bluuebunny/crossref_metadata_2025 huggingface dataset:
Zwitterionic Polymer‐Coated Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Low Protein Interaction and High Biocompatibility
Authors: Pombo‐García Karina , Weiss Stephan , Zarschler Kristof , Ang Ching‐Seng , Hübner René , Pufe Johanna , Meister Sebastian , Seidel Jürgen , Pietzsch Jens , Spiccia Leone , Stephan Holger , Graham Bim
Published: August 2016

We report the synthesis and detailed in vitro evaluation of zwitterionic ultrasmall superparamagnetic iron oxide NPs (USPIONs) comprising oleic acid/oleyl alcohol‐stabilized magnetite particles (5 nm core diameter) coated with an amphiphilic zwitterionic polymer, poly(maleic anhydride‐alt‐1‐decene) substituted with 3‐(dimethylamino)propylamine (PMAL). These particles display a near‐neutral zeta potential at pH≥7 and possess high colloidal stability, maintaining a hydrodynamic diameter of ca. 15–20 nm over a wide range of pHs (4–10) and ionic strength (up to 1 m NaCl). They exhibit very low levels of nonspecific protein binding upon exposure to serum, and negligible uptake by phagocytic and non‐phagocytic hepatocarcinoma cells, which suggests that they may be able to resist rapid accumulation in the liver and spleen, a common in vivo fate for NPs. The PMAL‐USPIONs exhibit very low cytotoxicity and do not elicit an inflammatory response or display hemolytic activity in vitro. Minimal nonspecific uptake by either cancerous or non‐cancerous cell lines was observed, an important precondition to achieve highly selective targeting upon further functionalization with an active targeting agent (e.g., antibody or peptide). Overall, this study establishes the considerable potential of PMAL‐USPIONs as a platform for the future development of “stealth” NP‐based imaging and/or therapeutic agents.
From the Superatom Model to a Diverse Array of Super‐Elements: A Systematic Study of Dopant Influence on the Electronic Structure of Thiolate‐Protected Gold Clusters
Authors: Schacht Julia , Gaston Nicola
Published: August 2016

The electronic properties of doped thiolate‐protected gold clusters are often referred to as tunable, but their study to date, conducted at different levels of theory, does not allow a systematic evaluation of this claim. Here, using density functional theory, the applicability of the superatomic model to these clusters is critically evaluated, and related to the degree of structural distortion and electronic inhomogeneity in the differently doped clusters, with dopant atoms Pd, Pt, Cu, and Ag. The effect of electron number is systematically evaluated by varying the charge on the overall cluster, and the nominal number of delocalized electrons, employed in the superatomic model, is compared to the numbers obtained from Bader analysis of individual atomic charges. We find that the superatomic model is highly applicable to all of these clusters, and is able to predict and explain the changing electronic structure as a function of charge. However, significant perturbations of the model arise due to doping, due to distortions of the core structure of the Au13[RS(AuSR)2]6− cluster. In addition, analysis of the electronic structure indicates that the superatomic character is distributed further across the ligand shell in the case of the doped clusters, which may have implications for the self‐assembly of these clusters into materials. The prediction of appropriate clusters for such superatomic solids relies critically on such quantitative analysis of the tunability of the electronic structure.
Across the Board: Nam‐Gyu Park
Authors: Park Nam‐Gyu
Published: August 2016

In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Prof. Nam‐Gyu Park, who highlights the recent work on mixed‐cation mixed‐anion perovskite materials toward high efficiency perovskite solar cells. He summarizes the work that has brought us to the current stage of research and suggests possible future paths for further advancement.
Video transmission in mobile ad hoc networks using multiple interfaces and multiple channels
Authors: Bouras C. , Gkamas A. , Kapoulas V. , Politaki D. , Tsanai E.
Published: August 2016

Mobile Ad hoc NETworks (MANETs) are an important part of wireless communications and the increasing use of mobile devices is confirming that. MANETs can be of great value in Emergency Response situations where communication between mobile deployed units is critical and wired or wireless infrastructures may not be present or functional. In emergency scenarios, multimedia communication is very important for decision making and situation assessment. This requires up‐to‐date (on‐line) information feed on the situation, including voice and video from the affected zone. However, MANETs do not seem to efficiently support multimedia applications, and this is quite evident in video transmission. One way to remedy this is to use more (wireless) interfaces per mobile node and consequently more communication channels. In this work, we perform an analytical study on the use of multiple interfaces and multiple channels (MIMC) in video transmission with respect to the requirements of Emergency Response Ad hoc Networks. More specifically, we examine and present the impact of using MIMC on MANETs during video transmission applications, we evaluate the performance of three basic routing protocols in MANETs, and we propose a channel selection mechanism in MANET nodes with MIMC for enhanced video transmission. In addition, we evaluate video transmission streams with rate adaptation and present comparative results. The proposed mechanism is evaluated using the ns‐2 network simulator and the simulations are performed for a variety of topologies. Simulation results show that the different routing protocols respond differently when MIMC is introduced. The Ad hoc On‐Demand Multipath Distance Vector and (especially) the Ad hoc On‐Demand Distance Vector routing protocols benefit significantly, while the Destination Sequenced Distance Vector shows fewer improvements. The proposed mechanism is shown to be beneficial for transmitting video streams and enhances the network's ability to accommodate more streams and reduce packet delay. Copyright © 2016 John Wiley & Sons, Ltd.
Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders
Authors: Adzic Miroslav , Brkic Zeljka , Bulajic Sonja , Mitic Milos , Radojcic Marija B.
Published: August 2016

