/ERK activation were observed in shikonin‐treated cells. Co‐treatment of PI3K/Akt inhibitor or ERK inhibitor with shikonin enhanced shikonin‐reversed HGF‐regulated EMT marker expression. Taken together, the results suggested that the anti‐migration and anti‐invasion activities of shikonin was through c‐Met inhibition and following by EMT suppression in lung cancer. J. Cell. Biochem. 118: 4639–4651, 2017. © 2017 Wiley Periodicals, Inc.
Decreased expression of hsa_circ_0003570 in hepatocellular carcinoma and its clinical significance
Authors: Fu Liyun , Wu Shengdong , Yao Ting , Chen Qingqing , Xie Yi , Ying Sheng , Chen Zhigang , Xiao Bingxiu , Hu Yaoren
Published: May 2017

Background

Circular RNAs (circRNAs) constitute a class of non‐coding RNAs recently discovered to be widespread and abundant in mammalian cells. However, the expression features of most of circRNAs in hepatocellular carcinoma (HCC) are unraveled. In this study, we focused on hsa_circ_0003570, which was found to be down‐regulated in HCC tissues in our previous microarray screening.

Methods

The hsa_circ_0003570 levels in HCC cell lines, HepG2, SMMC‐7721, MHCC97L, MHCC97H, and HCCLM3, and human normal hepatic cell line L02 were detected by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Then, its levels in 107 paired HCC tissues and adjacent non‐tumor tissues, 60 liver biopsy samples from patients with chronic liver diseases were detected by qRT‐PCR. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of hsa_circ_0003570 for HCC.

Results

Hsa_circ_0003570 was not only first found down‐regulated in HCC cell lines (P<.001) but also in HCC tissues (P<.001). Moreover, hsa_circ_0003570 was gradually decreased from chronic hepatitis (CH), to liver cirrhosis (LC) and to HCC tissues (P<.01). Its expression levels were significantly correlated with tumor diameter (P=.035), differentiation (P=.013), microvascular invasion (P=.045), Barcelona Clinic Liver Cancer stages (P=.011), tumor‐node‐metastasis stages (P=.016), and serum alpha‐fetoprotein levels (P=.031). The ROC curve demonstrated that hsa_circ_0003570 had poor performance for differentiating HCC from LC and CH, but had relatively good performance for differentiating LC from CH.

Conclusions

These results indicated that hsa_circ_0003570 expression levels were associated with HCC clinicopathological characteristics.
What would your neighbor do? An experimental approach to the study of informal social control of intimate partner violence in South Korea
Authors: Emery Clifton R. , Yang Hyerin , Kim Oksoo , Arenas Carmen , Astray Andres
Published: May 2017

Although research on bystander intervention and informal social control of intimate partner violence (IPV) is increasingly common, empirical anomalies remain and experimental studies on population samples are rare. This study reports the effects of a new experimental approach to the study of informal social control of IPV by neighbors on a small population sample of 100 married men in Seoul, South Korea. We hypothesized that men randomly assigned to a high‐perceived informal social control condition would have lower self‐estimated likelihoods of IPV perpetration in response to a vignette. We also hypothesized that the effect of random assignment would be different for that portion of the sample that reported perpetration of family violence (IPV or child abuse). Compared to the nonperpetrating portion of the sample, perpetrators of family violence in the sample randomly assigned to the high perceived control condition experienced a significant drop in self‐estimated likelihood of IPV perpetration.
Removal of arsenic (III) and arsenic (V) from aqueous solutions through adsorption by Fe/Cu nanoparticles
Authors: Babaee Yassaman , Mulligan Catherine N , Rahaman Md Saifur
Published: May 2017

BACKGROUND

While various iron‐based nanomaterials have been studied for the removal of arsenic from groundwater or its immobilization in soils, this study focuses on the applicability of iron/copper bimetallic nanoparticles for removal of arsenic from synthetic contaminated waters. In order to determine the effectiveness of these nanoparticles for arsenic removal, after synthesis, various sorption tests were performed with aqueous arsenic solutions.

