bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Parietin Transfer Energy Radiatively to Photosynthetic Pigments?
Authors: Fernández-Marín Beatriz , Artetxe Unai , Becerril José María , Martínez-Abaigar Javier , Núñez-Olivera Encarnación , García-Plazaola José Ignacio
Published: July 2018

The main role of lichen anthraquinones is in protection against biotic and abiotic stresses, such as UV radiation. These compounds are frequently deposited as crystals outside the fungal hyphae and most of them emit visible fluorescence when excited by UV. We wondered whether the conversion of UV into visible fluorescence might be photosynthetically used by the photobiont, thereby converting UV into useful energy. To address this question, thalli of Xanthoria parietina were used as a model system. In this species the anthraquinone parietin accumulates in the outer upper cortex, conferring the species its characteristic yellow-orange colouration. In ethanol, parietin absorbed strongly in the blue and UV-B and emitted fluorescence in the range 480–540 nm, which partially matches with the absorption spectra of photosynthetic pigments. In intact thalli, it was determined by confocal microscopy that fluorescence emission spectra shifted 90 nm towards longer wavelengths. Then, to study energy transfer from parietin, we compared the response to UV of untreated and parietin-free thalli (removed with acetone). A chlorophyll fluorescence kinetic assessment provided evidence of UV-induced electron transport, though independently of the presence of parietin. Thus, a role for anthraquinones in energy harvesting is not supported for X. parietina under presented experimental conditions.
Inactivation, Aggregation and Conformational Changes of Polyphenol Oxidase from Quince (Cydonia oblonga Miller) Juice Subjected to Thermal and High-Pressure Carbon Dioxide Treatment
Authors: Iqbal Aamir , Murtaza Ayesha , Muhammad Zafarullah , Elkhedir Abdeen E. , Tao Mingfang , Xu Xiaoyun
Published: July 2018

Polyphenol oxidase (PPO) causes the browning reaction in fruits and vegetables and deteriorates the quality. Thermal treatment for enzyme inactivation may result in defects as opposed to high pressure CO2 (HPCD) processing. In this study, the changes in activity, dissociation, aggregation and conformation of purified PPO from thermal and HPCD treated juice were investigated. HPCD exhibited inactivation of PPO at 55–65 °C whereas thermal processing alone at the same temperature resulted in PPO still showing activity. Under thermal treatment at 25 and 65 °C, the browning degree was higher (0.39 and 0.24) than for HPCD-treated juice (0.23 and 0.12). Fluorescence and circular dichroism spectral results indicated that HPCD induced large decreases in intensities, revealing a rearrangement of the secondary structure and destruction of the native configuration of the PPO molecule. The particle size distribution (PSD) pattern revealed structural modification leading to initial dissociation and subsequent aggregation of PPO after HPCD treatment. Polyacrylamide gel electrophoresis (PAGE) analysis exhibited that molecular size of protein was 40 kDa. In conclusion, the HPCD method was found to be more effective than thermal treatment to inactivate PPO. Structural modifications provided better insights into the phenomena of activation and inactivation of PPO.
Analytical and Sample Preparation Protocol for Therapeutic Drug Monitoring of 12 Thiopurine Metabolites Related to Clinical Treatment of Inflammatory Bowel Disease
Authors: Pecher Daniel , Dokupilová Svetlana , Zelinková Zuzana , Peppelenbosch Maikel , Lučeničová Jana , Mikušová Veronika , Mikuš Peter
Published: July 2018

Thiopurines (TP) represent an important therapeutic tool for the treatment of inflammatory bowel diseases (IBD) in the current situation of rising incidence and health care costs. The results of multiple clinical studies aimed at finding correlations between levels of TP metabolites and response of IBD patients to the treatment are, however, often controversial due to variability in analytical and sample preparation procedures among these studies. In this work, therefore, an updated analytical and sample preparation procedure for therapeutic drug monitoring (TDM) of TP metabolites in blood samples obtained from patients with IBD was proposed to establish a unified protocol. An advanced analytical method based on ion-exchange liquid chromatography hyphenated with tandem mass spectrometry (IEC-ESI-MS/MS) was used for the determination of the profiles of 12 individual TP metabolites in the particular steps of sample preparation procedure including blood collection, red blood cells (RBC) isolation, lysis, and storage. Favorable performance parameters of the IEC-ESI-MS/MS method (LLOQs 1–10 nmol/L, accuracy 95–105%, intra-day and inter-day precision < 10%, selectivity demonstrated via no sample matrix interferences) and acceptable stability (peak area fluctuations < 15%) of clinical samples under the proposed sample preparation conditions {(i) EDTA anticoagulant tube for the blood collection; (ii) 4 °C and 4 h between the sample collection and RBC isolation; (iii) phosphate-buffered saline for RBC washing and re-suspendation; (iv) −20 °C for RBC lysis and short-term storage; (v) 50 mmol/L phosphate buffer, pH 7.4, 10 mmol/L DTT as a stabilizing medium for TPN in RBC lysates} demonstrated the suitability of such protocol for a well-defined and reliable routine use in studies on thiopurines TDM.
Authentication of Herbal Medicines Dipsacus asper and Phlomoides umbrosa Using DNA Barcodes, Chloroplast Genome, and Sequence Characterized Amplified Region (SCAR) Marker
Authors: Park Inkyu , Yang Sungyu , Kim Wook Jin , Noh Pureum , Lee Hyun Oh , Moon Byeong Cheol
Published: July 2018

