bluuebunny/crossref_metadata_2025 huggingface dataset:
FTO variant associated with malformation syndrome
Authors: Rohena Luis , Lawson Michelle , Guzman Edwin , Ganapathi Mythily , Cho Megan T. , Haverfield Eden , Anyane‐Yeboa Kwame
Published: December 2015

Common FTO variants are associated with obesity. However, it has recently been shown that homozygous FTO c.947G>A variant, which predicts p.R316Q, and c.956C>T, which predicts p.S319F, are associated with a malformation syndrome inherited in an autosomal recessive pattern. We present a similar homozygous FTO c.965G>A variant that predicts p.R322Q, associated with a lethal malformation syndrome in a consanguineous Yemeni family. Functional studies showed that the p.R316Q, p.S219F, and p.R322Q variants render the FTO protein inactive. We further expand on the phenotype of homozygous FTO loss‐of‐function mutations to include eye abnormalities, gingival overgrowth, craniosynostosis, and cutaneous photosensitivity. © 2015 Wiley Periodicals, Inc.
Response to treatment in a prospective national infantile spasms cohort
Authors: Knupp Kelly G. , Coryell Jason , Nickels Katherine C. , Ryan Nicole , Leister Erin , Loddenkemper Tobias , Grinspan Zachary , Hartman Adam L. , Kossoff Eric H. , Gaillard William D. , Mytinger John R. , Joshi Sucheta , Shellhaas Renée A. , Sullivan Joseph , Dlugos Dennis , Hamikawa Lorie , Berg Anne T. , Millichap John , Nordli Douglas R. , Wirrell Elaine ,   and the Pediatric Epilepsy Research Consortium
Published: December 2015

Objective

Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status.

Methods

The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi‐square tests and multivariate logistic regression models.

Results

Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p < 0.001). Fifty‐five percent of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p < 0.001). Neither etiology nor development significantly modified the response pattern by treatment group.

Interpretation

Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies. ANN NEUROL 2016;79:475–484
Stretchable conductive films based on carbon nanomaterials prepared by spray coating
Authors: Bu Qiang , Zhan Yanhu , He Fangfang , Lavorgna Marino , Xia Hesheng
Published: December 2015

Stretchable conductive films consisting of a layer of carbon nanomaterials, that is, carbon nanotubes (CNTs), mechanically exfoliated graphene (GE), or chemically reduced graphene oxide (rGO), deposited on polydimethylsiloxane (PDMS) films were prepared by spray coating. The correlations among the concentration of the carbon nanomaterials, the electrical resistance and the optical transmittance of the spray‐coated films were investigated. The results show that the conductivity of the CNT coatings was better than that of the GE‐based coatings. When the CNT concentration of the dispersion for spraying increased from 0.01 to 0.075 mg/mL, the surface electrical resistance decreased from 7.8 × 103 to 6.7 × 102 Ω, whereas for the GE or rGO coatings, the electrical resistance was several orders higher than that of the CNT coatings. The CNT spray‐coated films exhibited an optical transmittance of about 60% at a wavelength of 550 nm; this was higher than that of the GE or rGO spray‐coated films. The electric heating behaviors of the stretchable conductive films as functions of the applied voltage and the concentration of carbon nanomaterials and the electrical conductivity under tensile and bending strains were also investigated. The surface temperature of the CNT‐coated films rose rapidly up to 200°C within about 40 s when the applied voltage was 110 V. The stretchable conductive films have potential as electric heating elements because of their excellent conductive properties. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43243.
PVDF piezoelectric voltage coefficient in situ measurements as a function of applied stress
Authors: Gusarov Boris , Gusarova Elena , Viala Bernard , Gimeno Leticia , Cugat Orphée
Published: December 2015

Direct piezoelectric g31 voltage coefficient was measured in situ as a function of applied tensile stress for films of polyvinylidene fluoride (PVDF). Measurements were performed under quasi‐static conditions with applied strain rates of 0.5–1.5 mm/min for strains up to 12%. Open‐circuit voltage was measured with a contact‐less electrostatic voltmeter. Obtained results show a strong dependence of the g31 coefficient of mono‐oriented PVDF films on the applied stress, with a maximum value of the coefficient in the transition region between elastic and plastic deformation zones. The effect of sample geometry on the apparent g31 coefficient is shown and discussed. The anisotropy of the piezoelectric effect is studied by means of g31 and g32 measurements. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43248.
Rheological study of copovidone and solid dispersion blend used for hot melt extrusion
Authors: Dudhedia Mayur S. , Agrawal Anjali M.
Published: December 2015

The focus of this work is to generate rheological parameters using AR 2000EX rheometer for PVP VA64 and Compound A – PVP VA64 blend at different temperatures, which can then be subsequently used to identify hot melt extrusion process conditions. Addition of Compound A to the neat PVP VA64 shows a drop in storage modulus and loss modulus as compared to the neat PVP VA64. It appears that Compound A is acting as a plasticizer by increasing the separation of the polymer chains and thus results in reduction of viscosity of Compound A blends compared to polymer only samples. For both systems, based on low standard error of fit, Cross model was chosen as the best fit for the rheological data and temperature dependency of viscosity was assessed by Williams–Landel–Ferry (WLF) model. This approach can be applied to screen formulations with new chemical entities (NCEs) and generate rheological information with various extruding polymers at fixed/variable drug loading in polymer matrix to determine suitability for hot melt extrusion process and appropriate temperature for conducting hot melt extrusion. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43278.
A facile preparation of pH‐temperature dual stimuli‐responsive supramolecular hydrogel and its controllable drug release
Authors: Zhou Mi , Liu Kaiyue , Qian Xin
Published: December 2015

