bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract
Authors: Kareh Mike , El Nahas Rana , Al-Aaraj Lamis , Al-Ghadban Sara , Naser Al Deen Nataly , Saliba Najat , El-Sabban Marwan , Talhouk Rabih 
Published: November 2018

Objective: Sea cucumbers are considered among the most important functional foods. Following bioassay guided fractionation, we assessed the anti-proliferative and anti-inflammatory activities of Holothuria polii ( H. polii) extracts. Methods: Sea cucumber ethanolic extract and the partially purified aqueous fractions were assessed for their anti-proliferative activities. These latter bioactivities were evaluated in the highly invasive MDA-MB-231 human breast cancer cells in two-dimensional and three-dimensional cultures using trypan blue exclusion assay. The tumor-suppressive effects of sea cucumber ethanolic extract and aqueous fractions were assayed by measuring the trans-well invasion of MDA-MB-231 cells and the expression of some epithelial mesenchymal transition markers using quantitative reverse-transcription polymerase chain reaction and western blot analysis. The anti-inflammatory activity of the aqueous fraction was tested by measuring the secreted levels of interleukin-6, nitric oxide, and matrix metalloproteinase 9 in endotoxin-induced mammary epithelial SCp2 cells and interleukin-1β in phorbol-12-myristate-13-acetate-activated human monocytic THP-1 cells. Results: Sea cucumber ethanolic extract and the aqueous fraction significantly decreased the proliferation of MDA-MB-231 cells by more than 50% at similar and noncytotoxic concentrations and caused an arrest in the S-phase of the cell cycle of treated cells. In contrast, petroleum ether, chloroform, ethyl acetate, and n-butanol organic fractions did not show any significant activity. Furthermore, sea cucumber ethanolic extract and aqueous fraction reduced the proliferation of MDA-MB-231 cells in three-dimensional cultures by more than 60% at noncytotoxic concentrations. In addition, treatment with these concentrations resulted in the loss of stellate outgrowths in favor of spherical aggregates and a 30% decrease in invasive properties. Both sea cucumber ethanolic extract and aqueous decreased the transcription of vimentin and the protein expression levels of vimentin and N-cadherin in three-dimensional cultures. The aqueous fraction decreased the levels of inflammatory markers interleukin-6, nitric oxide, and matrix metalloproteinase 9 in the mouse mammary SCp2 cells, and the level of interleukin-1β produced by phorbol-12-myristate-13-acetate-activated THP-1 human monocytic cells. Conclusion: The data reveal for the first time promising anti-proliferative and anti-inflammatory activities in H. polii water extract in two-dimensional and three-dimensional culture models.
Poor Readability of AOSSM Patient Education Resources and Opportunities for Improvement
Authors: Kakazu Rafael , Schumaier Adam , Minoughan Chelsea , Grawe Brian 
Published: November 2018

Background: Appropriate education on the disease processes associated with orthopaedic pathology can affect patient expectations and functional outcome. Hypothesis: Patient education resources from the American Orthopaedic Society for Sports Medicine (AOSSM) are too complex for comprehension by the average orthopaedic patient. Study Design: Cross-sectional study. Methods: Patient education resources provided by the AOSSM were analyzed with software that provided 10 readability scores as well as opportunities for improving readability. The readability scores were compared with the recommended eighth-grade reading level. Results: A total of 39 patient education resources were identified and evaluated. The mean ± SD reading grade-level scores were as follows: Coleman-Liau Index, 12.5 ± 1.11; New Dale-Chall Readability Formula, 10.9 ± 1.37; Flesch-Kincaid Grade Level, 9.9 ± 1.06; FORCAST Readability Formula, 11.4 ± 0.51; Fry Readability Formula, 12.8 ± 2.79; Gunning Fog Index, 11.9 ± 1.37; Raygor Readability Index, 13.1 ± 2.37; Simple Measure of Gobbledygook, 12.3 ± 0.90; Automated Readability Index, 11.2 ± 1.18; and New Automated Readability Index, 10.6 ± 1.27. After averaging the reading grade-level scores, only 1 patient education resource was found to be written at an 8th- to 9th-grade level, and 14 (36%) were written above a 12th-grade level. All scores were significantly different from the eighth-grade level ( P < .0065). The percentage of complex words and long words were 19.6% ± 2.67% and 41.4% ± 3.18%, respectively. Conclusion: Patient education resources provided by the AOSSM are at a significantly higher reading level than recommended. Simple changes can drastically improve these scores to increase health literacy and possibly outcome.
Estimated Cost of Anticancer Therapy Directed by Comprehensive Genomic Profiling in a Single-Center Study
Authors: Chawla Anita , Janku Filip , Wheler Jennifer J. , Miller Vincent A. , Ryan Jason , Anhorn Rachel , Zhou Zhou , Signorovitch James 
Published: November 2018