Dried roots of Dipsacus asper (Caprifoliaceae) are used as important traditional herbal medicines in Korea. However, the roots are often used as a mixture or contaminated with Dipsacus japonicus in Korean herbal markets. Furthermore, the dried roots of Phlomoides umbrosa (Lamiaceae) are used indiscriminately with those of D. asper, with the confusing Korean names of Sok-Dan and Han-Sok-Dan for D. asper and P. umbrosa, respectively. Although D. asper and P. umbrosa are important herbal medicines, the molecular marker and genomic information available for these species are limited. In this study, we analysed DNA barcodes to distinguish among D. asper, D. japonicus, and P. umbrosa and sequenced the chloroplast (CP) genomes of D. asper and D. japonicus. The CP genomes of D. asper and D. japonicus were 160,530 and 160,371 bp in length, respectively, and were highly divergent from those of the other Caprifoliaceae species. Phylogenetic analysis revealed a monophyletic group within Caprifoliaceae. We also developed a novel sequence characterised amplified region (SCAR) markers to distinguish among D. asper, D. japonicus, and P. umbrosa. Our results provide important taxonomic, phylogenetic, and evolutionary information on the Dipsacus species. The SCAR markers developed here will be useful for the authentication of herbal medicines.
TRPA1 Modulating C14 Polyacetylenes from the Iranian Endemic Plant Echinophora platyloba
Authors: Chianese Giuseppina , Sirignano Carmina , Shokoohinia Yalda , Mohammadi Zeynab , Bazvandi Leili , Jafari Fataneh , Jalilian Fereshteh , Schiano Moriello Aniello , De Petrocellis Luciano , Taglialatela-Scafati Orazio , Rigano Daniela
Published: July 2018

Phytochemical investigation of the apolar extract obtained from aerial parts of the Iranian endemic plant Echinophora platyloba DC (Apiaceae) resulted in the characterization of the polyacetylene fraction of this plant. This resulted to be composed of the known echinophorins A and B, embedding the very rare α-pyrone terminal, and of the new echinophorin D (3), including also three conjugated triple bonds. The chemical structures of these compounds were secured by detailed inspection of MS and 1D/2D NMR spectra. The isolated polyacteylenes were evaluated for their modulation of six thermo-TRP channels and they revealed a selective activity on TRPA1, an ion channel involved in the mediation of neuropathic and inflammatory pain. This is the first report on the activity of plant polyacetylenes on transient receptor potential (TRP) channels.
Antiulcer Agents: From Plant Extracts to Phytochemicals in Healing Promotion
Authors: Sharifi-Rad Mehdi , Fokou Patrick Valere Tsouh , Sharopov Farukh , Martorell Miquel , Ademiluyi Adedayo Oluwaseun , Rajkovic Jovana , Salehi Bahare , Martins Natália , Iriti Marcello , Sharifi-Rad Javad
Published: July 2018

In this narrative review, we have comprehensively reviewed the plant sources used as antiulcer agents. From traditional uses as herbal remedies, we have moved on to preclinical evidence, critically discussing the in vitro and in vivo studies focusing on plant extracts and even isolated phytochemicals with antiulcerogenic potential. A particular emphasis was also paid to Helicobacter pylori activity, with emphasis on involved mechanisms of action. Lastly, the issue of safety profile of these plant products has also been addressed.
Synthesis and Biological Activity of Sterol 14α-Demethylase and Sterol C24-Methyltransferase Inhibitors
Authors: Leaver David J.
Published: July 2018

Sterol 14α-demethylase (SDM) is essential for sterol biosynthesis and is the primary molecular target for clinical and agricultural antifungals. SDM has been demonstrated to be a valid drug target for antiprotozoal therapies, and much research has been focused on using SDM inhibitors to treat neglected tropical diseases such as human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis. Sterol C24-methyltransferase (24-SMT) introduces the C24-methyl group of ergosterol and is an enzyme found in pathogenic fungi and protozoa but is absent from animals. This difference in sterol metabolism has the potential to be exploited in the development of selective drugs that specifically target 24-SMT of invasive fungi or protozoa without adversely affecting the human or animal host. The synthesis and biological activity of SDM and 24-SMT inhibitors are reviewed herein.
The History of the Decline and Fall of the Glial Numbers Legend
Authors: Verkhratsky Alexei , Butt Arthur
Published: July 2018

