bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Feel the Knife Pierce You Intensely’: Slayer’s ‘Angel of Death’—Holocaust Representation or Metal Affects?
Authors: Williams Dominic
Published: November 2019

This article tackles a well-known but little-studied phenomenon: the importance of Holocaust themes to heavy metal. The fascination of metal bands with evil and death has until recently been met outside the scene with such reactions as moral panic, disgust or indifference. In the last ten years, however, scholars in an emerging discourse of Metal Studies have attempted to engage more critically with the social and musical dimensions of metal, in order to contextualise and understand its lyrics and imagery. Although a number of writers have touched upon the recurrence of Holocaust imagery, no one has dealt at any length with extreme metal as a form of Holocaust memory. My article focuses on what might be called the founding text of extreme metal, Slayer’s ‘Angel of Death’, which lived up to the sub-genre’s name by pushing both its musical form and its lyrical content beyond previously maintained limits and taboos. It considers the song’s mobilisation of affective intensities as involving problematic politics, but also a challenge to conceptions of Holocaust representation. I consider how affects are evoked by ‘Angel of Death’ through offering readings of the song itself as well as of ways that its reception have been recorded on social media, in concert videos, and reaction videos uploaded to YouTube.
Tomato Natural Resistance Genes in Controlling the Root-Knot Nematode
Authors: El-Sappah Ahmed H. , M. M. Islam , H. El-awady Hamada , Yan Shi , Qi Shiming , Liu Jingyi , Cheng Guo-ting , Liang Yan
Published: November 2019

The root-knot nematode (RKN) is one of the most dangerous and widespread types of nematodes affecting tomatoes. There are few methods for controlling nematodes in tomatoes. Nature resistance genes (R-genes) are important in conferring resistance against nematodes. These genes that confer resistance to the RKN have already been identified as Mi-1, Mi-2, Mi-3, Mi-4, Mi-5, Mi-6, Mi-7, Mi-8, Mi-9, and Mi-HT. Only five of these genes have been mapped. The major problem is that their resistance breaks down at high temperatures. Some of these genes still work at high temperatures. In this paper, the mechanism and characteristics of these natural resistance genes are summarized. Other difficulties in using these genes in the resistance and how to improve them are also mentioned.
A Novel Approach to Isolation and Screening of Calcifying Bacteria for Biotechnological Applications
Authors: Cacchio Paola , Del Gallo Maddalena
Published: November 2019

Bacterial calcium-carbonate precipitation (BCP) has been studied for multiple applications such as remediation, consolidation, and cementation. Isolation and screening of strong calcifying bacteria is the main task of BCP-technique. In this paper, we studied CaCO3 precipitation by different bacteria isolated from a rhizospheric soil in both solid and liquid media. It has been found, through culture-depending studies, that bacteria belonging to Actinobacteria, Gammaproteobacteria, and Alphaproteobacteria are the dominant bacteria involved in CaCO3 precipitation in this environment. Pure and mixed cultures of selected strains were applied for sand biocementation experiments. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analyses of the biotreated samples revealed the biological nature of the cementation and the effectiveness of the biodeposition treatment by mixed cultures. X-ray diffraction (XRD) analysis confirmed that all the calcifying strains selected for sand biocementation precipitated CaCO3, mostly in the form of calcite. In this study, Biolog® EcoPlate is evaluated as a useful method for a more targeted choice of the sampling site with the purpose of obtaining interesting candidates for BCP applications. Furthermore, ImageJ software was investigated, for the first time to our knowledge, as a potential method to screen high CaCO3 producer strains.
Impact of Media Reports and Environmental Pollution on Health and Health Expenditure Efficiency
Authors: Li Ying , Chiu Yung-Ho , Chen Huaming , Lin Tai-Yu
Published: November 2019

Over the past few decades, China’s rapid economic, energy, and industrial developments have caused serious environmental damage. However, as there are large resource, energy use, economic, and environmental damage differences across Chinese regions, the Chinese government is seeking to reduce city pollution across the country. Most previous analyses have only looked at these issues on a single level; for example, the impact of environmental pollution on health, or energy and environmental efficiency analyses, but there have been few studies that have conducted overall analyses. Further, many of the methods that have been used in previous research have employed one-stage radial or non-radial analyses without considering regional differences. Therefore, this paper developed a meta undesirable two-stage EBM DEA model to analyze the energy, environment, health, and media communication efficiencies in 31 Chinese cities, from which it was found that the productivity efficiency in most cities was better than the health treatment efficiencies, the GDP and fixed asset efficiency improvements were small, the air quality index (AQI) and CO2 efficiencies varied widely between the cities, media report and governance inputs were generally inefficient, the birth rate efficiencies were better than the respiratory disease efficiencies, and the technical gap was best in Guangzhou, Shanghai, and Lhasa. Also, it found that high-income cities have a higher technology gap than upper middle–income cities, and media reports efficiency have a high correlation with respiratory diseases and CO2.
Bayesian Spatial Joint Model for Disease Mapping of Zero-Inflated Data with R-INLA: A Simulation Study and an Application to Male Breast Cancer in Iran
Authors: Asmarian Naeimehossadat , Ayatollahi Seyyed Mohammad Taghi , Sharafi Zahra , Zare Najaf
Published: November 2019

