bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of salivary metabolomic biomarkers for oral cancer screening
Authors: Ishikawa Shigeo , Sugimoto Masahiro , Kitabatake Kenichiro , Sugano Ayako , Nakamura Marina , Kaneko Miku , Ota Sana , Hiwatari Kana , Enomoto Ayame , Soga Tomoyoshi , Tomita Masaru , Iino Mitsuyoshi 
Published: August 2016

AbstractThe objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726–0.928,P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.
Negative Feedback Regulation of HIV-1 by Gene Editing Strategy
Authors: Kaminski Rafal , Chen Yilan , Salkind Julian , Bella Ramona , Young Won-bin , Ferrante Pasquale , Karn Jonathan , Malcolm Thomas , Hu Wenhui , Khalili Kamel 
Published: August 2016

AbstractThe CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein. We demonstrate that functional activation of CRISPR/Cas9 by Tat during the course of viral infection excises the designated segment of the integrated viral DNA and consequently suppresses viral expression. This strategy was also used in a latently infected CD4+ T-cell model after treatment with a variety of HIV-1 stimulating agents including PMA and TSA. Controlled expression of Cas9 by Tat offers a new strategy for safe implementation of the Cas9 technology for ablation of HIV-1 at a very early stage of HIV-1 replication during the course of the acute phase of infection and the reactivation of silent proviral DNA in latently infected cells.
Differences among lesions with exon 19, exon 21 EGFR mutations and wild types in surgically resected non-small cell lung cancer
Authors: Jin Ying , Chen Ming , Yu Xinmin 
Published: August 2016

AbstractThe clinical behavior of patients with advanced non-small cell lung cancer (NSCLC) differ between epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19) and EGFR exon 21 L858R mutation (Ex21). This study aimed to evaluate whether these differences exist in surgically resected NSCLC. A total of 198 patients with surgically resected NSCLC harbouring Ex19 (n = 53), Ex21 (n = 51), and EGFR wild-type (Wt) (n = 94) were analyzed. The clinicopathological features, laboratory parameters, recurrent sites and disease-free survival (DFS) were compared according to mutational EGFR status. Ex21 occurred more frequently in female (p < 0.001), never-smokers (p < 0.001), adenocarcinoma (p < 0.001), low grade (p = 0.013) than Wt lesions. Ex19 occurred more frequently in female (p = 0.016), never-smokers (p = 0.008), adenocarcinoma (p < 0.001), low grade (p = 0.025) than Wt lesions. Ex 21 lesions (p = 0.026) had larger lepidic components than Wt lesions. Wt lesions had larger mucinous variant components than Ex21 lesions (p = 0.045) and Ex19 lesions (p = 0.015). Ex21 lesions were associated with lower pretreatment neutrophil: lymphocyte ratio (NLR) than Wt lesions (p = 0.017). The recurrent sites and DFS were similar among patients with Wt, Ex19 and Ex21.
Super-focusing of center-covered engineered microsphere
Authors: Wu Mengxue , Chen Rui , Soh Jiahao , Shen Yue , Jiao Lishi , Wu Jianfeng , Chen Xudong , Ji Rong , Hong Minghui 
Published: August 2016

AbstractEngineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere.
Microbial Cryptotopes are Prominent Targets of B-cell Immunity
Authors: Rieder Franz J. J. , Biebl Julia , Kastner Marie-Theres , Schneider Martina , Jungbauer Christof , Redlberger-Fritz Monika , Britt William J. , Kundi Michael , Steininger Christoph 
Published: August 2016

