bluuebunny/crossref_metadata_2025 huggingface dataset:
Physics of “Cold” Disk Accretion onto Black Holes Driven by Magnetized Winds
Authors: Bogovalov Sergey
Published: January 2019

Disk accretion onto black holes is accompanied by collimated outflows (jets). In active galactic nuclei (AGN), the kinetic energy flux of the jet (jet power or kinetic luminosity) may exceed the bolometric luminosity of the disk by a few orders of magnitude. This may be explained in the framework of the so called “cold” disk accretion. In this regime of accretion, the disk is radiatively inefficient because practically all the energy released at the accretion is carried out by the magnetized wind. This wind also provides efficient loss of the angular momentum by the matter in the disk. In this review, the physics of the accretion driven by the wind is considered from first principles. It is shown that the magnetized wind can efficiently carry out angular momentum and energy of the matter of the disk. The conditions when this process dominates conventional loss of the angular momentum due to turbulent viscosity are discussed. The “cold” accretion occurs when the viscous stresses in the disk can be neglected in comparison with impact of the wind on the accretion. Two problems crucial for survival of the model of “cold” accretion are considered. The first one is existence of the magnetohydrodynamical solutions for disk accretion purely due to the angular momentum loss by the wind. Another problem is the ability of the model to reproduce observations which demonstrate existence of the sources with kinetic power of jets 2–3 orders of magnitude exceeding the bolometric luminosity of disks. The solutions of the problem in similar prescriptions and numerical solutions without such an assumption are discussed. Calculations of the “unavoidable” radiation from the “cold” disk and the ratio of the jet power of the SMBH to the bolometric luminosity of the accretion disk around a super massive black hole are given in the framework of the Shakura and Sunyaev paradigm of an optically thick α -disk. The exploration of the Fundamental Plane of Black Holes allows us to obtain semi empirical equations that determine the bolometric luminosity and the ratio of the luminosities as functions of the black hole mass and accretion rate.
Genomic Enhancers in Brain Health and Disease
Authors: Carullo Nancy V. N. , Day Jeremy J.
Published: January 2019

Enhancers are non-coding DNA elements that function in cis to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate regulation of these intricate expression programs across different neuronal classes gives rise to an incredible cellular and functional diversity. Newly developed technologies have recently allowed more accurate enhancer mapping and more sophisticated enhancer manipulation, producing rapid progress in our understanding of enhancer biology. Furthermore, identification of disease-linked genetic variation in enhancer regions has highlighted the potential influence of enhancers in brain health and disease. This review outlines the key role of enhancers as transcriptional regulators, reviews the current understanding of enhancer regulation in neuronal development, function and dysfunction and provides our thoughts on how enhancers can be targeted for technological and therapeutic goals.
A Sequence-Based Novel Approach for Quality Evaluation of Third-Generation Sequencing Reads
Authors: Zhang Wenjing , Huang Neng , Zheng Jiantao , Liao Xingyu , Wang Jianxin , Li Hong-Dong
Published: January 2019

The advent of third-generation sequencing (TGS) technologies, such as the Pacific Biosciences (PacBio) and Oxford Nanopore machines, provides new possibilities for contig assembly, scaffolding, and high-performance computing in bioinformatics due to its long reads. However, the high error rate and poor quality of TGS reads provide new challenges for accurate genome assembly and long-read alignment. Efficient processing methods are in need to prioritize high-quality reads for improving the results of error correction and assembly. In this study, we proposed a novel Read Quality Evaluation and Selection Tool (REQUEST) for evaluating the quality of third-generation long reads. REQUEST generates training data of high-quality and low-quality reads which are characterized by their nucleotide combinations. A linear regression model was built to score the quality of reads. The method was tested on three datasets of different species. The results showed that the top-scored reads prioritized by REQUEST achieved higher alignment accuracies. The contig assembly results based on the top-scored reads also outperformed conventional approaches that use all reads. REQUEST is able to distinguish high-quality reads from low-quality ones without using reference genomes, making it a promising alternative sequence-quality evaluation method to alignment-based algorithms.
Patterns of Cyclist and Pedestrian Street Crossing Behavior and Safety on an Urban Greenway
Authors: Anderson Christopher E , Zimmerman Amanda , Lewis Skylar , Marmion John , Gustat Jeanette
Published: January 2019

Greenways are linear open spaces, which are often used as trails for pedestrians and cyclists, but junctions with roads are a safety concern and act as a potential impediment to active transportation. This study evaluated crossing behavior patterns and safety at greenway–road junctions in New Orleans, LA. Crossing behaviors, safety and motor vehicle behavior were collected using direct observation methods. Intercept surveys were conducted to assess greenway use and safety perceptions. Logistic and negative binomial regression were used to assess the relationships between crossing signal (rectangular rapid flash beacon) activation and motor vehicle behavior. Fewer unsafe crossings occurred when the crossing signals were activated for cyclists and pedestrians (p-values of 0.001 and 0.01, respectively). There was no association between pedestrian use of crossing signals and motor vehicle stopping behavior but cyclists had significantly higher odds of motor vehicles failing to stop when the signal was activated (OR 5.12, 95% CI 2.86–9.16). The activation of rectangular rapid flash beacons at urban greenway junctions with roads did not influence motor vehicle behavior. Differences in crossing safety by signal use cannot be attributed to the signal’s influence on motor vehicle stopping behavior.
The Short-Term Effects of Ambient Air Pollutants on Childhood Asthma Hospitalization in Taiwan: A National Study
Authors: Kuo Ching-Yen , Chan Chin-Kan , Wu Chiung-Yi , Phan Dinh-Van , Chan Chien-Lung
Published: January 2019

