bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension
Authors: Buss Nicholas , Ryan Patricia , Baughman Todd , Roy Denis , Patterson Claire , Gordon Carolyn , Dixit Rakesh
Published: May 2018

Exenatide, a glucagon‐like peptide‐1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension was developed for use with an autoinjector device, in which the microspheres are suspended in Miglyol 812, a mixture of medium chain triglycerides (MCTs). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFAs). While MCTs are edible oils present in many foods, including foodstuffs containing coconut and palm kernel oils, limited information is available regarding the oral and subcutaneous bioavailability of MCTs as well as safety following subcutaneous injection. These studies were designed to investigate the non‐clinical pharmacokinetics and safety of MCTs. In a single dose pharmacokinetic study, MCFAs were rapidly detected in the plasma of rats following oral administration of either Miglyol 812 or tricaprylin at doses of 10 or 9.48 g kg−1, respectively. Following subcutaneous dosing with Miglyol 812, MCFAs were rapidly absorbed with a similar profile to that following oral dosing. Furthermore, the toxicity of Miglyol 812 alone was evaluated in a 3 month repeat dose toxicology studies in cynomolgus monkeys. In this study, weekly subcutaneous doses of 0.15 g kg−1 did not elicit any treatment‐related effects in cynomolgus monkeys. In conclusion, these studies alongside the available literature data show that Miglyol 812 is a safe excipient for use in subcutaneously administered therapeutics.
Testing and refining the Science in Risk Assessment and Policy (SciRAP) web‐based platform for evaluating the reliability and relevance of in vivo toxicity studies
Authors: Beronius Anna , Molander Linda , Zilliacus Johanna , Rudén Christina , Hanberg Annika
Published: May 2018

The Science in Risk Assessment and Policy (SciRAP) web‐based platform was developed to promote and facilitate structure and transparency in the evaluation of ecotoxicity and toxicity studies for hazard and risk assessment of chemicals. The platform includes sets of criteria and a colour‐coding tool for evaluating the reliability and relevance of individual studies. The SciRAP method for evaluating in vivo toxicity studies was first published in 2014 and the aim of the work presented here was to evaluate and develop that method further. Toxicologists and risk assessors from different sectors and geographical areas were invited to test the SciRAP criteria and tool on a specific set of in vivo toxicity studies and to provide feedback concerning the scientific soundness and user‐friendliness of the SciRAP approach. The results of this expert assessment were used to refine and improve both the evaluation criteria and the colour‐coding tool. It is expected that the SciRAP web‐based platform will continue to be developed and enhanced to keep up to date with the needs of end‐users.
Retracted: Ligustrazine protects chondrocyte against IL‐1β induced injury by regulation of SOX9/NF‐κB signaling pathway
Authors: Yu Tao , Qu Ji , Wang Yang , Jin Hui
Published: May 2018

Ligustrazine is extracted from rhizoma ligustici wallichii, is known for its vasodilatory properties in the traditional Chinese herbal medicine. The study aimed to determine the effect and the underlying mechanism of ligustrazine on interleukin‐1β (IL‐1β)‐induced injury in osteoarthritis (OA). Human articular cartilages and joint effusion were obtained from patients with OA, and the chondrocytes were isolated and treated with IL‐1β. The different inflammatory cytokines were analyzed by ELISA. Cell viability, apoptosis, and apoptosis‐related factors were examined by MTT, flow cytometry, and Western blot. Then, the expressions of COL2A1 and ACAN, and the concentrations of sGAG and MMP‐13 were measured. The level of SOD and MDA and ROS production were then analyzed. Furthermore, the protein levels of SOX9 and NF‐κB pathway were detected by Western blot. Ligustrazine significantly suppressed inflammatory reaction in joint effusion of OA patients. Moreover, ligustrazine attenuated IL‐1β‐induced chondrocytes injury and matrx degradation in chondrocytes. Ligustrazine promoted oxidative stress response by increasing SOD level, decreasing MDA level, and inhibiting ROS production in IL‐1β‐induced chondrocytes. Besides, ligustrazine increased SOX9 expression, and SOX9 silencing reversed the effect of ligustrazine on matrx degradation in IL‐1β‐injured chondrocytes. Furthermore, ligustrazine blocked NF‐κB pathway in IL‐1β‐induced chondrocytes, and PTDC (NF‐κB inhibitor) enhanced the effect of ligustrazine on viability, apoptosis, SOX9 expression, and ROS production in IL‐1β‐induced chondrocytes. These results indicated that ligustrazine protected chondrocytes against IL‐1β‐induced injury possibly by regulation of SOX9 and inactivation of NF‐κB signaling pathway. It could act as a therapeutic agent for the treatment of OA.
The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity
Authors: Azizi Gholamreza , Mirshafiey Abbas , Abolhassani Hassan , Yazdani Reza , Ghanavatinejad Alireza , Noorbakhsh Farshid , Rezaei Nima , Aghamohammadi Asghar
Published: May 2018

