bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat stress hardening of oriental armyworms is induced by a transient elevation of reactive oxygen species during sublethal stress
Authors: Matsumura Takashi , Matsumoto Hitoshi , Hayakawa Yoichi
Published: September 2017

Pre‐exposure to mild heat stress enhances the thermotolerance of insects. Stress hardening is a beneficial physiological plasticity, but the mechanism underlying it remains elusive. Here we report that reactive oxygen species (ROS) concentrations were quickly and transiently elevated in the armyworms, Mythimna separata, by exposing them to 40°C, but not other tested temperatures. Larvae exposed to 40°C had subsequently elevated antioxidant activity and the highest survival of all tested heating conditions. The elevation of ROS after lethal heating at 44°C for 1 h was approximately twofold compared to heating at 40°C. Injection of an optimal amount of hydrogen peroxide (H2O2) similarly caused sequential elevation of ROS and antioxidant activity in the test larval hemolymph, which led to significantly enhanced survival after lethal heat stress. The H2O2‐induced thermotolerance was abolished by coinjection of potent antioxidants such as ascorbic acid or N‐acetylcysteine. Both preheating at 40°C and H2O2 injection enhanced expression of genes encoding superoxide dismutase 1, catalase, and heat shock protein 70 in the fat body of test larvae, indicating the adequate heat stress induced a transient elevation of ROS, followed by upregulation of antioxidant activity. We infer that thermal stress hardening is induced by a small timely ROS elevation that triggers a reduction–oxidation signaling mechanism.
Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX‐2 Inhibitors
Authors: Ahmaditaba Mohammad A. , Shahosseini Soraya , Daraei Bahram , Zarghi Afshin , Houshdar Tehrani Mohammad H.
Published: September 2017

A new class of peptide derivatives possessing SO2Me and N3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid‐phase synthesis methodology, and evaluated as selective cyclooxygenase‐2 (COX‐2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX‐2 inhibitor with a COX‐2 selectivity index of >500. The structure–activity relationships (SARs) acquired indicated that compound 2a containing a 4‐(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ring bearing amino acid in the second position and glutamic acid as the C‐terminal amino acid can give the essential geometry to provide selective COX‐2 inhibitory activity. Antiproliferative activity of the synthesized peptides (1a–7b) was also determined against four different human cancer cell lines, including MCF‐7, HepG2, A549, and HeLa. According to our results, A549, HepG2, and MCF7 seemed to be more sensitive cell lines than HeLa cells encountering these compounds, which gave inhibitory action with IC50 values from 4.8 to 64.4 µM. In this regard, compounds 3a and 2b displayed the best inhibitory activity against the cell lines. Moreover, a good correlation was observed between the antiproliferative potency and the COX‐2 inhibitory activity of compounds 1a, 2a, 2b, and 5b. Such findings suggest that one of the mechanism of anticancer activity of these peptides may be through the COX‐2 inhibitory action.
The Effect of Transparency on Framing Effects in Within‐Subject Designs
Authors: Aczel Balazs , Szollosi Aba , Bago Bence
Published: September 2017

A long‐lasting assumption about the framing effect is that if the participants discover the purpose of the experiment in a within‐subject design, then this test transparency would trigger them to override their initial answer and make coherent choices. For this reason, researchers try to mask the connection between the two parts of the test by inserting filling questions or a time delay between the two parts of the test. In this research, we explored the extent to which these customarily used masking solutions are effective in increasing test sensitivity for the framing effect. In three experiments, we assessed the effect of masking on the tests of the attribute framing and the risky‐choice framing effects. Contradicting the general belief, our results indicate that these effects are already measurable without any masking or delay and we found no convincing evidence that the attempts to decrease task transparency provide worthwhile benefits for general tests of the effect. Beyond their practical relevance, the results question whether the test is a good measure of coherence rationality and better suit those accounts that suggest that the two parts of the framing tasks cannot be regarded as identical. Copyright © 2017 John Wiley & Sons, Ltd.
Consideration of the Development of the Gastrointestinal Tract in the Choice of Species for Regulatory Juvenile Studies
Authors: Downes Noel John
Published: September 2017

Although the rat is close to being the automatic choice for regulatory juvenile toxicity studies, there are several shortcomings in this model. Choosing a species should take into serious consideration the importance of gastrointestinal tract development in the period before weaning as this may have a major effect on exposure. A comparison of the anatomical changes in the stomach and small intestine of mini‐pig and rat show that the mini‐pig is a far closer model for man than is the rat, although there are a few unusual aspects of small intestinal development in the mini‐pig. Considerations of the development of the gastrointestinal tract and choice of species have the potential to affect safety assessment and should be a prime consideration when planning an investigation. Birth Defects Research 110:56–62, 2018. © 2017 Wiley Periodicals, Inc.
Fabricating PLGA microparticles with high loads of the small molecule antioxidant N‐acetylcysteine that rescue oligodendrocyte progenitor cells from oxidative stress
Authors: Murphy Nicholas P. , Lampe Kyle J.
Published: September 2017