AbstractB-cell recognition of microbial antigens may be limited by masking of epitopes within three-dimensional structures (cryptotopes). Here we report that unmasking of cryptotopes by unfolding whole cytomegalovirus (CMV) antigen preparations with the chaotropic reagent Urea and probing with immune sera from healthy individuals (n = 109) increased ELISA signals by 36% in comparison to folded CMV antigens (P < 0.001). ELISA signals increased also significantly upon unfolding of S. aureus or E. coli antigens, whereas unfolded influenza H1N1 or respiratory syncitial virus antigens yielded reduced or unchanged reactivity in comparison to folded ones, respectively. Blocking of CMV cryptotope-specific Abs by incubation of an immunoglobuline preparation and three sera with unfolded CMV antigens enhanced clearly the neutralizing capacity of this immunoglobuline preparation against CMV infection. Thus, B-cell immunity frequently targets cryptotopes on CMV but these Abs are non-neutralizing, may reduce the neutralizing effectiveness of pathogen-specific Abs and increase during immune maturation following primary CMV infection. The observation of functional consequences of Abs specific for cryptotopes may open whole new avenues to a better understanding of the humoral immune response to CMV and development of more effective vaccines and immunoglobuline preparations.
Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process
Authors: Yang Liu , He Jianfeng , Shen Yi , Li Xiaowei , Sun Jielin , Czajkowsky Daniel M. , Shao Zhifeng 
Published: August 2016

AbstractOur quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition.
Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
Authors: Lizotte Patrick H. , Jones Robert E. , Keogh Lauren , Ivanova Elena , Liu Hongye , Awad Mark M. , Hammerman Peter S. , Gill Ritu R. , Richards William G. , Barbie David A. , Bass Adam J. , Bueno Raphael , English Jessie M. , Bittinger Mark , Wong Kwok-Kin 
Published: August 2016

AbstractWith the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials.
Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
Authors: Wei Y B , Liu J J , Villaescusa J C , Åberg E , Brené S , Wegener G , Mathé A A , Lavebratt C 
Published: August 2016

AbstractElevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms.
Synthesis and characterisation of dual plasmonic gold nanostars as high‐performance surface‐enhanced Raman spectroscopy substrate
Authors: Raghavan Vijay , Fan Hai Ming , McCarthy Eoin K. , Dockery Peter , Wheatley Antony , Keogh Ivan , Olivo Malini 
Published: August 2016

Synthesising gold nanoprobes in the near infrared (NIR) region is of particular interest in developing nanosensors due to the minimal light attenuation from biomolecules. Here, the controlled synthesis and tunability of gold nanostars’ two distinct localised surface plasmon resonances (LSPRs) at around 700 and 1100 nm is reported. By using UV–Vis–NIR absorption measurements and finite‐difference time‐domain calculations, the induction of the LSPR and the multipolar nature of the resonances have been investigated experimentally and theoretically. Simulation results demonstrate that large electric fields are confined at the tips of the branches, where the LSPR can be induced specifically by controlling the polarisation of the incident electric field. The surface‐enhanced Raman scattering (SERS) capability of these dual plasmonic gold nanostars (DPGNS) has also been demonstrated using a Raman reporter, diethylthiatricarbocyanine iodide and high SERS enhancement factor (EF) of 2 × 107 is obtained with 785 nm excitation. With ease of synthesis, LSPR at NIR and high SERS EF, DPGNS demonstrated the capability to be an effective SERS substrate and the potential to elicit the highest SERS EF ever reported for gold nanoparticles, with further longer wavelength excitations at and beyond 1064 nm.
Comparison of ONIX simulation results with experimental data from the BATMAN testbed for the study of negative ion extraction
Authors: Mochalskyy Serhiy , Fantz Ursel , Wünderlich Dirk , Minea Tiberiu 
Published: August 2016

