bluuebunny/crossref_metadata_2025 huggingface dataset:
Nut‐cracking behaviour in wild‐born, rehabilitated bonobos (Pan paniscus): a comprehensive study of hand‐preference, hand grips and efficiency
Authors: Neufuss Johanna , Humle Tatyana , Cremaschi Andrea , Kivell Tracy L.
Published: August 2016

There has been an enduring interest in primate tool‐use and manipulative abilities, most often with the goal of providing insight into the evolution of human manual dexterity, right‐hand preference, and what behaviours make humans unique. Chimpanzees (Pan troglodytes) are arguably the most well‐studied tool‐users amongst non‐human primates, and are particularly well‐known for their complex nut‐cracking behaviour, which has been documented in several West African populations. However, their sister‐taxon, the bonobos (Pan paniscus), rarely engage in even simple tool‐use and are not known to nut‐crack in the wild. Only a few studies have reported tool‐use in captive bonobos, including their ability to crack nuts, but details of this complex tool‐use behaviour have not been documented before. Here, we fill this gap with the first comprehensive analysis of bonobo nut‐cracking in a natural environment at the Lola ya Bonobo sanctuary, Democratic Republic of the Congo. Eighteen bonobos were studied as they cracked oil palm nuts using stone hammers. Individual bonobos showed exclusive laterality for using the hammerstone and there was a significant group‐level right‐hand bias. The study revealed 15 hand grips for holding differently sized and weighted hammerstones, 10 of which had not been previously described in the literature. Our findings also demonstrated that bonobos select the most effective hammerstones when nut‐cracking. Bonobos are efficient nut‐crackers and not that different from the renowned nut‐cracking chimpanzees of Bossou, Guinea, which also crack oil palm nuts using stones.
First insight into the Neolithic subsistence economy in the north‐east Iberian Peninsula: paleodietary reconstruction through stable isotopes
Authors: Fontanals‐Coll Maria , Eulàlia Subirà M. , Díaz‐Zorita Bonilla Marta , Gibaja Juan F.
Published: August 2016

Objectives

The study of subsistence strategies among Neolithic communities in north‐east Iberia, late‐fifth to early‐fourth millennia cal BC, enables a more in‐depth study of the activities and behavior of the inhabitants of this region, where paleodiets have been little studied. The objectives of this study are, therefore, to determine the diet and subsistence patterns of those communities and to consider whether any relation existed between their subsistence strategies and environmental, geographic, and/or social factors.

Materials and Methods

Bone samples from 25 middle Neolithic human individuals at seven archeological sites and comparative faunal samples were analyzed, and compared with contemporary series in Mediterranean Europe. Carbon and nitrogen isotope ratios (δ13C and δ15N) of bone collagen were studied to determine the dietary patterns.

Results

Dietary habits proved to be similar between communities, apart from some interpopulational variations in subsistence strategies. Their diet was based on C3 terrestrial resources with a major vegetal protein component.

Discussion

The reported variations in interpopulational subsistence strategies among the compared Mediterranean societies do not seem to be directly related to the settlement region. Together with archeological data, this indicates the influence of socioeconomic factors in the Neolithic human diet. A general tendency toward a lesser use of aquatic resources is seen in this period in Iberia and the rest of the Mediterranean, as also documented for contemporary communities in the west and north of Europe. The data obtained will be important for further studies of socioeconomic patterns in European Neolithic societies.
Aquatische Ökotoxizität von Nanopartikeln – Versuche zur Aufklärung von Nanopartikeleffekten
Authors: Skjolding Lars Michael , Sørensen Sara Nørgaard , Hartmann Nanna Bloch , Hjorth Rune , Hansen Steffen Foss , Baun Anders
Published: August 2016

Die Zahl von Produkten, die synthetische Nanopartikel (engineered nanoparticles, ENPs) enthalten, ist stark gestiegen, und damit wachsen auch die Bedenken im Hinblick auf mögliche ökotoxikologische Wirkungen von ENPs. Die Gewährleistung einer sicheren und nachhaltigen Nutzung von ENPs erfordert Umweltverträglichkeitsprüfungen und damit auch relevante und zuverlässige ökotoxikologische Daten. Während die Zahl an Publikationen über ökotoxikologische Effekte und die Aufnahme von ENPs schnell wächst, bleibt die Eignung von ENP‐Daten für die Risikobewertung fraglich. Eine bedeutende Wissenslücke betrifft mögliche Nanopartikeleffekte, wenn Testorganismen ENPs in aquatischen Testsystemen ausgesetzt sind. Diese Lücke ist wegen der großen Bandbreite von ENP‐Typen und ihres andersartigen Verhaltens gegenüber demjenigen gelöster Chemikalien in den Ökotoxizitäts‐Testsystemen schwer zu füllen. Das Risiko falsch‐negativer wie auch falsch‐positiver Resultate ist hoch und meist schwer abzuschätzen. Dieser Aufsatz skizziert einige der Tücken von ENP‐Toxizitätstests, die zu Fehlinterpretationen führen könnten. Des Weiteren schlägt er biologische Reaktionen vor, die es zu berücksichtigen gilt, um mögliche Effekte von Nanopartikeln in den aquatischen Testorganismen aufzuzeigen.
Aquatic Ecotoxicity Testing of Nanoparticles—The Quest To Disclose Nanoparticle Effects
Authors: Skjolding Lars Michael , Sørensen Sara Nørgaard , Hartmann Nanna Bloch , Hjorth Rune , Hansen Steffen Foss , Baun Anders
Published: August 2016

