bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of Frontal Eye Fields Activation and Very Low-Frequency Oscillations Observed during Vergence Eye Movements: an fNIRS Study
Authors: Yaramothu Chang , Li Xiaobo , Morales Cristian , Alvarez Tara L. 
Published: January 2020

AbstractFunctional near-infrared spectroscopy (fNIRS), an imaging tool that utilizes infrared light to measure changes within the concentration of oxygenated (HbO) and deoxygenated (HbR) hemoglobin, holds promise to study functional activity from motor, visual, and memory cortical regions using stimulus-induced tasks. This study investigated the reliability for fNIRS to examine cortical activations within the frontal eye fields (FEF) while initiating vergence eye movements, the inward and outward rotation of the eyes. FNIRS data were collected from twenty participants with normal binocular vision while performing vergence eye movements compared to sustained gaze fixation within a block design during two different sessions. Reliability of the experimental protocol was assessed using the intraclass correlation coefficient (ICC). The ICC values ranged from 0.6 to 0.7 for measuring the HbO activation within the vicinity of the FEF. A frequency power spectrum analysis revealed two predominant frequencies within the functional activation signals from the FEF. One high-intensity signal was present at 0.029 Hz, centering around the block design frequency. The peak-intensity signal was observed between 0.012 and 0.018 Hz where this very low-frequency oscillation (VLFO) was hypothesized to be generated by the macrovasculature present near the FEF and should be avoided as a block design frequency in future fNIRS studies to avoid false positive results.
Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib
Authors: Ishii Hidenobu , Azuma Koichi , Sakai Kazuko , Naito Yoshiko , Matsuo Norikazu , Tokito Takaaki , Yamada Kazuhiko , Hoshino Tomoaki , Nishio Kazuto 
Published: January 2020

AbstractThird-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were developed to target the EGFR T790M resistance mutation in non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation EGFR-TKIs. To investigate the efficacy of afatinib treatment for EGFR T790M-positive NSCLC patients showing resistance to osimertinib and alterations in somatic mutations and tumor mutation burden (TMB) in plasma circulating tumor DNA (ctDNA) during afatinib treatment, we conducted a prospective study using Cancer Personalized Profiling by deep Sequencing (CAPP-Seq). Nine NSCLC patients with EGFR T790M mutation who showed resistance to third-generation EGFR-TKIs were enrolled in this study and treated with afatinib. Plasma samples were collected before treatment, 4 weeks after treatment, and at disease progression. The mutation profile and TMB in plasma ctDNA were analyzed by CAPP-Seq. The objective response rate and median progression-free survival associated with afatinib were 0% and 2.0 months, respectively. The C797S mutation-mediated resistance to osimertinib was observed in one patient and following afatinib treatment in two patients; the C797S mutations occurred in the same allele as the T790M mutation. After afatinib treatment, afatinib-sensitive mutant alleles, such as ERBB2, and TMB decreased. We have demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. Although afatinib monotherapy for T790M-positive NSCLC resistant to osimertinib was less effective, the action for multiclonal mutant alleles and TMB might contribute to further treatment strategy.
Significant enhancement of the bias stability of Zn-O-N thin-film transistors via Si doping
Authors: Song Aeran , Park Hyun-Woo , Kim Hyoung-Do , Kim Hyun-Suk , Chung Kwun-Bum 
Published: January 2020

AbstractSi doping was used to significantly improve the bias stability of ZnON thin-film transistors. Si 3 W (~1%) doped ZnON TFTs showed a saturation mobility of 19.70 cm2/Vs along with remarkable improvements in the threshold voltage shift for negative gate bias stress (NBS) within 1.69 V. The effects of Si doping were interpreted by the experimental correlation between device performance and physical analysis, as well as by the theoretical calculation. Si doping induces the reduction of N-related defects by increasing stoichiometric Zn3N2, and decreasing nonstoichiometric ZnxNy. In addition, Si doping reduces the band edge states below the conduction band. According to density functional theory (DFT) calculations, Si, when it substitutes for Zn, acts as a carrier suppressor in the ZnON matrix.
Prototheca zopfii genotype II induces mitochondrial apoptosis in models of bovine mastitis
Authors: Shahid Muhammad , Cobo Eduardo R. , Chen Liben , Cavalcante Paloma A. , Barkema Herman W. , Gao Jian , Xu Siyu , Liu Yang , Knight Cameron G. , Kastelic John P. , Han Bo 
Published: January 2020