Abstract
The development of negative ion (NI) sources for the ITER neutral beam injector is strongly accompanied by modelling activities. The ONIX (Orsay Negative Ion eXtraction) code simulates the formation and extraction of negative hydrogen ions and co-extracted electrons produced in caesiated sources. In this paper the 3D geometry of the BATMAN extraction system, and the source characteristics such as the extraction and bias potential, and the 3D magnetic field were integrated in the model. Calculations were performed using plasma parameters experimentally obtained on BATMAN. The comparison of the ONIX calculated extracted NI density with the experimental results suggests that predictive calculations of the extraction of NIs are possible. The results show that for an ideal status of the Cs conditioning the extracted hydrogen NI current density could reach ~30 mA cm−2 at 10 kV and ~20 mA cm−2 at 5 kV extraction potential, with an electron/NI current density ratio of about 1, as measured in the experiments under the same plasma and source conditions. The dependency of the extracted NI current on the NI density in the bulk plasma region from both the modeling and the experiment was investigated. The separate distributions composing the NI beam originating from the plasma bulk region and the PG surface are presented for different NI plasma volume densities and NI emission rates from the plasma grid (PG) wall, respectively. The extracted current from the NIs produced at the Cs covered PG surface, initially moving towards the bulk plasma and then being bent towards the extraction surfaces, is lower compared to the extracted NI current from directly extracted surface produced ions.
Experimental investigation of geodesic acoustic modes on JET using Doppler backscattering
Authors: Silva C. , Hillesheim J.C. , Hidalgo C. , Belonohy E. , Delabie E. , Gil L. , Maggi C.F. , Meneses L. , Solano E. , Tsalas M. 
Published: August 2016

Abstract
Geodesic acoustic modes (GAMs) have been investigated in JET ohmic discharges using mainly Doppler backscattering. Characteristics and scaling properties of the GAM are studied. Time and spatial resolved measurements of the perpendicular velocity indicate that GAMs are located in a narrow layer at the edge density gradient region with amplitude corresponding to about 50% of the mean local perpendicular velocity. GAMs on JET appear to be regulated by the turbulence drive rather than by their damping rate. It is also shown that the GAM amplitude is ~20% larger in deuterium than in hydrogen plasmas.
Hydrogen isotope effect on the Dimits shift
Authors: Itoh S.-I. , Itoh K. 
Published: August 2016

Abstract
The hydrogen isotope effect on the Dimits shift in drift wave turbulence (Dimits et al 2000 Phys. Plasmas
7 969) is discussed using the theory of zonal flows, in which the nonlinear damping rate of zonal flows is taken into account. The up-shift of the critical linear growth rate of the drift waves, above which drift wave fluctuations develop, is investigated. The dependence on the mass number of the hydrogen isotope is discussed.
The upgraded JET toroidal Alfvén eigenmode diagnostic system
Authors: Puglia P. , Pires de Sa W. , Blanchard P. , Dorling S. , Dowson S. , Fasoli A. , Figueiredo J. , Galvão R. , Graham M. , Jones G. , Perez von Thun C. , Porkolab M. , Ruchko L. , Testa D. , Woskov P. , Albarracin-Manrique M.A. 
Published: August 2016

Abstract
The main characteristics of toroidal Alfvén eigenmodes (TAEs) have been successfully investigated in JET (Joint European Torus) using the scheme of sweeping-frequency external excitation with tracking of the synchronously-detected resonances. However, due to technical limitations, only modes with low values of the toroidal mode number

n
⩽
7

could be effectively excited and unambiguously identified by the Alfvén Eigenmode Active Diagnostic (AEAD) system. This represents a serious restriction because theoretical models indicate that medium-n Alfvén eigenmodes (AEs) are the most prone to be destabilized by energetic particles in ignited plasmas and, therefore, reliable measurement of their damping rates remains a relevant issue to properly access their effect in ignited plasmas. For this reason, a major upgrade of the AEAD system has been carried out aiming at providing a state-of-the-art excitation and real-time detection system for the planned DT campaign in JET. This required the development of a new type of radio frequency amplifier and filter, not commercially available, and also a control system. In this paper, details of the concepts that are relevant to understand the operation of the new system in the next experimental campaigns are presented, as are the results of numerical simulations to model its performance.
Sympathoinhibitory Effect of Radiofrequency Renal Denervation in Spontaneously Hypertensive Rats With Established Hypertension
Authors: Gao Juan , Kerut Edmund K. , Smart Frank , Katsurada Akemi , Seth Dale , Navar L. Gabriel , Kapusta Daniel R. 
Published: August 2016

BACKGROUND
Radiofrequency ablation of the renal arteries (RF-ABL) has been shown to decrease blood pressure (BP) in drug-resistant hypertensive patients who receive antihypertensive drug therapy. However, there remain questions regarding how RF-ABL influences BP independent of drug therapy and whether complete renal denervation is necessary to maximally lower BP. To study these questions, we examined the cardiovascular, sympathetic, and renal effects produced by RF-ABL of the proximal renal arteries in spontaneously hypertensive rats (SHR) with established hypertension.