This investigation determined the effects of air pollution on childhood asthma hospitalization in regions with differing air pollution levels in Taiwan over a long time period. Data of childhood hospital admissions for asthma in patients aged 0–18 years and air quality in eight regions for the period 2001–2012 in Taiwan were collected. Poisson generalized linear regression analysis was employed to identify the relative risks of hospitalization due to asthma in children associated with exposure to varying levels of air pollutants with a change in the interquartile range after adjusting for temperature and relative humidity. Particulate matter ≤2.5 μm (PM2.5), particulate matter ≤10 μm (PM10), ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were positively associated with childhood asthma hospitalization, while O3 was negatively associated with childhood asthma hospitalization. SO2 was identified as the most significant risk factor. The relative risks for asthma hospitalization associated with air pollutants were higher among children aged 0–5 years than aged 6–18 years and were higher among males than females. The effects of air pollution on childhood asthma were greater in the higher-level air pollution regions, while no association was observed in the lower-level air pollution regions. These findings may prove important for policymakers involved in implementing policies to reduce air pollution.
Effect of Taekwondo Practice on Cognitive Function in Adolescents with Attention Deficit Hyperactivity Disorder
Authors: Kadri Abdelmotaleb , Slimani Maamer , Bragazzi Nicola , Tod David , Azaiez Fairouz
Published: January 2019

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neuro-developmental/behavioral disorders among adolescents. Sport and physical activity seem to play a major role in the development of cognition, memory, selective attention and motor reaction time, especially among adolescents with ADHD. In this context, the objective of this study was to investigate the effects of a one-and-a-half-year-long Taekwondo (TKD) intervention on cognitive function in adolescents with ADHD. Two cognitive instruments, namely the Stroop and the Ruff 2 and 7 tests, were administered to assess attentional inhibitory control and sustained and selective visual attention, respectively. Comparisons between the TKD and control groups at baseline did not reveal significant differences. For post-test scores, there were statistically significant differences on the Stroop color block test (large effect size or ES = 1.26 [95% confidence interval or CI 0.30–2.22]), the color-word interference test (large ES = 2.16 [95% CI 1.10–3.26]), the interference test (large ES = 1.63 [95% CI 0.62–2.64]) and error (large ES = −2.20 [95% CI −3.31 to −1.10]). Similar trends were reported for the Ruff 2 and 7 automated detection trials (large ES = 2.78 [95% CI 1.55–4.01]), controlled search trials (large ES = 2.56 [95% CI 1.38–3.75]) and total speed (large ES = −2.90 [95% CI −4.15 to −1.64]). In conclusion, TKD practice increased selective attention in adolescents with ADHD. Practitioners should implement martial art programs in their general plans to favorably influence attention and health in adolescents with ADHD.
Effects of Pretreatment Methods of Wheat Straw on Adsorption of Cd(II) from Waterlogged Paddy Soil
Authors: Wu Mengjie , Liu Hongyu , Yang Chunping
Published: January 2019

Two types of pretreatment categories, namely microwave-assisted alkalization and microwave-assisted acid oxidation, were used to synthesize novel wheat straw adsorbents for the effective removal of Cd(II) in simulated waterlogged paddy soil. A systematic adsorption behavior study, including adsorption kinetics and adsorption isotherms was conducted. Results showed that wheat straw pretreated by microwave-assisted soaking of NaOH and ethanol solution obtained the highest Cd(II) removal efficiency of 96.4% at a reaction temperature of 25 ℃, pH of 7.0, initial Cd(II) concentration of 50 mg/L, and adsorbent/adsorbate ratio of 10 g/L. Sequential extraction experiment was carried out to analyze the changes of different of Cd(II) in soil, the aim of which was to study the mobility of Cd(II) and then evaluate the toxicity that Cd(II) might bring to plants. A 60-day incubation was performed to investigate the dynamic variations of soil pH and dissolved organic carbon content over incubation time. Characterization analyses revealed the morphological changes of wheat straw adsorbents, which suggested that those pretreatment methods were of significance. This study provided an environmentally friendly way to reuse agricultural wastes and remedy Cd(II) contaminated soil.
Acute and Chronic Toxicity of Carbamazepine on the Release of Chitobiase, Molting, and Reproduction in Daphnia similis
Authors: Chen Huihui , Gu Xiaohong , Zeng Qingfei , Mao Zhigang
Published: January 2019

