bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological, mechanical, and thermal features of PMMA nanocomposites containing two‐dimensional Co–Al layered double hydroxide
Authors: Kumar Manish , Chakraborty Samarshi , Upadhyaya Pradeep , Pugazhenthi G.
Published: September 2017

The focus of the current study is to investigate the influence of Co–Al layered double hydroxide (LDH) on the morphological, thermal, and mechanical features of poly(methyl methacrylate) (PMMA)‐based nanocomposites. Sodium dodecyl sulfate modified Co–Al LDH was synthesized by single step coagulation method. The PMMA nanocomposites containing different loadings of nanofiller (1–7 wt %) and polystyrene‐grafted maleic anhydride compatibilizer (5 wt %) were melt intercalated via twin screw extruder and later subjected to injection molding to prepare mechanical testing samples. The different properties of PMMA nanocomposites were studied by using XRD, TEM, FTIR, DSC, TGA, tensile, flexural, impact, and flammability analysis. The result of XRD analysis suggested the exfoliated morphology of the nanocomposite while the TEM demonstrated the intercalated structure at higher loading of LDH. The thermal characterization results revealed that thermal properties were improved by the addition of Co–Al LDH, whereas the flammability test exposed that dripping was minimum at 7 wt % loading. The mechanical properties exhibited that optimum results were obtained at 1 wt % loading of Co–Al LDH. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45774.
Thermal, mechanical, and water vapor barrier behavior of polypropylene composite containing modified kaolinite
Authors: Albach Breidi , Munaro Marilda , Santos Pedro H. , Zawadzki Sônia F. , Schreiner Wido H. , Rampon Daniel S. , Barbosa Ronilson V.
Published: September 2017

Polypropylene composites containing modified kaolinite were prepared using melt processing and the morphological, thermal, mechanical and their water barrier properties were analyzed. To improve compatibility with polypropylene, kaolinite was modified with silane as a coupling agent. Characterization techniques (X‐ray diffraction, Fourier transform infrared spectroscopy, and X‐ray photoelectron spectroscopy) confirmed the effective grafting of these compounds on the surface and edges of the kaolinite with no functionalization on the inner surface. The differential scanning calorimetry and X‐ray diffraction techniques demonstrated that the addition of grafted kaolinite affected the iPP crystallinity. The thermogravimetric analysis helped to determine the thermal stability of the composites, being this, dependent on the amount of kaolinite and silane. The stress–strain tests demonstrated an increase in Young's modulus and obtained a 70% reduction in water vapor permeation. These improvements were mainly related to the increased compatibility between the iPP/Kaol interfaces promoted by the silane. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45785.
Influence of body composition on disposition of the highly fat distributed compound as analysed by physiologically based pharmacokinetic (PBPK) modeling and simulation
Authors: Goto Akihiko , Tagawa Yoshihiko , Moriya Yuu , Sato Sho , Yamamoto Masami , Wakabayashi Takeshi , Tsukamoto Tetsuya , DeJongh Joost , van Steeg Tamara J. , Moriwaki Toshiya , Asahi Satoru
Published: September 2017

A recent study suggested that the pharmacokinetics (PK) of highly fat distributed compounds can be affected by acute changes in the volume of adipose tissue. The present study investigates possible influences of body composition on the disposition of the highly lipophilic compound TAK‐357 in two rat strains. Physiologically based PK (PBPK) modeling and simulation was applied on single and multiple dose PK data of TAK‐357 in obese Wistar fatty rats and Wistar lean rats having approximately 45% and 13% body fat, respectively. The observed effects of an elevated fat mass in Wistar fatty rats on the plasma concentrations appeared to be partly compensated for by other differences between the two rat strains. A decrease in the tissue to blood partition coefficients under high body fat conditions was identified as another factor contributing to the difference in PK. A higher lipid content in the plasma in high body fat animals may result in relatively lower tissue to blood partition coefficients. PBPK‐based simulations indicate that the plasma concentrations of lipophilic compounds in high body fat conditions can differ by up to two‐times at steady‐state. This confirms that there is only a small impact of body composition change on the plasma concentration of highly lipophilic drugs and that the need for therapeutic dose adjustments may be limited.
Antimicrobial activity of lysozyme isoforms: Key molecular features
Authors: Derde Melanie , Vié Véronique , Walrant Astrid , Sagan Sandrine , Lechevalier Valérie , Guérin‐Dubiard Catherine , Pezennec Stéphane , Cochet Marie‐Françoise , Paboeuf Gilles , Pasco Maryvonne , Baron Florence , Gautier Michel , Jan Sophie , Nau Françoise
Published: September 2017

Increasing bacterial resistance towards antibiotics has stimulated research for novel antimicrobials. Proteins acting on bacterial membranes could be a solution. Lysozyme has been proven active against E. coli by disruption of both outer and cytoplasmic membranes, with dry‐heating increasing lysozyme activity. Dry‐heated lysozyme (DH‐L) is a mixture of isoforms (isoaspartyl, native‐like and succinimide lysozymes), giving rise to two questions: what effects does each form have, and which physicochemical properties are critical as regards the antibacterial activity? These issues were investigated by fractionating DH‐L, analyzing structural properties of each fraction, and testing each fraction in vivo on bacteria and in vitro on membrane models. Positive net charge, hydrophobicity and molecular flexibility of the isoforms seem key parameters for their interaction with E. coli membranes. The succinimide lysozyme fraction, the most positive, flexible and hydrophobic, shows the highest antimicrobial activity, induces the strongest bacterial membrane disruption and is the most surface active on model lipid monolayers. Moreover, each fraction appears less efficient than DH‐L against E. coli, indicating a synergetic cooperation between lysozyme isoforms. The bacterial membrane modifications induced by one isoform could facilitate the subsequent action of the other isoforms.
Factors associated with motor complications in Parkinson's disease
Authors: Kadastik‐Eerme Liis , Taba Nele , Asser Toomas , Taba Pille
Published: September 2017

Objectives

Levodopa is the most effective therapy for treating Parkinson's disease (PD); however, side effects such as dyskinesias and motor fluctuations may occur after some years of its usage. The aims of this study were to assess the frequency of and factors associated with motor complications among PD patients on levodopa treatment.

