bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability
Authors: Lim Sin Yin , Sharan Satish , Woo Sukyung 
Published: February 2020

IntroductionThere is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose‐exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption.MethodsSingle‐dose (range: 5–6000 mg) CBD plasma concentration‐time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose‐exposure proportionality assessment was performed, and a population‐based meta‐analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed‐effects modeling. A three‐compartment model with a Weibull or zero‐order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation.ResultsOral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed‐state OM (6.2%) were similar, whereas it was lower in fasted‐state OM (0.9%). The Weibull absorption model best described OS, OC, and fed‐state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed‐state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted‐state OM was best described by a zero‐order absorption for the duration of 1.71 hours.ConclusionThe effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.
Halogenation effect promoted low bandgap polymers based on asymmetric isoindigo unit with low energy loss
Authors: Shahid Bilal , Zhu Dangqiang , Wang Qian , Yuan Xiyue , Ismail Irfan , Wu Yao , Du Zurong , Yang Renqiang 
Published: February 2020

AbstractTo optimize the energy levels of the structural framework of isoindigo polymers, a series of asymmetric isoindigo based low bandgap polymers with chlorine, fluorine and thiazole substituents was constructed and their optical, electrochemical and photovoltaic properties were comparatively evaluated for the impact of different substitutions. In comparison with the polymer based on 2,2'‐bithiophene and isoindigo unit (PTi) with non‐substituted bithiophene as the donor moiety, the highest occupied molecular orbital energy level for the newly synthesized polymers is significantly decreased, and in turn an improvement of the open‐circuit voltage (VOC) is noted in the corresponding photovoltaic devices. More importantly, combined with a low bandgap of 1.32 eV, the energy losses (Eloss) could be reduced to 0.61 eV for polymer based on chlorinated 2,2'‐bithiophene and isoindigo unit (PCl). In addition, the halogen moieties are observed to be superior in device fabrication and give better values than the thiazole substituent. Both fluorinated and chlorinated polymer donors exhibited improved performance compared with the original polymer PTi. Consequently, this work not only presents the influence of different electron withdrawing substituents on the physicochemical and photovoltaic performance, but also backs the concept of how to reduce the energy loss via the heteroatom effect. © 2020 Society of Chemical Industry
Rapid microwave controlled polyesterification of aconitic acid and ethylene glycol
Authors: Orozco Ferley , Andrade Andrés , Delgado Lina M , Rojas Giovanni 
Published: February 2020

AbstractMicrowave polyesterification of trans‐aconitic acid and ethylene glycol was carried out by controlling two parameters: temperature and exposure to irradiation. A series of crosslinked materials was obtained showing diverse behavior in terms of solubility, glass transition temperature and decomposition temperature. In contrast to heating by convection that could last hours, polyesters obtained by microwave irradiation were obtained after a maximum of 30 min of reaction. More importantly, the polyesterifications were carried out in bulk, with no solvent involved and without the use of any catalyst. © 2020 Society of Chemical Industry
Rapid differentiation of graft Citrus sinensis with and without Xylella fastidiosa infection by mass spectrometry
Authors: Soares Márcio Santos , da Silva Danielle Fernandes , Amaral Jéssica Cristina , da Silva Michelli Masaroli , Forim Moacir Rossi , Rodrigues‐Filho Edson , das Graças Fernandes da Silva Maria Fátima , Fernandes João Batista , Machado Marcos Antônio , de Souza Alessandra Alves , Martins Carlos Henrique Gomes 
Published: February 2020