RESULTS

Detailed physicochemical characterization of synthesized nanoparticles confirmed the successful formation of Fe/Cu nanoparticles with a mean diameter of 13.17 nm. These nanoparticles were found to be effective for removing arsenic from aqueous solutions. The maximum sorption capacities for As(III) and As(V) were 19.68 mg g−1 and 21.32 mg g−1, respectively, at a pH of 7.0. Adsorption isotherms fit well into the Langmuir equation, and sorption follows pseudo‐second‐order kinetics. Coexisting carbonate, sulfate, and phosphate ions had no significant effect on the removal efficiency of arsenic at the concentrations studied. Arsenic removal efficiency by Fe/Cu nanoparticles is enhanced in acidic environments and in basic conditions, desorption of arsenic is possible.

CONCLUSION

The Fe/Cu nanoparticle powder was found to be effective for removal of arsenic from water and has potential to be used for arsenic remediation from the aquatic environment or in situ immobilization of arsenic. © 2017 Society of Chemical Industry
Sonographic findings of IgG4‐related disease of the salivary glands: Case report and review of the literature
Authors: Narayan Anand K. , Baer Alan , Fradin Joel
Published: May 2017

IgG4‐related disease is a relatively newly described entity with findings that historically have been confused with a variety of other diseases with markedly different treatments and prognoses, including Sjogren's syndrome and MALT lymphoma. We present a case of IgG4‐related disease of the salivary glands and review the literature on sonographic findings of IgG4‐related disease. By connecting sonographic features of IgG4 disease with common ancillary features of IgG4 disease in other sites (pancreas, hilar lymph nodes, biliary tree, thyroid, and retroperitoneum), radiologists can play a pivotal role in the early diagnosis and identification of IgG4‐related disease. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:73–77, 2018;
Pyrazolo[5,1‐c][1,2,4]triazoles: Antimicrobial, Antitumor Activities, and Computational Docking Studies
Authors: Farghaly Thoraya A. , Abdallah Magda A. , Mahmoud Huda K. , El‐Metwaly Nashwa , Elaasser Mahmoud
Published: May 2017

A new series of pyrazolotriazoles 7a–l, 11, and 15a–c derived from the reaction of 3‐amino‐4‐(arylhydrazono)‐4,5‐dihydropyrazol‐5‐one 3a,b with various types of hydrazonoyl chlorides 4, 10, 12, and 13 was being synthesized in existence of triethylamine. The spectral data were assured the postulated structures for all compounds. All 7‐arylazopyrazolo[5,1‐c][1,2,4]triazole derivatives 7a–l, 11, and 15a–c have been evaluated for their antimicrobial and antitumor activities, and the results show that some derivatives have good to mild utility as antitumor and antibacterial operators. Moreover, the computational studies using AutoDock tools 4.2 are confirming the results in biological activity.
Electrothermal formulation of the partial element equivalent circuit method
Authors: Lombardi Luigi , Raimondo Raffaele , Antonini Giulio
Published: May 2017

This paper presents a combined electrothermal formulation of the partial element equivalent circuit (PEEC) method. It is shown that the distributed thermal problem can be formulated as an equivalent thermal network that shares the same topological and geometrical properties of the PEEC equivalent model. Temperature‐dependent thermal heat conduction and convection models are adopted thus leading to a time‐varying thermal network, which is studied by using pertinent techniques along with the electrical equivalent circuit. The proposed electrothermal PEEC solver is used to analyze 2 problems of interest and verified through comparison with a commercial software.
Assessment of thermal damage in total knee arthroplasty using an osteocyte injury model
Authors: Kurata Kosaku , Matsushita Junpei , Furuno Atsushi , Fujino Junichi , Takamatsu Hiroshi
Published: May 2017

