bluuebunny/crossref_metadata_2025 huggingface dataset:
On the modeling of the co2‐catalyzed sintering of calcium oxide
Authors: Maya Juan C. , Chejne Farid , Bhatia Suresh K.
Published: March 2017

A comprehensive mathematical model for the CO2‐catalyzed sintering of CaO is proposed. It takes into account the mechanisms of surface diffusion and grain boundary diffusion, catalyzed by CO2 chemisorption and dissolution, respectively. In addition, the model proposed here considers the change in pore size distribution during sintering, grain growth, and the densification by lattice diffusion, which is the intrinsic sintering mechanism of the CaO. Model predictions are validated using experimental data on the sintering of two CaO samples, one of them derived from pure CaCO3 and the other from limestone. It is found that impurities in limestone‐derived CaO do not significantly affect the CO2 dissolution or chemisorption processes; however, they strongly increase the rate of sintering by lattice diffusion. It is also established that low temperatures and CO2 partial pressures promote the coarsening by surface diffusion, whereas high temperatures and CO2 partial pressures favor densification. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3286–3296, 2017
BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab
Authors: Huet Sarah , Szafer‐Glusman Edith , Tesson Bruno , Xerri Luc , Fairbrother Wayne J. , Mukhyala Kiran , Bolen Chris , Punnoose Elizabeth , Tonon Laurie , Chassagne‐Clément Catherine , Feugier Pierre , Viari Alain , Jardin Fabrice , Salles Gilles , Sujobert Pierre
Published: March 2017

BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab‐containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA‐targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over‐activation of AICDA (activation‐induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N‐terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow‐up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression‐free survival.
An Aluminum Fluoride Complex with an Appended Ammonium Salt as an Exceptionally Active Cooperative Catalyst for the Asymmetric Carboxycyanation of Aldehydes
Authors: Brodbeck Daniel , Broghammer Florian , Meisner Jan , Klepp Julian , Garnier Delphine , Frey Wolfgang , Kästner Johannes , Peters René
Published: March 2017

Al−F bonds are among the most stable σ bonds known, exhibiting an even higher bond energy than Si−F bonds. Despite a stability advantage and a potentially high Lewis acidity of Al−F complexes, they have not been described as structurally defined catalysts for enantioselective reactions. We show that Al−F salen complexes with appended ammonium moieties give exceptional catalytic activity in asymmetric carboxycyanations. In addition to aromatic aldehydes, enal and aliphatic substrates are well accepted. Turnover numbers up to around 104 were achieved, whereas with previous catalysts 101–102 turnovers were typically attained. In contrast to Al−Me and Al−Cl salen complexes, the analogous Al−F species are remarkably stable towards air, water, and heat, and can be recovered unchanged after catalysis. They possess a considerably increased Lewis acidity as shown by DFT calculations.
Cardiovascular Safety of Tocilizumab Versus Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis: A Multi‐Database Cohort Study
Authors: Kim Seoyoung C. , Solomon Daniel H. , Rogers James R. , Gale Sara , Klearman Micki , Sarsour Khaled , Schneeweiss Sebastian
Published: March 2017

Objective

While tocilizumab (TCZ) is known to increase low‐density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi).

Methods

To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome measure was a composite cardiovascular end point of hospitalization for myocardial infarction or stroke. TCZ initiators were propensity score matched to TNFi initiators with a variable ratio of 1:3 within each database, controlling for >65 baseline characteristics. A fixed‐effects model combined database‐specific hazard ratios (HRs).

Results

We included 9,218 TCZ initiators propensity score matched to 18,810 TNFi initiators across all 3 databases. The mean age was 72 years in Medicare, 51 in PharMetrics, and 53 in MarketScan. Cardiovascular disease was present at baseline in 14.3% of TCZ initiators and 13.5% of TNFi initiators. During the study period (mean ± SD 0.9 ± 0.7 years; maximum 4.5 years), 125 composite cardiovascular events occurred, resulting in an incidence rate of 0.52 per 100 person‐years for TCZ initiators and 0.59 per 100 person‐years for TNFi initiators. The risk of cardiovascular events associated with TCZ use versus TNFi use was similar across all 3 databases, with a combined HR of 0.84 (95% confidence interval 0.56–1.26).

Conclusion

This multi‐database population‐based cohort study showed no evidence of an increased cardiovascular risk among RA patients who switched from a different biologic drug or tofacitinib to TCZ versus to a TNFi.
A dynamic linear model for the estimation of time‐varying origin–destination matrices from link counts
Authors: Pitombeira‐Neto Anselmo Ramalho , Loureiro Carlos Felipe Grangeiro
Published: March 2017

We propose a dynamic linear model (DLM) for the estimation of day‐to‐day time‐varying origin–destination (OD) matrices from link counts. Mean OD flows are assumed to vary over time as a locally constant model. We take into account variability in OD flows, route flows, and link volumes. Given a time series of observed link volumes, sequential Bayesian inference is applied in order to estimate mean OD flows. The conditions under which mean OD flows may be estimated are established, and computational studies on two benchmark transportation networks from the literature are carried out. In both cases, the DLM converged to the unobserved mean OD flows when given sufficient observations of traffic link volumes despite assuming uninformative prior OD matrices. We discuss limitations and extensions of the proposed DLM. Copyright © 2017 John Wiley & Sons, Ltd.
Fetal Exposure to Montelukast and Congenital Anomalies: A Population Based Study in Denmark
Authors: Cavero‐Carbonell Clara , Vinkel‐Hansen Anne , Rabanque‐Hernández Mª José , Martos Carmen , Garne Ester
Published: March 2017

Background

The objective was to study pregnancy outcomes between groups of Danish women, with pregnancy ending between 1998 and 2009, according to their exposure to montelukast.