Reactive oxygen species (ROS), encompassing all oxygen radical or non‐radical oxidizing agents, play key roles in disease progression. Controlled delivery of antioxidants is therapeutically relevant in such oxidant‐stressed environments. Encapsulating small hydrophilic molecules into hydrophobic polymer microparticles via traditional emulsion methods has long been a challenge due to rapid mass transport of small molecules out of particle pores. We have developed a simple alteration to the existing water‐in‐oil‐in‐water (W/O/W) drug encapsulation method that dramatically improves loading efficiency: doping external water phases with drug to mitigate drug diffusion out of the particle during fabrication. PLGA microparticles with diameters ranging from 0.6 to 0.9 micrometers were fabricated, encapsulating high loads of 0.6–0.9 µm diameter PLGA microparticles were fabricated, encapsulating high loads of the antioxidant N‐acetylcysteine (NAC), and released active, ROS‐scavenging NAC for up to 5 weeks. Encapsulation efficiencies, normalized to the theoretical load of traditional encapsulation without doping, ranged from 96% to 400%, indicating that NAC‐loaded external water phases not only prevented drug loss due to diffusion, but also doped the particles with additional drug. Antioxidant‐doped particles positively affected the metabolism of oligodendrocyte progenitor cells (OPCs) under H2O2‐mediated oxidative stress when administered both before (protection) or after (rescue) injury. Antioxidant doped particles improved outcomes of OPCs experiencing multiple doses of H2O2 by increasing the intracellular glutathione content and preserving cellular viability relative to the injury control. Furthermore, antioxidant‐doped particles preserve cell number, number of process extensions, cytoskeletal morphology, and nuclear size of H2O2‐stressed OPCs relative to the injury control. These NAC‐doped particles have the potential to provide temporally‐controlled antioxidant therapy in neurodegenerative disorders such as multiple sclerosis (MS) that are characterized by continuous oxidative stress.
Simultaneous determination of glaucocalyxin A and glaucocalyxin B in rat plasma by LC‐MS/MS and its application to a pharmacokinetic study after oral administration of Rabdosia japonica extract
Authors: Huang Weili , Guan Xiaohui , Lv Yongchen
Published: September 2017

A specific and sensitive liquid chromatography tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the analysis of glaucocalyxin A and glaucocalyxin B in rat plasma using praeruptorin A as an internal standard. Separation was performed on a Hypurity C18 column (2.1 × 50 mm, 5 μm) with isocratic elution using 0.2% formic acid in water–acetonitrile (20:80, v/v). Mass spectrometric detection was conducted using selected reaction monitoring via an electrospray ionization source. Both analytes exhibited good linearity within their concentration ranges (r2 > 0.9932). The lower limit of quantitation of glaucocalyxin A and glaucocalyxin B was 1.10 ng/mL. Intra‐ and inter‐day precision exhibited an RSD within 14.5%, and the accuracy (RE) ranged from –12.1 to 15.0% at the lower limit of quantitation and three quality control levels. The developed assay was successfully applied to a pharmacokinetic study of glaucocalyxin A and glaucocalyxin B in rats after oral administration of Rabdosia japonica extract.
Parent Thioketene S‐Oxide H2CCSO: Gas‐Phase Generation, Structure, and Bonding Analysis
Authors: Wu Zhuang , Xu Jian , Sokolenko Liubov , Yagupolskii Yurii L. , Feng Ruijuan , Liu Qian , Lu Yan , Zhao Lili , Fernández Israel , Frenking Gernot , Trabelsi Tarek , Francisco Joseph S. , Zeng Xiaoqing
Published: September 2017

The parent thioketene S‐oxide H2CCSO has been generated in the gas phase through flash vacuum pyrolysis (ca. 1000 K) of vinyl sulfoxide H2CC(Br)−S(O)CF3 via the intermediacy of a novel vinyl sulfinyl radical H2C=C(Br)−SO (syn and anti conformers). Upon irradiation at 266 nm, H2CCSO decomposes into HCCH/SO and H2CS/CO in cryogenic Ar matrix. Whereas, visible‐light irradiations result in syn↔anti conformational interconversion in H2C=C(Br)−SO. The molecular structures of H2CCSO and isomers are computationally studied at the CCSD(T)‐F12/VTZ‐F12 level of theory, and the bonding properties of H2CCSO are analyzed with the EDA‐NOCV method at the M06‐2X/TZ2P level.
Reduction of Carbonyl Groups by Uranium(III) and Formation of a Stable Amide Radical Anion
Authors: Mullane Kimberly C. , Cheisson Thibault , Nakamaru‐Ogiso Eiko , Manor Brian C. , Carroll Patrick J. , Schelter Eric J.
Published: September 2017