Purpose Comprehensive genomic profiling (CGP) detects several classes of genomic alterations across numerous genes simultaneously and can match more patients with genomically targeted therapies than conventional molecular profiling. The current study estimated the costs of anticancer drugs and overall survival (OS) for patients who were treated with matched and unmatched therapy. Methods Costs were estimated for patients with complete data (188 of 500 patients) from a prospective, nonrandomized study of patients with diverse refractory cancers who underwent CGP and were treated with matched or unmatched therapy. We assessed mean time to treatment failure (TTF) and mean observed OS. Patient-specific drug and administration costs were imputed for the first regimen after CGP on the basis of drug classes, unit costs, and time on treatment. Results Patients on matched (n = 122) versus unmatched (n = 66) therapy had longer mean TTF (+1.5 months) and observed OS (+2.4 months) and higher drug costs (+$38,065; all P < .01). Increased drug costs were largely attributable to the longer duration of therapy associated with extended TTF (66.3%) rather than higher monthly drug costs (33.7%). Incremental increases in TTF (+1.9 months v +1.2 months) and observed OS (+2.5 months v +2.1 months) between matched and unmatched therapies were larger for those who underwent CGP in earlier- versus later-line therapy. Incremental increases in drug costs between matched and unmatched therapies were lower for earlier- compared with later-line therapy (+$27,000 v +$43,000, respectively). Conclusion Matched therapy was associated with longer TTF, increased OS, and manageable incremental cost increases compared with unmatched therapy. Most of these increased costs were a result of the longer duration of therapy rather than higher monthly drug costs. The benefits of matching were numerically greater in earlier versus later lines of therapy, which is consistent with the value of early use of CGP.
Enhanced Activity of Alcohol Dehydrogenase in Porous Silica Nanosheets with Wide Size Distributed Mesopores
Authors: Sun Jiao , Zhang Dao , Zhao Wenli , Ji Qingmin , Ariga Katsuhiko 
Published: November 2018

Abstract
Optimized pore size is essential for maximizing the encapsulation efficiency of molecules in solid supports. In this work, we prepared porous silica nanosheets with mesopore in the size range from several to dozens of nanometers, which may provide suitable spaces for loading of various molecules. Without any surface modification, the porous silica nanosheets show excellent immobilization capability (27 wt%) of enzymes with large molecular sizes (&gt;10 nm). An enhanced activity of alcohol dehydrogenase (ADH) in the porous silica nanosheets was also achieved in compared with free ADH or ADH in mesoporous silica nanoparticles with average pore size of 12 nm. In addition, this ADH-silica nanosheets system showed effective catalytic performance not only with pure ethanol, but also alcohol drinks with complicated gradients or after relative harsh treatments. The efficient supporting of this inorganic porous structure to enzymes might also lead to its potentials for other biocatalysis, biosensing and enzymatic determination of alcohols etc.
Formal Synthesis of Borrelidin: A Highly Enantio- and Diastereoselective Access to the Morken’s C2–C12 Intermediate
Authors: Gembus Vincent , Karmazin Lydia , Uguen Daniel , Zoller Thomas 
Published: November 2018

Abstract
In contrast to methyl and isobutyl phenyl sulfone, condensing under basic conditions higher alkyl sulfones and trans-2,3-epoxy-butanol 13c (or its O-benzyl and O-silyl derivatives) proved unfeasible, a difficulty that was overcome by using mono ethers of trans-2,3-epoxy-butane-1,4-diol 35c as the electrophilic reagents. Thus, adding excess BuLi to a mixture of the benzyl ether 35b and sulfone ent-12a, a stereodiad sulfone prepared in pure state from the R-Roche ester, via the O-trityloxy-sulfone ent-12c (X-ray), gave, after elimination by column chromatography of the side-formed regioisomer, a diol-sulfone that was next converted to sulfone 20 by means of conventional functional-group modifications. Reacting likewise this sulfone with the parent O-PMB derivative 35a, and then proceeding to the same purification process and function adjustment, delivered the title fragment in virtually pure state.
Raylı sistem yatırımlarının emlak vergilerine etkisi ve mekânsal değişim potansiyellerinin değerlendirilmesi: Kazlıçeşme–Söğütlüçeşme Metro Hattı örneği
Authors: Gulhan Gorkem 
Published: November 2018

