bluuebunny/crossref_metadata_2025 huggingface dataset:
On the impact of sample size on median lethal concentration estimation in acute fish toxicity testing: Is n = 7/group enough?
Authors: Carr Gregory J. , Bailer A. John , Rawlings Jane M. , Belanger Scott E.
Published: January 2018

The fish acute toxicity test method is foundational to aquatic toxicity testing strategies, yet the literature lacks a concise sample size assessment. Although various sources address sample size, historical precedent seems to play a larger role than objective measures. We present a novel and comprehensive quantification of the effect of sample size on estimation of the median lethal concentration (LC50), covering a wide range of scenarios. The results put into perspective the practical differences across a range of sample sizes, from n = 5/concentration up to n = 23/concentration. We also provide a framework for setting sample size guidance illustrating ways to quantify the performance of LC50 estimation, which can be used to set sample size guidance given reasonably difficult (or worst-case) scenarios. There is a clear benefit to larger sample size studies: they reduce error in the determination of LC50s, and lead to more robust safe environmental concentration determinations, particularly in cases likely to be called worst-case (shallow slope and true LC50 near the edges of the concentration range). Given that the use of well-justified sample sizes is crucial to reducing uncertainty in toxicity estimates, these results lead us to recommend a reconsideration of the current de minimis 7/concentration sample size for critical studies (e.g., studies needed for a chemical registration, which are being tested for the first time, or involving difficult test substances). Environ Toxicol Chem 2018;37:1565–1578. © 2018 SETAC
Potency of polycyclic aromatic hydrocarbons in chicken and Japanese quail embryos
Authors: Franci Cynthia D. , Aleksieva Angelika , Boulanger Emily , Brandenburg Jonas , Johnston Theresa , Malinova Asya , Head Jessica A.
Published: January 2018

Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), yet limited data describing the relative potency of PAH congeners are available for avian species. In the present study, we determined embryonic median lethal dose (LD50) values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener in Japanese quail (Coturnix japonica). Graded concentrations of each test compound were injected into the air cell of chicken or quail eggs before incubation. Embryos were monitored through development (quail) or hatching (chicken). All PAHs tested caused dose-dependent increases in embryo mortality, but few other effects (e.g., weight changes, deformities) were observed. In chicken, windows of developmental sensitivity were identified between embryonic days 4 and 9 and between embryonic days 20 and 22. The rank order potency of benzo[k]fluoranthene (BkF; 76 μg/kg) ≈ dibenz[ah]anthracene (83 μg/kg) > indeno[1,2,3-cd]pyrene (325 μg/kg) > benzo[a]pyrene (461 μg/kg) > benz[a]anthracene (529 μg/kg) corresponded well with previous in vitro estimates in birds. Previously published ethoxyresorufin-O-deethylase median effect concentrations from cultured chicken embryo hepatocytes were highly predictive of our LD50s (p < 0.001, r2 = 0.99). To explore differences in sensitivity between species, Japanese quail eggs were injected with BkF, the most potent PAH. We found that chicken and quail were nearly equally sensitive to BkF. The present results contribute to our developing understanding of variability in responses to PAHs among congeners and species. Environ Toxicol Chem 2018;37:1556–1564. © 2018 SETAC
Construction of a network describing asparagine metabolism in plants and its application to the identification of genes affecting asparagine metabolism in wheat under drought and nutritional stress
Authors: Curtis Tanya Y. , Bo Valeria , Tucker Allan , Halford Nigel G.
Published: January 2018

A detailed network describing asparagine metabolism in plants was constructed using published data from Arabidopsis (Arabidopsis thaliana) maize (Zea mays), wheat (Triticum aestivum), pea (Pisum sativum), soybean (Glycine max), lupin (Lupus albus), and other species, including animals. Asparagine synthesis and degradation is a major part of amino acid and nitrogen metabolism in plants. The complexity of its metabolism, including limiting and regulatory factors, was represented in a logical sequence in a pathway diagram built usingyEDgraph editor software. The network was used with a Unique Network Identification Pipeline in the analysis of data from 18 publicly available transcriptomic data studies. This identified links between genes involved in asparagine metabolism in wheat roots under drought stress, wheat leaves under drought stress, and wheat leaves under conditions of sulfur and nitrogen deficiency. The network represents a powerful aid for interpreting the interactions not only between the genes in the pathway but also among enzymes, metabolites and smaller molecules. It provides a concise, clear understanding of the complexity of asparagine metabolism that could aid the interpretation of data relating to wider amino acid metabolism and other metabolic processes.
DSP30 and interleukin‐2 as a mitotic stimulant in B‐cell disorders including those with a low disease burden
Authors: Dun Karen A. , Riley Louise A. , Diano Giuseppe , Adams Leanne B. , Chiu Eleanor , Sharma Archna
Published: January 2018

