bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Fabrication of Stable Graphene‐Molecule‐Graphene Single‐Molecule Junctions at Room Temperature
Authors: Sun Hantao , Jiang Zhuoling , Xin Na , Guo Xuefeng , Hou Shimin , Liao Jianhui
Published: May 2018

We present a robust approach to fabricate stable single‐molecule junctions at room temperature using single‐layer graphene as nanoelectrodes. Molecular scale nano‐gaps in graphene were generated using an optimized fast‐speed feedback‐controlled electroburning process. This process shortened the time for creating a single nano‐gap to be less than one minute while keeping a yield higher than 97 %. To precisely control the gap position and minimize the effects of edge defects and the quantum confinement, extra‐narrow grooves were pre‐patterned in the graphene structures with oxygen plasma etching. Molecular junctions were formed by bridging the nano‐gaps with amino‐functionalized hexaphenyl molecules by taking advantage of chemical reactions between the amino groups at the two ends of the molecules and the carboxyl groups at the edges of graphene electrodes. Electronic transport measurements and transition voltage spectroscopy analysis verified the formation of single‐molecule devices. First‐principles quantum transport calculations show that the highest occupied molecular orbital of hexaphenyl is closer to the Fermi level of the graphene electrodes and thus the devices exhibit a hole‐type transport characteristics. Some of these molecular devices remained stable up to four weeks, highlighting the potential of graphene nano‐electrodes in the fabrication of stable single‐molecule devices at room temperature.
Chromatographic behavior of new deazapurine ribonucleosides in hydrophilic interaction liquid chromatography
Authors: Kalíková Květa , Voborná Markéta , Tesařová Eva
Published: May 2018

The chromatographic behavior of new biogenic purine nucleosides in hydrophilic interaction liquid chromatography was examined on three different stationary phases, namely bare silica, and amide‐ and cyclofructan‐based stationary phases. The effects of buffer concentration, pH and acetonitrile‐to‐aqueous‐part ratio in the mobile phase on retention and peak shape were assessed. The retention coefficients and peak symmetry values substantially differed with respect to analytes´ structures, stationary phase properties and mobile phase composition. The bare silica column was unsuitable for these compounds under the chromatographic conditions tested due to very broad and asymmetrical peaks. Furthermore, the cyclofructan‐based stationary phase provided almost Gaussian peak shapes of all deazapurine nucleosides under most conditions tested. Therefore, the cyclofructan‐based stationary phase is the most suitable choice for the chromatographic analysis of nucleosides.
Non‐Gaussian autoregressive processes with Tukey ‐and‐htransformations
Authors: Yan Yuan , Genton Marc G.
Published: May 2018

When performing a time series analysis of continuous data, for example, from climate or environmental problems, the assumption that the process is Gaussian is often violated. Therefore, we introduce two non‐Gaussian autoregressive time series models that are able to fit skewed and heavy‐tailed time series data. Our two models are based on the Tukey‐and‐htransformation. We discuss parameter estimation, order selection, and forecasting procedures for our models and examine their performances in a simulation study. We demonstrate the usefulness of our models by applying them to two sets of wind speed data.
Resilience and social support as protective factors against abuse of patients with dementia: A study on family caregivers
Authors: Serra Lídia , Contador Israel , Fernández‐Calvo Bernardino , Ruisoto Pablo , Jenaro Cristina , Flores Noelia , Ramos Francisco , Rivera‐Navarro Jesús
Published: May 2018

Objective

Scientific literature has identified different vulnerability factors associated to abuse in people with dementia (PWD), but little is known about the psychosocial protective variables against abuse. The main objective of this study is to investigate a set of caregiver and patient factors linked to abuse‐related behavior of PWD.

Methods

A total of 326 primary and family caregivers, residents of the Castilla and León community (Spain), were evaluated. All participants filled out a standardized protocol, which assessed the sociodemographic characteristics, patient and care‐related variables, as well as the perceived burden, resilience, and social support. Abuse‐related behavior was evaluated using the Caregiver Abuse Screen.

Results

Results show that the severity of cognitive impairment and behavior disorders of PWD, a greater number of caregiving hours, a worse previous relationship with the caregiver, and perceived burden are positively related with abuse. However, resilience and social support showed a negative relationship with Caregiver Abuse Screen scores, suggesting a protective effect on abuse, even after controlling the effect of a number of covariates. Indeed, resilience was the only variable that remained significant after including the effect of burden.