Methyl benzoate, N,N‐dimethylbenzamide, and benzophenone were reduced by UIII[N(SiMe3)2]3 resulting in uranium(IV) products. Reduction of benzophenone lead to UIV[OC⋅Ph2)][N(SiMe3)2]3, (1.1) which forms the dinuclear complex, [N(SiMe3)2]3UIV(OCPhPh‐CPh2O)UIV[N(SiMe3)2]3 (1.2), through coupling of the ketyl radical species upon crystallization. Reaction of N,N‐dimethylbenzamide with UIII[N(SiMe3)2]3 resulted in UIV[OC⋅(Ph)(NMe2)][N(SiMe3)2]3 (2), a uranium(IV) compound and the first example of a charge‐separated amide radical. In the case of methyl benzoate, the reduction resulted in UIV(OMe)[N(SiMe3)2]3 (3) and benzaldehyde as the reduced organic fragment. Compound 2 showed the ability to act as a uranium(III) synthon in its reactivity with trimethylsilyl azide, a reaction that yielded UV(=NSiMe3)[N(SiMe3)2]3. Additionally, 2 was reduced with potassium graphite resulting in [U(μ‐O)[O=C(NMe2)(Ph)][N(SiMe3)2]2]2 (4), a dinuclear uranium compound bridged by oxo ligands. Reduction of 2 in the presence of 15‐crown‐5 afforded isolation of the mono‐oxo compound, [(15‐crown‐5)2K][UO[N(SiMe3)2]3] (5). The results expand the reduction capabilities of UIII complexes and demonstrate a strategy for isolating novel metal‐stabilized radicals.
Histopathological and genotypic characterization of metastatic colorectal carcinoma with PD‐L1 (CD274)‐expression: Possible roles of tumour micro environmental factors for CD274 expression
Authors: Inaguma Shingo , Lasota Jerzy , Felisiak‐Golabek Anna , Kowalik Artur , Wang Zengfeng , Zieba Sebastian , Kalisz Joanna , Ikeda Hiroshi , Miettinen Markku
Published: September 2017

Aberrant PD‐L1 (CD274) expression has been described in different types of tumour and linked to tumour aggressiveness and a poor prognosis. In primary colorectal carcinomas (CRCs), CD274 expression was reported to be associated with mismatch repair (MMR)‐deficiency, BRAF mutation, and “stem‐like” immunophenotype defined by down‐regulation of homeobox protein CDX2 and membranous expression of activated leukocyte cell adhesion molecule (ALCAM). However, the immunophenotype and genotype of CD274‐positive metastatic CRC have not been extensively analysed. In this study, 189 CRC metastases were evaluated immunohistochemically for CD274, MMR proteins, CDX2, and ALCAM expression. Immunostaining for CD4, CD8, and FOXP3 was also performed to characterize tumour‐associated immune cells. In addition, 34 arbitrarily selected lesions were genotyped using Sanger‐ and next‐generation sequencing. Univariate analyses showed no clear association between CD274 expression and clinicopathological parameters including MMR‐deficiency or “stem‐like” immunophenotype after adjustment for multiple testing. Comparison of the clinicopathological profiles of CD274‐positive primary and metastatic tumours revealed in the latter younger age of occurrence (60.9 ± 13.3 versus 72.6 ± 13.1 years, p = 0.001), cytoplasm‐dominant CD274 expression (p < 0.001), infrequent MMR‐deficiency (p < 0.001), and common KRAS mutations (54%, p < 0.001). In five cultured colon cancer cell lines, CD274 was expressed and modulated after exogenous exposure to IFNγ and TGF‐β1. Thus, CD274 regulation mechanisms might include tumour micro environmental factors. Based on significantly different characteristics in CD274‐positive metastatic and primary CRCs, evaluation of metastases should also be considered when planning immune checkpoint inhibitor therapy.
Experimente zu Eigenschaften von Nanomaterialien in Chemieunterricht und Schülerlabor
Authors: Wilke Timm , Dege Janina , Waitz Thomas
Published: September 2017

Im Beitrag werden Perspektiven zum Thema Nanotechnologie im Chemieunterricht beschrieben, die im Rahmen Fachdidaktischer Transferforschung innerhalb einer Kooperation zwischen Fachdidaktik und Fachwissenschaft erarbeitet wurden. Ein besonderer Fokus wird dabei auf die experimentelle Erschließung von Eigenschaften verschiedener nanoskaliger Materialien wie etwa Titandioxid, Zinkoxid und Silica gelegt. Über die Verwendung dieser Materialien können Themen wie Adsorption, Fluoreszenz, (Photo‐) Katalyse und Toxizität mit einem aktuellen Forschungsthema vernetzt und in eine Vielfalt von Kontexten eingebettet werden.
Don't let perfect be the enemy of good: How to improve prognostic communication in pediatric oncology
Authors: Lee Brittany M. , Rosenberg Abby R.
Published: September 2017

Parents of children with cancer desire detailed and honest information about their child's prognosis throughout the cancer experience and regardless of race or ethnicity. This essay describes barriers and opportunities for pediatric oncologists to meet their obligations of prognostic disclosure.

See also pages 3995‐4003 and 4031‐8.
Disparities in prognosis communication among parents of children with cancer: The impact of race and ethnicity
Authors: Ilowite Maya F. , Cronin Angel M. , Kang Tammy I. , Mack Jennifer W.
Published: September 2017

BACKGROUND

Most parents of children with cancer say they want detailed information about their child's prognosis. However, prior work has been conducted in populations of limited diversity. The authors sought to evaluate the impact of parental race/ethnicity on prognosis communication experiences among parents of children with cancer.

METHODS

In total, 357 parents of children with cancer and the children's physicians were surveyed at Dana‐Farber Cancer Institute/Boston Children's Hospital and Children's Hospital of Philadelphia. Outcome measures were parental preferences for prognostic information, physician beliefs about parental preferences, prognosis communication processes, and communication outcomes. Associations were assessed by logistic regression with generalized estimating equations to correct for physician clustering.

