bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients
Authors: Becher François , Ciccolini Joseph , Imbs Diane-Charlotte , Marin Clémence , Fournel Claire , Dupuis Charlotte , Fakhry Nicolas , Pourroy Bertrand , Ghettas Aurélie , Pruvost Alain , Junot Christophe , Duffaud Florence , Lacarelle Bruno , Salas Sebastien 
Published: May 2017

AbstractAdministration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice. When tested prospectively in a pilot study in 25 head-and-neck cancer patients, this method showed that patients with clinical benefit had cetixumab residual concentrations higher than non-responding patients (i.e., 49 ± 16.3 µg/ml VS. 25.8 ± 17 µg/ml, p < 0.01 t test). Further ROC analysis showed that 33.8 µg/ml was the Cmin threshold predictive of response with an acceptable sensitivity (87%) and specificity (78%). Mass spectrometry-based therapeutic drug monitoring of cetuximab in head-and-neck cancer patients could therefore help to rapidly predict cetuximab efficacy and to adapt dosing if required.
Transcription Factor Forkhead Regulates Expression of Antimicrobial Peptides in the Tobacco Hornworm, Manduca sexta
Authors: Zhong Xue , Chowdhury Munmun , Li Chun-Feng , Yu Xiao-Qiang 
Published: May 2017

AbstractAntimicrobial peptides (AMPs) play an important role in defense against microbial infections in insects. Expression of AMPs is regulated mainly by NF-κB factors Dorsal, Dif and Relish. Our previous study showed that both NF-κB and GATA-1 factors are required for activation of moricin promoter in the tobacco hornworm, Manduca sexta, and a 140-bp region in the moricin promoter contains binding sites for additional transcription factors. In this study, we identified three forkhead (Fkh)-binding sites in the 140-bp region of the moricin promoter and several Fkh-binding sites in the lysozyme promoter, and demonstrated that Fkh-binding sites are required for activation of both moricin and lysozyme promoters by Fkh factors. In addition, we found that Fkh mRNA was undetectable in Drosophila S2 cells, and M. sexta Fkh (MsFkh) interacted with Relish-Rel-homology domain (RHD) but not with Dorsal-RHD. Dual luciferase assays with moricin mutant promoters showed that co-expression of MsFkh with Relish-RHD did not have an additive effect on the activity of moricin promoter, suggesting that MsFkh and Relish regulate moricin activation independently. Our results suggest that insect AMPs can be activated by Fkh factors under non-infectious conditions, which may be important for protection of insects from microbial infection during molting and metamorphosis.
A proof-of-concept study for developing integrated two-photon microscopic and magnetic resonance imaging modality at ultrahigh field of 16.4 tesla
Authors: Cui Meng , Zhou Yifeng , Wei Bowen , Zhu Xiao-Hong , Zhu Wei , Sanders Mark A. , Ugurbil Kamil , Chen Wei 
Published: May 2017

AbstractFunctional magnetic resonance imaging (fMRI) based on the blood oxygen level dependent (BOLD) contrast has gained a prominent position in neuroscience for imaging neuronal activity and studying effective brain connectivity under working state and functional connectivity at resting state. However, the fundamental questions in regards to fMRI technology: how the BOLD signal inferences the underlying microscopic neuronal activity and physiological changes and what is the ultimate specificity of fMRI for functional mapping of microcircuits, remain unanswered. The capability of simultaneous fMRI measurement and functional microscopic imaging in a live brain thus holds the key to link the microscopic and mesoscopic neural dynamics to the macroscopic brain activity at the central nervous system level. Here we report the first demonstration to integrate high-resolution two-photon fluorescence microscopy (TPM) with a 16.4 tesla MRI system, which proves the concept and feasibility for performing simultaneous high-resolution fMRI and TPM imaging at ultrahigh magnetic field.
Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE
Authors: Pestana Diogo , Teixeira Diana , Meireles Manuela , Marques Cláudia , Norberto Sónia , Sá Carla , Fernandes Virgínia C. , Correia-Sá Luísa , Faria Ana , Guardão Luísa , Guimarães João T. , Cooper Wendy N. , Sandovici Ionel , Domingues Valentina F. , Delerue-Matos Cristina , Monteiro Rosário , Constância Miguel , Calhau Conceição 
Published: May 2017