Methods

In a cross‐sectional study carried out in 2010–2013, clinical data and treatment details were collected. Logistic regression expressed by odd ratios (OR) and 95% confidence intervals (CI) was conducted to examine the effects of several independent variables on the occurrence of motor complications.

Results

A total of 455 patients were enrolled, among whom 374 were on levodopa. Analysis was performed in 328 patients whose exact duration of levodopa treatment was known. Among patients included in the analysis, 25.9% experienced motor complications; of these, 21% had dyskinesias and 20.1% had motor fluctuations. Based on logistic regression, statistically significant factors associated with the occurrence of motor complications were younger age at onset of the disease, higher levodopa equivalent daily dose (LEDD), shorter time to levodopa initiation, and akinetic‐rigid dominant phenotype of PD.

Conclusions

This study suggests that postponing the start of levodopa therapy and maintaining low daily doses of levodopa might reduce the risk of motor complications. Our results confirm that due to higher risk of motor complications, effectively treating patients with akinetic‐rigid dominant phenotype of PD might be more challenging than for patients whose dominant symptom is tremor.
Involvement of RPL11 in the enhancement of P53 stability by a podophyllum derivative, a topoisomerase II inhibitor
Authors: Wang Huai , Feng Jiang , Zhou Tong , Wei Lijun , Zhou Jianming
Published: September 2017

In previous work, we presented experimental and theoretical evidence that D‐3F or 4‐N‐(2‐Amino‐3‐fluoropyridine)‐4‐deoxidation‐4′‐demethylepipofophyllotoxin induced G2/M phase arrest and apoptosis, purportedly by increasing the expression of P53. However, the precise mechanism of D‐3F action is currently unknown. Here, we investigated the mechanism by which D‐3F treatment induces increased expression of P53. This study showed that D‐3F definitively inhibited the activity of topoisomerase II in a dose‐dependent manner and resulted in DNA damage. The results were in overall agreement with modeling and docking studies performed on D‐3F. In addition, D‐3F increased the levels of P53 and P21 in HeLa cells in a dose‐dependent manner, this in turn prolonged the half‐life of P53. Taken together, these data suggested that D‐3F‐mediated transient enhancement of P53 stabilization may be critical for the P53/P21 signalling pathway leading to G2/M phase arrest on HeLa cells. Furthermore, D‐3F downregulated the phosphorylation of E3 ubiquitin‐protein ligase murine double minute 2 (Mdm2) at Ser166, inhibited Mdm2‐mediated ubiquitination of P53, and released 60S ribosomal protein L11 (RPL11) from the nucleolus into the nucleoplasm. To conclude, the topoisomerase II inhibitor D‐3F causes P53 to accumulate in HeLa cell lines by enhancing its stability as a result of DNA‐damage induced RPL11 relocalization and subsequent blocking of the P53‐Mdm2 feedback loop.
Cervical cancer stem‐like cells: systematic review and identification of reference genes for gene expression
Authors: de Campos Rafael P. , Schultz Iago C. , de Andrade Mello Paola , Davies Samuel , Gasparin Manuela S. , Bertoni Ana P. S. , Buffon Andréia , Wink Márcia R.
Published: September 2017

Cervical cancer is the fourth most common cancer affecting women worldwide. Among many factors, the presence of cancer stem cells, a subpopulation of cells inside the tumor, has been associated with a worse prognosis. Considering the importance of gene expression studies to understand the biology of cervical cancer stem cells (CCSC), this work identifies stable reference genes for cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective cancer stem‐like cells. A literature review was performed to identify validated reference genes currently used to normalize RT‐qPCR data in cervical cancer cell lines. Then, cell lines were cultured in regular monolayer or in a condition that favors tumor sphere formation. RT‐qPCR was performed using five reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed to validate the selected genes as suitable reference genes. The evaluation validated B2M, GAPDH, HPRT1, and TBP in these experimental conditions. Among them, GAPDH and TBP presented the lowest variability according to the analysis by Normfinder, Bestkeeper, and ΔCq methods, being therefore the most adequate genes to normalize the combination of all samples. These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT‐qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem‐like cells. Indeed, GAPDH and TBP seem to be the most convenient choices for studying gene expression in these cells in monolayers or spheres.
A new one‐step procedure for pulmonary valve implantation of the melody valve: Simultaneous prestenting and valve implantation
Authors: Boudjemline Younes
Published: September 2017

Objectives

To describe a new modification, the one‐step procedure, that allows interventionists to pre‐stent and implant a Melody valve simultaneously.

Background

Percutaneous pulmonary valve implantation (PPVI) is the standard of care for managing patients with dysfunctional right ventricular outflow tract, and the approach is standardized.