Conclusions

This paper states the role of burden in abuse of PWD, while resilience and social support are abuse protective factors. These variables should be considered in future guidelines for the prevention of abuse against PWD.
Hemin provides protection against lead neurotoxicity through heme oxygenase 1/carbon monoxide activation
Authors: Ye Fang , Li Xiaoyi , Liu Yawen , Chang Wei , Liu Wenqi , Yuan Jing , Chen Jun
Published: May 2018

The neurotoxicity of lead (Pb) is well established, and oxidative stress is strongly associated with Pb‐induced neurotoxicity. Heme oxygenase 1 (HO‐1) is an important antioxidative enzyme for protection against oxidative stress in many disease models. In this study, we applied hemin, the substrate and a well‐known inducer of HO‐1, to investigate the possible role of HO‐1 in protecting against Pb neurotoxicity. Hemin can significantly attenuate Pb acetate‐induced cell death and oxidative stress in the hippocampus and frontal cortex of developmental rats. Consistent with in vivo results, the protective effects of hemin were also observed in SH‐SY5Y cells after inducing cell survival and maintaining redox balance. However, knocking down HO‐1 could significantly abolish the cytoprotective action of hemin against Pb toxicity, confirming HO‐1 contributed to the protection. Finally, the HO‐1‐derived production of carbon monoxide, but not of bilirubin or Fe2+, mediated the protective effects of HO‐1 activation induced by hemin treatment against Pb‐induced cell death and oxidative stress in SHSY5Y cells. Overall, this study showed that hemin provided protection against Pb neurotoxicity by HO‐1/carbon monoxide activation.
Genome‐wide analysis reveals that altered methylation in specific CpG loci is associated with childhood obesity
Authors: Li Yun , Zhou Yahui , Zhu Lijun , Liu Guiyou , Wang Xing , Wang Xingyun , Wang Jian , You Lianghui , Ji Chenbo , Guo Xirong , Zhao Yingmin , Cui Xianwei
Published: May 2018

Over the past decades, the epidemic of childhood obesity has greatly increased, and it has recently become a global public health concern. Methylation, serving as a crucial regulator of the gene‐environment interaction, has exhibited a strong association with obesity. In this study, we aimed to evaluate the relationship between DNA methylation and childhood obesity, and further uncover the potential association of aberrantly methylated genes with obesity. DNA samples of peripheral blood leukocytes from three obese subjects (mean BMI: 21.67) and 4 age/sex matched controls (mean BMI: 14.92) were subjected to Infinium Human Methylation 450 Bead Array analysis. A total of more than 4 85 000 methylation sites were identified across the genome, and 226 methylated CpGs (DMCpGs) were differentially methylated between these two groups. Subsequent Gene Ontology (GO) and KEGG Pathway analyses showed that these DMCpGs were mainly engaged in immunity and lipoprotein metabolism, indicating their physiological significance. Further verification of the candidate CpG sites within the HDAC4, RAX2, APOA5, CES1, and SLC25A20 gene loci, were performed using bisulfite sequencing PCR (BSP) in a cohort of 42 controls and 39 obese cases. The results revealed that methylation levels within HDAC4 and RAX2 loci were positively associated with obesity, while the methylation levels of loci within APOA5 and CES1 loci were negatively correlated with obesity. Thus, alterations in methylation of CpG sites of specific genes may contribute to childhood obesity, which provide novel insights into the aetiology of obesity.
High accuracy of proximity extension assay technology for the quantification of plasma brain natriuretic peptide
Authors: Arrigo Mattia , Vodovar Nicolas , Von Moos Seraina , Masson Elisabeth , Segerer Stephan , Cippà Pietro E. , Mebazaa Alexandre
Published: May 2018

Background

Novel multiplex assays allow the simultaneous identification of a large number of plasma proteins. While these new technologies have been shown to be highly sensitive and accurate for the identification of plasma proteins, the use of this technology to quantify those proteins has not been properly investigated. In this pilot study, we tested the accuracy of the proximity extension assay (PEA) for the quantification of the cardiac biomarker brain natriuretic peptide (BNP) compared to a standard clinically approved method.

Methods

Concentrations of BNP were assessed in 120 plasma samples from 30 patients with PEA and compared to chemiluminescent microparticle immunoassay (CMIA). Venous blood samples were collected from in tubes containing ethylenediaminetetraacetic acid, centrifuged within 6 hours at 3,500 rpm for 15 minutes at 4°C, frozen and stored at −80°C until analyzed. Correlation between the CMIA and PEA techniques was tested using the Spearman’s rank correlation coefficient (rho) and the agreement was described with a Bland‐Altman plot.

Results

Brain natriuretic peptide values obtained by CMIA and PEA were highly correlated (Spearman’s rho = 0.865, P < .0001). In two patients, PEA consistently overestimated resp. underestimated BNP values compared to CMIA. After removal of those two patients, a very high correlation between the two techniques was shown (rho = 0.966, P < .0001). A high agreement between the two techniques over the whole range of tested concentrations was shown.