In the field of neuroscience and, more specifically glial cell biology, one of the most fundamentally intriguing and enduring questions has been “how many neuronal cells—neurones and glia—are there in the human brain?”. From the outset, the driving force behind this question was undoubtedly the scientific quest for knowledge of why humans are more intelligent than even our nearest relatives; the ‘neuronal doctrine’ dictated we must have more neurones than other animals. The early histological studies indicated a vast space between neurones that was filled by ‘nervenkitt’, later identified as neuroglia; arguably, this was the origin of the myth that glia massively outnumber neurones in the human brain. The myth eventually became embedded in ideology when later studies seemed to confirm that glia outnumber neurones in the human cortex—the seat of humanity—and that there was an inevitable rise in the glia-to-neurone ratio (GNR) as we climbed the evolutionary tree. This could be described as the ‘glial doctrine’—that the rise of intelligence and the rise of glia go hand-in-hand. In many ways, the GNR became a mantra for working on glial cells at a time when the neuronal doctrine ruled the world. However, the work of Suzana Herculano-Houzel which she reviews in this first volume of Neuroglia has led the way in demonstrating that neurones and glia are almost equal in number in the human cortex and there is no inexorable phylogenetic rise in the GNR. In this commentary we chart the fall and decline of the mythology of the GNR.
Comparison of Accuracy of NUTRIC and Modified NUTRIC Scores in Predicting 28-Day Mortality in Patients with Sepsis: A Single Center Retrospective Study
Authors: Jeong Dae Hyun , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck , Seo Jarim , Kim Younkyoung , Min Ji-Yeon , Huh Jin Won
Published: July 2018

The NUTRIC (Nutrition Risk in the Critically Ill) and modified NUTRIC scores are nutrition risk assessment tools specifically for intensive care unit (ICU) patients. A modified NUTRIC score is composed of all variables except for IL-6 level in the NUTRIC score. Their use in qualifying critically ill patients at nutritional risk has been extensively evaluated, although not in studies of patients with sepsis, when interleukin 6 levels, which are not included in the modified NUTRIC score, may be elevated. The present study was a retrospective comparison of the accuracy of the NUTRIC and modified NUTRIC scores in predicting 28-day mortality of 482 adult patients with sepsis who were admitted to the medical ICU of a tertiary referral hospital in South Korea between January 2011 and June 2017 and who had ICU stays longer than 24 h. The NUTRIC and modified NUTRIC scores were calculated using data from the patients’ electronic medical records relating to the first 24 h of admission to the ICU. The area under the curve of the NUTRIC Score for predicting 28-day mortality was 0.762 (95% confidence interval (CI): 0.718–0.806) and of the modified NUTRIC Score 0.757 (95% CI: 0.713–0.801). There was no significant difference between the two scores (p = 0.45). The modified NUTRIC score was a good nutritional risk assessment tool for critically ill septic patients.
Bioaccessibility and Bioavailability of a Marine-Derived Multimineral, Aquamin-Magnesium
Authors: Felice Valeria D. , O’Gorman Denise M. , O’Brien Nora M. , Hyland Niall P.
Published: July 2018

Introduction: Magnesium is an essential mineral involved in a range of key biochemical pathways. Several magnesium supplements are present on the market and their degree of bioavailability differs depending on the form of magnesium salt used. Aquamin-Mg is a natural source of magnesium, containing 72 additional trace minerals derived from the clean waters off the Irish coast. However, the in vitro bioaccessibility and bioavailability of Aquamin-Mg in comparison with other supplement sources of magnesium has yet to be tested. Method: Aquamin-Mg, magnesium chloride (MgCl2) and magnesium oxide (MgO) were subjected to gastrointestinal digestion according to the harmonized INFOGEST in vitro digestion method and in vitro bioavailability tested using the Caco-2 cell model. Magnesium concentration was measured by atomic absorption spectrophotometry (AAS). Results: Magnesium recovery from both Aquamin-Mg and MgCl2 was greater than for MgO. Magnesium from all three sources was transported across the epithelial monolayer with Aquamin-Mg displaying a comparable profile to the more bioavailable MgCl2. Conclusions: Our data support that magnesium derived from a marine-derived multimineral product is bioavailable to a significantly greater degree than MgO and displays a similar profile to the more bioavailable MgCl2 and may offer additional health benefits given its multimineral profile.
Electromagnetic Vacuum Densities Induced by a Cosmic String
Authors: Saharian Aram , Manukyan Vardan , Saharyan Nvard
Published: July 2018

We investigate the influence of a generalized cosmic string in (D+1)-dimensional spacetime on the local characteristics of the electromagnetic vacuum. Two special cases are considered with flat and locally de Sitter background geometries. The topological contributions in the vacuum expectation values (VEVs) of the squared electric and magnetic fields are explicitly separated. Depending on the number of spatial dimensions and on the planar angle deficit induced by the cosmic string, these contributions can be either negative or positive. In the case of the flat bulk, the VEV of the energy–momentum tensor is evaluated as well. For the locally de Sitter bulk, the influence of the background gravitational field essentially changes the behavior of the vacuum densities at distances from the string larger than the curvature radius of the spacetime.
Dynamic Light Scattering of Biopharmaceutics—Can Analytical Performance Be Enhanced by Laser Power?
Authors: Aleandri Simone , Vaccaro Andrea , Armenta Ricardo , Völker Andreas Charles , Kuentz Martin
Published: July 2018