The number of products on the market containing engineered nanoparticles (ENPs) has increased significantly, and concerns have been raised regarding their ecotoxicological effects. Environmental safety assessments as well as relevant and reliable ecotoxicological data are required for the safe and sustainable use of ENPs. Although the number of publications on the ecotoxicological effects and uptake of ENPs is rapidly expanding, the applicability of the reported data for hazard assessment is questionable. A major knowledge gap is whether nanoparticle effects occur when test organisms are exposed to ENPs in aquatic test systems. Filling this gap is not straightforward, because of the broad range of ENPs and the different behavior of ENPs compared to “ordinary” (dissolved) chemicals in the ecotoxicity test systems. The risk of generating false negatives, and false positives, in the currently used tests is high, and in most cases difficult to assess. This Review outlines some of the pitfalls in the aquatic toxicity testing of ENPs which may lead to misinterpretation of test results. Response types are also proposed to reveal potential nanoparticle effects in the aquatic test organisms.
Iridium(III)‐Catalyzed Regioselective Intermolecular Unactivated Secondary Csp3−H Bond Amidation
Authors: Xiao Xinsheng , Hou Cheng , Zhang Zhenhui , Ke Zhuofeng , Lan Jianyong , Jiang Huanfeng , Zeng Wei
Published: August 2016

For the first time, a highly regioselective intermolecular sulfonylamidation unactivated secondary Csp3−H bond has been achieved using IrIII catalysts. The introduced N,N’‐bichelating ligand plays a crucial role in enabling iridium–nitrene insertion into a secondary Csp3−H bond via an outer‐sphere pathway. Mechanistic studies and density functional theory (DFT) calculations demonstrated that a two‐electron concerted nitrene insertion was involved in this Csp3−H amidation process. This method tolerates a broad range of linear and branched‐chain N‐alkylamides, and provides efficient access to diverse γ‐sulfonamido‐substituted aliphatic amines.
Re‐elucidation of the acid‐catalyzed urea–formaldehyde reactions: A theoretical and13C‐NMR study
Authors: Li Taohong , Liang Jiankun , Cao Ming , Guo Xiaoshen , Xie Xiaoguang , Du Guanben
Published: August 2016

The acid‐catalyzed urea–formaldehyde reactions were reexamined in detail by using quantum chemistry method and13C‐NMR determinations. Some issues in the synthesis theory that were not well understood previously have been addressed and clarified. The identified reaction mechanisms and calculated energy barriers suggest that the competitive formations of methylene and methylene ether linkages are kinetically affected by both reaction energy barriers and steric hindrance effect. The thermodynamic properties determine that the methylene linkages are dominant at the late condensation stage. The theoretical results well rationalized the observed different changing processes of resin structures with different F/U molar ratios. The previously proposed mechanism for transformation of methylene ether linkage to methylene linkage cannot explain the structural changes during condensation, and thus, other mechanisms were proposed. The calculated results for uron explained the fact that the formation of such structure is much slower than other structures under weak acidic condition. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 44339.
Effects of butyl acrylate modified polypropylene on structural and thermal properties of foamed polypropylene
Authors: Su Lifen , Zhang Wei , Xia Ru , Miao Jibin , Yang Bin , Qian Jiasheng , Ruan Fang , Zheng Zhengzhi
Published: August 2016

In this work, the melt strength of PP matrix was reinforced by crosslinking‐modified PP (CM‐PP) which was yielded by peroxide‐initiated crosslinking of linear PP with butyl acrylate (BA). The nano‐silica aerogel (nano‐SiO2) worked as a nucleating agent for foaming. The effects of CM‐PP with the various contents of BA on the foaming behavior and thermal property of PP were studied by measurements of density, thermal conductivity, Vicat softening temperature and SEM. The results showed that the foamed PP got the best properties when the crosslinking PP modified with the weight ratio of butyl acrylate was 10 wt %. The density of the obtained foamed PP with uniform closed cells was as low as 0.23 g/cm3, the thermal conductivity was 0.044 W/(m K), and the Vicat softening temperature was 120  °C. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44340.
Brief Report: Sex Ratio of Offspring Born to Women With Systemic Lupus Erythematosus or Rheumatoid Arthritis
Authors: Arkema Elizabeth V. , Askling Johan , Salmon Jane E. , Simard Julia F.
Published: August 2016

Objective

To determine whether the sex ratio among offspring born to women with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) is different from that in the general population.

Methods

Women with a singleton delivery were identified from the Swedish Medical Birth Register (1973–2012) and linked to the National Patient Register (1964–2012) to identify those with prevalent SLE or RA. A sample of general population comparators was identified from the Swedish Total Population Register. We calculated the percentages of males born to women with SLE, women with RA, and women in the general population, as well as the risk ratio (RR) for having a male child among first births and all births. We also examined a history of antiphospholipid syndrome in the SLE population, using International Classification of Disease codes before or at delivery.

