bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Utilization of the First Biosimilar Infliximab Since Its Approval in South Korea
Authors: Kim Seoyoung C. , Choi Nam‐Kyong , Lee Joongyub , Kwon Kyoung‐Eun , Eddings Wesley , Sung Yoon‐Kyoung , Ji Song Hong , Kesselheim Aaron S. , Solomon Daniel H.
Published: December 2015

Objective

The US Food and Drug Administration is considering an application for a biosimilar version of infliximab, which has been available in South Korea since November 2012. The aim of the present study was to examine the utilization patterns of both branded and biosimilar infliximab and other tumor necrosis factor (TNF) inhibitors in South Korea before and after the introduction of this biosimilar infliximab.

Methods

Using claims data from April 2009 to March 2014 from the Korean Health Insurance Review and Assessment Service database, which includes the entire South Korean population, the number of claims for biosimilar infliximab was assessed. A segmented linear regression model was used to examine the utilization patterns of infliximab (the branded and biosimilar versions) and other TNF inhibitors (adalimumab and etanercept) before and after the introduction of the biosimilar infliximab.

Results

In total, 20,976 TNF inhibitor users were identified from the South Korean claims database, including 983 with a prescription claim for biosimilar infliximab. Among all of the claims for any version of infliximab, the proportion of biosimilar infliximab claims increased to 19% through March 2014. Before November 2012, each month there were 33 (95% confidence interval [95% CI] 32, 35) more infliximab claims, 44 (95% CI 40, 48) more etanercept claims, and 50 (95% CI 47, 53) more adalimumab claims. After November 2012, there were significant changes in the slopes for trend in usage, with additional increases in the use of branded and biosimilar infliximab (9 more claims per month, 95% CI 2, 17) and decreases in the use of etanercept (−52 claims per month, 95% CI −66, −38) and adalimumab (−21 claims per month, 95% CI −35, −6).

Conclusion

During the first 15 months since its introduction in South Korea, one‐fifth of all infliximab claims were for the biosimilar version. Introduction of biosimilar infliximab may affect the use of other TNF inhibitors, and the magnitude of change in usage will likely differ in other countries.
Correlation between lignin physicochemical properties and inhibition to enzymatic hydrolysis of cellulose
Authors: Yang Qiang , Pan Xuejun
Published: December 2015

Using isolated organosolv lignins from hardwood poplar and softwood lodgepole pine with varied physicochemical properties (molecular weight, aliphatic hydroxyl, phenolic hydroxyl, and hydrophobicity), the inhibitory effect of the lignins on enzymatic hydrolysis of cellulose was investigated and the relationship between lignin properties and the inhibitory effect was elucidated. The results indicated that the lignin inhibition to enzymatic hydrolysis of cellulose was closely related to the hydrophobicity and the phenolic hydroxyl groups of the lignin. The overall hydrophobicity of the lignin quantified by contact angle could serve as a predictor of the inhibitory effect of lignin. Hydrophilic modification of the lignin by carboxylation and sulfonation reduced the hydrophobicity by 22–30% and thereby removed the lignin inhibition by 76–96%. Phenolic hydroxyl group was a crucial factor affecting the inhibitory effect of lignin. Blocking free phenolic hydroxyl group by chemical reaction such as hydroxypropylation significantly (65–91%) reduced the inhibitory effect of lignin. Biotechnol. Bioeng. 2016;113: 1213–1224. © 2015 Wiley Periodicals, Inc.
A simple LabVIEW‐MATLAB implementation to observe the wavelength tunability of a laser diode with a diffraction grating
Authors: Rivera‐Ortega Uriel
Published: December 2015

It is well known that one of the features of a laser diode is its wavelength tunability, which can be modulated with a variable injection current and/or temperature of its active region. The wavelength of a laser source is commonly associated with its output color in the visible spectrum; however, if a wavelength change is not long enough to be observed as a color variation in the output beam, a wavelength meter or an interferometer setup should be needed for a quantitative or qualitative observation, respectively. In this manuscript, it is described a simple method to observe the wavelength tunability of a laser diode when a variable voltage is applied to its input by analyzing the diffraction orders displacements produced when the output beam passes through a transmissive diffraction grating. This demonstration is suitable to be implemented in undergraduate engineering laboratories for topics related to optics, helping students understand basic physics concepts such as diffraction and wavelength. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:365–370, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21714
Onocerin Biosynthesis Requires Two Highly Dedicated Triterpene Cyclases in a Fern Lycopodium clavatum
Authors: Araki Takeshi , Saga Yusuke , Marugami Momo , Otaka Junnosuke , Araya Hiroshi , Saito Kazuki , Yamazaki Mami , Suzuki Hideyuki , Kushiro Tetsuo
Published: December 2015

Onocerin is known for its unusual structure among triterpenoids, with a symmetrical structure that is formed by cyclizations at the both termini of dioxidosqualene. The nature of the enzyme catalyzing these unusual cyclizations has remained elusive for decades. Here, we report the cloning of genes responsible for these reactions; they exhibited unprecedented substrate specificities among oxidosqualene cyclase family members. Two genes, LCC and LCD, were identified from the fern Lycopodium clavatum. Expression in yeast revealed that both were required to produce α‐onocerin. LCC, the first dioxidosqualene cyclase, catalyzed the production of a novel intermediate pre‐α‐onocerin from only dioxidosqualene as a substrate; LCD catalyzed the second half of the cyclization, exclusively from pre‐α‐onocerin. These results demonstrated that these two most unusual oxidosqualene cyclases were involved in onocerin biosynthesis.
A Facile Approach to Optically Active Hydroquinoline‐2‐carboxylates by a One‐Pot Asymmetric Michael/Transamination/Cyclization Process
Authors: Rong Chao , Pan Hongjie , Liu Mao , Tian Hua , Shi Yian
Published: December 2015