Conclusion

This pilot study showed for the first time an excellent correlation between a clinically approved method and the PEA‐based approach for quantification of circulating plasma BNP.
Human cytomegalovirus (HCMV)‐specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid‐organ transplant recipients
Authors: Lilleri Daniele , Zelini Paola , Fornara Chiara , Zavaglio Federica , Rampino Teresa , Perez Laurent , Gabanti Elisa , Gerna Giuseppe
Published: May 2018

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1‐year follow‐up, all LVL patients had levels of HCMV‐specific CD4+ (and CD8+) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme‐linked immunosorbent assay‐IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV‐specific T‐cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T‐cell response. Antibody responses did not appear to be associated directly or indirectly with protection.
Antitumor‐specific T‐cell responses induced by oncolytic adenovirus ONCOS‐102 (AdV5/3‐D24‐GM‐CSF) in peritoneal mesothelioma mouse model
Authors: Kuryk Lukasz , Møller Anne‐Sophie W. , Garofalo Mariangela , Cerullo Vincenzo , Pesonen Sari , Alemany Ramon , Jaderberg Magnus
Published: May 2018

Oncolytic adenoviral immunotherapy activates the innate immune system with subsequent induction of adaptive tumor‐specific immune responses to fight cancer. Hence, oncolytic viruses do not only eradicate cancer cells by direct lysis, but also generate antitumor immune response, allowing for long‐lasting cancer control and tumor reduction. Their therapeutic effect can be further enhanced by arming the oncolytic adenovirus with costimulatory transgenes and/or coadministration with other antitumor therapies. ONCOS‐102 has already been found to be well tolerated and efficacious against some types of treatment‐refractory tumors, including mesothelin‐positive ovarian cancer (NCT01598129). It induced local and systemic CD8+ T‐cell immunity and upregulated programmed death ligand 1. These results strongly advocate the use of ONCOS‐102 in combination with other therapeutic strategies in advanced and refractory tumors, especially those expressing the mesothelin antigen. The in vivo work presented herein describes the ability of the oncolytic adenovirus ONCOS‐102 to induce mesothelin‐specific T‐cells after the administration of the virus in bagg albino (BALB/c) mice with mesothelin‐positive tumors. We also demonstrate the effectiveness of the interferon‐γ the enzyme‐linked immunospot (ELISPOT) assay to detect the induction of T‐cells recognizing mesothelin, hexon, and E1A antigens in ONCOS‐102‐treated mesothelioma‐bearing BALB/c mice. Thus, the ELISPOT assay could be useful to monitor the progress of therapy with ONCOS‐102.
Sequence variations of Epstein‐Barr virus‐encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China
Authors: Liu Jincheng , Ji Xinqiang , Shen Zhichao , Wang PhD Yun , Luo PhD Bing
Published: May 2018

The BamHI A rightward frame 1 (BARF1) gene of the Epstein‐Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV‐associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non‐endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95‐8 and V29A) and 2 B95‐8 subtypes (B95‐8t165545c and B95‐8P) were classified. For Chinese isolates, the B95‐8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95‐8t165545c subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95‐8t165545c subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95‐8P subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95‐8t165545c subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95‐8t165545c subtype in NPC cases, without biological or pathogenic implications.
Determinants of the presence of human papillomaviruses in the anal canal of Russian men
Authors: Smelov Vitaly , Elfström K. Miriam , Eklund Carina , Sokolova Olga , Dillner Joakim
Published: May 2018

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high‐risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]‐negative and 27 HIV‐positive, aged 18‐67 years) men attending a sexually transmitted infection clinic 36 HPV types using a proficient Luminex assay. HPV‐positivity in anal samples was common for 332 HIV‐negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV‐positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV‐negative men favoring further studies on transmission routes to discriminate between contamination and true HPV infection.
Anterior longitudinal ligament in diffuse idiopathic skeletal hyperostosis: Ossified or displaced?
Authors: Kuperus Jonneke S. , Smit Esther J. M. , Pouran Behdad , van Hamersvelt Robbert W. , van Stralen Marijn , Seevinck Peter R. , Buckens Constantinus F. , Bleys Ronald L. A. W. , Weinans Harrie H. , Oner F. Cumhur , de Jong Pim A. , Verlaan Jorrit‐Jan
Published: May 2018