A series of pH‐temperature dual stimuli‐responsive random copolymers poly[N,N‐dimethylaminoethyl methacrylate‐co‐poly(poly(ethylene glycol) methyl ether methacrylate][poly(DMAEMA‐co‐MPEGMA)] were synthesized by free radical polymerization. The supramolecular hydrogel was formed by pseudopolyrotaxane, which was prepared with the host‐guest interactions between α‐cyclodextrin (α‐CD) and poly(ethylene glycol) (PEG) side chains. Fourier transform infrared (FT‐IR), nuclear magnetic resonance (1H NMR), and X‐ray diffraction (XRD) confirmed the structures of the hydrogels. The pH‐temperature dual stimuli responsive properties of the hydrogels were characterized by rheometer. Finally, the controllable drug release behavior of the hydrogel, which was used 5‐fluorouracil (5‐Fu) as the model drug, was investigated at different temperatures and different pH values. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43279.
Influence of 1,2‐polybutadiene on properties of dicumyl peroxide cured brominated butyl rubber
Authors: Yuan Xia , Wang Jinyuan , Wang Chunwei , Gao Steven , Guo Sharon , Zhang Yong
Published: December 2015

Peroxide curing of brominated butyl rubber (BIIR) is an attractive topic, but the degradation of BIIR during the curing is a drawback needed to be overcome. Coagent assisted peroxide curing system is an attractive and effective choice in order to increase the crosslink density of rubbers. 1,2‐polybutadiene (1,2‐PB) is used as a crosslinking coagent for the curing of BIIR by dicumyl peroxide (DCP), and the effect of 1,2‐PB on the curing characteristics, crosslink density, and mechanical properties is investigated. The addition of 1,2‐PB affects the curing characteristics of BIIR compound and significantly increases the crosslink density of BIIR vulcanizates. With increasing 1,2‐PB content, the tensile strength and stresses at a given extension of BIIR vulcanizates increase, but the elongation at break decreases. A stress‐softening effect of the carbon black filled BIIR vulcanizates is observed and becomes more pronounced with increasing 1,2‐PB content. The addition of 1,2‐PB increases the stress relaxation index of BIIR. GPC and 13C‐NMR results indicate 1,2‐PB participates in the crosslinking reaction, and the existence of 1,2‐PB component in the insoluble fraction of BIIR/1,2‐PB vulcanizates is confirmed by solid‐state 13C‐NMR. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43280.
Heavy metal removal using hydroxypropyl cellulose and polyacrylamide gels, kinetical study
Authors: Zamarripa–Cerón José Luis , García‐Cruz Juan Carlos , Martínez–Arellano Alfredo Carlos , Castro–Guerrero Carlos Fernando , Ángeles–San Martín Marisela Estefanía , Morales–Cepeda Ana Beatriz
Published: December 2015

In this article we report the removal of Pb, Ni and Cu using a hydrogel made with hydroxypropyl cellulose (HPC) and polyacrylamide (PAAm). The hydrogel successfully removed those metals, as shown by the results of atomic absorption spectroscopy; the polymer removed 53% of Pb, 52% of Ni and 51% of Cu. Different pHs were tried for these polymers. The highest metal removal was found at 40°C. The adsorption kinetics fitted Langmuir and Freundlich isotherms. Metal particles were detected on the hydrogel with electron microscopy and energy–dispersive X–ray spectroscpy, confirming that the gel removed the metals from the testing solutions. This polymer is a good option for treating wastewater and industrial waters as it removes metals and is composed of nontoxic materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43285.
Chemical modifications of lignocellulosic materials and their application for removal of cations and anions from aqueous solutions
Authors: de Quadros Melo Diego , de Oliveira Sousa Neto Vicente , de Freitas Barros Francisco Claudio , Raulino Giselle Santiago Cabral , Vidal Carla Bastos , do Nascimento Ronaldo Ferreira
Published: December 2015

This review discussed the last 10 years progress in the use of lignocellulosic materials chemically modified as low‐cost biosorbents. Thus, the chemical modifications, such as chemical pretreatment, oxidation, as well as the grafting of carboxyl groups, amines, amides, etc., on lignocellulosic fibers, that aim to increase the number of adsorption sites and maximize toxic metal ion adsorption capacity have been addressed. The literature presents results that indicated performances of biosorbents equal to or even higher than conventional methods and adsorbents. Many efforts have been concentrated on the improvements of these biosorbents through chemical modifications. However, some difficulties still exist, including the discharge of colored organic compounds resulting from the pretreatments and the development of fast, clean, and low‐cost synthesis of selective and multifunctional adsorbents. Thus, the challenge for future research is to find solutions to these difficulties in order to finally make lignocellulosics biosorbents that can replace conventional adsorbent materials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43286.
How the infrared radiation affects the film formation process from latexes?
Authors: Yargi O. , Gelir A. , Ozdogan M. , Nuhoglu C. , Elaissari A.
Published: December 2015