Methods

Patients undergoing PPVI using the one‐step procedure were identified in our database. Procedural data and radiation exposure were compared to those in a matched group of patients who underwent PPVI using the conventional two‐step procedure.

Results

Between January 2016 and January 2017, PPVI was performed in 27 patients (median age/range, 19.1/10–55 years) using the one‐step procedure involving manual crimping of one to three bare metal stents over the Melody valve. The stent and Melody valve were delivered successfully using the Ensemble delivery system. No complications occurred. All patients had excellent hemodynamic results (median/range post‐PPVI right ventricular to pulmonary artery gradient, 9/0–20 mmHg). Valve function was excellent. Median procedural and fluoroscopic times were 56 and 10.2 min, respectively, which significantly differed from those of the two‐step procedure group. Similarly, the dose area product (DAP), and radiation time were statistically lower in the one‐step group than in the two‐step group (P < 0.001 for all variables). After a median follow‐up of 8 months (range, 3–14.7), no patient underwent reintervention, and no device dysfunction was observed.

Conclusions

The one‐step procedure is a safe modification that allows interventionists to prestent and implants the Melody valve simultaneously. It significantly reduces procedural and fluoroscopic times, and radiation exposure.
Uveal myxoid leiomyosarcoma in a horse
Authors: Grosås Siv , Østevik Liv , Revold Tobias , Ottesen Nina , Ropstad Ernst‐Otto
Published: September 2017

Key Clinical Message

A uveal leiomyosarcoma of a horse is reported. There are few published reports of intraocular tumors in horses. Intraocular tumors challenge animal welfare by causing uveitis, glaucoma, and loss of vision. Knowledge regarding treatment of intraocular tumors with globe preservation is sparse, and further investigations on this topic are required.
Photocatalytic CO2 Reduction under Continuous Flow High‐Purity Conditions: Influence of Light Intensity and H2O Concentration
Authors: Dilla Martin , Mateblowski Alina , Ristig Simon , Strunk Jennifer
Published: September 2017

The present study deals with fundamental investigations on the effect of light energy and intensity on the photocatalytic reduction of CO2 on TiO2 P25 under high purity continuous flow conditions. In accordance with previous works, gas chromatographic (GC) online detection identified CH4 as the main product of photocatalytic CO2 reduction. It was found that the product formation is dependent on the light intensity, which verifies that CH4 is formed in a photon induced process on TiO2. A variation of the light intensity revealed that charge carrier recombination is more strongly enhanced compared to the charge transfer reaction to adsorbed species. On these grounds, the rate of CH4 formation increases only by the square root of the light intensity. Furthermore, product formation is predominantly a UV photon driven process. A further part of this study investigated the effect of H2O on the CH4 formation. The photocatalytic removal of carbon‐containing species and the CO2 reduction can already proceed with traces of adsorbed H2O, whereas a continuous flow of gaseous H2O results in an inhibition of product formation. Based on our study, we can identify highly promising routes for photocatalyst improvement.
Characterization of Carbenes via Hydrogenation Energies, Stability, and Reactivity: What's in a Name?
Authors: Vasiliu Monica , Peterson Kirk A. , Arduengo Anthony J. , Dixon David A.
Published: September 2017

The hydrogenation energies and singlet–triplet (S–T) splittings at the G3MP2 level of theory have been calculated for a wide range of carbenes. The carbene, :CXY with different substituents (X, Y=H, CN, NC, F, Cl, OH, OCH3, CH3, CF3, SiH3, SiMe3, phenyl, CH=O, PH2, and NH2) at the carbenic carbon center, immidazole‐based carbenes, Bertrand's carbenes, and Seppelt's CF3CSF3 were studied. The stable carbenes are singlets with large S–T splittings and with the least exothermic hydrogenation energies. The singlet ground state immidazole‐based carbenes are calculated to have the least exothermic hydrogenation energies (−15 to −30 kcal mol−1) and the largest S–T gaps. The singlet ground states of the Bertrand carbenes have more exothermic hydrogenation (ca. −67 kcal mol−1) energies and much smaller S–T gaps. The more exothermic reaction energies arise due to the need to make the phosphorus planar in the carbene so that it can donate into the empty p‐orbital at the carbene carbon center. The bending potential at the carbene carbon center in the Bertrand compounds is very flat with a large XC:Y angle. Seppelt's CF3CSF3 appears to be energetically similar to the Bertrand system, probably due to the required adjustments for geometric distortions at the sulfur center.
Difluoroacetic Acid as a New Reagent for Direct C−H Difluoromethylation of Heteroaromatic Compounds
Authors: Tung Truong Thanh , Christensen Søren Brøgger , Nielsen John
Published: September 2017

A technically simple procedure for direct C−H difluoromethylation of heteroaromatic compounds using off‐the‐shelf difluoroacetic acid as the difluoromethylating reagent has been developed. Mono‐difluoromethylation versus bis‐difluoromethylation is controlled as the result of the reaction temperature. The reactions described here enable access to the late‐stage C−H mono‐ and bis‐difluoromethylation for preparation of tool compounds for chemical biology and provide access to this hitherto untapped substituent for drug discovery.
Systematic Design of a Butadiene Telomerization Process: The Catalyst Makes the Difference
Authors: Recker Sebastian , Gordon Charles M. , Peace Amy , Redepenning Christian , Marquardt Wolfgang
Published: September 2017