Diffuse idiopathic skeletal hyperostosis (DISH) is often theorized to be an ossification of the anterior longitudinal ligament (ALL). Using computed tomography (CT) imaging and cryomacrotome sectioning, we investigated the spatial relationship between the ALL and newly formed bone in DISH to test this hypothesis. In the current study, four human cadaveric spines diagnosed with DISH using CT imaging were frozen and sectioned using a cryomacrotome. Photographs were obtained of the specimen at 125 µm intervals. Manual segmentations of the ALL on cryomacrotome photographs were projected onto the three‐dimensional reconstructed CT scans. The presence and location of newly formed bone were assessed in relationship to the location of the ALL. The ALL could be identified and segmented on the photographs at all levels. The ALL was located at the midline at levels where no new bone had formed. At the locations where new bone had abundantly formed, the ALL was displaced towards to the contralateral side and not replaced by bony tissue. The displacement of the—morphologically normal appearing—ALL away from the newly formed bone implies that newly formed bone in DISH may not originate from the ALL. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 36:2491–2496, 2018.
Evaluating the role of subacromial impingement in rotator cuff tendinopathy: Development and analysis of a novel murine model
Authors: Cong Guang‐Ting , Lebaschi Amir H. , Camp Christopher L. , Carballo Camila B. , Nakagawa Yusuke , Wada Susumu , Deng Xiang‐Hua , Rodeo Scott A.
Published: May 2018

Subacromial impingement of the rotator cuff is understood as a contributing factor in the development of rotator cuff tendinopathy. However, changes that occur in the impinged tendon are poorly understood and warrant further study. To enable further study of rotator cuff tendinopathy, we performed a controlled laboratory study to determine feasibility and baseline characteristics of a new murine model for subacromial impingement. This model involves surgically inserting a microvascular clip into the subacromial space in adult C57Bl/6 mice. Along with a sham surgery arm, 90 study animals were distributed among time point groups for sacrifice up to 6 weeks. All animals underwent bilateral surgery (total N = 180). Biomechanical, histologic, and molecular analyses were performed to identify and quantify the progression of changes in the supraspinatus tendon. Decreases in failure force and stiffness were found in impinged tendon specimens compared to sham and no‐surgery controls at all study time points. Semi‐quantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 6 weeks. Quantitative real‐time polymerase chain reaction analysis of impinged tendon specimens demonstrated persistently increased expression of genes related to matrix remodeling, inflammation, and tendon development. Overall, this novel murine subacromial impingement model creates changes consistent with acute tendonitis, which may mimic the early stages of rotator cuff tendinopathy. A robust, simple, and reproducible animal model of rotator cuff tendinopathy is a valuable research tool to allow further studies of cellular and molecular mechanisms and evaluation of therapeutic interventions in rotator cuff tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2780–2788, 2018.
SILAR grown Ag nanoparticles as an efficient large area SERS substrate
Authors: Shaikh Imran M. , Sartale Shrikrishna D.
Published: May 2018

Ag nanoparticles having different size and coverage are grown on large area glass substrate (~10 cm2) using low cost successive ionic layer adsorption and reduction (SILAR) method. The SILAR parameters, such as reduction time and growth cycles are optimized to grow Ag nanoparticles with appropriate size and coverage showing maximum surface enhanced Raman scattering (SERS) enhancement of Rhodamine 6 G(R6G). For fixed growth cycles, the size and the coverage of the grown Ag nanoparticles are found to increase with the reduction time and then saturate. The size and coverage of the grown Ag nanoparticles monotonically increase with growth cycles. However, for higher growth cycles, the shape of Ag nanoparticles could not maintain their sphericity and became rock shaped/nonspherical particles, giving rise to intense quadruple plasmon resonance. The growth mechanism is proposed. Further, SERS activity of the grown Ag nanoparticles is studied for an industrial pollutant methylene blue (MB). The observed SERS enhancement factor (~109) for MB is much higher than the reported values in literature. Measured relative standard deviations values of Ag nanoparticles grown with optimum SILAR parameters suggest the excellent homogeneity and reproducibility of the SERS signal.
Jussara berry (Euterpe edulis M.) oil‐in‐water emulsions are highly stable: the role of natural antioxidants in the fruit oil
Authors: Carvalho Aline GA , Silva Kelly A , Silva Laís O , Costa André MM , Akil Emília , Coelho Maria AZ , Torres Alexandre G
Published: May 2018

BACKGROUND

Antioxidants help prevent lipid oxidation, and therefore are critical to maintain sensory quality and chemical characteristics of edible oils. Jussara berry (Euterpe edulis M.) oil is a source of minor compounds with potential antioxidant activity. The aim of this work was to investigate the role of such compounds on the effectiveness to prevent or delay oxidation of oil present in oil‐in‐water emulsions, and how the emulsions' physical stability would be affected.