RESULTS

Two hundred eighty‐one parents (79%) were white, 23 (6%) were black, 29 (8%) were Hispanic, and 24 (7%) were Asian/other. Eighty‐seven percent of parents wanted as much detail as possible about their child's prognosis, with no significant differences by race/ethnicity (P = .75). However, physician beliefs about parental preferences for prognosis communication varied based on parent race/ethnicity, with physicians considering black and Hispanic parents less interested in details about prognosis than whites (P = .003). Accurate understanding of a less favorable prognosis was greater among white (49%) versus nonwhite parents (range, 20%‐29%), although this difference was not statistically significant (P = .14).

CONCLUSIONS

Most parents, regardless of racial and ethnic background, want detailed prognostic information about their child's cancer. However, physicians underestimate the information needs of black and Hispanic parents. To meet parents' information needs, physicians should ask about parents' information preferences before prognosis discussions. Cancer 2017;123:3995‐4003. © 2017 American Cancer Society.
Electrochemical CO2 Reduction: A Classification Problem
Authors: Bagger Alexander , Ju Wen , Varela Ana Sofia , Strasser Peter , Rossmeisl Jan
Published: September 2017

In this work, we propose four non‐coupled binding energies of intermediates as descriptors, or “genes”, for predicting the product distribution in CO2 electroreduction. Simple reactions can be understood by the Sabatier principle (catalytic activity vs. one descriptor), while more complex reactions tend to give multiple very different products and consequently the product selectivity is a more complex property to understand. We approach this, as a logistical classification problem, by grouping metals according to their major experimental product from CO2 electroreduction: H2, CO, formic acid and beyond CO* (hydrocarbons or alcohols). We compare the groups in terms of multiple binding energies of intermediates calculated by density functional theory. Here, we find three descriptors to explain the grouping: the adsorption energies of H*, COOH*, and CO*. To further classify products beyond CO*, we carry out formaldehyde experiments on Cu, Ag, and Au and combine these results with the literature to group and differentiate alcohol or hydrocarbon products. We find that the oxygen binding (adsorption energy of CH3O*) is an additional descriptor to explain the alcohol formation in reduction processes. Finally, the adsorption energy of the four intermediates, H*, COOH*, CO*, and CH3O*, can be used to differentiate, group, and explain products in electrochemical reduction processes involving CO2, CO, and carbon–oxygen compounds.
Transport Matters: Boosting CO2 Electroreduction in Mixtures of [BMIm][BF4]/Water by Enhanced Diffusion
Authors: Rudnev Alexander V. , Fu Yong‐Chun , Gjuroski Ilche , Stricker Florian , Furrer Julien , Kovács Noémi , Vesztergom Soma , Broekmann Peter
Published: September 2017

Room‐temperature ionic liquids (RTILs) are promising new electrolytes for efficient carbon dioxide reduction. However, due to their high viscosity, the mass transport of CO2 in RTILs is typically slow, at least one order of magnitude slower than in aqueous systems. One possibility to improve mass transport in RTILs is to decrease their viscosity through dilution with water. Herein, defined amounts of water are added to 1‐butyl‐3methylimidazolium tetrafluoroborate ([BMIm][BF4]), which is a hydrophilic RTIL. Electrochemical measurements on quiescent and hydrodynamic systems both indicate enhanced CO2 electroreduction. This enhancement has its origin in thermodynamic/kinetic effects (the addition of water increases the availability of H+, which is a reaction partner of CO2 electroreduction) and in an increased rate of transport due to lower viscosity. Electrochemically determined diffusion coefficients for CO2 in [BMIm][BF4]/water systems agree well with values determined by NMR spectroscopy.
Porphyrins as Multifunctional Interconnects in Networks of ZnO Nanoparticles and their Application in Dye‐Sensitized Solar Cells
Authors: Düring Jasmin , Kunzmann Andreas , Killian Manuela S. , Costa Rubén D. , Guldi Dirk M. , Gröhn Franziska
Published: September 2017

ZnO nanoparticles of 2.6 to 4.0 nm in size were interconnected by meso‐tetra(4‐carboxyphenyl)porphyrin (TCPP) for the realization of novel ZnO–TCPP networks, reaching lateral dimensions ranging from 50 to 800 nm. The resulting ZnO–TCPP networks were probed by dynamic light‐scattering experiments, transmission electron microscopy, and spectroscopy, and were also tested as photoactive top layers in TiO2 and ZnO dye‐sensitized solar cells (DSSCs). Control over these ZnO–TCPP networks on top of the semiconductor electrodes enables efficiency increases of 10 % and 46 % for TiO2‐ and ZnO‐based photoelectrodes, respectively. In other words, effects, such as reducing the electron recombination and increasing the electron lifetime, document the benefits of using tailored functional hybrid systems in DSSCs.
Power‐efficient burst‐mode RF transmitter based on reference‐adaptive multilevel pulse‐width modulation
Authors: Arian Amir , Jannesari Abumoslem
Published: September 2017