Preclinical Research

Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co‐morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms. Additionally, psychotropic drug treatments can alter energy metabolism and may affect mitochondrial processes. This review focuses on recent findings regarding the effects of antidepressants on mitochondrial processes in psychiatric disorders. Drug Dev Res 77 : 400–406, 2016. © 2016 Wiley Periodicals, Inc.
Perspectives in Designing Multifunctional Molecules in Antipsychotic Drug Discovery
Authors: Milelli Andrea , Turrini Eleonora , Catanzaro Elena , Maffei Francesca , Fimognari Carmela
Published: August 2016

Preclinical Research

A novel and promising approach to overcome the limits of single‐target therapy is represented by the multitarget approach. This strategy aims to simultaneously modulate several targets involved in the pathophysiology of a multifactorial disease, with the potential to enhance therapeutic effectiveness and improve drug safety. Although there has been a marked growth in the design of multitarget drugs (MTDs) in the last years in the context of anti‐Alzheimer and anti‐cancer drug discovery, a parallel expansion was not observed in antipsychotic drugs, even that for psychiatric disorders there is a cogent medical need for new treatments. The discovery of new MTDs is a challenging task and we will describe the main strategies that have been developed over the years for the design of multifunctional molecules in antipsychotic drug discovery. In particular, we will focus on the few available MTDs based on the design of selective serotonin re‐uptake inhibitors, used as antidepressants and in the treatment of schizophrenia. Drug Dev Res 77 : 437–443, 2016. © 2016 Wiley Periodicals, Inc.
Long‐term stability of cannabinoids in oral fluid after controlled cannabis administration
Authors: Scheidweiler Karl B. , Andersson Maria , Swortwood Madeleine J. , Sempio Cristina , Huestis Marilyn A.
Published: August 2016

Cannabinoid stability in oral fluid (OF) is important for assuring accurate results since OF has become a valid alternative matrix of choice for drug testing. We previously published OF cannabinoid stability studies using Quantisal™, Oral‐Eze®, and StatSure™ devices stored at room temperature for 1 week, 4 °C for up to 4 weeks, and at ‐20 °C up to 24 weeks. Extending refrigerated stability up to 3 months would be helpful for clinical and forensic testing, for re‐analysis of OF samples and for batching research analyses. Individual authentic OF pools were prepared after controlled smoking of a 6.9% ∆9‐tetrahydracannabinol cannabis cigarette; the Quantisal™ device was utilized for OF collection. Fifteen healthy volunteers participated in the Institutional Review Board‐approved study. Stability for THC, 11‐nor‐9‐carboxy‐THC (THCCOOH), ∆9‐tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabigerol (CBG) were determined after storage at 4 °C for 1, 2, and 3 months. Results within ±20% of baseline concentrations were considered stable. All analytes were stable for up to 2 months at 4 °C for all participants with positive baseline concentrations. Baseline concentrations were highly variable. In total, THC, THCCOOH, THCV, CBD, and CBG were stable for 3 months at 4 °C for pooled positive specimens from 14 of 15, 8 of 9, 7 of 8, 8 of 9, and 9 of 10 participants, respectively. In conclusion, Quantisal™‐collected OF specimens should be stored at 4 °C for no more than two months to assure accurate THC, THCCOOH, THCV, CBD, and CBG quantitative results; only one participant's OF was unstable at three months. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Evaluating the influence of life‐history characteristics on genetic structure: a comparison of small mammals inhabiting complex agricultural landscapes
Authors: Kierepka Elizabeth M. , Anderson Sara J. , Swihart Robert K. , Rhodes Olin E.
Published: August 2016