Methods

Cross‐sectional observational study in Danish women, selecting live births and stillbirths (Birth Registry) and spontaneous abortions and induced terminations (Patient Registry). Montelukast exposure was obtained from the Prescription Registry (ATC code R03DC03). Exposure period was from 3 months before the last menstrual period until the end of the first trimester. Four groups were studied: (1) women with prescription for montelukast, (2) women with prescription for montelukast and other anti‐asthmatic medications, (3) women with prescription for other anti‐asthmatic medications, (4) women without prescription for any anti‐asthmatic medications.

Results

A total of 754,300 singleton pregnancies (> 12 weeks) were identified: 401 pregnancies in group 1, 426 pregnancies in group 2, 24878 in group 3 and 728,595 in group 4. Risk of preterm birth, maternal preeclampsia and gestational diabetes was increased for pregnancies exposed to montelukast. No significant differences were found for the risk of major congenital anomalies (CA). Adjusted odds ratio for CA was 1.4 (95% CI 0.9–2.3) for the group 1 and 1.0 (95% CI 0.6–1.8) for group 2.

Conclusion

Pregnant women with prescriptions for montelukast had a higher risk of preterm birth and maternal complications. These risks are known to be associated with maternal asthma, no increased risk of CA was found. Further analysis including more exposed pregnancies will be needed to determine the risk of specific CA. Birth Defects Research 109:452–459, 2017. © 2017 Wiley Periodicals, Inc.
Hydrogel‐based three‐dimensional cell culture for organ‐on‐a‐chip applications
Authors: Lee Seung Hwan , Shim Kyu Young , Kim Bumsang , Sung Jong Hwan
Published: March 2017

Recent studies have reported that three‐dimensionally cultured cells have more physiologically relevant functions than two‐dimensionally cultured cells. Cells are three‐dimensionally surrounded by the extracellular matrix (ECM) in complex in vivo microenvironments and interact with the ECM and neighboring cells. Therefore, replicating the ECM environment is key to the successful cell culture models. Various natural and synthetic hydrogels have been used to mimic ECM environments based on their physical, chemical, and biological characteristics, such as biocompatibility, biodegradability, and biochemical functional groups. Because of these characteristics, hydrogels have been combined with microtechnologies and used in organ‐on‐a‐chip applications to more closely recapitulate the in vivo microenvironment. Therefore, appropriate hydrogels should be selected depending on the cell types and applications. The porosity of the selected hydrogel should be controlled to facilitate the movement of nutrients and oxygen. In this review, we describe various types of hydrogels, external stimulation‐based gelation of hydrogels, and control of their porosity. Then, we introduce applications of hydrogels for organ‐on‐a‐chip. Last, we also discuss the challenges of hydrogel‐based three‐dimensional cell culture techniques and propose future directions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:580–589, 2017
Carpal tunnel release: Safe and simple identification of the flexor retinaculum based on superficial anatomical landmarks
Authors: Hohenberger G.M. , Maier M.J. , Grechenig C. , Schwarz A.M. , Matzi V. , Weiglein A.H.
Published: March 2017

The aim of our study was to project the borders of the flexor retinaculum (FR) onto superficial landmarks since its insufficient splitting is the most common reason for persistence of symptoms after carpal tunnel release. In 60 hands the radial and ulnar styloid processes were linked by a horizontal line and a longitudinal line was laid through the ring finger's radial side. These were intersected resulting in the reference point “A” on the forearm. As the second basing point “B”, the radial margin of the ring finger at the palmar digital crease was chosen. Measurement of the FR was carried out with regard to the reference points. The proximal margin of the FR was located at 4% of the reference line A‐B starting from point A and extended up to 52% of this total length. Results indicate that splitting alongside the proximal half of line A‐B divides the FR completely. Clin. Anat. 30:512–516, 2017. © 2017 Wiley Periodicals, Inc.
Azido Pentoses: A New Tool To Efficiently Label Mycobacterium tuberculosis Clinical Isolates
Authors: Kolbe Katharina , Möckl Leonhard , Sohst Victoria , Brandenburg Julius , Engel Regina , Malm Sven , Bräuchle Christoph , Holst Otto , Lindhorst Thisbe K. , Reiling Norbert
Published: March 2017

Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (Tb), has a complex cell envelope which forms an efficient barrier to antibiotics, thus contributing to the challenges of anti‐tuberculosis therapy. However, the unique Mtb cell wall can be considered an advantage and be utilized to selectively label Mtb bacteria. Here we introduce three azido pentoses as new compounds for metabolic labeling of Mtb: 3‐azido arabinose (3AraAz), 3‐azido ribose (3RiboAz), and 5‐azido arabinofuranose (5AraAz). 5AraAz demonstrated the highest level of Mtb labeling and was efficiently incorporated into the Mtb cell wall. All three azido pentoses can be easily used to label a variety of Mtb clinical isolates without influencing Mtb‐dependent phagosomal maturation arrest in infection studies with human macrophages. Thus, this metabolic labeling method offers the opportunity to attach desired molecules to the surface of Mtb bacteria in order to facilitate investigation of the varying virulence characteristics of different Mtb clinical isolates, which influence the outcome of a Tb infection.
Hyperpolarized 129Xe Magnetic Resonance Imaging Sensor for H2S
Authors: Yang Shengjun , Yuan Yaping , Jiang Weiping , Ren Lili , Deng He , Bouchard Louis S. , Zhou Xin , Liu Maili
Published: March 2017

A new magnetic resonance imaging (MRI) molecular sensor for hydrogen sulfide detection and imaging using the nuclear spin resonance of hyperpolarized 129Xe is developed. The designed MRI sensor employs cryptophane for NMR sensing, together with an azide group serving as a reaction site. It demonstrates a “proof‐of‐concept” that a fluorescent H2S probe can be linked to a xenon‐binding cryptophane and thereby converted into an MRI probe, which could provide a very generalizable template.
Controlled Interconversion of a Dinuclear Au Species Supported by a Redox‐Active Bridging PNP Ligand Facilitates Ligand‐to‐Gold Electron Transfer
Authors: Vreeken Vincent , Siegler Maxime A. , van der Vlugt Jarl Ivar
Published: March 2017

Redox non‐innocent ligands have recently emerged as interesting tools to obtain new reactivity with a wide variety of metals. However, gold has almost been neglected in this respect. Here, we report mechanistic investigations related to a rare example of ligand‐based redox chemistry in the coordination sphere of gold. The dinuclear metal‐centered mixed‐valent AuI–AuIII complex 1, supported by monoanionic diarylamido‐diphosphine ligand PNPPr and with three chlorido ligands overall, undergoes a complex series of reactions upon halide abstraction by silver salt or Lewis acids such as gallium trichloride. Formation of the ultimate AuI–AuI complex 2 requires the intermediacy of AuI–AuI dimers 5 and 7 as well as the unique AuIII–AuIII complex 6, both of which are interconverted in a feedback loop. Finally, unprecedented ortho‐selective C−H activation of the redox‐active PNP ligand results in the carbazolyldiphosphine derivative PN*PPr via ligand‐to‐metal two‐electron transfer. This work demonstrates that the redox‐chemistry of gold may be significantly expanded and modified when using a reactive ligand scaffold.
Recent Advances of Transition Metal‐Mediated Oxidative Radical Reactions in Total Synthesis of Indole Alkaloids
Authors: Liang Kangjiang , Xia Chengfeng
Published: March 2017

Over the past decades, transition metal‐mediated oxidative radical reactions have been discovered and developed as a robust and conceptually novel approach for organic synthesis. This mini‐review details the background, recent advances, and synthetic applications of transition metal‐mediated oxidative radical reactions in indole alkaloids biomimetic synthesis. The organization of each section is based on the kind of indole alkaloids.
Riemann‐Hilbert Problems for the Shapes Formed by Bodies Dissolving, Melting, and Eroding in Fluid Flows
Authors: Moore M. Nicholas J.
Published: March 2017

The classical Stefan problem involves the motion of boundaries during phase transition, but this process can be greatly complicated by the presence of a fluid flow. Here we consider a body undergoing material loss due to either dissolution (from molecular diffusion), melting (from thermodynamic phase change), or erosion (from fluid‐mechanical stresses) in a fast‐flowing fluid. In each case, the task of finding the shape formed by the shrinking body can be posed as a singular Riemann‐Hilbert problem. A class of exact solutions captures the rounded surfaces formed during dissolution/melting, as well as the angular features formed during erosion, thus unifying these different physical processes under a common framework. This study, which merges boundary‐layer theory, separated‐flow theory, and Riemann‐Hilbert analysis, represents a rare instance of an exactly solvable model for high‐speed fluid flows with free boundaries.© 2017 Wiley Periodicals, Inc.
Simulacra and Sustainability Disclosure: Analysis of the Interpretative Models of Creating Shared Value
Authors: Corazza Laura , Scagnelli Simone Domenico , Mio Chiara
Published: March 2017

Business scandals, environmental disasters, and the growing attention to malnutrition and starvation around the world, are emphasizing the criticism toward capitalism and the way business is approached. Corporate social responsibility (CSR) and sustainability theories are becoming understated, as Porter and Kramer's emerging concept of Creating Shared Value (CSV) has argued. Indeed, CSV is attracting increasing attention from the corporate and professional world as well as getting controversial judgments and reviews by CSR and sustainability scholars. Indeed, CSV appears more a buzzword than a theoretical concept. After outlining the underlying debate, our study critically examines how worldwide organizations have approached and interpreted CSV in their sustainability disclosure practices. In that sense, similarly to Plato and Baudrillard's concept of ‘simulacrum’, companies adopting CSV create an interpretation of their practical reality through definitions and images. Qualitative and rather innovative techniques are applied to analyze and categorize the narrative and graphical signals provided by a sample of leading organizations within their sustainability disclosure. Our findings show that, overall, CSV is not viewed as something unrelated to CSR, not just philanthropy, but is a strategically oriented shift from sustainability which stresses the inclusion of stakeholders' needs. Given the current lack of research addressing how CSV has been interpreted and disclosed, our study provides a significant contribution to the current academic debate. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Does Specific CSR Training for Managers Impact Shareholder Value? Implications for Education in Sustainable Development
Authors: López‐Pérez Mª. Eugenia , Melero Iguácel , Javier Sesé F.
Published: March 2017

