bluuebunny/crossref_metadata_2025 huggingface dataset:
Avaliação neuropsicológica abrangente de crianças e adolescentes com anemia falciforme e acidentes vasculares encefálicos: relato de casos
Authors: Nunes Samantha , Nogueira Zeni Drubi , Toralles Maria Betânia Pereira , Argollo Nayara , Sena Eduardo Pondé de
Published: January 2017

Introdução: em crianças e adolescentes com Anemia Falciforme, características específicas como anemia, hipoxemia crônica, infartos cerebrais e alterações nutricionais sobre o cérebro têm repercussão negativa no desenvolvimento neurocognitivo. Objetivo: avaliar inteligência, cognição e comportamento de crianças e adolescentes com Anemia Falciforme, acometidos por infartos cerebrais. Metodologia: estudo observacional, descritivo, tipo casuística hospitalar realizado com crianças e adolescentes com hemoglobinopatia do tipo Hb SS, idade 6 a 15 anos. Foi aplicado o questionário Critério Brasil de Classificação Socioeconômica. A avaliação neuropsicológica foi realizada através do teste NEPSY-II, o Quociente Intelectivo estimado foi obtido através das Escalas Weschsler de Inteligência-III e aplicado aos responsáveis o questionário Child Behavior Checklist, para avaliação comportamental. Discussão: nenhum paciente atingiu escores esperados para idade nos domínios avaliados, bem como não alcançou resposta dentro da média em todos subtestes de um domínio. Todos os casos apresentaram baixos índices de QI, indicando presença de déficit cognitivo global. Um indivíduo apresentou transtorno de ansiedade, depressão e problemas sociais. A ocorrência de infarto cerebral predispõe a alterações mais graves no desenvolvimento intelectivo e/ou cognitivo, reduzindo possibilidades de desenvolvimento acadêmico e de competitividade no mercado de trabalho. Conclusão: todos os pacientes demonstraram comprometimento cognitivo global. Nenhum paciente atingiu os escores esperados para idade em pelo menos um dos domínios avaliados. Além dos déficits cognitivos, sintomas de Transtorno de Ansiedade, Transtorno Depressivo e Problemas sociais foram identificados em um dos casos.

 
NEAT1 induces epithelial‐mesenchymal transition and 5‐FU resistance through the miR‐129/ZEB2 axis in breast cancer
Authors: Li Xuerui , Wang Shuxia , Li Zhenzhong , Long Xiaoyu , Guo Zibai , Zhang Guochun , Zu Jian , Chen Yu , Wen Linzhu
Published: January 2017

DOI: 10.1002/1873‐3468.12474

The above article from FEBS Letters, published online on 1 November 2016 in Wiley Online Library (http://wileyonlinelibrary.com), has been withdrawn by agreement between the Journal Managing Editor, Felix Wieland, and John Wiley & Sons Ltd., on behalf of Federation of European Biochemical Societies. The withdrawal has been agreed following an investigation by the Journal's Editorial Office that found that the data in Figures 4C and 4E appears to have been manipulated.
Observations of the shape and group dynamics of rogue waves
Authors: Gemmrich Johannes , Thomson Jim
Published: January 2017

Surface elevation records from two locations in the northeast Pacific are used to examine rogue waves and the relationship to wave groups. Three hundred individual rogue waves with heights greater than 2.2 times the significant wave height are found in analyzing >2 × 106 wave groups. In contrast to recent nonlinear modeling results, we do not find that rogue waves occur at the front of wave groups. There is a tendency for steep waves to occur at the front of a group, but these are not the largest waves of the group and do not meet the rogue wave criterion. Rogue waves are most commonly located in the center of the group, but their height ratio to the neighboring crest is greater than in the average wave group. Assessing group dynamics in terms of spectral width suggests that random superposition of nonlinear waves is sufficient to explain the observations of individual rogue waves.
Assessment of uncertainties in global land cover products for hydro‐climate modeling in India
Authors: Madhusoodhanan C. G. , Sreeja K. G. , Eldho T. I.
Published: January 2017

Earth's land cover (LC) has significant influence on land‐atmospheric processes and affects the climate at multiple scales. There are multiple global LC (GLC) data sets which are yet to be evaluated for uncertainties and their propagation into the simulation of land surface fluxes (LSFs) in land surface/climate modeling. The present study assesses the uncertainties in seven GLC products with reference to a regional data set for the simulation of LSFs in India using a macro‐scale land surface model. There is considerable overestimation of the extent of croplands in most of the GLCs. The uncertainties in LCs exert significant bias in the simulation of the LSFs of actual evapotranspiration (ETa), latent heat (LE), and sensible heat (H) fluxes. Uncertainty propagation in LSFs is proportional to the bias in cropping intensity under rainfed condition. The high underrepresentation of cropland area in the UMd data set results in highest bias in LSFs whereas the least cropland bias in Globland30 leads to least bias. Irrigation has higher potential to alter the LSFs than uncertainties related to LC especially in regions with large area under irrigation like India. The changes in LSFs are higher in arid/semiarid regions with medium irrigation intensity than in subhumid regions with high irrigation intensity. This has significant implications for the country's future irrigation expansion plans in the arid/semiarid regions. The study also emphasizes the need for focused efforts to quantify the uncertainties from varying irrigation intensities in the next generation CMIP6 experiments.
A de novo splice site mutation in CASK causes FG syndrome‐4 and congenital nystagmus
Authors: Dunn P. , Prigatano G. P. , Szelinger S. , Roth J. , Siniard A. L. , Claasen A. M. , Richholt R. F. , De Both M. , Corneveaux J. J. , Moskowitz A. M. , Balak C. , Piras I. S. , Russell M. , Courtright A. L. , Belnap N. , Rangasamy S. , Ramsey K. , Opitz J. M. , Craig D. W. , Narayanan V. , Huentelman M. J. , Schrauwen I.
Published: January 2017