The rail system generates an increase in accessibility by reducing transport costs and travel times. It also has an economically positive return to urban areas for public transport investments. Such public transportation investments; it is important for the planning process to know the effects of changes in land use, income, employment, intensity and monetary values. In this study, for the "Kazlıçeşme - Söğütlüçeşme Subway Line (1st Stage)", taxable gains for the years 2022-2038 are explained and linear increase rates are found. Areas with potential for real estate investment and transformation around the stations were examined and the exchange potentials and land use possibilities of residential areas were investigated. According to the findings of the study, the increase in real estate tax will reach up to four times; at the same time it was determined that there would be an increase in land-use attraction in the recreation, commercial and residential etc. areas around 14 stations.Extended English summary is in the end of Full Text PDF (TURKISH) file. ÖzetRaylı sistem toplu taşıma yatırımlarının kentsel alanlara ekonomik açıdan pozitif getirileri olmakla birlikte, ulaşım maliyetlerinin ve seyahat zamanlarının azalmasını sağlayarak erişilebilirlik artışı oluşturmaktadır. Bu tür kamu ulaşım yatırımlarının; arazi kullanım, gelir, istihdam, yoğunluk ve parasal değerlerde meydana gelen değişimler açısından etkilerinin bilinmesi planlama süreci için önemlidir. Bu çalışmada, “Kazlıçeşme – Söğütlüçeşme Metro Hattı (1. Aşama)” için 2022-2038 yılları arası vergisel kazanımlar açıklanmış ve doğrusal artış oranları bulunmuştur. İstasyonların çevresindeki gayrimenkul yatırım ve dönüşüm potansiyeli bulunan alanlar incelenmiş ve konut alanlarının değişim potansiyelleri ile arazi kullanım olanakları araştırılmıştır.Çalışma bulgularına göre emlak vergisinin 2019 yılından 2022 yılına kadar 4 kata yakın artış yaşayacağı ve 14 istasyon çevresindeki rekreasyon, ticaret ve konut alanlarında arazi kullanım çekiciliği artışı doğacağı devamla potansiyel konut alanı, ticaret alanı, kentsel rekreasyon alanları ve ulaşım yatırımları önerileri oluşturulabileceği tespit edilmiştir.
Survival mechanisms to selective pressures and implications
Authors: Xie Songbo , Liu Min 
Published: November 2018

AbstractOrganisms have evolved a spectrum of strategies that facilitate survival in the face of adverse environmental conditions. In order to make full use of the unfavorable resources of nature, human beings usually impose selective pressures to breed phenotypic traits that can survive in adverse environments. Animals are frequently under attack by biotic stress, such as bacterial and viral infections, while plants are more often subjected to abiotic stress, including high salinity, drought, and cold. In response to these diverse stresses, animals and plants initiate wide-ranging changes in gene expression by altering regulation of transcriptional and post-transcriptional activities. Recent studies have identified a number of key responsive components that promote survival of animals and plants in response to biotic and abiotic stresses. Importantly, with recent developments in genome-editing technology based on the CRISPR/Cas9 system, manipulation of genetic elements to generate stress-resistant animals and plants has become both feasible and cost-effective. Herein, we review important mechanisms that govern the response of organisms to biotic and abiotic stresses with the aim of applying our understanding to the agriculture and animal husbandry industries.
Antihyperglycemic and antihyperlipidemic effects of low-molecular-weight carrageenan in rats
Authors: Qiu Xia , Zhong Wenwen 
Published: November 2018