This study aims to analyze whether specific corporate social responsibility +CSR) training in sustainable development can boost the potential impact of CSR on shareholder value (i.e., corporate reputation, brand image, and financial value) for small and medium enterprises (SMEs). We also aim to determine the main implications from an educational point of view and in terms of training program and curriculum design related to sustainable development. We carry out a quantitative study using partial least squares (PLS) techniques to analyze a sample of SME owners and managers. Results suggest that specific CSR training matters, making this type of training a valuable resource for business management and for society. Therefore, it is possible to promote business management models in which sustainability and profit can coexist. However, there are still sizeable education/training gaps, especially in the field of SMEs. Our results provide a foundation for solid arguments in defense of more widespread, in‐depth implementation of sustainability education – not only at universities and business schools, but at all levels of education. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Towards an Understanding of Li2O2 Evolution in Li–O2 Batteries: An In Operando Synchrotron X‐ray Diffraction Study
Authors: Liu Chenjuan , Brant William R. , Younesi Reza , Dong Yanyan , Edström Kristina , Gustafsson Torbjörn , Zhu Jiefang
Published: March 2017

One of the major challenges in developing high‐performance Li–O2 batteries is to understand the Li2O2 formation and decomposition during battery cycling. In this study, this issue was investigated by synchrotron radiation powder X‐ray diffraction. The evolution of Li2O2 morphology and structure was observed under actual electrochemical conditions of battery operation. By quantitatively tracking Li2O2 during discharge and charge, a two‐step process was suggested for both growth and oxidation of Li2O2 owing to different mechanisms during two stages of both oxygen reduction reaction and oxygen evolution reaction. From an observation of the anisotropic broadening of Li2O2 in XRD patterns, it was inferred that disc‐like Li2O2 grains are formed rapidly in the first step of discharge. These grains can stack together so that they facilitate the nucleation and growth of toroidal Li2O2 particles with a LiO2‐like surface, which could cause parasitic reactions and hinder the formation of Li2O2. During the charge process, Li2O2 is firstly oxidized from the surface, followed by a delithiation process with a faster oxidation of the bulk by stripping the interlayer Li atoms to form an off‐stoichiometric intermediate. This fundamental insight brings new information on the working mechanism of Li–O2 batteries.
Remarkably Efficient Microwave‐Assisted Cross‐Metathesis of Lipids under Solvent‐Free Conditions
Authors: Ullah Aman , Arshad Muhammad
Published: March 2017

Catalytic transformation of renewable feedstocks into fine chemicals is in high demands and olefin metathesis is a sophisticated tool for biomass conversion. Nevertheless, the large‐scale viability of such processes depends on the conversion efficiency, energy efficiency, catalytic activity, selective conversion into desired products, and environmental footprint of the process. Therefore, conversions of renewables by using simple, swift, and efficient methods are desirable. A microwave‐assisted ethenolysis and alkenolysis (using 1,5‐hexadiene) of canola oil and methyl esters derived from canola oil (COME) and waste/recycled cooking oil (WOME) was carried out by using ruthenium‐based catalytic systems. A systematic study using 1st and 2nd generation Grubbs and Hoveyda–Grubbs catalysts was carried out. Among all ruthenium catalysts, 2nd generation Hoveyda–Grubbs catalyst was found to be highly active in the range of 0.002–0.1 mol % loading. The conversions proved to be rapid providing unprecedented turnover frequencies (TOFs). High TOFs were achieved for ethenolysis of COME (21 450 min−1), direct ethenolysis of canola oil (19 110 min−1), for WOME (15 840 min−1) and for cross‐metathesis of 1,5‐hexadiene with COME (10 920 min−1). The ethenolysis of commercial methyl oleate was also performed with a TOF of 8000 min−1 under microwave conditions.
Hydrogen‐Treated Rutile TiO2 Shell in Graphite‐Core Structure as a Negative Electrode for High‐Performance Vanadium Redox Flow Batteries
Authors: Vázquez‐Galván Javier , Flox Cristina , Fàbrega Cristian , Ventosa Edgar , Parra Andres , Andreu Teresa , Morante Joan Ramón
Published: March 2017

Hydrogen‐treated TiO2 as an electrocatalyst has shown to boost the capacity of high‐performance all‐vanadium redox flow batteries (VRFBs) as a simple and eco‐friendly strategy. The graphite felt‐based GF@TiO2:H electrode is able to inhibit the hydrogen evolution reaction (HER), which is a critical barrier for operating at high rate for long‐term cycling in VRFBs. Significant improvements in charge/discharge and electron‐transfer processes for the V3+/V2+ reaction on the surface of reduced TiO2 were achieved as a consequence of the formation of oxygen functional groups and oxygen vacancies in the lattice structure. Key performance indicators of VRFB have been improved, such as high capability rates and electrolyte‐utilization ratios (82 % at 200 mA cm−2). Additionally, high coulombic efficiencies (ca. 100 % up to the 96th cycle, afterwards >97 %) were obtained, demonstrating the feasibility of achieving long‐term stability.
Introduction of liquid‐based cytology and human papillomavirus testing in cervical cancer screening in Luxembourg
Authors: Latsuzbaia Ardashel , Hebette Gaëtan , Fischer Marc , Arbyn Marc , Weyers Steven , Vielh Philippe , Schmitt Fernando , Mossong Joël
Published: March 2017