Mutations in CASK cause X‐linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl‐terminus splice site mutation in CASK (c.2521‐2A>G) and clinical features of the rare FG syndrome‐4 (FGS4). We provide further characterization of genotype–phenotype correlations in CASK mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a CASK mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual‐motor, motor development, behavior, and working memory were impaired. The c.2521‐2A>G splice mutation leads to skipping of exon 26 and a 9 base‐pair deletion associated with a cryptic splice site, leading to a 28‐AA and a 3‐AA in‐frame deletion, respectively (p.Ala841_Lys843del and p.Ala841_Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of CASK as well as dysregulation among a number of interactors is also evident by RNA‐seq. This is the second CASK mutation known to us as cause of FGS4. © 2017 Wiley Periodicals, Inc.
Why were Sardinians the shortest Europeans? A journey through genes, infections, nutrition, and sex
Authors: Pes Giovanni Mario , Tognotti Eugenia , Poulain Michel , Chambre Dany , Dore Maria Pina
Published: January 2017

Since ancient times the Mediterranean island of Sardinia has been known for harboring a population with an average body height shorter than almost every other ethnic group in Europe. After over a century of investigations, the cause(s) at the origin of this uniqueness are not yet clear. The shorter stature of Sardinians appears to have been documented since prehistoric times, as revealed by the analysis of skeletal remains discovered in archaeological sites on the island. Recently, a number of genetic, hormonal, environmental, infective and nutritional factors have been put forward to explain this unique anthropometric feature, which persisted for a long time, even when environmental and living conditions improved around 1960. Although some of the putative factors are supported by sound empirical evidence, weaker support is available for others. The recent advent of whole genome analysis techniques shed new light on specific variants at the origin of this short stature. However, the marked geographical variability of stature across time and space within the island, and the well‐known presence of pockets of short height in the population of the southern districts, are still puzzling findings that have attracted the interest of anthropologists and geneticists. The purpose of this review is to focus on the state‐of‐the‐art research on stature, as well as the factors that made Sardinians the shortest among Europeans.
One‐Pot N‐Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines
Authors: Zhou Huan , Liu Yuan , Yang Suhua , Zhou Le , Chang Mingxin
Published: January 2017

A one‐pot N‐Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine‐bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p‐toluenesulfonic acid contributed to the stereocontrol.
Efficient Hydrogen Evolution Electrocatalysis Using Cobalt Nanotubes Decorated with Titanium Dioxide Nanodots
Authors: Feng Jin‐Xian , Xu Han , Dong Yu‐Tao , Lu Xue‐Feng , Tong Ye‐Xiang , Li Gao‐Ren
Published: January 2017

TiO2 Co nanotubes decorated with nanodots (TiO2 NDs/Co NSNTs‐CFs) are reported as high‐performance earth‐abundant electrocatalysts for the hydrogen evolution reaction (HER) in alkaline solution. TiO2 NDs/Co NSNTs can promote water adsorption and optimize the free energy of hydrogen adsorption. More importantly, the absorbed water can be easily activated in the presence of the TiO2–Co hybrid structure. These advantages will significantly promote HER. TiO2 NDs/Co NSNTs‐CFs as electrocatalysts show a high catalytic performance towards HER in alkaline solution. This study will open up a new avenue for designing and fabricating low‐cost high‐performance HER catalysts.
Supramolecular Vesicles Coassembled from Disulfide‐Linked Benzimidazolium Amphiphiles and Carboxylate‐Substituted Pillar[6]arenes that Are Responsive to Five Stimuli
Authors: Jiang Long , Huang Xuan , Chen Dong , Yan Hua , Li Xueyuan , Du Xuezhong
Published: January 2017

Novel supramolecular vesicles based on host–guest systems were coassembled from carboxylate‐substituted pillar[6]arene (CPA[6]) and disulfide‐linked benzimidazolium amphiphiles, and the microstructures of the CPA‐based supramolecular vesicles were clearly elaborated. The supramolecular vesicles showed controlled drug release in response to five stimuli, with glutathione, pH, CO2, Zn2+ ions, and hexanediamine, leading to cleavage of the disulfide bonds, protonation of the carboxylate groups, metal chelation, and competitive binding. This is the first case of a smart pillararene‐based supramolecular vesicle being integrated with five stimuli‐responsive functions to meet the diverse requirements of controlled drug release. Importantly, each of the five stimuli is closely related to microenvironments of tumors and diseases of the human body. The smart stimuli‐responsive supramolecular vesicles have promising applications in drug therapy of tumors and relevant diseases.
Poly(p‐phenylene iminoborane): A Boron–Nitrogen Analogue of Poly(p‐phenylene vinylene)
Authors: Lorenz Thomas , Crumbach Merian , Eckert Thomas , Lik Artur , Helten Holger
Published: January 2017