Polymethylmethacrylate bone cement has been widely used for the anchorage of artificial implants in various orthopedic surgeries. Although it is one of the most successful biomaterials in use, excess heat generation intrinsically causes thermal damage to bone cells adjacent to the bone cement. To estimate a risk of thermal injury, a response of bone cells to cement polymerization must be elucidated because of the occurrence of thermal damage. Thermal damage is affected not only by maximal temperature but also by exposure time, temperature history, and cell type. This study aimed at quantifying the thermal tolerance of bone cells for the development of a thermal injury model, and applying this model for the estimation of thermal damage during cement polymerization in total knee arthroplasty. Osteocytes, osteoblasts, and fibroblasts were respectively subjected to steady supraphysiological temperatures ranging from 45 to 50°C. Survival curves of each cell and temperatures were used to formulate the Arrhenius model. A three‐dimensional heat conduction analysis for total knee arthroplasty was conducted using the finite element model based on serial CT images of human knee. A maximal temperature rise of 50°C was observed at the interface between the 3‐mm thick cement and the tissue immediately beneath the tibial tray of the prosthesis. The probability of thermal damage to the osteocyte, which was calculated using the Arrhenius model, was negligible at a distance of at least 1 mm away from the cement–bone interface. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2799–2807, 2017.
Effect of impact assembly on the interface deformation and fretting corrosion of modular hip tapers: An in vitro study
Authors: Panagiotidou Anna , Cobb Timothy , Meswania Jay , Skinner John , Hart Alister , Haddad Fares , Blunn Gordon
Published: May 2017

Wear and corrosion at the modular head–neck junction has been recognised to be a potential clinical concern, with multiple reports on adverse local tissue reactions and subsequent early failure of metal‐on‐metal hip replacements. Furthermore, reports on head–neck taper corrosion are also being described with conventional metal‐on‐polyethylene bearings. Manufacturing tolerances, surgical technique, non‐axial alignment, material combination, high frictional torque and high bending moment have all been implicated in the failure process. There is limited guidance on the force of impaction with which surgeons should assemble modular hip prostheses. This study aims to investigate the effect of impaction force on the deformation and corrosion of modular tapers. Short neck tapers with high surface roughness (average Rz = 16.58 μm, Ra = 4.14μm) and long neck tapers with low surface roughness (average Rz = 3.82 μm, Ra = 0.81μm), were assembled with CoCrMo alloy heads (smooth finish) under controlled conditions with 2, 4 or 8 kN of impaction force. Material combinations tested included CoCrMo‐head/CoCrMo‐neck and CoCrMo‐head/Ti‐6Al‐4V‐neck. Assessment of surface deformation before and after impaction was made using surface profilometry. Measurement of fretting current during sinusoidal cyclic loading evaluated mechanically assisted corrosion for each assembly load during short‐term cyclic loading (1000‐cycles) and long‐term cyclic loading (5 million‐cycles). Deformation on head and neck tapers increased with assembly load. Fretting currents during short term simulation testing showed significantly lower currents (p < 0.05), in 8 kN assemblies when compared to 2 and 4 kN, especially for the short‐rough tapers. Long‐term simulator testing demonstrated a progressive reduction in fretting corrosion for samples impacted with 4 and 8 kN; however, this reduction was greater for samples impacted at 8 kN even at the start of testing. Based on our results, surgeons could minimise mechanically assisted crevice corrosion by using higher impact loads when assembling the head to the stem in total hip arthroplasty. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:405–416, 2018.
Metabolomics approach based on ultra‐high‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry to identify the chemical constituents of the Traditional Chinese Er‐Zhi‐Pill
Authors: Zhong Xunlong , Zhong Yanmei , Yan Kangqi , Xiao Xuerong , Duan Lian , Wang Ruolun , Wang Laiyou
Published: May 2017