AbstractPrototheca zopfii is an alga increasingly isolated from bovine mastitis. Of the two genotypes of P. zopfii (genotype I and II (GT-I and -II)), P. zopfii GT-II is the genotype associated with acute mastitis and decreased milk production, although its pathogenesis is not well known. The objective was to determine inflammatory and apoptotic roles of P. zopfii GT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii GT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. This P. zopfii GT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects by P. zopfii GT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α, IL-1β and Cxcl-1) and also apoptosis of epithelial cells. Thus, we concluded P. zopfii GT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.
Choroidoscleral Interface Irregularity Index: A novel optical coherence tomography-based parameter in patients with epiretinal membrane
Authors: Kim Mirinae , Lee Yohan , Kim Rae-Young , Kwak Jae Hyuck , Park Young-Hoon 
Published: January 2020

AbstractThis study aimed to assess the regularity of the choroidoscleral interface (CSI) using a novel parameter, CSI irregularity index, before and after epiretinal membrane (ERM) surgery. This study included 36 patients with idiopathic ERM who underwent pars plana vitrectomy and ERM removal. All subjects underwent ocular examinations at baseline and at 1, 2, 4, and 6 months after surgery. The regular contour of the CSI was found in 14 patients (38.9%); mean CSI irregularity index was 14.84 ± 11.01 in this group. The irregular contour of the CSI was found in 22 patients (61.1%); mean CSI irregularity index was 33.96 ± 20.64 in this group. The CSI irregularity index decreased gradually after ERM surgery, and was correlated with postoperative best-corrected visual acuity. The CSI irregularity index could serve as a surrogate marker to quantitatively represent the CSI morphology. We observed the gradual decrease of the CSI irregularity index after ERM surgery in quantitative manner. This study showed correlations between the CSI irregularity index and visual outcomes after ERM surgery. Our results suggest that the CSI irregularity index might be an intuitive anatomic indicator of the CSI and might be useful as a possible prognostic marker for patients undergoing ERM surgery.
Augmented reality navigation with intraoperative 3D imaging vs fluoroscopy-assisted free-hand surgery for spine fixation surgery: a matched-control study comparing accuracy
Authors: Elmi-Terander Adrian , Burström Gustav , Nachabé Rami , Fagerlund Michael , Ståhl Fredrik , Charalampidis Anastasios , Edström Erik , Gerdhem Paul 
Published: January 2020

AbstractThis study aimed to compare screw placement accuracy and clinical aspects between Augmented Reality Surgical Navigation (ARSN) and free-hand (FH) technique. Twenty patients underwent spine surgery with screw placement using ARSN and were matched retrospectively to a cohort of 20 FH technique cases for comparison. All ARSN and FH cases were performed by the same surgeon. Matching was based on clinical diagnosis and similar proportions of screws placed in the thoracic and lumbosacral vertebrae in both groups. Accuracy of screw placement was assessed on postoperative scans according to the Gertzbein scale and grades 0 and 1 were considered accurate. Procedure time, blood loss and length of hospital stay, were collected as secondary endpoints. A total of 262 and 288 screws were assessed in the ARSN and FH groups, respectively. The share of clinically accurate screws was significantly higher in the ARSN vs FH group (93.9% vs 89.6%, p < 0.05). The proportion of screws placed without a cortical breach was twice as high in the ARSN group compared to the FH group (63.4% vs 30.6%, p < 0.0001). No statistical difference was observed for the secondary endpoints between both groups. This matched-control study demonstrated that ARSN provided higher screw placement accuracy compared to free-hand.
TAK-242, a specific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-induced skeletal muscle wasting in mice
Authors: Ono Yuko , Maejima Yuko , Saito Masafumi , Sakamoto Kazuho , Horita Shoichiro , Shimomura Kenju , Inoue Shigeaki , Kotani Joji 
Published: January 2020