Chromosome abnormalities detected during cytogenetic investigations for B‐cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B‐cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B‐cell malignancies. Here, we describe the comparison of two B‐cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B‐cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B‐cell disorders, revealing abnormal cytogenetic results in a range of B‐cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B‐cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B‐cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease.
The morphometric co‐atrophy networking of schizophrenia, autistic and obsessive spectrum disorders
Authors: Cauda Franco , Nani Andrea , Costa Tommaso , Palermo Sara , Tatu Karina , Manuello Jordi , Duca Sergio , Fox Peter T. , Keller Roberto
Published: January 2018

By means of a novel methodology that can statistically derive patterns of co‐alterations distribution from voxel‐based morphological data, this study analyzes the patterns of brain alterations of three important psychiatric spectra—that is, schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and obsessive‐compulsive spectrum disorder (OCSD). Our analysis provides five important results. First, in SCZD, ASD, and OCSD brain alterations do not distribute randomly but, rather, follow network‐like patterns of co‐alteration. Second, the clusters of co‐altered areas form a net of alterations that can be defined as morphometric co‐alteration network or co‐atrophy network (in the case of gray matter decreases). Third, within this network certain cerebral areas can be identified as pathoconnectivity hubs, the alteration of which is supposed to enhance the development of neuronal abnormalities. Fourth, within the morphometric co‐atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of eleven highly connected nodes can be distinguished. This subnetwork encompasses the anterior insulae, inferior frontal areas, left superior temporal areas, left parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co‐altered areas also exhibit a normal structural covariance pattern which overlaps, for some of these areas (like the insulae), the co‐alteration pattern. These findings reveal that, similarly to neurodegenerative diseases, psychiatric disorders are characterized by anatomical alterations that distribute according to connectivity constraints so as to form identifiable morphometric co‐atrophy patterns.
Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection
Authors: Yen Chia‐Jui , Ai Yu‐Lin , Tsai Hung‐Wen , Chan Shih‐Huang , Yen Chia‐Sheng , Cheng Kuang‐Hsiung , Lee Yun‐Ping , Kao Chia‐Wei , Wang Yu‐Chun , Chen Yi‐Lin , Lin Cheng‐Han , Liu Tsunglin , Tsai Huey‐Pin , Wang Jen‐Ren , Su Ih‐Jen , Huang Wenya
Published: January 2018

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre‐S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre‐S2 region as a high‐risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV‐related HCC who underwent curative hepatic resection was analyzed for pre‐S gene mutations using Pre‐S Gene Chip. Results of the multivariate regression analysis showed that the serum pre‐S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high‐risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence‐free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV‐induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre‐S2 mutant in serum is, independently of tumor stage, an important high‐risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).
Quality of life assumptions determine which cervical cancer screening strategies are cost‐effective
Authors: de Kok Inge M.C.M. , Korfage Ida J. , van den Hout Wilbert B. , Helmerhorst Theo J.M. , Habbema J. Dik F. , Essink‐Bot Marie‐Louise , van Ballegooijen Marjolein
Published: January 2018

Quality‐adjusted life years are used in cost‐effectiveness analyses (CEAs). To calculate QALYs, a “utility” (0–1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF‐6D and EQ‐5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality‐adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study‐specific assumed disutilities (i.e., 1‐utility) with study‐specific durations of the loss in QoL, resulting in 14 “QADL‐sets.” With microsimulation model MISCAN we calculated cost‐effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL‐sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL‐sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF‐6D empirical QADL‐set resulted in cytology and the EQ‐5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost‐effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.
Effect of titanium dioxide nanoparticles on glucose homeostasis after oral administration
Authors: Chen Zhangjian , Wang Yun , Wang Xiang , Zhuo Lin , Chen Shi , Tang Shichuan , Zhao Lin , Luan Xianguo , Jia Guang
Published: January 2018