Burst‐mode operation of power amplifier (PA) based on multilevel pulse‐width modulation (MPWM) has been frequently discussed as a potential solution to achieve higher efficiency in radio frequency (RF) transmitters. In this paper, a novel multilevel PWM modulator is proposed that utilizes adaptive triangular reference waveforms. As compared with conventional MPWM modulators, the proposed architecture provides significant wider design space such that the efficiency of system can be effectively optimized. A general transmitter architecture based on the proposed concept is analyzed in terms of power efficiency. Efficiency optimization procedures are presented according to input magnitude statistics. Based on the proposed modulator, an optimized 2.4‐GHz RF transmitter is designed in a 0.18‐μm complementary metal‐oxide‐semiconductor (CMOS) process. The circuit‐level simulations show that it delivers 25.8‐dBm peak output power with 46.1% peak efficiency. For a 20‐MHz worldwide interoperability for microwave access (WiMAX) signal with 8.5‐dB peak‐to‐average‐power ratio (PAPR), this transmitter achieves 28.8% (average) efficiency at 17.3‐dBm (average) output power with an error vector magnitude (EVM) of 2.97% rms.
High genetic risk scores for impaired insulin secretory capacity doubles the risk for type 2 diabetes in Asians and is exacerbated by Western‐type diets
Authors: Kim Da Sol , Kim Byoung Chul , Daily James W. , Park Sunmin
Published: September 2017

Background

Asians have among the highest incidence of type 2 diabetes (T2DM) in the world, partly due to low β‐cell function, causing them to rapidly develop T2DM when insulin resistant. This study tested the hypothesis that genetic polymorphisms are responsible for the low β‐cell function and that dietary factors interact with the genes to exacerbate their risk of T2DM.

Methods

We selected 10 genetic variants of 5 genes involved in insulin secretion (CDKAL1, KCNQ1, IDE, HHEX, and ABCA1) from the genome‐wide association studies to calculate the genetic risk scores (GRSs) in 8842 Korean adults in the Ansan/Ansung cohort in the Korean Genome Epidemiology Study. The genetic risk score were divided into low, medium, and high groups, and the association between T2DM and the genetic risk score was measured using logistic regression. We also analysed the interaction between the genetic risk score and the nutrition intakes.

Results

The individual genetic variants were positively associated with T2DM even when adjusted for covariates. Individuals with medium and high genetic risk score had higher T2DM risk by 1.68 and 2.17 folds compared to those with the low genetic risk score after adjusting for covariates. The increased risk was mainly associated with lower HOMA‐B, an indicator of insulin secretion capacity, but not HOMA‐IR, an indicator of insulin resistance. Subjects with high carbohydrate intakes and a medium genetic risk score did not have a higher risk of T2DM, and the risk was partially mitigated in the high genetic risk score group.

Conclusion

Seventy‐two percent of the Korean population had either medium or high genetic risk scores for impaired insulin secretion, which approximately doubled their risk of type 2 diabetes, and the risk was exacerbated by consuming a low carbohydrate Western‐style diets.
What mediates tree mortality during drought in the southern Sierra Nevada?
Authors: Paz‐Kagan Tarin , Brodrick Philip G. , Vaughn Nicholas R. , Das Adrian J. , Stephenson Nathan L. , Nydick Koren R. , Asner Gregory P.
Published: September 2017

Severe drought has the potential to cause selective mortality within a forest, thereby inducing shifts in forest species composition. The southern Sierra Nevada foothills and mountains of California have experienced extensive forest dieback due to drought stress and insect outbreak. We used high‐fidelity imaging spectroscopy (HiFIS) and light detection and ranging (LiDAR) from the Carnegie Airborne Observatory (CAO) to estimate the effect of forest dieback on species composition in response to drought stress in Sequoia National Park. Our aims were (1) to quantify site‐specific conditions that mediate tree mortality along an elevation gradient in the southern Sierra Nevada Mountains, (2) to assess where mortality events have a greater probability of occurring, and (3) to estimate which tree species have a greater likelihood of mortality along the elevation gradient. A series of statistical models were generated to classify species composition and identify tree mortality, and the influences of different environmental factors were spatially quantified and analyzed to assess where mortality events have a greater likelihood of occurring. A higher probability of mortality was observed in the lower portion of the elevation gradient, on southwest‐ and west‐facing slopes, in areas with shallow soils, on shallower slopes, and at greater distances from water. All of these factors are related to site water balance throughout the landscape. Our results also suggest that mortality is species‐specific along the elevation gradient, mainly affecting Pinus ponderosa and Pinus lambertiana at lower elevations. Selective mortality within the forest may drive long‐term shifts in community composition along the elevation gradient.
Long‐term trends in trait structure of riverine communities facing predation risk increase and trophic resource decline
Authors: Latli Adrien , Descy Jean‐Pierre , Mondy Cédric P. , Floury Mathieu , Viroux Laurent , Otjacques William , Marescaux Jonathan , Depiereux Eric , Ovidio Michael , Usseglio‐Polatera Philippe , Kestemont Patrick
Published: September 2017

