bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Attitudes toward Mental Illness in Healthcare Professionals and Students
Authors: Lien Yin-Yi , Lin Hui-Shin , Tsai Chi-Hsuan , Lien Yin-Ju , Wu Ting-Ting
Published: November 2019

Mental-illness-related stigma not only exists in the public but also in healthcare systems. Healthcare providers (HCPs) who have stigmatizing attitudes or behaviors might be thought of as a key barrier to mental health service use, and influence the quality of healthcare. Although cumulative projects have been conducted to reduce stigma related to mental illness among HCPs around the world, little is known about whether the attitudes of HCPs toward mental illness have changed over time. Research on this topic is mixed with respect to whether attitudes of HCPs toward mental illness have become more or less positive. The aim of the current study was to help clarify this issue using a cross-temporal meta-analysis of scores on the Social Distance Scale (SDS), Opinions about Mental Illness (OMI), and Community Attitudes towards Mental Illness (CAMI) measures among health care professionals and students (N = 15,653) from 1966 to 2016. Our results indicated that both social distance (β = −0.32, p < 0.001) and attitudes (β = 0.43, p = 0.007) of HCPs toward mental illness have become increasingly positive over time. These findings provide empirical evidence to support that the anti-stigma programs and courses have positive effects on HCPs and can inform future anti-stigma programs focusing on improving the attitudes of HCPs toward mental illness, thereby improving the quality of healthcare provided.
Bring More Data!—A Good Advice? Removing Separation in Logistic Regression by Increasing Sample Size
Authors: Šinkovec Hana , Geroldinger Angelika , Heinze Georg
Published: November 2019

The parameters of logistic regression models are usually obtained by the method of maximum likelihood (ML). However, in analyses of small data sets or data sets with unbalanced outcomes or exposures, ML parameter estimates may not exist. This situation has been termed ‘separation’ as the two outcome groups are separated by the values of a covariate or a linear combination of covariates. To overcome the problem of non-existing ML parameter estimates, applying Firth’s correction (FC) was proposed. In practice, however, a principal investigator might be advised to ‘bring more data’ in order to solve a separation issue. We illustrate the problem by means of examples from colorectal cancer screening and ornithology. It is unclear if such an increasing sample size (ISS) strategy that keeps sampling new observations until separation is removed improves estimation compared to applying FC to the original data set. We performed an extensive simulation study where the main focus was to estimate the cost-adjusted relative efficiency of ML combined with ISS compared to FC. FC yielded reasonably small root mean squared errors and proved to be the more efficient estimator. Given our findings, we propose not to adapt the sample size when separation is encountered but to use FC as the default method of analysis whenever the number of observations or outcome events is critically low.
Ownership of Assets in Chinese Shipping Funds
Authors: Jin Hai , Schinas Orestis
Published: November 2019

As the importance of Chinese financial schemes in maritime business increases, and many issues on the ownership of the assets under the current Law remain obscured for international investors, this work argues that a streamlining to international practice is required; therefore, the ownership of the trust property under the shipping fund in China should be transferred to the trustee from the client. The trustee shall possess, employ, benefit, and dispose the trust property in his/her own name, which links up with China’s current property legislation, ship registration, and ship arrest regulations. The trust property under the shipping fund in China is independent of the fixed property or other management property of the trustee, the beneficiary, and the custodian. This gives full play to functional advantages of the trust system of the shipping fund, contributes to the expansion of financing channels in the shipping industry in China, guarantees the specialization and flexibility of shipping investment activities and the diversity of the investment subject, promotes development of China’s policies about the shipping industry and financial innovation, and boosts the realization of “The Strategy of National Revitalization Based on Marine Industry Development” and “The Belt and Road Initiatives” and construction of Shanghai International Shipping Center and International Finance Center.
The Ecology of Salicylic Acid Signaling: Primary, Secondary and Tertiary Effects with Applications in Agriculture
Authors: Filgueiras Camila C. , Martins Adalvan D. , Pereira Ramom V. , Willett Denis S.
Published: November 2019

The salicylic acid pathway is one of the primary plant defense pathways, is ubiquitous in vascular plants, and plays a role in rapid adaptions to dynamic abiotic and biotic stress. Its prominence and ubiquity make it uniquely suited for understanding how biochemistry within plants can mediate ecological consequences. Induction of the salicylic acid pathway has primary effects on the plant in which it is induced resulting in genetic, metabolomic, and physiologic changes as the plant adapts to challenges. These primary effects can in turn have secondary consequences for herbivores and pathogens attacking the plant. These secondary effects can both directly influence plant attackers and mediate indirect interactions between herbivores and pathogens. Additionally, stimulation of salicylic acid related defenses can affect natural enemies, predators and parasitoids, which can recruit to plant signals with consequences for herbivore populations and plant herbivory aboveground and belowground. These primary, secondary, and tertiary ecological consequences of salicylic acid signaling hold great promise for application in agricultural systems in developing sustainable high-yielding management practices that adapt to changing abiotic and biotic environments.
The Changing Landscape of Pharmacotherapy for Diabetes Mellitus: A Review of Cardiovascular Outcomes
Authors: Wu Linda , Gunton Jenny E.
Published: November 2019