AbstractCirculating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or various endogenous diseases related to bacterial translocation from the gut. Systemic inflammatory responses induced by endotoxemia induce severe involuntary loss of skeletal muscle, termed muscle wasting, which adversely affects the survival and functional outcomes of these patients. Currently, no drugs are available for the treatment of endotoxemia-induced skeletal muscle wasting. Here, we tested the effects of TAK-242, a Toll-like receptor 4 (TLR4)-specific signalling inhibitor, on myotube atrophy in vitro and muscle wasting in vivo induced by endotoxin. LPS treatment of murine C2C12 myotubes induced an inflammatory response (increased nuclear factor-κB activity and interleukin-6 and tumour necrosis factor-α expression) and activated the ubiquitin–proteasome and autophagy proteolytic pathways (increased atrogin-1/MAFbx, MuRF1, and LC-II expression), resulting in myotube atrophy. In mice, LPS injection increased the same inflammatory and proteolytic pathways in skeletal muscle and induced atrophy, resulting in reduced grip strength. Notably, pretreatment of cells or mice with TAK-242 reduced or reversed all the detrimental effects of LPS in vitro and in vivo. Collectively, our results indicate that pharmacological inhibition of TLR4 signalling may be a novel therapeutic intervention for endotoxemia-induced muscle wasting.
Ontology-driven integrative analysis of omics data through Onassis
Authors: Galeota Eugenia , Kishore Kamal , Pelizzola Mattia 
Published: January 2020

AbstractPublic repositories of large-scale omics datasets represent a valuable resource for researchers. In fact, data re-analysis can either answer novel questions or provide critical data able to complement in-house experiments. However, despite the development of standards for the compilation of metadata, the identification and organization of samples still constitutes a major bottleneck hampering data reuse. We introduce Onassis, an R package within the Bioconductor environment providing key functionalities of Natural Language Processing (NLP) tools. Leveraging biomedical ontologies, Onassis greatly simplifies the association of samples from large-scale repositories to their representation in terms of ontology-based annotations. Moreover, through the use of semantic similarity measures, Onassis hierarchically organizes the datasets of interest, thus supporting the semantically aware analysis of the corresponding omics data. In conclusion, Onassis leverages NLP techniques, biomedical ontologies, and the R statistical framework, to identify, relate, and analyze datasets from public repositories. The tool was tested on various large-scale datasets, including compendia of gene expression, histone marks, and DNA methylation, illustrating how it can facilitate the integrative analysis of various omics data.
Evidence of extrinsic factors dominating intrinsic blood host preferences of major African malaria vectors
Authors: Orsborne James , Mohammed Abdul Rahim , Jeffries Claire L. , Kristan Mojca , Afrane Yaw A. , Walker Thomas , Yakob Laith 
Published: January 2020