Patients with lipopolysaccharides responsive beige‐like anchor protein (LRBA) deficiency suffer from a variety of immunological abnormalities. In the current study, we investigated the role of T helper (Th) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in the immune dysregulation of LRBA deficiency. The study population comprised of 13 LRBA‐deficient patients and 13 age‐ and sex‐matched healthy controls (HCs). Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (interferon‐γ [IFN‐γ], interleukin [IL]‐17, IL‐22, and IL‐10), and cell subset–specific transcription factors were evaluated before and after proliferation and activation stimuli. The frequencies of Th1, Th1‐like Th17 and Th22 cells along with the expression of T‐box transcription factor (TBET) and runt‐related transcription factor 1 (RUNX1) were significantly increased in patients with LRBA. Moreover, IFN‐γ and IL‐22 production in LRBA‐deﬁcient CD4+ T cells were elevated after lymphocyte stimulation, particularly in patients with enteropathy. However, CD4+CD25+FoxP3+CD127− cells were significantly decreased in LRBA‐deficient patients compared with those of HCs, particularly in patients with autoimmunity. There was a negative correlation between the frequencies of CD4+CD25+FoxP3+CD127− cells and Th1‐like Th17 cells in LRBA‐deficient patients, and an overlapping phenotype of autoimmunity and enteropathy were observed in ~70% of patients. The frequency of Th17 cells was lower in patients with enteropathy, while Th1‐like Th17 cells were higher than in those without enteropathy. Our findings demonstrated an imbalance in Th subsets, mainly in Th1‐like Th17 and Treg cells and their corresponding cytokines in LRBA deficiency, which might be important in the immunopathogenesis of autoimmunity and enteropathy.
Artificial light at night alters behavior in laboratory and wild animals
Authors: Russart Kathryn L.G. , Nelson Randy J.
Published: May 2018

Life has evolved to internalize and depend upon the daily and seasonal light cycles to synchronize physiology and behavior with environmental conditions. The nightscape has been vastly changed in response to the use of artificial lighting. Wildlife is now often exposed to direct lighting via streetlights or indirect lighting via sky glow at night. Because many activities rely on daily and seasonal light cues, the effects of artificial light at night could be extensive, but remain largely unknown. Laboratory studies suggest exposure to light at night can alter typical timing of daily locomotor activity and shift the timing of foraging/food intake to the daytime in nocturnal rodents. Additionally, nocturnal rodents decrease anxiety‐like behaviors (i.e., spend more time in the open and increase rearing up) in response to even dim light at night. These are all likely maladaptive responses in the wild. Photoperiodic animals rely on seasonal changes in day length as a cue to evoke physiological and behavioral modifications to anticipate favorable and unfavorable conditions for survival and reproduction. Light at night can mask detection of short days, inappropriately signal long days, and thus desynchronize seasonal reproductive activities. We review laboratory and the sparse field studies that address the effects of exposure to artificial light at night to propose that exposure to light at night disrupts circadian and seasonal behavior in wildlife, which potentially decreases individual fitness and modifies ecosystems.
Incubation temperature influences the behavioral traits of a young precocial bird
Authors: Hope Sydney F. , Kennamer Robert A. , Moore Ignacio T. , Hopkins William A.
Published: May 2018

The environment in which animals develop can have important consequences for their phenotype. In reptiles, incubation temperature is a critical aspect of the early developmental environment. Incubation temperature influences morphology, physiology, and behavior of non‐avian reptiles, however, little is known about how incubation temperature influences offspring phenotype and behaviors important to avian survival. To investigate whether incubation temperature influences avian behaviors, we collected wood duck (Aix sponsa) eggs from the field and incubated them at three naturally occurring incubation temperatures (35.0, 35.8, and 37.0°C). We conducted multiple repeated behavioral trials on individual ducklings between 5 and 15 days post‐hatch to assess activity, exploratory, and boldness behaviors, classified along a proactive‐reactive continuum. We measured growth rates and circulating levels of baseline and stress‐induced corticosterone levels to investigate possible physiological correlates of behavior. Ducklings incubated at the lowest temperature displayed more proactive behaviors than those incubated at the two higher temperatures. We also found that younger ducklings exhibited more proactive behavior than older ducklings and males exhibited more proactive behavior than females. Further, duckling behaviors were repeatable across time and contexts, indicative of a proactive–reactive continuum of behavioral tendencies. However, neither corticosterone levels nor growth rates were related to behavior. This provides some of the first evidence that incubation temperature, a critical parental effect, influences avian offspring behaviors that may be important for survival. Our results identify incubation temperature as a mechanism that contributes to the development of behavioral traits and, in part, explains how multiple behavioral types may be maintained within populations.
Does repeated human handling of study animals during the mating season affect their offspring?
Authors: Swierk Lindsey , Langkilde Tracy
Published: May 2018

Minimizing disturbance of study animals is a major consideration in ethological and ecological research design. One nearly universal type of disturbance is the handling of study animals as a component of trial setup. Even low to moderate levels of handling can be a substantial stressor to study animals, which may negatively affect their offspring via maternal effects. Understanding how routine human handling and manipulation may affect the outcome of research studies is therefore critical for interpreting study outcomes. We tested whether repeatedly handling and manipulating (i.e., manually disengaging) amplexed pairs of wood frogs (Rana sylvatica [Lithobates sylvaticus]), which have an explosive breeding season, would affect their reproductive output and offspring fitness. Handling and manipulation did not alter any parameter that we measured: reproductive timing, hatching success, and offspring larval duration, survival, and size at metamorphosis. These results suggest that handling and manipulation by researchers may have a negligible effect on wood frog reproduction and offspring fitness. It is possible that many species that are commonly used in reproductive studies because they suppress behavioral and physiological responses during the mating season are likewise unaffected by human handling. Nevertheless, researchers should examine possible consequences of methodological interventions on their study species in order to determine any potential influence on their results. Having a broad understanding of these effects on species that have robust or dampened stress responsiveness during the breeding season would be useful for making generalizations about potential effects.
The vulnerability of developing embryos to simulated climate warming differs between sympatric desert lizards
Authors: Ma Liang , Sun Bao‐Jun , Li Shu‐Ran , Hao Xin , Bi Jun‐Huai , Du Wei‐Guo
Published: May 2018