METHODS
SHR were instrumented (telemetry) for measurement of systolic/diastolic BP (SBP/DBP). Rats then underwent Sham-ABL or RF-ABL adjacent to the renal ostium and BP was recorded for 8 weeks. Changes in sympathetic activity, 24-hour water/sodium excretion, and levels of urinary angiotensinogen (AGT), plasma renin activity, and kidney renin content (KRC) were measured in SHR.

RESULTS
Compared with Sham-ABL, RF-ABL produced a sustained decrease in BP. At 8 weeks, SBP/DBP was 171±6/115±3 and 183±4/129±3mm Hg for RF-ABL and Sham-ABL SHR, respectively. Correlating with the reduction in BP, RF-ABL significantly decreased the low frequency/total and low frequency/high frequency of BP variability and attenuated the hypotensive response to chlorisondamine. Kidney norepinephrine levels were markedly decreased at 8 weeks in RF-ABL vs. Sham-ABL SHR. There were no group differences in 24-hour sodium/water excretion or urinary AGT excretion rate (6 weeks) or plasma renin activity or KRC (8 weeks). In other studies, concurrent RF-ABL plus surgical denervation initially decreased BP to a greater level than RF-ABL alone, but thereafter the reduction in BP between groups was not different.

CONCLUSIONS
In hypertensive SHR, bilateral RF-ABL of the proximal renal arteries produced a sustained decease in sympathetic activity and BP without changes in sodium/water excretion or activity of the systemic/renal renin–angiotensin system.
The Mediation of Racial Differences in Hypertension by Sleep Characteristics: Chicago Area Sleep Study
Authors: Rasmussen-Torvik Laura J , De Chavez Peter John D , Kershaw Kiarri N , Montag Samantha E , Knutson Kristen L , Kim Kwang-Youn A , Zee Phyllis C , Carnethon Mercedes R 
Published: August 2016

Abstract

BACKGROUND
Racial disparities in hypertension prevalence in the United States are established. Given our understanding of racial and ethnic disparities in sleep characteristics and demonstrated associations between sleep characteristics and hypertension, we tested whether sleep characteristics mediated racial disparities in hypertension.

METHODS
Analyses were performed in the Chicago Area Sleep Study, a population-based cohort study of 154 Blacks, 128 Whites, 103 Hispanics, and 109 Asians without obstructive sleep apnea. Participants underwent 7 days of wrist actigraphy monitoring. Algorithms were used to determine sleep duration and sleep maintenance (the percent of sleep in the sleep period). Hypertension was determined as systolic blood pressure &gt;140mm Hg or diastolic blood pressure &gt;90mm Hg or the use of antihypertensive medications. We estimated sample prevalence ratios for hypertension before and after adjustment for sleep characteristics and also conducted mediation analysis.

RESULTS
The sample prevalence of hypertension was highest in Blacks (36%), followed by Hispanics (14%), Asians (8%), and Whites (5%). The sample prevalence ratio for hypertension for Blacks vs. Whites was 5.52 (95% confidence interval (CI): 2.36, 13.23) after adjusting for age, sex, and education. Adjustment for sleep duration had no influence on the effect estimate, but adjustment for sleep maintenance attenuated the sample prevalence ratio to 4.55 (95% CI: 1.91, 11.14). Sleep maintenance mediated 11.4% of the difference in hypertension prevalence between Blacks and Whites in this sample.

CONCLUSIONS
Sleep maintenance mediated a small but significant portion of the disparity in hypertension between Blacks and Whites. Future research should investigate the mechanisms underlying these findings.