Substitution of selected CC units in π‐conjugated organic frameworks by their isoelectronic and isosteric BN units (BN/CC isosterism) has proven to be a successful concept for the development of BN‐doped polycyclic aromatic hydrocarbons (PAHs) with intriguing properties and functions. The first examples have just demonstrated the applicability of this approach to polymer chemistry. Herein, we present the synthesis and comprehensive characterization of the first poly(p‐phenylene iminoborane). This novel inorganic–organic hybrid polymer can be regarded as a BN analogue of the well‐known poly(p‐phenylene vinylene) (PPV). Photophysical investigations on the polymer and a series of model oligomers provide clear evidence of some π‐conjugation across the B=N bonds and extension of the conjugation path with increasing chain length. TD‐DFT calculations provide deeper insight into the electronic structure of the new materials.
Efficient Solar Light Harvesting CdS/Co9S8 Hollow Cubes for Z‐Scheme Photocatalytic Water Splitting
Authors: Qiu Bocheng , Zhu Qiaohong , Du Mengmeng , Fan Linggang , Xing Mingyang , Zhang Jinlong
Published: January 2017

Hollow structures with an efficient light harvesting and tunable interior component offer great advantages for constructing a Z‐scheme system. Controlled design of hollow cobalt sulfide (Co9S8) cubes embedded with cadmium sulfide quantum dots (QDs) is described, using hollow Co(OH)2 as the template and a one‐pot hydrothermal strategy. The hollow CdS/Co9S8 cubes utilize multiple reflections of light in the cubic structure to achieve enhanced photocatalytic activity. Importantly, the photoexcited charge carriers can be effectively separated by the construction of a redox‐mediator‐free Z‐scheme system. The hydrogen evolution rate over hollow CdS/Co9S8 is 134 and 9.1 times higher than that of pure hollow Co9S8 and CdS QDs under simulated solar light irradiation, respectively. Moreover, this is the first report describing construction of a hollow Co9S8 based Z‐scheme system for photocatalytic water splitting, which gives full play to the advantages of light‐harvesting and charges separation.
Copper(II) Schiff Base Complex Immobilized on Superparamagnetic Fe3O4@SiO2 as a Magnetically Separable Nanocatalyst for Oxidation of Alkenes and Alcohols
Authors: Sarkheil Marzieh , Lashanizadegan Maryam
Published: January 2017

A new heterogeneous catalyst containing a copper(II) Schiff base complex covalently immobilized on the surface of silica‐coated Fe3O4 nanoparticles (Fe3O4@SiO2‐Schiff base‐Cu(II)) was synthesized. Characterization of this catalyst was performed using various techniques. The catalytic potential of the catalyst was investigated for the oxidation of various alkenes (styrene, α‐methylstyrene, cyclooctene, cyclohexene and norbornene) and alcohols (benzyl alcohol, 3‐methoxybenzyl alcohol, 3‐chlorobenzyl alcohol, benzhydrol and n‐butanol) using tert‐butyl hydroperoxide as oxidant. The catalytic investigations revealed that Fe3O4@SiO2‐Schiff base‐Cu(II) was especially efficient for the oxidation of norbornene and benzyl alcohol. The results showed that norbornene epoxide and benzoic acid were obtained with 100 and 87% selectivity, respectively. Moreover, simple magnetic recovery from the reaction mixture and reuse for several times with no significant loss in catalytic activity were other advantages of this catalyst
Process development unit experimental studies of a split‐flow modification for the post‐combustion CO2 capture process
Authors: Stec M. , Tatarczuk A. , Więcław‐Solny L. , Krótki A. , Spietz T. , Wilk A.
Published: January 2017

A process development unit (PDU) for amine‐based post‐combustion carbon capture located at Clean Coal Technologies Centre in Zabrze, Poland, was used to validate split‐stream configuration. A PDU having capacity up to 100 m3n/h was designed to test the amine scrubbing carbon capture process from flue gases or mixtures of technical gases. Flexible process flow sheet of the unit allowed investigation of the split flow process.