Er‐Zhi‐Pill, which consists of Ligustri lucidi fructus and Ecliptae prostratae herba, is a classical traditional Chinese medicinal formulation widely used as a liver‐nourishing and kidney‐enriching tonic. To identify the bioactive ingredients of Er‐Zhi‐Pill and characterize the variation of chemical constituents between co‐decoction and mix of individually decocted L. lucidi fructus and E. prostratae herba, a novel metabolomics approach based on ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry in both positive and negative ion modes, was established to comprehensively analyze chemical constituents and probe distinguishable chemical markers. In total, 68 constituents were unambiguously or tentatively identified through alignment of accurate molecular weights within an error margin of 5 ppm, elemental composition and fragmentation characteristics, including eight constituents, which were confirmed by comparing to reference standards. Furthermore, principal component analysis and partial least squares discriminant analysis using Simca‐p+ 12.0 software were applied to investigate chemical differences between formulations obtained by co‐decoction and a mixture of individual decoctions. Global chemical differences were found in samples of two different decoction methods, and 16 components, including salidroside, specneuzhenide and wedelolactone, contributed most to the observed differences. This study provides a basic chemical profile for the quality control and further mechanism research of Er‐Zhi‐Pill.
Enantioselective analysis of bambuterol in human plasma using microwave‐assisted chiral derivatization coupled with ultra high performance liquid chromatography and tandem mass spectrometry
Authors: Zhou Ting , Zeng Jing , Zhao Ting , Zhong Qisheng , Yang Yang , Tan Wen
Published: May 2017

In this study, an enantioselective analytical method based on microwave‐assisted chiral derivatization coupled with ultra high performance liquid chromatography and tandem mass spectrometry was developed for the determination of bambuterol enantiomers in human plasma. The chiral derivatization reaction was greatly accelerated by microwave irradiation. Under the optimized conditions, both the derivatization time and separation time on column was only 3 min, and the lower limit of quantification was 2.5 pg/mL. The recoveries were in the range of 90.1–93.0% without significant matrix effect. Compared with the conventional heating chiral derivatization, microwave‐assisted chiral derivatization obtained higher chiral derivatization yields with much shorter time due to the effect of microwave irradiation. Furthermore, the racemization during the derivatization reaction was systematically investigated. The results showed the concentration of acetic acid and the reaction time had significant effects on the racemization, which could be well controlled during microwave‐assisted chiral derivatization for the short reaction time. Finally, this novel approach was demonstrated by determining bambuterol in human plasma of a clinical pharmacokinetic study in eight healthy volunteers. On the basis of the results, microwave‐assisted chiral derivatization coupled with ultra high performance liquid chromatography and tandem mass spectrometry as a simple and effective enantioselective analysis technique for the determination of chiral drugs in complex biological samples showed great promise.
Trophic niche separation that facilitates co‐existence of high and low microbial abundance sponges is revealed by in situ study of carbon and nitrogen fluxes
Authors: Morganti T. , Coma R. , Yahel G. , Ribes M.
Published: May 2017

Sponges are commonly divided into high (HMA) and low (LMA) microbial‐abundance species according to the bacterial biomass in their tissue. These two groups reflect distinct aquiferous structures and feeding strategies. In the NW Mediterranean coralligenous community, HMA and LMA sponges are often packed in dense, multispecies assemblages that cover many pinnacles and overhangs. We investigated the metabolism of HMA and LMA species that cohabitate the coralligenous community by sampling in situ the inhaled and exhaled water. Sponges consumed plankton, dissolved organic carbon (DOC), and ammonium in relation to their abundance in ambient water. The plankton retention efficiency was high for all species. DOC was the main source of C for the sponge species, accounting for ∼ 90% of the examined sources. Nitrogen fluxes markedly differed between the two groups: plankton was the main source of nitrogen for LMAs that excreted dissolved organic nitrogen (DON) and ammonium. The nitrogenous waste products of LMAs were found to be the major source of nitrogen (up to 97%) for HMAs that efficiently removed DON and ammonium and excreted nitrate. The different capacity of both sponge strategies to use dissolved resources suggests a partial trophic niche separation related to HMA‐LMA dichotomy as a mechanism facilitating their dense co‐existence in the community. Our findings suggest that a mixed assemblage of sponges (and their associated microbes) is able to utilize the suspended particulate and dissolved material more efficiently than a single species population and may contribute to the understanding of the phenomena of the stability and diversity of dense sponge assemblages in oligotrophic habitats.
Metal‐Free Poly‐Cycloaddition of Activated Azide and Alkynes toward Multifunctional Polytriazoles: Aggregation‐Induced Emission, Explosive Detection, Fluorescent Patterning, and Light Refraction
Authors: Wu Yongwei , He Benzhao , Quan Changyun , Zheng Chao , Deng Haiqin , Hu Rongrong , Zhao Zujin , Huang Fei , Qin Anjun , Tang Ben Zhong
Published: May 2017