In this study, the effect of the infrared radiative heating (IRH) was investigated on the film formation from composites of polystyrene (PS) latex particles and poly vinyl alcohol (PVA). The films were prepared as a pure PS and a mixture of PS and PVA particles at equal compositions at room temperature and they were annealed at elevated temperatures above the glass transition temperature (Tg) of PS for 10 min by using IRH technique. Identical experiments were performed by using standard convectional heating technique in oven as comparison. It was shown that the activation energy for the film formation from PS latex particles decreased considerably in IRH annealing technique. Photon transmission (PT) and steady state fluorescence (SSF) techniques were used to monitor the film formation process at each sintering step. Minimum film formation temperature, To, and healing temperature, Th, were determined by the data obtained from the SSF and the PT measurements for each heating processes. The film formation was modeled as a void closure and as an interdiffusion stage below and above Th, respectively. Scanning electron microscopy (SEM) was used to examine the variation in morphological structure of annealed composite films. It was observed that IRH heating causes more homogenous and more flat film surface than films annealed in the oven. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43289.
Laccase‐catalyzed synthesis of polypyrrole‐multiwalled carbon nanotube composites as energy storage materials for capacitors
Authors: Park Junghee , Raseda Nasrin , Oh Eun Suok , Ryu Keungarp
Published: December 2015

Multiwalled carbon nanotubes (MWNTs) were coated with polypyrrole (PPy) using in situ enzymatic polymerization of pyrrole catalyzed by a laccase (benzenediol:oxygen oxidoreductase, EC 1.10.3.2) from Trametes versicolor. Transmission electron microscopy revealed that the MWNTs were uniformly coated with very thin layers of PPy without any indication of globular polymer aggregate formations. The enzymatic synthesis of the MWNTs/PPy composites was quite simple being performed in a one‐pot aqueous solution (pH 4.0) under mild reaction conditions. The potential of the composites with respect to the development of energy storage devices was demonstrated by fabricating a two‐electrode coin cell capacitor (diameter 20 mm, thickness 1.6 mm) utilizing the composites as electrode materials. The capacitance of the cell was 28.0 F g−1 for the electrode material as measured by a galvanostatic charge–discharge method. The energy density and power density were 2.55 and 805 W kg−1, respectively, which were close to those of the capacitors classified as ultracapacitors. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43307.
Stepwise cure and properties of silicone resin for high‐ultraviolet‐transmission optical elements
Authors: Lv Zhiyong , Wu Chonggang , Li Jing , Fang Xiao , Yu Dongdong , Qin Huchuan , Yu Peng , Chen Xuhuang
Published: December 2015

A new high‐ultraviolet (UV)‐transmission silicone‐resin polymeric material was prepared via curing during hydrosilylation of tetramethyltetravinylcyclotetrasiloxane with tetramethylcyclotetrasiloxane by a liquid‐surface supernatant method, using a stepwise heating program to avoid spontaneous combustion of the reaction mixture. The relationships were investigated in detail between reactive groups, cross‐linking density, mechanical and UV‐transmission properties. For this purpose, UV transmittance and dynamic mechanical properties, respectively, of the silicone resin were measured with UV–visible spectrophotometry and dynamic mechanical thermal analysis. In addition, surface roughness was evaluated with an atomic force microscope as well as an interferometer. The curing process was monitored by Fourier transform infrared spectroscopy and rotational rheometry. The cyclic silicone oils were compared with linear ones in structure and product properties. The results indicated that stepwise temperature control during curing process was particularly indispensible due to the presence of active SiH bonds, and that the silicone resin of high modulus, high UV transmittance (92.7%) and low surface‐roughness was largely homogeneous in cross‐linking points distribution. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43308.
Effect of polymer matrix on the performance of pressure‐sensitive paint comprising 5,10,15,20‐tetrakis(pentafluorophenyl)porphinato platinum(II) and poly(1,1,1,3,3,3‐hexafluoroisopropyl‐co‐tert‐butyl methacrylates)
Authors: Obata Makoto , Asato Ryo , Hirohara Shiho , Mitsuo Kazunori
Published: December 2015

Copolymers of 1,1,1,3,3,3‐hexafluoroisopropyl methacrylate (HFIPM) and tert‐butyl methacrylate (TBM) were prepared by conventional radical copolymerization as a novel binders for pressure‐sensitive paints (PSP). The monomer reactivity ratios rHFIPM and rTBM were determined as 0.45 and 0.67, respectively. The glass transition temperature of the copolymers increased from 77 to 126°C with increasing mole fraction of TBM units in the copolymer. The PSP were formed by combining the resulting copolymers and 5,10,15,20‐tetrakis(pentafluorophenyl)porphinato platinum(II). The pressure and temperature sensitivities of the PSPs were measured at air pressures ranging from 5 to 120 kPa and at temperatures ranging from 0 to 60°C. Modified Stern–Volmer plots indicated slight increases in the pressure sensitivity, but significant decrease in the temperature sensitivity as the mole fraction of HFIPM units increased in the copolymer. Applying a theoretical model to our calibration data, we inferred that luminescence quenching is primarily responsible for increasing the temperature sensitivity in the resulting copolymers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43316.
Toughening of epoxy novolac resin using cardanol based flexibilizers
Authors: Gour Rajeshwari S. , Kodgire Vivek V. , Badiger Manohar V.
Published: December 2015