Conversion of formerly continuous native habitats into highly fragmented landscapes can lead to numerous negative demographic and genetic impacts on native taxa that ultimately reduce population viability. In response to concerns over biodiversity loss, numerous investigators have proposed that traits such as body size and ecological specialization influence the sensitivity of species to habitat fragmentation. In this study, we examined how differences in body size and ecological specialization of two rodents (eastern chipmunk; Tamias striatus and white‐footed mouse; Peromyscus leucopus) impact their genetic connectivity within the highly fragmented landscape of the Upper Wabash River Basin (UWB), Indiana, and evaluated whether landscape configuration and complexity influenced patterns of genetic structure similarly between these two species. The more specialized chipmunk exhibited dramatically more genetic structure across the UWB than white‐footed mice, with genetic differentiation being correlated with geographic distance, configuration of intervening habitats, and complexity of forested habitats within sampling sites. In contrast, the generalist white‐footed mouse resembled a panmictic population across the UWB, and no landscape factors were found to influence gene flow. Despite the extensive previous work in abundance and occupancy within the UWB, no landscape factor that influenced occupancy or abundance was correlated with genetic differentiation in either species. The difference in predictors of occupancy, abundance, and gene flow suggests that species‐specific responses to fragmentation are scale dependent.
A simple framework for a complex problem? Predicting wildlife–vehicle collisions
Authors: Visintin Casey , van der Ree Rodney , McCarthy Michael A.
Published: August 2016

Collisions of vehicles with wildlife kill and injure animals and are also a risk to vehicle occupants, but preventing these collisions is challenging. Surveys to identify problem areas are expensive and logistically difficult. Computer modeling has identified correlates of collisions, yet these can be difficult for managers to interpret in a way that will help them reduce collision risk. We introduce a novel method to predict collision risk by modeling hazard (presence and movement of vehicles) and exposure (animal presence) across geographic space. To estimate the hazard, we predict relative traffic volume and speed along road segments across southeastern Australia using regression models based on human demographic variables. We model exposure by predicting suitable habitat for our case study species (Eastern Grey Kangaroo Macropus giganteus) based on existing fauna survey records and geographic and climatic variables. Records of reported kangaroo–vehicle collisions are used to investigate how these factors collectively contribute to collision risk. The species occurrence (exposure) model generated plausible predictions across the study area, reducing the null deviance by 30.4%. The vehicle (hazard) models explained 54.7% variance in the traffic volume data and 58.7% in the traffic speed data. Using these as predictors of collision risk explained 23.7% of the deviance in incidence of collisions. Discrimination ability of the model was good when predicting to an independent dataset. The research demonstrates that collision risks can be modeled across geographic space with a conceptual analytical framework using existing sources of data, reducing the need for expensive or time‐consuming field data collection. The framework is novel because it disentangles natural and anthropogenic effects on the likelihood of wildlife–vehicle collisions by representing hazard and exposure with separate, tunable submodels.
Correlated evolution between targets of pre‐ and postcopulatory sexual selection across squamate reptiles
Authors: Kahrl Ariel F. , Cox Christian L. , Cox Robert M.
Published: August 2016

Sexual selection reflects the joint contributions of precopulatory selection, which arises from variance in mating success, and postcopulatory selection, which arises from variance in fertilization success. The relative importance of each episode of selection is variable among species, and comparative evidence suggests that traits targeted by precopulatory selection often covary in expression with those targeted by postcopulatory selection when assessed across species, although the strength and direction of this association varies considerably among taxa. We tested for correlated evolution between targets of pre‐ and postcopulatory selection using data on sexual size dimorphism (SSD) and testis size from 151 species of squamate reptiles (120 lizards, 31 snakes). In squamates, male–male competition for mating opportunities often favors large body size, such that the degree of male‐biased SSD is associated with the intensity of precopulatory selection. Likewise, competition for fertilization often favors increased sperm production, such that testis size (relative to body size) is associated with the intensity of postcopulatory selection. Using both conventional and phylogenetically based analyses, we show that testis size consistently decreases as the degree of male‐biased SSD increases across lizards and snakes. This evolutionary pattern suggests that strong precopulatory selection may often constrain the opportunity for postcopulatory selection and that the relative importance of each selective episode may determine the optimal resolution of energy allocation trade‐offs between traits subject to each form of sexual selection.
Seed set variation in wildClarkiapopulations: teasing apart the effects of seasonal resource depletion, pollen quality, and pollen quantity
Authors: Hove Alisa A. , Mazer Susan J. , Ivey Christopher T.
Published: August 2016