Many large European rivers have undergone multiple pressures that have strongly impaired ecosystem functioning at different spatial and temporal scales. Global warming and other environmental changes have favored the success of invasive species, deeply modifying the structure of aquatic communities in large rivers. Some exogenous species could alter trophic interactions within assemblages by increasing the predation risk for potential prey species (top‐down effect) and limiting the dynamics of others via resource availability limitation (bottom‐up effect). Furthermore, large transboundary rivers are complex aquatic ecosystems that have often been poorly investigated so that data for assessing long‐term ecological trends are missing. In this study, we propose an original approach for investigating long‐term combined effects of global warming, trophic resource decrease, predation risk, and water quality variations on the trait‐based structure of macroinvertebrate and fish assemblages over 26 yr (1985–2011) and 427‐km stretch of the river Meuse (France and Belgium). The study of temporal variations in biological, physiological, and ecological traits of macroinvertebrate and fish allowed identifying community trends and distinguishing impacts of environmental perturbations from those induced by biological alterations. We provide evidence, for this large European river, of an increase in water temperature (close to 1°C) and a decrease in phytoplankton biomass (−85%), as well as independent effects of these changes on both invertebrate and fish communities. The reduction of trophic resources in the water column by invasive molluscs has dramatically affected the density of omnivorous fish in favor of invertebrate feeders, while scrapers became the major feeding guild among invertebrates. Macroinvertebrate and fish communities have shifted from large‐sized organisms with low fecundity to prolific, small‐sized organisms, with early maturity, as a response to increased predation pressure.
Impaired renal function affects clinical outcomes and management of patients with heart failure
Authors: Jenkins Rebeka , Mandarano Lilly , Gugathas Saraniga , Kaski Juan Carlos , Anderson Lisa , Banerjee Debasish
Published: September 2017

Aims

Inpatients with heart failure and renal impairment have poor outcomes and variable quality of care. We investigate treatment practice and outcomes in an unselected real‐world cohort using historical creatinine measurements.

Methods and results

Admissions between 1/4/2013 and 30/4/2015 diagnosed at discharge with heart failure were retrospectively analysed. Stages of chronic kidney disease (CKD) and acute kidney injury (AKI) were calculated from creatinine at discharge and 3–12 months before admission. We identified 1056 admissions of 851 patients (mean age 76 years, 56% Caucasian, 36% with diabetes mellitus, 54% with ischaemic heart disease, and 57% with valvular heart disease). CKD was common; 36%—Stage 3a/b, 11%—Stage 4/5; patients were older, more often diabetic, with higher potassium, lower haemoglobin, and more oedema but similar prevalence of left ventricular systolic dysfunction (LVSD) compared patients with Stages 0–2. AKI was present in 17.0% (10.4%—Stage 1, 3.7%—Stage 2, and 2.9%—Stage 3); these had higher potassium and lower haemoglobin than patients with no AKI. Length of stay was longer in Stage 4/5 CKD [11 days; P = 0.008] and AKI [13 days; P = 0.006]. Mortality was higher with Stage 4/5 CKD (13.8% compared with 7.7% for Stages 0–2 CKD (P = 0.036)] and increased with AKI (5%—no AKI, 20.9%—Stage 1, 35.9%—Stage 2, and 48.4%—Stage 3; P < 0.001). Adjusted for age, diabetes, and LVSD, both AKI and Stage 4/5 CKD were independent predictors of in‐hospital mortality. In survivors with LVSD, the discharge prescription of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers decreased with progressive CKD, [84%—no‐mild, 59%—moderate, and 36%—severe CKD; P < 0.001]; this was not purely explained by hyperkalaemia.

Conclusions

Inpatients with heart failure and renal impairment, acute and chronic, failed to receive recommended therapy and had poor outcomes.
Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?
Authors: Cotter Gad , Metra Marco , Davison Beth A. , Jondeau Guillaume , Cleland John G.F. , Bourge Robert C. , Milo Olga , O'Connor Christopher M. , Parker John D. , Torre‐Amione Guillermo , van Veldhuisen Dirk J. , Kobrin Isaac , Rainisio Maurizio , Senger Stefanie , Edwards Christopher , McMurray John J.V. , Teerlink John R. ,   for the VERITAS Investigators
Published: September 2017

Aims

Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes.

Methods and results

We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time‐point available (72 h), using linear regression, and with 30‐ and 180‐day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30‐day all‐cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30‐day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180‐day all‐cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h.

Conclusions

In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients.
Prevalence and prognostic importance of precipitating factors leading to heart failure hospitalization: recurrent hospitalizations and mortality
Authors: Platz Elke , Jhund Pardeep S. , Claggett Brian L. , Pfeffer Marc A. , Swedberg Karl , Granger Christopher B. , Yusuf Salim , Solomon Scott D. , McMurray John J.
Published: September 2017

Aims

Hospitalizations for heart failure (HF) are common and are associated with significant morbidity, mortality and cost. However, precipitating factors leading to HF hospitalization and their importance with respect to subsequent outcomes are not well understood.

Methods and results

The symptoms and signs present at admission and investigator‐identified factors thought to have contributed to the first adjudicated HF hospitalization in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) programme were prospectively collected and stratified by ejection fraction (EF). Potential precipitants were collected using a specifically designed case report form and categorized according to the presence of cardiovascular (CV), non‐CV and unknown factors. Associations between these factors and subsequent rehospitalization and mortality rates were examined. Of 1668 patients who experienced HF hospitalization, 1152 had reduced EF (≤40%, HFrEF) and 516 had preserved EF (HFpEF). Overall, 54% had CV, 32% had non‐CV and 14% had unknown factors thought to have precipitated HF, with similar proportions in the HFrEF and HFpEF groups. The most common precipitants were arrhythmia (15%), other non‐CV factors (11%) and respiratory infection (10%). Subsequent CV readmission rates were highest in those whose initial HF hospitalization was precipitated by CV factors. However, mortality rates were similar among patients with any of the three categories of precipitating factors. Results were similar in HFrEF and HFpEF.