A conceptual design study for a butadiene telomerization process is presented. The impact of catalyst selection on the process economics is included into the design study by an optimization‐based approach relying on shortcut models. In comparison to the established process, investment cost of the novel designed process increase only marginally, while operating costs decrease by more than 75 %. Preliminary pilot‐plant experiments indicate, however, that the economically favorable reaction concept is not stable. Consequently, alternative immobilization strategies are briefly investigated to guide future research.
Characterization of four petrologic end members from Alberta oil sands and comparison between different mines and sampling times
Authors: Geramian Mirjavad , Ivey Douglas G. , Liu Qi , Etsell Thomas H.
Published: September 2017

The current research was performed on four petrologic end members samples from Syncrude's North Mine collected in 2012 (NM12), i.e. marine clay (MC), marine sand (MS), estuarine clay (EC), and estuarine sand (ES). The mineralogical compositions of the four petrological end members were determined using X‐ray diffraction (XRD), quantitative XRD (QXRD), elemental analysis, and particle size distribution (PSD) measurements.

Bulk samples from the four petrologic end members, after bitumen removal, were mainly composed of clay minerals (kaolinite, illite, chlorite, and mixed‐layer expandable clays) and non‐clay minerals such as quartz, carbonates, feldspars, and traces of TiO2 minerals, gypsum, and pyrite. Bulk samples of the clay end members were composed of significantly higher amounts of clay minerals and lower amounts of quartz compared with the bulk samples of the sand end members. XRD analysis of oriented preparations (air dried‐54 % RH and ethylene glycolated) of the < 0.2 μm fractions of the four end members showed that interstratified illite‐smectite of high (∼30 %) and low (∼10 %) expandability were observed only in clay‐rich end members, i.e. NM12‐EC and MC, respectively. Kaolinite‐smectite was only found in the < 0.2 μm fraction of the NM12‐MC with an expandability between 5 and 10 %. Interstratification of illite‐smectite was observed in the < 0.2 μm fraction of NM09‐MC and EC samples but the expandability was only 10 % for both fractions. However, kaolinite‐smectite was not found in the same fraction for NM09‐MC and EC. ES and EC had the highest and lowest bitumen contents, respectively, for the NM12, NM09, and AM10 samples.
From clinical epidemiology to practice recommendations: Knowledge gaps and uncertainty in the management of anal precancers
Authors: Wentzensen Nicolas , Clarke Megan A.
Published: September 2017

This editorial discusses the existing data on anal precancers and demonstrates the impact of evidence gaps and uncertainty on a clinical decision model developed to provide clinical guidance for the management of anal precancers. See also pages 4709‐19.
Insight into the Interactions of Amyloid β‐Sheets with Graphene Flakes: Scrutinizing the Role of Aromatic Residues in Amyloids that Interact with Graphene
Authors: Božinovski Dragana M. , Petrović Predrag V. , Belić Milivoj R. , Zarić Snežana D.
Published: September 2017

The interaction of amyloid β‐sheet segments with graphene‐flake models is investigated by using DFT calculations. The structure of β‐sheets of selected amyloid segments is based on crystal structures obtained from the Protein Data Bank. Our study, based on DFT calculations for model systems, indicates that the interaction in amyloid–graphene aggregates can be stronger than the interaction in the respective amyloid–amyloid aggregates. The results also indicate an important specific role of aromatic sidechains in amyloid–graphene interactions. This work confirms recent experimental evidence that graphene and its modifications inhibit the aggregation of β‐amyloid peptides.
Iridium Clusters Encapsulated in Carbon Nanospheres as Nanocatalysts for Methylation of (Bio)Alcohols
Authors: Liu Qiang , Xu Guoqiang , Wang Zhendong , Liu Xiaoran , Wang Xicheng , Dong Linlin , Mu Xindong , Liu Huizhou
Published: September 2017

C−H methylation is an attractive chemical transformation for C−C bonds construction in organic chemistry, yet efficient methylation of readily available (bio)alcohols in water using methanol as sustainable C1 feedstock is limited. Herein, iridium nanocatalysts encapsulated in yolk–shell‐structured mesoporous carbon nanospheres (Ir@YSMCNs) were synthesized for this transformation. Monodispersed Ir clusters (ca. 1.0 nm) were encapsulated in situ and spatially isolated within YSMCNs by a silica‐assisted sol–gel emulsion strategy. A selection of (bio)alcohols (19 examples) was selectively methylated in aqueous phase with good‐to‐high yields over the developed Ir@YSMCNs. The improved catalytic efficiencies in terms of activity and selectivity together with the good stability and recyclability were contributable to the ultrasmall Ir clusters with oxidation chemical state as a consequence of the confinement effect of YSMCNs with interconnected nanostructures.
Light‐Driven Hydrogen Evolution by Nickel‐Substituted Rubredoxin
Authors: Stevenson Michael J. , Marguet Sean C. , Schneider Camille R. , Shafaat Hannah S.
Published: September 2017