The prevention of cardiovascular morbidity and mortality has always been a primary concern in patients with type 2 diabetes. Modern trials of glucose-lowering therapies now assess major adverse cardiac events as an endpoint in addition to the effects on glycaemic control. Whilst the data on the efficacy of intensive glucose lowering on reducing cardiovascular risk are limited, there are now increasing numbers of glucose-lowering therapies that have proven cardiovascular benefit independent of glucose lowering. This review will summarise the available literature on cardiovascular outcomes in relation to metformin, sulphonylureas, di-peptidyl peptidase-4 inhibitors, glucagon-like peptide receptor agonists, sodium-glucose co-transporter 2 inhibitors, thiazolidinediones, acarbose and insulin. In addition, new paradigms in diabetes management and the importance of treatment selection based on considerations including but not limited to glycaemic control will be discussed.
Privacy Preserving Data Publishing with Multiple Sensitive Attributes based on Overlapped Slicing
Authors: Widodo  , Budiardjo Eko Kuswardono , Wibowo Wahyu Catur
Published: November 2019

Investigation into privacy preserving data publishing with multiple sensitive attributes is performed to reduce probability of adversaries to guess the sensitive values. Masking the sensitive values is usually performed by anonymizing data by using generalization and suppression techniques. A successful anonymization technique should reduce information loss due to the generalization and suppression. This research attempts to solve both problems in microdata with multiple sensitive attributes. We propose a novel overlapped slicing method for privacy preserving data publishing with multiple sensitive attributes. We used discernibility metrics to measure information loss. The experiment result shows that our method obtained a lower discernibility value than other methods.
Spatial Vision and Visually Guided Behavior in Apidae
Authors: Kelber Almut , Somanathan Hema
Published: November 2019

The family Apidae, which is amongst the largest bee families, are important pollinators globally and have been well studied for their visual adaptations and visually guided behaviors. This review is a synthesis of what is known about their eyes and visual capabilities. There are many species-specific differences, however, the relationship between body size, eye size, resolution, and sensitivity shows common patterns. Salient differences between castes and sexes are evident in important visually guided behaviors such as nest defense and mate search. We highlight that Apis mellifera and Bombus terrestris are popular bee models employed in the majority of studies that have contributed immensely to our understanding vision in bees. However, other species, specifically the tropical and many non-social Apidae, merit further investigation for a better understanding of the influence of ecological conditions on the evolution of bee vision.
Effects of Simulated Heat Waves on Life History Traits of a Host Feeding Parasitoid
Authors: Zhang Yi-Bo , Yang An-Pei , Zhang Gui-Fen , Liu Wan-Xue , Wan Fang-Hao
Published: November 2019

The frequency and amplitude of heat waves are predicted to increase under future climate change conditions. We still lack a detailed understanding of how changes in the frequency and amplitude of heat waves are linked to the life history traits and biocontrol efficiency of host-feeding parasitoids. In the present study, we simulated a series of heat waves as a function of amplitude and frequency to investigate the effects on the life history traits of the host-feeding parasitoid Eretmocerus hayati. We found that both the amplitude and frequency of heat waves significantly affected the adult phenotypes. In the low-amplitude heat wave group, the frequency of heat waves did not change the life history traits of the parasitoid; however, when the heat amplitude reached 42 °C, medium (four times/week) and high frequencies (seven times/week) of heat waves detrimentally affected these parameters. Hence, these findings suggest that to obtain optimal biological control with this parasitoid, we need to carefully monitor heat wave pattern (especially the amplitude and frequency) over the short term (usually 7–10 days) before releasing a host-feeding parasitoid.
Acetylcholine and Its Receptors in Honeybees: Involvement in Development and Impairments by Neonicotinoids
Authors: Grünewald Bernd , Siefert Paul
Published: November 2019

Acetylcholine (ACh) is the major excitatory neurotransmitter in the insect central nervous system (CNS). However, besides the neuronal expression of ACh receptors (AChR), the existence of non-neuronal AChR in honeybees is plausible. The cholinergic system is a popular target of insecticides because the pharmacology of insect nicotinic acetylcholine receptors (nAChRs) differs substantially from their vertebrate counterparts. Neonicotinoids are agonists of the nAChR and are largely used in crop protection. In contrast to their relatively high safety for humans and livestock, neonicotinoids pose a threat to pollinating insects such as bees. In addition to its effects on behavior, it becomes increasingly evident that neonicotinoids affect developmental processes in bees that appear to be independent of neuronal AChRs. Brood food (royal jelly, worker jelly, or drone jelly) produced in the hypopharyngeal glands of nurse bees contains millimolar concentrations of ACh, which is required for proper larval development. Neonicotinoids reduce the secreted ACh-content in brood food, reduce hypopharyngeal gland size, and lead to developmental impairments within the colony. We assume that potential hazards of neonicotinoids on pollinating bees occur neuronally causing behavioral impairments on adult individuals, and non-neuronally causing developmental disturbances as well as destroying gland functioning.
SWOT Analysis of Blended Learning in Public Universities of Uganda: A Case Study of Muni University
Authors: Ali Guma , Buruga Bosco Apparatus , Habibu Taban
Published: November 2019