In this work, two different cardanol based epoxies (Cardolite NC‐514 and Cardanol NC‐547) were employed as flexibilizers to toughen an epoxy novolac resin namely, poly[(phenylglycidyl ether)‐co‐formaldehyde] (PPGEF). 4,4′‐Diamino‐3,3′‐dimethyl dicyclohexyl methane (BMCHA) was used as a curing agent. Differential scanning calorimetry and dynamic mechanical thermal analysis of the composites showed a gradual decrease in glass transition temperatures (Tg) with increase in cardolite content confirming the incorporation of flexible moieties into the brittle resin matrix. Improvement in toughening of PPGEF/Cardolite composites was manifested by increase in the izod impact strength of both the composites. The tensile strength increased marginally for composites with increasing amount of Cardolite NC‐514 but decreased for the composites containing Cardolite NC‐547. This was attributed to the lack of rotational motion in the chain due to close proximity of rigid phenyl rings in NC‐547. SEM of the cryo‐fractured surfaces of composites showed good compatibility between PPGEF and cardanol based flexibilizers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43318.
Role of receptor occupancy assays by flow cytometry in drug development
Authors: Stewart Jennifer J. , Green Cherie L. , Jones Nicholas , Liang Meina , Xu Yuanxin , Wilkins Danice E. C. , Moulard Maxime , Czechowska Kamila , Lanham David , McCloskey Thomas W. , Ferbas John , van der Strate Barry. W. A. , Högerkorp Carl‐Magnus , Wyant Timothy , Lackey Alan , Litwin Virginia
Published: December 2015

The measurement of the binding of a biotherapeutic to its cellular target, receptor occupancy (RO), is increasingly important in development of biologically‐based therapeutic agents. Receptor occupancy (RO) assays by flow cytometry describe the qualitative and/or quantitative assessment of the binding of a therapeutic agent to its cell surface target. Such RO assays can be as simple as measuring the number of cell surface receptors bound by an antireceptor therapeutic agent or can be designed to address more complicated scenarios such as internalization or shedding events once a receptor engages the administered therapeutic agent. Data generated from RO assays can also be used to model whether given doses of an experimental therapeutic agent and their administration schedules lead to predicted levels of receptor occupancy and whether the receptor is modulated (up or down) on cells engaged by the therapeutic agent. There are a variety of approaches that can be used when undertaking RO assays and with the ability to measure distinct subsets in heterogeneous populations, flow cytometry is ideally suited to RO measurements. This article highlights the importance of RO assays on the flow cytometric platform in the development of biotherapeutic agents. © 2016 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.
Simultaneous use of sodium nitrate and urea as nitrogen sources improves biomass composition of Arthrospira platensis cultivated in a tubular photobioreactor
Authors: Morocho‐Jácome Ana Lucía , Sato Sunao , de Lara Capurro Guimarães Laís , Knysak Camargo de Jesus Camila , Monteiro de Carvalho João Carlos
Published: December 2015

Arthrospira platensis is widely cultivated in open ponds for industrial purposes. However, high‐protein A. platensis biomass produced in photobioreactors (PBRs) is recommended for pharmaceutical and cosmetic formulations. A. platensis was cultivated in a 3.5 L tubular airlift PBR using both sodium nitrate and urea as nitrogen sources. Sodium nitrate was added from the start of the cultivation using a batch process. Urea was supplied daily at exponentially increasing feeding rate using a fed‐batch process. The simultaneous optimization of the independent variables, namely, total quantity of sodium nitrate (mT1) and total quantity of urea (mT2), led to an optimal condition of mT1 = 15.0 mmol/L and mT2 = 7.5 mmol/L. Maximum biomass concentration (5183 ± 94 mg/L) corresponding to the highest biomass productivity (683 ± 13 mg/L/day) was obtained under such condition. The addition protocol of both nitrogen sources resulted in high productivities of protein (6.2 ± 0.4 mg/L/day) as well as chlorophyll‐a (372.2 ± 7.7 mg/L/day). Such innovative process could be applied in the large‐scale production of A. platensis using tubular PBR for novel applications.
The UN COP21 Climate Change Conference and the role of CCS
Authors: Cozier Muriel
Published: December 2015

The United Nations Conference of Parties 21 (UN COP21) Climate Change Conference, which runs from 30 November to 11 December in Paris, France, has set out to reach a binding agreement to cut emissions of greenhouse gases (GHGs) and to set goals for economic development and social and environmental issues. Muriel Cozier takes a look how the major players have positioned themselves to influence and bring about an agreement and how carbon capture and storage (CCS) is very much part of the toolkit required to help keep greenhouses GHGs in check. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd
Dopaminergic system and dream recall: An MRI study in Parkinson's disease patients
Authors: De Gennaro Luigi , Lanteri Olimpia , Piras Fabrizio , Scarpelli Serena , Assogna Francesca , Ferrara Michele , Caltagirone Carlo , Spalletta Gianfranco
Published: December 2015