Background

In 2014, liquid‐based cytology with HPV triage replaced conventional cytology. The aim of our study was to compare conventional and liquid‐based cytology (LBC), estimate the prevalence of abnormal cervical cytology and high risk HPV (hrHPV) infection and their correlation, among screened women in Luxembourg.

Methods

Between the first January 2013 and 31st December 2015, 315,868 cervical samples from 150,815 women (mean age 42.2 years) were investigated by the national cytology laboratory. Slides were prepared and screened according to European Guidelines. All cytological results were classified according to the Bethesda 2001 system terminology.

Results

The prevalence of abnormal cervical lesions was as follows: atypical squamous cells of undetermined significance (ASC‐US), 1.3%; low‐grade squamous intraepithelial lesion (LSIL), 1.9%; high‐grade squamous intraepithelial lesion (HSIL), 0.4%. The detection rate of cytological lesions was significantly higher with LBC than with conventional cytology. Based on 11,838 samples with concomitant cytology and HPV testing, hrHPV was detected in 9.5, 45.3, 70.0, and 92.6% of women with negative cytology, ASC‐US, LSIL, and HSIL, respectively.

Conclusion

More cervical lesions were identified using LBC compared to conventional cytology. HrHPV infection was correlated with the severity of intraepithelial lesions. The current findings provide important information to evaluate the prevention of cervical cancer in Luxembourg and for monitoring the future impact of HPV vaccination. Diagn. Cytopathol. 2017;45:384–390. © 2017 Wiley Periodicals, Inc.
Advanced glycation end‐products (AGEs) and associations with cardio‐metabolic, lifestyle, and dietary factors in a general population: the NQplus study
Authors: Botros Nadia , Sluik Diewertje , van Waateringe Robert P. , de Vries Jeanne H.M. , Geelen Anouk , Feskens Edith J.M.
Published: March 2017

Background

Advanced glycation end‐products are a heterogeneous group of molecules that are formed during reactions between reducing sugars and proteins. Advanced glycation end‐products are thought to play a role in several diseases, including diabetes mellitus and can be measured non‐invasively using skin autofluorescence (AF). The aim of this cross‐sectional study was to investigate associations between skin AF and cardio‐metabolic, lifestyle, and dietary factors within a general population.

Methods

The NQplus study is an ongoing longitudinal study in the surroundings of Wageningen, the Netherlands. In this cross‐sectional study, skin AF was measured in 957 participants, aged 20 to 77 years, with the AGE Reader. Logistic regression was used to assess associations between skin AF and the following factors: demographics, adiposity, blood lipids, fasting glucose, HbA1c, blood pressure, dietary intake, and disease history. Stepwise linear regression was used to identify factors correlating with skin AF.

Results

In males, skin AF was significantly associated with age, coffee intake, systolic and diastolic blood pressure, body fat, full fat dairy, and educational level. In females, significant associations were found with age, coffee intake, HbA1c, diabetes, and eGFR. In the total population, current smoking was positively associated with skin AF.

Conclusions

This cross‐sectional study in a general population showed that age and coffee intake were associated with skin AF in both males and females. We observed a gender disparity for some of the associations with skin AF, which need to be confirmed by further research. More detailed research is needed to assess the association between skin AF and diet.
Synchrony and so much more: Diverse roles for electrical synapses in neural circuits
Authors: Connors Barry W.
Published: March 2017

Electrical synapses are neuronal gap junctions that are ubiquitous across brain regions and species. The biophysical properties of most electrical synapses are relatively simple—transcellular channels allow nearly ohmic, bidirectional flow of ionic current. Yet these connections can play remarkably diverse roles in different neural circuit contexts. Recent findings illustrate how electrical synapses may excite or inhibit, synchronize or desynchronize, augment or diminish rhythms, phase‐shift, detect coincidences, enhance signals relative to noise, adapt, and interact with nonlinear membrane and transmitter‐release mechanisms. Most of these functions are likely to be widespread in central nervous systems. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 610–624, 2017
Redox‐Active Metal Complexes for Anticancer Therapy
Authors: Zhang Pingyu , Sadler Peter J.
Published: March 2017