The metal‐free click polymerization (MFCP) of activated alkynes and azides or activated azide and alkynes have been developed into powerful techniques for the construction of polytriazoles without the obsession of metallic catalyst residues problem. However, the MFCP of activated azides and alkynes is rarely applied in preparation of functional polytriazoles. In this paper, soluble multifunctional polytriazoles (PIa and PIb) with high weight‐average molecular weights (Mw up to 32 000) are prepared via the developed metal‐free poly‐cycloaddition of activated azide and alkynes in high yields (up to 90%). The resultant PIa and PIb are thermally stable, and show aggregation‐induced emission characteristics, enabling their aggregates to detect explosives with superamplification effect. Moreover, thanks to their containing aromatic rings and polar moieties, PIa and PIb exhibit high refractive indices. In addition, they can also be cross‐linked upon UV irradiation to generate 2D fluorescent patterning due to their remaining azide groups and containing ester groups. Thus, these multifunctional polytriazoles are potentially applicable in the optoelectronic and sensing fields.

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An Open‐Circuit Voltage and Power Conversion Efficiency Study of Fullerene Ternary Organic Solar Cells Based on Oligomer/Oligomer and Oligomer/Polymer
Authors: Zhang Guichuan , Zhou Cheng , Sun Chen , Jia Xiaoe , Xu Baomin , Ying Lei , Huang Fei , Cao Yong
Published: May 2017

Variations in the open‐circuit voltage (Voc) of ternary organic solar cells are systematically investigated. The initial study of these devices consists of two electron‐donating oligomers, S2 (two units) and S7 (seven units), and the electron‐accepting [6,6]‐phenyl C71 butyric acid methyl ester (PC71BM) and reveals that the Voc is continuously tunable due to the changing energy of the charge transfer state (Ect) of the active layers. Further investigation suggests that Voc is also continuously tunable upon change in Ect in a ternary blend system that consists of S2 and its corresponding polymer (P11):PC71BM. It is interesting to note that higher power conversion efficiencies can be obtained for both S2:S7:PC71BM and S2:P11:PC71BM ternary systems compared with their binary systems, which can be ascribed to an improved Voc due to the higher Ect and an improved fill factor due to the improved film morphology upon the incorporation of S2. These findings provide a new guideline for the future design of conjugated polymers for achieving higher performance of ternary organic solar cells.

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Long noncoding RNA HAS2‐AS1 mediates hypoxia‐induced invasiveness of oral squamous cell carcinoma
Authors: Zhu Guiquan , Wang Shaoxin , Chen Jin , Wang Zhaohui , Liang Xinhua , Wang Xiaoyi , Jiang Jian , Lang Jinyi , Li Ling
Published: May 2017