The split‐flow flowsheet modification was compared with a standard system for chemical absorption‐based CO2 capture. The tests were conducted using well‐accepted baseline solvent: 30 wt% aqueous monoethanolamine solution. The flow sheet modification resulted in a decrease of reboiler heat duty by ~1.6% and an increase in CO2 recovery by ~1.2 p.p. Split‐flow process modification was examined together with standard process flow sheet, and vast number of process parameters recorded during the trials have been presented. The explanation of beneficial effects of split‐flow designs have been shown together with detailed analysis of experimental trials carried out using PDU for amine‐based post‐combustion carbon capture. This paper is also a valuable source of experimental data useful during validation of models. Copyright © 2017 Curtin University of Technology and John Wiley & Sons, Ltd.
Innovative detector layout for automated traffic turning volume counting
Authors: Gholami Ali , Tian Zong , Andalibian Rasool
Published: January 2017

Because of many advantages, loop detectors are the most common practice for obtaining data to control intersections. However, they have some drawbacks, including the fact that multiple detectors are usually required to monitor a location. The current practice in many cities is to install four consecutive loop detectors per lane, or two at the stop bar and one as an advanced detector. In some cities, there are also departure detectors. All these configurations have some practical problems and do not produce accurate counts especially in shared lanes. In this paper, a new placement configuration for departure detectors is proposed and named the mid‐intersection detector (MID). In this configuration, departure detectors are moved back to the middle of the intersection in such a way that they can be activated by more than one movement at different times. In some cases, departure detectors lack equations for calculating turning movements, a problem solved by MIDs because each movement passes more detectors along its path (without increasing the number of loops), and therefore they can produce more accurate and reliable data for obtaining turning movement counts. Copyright © 2017 John Wiley & Sons, Ltd.
Genomic integration of the full‐length dystrophin coding sequence in Duchenne muscular dystrophy induced pluripotent stem cells
Authors: Farruggio Alfonso P. , Bhakta Mital S. , du Bois Haley , Ma Julia , Calos Michele P.
Published: January 2017

Plasmid vectors that express the full‐length human dystrophin coding sequence in human cells were developed. Dystrophin, the protein mutated in Duchenne muscular dystrophy, is extraordinarily large, providing challenges for cloning and plasmid production in Escherichia coli. The authors expressed dystrophin from the strong, widely expressed CAG promoter, along with co‐transcribed luciferase and mCherry marker genes useful for tracking plasmid expression. Introns were added at the 3' and 5' ends of the dystrophin sequence to prevent translation in E. coli, resulting in improved plasmid yield. Stability and yield were further improved by employing a lower‐copy number plasmid origin of replication. The dystrophin plasmids also carried an attB site recognized by phage phiC31 integrase, enabling the plasmids to be integrated into the human genome at preferred locations by phiC31 integrase. The authors demonstrated single‐copy integration of plasmid DNA into the genome and production of human dystrophin in the human 293 cell line, as well as in induced pluripotent stem cells derived from a patient with Duchenne muscular dystrophy. Plasmid‐mediated dystrophin expression was also demonstrated in mouse muscle. The dystrophin expression plasmids described here will be useful in cell and gene therapy studies aimed at ameliorating Duchenne muscular dystrophy.
Development of the Regiodivergent Asymmetric Prenylation of 3‐Substituted Oxindoles
Authors: Trost Barry M. , Chan Walter H. , Malhotra Sushant
Published: January 2017

This paper describes our efforts to design a Pd‐catalyzed asymmetric prenylation of 3‐substituted oxindoles that affords access to both the linear and reverse‐prenylated products. Both 3‐alkyl‐ and 3‐aryloxindoles performed well under our optimized reaction conditions. The regiodivergent alkylation of monoterpene‐derived electrophiles using this methodology was also investigated. The utility of this methodology in natural product synthesis was demonstrated through the efficient total syntheses of four Flustra alkaloids, which also allowed the absolute stereochemistry of the prenylated oxindole products to be assigned. Surprisingly, the same enantiomer of ligand produced linear and branched regioisomers of opposite chirality.
Aqueous Instability of δ‐Fluorobutylpiperidines
Authors: Vorberg Raffael , Carreira Erick M. , Müller Klaus
Published: January 2017

In a series of partially fluorinated N‐propyl‐ and N‐butylpiperidine derivatives, three compounds were found to exhibit unexpected instability under mild biophysical assay conditions. These compounds carry a single terminal fluorine in the δ‐position of an N‐butyl group as a common structural feature. An adjacent fluorine substituent at the γ‐position significantly slows down the reactivity. All other compounds, having either no or more than one fluorine substituent at the δ‐position are chemically inert under all assay conditions. The reactivity of the labile compounds is traced to an intramolecular ring‐closing fluorine substitution reaction by the moderately basic piperidine unit, leading to a spiro‐pyrrolidinium salt. The chemical lability of δ‐monofluorinated or γ,δ‐difluorinated N‐butylpiperidine derivatives even under very mild biophysical assay conditions constitutes a caveat to the molecular design of partially fluorinated alkylamines.
Discussing molecular testing in oncology care: Comparing patient and physician information preferences
Authors: Pinheiro Ana P. M. , Pocock Rachel H. , Switchenko Jeffrey M. , Dixon Margie D. , Shaib Walid L. , Ramalingam Suresh S. , Pentz Rebecca D.
Published: January 2017

BACKGROUND

Molecular testing to inform treatment and clinical trial choices is now the standard of care for several types of cancer. However, no established guidelines exist for the type of information physicians should cover during discussions with the patient about the test or its results. The objectives of this study were to identify physician and patient preferences regarding information and who should communicate this information and how to inform guidelines for these conversations.