The redox properties of both metals and ligands in transition metal complexes offer unusual routes for new mechanisms of anticancer therapy. Metal complexes can introduce artificial reductive and oxidative stress into cancer cells, including behavior as photoactivatable agents and catalysts. Relatively inert metal complexes (“prodrugs”) can be activated by redox processes within cancer cells. Examples of pharmaceuticals activated by bioreduction include three PtIV and two RuIII compounds that have already entered clinical trials. More recently, novel CoIII, FeIII, PtIV, Ru(III/II), OsII, and IrIII complexes have been reported to exhibit redox‐mediated anticancer activity. Redox activation strategies can introduce new methods to increase cancer cell selectivity and combat drug resistance. Using combination therapy together with redox modulators to increase potency is also possible. This essay focuses on metal complexes that are activated in the reducing environment of cancer cells.
Cubic Bixbyite‐Structured Phases of Yb6MoO12 and Y6MoO12 Prepared by the Solution Combustion Method at Low Temperatures
Authors: Schildhammer Daniel , Fuhrmann Gerda , Petschnig Lucas , Partl Gabriel , Götsch Thomas , Penner Simon , Schaur Andreas , Saxer Andreas , Schottenberger Herwig , Huppertz Hubert
Published: March 2017

For the first time, Yb6MoO12 was synthesized in the cubic bixbyite structure type (Ia3) under low‐temperature conditions. The solution combustion method was used to prepare an amorphous precursor at a temperature of 400 °C. Subsequent calcination at around 600 °C initiated the crystallization process, accompanied by the decomposition of remnant organic material, leading to a carbonate precursor. Further increase of the temperature to 800 °C resulted in a decarboxylation of the precursor, converting it into a highly crystalline cubic phase. A second phase transition into a rhombohedral structure was observed at a temperature around 1000 °C. Detailed phase transition studies were performed by powder X‐ray diffraction (PXRD), thermal analysis (TG‐DTA), attenuated total reflection infrared spectroscopy (ATR‐IR), and X‐ray photoelectron spectroscopy (XPS) analysis. Furthermore, the analogous yttrium compound Y6MoO12 was prepared by the same method. Contrary to previous reports, the structure analysis revealed that Y6MoO12 crystallizes in the same highly symmetric cubic structure (Ia3). Due to the thermal stability differences of the corresponding rare earth oxides and molybdenum oxide, both cubic low‐temperature phases Yb6MoO12 and Y6MoO12 are presumably not attainable by classical solid‐state reactions.
Controlling the Substitution Pattern of Hexasubstituted Naphthalenes by Aryne/Siloxyfuran Diels–Alder Additions: Regio‐ and Stereocontrolled Synthesis of Arizonin C1 Analogs
Authors: Neumeyer Markus , Kopp Julia , Brückner Reinhard
Published: March 2017

3,4‐Dimethoxybenz‐1‐yne and 2‐siloxylated furans without or with a bromine atom at C‐3 undergo Diels–Alder reactions with orientational selectivity. Hydrolysis furnished a bromine‐free or a bromine‐containing naphthalene, respectively. Bromination of the former provided a regioisomer of the latter. Either of the two compounds was processed to give a variety of unnatural naphthoquinonopyrano‐γ‐lactones. This occurred by a succession of (1) Heck coupling, (2) asymmetric dihydroxylation, (3) oxa‐Pictet–Spengler cyclization, and (4) oxidation. The fifteen monomeric naphthoquinonopyrano‐γ‐lactone structures that we prepared resemble the natural product (–)‐arizonin C1 or its C‐5 epimer. Accordingly, they represent hexasubstituted naphthalenes likewise. The sixteenth naphthoquinonopyrano‐γ‐lactone that we synthesized is a kind of dimer. Its moieties are bridged differently than those in naturally occurring naphthoquinonopyrano‐γ‐lactone dimers.
Sublethal effects on wood frogs chronically exposed to environmentally relevant concentrations of two neonicotinoid insecticides
Authors: Robinson Stacey A. , Richardson Sarah D. , Dalton Rebecca L. , Maisonneuve France , Trudeau Vance L. , Pauli Bruce D. , Lee-Jenkins Stacey S.Y.
Published: March 2017

Neonicotinoids are prophylactically used globally on a variety of crops, and there is concern for the potential impacts of neonicotinoids on aquatic ecosystems. The intensive use of pesticides on crops has been identified as a contributor to population declines of amphibians, but currently little is known regarding the sublethal effects of chronic neonicotinoid exposure on amphibians. The objective of the present study was to characterize the sublethal effect(s) of exposure to 3 environmentally relevant concentrations (1 μg/L, 10 μg/L, and 100 μg/L) of 2 neonicotinoids on larval wood frogs (Lithobates sylvaticus) using outdoor mesocosms. We exposed tadpoles to solutions of 2 commercial formulations containing imidacloprid and thiamethoxam, and assessed survival, growth, and development. Exposure to imidacloprid at 10 μg/L and 100 μg/L increased survival and delayed completion of metamorphosis compared with controls. Exposure to thiamethoxam did not influence amphibian responses. There was no significant effect of any treatment on body mass or size of the metamorphs. The results suggest that current usage of imidacloprid and thiamethoxam does not pose a threat to wood frogs. However, further assessment of both direct and indirect effects on subtle sublethal endpoints, and the influence of multiple interacting stressors at various life stages, is needed to fully understand the effects of neonicotinoids on amphibians. Environ Toxicol Chem 2017;36:1101–1109. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Identifying high risk individuals for targeted lung cancer screening: Independent validation of the PLCOm2012 risk prediction tool
Authors: Weber Marianne , Yap Sarsha , Goldsbury David , Manners David , Tammemagi Martin , Marshall Henry , Brims Fraser , McWilliams Annette , Fong Kwun , Kang Yoon Jung , Caruana Michael , Banks Emily , Canfell Karen
Published: March 2017