The vulnerability of species to climate warming varies along latitudinal and elevational clines, but how sympatric species vary in vulnerability to climate warming remains largely unknown. We experimentally simulated nest temperatures of two sympatric lizards with divergent microhabitat preferences (Phrynocephalus przewalskii and Eremias argus), under climate warming senarios, to determine the response of embryos to increased mean temperatures and heat waves. Our study demonstrated that simulated climate warming reduced hatching success and hatchling size and growth in E. argus (that prefers closed microhabitats), but had less effect in P. przewalskii (that occupies open microhabitats). The reduced growth rate of E. argus hatchlings was associated with a decrease in metabolic rate, which was more evident in hatchling E. argus than in P. przewalskii. Our results suggest lizards that prefer closed microhabitats may be more vulnerable to climate warming than those that prefer open microhabitats; further studies are needed to test this hypothesis. More generally, the divergent responses of sympatric species to climate warming highlights the importance of distinguishing the thermal sensitivity of behavior and physiology for each species of a community, in order to make predictions about the impacts of climate warming at regional scales.
Patterns of developmental plasticity in response to incubation temperature in reptiles
Authors: While Geoffrey M. , Noble Daniel W.A. , Uller Tobias , Warner Daniel A. , Riley Julia L. , Du Wei‐Guo , Schwanz Lisa E.
Published: May 2018

Early life environments shape phenotypic development in important ways that can lead to long‐lasting effects on phenotype and fitness. In reptiles, one aspect of the early environment that impacts development is temperature (termed ‘thermal developmental plasticity’). Indeed, the thermal environment during incubation is known to influence morphological, physiological, and behavioral traits, some of which have important consequences for many ecological and evolutionary processes. Despite this, few studies have attempted to synthesize and collate data from this expansive and important body of research. Here, we systematically review research into thermal developmental plasticity across reptiles, structured around the key papers and findings that have shaped the field over the past 50 years. From these papers, we introduce a large database (the ‘Reptile Development Database’) consisting of 9,773 trait means across 300 studies examining thermal developmental plasticity. This dataset encompasses data on a range of phenotypes, including morphological, physiological, behavioral, and performance traits along with growth rate, incubation duration, sex ratio, and survival (e.g., hatching success) across all major reptile clades. Finally, from our literature synthesis and data exploration, we identify key research themes associated with thermal developmental plasticity, important gaps in empirical research, and demonstrate how future progress can be made through targeted empirical, meta‐analytic, and comparative work.
Increasing radiology capacity within the lung cancer pathway: centralised work‐based support for trainee chest X‐ray reporting radiographers
Authors: Woznitza Nick , Steele Rebecca , Piper Keith , Burke Stephen , Rowe Susan , Bhowmik Angshu , Maughn Sue , Springett Kate
Published: May 2018

Introduction

Diagnostic capacity and time to diagnosis are frequently identified as a barrier to improving cancer patient outcomes. Maximising the contribution of the medical imaging workforce, including reporting radiographers, is one way to improve service delivery.

Methods

An efficient and effective centralised model of workplace training support was designed for a cohort of trainee chest X‐ray (CXR) reporting radiographers. A comprehensive schedule of tutorials was planned and aligned with the curriculum of a post‐graduate certificate in CXR reporting. Trainees were supported via a hub and spoke model (centralised training model), with the majority of education provided by a core group of experienced CXR reporting radiographers. Trainee and departmental feedback on the model was obtained using an online survey.

Results

Fourteen trainees were recruited from eight National Health Service Trusts across London. Significant efficiencies of scale were possible with centralised support (48 h) compared to traditional workplace support (348 h). Trainee and manager feedback overall was positive. Trainees and managers both reported good trainee support, translation of learning to practice and increased confidence. Logistics, including trainee travel and release, were identified as areas for improvement.

Conclusion

Centralised workplace training support is an effective and efficient method to create sustainable diagnostic capacity and support improvements in the lung cancer pathway.
Stability of intrinsic rhythm in pacemaker‐dependent patients during pacemaker replacement: Can we predict the need for temporary pacing?
Authors: Kimura Yuki , Sumiyoshi Masataka , Inoue Kenji , Shiozaki Masayuki , Fukuda Kentaro , Fujiwara Yasumasa , Tabuchi Haruna , Hayashi Hidemori , Sekita Gaku , Tokano Takashi , Nakazato Yuji , Daida Hiroyuki
Published: May 2018

Background

In pacemaker‐dependent patients, the risk of asystole must be managed during device replacement. This study aimed to examine whether we could predict the indication for temporary pacing (TP) during the generator replacement.