METHODS

Physicians and patients who participated in discussions regarding molecular testing were asked to choose 8 topics of most relevance out of a list of 18. The McNemar test was used to determine their top preferences. Patients were asked to identify what information they wanted to receive and who should inform them, and physicians were asked to identify the best aid to communication.

RESULTS

Sixty‐six patients identified 12 preferred topics: the benefits of testing (88%), how testing determines treatment (88%), implications for family (71%), whether a test indicates the seriousness of disease (68%), purpose of the test (64%), incidental findings (56%), explanation of cancer genetics (53%), how the test is done (46%), limitations (44%), explanation of biomarker (42%), risks (42%), and uninformative results (38%). Physicians added cost (59%). Patients preferred receiving information about molecular testing from their nurse or physician (85%), and physicians preferred using a pamphlet (67%) to augment communication.

CONCLUSIONS

The topics identified as important to discuss can inform future guidelines and can contribute to effective communication regarding molecular testing. Cancer 2017;123:1610–1616. © 2017 American Cancer Society.
Low‐Dose Aspirin Acetylates Cyclooxygenase‐1 in Human Colorectal Mucosa: Implications for the Chemoprevention of Colorectal Cancer
Authors: Patrignani P , Sacco A , Sostres C , Bruno A , Dovizio M , Piazuelo E , Di Francesco L , Contursi A , Zucchelli M , Schiavone S , Tacconelli S , Patrono C , Lanas A
Published: January 2017

The mechanism of action of low‐dose aspirin in the prevention of colorectal cancer (CRC) remains largely hypothetical. We aimed to compare the effects of low‐dose aspirin (100 mg/day for 7 days) given to 40 individuals undergoing CRC screening on the extent of cyclooxygenase (COX)‐1 acetylation at serine‐529 (AceCOX‐1), in blood platelets vs. colorectal mucosa, at 7 (group 1) and 24 h (group 2) after dosing. A significantly (P < 0.01) lower %AceCOX‐1 was detected in colonic and rectal mucosa (average 64%) vs. platelets (average 75%) in both groups. This effect was associated with an average 46% (P < 0.01) and 35% (P < 0.05) reduction in prostaglandin (PG) E2 levels and phosphorylated S6 (p‐S6) levels, respectively. Rectal mucosal levels of p‐S6/S6 significantly (P < 0.01) correlated with PGE2. These findings demonstrate that low‐dose aspirin produces long‐lasting acetylation of COX‐1 and downregulation of p‐S6 in human colorectal mucosa, an effect that may interfere with early colorectal carcinogenesis.
Novel Genetic Variants in Carboxylesterase 1 Predict Severe Early‐Onset Capecitabine‐Related Toxicity
Authors: Hamzic S , Kummer D , Milesi S , Mueller D , Joerger M , Aebi S , Amstutz U , Largiader CR
Published: January 2017

An important concern with the anticancer drug capecitabine (Cp), an oral prodrug of 5‐fluorouracil, are dose‐limiting adverse effects, in particular hand‐foot syndrome (HFS) and diarrhea. Here we evaluated the association of genetic variability in all enzymes of the Cp‐activation pathway to 5‐fluorouracil with Cp‐related early‐onset toxicity in 144 patients receiving Cp. We identified a haplotype encompassing five variants in the carboxylesterase 1 (CES1) gene region including an expression quantitative trait locus associated with early‐onset Cp‐toxicity (Haplotype A3: ORadditive = 2.2, 95% CI 1.2–4.0, Padjusted = 0.012; ORrecessive = 10.3, 95% CI 2.1–49.4, Padjusted = 0.0038). Furthermore, the association of two linked cytidine deaminase (CDA) promoter variants (c.1‐451C>T: ORdominant = 4.3, 95% CI 1.3–14.2, Padjusted = 0.017; and c.1‐92A>G: ORdominant = 4.4, 95% CI 1.3–14.5, Padjusted = 0.015) with Cp‐related diarrhea was replicated. This first study identifying an association of genetic variation in CES1 with Cp‐related toxicity provides further evidence for the existence of a functional noncoding CES1‐variant with a possible regulatory impact.
Continuous‐Flow O‐Alkylation of Biobased Derivatives with Dialkyl Carbonates in the Presence of Magnesium–Aluminium Hydrotalcites as Catalyst Precursors
Authors: Cattelan Lisa , Perosa Alvise , Riello Piero , Maschmeyer Thomas , Selva Maurizio
Published: January 2017

The base‐catalysed reactions of OH‐bearing biobased derivatives (BBDs) including glycerol formal, solketal, glycerol carbonate, furfuryl alcohol and tetrahydrofurfuryl alcohol with non‐toxic dialkyl carbonates (dimethyl and diethyl carbonate) were explored under continuous‐flow (CF) conditions in the presence of three Na‐exchanged Y‐ and X‐faujasites (FAUs) and four Mg–Al hydrotalcites (HTs). Compared to previous etherification protocols mediated by dialkyl carbonates, the reported procedure offers substantial improvements not only in terms of (chemo)selectivity but also for the recyclability of the catalysts, workup, ease of product purification and, importantly, process intensification. Characterisation studies proved that both HT30 and KW2000 hydrotalcites acted as catalyst precursors: during the thermal activation pre‐treatments, the typical lamellar structure of the hydrotalcite was broken down gradually into a MgO‐like phase (periclase) or rather a magnesia–alumina solid solution, which was the genuine catalytic phase.
Cytopathologic analysis of pericardial effusions in 116 cases: Implications for poor prognosis in lung cancer patients with positive interpretations
Authors: He Bing , Yang Zhen , Zhao Peng , Li Yu‐Jun , Wang Ji‐Gang
Published: January 2017

Background

Few studies have evaluated the cytology of pericardial effusions. The aim of this study is to investigate the etiologies of pericardial effusions and to establish the relationship between cytopathologic interpretations and outcome patterns among patients with pericardial effusions.