An enzymatic system for light‐driven hydrogen generation has been developed through covalent attachment of a ruthenium chromophore to nickel‐substituted rubredoxin (NiRd). The photoinduced activity of the hybrid enzyme is significantly greater than that of a two‐component system and is strongly dependent on the position of the ruthenium phototrigger relative to the active site, indicating a role for intramolecular electron transfer in catalysis. Steady‐state and time‐resolved emission spectra reveal a pathway for rapid, direct quenching of the ruthenium excited state by nickel, but low overall turnover numbers suggest initial electron transfer is not the rate‐limiting step. This approach is ideally suited for detailed mechanistic investigations of catalysis by NiRd and other molecular systems, with implications for generation of solar fuels.
Cervical cancer screening cotesting with cytology and MRNA HPV E6/E7 yields high rates of CIN2+ lesions in young women
Authors: Granados Rosario , Tellez‐Safina Hilda , Solis Isabel , Mateos Francisco , Rodriguez‐Barbero Jose Maria , Aramburu Jose Antonio , Huertas Miguel Angel , Bajo Paloma , Camarmo Encarnacion , Corrales Teresa , Medina Pedro , Calvo Beatriz , Martin Esther , Anta Laura , Zamora Manuel , Alcaide Teresa
Published: September 2017

Background

European guidelines recommend primary HPV testing for cervical cancer screening. However, the starting age remains to be defined, with an undecided window between 30 and 35 years. This pilot study compares the effectiveness of primary HPV testing to that of cytology for the detection of high‐grade (CIN2+) lesions stratified by age.

Methods

Cotesting with LBC cytology and APTIMA® HPV (AHPV) was performed in 5053 women aged 25–65 in an opportunistic screening program in Madrid. AHPV‐positive cases were referred to colposcopy and genotyped for HPV16 and 18/45 (AHPV‐GT). Results were analyzed stratified in four age groups.

Results

454 cases (9.0%) were AHPV‐positive. Women under 35 had a 30.2% CIN2+ rate, compared to 21.9% and 20.4% for women aged 35‐44 or 45‐54. There was a significant increase (P < .05) in the rate of CIN2+ in AHPV‐GT‐positive women when compared to that for other HPV types (AHPV‐other), being 43.3% versus 15.7%. AHPV‐GT‐positive women under 35 had significantly higher rates of CIN2+ lesions than any other age‐group. The sensitivity of cytology for cervical CIN2+ in APHV‐positive women was 60.6%. All 4 carcinomas, including one AHPV‐negative endometrial adenocarcinoma, had abnormal cytology. All cervical CIN2+ lesions biopsied were AHPV‐positive.

Conclusions

Aptima HPV shows a significantly higher sensitivity for cervical CIN2+ lesions than cytology alone. Unexpectedly, AHPV‐positive women under 35 had the highest incidence of CIN2+ lesions, particularly when they are HPV16/18/45‐positive. Reconsidering HPV primary screening before the recommended age of 35 is warranted.
Value of cytopathologist review of ultrasound examinations in non‐diagnostic/unsatisfactory thyroid FNA
Authors: Poller David N.
Published: September 2017

Background

Correlation of cytologic and ultrasound findings is extremely valuable for the cytopathologist in management of thyroid nodules.

Methods

Ultrasound scans (US) of all thyroid FNA taken over a 13 month period and reported by a single cytologist were reviewed at the time of reporting, focusing on aspirates that were non‐diagnostic/unsatisfactory, equivalent to Bethesda Class I, UK Royal College of Pathologists Class Thy1 or Thy1c.

Results

FNA cases [68 (40.7%)] were classified as Thy1, equivalent to Bethesda Class I. US of 3 Thy1 cases were not available for review. On cytologist US review 9 cases were classified as pure cystic, 28 as mixed cystic/solid, 12 as predominantly solid/focally cystic and 16 as purely solid. 27 (41.5%) of cases on cytological assessment were Thy1 and showed no evidence of a cyst on US, 17 (26.1%) were Thy1/Thy1c showing features suggestive of a possible cyst and 21 (32.3%) were Thy1c showing definite features of a cyst. Fifteen of 16 (93.7%) of pure solid cases on US were Thy1, equivalent to Bethesda Class I and all 9 (100%) of cases that were pure cystic on US were reported as Thy1c—equivalent to Bethesda Category I—cyst fluid only (P < .001).

Conclusion

Cytopathologist review of thyroid US is extremely useful and can be helpful in triaging patients for further management in cases of solid, mixed cystic and/or solid, and pure cystic thyroid lesions with non‐diagnostic/unsatisfactory thyroid FNA.
Last‐century forest productivity in a managed dry‐edge Scots pine population: the two sides of climate warming
Authors: Marqués Laura , Madrigal‐González Jaime , Zavala Miguel A. , Camarero Jesús Julio , Hartig Florian
Published: September 2017

Climate change in the Mediterranean, associated with warmer temperatures and more frequent droughts, is expected to impact forest productivity and the functioning of forests ecosystems as carbon reservoirs in the region. Climate warming can positively affect forest growth by extending the growing season, whereas increasing summer drought generally reduces forest productivity and may cause growth decline, trigger dieback, hamper regeneration, and increase mortality. Forest management could potentially counteract such negative effects by reducing stand density and thereby competition for water. The effectiveness of such interventions, however, has so far mostly been evaluated for short time periods at the tree and stand levels, which limits our confidence regarding the efficacy of thinning interventions over longer time scales under the complex interplay between climate, stand structure, and forest management. In this study, we use a century‐long historical data set to assess the effects of climate and management on forest productivity. We consider rear‐edge Scots pine (Pinus sylvestris) populations covering continental and Mediterranean conditions along an altitudinal gradient in Central Spain. We use linear mixed‐effects models to disentangle the effects of altitude, climate, and stand volume on forest growth and ingrowth (recruitment and young trees’ growth). We find that warming tends to benefit these tree populations, warmer winter temperature has a significant positive effect on both forest growth and ingrowth, and the effect is more pronounced at low elevations. However, drought conditions severely reduce growth and ingrowth, in particular when competition (stand volume) is high. We conclude that summer droughts are the main threat to Scots pine populations in the region, and that a reduction of stand volume can partially mitigate the negative impacts of more arid conditions. Mitigation and adaptation measures could therefore manage stand structure to adopt for the anticipated impacts of climate change in Mediterranean forest ecosystems.
Does energy flux predict density‐dependence? An empirical field test
Authors: Ghedini Giulia , White Craig R. , Marshall Dustin J.
Published: September 2017