As one of the most frequently detected pharmaceutical compounds in aquatic environments, carbamazepine (CBZ) has recently been shown to cause acute and chronic toxicity in a variety of non-target aquatic organisms. However, little is known about the ecotoxicological effects it has on the molting and reproduction of crustaceans. The aim of the present work was to evaluate the acute and chronic toxic responses to CBZ in the crustacean Daphnia similis. After acute exposure (4 days), CBZ did not cause lethal toxicity at the tested concentrations. However, CBZ did inhibit the molting and release of chitobiase at concentrations higher than 6.25 μg/L, with 96 h EC50 (median effective concentration) values of 864.38 and 306.17 μg/L, respectively. The results of chronic exposure showed that the mean number of molts, size of the first brood, mean number of offspring per brood, mean number of broods per female, and total offspring per female decreased significantly with increasing CBZ concentrations. Significant effects of CBZ on the molting or fecundity in D. similis were observed even at concentrations as low as 0.03 μg/L. In conclusion, CBZ can cause inhibition of molting, delayed reproduction, and reduced fecundity in D. similis. CBZ toxicity to D. similis depends on the timing and duration of the exposure. Moreover, our results indicated that CBZ would act as an endocrine disrupter in D. similis, as with vertebrates (e.g., fish).
The Effectiveness of Laser-Assisted Surgical Excision of Leukoplakias and Hyperkeratosis of Oral Mucosa: A Case Series in A Group of Patients
Authors: Lauritano Dorina , Lucchese Alberta , Gabrione Federica , Di Stasio Dario , Silvestre Rangil Javier , Carinci Francesco
Published: January 2019

Introduction: In the different branches of dentistry, the use of laser to solve different clinical situations is increasing due to numerous advantages that have been studied in literature since the 70s. Leucoplakia and hyperkeratosis can benefit from laser-assisted treatment. In most cases biopsy sampling, histological examination and, if no malignant cells are present, the follow-up is needed. However, even if the lesion is free of dysplasia patients often ask to eliminate these white spots that are always a cause of concern. Aim: From these numerous requests comes the idea of setting up a laser-assisted protocol as less invasive as possible to be offered to patients. The aim of the study is to find a laser-assisted protocol for the surgical excision of leucoplakia and hyperkeratosis that can both improve the clinical aspect of the lesion and be sustainable for patients. The null hypothesis has been identified in the following statement: the treatment is effective and efficient at the same time; where effectiveness was tested with the following criteria: size of the lesion, tactile perception, discomfort, pain; and efficiency with the following criteria: pain and discomfort perceived during the treatment. Materials and methods: To collect all data, a specially designed medical record was used. The diode laser was used with a pulsed mode and the maximum power corresponds to 1.8 W. No anaesthesia was used. Before laser-assisted treatment, the fibre was activated and was used with a contact overflowing. Results: Our results show a decrease in the size of the lesion statistically significant. No pain was referred during treatment, except for a slight burning sensation. Conclusion: In conclusion we can state that the treatment is both efficient and effective.
Primary Reason for Drinking Among Current, Former, and Never Flushing College Students
Authors: Oh Sarah Soyeon , Ju Yeong Jun , Lee San , Park Eun-Cheol
Published: January 2019

Alcohol consumption among individuals who experience a flushing response (reddening of the face, nausea, dizziness, headache, anxiety, and increased heartbeat) can result in serious health problems. However, studies on reasons for drinking among flushers, especially in the college context, are limited. Thus, this study investigated the association between primary reason for drinking and alcohol use among a nationally representative sample of current, former, and never flushing college students. The aim was to measure whether college students with current or former experience of facial flushing have different primary reasons for drinking compared to students with no experience of facial flushing. We surveyed and analyzed the data of 4590 students in a nationally representative sample of 82 colleges in South Korea. Multiple regression analysis was used to identify the association between primary reason for drinking and alcohol intake. Alcohol intake was measured using the Alcohol Use Disorders Identification Test (AUDIT). Among 1537 current (33.5%), 152 former (3.3%), and 2901 (63.2%) never flushers, mean AUDIT scores were 7.715 ± 5.434, 11.039 ± 6.405, and 10.465 ± 5.779, respectively. Current flushers had significantly higher AUDIT scores when drinking for pleasure (β = 2.696, p < 0.0001) or stress/depression (β = 2.578, p < 0.0001). Primary reasons for drinking were not associated with alcohol intake for former flushers. Never flushers had significantly higher AUDIT scores when drinking for pleasure (β = 2.696, p < 0.0001), stress/depression (β = 2.578, p < 0.0001), or boredom (β = 0.740, p = 0.029) than peer pressure. Our results suggest that former and never flushers consume higher amounts of alcohol on average than never flushers. For current flushers, drinking for pleasure or stress/depression may increase alcohol intake, while for never flushers, drinking for pleasure, stress/depression, as well as boredom may have the same effect.
Doxing: What Adolescents Look for and Their Intentions
Authors: Chen Mengtong , Cheung Anne Shann Yue , Chan Ko Ling
Published: January 2019