RationaleXylella fastidiosa causes citrus variegated chlorosis (CVC) in sweet orange trees. A diagnostic method for detecting CVC before the symptoms appear, which would inform citrus producers in advance about when the plant should be removed from the orchard, is essential for reducing pesticide application costs.MethodsChemometrics was applied to high‐performance liquid chromatography diode array detector (HPLC‐DAD) data to evaluate the similarities and differences between the chromatographic profiles. A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry selected reaction monitoring (LC/APCI‐MS‐SRM) method was developed to identify the major compounds and to determine their amounts in all samples.ResultsWe evaluated the effect of this bacterium on the variation in the chemical profile in citrus plants. The organs of C. sinensis grafted on C. limonia were analyzed. Chemometrics was applied to the obtained data, and two major groups were differentiated. Flavonoids were observed in one group (leaves) and coumarins in the second (roots), both at higher concentrations in the plants with CVC symptoms than in those without the symptoms and those in the negative control. The rootstocks also interfered in the metabolism of the scion.ConclusionsThe developed LC/APCI‐MS‐SRM method for detecting CVC before the symptoms appear is simple and accurate. It is inexpensive, and many samples can be screened per hour using 1 mg of leaves. Knowledge of the influence of the rootstock on the chemical profile of the graft is limited. This study demonstrates the effect of the rootstock in synthesizing flavonoids and increasing its content in all parts of the graft.
Feasibility and necessity of the fourth arm of the da Vinci Si surgical system for robot‐assisted partial nephrectomy
Authors: Kira Satoru , Mitsui Takahiko , Sawada Norifumi , Nakagomi Hiroshi , Ihara Tatsuya , Takahashi Nobuhiro , Takeda Masayuki 
Published: February 2020

AbstractBackgroundTo investigate the feasibility of the fourth arm of the da Vinci Si system for robot‐assisted partial nephrectomy (RAPN).MethodsFifty‐eight consecutive patients underwent RAPN with the same port placements. After reviewing the surgical videos and records, 38 patients showing usefulness of the fourth arm were categorized into Group A and those not showing usefulness into Group B. The background data, tumor characteristics, and perioperative outcomes were compared between the groups.ResultsGroup B had a larger proportion of tumors located on the inner side of the kidney, and the console time was significantly longer. Multivariable logistic regression analysis showed that tumors located on the inner side of the kidney were associated with the non‐use of the fourth arm of the da Vinci Si system during RAPN.ConclusionsOur findings suggested that use of fourth arm in RAPN by da Vinci Si should be considered for each tumor location.
Does information and communication technology affect CO2 mitigation under the pathway of sustainable development during the mode of globalization?
Authors: Ulucak Recep , Danish  , Khan Salah Ud‐Din 
Published: February 2020

AbstractThe rapid developments of globalization promote interaction among countries and people around the globe through the fast mode of information and telecommunication technology (ICT). ICT development also contributes to economic growth through various channels, but it may influence the environment on the other hand. Considering this concern, the present study focuses on examining the relationship between ICT developments and carbon emissions through the globalization channel. The study employs robust panel data estimation methods, continuously updated fully modified, and continuously updated bias corrected estimators, for the data set of Brazil, Russia, India, China, and South Africa (BRICS) economies spanning from 1990 to 2015. Findings of the study are robust against heteroskedasticity, endogeneity, and cross‐sectional dependence issues. The robust panel data estimators reveal that ICT has a favourable effect on carbon emissions in BRICS countries. Also, globalization leads to environmental pollution by contributing to an increase in CO2 emissions. These findings provide new insights to the policymakers in combatting environmental challenges.
MMLT: A mutual multilevel trust framework based on trusted third parties in multicloud environments
Authors: Aghaee Ghazvini Golnaz , Mohsenzadeh Mehran , Nasiri Ramin , Masoud Rahmani Amir 
Published: February 2020

SummaryIn this article, a mutual multilevel trust framework is proposed, which involves managing trust from the perspective of cloud users (CUs) and cloud service providers (CSPs) in a multicloud environment based on a set of trusted third parties (TTPs). These independent agents are trusted by CUs and CSPs and distributed on different clouds. The TTPs evaluate the CUs' trustworthiness based on the accuracy of feedback ratings and assess the CSPs' trustworthiness based on the quality of service monitoring information. They are connected themselves through the trusted release network, which enables a TTP to obtain trust information about CSPs and CUs from other clouds. With the objective of developing an effective trust management framework, a new approach has been provided to improve trust‐based interactions, that is, able to rank the trusted cloud services (CSs) based on CU's priorities via fuzzy logic. Fuzzy logic is applied to manage the different priorities of CUs, all the CUs do not have the same priorities to use trusted CSs. Customizing service ranking allows CUs to apply trusted CSs based on their priorities. Experiments on real datasets well matched the analytical results, indicating that our proposed approach is effective and outperforms the existing approaches.
Fully Automated HTML and JavaScript Rewriting for Constructing a Self‐healing Web Proxy
Authors: Durieux Thomas , Hamadi Youssef , Monperrus Martin 
Published: February 2020