With the fusion of information communication technology (ICT) in higher institutions of learning, new teaching and learning practices have developed—often called blended learning—allowing students and teachers to interact with information and each other more independently. This study, therefore, analyses the strengths, weaknesses, opportunities and threats (SWOT) of blended learning in the Public Universities of Uganda, in a case study of Muni University. Descriptive survey design was employed in the research. The target sample of the survey was 25 lecturers and 189 students selected using a stratified random sampling technique from the three faculties. A questionnaire was employed in this study and the data collected were analyzed using SPSS Version 25. The findings of the study identified accessibility, positive attitude, and knowledge and skills as the major motivators for blended learning. The strengths of blended learning found included serving many students in a short time, university readiness, connected both in and out of class, basic IT skills and top management commitment. The weaknesses included low bandwidth and unstable internet, lack of a plagiarism tool, insufficient numbers of computers and dependent on internet connectivity. Opportunities cited were competency-based systems that made it easier to manage individual progress in line with university expansion plans, an accessible way of learning regardless of location and available external support. The threats included unreliable power supply, unreliable internet connection, exchanges of username and passwords by students, internet shorthand used in student assignments. Based on these results, the study provides a baseline to help government and public universities that would like to implement or newly incorporate blended learning to identify strengths, weaknesses, opportunities and threats associated with the blended learning approach. The survey urges that plagiarism plugins for Moodle and BigBlue Button should be added, steady power supply should be provided, internet accessibility should be improved, blended learning training and workshops need to be improved and finally, policies, rules and standards pertaining to blended learning should be enacted.
Cancer Risk in Children and Young Adults (Offspring) Born after Medically Assisted Reproduction: A Systematic Review and Meta-Analysis
Authors: Chiavarini Manuela , Ostorero Andrea , Naldini Giulia , Fabiani Roberto
Published: November 2019

Many studies have investigated the relationship between medically assisted reproduction (MAR) and health outcomes, particularly cancer, in the offspring. This meta-analysis investigated the association between MAR and childhood cancer. Data sources were PubMed, Scopus, and Web of Science up until June 2018. From the selected studies, we extracted the cancer risk estimates of the exposure of interest (MAR, assisted reproductive technology—ART, and in fitro fertilization—IVF). We conducted the meta-analysis using a random effects model. The outcomes of interest were childhood cancers, classified according to the international classification of childhood cancer (ICCC-3). In our meta-analysis (18 cohort and 15 case-control studies) the overall cancer risk was significantly increased in children conceived by MAR, ART, or IVF. MAR and ART significantly increased the risk for hematological tumors, hepatic tumors, and sarcomas (odds ratio (OR) 1.54; 95% CI 1.18–2.02 and OR 1.92; 95% CI 1.34–2.74, respectively). MAR increased acute myeloid leukemia risk (OR 1.41; 95% CI 1.02–1.95) and ART increased neural cancer risk (OR 1.21; 95% CI 1.01–1.46). Our results suggest an increased risk of cancer in children conceived by MAR. Further studies are needed to investigate the impact of fertility treatments, parental subfertility status, and their association on health outcomes in the offspring.
Ant Forest through the Haze: A Case Study of Gamified Participatory Pro-Environmental Communication in China
Authors: Chen Yang , Cai Danqing
Published: November 2019

Increasing energy consumption and growing pollutant emissions speak volumes about the environmental challenges in various countries and regions. As one of the fastest-developing countries, China has been facing a serious environmental crisis, with many parts of the country constantly shrouded in a heavy haze. In order to improve the public’s pro-environmental awareness and encourage people to take action to contribute to energy conservation and emissions reduction, Ant Forest, a gamified participatory communication program, was launched on the top mobile payment service Alipay. This innovative approach links people’s low-carbon lifestyles with afforestation and haze control in the real world through virtual gaming experiences. This case study explains the working mechanism of Ant Forest in pro-environmental communication and investigates its effectiveness in motivating the public to engage in pro-environmental activities. Focus groups and interviews were adopted in this study to collect qualitative data. The results indicate that Ant Forest plays an encouraging role in Chinese users’ pro-environmental awareness and behaviors, but improvements in user experiences are still needed in some aspects. By introducing the haze problem in China and the practice of gamified participatory pro-environmental communication, this paper is expected to provide inspiration and reference for future efforts to promote public participation in environmental protection.
A Set of State–Space Models at a High Disaggregation Level to Forecast Italian Industrial Production
Authors: Corradini Riccardo
Published: November 2019