RESULTS

Jussara berry oil extracted by ethanol extraction, its stripped variations (partially stripped, highly stripped and highly stripped with added butylhydroxytoluene), and expeller‐pressed oil were used to prepare oil‐in‐water emulsions. Jussara berry oils were analyzed before emulsions preparation to ensure their initial quality and composition, and oil‐in‐water emulsions were analyzed regarding their oxidative and physical stability. Ethanol extracted oil emulsion presented higher oxidative stability than highly stripped oil emulsion with added synthetic antioxidant butylahydroxytoluene (oxidative stability index 45% lower, after 60 days, and reached undetectable levels after 90 days). All emulsions remained physically stable for up to 120 days of storage.

CONCLUSION

Our results indicate that natural antioxidants in jussara berry oil protect emulsions from oxidation while keeping physical stability unchanged. © 2018 Society of Chemical Industry
Mechanism of peptide absorption in the isolated forestomach epithelial cells of dairy cows
Authors: Xu Qingbiao , Liu Hongyun , Zhao Fengqi , Wu Yueming , Huang Xinbei , Liu Zhixuan , Liu Jianxin
Published: May 2018

BACKGROUND

Peptide absorption from the forestomach plays a vital role in protein nutrition of dairy cows. This study was conducted to investigate the mechanism of dipeptide absorption in the forestomach of dairy cows using isolated omasal epithelial cells (OECs) and ruminal epithelial cells (RECs).

RESULTS

Compared with RECs, the OECs formed a less tight monolayer, but had greater ability to transport glycylsarcosine (Gly‐Sar) (P < 0.05). The OEC monolayers were immunopositive for the antibodies of anti‐junction proteins. Gly‐Sar transport was significantly greater at 37 °C than that at 4 °C, with an optimal pH of 6.0–6.5, and was decreased significantly by diethylpyrocarbonate and dipeptide Met‐Gly (P < 0.05). The apical‐to‐basolateral transport was significantly greater than basolateral‐to‐apical transport (P < 0.05). Knockdown of peptide transporter 1 (PepT1) resulted in less Gly‐Sar uptake in OECs, whereas overexpression of PepT1 in OECs resulted in higher Gly‐Sar uptake (P < 0.05). Additionally, the expression of PepT1 was upregulated by the treatment with various dipeptides (P < 0.05).

CONCLUSION

The OECs have a greater ability to transport Gly‐Sar than RECs do. Both passive and active routes are involved in the process of Gly‐Sar absorption in the isolated cultured forestomach epithelial cells from dairy cows. © 2018 Society of Chemical Industry
Effect of heat treatment on the δ phase distribution and corrosion resistance of selective laser melting manufactured Inconel 718 superalloy
Authors: Li Huixiang , Feng Shengnan , Li Jiahui , Gong Jianhong
Published: May 2018

The microstructure, δ phase precipitating behavior and marine corrosion resistance of selective laser melted (SLM) Inconel 718 alloy were studied in two different heat treatment conditions. The SLM as‐printed microstructures exhibited columnar grain structures with fine dendritic structure and recrystallization occurred after the heat treatments. The results of 6% FeCl3 immersion test and 3.5 wt% NaCl solution electrochemical corrosion test show that the corrosion resistance of the specimens with 950 °C solution + double aging (HT950) is better than that of 1050 °C solution + double aging (HT1050). Metallographic microscopy (OM) photographs show that due to the solution temperature is not high enough, the HT950 heat treated samples maintain columnar structures with irregular grain boundaries. Scanning electron microscopy (SEM) images indicated that it is the fine δ phase pinning effect that caused irregular grain boundaries. Meanwhile the HT1050 heat treated samples have a wide range of non‐precipitated grain boundaries with few δ phase precipitation, and it will couple a “large cathode and small anode “ galvanic corrosion form, which will accelerate corrosion rate.
The Aqueous Barbier Polycondensation of Biomass‐Derived 5‐Chloromethylfurfural: A Proof of Concept Study to Access Functional Polymers
Authors: Arslan Mehmet
Published: May 2018

