bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐clinical safety assessment of single and repeated intramuscular administration of a human papillomavirus‐16/18 vaccine in rabbits and rats
Authors: Segal Lawrence , Morelle Danielle , Kaaber Kari , Destexhe Eric , Garçon Nathalie 
Published: March 2015

AbstractThe human papillomavirus (HPV)‐16/18 vaccine (Cervarix®) is a prophylactic vaccine for the prevention of cervical cancer. The vaccine contains recombinant virus‐like particles assembled from the L1 major capsid proteins of the cervical cancer‐causing viral types HPV‐16 and HPV‐18, and Adjuvant System 04 (AS04), which contains the immunostimulant MPL and aluminium salt. To evaluate potential local and systemic toxic effects of the HPV‐16/18 vaccine or AS04 alone, three repeated‐dose studies were performed in rabbits and rats. One rabbit study also included a single‐dose evaluation. In rabbits (~2.5 kg), the full human dose (HD) of the vaccine was evaluated (0.5 ml per injection site), and in rats (~250 g), 1/5 HD of vaccine was evaluated, corresponding to ≥ 12 times the dosage in humans relative to body weight. In both animal models, the treatment‐related changes included a slight transient increase in the number of circulating neutrophils as well as a local inflammatory reaction at the injection site. These treatment‐related changes were less pronounced after four doses of AS04 alone than after four doses of the HPV‐16/18 vaccine. Additional treatment‐related changes in the rat included lower albumin/globulin ratios and microscopic signs of inflammation in the popliteal lymph nodes. In both animal models, 13 weeks after the fourth dose, recovery was nearly complete, although at the injection site in some animals there were signs of discoloration, muscle‐fibre regeneration and focal points of macrophage infiltration. Therefore, in these non‐clinical models, the single and repeated dose administrations of the HPV‐16/18 vaccine or AS04 alone were safe and well tolerated. Copyright © 2015 John Wiley & Sons, Ltd.
Chemotherapy for advanced poorly differentiated pancreatic neuroendocrine carcinoma
Authors: Ikeda Masafumi , Okuyama Hiroyuki , Takahashi Hideaki , Ohno Izumi , Shimizu Satoshi , Mitsunaga Shuichi , Kondo Shunsuke , Morizane Chigusa , Ueno Hideki , Okusaka Takuji 
Published: March 2015

AbstractPancreatic neuroendocrine carcinoma (P‐NEC) resembles small cell lung carcinoma in its biologic and clinical features, such as rapid growth and relatively high sensitivity to platinum‐based chemotherapy. And, etoposide plus cisplatin (EP) or irinotecan plus cisplatin (IP), recommended by guidelines for the treatment of small cell lung carcinoma, has also been widely used for the treatment of unresectable NEC. Both regimens have been demonstrated to show favorable efficacy and have been acknowledged as de facto standard regimens for unresectable NEC, although it remains unclear which of the two regimens might yield more favorable outcomes. Therefore, a phase III trial of EP vs. IP has been planned for unresectable gastrointestinal, hepatobiliary or pancreatic NEC by the Japan Clinical Oncology Group. For patients with unresectable NEC who are refractory or intolerant to these regimens, no standard regimens have been established. Everolimus, an mTOR inhibitor, is likely to be effective in such patients, as there have been sporadic reports of the usefulness of everolimus in the treatment of P‐NEC. A multicenter phase II trial is underway to elucidate the efficacy and safety of everolimus in patients with P‐NEC who are refractory or intolerant to EP or IP.
A time‐lagged investigation of the impact of coworker behavior on the effects of demographic dissimilarity
Authors: David Emily M. , Avery Derek R. , Witt L. A. , McKay Patrick F. 
Published: March 2015