Doxing is a form of cyberbullying in which personal information on others is sought and released, thereby violating their privacy and facilitating further harassment. This study examined adolescents’ doxing participation using a representative sample of 2120 Hong Kong secondary school students. Just over one in 10 had engaged in doxing, and doxing behavior significantly increased the probability of disclosing personal information on others (odds ratio ranged between 2.705 and 5.181). Social and hostile doxing were the two most common forms of doxing. Girls were significantly more likely to conduct social doxing (χ2 = 11.84, p < 0.001), where their target was to obtain social information (χ2 = 4.79, p = 0.029), whereas boys were more likely to engage in hostile doxing aimed at obtaining personally identifiable information (χ2 = 4.31, p = 0.038) and information on others’ current living situations (χ2 = 4.17, p = 0.041). Students who had perpetrated doxing acts were more likely to have experienced information disclosure as victims, perpetrators, or bystanders. Future studies should examine doxing’s impacts and its relationship with other forms of cyberbullying and traditional bullying. Because doxing may lead to on- and off-line harassment, family, adolescents, schools, and communities must work together to develop effective approaches for combating it.
Are Parent-Held Child Health Records a Valuable Health Intervention? A Systematic Review and Meta-Analysis
Authors: Chutiyami Muhammad , Wyver Shirley , Amin Janaki
Published: January 2019

Parent-held child health record (PHCHR), a public health intervention for promoting access to preventive health services, have been in use in many developed and developing countries. This review aimed to evaluate the use of the records toward promoting child health/development. We searched PubMed, PsycINFO, CINAHL, Cochrane Library and Google Scholar to identify relevant articles, of which 32 studies met the inclusion criteria. Due to considerable heterogeneity, findings were narratively synthesised. Outcomes with sufficient data were meta-analysed using a random-effects model. Odds Ratio (OR) was used to compute the pooled effect sizes at 95% confidence interval (CI). The pooled effect of the PHCHR on the utilisation of child/maternal healthcare was not statistically significant (OR = 1.31, 95% CI 0.92–1.88). However, parents who use the record in low- and middle-income countries (LMIC) were approximately twice as likely to adhere to child vaccinations (OR = 1.93, 95% CI 1.01–3.70), utilise antenatal care (OR = 1.60, 95% CI 1.23–2.08), and better breastfeeding practice (OR = 2.82, 95% CI 1.02–7.82). Many parents (average-72%) perceived the PHCHR as useful/important and majority (average-84%) took it to child clinics. Health visitors and nurses/midwives were more likely to use the record than hospital doctors. It is concluded that parents generally valued the PHCHR, but its effect on child health-related outcomes have only been demonstrated in LMIC.
Impacts of Lean Construction on Safety Systems: A System Dynamics Approach
Authors: Wu Xiuyu , Yuan Hongping , Wang Ge , Li Shuquan , Wu Guangdong
Published: January 2019

Lean construction has been viewed as an effective management approach for reducing the occurrence of no-value or destructive activities, such as wasting resources and safety-related accidents. However, few studies have systematically addressed how and to what extent lean construction practices influence construction safety. To bridge this gap, a conceptual model is developed and validated using a system dynamics approach. The construction system in this model comprises four sub-systems (i.e., environment system, equipment system, management system, and employee system). Data were collected from 448 projects in China. Simulations were conducted to determine the correlations between five types of lean tools and the four construction sub-systems. The results show that: (a) 5S management has significant positive impacts on the control of key locations and facilities at construction sites, and contributes to the mitigation of environmental impacts; (b) visual management can significantly improve safety compliance and safety management; (c) just-in-time management has significantly positive influences on the safety facilities layout and formulation of the safety plan; and (d) the Last Planner® System and conference management are effective in improving safety training and the implementation of the safety plan. These findings provide new insights into the use of lean construction for improving construction safety through the implementation of a targeted lean approach.
Abuses and Penalties of a Corporate Tax Inversion
Authors: Yang James G. S. , Lauricella Leonard J. , Aquilino Frank J.
Published: January 2019

There is a serious problem in international taxation today. Many United States (U.S.) multinational corporations have moved abroad to take advantage of a lower tax rate in a foreign country. As a consequence, the tax base in the U.S. has been seriously eroded. This practice is known as “corporate tax inversion”. This paper discusses the abuses and penalties of this phenomenon. It is rooted in some deficiencies in the U.S. tax law. This paper points out that the U.S. has the highest corporate tax rate in the world. It imposes tax on worldwide income. It permits deferral of tax on foreign-sourced income until dividends are repatriated back to the U.S. As a result, it creates tax loopholes. This paper reveals six actual cases of corporate tax inversion. This practice has triggered the Congress to enact §7874, the Internal Revenue Service (IRS) to issue Notices IR 2014-52 and IR 2015-79, and the U.S. Treasury Department to promulgate TD 9761. This paper investigates some details of these penalties. This paper further demonstrates an example in determining the amount of tax savings by engaging in a corporate tax inversion. It also offers many strategies.
Processability and Degradability of PHA-Based Composites in Terrestrial Environments
Authors: Cinelli Patrizia , Seggiani Maurizia , Mallegni Norma , Gigante Vito , Lazzeri Andrea
Published: January 2019