SummaryOver the last few years, the complexity of web applications has increased to provide more dynamic web applications to users. The drawback of this complexity is the growing number of errors in the front‐end applications. In this paper, we present an approach to provide self‐healing for the web. We implemented this approach in two different tools: (i) BikiniProxy, an HTTP repair proxy, and (ii) BugBlock, a browser extension. They use five self‐healing strategies to rewrite the buggy HTML and JavaScript code to handle errors in web pages. We evaluate BikiniProxy and BugBlock with a new benchmark of 555 reproducible JavaScript errors of which 31.76% can be automatically self‐healed by BikiniProxy and 15.67% by BugBlock.
Production and clinical evaluation of breast lesion skin markers for automated three-dimensional ultrasonography of the breast: a pilot study
Authors: de Jong Leon , Welleweerd Marcel K. , van Zelst Jan C.M. , Siepel Francoise J. , Stramigioli Stefano , Mann Ritse M. , de Korte Chris L. , Fütterer Jurgen J. 
Published: February 2020

Abstract
Objectives
Automated ultrasound of the breast has the advantage to have the whole breast scanned by technicians. Consequently, feedback to the radiologist about concurrent focal abnormalities (e.g., palpable lesions) is lost. To enable marking of patient- or physician-reported focal abnormalities, we aimed to develop skin markers that can be used without disturbing the interpretability of the image.

Methods
Disk-shaped markers were casted out of silicone. In this IRB-approved prospective study, 16 patients were included with a mean age of 57 (39–85). In all patients, the same volume was imaged twice using an automated breast ultrasound system, once with and once without a marker in place. Nine radiologists from two medical centers filled scoring forms regarding image quality, image interpretation, and confidence in providing a diagnosis based on the images.

Results
Marker adhesion was sufficient for automated scanning. Observer scores showed a significant shift in scores from excellent to good regarding diagnostic yield/image quality (χ2, 15.99, p < 0.01), and image noise (χ2, 21.20, p < 0.01) due to marker presence. In 93% of cases, the median score of observers “agree” with the statement that marker-induced noise did not influence image interpretability. Marker presence did not interfere with confidence in diagnosis (χ2, 6.00, p = 0.20).

Conclusion
Inexpensive, easy producible skin markers can be used for accurate lesion marking in automated ultrasound examinations of the breast while image interpretability is preserved. Any marker-induced noise and decreased image quality did not affect confidence in providing a diagnosis.

Key Points
• The use of a skin marker enables the reporting radiologist to identify a location which a patient is concerned about.
• The developed skin marker can be used for accurate breast lesion marking in ultrasound examinations.
Interpretation of Tonsillectomy Outcome Inventory-14 scores: a prospective matched cohort study
Authors: Laajala Aleksi , Autio Timo J. , Ohtonen Pasi , Alho Olli-Pekka , Koskenkorva Timo J. 
Published: February 2020

Abstract
Purpose
Knowledge of disease-specific instruments enables the evaluation of health- related quality-of-life (QoL) change associated with chronic and recurrent tonsillitis in adults. The main objective was to explore the interpretation of scores according to the throat-related QoL instrument, Tonsillectomy Outcome Inventory-14 (TOI-14), by determining the typical scores in healthy subjects and patients and define the minimum important change (MIC).

Methods
We performed a prospective matched cohort study in a secondary care area of Oulu University Hospital. The surgical cohort consisted of 42 patients referred to tonsillectomy due to recurrent or chronic tonsillitis. The control cohort consisted of 42 age- and sex-matched healthy controls obtained from the escorts of patients in the same hospital. We translated and validated the Finnish TOI-14 instrument and collected TOI-14 scores at entry and at 6 months and compared results to the anchor question.