Methods

We studied 105 consecutive patients who underwent pacemaker replacement due to battery depletion at Juntendo Nerima Hospital between September 2005 and December 2016. We examined the relationship between the stability of the intrinsic rhythm (IR) during pacemaker replacement and several clinical factors including age, gender, sick sinus syndrome or atrioventricular (AV) block, duration of pacing, structural heart disease, use of anti‐arrhythmic drugs, and the presence/absence of a stable IR (>40 bpm) at the outpatient clinic (OPC) just before pacemaker replacement.

Results

Of the 105 patients, we excluded 1 patient who required TP because of bradycardia‐dependent torsades de points. Therefore, we evaluated 104 patients for the indication for TP. TP was underwent in 19 patients (18%) because of an absence or instability of the IR during pacemaker replacement. The indication for TP was significantly correlated with AV block (84% vs 48%, P = .0044) and the absence of a stable IR at the last OPC visit (89% vs 24%, P < .0001). For predicting the indication for TP, the following values of no stable IR at the last OPC visit were obtained: 89% sensitivity, 77% specificity, 46% positive predictive value, and 97% negative predictive value.

Conclusions

The presence of a stable IR at the last OPC visit was a good predictor (97%) of no indication for TP during pacemaker replacement.
Determination of soil salinity based on WET measurements using the concept of salinity index
Authors: Kargas George , Kerkides Petros
Published: May 2018

We evaluated the Malicki and Walczak model (MW) and its appropriately modification (MMW) in the prediction of the electrical conductivity of the soil solution (σp), utilizing the WET dielectric sensor. In the MMW approach, the prediction of σp requires determination of the WET‐based salinity index (Xs) and clay and sand contents of the soil. MMW appears to be more effective than MW in all cases except for the cases of finer soils when σp > 3 dS m−1.
Synthesis and Surface Properties of a Novel Anionic Gemini Surfactant using Dioxaoctane as a Linking Group
Authors: Sun Ruixia , Hong Kwon Ho , Lv Zhenbo , Ding Xiaoguang , Wu Xuedong , Yu Fang
Published: May 2018

A novel anionic Gemini surfactant containing oxygen atoms in the linking group was designed and synthesized. The surface properties of the anionic Gemini surfactant were investigated by measuring the surface tension and conductivity. The Gemini surfactant showed a low critical micelle concentration value, which decreases with increasing concentration of NaCl. The calculated physicochemical properties indicate that oxygen atoms in the linking group interact with water molecules stronger than CH2.
Alignment materials with controllable anchoring energy
Authors: Bezruchenko Veronika , Muravsky Alexander , Murauski Anatoli , Stankevich Alexander , Mahilny Uladzimir
Published: May 2018

New polymers with photo‐controllable anchoring energy and tunable pretilt angle within 90°–0° range for nematic liquid crystals alignment were developed. The functional properties of polymers are provided by the effect of photoinduced planar alignment and the presence of side hydrocarbon chains in macromolecules that create a homeotropic alignment effect. Applying photosensitive alignment layers based on polymers with side benzaldehyde and hydrocarbon groups, fabrication of optical devices with refractive index gradient, uniform cell gap, and low operation voltage is possible. The developed materials are suitable for simple fabrication of tunable liquid crystal lenses.
Phase‐Selective Nanocrystallization of NaLnF4 in Aluminosilicate Glass for Random Laser and 940 nm LED‐Excitable Upconverted Luminescence
Authors: Li Xinyue , Chen Daqin , Huang Feng , Chang Guangcai , Zhao Junjie , Qiao Xvsheng , Xu Xuhui , Du Jincheng , Yin Min
Published: May 2018

Yb/Er doped hexagonal β‐NaLnF4 (Ln = Gd, Y, Lu) are regarded as the most efficient green upconversion (UC) materials. Unfortunately, β‐NaLnF4 is quite difficult to grow as monocrystal owing to cubic‐to‐hexagonal phase transition during cooling. As an alternative, herein a nanocrystallization controllable strategy to synthesize monodisperse whole‐family β‐NaLnF4 (from NaLaF4 to NaLuF4) embedded bulky glass ceramics is reported. A series of structural and spectroscopic characterizations indicate that Na content and Al/Si ratio are the most important factors to determine phase‐selective NaLnF4 crystallization in the aluminosilicate oxyfluoride glasses. Impressively, such nanocomposites are evidenced to be ideal hosts for upconversion luminescence of Yb3+/Er3+ dopants and as the proof‐of‐concept experiments, their applications in a random laser and incoherent LED‐excitable upconverting device as emitting media are demonstrated. It is expected that this study will provide a deep understanding for controllable crystallization in glass and extend the practical applications of glass ceramics in optoelectronic fields.
High‐Throughput Miniaturized Screening of Nanoparticle Formation via Inkjet Printing
Authors: Styliari Ioanna D. , Conte Claudia , Pearce Amanda K. , Hüsler Amanda , Cavanagh Robert J. , Limo Marion J. , Gordhan Dipak , Nieto‐Orellana Alejandro , Suksiriworapong Jiraphong , Couturaud Benoit , Williams Phil , Hook Andrew L. , Alexander Morgan R. , Garnett Martin C. , Alexander Cameron , Burley Jonathan C. , Taresco Vincenzo
Published: May 2018