AbstractOne of the key determinants of a haematophagous vector’s capacity to transmit pathogens is its selection of which host to secure a blood meal from. This choice is influenced by both intrinsic (genetic) and extrinsic (environmental) factors, but little is known of their relative contributions. Blood fed Anopheles mosquitoes were collected from a malaria endemic village in Ghana. Collections were conducted across a range of different host availabilities and from both indoor and outdoor locations. These environmental factors were shown to impact dramatically the host choice of caught malaria vectors: mosquitoes caught indoors were ten-fold more likely to have sourced their blood meal from humans; and a halving in odds of being human-fed was found for mosquitoes caught only 25 m from the centre of the village. For the first time, we demonstrate that anthropophagy was better explained by extrinsic factors (namely, local host availability and indoor/outdoor trapping location) than intrinsic factors (namely, the (sibling) species of the mosquito caught) (respective Akaike information criterion estimates: 243.0 versus 359.8). Instead of characterizing biting behaviour on a taxonomic level, we illustrate the importance of assessing local entomology. Accounting for this behavioural plasticity is important, both in terms of measuring effectiveness of control programmes and in informing optimal disease control strategies.
Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway
Authors: Huang Yun , Liu Chen , Zeng Wu-Cha , Xu Guo-Yan , Wu Jian-Min , Li Zhi-Wen , Huang Xuan-Yu , Lin Rong-Jin , Shi Xi 
Published: January 2020

Abstract
The overall survival rate of patients with hepatocellular carcinoma (HCC) has remained unchanged over the last several decades. Therefore, novel drugs and therapies are required for HCC treatment. Isoliquiritigenin (ISL), a natural flavonoid predominantly isolated from the traditional Chinese medicine Glycyrrhizae Radix (Licorice), has a high anticancer potential and broad application value in various cancers. Here, we aimed to investigate the anticancer role of ISL in the HCC cell line Hep3B. Functional analysis revealed that ISL inhibited the proliferation of Hep3B cells by causing G1/S cell cycle arrest in vitro. Meanwhile, the inhibitory effect of ISL on proliferation was also observed in vivo. Further analysis revealed that ISL could suppress the migration and metastasis of Hep3B cells in vitro and in vivo. Mechanistic analysis revealed that ISL inhibited cyclin D1 and up-regulated the proteins P21, P27 that negatively regulate the cell cycle. Furthermore, ISL induced apoptosis while inhibiting cell cycle transition. In addition, phosphatidylinositol 3′-kinase/protein kinase B (PI3K/AKT) signal pathway was suppressed by ISL treatment, and the epithelial marker E-cadherin was up-regulated when the mesenchymal markers Vimentin and N-cadherin were down-regulated. In brief, our findings suggest that ISL could be a promising agent for preventing HCC tumorigenesis and metastasis.
The ALMA-PILS survey: inventory of complex organic molecules towards IRAS 16293–2422 A
Authors: Manigand S. , Jørgensen J. K. , Calcutt H. , Müller H. S. P. , Ligterink N. F. W. , Coutens A. , Drozdovskaya M. N. , van Dishoeck E. F. , Wampfler S. F. 
Published: January 2020

Context.Complex organic molecules are detected in many sources in the warm inner regions of envelopes surrounding deeply embedded protostars. Exactly how these species form remains an open question.Aims.This study aims to constrain the formation of complex organic molecules through comparisons of their abundances towards the Class 0 protostellar binary IRAS 16293–2422.Methods.We utilised observations from the ALMA Protostellar Interferometric Line Survey of IRAS 16293–2422. The species identification and the rotational temperature and column density estimation were derived by fitting the extracted spectra towards IRAS 16293–2422 A and IRAS 16293–2422 B with synthetic spectra. The majority of the work in this paper pertains to the analysis of IRAS 16293–2422 A for a comparison with the results from the other binary component, which have already been published.Results.We detect 15 different complex species, as well as 16 isotopologues towards the most luminous companion protostar IRAS 16293–2422 A. Tentative detections of an additional 11 isotopologues are reported. We also searched for and report on the first detections of methoxymethanol (CH3OCH2OH) and trans-ethyl methyl ether (t-C2H5OCH3) towards IRAS 16293–2422 B and the follow-up detection of deuterated isotopologues of acetaldehyde (CH2DCHO and CH3CDO). Twenty-four lines of doubly-deuterated methanol (CHD2OH) are also identified.Conclusions.The comparison between the two protostars of the binary system shows significant differences in abundance for some of the species, which are partially correlated to their spatial distribution. The spatial distribution is consistent with the sublimation temperature of the species; those with higher expected sublimation temperatures are located in the most compact region of the hot corino towards IRAS 16293–2422 A. This spatial differentiation is not resolved in IRAS 16293–2422 B and will require observations at a higher angular resolution. In parallel, the list of identified CHD2OH lines shows the need of accurate spectroscopic data including their line strength.
Gravity and limb-darkening coefficients for compact stars: DA, DB, and DBA eclipsing white dwarfs
Authors: Claret A. , Cukanovaite E. , Burdge K. , Tremblay P.-E. , Parsons S. , Marsh T. R. 
Published: January 2020