Background: Dynamic light scattering (DLS) is an important tool to characterize colloidal systems and adequate sizing is particularly critical in the field of protein formulations. Among the different factors that can influence the measurement result, the effect of laser power has so far not been studied thoroughly. Methods: The sensitivity of a DLS instrument was first considered on a theoretical level, followed by experiments using DLS instruments, equipped with two different lasers of (nominal) 45 mW, and 100 mW, respectively. This work analyzes dilute colloidal dispersions of lysozyme as model protein. Results: Theoretical findings agreed with experiments in that only enhanced laser power of 100 mW laser allowed measuring a 0.1 mg/mL protein dispersion in a reliable manner. Results confirmed the usefulness of the presented theoretical considerations in improving a general understanding of the limiting factors in DLS. Conclusions: Laser power is a critical aspect regarding adequate colloidal analysis by DLS. Practical guidance is provided to help scientists specifically with measuring dilute samples to choose both an optimal instrument configuration as well as a robust experimental procedure.
Modeling of Laser Beam Absorption in a Polymer Powder Bed
Authors: Osmanlic Fuad , Wudy Katrin , Laumer Tobias , Schmidt Michael , Drummer Dietmar , Körner Carolin
Published: July 2018

In order to understand the absorption characteristic, a ray trace model is developed by taking into account the reflection, absorption and refraction. The ray paths are resolved on a sub-powder grid. For validation, the simulation results are compared to analytic solutions of the irradiation of the laser beam onto a plain surface. In addition, the absorptance, reflectance and transmittance of PA12 powder layers measured by an integration sphere setup are compared with the numerical results of our model. It is shown that the effective penetration depth can be lower than the penetration depth in bulk material for polymer powders and, therefore, can increase the energy density at the powder bed surface. The implications for modeling of the selective laser sintering (SLS) process and the processability of fine powder distributions and high powder bed densities are discussed.
Extreme Portfolio Loss Correlations in Credit Risk
Authors: Mühlbacher Andreas , Guhr Thomas
Published: July 2018

The stability of the financial system is associated with systemic risk factors such as the concurrent default of numerous small obligors. Hence, it is of utmost importance to study the mutual dependence of losses for different creditors in the case of large, overlapping credit portfolios. We analytically calculate the multivariate joint loss distribution of several credit portfolios on a non-stationary market. To take fluctuating asset correlations into account, we use an random matrix approach which preserves, as a much appreciated side effect, analytical tractability and drastically reduces the number of parameters. We show that, for two disjoint credit portfolios, diversification does not work in a correlated market. Additionally, we find large concurrent portfolio losses to be rather likely. We show that significant correlations of the losses emerge not only for large portfolios with thousands of credit contracts, but also for small portfolios consisting of a few credit contracts only. Furthermore, we include subordination levels, which were established in collateralized debt obligations to protect the more senior tranches from high losses. We analytically corroborate the observation that an extreme loss of the subordinated creditor is likely to also yield a large loss of the senior creditor.
Gold Nanocage-Based Electrochemical Sensing Platform for Sensitive Detection of Luteolin
Authors: Li Xiaobao , Zou Ruyi , Niu Yanyan , Sun Wei , Shao Taiming , Chen Xiaoqin
Published: July 2018

A simple and sensitive electrochemical sensor was developed for the detection of tracelevels of luteolin. The sensoris based on a novel type of chemically modified electrode: gold nanocage (AuNCs)-modified carbon ionic liquid electrode (CILE). To construct this electrochemical sensing platform for luteolin, CILE is initially prepared by using 1-hexylpyridinium hexafluorophosphate as the binder and then AuNCs are coated on the surface of CILE to fabricate AuNCs-modified CILE (AuNCs/CILE). Electrochemical studies have shown that AuNCs/CILE can exhibit enhanced electrocatalytic activity toward the redox reaction of luteolin, therefore, the redox peak current of luteolin can be greatly improved, resulting in the high sensitivity of the developed sensor. Under the optimal conditions, the oxidation peak currents of the sensor increase linearly with an increase in the luteolin concentration in a range from 1 to 1000 nM with a detection limit of 0.4 nM, which is lower than those of most reported electrochemical luteolin sensors. Moreover, the reproducibility, precision, selectivity, and stability of this sensor are excellent. Finally, the sensing system was applied to the analysis of luteolin-spiked drug samples and the recovery in all cases was 95.0–96.7%, indicating the potential application of this simple, facile, and sensitive sensing system in pharmaceutical analysis.
Sensitivity-Improved Ultrasonic Sensor for 3D Imaging of Seismic Physical Model Using a Compact Microcavity
Authors: Gang Tingting , Hu Manli , Bai Xiaohong , Rong Qiangzhou
Published: July 2018

A sensitivity-improved ultrasonic sensor is proposed and demonstrated experimentally in this present study. The device is comprised only a fiber-optic microcavity that is formed by discharging a short section of hollow core fiber (HCF). The key to ensuring the success of the sensor relies on the preprocessing of hydrogen loading for HCF. When discharging the HCF, the hydrogen is heated up during the formation of the air bubble, which enlarges the bubble diameter, smoothens its surfaces simultaneously and decreases Young’s modulus of the material of the bubble. Ultimately, this results in the probe being highly sensitive to ultrasound with a SNR of 69.28 dB. Once the compact air cavity is formed between the end face of the leading-in fiber and the top wall of the bubble, a well-defined interference spectrum is achieved based on the Fabry–Perot interference. By using spectral side-band filtering technology, we detect the ultrasonic waves reflected by the seismic physical model (SMF) and then reconstruct its three-dimensional image.
Redefining the Smart City: Culture, Metabolism and Governance
Authors: Allam Zaheer , Newman Peter
Published: July 2018