An efficient one‐pot synthesis of optically active hydroquinoline‐2‐carboxylates from 1,3‐cyclohexanediones, β,γ‐unsaturated α‐keto ester, and benzylamine in the presence of a chiral base catalyst and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) with good diastereoselectivity and high enantioselectivity is described. The reaction proceeds by a sequential asymmetric Michael/transamination/cyclization process.
CaII Binding Regulates and Dominates the Reactivity of a Transition‐Metal‐Ion‐Dependent Diesterase from Mycobacterium tuberculosis
Authors: Pedroso Marcelo M. , Larrabee James A. , Ely Fernanda , Gwee Shuhui E. , Mitić Nataša , Ollis David L. , Gahan Lawrence R. , Schenk Gerhard
Published: December 2015

The diesterase Rv0805 from Mycobacterium tuberculosis is a dinuclear metallohydrolase that plays an important role in signal transduction by controlling the intracellular levels of cyclic nucleotides. As Rv0805 is essential for mycobacterial growth it is a promising new target for the development of chemotherapeutics to treat tuberculosis. The in vivo metal‐ion composition of Rv0805 is subject to debate. Here, we demonstrate that the active site accommodates two divalent transition metal ions with binding affinities ranging from approximately 50 nm for MnII to about 600 nm for ZnII. In contrast, the enzyme GpdQ from Enterobacter aerogenes, despite having a coordination sphere identical to that of Rv0805, binds only one metal ion in the absence of substrate, thus demonstrating the significance of the outer sphere to modulate metal‐ion binding and enzymatic reactivity. CaII also binds tightly to Rv0805 (Kd≈40 nm), but kinetic, calorimetric, and spectroscopic data indicate that two CaII ions bind at a site different from the dinuclear transition‐metal‐ion binding site. CaII acts as an activator of the enzymatic activity but is able to promote the hydrolysis of substrates even in the absence of transition‐metal ions, thus providing an effective strategy for the regulation of the enzymatic activity.
An Experimental and Theoretical Investigation on Pentacoordinated Cobalt(III) Complexes with an Intermediate S=1 Spin State: How Halide Ligands Affect their Magnetic Anisotropy
Authors: Brazzolotto Deborah , Gennari Marcello , Yu Shengying , Pécaut Jacques , Rouzières Mathieu , Clérac Rodolphe , Orio Maylis , Duboc Carole
Published: December 2015

Invited for the cover of this issue are the groups of Maylis Orio at the Aix‐Marseille University and Carole Duboc at the University of Grenoble Alpes. The image depicts the magnetic behavior dependence to the halide nature in CoIII species represented by ribbons as “double‐well” diagrams, which are traditionally used to depict magnetization processes. Read the full text of the article at 10.1002/chem.201502997.
Smart and Covalently Cross‐Linked: Hybrid Shape Memory Materials Reinforced through Covalent Bonds by Zirconium Oxoclusters
Authors: Gibin Giacomo , Lorenzetti Alessandra , Callone Emanuela , Dirè Sandra , Dolcet Paolo , Venzo Alfonso , Causin Valerio , Marigo Antonio , Modesti Michele , Gross Silvia
Published: December 2015

The first examples of organic–inorganic hybrid materials reinforced by transition‐metal oxoclusters that exhibit shape memory properties, based on the covalent incorporation of zirconium‐based inorganic building blocks, are reported. Methacrylate‐functionalized zirconium oxoclusters Zr4O2(OMc)12 and [Zr6O4(OH)4(OOCCH2CH3)3{OOCC(CH3)=CH2}9]2, with the covalent incorporation in a butyl acrylate (BA)/polycaprolactone dimethacrylate (PCLDMA) copolymer and the noncovalent incorporation of [Zr6O4(OH)4(OOCCH2CH3)12]2 are focused upon herein. Shape recovery and fixity rates are studied to observe if the shape memory properties are preserved upon going from a simple copolymer to noncovalent or covalent‐based hybrids. These rates display values higher than 90 %, which provides evidence that the oxocluster does not hinder the shape memory properties in the hybrid materials. The introduction of an inorganic phase and the progressively more stable interactions between organic and inorganic parts lead to an enhancement of the thermomechanical properties. The materials are characterized through FTIR spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and swelling tests. Dynamic–mechanical analyses are used to investigate whether the hybrid materials display thermally activated shape memory properties. The stability of the hybrid materials are evaluated by a combined spectroscopic approach based on FTIR, solid‐state NMR, and X‐ray absorption spectroscopy.
Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study
Authors: Elder Douglas H.J. , Singh Jagdeep S.S. , Levin Daniel , Donnelly Louise A. , Choy Anna‐Maria , George Jacob , Struthers Allan D. , Doney Alex S.F. , Lang Chim C.
Published: December 2015

Aims

Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c). Using the time‐weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF.