AbstractThis study investigated the antihyperglycemic and antihyperlipidemic effects of low-molecular-weight carrageenan (LC) on rats fed a high-fat diet. Wistar rats were divided into five groups: normal control group (NC), high-fat diet control group (HC), carrageenan-treated control group (CC), 1% LC group (1% LC), and 3% LC-groups (3% LC). Body weight, food intake, fecal weight, blood glucose, and serum lipid levels were measured. After 30 days, body weight significantly decreased in the LC-treated groups than in the HC group. Moreover, in the LC-treated groups, postprandial blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels decreased, whereas high-density lipoprotein cholesterol (HDL-C) levels increased. From this study, our data suggest that LC has antihyperglycemic and hypolipidemic effects when compared to carrageenan, likely related to its increased absorption due to its lower molecular weight.
Modelling Porosity Permeability of Ceramic Tiles using Fuzzy Taguchi Method
Authors: Kokcam Abdullah Hulusi , Uygun Özer , Taskin Mehmet Fatih , Demir Halil Ibrahim , Demir Zeynep 
Published: November 2018

Abstract
Taguchi experiment design in quality development studies, is an approach to engineering that supports research and development, product design and product development activities by enabling fewer trials of experiments to determine the best combinations of inputs that affect the outcome. In this study, the factors affecting the porosity were studied in a firm that produces ceramic tile. There were 6 factors considered to be important in total and 2 levels in each factor. L8 orthogonal array were used during the experiment design, which proposes 8 experiment types with different factor levels. The results of the experiments were analyzed so that important factors were determined. Significance of factors were tested by ANOVA and 4 of them were found to be significant. These factors were fuzzified by assessing the factors using linguistic expressions and then triangular fuzzy numbers. A model with 4 inputs and 1 output was built and 34 rules were generated for this model. The developed model was shown to be a useful approach in modeling the porosity permeability of ceramic tiles.
Brauchen wir zur Moralbegründung eine „Metanorm“?
Authors: Hoerster Norbert 
Published: November 2018

Abstract
Peter Stemmer advocates a new foundation of morality. He claims that any moral principle is justified only if every person to whom the principle applies consents to it on the basis of his or her own interests. But how can this ‘metanorm’ of unanimous consent be justified? Since Stemmer decisively rejects all objectivist foundations of morality, the only justification for his ‘metanorm’ can again be nothing but a unanimous consent. Through numerous examples I hope to have shown in my article that the alleged connexion of all our moral demands with a general, unanimous consent is not realistic – no matter whether these demands are based on our spontaneous or on our well considered attitudes. And this holds no less for legal norms with their hard sanctions than for moral principles.
Der Status von Peter Stemmers Metaethik
Authors: Wendelborn Christian 
Published: November 2018

AbstractPeter Stemmer provides a moral theory that construes moral normativity and correlated phenomenona as essentially constituted by sanctions. Neither Stemmer nor his critics reflect sufficiently on the metaethical status of these claims, even though it is important to be clear about this status to evaluate the approach. I argue that there are two different readings of the theory: Either the “Sanktionstheorie” is a kind ofdescriptivemetaethical theory or it is what I call aconstructive(orrevisionary) theory. Stemmer’s approach is better understood as a constructive metaethical theory, whereas critics mainly focus on a descriptive reading.
Mathematical modelling of platelet rich plasma clotting. Pointwise unified model
Authors: Andreeva Anna A. , Anand Mohan , Lobanov Alexey I. , Nikolaev Andrey V. , Panteleev Mikhail A. , Susree Modepalli 
Published: November 2018

AbstractThe mechanistic modelling of blood clotting and fibrin-polymer mesh formation is of significant value for medical and biophysics applications. This paper presents a combination of two pointwise kinetic models represented by system of ODEs. One of them represents the reaction dynamics of clotting factors including the role of the platelet membranes. The second one describes the fibrin-polymer formation as a multistage polymerization process with a sol-gel transition at the final stage. Complex-value second order Rosenbrock method (CROS) is employed for the computational experiments. A sensitivity analysis method built into the computational scheme helps clarify non-evident dependencies in the exhaustive system of ODEs. The unified model was primarily verified using conditions of factor VII deficiency. The model, however requires a significant effort to be tested against experimental data available.
Stochastic modelling of age-structured population with time and size dependence of immigration rate
Authors: Pichugin Boris J. , Pertsev Nikolai V. , Topchii Valentin A. , Loginov Konstantin K. 
Published: November 2018