The Smart City concept is still evolving and can be viewed as a branding exercise by big corporations, which is why the concept is not being used by the United Nations (U.N.). Smart Cities tend to represent the information, communication, and technological (ICT) industry alone without considering the values and cultural and historical profiles that some cities hold as legacies. However, the technology inherent in Smart Cities promises efficiencies and options that could allow cities to be more “inclusive, safe, resilient, and sustainable” as required by the U.N. agenda including cultural heritage. There is a notable lack of Smart City application to cultural and historical urban fabrics. Instead, the modernist new town approach has emerged under this new rubric leading to many problems such as urban decay and unsustainable car dependence. This study therefore presents a review of the literature on the nature, challenges, and opportunities of Smart Cities. A new Smart Cities framework is proposed based on the dimensions of culture, metabolism, and governance. These findings seek to inform policy makers of an alternative viewpoint on the Smart City paradigm, which focuses on urban outcomes rather than technology in isolation.
Exploring Community of Practice in Uganda’s Public Sector: Environmental Impact Assessment Case Study
Authors: Cirella Giuseppe T. , Iyalomhe Felix O. , Jensen Anne , Akiyode Oluwole O.
Published: July 2018

The utilisation of typological concepts of participation-based research on the community of practice (CoP) examines Uganda’s public sector in relation to environmental impact assessment (EIA) of national projects. The re-assessment of participatory knowledge is analysed and incorporated into EIA project planning, design and implementation. A case study within the five divisions of the Kampala District used 250 semi-structured and open-ended survey questionnaires and 20 key informants by way of piecewise random sampling. The findings suggest that the majority of respondents were non-informed, on components of CoP, within the selected EIA projects. The CoP revealed concerns regarding Uganda’s security and corruption which intertwined on how the CoP was conducted. We provide original data on the CoP in relation to EIA projects with the intention of facilitating public sector entities a suitable level of knowledge in aiding affected communities.
Properties of Fired Bricks Incorporating TFT-LCD Waste Glass Powder with Reservoir Sediments
Authors: Tang Chao-Wei
Published: July 2018

In view of increasing concerns over nonrenewable resource depletion and waste management, this study aimed to apply the Taguchi optimization technique to determine the process conditions for producing bricks by incorporating thin-film transition liquid crystal display (TFT-LCD) waste glass powder with reservoir sediments. An orthogonal array L16(45) was adopted, which consisted of five controllable four-level factors (i.e., cullet content, drying method, preheat time, sintering temperature, and error). Moreover, the analysis of variance method was used to explore the effects of the experimental factors on the density, water absorption, shrinkage ratio, loss on ignition, porosity, and compressive strength of the fired bricks. The microstructures of the fired specimens were investigated by scanning electron microscopy. Then, large-scale production techniques for fired bricks containing recycled TFT-LCD glass cullet and reservoir sediments were developed in a commercially available tunnel kiln. The test results showed that the structure of the fired specimen was loose at a sintering temperature ranging from 900 to 950 °C. However, the fired specimen showed a significant densification at the sintering temperature of 1050 °C. In addition, the Taguchi method was found to be a feasible approach for optimizing the process condition of bricks using recycled TFT-LCD glass cullet and reservoir sediments and it significantly reduced the number of tests. Further, the characteristics of fired bricks developed in the tunnel kiln were in compliance with Chinese National Standards class Ι building bricks criteria.
Analysis of Sustainability Decision Trees Generated by Qualitative Models Based on Equationless Heuristics
Authors: Doubravský Karel , Kocmanová Alena , Dohnal Mirko
Published: July 2018

Sustainability processes are complex and therefore ill-known, inconsistent, and subjective, and must be studied despite a shortage of information. It is prohibitively difficult to study them on quantitative levels using quantitative methods. The presented qualitative approach enables us to solve these issues. There are just three values used to describe the qualitative variables and their derivatives, plus/increasing, zero/constant, and negative/decreasing. An n-dimensional equation-less qualitative model is a set of pairwise relations. Such relations represent a shallow knowledge of the sustainability systems being studied. The solution of the qualitative model is a set of scenarios. The behaviour of this model is described by all of the possible transitions among these scenarios. A decision maker can easily compile a decision tree if he/she knows all of the possible transitions. The generated tree can be evaluated using traditional methods if all of the relevant probabilities are known. Otherwise, some heuristics are used to evaluate the best decision.
On Neutrosophic Triplet Groups: Basic Properties, NT-Subgroups, and Some Notes
Authors: Zhang Xiaohong , Hu Qingqing , Smarandache Florentin , An Xiaogang
Published: July 2018