As food additives, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various products that are usually simultaneously consumed with a high content of sugar, thus necessitating research on the effect of TiO2 NPs on glucose homeostasis. We conducted an animal study to explore the effect of orally administrated TiO2 NPs on glucose absorption and metabolism in rats at 0, 2, 10 and 50 mg kg–1 body weight day–1 for 30 and 90 days. The results showed that oral exposure to TiO2 NPs caused a slight and temporary hypoglycemic effect in rats at 30 days post‐exposure but recovered at 90 days post‐exposure. Decreased levels of intestinal glucose absorption and increased levels of hepatic glucose metabolism may be responsible for the hypoglycemic effect. Remodeling of the villi in the small intestine that decreased the surface area available for glucose absorption and increased levels of hepatic glucose uptake, utilization and storage related to hepatocellular injury are supposed to be the mechanisms. Our results demonstrated that dietary intake of TiO2 NPs as food additives could affect the absorption and metabolism of glucose.
Reproductive toxic impact of subchronic treatment with combined butylparaben and triclosan in weanling male rats
Authors: Riad Madeha A. , Abd‐Rabo Marwa M. , Abd El Aziz Samy A. , El Behairy Adel M. , Badawy Mohamed M.
Published: January 2018

The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle‐stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the E2 level, whereas combined treatment did not alter the E2 level. Testicular DNA damage was recorded in all treated groups. Moreover, the testicular malondialdehyde level was significantly elevated, along with a significant decrease in catalase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly decreased in the butylparaben‐treated group, increased in the triclosan‐treated group, and nonsignificantly changed the butylparaben‐triclosan‐treated group. The combined treatment produced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which may represent a common mechanism of endocrine disruptor‐mediated dysfunction.
Effectiveness and safety of original and generic sofosbuvir for the treatment of chronic hepatitis C: A real world study
Authors: Marciano Sebastián , Haddad Leila , Reggiardo María V. , Peralta Mirta , Vistarini Cecilia , Marino Mónica , Descalzi Valeria I. , D'Amico Claudia , Figueroa Escuti Sebastián , Gaite Luis A. , Perez Ravier Roberto , Longo Cristina , Borzi Silvia M. , Galdame Omar A. , Bessone Fernando , Fainboim Hugo A. , Frías Silvia , Cartier Mariano , Gadano Adrián C.
Published: January 2018

We report the first real‐world prospective multicenter cohort study that evaluated the effectiveness and safety of original or generic sofosbuvir‐based regimens in patients with chronic hepatitis C in Latin America. The main endpoints were assessment of sustained virological response and serious adverse events rates. A total of 321 patients with chronic hepatitis C treated with the following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or 24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or 24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2) weeks. Patients received either original sofosbuvir (Sovaldi®, Gilead Sciences, n = 135) or generic sofosbuvir (Probirase®, Laboratorios RICHMOND, n = 184) which were randomly assigned by the National Ministry of Health. Overall, 292 (91%) patients had cirrhosis, 136 (42%) were treatment experienced, and 240 (75%) genotype 1. The overall sustained virological response was 90% (95% CI 86‐93%); 91% (95% CI 84‐95%) in patients who received Sovaldi®, and 89% (95% CI 84‐93%) in patients who received Probirase®. Anemia was the most common adverse event and was reported in 52 (17%) patients. Bacterial infection, gastrointestinal bleeding, worsening of ascites or encephalopathy occurred in less than 5% of the patients. During the study, seven (2%) patients died, four of whom died of cirrhosis‐related complications. In summary, we observed similar sustained virological response rates than prior studies, both in patients who received Sovaldi® or Probirase®. Serious adverse events were infrequent, in line with prior studies that included patients with cirrhosis treated with protease‐inhibitor‐free regimes.
Feeling insulted? Examining end‐of‐work anger as a mediator in the relationship between daily illegitimate tasks and next‐day CWB
Authors: Zhou Zhiqing E. , Eatough Erin M. , Wald Danielle R.
Published: January 2018