The self‐assembly of specific polymers into well‐defined nanoparticles (NPs) is of great interest to the pharmaceutical industry as the resultant materials can act as drug delivery vehicles. In this work, a high‐throughput method to screen the ability of polymers to self‐assemble into NPs using a picoliter inkjet printer is presented. By dispensing polymer solutions in dimethyl sulfoxide (DMSO) from the printer into the wells of a 96‐well plate, containing water as an antisolvent, 50 suspensions are screened for nanoparticle formation rapidly using only nanoliters to microliters. A variety of polymer classes are used and in situ characterization of the submicroliter nanosuspensions shows that the particle size distributions match those of nanoparticles made from bulk suspensions. Dispensing organic polymer solutions into well plates via the printer is thus shown to be a reproducible and fast method for screening nanoparticle formation which uses two to three orders of magnitude less material than conventional techniques. Finally, a pilot study for a high‐throughput pipeline of nanoparticle production, physical property characterization, and cytocompatibility demonstrates the feasibility of the printing approach for screening of nanodrug delivery formulations. Nanoparticles are produced in the well plates, characterized for size and evaluated for effects on metabolic activity of lung cancer cells.
Sustainable Polymers from Renewable Resources: Polymer Blends of Furan‐Based Polyesters
Authors: Poulopoulou Niki , Kasmi Nejib , Bikiaris Dimitrios N. , Papageorgiou Dimitrios G. , Floudas George , Papageorgiou George Z.
Published: May 2018

A series of blends of furan‐based green polyesters, for eco‐friendly packaging materials, are synthesized. Poly(ethylene 2,5‐furandicarboxylate) (PEF), poly(propylene 2,5‐furandicarboxylate) (PPF), and poly(butylene 2,5‐furandicarboxylate) (PBF) are synthesized by applying melt polycondensation. Blends of the above polyesters with 50/50 w/w composition as well as blends of furanoate/terephthalate (PPF/PPT) are also prepared. The glass temperature along with the crystallization and melting behaviors of melt quenched blends are studied aiming at understanding their dynamic state and miscibility. Based on their Tg and crystallization behavior, PEF/PPF shows dynamic homogeneity and miscibility whereas PPF/PBF and PEF/PBF exhibit partial miscibility and immiscibility, respectively. In an effort to dynamically homogenize the compounds, reactive blending is applied and the behavior of the resulting blends is monitored following quenching. A profound improvement in blend homogenization is observed with increasing melt mixing time for the PPF/PPT sample, evidenced by the single glass temperature and by the narrowing in liquid‐to‐glass regime. The obtained single glass temperature together with the suppressed tendency for crystallization with increasing mixing time are taken as evidences of dynamic and thermodynamic homogeneity.
Surface‐Selective Grafting of Crosslinking Layers on Hydrogel Surfaces via Two Different Mechanisms of Photopolymerization for Site‐Controllable Release
Authors: Zhang Jiaojiao , Nie Jun , Zhu Xiaoqun
Published: May 2018

This study reports an effective method for controlling substance‐release sites of hydrogel. Glycidyl methacrylate, which contains two functional groups, namely, double‐bond acrylate and epoxide, is photografted on a hydrogel surface through hydrogen abstraction photopolymerization due to the existence of a hydrogen donor, such as an amine, in the hydrogel matrix. The remaining epoxide group crosslinks the polymer chain of polyglycidyl methacrylate. Substance release of hydrogel is changed due to the altered surface texture of hydrogel. Rate and site‐controlled substance release are achieved by controlling the thickness and site of surface grafting and the extent of epoxide ring opening. This study may provide a novel method for achieving hydrogel function or modified performance of other biomaterials to meet biological activity requirements.
Exploiting the Versatility of Polydopamine‐Coated Nanoparticles to Deliver Nitric Oxide and Combat Bacterial Biofilm
Authors: Adnan Nik Nik. M. , Sadrearhami Zahra , Bagheri Ali , Nguyen Thuy‐Khanh , Wong Edgar H. H. , Ho Kitty K. K. , Lim May , Kumar Naresh , Boyer Cyrille
Published: May 2018

In this study, an antimicrobial platform in the form of nitric oxide (NO) gas‐releasing polydopamine (PDA)‐coated iron oxide nanoparticles (IONPs) is developed for combating bacterial biofilms. NO is bound to the PDA‐coated IONPs via the reaction between NO and the secondary amine moieties on PDA to form N‐diazeniumdiolate (NONOate) functionality. To impart colloidal stability to the nanoparticles in aqueous solutions (e.g., phosphate buffered saline (PBS) and bacteria cell culture media M9), a polymer bearing hydrophilic and amine pendant groups, P(OEGMA)‐b‐P(ABA), is synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization and is subsequently grafted onto the PDA‐coated IONPs by employing the Schiff base/Michael addition reaction between o‐quinone and a primary amine. These nanoparticles are able to effectively disperse Pseudomonas aeruginosa biofilms (up to 79% dispersal) at submicromolar NO concentrations. In addition, the nanoparticles demonstrate excellent bactericidal activity toward P. aeruginosa planktonic and biofilm cells (up to 5‐log10 reduction).
Poly(vinyl diaminotriazine): From Molecular Recognition to High‐Strength Hydrogels
Authors: Liu Bo , Liu Wenguang
Published: May 2018