Methods and results

A time‐weighted mean HbA1c was calculated using all HbA1c measurements following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1–7.0%, 7.1–8.0%, 8.1–9.0%, and >9.0%). The relationship between time‐weighted mean HbA1c and all‐cause death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the study criteria. During a median follow‐up of 2.8 years, there were 826 (57.1%) deaths, with a crude death rate of 155 deaths per 1000 person‐years [95% confidence interval (CI) 144–166]. A Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1–8.0%) as the reference, showed a U‐shaped relationship between HbA1c and outcome [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8–3.4; HbA1c 6.1–7.0%, HR 1.4, 95% 1.1–1.7; HbA1c 8.1–9.0%, HR 1.3, 95% CI 1.0–1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4–2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 0.61–0.93) but not other drug classes.

Conclusions

In patients with T2DM and CHF, our study shows a U‐shaped relationship between HbA1c and mortality, with the lowest risk in patients with modest glycaemic control (HbA1c 7.1–8.0%) and those treated with insulin sensitizers.
Probing the Influence of N‐Donor Capping Ligands on Supramolecular Assembly in Molecular Uranyl Materials
Authors: Carter Korey P. , Kalaj Mark , Cahill Christopher L.
Published: December 2015

The syntheses and crystal structures of six new compounds containing the UO22+ cation, 3,5‐dichlorobenzoic acid, and a chelating N‐donor [2,2′‐bipyridine (bipy), 1,10‐phenanthroline (phen), 4,7‐dimethyl‐1,10‐phenanthroline (dimethylphen), 2,2′:6′,2″‐terpyridine (terpy), 4′‐chloro‐2,2′:6′,2″‐terpyridine (Cl–terpy), or 2,4,6‐tris(2‐pyridyl)‐s‐triazine (TPTZ)] are reported. Single‐crystal X‐ray diffraction analysis of these materials enabled the exploration of the structural relationship between the benzoic acids and the chelating N‐donor as well as providing a platform to evaluate the effects of ligand choice on uranyl hydrolysis and subsequent oligomerization. At an unadjusted pH (ca. 3), a mix of uranyl monomers and dimers are observed, dimer formation resulting from both bridging carboxylate linkers and hydroxo bridges. Assembly by halogen‐ and hydrogen‐bonding interactions as well as π–π interactions was observed depending on the experimental conditions utilized. Further, spectroscopic characterization (both vibrational and luminescence) of complexes 1, 4, and 5 to explore the effects of the electron‐donating ability of the capping ligand on the corresponding uranyl luminescence and vibrational spectra suggests that there is a relationship between the observed bathochromic shifts and the electron‐donating ability of the capping ligands.
Framework Isomerism: Highly Augmented Copper(II)‐Paddlewheel‐­Based MOF with Unusual (3,4)‐Net Topology
Authors: Zhu Nianyong , Sensharma Debobroto , Wix Paul , Lennox Matthew J. , Düren Tina , Wong Wai‐Yeung , Schmitt Wolfgang
Published: December 2015

The synthesis and structure of a new, highly augmented {Cu2}‐“paddlewheel”‐based metal–organic framework (MOF) that is stabilized by tritopic benzoate ligands is reported. The structure adopts an uncommon, less symmetrical, (3,4)‐connected net topology and represents a rare framework isomer of the extensively studied {Cu2}‐based pto and tbo analogues related to the purely inorganic, solid‐state structures of platinum oxide or the twisted boracite. The concomitant formation of three isomeric forms by using {Cu}2‐“paddlewheel” complexes and a single triangular, trifunctional ligand is unique and stems from the rotational flexibility of the benzoate moieties. Computational analyses support the structural studies and underline that this observed net topology can give rise to an exceptionally high surface area (greater than 3500 m2/g) despite the triple‐interpenetrated nature of the compound.
Facile Synthesis of Carbon–Metal Fluoride Nanocomposites for Lithium‐Ion Batteries
Authors: Reddy M. Anji , Breitung Ben , Wall Clemens , Trivedi Shivam , Chakravadhanula Venkata Sai Kiran , Helen M. , Fichtner Maximilian
Published: December 2015

Metal‐fluoride‐based conversion materials have gained interest as cathode materials for lithium‐ion batteries due to their high theoretical energy densities. However, metal fluorides are electrically insulating and experience large volume changes during the charge and discharge processes. Effective synthesis of carbon–metal fluoride nanocomposites (CMFNCs) with stable morphology is one of the keys to achieve high capacities with sustainable cycle life. A general method for the synthesis of CMFNCs is described here. The redox‐mediated reaction between CFx and metal‐carbonyl precursors at relatively low temperatures leads to the formation of the respective CMFNCs. The reaction mechanism for the formation of CFx‐derived C–FeF2 nanocomposites has been investigated. Also, the synthesis and lithium‐storage properties of C–CoF2 and C–MoF3 nanocomposites are reported. In addition, by changing from CFx to graphite oxide and sulfur‐infused porous carbon, the synthesis of C–FeOx and C–FeS nanocomposites is reported.
Crustal thinning and extension in the northwestern continental margin of the South China Sea
Authors: Zhu Junjiang , Li Jian , Sun Zongxun , Li Sanzhong
Published: December 2015