AbstractEndocrine-disrupting chemicals such as p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p’-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats’ metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p’-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension. A transcriptome analysis comparing mesenteric visceral AT (vAT) of HF and HF/DDE groups revealed a decrease in expression of nervous system and tissue development-related genes, with special relevance for the neuropeptide galanin that also revealed DNA methylation changes at its promoter region. Additionally, we observed an increase in transcription of dipeptidylpeptidase 4, as well as a plasmatic increase of the pro-inflammatory cytokine IL-1β. Our results suggest that p,p’-DDE impairs vAT normal function and effectively decreases the dynamic response to energy surplus. We conclude that p,p’-DDE does not merely accumulate in fat, but may contribute significantly to the development of metabolic dysfunction and inflammation. Our findings reinforce their recognition as metabolism disrupting chemicals, even in non-obesogenic contexts.
Chicken IFN Kappa: A Novel Cytokine with Antiviral Activities
Authors: Santhakumar Diwakar , Iqbal Munir , Nair Venugopal , Munir Muhammad 
Published: May 2017

AbstractInterferons (IFNs) are essential components of the host innate immune system and define first-line of defence against pathogens. In mammals, several type I IFNs are identified, however, only limited data is available on the repertoire of IFNs in avian species. Here we report the characterization of chicken IFN-κ (chIFN-κ) near the type I IFN locus on the sex-determining Z chromosome. Genetic, evolutionary and syntenic analyses indicate that chIFN-κ is a type I IFN with conserved genetic features and promoter binding sites. chIFN-κ regulated the IFN-stimulated response element signalling pathways and activated a panel of IFN-regulated genes, antiviral mediators and transcriptional regulators. Priming of chicken primary fibroblasts and tracheal organ cultures with chIFN-κ imparted cellular protections against viral infections both in vitro and ex vivo. To determine whether chIFN-κ defines the antiviral state in developing chicken embryos, we used replication-competent retroviral RCAS vector system to generate transgenic chicken embryos that constitutively and stably expressed chIFN-κ. We could demonstrate that chIFN-κ markedly inhibited the replication of avian RNA viruses in ovo. Collectively, these results shed the light on the repertoire of IFNs in avian species and provide functional data on the interaction of the chIFN-κ with RNA viruses of poultry and public health importance.
Influences of glutamine administration on response selection and sequence learning: a randomized-controlled trial
Authors: Jongkees Bryant J. , Immink Maarten A. , Colzato Lorenza S. 
Published: May 2017

AbstractPrecursors of neurotransmitters are increasingly often investigated as potential, easily-accessible methods of neuromodulation. However, the amino-acid glutamine, precursor to the brain’s main excitatory and inhibitory neurotransmitters glutamate and GABA, remains notably little investigated. The current double-blind, randomized, placebo-controlled study provides first evidence 2.0 g glutamine administration in healthy adults affects response selection but not motor sequence learning in a serial reaction time task. Specifically, glutamine increased response selection errors when the current target response required a different hand than the directly preceding target response, which might indicate enhanced cortical excitability via a presumed increase in glutamate levels. These results suggest glutamine can alter cortical excitability but, despite the critical roles of glutamate and GABA in motor learning, at its current dose glutamine does not affect sequence learning.
Alternative splicing shapes transcriptome but not proteome diversity in Physcomitrella patens
Authors: Fesenko Igor , Khazigaleeva Regina , Kirov Ilya , Kniazev Andrey , Glushenko Oksana , Babalyan Konstantin , Arapidi Georgij , Shashkova Tatyana , Butenko Ivan , Zgoda Victor , Anufrieva Ksenia , Seredina Anna , Filippova Anna , Govorun Vadim 
Published: May 2017