Methods

We identified 116 patients with pericardial effusions at a single institution over a 4‐year period and carefully analyzed all available clinical documents, including clinical diagnoses, cytopathologic findings, and outcome patterns.

Results

The cohort was made up of 74 patients with malignancies, 39 with non‐malignancy diseases, and 3 without available clinical diagnosis. Lung cancer was the most common malignancy (58 cases), followed by breast cancer (4 cases) and lymphoma/leukemia (4 cases). Among the 116 fluid samples, 43 cases were diagnosed as malignant, 66 were diagnosed as benign, and seven were diagnosed as ambiguous. The nature of the hemorrhage was an important feature of cytopathology‐positive effusions. Patients with detectable malignant cells in pericardial effusions have a significantly poorer prognosis than those without malignant cells.

Conclusions

Lung cancer is the most common cause of large quantities of pericardial effusions. The present findings suggest that cytopathologic evaluation is valuable to predict the prognosis of cancer patients with pericardial effusions. Diagn. Cytopathol. 2017;45:287–293. © 2016 Wiley Periodicals, Inc.
Effects of sulforaphane on neural stem cell proliferation and differentiation
Authors: Han Zhenxian , Xu Qian , Li Changfu , Zhao Hong
Published: January 2017

Sulforaphane (SFN) is a natural organosulfur compound with anti‐oxidant and anti‐inflammation properties. The objective of this study is to investigate the effect of SFN on the proliferation and differentiation of neural stem cells (NSC). NSCs were exposed to SFN at the concentrations ranging from 0.25 to 10 µM. Cell viability was evaluated with MTT assay and lactate dehydogenase (LDH) release assay. The proliferation of NSCs was evaluated with neurosphere formation assay and Ki‐67 staining. The level of Tuj‐1 was evaluated with immunostaining and Western blot to assess NSC neuronal differentiation. The expression of key proteins in the Wnt signaling pathway, including β‐catenin and cyclin D1, in response to SFN treatment or the Wnt inhibitor, DKK‐1, was determined by Western blotting. No significant cytotoxicity was seen for SFN on NSCs with SFN at concentrations of less than 10 µM. On the contrary, SFN of low concentrations stimulated cell proliferation and prominently increased neurosphere formation and NSC differentiation to neurons. SFN treatment upregulated Wnt signaling in the NSCs, whereas DKK‐1 attenuated the effects of SFN. SFN is a drug to promote NSC proliferation and neuronal differentiation when used at low concentrations. These protective effects are mediated by Wnt signaling pathway.
Optimization of bioprocess variables for production of a thermostable and wide range pH stable carboxymethyl cellulase from Bacillus subtilis MS 54 under solid state fermentation
Authors: Sharma Mukul , Kumar Bajaj Bijender
Published: January 2017

Vast application spectrum of cellulases especially for bioconversion of lignocellulosics into simple sugars for production of biofuel, chemicals, and other industrial products in an environmentally benign manner, faces bottleneck due to unavailability of process‐apt cellulases, and high production cost of enzymes. Solid state fermentation (SSF) offers several advantages over submerged fermentation (SmF) including the cost‐effective production of enzymes particularly using agricultural residues as substrates. Bacillus subtilis MS 54, a recently isolated bacterium was previously shown to produce thermostable and wide range pH stable cellulase under SmF. This study reports the Design of experiments (DoE) based optimization of process variables for cellulase production from B. subtilis MS 54 under SSF. Plackett–Burman (PB) design and response surface methodology (RSM) were used, respectively, for selection of significant process variables, and for optimization of the selected variables. Three process variables, that is, moisture content, maize bran and almond shell, earmarked based on PB‐design, were optimized by RSM to achieve cellulase yield enhancement by 2.02‐fold as compared with that under unoptimized conditions. Application of maize bran and almond shells as substrates for bacterial cellulase production under SSF is being reported for the first time. Solid‐state fermentation coupled with DoE tools represents a cost‐effective strategy for production of industrial enzymes. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 1123–1130, 2017
Wildtype motoneurons, ALS‐Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling
Authors: Madji Hounoum Blandine , Mavel Sylvie , Coque Emmanuelle , Patin Franck , Vourc'h Patrick , Marouillat Sylviane , Nadal‐Desbarats Lydie , Emond Patrick , Corcia Philippe , Andres Christian R , Raoul Cédric , Blasco Hélène
Published: January 2017