Normally, econometric models that forecast the Italian Industrial Production Index do not exploit information already available at time t + 1 for their own main industry groupings. The new strategy proposed here uses state–space models and aggregates the estimates to obtain improved results. The performance of disaggregated models is compared at the same time with a popular benchmark model, a univariate model tailored on the whole index, with persistent not formally registered holidays, a vector autoregressive moving average model exploiting all information published on the web for main industry groupings. Tests for superior predictive ability confirm the supremacy of the aggregated forecasts over three steps horizon using absolute forecast error and quadratic forecast error as a loss function. The datasets are available online.
Electrochemical Disinfection of Experimentally Infected Teeth by Boron-Doped Diamond Electrode Treatment
Authors: Böhm Anna-Lena , Koch Maximilian , Rosiwal Stefan , Burkovski Andreas , Karl Matthias , Grobecker-Karl Tanja
Published: November 2019

Disinfection and prevention of re-infection are the decisive treatment steps in endodontic therapy. In this study, boron-doped diamond (BDD) electrodes have been fabricated and used for disinfecting the root canals of extracted human teeth, which had been covered with bacterial biofilms formed by Bacillus subtilis and Staphylococcus epidermidis. The growth of B. subtilis could be successfully impaired, achieving a complete disinfection after 8.5 min treatment time with the success of disinfection depending on the insertion depth of the electrode in the root canal. S. epidermidis could completely be removed after 3.5 min treatment time. A clinically applicable electrode array led to complete disinfection after treatment times of 10 min for S. epidermidis and 25 min for B. subtilis. BDD electrode application allowed for the improved disinfection of root canals and dentin tubules based on a continuous production of reactive oxygen species and their enhanced penetration of dentin tubules most likely due the formation of a continuous stream of small gas bubbles. The treatment times that are required here will be shortened in clinical application, as mechanical shaping of the canal system would precede the disinfection process.
Low Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis
Authors: Eck Ruben J. , Bult Wouter , Wetterslev Jørn , Gans Reinold O. B. , Meijer Karina , van der Horst Iwan C.C. , Keus Frederik
Published: November 2019

International guidelines recommend low-molecular-weight heparin (LMWH) as first-line pharmacological option for the prevention of venous thromboembolism (VTE) in many patient categories. Guidance on the optimal prophylactic dose is lacking. We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials to assess benefits and harms of low-dose LMWH versus placebo or no treatment for thrombosis prophylaxis in patients at risk of VTE. PubMed, Cochrane Library, Web of Science, and Embase were searched up to June 2019. Results were presented as relative risk (RR) with conventional and TSA-adjusted confidence intervals (CI). Forty-four trials with a total of 22,579 participants were included. Six (14%) had overall low risk of bias. Low-dose LMWH was not statistically significantly associated with all-cause mortality (RR 0.99; 95%CI 0.85–1.14; TSA-adjusted CI 0.89–1.16) but did reduce symptomatic VTE (RR 0.62; 95%CI 0.48–0.81; TSA-adjusted CI 0.44–0.89) and any VTE (RR 0.61; 95%CI 0.50–0.75; TSA-adjusted CI 0.49–0.82). Analyses on major bleeding (RR 1.07; 95%CI 0.72–1.59), as well as serious adverse events (SAE) and clinically relevant non-major bleeding were inconclusive. There was very low to moderate-quality evidence that low-dose LMWH for thrombosis prophylaxis did not decrease all-cause mortality but reduced the incidence of symptomatic and asymptomatic VTE, while the analysis of the effects on bleeding and adverse events remained inconclusive.
Rehabilitation Succeeds Where Technology and Pharmacology Failed: Effective Treatment of Persistent Pain across the Lifespan
Authors: Ickmans Kelly , Voogt Lennard , Nijs Jo
Published: November 2019

Chronic pain affects up to 30% of the adult population [...]
A Nomogram to Predict the Outcome of Fine Needle Aspiration Cytology in Head and Neck Masses
Authors: Kotowski Ulana , Brkic Faris F. , Koperek Oskar , Pablik Eleonore , Grasl Stefan , Grasl Matthaeus Ch. , Erovic Boban M.
Published: November 2019

Fine needle aspiration cytology (FNAC) is an important diagnostic tool for tumors of the head and neck. However, non-diagnostic or inconclusive results may occur and lead to delay in treatment. The aim of this study was to evaluate the factors that predict a successful FNAC. A retrospective search was performed to identify all patients who received an FNAC at the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna. The variables were patients’ age and sex, localization and size of the punctured structure, previous radiotherapy, experience of the head and neck surgeon, experience of the pathologist and the FNAC result. Based on these parameters, a nomogram was subsequently created to predict the probability of accurate diagnosis. After performing 1221 FNACs, the size of the punctured lesion (p = 0.0010), the experience of the surgeon and the pathologist (p = 0.00003) were important factors for a successfully procedure and reliable result. FNACs performed in nodes smaller than 20 mm had a significantly worse diagnostic outcome compared to larger nodes (p = 0.0004). In conclusion, the key factors for a successful FNAC are nodal size and the experience of the head and neck surgeon and the pathologist.
Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer
Authors: Jiménez-Vacas Juan M. , Gómez-Gómez Enrique , Montero-Hidalgo Antonio J. , Herrero-Aguayo Vicente , L-López Fernando , Sánchez-Sánchez Rafael , Guler Ipek , Blanca Ana , Méndez-Vidal María José , Carrasco Julia , Lopez-Miranda José , Requena-Tapia María J. , Castaño Justo P. , Gahete Manuel D. , Luque Raúl M.
Published: November 2019