In this work, composites based on poly(3-hydroxybutyrate-3-hydroxyvalerate) (PHB-HV) and waste wood sawdust (SD) fibers, a byproduct of the wood industry, were produced by melt extrusion and characterized in terms of processability, thermal stability, morphology, and mechanical properties in order to discriminate the formulations suitable for injection molding. Given their application in agriculture and/or plant nursery, the biodegradability of the optimized composites was investigated under controlled composting conditions in accordance with standard methods (ASTM D5338-98 and ISO 20200-2004). The optimized PHB-HV/SD composites were used for the production of pots by injection molding and their performance was qualitatively monitored in a plant nursery and underground for 14 months. This study presents a sustainable option of valuation of wood factory residues and lowering the production cost of PHB-HV-based compounds without affecting their mechanical properties, improving their impact resistance and biodegradability rates in terrestrial environments.
Metabolomic Approach in STEMI-Patients Undergoing Left Ventricular Remodeling
Authors: Garcia Gabriel , Chao de la Barca Juan Manuel , Mirebeau-Prunier Delphine , Reynier Pascal , Furber Alain , Prunier Fabrice , Bière Loïc
Published: January 2019

Left ventricular remodeling (LVR) occurring after ST-segment elevation myocardial infarction (STEMI) is frequent and severe. We present a metabolomic approach as an attempt to reveal unknown biomarkers associated with post-STEMI LVR. Out of 192 consecutive patients with successfully revascularized STEMI, 32 presented LVR and were clinically matched with 32 no-LVR patients. They underwent cardiac magnetic resonance at baseline, three months and 12 months. Blood samples were collected during index hospitalization. Creatine kinase (CK) peak and inflammatory markers were higher for LVR patients compared to no-LVR patients (mean 3466 ± 2211 and 2394 ± 1615 UI/L respectively, p = 0.005 for CK peak; mean 35.9 ± 44.3 vs. 21.7 ± 30.4 mg/L respectively, p = 0.020 for C-reactive protein). Leukocyte and neutrophil counts were also higher for LVR patients (mean 12028 ± 2593/mL vs. 10346 ± 3626/mL respectively, p = 0.028 and mean 9035 ± 3036/mL vs. 7596 ± 3822/mL respectively, p < 0.001). For metabolomic analysis, sphingomyelin C20:2 and symmetrical dimethylarginine were higher for LVR patients, but did not reach significance after the correction for the alpha risk. The metabolomic approach did not discriminate patients with and without LVR. However, common parameters that focus on infarction severity, such as infarct size and inflammatory markers, differed between the groups.
Hepatocyte Growth Factor: A Microenvironmental Resource for Leukemic Cell Growth
Authors: Giannoni Paolo , Fais Franco , Cutrona Giovanna , Totero Daniela
Published: January 2019

Chronic lymphocytic leukemia (CLL) is characterized by the progressive expansion of B lymphocytes CD5+/CD23+ in peripheral blood, lymph-nodes, and bone marrow. The pivotal role played by the microenvironment in disease pathogenesis has become increasingly clear. We demonstrated that bone marrow stromal cells and trabecular bone cells sustain survival of leukemic B cells through the production of hepatocyte growth factor (HGF). Indeed the trans-membrane kinase receptor for HGF, c-MET, is expressed on CLL cells and STAT3 TYR705 or AKT phosphorylation is induced after HGF/c-MET interaction. We have further observed that c-MET is also highly expressed in a peculiar type of cells of the CLL-microenvironment showing nurturing features for the leukemic clone (nurse-like cells: NLCs). Since HGF treatment drives monocytes toward the M2 phenotype and NLCs exhibit features of tumor associated macrophages of type 2 we suggested that HGF, released either by cells of the microenvironment or leukemic cells, exerts a double effect: i) enhances CLL cells survival and ii) drives differentiation of monocytes-macrophages to an oriented immune suppressive phenotype. We here discuss how paracrine, but also autocrine production of HGF by malignant cells, may favor leukemic clone expansion and resistance to conventional drug treatments in CLL, as well as in other hematological malignancies. Novel therapeutic approaches aimed to block HGF/c-MET interactions are further proposed.
miRNA Polymorphisms and Risk of Cardio-Cerebrovascular Diseases: A Systematic Review and Meta-Analysis
Authors: Bastami Milad , Choupani Jalal , Saadatian Zahra , Zununi Vahed Sepideh , Mansoori Yaser , Daraei Abdolreza , Samadi Kafil Hossein , Masotti Andrea , Nariman-saleh-fam Ziba
Published: January 2019

Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.
High-Throughput Omics and Statistical Learning Integration for the Discovery and Validation of Novel Diagnostic Signatures in Colorectal Cancer
Authors: Long Nguyen Phuoc , Park Seongoh , Anh Nguyen Hoang , Nghi Tran Diem , Yoon Sang Jun , Park Jeong Hill , Lim Johan , Kwon Sung Won
Published: January 2019