Poly(2‐vinyl‐4,6‐diamino‐1,3,5‐triazine), (PVDT) with diaminotriazine residues is found to form not only intramolecular hydrogen bonds, but also three robust, complementary hydrogen bonds with nucleobases such as thymine and uracil. Taking advantage of the three complementary hydrogen bonds, molecular recognition of a nucleic acid base has been investigated in previous work. Over the past few years, the use of PVDT has been extended to the construction of gene delivery vectors and nonswellable, high‐strength hydrogels by copolymerization with a hydrophilic monomer and/or crosslinker. In particular, many fascinating properties, such as excellent mechanical properties, stimuli responsiveness, the shape memory effect, and biodegradability, have emerged in PVDT‐based hydrogels. In this article, the molecular recognition and self‐assembly of diaminotriazine are introduced first, and then a particular focus is placed on the development of PVDT‐based high performance hydrogels, especially their biorelated applications.
Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages
Authors: Cheng Hongwei , Fan Xiaoshan , Wu Caisheng , Wang Xiaoyuan , Wang Li‐Juan , Loh Xian Jun , Li Zibiao , Wu Yun‐Long
Published: May 2018

Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star‐like amphiphilic biocompatible β‐cyclodextrin‐graft‐(poly(ε‐caprolactone)‐block‐poly(2‐(dimethylamino) ethyl methacrylate)x (β‐CD‐g‐(PCL‐b‐PDMAEMA)x) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε‐caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, β‐CD‐g‐(PCL‐b‐PDMAEMA)x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by β‐CD‐g‐(PCL‐b‐PDMAEMA)x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.
Wurster‐Type Anthanthrene Polyradicaloid Cations
Authors: Desroches Maude , Morin Jean‐François
Published: May 2018

4,10‐dibromoanthanthrone, a highly robust building block, is used to synthesize a bis(triarylamine) polymer. The polymer can be oxidized twice to form a polycationic macromolecule showing magnetic properties by electron paramagnetic resonance spectroscopy. In its dicationic state, the presence of isolated radicals is possible because of the interrupted conjugation between the diphenylamine with the anthanthrone core. The high steric hindrance prevents the planarity of the adjacent groups resulting in a polyradical cationic polymer. The oxidized polymer has a strong absorption in the near‐infrared region along with reversible redox stages.
Gut Glucosinolate Metabolism and Isothiocyanate Production
Authors: Narbad Arjan , Rossiter John Trevor
Published: May 2018

The glucosinolate‐myrosinase system in plants has been well studied over the years while relatively little research has been undertaken on the bacterial metabolism of glucosinolates. The products of myrosinase‐based glucosinolate hydrolysis in the human gut are important to health, particularly the isothiocyanates, as they are shown to have anticancer properties as well as other beneficial roles in human health. This review is concerned with the bacterial metabolism of glucosinolates but is not restricted to the human gut. Isothiocyanate production and nitrile formation are discussed together with the mechanisms of the formation of these compounds. Side chain modification of the methylsulfinylalkyl glucosinolates is reviewed and the implications for bioactivity of the resultant products are also discussed.
Design and development of a nonrigid phantom for the quantitative evaluation of DIR‐based mapping of simulated pulmonary ventilation
Authors: Miyakawa Shin , Tachibana Hidenobu , Moriya Shunsuke , Kurosawa Tomoyuki , Nishio Teiji , Sato Masanori
Published: May 2018

Purpose

The validation of deformable image registration (DIR)‐based pulmonary ventilation mapping is time consuming and prone to inaccuracies and is also affected by deformation parameters. In this study, we developed a nonrigid phantom as a quality assurance (QA) tool that simulates ventilation to evaluate DIR‐based images quantitatively.

Methods

The phantom consists of an acrylic cylinder filled with polyurethane foam designed to simulate pulmonic alveoli. A polyurethane membrane is attached to the inferior end of the phantom to simulate the diaphragm. In addition, tracheobronchial‐tree‐shaped polyurethane tubes are inserted through the foam and converge outside the phantom to simulate the trachea. Solid polyurethane is also used to model arteries, which closely follow the model airways. Two three‐dimensional (3D) CT scans were performed during exhalation and inhalation phases using xenon (Xe) gas as the inhaled contrast agent. The exhalation 3D‐CT image is deformed to an inhalation 3D‐CT image using our in‐house program based on the NiftyReg open‐source package. The target registration error (TRE) between the two images was calculated for 16 landmarks located in the simulated lung volume. The DIR‐based ventilation image was generated using Jacobian determinant (JD) metrics. Subsequently, differences in the Hounsfield unit (HU) values between the two images were measured. The correlation coefficient between the JD and HU differences was calculated. In addition, three 4D‐CT scans are performed to evaluate the reproducibility of the phantom motion and Xe gas distribution.

Results

The phantom exhibited a variety of displacements for each landmark (range: 1–20 mm). The reproducibility analysis indicated that the location differences were <1 mm for all landmarks, and the HU variation in the Xe gas distribution was close to zero. The mean TRE in the evaluation of spatial accuracy according to the DIR software was 1.47 ± 0.71 mm (maximum: 2.6 mm). The relationship between the JD and HU differences had a large correlation (R = −0.71) for the DIR software.