We investigated the role of the dopamine system [i.e., subcortical‐medial prefrontal cortex (mPFC) network] in dreaming, by studying patients with Parkinson's Disease (PD) as a model of altered dopaminergic transmission. Subcortical volumes and cortical thickness were extracted by 3T‐MR images of 27 PD patients and 27 age‐matched controls, who were asked to fill out a dream diary upon morning awakening for one week. PD patients do not substantially differ from healthy controls with respect to the sleep, dream, and neuroanatomical measures. Multivariate correlational analyses in PD patients show that dopamine agonist dosage is associated to qualitatively impoverished dreams, as expressed by lower bizarreness and lower emotional load values. Visual vividness (VV) of their dream reports positively correlates with volumes of both the amygdalae and with thickness of the left mPFC. Emotional load also positively correlates with hippocampal volume. Beside the replication of our previous finding on the role of subcortical nuclei in dreaming experience of healthy subjects, this represents the first evidence of a specific role of the amygdala‐mPFC dopaminergic network system in dream recall. The association in PD patients between higher dopamine agonist dosages and impoverished dream reports, however, and the significant correlations between VV and mesolimbic regions, however, provide an empirical support to the hypothesis that a dopamine network plays a key role in dream generation. The causal relation is however precluded by the intrinsic limitation of assuming the dopamine agonist dosage as a measure of the hypodopaminergic state in PD. Hum Brain Mapp 37:1136–1147, 2016. © 2015 Wiley Periodicals, Inc.
Major depressive disorder: Findings of reduced homotopic connectivity and investigation of underlying structural mechanisms
Authors: Hermesdorf Marco , Sundermann Benedikt , Feder Stephan , Schwindt Wolfram , Minnerup Jens , Arolt Volker , Berger Klaus , Pfleiderer Bettina , Wersching Heike
Published: December 2015

Depression has been associated with various alterations in magnetic resonance imaging (MRI) derived resting‐state functional connectivity. Recently, homotopic connectivity, defined as functional connectivity between homotopic regions across hemispheres, has been reported to be reduced in patients with major depressive disorder (MDD). However, little is known about structural factors underlying alterations of homotopic connectivity, which would contribute to the understanding of the altered neurophysiological architecture in patients with MDD. We compared 368 patients with MDD and 461 never‐depressed controls regarding voxel‐mirrored homotopic connectivity (VMHC) and potential underlying mechanisms such as the structural connectivity of the corpus callosum, measured by DTI‐derived fractional anisotropy (FA), and left–right symmetries in homotopic gray matter volumes. Compared to controls, patients with MDD exhibited reduced VMHC in the cuneus, putamen, superior temporal gyrus, insula, and precuneus. Within these regions, no differences in left–right symmetries in homotopic gray matter volumes were evident across cohorts. FA of the corpus callosum correlated with VMHC in the entire sample. However, patients with MDD and controls did not differ with regard to callosal FA. The findings indicate that MDD is associated with a loss of interhemispheric synchrony in regions known to be implicated in self‐referential and reward processing. They also suggest that additional mechanisms are implicated in altered homotopic connectivity of patients with MDD, other than direct callosal fiber pathways or asymmetries in homotopic gray matter volumes. Hum Brain Mapp 37:1209–1217, 2016. © 2015 Wiley Periodicals, Inc.
Three‐dimensional endoscopy in transnasal transsphenoidal approach to clival chordomas
Authors: Garzaro Massimiliano , Zenga Francesco , Raimondo Luca , Pacca Paolo , Pennacchietti Valentina , Riva Giuseppe , Ducati Alessandro , Pecorari Giancarlo
Published: December 2015

Background

The purpose of this prospective, observational study was to evaluate the management of skull base chordomas surgically resected via a 3D‐endoscopic transnasal approach.

Methods

Thirteen consecutive patients were observed and only 9 were surgically treated using a 3D‐endoscopic transnasal approach assisted by a novel 3D visualization system.

Results

Nine consecutive male patients (mean age, 57.4 years) underwent exclusive 3D‐endoscopic transnasal transsphenoidal resection of clival chordomas; gross total resection was achieved in 66.6% of cases (6 of 9 patients), near‐total resection in 11.2% (1 of 9 patients), and partial resection in 22.2% (2 of 9 patients). The complications observed were 2 cases of postoperative cerebrospinal fluid (CSF) leaks and 1 case of temporary VI cranial nerve palsy.

Conclusion

No discomfort was recorded; when a dura opening was required, 3D vision allowed an accurate intradural sharp dissection and a precise repair of the skull base. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1814–E1819, 2016
Primary inverted papilloma of the middle ear with intracranial invasion
Authors: Coca‐Pelaz Andrés , Gómez–Martínez Justo , Vivanco–Allende Blanca , Hermsen Mario , Llorente Jose Luis
Published: December 2015

Background

Primary inverted papillomas of the middle ear are extremely rare tumors, with only few cases published in the literature. They have a characteristic epithelium surface inversion to the inside of the stroma. Inverted papillomas are benign lesions but have a high propensity of recurrence, local aggressiveness, and association with malignancy.

Methods

We present a patient with an inverted papilloma originating in the middle ear producing chronic otorrhea and facial nerve palsy treated with a subtotal petrosectomy.