A hypoxic microenvironment plays important roles in the progression of solid tumors, including oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. However, it is not clear whether lncRNAs can regulate hypoxia adaptation of OSCC or which lncRNAs participate in this process. Using a lncRNA microarray, we analyzed the aberrant lncRNA expression profiles in OSCC tissues compared with paired normal oral mucosa and in hypoxic OSCC cells compared with normoxic OSCC cells. The top 10 lncRNAs that had more than threefold increase with P‐value <0.01 in both microarray data were validated by qRT‐PCR. Among the top 10 lncRNAs, hyaluronan synthase 2 antisense 1 (HAS2‐AS1) was the only one that has a hypoxia‐responsive element (HRE) on its promoter region and has been validated to increase in OSCC tissues and in cells cultured under hypoxia. Tumor HAS2‐AS1 levels were closely associated with lymph node metastasis and hypoxic tumor status in patients with OSCC. Moreover, the hypoxia‐induced HAS2‐AS1 expression is dependent on HIF‐1α which directly binds to and activates the transcription of HAS2‐AS1. In addition, HAS2‐AS1 mediates hypoxia‐induced epithelial mesenchymal transition of OSCC cells via stabilizing HAS2. In conclusion, our results suggest that hypoxia would induce an overexpression of HAS2‐AS1 in an HIF‐1α dependent manner. The increase of HAS2‐AS1 plays important roles mediating the hypoxia‐regulated EMT and invasiveness of OSCC.
Flexible collective bargaining agreements: Still a moderating effect on works council behaviour?
Authors: Brändle Tobias
Published: May 2017

We analyse the interaction between different labour market institutions in Germany, namely, industry‐level bargaining and firm‐level codetermination by works councils. In particular, we are interested in the moderating effect of flexibility measures on the link between the existence works councils and collective agreements on wages and productivity. In presence of institutional changes, the question is whether works councils in covered plants still generate rather than redistribute rents, given recent decentralisation processes in the German system of industrial relations. We augment a theoretical model to provide hypotheses, which are then tested using empirical analysis of representative German plant level data. We find that the existence of flexibility provisions in collective bargaining agreements does not alter the effect of works council on firms' wages. We find, however, that with flexibility provisions works council presence is associated with higher productivity levels than without such provisions. These findings, however, depend on the level of collective bargaining: they can only be observed in plants covered by industry‐level contracts, but do not hold in plants covered by firm‐level contracts.
Consideration of difficulties and exit strategies in a case of face allotransplantation resulting in failure
Authors: Özkan Özlenen , Özkan Ömer , Doğan Umuttan , Yılmaz Vural Taner , Uysal Hilmi , Ündar Levent , Doğan Ebru Apaydın , Salim Ozan , Çinpolat Anı , Ramazanoglu Atilla
Published: May 2017

We describe the first rescue procedure in a case of total face allotransplantation. The recipient was a 54‐year‐old man with severe disfigurement of the entire face following an accidental gunshot injury 5 years previously. The large defect included the maxilla, mandible, and mid‐face. Full face procurement was performed from a multiorgan cadaveric donor and was allotransplanted to the recipient. The post‐transplant induction immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate mofetil, and prednisone, while maintenance was provided by the last three of these. Although the early postoperative period was uneventful, squamous cell carcinoma developed in the upper and lower extremities in the fifth postoperative month, and post‐transplant lymphoproliferative disorder (PTLD) occurred in the sixth month postoperatively. Malignancies were treated, involving both surgical and medical approaches. The patient developed opportunistic pulmonary and cerebellar aspergillosis. In order to reduce the adverse affects and metabolic and immunological load, the transplanted face was removed and replaced with a free flap. Although the early postoperative period was promising, with the transferred flap surviving totally and all vital signs and general status appearing to be improving, the patient was eventually lost due to complicated infectious and metabolic events. Although this case was unsuccessful, we suggest that the immunological and metabolic load should be reduced as soon as stable medical conditions are established in case of diagnosis of a situation involving a high rate of mortality, such as PTLD and untreatable opportunistic infections. This should include withdrawal of all immunosuppressive drugs and removal of all allotransplanted tissues.
Disclosure of industry payments to prescribers: industry payments might be a factor impacting generic drug prescribing
Authors: Qian Jingjing , Hansen Richard A. , Surry Daniel , Howard Jennifer , Kiptanui Zippora , Harris Ilene
Published: May 2017

Purpose

Pharmaceutical companies paid at least $3.91bn to prescribers in 2013, yet evidence indicating whether industry payments shift prescribing away from generics is limited. This study examined the association between amount of industry payments to prescribers and generic drug prescribing rates among Medicare Part D prescribers.