Results

We identified 661 women with SLE and 1,136 women with RA before their first delivery. There were a total of 1,401 deliveries to women with SLE and a total of 2,674 deliveries to women with RA. Compared with women in the general population, women with SLE and those with RA had a lower risk of having a first‐born male (RR 0.92 [95% confidence interval 0.85–1.00] and RR 0.93 [95% confidence interval 0.87–0.99], respectively). Among all births, the percentage of male offspring remained lower than that in the general population, but the difference was not statistically significant for RA.

Conclusion

The proportion of male offspring born to women with prevalent SLE or RA at delivery was lower than that in the general population, although the difference was small. Chronic inflammation may affect the sex ratio through fetal loss in early gestation.
Regioselective Functionalization of 3‐Hydroxy‐pyridine Carboxylates by Neighboring Group Assistance
Authors: Wojtas K. Philip , Lu Jin‐Yong , Krahn Daniel , Arndt Hans‐Dieter
Published: August 2016

Regioselective hydrolysis, transesterification, and aminolysis of unactivated, highly substituted pyridine esters were realized under mild conditions by employing neighboring group assisted catalysis. Excellent yields were achieved without active removal of the alcohol byproduct. Regioselective aminolysis had a considerable substrate scope ([hetero]aryl, alkyl and amino acid). A mechanism involving assistance by the deprotonated phenolic OH‐group is suggested for hydrolysis and transesterification.
Embracing Chance Tactically: A Different Perspective on Risk Taking
Authors: Tykocinski Orit E. , Amir Inbal , Ayal Shahar
Published: August 2016

Although they value certainty, people are willing to take risks to avoid losses. Consequently, they are risk‐seeking in the domain of losses but risk‐avoidant in the domain of gains. This behavior, frequently demonstrated in framing experiments, is traditionally explained in terms of prospect theory. We suggest a different account whereby involving chance in one's decisions may serve a strategic impression‐formation function. In the domain of losses actors may embrace chance to distance themselves from the outcomes and deflect possible blame. Given potential gains, however, actors may avoid uncertainty to enhance their association with valued outcomes. We test this idea by manipulating the level of actors' personal responsibility for the decision outcomes. The results of four studies consistently showed that when personal responsibility is high, the original framing effect is replicated (i.e., greater risk‐taking when choices are framed in terms of losses rather than gains). However, when because of assigned role or decision circumstances, actors experience low personal responsibility for the outcomes, and the classic framing effect is eliminated. Copyright © 2016 John Wiley & Sons, Ltd.
Anti‐inflammatory effects of melatonin in multiple sclerosis
Authors: Farez Mauricio F. , Calandri Ismael L. , Correale Jorge , Quintana Francisco J.
Published: August 2016

Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4+ T cells secreting IFN‐γ (TH1) or IL‐17 (TH17); and FoxP3+ regulatory T cells and IL‐10+ type 1 regulatory T cells (Tr1 cells) is thought to play an important role in disease activity. Recent evidence suggests that melatonin ameliorates multiple sclerosis by controlling the balance between effector and regulatory cells, suggesting that melatonin‐triggered signaling pathways are potential targets for therapeutic intervention. Here, we review the available data on the effects of melatonin on immune processes relevant for MS and discuss its therapeutic potential.
Two liquid chromatographic approaches for the simultaneous determination of xipamide and its degradation product (2,6‐xylidine) using time‐programmed fluorescence detection
Authors: Tolba M.M. , Belal F.
Published: August 2016

A study of the performance of reversed‐phase chromatography with a programmable multiwavelength fluorimetric technique using either conventional hydro‐organic or micellar eluent is established for the determination of xipamide (XIP) in the presence of its degradation product, 2,6‐xylidine (XY). In conventional liquid chromatography (CLC), the analyses were carried out on a Promosil ODS 100 Å column (250 mm × 4.6 mm i.d., 5 μm) using a mobile phase consisting of methanol/0.1 M phosphate buffer (65: 35, v/v) at pH 4.0. For micellar liquid chromatography (MLC), a short Spherisorb column (150 mm × 4.6 mm i.d., 5 μm) was employed in conjunction with a greener mobile phase (pH 5.0) containing 0.1 M sodium dodecyl sulfate and 15% n‐propanol. CLC proved to be superior to MLC in terms of sensitivity for the determination of the degradation product because it could detect trace amounts down to 10.0 ng/ml of XY as a degradation product in XIP. However, MLC represents an eco‐friendly approach for the simultaneous determination of XIP and XY. In addition, the opportunity for the direct introduction of biological matrices into the chromatographic system is one of the distinctive benefits of MLC. The proposed methods were applied for the determination of XIP in its tablets, human urine and content uniformity testing. The results of the proposed methods were statistically compared with those obtained using the comparison fluorimetric method, revealing no significant differences in the performance of the methods regarding accuracy and precision.
The N‐terminal pro‐domain of the kalata B1 cyclotide precursor is intrinsically unstructured
Authors: Daly Norelle L. , Gunasekera Sunithi , Clark Richard J. , Lin Feng , Wade John D. , Anderson Marilyn A. , Craik David J.
Published: August 2016

