bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐PD‐1 antibodies in metastatic uveal melanoma: a treatment option?
Authors: Bender Carolin , Enk Alexander , Gutzmer Ralf , Hassel Jessica C.
Published: June 2017

Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti‐PD‐1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals. Therapy was administered at the approved dosing schedules of 2 mg/kg q3w for pembrolizumab and 3 mg/kg q2w for nivolumab. Treatment was given until first tumor assessment and continued if tumor assessment showed disease control. Tumor assessments were performed at baseline and following scans every 12 weeks. Patients were monitored throughout for adverse events. Best response to treatment was stable disease in four patients. Eight out of 15 (53%) patients received treatment until first tumor assessment. As of February 2016, median progression‐free survival (PFS) is 3 months (range 0.75–6.75 months) and overall survival (OS) is 5 months (range 1–16 months). Eight out of 15 (53%) patients are still alive (two patients lost to follow‐up) with one out of four patients is in ongoing disease control. Patients with multiple organ metastases and elevated serum lactate dehydrogenase did not respond well to treatment. No objective response to PD‐1 Ab therapy was seen. Best response to treatment was stable disease in four patients. Treatment was well tolerated with manageable toxicity.
New Carbon Nanodots‐Silica Hybrid Photocatalyst for Highly Selective Solar Fuel Production from CO2
Authors: Yadav Rajesh K. , Kumar Abhishek , Park No‐Joong , Yadav Dolly , Baeg Jin‐Ook
Published: June 2017

Photocatalytic CO2 reduction for solar fuel production has attracted considerable attention as it can simultaneously reduce the effects of worldwide fossil‐fuel shortage and global warming. As a means to achieve this we herein report the facile and eco‐friendly synthesis of highly active carbon nanodots‐silica hybrid photocatalyst (CNDSH) by a reverse microemulsion method with a nonionic surfactant. The photocatalyst‐biocatalyst coupled system developed using CNDSH as photocatalyst functions efficiently to carry out high NADH regeneration (74.10±0.17 %) followed by its consumption in exclusive formic acid production (203.33±1.9 μmol) from CO2. This research work is a benchmark example of carbon nanodots‐silica hybrid photocatalyst system for solar fuel production and expected to trigger further interest in the development of efficient and eco‐friendly CO2 reduction systems.
PEGylation Greatly Enhances Laccase Polymerase Activity
Authors: Su Jing , Noro Jennifer , Loureiro Ana , Martins Madalena , Azoia Nuno G. , Fu Jiajia , Wang Qiang , Silva Carla , Cavaco‐Paulo Artur
Published: June 2017

Laccase catalyzes the oxidation and polymerization of phenolic compounds in the presence of oxygen. Herein, we report for the first time that a previous PEGylation of laccase enhances the polymerase activity 3‐fold compared with the reaction of the native enzyme, as confirmed by UV/Vis spectroscopy. The polymerization of catechol increased only 1.5‐fold if poly(ethylene glycol) (PEG) was added to the medium reaction. Molecular‐dynamics simulations suggest the formation of a miscible complex of polycatechol and PEG, which is responsible to push the reaction forward. In a negative control experiment set, all catalysts were entrapped inside polyacrylamide gels and here the native laccase showed a relatively higher activity. These results suggest that the mobility of PEG is a key feature for the enhancement of the reaction.
Ternary NixCo3−xS4 with a Fine Hollow Nanostructure as a Robust Electrocatalyst for Hydrogen Evolution
Authors: Wang Min‐Qiang , Ye Cui , Bao Shu‐Juan , Chen Zhao‐Yang , Liu Heng , Xu Mao‐Wen
Published: June 2017

The elaborate design of efficient and stable electrocatalysts from earth‐abundant elements to replace precious Pt for the hydrogen evolution reaction (HER) is an ongoing challenge. Doping metallic compounds with additional metal atoms provides the opportunity to tune their electronic and crystal structures, which thus ameliorates their electrocatalytic properties. Herein, we report for the first time a robust and earth‐abundant Ni‐doped Co3S4 catalyst grown on carbon cloth that shows high HER activity in 1 m KOH. Morphology evolution and HER activity were found to be strongly related to the Ni substitution ratio. Electrochemical tests showed a low overpotential of 72.82 mV at 10 mA cm−2, a small Tafel slope of 49.44 mV dec−1, and long‐term durability over 46 h HER operation for the Ni0.5Co2.5S4 nanotube array self‐standing on carbon cloth. These data indicate that atomic modulation of Ni plays an important role in optimizing the morphology and electrocatalytic activity by greatly expanding the active sites in the electrocatalyst. Further, the 3 D self‐standing nanotube array highly aids in the exposure of active species and the transfer of electrons and charges, which substantially boosts the reaction kinetics and stability of the structure.
ASCA+ and APCA+: Extensions of ASCA and APCA in the analysis of unbalanced multifactorial designs
Authors: Thiel Michel , Féraud Baptiste , Govaerts Bernadette
Published: June 2017