Multichannel seismic data on the continental shelf have been used to image the rift‐related shallow structural units of the Pearl River Mouth Basin across the northwestern margin of the South China Sea. The Hainan Uplift, Zhu 3 Depression and Shenhu‐Ansha Uplift zones are bounded by normal faults or listric‐normal faults, which suggest lithospheric extension on the continental shelf. Graben structures 10–15 km wide are imaged on the Wanshan Uplift and Northern Fault Terrace from the reflection data. The thinned continental crust and anomaly rift‐related crust in the depression zone and the transitional crust indicated by the wide‐angle OBS velocity model dominate the crustal structure of the continental shelf in the continental margin of the South China Sea. The different total crustal stretching factors in different shallow structural units suggest that non‐uniform horizontal stretching controls the crustal thinning. The total crustal stretching factor is ca. 1.4–1.6 at the coast area, ca. 1.67–1.8 in the rift‐depression zone and ca. 1.7–1.75 in the transitional crustal domain. Pure‐shear crustal thinning controls the crustal extension in the rift‐depression zone. The high heat flow anomaly in the vicinity of the seismic lines and anomaly rift‐depression velocity structure suggest that the crustal thinning on the continental shelf of the South China Sea can be produced by lateral mantle flow within the hotter regional lithospheric background. Copyright © 2015 John Wiley & Sons, Ltd.
Whatever Happened to Human Experimentation?
Authors: Elliott Carl
Published: December 2015

Several years ago, the University of Minnesota hosted a lecture by Alan Milstein, a Philadelphia attorney specializing in clinical trial litigation. Milstein, who does not mince words, insisted on calling research studies “experiments.” “Don't call it a study,” Milstein said. “Don't call it a clinical trial. Call it what it is. It's an experiment.” Milstein's comments made me wonder: when was the last time I heard an ongoing research study described as a “human experiment”? The phrase is now almost always associated with abuses. Asking a prospective subject to sign up for a medical experiment would probably get roughly the same response as asking him or her to sign up for a police interrogation.

It wasn't always this way. In the early days of American bioethics, scholars used the word “experimentation” in the same neutral way that they later began to use “research study” and “clinical trial.”
Hippocalcin‐like 1 suppresses hepatocellular carcinoma progression by promoting p21Waf/Cip1 stabilization by activating the ERK1/2‐MAPK pathway
Authors: Zhang Yonglong , Liu Yanfeng , Duan Jinlin , Yan Haibo , Zhang Jun , Zhang Huilu , Fan Qi , Luo Feifei , Yan Guoquan , Qiao Ke , Liu Jie
Published: December 2015

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death. However, the underlying mechanism during hepatocarcinogenesis remains unclarified. Stable isotope labeling by amino acids in cell culture (SILAC) is a powerful quantitative strategy for proteome‐wide discovery of novel biomarkers in cancers. Hippocalcin‐like 1 (HPCAL1) is a calcium sensor protein. However, the biological function of HPCAL1 is poorly understood in cancers, including HCC. Herein, HPCAL1 was identified by SILAC as a novel hepatocarcinogenesis suppressor down‐regulated in HCC cell lines and tissues. Importantly, lost expression of HPCAL1 was associated with worse prognosis of HCC patients. Interestingly, secreted HPCAL1 protein in the plasma dropped dramatically in HCC patients compared with healthy donors. Receiver operating characteristic curve analysis showed that serum HPCAL1 at a concentration of 8.654 ng/mL could better predict HCC. Furthermore, ectopic expression of HPCAL1 suppresses cell proliferation, while depletion of HPCAL1 led to increased cell growth both in vitro and in vivo. Mechanistically, HPCAL1 directly interacted with p21Waf/Cip1 in the nucleus, which requires the EF‐hand 4 motif of HPCAL1 and the Cy1 domain of p21. This interaction stabilized p21Waf/Cip1 in an extracellular signal‐regulated kinase 1/2‐mitogen‐activated protein kinase‐dependent manner, which subsequently prevented p21Waf/Cip1 proteasomal degradation by disrupting SCFSkp2 and CRL4Cdt2 E3 ligase complexes, resulting in increased protein stability and inhibitory effect of p21Waf/Cip1. Notably, the tumor suppressive function of HPCAL1 was dependent on p21 in vitro and in vivo. Consistent with this observation, expression of HPCAL1 and p21Waf/Cip1 was positively correlated in HCC tissues. Conclusion: These findings highlight a novel tumor suppressor upstream of p21Waf/Cip1 in attenuating cell cycle progression and provide a promising diagnostic and prognostic factor, as well as a potential therapeutic target for HCC. (Hepatology 2016;63:880–897)
MEP1A contributes to tumor progression and predicts poor clinical outcome in human hepatocellular carcinoma
Authors: OuYang Han‐Yue , Xu Jing , Luo Jun , Zou Ru‐Hai , Chen Keng , Le Yong , Zhang Yong‐Fa , Wei Wei , Guo Rong‐Ping , Shi Ming
Published: December 2015

Although many staging classifications have been proposed for hepatocellular carcinoma (HCC), determining a patient's prognosis in clinical practice is a challenge due to the molecular diversity of HCC. We investigated the relationship between MEP1A, a candidate oncogene, and clinical outcomes of HCC patients; furthermore, we explored the role of MEP1A in HCC. In this report, it was demonstrated by quantitative real‐time polymerase chain reaction that MEP1A messenger RNA levels were significantly elevated in HCC tumor tissues compared with matched adjacent nonneoplastic tissues and nonmalignant liver disease tissues. Immunohistochemical analyses of tissue samples from two independent groups of 394 HCC patients showed that positive expression of MEP1A in tumor cells was an independent and significant risk factor affecting survival after curative resection in both cohort 1 (hazard ratio = 2.05, 95% confidence interval 1.427‐2.946; P < 0.001) and cohort 2 (hazard ratio = 1.89, 95% confidence interval 1.260‐2.833; P = 0.002). Analysis of Barcelona Clinic Liver Cancer stage 0‐A subgroup further showed that patients with positive MEP1A expression in tumor cells had poorer surgical prognoses than those with negative MEP1A expression in tumor cells (cohort 1 P = 0.001, cohort 2 P < 0.001). Both in vitro and in vivo assays showed that MEP1A promoted HCC cell proliferation, migration, and invasion. Further analyses found that MEP1A played an important role in regulating cytoskeletal events and induced epithelial‐mesenchymal transition in HCC cells. Conclusion: MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC. (Hepatology 2016;63:1227‐1239)
Maternal Emotion Socialization: The Contribution of Inhibited Behaviour and Mothers' Dissatisfaction with the Parent–Child Relationship
Authors: Root Amy E. , Rasmussen Katie E.
Published: December 2015