Cyclotides are plant‐derived, gene‐encoded, circular peptides with a range of host‐defense functions, including insecticidal activity. They also have potential as pharmaceutical scaffolds and understanding their biosynthesis is important to facilitate their large‐scale production. Insights into the biosynthesis of cyclotides are emerging but there are still open questions, particularly regarding the influence of the structure of the precursor proteins on processing/biosynthetic pathways. The precursor protein of kalata B1, encoded by the plant Oldenlandia affinis, contains N‐ and C‐terminal propeptides that flank the mature cyclotide domain. The C‐terminal region (ctr) is important for the cyclization process, whereas the N‐terminal repeat (ntr) has been implicated in vacuolar targeting. In this study we examined the structure and folding of various truncated constructs of the ntr coupled to the mature domain of kalata B1. Despite the ntr having a well‐defined helical structure in isolation, once coupled to the natively folded mature domain there is no evidence of an ordered structure. Surprisingly, the ntr appears to be highly disordered and induces self‐association of the precursor. This self‐association might be associated with the role of the ntr as a vacuolar‐targeting signal, as previously shown for unrelated storage proteins.
To see or not to see; the ability of the magno‐ and parvocellular response to manifest itself in the VEP determines its appearance to a pattern reversing and pattern onset stimulus
Authors: Marcar Valentine L. , Jäncke Lutz
Published: August 2016

Introduction

The relationship between stimulus property, brain activity, and the VEP is still a matter of uncertainty.

Method

We recorded the VEP of 43 volunteers when viewing a series of dartboard images presented as both a pattern reversing and pattern onset/offset stimulus. Across the dartboard images, the total stimulus area undergoing a luminance contrast change was varied in a graded manner.

Results

We confirmed the presence of two independent neural processing stages. The amplitude of VEP components across our pattern reversing stimuli signaled a phasic neural response based on a temporal luminance contrast selective mechanism. The amplitude of VEP components across the pattern onset stimuli signaled both a phasic and a tonic neural response based on a temporal‐ and spatial luminance contrast selective mechanism respectively. Oscillation frequencies in the VEP suggested modulation of the phasic neural response by feedback from areas of the dorsal stream, while feedback from areas of the ventral stream modulated the tonic neural response. Each processing stage generated a sink and source phase in the VEP. Source localization indicated that during the sink phase electric current density was highest in V1, while during the source phase electric current density was highest in extra‐striate cortex. Our model successfully predicted the appearance of the VEP to our images whether presented as a pattern reversing or a pattern onset/offset stimulus.

Conclusions

Focussing on the effects of a phasic and tonic response rather than contrast response function on the VEP, enabled us to develop a theory linking stimulus property, neural activity and the VEP.
A functional and clinical reinterpretation of human perineal neuromuscular anatomy: Application to sexual function and continence
Authors: PLOCHOCKI JEFFREY H. , RODRIGUEZ‐SOSA JOSE R. , ADRIAN BRENT , RUIZ SAUL A. , HALL MARGARET I.
Published: August 2016

Modern anatomical and surgical references illustrate perineal muscles all innervated by branches of the pudendal nerve but still organized into anatomically distinct urogenital and anal triangles with muscles inserting onto a central perineal body. However, these conflict with the anatomy commonly encountered during dissection. We used dissections of 43 human cadavers to characterize the anatomical organization of the human perineum and compare our findings to standard references. We found bulbospongiosus and the superficial portion of the external anal sphincter (EAS) were continuous anatomically with a common innervation in 92.3% of specimens. The superficial transverse perineal muscle inserted anterior and lateral to the midline, interdigitating with bulbospongiosus. The three EAS subdivisions were anatomically discontinuous. Additionally, in 89.2% of our sample the inferior rectal nerve emerged as a branch of S3 and S4 distinct from the pudendal nerve and innervated only the subcutaneous EAS. Branches of the perineal nerve innervated bulbospongiosus and the superficial EAS and nerve to levator ani innervated the deep EAS. In conclusion, we empirically demonstrate important and clinically relevant differences with perineal anatomy commonly described in standard texts. First, independent innervation to the three portions of EAS suggests the potential for functional independence. Second, neuromuscular continuity between bulbospongiosus and superficial EAS suggests the possibility of shared or overlapping function of the urogenital and anal triangles. Clin. Anat. 29:1053–1058, 2016. © 2016 Wiley Periodicals, Inc.
Variations of Leaf Cuticular Waxes Among C3 and C4 Gramineae Herbs
Authors: He Yuji , Gao Jianhua , Guo Na , Guo Yanjun
Published: August 2016