In habitats where resource availability declines during the growing season,selection may favor early‐flowering individuals. Under such ephemerally favorable conditions, late‐blooming species (and individuals) may be particularly vulnerable to resource limitation of seed production. In California, a region prone to seasonal drought, members of the annual genusClarkiaare among the last to flower in the spring. We compared pollen limitation (PL) of seed set and outcrossing rates between early‐ and late‐flowering individuals in two mixed‐matingClarkiataxa to detect whether flowering time is associated with changes in seed set due to resource depletion,PL, or increased selfing. In 2008–2010, we hand‐pollinated one flower on a total of 1855 individual plants either Early (near the onset of flowering) or Late (near the end of flowering) in the flowering season and compared seed set to adjacent, open‐pollinated flowers on the same stem. To assess the contribution of pollen quality to reproduction, we first (2008) used allozymes to estimate outcrossing rates of seeds produced by Early and Late open‐pollinated flowers. Second (2009), we conducted an anther‐removal experiment to estimate self‐pollen deposition. Seed set inClarkia unguiculatawas not pollen‐limited.Clarkia xantianassp. xantianawas pollen‐limited in 2008 and 2010, but not 2009.PLdid not differ between Early and Late treatments. In both taxa, seed set of Early flowers was greater than Late flowers, but not due toPLin the latter. Reproduction was generally pollinator‐dependent. Most pollen deposition was xenogamous, and outcrossing rates were >0.7 – and similar between Early and Late periods. These results suggest that pollen receipt and pollen quality remain seasonally consistent. By contrast, the resources necessary to provision seeds decline, reducing the fitness benefits associated with resource allocation to ovules.
Preserving prairies: understanding temporal and spatial patterns of invasive annual bromes in the Northern Great Plains
Authors: Ashton Isabel W. , Symstad Amy J. , Davis Christopher J. , Swanson Daniel J.
Published: August 2016

Two Eurasian invasive annual brome grasses, cheatgrass (Bromus tectorum) and Japanese brome (Bromus japonicus), are well known for their impact in steppe ecosystems of the western United States where these grasses have altered fire regimes, reduced native plant diversity and abundance, and degraded wildlife habitat. Annual bromes are also abundant in the grasslands of the Northern Great Plains (NGP), but their impact and ecology are not as well studied. It is unclear whether the lessons learned from the steppe will translate to the mixed‐grass prairie where native plant species are adapted to frequent fires and grazing. Developing a successful annual brome management strategy for National Park Service units and other NGP grasslands requires better understanding of (1) the impact of annual bromes on grassland condition; (2) the dynamics of these species through space and time; and (3) the relative importance of environmental factors within and outside managers' control for these spatiotemporal dynamics. Here, we use vegetation monitoring data collected from 1998 to 2015 in 295 sites to relate spatiotemporal variability of annual brome grasses to grassland composition, weather, physical environmental characteristics, and ecological processes (grazing and fire). Concern about the impact of these species in NGP grasslands is warranted, as we found a decline in native species richness with increasing annual brome cover. Annual brome cover generally increased over the time of monitoring but also displayed a 3‐ to 5‐yr cycle of reduction and resurgence. Relative cover of annual bromes in the monitored areas was best predicted by park unit, weather, extant plant community, slope grade, soil composition, and fire history. We found no evidence that grazing reduced annual brome cover, but this may be due to the relatively low grazing pressure in our study. By understanding the consequences and patterns of annual brome invasion, we will be better able to preserve and restore these grassland landscapes for future generations.
Programmed Molecular Engineering: Stepwise, Multicomponent Assembly of a Dimetallic Metallotriangulane
Authors: Chakraborty Sourav , Sarkar Rajarshi , Endres Kevin , Xie Ting‐Zheng , Ghosh Monoj , Moorefield Charles N. , Saunders Mary Jane , Wesdemiotis Chrys , Newkome George R.
Published: August 2016

The design and construction of a novel terpyridine‐based, dimetallic, 2D [4]triangulane architecture are reported. Synthesis of the metallotriangulane is achieved by multicomponent stepwise assembly of six bidentate and three tetradentate monomers. Characterization was accomplished by NMR spectroscopy, mass spectrometry and TEM microscopy.
Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes
Authors: Hayashi Mikayo , Brown Lauren E. , Porco John A.
Published: August 2016

Enantioenriched, polycyclic compounds were obtained from a simple acylphloroglucinol scaffold. Highly enantioselective dearomatization was accomplished using a Trost ligand–palladium(0) complex. A computational DFT model was developed to rationalize observed enantioselectivities and revealed a key reactant‐ligand hydrogen bonding interaction. Dearomatized products were used in visible light‐mediated photocycloadditions and oxidative free radical cyclizations to obtain novel polycyclic chemotypes including tricyclo[4.3.1.01,4]decan‐10‐ones, bicyclo[3.2.1]octan‐8‐ones and highly substituted cycloheptanones.
Larval aquatic insect responses to cadmium and zinc in experimental streams
Authors: Mebane Christopher A. , Schmidt Travis S. , Balistrieri Laurie S.
Published: August 2016