As a new generalization of the notion of the standard group, the notion of the neutrosophic triplet group (NTG) is derived from the basic idea of the neutrosophic set and can be regarded as a mathematical structure describing generalized symmetry. In this paper, the properties and structural features of NTG are studied in depth by using theoretical analysis and software calculations (in fact, some important examples in the paper are calculated and verified by mathematics software, but the related programs are omitted). The main results are obtained as follows: (1) by constructing counterexamples, some mistakes in the some literatures are pointed out; (2) some new properties of NTGs are obtained, and it is proved that every element has unique neutral element in any neutrosophic triplet group; (3) the notions of NT-subgroups, strong NT-subgroups, and weak commutative neutrosophic triplet groups (WCNTGs) are introduced, the quotient structures are constructed by strong NT-subgroups, and a homomorphism theorem is proved in weak commutative neutrosophic triplet groups.
Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Use of Expanded Repertoires of Type I and Type III Interferon Cytokines
Authors: Wendel Emily S. , Yaparla Amulya , Melnyk Mattie L. S. , Koubourli Daphne V. , Grayfer Leon
Published: July 2018

While amphibians around the globe are facing catastrophic declines, in part because of infections with pathogens such as the Frog Virus 3 (FV3) ranavirus; the mechanisms governing amphibian susceptibility and resistance to such pathogens remain poorly understood. The type I and type III interferon (IFN) cytokines represent a cornerstone of vertebrate antiviral immunity, while our recent work indicates that tadpoles and adult frogs of the amphibian Xenopus laevis may differ in their IFN responses to FV3. In this respect, it is notable that anuran (frogs and toads) tadpoles are significantly more susceptible to FV3 than adult frogs, and thus, gaining greater insight into the differences in the tadpole and adult frog antiviral immunity would be invaluable. Accordingly, we examined the FV3-elicited expression of a panel of type I and type III IFN genes in the skin (site of FV3 infection) and kidney (principal FV3 target) tissues and isolated cells of X. laevis tadpoles and adult frogs. We also examined the consequence of tadpole and adult frog skin and kidney cell stimulation with hallmark pathogen-associated molecular patterns (PAMPs) on the IFN responses of these cells. Together, our findings indicate that tadpoles and adult frogs mount drastically distinct IFN responses to FV3 as well as to viral and non-viral PAMPs, while these expression differences do not appear to be the result of a distinct pattern recognition receptor expression by tadpoles and adults.
Antiangiogenic Therapies in Non-Small-Cell Lung Cancer
Authors: Alshangiti A. , Chandhoke G. , Ellis P.M.
Published: July 2018

Angiogenesis is frequent in non-small-cell lung cancer (NSCLC) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with NSCLC. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin–paclitaxel chemotherapy, has been shown to improve survival for patients with NSCLC. However, bevacizumab-based therapy is not suitable for many NSCLC patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders. Similar efficacy has also been seen with carboplatin–pemetrexed followed by maintenance pemetrexed chemotherapy. In the second-line setting, the addition of ramucirumab to docetaxel—or the addition of bevacizumab to paclitaxel—has resulted in a modest improvement in efficacy, although the clinical importance of those findings is questionable. Many trials in NSCLC have also evaluated oral antiangiogenic compounds, both in the first line in combination with chemotherapy and upon disease progression either as combination or single-agent therapy. No clear improvements in overall survival have been observed, although a subgroup analysis of a trial evaluating the addition of nintedanib to docetaxel showed improved survival that was limited to patients with adenocarcinoma. Those findings require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with NSCLC, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy.
Circulating Tumour DNA in EGFR-Mutant Non-Small-Cell Lung Cancer
Authors: Cabanero M. , Tsao M.S.
Published: July 2018

The advent of targeted therapy in non-small-cell lung cancer (NSCLC) has made the routine molecular diagnosis of EGFR mutations crucial for optimal patient management. Obtaining tumour tissue for biomarker testing, especially in the setting of re-biopsy, can present many challenges. A potential alternative source of tumour dna is circulating cell-free tumour-derived DNA (CTDNA). Although CTDNA is present in low quantities in plasma, the convenience of sample acquisition and the increasing reliability of detection methods make this approach a promising one. The various performance characteristics of both digital and nondigital platforms are still variable, and a standardized approach is needed that will make those platforms reliable clinical tools for the detection of EGFR sensitizing mutations and resistance mutations, including the T790M resistance mutation. Information derived from ctdna can be used to assess tumour burden, to identify genomic-based resistance mechanisms, and to track dynamic changes during therapy.
Screening for Breast Cancer in 2018—What Should We be Doing Today?
Authors: Seely J.M. , Alhassan T.
Published: July 2018

Although screening mammography has delivered many benefits since its introduction in Canada in 1988, questions about perceived harms warrant an up-to-date review. To help oncologists and physicians provide optimal patient recommendations, the literature was reviewed to find the latest guidelines for screening mammography, including benefits and perceived harms of overdiagnosis, false positives, false negatives, and technologic advances. For women 40–74 years of age who actually participate in screening every 1–2 years, breast cancer mortality is reduced by 40%. With appropriate corrections, overdiagnosis accounts for 10% or fewer breast cancers. False positives occur in about 10% of screened women, 80% of which are resolved with additional imaging, and 10%, with breast biopsy. An important limitation of screening is the false negatives (15%–20%). The technologic advances of digital breast tomosynthesis, breast ultrasonography, and magnetic resonance imaging counter the false negatives of screening mammography, particularly in women with dense breast tissue.
Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, T790M, and Clinical Trials
Authors: O’Kane G.M. , Barnes T.A. , Leighl N.B.
Published: July 2018