AbstractAlternative splicing (AS) can significantly impact the transcriptome and proteome of a eukaryotic cell. Here, using transcriptome and proteome profiling data, we analyzed AS in two life forms of the model moss Physcomitrella patens, namely protonemata and gametophores, as well as in protoplasts. We identified 12 043 genes subject to alternative splicing and analyzed the extent to which AS contributes to proteome diversity. We could distinguish a few examples that unambiguously indicated the presence of two or more splice isoforms from the same locus at the proteomic level. Our results indicate that alternative isoforms have a small effect on proteome diversity. We also revealed that mRNAs and pre-mRNAs have thousands of complementary binding sites for long non-coding RNAs (lncRNAs) that may lead to potential interactions in transcriptome. This finding points to an additional level of gene expression and AS regulation by non-coding transcripts in Physcomitrella patens. Among the differentially expressed and spliced genes we found serine/arginine-rich (SR) genes, which are known to regulate AS in cells. We found that treatment with abscisic (ABA) and methyl jasmonic acids (MeJA) led to an isoform-specific response and suggested that ABA in gametophores and MeJA in protoplasts regulate AS and the transcription of SR genes.
One-Step Fabrication of Pyranine Modified- Reduced Graphene Oxide with Ultrafast and Ultrahigh Humidity Response
Authors: Chen Zhuo , Wang Yao , Shang Ying , Umar Ahmad , Xie Peng , Qi Qi , Zhou Guofu 
Published: May 2017

AbstractA facile one-step supramolecular assembly method is adopted to modify reduced graphene oxide (rGO) with functional organic molecule pyranine for achieving comprehensive humidity sensing performance. The fabricated humidity sensor based on pyranine modified-reduced graphene oxide (Pyr-rGO) exhibits excellent sensing performance with ultrafast (<2 s) and ultrahigh response of IL/IH = 6000 as relative humidity (RH) consecutively changes between 11% and 95%; small hysteresis of 8% RH; reliable repeatability and stability. In addition, a detailed mechanism analysis is performed to investigate the difference in water adsorption and ions transfer under various RH levels. Notably, the one-step supramolecular assembly method to prepare Pyr-rGO provides a new insight into developing novel functional humidity sensing materials with enhanced device performance.
Polycyclic aromatic hydrocarbons (PAHs) in Chinese forest soils: profile composition, spatial variations and source apportionment
Authors: Syed Jabir Hussain , Iqbal Mehreen , Zhong Guangcai , Katsoyiannis Athanasios , Yadav Ishwar Chandra , Li Jun , Zhang Gan 
Published: May 2017

AbstractPrevious studies reported that forest ecosystems can play a vital role in scavenging anthropogenic polycyclic aromatic hydrocarbons (PAHs) and act as primary reservoirs of these environmental pollutants. The present study aimed to investigate the occurrence, spatial pattern and source apportionment of PAHs across Chinese background forest soils (O- & A-horizons). The 143 soils collected from 30 mountains showed significantly (p < 0.05) higher levels of ∑15PAHs (ng g−1 dw) in O-horizon (222 ± 182) than A-horizon (168 ± 161). A progressive increase in the levels of lighter PAHs was observed along altitudinal gradient, however heavier PAHs did not show any variations. Carbon contents (TOC & BC) of forest soils were found weakly correlated (p < 0.01) with low molecular weight (LMW)-PAHs but showed no relation with high molecular weight (HMW)-PAHs. Source apportionment results using PMF and PCA revealed that PAHs in forest soils mainly come from local biomass burning and/or coal combustion and attributed that forest soils may become a potential sink for PAHs in the region.
Wide-angle scanning planar array with quasi-hemispherical-pattern elements
Authors: Wang Ren , Wang Bing-Zhong , Hu Changhai , Ding Xiao 
Published: May 2017