Abstract
A stochastic age-structured population model with immigration of individuals is considered. We assume that the lifespan of each individual is a random variable with a distribution function which may differ fromthe exponential one. The immigration rate of individuals depends on the time and total population size. Upper estimates for the mean and variance of the population size are established based on the theory of branching processes with constant immigration rate. A Monte Carlo simulation algorithm of population dynamics is developed. The results of numerical experiments with the model are presented.
Top-down and Bottom-up Regulated Auditory Phantom Perception
Authors: Vanneste Sven , Alsalman Ola , De Ridder Dirk 
Published: November 2018

Auditory phantom percepts such as tinnitus are associated with auditory deafferentation. The idea is that auditory deafferentation limits the amount of information the brain can acquire to make sense of the world. Because of this, auditory deafferentation increases the uncertainty of the auditory environment. To minimize uncertainty, the deafferented brain will attempt to obtain or fill in the missing information. A proposed multiphase compensation model suggests two distinct types of bottom-up related tinnitus: an auditory cortex related tinnitus and a parahippocampal cortex related tinnitus. The weakness of this model is that it cannot explain why some people without hearing loss develop tinnitus, whereas conversely others with hearing loss do not develop tinnitus. In this human study, we provide evidence for a top-down type of tinnitus associated with a deficient noise-cancelling mechanism. A total of 72 participants (age: 40.96 ± 7.67 years; males: 48; females: 24) were recruited for this study. We demonstrate that top-down related tinnitus is related to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex. This is in accordance with the idea that tinnitus can have different generators as proposed in a recent model that suggests that different compensation mechanisms at a cortical level can be linked to phantom percepts.SIGNIFICANCE STATEMENTChronic tinnitus affects 15% of the population worldwide. The term “tinnitus” however represents a highly heterogeneous condition, as evidenced by the fact that there are no effective treatments or even an adequate understanding of the underlying neural mechanisms. Consistent with this idea, our research shows that tinnitus indeed has different subtypes related to hearing loss. In a human study tightly controlled for hearing loss, we establish a tinnitus subtype associated with a deficient top-down noise-cancelling mechanism, which distinguishes it from bottom-up subtypes. We demonstrate that top-down related tinnitus relates to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex, whereas bottom-up tinnitus instead relates to changes in the parahippocampal cortex.
Voltage-Independent SK-Channel Dysfunction Causes Neuronal Hyperexcitability in the Hippocampus ofFmr1Knock-Out Mice
Authors: Deng Pan-Yue , Carlin Dan , Oh Young Mi , Myrick Leila K. , Warren Stephen T. , Cavalli Valeria , Klyachko Vitaly A. 
Published: November 2018

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K+)-channel dysfunction in hyperexcitability of CA3 pyramidal neurons inFmr1knock-out (KO) mice. We observed a reduction of voltage-independent small conductance calcium (Ca2+)-activated K+(SK) currents in both male and female mice, leading to decreased action potential (AP) threshold and reduced medium afterhyperpolarization. These SK-channel-dependent deficits led to markedly increased AP firing and abnormal input–output signal transmission of CA3 pyramidal neurons. The SK-current defect was mediated, at least in part, by loss of FMRP interaction with the SK channels (specifically the SK2 isoform), without changes in channel expression. Intracellular application of selective SK-channel openers or a genetic reintroduction of an N-terminal FMRP fragment lacking the ability to associate with polyribosomes normalized all observed excitability defects in CA3 pyramidal neurons ofFmr1KO mice. These results suggest that dysfunction of voltage-independent SK channels is the primary cause of CA3 neuronal hyperexcitability inFmr1KO mice and support the critical translation-independent role for the fragile X mental retardation protein as a regulator of neural excitability. Our findings may thus provide a new avenue to ameliorate hippocampal excitability defects in FXS.SIGNIFICANCE STATEMENTDespite two decades of research, no effective treatment is currently available for fragile X syndrome (FXS). Neuronal hyperexcitability is widely considered one of the hallmarks of FXS. Excitability research in the FXS field has thus far focused primarily on voltage-gated ion channels, while contributions from voltage-independent channels have been largely overlooked. Here we report that voltage-independent small conductance calcium-activated potassium (SK)-channel dysfunction causes hippocampal neuron hyperexcitability in the FXS mouse model. Our results support the idea that translation-independent function of fragile X mental retardation protein has a major role in regulating ion-channel activity, specifically the SK channels, in hyperexcitability defects in FXS. Our findings may thus open a new direction to ameliorate hippocampal excitability defects in FXS.