Many modern analytical methods are used to analyse samples coming from an experimental design, for example, in medical, biological, or agronomic fields. Those methods generate most of the time highly multivariate data like spectra or images. This is the case of “omics” technologies used to detect genes (genomics), mRNA (transcriptomics), proteins (proteomics), or metabolites (metabolomics) in a specific biological sample. Those technologies produce high‐dimensional multivariate databases where the number of variables (descriptors) tends to be much larger than the number of experimental units. Moreover, experiments in omics often follow designs aimed at understanding the effect of several factors on biological systems. Therefore, multivariate statistical tools are needed to highlight variables that are consistently modified by different biological states. It is in this context that 2 recent methods combine analysis of variance (ANOVA) and principal component analysis (PCA), namely, ASCA (ANOVA–simultaneous component analysis) and APCA (ANOVA‐PCA). They provide powerful tools to visualize multivariate structures in the space of each effect of the statistical model linked to the experimental design. Their main limitation is that they provide biased estimators of the factor effects when the design of experiment is unbalanced. This paper introduces 2 new methods, ASCA+ and APCA+, that allow, respectively, to extend the use of ASCA and APCA to unbalanced designs using several principles from the theory of general linear models. Both methods are applied on real‐life metabolomics data, clearly demonstrating the capacity of ASCA+ and APCA+ methods to highlight correct biomarkers corresponding to effects of interest in unbalanced designs.
Correction of mosaicking artifacts in multimodal images caused by uneven illumination
Authors: Chernavskaia Olga , Guo Shuxia , Meyer Tobias , Vogler Nadine , Akimov Denis , Heuke Sandro , Heintzmann Rainer , Bocklitz Thomas , Popp Jürgen
Published: June 2017

Recent advances in nonlinear multimodal imaging, eg, the combination of coherent anti‐Stokes Raman scattering, 2‐photon excited autofluorescence, and second‐harmonic generation, have shown the great potential of this imaging technique for medical diagnostics. To extract reliable diagnostic information from these multimodal images, a complex image‐processing pipeline is necessary. A major part of this image‐processing pipeline is the elimination of the mosaicking artifact caused by an uneven illumination within the images. While this problem is well known in image processing of photographic images and methods to solve it were developed, their direct application to multimodal images does not yield satisfactory results. This fact results from the nonlinearity of the measurement modalities and characteristics of the multimodal images itself. In this contribution, different approaches to correct the mosaicking are considered and adapted to multimodal images. In this tutorial article, an investigation and comparative analysis of correction methods were performed, and practical recommendations for the application of different methods are given. The results of this paper can be applied to the development of complete or partial automatic software for medical diagnostics using nonlinear multimodal imaging techniques.
β‐Hydroxy‐tetrahydroquinolines from Quinolines Using Chloroborane: Synthesis of the Peptidomimetic FISLE‐412
Authors: Altiti Ahmad S. , Cheng Kai Fan , He Mingzhu , Al‐Abed Yousef
Published: June 2017

A new synthetic protocol provides a simple and direct method to generate functionalized β‐hydroxy‐tetrahydroquinolines (THQs). Hydroboration of quinolines using chloroboranes followed by oxidation with NaBO3⋅H2O led to the formation of functionalized β‐hydroxy THQs. High regio‐ and diastereoselectivities were observed in α and γ substituted quinolines and the trans diastereomer of the β‐hydroxy‐THQ was the major isostere. This new protocol was utilized to build the novel antibody‐targeted lupus peptidomimetic, FISLE‐412.
Photoactive Surface‐Grafted Polymer Brushes with Phthalocyanine Bridging Groups as an Advanced Architecture for Light‐Harvesting
Authors: Szuwarzyński Michał , Wolski Karol , Pomorska Agata , Uchacz Tomasz , Gut Arkadiusz , Łapok Łukasz , Zapotoczny Szczepan
Published: June 2017

Surface‐grafted polymer brushes of novel ladder‐like architecture were proposed for inducing ordering of chromophores embedded therein. The brushes with acetylene side groups were obtained by surface‐initiated photoiniferter‐mediated polymerization. The acetylene moieties reacted then through a “click” process with an axially azide‐bifunctionalized silicon phthalocyanine bridging the neighboring chains that inherently adopt extended conformations in dense brushes. FTIR, quartz crystal microbalance, and atomic force microscopy were used to study formation and structure of the photoactive brushes varying in grafting densities. Importantly, photophysical properties of the chromophores were virtually unaffected upon embedding them into the brushes, as evidenced by UV/Vis absorption and emission spectroscopy. Owing to the unique ordering of the chromophores, the proposed method may open new opportunities for the fabrication of light‐harvesting systems suitable for photovoltaic or sensing applications.
Preparation, Single‐Molecule Manipulation, and Energy Transfer Investigation of a Polyfluorene‐graft‐DNA polymer
Authors: Madsen Mikael , Christensen Rasmus S. , Krissanaprasit Abhichart , Bakke Mette R. , Riber Camilla F. , Nielsen Karina S. , Zelikin Alexander N. , Gothelf Kurt V.
Published: June 2017