Modern C4 plants are commonly distributed in hot and dry environments whereas C3 plants predominate in cool and shade areas. At the outmost of plant surface, the deposition and chemical composition of cuticular waxes vary under different environmental conditions. However, whether such variation of cuticular wax is related to the distribution of C3 and C4 under different environmental conditions is still not clear. In this study, leaves of six C3 Gramineae herbs distributed in spring, Roegneria kamoji, Polypogon fugax, Poa annua, Avena fatua, Alopecurus aequalis, and Oplismenus undulatifolius, and four C4 and one C3 Gramineae herbs distributed in summer, Digitaria sanguinalis, Eleusine indica, Setaria viridis, S. plicata, and O. undulatifolius, were sampled and analyzed for cuticular wax. Plates were the main epicuticular wax morphology in both C3 and C4 plants except S. plicata. The plates melted in C4 plants but not in C3 plants. The total cuticular wax amounts in C4 plants were significantly lower than those in C3 plants, except for O. undulatifolius. Primary alcohols were the most abundant compounds in C3 plants, whereas n‐alkanes were relatively the most abundant compounds in C4 plants. C29 was the most abundant n‐alkane in C3 plants except for O. undulatifolius, whereas the most abundant n‐alkane was C31 or C33 in C4 plants. The average chain length (ACL) of n‐alkanes was higher in C4 than in C3 plants, whereas the ACL of n‐alkanoic acids was higher in C3 than C4 plants. The cluster analysis based on the distribution of n‐alkanes clearly distinguished C3 and C4 plants into two groups, except for O. undulatifolius which was grouped with C4 plants. These results suggest that the variations of cuticular waxes among C3 and C4 Gramineae herbs are related to the distribution of C3 and C4 plants under different environmental conditions.
Innovative use of a guideliner catheter to assist in snare retrieval of an entrapped kinked guide catheter during transradial coronary intervention
Authors: Korabathina Ravi , Levine Jason C. , Coppola John T.
Published: August 2016

Rescue techniques that enable removal of severe intravascular catheter kinking are always worthwhile. We herein demonstrate the novel employment of a GuideLiner support catheter to assist in the removal of a kinked and entrapped guide catheter within the radial artery during coronary intervention. © 2016 Wiley Periodicals, Inc.
Synthesis and Solid‐State NMR Characterization of a Robust, Pyridyl‐Based Immobilized Wilkinson's Type Catalyst with High Catalytic Performance
Authors: Srour Mohamad , Hadjiali Sara , Sauer Grit , Brunnengräber Kai , Breitzke Hergen , Xu Yeping , Weidler Heiko , Limbach Hans‐Heinrich , Gutmann Torsten , Buntkowsky Gerd
Published: August 2016

A novel strategy for the immobilization of Wilkinson's catalyst on silica nanoparticles is presented, employing pyridyl linkers as anchoring groups. The coordination binding of the catalyst to the pyridyl linker via ligand exchange of the trans‐phosphine group is verified by 1 D and 2 D solid‐state NMR spectroscopy. Catalytic activities are monitored by GC employing the hydrogenation of styrene as model reaction, and the leaching properties as well as the robustness of the catalyst are investigated. The resulting immobilized catalyst shows high catalytic activity, which is within a factor of three comparable to the homogeneous catalyst, and excellent stability in leaching tests. Finally, it is efficient to produce hyperpolarization in solution by employing parahydrogen‐enriched hydrogen gas for hydrogenation.
Effect of the fluid shear rate on the induction time of CO2‐THF hydrate formation
Authors: Douïeb Sélim , Archambault Simon , Fradette Louis , Bertrand François , Haut Benoît
Published: August 2016

A method that allows the effect of the fluid shear rate on the induction time of gas hydrate formation to be characterized was developed and applied to CO2‐THF hydrate formation. The investigation of the effect of the application of a constant shear rate (50 to 300 s−1) to the liquid phase from which the hydrates are formed revealed that the mean induction time decreases significantly as the applied shear rate increases. This could primarily be attributed to a decrease in the time required for stable gas hydrate nuclei to be generated and to grow to a macroscopically detectable size. The induction time could also be significantly reduced by the application of a high shear rate (900 s−1) to the liquid phase for a relatively short, defined period of time.
Design and Rationale of the RE‐DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting
Authors: Cannon Christopher P. , Gropper Savion , Bhatt Deepak L. , Ellis Stephen G. , Kimura Takeshi , Lip Gregory Y.H. , Steg Ph. Gabriel , ten Berg Jurriën M. , Manassie Jenny , Kreuzer Jörg , Blatchford Jon , Massaro Joseph M. , Brueckmann Martina , Ferreiros Ripoll Ernesto , Oldgren Jonas , Hohnloser Stefan H. ,   on behalf of the RE‐DUAL PCI Steering Committee and Investigators
Published: August 2016

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest‐sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE‐DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open‐label, blinded‐endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibitor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibitor (either clopidogrel or ticagrelor, and low‐dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ∼ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.
Development of Dipeptidic hGPR54 Agonists
Authors: Doebelin Christelle , Bertin Isabelle , Schneider Séverine , Schmitt Martine , Bourguignon Jean‐Jacques , Ancel Caroline , Simonneaux Valerie , Simonin Frédéric , Bihel Frédéric
Published: August 2016