Changes in population density alter the availability, acquisition, and expenditure of resources by individuals, and consequently their contribution to the flux of energy in a system. While both negative and positive density‐dependence have been well studied in natural populations, we are yet to estimate the underlying energy flows that generate these patterns and the ambivalent effects of density make prediction difficult. Ultimately, density‐dependence should emerge from the effects of conspecifics on rates of energy intake (feeding) and expenditure (metabolism) at the organismal level, thus determining the discretionary energy available for growth. Using a model system of colonial marine invertebrates, we measured feeding and metabolic rates across a range of population densities to calculate how discretionary energy per colony changes with density and test whether this energy predicts observed patterns in organismal size across densities. We found that both feeding and metabolic rates decline with density but that feeding declines faster, and that this discrepancy is the source of density‐dependent reductions in individual growth. Importantly, we could predict the size of our focal organisms after eight weeks in the field based on our estimates of energy intake and expenditure. The effects of density on both energy intake and expenditure overwhelmed the effects of body size; even though higher density populations had smaller colonies (with higher mass‐specific biological rates), density effects meant that these smaller colonies had lower mass‐specific rates overall. Thus, to predict the contribution of organisms to the flux of energy in populations, it seems necessary not only to quantify how rates of energy intake and expenditure scale with body size, but also how they scale with density given that this ecological constraint can be a stronger driver of energy use than the physiological constraint of body size.
The effect of intracoronary infusion of bone marrow‐derived mononuclear cells on all‐cause mortality in acute myocardial infarction: rationale and design of the BAMI trial
Authors: Mathur Anthony , Arnold Roman , Assmus Birgit , Bartunek Jozef , Belmans Ann , Bönig Halvard , Crea Filippo , Dimmeler Stefanie , Dowlut Sheik , Fernández‐Avilés Francisco , Galiñanes Manuel , Garcia‐Dorado David , Hartikainen Juha , Hill Jonathan , Hogardt‐Noll Annette , Homsy Christian , Janssens Stefan , Kala Petr , Kastrup Jens , Martin John , Menasche Philippe , Miklik Roman , Mozid Abdul , San Román J. Alberto , Sanz‐Ruiz Ricardo , Tendera Michal , Wojakowski Wojtek , Ylä‐Herttuala Seppo , Zeiher Andreas
Published: September 2017

Over the past 13 years bone marrow‐derived mononuclear cells (BM‐MNCs) have been widely investigated for clinical efficacy in patients following acute myocardial infarction (AMI). These early phase II trials have used various surrogate markers to judge efficacy and, although promising, the results have been inconsistent. The phase III BAMI trial has therefore been designed to demonstrate that intracoronary infusion of BM‐MNCs is safe and will significantly reduce the time to first occurrence of all‐cause death in patients with reduced left ventricular ejection fraction after successful reperfusion for ST‐elevation AMI (powered with the aim of detecting a 25% reduction in all‐cause mortality). This is a multinational, multicentre, randomized, open‐label, controlled, parallel‐group phase III study aiming to enrol approximately 3000 patients in 11 European countries with at least 17 sites. Eligible patients who have impaired left ventricular ejection (≤45%) following successful reperfusion for AMI will be randomized to treatment or control group in a 1:1 ratio. The treatment group will receive intracoronary infusion of BM‐MNCs 2–8 days after successful reperfusion for AMI added on top of optimal standard of care. The control group will receive optimal standard of care. The primary endpoint is time from randomization to all‐cause death. The BAMI trial is pivotal and the largest trial to date of BM‐MNCs in patients with impaired left ventricular function following AMI. The aim of the trial is to provide a definitive answer as to whether BM‐MNCs reduce all‐cause mortality in this group of patients.
Aliskiren alone or in combination with enalapril vs. enalapril among patients with chronic heart failure with and without diabetes: a subgroup analysis from the ATMOSPHERE trial
Authors: Kristensen Søren L. , Mogensen Ulrik M. , Tarnesby Georgia , Gimpelewicz Claudio R. , Ali Mohammed A. , Shao Qing , Chiang YannTong , Jhund Pardeep S. , Abraham William T. , Dickstein Kenneth , McMurray John J.V. , Køber Lars
Published: September 2017

Aims

Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes.

Methods and results

ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow‐up was shorter in patients with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67–1.00; P = 0.053], and 196 (29.5%) in the combination group (HR 0.86, 95% CI 0.71–1.04; P = 0.13). The effects of the treatments studied did not differ significantly compared with patients without diabetes. In patients with diabetes, aliskiren monotherapy was associated with a lower risk of symptomatic hypotension compared to enalapril [42 (6.7%) vs. 65 (10.0%); P = 0.04], whereas other adverse events were generally balanced between the three groups.