The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non‐cell‐autonomous effects of astrocytes. However, mechanisms underlying astrocyte‐mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS‐associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS‐causing mutated superoxide dismutase‐1 (SOD1) when co‐cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra‐ and intra‐cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592–605
Betacellulin regulates schwann cell proliferation and myelin formation in the injured mouse peripheral nerve
Authors: Vallières Nicolas , Barrette Benoit , Wang Linda Xiang , Bélanger Erik , Thiry Louise , Schneider Marlon R. , Filali Mohammed , Côté Daniel , Bretzner Frédéric , Lacroix Steve
Published: January 2017

When a nerve fiber is cut or crushed, the axon segment that is separated from the soma degenerates distal from the injury in a process termed Wallerian degeneration (WD). C57BL/6OlaHsd‐WldS (WldS) mutant mice exhibit significant delays in WD. This results in considerably delayed Schwann cell and macrophage responses and thus in impaired nerve regenerations. In our previous work, thousands of genes were screened by DNA microarrays and over 700 transcripts were found to be differentially expressed in the injured sciatic nerve of WldS compared with wild‐type (WT) mice. One of these transcripts, betacellulin (Btc), was selected for further analysis since it has yet to be characterized in the nervous system, despite being known as a ligand of the ErbB receptor family. We show that Btc mRNA is strongly upregulated in immature and dedifferentiated Sox2+ Schwann cells located in the sciatic nerve distal stump of WT mice, but not WldS mutants. Transgenic mice ubiquitously overexpressing Btc (Tg‐Btc) have increased numbers of Schmidt‐Lantermann incisures compared with WT mice, as revealed by Coherent anti‐Stokes Raman scattering (CARS). Tg‐Btc mice also have faster nerve conduction velocity. Finally, we found that deficiency in Btc reduces the proliferation of myelinating Schwann cells after sciatic nerve injury, while Btc overexpression induces Schwann cell proliferation and improves recovery of locomotor function. Taken together, these results suggest a novel regulatory role of Btc in axon‐Schwann cell interactions involved in myelin formation and nerve repair. GLIA 2017 GLIA 2017;65:657–669
Key Recommendations from the MedtecHTA Project
Authors: Tarricone Rosanna , Torbica Aleksandra , Drummond Michael ,   for the MedtecHTA Project Group
Published: January 2017

There are particular characteristics of Medical Devices, such as the device–user interaction, the incremental nature of innovation and the broader organizational impact that lead to additional challenges for health technology assessment (HTA). The project explored key aspects of the conduct and methods of HTA for MDs. Systematic reviews and original research studies were conducted to determine improvements in processes and methods that could enhance the potential for HTA and optimize the diffusion of MDs.

Regulatory processes for MDs should be more closely aligned, the HTA evaluative framework should be harmonized and processes for conditional coverage and evidence development should be used. The methods for HTA should consider MDs as complex interventions, require the establishment of high quality registries, consider an iterative approach to the evaluation over time, recognize and allow for the particular characteristics of devices and use appropriate approaches for confounder adjustment in comparative effectiveness studies. To optimize the diffusion, a common classification should be developed across countries in order to facilitate international comparisons, factors driving diffusion should be explored in HTA reports and physicians' personal goals and motivation should be better understood.

The key recommendations of the MedtecHTA project should improve the conduct and use of HTA for MDs. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.
Adoption Decisions for Medical Devices in the Field of Cardiology: Results from a European Survey
Authors: Hatz Maximilian H. M. , Schreyögg Jonas , Torbica Aleksandra , Boriani Giuseppe , Blankart Carl R. B.
Published: January 2017

Decisions to adopt medical devices at the hospital level have consequences for health technology assessment (HTA) on system level and are therefore important to decision makers. Our aim was to investigate the characteristics of organizations and individuals that are more inclined to adopt and utilize cardiovascular devices based on a comprehensive analysis of environmental, organizational, individual, and technological factors and to identify corresponding implications for HTA. Seven random intercept hurdle models were estimated using the data obtained from 1249 surveys completed by members of the European Society of Cardiology. The major findings were that better manufacturer support increased the adoption probability of ‘new’ devices (i.e. in terms of CE mark approval dates), and that budget pressure increased the adoption probability of ‘old’ devices. Based on our findings, we suggest investigating the role of manufacturer support in more detail to identify diffusion patterns relevant to HTA on system level, to verify whether it functions as a substitute for medical evidence of new devices, and to receive new insights about its relationship with clinical effectiveness and cost‐effectiveness. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.
The effect of siblings on children's social skills and perspective taking
Authors: Sang Samantha A. , Nelson Jackie A.
Published: January 2017

The current study examined associations between sibling characteristics (being an only child, having an older brother, younger brother, older sister, or younger sister) and two aspects of social competence, and how these processes may differ based on child gender. Participants included 112 children ages 5 to 7 with either one or no siblings. Results suggested that siblings' influence on social competence is complex. For perspective taking, sibling characteristics and child's gender did not have significant main effects. However, interactions between older brother and child gender and between younger brother and child gender showed that girls without a sibling had greater perspective taking than girls with brothers, whereas, boys with brothers seemed to benefit somewhat from their presence. Furthermore, increases in social skills over one year were observed among children with a younger sister compared to only children. Implications of siblings' influence on children's perspective taking and social skills are discussed.