Conclusions

Among chronic HF patients hospitalized for decompensation, the investigator‐reported precipitating factor was not associated with the subsequent mortality rate, but was associated with type of readmission: readmissions for CV reasons were more likely when the index precipitant was CV.
TCR‐pMHC encounter differentially regulates transcriptomes of tissue‐resident CD8 T cells
Authors: Yoshizawa Akihiro , Bi Kevin , Keskin Derin B. , Zhang Guanglan , Reinhold Bruce , Reinherz Ellis L.
Published: September 2017

To investigate the role of TCR‐pMHC interaction in regulating lung CD8 tissue‐resident T cell (TR) differentiation, polyclonal responses were compared against NP366‐374/Db and PA224‐233/Db, two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103+ and CD103− CD8 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co‐expression network analysis (WGCNA) identify dominant TCR, adherens junction, RIG‐I‐like and NOD‐like pattern recognition receptor as well as TGF‐β signaling pathways and memory signatures among PA224‐233/Db T cells consistent with T resident memory (TRM) status. In contrast, NP366‐374/Db T cells exhibit enrichment of effector signatures, upregulating pro‐inflammatory mediators even among TRM. While NP366‐374/Db T cells manifest transcripts linked to canonical exhaustion pathways, PA224‐233/Db T cells exploit P2rx7 purinoreceptor attenuation. The NP366‐374/Db CD103+ subset expresses the antimicrobial lactotransferrin whereas PA224‐233/Db CD103+ utilizes pore‐forming mpeg‐1, with <22% of genes correspondingly upregulated in CD103+ (or CD103−) subsets of both specificities. Thus, TCR‐pMHC interactions among TR and antigen presenting cells in a tissue milieu strongly impact CD8 T cell biology.
Coomassie staining provides routine (sub)femtomole in‐gel detection of intact proteoforms: Expanding opportunities for genuine Top‐down Proteomics
Authors: Noaman Nour , Abbineni Prabhodh S. , Withers Michael , Coorssen Jens R.
Published: September 2017

Modified colloidal Coomassie Brilliant Blue (cCBB) staining utilising a novel destain protocol and near‐infrared fluorescence detection (nIRFD) rivals the in‐gel protein detection sensitivity (DS) of SYPRO Ruby. However, established DS estimates are likely inaccurate in terms of 2DE‐resolved proteoform ‘spots’ since DS is routinely measured from comparatively diffuse protein ‘bands’ following wide‐well 1DE. Here, cCBB DS for 2DE‐based proteomics was more accurately determined using narrow‐well 1DE. As precise estimates of protein standard monomer concentrations are essential for accurate quantitation, coupling UV absorbance with gel‐based purity assessments is described. Further, as cCBB is compatible with both nIRFD and densitometry, the impacts of imaging method (and image resolution) on DS were assessed. Narrow‐well 1DE enabled more accurate quantitation of cCBB DS for 2DE, achieving (sub)femtomole DS with either nIRFD or densitometry. While densitometry offers comparative simplicity and affordability, nIRFD has the unique potential for enhanced DS with Deep Imaging. Higher‐resolution nIRFD also improved analysis of a 2DE‐resolved proteome, surpassing the DS of standard nIRFD and densitometry, with nIRFD Deep Imaging further maximising proteome coverage. cCBB DS for intact proteins rivals that of mass spectrometry (MS) for peptides in complex mixtures, reaffirming that 2DE‐MS currently provides the most routine, broadly applicable, robust, and information‐rich Top‐down approach to Discovery Proteomics.
Effect of pore size on performance of monolithic tube chromatography of large biomolecules
Authors: Podgornik Ales , Hamachi Masataka , Isakari Yu , Yoshimoto Noriko , Yamamoto Shuichi
Published: September 2017

Effect of pore size on the performance of ion‐exchange monolith tube chromatography of large biomolecules was investigated. Radial flow 1 mL polymer based monolith tubes of different pore sizes (1.5, 2, and 6 μm) were tested with model samples such as 20 mer poly T‐DNA, basic proteins, and acidic proteins (molecular weight 14 000–670 000). Pressure drop, pH transient, the number of binding site, dynamic binding capacity, and peak width were examined. Pressure drop–flow rate curves and dynamic binding capacity values were well correlated with the nominal pore size. While duration of the pH transient curves depends on the pore size, it was found that pH duration normalized on estimated surface area was constant, indicating that the ligand density is the same. This was also confirmed by the constant number of binding site values being independent of pore size. The peak width values were similar to those for axial flow monolith chromatography. These results showed that it is easy to scale up axial flow monolith chromatography to radial flow monolith tube chromatography by choosing the right pore size in terms of the pressure drop and capacity.
Quality of life after thyroidectomy in patients with nontoxic nodular goiter: A prospective cohort study
Authors: Sorensen Jesper Roed , Watt Torquil , Cramon Per , Døssing Helle , Hegedüs Laszlo , Bonnema Steen Joop , Godballe Christian
Published: September 2017

Background

Using the thoroughly validated Thyroid‐Related Quality‐of‐Life Patient‐Reported Outcome (ThyPRO) questionnaire, the purpose of this study was to investigate changes in disease‐specific quality of life (QOL) after surgical treatment in patients with benign nontoxic multinodular goiters.