Tumours with sensitizing mutations in the EGFR gene constitute a distinct molecular subgroup of non-small-cell lung cancers (NSCLCS) that benefit from precision medicine. First- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIS) are recommended as upfront therapy for EGFR-mutated advanced NSCLC and, compared with chemotherapy, have resulted in superior progression-free survival, improved tumour response rates, and improved quality of life. However, resistance inevitably develops, and the third-generation tki osimertinib has been approved to target the gatekeeper EGFR mutation T790M, which is responsible for resistance in 60% of cases. Multiple drivers of tki resistance have now been identified, and many new drugs are in development. With respect to this rapidly evolving field, our review highlights the current status of treatment options for patients with EGFR-mutated advanced nsclc, focusing especially on identified causes of resistance, challenges, and clinical trials aiming to improve outcomes in this patient population.
Advanced Typical and Atypical Carcinoid Tumours of the Lung: Management Recommendations
Authors: Melosky B.
Published: July 2018

Background: Neuroendocrine tumours (NETS) are classified by site of origin, with lung being the second most common primary site after the gastrointestinal tract. Lung nets are rare and heterogeneous, with varied pathologic and clinical features. Typical and atypical carcinoid tumours are low-grade lung nets which, compared with the more common high-grade nets, are associated with a more favourable prognosis. Still, optimal treatment strategies are lacking. Methods: This review concentrates on classification and treatment strategies for metastatic low-grade lung nets, considering both typical and atypical carcinoids. The terminology can be confusing, and an attempt is made to simplify it. Promising results from recent trials that included lung nets are presented and discussed. Finally, guidelines from Europe and North America are discussed, and differences are noted. Results: Even within the group of patients with low-grade nets, the presentation, the locations of metastasis, and the speed of progression can be very different. The initial work-up and an understanding of the tumour’s biology are key in making management decisions. Various treatment options—including somatostatin analogs, peptide receptor radioligand therapy, and biologic systemic therapy, specifically with the mtor (mechanistic target of rapamycin) inhibitor everolimus—are now available and are presented in a treatment algorithm. Summary: Although lung nets are rare and evidence supporting optimal treatment strategies is lacking, the recent publication of trials that have included patients with lung nets advances evidence-based therapy for these tumours. Many variables have to be considered in managing these tumours that have received little attention. Education for treating physicians is needed.
Clinical Application and Utility of Genomic Assays in Early-Stage Breast Cancer: Key Lessons Learned to Date
Authors: Chia S.K.L.
Published: July 2018

Early-stage hormone receptor–positive breast cancer is the most common subtype and stage presenting in countries with organized screening programs. Standard clinical and pathologic factors are routinely used to support prognosis and decisions about adjuvant therapies. Hormone receptor and HER2 status are essential for decision-making about the use of adjuvant hormonal and anti-HER2 therapies respectively. Genomic assays are now commercially available to aid in either further prognostication or in refining the potential benefit of adjuvant chemotherapy. The current genomic assays all generally quantify estrogen receptor and proliferation gene sets (among others) by rna expression, although the specific genes assayed are quite discordant. The present review focuses on the pivotal studies in which each assay attempted to demonstrate clinical utility, with an emphasis on prospective trial data for each assay, if available. Using genomic assays, health care providers will increasingly be able to individualize therapy or de-escalate therapy, optimizing clinic benefit while minimizing toxicities from systemic therapies.
Rapidly Changing Treatment Algorithms for Metastatic Nonsquamous Non-Small-Cell Lung Cancer
Authors: Melosky B.
Published: July 2018

Background: The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (NSCLC) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective. Methods: This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic NSCLC of nonsquamous histology. Algorithms continue to change quickly, and an attempt is made to keep the paradigm current and applicable into the near future. Results: Treatment algorithms for nsclc tumours with EGFR mutations, ALK rearrangements, and ROS1 rearrangements, and for wild-type tumours are presented. A future algorithm based on new immunotherapy data is proposed. The treatment algorithm for EGFR mutation is changing with the proven efficacy of osimertinib for the acquired T790M mutation. All patients taking first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors must be tested. Conclusions: The treatment algorithm for ALK rearrangement has changed with the proven superiority of alectinib compared with crizotinib in the first-line setting. The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation. The biomarker for checkpoint inhibitors continues to be PD-L1 by immunohistochemistry stain, but whether testing will be necessary for patient selection if chemotherapy combinations are implemented will be determined soon.
Value Assessment in Oncology Drugs: Funding of Drugs for Metastatic Breast Cancer in Canada
Authors: Lemieux J. , Audet S.
Published: July 2018