In this daily diary study, we investigated the within‐person relationship between daily illegitimate tasks and next‐day counterproductive work behavior (CWB). We explored a moderated mediation model where the link between illegitimate tasks and CWB is mediated by daily end‐of‐work anger, with daily time pressure moderating the relationship between illegitimate tasks and end‐of‐work anger. We collected data from 114 full‐time employees across 10 consecutive working days. Results showed that within individuals, daily illegitimate tasks positively predicted next‐day CWB, and the relationship was mediated by daily end‐of‐work anger. Further, daily time pressure moderated the relationship between daily illegitimate tasks and daily end‐of‐work anger with the relationship being stronger when daily time pressure was high.
Climate change projections over China using regional climate models forced by two CMIP5 global models. Part II: projections of future climate
Authors: Hui Pinhong , Tang Jianping , Wang Shuyu , Niu Xiaorui , Zong Peishu , Dong Xinning
Published: January 2018

The changes in mean and extreme climate in China during 2020–2060 are detected with both Weather Research and Forecasting and RegCM4, by downscaling the simulations from EC‐EATTH and IPSL‐CM5A under both the RCP4.5 and RCP8.5 scenarios. The climate changes under the two scenarios exhibit similar patterns, with stronger intensity under the RCP8.5 scenario. For the mean precipitation, increases are projected in most regions, with the largest relative increase in the Tarim Basin. Slight drought mainly occurs in the south‐eastern part of China. The frequency of drizzle rain is expected to decrease in all the sub‐regions, but the moderate to heavy rainfall as well as the storm would occur more frequently, especially on the Tibetan Plateau. The whole country would experience much warmer climate in the future, with the strongest warming over the Tibetan Plateau. By detecting the changes in climate extremes, it is indicated that less dry extremes would occur in the wet areas of China, while more dry events in the arid and semiarid regions. The wet extreme indices would increase in most regions, especially in the wet areas. The surface air temperature tends to become extremely warmer in the future over the whole country, with the strongest change over the Tibetan Plateau. The changes in mean and extreme climate depend strongly on the driving global climate models, with wetter and warmer climate in the downscalings over IPSL‐CM5A, and the model physics of the regional climate models also exert great impact on the projections. Finally, the possible mechanisms for the changes of extreme precipitation are discussed. The enhanced summer monsoon in the future transports more moisture to China, which could lead to more summer precipitation. As a result, the wet extremes tend to increase.
Bodenchemische Vertikalgradienten als charakteristische Zustandsgrößen von Waldökosystemen
Authors: Kölling Christian , Hoffmann Manuela , Gulder Hans‐Jürgen
Published: January 2018

Anhand von Lysimeteruntersuchungen der Bodenlösung, Untersuchungen der Bodenfestphase und unter Verwendung von Modellvorstellungen wird die Möglichkeit demonstriert, die Zusammensetzung der Bodenlösung teilweise aus den Eigenschaften der Bodenfestphase vorherzusagen. Als Vorhersageparameter erweist sich die im NH4CI‐Extrakt ermittelte Aluminium‐(Basen)sättigung der Kationenaustauscher als besonders geeignet. Der Parameter zeigt ausgeprägte Tiefengradienten, die als charakteristische Zustandsgrößen der jeweiligen Waldökosysteme gelten können. Es wird vorgeschlagen, diese bodenchemische Zustandsgröße aufgrund ihrer ökologischen Bedeutung bei der forstlichen Standortsklassifikation zusätzlich zu den herkömmlichen Klassifikationskriterien zu verwenden.
Unravelling external perturbation effects on the optical phonon response of graphene
Authors: Bendiab Nedjma , Renard Julien , Schwarz Cornelia , Reserbat‐Plantey Antoine , Djevahirdjian Léo , Bouchiat Vincent , Coraux Johann , Marty Laëtitia
Published: January 2018

Raman spectroscopy is a powerful and nondestructive probe that demonstrates its efficiency in revealing the physical properties of low‐dimensional sp2 carbon systems. It gives access to the number of layers, the quality and the nature of defects of all carbon allotropes, but also to the understanding of the influence of perturbations such as strain and/or doping. In this paper, we review the state of the art regarding the effect of external perturbations on the optical phonons of graphene. We describe how doping can tune the unusual electron–phonon coupling in graphene and thus modify not only the resonance conditions but also the phonon intensities thanks to quantum interferences. We also review the impact of strain on optical phonons and how one can disentangle strain and doping thanks to optical phonons. Last, implementations of this field to strain engineering or to graphene‐based mechanical resonators will be presented. Copyright © 2018 John Wiley & Sons, Ltd.
Why wine tourists visit cellar doors: Segmenting motivation and destination image
Authors: Bruwer Johan , Prayag Girish , Disegna Marta
Published: January 2018