Lung cancer screening with computerised tomography holds promise, but optimising the balance of benefits and harms via selection of a high risk population is critical. PLCOm2012 is a logistic regression model based on U.S. data, incorporating sociodemographic and health factors, which predicts 6‐year lung cancer risk among ever‐smokers, and thus may better predict those who might benefit from screening than criteria based solely on age and smoking history. We aimed to validate the performance of PLCOm2012 in predicting lung cancer outcomes in a cohort of Australian smokers. Predicted risk of lung cancer was calculated using PLCOm2012 applied to baseline data from 95,882 ever‐smokers aged ≥45 years in the 45 and Up Study (2006–2009). Predictions were compared to lung cancer outcomes captured to June 2014 via linkage to population‐wide health databases; a total of 1,035 subsequent lung cancer diagnoses were identified. PLCOm2012 had good discrimination (area under the receiver‐operating‐characteristic‐curve; AUC 0.80, 95%CI 0.78–0.81) and excellent calibration (mean and 90th percentiles of absolute risk difference between observed and predicted outcomes: 0.006 and 0.016, respectively). Sensitivity (69.4%, 95%CI, 65.6–73.0%) of the PLCOm2012 criteria in the 55–74 year age group for predicting lung cancers was greater than that using criteria based on ≥30 pack‐years smoking and ≤15 years quit (57.3%, 53.3‐61.3%; p < 0.0001), but specificity was lower (72.0%, 71.7–72.4% versus 75.2%, 74.8–75.6%, respectively; p < 0.0001). Targeting high risk people for lung cancer screening using PLCOm2012 might improve the balance of benefits versus harms, and cost‐effectiveness of lung cancer screening.
Therapeutic plasma exchange in chronic dysimmune peripheral neuropathies: A 10‐year retrospective study
Authors: Codron Philippe , Cousin Maud , Subra Jean‐François , Pautot Vivien , Letournel Franck , Verny Christophe , Cassereau Julien
Published: March 2017

Introduction

Therapeutic plasma exchange (TPE) can be proposed in the treatment of chronic dysimmune peripheral neuropathies (CDPN). Actual guidelines are however based on few studies, and indications and protocols still remain to be clarified. We conducted a 10‐year retrospective study in order to assess the effectiveness and tolerance of TPE in CDPN.

Methods

All patients treated for CDPN with TPE from October 2006 to March 2016 in the university hospital of Angers were included. Patients were considered responders when they presented a clinical improvement substantial enough to continue the treatment. The Hughes functional grading score was also determined for each patient before and after TPE initiation.

Results

Among the 206 patients who received TPE during the study period, 30 (14.6%) met the diagnostic criteria of CDPN. Four of the five paraprotein neuropathies (PPN) patients (80%) and 8 of the 11 chronic inflammatory demyelinating polyneuropathies (CIDP) patients (72.7%) were responders, with a significant improvement of the Hughes score for the latter (P = 0.013). None of the three Lewis–Sumner and the two POEMS patients showed substantial improvement. Six of the nine anti‐MAG neuropathy patients (66.7%) responded to treatment, with a trend towards improvement of the Hughes score (P = 0.072).

Conclusion

TPE appears to be effective in CIDP and PPN, and ineffective in Lewis‐Sumner and POEMS syndromes. Interestingly, anti‐MAG neuropathy patients showed a good rate of response to TPE. Regarding these preliminary results, a randomized trial would be very worthwhile in this disease for which there is no evidence based treatment to date.
Identification of murine phosphodiesterase 5A isoforms and their functional characterization in HL‐1 cardiac cell line
Authors: Campolo Federica , Zevini Alessandra , Cardarelli Silvia , Monaco Lucia , Barbagallo Federica , Pellegrini Manuela , Cornacchione Marisa , Di Grazia Antonio , De Arcangelis Valeria , Gianfrilli Daniele , Giorgi Mauro , Lenzi Andrea , Isidori Andrea M. , Naro Fabio
Published: March 2017

Phosphodiesterase 5A (PDE5A) specifically degrades the ubiquitous second messenger cGMP and experimental and clinical data highlight its important role in cardiac diseases. To address PDE5A role in cardiac physiology, three splice variants of the PDE5A were cloned for the first time from mouse cDNA library (mPde5a1, mPde5a2, and mPde5a3). The predicted amino acidic sequences of the three murine isoforms are different in the N‐terminal regulatory domain. mPDE5A isoforms were transfected in HEK293T cells and they showed high affinity for cGMP and similar sensitivity to sildenafil inhibition. RT‐PCR analysis showed that mPde5a1, mPde5a2, and mPde5a3 had differential tissue distribution. In the adult heart, mPde5a1 and mPde5a2 were expressed at different levels whereas mPde5a3 was undetectable. Overexpression of mPDE5As induced an increase of HL‐1 number cells which progress into cell cycle. mPDE5A1 and mPDE5A3 overexpression increased the number of polyploid and binucleated cells, mPDE5A3 widened HL‐1 areas, and modulated hypertrophic markers more efficiently respect to the other mPDE5A isoforms. Moreover, mPDE5A isoforms had differential subcellular localization: mPDE5A1 was mainly localized in the cytoplasm, mPDE5A2 and mPDE5A3 were also nuclear localized. These results demonstrate for the first time the existence of three PDE5A isoforms in mouse and highlight their potential role in the induction of hypertrophy.
Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells
Authors: Bourdieu Antonin , Avalon Maryse , Lapostolle Véronique , Ismail Sadek , Mombled Margaux , Debeissat Christelle , Guérinet Marianne , Duchez Pascale , Chevaleyre Jean , Vlaski‐Lafarge Marija , Villacreces Arnaud , Praloran Vincent , Ivanovic Zoran , Brunet de la Grange Philippe
Published: March 2017

Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non‐SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non‐SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia‐induced factors HIF‐1α and HIF‐2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non‐SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy.
Plasma membrane calcium ATPase 4 (PMCA4) co‐ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity
Authors: Olli Kristine E. , Li Kun , Galileo Deni S. , Martin‐DeLeon Patricia A.
Published: March 2017

Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca2+‐ATPase 4 (Pmca4) gene which encodes the highly conserved Ca2+ efflux pump, PMCA4. This is the major Ca2+ clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased. Using co‐immunoprecipitation (Co‐IP) and Fluorescence Resonance Energy Transfer (FRET), we show an association of PMCA4 with the NOSs in elevated cytosolic [Ca2+] in capacitated and Ca2+ ionophore‐treated sperm and with neuronal (nNOS) at basal [Ca2+] (ucapacitated sperm). FRET efficiencies for PMCA4‐eNOS were 35% and 23% in capacitated and uncapacitated sperm, significantly (p < 0.01) different, with the molecules being <10 nm apart. For PMCA4‐nNOS, this interaction was seen only for capacitated sperm where FRET efficiency was 24%, significantly (p < 0.05) higher than in uncapacitated sperm (6%). PMCA4 and the NOSs were identified as interacting partners in a quaternary complex that includes Caveolin1, which co‐immunoprecipitated with eNOS in a Ca2+‐dependent manner. In Pmca4−/− sperm NOS activity was elevated twofold in capacitated/uncapacitated sperm (vs. wild‐type), accompanied by a twofold increase in peroxynitrite levels and significantly (p < 0.001) increased numbers of apoptotic germ cells. The data support a quaternary complex model in which PMCA4 co‐ordinates Ca2+ and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4−/− males. They suggest the involvement of PMCA4 mutations in human asthenospermia, with diagnostic relevance.
The involvement of coordinative interactions in the binding of dihydrolipoamide dehydrogenase to titanium dioxide—Localization of a putative binding site
Authors: Dayan Avraham , Babin Gilad , Ganoth Assaf , Kayouf Nivin Samir , Nitoker Eliaz Neta , Mukkala Srijana , Tsfadia Yossi , Fleminger Gideon
Published: March 2017

Titanium (Ti) and its alloys are widely used in orthodontic and orthopedic implants by virtue to their high biocompatibility, mechanical strength, and high resistance to corrosion. Biointegration of the implants with the tissue requires strong interactions, which involve biological molecules, proteins in particular, with metal oxide surfaces. An exocellular high‐affinity titanium dioxide (TiO2)–binding protein (TiBP), purified from Rhodococcus ruber, has been previously studied in our lab. This protein was shown to be homologous with the orthologous cytoplasmic rhodococcal dihydrolipoamide dehydrogenase (rhDLDH). We have found that rhDLDH and its human homolog (hDLDH) share the TiO2‐binding capabilities with TiBP. Intrigued by the unique TiO2‐binding properties of hDLDH, we anticipated that it may serve as a molecular bridge between Ti‐based medical structures and human tissues. The objective of the current study was to locate the region and the amino acids of the protein that mediate the protein‐TiO2 surface interaction. We demonstrated the role of acidic amino acids in the nonelectrostatic enzyme/dioxide interactions at neutral pH. The observation that the interaction of DLDH with various metal oxides is independent of their isoelectric values strengthens this notion. DLDH does not lose its enzymatic activity upon binding to TiO2, indicating that neither the enzyme undergoes major conformational changes nor the TiO2 binding site is blocked. Docking predictions suggest that both rhDLDH and hDLDH bind TiO2 through similar regions located far from the active site and the dimerization sites. The putative TiO2‐binding regions of both the bacterial and human enzymes were found to contain a CHED (Cys, His, Glu, Asp) motif, which has been shown to participate in metal‐binding sites in proteins.
A schistosomiasis compartment model with incubation and its optimal control
Authors: Ding Chunxiao , Sun Yun , Zhu Yuanguo
Published: March 2017

A new mathematical model included an exposed compartment is established in consideration of incubation period of schistosoma in human body. The basic reproduction number is calculated to illustrate the threshold of disease outbreak. The existence of the disease free equilibrium and the endemic equilibrium are proved. Studies about stability behaviors of the model are exploited. Moreover, control measure assessments are investigated in order to seek out effective control interventions for anti‐schistosomiasis. Then, the corresponding optimal control problem according to the model is presented and solved. Theoretical analyses and numerical simulations induce several prevention and control strategies for anti‐schistosomiasis. At last, a discussion is provided about our results and further work. Copyright © 2017 John Wiley & Sons, Ltd.