Background: Life expectancy for women with metastatic breast cancer has improved since the early 2000s, in part because of the introduction of novel therapies, including chemotherapy, hormonal therapy, and targeted agents. However, those treatments can come at a cost for the patient (short- and long-term toxicities from treatment) and at a financial cost for the health care system. Given the increase in the number of costly anticancer agents being introduced into the clinical setting, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed a system to quantify the value of new cancer treatments in terms of benefit, toxicities, and costs. Methods: In our value-assessment analysis, we included drugs that were funded in Canada between 2012 and 2017 for metastatic breast cancer. We reviewed the clinical benefit of those agents (survival, progression, quality of life), their costs, their value according to the asco and esmo value frameworks, and their assessments from the pan-Canadian Oncology Drug Review [pcodr (in Canada, except Quebec)] and the Institut national d’excellence en santé et en services sociaux [iness (in Quebec)]. Results: Drugs funded in Canada showed variation in their asco net health benefit scores and esmo magnitude of clinical benefit scores, but all had a cost-effectiveness ratio greater than $100,000 per quality-adjusted life–year. The strength and magnitude of the clinical benefit (for example, overall survival benefit vs. progression-free survival benefit) was not necessarily associated with a higher value score. Conclusions: Although great progress has been made in developing value frameworks, use of those frameworks has to be refined to help patients and health care providers make informed decisions about the benefit of novel cancer therapies and to help policymakers make decisions about the societal benefit of funding those therapies.
Comparing Enrolees with Non-Enrolees of Cancer-Patient Navigation at End of Life
Authors: Park G. , Johnston G.M. , Urquhart R. , Walsh G. , McCallum M.
Published: July 2018

Background: Cancer-patient navigators who are oncology nurses support and connect patients to resources throughout the cancer care trajectory, including end of life. Although qualitative and cohort studies of navigated patients have been reported, no population-based studies were found. The present population-based study compared demographic, disease, and outcome characteristics for decedents who had been diagnosed with cancer by whether they did or did not see a navigator. Methods: This retrospective study used patient-based administrative data in Nova Scotia (cancer registry, death certificates, navigation visits) to generate descriptive statistics. The study population included all adults diagnosed with cancer who died during 2011–2014 of a cancer or non-cancer cause of death. Results: Of the 7694 study decedents, 74.9% had died of cancer. Of those individuals, 40% had seen a navigator at some point in their disease trajectory. The comparable percentage for those who did not die of cancer was 11.9%. Decedents at the oldest ages had the lowest navigation rates. Navigation rates, time from diagnosis to death, and time from last navigation visit to death varied by disease site. Conclusions: This population-based study of cancer-patient navigation enrolees compared with non-enrolees is the first of its kind. Most findings were consistent with expectations. However, we do not know whether the rates of navigation are consistent with the navigation needs of the population diagnosed with cancer. Because more people are living longer with cancer and because the population is aging, ongoing surveillance of who requires and who is using navigation services is warranted.
Anastomosing Hemangioma of the Kidney: Radiologic and Pathologic Distinctions of a Kidney Cancer Mimic
Authors: Cheon P.M. , Rebello R. , Naqvi A. , Popovic S. , Bonert M. , Kapoor A.
Published: July 2018

Anastomosing hemangioma (AH) is a rare subtype of primary vascular tumour that can, clinically and radiologically, present similarly to malignant renal tumours such as renal cell carcinoma (RCC) and angiosarcoma. Rarely seen in the genitourinary system, the ah we report here occurred in a 40-year-old male patient diagnosed initially with rcc based on imaging and successfully treated by laparoscopic left radical nephrectomy, with adrenal sparing and perihilar lymph node dissection. The pathologic diagnosis of ah can be challenging on small biopsy specimens; we therefore opine that it is appropriate to excise these lesions to facilitate diagnosis and definitively exclude common renal cancers. However, in this review, we describe some radiologic and pathologic distinctions between ah and malignant tumours.
The Evolution of Biosimilars in Oncology, with a Focus on Trastuzumab
Authors: Nixon N.A. , Hannouf M.B. , Verma S.
Published: July 2018

Cancer therapy has evolved significantly with increased adoption of biologic agents (“biologics”). That evolution is especially true for HER2 (human epidermal growth factor receptor-2)–positive breast cancer with the introduction of trastuzumab, a monoclonal antibody against the HER2 receptor, which, in combination with chemotherapy, significantly improves survival in both metastatic and early disease. Although the efficacy of biologics is undeniable, their expense is a significant contributor to the increasing cost of cancer care. Across disease sites and indications, biosimilar agents are rapidly being developed with the goal of offering cost-effective alternatives to biologics. Biosimilars are pharmaceuticals whose molecular shape, efficacy, and safety are similar, but not identical, to those of the original product. Although these agents hold the potential to improve patient access, complexities in their production, evaluation, cost, and clinical application have raised questions among experts. Here, we review the landscape of biosimilar agents in oncology, with a focus on trastuzumab biosimilars. We discuss important considerations that must be made as these agents are introduced into routine cancer care.
Comprehensive Metastatic Lung Cancer Care Must Include Palliative Care
Authors: Rosenblum A. M. , Chasen M.
Published: July 2018

The Canadian Lung Cancer Conference, held in Vancouver, 8–9 February 2018, was a successful, informative, and well-organized meeting. [...]