Conjugated polymers have been intensively studied due to their unique optical and electronic properties combined with their physical flexibility and scalable bottom up synthesis. Although the bulk qualities of conjugated polymers have been extensively utilized in research and industry, the ability to handle and manipulate conjugated polymers at the nanoscale lacks significantly behind. Here, the toolbox for controlled manipulation of conjugated polymers was expanded through the synthesis of a polyfluorene‐DNA graft‐type polymer (poly(F‐DNA)). The polymer possesses the characteristics associated with the conjugated polyfluorene backbone, but the protruding single‐stranded DNA provides the material with an exceptional addressability. This study demonstrates controlled single‐molecule patterning of poly(F‐DNA), as well as energy transfer between two different polymer–DNA conjugates. Finally, highly efficient DNA‐directed quenching of polyfluorene fluorescence was shown.
Treatment at high‐volume facilities and academic centers is independently associated with improved survival in patients with locally advanced head and neck cancer
Authors: David John M. , Ho Allen S. , Luu Michael , Yoshida Emi J. , Kim Sungjin , Mita Alain C. , Scher Kevin S. , Shiao Stephen L. , Tighiouart Mourad , Zumsteg Zachary S.
Published: June 2017

BACKGROUND

The treatment of head and neck cancers is complex and associated with significant morbidity, requiring multidisciplinary care and physician expertise. Thus, facility characteristics, such as clinical volume and academic status, may influence outcomes.

METHODS

The current study included 46,567 patients taken from the National Cancer Data Base who were diagnosed with locally advanced invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx and were undergoing definitive radiotherapy. High‐volume facilities (HVFs) were defined as the top 1% of centers by the number of patients treated from 2004 through 2012. Multivariable Cox regression and propensity score matching were performed to account for imbalances in covariates.

RESULTS

The median follow‐up was 55.1 months. Treatment at a HVF (hazard ratio, 0.798; 95% confidence interval, 0.753‐0.845 [P<.001]) and treatment at an academic facility (hazard ratio, 0.897; 95% confidence interval, 0.871‐0.923 [P<.001]) were found to be independently associated with improved overall survival in multivariable analysis. In propensity score‐matched cohorts, the 5‐year overall survival rate was 61.6% versus 55.5% for patients treated at an HVF versus lower‐volume facilities, respectively (P<.001). Similarly, the 5‐year overall survival rate was 52.3% versus 49.7% for patients treated at academic versus nonacademic facilities (P<.001). Analysis of facility volume as a continuous variable demonstrated continual improvement in survival with an increased number of patients treated. The impact of facility volume and academic designation on survival was observed when using a variety of thresholds to define HVF, and across the vast majority of subgroups, including both oropharyngeal and nonoropharyngeal subsites.

CONCLUSIONS

Patients with locally advanced head and neck squamous cell carcinoma who are undergoing curative radiotherapy at HVFs and academic centers appear to have improved survival. Cancer 2017;123:3933‐42. © 2017 American Cancer Society.
Challenges in the Development of Novel Cardiovascular Therapies
Authors: Hwang TJ , Kesselheim AS
Published: June 2017

Cardiovascular disease accounts for nearly one in three deaths globally, but few novel therapies have reached patients and clinicians in recent years. This translational report reviews trends in the development and approval of cardiovascular drugs and evaluates recent innovation in the field of cardiovascular disease therapeutics. New policies are needed to better support the development of safe and effective therapies with the greatest potential to improve patient health outcomes.
Quantitative Insights into the Fast Pyrolysis of Extracted Cellulose, Hemicelluloses, and Lignin
Authors: Carrier Marion , Windt Michael , Ziegler Bernhard , Appelt Jörn , Saake Bodo , Meier Dietrich , Bridgwater Anthony
Published: June 2017

The transformation of lignocellulosic biomass into bio‐based commodity chemicals is technically possible. Among thermochemical processes, fast pyrolysis, a relatively mature technology that has now reached a commercial level, produces a high yield of an organic‐rich liquid stream. Despite recent efforts to elucidate the degradation paths of biomass during pyrolysis, the selectivity and recovery rates of bio‐compounds remain low. In an attempt to clarify the general degradation scheme of biomass fast pyrolysis and provide a quantitative insight, the use of fast pyrolysis microreactors is combined with spectroscopic techniques (i.e., mass spectrometry and NMR spectroscopy) and mixtures of unlabeled and 13C‐enriched materials. The first stage of the work aimed to select the type of reactor to use to ensure control of the pyrolysis regime. A comparison of the chemical fragmentation patterns of “primary” fast pyrolysis volatiles detected by using GC‐MS between two small‐scale microreactors showed the inevitable occurrence of secondary reactions. In the second stage, liquid fractions that are also made of primary fast pyrolysis condensates were analyzed by using quantitative liquid‐state 13C NMR spectroscopy to provide a quantitative distribution of functional groups. The compilation of these results into a map that displays the distribution of functional groups according to the individual and main constituents of biomass (i.e., hemicelluloses, cellulose and lignin) confirmed the origin of individual chemicals within the fast pyrolysis liquids.
Cell lineage tracing in the retina: Could material transfer distort conclusions?
Authors: Boudreau‐Pinsonneault Camille , Cayouette Michel
Published: June 2017