Context. The distribution of the specific intensity over the stellar disk is an essential tool for modeling the light curves in eclipsing binaries, planetary transits, and stellar diameters through interferometric techniques, line profiles in rotating stars, gravitational microlensing, etc. However, the available theoretical calculations are mostly restricted to stars on the main sequence or the giant branch, and very few calculations are available for compact stars.
Aims. The main objective of the present work is to extend these investigations by computing the gravity and limb-darkening coefficients for white dwarf atmosphere models with hydrogen, helium, or mixed compositions (types DA, DB, and DBA).
Methods. We computed gravity and limb-darkening coefficients for DA, DB, and DBA white dwarfs atmosphere models, covering the transmission curves of the Sloan, UBVRI, Kepler, TESS, and Gaia photometric systems. Specific calculations for the HiPERCAM instrument were also carried out. For all calculations of the limb-darkening coefficients we used the least-squares method. Concerning the effects of tidal and rotational distortions, we also computed for the first time the gravity-darkening coefficients y(λ) for white dwarfs using the same models of stellar atmospheres as in the case of limb-darkening. A more general differential equation was introduced to derive these quantities, including the partial derivative (∂ln Io(λ)/∂ln g)Teff.
Results. Six laws were adopted to describe the specific intensity distribution: linear, quadratic, square root, logarithmic, power-2, and a more general one with four coefficients. The computations are presented for the chemical compositions log[H/He] = −10.0 (DB), −2.0 (DBA) and He/H = 0 (DA), with log g varying between 5.0 and 9.5 and effective temperatures between 3750 and 100 000 K. For effective temperatures higher than 40 000 K, the models were also computed adopting nonlocal thermal equilibirum (DA). The adopted mixing-length parameters are ML2/α = 0.8 (DA case) and 1.25 (DB and DBA). The results are presented in the form of 112 tables. Additional calculations, such as for other photometric systems and/or different values of log[H/He], log g, and Teff can be performed upon request.
Therapieresistente und ‑refraktäre Hypertonie
Authors: Düsing Rainer 
Published: January 2020

AbstractHypertension is defined as resistant to treatment when treatment fails to lower office systolic and diastolic blood pressure values to < 140/90 mmHg. The treatment strategy should include lifestyle measures and appropriate doses of three or more drugs acting by different mechanisms including a diuretic. An updated definition of treatment resistance includes all patients with ≥ 4 antihypertensive agents of different classes irrespective of their on-treatment blood pressure. The term “refractory” hypertension has been suggested for patients with uncontrolled blood pressure on ≥ 5 antihypertensive drugs including the thiazide-like diuretic chlorthalidone and the mineralocorticoid receptor antagonist spironolactone. “Pseudo resistance” especially due to white coat hypertension and non-adherence with the prescribed medication has to be ruled out to be able to identify patients with “true” treatment resistance. Therefore, before distinguishing true from pseudo resistance, the term “apparent” resistance should be used. While the prevalence of apparent resistance may be in the range of 10–15 % of treated patients, the exact prevalence of true resistance remains unknown due to the lack of appropriate studies but is likely to be rather small including a high proportion of patients with secondary forms of hypertension. Once identified most patients with true treatment resistance should receive intensified drug treatment primarily by expanded diuretic usage. Thus, resistant hypertension is primarily a diagnostic challenge: identifying patients with true resistance and those with secondary hypertension.