This study examines the relationship between the motivation of wine tourists to visit cellar doors and destination image perception. A survey of tourists resulted in 676 useable questionnaires. Using a novel segmentation method, self‐organizing maps, and bagged clustering, the study identified 5 distinct motivation clusters. These clusters were different on only gender and previous visit to the wine region. Three clusters of destination image were identified using the same segmentation method. Significant relationships were found between the motivation and destination image clusters. Implications for destination marketing and managing the tourist experience at the winery cellar door are discussed.
Maturity of the book purchasing process in university libraries
Authors: Drumond Geisa Meirelles , Méxas Mirian Picinini , Meiriño Marcelo Jasmim , Quelhas Osvaldo Luiz Gonçalves
Published: January 2018

In organizational management, operational performance and the maturity level of processes should be considered for improving quality and productivity. The present research has the overall objective of analyzing the level of maturity of the purchasing process of bibliographic material, developed in the university libraries of a Federal University. Based on the overall objective, we aim to identify maturity models used in process management in the scientific literature, as well as proposing a way of collecting and treating the perception of maturity of the purchasing process of bibliographic material. To achieve these objectives, we adopted as methodological procedures the bibliographic research in the SciELO, SCOPUS, and DOAJ bases and the case study on the perception of maturity of the purchasing process of books from the university libraries, using the interview and closed questionnaire. The questionnaire was applied to 40 staff members of the system of university libraries. The results indicate that the majority of activities carried out for the purchase of books present levels of maturity above Level 1. This shows that the processes performed in libraries for the purchase of books are defined, planned, and controlled, although there is a considerable number of aspects that can be improved. In terms of relevance for library management, the research intends to provide subsidies for the planning and management of the purchasing process of bibliographic material and the optimization of resources, as well as understanding and assessing the process carried out, identifying its maturity levels.
Characterization of the Slow Molecular Dynamics of Poly(l‐Lactic Acid) in α and α′ Phases, in a Glassy State, and in a Complex with Poly(d‐Lactic Acid) by Solid‐State NMR
Authors: Chen Wei , Zhou Wenxuan , Makita Yuta , Wang Shijun , Yuan Shichen , Konishi Takashi , Miyoshi Toshikazu
Published: January 2018

Recently, slow molecular dynamics of poly(l‐lactic acid) (PLLA) by using 1D and 2D exchange NMR are investigated. In this work, slow molecular dynamics of PLLA chains in the α′, a stereocomplex (SC) with poly(d‐lactic acid), and glassy states are investigated in terms of centerband‐only detection of exchange (CODEX) NMR. The mixing‐time dependence of the CODEX data demonstrates that the molecular dynamics of stems become slower in the order of α′, α, and SC. The temperature dependence of the correlation time 〈τc〉 of the helical jump motions in the α and SC phases simply exhibits Arrhenius behaviors, with activation energy, Ea, values of 91 ± 1 and 97 ± 1 kJ mol−1, respectively. In contrast, the temperature dependence of 〈τc〉 in the α′ sample exhibits two Arrhenius lines with substantially different Ea values of 273 ± 12 and 16 ± 14 kJ mol−1 at temperatures below and above 84 °C. The obtained kinetics of molecular dynamics not only establish the relationship between packing structure and dynamics in PLLA polymorphs and in the SC, but also allow for an understanding of the coupled dynamics between the crystalline and amorphous regions at approximately Tg.
miFAST: A novel and rapid microRNA target capture method
Authors: Poenitzsch Strong Ashley M. , Berry Scott M. , Beebe David J. , Li Jian‐Liang , Spiegelman Vladimir S.
Published: January 2018

MicroRNAs (miRNAs), small 22‐25 nucleotide non‐coding RNAs, play important roles in cellular and tumor biology. However, characterizing miRNA function remains challenging due to an abundance of predicted targets and an experimental bottleneck in identifying biologically relevant direct targets. Here, we developed a novel technique (miFAST) to identify direct miRNA target genes. Using miFAST, we confirmed several previously reported miR‐340 target genes and identified five additional novel direct miR‐340 targets in melanoma cells. This methodology can also be efficiently applied for the global characterization of miRNA targets. Utilizing miFAST to characterize direct miRNA targetomes will further our understanding of miRNA biology and function.
Global attractivity of a delayed Nicholson‐type system involving nonlinear density‐dependent mortality terms
Authors: Yao Luogen
Published: January 2018