Results

During the follow‐up, the patient developed an intracranial invasion of the tumor causing his death.

Conclusion

Primary inverted papillomas of the middle ear can have an extremely aggressive behavior despite their benign characteristics; therefore, an aggressive treatment must be performed in order to minimize the possibility of recurrence. © 2015 Wiley Periodicals, Inc. Head Neck 38: E105–E107, 2016
Near infrared fluorescent imaging after intravenous injection of indocyanine green during neck dissection in patients with head and neck cancer: A feasibility study
Authors: Digonnet Antoine , van Kerckhove Sophie , Moreau Michel , Willemse Esther , Quiriny Marie , Ahmed Bissan , de Saint Aubain Nicolas , Andry Guy , Bourgeois Pierre
Published: December 2015

Background

Indocyanine green (ICG) has not been studied during therapeutic lymph node dissections after intravenous injection. The purpose of this study was to explore the distribution of ICG in lymphatic nodes during neck dissection.

Methods

Eleven patients requiring neck dissection with or without resection of the primary lesion were included. ICG was intravenously injected at induction time of anesthesia. Imaging was performed before and after surgical resection. Fluorescence was measured in arbitrary units (AUs) in the pathology department. Mixed linear model and generalized estimating equations (GEEs) were used.

Results

Mean fluorescence of invaded nodes was 22.6 AUs (SD = 24.9) and 3.9 AUs (SD = 8.1) in negative nodes (p = .016). After adjustment for the size of the node, the risk of invasion when fluorescence was observed was 12.2 (95% confidence interval [CI] = 5.3–28.2; p < .0001).

Conclusion

This study demonstrates the feasibility of ICG to bring a contrast during surgery between healthy and invaded nodes after i.v. injection. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1833–E1837, 2016
Features and prognostic utility of biopsy in oral squamous cell carcinoma
Authors: Dhanda Jagtar , Uppal Nugdeep , Chowlia Harpreet , Opie Neil , Al‐Qamachi Laith , Shelat Devesh , Aslam Adil , Yuffa Arie , Martin Timothy , Risk Janet , Triantafyllou Asterios , Shaw Richard , Parmar Satyesh , Mehanna Hisham
Published: December 2015

Background

Traditional approaches in oral squamous cell carcinoma (OSCC) management utilize biopsy tissue for diagnostic purposes only. Adverse prognostic features, such as the tumor depth, are usually determined from final resection specimens, but are seldom studied in biopsy tissue.

Methods

A preliminary study of 139 consecutive biopsies compared biopsy size with T classification, tumor site, and operator grade, and biopsy tumor depth with the true tumor depth.

Results

This study demonstrated that biopsy size is independent of T classification (p = .44), subsite (p = .86), and operator grade (p = .10). The biopsy tumor depth significantly underrepresented true tumor depth (2.5 mm, 95% confidence interval [CI] = 2.4–2.9 vs 8.2 mm, 95% CI = 6.5–9.9; p < .001), confirming the limited prognostic utility of biopsies in OSCC.

Conclusion

A future clinical trial will compare the routine biopsy technique with standardized deeper biopsy techniques using punch biopsy to sample invasive fronts and investigate opportunities for up‐front staging using a combination of histological features and epithelial and stromal molecular biomarkers in OSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1857–E1862, 2016
Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2)
Authors: Lawitz Eric , Matusow Gary , DeJesus Edwin , Yoshida Eric M. , Felizarta Franco , Ghalib Reem , Godofsky Eliot , Herring Robert W. , Poleynard Gary , Sheikh Aasim , Tobias Hillel , Kugelmas Marcelo , Kalmeijer Ronald , Peeters Monika , Lenz Oliver , Fevery Bart , De La Rosa Guy , Scott Jane , Sinha Rekha , Witek James
Published: December 2015

Hepatitis C virus (HCV)–infected patients with cirrhosis are historically a difficult‐to‐treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1–infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open‐label, single‐arm study (OPTIMIST‐2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1–infected treatment‐naive or treatment‐experienced patients with cirrhosis. Patients (aged 18‐70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient‐reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%‐91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment‐naive and treatment‐experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient‐reported outcomes improved from baseline to follow‐up week 12. Conclusion: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment‐naive and treatment‐experienced HCV GT1‐infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360‐369)
HDAC5 controls the functions of Foxp3+ T‐regulatory and CD8+ T cells
Authors: Xiao Haiyan , Jiao Jing , Wang Liqing , O'Brien Shaun , Newick Kheng , Wang Liang‐Chuan S. , Falkensammer Eva , Liu Yujie , Han Rongxiang , Kapoor Veena , Hansen Finn K. , Kurz Thomas , Hancock Wayne W. , Beier Ulf H.
Published: December 2015