In the present study, we examined the associations between children's inhibited behaviour, mothers' dissatisfaction with the parent–child relationship and mothers' self‐reported reactions to children's emotions. Fifty‐three mother–child dyads visited the laboratory, and mothers completed questionnaires about child temperament and emotion socialization. Maternal stress stemming from dissatisfaction with the parent–child relationship was negatively predictive of mothers' supportive reactions to happiness. In addition, the interaction between children's inhibited behaviour and parent–child relationship dissatisfaction significantly predicted mothers' supportive reactions to children's fear; specifically, mothers who reported the highest levels of dissatisfaction in their relationship with their children and had children who exhibited low levels of inhibition reported the lowest levels of supportive responses to their children's fear. Importantly, mothers reported the highest levels of supportive reactions to children's fear when their children were low in inhibition, and they reported low levels of dissatisfaction in their relationship with their child. Copyright © 2015 John Wiley & Sons, Ltd.
Association between genes encoding components of the Leutinizing hormone/Luteinizing hormone–choriogonadotrophin receptor pathway and polycystic ovary syndrome in Egyptian women
Authors: El‐Shal Amal S. , Zidan Haidy E. , Rashad Nearmeen M. , Abdelaziz Ahmed M. , Harira Mervat M.
Published: December 2015

Polycystic ovary syndrome (PCOS) is one of the most common endocrine–metabolic disorders; however, its pathophysiology is still unclear. Certain polymorphisms of luteinizing hormone beta‐subunit (LHβ) and LH/choriogonadotrophin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. We aimed to investigate possible associations between polymorphisms in the LHβ and LHCGR genes and PCOS among Egyptian women. We also aimed to shed light on the impact of these polymorphisms on LH level, hormonal, and metabolic features of PCOS. A case–control study included unrelated 210 patients with PCOS and 200 healthy controls, and they were stratified according to their body mass index into two subgroups: lean and obese. Polymorphisms of LHβ G1502A and LHCGR [G935A, and ins18LQ] genes were genotyped using polymerase chain reaction–restriction fragment length polymorphism. Our results revealed that LHβ G1052A GA genotype and A allele, LHCGR G935A GA, AA genotypes, or A allele were significantly associated with PCOS risk, while the LHCGR ins18LQ polymorphism was not. Additionally, there is a synergism between LHβ G1052A minor A and minor A allele of LHCGR G935A or minor ins allele of LHCGR ins18LQ and susceptibility to PCOS. When we stratified PCOS women or controls into obese and lean subjects, we found that LHβ G1502A GA genotype and A allele being more frequent in the obese group when compared with lean patients with PCOS [The odds ratio and 95% confidence interval were 5.6 (1.30–24.56) and 5.15 (1.21–21.90), respectively, P = 0.01, for each group.] These results suggested that LHβ G1052A and LHCGR G935A genes polymorphisms are associated with increased risk of PCOS in Egyptian women especially in obese cases. There was a synergism between LHβ G1052A minor A allele and of LHCGR G935A minor A or minor ins alleles of LHCGR ins18LQ and PCOS risk. © 2015 IUBMB Life, 68(1):23–36, 2016
Synthesis and Characterization of New Xanthene Derivatives, and Their Electrochemical Study
Authors: Saeed Aamer , Shabir Ghulam , Shehzadi Syeda Aaliya
Published: December 2015

This work investigated the synthesis of biphenyl‐3,3′,4,4′‐tetracarboxylic dianhydride and benzophenone‐3,3′,4,4′‐tetracarboxylic dianhydride derivatives (3a–e and 6a–e) with different substituted phenols via Friedel‐Crafts acylation reaction in the presence of dilute sulfuric acid. Dianhydride derivatives with 3‐N,N′‐dimethylamino phenol (3d and 6d) and resorcinol (3e and 6e) have been found to be highly fluorescent. The structures of all newly synthesized compounds were confirmed by the chromatographic, spectral and elemental data. Electrochemical study was done to determine to band gap energy, LUMO and HOMO levels energy. Band gap and LUMO energy levels were found to be lowest in xanthene derivatives substituted with 3‐N,N′‐dimethylamino group having value 2.24 and 4.85 eV respectively.
Tips of totally laparoscopic left hepatectomy
Authors: Cherqui Daniel , Figueroa Rodrigo , Gelli Maximiliano
Published: December 2015

Growing data suggest that minimally invasive approaches in hepatic surgery may improve postoperative outcomes without differences in terms of oncological results compared to open resections. These facts have contributed to the growing adoption of this technique for selected patients.However, expertise in both hepatic and advanced laparoscopic surgery is required in order to safely perform laparoscopic liver resections. We present a video depicting technical details for a totally laparoscopic left hepatectomy for hepatocellular carcinoma with left portal vein thrombosis in a cirrhotic patient.
Predictors of warfarin‐associated adverse events in hospitalized patients: Opportunities to prevent patient harm
Authors: Metersky Mark L. , Eldridge Noel , Wang Yun , Jaser Lisa , Bona Robert , Eckenrode Sheila , Bakullari Anila , Andrawis Mary , Classen David , Krumholz Harlan M.
Published: December 2015

BACKGROUND

The optimum international normalized ratio (INR) monitoring frequency for hospitalized patients receiving warfarin is unknown.