Recent studies reported the transfer of fluorescent labels between grafted and host cells after transplantation of photoreceptor precursor cells in the mouse retina. While clearly impacting the interpretation of transplantation studies in the retina, the potential impact of material transfer in other experimental paradigms using cell‐specific labels remains uncertain. Here, we briefly review the evidence supporting material transfer in transplantation studies and discuss whether it might influence retinal cell lineage tracing experiments in developmental and regeneration studies. We also propose ways to control for the possible confounding occurrence of label exchange in such experiments. Developmental Dynamics 247:10–17, 2018. © 2017 Wiley Periodicals, Inc.
IRF6 expression in basal epithelium partially rescues Irf6 knockout mice
Authors: Kousa Youssef A. , Moussa Dina , Schutte Brian C.
Published: June 2017

Background: Mutations in IRF6, CHUK (IKKA), and RIPK4 can lead to a disease spectrum that includes cutaneous, limb, and craniofacial malformations. Loss of these alleles in the mouse leads to perinatal lethality and severe cutaneous, limb, and craniofacial defects also. Genetic rescue in the mouse has been shown for Ikka and Ripk4. Results: Here, we show partial genetic rescue of Irf6 knockout embryos using the KRT14 promoter to drive Irf6 expression in the basal epithelium. In contrast to Irf6 knockout embryos, rescue embryos survive the immediate perinatal period. Macroscopic examination reveals rescue of skin adhesions between the axial and appendicular skeleton. Unexpectedly, KRT14‐driven Irf6 expression does not completely rescue orofacial clefting and adhesions between the palate and tongue, suggesting the importance of cell‐autonomous IRF6 expression in periderm. Like knockout embryos, Irf6 rescue embryos also have persistent esophageal adhesions, which likely contribute to postnatal demise. Conclusions: Together, these data suggest that targeted expression of IRF6 can significantly reduce disease severity, but that a minimum level of Irf6 in both periderm and basal epithelial cells is necessary for orofacial development. Therefore, homologous human and mouse phenotypes are observed for IRF6, IKKA, and RIPK4. In this work, we show that altering the expression level of IRF6 dramatically modified this phenotype in utero. Developmental Dynamics 246:670–681, 2017. © 2017 Wiley Periodicals, Inc.
Mitochondrial dynamics in the regulation of neurogenesis: From development to the adult brain
Authors: Khacho Mireille , Slack Ruth S.
Published: June 2017

Mitochondria are classically known to be the cellular energy producers, but a renewed appreciation for these organelles has developed with the accumulating discoveries of additional functions. The importance of mitochondria within the brain has been long known, particularly given the high‐energy demanding nature of neurons. The energy demands imposed by neurons require the well‐orchestrated morphological adaptation and distribution of mitochondria. Recent studies now reveal the importance of mitochondrial dynamics not only in mature neurons but also during neural development, particularly during the process of neurogenesis and neural stem cell fate decisions. In this review, we will highlight the recent findings that illustrate the importance of mitochondrial dynamics in neurodevelopment and neural stem cell function. Developmental Dynamics 247:47–53, 2018. © 2017 Wiley Periodicals, Inc.
Assessment of executive functioning in binge‐eating disorder independent of weight status
Authors: Eneva Kalina T. , Arlt Jean M. , Yiu Angelina , Murray Susan M. , Chen Eunice Y.
Published: June 2017

Objective

Executive functioning (EF) problems may serve as vulnerability or maintenance factors for Binge‐Eating Disorder (BED). However, it is unclear if EF problems observed in BED are related to overweight status or BED status. The current study extends this literature by examining EF in overweight and normal‐weight BED compared to weight‐matched controls.

Method

Participants were normal‐weight women with BED (n = 23), overweight BED (n = 32), overweight healthy controls (n = 48), and normal‐weight healthy controls (n = 29). The EF battery utilized tests from the National Institutes of Health (NIH) Toolbox and Delis‐Kaplan Executive Function System (D‐KEFS).

Results

After controlling for years of education and minority status, overweight individuals performed more poorly than normal‐weight individuals on a task of cognitive flexibility requiring generativity (p < .01), and speed on psychomotor performance tasks (p = .01). Normal‐weight and overweight BED performed worse on working memory tasks compared to controls (p = .04). Unexpectedly, normal‐weight BED individuals out‐performed all other groups on an inhibitory control task (p < .01). No significant differences were found between the four groups on tasks of planning.