Hierarchical Bayesian log-linear models for Poisson-distributed response data, especially Besag, York and Mollié (BYM) model, are widely used for disease mapping. In some cases, due to the high proportion of zero, Bayesian zero-inflated Poisson models are applied for disease mapping. This study proposes a Bayesian spatial joint model of Bernoulli distribution and Poisson distribution to map disease count data with excessive zeros. Here, the spatial random effect is simultaneously considered into both logistic and log-linear models in a Bayesian hierarchical framework. In addition, we focus on the BYM2 model, a re-parameterization of the common BYM model, with penalized complexity priors for the latent level modeling in the joint model and zero-inflated Poisson models with different type of zeros. To avoid model fitting and convergence issues, Bayesian inferences are implemented using the integrated nested Laplace approximation (INLA) method. The models are compared according to the deviance information criterion and the logarithmic scoring. A simulation study with different proportions of zero exhibits INLA ability in running the models and also shows slight differences between the popular BYM and BYM2 models in terms of model choice criteria. In an application, we apply the fitting models on male breast cancer data in Iran at county level in 2014.
Current Effects of Cyanobacteria Toxin in Water Sources and Containers in the Hartbeespoort Dam Area, South Africa
Authors: Mokoena Matodzi Michael , Mukhola Murembiwa Stanley
Published: November 2019

The study investigated the effects of cyanobacteria toxins such as microcystins in water sources and water stored in containers during its blooming and decaying seasons. Samples from water sources and containers near the Hartbeespoort Dam in South Africa were analysed using a microcystin ELIZA test kit. Microcystins were present in water sources used by the community, with an average of 4.3 μg/L in communal tap water and 4.8 μg/L in the water stored in tanks. The concentration of microcystins was lower in groundwater in the decaying season (0.38 μg/L) than in the blooming season (1.4 μg/L). Although microcystins were present in the storage containers, the average levels in all water samples were below the acceptable limit of 1 μg/L. The present study confirmed the presence of microcystins in the water storage containers. Therefore, it is suggested that water used for drinking from community water sources should be treated before storage to eliminate microcystins.
Competitive Inhibitory Effect of Calcium Polypeptides on Cd Enrichment of Brassia campestris L.
Authors: Chen Hongbing , Shu Fangfang , Yang Sheng , Li Yadong , Wang Shilin
Published: November 2019

Most cadmium-polluted farmland and land surrounding mining areas are difficult to repair and control, seriously threatening the food safety of the crops planted in these regions. As an essential element for plant growth, calcium plays an important role in stress-resistance regulation. In this study, Brassia campestris L. was used as the experimental material and polluted soil with cadmium was used as the experimental soil sample, to explore the competition inhibition of calcium polypeptide application on the absorption of Cd2+ by Brassia campestris L. in the growth process, as well as the effect of calcium application on the growth. Results showed that the application of calcium polypeptides significantly promoted the growth of Brassia campestris L. Calcium polypeptides could be used as high-quality fertilizer, alleviating the effect of Cd2+ stress on the growth of Brassia campestris L., and promoting the absorption of K+, Ca2+, and other nutrients by Brassia campestris L. Under different calcium polypeptide application conditions, the effective state of Cd2+ in the soil showed less significant difference, indicating that the calcium polypeptide had weak or limited passivation effects on Cd2+. There was a significantly negative correlation between Cd concentration in Brassia campestris L. and calcium application (r = −0.99, p < 0.01) when calcium polypeptide was over-applied, which indicates that the inhibition effect of Cd2+ absorption on Brassia campestris L. is mainly through competitive inhibition rather than passivation. The results showed that calcium polypeptide has dual functions on the competitive inhibition of heavy metals and a good fertilizer effect, providing a new technology for in situ remediation of heavy-metal pollution, and a new approach for the treatment of cadmium-contaminated farmland and surrounding mining land.
Multi-Dimensional Factors Associated with Illegal Substance Use Among Gay and Bisexual Men in Taiwan
Authors: Li Dian-Jeng , Chen Shiou-Lan , Yen Cheng-Fang
Published: November 2019