OBJECTIVE

Assess relationship between daily versus less frequent INR monitoring and overanticoagulation and warfarin‐related adverse events.

DESIGN

Retrospective cohort study using Medicare Patient Safety Monitoring System data.

SETTING

Randomly selected acute care hospitals across the United States.

PATIENTS

Patients hospitalized from 2009 to 2013 for pneumonia, acute cardiac disease, or surgery who received warfarin.

INTERVENTIONS

None.

MEASUREMENTS

(1) Association between frequency of INR monitoring and an INR ≥6.0 or warfarin‐related adverse event. (2) Association between the rate of change of the INR and a subsequent INR ≥5.0 and ≥6.0.

RESULTS

Among 8529 patients who received warfarin for ≥3 days, for 1549 (18.2%) the INR was not measured on 2 or more days. These patients had higher propensity‐adjusted odds ratios (ORs) of having a warfarin‐associated adverse event (OR: 1.48, 95% confidence interval [CI]: 1.02‐2.17) for cardiac patients and surgical patients (OR: 1.73, 95% CI: 1.20‐2.48), with no significant association for pneumonia patients. Cardiac and pneumonia patients with 1 day or more without an INR measurement had higher propensity‐adjusted ORs of having an INR ≥6.0 (OR: 1.61, 95% CI: 1.07‐2.41 and OR: 1.92, 95% CI: 1.36‐2.71, respectively). A 1‐day increase in the INR of ≥0.9 occurred in 621 patients (12.5%) and predicted a subsequent INR of ≥6.0 (positive likelihood ratio of 4.2).

CONCLUSION

Daily INR measurement and recognition of a rapidly rising INR might decrease the frequency of warfarin‐associated adverse events in hospitalized patients. Journal of Hospital Medicine 2016;11:276–282. © 2015 Society of Hospital Medicine
Set‐valued estimation of switching linear system: an application to an automotive throttle valve
Authors: Podivilova Elena , Vargas Alessandro N. , Shiryaev Vladimir , Acho Leonardo
Published: December 2015

This paper introduces a polyhedral approximation algorithm for set‐valued estimation of switching linear systems. The algorithm generates set‐valued estimates for any possible sequence of switching parameters, under the assumption that the system has unknown but bounded disturbances and measurement noises. Our algorithm has practical implications; namely, set‐valued estimates were generated for the position and electrical current of a real‐time automotive electronic throttle valve, and the corresponding experimental data demonstrate the practical benefits of our approach. Copyright © 2015 John Wiley & Sons, Ltd.
Can self‐sacrificial leadership promote subordinate taking charge? The mediating role of organizational identification and the moderating role of risk aversion
Authors: Li Rui , Zhang Zi‐Yuan , Tian Xiao‐Ming
Published: December 2015

The extant literature on the relationship between self‐sacrificial leadership and subordinate behavioral outcomes has primarily focused on the influence of this leadership on subordinate affiliative behaviors. Our research proposed a theoretical model explaining why and when self‐sacrificial leadership might promote taking charge, an exemplar of challenging behaviors. We tested this model across two studies conducted in China. In addition, we also examined the differences in the boundary conditions for self‐sacrificial leadership to influence taking charge and affiliative behaviors (cooperation in Study 1 and helping in Study 2). Our results revealed that (i) self‐sacrificial leadership was positively related to subordinate taking charge, with organizational identification acting as a mediator for this relationship, and (ii) risk aversion moderated both the self‐sacrificial leadership–subordinate taking charge relationship and the mediating effect of organizational identification, such that the relationship and its mediating mechanism were weaker for subordinates high rather than low in risk aversion. These moderating effects, however, could not generalize to cooperation and helping. Finally, the theoretical and practical implications of our results and directions for future research were discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Contextualizing leaders' interpretations of proactive followership
Authors: Benson Alex J. , Hardy James , Eys Mark
Published: December 2015

Although proactive followership behavior is often viewed as instrumental to group success, leaders do not always respond favorably to the actions of overly eager followers. Guided by a constructivist perspective, we investigated how interpretations of followership differ across the settings in which acts of leadership and followership emerge. In thematically analyzing data from semi‐structured interviews with leaders of high‐performing teams, we depict how the construal of follower behaviors relates to various contextual factors underscoring leader–follower interactions. Prototypical characteristics were described in relation to ideal followership (i.e., active independent thought, ability to process self‐related information accurately, collective orientation, and relational transparency). However, proactive followership behaviors were subject to the situational and relational demands that were salient during leader–follower interactions. Notably, the presence of third‐party observers, the demands of the task, stage in the decision‐making process, suitability of the targeted issue, and relational dynamics influenced which follower behaviors were viewed as appropriate from the leader's perspective. These findings provide insight into when leaders are more likely to endorse proactive followership, suggesting that proactive followership requires an awareness of how to calibrate one's actions in accordance with prevailing circumstances. Copyright © 2015 John Wiley & Sons, Ltd.
Real‐time PCR based analysis of metal resistance genes in metal resistant Pseudomonas aeruginosa strain J007
Authors: Choudhary Sangeeta , Sar Pinaki
Published: December 2015