Discussion

Regardless of weight status, BED is associated with working memory problems. Replication of the finding that normal‐weight BED is associated with enhanced inhibitory control is needed.
Parasite and host elemental content and parasite effects on host nutrient excretion and metabolic rate
Authors: Chodkowski Nicole , Bernot Randall J.
Published: June 2017

Ecological stoichiometry uses the mass balance of elements to predict energy and elemental fluxes across different levels of ecological organization. A specific prediction of ecological stoichiometry is the growth rate hypothesis (GRH), which states that organisms with faster growth or reproductive rates will require higher phosphorus content for nucleic acid and protein synthesis. Although parasites are found ubiquitously throughout ecosystems, little is understood about how they affect nutrient imbalances in ecosystems. We (1) tested the GRH by determining the carbon (C), nitrogen (N), and phosphorus (P) content of parasitic trematodes and their intermediate host, the freshwater snail Elimia livescens, and (2) used this framework to determine the trematode effects on host nutrient excretion and metabolism. Snail and parasite tissues were analyzed for elemental content using a CHN analyzer and soluble reactive phosphorus (SRP) methods. Ammonium and SRP assays were used to estimate N and P excretion rates. A respirometer was used to calculate individual snail metabolism. Trematode tissues contained lower C:P and N:P (more P per unit C and N) than the snail tissues. Snail gonadal tissues more closely resembled the elemental content of parasite tissues, although P content was 13% higher in the gonad than the trematode tissues. Despite differences in elemental content, N and P excretion rates of snails were not affected by the presence of parasites. Parasitized snails maintained faster metabolic rates than nonparasitized snails. However, the species of parasite did not affect metabolic rate. Together, this elemental imbalance between parasite and host, and the altered metabolic rate of infected snails may lead to broader parasite effects in stream ecosystems.
Genome size in arthropods; different roles of phylogeny, habitat and life history in insects and crustaceans
Authors: Alfsnes Kristian , Leinaas Hans Petter , Hessen Dag Olav
Published: June 2017

Despite the major role of genome size for physiology, ecology, and evolution, there is still mixed evidence with regard to proximate and ultimate drivers. The main causes of large genome size are proliferation of noncoding elements and/or duplication events. The relative role and interplay between these proximate causes and the evolutionary patterns shaped by phylogeny, life history traits or environment are largely unknown for the arthropods. Genome size shows a tremendous variability in this group, and it has a major impact on a range of fitness‐related parameters such as growth, metabolism, life history traits, and for many species also body size. In this study, we compared genome size in two major arthropod groups, insects and crustaceans, and related this to phylogenetic patterns and parameters affecting ambient temperature (latitude, depth, or altitude), insect developmental mode, as well as crustacean body size and habitat, for species where data were available. For the insects, the genome size is clearly phylogeny‐dependent, reflecting primarily their life history and mode of development, while for crustaceans there was a weaker association between genome size and phylogeny, suggesting life cycle strategies and habitat as more important determinants. Maximum observed latitude and depth, and their combined effect, showed positive, and possibly phylogenetic independent, correlations with genome size for crustaceans. This study illustrate the striking difference in genome sizes both between and within these two major groups of arthropods, and that while living in the cold with low developmental rates may promote large genomes in marine crustaceans, there is a multitude of proximate and ultimate drivers of genome size.
Seedling tolerance to cotyledon removal varies with seed size: A case of five legume species
Authors: Hu Xiao Wen , Zhang Rui , Wu Yan Pei , Baskin Carol C.
Published: June 2017

It is generally accepted that seedlings from large seeds are more tolerant to defoliation than those from small seeds due to the additional metabolic reserves present in the large seeds. However, information on the effects of amount of seed reserves (cotyledon removal) from seedlings resulting from large vs. small seeds on seedling growth and long‐term survival in the field is limited. Five legume species with different sizes of seeds were sown in the field and none, one, or both cotyledons removed 7 days after seedling emergence. Seedling biomass, relative growth rate (RGR) and survival were determined at different time. Cotyledon removal, species, and their interaction had significant effects on seedling growth and survival. During the period between 33 and 70 days, seedlings from large seeds had a significantly lower RGR than those from small seeds. Biomass, RGR, and survival of seedlings from large seeds were significantly reduced by removal one or both cotyledons, whereas those of seedlings from small seeds were not affected. Seed energy reserves are more important for the early growth of seedlings from large seeds than for those from small seeds. The overall effect of cotyledon removal on growth and survival varies with seed size (i.e., energy reserves) with seedlings from small seeds being less sensitive than those from large seeds under field conditions.
Oxygen Reduction Reaction (ORR) Activity of a Phenol‐Substituted Linear FeIII–Porphyrin Dimer
Authors: Tei Go , Tamaki Takashi , Hayashi Takao , Nakajima Kosuke , Sakai Akihiro , Yotsuhashi Satoshi , Ogawa Takuji
Published: June 2017