A series of dipeptides were designed as potential agonists of the human KiSS1‐derived peptide receptor (hGPR54). While the sequence Arg‐Trp‐NH2 was the most efficient in terms of affinity, we established a convergent synthetic strategy to optimize the N terminus. Using two successive Sonogashira cross‐coupling reactions on a solid‐supported peptide, we were able to introduce various alkynes at the N terminus to afford compounds with sub‐micromolar affinities for hGPR54. However, functional assays indicated the benzoylated dipeptide Bz‐Arg‐Trp‐NH2 as the most promising compound in terms of agonistic properties. Interestingly, this compound appeared much more stable than the endogenous neuropeptide kisspeptin, both in serum and in liver microsomes of rats. This compound was also found to be able to induce a significant in vivo increase in testosterone levels in male rats.
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST): Scale development and validation
Authors: Hutcheson Katherine A. , Barrow Martha P. , Barringer Denise A. , Knott Jodi K. , Lin Heather Y. , Weber Randal S. , Fuller Clifton D. , Lai Stephen Y. , Alvarez Clare P. , Raut Janhavi , Lazarus Cathy L. , May Annette , Patterson Joanne , Roe Justin W. G. , Starmer Heather M. , Lewin Jan S.
Published: August 2016

BACKGROUND

The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) is the universal framework for toxicity reporting in oncology trials. The objective of this study was to develop a CTCAE‐compatible modified barium swallow (MBS) grade for the purpose of grading pharyngeal dysphagia as a toxicity endpoint in cooperative‐group organ‐preservation trials for head and neck cancer (HNC). It was hypothesized that a 5‐point, CTCAE‐compatible MBS grade (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]) based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings would be feasible and psychometrically sound.

METHODS

A modified Delphi exercise was conducted for content validation, expert consensus, and operationalization of DIGEST criteria. Two blinded raters scored 100 MBSs conducted before or after surgical or nonsurgical organ preservation. Intrarater and interrater reliability was tested with weighted κ values. Criterion validity against oropharyngeal swallow efficiency (OPSE), the Modified Barium Swallow Impairment Profile (MBSImP™©), the MD Anderson Dysphagia Inventory (MDADI), and the Performance Status Scale for Head and Neck Cancer Patients (PSS‐HN) was assessed with a 1‐way analysis of variance and post hoc pairwise comparisons between DIGEST grades.

RESULTS

Intrarater reliability was excellent (weighted κ = 0.82‐0.84) with substantial to almost perfect agreement between raters (weighted κ = 0.67‐0.81). DIGEST significantly discriminated levels of pharyngeal pathophysiology (MBSImP™©: r = 0.77; P < .0001), swallow efficiency (OPSE: r = –0.56; P < .0001), perceived dysphagia (MDADI: r = –0.41; P < .0001), and oral intake (PSS‐HN diet: r = –0.49; P < .0001).

CONCLUSIONS

With the development of DIGEST, the MBS rating has been adapted to the CTCAE nomenclature of ordinal toxicity grading used in oncology trials. DIGEST offers a psychometrically sound measure for HNC clinical trials and investigations of toxicity profiles, dose responses, and predictive modeling. Cancer 2017;62–70. © 2016 American Cancer Society.
Coming to terms with NIFTP: A provisional approach for cytologists
Authors: Krane Jeffrey F. , Alexander Erik K. , Cibas Edmund S. , Barletta Justine A.
Published: August 2016

The new term NIFTP (noninvasive follicular thyroid neoplasm with papillary‐like nuclear features) for some thyroid tumors poses significant challenges for cytopathologists. This commentary represents a provisional approach to NIFTP that others may consider adopting and that will hopefully prompt further discussion and research on how NIFTP should fit into future cytology practice.
Emotional Processing Theory Put to Test: A Meta‐Analysis on the Association Between Process and Outcome Measures in Exposure Therapy
Authors: Rupp Christian , Doebler Philipp , Ehring Thomas , Vossbeck‐Elsebusch Anna N.
Published: August 2016

In order to test the predictions derived from emotional processing theory (EPT), this meta‐analysis examined correlations between outcome of exposure therapy and three process variables: initial fear activation (IFA), within‐session habituation (WSH) and between‐session habituation (BSH). Literature search comprised a keyword‐based search in databases, a reverse search and the examination of reference lists. Of the 21 studies included in the analyses, 17 provided data concerning IFA (57 endpoints, total N = 490), five concerning WSH (7 endpoints, total N = 116) and eight concerning BSH (22 endpoints, total N = 304). Owing to this data structure, analyses were performed using robust variance estimation with random‐effects models being assumed a priori.

Results indicated that WSH and BSH are positively related to treatment outcome. By contrast, the statistical association between IFA and outcome of exposure was not confirmed, whereas our moderator analysis suggested that physiological process measures lead to higher correlations than non‐physiological ones. The results for IFA and BSH were affected by selective reporting. In sum, our results do not specifically strengthen EPT while matching other theoretical perspectives such as inhibitory learning and reality testing. Further research is needed to provide recommendations concerning the best way of delivering exposure therapy. Copyright © 2016 John Wiley & Sons, Ltd.

Key Practitioner Message

This meta‐analysis examined three variables of emotional processing theory (EPT).

Initial fear activation was not linearly related to outcomes of exposure therapy.

Habituation within and between sessions were shown to correlate with outcome.

Outcome reporting bias was shown to play a crucial role in this meta‐analysis.