To evaluate the risks of metal mixture effects to natural stream communities under ecologically relevant conditions, the authors conducted 30-d tests with benthic macroinvertebrates exposed to cadmium (Cd) and zinc (Zn) in experimental streams. The simultaneous exposures were with Cd and Zn singly and with Cd+Zn mixtures at environmentally relevant ratios. The tests produced concentration–response patterns that for individual taxa were interpreted in the same manner as classic single-species toxicity tests and for community metrics such as taxa richness and mayfly (Ephemeroptera) abundance were interpreted in the same manner as with stream survey data. Effect concentrations from the experimental stream exposures were usually 2 to 3 orders of magnitude lower than those from classic single-species tests. Relative to a response addition model, which assumes that the joint toxicity of the mixtures can be predicted from the product of their responses to individual toxicants, the Cd+Zn mixtures generally showed slightly less than additive toxicity. The authors applied a modeling approach called Tox to explore the mixture toxicity results and to relate the experimental stream results to field data. The approach predicts the accumulation of toxicants (hydrogen, Cd, and Zn) on organisms using a 2-pKa bidentate model that defines interactions between dissolved cations and biological receptors (biotic ligands) and relates that accumulation through a logistic equation to biological response. The Tox modeling was able to predict Cd+Zn mixture responses from the single-metal exposures as well as responses from field data. The similarity of response patterns between the 30-d experimental stream tests and field data supports the environmental relevance of testing aquatic insects in experimental streams. Environ Toxicol Chem 2017;36:749–762. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Reducing the acrylamide‐forming potential of wheat
Authors: Curtis Tanya Y. , Halford Nigel G.
Published: August 2016

Acrylamide is a Class 2a carcinogen that was discovered in a variety of popular foods, including baked cereal products, in 2002. The predominant route for its formation is from free asparagine and reducing sugars in the Maillard reaction, with free asparagine concentration being the main determinant of acrylamide‐forming potential in cereal products. The European Commission set “indicative” levels for acrylamide in food in 2011 and 2013, and is currently reviewing its options for further measures. Agronomic and genetic approaches to reducing the acrylamide‐forming potential of wheat include the evaluation of existing varieties for low asparagine accumulation in the grain, ensuring adequate sulfur fertilization in relation to nitrogen supply, developing an understanding of the genetic control of asparagine metabolism, and identifying quantitative trait loci or molecular markers for low asparagine accumulation in the grain. Asparagine concentration in grain is affected by environmental factors (E), genetic factors (G), and interactions between the two (G × E). This paper reviews the continuing efforts being made to reduce the acrylamide‐forming potential of wheat, and to increase awareness of the issue among wheat breeders, farmers, and the food industry.
Short rotation plantations policy history in Europe: lessons from the past and recommendations for the future
Authors: Lindegaard Kevin N. , Adams Paul W. R. , Holley Martin , Lamley Annette , Henriksson Annika , Larsson Stig , von Engelbrechten Hans‐Georg , Esteban Lopez Gonzalo , Pisarek Marcin
Published: August 2016

Short rotation plantations (SRPs) are fast‐growing trees (such as willow (Salix spp.), poplar (Populus spp.) and Eucalyptus) grown closely together and harvested in periods of 2–20 years. There are around 50,000 hectares of SRPs in Europe, a relatively small area considering that there have been supportive policy measures in many countries for 30 years. This paper looks at the effect that the policy measures used in different EU countries have had, and how other external factors have impacted on the development of the industry. Rokwood was a 3‐year European funded project which attempted to understand the obstacles and barriers facing the woody energy crops sector using well established methods of SWOT and PESTLE analysis. Stakeholder groups were formed in six different European regions to analyze the market drivers and barriers for SRP and propose ways that the industry could make progress through targeted research and development and an improved policy framework. Based upon the outcomes of the SWOT and PESTLE analysis, each region produced a series of recommendations for policymakers, public authorities, and government agencies to support the development, production, and use of SRP‐derived wood fuel in each of the partner countries. This study provides details of the SRP policy analysis and reveals that each region shared a number of similarities with broad themes emerging. There is a need to educate farmers and policymakers about the multifunctional benefits of SRPs. Greater financial support from regional and/or national government is required in order to grow the SRP market. Introducing targeted subsidies as an incentive for growers could address lack of local supply chains. Long‐term policy initiatives should be developed while increasing clarity within Government departments. Research funding should enable closer working between universities and industry with positive research findings developed into supportive policy measures.
The essential oil of Achillea ageratifolia (Sm.) Boiss. subsp. serbica (Nyman) Heimerl (Asteraceae) revisited: the stereochemical nomenclature issues, structural elucidation and synthesis of (new) sabinyl esters
Authors: Mladenović Marko Z. , Radulović Niko S.
Published: August 2016