Methods

A cross‐sectional analysis was conducted among 770 095 Medicare Part D prescribers after linking the 2013 national Open Payments data with 2013 Medicare Provider Utilization and Payment data. The exposure variable was the categorized amount of total industry payments to prescribers (i.e., meals, travel, research, and ownership). The outcome was prescriber's annual generic drug prescribing rate. Multivariable generalized linear regression models were used to examine the association between the amount of industry payments and prescriber's annual generic drug prescribing rates, controlling for prescriber's demographic and practice characteristics.

Results

In this sample, over one‐third (38.0%) of Medicare Part D prescribers received industry payments in 2013. The mean annual generic drug prescribing rate was highest among prescribers receiving no payments and lowest among those receiving more than $500 of industry payments (77.5% vs. 71.3%, respectively; p < 0.001). The receipt of industry payments was independently associated with prescribers' generic drug prescribing rate; higher payments corresponded with lower generic drug prescribing rates. Other prescriber characteristics associated with higher annual generic drug prescribing rate included male sex, non‐northeast region, specialty, and patient volume.

Conclusions

Receipt of industry payments was associated with a decreased rate of generic drug prescribing. How this affects patient care and total medical costs warrants further study. Copyright © 2017 John Wiley & Sons, Ltd.
Law enforcement‐derived data on gabapentin diversion and misuse, 2002‐2015: diversion rates and qualitative research findings
Authors: Buttram Mance E. , Kurtz Steven P. , Dart Richard C. , Margolin Zachary R.
Published: May 2017

Purpose

Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especially among prescription opioid misusers. However, no apparent studies have reported data from law enforcement on the diversion and misuse of gabapentin.

Methods

Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Rates of gabapentin diversion per 100 000 population were calculated for each quarter from 2002 through 2015. Qualitative data are drawn from a brief questionnaire completed by a subsample of survey respondents and were organized and presented by theme.

Results

In total, 407 new cases of diverted gabapentin were reported during the time period, with diversion rates steadily increasing from zero cases in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population in the fourth quarter of 2015. Qualitative data suggest that gabapentin is being misused in conjunction with prescription opioids and that gabapentin and heroin are being combined and consumed together. Law enforcement reporters found these drug use trends to be contributing to gabapentin diversion.

Conclusions

The recent increase in gabapentin diversion appears to be related to the opioid epidemic, based on law enforcement descriptions of gabapentin being misused in combination with opioids. Yet epidemiological data related to this finding is limited and research conducted among gabapentin misusers is needed to understand this problem in more depth. Greater monitoring of gabapentin abuse and diversion appear warranted.
Exploring the expression bar code of SAA variants for gastric cancer detection
Authors: Wu Deng‐Chyang , Wang Kai‐Yi , Wang Sophie S.W. , Huang Ching‐Min , Lee Yi‐Wei , Chen Michael Isaac , Chuang Szu‐An , Chen Shu‐Hua , Lu Ying‐Wei , Lin Chun‐Cheng , Lee Ka‐Wo , Hsu Wen‐Hung , Wu Kun‐Pin , Chen Yu‐Ju
Published: May 2017

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe‐based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1‐ and SAA2‐encoded products, polymorphic isoforms, N‐terminal–truncated forms, and three novel SAA oxidized isotypes, in which the variant‐specific peptide sequence were also confirmed by LC‐MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA‐variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E−3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under‐represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.
Small airway function before and after cold dry air challenge in pediatric asthma patients during remission
Authors: Steinbacher Michael , Pfleger Andreas , Schwantzer Gerold , Jauk Stefanie , Weinhandl Elisabeth , Eber Ernst
Published: May 2017

Background

We wanted to compare cold dry air challenge (CACh) induced changes in spirometric parameters with changes in nitrogen multiple breath washout (N2MBW) parameters in pediatric asthma patients during clinical remission over the past year (ie, with “inactive asthma”). As N2MBW assesses ventilation heterogeneity we expected to gain detailed information about peripheral airways contribution.