Invited for the cover of this issue are the groups of Go Tei (Panasonic Corporation, Osaka) and Takuji Ogawa (University of Osaka), Japan. The cover image shows the mechanism of the oxygen reduction reaction (ORR) on the phenol‐substituted Fe–porphyrin dimer catalyst.
Passerini/Tsuji–Trost Strategy towards Pyrrole Derivatives
Authors: Narboni Noisette , El Kaim Laurent
Published: June 2017

The Passerini reaction of α,β‐unsaturated aldehydes affords suitable substrates for a Tsuji–Trost reaction with NH‐enamines. The latter behave as a 1,3‐bisnucleophile, which leads to the formation of pyrrole derivatives with five points of diversity through a Tsuji–Trost/Michael addition/aromatization cascade.
Cyclic tests of steel plate shear walls using box‐shape vertical boundary elements with or without infill concrete
Authors: Li Chao‐Hsien , Tsai Keh‐Chyuan , Huang Hsuan‐Yu , Tsai Ching‐Yi
Published: June 2017

The steel plate shear wall (SPSW) is an effective lateral force resisting system in which unstiffened steel infill plates are connected to the horizontal and vertical boundary elements (VBEs) on all sides of the plates. The boundary elements must be designed to resist the tension field force of the infill panels. When the VBEs are made from a steel box section, the flange of each box VBE connected with the infill panels can be pulled out‐of‐plane by significant panel forces, called pull‐out action. This study investigates capacity design methods for box VBEs in SPSWs. Simplified fixed beam and portal frame models aim to estimate the pull‐out responses of the flange of the box sections with and without infill concrete, respectively. In this study, cyclic tests of three full‐scale two‐story SPSWs using box VBEs with or without the infill concrete are conducted. Inelastic pushover analyses of the finite element models are conducted. The tests and analytical results confirm that the proposed design methods, which aimed to prevent the full yield of the flange under the pull‐out action, are applicable. Furthermore, the test and analytical results suggest that the initial yielding of the flange of box VBEs under the collective effects of the pull‐out action on the flange, the gravity load, and the sway action on the SPSW represents a local yielding. A strict prohibition of the initial yielding on the flange under the aforementioned collective effects is not recommended for pursuing a cost‐effective design. Copyright © 2017 John Wiley & Sons, Ltd.
Variability in Percentage Above Cut Scores Due to Discreteness in Score Scale
Authors: Lu Ying
Published: June 2017

For standard‐ or criterion‐based assessments, the use of cut scores to indicate mastery, nonmastery, or different levels of skill mastery is very common. As part of performance summary, it is of interest to examine the percentage of examinees at or above the cut scores (PAC) and how PAC evolves across administrations. This paper shows that discreteness in score scales can affect the PAC statistics considerably, especially when the test is short and when there are high examinee density and low item density near the cut score on the reporting score scale. This paper also includes recommendations on how to adjust the PAC statistics when they are used in trend analyses.
Unified one‐fluid formulation for incompressible flexible solids and multiphase flows: Application to hydrodynamics using the immersed structural potential method (ISPM)
Authors: Yang Liang , Gil Antonio J. , Carreño Aurelio Arranz , Bonet Javier
Published: June 2017

In this paper, we present a two‐dimensional computational framework for the simulation of fluid‐structure interaction problems involving incompressible flexible solids and multiphase flows, further extending the application range of classical immersed computational approaches to the context of hydrodynamics. The proposed method aims to overcome shortcomings such as the restriction of having to deal with similar density ratios among different phases or the restriction to solve single‐phase flows. First, a variation of classical immersed techniques, pioneered with the immersed boundary method (IBM), is presented by rearranging the governing equations, which define the behaviour of the multiple physics involved. The formulation is compatible with the “one‐fluid” formulation for two‐phase flows and can deal with large density ratios with the help of an anisotropic Poisson solver. Second, immersed deformable structures and fluid phases are modelled in an identical manner except for the computation of the deviatoric stresses. The numerical technique followed in this paper builds upon the immersed structural potential method developed by the authors, by adding a level set–based method for the capturing of the fluid‐fluid interfaces and an interface Lagrangian‐based meshless technique for the tracking of the fluid‐structure interface. The spatial discretisation is based on the standard marker‐and‐cell method used in conjunction with a fractional step approach for the pressure/velocity decoupling, a second‐order time integrator, and a fixed‐point iterative scheme. The paper presents a wide d range of two‐dimensional applications involving multiphase flows interacting with immersed deformable solids, including benchmarking against both experimental and alternative numerical schemes.
Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology
Authors: Pfarr Nicole , Darb‐Esfahani Silvia , Leichsenring Jonas , Taube Eliane , Boxberg Melanie , Braicu Ioana , Jesinghaus Moritz , Penzel Roland , Endris Volker , Noske Aurelia , Weichert Wilko , Schirmacher Peter , Denkert Carsten , Stenzinger Albrecht
Published: June 2017

Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in‐situ hybridization (FISH) and quantitative PCR‐based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%‐75% of urothelial carcinoma and in 16% of ovarian clear‐cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting.
TRPV4 channels contribute to calcium transients in astrocytes and neurons during peri‐infarct depolarizations in a stroke model
Authors: Rakers Cordula , Schmid Matthias , Petzold Gabor C.
Published: June 2017

Stroke is one of the leading causes of death and long‐term disability. In the penumbra, that is, the area surrounding the infarct core, peri‐infarct depolarizations (PIDs) are accompanied by strong intracellular calcium elevations in astrocytes and neurons, thereby negatively affecting infarct size and clinical outcome. The dynamics of PIDs and the cellular pathways that are involved during PID formation and progression remain incompletely understood. We have previously shown that inositol triphosphate‐gated calcium release from internal stores is a major component of PID‐related astroglial calcium signals, but whether external calcium influx through membrane‐localized channels also contributes to PIDs has remained unclear. In this study, we investigated the role of two astroglial membrane channels, transient receptor vanilloid 4 (TRPV4) channel and aquaporin‐4 (AQP4). We combined in vivo multiphoton microscopy, electrophysiology as well as laser speckle contrast imaging with the middle cerebral artery occlusion stroke model. Using knockout mice and pharmacological inhibitors, we found that TRPV4 channels contribute to calcium influx into astrocytes and neurons and subsequent extracellular glutamate accumulation during PIDs. AQP4 neither influenced PID‐related calcium signals nor PID‐related edema of astrocyte somata. Both channels did not alter the dynamics, frequency and cerebrovascular response of PIDs in the penumbra. These data indicate that TRPV4 channels may represent a potential target to ameliorate the PID‐induced calcium overload of astrocytes and neurons during acute stroke.
Investigating the separate and interactive associations of trauma and depression on brain structure: implications for cognition and aging
Authors: Karstens Aimee J. , Ajilore Olusola , Rubin Leah H. , Yang Shaolin , Zhang Aifeng , Leow Alex , Kumar Anand , Lamar Melissa
Published: June 2017

Objective

Trauma and depression are associated with brain structural alterations; their combined effects on these outcomes are unclear. We previously reported a negative effect of trauma, independent of depression, on verbal learning and memory; less is known about underlying structural associates. We investigated separate and interactive associations of trauma and depression on brain structure.

Methods

Adults aged 30–89 (N = 203) evaluated for depression (D+) and trauma history (T+) using structured clinical interviews were divided into 53 D+T+, 42 D+T−, 50 D−T+, and 58 D−T−. Multivariable linear regressions examined the separate and interactive associations of depression and trauma with prefrontal and temporal lobe cortical thickness composites and hippocampal volumes adjusting for age, sex, predicted verbal IQ, comorbid anxiety, and vascular risk. Significant results informed analyses of tract‐based structural connectomic measures of efficiency and centrality.

Results

Trauma, independent of depression, was associated with greater left prefrontal cortex (PFC) thickness, in particular the medial orbitofrontal cortex and pars orbitalis. A trauma × depression interaction was observed for the right PFC in age‐stratified analyses: Older D + T+ had reduced PFC thickness compared with older D − T+ individuals. Regardless of age, trauma was associated with more left medial orbitofrontal cortex efficiency and less pars orbitalis centrality. In the T+ group, left pars orbitalis cortical thickness and centrality negatively correlated with verbal learning.

Conclusions

Trauma, independent of depression, associated with altered PFC characteristics, morphologically and in terms of structural network communication and influence. Additionally, findings suggest that there may be a combined effect of trauma and depression in older adults. Copyright © 2017 John Wiley & Sons, Ltd.
The emergence of NS5B resistance associated substitution S282T after sofosbuvir‐based treatment
Authors: Gane Edward J. , Metivier Sophie , Nahass Ronald , Ryan Michael , Stedman Catherine A. , Svarovskaia Evguenia S. , Mo Hongmei , Doehle Brian , Dvory‐Sobol Hadas , Hedskog Charlotte , Lin Ming , Brainard Diana M. , Yang Jenny C. , McHutchison John G. , Sulkowski Mark , Younes Ziad , Lawitz Eric
Published: June 2017