This paper investigates the asymptotic behavior of a delayed Nicholson‐type system involving patch structure and nonlinear density‐dependent mortality terms. Based on the fluctuation lemma and some differential inequality techniques, delay‐dependent criteria are deduced for the global attractivity of the addressed system, which indicate that small delays have no effect on the attractivity of the system. Meanwhile, an illustrative numerical example is given to illustrate the feasibility of the theoretical results.
Understanding Resource-Conserving Behaviors Among Fishers: Barotrauma Mitigation and the Power of Subjective Norms in Florida's Reef Fisheries
Authors: Crandall Chelsey A. , Garlock Taryn M. , Lorenzen Kai
Published: January 2018

Understanding the factors underlying fishers’ decisions to adopt resource-conserving behaviors is important to successful fisheries management. This study used an online survey to explore factors motivating decisions to use alternative barotrauma mitigation measures (venting and descending) to improve discarded reef fish survival across recreational, charter, and commercial fishers in the state of Florida. A majority of respondents (66–69%) had experienced fish showing gross signs of barotrauma, and more than half of those (52–69%) reported using barotrauma mitigation most of the time when needed. Use of mitigation by other fishers was perceived to be lower (30–57%) and to have declined after removal of a venting tool requirement. Overall, respondents were more likely to have used venting tools (96–99%) than fish descenders (14–27%), and most respondents (81–86%) intended to use venting tools in the future. The theory of planned behavior was used to predict and explain intentions to use venting tools and/or fish descenders based on three variables: attitudes toward the method, subjective norms (i.e., social pressure), and perceived control (i.e., confidence in their ability to use the method). Fishers across sectors perceived venting tools and descenders to be similarly effective in improving released fish survival, but they felt that descenders were more time consuming, difficult to use, and expensive. Subjective norms and perceived control were stronger for venting tools than for descenders. Overall, subjective norms had the strongest influence on fishers’ intention to use either form of mitigation; attitudes and perceived control were also important in the case of descenders. Outreach efforts focusing on re-enforcing subjective norms should have the greatest impact on increasing fishers’ use of barotrauma mitigation methods. Comparatively greater efforts are required to increase the use of descending gear than to increase the use of venting, and care should be taken to avoid strategies that could result in an overall decline of barotrauma mitigation.
Comparison of Diploid and Triploid Saugeye Recruitment, Growth, and Condition in Kansas Impoundments
Authors: Koch Jeff , Steffen Chris , Goeckler Jason , Marteney Ron , Jagels Josh , Brown Bonnie
Published: January 2018

Saugeyes (Walleye Sander vitreus × Sauger S. canadensis) are stocked by natural resource agencies to provide angling opportunities and biological control of abundant small-bodied fishes. Concern has been raised regarding the stocking of fertile diploid saugeyes in Kansas waters due to potential genetic introgression into wild parental stocks and unintended natural reproduction in ecologically sensitive systems. As such, triploid saugeyes have been stocked in Kansas since 2006 but with minimal evaluation. We compared relative recruitment, growth, and condition of diploid and triploid saugeyes after stocking equal numbers of 3–6-d-old diploid and triploid saugeye fry in four Kansas reservoirs for 3 years. Saugeyes were sampled from study reservoirs annually (2014–2016) with autumn night electrofishing, and flow cytometry was used to determine the ploidy of sampled fish. Throughout the study, diploid fish composed approximately 80% of sampled saugeyes. Age-0 year-classes consisted of 67–100% diploid fish, depending on the study reservoir and sampling year. As saugeyes reached ages 1 and 2, similar patterns in relative recruitment were indicated, with diploids outnumbering triploids by approximately four times. At individual study impoundments, diploid saugeyes composed 75–87% of fish from all study year-classes. Mean length of diploid saugeyes was generally greater than that of triploids at age 0, whereas mean lengths at ages 1 and 2 were similar for the two groups. Our results indicate that diploid saugeye fry represent a more efficient stocking option than triploid fry and that managers should carefully balance consideration of the relative recruitment of diploid and triploid saugeyes with potential genetic integration between Sander spp. when conducting supplemental stockings.
Role of microglia in the spinal cord in colon‐to‐bladder neural crosstalk in a rat model of colitis
Authors: Majima Tsuyoshi , Funahashi Yasuhito , Kawamorita Naoki , Takai Shun , Matsukawa Yoshihisa , Yamamoto Tokunori , Yoshimura Naoki , Gotoh Momokazu
Published: January 2018

Aims

We investigated whether spinal cord microglia are involved in colon‐to‐bladder neural crosstalk in a rat model of colitis.