Results
At entry, the mean TOI-14 scores were significantly higher in the surgical cohort than in the control cohort [mean (95% confidence interval)] 33.0 (27.0–39.1) vs. 5.0 (3.6–6.4), respectively. At 6 months follow-up, the mean TOI-14 scores had improved markedly after tonsillectomy to the level of the control cohort. In the healthy population, the score was in most cases under 15.0 points. In patients, a score of about 20.0 indicated mild symptoms, 30.0 moderate symptoms and 40.0 or higher intense symptoms. The MIC value was 10.0 points.

Conclusions
These results enable the more accurate interpretation of the scores of the only disease-specific QoL instrument for adult throat-related diseases.
Changing phase relationship of the stepping rhythm to neuronal oscillatory theta activity in the septo-hippocampal network of mice
Authors: Joshi Abhilasha , Somogyi Peter 
Published: February 2020

AbstractMovement-related sensory and motor activity in the brain contributes to cognitive processes. We have observed that the frequency of stepping rhythm in head-fixed mice running on a jetball overlaps with the range of frequencies that characterize hippocampal rhythmic slow activity, including theta (~ 3 to 10 Hz). On average, step-cycle troughs (i.e. when the paw touches the ground) were weakly coupled to hippocampal theta oscillations. This weak coupling was sustained during a range of running speeds. In short temporal windows, step-cycle troughs were synchronous with hippocampal theta oscillatory cycle troughs, while during other periods they led or lagged behind theta cycles. Furthermore, simultaneously recorded theta rhythmic medial septal neurons in the basal forebrain were phase-coupled to both step-cycles and theta-cycles. We propose that the weak overall phase relationship of step-cycles with theta-cycles signifies a distinct mode of information processing. Transient synchronization of the step-cycle with theta may indicate the engagement of septo-hippocampal-entorhinal network with the current heading of the animal.
Defining the hydrogeological behavior of karst springs through an integrated analysis: a case study in the Berici Mountains area (Vicenza, NE Italy)
Authors: Torresan Filippo , Fabbri Paolo , Piccinini Leonardo , Dalla Libera Nico , Pola Marco , Zampieri Dario 
Published: February 2020

AbstractKnowledge of the hydraulic and geological properties of karst systems is particularly valuable to hydrogeologists because these systems represent an important source of potable water in many countries. However, the high heterogeneity that characterizes karst systems complicates the definition of karst hydrogeological properties, and their estimation involves complex and expensive techniques. In this study, a workflow for karst spring characterization was used to analyze two springs, Nanto spring and Mossano spring, located in the Berici Mountains (NE Italy). Based on the data derived from 4 years of continuous hourly monitoring of discharge, water temperature and specific electrical conductivity, a hydrogeological conceptual model for the monitored springs was proposed. Flow rate measurements, which combined recession curve, flow duration curve and autocorrelation function techniques, were used to evaluate the spring discharge variability. Changes in spring discharge can be related both to the degree of karstification/permeability and to the size of the karst aquifer. Moreover, combining monitored parameters and rainfall—analyzed by the cross-correlation function and VESPA (Vulnerability Estimator for Spring Protection Areas) index approach—permitted assessment of the spring response to recharge and the behavior of the drainage system. Although the responses to the recharge events were quite similar, the two springs showed some differences in terms of the degree of karstification. In fact, Mossano spring showed a more developed karst system than Nanto spring. Three systems (two karsts and one matrix/fractured) are outlined for Mossano spring, while two systems (one karst and one matrix/fractured) are outlined for Nanto spring.
Strategyproof and fair matching mechanism for ratio constraints
Authors: Yahiro Kentaro , Zhang Yuzhe , Barrot Nathanaël , Yokoo Makoto 
Published: February 2020

AbstractWe introduce a new type of distributional constraints called ratio constraints, which explicitly specify the required balance among schools in two-sided matching. Since ratio constraints do not belong to the known well-behaved class of constraints called M-convex set, developing a fair and strategyproof mechanism that can handle them is challenging. We develop a novel mechanism called quota reduction deferred acceptance (QRDA), which repeatedly applies the standard DA by sequentially reducing artificially introduced maximum quotas. As well as being fair and strategyproof, QRDA always yields a weakly better matching for students compared to a baseline mechanism called artificial cap deferred acceptance (ACDA), which uses predetermined artificial maximum quotas. Finally, we experimentally show that, in terms of student welfare and nonwastefulness, QRDA outperforms ACDA and another fair and strategyproof mechanism called Extended Seat Deferred Acceptance (ESDA), in which ratio constraints are transformed into minimum and maximum quotas.
United Kingdom Patent Decisions 2019
Authors: Trigg Robyn 
Published: February 2020