SummaryAlthough it is clear that coworker absenteeism, tardiness, and turnover can influence an employee's actions, scholars have yet to consider the impact of relational demography on the adoption of these behavioral norms. Inspired by social identity, situational strength, and attraction‐selection‐attrition theories, we proposed that individuals who differ from their coworkers in age, sex, or racioethnicity would feel threatened by their outnumbered status and subsequently motivated to be absent, tardy, or more likely to turnover. However, we expected coworker withdrawal behavior to moderate whether or not dissimilar personnel act on these desires. Results from hierarchical multilevel modeling analyses of data from 470 U.S. call center workers nested in 51 work groups revealed that racioethnic dissimilarity was positively related to time‐lagged changes in absenteeism and tardiness as well as heightened turnover likelihood. These effects emerged only among employees whose coworkers engaged in greater withdrawal behavior. Importantly, racioethnically dissimilar employees working in more permissive climates (i.e., those with high levels of coworker absenteeism, tardiness, or turnover) exhibited the greatest increases in absenteeism and tardiness over three months and had the highest supervisor‐rated turnover likelihood. Implications for diversity management are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Active learning climate and employee errors: The moderating effects of personality traits
Authors: Naveh Eitan , Katz‐Navon Tal , Stern Zvi 
Published: March 2015

SummaryThis study developed and tested a cross‐level model of the relationship between two components of active learning climate—enactive exploration and guided learning—and employee errors, and the moderating roles of the individual's traits of openness to experience and conscientiousness. The study examined the medical errors made by 142 resident physicians in 22 hospital departments. Results demonstrated significant interactions between climate and traits: when an individual had a low level of the trait of openness to experience, there was a curvilinear relationship between enactive exploration climate and number of errors. With a high level of openness to experience, the enactive exploration climate was positively associated with the number of errors up to a certain point. In addition, when an individual had a low level of conscientiousness, there was a negative association between guided learning climate and number of errors; with a high level of conscientiousness, there was a positive association between guided learning climate and number of errors. Thus, individual performance was better when the climate complemented the individual's lack of a trait. When the level of the individual's trait was high, the climate intensified the already pronounced trait up to an extent that impaired the individual's performance. Copyright © 2015 John Wiley & Sons, Ltd.
Interpersonal harmony and creativity in China
Authors: Chen Tingting , Leung Kwok , Li Fuli , Ou Zhanying 
Published: March 2015

SummaryThis research examined the influence of interpersonal harmony on employee creativity in China. The dualistic model of harmony differentiates harmony enhancement, a genuine desire for a harmonious and mutually beneficial interpersonal relationship, from disintegration avoidance, a tendency to avoid the disruption of an interpersonal relationship to protect self‐interest. A survey in China showed that the harmony enhancement motive had a positive relationship, and the disintegration avoidance motive had a negative relationship, with creativity mediated by creative effort. Reward for creativity showed different moderating effects on the two mediated relationships, such that it mitigated the positive relationship between harmony enhancement and creativity mediated by creative effort, and buffered the negative relationship between disintegration avoidance and creativity mediated by creative effort. We replicated some major findings with a multi‐wave survey study and provided direct evidence for the underlying mechanisms that account for the opposite relationships between the two harmony motives and creative effort. Copyright © 2015 John Wiley & Sons, Ltd.
Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide
Authors: Xue Yan‐Feng , Zhang Meng , Qi Zhong‐Qiang , Li You‐Qin , Shi Zhiqi , Chen Jian 
Published: March 2015

AbstractBACKGROUNDCinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism.RESULTSThe lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of l‐cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA‐induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation.CONCLUSIONCA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching. © 2015 Society of Chemical Industry
Functional consequences of transferrin receptor‐2 mutations causing hereditary hemochromatosis type 3
Authors: Joshi Ricky , Shvartsman Maya , Morán Erica , Lois Sergi , Aranda Jessica , Barqué Anna , de la Cruz Xavier , Bruguera Miquel , Vagace José Manuel , Gervasini Guillermo , Sanz Cristina , Sánchez Mayka 
Published: March 2015