Method

Patients with goiters scheduled for thyroid surgery (n = 106) and individuals from the general population (n = 739) were studied. The ThyPRO data before, 3 months, and 6 months after surgery were compared with normative scores from the general population using a linear mixed model and t tests.

Results

Before surgery, patients with goiters experienced poorer scores on all scales compared to the general population. After surgery, moderate to large improvements were seen in goiter symptoms, tiredness, anxiety, and overall QOL. After surgery, all scales returned to values equal to the general population. The degree of anxiety was, in fact, lower than in the general population.

Conclusion

Thyroid surgery leads to significant benefit among patients with benign nontoxic goiters by restoring QOL equal to that in the general population.
Validation of an automated immune turbidimetric assay for serum gelsolin and its possible clinical utility in sepsis
Authors: Horváth‐Szalai Zoltán , Kustán Péter , Szirmay Balázs , Lakatos Ágnes , Christensen Per H. , Huber Tamás , Bugyi Beáta , Mühl Diána , Ludány Andrea , Miseta Attila , Kovács Gábor L. , Kőszegi Tamás
Published: September 2017

Background

Studies showing the potential predictive value of the actin‐binding protein gelsolin, in critically ill patients are scarce. Moreover, even up to now a rapid automated measurement of gelsolin has still remained a challenge. Therefore, we developed and validated an automated serum gelsolin immune turbidimetric assay for possible clinical use.

Methods

Validation of serum gelsolin assay was performed on a Cobas 8000/c502 analyzer (Roche) according to the second edition of Eurachem guidelines. Furthermore, we also studied the diagnostic value of serum gelsolin in sepsis when investigating sera of septic (n = 25), systemic inflammatory response syndrome (SIRS; n = 8) and control patients (n = 14). We compared our previously published Western blot data with those of the new turbidimetric assay.

Results

The sample volume was 7 μL and the assay time was 10 minutes. The detection limit was 0.72 mg/L, intra‐ and inter‐assay imprecision remained in most cases less than 5% expressed as CV. Recovery was found to be 84.56%‐93.52% and linearity study gave an appropriate correlation coefficient by linear regression analysis (r2 = .998). Septic patients exhibited lower (P = .015) first‐day serum gelsolin levels than SIRS patients, which confirmed our previous Western blot results. The determined cut‐off point for serum gelsolin was 14.05 mg/L (sensitivity: 75%; specificity: 60%) when investigating its diagnostic value in sepsis.

Conclusion

Based on the results, our immune turbidimetric measurement offers a rapid and accurate quantitation of gelsolin in human serum samples. Serum gelsolin seems a promising additional diagnostic marker of sepsis which has to be further investigated.
Rationing of Formal Sector Jobs and Informality: The Colombian Case
Authors: García Gustavo A. , Badillo Erika Raquel
Published: September 2017

We analyse the factors that affect the decision to find employment in the formal or informal sectors taking into account the fact that there is a rationing of formal sector jobs and hence a job queue to enter that sector. Using data from Colombia, we confirm that formal job rationing does exist and that it affects around 62 per cent of the workers that find themselves in the informal labour market. Further factors determining actively seeking formal employment include personal traits, the characteristics of human capital and of the household and the wage premiums associated with working in the formal sector. Copyright © 2017 John Wiley & Sons, Ltd.
Prebiopsy multiparametric MRI‐based risk score for predicting prostate cancer in biopsy‐naive men with prostate‐specific antigen between 4–10 ng/mL
Authors: Dwivedi Durgesh Kumar , Kumar Rajeev , Dwivedi Alok Kumar , Bora Girdhar S. , Thulkar Sanjay , Sharma Sanjay , Gupta Siddhartha Datta , Jagannathan Naranamangalam R.
Published: September 2017

Background

Risk calculators have traditionally utilized serum prostate‐specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa).

Purpose

To develop a prebiopsy multiparametric MRI (mpMRI)‐based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy‐naive men with serum PSA between 4–10 ng/mL that may help reduce unnecessary biopsies.

Study Type

Prospective cross‐sectional study.

Subjects

In all, 137 consecutive men with PSA between 4–10 ng/mL underwent prebiopsy mpMRI (diffusion‐weighted [DW]‐MRI and MR spectroscopic imaging [MRSI]) during 2009–2015 were recruited for this study.

Field Strength/Sequence

1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1‐weighted, T2‐weighted, DW‐MRI, and MRSI sequences were used.

Assessment

All eligible patients underwent mpMRI‐directed, cognitive‐fusion transrectal ultrasound (TRUS)‐guided biopsies.

Statistical Tests

An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10‐fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters.

Results

Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6‐point mpMRI‐based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24–6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis.

Data Conclusion

A statistical equation and a simple 6‐point mpMRI‐based RS can be used as a point‐of‐care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:1227–1236.