Methods

Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group. The following investigations were performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2) nociceptive behavior observation induced by intravesical instillation of resiniferatoxin; (3) toluidine blue staining in the bladder; (4) Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord sections; and (5) quantitative RT‐PCR to investigate interleukin‐1β (IL‐1β), chemokine ligand 3 (CCL3), and brain‐derived neurotrophic factor (BDNF) gene expression in the L6 spinal cord.

Results

In comparison with the control group, the colitis group showed significant increases in (1) micturition frequency during cystometry; (2) resiniferatoxin‐induced freezing behavior (bladder pain); (3) the number of total and degranulated mast cells in the bladder; (4) the number of microglia in the L6 spinal cord, and (5) the expression of IL‐1β, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover, intrathecal administration of minocycline alleviated these pathophysiological findings caused by experimental colitis.

Conclusions

Spinal microglia may play an important role in colitis‐induced bladder overactivity and enhanced bladder pain sensitivity in colitis rats.
Predictors of response, progression‐free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high‐risk neuroblastoma
Authors: Villablanca Judith G. , Ji Lingyun , Shapira‐Lewinson Adi , Marachelian Araz , Shimada Hiroyuki , Hawkins Randall A. , Pampaloni Miguel , Lai Hollie , Goodarzian Fariba , Sposto Richard , Park Julie R. , Matthay Katherine K.
Published: January 2018

Purpose

The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed.

Methods

A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology).

Results

Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five‐year progression‐free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG‐avid lesions (100% MIBG trials; 84% non‐MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non‐PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS.

Conclusions

NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.
BRIM‐P: A phase I, open‐label, multicenter, dose‐escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation‐positive melanoma
Authors: Chisholm Julia C. , Suvada Jozef , Dunkel Ira J. , Casanova Michela , Zhang Weijiang , Ritchie Natasha , Choi YounJeong , Park Jane , Das Thakur Meghna , Simko Stephen , Wan Rachel Tam Nga , Ferrari Andrea
Published: January 2018

Background

Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation‐positive melanoma. We conducted a phase I, open‐label, dose‐escalation study in pediatric patients aged 12–17 years with this tumor type (NCT01519323).

Procedure

Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose‐limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated.

Results

Six patients were enrolled (720 mg twice daily [BID], n = 3; 960 mg BID [n = 3]). The study was terminated prematurely due to low enrollment. No DLTs were observed; thus, the MTD could not be determined. All patients experienced at least one adverse event (AE); the most common were diarrhea, headache, photosensitivity, rash, nausea, and fatigue. Three patients experienced serious AEs, one patient developed secondary cutaneous malignancies, and five patients died following disease progression. Mean steady‐state plasma concentrations of vemurafenib following 720 mg and 960 mg BID dosing were similar or higher, respectively, than in adults. There were no objective responses. Median progression‐free survival and overall survival were 4.4 months (95% confidence interval [CI] = 2.7–5.2) and 8.1 months (95% CI = 5.1–12.0), respectively.

Conclusions

A recommended and effective dose of vemurafenib for patients aged 12–17 years with metastatic or unresectable melanoma was not identified. Extremely low enrollment in this trial highlights the importance of considering the inclusion of adolescents with adult cancers in adult trials.
Emotion regulation and positive affect in the context of salivary alpha‐amylase response to pain in children with cancer
Authors: Jenkins Brooke N. , Granger Douglas A. , Roemer Ryan J. , Martinez Ariana , Torres Tara K. , Fortier Michelle A.
Published: January 2018

Background

Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect.

Procedure

This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)—a surrogate marker for autonomic/sympathetic nervous system activity and regulation.

Results

Children in the reassurance group had sAA levels that continued to rise after completion of the CPT compared to children in the distraction (b = –1.68, P = 0.021) and reappraisal conditions (b = –1.24, P = 0.084). Furthermore, dispositional positive affect moderated the effect of condition such that children in the reassurance group with lower levels of positive affect had sAA levels that continued to rise after completion of the CPT (dy/dx = 1.56, P = 0.027), whereas children in the reassurance condition with higher levels of positive affect did not exhibit this rise (P > 0.05).