The versatility of the zinc‐mediated aqueous Barbier reaction in functional polymer synthesis is demonstrated in instance of a biomass‐derived bifunctional monomer, 5‐chloromethylfurfural (CMF). CMF is a renewable furan derivative that can be directly obtained from various sugars and cellulose in high yields and is a versatile precursor that can be converted into several valuable building blocks. In this study, CMF is utilized as a monomer in metal‐catalyzed conditions to access both furan and hydroxyl functional polymers. The effect of different reaction conditions on polymerization is explored. Polymers through Barbier polycondensation of bifunctional monomer are obtained with moderately good polymer conversions (54–89%) and molecular weights (8.7–15.1 kDa). The crosslinking of obtained functional polymers is studied by employing bismaleimide and dianhydride crosslinkers for possible application of synthesized polymers as hydrophilically modified membrane materials. The crosslinked materials are obtained by reaction of furan and alcohol groups through Diels–Alder and ester formation reactions, respectively. Synthesis and characterization procedures of linear and crosslinked polymers are described. The reported proof of concept study demonstrates the efficiency of aqueous Barbier reaction in functional polymer synthesis.
Value co‐creation in online healthcare communities: The impact of patients’ reference frames on cure and care
Authors: Van Oerle Sarah , Lievens Annouk , Mahr Dominik
Published: May 2018

The gradual transition of health care toward businesses during the past 50 years has converted passive patients into active customers. In our digital society, patients increasingly use online health communities to satisfy complex needs that healthcare professionals leave unmet, including the creation of cure‐oriented (i.e., functional) and care‐oriented (i.e., emotion) value. This research investigates patients’ reference frames (self versus other) as an information processing mechanism and their impact on value creation in online communities. The analysis of 1,687 online postings of a leading healthcare platform shows that self‐referencing is typical for information obtained through an individualistic, patient–doctor encounter; other‐referencing emerges when patients focus on the needs of their peers. Information gathered through the patient–doctor encounter and processed with a self‐referencing frame accordingly enhances cure‐related value, but limits care‐oriented value co‐creation. Other‐referencing does exactly the opposite: it creates a barrier to cure‐related value, but stimulates care‐related value. A patient's experience with the community largely moderates the impact of both self‐ and other‐referencing on cure‐ and care‐related value. These findings show that online health communities can identify and address unmet patient needs, but healthcare professionals still play a critical role in terms of ensuring information quality in online health communities.
Theobromine Does Not Affect Fasting and Postprandial HDL Cholesterol Efflux Capacity, While It Decreases Fasting miR‐92a Levels in Humans
Authors: Talbot Charlotte P.J. , Mensink Ronald P. , Smolders Lotte , Bakeroot Virginie , Plat Jogchum
Published: May 2018

Scope

Chocolate consumption lowers cardiovascular disease risk, which might be attributed to the methylxanthine theobromine. These effects may be mediated through effects on HDL‐mediated cholesterol efflux, which may be affected by microRNA (miRNA) levels in the HDL particles. Therefore, the aim of this study is to investigate effects of theobromine consumption on fasting and postprandial cholesterol efflux and miRNAs levels.

Methods and results

Thirty overweight and 14 obese healthy men and women participated in this randomized, double‐blind crossover study. Participants consumed 500 mg d−1 of theobromine or placebo for 4 weeks. ABCA1‐mediated cholesterol efflux was measured using J774 macrophages. MiRNAs levels (miR‐92a, miR‐223, miR‐135a*) were quantified in apolipoprotein B‐depleted serum. Theobromine consumption did not affect fasting and postprandial cholesterol efflux. Fasting miR‐223 and miR‐135a levels were unchanged, while miR‐92a levels were decreased (−0.21; p < 0.05). The high‐fat meal increased postprandial cholesterol efflux capacity (+4.3 percentage points; p ≤ 0.001), miR‐92a (+1.21; p < 0.001), and miR‐223 (+1.79; p < 0.001) levels, while a trend was found for miR‐135a (+1.08; p = 0.06).

Conclusion

Theobromine did not improve fasting and postprandial ABCA1‐mediated cholesterol efflux capacity, but decreased fasting miR‐92a levels. High‐fat meal intake increased postprandial cholesterol efflux and the three selected miRNAs levels.
Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction
Authors: Eberli Daniel , Horst Maya , Mortezavi Ashkan , Andersson Karl‐Erik , Gobet Rita , Sulser Tullio , Simon Hans‐Uwe , Salemi Souzan
Published: May 2018

Aims

To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population.

Methods

Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated.

Results

ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls.

Conclusions

Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle.
Therapeutic effect of urethral sphincter onabotulinumtoxinA injection for urethral sphincter hyperactivity
Authors: Jiang Yuan‐Hong , Chen Sheng‐Fu , Jhang Jia‐Fong , Kuo Hann‐Chorng
Published: May 2018

Purpose

Urethral sphincter hyperactivity resulting in voiding dysfunction is frequently encountered. Medical treatment might not achieve a satisfactory result. OnabotlinumtoxinA urethral sphincter injection relaxes sphincter tonicity and possibly resumes efficient voiding. This study analyzed the treatment outcomes and predictor for successful onabotulinumtoxinA treatment on these patients.