AbstractA compact quasi-hemispherical-pattern antenna, two linear wide-angle scanning arrays, and a planar wide-angle scanning array are proposed. To increase the field-of-view scanning range of arrays, a compact low-profile antenna with a quasi-hemispherical pattern is introduced firstly. When the ground is infinite, the proposed antenna has a quasi-hemispherical pattern, i.e., an approximately uniform radiation in the upper half space. Afterward, two linear arrays arranged along the length and width of the proposed antenna’s radiation patch are presented. The main beams of the two arrays with 16 active elements can scan from less than −75° to more than +75°. When the linear array element number is 128, the maximum scanning angle can reach 86°. At last, a planar array with 16 × 16 active elements is proposed. In two special planes, xz plane and yz plane, the main beams of the planar array can scan from less than −77° to more than +77° with a gain fluctuation less than 5 dB and a maximum side lobe level (SLL) less than −10 dB. An excellent wide-angle-scanning performance both in linear and planar arrays can be obtained using the proposed method.
Metabolic responses of a phototrophic sponge to sedimentation supports transitions to sponge-dominated reefs
Authors: Biggerstaff Andrew , Smith David J. , Jompa Jamaluddin , Bell James J. 
Published: May 2017

AbstractDeclines in coral abundance have been linked to increased sedimentation at many locations across the world and at some of these locations there have been subsequent increases in sponge abundance. These shifts appear counterintuitive as sponges are suspension feeders and many rely on photosymbionts for carbon. At a sedimented reef in Indonesia (Wakatobi) corals have declined and the photoautotrophic sponge Lamellodysidea herbacea is now abundant. We hypothesise that this is partly due to L. herbacea’s ability to clear its tissues of high levels of settled-sediment and compensate for associated metabolic demands by altering its respiration rate. Negligible detrimental effects to sponge tissue were observed after treatments up to five times the sedimentation rate of the highly sedimented reef. Rapid sediment clearance occurred that was potentially aided by mucus production. Finally, high sediment exposure caused an immediate reduction in respiration rate, likely due to reduced pumping to prevent clogging, whereas sustained high sedimentation caused an increase in respiration rate, potentially due to the energetic cost of mucus production. Our study provides evidence that some sponges can tolerate environments that appear unsuitable to many corals and with increased sedimentation this acclimation may support further transitions to sponge dominated reefs in the future.
Lower SHBG level is associated with higher leptin and lower adiponectin levels as well as metabolic syndrome, independent of testosterone
Authors: Liu Chia-Chu , Huang Shu-Pin , Cheng Kai-Hung , Hsieh Tusty-Jiuan , Huang Chun-Nung , Wang Chii-Jye , Yeh Hsin-Chih , Tsai Chia-Chun , Bao Bo-Ying , Wu Wen-Jeng , Lee Yung-Chin 
Published: May 2017

AbstractIn addition to testosterone (T), the emerging role of sex hormone-binding globulin (SHBG) in pathogenesis of metabolic syndrome (MetS) has been noted recently. However, reports of associations with serum adipocytokine levels are still limited. Therefore, we conducted this study to evaluate whether serum T and SHBG levels are independent predictors for the risk of MetS that are associated with adiponectin and leptin levels in 614 Taiwanese men over 40 years old collected from a free health screening. Subjects in the lowest quartile of TT and SHBG levels are exposed to a 1.58 and 3.22 times risk of developing MetS, as compared to those in the highest quartile of TT and SHBG levels. However, SHBG retains its significance independent of TT as a MetS risk predictor, but not vice versa. In addition, SHBG was significantly correlated with both adiponectin and leptin levels even after adjusting for TT levels. In conclusion, SHBG served as a major predictor for the risk of MetS and was correlated with serum adiponectin and leptin levels that are independent of T. Further studies are needed to elucidate the true role of SHBG in the pathogenesis of MetS and possible mechanisms associated with serum adiponectin and leptin levels.
Overexpression of CIP2A is associated with poor prognosis in multiple myeloma
Authors: Liu Xuewen , Cao Wei , Qin Shanshan , Zhang Te , Zheng Junnian , Dong Ying , Ming Pinghong , Cheng Qian , Lu Zheng , Guo Yang , Zhang Baofu , Liu Ying 
Published: May 2017

AbstractCancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous protein phosphatase 2A (PP2A) inhibitor, has been identified as an oncoprotein in promoting cancer initiation and progression of several types of cancer. However, the expression and the role played by CIP2A in the pathogenesis of multiple myeloma (MM) remain unclear. In this study, we showed that CIP2A was overexpressed in human MM cell lines and MM patients’ bone marrow tissues. Clinicopathologic analysis showed that CIP2A expression was significantly correlated with clinical stage and percent of plasma cells in bone marrow. Kaplan–Meier analysis revealed that patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. Moreover, CIP2A knockdown in MM cells resulted in attenuated proliferative abilities. In addition, CIP2A depletion sensitizes dexamethasone (Dex)-resistant cells to Dex. The effect of CIP2A on proliferation and Dex therapy was mediated by the inhibition of PP2A, which in turn activated Akt. In vivo studies confirmed that CIP2A regulated MM tumorigenesis and the phosphorylation of Akt. Taken together, our results suggest that CIP2A oncoprotein plays an important role in MM progression and could serve as a prognosis marker and a novel therapeutic target for the treatment of patients with MM.
Miniaturised Wilkinson power divider with wide‐stopband using synthetic transmission line
Authors: Chen C.‐C. , Sim C.Y.D. , Chen J.‐W. , Lin J.‐H. 
Published: May 2017

A wide‐stopband Wilkinson power divider (WPD) is proposed, which can be realised by using open dual‐transmission line (TL) stub and L‐type artificial lowpass TL structures. To further achieve miniaturisation, synthetic TLs are also employed. The simulated and measured results are consistent, and the measured |S21| and |S31| (insertion losses) have shown stop‐bandwidth of larger than 18.33 GHz (1.67–20 GHz) and 18.28 GHz (1.72–20 GHz), respectively, under the condition of 30 dB harmonic suppression level. The wide‐stopband of the WPD can cover 2fo–22.2fo (fo = 0.9 GHz), and the occupied area of the WPD (not include the feeding network) is only 0.11λg × 0.06λg (λg: guided wavelength at fo).
Fall and Winter Survival of Brook Trout and Brown Trout in a North‐Central Pennsylvania Watershed
Authors: Sweka John A. , Davis Lori A. , Wagner Tyler 
Published: May 2017

AbstractStream‐dwelling salmonids that spawn in the fall generally experience their lowest survival during the fall and winter due to behavioral changes associated with spawning and energetic deficiencies during this time of year. We used data from Brook TroutSalvelinus fontinalisand Brown TroutSalmo truttaimplanted with radio transmitters in tributaries of the Hunts Run watershed of north‐central Pennsylvania to estimate survival from the fall into the winter seasons (September 2012–February 2013). We examined the effects that individual‐level covariates (trout species, size, and movement rates) and stream‐level covariates (individual stream and cumulative drainage area of a stream) have on survival. Brook Trout experienced significantly lower survival than Brown Trout, especially in the early fall during their peak spawning period. Besides a significant species effect, none of the other covariates examined influenced survival for either species. A difference in life history between these species, with Brook Trout having a shorter life expectancy than Brown Trout, is likely the primary reason for the lower survival of Brook Trout. However, Brook Trout also spawn earlier in the fall than Brown Trout and low flows during Brook Trout spawning may have resulted in a greater risk of predation for Brook Trout compared with Brown Trout, thereby also contributing to the observed differences in survival between these species. Our estimates of survival can aid parameterization of future population models for Brook Trout and Brown Trout through the spawning season and into winter.Received September 9, 2016; accepted March 6, 2017 Published online May 26, 2017