A uranium (U)‐resistant and ‐accumulating Pseudomonas aeruginosa strain was characterized to assess the response of toxic metals toward its growth and expression of metal resistance determinants. The bacterium showed MIC (minimum inhibitory concentration) values of 6, 3, and 2 mM for Zn, Cu, and Cd, respectively; with resistance phenotype conferred by periplasmic Cu sequestering copA and RND type heavy metal efflux czcA genes. Real‐time PCR‐based expression analysis revealed significant upregulation of both these genes upon exposure to low concentrations of metals for short duration, whereas the global stress response gene sodA encoding superoxide dismutase enzyme was upregulated only at higher metal concentrations or longer exposure time. It could also be inferred that copA and czcA are involved in providing resistance only at low metal concentrations, whereas involvement of “global stress response” phenomenon (expression of sodA) at higher metal concentration or increased exposure was evident. This study provides significant understanding of the adaptive response of bacteria surviving in metal and radionuclide contaminated environments along with the development of real‐time PCR‐based quantification method of using metal resistance genes as biomarker for monitoring relevant bacteria in such habitats.
Stereotactic body radiation therapy for small primary or recurrent hepatocellular carcinoma in 132 Chinese patients
Authors: Su Ting‐Shi , Liang Ping , Lu Huan‐Zhen , Liang Jian , Gao Ying‐Chuan , Zhou Ying , Huang Yong , Tang Min‐Yang , Liang Jian‐Ning
Published: December 2015

Aim

To evaluate the efficacy of stereotactic body radiation therapy (SBRT) in small hepatocellular carcinoma (HCC) patients.

Methods

From March 2009 to April 2015, we treated 132 small HCC patients with SBRT. Eligibility criteria included longest tumor diameter ≤5.0 cm; Child‐Turcotte‐Pugh (CTP) Class A or B; unfeasible, difficult or refusal to undergo other surgery or percutaneous ablative therapies; and tumor recurrence after other local treatment. The dose of 42–46 Gy in 3–5 fractions and 28–30 Gy in 1 fraction was prescribed.

Results

Of the treated patients, 114 were classified as CTP A and 18 as CTP B. Median tumor size was range 1.1–5.0 cm. The local control rate at 1 years was 90.9%. OS at 1, 3, and 5 years was 94.1%, 73.5%, and 64.3%, respectively. PFS at 1, 3, and 5 years was 82.7%, 58.3%, and 36.4%, respectively. Hepatic toxicity grade ≥3 was observed in 11 patients. Multivariate analysis revealed that CTP B was associated with worse OS (P < 0.001) and multiple nodules were associated with worse PFS (P = 0.001).

Conclusions

SBRT is a promising alternative treatment for patients with primary or recurrent small HCC who are unsuitable for surgical resection or local ablative therapy. J. Surg. Oncol. 2016;113:181–187. © 2015 Wiley Periodicals, Inc.
Higher order Borel–Pompeiu representations in Clifford analysis
Authors: Reyes Juan Bory , Schepper Hennie De , Adán Alí Guzmán , Sommen Frank
Published: December 2015

In this paper, we show that a higher order Borel–Pompeiu (Cauchy–Pompeiu) formula, associated with an arbitrary orthogonal basis (called structural set) of a Euclidean space, can be extended to the framework of generalized Clifford analysis. Furthermore, in lower dimensional cases, as well as for combinations of standard structural sets, explicit expressions of the kernel functions are derived. Copyright © 2015 John Wiley & Sons, Ltd.
Distributed key agreement for group communications based on elliptic curves. An application to sensor networks.
Authors: Álvarez‐Bermejo José Antonio , Lodroman Antonela , López‐Ramos Juan Antonio
Published: December 2015

Internet of Things is built on sensor networks, which are enabling a new variety of solutions for applications in several fields (defense, health, and industry). Wireless communications are key for taking full advantage of sensor networks but implies new challenges in the security and privacy of communications. Security in wireless sensor networks is a major challenge for extending its applications. Moreover, the restrictive processing capabilities of sensor nodes have made the encryption techniques devised for conventional networks not feasible. In such setting, symmetric‐key ciphers are preferred for key management in wireless sensor network; key distribution is therefore an issue solved by means of the protocols presented in this paper. Diffie–Hellman protocol (since its development) has been in the most important cryptographic primitive being the base for plenty of security protocols. In this paper, we proposed three key exchange protocols derived from the Diffie–Hellman method, applied to elliptic curves, named ECGDH‐1, ECGDH‐2, and ECGDH‐3. Each performs secure key distribution sharing a group key among different nodes optimizing different network parameters. The security of the methods is based upon the difficulty of solving the discrete logarithm problem on elliptic curves. Making its application feasible to restrictive environments. Copyright © 2015 John Wiley & Sons, Ltd.
Characterization of fast‐tumbling isotropic bicelles by PFG diffusion NMR
Authors: Liebau Jobst , Ye Weihua , Mäler Lena
Published: December 2015