Conclusion

The phantom implemented new features, namely, deformation and simulated ventilation. To assess the accuracy of the DIR‐based mapping of the simulated pulmonary ventilation, the phantom allows for simulation of Xe gas wash‐in and wash‐out. The phantom may be an effective QA tool, because the DIR algorithm can be quickly changed and its accuracy evaluated with a high degree of precision.
Libration of phenyl groups detected by VT‐SSNMR: Comparison with X‐ray crystallography
Authors: Nieto Carla I. , Cabildo Pilar , García M. Ángeles , Claramunt Rosa M. , Elguero José , Alkorta Ibon
Published: May 2018

The X‐ray crystal structure of 2‐benzyl‐1H‐benzimidazole, 2BnBzIm, was determined at 293 K showing no dynamic phenomena (disorder) of any class. On the other hand, some 13C NMR signals were absent in the CPMAS spectrum (100 MHz, 300 K). We decided to carry out variable‐temperature SSNMR and discovered that the missing signals are ortho and meta carbons of the phenyl ring of the benzyl group. Line‐shape analysis and the Eyring equation were used to determine the barrier, which was compared with the calculated DFT for the gas phase that it is much lower.
Estimation of Polymerization Rate Constants Using Experimental Residence Time Studies in Industrial Pilot Plant Equipment
Authors: Karjala Thomas W. , Kolthammer Brian W. S. , Zhang Min , Jain Pradeep
Published: May 2018

Estimation of polymerization rate constants is industrially important for reactor design, reactor control, and evaluation of the productivity and product properties of new catalyst systems. Propagation and catalyst deactivation rate constants are particularly important as they control how a given catalyst system will behave in a given reactor. Pilot scale reactors are used to investigate the kinetics of solution ethylene polymerization of several catalyst systems; a heterogeneous Ziegler–Natta (Ti/MgCl2) and two constrained‐geometry molecular catalysts. A model is developed to estimate the propagation and first order catalyst deactivation rate constants through carefully conducted residence time experiments. D‐optimal experimental design criteria is used to determine the appropriate experimental conditions. Analysis shows that the observed propagation rate constant is confounded by catalyst poisons while the catalyst deactivation rate constant is independent of these factors. This helps explain how to obtain significantly larger propagation rate constants than have been previously reported in the literature.
Association between overactive bladder treatment and falls among older adults
Authors: Jayadevappa Ravishankar , Chhatre Sumedha , Newman Diane K. , Schwartz Jerome Sanford , Wein Alan J.
Published: May 2018

Aims

To analyze the risk of falls associated with Overactive bladder (OAB), and the effects of OAB treatment on falls among older adult Medicare fee‐for‐service enrollees.

Methods

Population based retrospective longitudinal cohort design study using 5% Medicare claims between 2006 and 2010. Patients with a diagnosis of OAB (ICD 9: 596.51); Urinary Incontinence (ICD 9: 788.3); Urinary incontinence, unspecified (ICD 9: 788.30); Urge incontinence (ICD 9: 788.31); Mixed incontinence (male, female) (ICD 9: 788.33); Urinary frequency (ICD 9: 788.41); Nocturia (ICD 9: 788.43); or Urgency of urination (ICD 9: 788.63) were identified and followed retrospectively for 2 years. Falls was the main outcome of the study. Using logistic regressions, we analyzed the association between OAB and falls; and the protective effect of OAB treatment on falls. Propensity score and instrumental variable were used to minimize bias.

Results

We identified 33 631 Medicare enrollees (mean age = 77.8 years, sd = 7.6) with OAB. Higher proportion of OAB patients had falls, compared to those without OAB (11% vs 7%, P < 0.001). Diagnosis of OAB was associated with higher odds of falls (OR = 1.59; 95% CI = 1.53, 1.65) compared to those without OAB. Fourteen percent of OAB patients received OAB treatment. Treatment for OAB was associated with lower odds of falls (OR = 0.88; 95% CI = 0.80, 0.98) compared to those OAB patients who were not treated.

Conclusions

Older adults with OAB experience increased risk of falls. Treatment for OAB may reduce this risk. These findings emphasize the need to effectively identify and treat OAB in older adults.
Encoding and readout strategies in magnetic resonance elastography
Authors: Guenthner Christian , Kozerke Sebastian
Published: May 2018

Magnetic resonance elastography (MRE) has evolved significantly since its inception. Advances in motion‐encoding gradient design and readout strategies have led to improved encoding and signal‐to‐noise ratio (SNR) efficiencies, which in turn allow for higher spatial resolution, increased coverage, and/or shorter scan times. The purpose of this review is to summarize MRE wave‐encoding and readout approaches in a unified mathematical framework to allow for a comparative assessment of encoding and SNR efficiency of the various methods available. Besides standard full‐ and fractional‐wave‐encoding approaches, advanced techniques including flow compensation, sample interval modulation and multi‐shot encoding are considered. Signal readout using fast k‐space trajectories, reduced field of view, multi‐slice, and undersampling techniques are summarized and put into perspective. The review is concluded with a foray into displacement and diffusion encoding as alternative and/or complementary techniques.
Cellulose‐based hydrogels for personal care products
Authors: Bashari Azadeh , Rouhani Shirvan Anahita , Shakeri Mina
Published: May 2018