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.
Extended Rectangular Mrξ-Metric Spaces and Fixed Point Results
Authors: Asim Mohammad , Nisar Kottakkaran Sooppy , Morsy Ahmed , Imdad Mohammad
Published: November 2019

In this paper, we enlarge the classes of rectangular M b -metric spaces and extended rectangular b-metric spaces by considering the class of extended rectangular M r ξ -metric spaces and utilize the same to prove an analogue of Banach contraction principle in such spaces. We adopt an example to highlight the utility of our main result. Finally, we apply our result to examine the existence and uniqueness of solution for a system of Fredholm integral equation.
On the Inverse of the Caputo Matrix Exponential
Authors: Defez Emilio , Tung Michael M. , Chen-Charpentier Benito M. , Alonso José M.
Published: November 2019

Matrix exponentials are widely used to efficiently tackle systems of linear differential equations. To be able to solve systems of fractional differential equations, the Caputo matrix exponential of the index α > 0 was introduced. It generalizes and adapts the conventional matrix exponential to systems of fractional differential equations with constant coefficients. This paper analyzes the most significant properties of the Caputo matrix exponential, in particular those related to its inverse. Several numerical test examples are discussed throughout this exposition in order to outline our approach. Moreover, we demonstrate that the inverse of a Caputo matrix exponential in general is not another Caputo matrix exponential.
An Inverse Problem for a Generalized Fractional Derivative with an Application in Reconstruction of Time- and Space-Dependent Sources in Fractional Diffusion and Wave Equations
Authors: Kinash Nataliia , Janno Jaan
Published: November 2019

In this article, we consider two inverse problems with a generalized fractional derivative. The first problem, IP1, is to reconstruct the function u based on its value and the value of its fractional derivative in the neighborhood of the final time. We prove the uniqueness of the solution to this problem. Afterwards, we investigate the IP2, which is to reconstruct a source term in an equation that generalizes fractional diffusion and wave equations, given measurements in a neighborhood of final time. The source to be determined depends on time and all space variables. The uniqueness is proved based on the results for IP1. Finally, we derive the explicit solution formulas to the IP1 and IP2 for some particular cases of the generalized fractional derivative.
On the Matrix Mittag–Leffler Function: Theoretical Properties and Numerical Computation
Authors: Popolizio Marina
Published: November 2019

Many situations, as for example within the context of Fractional Calculus theory, require computing the Mittag–Leffler (ML) function with matrix arguments. In this paper, we collect theoretical properties of the matrix ML function. Moreover, we describe the available numerical methods aimed at this purpose by stressing advantages and weaknesses.
Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer Therapies
Authors: Gnoni Antonio , Licchetta Antonella , Memeo Riccardo , Argentiero Antonella , Solimando Antonio G. , Longo Vito , Delcuratolo Sabina , Brunetti Oronzo
Published: November 2019

The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor knowledge of its biology. For several years, sorafenib, a tyrosine kinase inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for advanced HCC patients. Its activity is the inhibition of the retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. However, the efficacy of sorafenib is limited by the development of drug resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a critical and central role in HCC escape from TKIs activity. Advanced HCC patients with a BRAF mutation display a multifocal and/or more aggressive behavior with resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF could be another mechanism of cancer proliferation and TKI escape in HCC and the inhibition could become a possible strategy treatment for HCC. Moreover, recent preclinical studies and clinical trials evidence that combined treatments, involving alternative pathways, have an important role of therapy for HCC and they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). These initial data must be confirmed in clinical studies, which are currently ongoing. Translational research discoveries could create new strategies of targeted therapy combinations, including BRAF pathway, and they could eventually bring light in new treatment of HCC.
Ultra-Early and Early Changes in Bile Acids and Insulin after Sleeve Gastrectomy among Obese Patients
Authors: Cӑtoi Adriana Florinela , Pârvu Alina Elena , Mironiuc Aurel , Silaghi Horațiu , Pop Ioana Delia , Andreicuț Andra Diana
Published: November 2019