The advancement of bioinformatics and machine learning has facilitated the discovery and validation of omics-based biomarkers. This study employed a novel approach combining multi-platform transcriptomics and cutting-edge algorithms to introduce novel signatures for accurate diagnosis of colorectal cancer (CRC). Different random forests (RF)-based feature selection methods including the area under the curve (AUC)-RF, Boruta, and Vita were used and the diagnostic performance of the proposed biosignatures was benchmarked using RF, logistic regression, naïve Bayes, and k-nearest neighbors models. All models showed satisfactory performance in which RF appeared to be the best. For instance, regarding the RF model, the following were observed: mean accuracy 0.998 (standard deviation (SD) < 0.003), mean specificity 0.999 (SD < 0.003), and mean sensitivity 0.998 (SD < 0.004). Moreover, proposed biomarker signatures were highly associated with multifaceted hallmarks in cancer. Some biomarkers were found to be enriched in epithelial cell signaling in Helicobacter pylori infection and inflammatory processes. The overexpression of TGFBI and S100A2 was associated with poor disease-free survival while the down-regulation of NR5A2, SLC4A4, and CD177 was linked to worse overall survival of the patients. In conclusion, novel transcriptome signatures to improve the diagnostic accuracy in CRC are introduced for further validations in various clinical settings.
Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease
Authors: Chao Hsu-Wen , Chao Shi-Wei , Lin Heng , Ku Hui-Chen , Cheng Ching-Feng
Published: January 2019

Industrialized society-caused dysregular human behaviors and activities such as overworking, excessive dietary intake, and sleep deprivation lead to perturbations in the metabolism and the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, affects around 30% and 25% of people in Western and Asian countries, respectively, which leads to numerous medical costs annually. Insulin resistance is the major hallmark of NAFLD and is crucial in the pathogenesis and for the progression from NAFLD to non-alcoholic steatohepatitis (NASH). Excessive dietary intake of saturated fats and carbohydrate-enriched foods contributes to both insulin resistance and NAFLD. Once NAFLD is established, insulin resistance can promote the progression to the more severe state of liver endangerment like NASH. Here, we review current and potential studies for understanding the complexity between insulin-regulated glycolytic and lipogenic homeostasis and the underlying causes of NAFLD. We discuss how disruption of the insulin signal is associated with various metabolic disorders of glucoses and lipids that constitute both the metabolic syndrome and NAFLD.
Selection of Membrane RNA Aptamers to Amyloid Beta Peptide: Implications for Exosome-Based Antioxidant Strategies
Authors: Janas Teresa , Sapoń Karolina , Stowell Michael H. B. , Janas Tadeusz
Published: January 2019

The distribution of amyloid beta peptide 42 (Aβ42) between model exosomal membranes and a buffer solution was measured. The model membranes contained liquid-ordered regions or phosphatidylserine. Results demonstrated that up to ca. 20% of amyloid peptide, generated in the plasma (or intracellular) membrane as a result of proteolytic cleavage of amyloid precursor proteins by β- and γ-secretases, can stay within the membrane milieu. The selection of RNA aptamers that bind to Aβ42 incorporated into phosphatidylserine-containing liposomal membranes was performed using the selection-amplification (SELEX) method. After eight selection cycles, the pool of RNA aptamers was isolated and its binding to Aβ42-containing membranes was demonstrated using the gel filtration method. Since membranes can act as a catalytic surface for Aβ42 aggregation, these RNA aptamers may inhibit the formation of toxic amyloid aggregates that can permeabilize cellular membranes or disrupt membrane receptors. Strategies are proposed for using functional exosomes, loaded with RNA aptamers specific to membrane Aβ42, to reduce the oxidative stress in Alzheimer’s disease and Down’s syndrome.
The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis
Authors: Moskot Marta , Jakóbkiewicz-Banecka Joanna , Kloska Anna , Piotrowska Ewa , Narajczyk Magdalena , Gabig-Cimińska Magdalena
Published: January 2019

Obstacles to effective therapies for mucopolysaccharidoses (MPSs) determine the need for continuous studies in order to enhance therapeutic strategies. Dimethyl sulfoxide (DMSO) is frequently utilised as a solvent in biological studies, and as a vehicle for drug therapy and the in vivo administration of water-insoluble substances. In the light of the uncertainty on the mechanisms of DMSO impact on metabolism of glycosaminoglycans (GAGs) pathologically accumulated in MPSs, in this work, we made an attempt to investigate and resolve the question of the nature of GAG level modulation by DMSO, the isoflavone genistein solvent employed previously by our group in MPS treatment. In this work, we first found the cytotoxic effect of DMSO on human fibroblasts at concentrations above 3%. Also, our results displayed the potential role of DMSO in the regulation of biological processes at the transcriptional level, then demonstrated a moderate impact of the solvent on GAG synthesis. Interestingly, alterations of lysosomal ultrastructure upon DMSO treatment were visible. As there is growing evidence in the literature that DMSO can affect cellular pathways leading to numerous changes, it is important to expand our knowledge concerning this issue.
G-Protein Coupled Estrogen Receptor in Breast Cancer
Authors: Hsu Li-Han , Chu Nei-Min , Lin Yung-Feng , Kao Shu-Huei
Published: January 2019