Results do not specifically support EPT.
Deconstructing Designer Drugs
Authors: Sellers EM
Published: August 2016

The concepts behind current “designer drugs” are not new. For several centuries, chemical synthesis has made drugs more specific and more selective. However, headline designer drugs now are different and a serious public health problem because they are illicit unregulated chemical knockoffs of approved psychoactive stimulant, sedative, or perception‐altering controlled substances.
A practical approach to symmorphism
Authors: Nespolo Massimo
Published: August 2016

A common misunderstanding in the nature of symmorphic space groups, often incorrectly defined as devoid of screw axes and glide planes, is pointed out and the origin of this misunderstanding is critically analysed. The features of symmorphic space groups are illustrated with concrete examples and a detailed classification is presented.
Shape‐selective Valorization of Biomass‐derived Glycolaldehyde using Tin‐containing Zeolites
Authors: Tolborg Søren , Meier Sebastian , Saravanamurugan Shunmugavel , Fristrup Peter , Taarning Esben , Sádaba Irantzu
Published: August 2016

A highly selective self‐condensation of glycolaldehyde to different C4 molecules has been achieved using Lewis acidic stannosilicate catalysts in water at moderate temperatures (40–100 °C). The medium‐sized zeolite pores (10‐membered ring framework) in Sn‐MFI facilitate the formation of tetrose sugars while hindering consecutive aldol reactions leading to hexose sugars. High yields of tetrose sugars (74 %) with minor amounts of vinyl glycolic acid (VGA), an α‐hydroxyacid, are obtained using Sn‐MFI with selectivities towards C4 products reaching 97 %. Tin catalysts having large pores or no pore structure (Sn‐Beta, Sn‐MCM‐41, Sn‐SBA‐15, tin chloride) led to lower selectivities for C4 sugars due to formation of hexose sugars. In the case of Sn‐Beta, VGA is the main product (30 %), illustrating differences in selectivity of the Sn sites in the different frameworks. Under optimized conditions, GA can undergo further conversion, leading to yields of up to 44 % of VGA using Sn‐MFI in water. The use of Sn‐MFI offers multiple possibilities for valorization of biomass‐derived GA in water under mild conditions selectively producing C4 molecules.
Low Temperature Solution‐Processed Sb:SnO2 Nanocrystals for Efficient Planar Perovskite Solar Cells
Authors: Bai Yang , Fang Yanjun , Deng Yehao , Wang Qi , Zhao Jingjing , Zheng Xiaopeng , Zhang Yang , Huang Jinsong
Published: August 2016

Inorganic metal oxide electron‐transport layers (ETLs) have the potential to yield perovskite solar cells with improved stability, but generally need high temperature to form conductive and defect‐less forms, which is not compatible with the fabrication of flexible and tandem solar cells. Here, we demonstrate a facile strategy for developing efficient inorganic ETLs by doping SnO2 nanocrystals (NCs) with a small amount of Sb using a low‐temperature solution‐processed method. The electrical conductivity was remarkably enhanced by Sb‐doping, which increased the carrier concentration in Sb:SnO2 NCs. Moreover, the upward shift of the Fermi level owing to doping results in improved energy level alignment, which led to reduced charge recombination, and thus longer electron recombination lifetime and improved open‐circuit voltage (VOC). Therefore, Sb‐doping of SnO2 significantly enhanced the photovoltaic performance of planar perovskite devices by increasing the fill factor and VOC, and reducing photocurrent hysteresis, extending the potential application of low‐temperature‐processed ETLs in future flexible and tandem solar cells.
Plexiform angiomyxoid myofibroblastic tumor of the stomach: A case report
Authors: Liang Li , Fanzong Lin , Peixi Zhang , Cuihong Han
Published: August 2016

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a rare mesenchymal tumor of the stomach. To date, about 40 cases of PAMT have been reported in the literature. This tumor is not specific in clinical manifestations and microscopically characterized by a plexiform growth pattern. Here, we report the case of an 11‐year‐old male patient who was diagnosed with PAMT. He had a complaint of right epigastric discomfort with episodic pain, gastroscopy displayed a submucosal bulge at the pylorus, and CT showed a mass in the right abdomen with uneven, delayed enhancement, and a partial gastrectomy revealed a tumor at the pylorus. Histologically, the tumor was multinodular and rich in blood vessels with thin wall; the interstitium had abundant myxomatous stroma; the tumor cells were spindle‐shaped, star‐shaped, or oval. Immunohistochemically, the tumor cells were positive for Calponin, Caldesmon, and SMA, but negative for CD34, ALK, S‐100, desmin, CD117, and Dog‐1. This patient was followed up for 12 months, and recurrence or metastasis was not observed. Diagn. Cytopathol. 2017;45:55–58. © 2016 Wiley Periodicals, Inc.
Genetic signatures of a range expansion in natura: when clones play leapfrog
Authors: Becheler Ronan , Xhaard Constance , Klein Etienne K. , Hayden Katherine J. , Frey Pascal , De Mita Stéphane , Halkett Fabien
Published: August 2016