Histone/protein deacetylases (HDACs) are frequently upregulated in human malignancies and have therefore become therapeutic targets in cancer therapy. However, inhibiting certain HDAC isoforms can have protolerogenic effects on the immune system, which could make it easier for tumor cells to evade the host immune system. Therefore, a better understanding of how each HDAC isoform affects immune biology is needed to develop targeted cancer therapy. Here, we studied the immune phenotype of HDAC5–/– mice on a C57BL/6 background. While HDAC5–/– mice replicate at expected Mendelian ratios and do not develop overt autoimmune disease, their T‐regulatory (Treg) cells show reduced suppressive function in vitro and in vivo. Likewise, CD4+ T‐cells lacking HDAC5 convert poorly to Tregs under appropriately polarizing conditions. To test if this attenuated Treg formation and suppressive function translated into improved anticancer immunity, we inoculated HDAC5–/– mice and littermate controls with a lung adenocarcinoma cell line. Cumulatively, lack of HDAC5 did not lead to better anticancer immunity. We found that CD8+ T cells missing HDAC5 had a reduced ability to produce the cytokine, IFN‐γ, in vitro and in vivo, which may offset the benefit of weakened Treg function and formation. Taken together, targeting HDAC5 weakens suppressive function and de‐novo induction of Tregs, but also reduces the ability of CD8+ T cells to produce IFN‐γ.
Beyond a tumor suppressor: Soluble E‐cadherin promotes the progression of cancer
Authors: Hu Qi‐Ping , Kuang Jing‐Ya , Yang Qing‐Kai , Bian Xiu‐Wu , Yu Shi‐Cang
Published: December 2015

E‐cadherin (E‐cad) plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. This protein exists in two forms: a membrane‐tethered form and a soluble form. Full‐length E‐cad is membrane tethered. As a type I transmembrane glycoprotein, E‐cad mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. Soluble E‐cad (sE‐cad) is the extracellular fragment of the protein that is cleaved from the membrane after proteolysis of full‐length E‐cad. The production of sE‐cad undermines adherens junctions, causing a reduction in cell aggregation capacity; furthermore, sE‐cad can diffuse into the extracellular environment and the blood. As a paracrine/autocrine signaling molecule, sE‐cad activates or inhibits multiple signaling pathways and participates in the progression of various types of cancer, such as breast cancer, ovarian cancer, and lung cancer, by promoting invasion and metastasis. This article briefly reviews the role of sE‐cad in tumorigenesis and tumor progression and its significance in clinical therapeutics.
Evaluation of the donor cell contribution in rhBMP‐2 mediated bone formation with chitosan thermogels using fluorescent protein reporter mice
Authors: Gohil Shalini V. , Kuo Chia‐Ling , Adams Douglas J. , Maye Peter , Rowe David W. , Nair Lakshmi S.
Published: December 2015

Our current understanding regarding the contribution of donor cells in growth factor and cell based tissue regeneration strategies is limited. The present study attempts to utilize fluorescent protein reporter mice [Col3.6Topaz (enhanced yellow fluorescent protein, EYFP) as host and Col3.6Cyan (enhanced cyan fluorescent protein, ECFP) as donor] to determine donor cell contribution in bone regeneration using a bilateral calvarial defect model. Thermogelling chitosan hydrogels (Chi‐AHP) were used as bone marrow stromal cell (BMSC) delivery vehicle in the presence and absence of recombinant human bone morphogenetic protein‐2 (rhBMP‐2). Co‐delivery of rhBMP‐2 and donor BMSCs led to a significant increase in bone formation indicating the potential of using the combination approach for improved regeneration. On a cellular level, presence of rhBMP‐2 resulted in an increased host cell derived osteoblast infiltration at 8 weeks. However, the new mineralized tissue presented two distinct morphological features based on its cellular origin. Regenerated tissue associated with ECFP positive donor cells showed a woven bone‐like structure with diffuse alizarin complexone (AC) label and minimal tartrate resistant acid phosphatase (TRAP) activity, indicating the presence of immature early osteoblast cells depositing mineralized tissue without progressing to a mature lamellar bone. Host derived bone showed sharp mineralization line (AC), strong alkaline phosphatase (ALP) and TRAP activity, indicating the presence of actively mineralizing and remodeling, mature lamellar bone matrix. The study demonstrated the remarkable potential of transgenic reporters to improve our understanding of donor cell contribution during bone formation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 928–941, 2016.
Regenerative endodontics—Creating new horizons
Authors: Dhillon Harnoor , Kaushik Mamta , Sharma Roshni
Published: December 2015

Trauma to the dental pulp, physical or microbiologic, can lead to inflammation of the pulp followed by necrosis. The current treatment modality for such cases is non‐surgical root canal treatment. The damaged tissue is extirpated and the root canal system prepared. It is then obturated with an inert material such a gutta percha. In spite of advances in techniques and materials, 10%–15% of the cases may end in failure of treatment. Regenerative endodontics combines principles of endodontics, cell biology, and tissue engineering to provide an ideal treatment for inflamed and necrotic pulp. It utilizes mesenchymal stem cells, growth factors, and organ tissue culture to provide treatment. Potential treatment modalities include induction of blood clot for pulp revascularization, scaffold aided regeneration, and pulp implantation. Although in its infancy, successful treatment of damaged pulp tissue has been performed using principles of regenerative endodontics. This field is dynamic and exciting with the ability to shape the future of endodontics. This article highlights the fundamental concepts, protocol for treatment, and possible avenues for research in regenerative endodontics. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 676–685, 2016.
Esophageal reconstruction by colon interposition after esophagectomy for cancer analysis of current indications, operative outcomes, and long‐term survival
Authors: Reslinger Vincent , Tranchart Hadrien , D'Annunzio Elsa , Poghosyan Tigran , Quero Laurent , Munoz‐Bongrand Nicolas , Corte Helene , Sarfati Emile , Cattan Pierre , Chirica Mircea
Published: December 2015

Introduction

Colon interposition is an alternative solution for esophageal reconstruction if the stomach cannot be used. The study reviews current indications and results of coloplasty for cancer.