Methods

In subjects with normal spirometry N2MBW, spirometry and body plethysmography were performed at baseline, after CACh, and after salbutamol inhalation. An initial measurement of the fraction of exhaled nitric oxide (FeNO) was conducted.

Results

Forty‐three (20 female) subjects, mean age 13.7 years (range 6.5‐18.6) performed reproducible N2MBW measurements. Ten were tested hyperresponsive (23.3%) and 33 normoresponsive (76.7%). Baseline spirometry and body plethysmography as well as FRC (N2MBW) were similar in both groups. Scond (0.031 vs 0.022), Sacin (0.057 vs 0.067), and FeNO (92.0 vs 28.5 ppb) were not statistically different between hyperresponsive and nomoresponsive subjects at baseline. Subjects with airway hyperresponsiveness (AHR) showed significant increases in lung clearance index (LCI, P = 0.011) and Scond (P = 0.008) after CACh, and significant decreases after salbutamol (LCI: P = 0.005; Scond: P = 0.005). In contrast, normoresponsive subjects showed no relevant changes after CACh, and only a decrease of Scond after salbutamol (P = 0.007). There were significant correlations between the CACh induced changes in FEV1 and changes in LCI (r = −0.45, P = 0.003), Scond (r = −0.30, P = 0.047), and Sacin (r = −0.47, P = 0.008), respectively.

Conclusion

Our study provides evidence of small airway involvement in children and adolescents with inactive asthma and airway hyperresponsiveness.
Field theoretical approach to gravitational waves
Authors: de Cesare M. , Oliveri R. , van Holten J.W.
Published: May 2017

The aim of these notes is to give an accessible and self‐contained introduction to the theory of gravitational waves as the theory of a relativistic symmetric tensor field in a Minkowski background spacetime. This is the approach of a particle physicist: the graviton is identified with a particular irreducible representation of the Poincaré group, corresponding to vanishing mass and spin two. It is shown how to construct an action functional giving the linear dynamics of gravitons, and how General Relativity can be obtained from it. The Hamiltonian formulation of the linear theory is examined in detail. We study the emission of gravitational waves and apply the results to the simplest case of a binary Newtonian system.
Role of N‐glycosylation in EGFR ectodomain ligand binding
Authors: Azimzadeh Irani Maryam , Kannan Srinivasaraghavan , Verma Chandra
Published: May 2017

The epidermal growth factor receptor (EGFR) is a tyrosine kinase protein, overexpressed in several cancers. The extracellular domain of EGFR is known to be heavily glycosylated. Growth factor (mostly epidermal growth factor or EGF) binding activates EGFR. This occurs by inducing the transition from the autoinhibited tethered conformation to an extended conformation of the monomeric form of EGFR and by stabilizing the flexible preformed dimer. Activated EGFR adopts a back‐to‐back dimeric conformation after binding of another homologous receptor to its extracellular domain as the dimeric partner. Several antibodies inhibit EGFR by targeting the growth factor binding site or the dimeric interfaces. Glycosylation has been shown to be important for modulating the stability and function of EGFR. Here, atomistic MD simulations show that N‐glycosylation of the EGFR extracellular domain plays critical roles in the binding of growth factors, monoclonal antibodies, and the dimeric partners to the monomeric EGFR extracellular domain. N‐glycosylation results in the formation of several noncovalent interactions between the glycans and EGFR extracellular domain near the EGF binding site. This stabilizes the growth factor binding site, resulting in stronger interactions (electrostatic) between the growth factor and EGFR. N‐glycosylation also helps maintain the dimeric interface and plays distinct roles in binding of antibodies to spatially separated epitopes of the EGFR extracellular domain. Analysis of SNP data suggests the possibility of altered glycosylation with functional consequences. Proteins 2017; 85:1529–1549. © 2017 Wiley Periodicals, Inc.