Name of cellulose is referred to a type of natural carbohydrate with many hydroxyl groups and high water absorption capacity. Cellulose is the most abundant natural polymer, found as the main constituent of plants (plant cellulose). Some bacteria such as Acetobacter xylinum are also able to synthesize bacterial cellulose. Cellulose‐based hydrogels are superabsorbent materials, which make 3D networks. Chemical bonds or other cohesive forces such as hydrogen bonding or ionic interactions connect the cellulose chains together. Hydrogels can swell and absorb water and other aqueous fluids in their 3D networks, but they are insoluble in them. Nowadays, an increasing demand emerges for biodegradable materials and products made from renewable resources such as cellulose. The excellent biocompatibility of cellulose has prompted the large use of cellulose‐based personal care products. Cellulose hydrogel is used for these products as the thickener and stabilizing agents or as moisturizing agent to improve the skin feel of the product. Hygienic cellulosic absorbent products such as diapers, panty liners, tampons, paper towels, and tissue papers are used as personal care products. These products are available in different absorbency ratings from junior to ultra‐absorbency. Using cellulose‐based hydrogel, superabsorbent products are made. In this review, applications of cellulose‐based hydrogels in personal care products were reviewed.
Electronic health record (EHR) based postmarketing surveillance of adverse events associated with pediatric off‐label medication use: A case study of short‐acting beta‐2 agonists and arrhythmias
Authors: Czaja Angela S. , Ross Michelle E. , Liu Weiwei , Fiks Alexander G. , Localio Russell , Wasserman Richard C. , Grundmeier Robert W. , Adams William G. ,   for the Comparative Effectiveness Research through Collaborative Electronic Reporting (CER) Consortium
Published: May 2018

Purpose

Use electronic health record (EHR) data to (1) estimate the risk of arrhythmia associated with inhaled short‐acting beta‐2 agonists (SABA) in pediatric patients and (2) determine whether risk varied by on‐label versus off‐label prescribing.

Methods

Retrospective cohort study of 335 041 children ≤18 years using EHR primary care data from 2 pediatric health systems (2011‐2013). A series of monthly pseudotrials were created, using propensity score methodology to balance baseline characteristics between SABA‐exposed (identified by prescription) and SABA‐unexposed children. Association between SABA and subsequent arrhythmia for each health system was estimated through pooled logistic regression with separate estimates for children initiating under and over 4 years old (off‐label and on‐label, respectively).

Results

Eleven percent of the cohort received a SABA prescription, 57% occurred under the age of 4 years (off‐label). During the follow‐up period, there were 283 first arrhythmia events, most commonly atrial tachyarrhythmias and premature ventricular/atrial contractions. In 1 health system, adjusted risk for arrhythmia was increased among exposed children (OR 1.89, 95% CI 1.31‐2.73) without evidence of interaction between label status and risk. The absolute adjusted rate difference was 3.6/10 000 person‐years of SABA exposure. The association between SABA exposure and arrhythmias was less strong in the second system (OR 1.26, 95% CI 0.30‐5.33).

Conclusion

Using EHR data, we could estimate the risk of a rare event associated with medication use and determine difference in risk related to on‐label versus off‐label status. These findings support the value of EHR‐based data for postmarketing drug studies in the pediatric population.
Organic tandem solar cells: How impedance analyses can improve the quality of external quantum efficiency measurements
Authors: Bahro Daniel , Wilck Manfred , Mertens Adrian , Ebenhoch Bernd , von Hauff Elizabeth , Colsmann Alexander
Published: May 2018

Tandem architectures are one of the most promising concepts towards superior power conversion efficiencies of organic solar cells. An accurate determination of the power conversion efficiency requires correction of the spectral mismatch and thus relies on accurate external quantum efficiency (EQE) spectra. Due to the series connection of 2 subcells in the tandem architecture, the EQE of the tandem solar cell reproduces the EQE of one subcell if an appropriate bias light is chosen to selectively illuminate and hence forward bias the other subcell. The resulting internal voltage drop is then compensated by applying an external voltage to the tandem solar cell. In this work, we use impedance spectroscopy to accurately predict the minimum bias light intensity and the external voltage to enable accurate EQE measurements on both subcells. We exemplify this procedure on organic tandem solar cells comprising spectrally complementary absorbers and suggest an extended protocol for future measurements of the EQE.
Passivating electron‐selective contacts for silicon solar cells based on an a‐Si:H/TiOx stack and a low work function metal
Authors: Cho Jinyoun , Melskens Jimmy , Debucquoy Maarten , Recamán Payo Maria , Jambaldinni Shruti , Bearda Twan , Gordon Ivan , Szlufcik Jozef , Kessels W.M.M. , Poortmans Jef
Published: May 2018

In this work, the ATOM (intrinsic a‐Si:H/TiOx/low work function metal) structure is investigated to realize high‐performance passivating electron‐selective contacts for crystalline silicon solar cells. The absence of a highly doped Si region in this contact structure is meant to reduce the optoelectrical losses. We show that a low contact resistivity (ρc) can be obtained by the combined effect of a low work function metal, such as calcium (Φ 2.9 eV), and Fermi‐level depinning in the metal‐insulator‐semiconductor contact structure (where in our case TiOx acts as the insulator on the intrinsic a‐Si:H passivating layer). TiOx grown by ALD is effective to achieve not only a low ρc but also good passivation properties. As an electron contact in silicon heterojunction solar cells, inserting interfacial TiOx at the i‐a‐Si:H/Ca interface significantly enhances the solar cell conversion efficiency. Consequently, the champion solar cell with the ATOM contact achieves a VOC of 711 mV, FF of 72.9%, JSC of 35.1 mA/cm2, and an efficiency of 18.2%. The achievement of a high VOC and reasonable FF without the need for a highly doped Si layer serves as a valuable proof of concept for future developments on passivating electron‐selective contacts using this structure.