Serbian Yarrow (Achillea ageratifolia (Sm.) Boiss. subsp. serbica (Nyman) Heimerl, Asteraceae) is a poorly investigated taxon, endemic to the Central Balkan Peninsula area. A combination of chromatographic and spectroscopic techniques enabled the identification of, in total, 300 constituents (comprising 95.5–97.2% of the total essential oil compositions) from the essential oils of the A. ageratifolia ssp. serbica dry aerial parts. A comparison of the essential‐oil compositions from plant material collected from two populations (Jelašnička klisura gorge and Suva Planina mountain, SE Serbia) in two consecutive years (2013 and 2014) confirmed that the biosynthesis/accumulation of the volatile metabolites for this species is not dependent on the environmental conditions and suggested the existence of a single chemotype of this species. The essential oil compositions were dominated by (1R*,3S*,5R*)‐sabinyl derivatives, including two completely new natural products: (1R*,3S*,5R*)‐sabinyl nonanoate and (1R*,3S*,5R*)‐sabinyl decanoate. The identity of these new esters was unambiguously confirmed by co‐injection of the essential oil samples with synthesized standards and their structure was elucidated by NMR (1D and 2D), IR and MS, whereas the stereochemistry of the esters was studied by an NMR methodology that employed lanthanide‐induced shift reagents. Additionally, a nomenclature confusion regarding the relative stereochemistry of sabinyl esters, that came from the opposing use of cis and trans for the parent alcohols and the derived esters, was addressed. We propose the use of CIP notation in connection with the trivial names to avoid further ambiguities. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis of α‐aminophosphonates from α‐hydroxyphosphonates; a theoretical study
Authors: Kiss Nóra Zsuzsa , Rádai Zita , Mucsi Zoltán , Keglevich György
Published: August 2016

Two types of reactions, namely the Pudovik reaction of benzaldehyde and acetophenone with diethyl phosphite as well as the substitution of the α‐hydroxyphosphonates so‐formed by primary amines to afford α‐aminophosphonates, were evaluated by quantum chemical calculations at the B3LYP/6‐31G(d,p) level. An unexpected neighboring group effect was found to enhance the substitution. A series of new α‐aminophosphonates was synthesized by the microwave‐assisted substitution of α‐hydroxyphosphonates by alkylamines.
Behind‐the‐Counter, but Over‐the‐Border? The Assessment of the Geographical Spillover Effects of Emergency Contraception on Abortions
Authors: Cintina Inna
Published: August 2016

Washington was the first state to ease the prescription requirements making emergency contraception (EC) available behind‐the‐counter at pharmacies to women of any age in 1998. Using county‐level vital statistics data in conjunction with the pharmacy specific location data from the Not‐2‐Late Hotline database, I study whether the increased access to EC affects fertility rates within the state and beyond the borders of the state that allows it. Unlike other studies that rely on geographic variations in access, I show that increased availability of EC in Washington, measured by the distance to the closest ‘no‐prescription EC pharmacy’, is associated with a statistically significant albeit economically moderate decrease in abortion rates in Washington counties where women had access to ‘no‐prescription EC’. These effects are localized (i.e., decrease with travel distance) and robust in a number of specifications. Finally, I find some evidence in support of geographical spillover effects in Idaho, but not in Oregon. However, after accounting for the availability of abortion services, the decrease in ‘treated’ Idaho counties is rather small. Copyright © 2016 John Wiley & Sons, Ltd.
Well‐Defined Amphiphilic C60‐PEG Conjugates: Water‐Soluble and Thermoresponsive Materials
Authors: Aroua Safwan , Tiu Elisha Gabrielle V. , Ishikawa Takashi , Yamakoshi Yoko
Published: August 2016

For the preparation of well‐defined H2O‐soluble C60 polymers, several C60‐PEG conjugates were prepared from a C60 biscarboxylic acid derivative and monodisperse NH2‐PEGs (NH2‐EGn, n = 4 – 36) via amide conjugation. When the relatively long PEGs (EGn, n ≥ 12) were employed, the C60‐PEG conjugates became completely H2O‐soluble by forming micelle‐like structure shown by the data of surface tension, DLS, and cryo‐TEM. Interestingly, these H2O‐soluble C60‐PEG conjugates (C60(EGn)2, n = 12 – 36) showed reversible thermoresponse to form larger aggregates (ca. 1 μm by DLS) at higher temperatures. The temperature for the aggregation was related to the lengths of PEGs attached to C60; 29 °C (C60(EGn)2, n = 12), 51 °C (n = 20), and 72 °C (n = 36). This thermoresponse was speculated to occur by dehydration of well‐organized PEG chains in the micelle‐type structure of monodisperse C60‐PEG caused by gauche‐to‐anti conformational change of PEG anchors. This thermoresponse of well‐defined amphiphilic C60‐PEG conjugates indicates potential applications in areas such as temperature sensors and thermoresponsive materials.
Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report
Authors: Tardy Magalie P. , Gastaud Lauris , Boscagli Annick , Peyrade Frederic , Gallamini Andrea , Thyss Antoine
Published: August 2016

The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune‐like syndromes.