Illegal substance use in sexual minorities is an important health issue worldwide. The present cross-sectional study aimed to investigate the multi-dimensional factors associated with illegal substance use among gay and bisexual men in Taiwan. This questionnaire-survey study recruited 500 gay or bisexual men aged between 20 and 25 years. Their experiences of using eight kinds of illegal substances in the preceding month were collected. Their previous experiences of homophobic bullying, satisfaction with academic performance, truancy, perceived family and peer support in childhood and adolescence, and social-demographic characteristics, were also collected. Potential factors associated with illegal substance use were identified using univariate logistic regression, and further selected into a forward stepwise logistic regression model to identify the factors most significantly related to illegal substance use. A total of 22 (4.4%) participants reported illegal substance use in the preceding month, and mean age was 22.9 ± 1.6. Forward stepwise logistic regression revealed that being victims of homophobic cyberbullying in childhood and adolescence (odds ratio (OR) = 1.26; p = 0.011), disclosure of sexual orientation at junior high school (OR = 4.67; p = 0.001), and missing classes or truancy in senior high school (OR = 2.52; p = 0.041) were significantly associated with illegal substance use in early adulthood. Multi-dimensional factors in childhood and adolescence that were significantly associated with illegal substance use in early adulthood among gay and bisexual men were identified. Besides traditional bullying, the effect of cyberbullying and school performance on illegal substance use should not be ignored. This study is limited to the cross-sectional design and possible recall bias. Mental health professionals must routinely assess these significant factors to prevent and intervene in illegal substance use among gay and bisexual men.
Improving the Efficiency of an Emergency Department Based on Activity-Relationship Diagram and Radio Frequency Identification Technology
Authors: Weng Shao-Jen , Tsai Ming-Che , Tsai Yao-Te , Gotcher Donald F. , Chen Chih-Hao , Liu Shih-Chia , Xu Yeong-Yuh , Kim Seung-Hwan
Published: November 2019

Emergency department crowding has been one of the main issues in the health system in Taiwan. Previous studies have usually targeted the process improvement of patient treatment flow due to the difficulty of collecting Emergency Department (ED) staff data. In this study, we have proposed a hybrid model with Discrete Event Simulation, radio frequency identification applications, and activity-relationship diagrams to simulate the nurse movement flows and identify the relationship between different treatment sections. We used the results to formulate four facility layouts. Through comparing four scenarios, the simulation results indicated that 2.2 km of traveling distance or 140 min of traveling time reduction per nurse could be achieved from the best scenario.
Evaluation of Physical Fitness, Body Composition, and Adherence to Mediterranean Diet in Adolescents from Estonia: The AdolesHealth Study
Authors: Galan-Lopez Pablo , Domínguez Raúl , Pihu Maret , Gísladóttir Thordis , Sánchez-Oliver Antonio J. , Ries Francis
Published: November 2019

Unhealthy lifestyles, low levels of physical fitness, and adherence to the Mediterranean diet (MD) are associated with bad quality of life and the development of a wide range of non-communicable diseases (NCDs). The current study aimed to evaluate the level of adherence to the MD in physical fitness performance and body composition parameters in children and adolescents of Estonia. Therefore, 413 adolescents (56% boys) from the city of Tartu completed the Mediterranean Diet Questionnaire (KIDMED) for analyzing the adherence to MD and performed the Alpha Fitness Test for measuring physical fitness and body composition. A 41.67% of low, 44.05% of average, and 14.28% of high adherence to MD was detected, without difference between genders (p = 0.747). In the Alpha Fitness battery, a higher performance was observed in all tests for boys vs. girls (p < 0.05). In relation to body composition, higher height, weight, and waist values were observed in boys (p < 0.05) and a lower body fat percentage (p < 0.01) without differences in body mass index (BMI; p = 0.906). The adherence to the MD is classified as average/low. Gender significantly influences all variables of the Alpha Fitness battery and anthropometrics measures excepting BMI. According the levels of adherence to the MD, no statistically different prevalence was observed for Non-Overweight (N-Oweight), Non-Overfat (N-Ofat), or Non-Overwaist (N-Owaist). Still, a risk factor for Overweight (Oweight) in boys with low adherence was observed in comparison to those with a mid-level of adherence to the MD.
Influence of Iron on Cytotoxicity and Gene Expression Profiles Induced by Arsenic in HepG2 Cells
Authors: Wang Yonghua , Liu Yuxuan , Liu Su , Wu Bing
Published: November 2019