Background and Objective: In obese patients, sleeve gastrectomy (SG) has shown mixed results on bile acid (BA) values. The aim of our study was to examine the potential ultra-early and early changes of the circulating total BA in relation with the changes of insulin resistance (IR) in obese patients submitted to laparoscopic SG. Materials and Methods: Twenty-four obese subjects were investigated for body mass index (BMI), total fasting BA, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and leptin before and at 7 and 30 d after SG. Results: After surgery, mean BMI decreased at the first (p < 0.001) and at the second time point (p < 0.001) relative to baseline. Total fasting BA values did not change significantly at 7 d (p = 0.938) and at 30 d (p = 0.289) after SG. No significant changes were found at 7 d (p = 0.194, p = 0.34) and 30 d (p = 0.329, p = 0.151) after surgery regarding fasting insulin and HOMA-IR, respectively. However, a trend of increased total fasting BA and decreased fasting insulin and HOMA- after laparoscopic SG has been found. Negative correlations between total fasting BA and insulin (r = −0.807, p = 0.009), HOMA-IR (r = −0.855, p = 0.014), and blood glucose (r = −0.761, p = 0.047), respectively, were observed at one month after SG. Conclusion: In conclusion, here, we found a lack of significant changes in total fasting BA, insulin, and HOMA-IR ultra-early and early after SG, which precluded us to consider a possible relation between the variations of BA and IR. However, the presence of the tendency for total fasting BA to increase and for insulin and HOMA-IR to decrease, as well as of the negative correlations one month after laparoscopic SG, suggest that this surgery brings about some changes that point towards the existence, and possibly towards the restoration, at least to some extent, of the link between BA and glucose metabolism.
Phenolic Compounds from the Aerial Parts of Blepharis linariifolia Pers. and Their Free Radical Scavenging and Enzyme Inhibitory Activities
Authors: Dirar Amina Ibrahim , Wada Mikiyo , Watanabe Takashi , Devkota Hari Prasad
Published: November 2019

Background: Blepharis linariifolia Pers. (Family: Acanthaceae) is used in traditional medicines as a general tonic and for the treatment of various health problems in Sudan. The main aim of this study was to isolate and identify the major chemical constituents from the aerial parts of B. linariifolia and evaluate their bioactivities. Methods: The dried aerial parts of the plant were extracted successively with 100% acetone and 50% acetone, and thereafter the combined extract was subjected to repeated column chromatography to isolate the main components. Free radical scavenging activity was evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical method, and in vitro enzyme inhibitory activities against α-glucosidase, pancreatic lipase, and mushroom tyrosinase were evaluated. Results: From the detailed chemical analysis, verbascoside (1), vanillic acid (2), apigenin (3), and 6″-O-p-coumaroylprunin (4), were isolated and their structures were identified on the basis of their nuclear magnetic resonance (NMR) spectral data. Among the isolated compounds, verbascoside (1) showed the most potent free radical scavenging activity (IC50 = 22.03 ± 0.04 μM). Apigenin (3) and 6″-O-p-coumaroylprunin (4) showed promising inhibitory activities against all tested enzymes. Apigenin (3) showed the most potent inhibitory activity against α-glucosidase and tyrosinase (IC50 = 34.73 ± 1.78 μM and 23.14 ± 1.83 μM, respectively), whereas 6″-O-p-coumaroylprunin (4) showed potent inhibition for lipase (IC50 = 2.25 ± 0.17 μM). Conclusions: Four phenolic compounds were isolated and identified from B. linariifolia acetone extract, which are reported for the first time from this plant. All compounds showed good DPPH free radical scavenging activities, with verbascoside (1) being the most potent. Apigenin (3) was the most active as α-glucosidase and mushroom tyrosinase inhibitor, while 6″-O-p-coumaroylprunin (4) showed potent inhibitory activity for pancreatic lipase.
Reconstruction of Complex Zygomatic Bone Defects Using Mirroring Coupled with EBM Fabrication of Titanium Implant
Authors: Moiduddin Khaja , Hammad Mian Syed , Umer Usama , Ahmed Naveed , Alkhalefah Hisham , Ameen Wadea
Published: November 2019

Reconstruction of zygomatic complex defects is a surgical challenge, owing to the accurate restoration of structural symmetry as well as facial projection. Generally, there are many available techniques for zygomatic reconstruction, but they hardly achieve aesthetic and functional properties. To our knowledge, there is no such study on zygomatic titanium bone reconstruction, which involves the complete steps from patient computed tomography scan to the fabrication of titanium zygomatic implant and evaluation of implant accuracy. The objective of this study is to propose an integrated system methodology for the reconstruction of complex zygomatic bony defects using titanium comprising several steps, right from the patient scan to implant fabrication while maintaining proper aesthetic and facial symmetry. The integrated system methodology involves computer-assisted implant design based on the patient computed tomography data, the implant fitting accuracy using three-dimensional comparison techniques, finite element analysis to investigate the biomechanical behavior under loading conditions, and finally titanium fabrication of the zygomatic implant using state-of-the-art electron beam melting technology. The resulting titanium implant has a superior aesthetic appearance and preferable biocompatibility. The customized mirrored implant accurately fit on the defective area and restored the tumor region with inconsequential inconsistency. Moreover, the outcome from the two-dimensional analysis provided a good accuracy within 2 mm as established through physical prototyping. Thus, the designed implant produced faultless fitting, favorable symmetry, and satisfying aesthetics. The simulation results also demonstrated the load resistant ability of the implant with max stress within 1.76 MPa. Certainly, the mirrored and electron beam melted titanium implant can be considered as the practical alternative for a bone substitute of complex zygomatic reconstruction.
Quantifying the Contribution of Crystallographic Texture and Grain Morphology on the Elastic and Plastic Anisotropy of bcc Steel
Authors: Diehl Martin , Niehuesbernd Jörn , Bruder Enrico
Published: November 2019