AbstractHereditary hemochromatosis (HH) type 3 is an autosomal recessive disorder of iron metabolism characterized by excessive iron deposition in the liver and caused by mutations in the transferrin receptor 2 (TFR2) gene. Here, we describe three new HH type 3 Spanish families with four TFR2 mutations (p.Gly792Arg, c.1606‐8A>G, Gln306*, and Gln672*). The missense variation p.Gly792Arg was found in homozygosity in two adult patients of the same family, and in compound heterozygosity in an adult proband that also carries a novel intronic change (c.1606‐8A>G). Two new nonsense TFR2 mutations (Gln306* and Gln672*) were detected in a pediatric case. We examine the functional consequences of two TFR2 variants (p.Gly792Arg and c.1606‐8A>G) using molecular and computational methods. Cellular protein localization studies using immunofluorescence demonstrated that the plasma membrane localization of p.Gly792Arg TFR2 is impaired. Splicing studies in vitro and in vivo reveal that the c.1606‐8A>G mutation leads to the creation of a new acceptor splice site and an aberrant TFR2 mRNA. The reported mutations caused HH type 3 by protein truncation, altering TFR2 membrane localization or by mRNA splicing defect, producing a nonfunctional TFR2 protein and a defective signaling transduction for hepcidin regulation. TFR2 genotyping should be considered in adult but also in pediatric cases with early‐onset of iron overload.
Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semi‐solid magnetization transfer reference (EMR) signals: Application to a rat glioma model at 4.7 tesla
Authors: Heo Hye‐Young , Zhang Yi , Lee Dong‐Hoon , Hong Xiaohua , Zhou Jinyuan 
Published: March 2015

PurposeTo quantify amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) contributions to in vivo chemical exchange saturation transfer MRI signals in tumors.Theory and MethodsTwo‐pool (free water and semi‐solid protons) and four‐pool (free water, semi‐solid, amide, and upfield NOE‐related protons) tissue models combined with the super‐Lorentzian lineshape for semi‐solid protons were used to fit wide and narrow frequency‐offset magnetization‐transfer (MT) data, respectively. Extrapolated semi‐solid MT signals at 3.5 and −3.5 ppm from water were used as reference signals to quantify APT and NOE, respectively. Six glioma‐bearing rats were scanned at 4.7 Tesla. Quantitative APT and NOE signals were compared at three saturation power levels.ResultsThe observed APT signals were significantly higher in the tumor (center and rim) than in the contralateral normal brain tissue at all saturation powers, and were the major contributor to the APT‐weighted image contrast (based on MT asymmetry analysis) between the tumor and the normal brain tissue. The NOE (a positive confounding factor) enhanced this APT‐weighted image contrast. The fitted amide pool sizes were significantly larger, while the NOE‐related pool sizes were significantly smaller in the tumor than in the normal brain tissue.ConclusionThe extrapolated semi‐solid magnetization transfer reference provides a relatively accurate approach for quantitatively measuring pure APT and NOE signals. Magn Reson Med 75:137–149, 2016. © 2015 Wiley Periodicals, Inc.
Arterial spin labeled perfusion imaging using three‐dimensional turbo spin echo with a distributed spiral‐in/out trajectory
Authors: Li Zhiqiang , Schär Michael , Wang Dinghui , Zwart Nicholas R. , Madhuranthakam Ananth J. , Karis John P. , Pipe James G. 
Published: March 2015