The G-protein coupled estrogen receptor (GPER), an alternate estrogen receptor (ER) with a structure distinct from the two canonical ERs, being ERα, and ERβ, is expressed in 50% to 60% of breast cancer tissues and has been presumed to be associated with the development of tamoxifen resistance in ERα positive breast cancer. On the other hand, triple-negative breast cancer (TNBC) constitutes 15% to 20% of breast cancers and frequently displays a more aggressive behavior. GPER is prevalent and involved in TNBC and can be a therapeutic target. However, contradictory results exist regarding the function of GPER in breast cancer, proliferative or pro-apoptotic. A better understanding of the GPER, its role in breast cancer, and the interactions with the ER and epidermal growth factor receptor will be beneficial for the disease management and prevention in the future.
Downregulation of Pro-Inflammatory and Pro-Angiogenic Pathways in Prostate Cancer Cells by a Polyphenol-Rich Extract from Olive Mill Wastewater
Authors: Baci Denisa , Gallazzi Matteo , Cascini Caterina , Tramacere Matilde , De Stefano Daniela , Bruno Antonino , Noonan Douglas M. , Albini Adriana
Published: January 2019

Dietary phytochemicals are particularly attractive for chemoprevention and are able to modulate several signal transduction pathways linked with cancer. Olive oil, a major component of the Mediterranean diet, is an abundant source of phenolic compounds. Olive oil production is associated with the generation of a waste material, termed ‘olive mill wastewater’ (OMWW) that have been reported to contain water-soluble polyphenols. Prostate cancer (PCa) is considered as an ideal cancer type for chemopreventive approaches, due to its wide incidence but relatively long latency period and progression time. Here, we investigated activities associated with potential preventive properties of a polyphenol-rich olive mill wastewater extract, OMWW (A009), on three in vitro models of PCa. A009 was able to inhibit PCa cell proliferation, adhesion, migration, and invasion. Molecularly, we found that A009 targeted NF-κB and reduced pro-angiogenic growth factor, VEGF, CXCL8, and CXCL12 production. IL-6/STAT3 axis was also regulated by the extract. A009 shows promising properties, and purified hydroxytyrosol (HyT), the major polyphenol component of A009, was also active but not always as effective as A009. Finally, our results support the idea of repositioning a food waste-derived material for nutraceutical employment, with environmental and industrial cost management benefits.
Genome-Wide Identification and Characterization of the AREB/ABF/ABI5 Subfamily Members from Solanum tuberosum
Authors: Liu Tengfei , Zhou Tingting , Lian Meiting , Liu Tiantian , Hou Juan , Ijaz Raina , Song Botao
Published: January 2019

Abscisic acid (ABA) plays crucial roles in plant development and adaption to environmental stresses. The ABA-responsive element binding protein/ABRE-binding factor and ABA INSENSITIVE 5 (AREB/ABF/ABI5) gene subfamily members, which belong to the basic domain/leucine zipper (bZIP) transcription factors family, participate in the ABA-mediated signaling pathway by regulating the expression of their target genes. However, information about potato (Solanum tuberosum) AREB/ABF/ABI5 subfamily members remains scarce. Here, seven putative AREB/ABF/ABI5 members were identified in the potato genome. Sequences alignment revealed that these members shared high protein sequence similarity, especially in the bZIP region, indicating that they might possess overlapping roles in regulating gene expression. Subcellular localization analysis illustrated that all seven AREB/ABF/ABI5 members were localized in the nucleus. Transactivation activity assays in yeast demonstrated that these AREB/ABF/ABI5 members possessed distinct transcriptional activity. Electrophoretic mobility shift assays (EMSA) confirmed that all of these AREB/ABF/ABI5 members could have an affinity to ABRE in vitro. The expression patterns of these AREB/ABF/ABI5 genes showed that they were in response to ABA or osmotic stresses in varying degrees. Moreover, most AREB/ABF/ABI5 genes were induced during stolon swelling. Overall, these results provide the first comprehensive identification of the potato AREB/ABF/ABI5 subfamily and would facilitate further functional characterization of these subfamily members in future work.
Fatty Acid Potassium Had Beneficial Bactericidal Effects and Removed Staphylococcus aureus Biofilms while Exhibiting Reduced Cytotoxicity towards Mouse Fibroblasts and Human Keratinocytes
Authors: Kawahara Takayoshi , Takita Miki , Masunaga Akihiro , Morita Hayato , Tsukatani Tadayuki , Nakazawa Kohji , Go Daisuke , Akita Sadanori
Published: January 2019