The influence of grain shape and crystallographic orientation on the global and local elastic and plastic behaviour of strongly textured materials is investigated with the help of full-field simulations based on texture data from electron backscatter diffraction (EBSD) measurements. To this end, eight different microstructures are generated from experimental data of a high-strength low-alloy (HSLA) steel processed by linear flow splitting. It is shown that the most significant factor on the global elastic stress–strain response (i.e., Young’s modulus) is the crystallographic texture. Therefore, simple texture-based models and an analytic expression based on the geometric mean to determine the orientation dependent Young’s modulus are able to give accurate predictions. In contrast, with regards to the plastic anisotropy (i.e., yield stress), simple analytic approaches based on the calculation of the Taylor factor, yield different results than full-field microstructure simulations. Moreover, in the case of full-field models, the selected microstructure representation influences the outcome of the simulations. In addition, the full-field simulations, allow to investigate the micro-mechanical fields, which are not readily available from the analytic expressions. As the stress–strain partitioning visible from these fields is the underlying reason for the observed macroscopic behaviour, studying them makes it possible to evaluate the microstructure representations with respect to their capabilities of reproducing experimental results.
Bias Controller of Mach–Zehnder Modulator for Electro-Optic Analog-to-Digital Converter
Authors: Shi Shuxin , Yuan Jun , Huang Qin , Shi Chongyu , Luo Xin , Lu Shan , Yuan Pengfei , Yu Hua , Yue Qiuqin
Published: November 2019

As one of the core devices for an electro-optic analog-to-digital converter (ADC), the Mach–Zehnder (MZ) modulator plays an important role, and the output stability of the MZ modulator has a decisive influence on the conversion accuracy of the ADC. This paper proposed a pilot tone-based method to stabilize the bias point of the modulator. This method could obtain the corresponding control voltage of the MZ modulator by adding a KHz-level dither tone to the bias end of the modulator and calculating the ratio of the first and second harmonic components. The experimental results showed that the output optical power of the modulator was stable at 3.2 dB when the bias point of the modulator was set at the orthogonal point. Moreover, the fluctuation range was not more than 0.15 dB, the first harmonic of the output signal was stable at 50.5 dB, and the fluctuation range was not more than 0.6 dB. The proposed bias controller based on the field programmable gate array (FPGA) and digital signal processing (DSP) can stabilize the modulator bias point at the orthogonal point and with a relatively high locking accuracy.
Investigation of the Young’s Modulus and the Residual Stress of 4H-SiC Circular Membranes on 4H-SiC Substrates
Authors: Ben Messaoud Jaweb , Michaud Jean-François , Certon Dominique , Camarda Massimo , Piluso Nicolò , Colin Laurent , Barcella Flavien , Alquier Daniel
Published: November 2019

The stress state is a crucial parameter for the design of innovative microelectromechanical systems based on silicon carbide (SiC) material. Hence, mechanical properties of such structures highly depend on the fabrication process. Despite significant progresses in thin-film growth and fabrication process, monitoring the strain of the suspended SiC thin-films is still challenging. However, 3C-SiC membranes on silicon (Si) substrates have been demonstrated, but due to the low quality of the SiC/Si heteroepitaxy, high levels of residual strains were always observed. In order to achieve promising self-standing films with low residual stress, an alternative micromachining technique based on electrochemical etching of high quality homoepitaxy 4H-SiC layers was evaluated. This work is dedicated to the determination of their mechanical properties and more specifically, to the characterization of a 4H-SiC freestanding film with a circular shape. An inverse problem method was implemented, where experimental results obtained from bulge test are fitted with theoretical static load-deflection curves of the stressed membrane. To assess data validity, the dynamic behavior of the membrane was also investigated: Experimentally, by means of laser Doppler vibrometry (LDV) and theoretically, by means of finite element computations. The two methods provided very similar results since one obtained a Young’s modulus of 410 GPa and a residual stress value of 41 MPa from bulge test against 400 GPa and 30 MPa for the LDV analysis. The determined Young’s modulus is in good agreement with literature values. Moreover, residual stress values demonstrate that the fabrication of low-stressed SiC films is achievable thanks to the micromachining process developed.
Au-Embedded and Carbon-Doped Freestanding TiO2 Nanotube Arrays in Dye-Sensitized Solar Cells for Better Energy Conversion Efficiency
Authors: Rho Won-Yeop , Lee Kang-Hun , Han Seung-Hee , Kim Hyo-Yeon , Jun Bong-Hyun
Published: November 2019