Conclusion

In patients with HFrEF and diabetes, there was no signal of harm and a trend towards benefit when direct renin inhibition monotherapy was compared with an angiotensin‐converting enzyme inhibitor, whereas combined aliskiren and enalapril treatment led to more adverse events with no improvement in outcomes. Treatment effects did not differ in patients with diabetes compared with those without. Clinical Trial Registration URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00853658.
IL‐2 is required for the generation of viral‐specific CD4+ Th1 tissue‐resident memory cells and B cells are essential for maintenance in the lung
Authors: Hondowicz Brian D. , Kim Karen S. , Ruterbusch Mikel J. , Keitany Gladys J. , Pepper Marion
Published: September 2017

CD4+ tissue resident cells are an important first line of defense against viral infections in the lungs and are critical for promoting the localization of lung resident CD8+ T cells. However, relatively little is known about the signaling programs required for the development of viral‐specific CD4+ tissue resident cells in the lungs. Recently, it was shown that signaling through the high affinity IL‐2 receptor is required for the differentiation of lung‐resident Th2 memory (Trm) cells in a murine model of airway inflammation. We therefore tested if IL‐2 signaling is also required for the development of viral antigen‐specific CD4+ Th1 cells in the lung after i.n. infection with lymphocytic choriomeningitis virus. These studies demonstrate that Th1 CD4+ T cells also require IL‐2 for lung Trm development. Additionally, they show that B cells potently inhibit early Th1 cell lung residency, but are required for the maintenance of a long‐lived population of CD4+ Th1 Trm.
Crystallographic Insights into the Synthesis and Magnetic Properties of Oxoverdazyl Radicals Functionalized by Benzoic Acid
Authors: Kumar Varun , Shova Sergiu , Maurel Vincent , Novitchi Ghenadie , Train Cyrille
Published: September 2017

The synthesis and crystallization of two verdazyl radicals, 1,5‐dimethyl‐3‐(4′‐carboxyphenyl)‐6‐oxoverdazyl HIMe and 1,5‐diisopropyl‐3‐(4′‐carboxyphenyl)‐6‐oxoverdazyl HIiPr, are described. The electrochemical studies reveal that the oxidation of the two radicals is reversible, whereas their reduction is irreversible. The EPR spectrum of both radicals essentially exhibits a nine‐line pattern related to the mean hyperfine interaction of the unpaired electron with the nitrogen atoms of the verdazyl cycle. The single‐crystal X‐ray diffraction of the intermediates towards HIiPr allows a fine description of the cyanoborane adduct, which is the key intermediate of this synthesis. The verdazyl radicals themselves are obtained as single crystals. In the case of HIiPr, depending on the solvent, two polymorphs are crystallized. The structure resolution reveals that, in the solid state, the organization of the verdazyl radicals is governed by both H‐bonding and π–π interactions and is reminiscent of the H‐bonded structures that can be present in solution. Within the 1D π stacks observed in the three compounds, the verdazyl–verdazyl distance varies from 4.88 Å in HIMe to 7.90 Å in HaIiPr. This modulation of the distance strongly influences the antiferromagnetic intermolecular exchange interaction between π‐stacked radicals, which goes from J = –90 cm–1 (H = –JΣSiSi+1) for HIMe to –12.96(3) cm–1 for HbIiPr and –0.92 cm–1 for HaIiPr.
Fluoride‐Catalyzed Nucleophilic Addition of PhSCF2SiMe3 to Isatins: Synthesis of 3‐(1′,1′‐Difluoroalkyl)‐3‐hydroxyindolin‐2‐ones
Authors: Keereewan Sirisuk , Soorukram Darunee , Kuhakarn Chutima , Reutrakul Vichai , Pohmakotr Manat
Published: September 2017

The synthesis of 3‐(1′,1′‐difluoroalkyl)‐3‐hydroxyindolin‐2‐ones by employing α,α‐difluoro‐α‐phenylsulfanyl‐α‐trimethylsilylmethane (PhSCF2SiMe3) as a gem‐difluoromethylene building block is described. The reaction involves a fluoride‐catalyzed nucleophilic addition of PhSCF2SiMe3 to various isatin derivatives followed by the reductive cleavage of the phenylsulfanyl group to lead to 3‐(difluoromethyl)‐3‐hydroxyindolin‐2‐ones in good yields. Under similar reduction conditions but in the presence of activated olefins, an intermolecular radical trapping reaction took place to yield 3‐(1′,1′‐difluoroalkyl)‐3‐hydroxyindolin‐2‐one derivatives.
Iodine‐Catalyzed Mono‐ and Disulfenylation of Indoles in PEG400 through a Facile Microwave‐Assisted Process
Authors: Rahaman Rajjakfur , Barman Pranjit
Published: September 2017

An iodine‐catalyzed versatile and green method for the synthesis of mono‐ and 2,3‐disulfenylindoles was developed. Various indoles reacted with sodium alkyl‐ and arylsulfinates by using hydrogen peroxide as the oxidizing agent in PEG400 under microwave conditions. This simple method enabled the rapid synthesis of mono‐ and 2,3‐disulfenylindoles in good to excellent yields under metal‐free conditions. Furthermore, this protocol is environmentally friendly, odorless, and operationally easy and can be performed within short reaction times under mild reaction conditions with excellent functional‐group tolerance.
DEAD‐Promoted Oxidative Ugi‐Type Reaction Including an Unprecedented Ugi Amidation Assisted by Dicarboxylic Acids
Authors: Wang Jiankun , Sun Yilin , Wang Guangji , Zhen Le
Published: September 2017