Conclusions

Specific emotion regulation strategies, such as distraction and reappraisal, may attenuate the stress response to pain in pediatric patients with cancer, and positive affect may confer resilience in response to pain even with use of less effective coping strategies such as reassurance.
Drug adherence in treatment resistant and in controlled hypertension—Results from the Swedish Primary Care Cardiovascular Database (SPCCD)
Authors: Holmqvist Lina , Boström Kristina Bengtsson , Kahan Thomas , Schiöler Linus , Qvarnström Miriam , Wettermark Björn , Hjerpe Per , Hasselström Jan , Manhem Karin
Published: January 2018

Purpose

To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence.

Methods

Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included.

Results

We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (<140/90 mm Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood pressure. The proportion of patients with PDC ≥ 80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1 year (RR 0.82; 95% CI, 0.68‐0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49‐2.82).

Conclusions

Patients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment.
Ammonia‐free, room temperature, and reusable photochemical bath for the deposition ofZn(S,O)buffer layers inCu(In,Ga)Se2thin‐film solar cells
Authors: Gallanti Serena , Chassaing Elisabeth , Loones Nicolas , Bouttemy Muriel , Etcheberry Arnaud , Lincot Daniel , Naghavi Negar
Published: January 2018

Today, chemical bath deposited (CBD) Zn(S,O) is used at the industrial level in Cu(In,Ga)Se2solar cells technology. The state‐of‐the‐art recipes of sulfur‐based buffer layers use thiourea as sulfide ions precursor and ammonia as complexing agent. However, such formulations require high concentrations of reactants, deposition temperatures between 60°C and 80°C with the problem of ammonia losses by evaporation and large water consumption. In this work, a novel bath chemistry for Zn(S,O) buffer layer deposition is developed where the thiourea is replaced by thioacetic acid as a sulfur precursor. The use of this compound allows the photochemical growth of a dense and homogenous Zn(S,O) layer on CIGSe absorbers. The main advantages of this solution compared to classical CBD‐Zn(S,O) bath are the deposition occurs at room temperature, the concentration of chemical precursors is 6 times lower, no use of a complexing agent such as ammonia, the reuse of the same bath at least for 4 consecutive times. The effect of the deposition time, the incident light power during deposition, and the successive use of the solutions on the thickness and composition of the film is discussed by means of scanning electron microscopy, and X‐ray photoelectron spectroscopy analyses. The photovoltaic performance shows conversion efficiencies similar to the classical thiourea/ammonia based process.
Radical polyaddition of difunctional vinyloxirane with thiols for synthesis of linear and networked polysulfides
Authors: Maeda Shinya , Sudo Atsushi , Endo Takeshi
Published: January 2018

Radical ring‐opening polyaddition of bifunctional vinyloxirane with multifunctional thiols was investigated. The polyaddition proceeded smoothly via the ring‐opening reaction of the oxirane moiety to afford the corresponding networked polymers bearing vinyl ether and sulfide moieties in the main chain. The thermal properties of the networked polymers and volume changes upon the polyaddition were investigated. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 783–788
Colloidal Clusters of Bimetallic Core–Shell Nanoparticles for Enhanced Sensing of Hydrogen in Aqueous Solution
Authors: Wy Younghyun , Lee Seunghoon , Wi Dae Han , Han Sang Woo
Published: January 2018

Developing sensitive and stable hydrogen sensors is of great importance for sustainable energy development. Here, a novel hydrogen sensing platform is described based on colloidal clusters of Au@Pd core–shell nanoparticles (Au@Pd NPCs) with characteristic localized surface plasmon resonance (LSPR) properties. Au@Pd NPCs with well‐controlled topologies exhibit highly pronounced sensitivity for LSPR‐based hydrogen sensing in aqueous solution in comparison to their nanoparticle counterparts and previously reported Au–Pd bimetallic nanostructures, which can be attributed to highly promoted plasmonic field resulting from the cluster formation. Furthermore, Au@Pd NPCs show stable sensing capability for repeated hydrogen sensing cycles. The present strategy for devising high‐performance LSPR‐based hydrogen sensors via the controlled assembly of bimetallic nanoparticles can be applied to the development of efficient plasmonic platforms for various sensing applications.