Highlights

Researchers examined how sibling characteristics influenced social competence based on child's gender.

Hierarchical regression analyses suggested girls without a sibling had greater perspective taking than girls with brothers, boys with brothers seemed to somewhat benefit in perspective taking and increases in social skills over one year were observed among children with a younger sister.

Findings suggest the influence of siblings are more complex than simply having a sibling or not.
Usefulness of the WHO C‐Model to optimize the cesarean delivery rate in a tertiary hospital setting
Authors: Abdel‐Aleem Hany , Darwish Atef , Abdelaleem Ahmad A. , Mansur Manal
Published: January 2017

Objective

To assess use of the C‐Model in a tertiary hospital setting in terms of its validity and utility for optimizing the cesarean delivery (CD) rate.

Methods

A prospective observational study included women admitted for delivery at a university teaching hospital in Assiut, Egypt, in 2015. The women were asked about the demographic and obstetric information needed to calculate the probability of CD using the WHO C‐Model. A receiver operating characteristic (ROC) curve comparing the predicted and observed CD rates was constructed. In addition, the mean predicted CD rates were compared with the mean observed CD rates in the 10 groups of the Robson classification.

Results

In total, 1000 women were recruited; 38.6% had a previous CD and 13.5% had complications during the current pregnancy. The final mode of delivery was vaginal delivery in 38.7% and CD in 61.3%; the predicted CD rate for this cohort was 45.0%. The area under the ROC curve was 0.928 (95% confidence interval 0.912–0.945). Comparison of the predicted and observed CD rates in the 10 Robson groups showed an overuse of CD ranging from 2% to 50%.

Conclusion

The WHO C‐Model is valid and can be used in hospital settings to optimize CD rates.
Lethal and sublethal effects of aniline and chlorinated anilines on zebrafish embryos and larvae
Authors: Horie Yoshifumi , Yamagishi Takahiro , Koshio Masaaki , Iguchi Taisen , Tatarazako Norihisa
Published: January 2017

Environmental risk assessments show increased attention to the sublethal effects of chemicals on aquatic organisms. The Organization for Economic Cooperation and Development (OECD) established the “Fish, Short‐term Toxicity Test on Embryo and Sac‐fry Stages” (OECD test 212) to predict lethal effects. It is still unclear, however, whether this test can predict sublethal effects. Although their sublethal effects are still unknown, chlorinated anilines are widely used in various fields. The purpose of this study, therefore, is to investigate sublethal effects of chlorinated anilines using OECD test 212 with zebrafish, and to examine the correlation of several sublethal effects between embryo and larval stages. Embryos were exposed to aniline and nine chlorinated anilines until 8 days post‐fertilization. A delayed lethal effect was observed from three of the 10 anilines tested. In the control group, the swim bladder inflated after hatching, but there was no swim‐bladder inflation after exposure to the chlorinated anilines. Fertilized eggs exposed to lower concentrations of test chemicals showed effects during embryogenesis that did not affect mortality rates, such as changes in body curvature and edema. Our results show that chlorinated anilines induce not only lethal effects but also a variety of sublethal effects. Moreover, a detailed estimate of these effects requires study during both embryonic and larval stages. OECD test 212 may therefore prove useful as a method for screening chemicals for lethal and sublethal effects. Copyright © 2017 John Wiley & Sons, Ltd.
Glaucarubulone glucoside from Castela macrophylla suppresses MCF‐7 breast cancer cell growth and attenuates benzo[a]pyrene‐mediated CYP1A gene induction
Authors: Badal Simone A. M. , Asuncion Valenzuela Malyn M. , Zylstra Dain , Huang George , Vendantam Pallavi , Francis Sheena , Quitugua Ashley , Amis Louisa H. , Davis Willie , Tzeng Tzuen‐Rong J. , Jacobs Helen , Gangemi David J. , Raner Greg , Rowland Leah , Wooten Jonathan , Campbell Petreena , Brantley Eileen , Delgoda Rupika
Published: January 2017

Quassinoids often exhibit antioxidant and antiproliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons into carcinogenic metabolites. Gg reduced the viability of MCF‐7 breast adenocarcinoma cells (IC50 = 121 nm) to a greater extent than standard of care anticancer agents 5‐fluorouracil, tamoxifen (IC50 >10 μm) and the tamoxifen metabolite 4‐hydroxytamoxifen (IC50 = 2.6 μm), yet was not cytotoxic to non‐tumorigenic MCF‐10A breast epithelial cells. Additionally, Gg induced MCF‐7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF‐10A cells mediated by the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) metabolite B[a]P 1,6‐quinone, yet downregulated the expression of genes that promote antioxidant activity in MCF‐7 cells. This implies that Gg exhibits antioxidant and cytoprotective actions in non‐tumorigenic breast epithelial cells and pro‐oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non‐competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF‐7 cells. These data indicate that Gg selectively suppresses MCF‐7 breast cancer cell growth without impacting non‐tumorigenic breast epithelial cells and blocks B[a]P‐mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.