The genetic consequences of range expansions have generally been investigated at wide geographical and temporal scales, long after the colonization event. A unique ecological system enabled us to both monitor the colonization dynamics and decipher the genetic footprints of expansion over a very short time period. Each year an epidemic of the poplar rust (Melampsora larici‐populina) expands clonally and linearly along the Durance River, in the Alps. The colonization dynamics observed in 2004 showed two phases with different genetic outcomes. Upstream, fast colonization maintained high genetic diversity. Downstream, the colonization wave progressively faltered, diversity eroded, and differentiation increased, as expected under recurrent founder events. In line with the high dispersal abilities of rust pathogens, we provide evidence for leapfrog dispersal of clones. Our results thus emphasize the importance of colonization dynamics in shaping spatial genetic structure in the face of high gene flow.
Top‐down limitation of lemmings revealed by experimental reduction of predators
Authors: Fauteux Dominique , Gauthier Gilles , Berteaux Dominique
Published: August 2016

It is generally recognized that delayed density‐dependence is responsible for cyclic population dynamics. However, it is still uncertain whether a single factor can explain why some rodent populations fluctuate according to a 3–4 yr periodicity. There is increasing evidence that predation may play a role in lemming population cycles, although this effect may vary seasonally. To address this issue, we conducted an experiment where we built a large exclosure (9 ha) to protect brown lemmings (Lemmus trimucronatus) from avian and terrestrial predators. We tested the hypothesis that predation is a limiting factor for lemmings by measuring the demographic consequences of a predator reduction during the growth and peak phases of the cycle. We assessed summer (capture‐mark‐recapture methods) and winter (winter nest sampling) lemming demography on two grids located on Bylot Island, Nunavut, Canada from 2008 to 2015. The predator exclosure became fully effective in July 2013, allowing us to compare demography between the control and experimental grids before and during the treatment. Lemming abundance, survival and proportion of juveniles were similar between the two grids before the treatment. During the predator‐reduction period, summer densities were on average 1.9× higher inside the experimental grid than the control and this effect was greatest for adult females and juveniles (densities 2.4× and 3.4× higher, respectively). Summer survival was 1.6× higher on the experimental grid than the control whereas body mass and proportion of juveniles were also slightly higher. Winter nest densities remained high inside the predator reduction grid following high summer abundance, but declined on the control grid. These results confirm that predation limits lemming population growth during the summer due to its negative impact on survival. However, it is possible that in winter, predation may interact with other factors affecting reproduction and ultimately population cycles.
Asymptomatic CMV infections in long‐term renal transplant recipients are associated with the loss of FcRγ from LIR‐1+ NK cells
Authors: Makwana Nandini B. , Foley Bree , Lee Silvia , Fernandez Sonia , Irish Ashley B. , Price Patricia
Published: August 2016

While it is established that cytomegalovirus (CMV) disease affects NK‐cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age‐matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR‐1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK‐cell function as assessed by TNF‐α and CD107a expression. The most active NK cells were FcRγ–LIR‐1+NKG2C– and displayed high antibody‐dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom‐free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR‐1.
An Off–On–Off Fluorescent Sensor for pH Windows Based on the 13aneN4–Zn2+ System
Authors: Amendola Valeria , Bergamaschi Greta , Dacarro Giacomo , Denat Franck , Boschetti Frederic , Nikolantonaki Maria , Gougeon Regis , D'Alessio Giulia , Viaux Anne‐Sophie , Bertheau Lucie , Guyot Stéphane , Sok Nicolas , Pallavicini Piersandro
Published: August 2016

The new ligand L was prepared and features a 13‐membered tetraaza macrocyclic ring with a 1,8‐naphthalimide fluorophore appended to a C atom of its backbone. The protonation constants of L as well as its complexation constants with Zn2+ ions were determined in 1:1 water/methanol solutions by potentiometric titrations. Fluorimetric pH titrations were performed with L alone and L in the presence of Zn2+ ions (1:1), and the species distributions (%) versus pH were compared. A window‐shaped fluorescence trend was observed with pH for the L/Zn2+ system, which behaves as an off–on–off pH sensor. The on window is centred in the 6.5–7.5 pH range, in correspondence with the formation of [ZnL]2+. The ligand L also works as a sensor for Zn2+ ions in this pH window, which includes the physiological pH value (7.4). Accordingly, L was used as a probe for the visualization of the Zn2+ pools in Saccharomyces cerevisiae yeast cells at pH 7.4 and has the additional ability to distinguish between living and dead cells.
Optimal Size Matching and Minimal Distortion Energy: Implications for Natural Selection by the Macrocycle of the Iron Species in Heme
Authors: Liu Qiuhua , Tang Min , Zeng Wennan , Zhang Xi , Wang Jianxiu , Zhou Zaichun
Published: August 2016

In heme, a porphyrin macrocycle naturally selects an iron ionic species. It was found that this natural combination is directly related to the geometry sizes of both components. Three series of monostrapped nonplanar metalloporphyrins [M = FeIIICl, CoII, NiII] and their metal‐free counterparts were synthesized as model systems, their core sizes were compared, and density functional theory computations were used to calculate the molecular distortion energies. The results indicate that optimal size matching of both is to maintain minimal distortion energy of the macrocycle. This shows that the mutual selection process between the macrocycle and the metal ion is mainly based on the principle of minimum energy to tune the electronic structure of the central metal ion; this may be a common principle in natural tetrapyrroles containing metal species. The structural parameters of all the model compounds were directly obtained from their crystal structures.