PurposeThe three‐dimensional (3D) spiral turbo spin echo (TSE) sequence is one of the preferred readout methods for arterial spin labeled (ASL) perfusion imaging. Conventional spiral TSE collects the data using a spiral‐out readout on a stack of spirals trajectory. However, it may result in suboptimal image quality and is not flexible in protocol design. The goal of this study is to provide a more robust readout technique without such limitation.MethodsThe proposed technique incorporates a spiral‐in/out readout into 3D TSE, and collects the data on a distributed spirals trajectory. The data set is split into the spiral‐in and ‐out subsets that are reconstructed separately and combined after image deblurring.ResultsThe volunteer results acquired with the proposed technique show no geometric distortion or signal pileup, as is present with GRASE, and no signal loss, as is seen with conventional spiral TSE. Examples also demonstrate the flexibility in changing the imaging parameters to satisfy various criteria.ConclusionThe 3D TSE with a distributed spiral‐in/out trajectory provides a robust readout technique and allows for easy protocol design, thus is a promising alternative to GRASE or conventional spiral TSE for ASL perfusion imaging. Magn Reson Med 75:266–273, 2016. © 2015 Wiley Periodicals, Inc.
The role of androgens in metabolism, obesity, and diabetes in males and females
Authors: Navarro Guadalupe , Allard Camille , Xu Weiwei , Mauvais‐Jarvis Franck 
Published: March 2015

ObjectiveIn men, androgen deprivation contributes to the development of metabolic syndrome and type 2 diabetes (T2D). In women, androgen excess predisposes to insulin resistance and T2D. There is a bidirectional modulation of glucose homeostasis by androgens in males and females that is analyzed in this review.MethodsWe reviewed the literature in both rodents and humans on the role of androgens and the androgen receptor (AR) in the control of glucose and energy metabolism in health, obesity, and T2D.ResultsSex‐specific activation of AR in the hypothalamus, skeletal muscle, liver, adipose tissue, and pancreatic islet β‐cells accounts for maintenance or disruption in energy metabolism and glucose homeostasis.ConclusionsWe argue that AR is a target to prevent androgen‐related metabolic disorders.
Usual breakfast eating habits affect response to breakfast skipping in overweight women
Authors: Thomas Elizabeth A. , Higgins Janine , Bessesen Daniel H. , McNair Bryan , Cornier Marc‐Andre 
Published: March 2015

ObjectiveThis randomized, cross‐over trial was designed to investigate the metabolic and appetitive responses to skipping breakfast in overweight women who were habitual breakfast Eaters or Skippers.MethodsNine Eaters and nine Skippers were studied on two separate days during which subjects ate breakfast (B) or had no breakfast (NB), followed by a standard lunch meal 4 h later. Blood sampling for hormones and metabolites was performed after lunch, and appetite was rated throughout the day.ResultsInteractions between day and habitual breakfast pattern were seen for area under the curve (AUC) for insulin and free fatty acids (FFA). Both insulin (P = 0.020) and FFA (P = 0.023) AUC were higher on the NB day for Eaters but similar on both days for Skippers. Eaters had higher pre lunch hunger AUC on the NB day (P = 0.015) as well as lower pre lunch satiety AUC under both conditions (P = 0.019).ConclusionsOverall, this study showed that the adverse effects of skipping breakfast (higher insulin and FFA responses to lunch, increased hunger, and decreased satiety) were found primarily in habitual breakfast eaters. This suggests that meal skipping may have enhanced effects in habitual Eaters due to entrainment of metabolic and appetitive regulatory systems.
Translating outdoor CPV I–V measurements to a CSTC power rating and the associated uncertainty
Authors: Muller Matthew , Kurtz Sarah , Steiner Marc , Siefer Gerald 
Published: March 2015

AbstractA complete procedure is presented for translating outdoor concentrator photovoltaic (CPV) I–V measurements to the Concentrator Standard Test Conditions (CTSC) (1000 W/m2 and 25 °C cell temperature). Methods are demonstrated for measuring all the necessary input parameters for the translation, including outdoor thermal transient measurements and indoor dark I–V curves. Four modules are subjected to the translation method based on multiple months of outdoor data, one module measured at National Renewable Energy Laboratory and three at Fraunhofer ISE. The modules are also characterized under a sun simulator to provide a comparison to the translation approach. The results show that translated CSTC efficiencies are in good agreement with the efficiencies from the solar simulator. Two of the modules agreed within 1%, whereas the other two modules agree within approximately 4%. An uncertainty analysis of the input parameters is discussed in the context of the total uncertainty associated with the translation to CSTC. The reference voltage and efficiency temperature coefficient are the key parameters impacting the translation uncertainty, whereas uncertainty in the outdoor data is driven by spectral and meteorological parameters. Copyright © 2015 John Wiley & Sons, Ltd.
Signaling pathways in HPV‐associated cancers and therapeutic implications
Authors: Chen Jiezhong 
Published: March 2015