A 75‐year‐old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third‐line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography‐computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography‐computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.
Gout and the Risk of Non-vertebral Fracture
Authors: Kim Seoyoung C , Paik Julie M , Liu Jun , Curhan Gary C , Solomon Daniel H
Published: August 2016

Prior studies suggest an association between osteoporosis, systemic inflammation, and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004–2013), we evaluated the risk of non-vertebral fracture (ie, forearm, wrist, hip, and pelvis) in patients with gout versus those without. Gout patients were identified with ≥2 diagnosis codes and ≥1 dispensing for a gout-related drug. Non-gout patients, identified with ≥2 visits coded for any diagnosis and ≥1 dispensing for any prescription drugs, were free of gout diagnosis and received no gout-related drugs. Hip fracture was the secondary outcome. Fractures were identified with a combination of diagnosis and procedure codes. Cox proportional hazards models compared the risk of non-vertebral fracture in gout patients versus non-gout, adjusting for more than 40 risk factors for osteoporotic fracture. Among gout patients with baseline serum uric acid (sUA) measurements available, we assessed the risk of non-vertebral fracture associated with sUA. We identified 73,202 gout and 219,606 non-gout patients, matched on age, sex, and the date of study entry. The mean age was 60 years and 82% were men. Over the mean 2-year follow-up, the incidence rate of non-vertebral fracture per 1,000 person-years was 2.92 in gout and 2.66 in non-gout. The adjusted hazard ratio (HR) was 0.98 (95% confidence interval [CI] 0.85–1.12) for non-vertebral fracture and 0.83 (95% CI 0.65–1.07) for hip fracture in gout versus non-gout. Subgroup analysis (n = 15,079) showed no association between baseline sUA and non-vertebral fracture (HR = 1.03, 95% CI 0.93–1.15), adjusted for age, sex, comorbidity score, and number of any prescription drugs. Gout was not associated with a risk of non-vertebral fracture. Among patients with gout, sUA was not associated with the risk of non-vertebral fracture. © 2016 American Society for Bone and Mineral Research.
A 10‐Year united network for organ sharing review of mortality and risk factors in young children awaiting liver transplantation
Authors: Leung Daniel H. , Narang Amrita , Minard Charles G. , Hiremath Girish , Goss John A. , Shepherd Ross
Published: August 2016

Young children < 2 years of age with chronic end‐stage liver disease (YC2) are a uniquely vulnerable group listed for liver transplantation, characterized by a predominance of biliary atresia (BA). To investigate wait‐list mortality, associated risk factors, and outcomes of YC2, we evaluated United Network for Organ Sharing registry data from April 2003 to March 2013 for YC2 listed for deceased donor transplant (BA = 994; other chronic liver disease [CLD] = 221). Overall, wait‐list mortality among YC2 was 12.4% and posttransplant mortality was 8%, accounting for an overall postlisting mortality of 19.6%. YC2 demonstrated 12.2%, 18.7%, and 20.6% wait‐list mortality by 90, 180, and 270 days, respectively. YC2 with CLD demonstrated significantly higher wait‐list mortality compared with BA among YC2 (23.9% versus 9.8%; P < 0.05). Multivariate analyses revealed that listing Pediatric End‐Stage Liver Disease [PELD] > 21 (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.6‐6.5), lack of exception (HR, 5.8; 95% CI, 2.8‐11.8), listing height < 60.6 cm (HR, 2.1; 95% CI, 1.4‐3.1), listing weight  > 10 kg (HR, 3.8; 95% CI, 1.5‐9.2), and initial creatinine > 0.5 (HR, 6.8; 95% CI, 3.4‐13.5) were independent risk factors for YC2 wait‐list mortality (P < 0.005 for all). Adjusting for all variables, the risk of death among CLD patients was 2 (95% CI, 1.3‐3.1) times greater than patients with BA + surgery (presumed Kasai). Furthermore, the risk of death in BA surgery was 1.9 (95% CI, 1‐3.4) times greater than BA with presumed Kasai. Our data highlight unacceptably high wait‐list and early post–liver transplant mortality in YC2 not predicted by PELD and suggest key risk factors deserving of further study in this age group. Liver Transplantation 22 1584–1592 2016 AASLD.
MicroRNA‐17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription‐3 expression
Authors: Li Shipeng , Zhang Jianjun , Wang Zhen , Wang Tengfei , Yu Yao , He Jindan , Zhang Haiming , Yang Tao , Shen Zhongyang
Published: August 2016