Methods

Patients who underwent colon interposition for gastro‐esophageal malignancy were included. Primary coloplasty was defined as upfront colon interposition. Salvage coloplasty was defined as colon interposition after primary reconstruction failure. Mortality, morbidity, function, and survival were evaluated.

Results

We included 28 patients (24 men, median age 61 years). Ten (36%) patients underwent primary coloplasty due to previous gastrectomy (n = 5), conduit gastric cancer (n = 2), extensive gastroesophageal involvement (n = 2), and gastric cancer recurrence (n = 1). Salvage coloplasty was performed in 18 (64%) patients for postoperative graft necrosis (n = 5) and intractable strictures (n = 3). Operative mortality, morbidity, and graft necrosis rates were 14% (4/28), 86% (24/28), and 14% (4/28), respectively; there were no significant differences between primary and salvage coloplasty. Survival rates at 1‐, 3‐, and 5 years were 81%, 51%, and 38%, respectively. Survival was decreased after primary coloplasty when compared to salvage coloplasty (P = 0.03). Nine patients experienced tumor recurrence (primary: n = 6, salvage: n = 3) after coloplasty and eight of them died.

Conclusion

Colon interposition after esophagectomy is a useful but morbid endeavor. Colon interposition as salvage therapy is associated with improved survival compared to its use as primary esophageal replacement, and colon interposition in the latter cohort should be used with caution due to poor cancer‐specific survival in this patient population. J. Surg. Oncol. 2016;113:159–164. © 2015 Wiley Periodicals, Inc.
Isotope dilution gas chromatography with mass spectrometry for the analysis of 4‐octyl phenol, 4‐nonylphenol, and bisphenol A in vegetable oils
Authors: Wu Pinggu , Zhang Liqun , Yang Dajin , Zhang Jing , Hu Zhengyan , Wang Liyuan , Ma Bingjie
Published: December 2015

By the combination of solid‐phase extraction as well as isotope dilution gas chromatography with mass spectrometry, a sensitive and reliable method for the determination of endocrine‐disrupting chemicals including bisphenol A, 4‐octylphenol, and 4‐nonylphenol in vegetable oils was established. The application of a silica/N‐(n‐propyl)ethylenediamine mixed solid‐phase extraction cartridge achieved relatively low matrix effects for bisphenol A, 4‐octylphenol, and 4‐nonylphenol in vegetable oils. Experiments were designed to evaluate the effects of derivatization, and the extraction parameters were optimized. The estimated limits of detection and quantification for bisphenol A, 4‐octylphenol, and 4‐nonylphenol were 0.83 and 2.5 μg/kg, respectively. In a spiked experiment in vegetable oils, the recovery of the added bisphenol A was 97.5–110.3%, recovery of the added 4‐octylphenol was 64.4–87.4%, and that of 4‐nonylphenol was 68.2–89.3%. This sensitive method was then applied to real vegetable oil samples from Zhejiang Province of China, and none of the target compounds were detected.
Associations Between Cardiovascular Events and Nonergot Dopamine Agonists in Parkinson's Disease
Authors: Crispo James A.G. , Willis Allison W. , Thibault Dylan P. , Fortin Yannick , Emons Matthew , Bjerre Lise M. , Kohen Dafna E. , Perez‐Lloret Santiago , Mattison Donald , Krewski Daniel
Published: December 2015

Background

Knowledge of possible cardiovascular risks from Parkinson's disease (PD) medications is critical to informing safe and effective treatment decisions. The objective of our study was to determine whether PD patients treated with nonergot dopamine agonists (DAs) are at increased risk of adverse cardiovascular or cerebrovascular outcomes, relative to PD patients receiving other treatments.

Methods

Matched case‐control studies were conducted within a cohort of 14,122 inpatients receiving treatment for PD who were identified in the Cerner Health Facts database. Primary outcomes were associations between nonergot DA use and diagnosis of adverse cardiovascular events (acute myocardial infarction, heart failure [HF], hypotension, and valvulopathy). Secondary outcomes included associations between nonergot DA use and diagnosis of adverse cerebrovascular events (cerebrovascular accident and ischemic stroke) and odds of significant exposure‐outcome relationships by patient factors.

Results

HF was the only adverse event that demonstrated a significant association with nonergot DA use. Individuals treated with pramipexole were more likely to be diagnosed with HF, relative to no use (adjusted odds ratio [AOR]: 1.28; 95% confidence interval [CI]: 1.07–1.53). The association between pramipexole and HF was greater among individuals treated with pramipexole monotherapy (relative to levodopa monotherapy) (AOR, 1.50; 95% CI: 1.09–2.06). Compared to nonusers, men and older individuals treated with pramipexole were more likely to be diagnosed with HF.

Conclusions

Results from our study suggest an association between pramipexole use and HF. Findings warrant replication; however, individuals with PD and independent risk factors for, or a history of, HF may benefit from limited use of this drug.