Small isotropic bicelles are versatile membrane mimetics, which, in contrast to micelles, provide a lipid bilayer and are at the same time suitable for solution‐state NMR studies. The lipid composition of the bilayer is flexible allowing for incorporation of various head groups and acyl chain types. In bicelles, lipids are solubilized by detergents, which are localized in the rim of the disk‐shaped lipid bilayer. Bicelles have been characterized by a broad array of biophysical methods, pulsed‐field gradient NMR (PFG NMR) being one of them. PFG NMR can readily be used to measure diffusion coefficients of macromolecules. It is thus employed to characterize bicelle size and morphology. Even more importantly, PFG NMR can be used to study the degree of protein association to membranes. Here, we present the advances that have been made in producing small, fast‐tumbling isotropic bicelles from a variety of lipids and detergents, together with insights on the morphology of such mixtures gained from PFG NMR. Furthermore, we review approaches to study protein–membrane interaction by PFG NMR. Copyright © 2015 John Wiley & Sons, Ltd.
Volumetric navigated MEGA‐SPECIAL for real‐time motion and shim corrected GABA editing
Authors: Saleh Muhammad G. , Alhamud A. , Near Jamie , van der Kouwe André J. W. , Meintjes Ernesta M.
Published: December 2015

Mescher–Garwood (MEGA) editing with spin echo full intensity acquired localization (MEGA‐SPECIAL, MSpc) is a technique to acquire γ‐aminobutyric acid (GABA) without macromolecule (MM) contamination at a TE of 68 ms. However, due to the requirement of multiple shot‐localization, it is often susceptible to subject motion and B0 inhomogeneity. A method is presented for real‐time shim and motion correction (ShMoCo) using volumetric navigators to correct for motion and motion‐related B0 inhomogeneity during MSpc acquisition. A phantom experiment demonstrates that ShMoCo restores the GABA peak and improves spectral quality in the presence of motion and zero‐ and first‐order shim changes. The ShMoCo scans were validated in three subjects who performed up–down and left–right head rotations. Qualitative assessment of these scans indicates effective reduction of subtraction artefacts and well edited GABA peaks, while quantitative analysis indicates superior fitting and spectral quality relative to scans with no correction. Copyright © 2015 John Wiley & Sons, Ltd.
Bulk quadrupole contribution to second harmonic generation from a microscopic response function
Authors: Bauer Klaus‐Dieter , Panholzer Martin , Hingerl Kurt
Published: December 2015

Even‐order nonlinear methods have proven useful tools for the analysis of centrosymmetric materials where the surface dipole contribution is often dominant. Quadrupole‐order contributions from the surface discontinuity and the bulk can be on the same order of magnitude however, yet have been largely ignored in modern numerical ab initio calculations. We find that the macroscopic bulk quadrupole term : can be related to the first order derivatives of the microscopic response function at the ‐point and outline how a quantum‐mechanical expression can be derived for a periodic system.
Spin effects in MoS2 and WS2 single layers
Authors: Kioseoglou G. , Korkusinski M. , Scrace T. , Hanbicki A. T. , Currie M. , Jonker B. T. , Petrou A. , Hawrylak P.
Published: December 2015

magnified image

Replacing the two sublattices of carbon atoms in graphene with transition metal atoms and chalcogenide dimers results in single layers of transition metal dichalcogenides (TMDCs). TMDCs are promising new materials for light and energy harvesting, transistors, sensors and quantum information processing. One way to access the distinctive functionality of these materials is via their optical selection rules. In particular, light with positive or negative helicity is absorbed differently, therefore, understanding the interaction of circularly polarized light with various TMDCs should enable future applications. Using the examples of MoS2 and WS2 we summarize some recent results that illustrate the potential of these materials. First, when optically excited with circularly polarized light, single layers of MoS2 can emit light with an appreciable polarization.

Depolarization mechanisms can be subsequently explored by monitoring the polarization of emitted photoluminescence as a function of the excess energy supplied to the system. As the energy of the pumping light increases further from the emission channel, the emission quickly becomes depolarized. The dominant relaxation mechanism is identified as phonon‐assisted intervalley scattering. In single layers of WS2 containing electron gas, the main emission channel is from negatively charged excitons, or trions. In the presence of a two‐dimensional electron gas this trion emission is circularly polarized at zero magnetic field, even when excited with linearly polarized light. This spontaneous circular polarization of the trion has a linear dependence on magnetic field and can be attributed to the existence of a valley polarized state of the two‐dimensional electron gas. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Graphical Analysis for Operation Management: A Graphical Method to Support Operation Decision Making
Authors: Viveros Gunckel Pablo , Crespo Márquez Adolfo , Barberá Martinez Luis , Gonzalez Rossel Juan Pablo
Published: December 2015

This paper proposes a graphical method to easy decision‐making in industrial plants operations. The proposed tool ‘Graphical Analysis for Operation Management (GAOM) method’ allows to visualizing and analyzing production‐related parameters, integrating assets/systems maintenance aspects. This integration is based on the Total Productive Maintenance model, using its quantitative management techniques for optimal decision‐making in day‐to‐day operations. On the one hand, GAOM monitors possible production target deviations, and on the other, the tool illustrates different aspects to gain control on the production process, such as availability, repair time, cumulative production, or overall equipment effectiveness. Through appropriate information filtering, individual analysis by class of intervention (corrective maintenance, preventive maintenance, or operational intervention) and production level can be developed.

Graphical Analysis for Operation Management (GAOM) integrates maintenance information (number of intervention, type of intervention, required/not required stoppage) with production information (cumulative production, cumulative defective products, and cumulative production target) during a certain timeframe (cumulative calendar time, duration of intervention). Then the tool computes basic performance indicators supporting operational decision‐making. GAOM provides interesting graphical outputs using scatter diagrams integrating indicators on the same graph. GAOM is inspired in the Graphical Analysis for Maintenance Management method, published by the authors (LB, AC, and PV) in 2012. Copyright © 2015 John Wiley & Sons, Ltd.