Wounds frequently become infected or contaminated with bacteria. Potassium oleate (C18:1K), a type of fatty acid potassium, caused >4 log colony-forming unit (CFU)/mL reductions in the numbers of Staphylococcus aureus and Escherichia coli within 10 min and a >2 log CFU/mL reduction in the number of Clostridium difficile within 1 min. C18:1K (proportion removed: 90.3%) was significantly more effective at removing Staphylococcus aureus biofilms than the synthetic surfactant detergents sodium lauryl ether sulfate (SLES) (74.8%, p < 0.01) and sodium lauryl sulfate (SLS) (78.0%, p < 0.05). In the WST (water-soluble tetrazolium) assay, mouse fibroblasts (BALB/3T3 clone A31) in C18:1K (relative viability vs. control: 102.8%) demonstrated a significantly higher viability than those in SLES (30.1%) or SLS (18.1%, p < 0.05). In a lactate dehydrogenase (LDH) leakage assay, C18:1K (relative leakage vs. control: 108.9%) was found to be associated with a significantly lower LDH leakage from mouse fibroblasts than SLES or SLS (720.6% and 523.4%, respectively; p < 0.05). Potassium oleate demonstrated bactericidal effects against various species including Staphylococcus aureus, Escherichia coli, Bacillus cereus, and Clostridium difficile; removed significantly greater amounts of Staphylococcus aureus biofilm material than SLES and SLS; and maintained fibroblast viability; therefore, it might be useful for wound cleaning and peri-wound skin.
Presence of Round Cells Proteins do not Interfere with Identification of Human Sperm Proteins from Frozen Semen Samples by LC-MS/MS
Authors: Panner Selvam Manesh Kumar , Agarwal Ashok , Dias Tânia R. , Martins Ana D. , Samanta Luna
Published: January 2019

In sperm proteomic experiments round cells and leukocyte proteins are profiled along with sperm proteome. The influence of round cell and leukocyte proteins on the sperm proteome has not been investigated. The objective of this study was to identify if the proteins from round cells, including leukocytes, interfere with the proteomic analysis of spermatozoa in frozen semen samples. Proteomic profiling of sperm was performed using liquid chromatography-tandem mass spectrometry in four groups: Group 1 contained neat semen with round cells and leukocytes ≥ 1 × 106/mL, group 2 contained neat semen with round cells ≥ 1 × 106/mL that was processed by 65% density gradient to remove the round cells and leukocytes, group 3 contained neat semen with round cells < 1 × 106/mL, and group 4 contained neat semen with round cells < 1 × 106/mL that was processed by 65% density gradient to remove the round cells. Pure leukocyte culture was used as control group. A total of 1638, 1393, 1755, and 1404 proteins were identified in groups 1, 2, 3, and 4, respectively. Comparative analysis of group 1 vs. 3 revealed 26 (1.18%) differentially expressed proteins (DEPs). On the other hand, only 6 (0.31%) DEPs were observed with group 2 vs. 4. Expression of these DEPs were either absent or very low in the control group. The results of our proteomics analysis failed to show any influence of non-spermatogenic round cell proteins on sperm proteome identification. These results validate the use of neat semen samples for sperm proteomic studies.
c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
Authors: Leonetti Erica , Gesualdi Luisa , Corano Scheri Katia , Dinicola Simona , Fattore Luigi , Masiello Maria Grazia , Cucina Alessandra , Mancini Rita , Bizzarri Mariano , Ricci Giulia , Catizone Angela
Published: January 2019

c-MET pathway over-activation is the signature of malignancy acquisition or chemotherapy resistance of many cancers. We recently demonstrated that type II Testicular Germ Cell Tumours (TGCTs) express c-MET receptor. In particular, we elucidated that the non-seminoma lesions express c-MET protein at higher level, compared with the seminoma ones. In line with this observation, NTERA-2 clone D1 (NT2D1) non-seminoma cells increase their proliferation, migration and invasion in response to Hepatocyte Growth Factor (HGF). One of the well-known adaptor-proteins belonging to c-MET signaling cascade is c-Src. Activation of c-Src is related to the increase of aggressiveness of many cancers. For this reason, we focused on the role of c-Src in c-MET-triggered and HGF-dependent NT2D1 cell activities. In the present paper, we have elucidated that this adaptor-protein is involved in HGF-dependent NT2D1 cell proliferation, migration and invasion, since Src inhibitor-1 administration abrogates these responses. Despite these biological evidences western blot analyses have not revealed the increase of c-Src activation because of HGF administration. However, notably, immunofluorescence analyses revealed that cytoplasmic and membrane-associated localization of c-Src shifted to the nuclear compartment after HGF stimulation. These results shed new light in the modality of HGF-dependent c-Src recruitment, and put the basis for novel investigations on the relationship between c-Src, and TGCT aggressiveness.
A Small Aromatic Compound Has Antifungal Properties and Potential Anti-Inflammatory Effects against Intestinal Inflammation
Authors: Bortolus Clovis , Billamboz Muriel , Charlet Rogatien , Lecointe Karine , Sendid Boualem , Ghinet Alina , Jawhara Samir
Published: January 2019

Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against C. albicans overgrowth and intestinal inflammation. Substitution on the aromatic ring of DHMB led to a strong decrease in its biological activity against C. albicans. The MIC of DHMB was highly effective at eliminating C. albicans when compared to that of caspofungin or fluconazole. Additionally, DHMB was also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. DHMB was administered to animals at high doses. This compound was not cytotoxic and was well-tolerated. In experimental dextran sodium sulphate (DSS)-induced colitis in mice, DHMB reduced the clinical and histological score of inflammation and promoted the elimination of C. albicans from the gut. This finding was supported by a decrease in aerobic bacteria while anaerobic bacteria populations were re-established in mice treated with DHMB. DHMB is a small organic molecule with antifungal properties and anti-inflammatory activity by exerting protective effects on intestinal epithelial cells.