Hepatic ischemia/reperfusion injury (IRI) represents an important clinical problem as related to liver resection or transplantation. However, the potential mechanism underlying hepatic IRI remains obscure. Recent evidence has indicated that microRNAs (miRNAs) participate in various hepatic pathophysiological processes via regulating autophagy. This relationship between MicroRNA‐17 (miR‐17) and hepatic autophagy prompted us to examine the role and potential mechanisms of miR‐17 regulating autophagy in hepatic IRI. MiR‐17 levels were significantly up‐regulated after hepatic ischemia/reperfusion (IR), and the number of autophagosomes increased in response to IR. These results demonstrate that miR‐17 could promote hepatic IRI as revealed by reductions in cell viability in vitro. The expression of microtubule‐associated protein 1 light B II (LC3BII) was gradually up‐regulated and peaked at 24 hours following reperfusion, a time point that was also associated with maximal miR‐17 levels. Overexpression of miR‐17 diminished signal transductions and activation of transcription‐3 (Stat3) and phosphorylated Stat3 (p‐Stat3) levels, an effect which promoted autophagy in response to IRI. However, low‐level expressions of miR‐17 were associated with increased Stat3 and p‐Stat3 levels and decreased autophagy. In conclusion, high levels of miR‐17 expression can function to up‐regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697–1709 2016 AASLD.
Low serum testosterone is associated with adverse outcome in men with cirrhosis independent of the model for end‐stage liver disease score
Authors: Sinclair Marie , Gow Paul J. , Grossmann Mathis , Shannon Adam , Hoermann Rudolf , Angus Peter W.
Published: August 2016

Low serum testosterone has been retrospectively associated with mortality in men on the liver transplant waiting list. The impact of testosterone deficiency on other outcomes has not previously been assessed. We conducted a single center prospective observational study of all men with cirrhosis seen between 2013 and 2014. Baseline data included sex hormone profile, Model for End‐Stage Liver Disease (MELD) score, and standard biochemistry. Outcomes were recorded over 12 months including major infection, liver transplantation, and death. Of 268 cirrhotic men, the median MELD score was 10 (interquartile range [IQR], 8‐15) and median serum testosterone was 17.4 nmol/L (IQR, 8.9‐25.0 nmol/L). During the study period, 32 (12%) men died, 18 (7%) received a liver transplant, and 51 (19%) suffered a major infection. Mortality markedly increased when total testosterone fell below a threshold value of 8.3 nmol/L, and this cutoff was used for further analysis. Testosterone below 8.3 nmol/L was associated with the combined outcome of death or transplantation independently of the MELD score (hazard ratio [HR], 2.36; IQR, 1.16‐4.81; P = 0.02) for testosterone (and HR, 1.22; IQR, 1.18‐1.27; P < 0.001 for MELD). Low total testosterone was also an independent risk factor for major infection (HR, 3.61; IQR, 1.61‐8.06; P < 0.001) and nearly significant for mortality alone (HR, 2.39; IQR, 0.97‐5.88; P = 0.057). Low free testosterone (<139 pmol/L) was similarly independently associated with death or transplantation (HR, 2.43; IQR, 1.12‐5.29; P = 0.03) and infection (HR, 3.3; IQR, 1.46‐7.46; P = 0.004). In conclusion, low testosterone is a novel prognostic marker in men with cirrhosis that is numerically associated with increased mortality or need for transplantation, as well as risk for major infection. Interventional studies of testosterone therapy are required to investigate whether correcting low testosterone can reduce mortality and improve other clinical outcomes. Liver Transplantation 22 1482–1490 2016 AASLD.
Macrovascular invasion is not an absolute contraindication for living donor liver transplantation
Authors: Lee Kwang‐Woong , Suh Suk‐Won , Choi YoungRok , Jeong Jaehong , Yi Nam‐Joon , Kim Hyeyoung , Yoon Kyung Chul , Hong Suk Kyun , Kim Hyo‐Sin , Lee Kyung‐Bun , Suh Kyung‐Suk
Published: August 2016

The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1‐, 3‐, and 5‐year recurrence‐free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1‐, 3‐, and 5‐year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha‐fetoprotein × protein induced by vitamin K absence/antagonist‐II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19–27 2017 AASLD.
Left lobe living donor liver transplantation in adults: What is the safety limit?
Authors: Ikegami Toru , Yoshizumi Tomoharu , Sakata Kazuhito , Uchiyama Hideaki , Harimoto Norifumi , Harada Noboru , Itoh Shinji , Nagatsu Akihisa , Soejima Yuji , Maehara Yoshihiko
Published: August 2016

Small‐for‐size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL‐LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL‐LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5‐year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL‐LDLT showed that donor age of ≥48 years (P = 0.01), Model for End‐Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL‐LDLT. Within such high‐risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL‐LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor‐recipient combinations. Liver Transplantation 22 1666–1675 2016 AASLD.