S282T in NS5B is the primary amino acid substitution associated with resistance to sofosbuvir (SOF) but has rarely been detected in patients treated with a SOF‐based regimen. Here, the emergence and fitness of the S282T substitution in virologic failure patients administered SOF‐based regimens across the SOF and ledipasvir (LDV)/SOF phase 2 and 3 programs was evaluated. Plasma samples collected at baseline and at virologic failure were amplified and deep sequenced (1% cutoff). To date, over 12,000 patients have been treated in SOF or LDV/SOF phase 2 and 3 studies. Of these, deep sequencing was available at baseline in 8598 patients (62.4% genotype [GT] 1, 10.7% GT2, 20.9% GT3, and 6.0% GT4‐6) and at virologic failure in 901 patients. In the 8598 patients, no S282T substitution was detected at baseline; at virologic failure, 10 of the 901 (1%) patients had S282T detected. The SOF‐based regimen associated with treatment‐emergent S282T was SOF monotherapy in two patients, retreatment with LDV/SOF in prior LDV/SOF failures in three patients, LDV/SOF for 8 weeks in 1 GT1 patient, LDV/SOF for 12 weeks in 1 patient each with GT3, GT4, and GT5, and LDV/SOF + ribavirin for 12 weeks in 1 GT6 patient. Nine of 10 patients with emergent S282T received an SOF‐based retreatment regimen, eight of whom achieved sustained virologic response 12 weeks after treatment and one of whom failed retreatment. Conclusion: The emergence of S282T substitution was rare in patients who fail SOF‐based regimens. Successful retreatment of prior SOF failure patients is possible in the presence of S282T substitution with SOF in combination with various direct‐acting antiviral agents. (Hepatology Communications 2017;1:538–549)
Tailoring of physicochemical properties of nanocarriers for effective anti‐cancer applications
Authors: Chakraborty Swaroop , Dhakshinamurthy Geethanjali S. , Misra Superb K.
Published: June 2017

Nanotechnology has emerged strongly as a viable option to overcome the challenge of early diagnosis and effective drug delivery, for cancer treatment. Emerging research articles have expounded the advantages of using a specific type of nanomaterial‐based system called as “nanocarriers,” for anti‐cancer therapy. The nanocarrier system is used as a transport unit for targeted drug delivery of the therapeutic drug moiety. In order for the nanocarriers to be effective for anticancer therapy, their physicochemical parameter needs to be tuned so that bio‐functionalisation can be achieved to (1) allow drugs being attached to the substrate and for their controlled release, (2) ensure the stability of the nanocarrier up to the point of delivery, and (3) clearance of the nanocarrier after the delivery. It is therefore envisaged that tailoring of the physicochemical properties of nanocarriers can greatly influence their reactivity and interaction in the biological milieu, and this is becoming an important parameter for increasing the efficacy of cancer therapy. This review emphasizes the importance of physicochemical properties of nanocarriers, and how they influence its usage as chemotherapeutic drug carriers. The goal of this review is to present a correlation between the physicochemical properties of the nanocarriers and its intended action, and how their design based on these properties can enhance their cancer combating abilities while minimizing damage to the healthy tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2906–2928, 2017.
The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients
Authors: Li Rui , Dai Jinna , Kang Hui
Published: June 2017

Background

Serum creatinine, urea, and cystatin‐c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases.

Methods

Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC‐MS/MS on MRM (+) mode.

Results

Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin‐c.

Conclusion

Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early‐stage chronic kidney disease.
Reassessment of the Access Testosterone chemiluminescence assay and comparison with LC‐MS method
Authors: Dittadi Ruggero , Matteucci Mara , Meneghetti Elisa , Ndreu Rudina
Published: June 2017

Aim of the study

To reassess the imprecision and Limit of Quantitation, to evaluate the cross‐reaction with dehydroepiandrosterone‐sulfate (DHEAS), the accuracy toward liquid chromatography‐mass spectrometry (LC‐MS) and the reference interval of the Access Testosterone method, performed by DxI immunoassay platform (Beckman Coulter).

Material and Methods

Imprecision was evaluated testing six pool samples assayed in 20 different run using two reagents lots. The cross‐reaction with DHEAS was studied both by a displacement curve and by spiking DHEAS standard in two serum samples with known amount of testosterone. The comparison with LC‐MS was evaluated by Passing‐Bablock analysis in 21 routine serum samples and 19 control samples from an External Quality Assurance (EQA) scheme. The reference interval was verified by an indirect estimation on 2445 male and 2838 female outpatients.

Results

The imprecision study showed a coefficient of variation (CV) between 2.7% and 34.7% for serum pools from 16.3 and 0.27 nmol/L. The value of Limit of Quantitation at 20% CV was 0.53 nmol/L. The DHEAS showed a cross‐reaction of 0.0074%. A comparison with LC‐MS showed a trend toward a slight underestimation of immunoassay vs LC‐MS (Passing‐Bablock equations: DxI=−0.24+0.906 LCMS in serum samples and DxI=−0.299+0.981 LCMS in EQA samples). The verification of reference interval showed a 2.5th‐97.5th percentile distribution of 6.6‐24.3 nmol/L for male over 14 years and <0.5‐2.78 nmol/L for female subjects, in accord with the reference intervals reported by the manufacturer.

Conclusions

The Access Testosterone method could be considered an adequately reliable tool for the testosterone measurement.