The toxicity of arsenic (As) could be influenced by many environmental factors and elements. Iron (Fe) is one of the elements that could be involved in As-induced toxicity. In this study, the interactive effects of Fe and As in HepG2 cells were analyzed based on cytotoxicity and transcriptomic analyses. The results showed that Fe could decrease cell viability and increase mitochondrial depolarization induced by As exposure. Oxidative stress and damage have been proven to be one of the main mechanisms of As toxicity. Our results showed that Fe increased the generation of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) induced by As exposure. Microarray analysis further verified that Fe increased the alteration of gene expression and biological processes related to oxidative stress, cell proliferation, and the apoptotic signaling pathway caused by As exposure. Both results of cytotoxicity and transcriptomic analyses suggest that an increase of Fe in the human body could increase the As-induced toxicity, which should be considered during the health risk assessment of As.
Role of the Balance of Akt and MAPK Pathways in the Exercise-Regulated Phenotype Switching in Spontaneously Hypertensive Rats
Authors: Zhang Lin , Zhang Yanyan , Wu Ying , Yu Jingjing , Zhang Yimin , Zeng Fanxing , Shi Lijun
Published: November 2019

The mechanisms regulating vascular smooth muscle cell (VSMC) phenotype switching and the critical signal modulation affecting the VSMCs remain controversial. Physical exercise acts as an effective drug in preventing elevated blood pressure and improving vascular function. This study was designed to explore the influence of aerobic exercise on the suppression of VSMC phenotype switching by balancing of the Akt, also known as PKB (protein kinase B) and mitogen-activated protein kinase (MAPK) signaling pathways. Spontaneously hypertensive rats (SHRs) and normotensive rats were subjected to exercise treatment before measuring the vascular morphological and structural performances. Exercise induced reverse expression of VSMC protein markers (α-SM-actin, calponin, and osteopontin (OPN)) in spontaneously hypertensive rats. It is noteworthy that the low expression of phosphorylated Akt significantly decreased the expression of VSMC contractile phenotype markers (α-SM-actin and calponin) and increased the expression of the VSMC synthetic phenotype marker (OPN). However, the MAPK signal pathway exerts an opposite effect. VSMCs and whole vessels were treated by inhibitors, namely the p-Akt inhibitor, p-ERK inhibitor, and p-p38 MAPK inhibitors. VSMC phenotype markers were reversed. It is important to note that a significant reverse regulatory relationship was observed between the expression levels of MAPK and the contractile markers in both normotensive and spontaneously hypertensive rats. We demonstrate that aerobic exercise regulates the VSMC phenotype switching by balancing the Akt and MAPK signaling pathways in SHRs.
Strategies to Obtain Designer Polymers Based on Cyanobacterial Extracellular Polymeric Substances (EPS)
Authors: Pereira Sara B. , Sousa Aureliana , Santos Marina , Araújo Marco , Serôdio Filipa , Granja Pedro , Tamagnini Paula
Published: November 2019

Biopolymers derived from polysaccharides are a sustainable and environmentally friendly alternative to the synthetic counterparts available in the market. Due to their distinctive properties, the cyanobacterial extracellular polymeric substances (EPS), mainly composed of heteropolysaccharides, emerge as a valid alternative to address several biotechnological and biomedical challenges. Nevertheless, biotechnological/biomedical applications based on cyanobacterial EPS have only recently started to emerge. For the successful exploitation of cyanobacterial EPS, it is important to strategically design the polymers, either by genetic engineering of the producing strains or by chemical modification of the polymers. This requires a better understanding of the EPS biosynthetic pathways and their relationship with central metabolism, as well as to exploit the available polymer functionalization chemistries. Considering all this, we provide an overview of the characteristics and biological activities of cyanobacterial EPS, discuss the challenges and opportunities to improve the amount and/or characteristics of the polymers, and report the most relevant advances on the use of cyanobacterial EPS as scaffolds, coatings, and vehicles for drug delivery.
Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity
Authors: Azambuja Juliana Hofstätter , Ludwig Nils , Braganhol Elizandra , Whiteside Theresa L.
Published: November 2019