Methods

Patients with voiding dysfunction due to urethral sphincter hyperactivity and treated with injections of 100 U onabotulinumtoxinA into the urethral sphincter were retrospectively reviewed. Treatment outcomes were assessed 1 month after injection using the Global Response Assessment and were analyzed by demographic and baseline video‐urodynamic characteristics.

Results

Of the 95 patients included, satisfactory outcomes were reported in 58 (61.1%) patients. Treatment outcome was not related to age, gender, or voiding dysfunction subtype. Patients with satisfactory outcomes had a significantly smaller volume at first sensation of filling (P = 0.046), greater detrusor pressure (P = 0.027), higher maximum flow rate (P = 0.017), and smaller post‐void residual (P = 0.006). In multivariate analysis, an open bladder neck during voiding was the only predictor for successful outcome (88% in satisfactory outcome, 12% in failure outcome, P < 0.001). Patients with non‐neurogenic voiding dysfunction had a significantly longer therapeutic duration than those with neurogenic voiding dysfunction (9.55 ± 4.18 vs 7.44 ± 2.91 months, P = 0.033). Increased urinary incontinence was reported in 18 patients, including 6 with stress urinary incontinence and 12 with urgency urinary incontinence.

Conclusion

Subjective improvement was reported in 61.1% of patients with voiding dysfunction due to urethral sphincter hyperactivity after onabotulinumtoxinA urethral sphincter injection. An open bladder neck during voiding at baseline predicts a successful outcome.
Morphological appearance of muscle attachment sites on lower limbs: Horse riders versus agricultural population
Authors: Djukic Ksenija , Miladinovic‐Radmilovic Natasa , Draskovic Marko , Djuric Marija
Published: May 2018

The present study analysed macromorphological characteristics of the muscle attachment sites of lower limbs, hypothesising that everyday physical activities influence the macromorphology of the bone at the entheses. Our specific goals were to investigate how different habitual activities influence the morphology of the muscle attachment sites of lower limbs in two different medieval populations from Serbia: agricultural versus horse‐riding populations.

The skeletal material used in this study comprised two different populations: a Medieval Avarian population of horse riders from two necropolises (Pionirska Ulica and Čik, in Bečeј) and an agricultural population represented by two sites—Medieval Vinča near Belgrade and Sirmium (Sremska Mitrovica), Site No. 85.

The macromorphological analysis of the entheseal changes (ECs) encompassed 10 entheses of the lower limbs. Morphological appearance of entheses was evaluated using the visual reference system proposed by Villotte.

The results revealed an age dependence in one muscle of the lower limbs (Musculus gluteus maximus) among the agricultural population, suggested by more pronounced ECs in the older age categories. Among the Avarian population, more pronounced EC scores were recorded in the older age groups for the attachment site of Musculus soleus, while in the case of the iliopsoas muscle, ECs were more common in younger ages. The results revealed more pronounced EC scores in males in both populations. Between the riders and agricultural populations, results indicated that only the adductor muscles which are specific for horse riders were singled out, showing a more pronounced ECs in the horse riders' population.

Results of our study showed that the level of physical activity mostly increased with age. In both investigated populations, EC scores were more pronounced in males compared with females. Moreover, we noted that the evaluation of entheses of adductor muscles could provide the most reliable criteria for the identification of riders among the general population.
Model‐free online tuning of controller parameters using a globalized local search algorithm
Authors: Butt Khurram , Sepehri Nariman
Published: May 2018

In an earlier work, the authors proposed a globalized bounded Nelder‐Mead algorithm with deterministic restarts and a linearly growing memory vector. It was shown that the algorithm was a favorable option for solving multimodal optimization problems like controller tuning because of the greater probability of finding the global minimum and lesser numerical cost. Therefore, the algorithm was successfully used for model‐based offline tuning of sliding mode controller parameters for a servo‐pneumatic position control application. However, such offline tuning requires a sufficiently adequate system model, which, in some applications, is difficult to attain. Moreover, it is not generally appreciated as an essential requirement for controller tuning by the end user like the industry. An improvement in performance of optimization algorithm for tuning is expected if it relies on measurements coming directly from an actual physical system and not just its mathematical model. Therefore, in this paper, we apply the aforementioned algorithm for model‐free online optimization of controller parameters. The application involves the programmatic control of a real‐time interface of a physical system by the algorithm for data flow and logical decisions for optimization. For comparison with the results of the model‐based offline tuning suggested in earlier work, the sliding mode controller parameters are tuned online for the same position control application. The experimental results reveal that the system performance with controller parameters tuned online using the algorithm compares favorably to the one with model‐based offline tuning especially at higher priority level for accuracy. The improvement in system performance amounts to 21%.
Winning hearts and minds: A commentary on circular cities
Authors: Jones Peter , Comfort Daphne
Published: May 2018