Dye-sensitized solar cells (DSSCs) are fabricated with freestanding TiO2 nanotube arrays (TNTAs) which are incorporated with Au nanoparticles (NPs) and carbon materials via electrodeposition and chemical vapor deposition (CVD) method to create a plasmonic effect and better electron transport that will enhance their energy conversion efficiency (ECE). The ECE of DSSCs based on the freestanding TNTAs is 5.87%. The ECE of DSSCs, based on the freestanding TNTAs with Au NPs or carbon materials, is 6.57% or 6.59%, respectively, and the final results of DSSCs according to the freestanding TNTAs with Au NPs and carbon materials is increased from 5.87% to 7.24%, which is an enhancement of 23.34% owing to plasmonic effect and better electron transport. Au NPs are incorporated into the channel of freestanding TNTAs and are characterized by CS-corrected-field emission transmission electron microscope (Cs-FE-TEM) and elemental mapping. Carbon materials are also well-incorporated in the channel of freestanding TNTAs and are analyzed by Raman spectroscopy.
MALDI-TOF Mass Spectrometry and Specific Biomarkers: Potential New Key for Swift Identification of Antimicrobial Resistance in Foodborne Pathogens
Authors: Feucherolles Maureen , Cauchie Henry-Michel , Penny Christian
Published: November 2019

Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is today the reference method for direct identification of microorganisms in diagnostic laboratories, as it is notably time- and cost-efficient. In the context of increasing cases of enteric diseases with emerging multi-drug resistance patterns, there is an urgent need to adopt an efficient workflow to characterize antimicrobial resistance (AMR). Current approaches, such as antibiograms, are time-consuming and directly impact the “patient-physician” workflow. Through this mini-review, we summarize how the detection of specific patterns by MALDI-TOF MS, as well as bioinformatics, become more and more essential in research, and how these approaches will help diagnostics in the future. Along the same lines, the idea to export more precise biomarker identification steps by MALDI-TOF(/TOF) MS data towards AMR identification pipelines is discussed. The study also critically points out that there is currently still a lack of research data and knowledge on different foodborne pathogens as well as several antibiotics families such as macrolides and quinolones, and many questions are still remaining. Finally, the innovative combination of whole-genome sequencing and MALDI-TOF MS could be soon the future for diagnosis of antimicrobial resistance in foodborne pathogens.
Gut Anaerobes Capable of Chicken Caecum Colonisation
Authors: Kubasova Tereza , Kollarcikova Miloslava , Crhanova Magdalena , Karasova Daniela , Cejkova Darina , Sebkova Alena , Matiasovicova Jitka , Faldynova Marcela , Sisak Frantisek , Babak Vladimir , Pokorna Alexandra , Cizek Alois , Rychlik Ivan
Published: November 2019

Chicks in commercial production are highly sensitive to enteric infections and their resistance can be increased by administration of complex adult microbiota. However, it is not known which adult microbiota members are capable of colonising the caecum of newly hatched chicks. In this study, we therefore orally inoculated chicks with pure cultures of 76 different bacterial isolates originating from chicken caecum on day 1 of life and determined their ability to colonise seven days later. The caecum of newly hatched chickens could be colonised by bacteria belonging to phyla Bacteroidetes, Proteobacteria, Synergistetes, or Verrucomicrobia, and isolates from class Negativicutes (phylum Firmicutes). On the other hand, we did not record colonisation with isolates from phyla Actinobacteria and Firmicutes (except for Negativicutes), including isolates from families Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Lactobacillaceae. Representatives of genera commonly used in probiotics such as Lactobacillus, Enterococcus, or Bacillus therefore did not colonise the chicken intestinal tract after a single dose administration. Following challenge with Salmonella enterica serovar Enteritidis, the best protecting isolates increased the chicken’s resistance to S. Enteritidis only tenfold, which, however, means that none of the tested individual bacterial isolates on their own efficiently protected chicks against S. Enteritidis.
Bifidobacterial Distribution Across Italian Cheeses Produced from Raw Milk
Authors: Milani Christian , Alessandri Giulia , Mancabelli Leonardo , Lugli Gabriele Andrea , Longhi Giulia , Anzalone Rosaria , Viappiani Alice , Duranti Sabrina , Turroni Francesca , Ossiprandi Maria Cristina , van Sinderen Douwe , Ventura Marco
Published: November 2019

Cheese microbiota is of high industrial relevance due to its crucial role in defining the organoleptic features of the final product. Nevertheless, the composition of and possible microbe–microbe interactions between these bacterial populations have never been assessed down to the species-level. For this reason, 16S rRNA gene microbial profiling combined with internally transcribed spacer (ITS)-mediated bifidobacterial profiling analyses of various cheeses produced with raw milk were performed in order to achieve an in-depth view of the bifidobacterial populations present in these microbially fermented food matrices. Moreover, statistical elaboration of the data collected in this study revealed the existence of community state types characterized by the dominance of specific microbial genera that appear to shape the overall cheese microbiota through an interactive network responsible for species-specific modulatory effects on the bifidobacterial population.