A mild and metal‐free DEAD‐promoted (DEAD = diethyl azodicarboxylate) oxidative Ugi‐type reaction of tertiary amines has been demonstrated. The reaction gives easy access to α‐amino amides and imides with diverse functional groups in good isolated yields. This Ugi‐type approach achieves an unprecedented synthesis of α‐amino amide analogues with the assistance of dicarboxylic acids, and not water, for the introduction of the carbonyl oxygen atom of the amide moiety. Mechanistic studies indicated that the dicarboxylic acids may readily undergo an intramolecular annulation, instead of the Mumm rearrangement, to give the desired amide with one molecule of anhydride released.
Polypyrrole Nanoparticles Based Disposable Potentiometric Sensors
Authors: Jaworska Ewa , Gniadek Marianna , Maksymiuk Krzysztof , Michalska Agata
Published: September 2017

In this work polypyrrole nanoparticles of high electrochemical activity were used to prepare disposable, potentiometric sensors with a paper support. The paper support modified with polypyrrole nanoparticles served as electrical lead and ion‐to‐electron transducer and it was covered by a typical poly(vinyl chloride) based ion‐selective membrane. The properties of this arrangement were tested on example of potassium‐selective electrodes. The sensors prepared benefited from the properties of conducting polymer nanostructures: high electrical conductivity and electroactivity as well as absence of suspension stabilizing agent. The obtained electrodes were characterized with analytical parameters well comparable with those of classical ion‐selective electrodes.
A continuous flow microfluidic device based on contactless dielectrophoresis for bioparticles enrichment
Authors: Rahmani Ali , Mohammadi Aliasghar , Kalhor Hamid Reza
Published: September 2017

In recent years, applications of dielectrophoresis‐based platforms have been recognized as effective and dependable approach to separate cells and bioparticles, suspended in different carrier fluids, based on particle size and electrical properties. In this study, a microfluidic device was fabricated by an unprecedented electrode pattern, and several experiments were performed to enrich samples including either of yeast, Escherichia coli, or latex particles. A chemical deposition‐based method was employed for fabrication of microelectrodes, inducing nonuniform electric field required for dielectrophoresis‐based separation. One major advantage of our employed method is low fabrication cost, in addition to its accuracy and operation at low voltages. The performance of the microfluidic device in enriching either of injected samples was studied using spectrophotometric techniques. The effects of experimentally controllable parameters (applied‐voltage amplitude and frequency, and flow rate) were studied by changing a parameter while keeping the others constant. It became evident that all the aforementioned parameters had modulating impact on the performance of the microfluidic device. Furthermore, to investigate binary interactions among the parameters, response surface methodology was exploited, resulting in a second‐order polynomial model for the performance of the device as a function of the parameters. The model was employed for finding the optimum values of the parameters at which the performance of the device is the highest. At optimum values for the experimentally controllable parameters, enrichment efficiencies of 87 ± 2, 82 ± 4, and 86 ± 3% for, respectively, yeast, E. coli, and latex particles were obtained experimentally, confirming the ability of the proposed method for biological and polymeric particles enrichment.
Association of with‐no‐lysine kinase 1 and Serine/Threonine kinase 39 gene polymorphisms and haplotypes with essential hypertension in Tibetans
Authors: Shi Rufeng , Li Jiangbo , He Jiyun , Meng Qingtao , Qian Zhiping , Shi Di , Liu Qi , Cai Yali , Li Xinran , Chen Xiaoping
Published: September 2017

Tibetans have a higher essential hypertension prevalence compared with other ethnics in China. The reason might be due to their unique environmental influence, as well as genetic factor. However, limited studies focus on Tibetan genetics and its association with hypertension. The aim of this study was to investigate the association between With‐No‐Lysine (K) Kinase 1 (WNK1), Serine/Threonine kinase 39(STK39) genes variants and hypertension in the Tibetan population. 204 Tibetan hypertensive patients and 305 normotensive controls were recruited in an epidemiological survey conducted at 2 sites in the Ganzi Tibetan autonomous region. Patients were genotyped for nineteen WNK1 candidate tag single nucleotide polymorphisms (SNPs) and three STK39 SNPs, and haplotype analysis was performed. Results showed that the allele A in rs1468326 was overrepresented in hypertensive patients versus control (53.4% vs 42.9%, P < 0.05). The multivariable‐adjusted odds ratio (OR) for hypertension among CA + AA genotypes carriers was 1.60 (95% CI: 1.02–2.62, P < 0.05), and they also had a higher systolic blood pressure (136.5 ± 28.6 vs 131.7 ± 24.8 mmHg, P < 0.05). However, the TT genotype ratio in rs6749447 was lower in hypertensives (5.4% vs 10.8%, P < 0.05), and the hypertension risk for the TT genotype carriers in rs6749447 decreased after adjustment (OR 0.49, 95% CI 0.19–0.95, P < 0.05). Subjects with haplotype AGACAGGAATCGT showed 1.57 times higher risk of hypertension (95% CI 1.02–2.41, P < 0.05). In conclusion, SNP rs1468326 of WNK1, rs6749447 of STK39, and WNK1 haplotype AGACAGGAATCGT were associated with hypertension in Tibetan individuals. Environ. Mol. Mutagen. 59:151–160, 2018. © 2017 Wiley Periodicals, Inc.