SummaryHuman papillomaviruses (HPVs) are small double‐stranded circular DNA viruses with 8 kb genomes. So far, more than 150 HPVs have been identified, and 12 types of HPVs have been conclusively linked to cancer by the International Agency for Research on Cancer/World Health Organization. Expression of HPV E5, E6 and E7 oncoproteins can alter multiple signaling pathways to cause cancer. In this review, the signaling pathways activated by these oncoproteins are summarized, and targeted therapy against key signaling molecules is described. E6 can inactivate tumor protein 53 and PDZ (post synaptic density protein–drosophila disk large tumor suppressor–zonula occludens‐1 proteins) while stimulating phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), Wnt and Notch pathways. E7 can inhibit retinoblastoma protein and stimulate the PI3K/Akt pathway. Both E6 and E7 can deregulate cellular microRNA expression, which can alter cellular signaling pathways. E5 can sensitize epidermal growth factor receptor to epidermal growth factor to increase activation of PI3K/Akt and mitogen‐activated protein kinase pathways. E5 can also inhibit the extrinsic apoptotic pathway. These altered signaling pathways could be critical for the initiation and maintenance of HPV‐associated cancers. Therefore, targeted therapy against the key signaling molecules has therapeutic implications. Among these, the possibilities of targeting PI3K/Akt, mammalian target of rapamycin, epidermal growth factor receptor and vascular endothelial growth factor have been extensively studied in many cancers. Some inhibitors have been studied in cervical cancer in both animal models and clinical trials. Although the results are promising, further investigation is warranted. Copyright © 2015 John Wiley & Sons, Ltd.
Recent progress in vaccination against human papillomavirus‐mediated cervical cancer
Authors: McKee Sara J. , Bergot Anne‐Sophie , Leggatt Graham R. 
Published: March 2015

SUMMARYIt has been more than 7 years since the commercial introduction of highly successful vaccines protecting against high‐risk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus‐like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross‐reactive antibody for oncogenic, non‐vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd.
Retrospective 2D frontomaxillary facial angle measurements in trisomy 21 fetuses during routine first‐trimester screening
Authors: Alphonse Jennifer , Cox Jenny , Clarke Jillian L. , Schluter Philip J. , McLennan Andrew 
Published: March 2015

AbstractObjectiveThe aim of this study is to assess the feasibility and utility of retrospective frontomaxillary facial angle measurement on two‐dimensional (2D) images from confirmed trisomy 21 fetuses.Materials and methodsOver a 27‐month period, stored 2D fetal profile images taken during routine first‐trimester screening were assessed. A single experienced operator utilising an offline digital measurement tool measured the frontomaxillary facial angle of 55 karyotypically proven trisomy 21 fetuses. The resultant measurements were compared with 2D prospectively collected frontomaxillary facial angle measurements in both trisomy 21 and euploid fetuses, which were also performed by the same operator.ResultsThe mean maternal age of both trisomy 21 cohorts [37 years old (prospective) and 37.7 years old (retrospective)] was similar (p = 0.72), and both were greater than those of the euploid group (32.2 years old) (p < 0.001). The median frontomaxillary facial angle measurement of the retrospective trisomy 21 cohort (90.5°) was greater than that of the euploid fetus group (87.1°) (p < 0.001) but has no difference to the median of the measurements collected prospectively from trisomy 21 fetuses (91.1°) (p = 0.86).ConclusionOverall, trisomy 21 fetuses have a larger frontomaxillary facial angle than euploid fetuses. Frontomaxillary facial angle measurements performed retrospectively in 2D were not different to prospective 2D frontomaxillary facial angle measurements.