AbstractThis report highlights the main UK patent decisions from 2019, including: two Supreme Court decisions, one concerning obviousness and another concerning employee invention compensation; Court of Appeal decisions relating to FRAND, insufficiency, and SPCs; and several High Court decisions relating to the application of the doctrine of equivalents to numerical values, plausibility of second medical use claims, SPCs, public disclosures, and Arrow declarations.
Nanoparticle-Decorated Ultrathin La2O3 Nanosheets as an Efficient Electrocatalysis for Oxygen Evolution Reactions
Authors: Yan Guangyuan , Wang Yizhan , Zhang Ziyi , Dong Yutao , Wang Jingyu , Carlos Corey , Zhang Pu , Cao Zhiqiang , Mao Yanchao , Wang Xudong 
Published: February 2020

AbstractElectrochemical catalysts for oxygen evolution reaction are a critical component for many renewable energy applications. To improve their catalytic kinetics and mass activity are essential for sustainable industrial applications. Here, we report a rare-earth metal-based oxide electrocatalyst comprised of ultrathin amorphous La2O3 nanosheets hybridized with uniform La2O3 nanoparticles (La2O3@NP-NS). Significantly improved OER performance is observed from the nanosheets with a nanometer-scale thickness. The as-synthesized 2.27-nm La2O3@NP-NS exhibits excellent catalytic kinetics with an overpotential of 310 mV at 10 mA cm−2, a small Tafel slope of 43.1 mV dec−1, and electrochemical impedance of 38 Ω. More importantly, due to the ultrasmall thickness, its mass activity, and turnover frequency reach as high as 6666.7 A g−1 and 5.79 s−1, respectively, at an overpotential of 310 mV. Such a high mass activity is more than three orders of magnitude higher than benchmark OER electrocatalysts, such as IrO2 and RuO2. This work presents a sustainable approach toward the development of highly efficient electrocatalysts with largely reduced mass loading of precious elements.
Metformin Promotes Anti-tumor Biomarkers in Human Endometrial Cancer Cells
Authors: Pabona John Mark P , Burnett Alexander F , Brown Dustin M , Quick Charles M , Simmen Frank A , Montales Maria Theresa E , Liu Shi J , Rose Tyler , Alhallak Iad , Siegel Eric R , Simmen Rosalia CM 
Published: February 2020

AbstractMetformin (MET) is increasingly implicated in reducing the incidence of multiple cancer types in patients with diabetes. However, similar effects of MET in non-diabetic women with endometrial cancer (EC) remain unknown. In a pilot study, obese non-diabetic women diagnosed with type 1, grade 1/2 EC, and consenting to participate were randomly assigned to receive MET or no MET (control (CON)) during the pre-surgical window between diagnosis and hysterectomy. Endometrial tumors obtained at surgery (MET, n = 4; CON, n = 4) were analyzed for proliferation (Ki67), apoptosis (TUNEL), and nuclear expression of ERα, PGR, PTEN, and KLF9 proteins in tumor glandular epithelial (GE) and stromal (ST) cells. The percentages of immunopositive cells for PGR and for KLF9 in GE and for PTEN in ST were higher while those for ERα in GE but not ST were lower, in tumors of MET vs. CON patients. The numbers of Ki67- and TUNEL-positive cells in tumor GE and ST did not differ between groups. In human Ishikawa endometrial cancer cells, MET treatment (60 μM) decreased cell numbers and elicited distinct temporal changes in ESR1, KLF9, PGR, PGR-B, KLF4, DKK1, and other tumor biomarker mRNA levels. In the context of reduced KLF9 expression (by siRNA targeting), MET rapidly amplified PGR, PGR-B, and KLF4 transcript levels. Our findings suggest that MET acts directly in EC cells to modify steroid receptor expression and signaling network and may constitute a preventative strategy against EC in high-risk non-diabetic women.