There is growing interest in the concept of the circular city, which looks to embed the principles of the circular economy across all urban functions. This commentary paper outlines the concept of the circular city, explores how 3 European cities, namely, Amsterdam, London, and Paris, are currently looking to develop a vision and an action plan for the transition to a circular city, and offers some general reflections on the role public relations and communications may play in the transition process. The findings reveal that each of the action plans has its own distinctive flavour but that a number of common elements can be identified. The paper suggests that public relations and communications will have an important role to play to in raising and building awareness and changing attitudes, with the ultimate goal of changing behaviour, within the corporate world and amongst public sector decision makers and policy makers and the general public.
Characteristics of drugs safety signals that predict safety related product information update
Authors: Insani Widya N. , Pacurariu Alexandra C. , Mantel‐Teeuwisse Aukje K. , Gross‐Martirosyan Liana
Published: May 2018

Purpose

Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.

Methods

A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.

Results

Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug‐event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05).

Conclusions

This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates.
Neuropathic pain is not adequately treated in the older general population: Results from the KORA F4 survey
Authors: Meisinger Christa , Bongaerts Brenda W.C. , Heier Margit , Amann Ute , Kowall Bernd , Herder Christian , Rückert‐Eheberg Ina‐Maria , Rathmann Wolfgang , Ziegler Dan
Published: May 2018

Purpose

We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population.

Methods

The study included subjects aged 61 to 82 years from the KORA F4 survey (2006‐2008). DSPN was defined as the presence of bilaterally impaired foot‐vibration perception and/or bilaterally impaired foot‐pressure sensation. Pain intensity was assessed with the painDETECT questionnaire.

Results

From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty‐eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti‐inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN.

Conclusions

In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs.
Increased virulence in the locust‐specific fungal pathogen Metarhizium acridum expressing dsRNAs targeting the host F1F0‐ATPase subunit genes
Authors: Hu Jun , Xia Yuxian
Published: May 2018

BACKGROUND

Metarhizium acridum is a host‐specific fungal pathogen with great potential for locust control. However, the slow killing action of M. acridum has impeded its widespread application. To enhance fungal virulence, we constructed transgenic M. acridum strains that express double‐stranded (ds)RNAs targeting the genes of the F1F0‐ATP synthase α and β subunits in Locusta migratoria.

RESULTS

The two host genes were transcriptionally suppressed in L. migratoria nymphs (instar V) infected by RNA interference (RNAi) strains targeting one or two subunit genes of the host ATP synthase, followed by reduced ATPase activity and ATP synthesis. Consequently, the RNAi strain targeting both subunit genes displayed high virulence that was 3.7‐fold that in the wild‐type strain.

CONCLUSION

Our results demonstrate that dsRNA expression in M. acridum can cause host RNA silencing during infection and greatly enhances the fungal virulence through interference with critical host genes, highlighting a new strategy for augmentation of fungal virulence against insect pests. © 2018 Society of Chemical Industry
Bayesian methods for analysis of biosimilar phase III trials
Authors: Weiss Robert E. , Xia Xiaomao , Zhang Nan , Wang Hui , Chi Eric
Published: May 2018

A biologic is a product made from living organisms. A biosimilar is a new version of an already approved branded biologic. Regulatory guidelines recommend a totality‐of‐the‐evidence approach with stepwise development for a new biosimilar. Initial steps for biosimilar development are (a) analytical comparisons to establish similarity in structure and function followed by (b) potential animal studies and a human pharmacokinetics/pharmacodynamics equivalence study. The last step is a phase III clinical trial to confirm similar efficacy, safety, and immunogenicity between the biosimilar and the biologic. A high degree of analytical and pharmacokinetics/pharmacodynamics similarity could provide justification for an eased statistical threshold in the phase III trial, which could then further facilitate an overall abbreviated approval process for biosimilars. Bayesian methods can help in the analysis of clinical trials, by adding proper prior information into the analysis, thereby potentially decreasing required sample size. We develop proper prior information for the analysis of a phase III trial for showing that a proposed biosimilar is similar to a reference biologic. For the reference product, we use a meta‐analysis of published results to set a prior for the probability of efficacy, and we propose priors for the proposed biosimilar informed by the strength of the evidence generated in the earlier steps of the approval process. A simulation study shows that with few exceptions, the Bayesian relative risk analysis provides greater power, shorter 90% credible intervals with more than 90% frequentist coverage, and better root mean squared error.