The adenosine pathway plays a key role in modulating immune responses in physiological and pathological conditions. Physiologically, anti-inflammatory effects of adenosine balance pro-inflammatory adenosine 5’-triphosphate (ATP), protecting tissues from damage caused by activated immune cells. Pathologically, increased adenosine monophosphatase (AMPase) activity in tumors leads to increased adenosine production, generating a deeply immunosuppressed microenvironment and promoting cancer progression. Adenosine emerges as a promising target for cancer therapy. It mediates protumor activities by inducing tumor cell proliferation, angiogenesis, chemoresistance, and migration/invasion by tumor cells. It also inhibits the functions of immune cells, promoting the formation of a tumor-permissive immune microenvironment and favoriting tumor escape from the host immune system. Pharmacologic inhibitors, siRNA or antibodies specific for the components of the adenosine pathway, or antagonists of adenosine receptors have shown efficacy in pre-clinical studies in various in vitro and in vivo tumor models and are entering the clinical arena. Inhibition of the adenosine pathway alone or in combination with classic immunotherapies offers a potentially effective therapeutic strategy in cancer.
Current Approaches in NSCLC Targeting K-RAS and EGFR
Authors: Aran Veronica , Omerovic Jasminka
Published: November 2019

The research and treatment of non-small cell lung cancer (NSCLC) have achieved some important advances in recent years. Nonetheless, the overall survival rates for NSCLC remain low, indicating the importance to effectively develop new therapies and improve current approaches. The understanding of the function of different biomarkers involved in NSCLC progression, survival and response to therapy are important for the development of early detection tools and treatment options. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (K-RAS) are two of the main significant biomarkers for the management of NSCLC. Mutations in these genes were associated with development and response to therapies. For example, the use of small molecule tyrosine kinase (TK) inhibitors and immunotherapy has led to benefits in some, but not all patients with altered EGFR. In contrast, there is still no effective approved drug to act upon patients harbouring K-RAS mutations. In addition, K-RAS mutations have been associated with lack of activity of TK inhibitors. However, promising approaches aimed to inhibit mutant K-RAS are currently under study. Therefore, this review will discuss these approaches and also EGFR therapies, and hopefully, it will draw attention to the need of continued research in the field in order to improve the outcomes in NSCLC patients.
rAAV Engineering for Capsid-Protein Enzyme Insertions and Mosaicism Reveals Resilience to Mutational, Structural and Thermal Perturbations
Authors: Feiner Rebecca C. , Teschner Julian , Teschner Kathrin E. , Radukic Marco T. , Baumann Tobias , Hagen Sven , Hannappel Yvonne , Biere Niklas , Anselmetti Dario , Arndt Katja M. , Müller Kristian M.
Published: November 2019

Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme β-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with β-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology.
Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility
Authors: Lesicka Monika , Jabłońska Ewa , Wieczorek Edyta , Pepłońska Beata , Gromadzińska Jolanta , Seroczyńska Barbara , Kalinowski Leszek , Skokowski Jarosław , Reszka Edyta
Published: November 2019

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility.
Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives
Authors: Condorelli Angelo Giuseppe , Dellambra Elena , Logli Elena , Zambruno Giovanna , Castiglia Daniele
Published: November 2019

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone. Disease hallmarks are skin fragility and unremitting blistering. The most disabling EB (sub)types show defective wound healing, fibrosis and inflammation at lesional skin. These features expose patients to serious disease complications, including the development of cutaneous squamous cell carcinomas (SCCs). Almost all subjects affected with the severe recessive dystrophic EB (RDEB) subtype suffer from early and extremely aggressive SCCs (RDEB-SCC), which represent the first cause of death in these patients. The genetic determinants of RDEB-SCC do not exhaustively explain its unique behavior as compared to low-risk, ultraviolet-induced SCCs in the general population. On the other hand, a growing body of evidence points to the key role of tumor microenvironment in initiation, progression and spreading of RDEB-SCC, as well as of other, less-investigated, EB-related SCCs (EB-SCCs). Here, we discuss the recent advances in understanding the complex series of molecular events (i.e., fibrotic, inflammatory, and immune processes) contributing to SCC development in EB patients, cross-compare tumor features in the different EB subtypes and report the most promising therapeutic approaches to counteract or delay EB-SCCs.
Blood Testis Barrier and Somatic Cells Impairment in a Series of 35 Adult Klinefelter Syndrome Patients
Authors: Giudice Maria Grazia , Vermeulen Maxime , Wyns Christine
Published: November 2019

Klinefelter Syndrome (KS) is the most common genetic cause of infertility in men. Degeneration of the testicular tissue starts in utero and accelerates at puberty with hyalinisation of seminiferous tubules, spermatogonia apoptosis and germ cell maturation arrest. Therefore, fertility preservation in young KS boys has been proposed, although this measure is still debated due to insufficient knowledge of the pathophysiology of the disease. To better understand the underlying mechanisms of testicular failure and germ cell loss, we analysed functional and morphological alterations in the somatic compartment of KS testis, i.e., Sertoli cells, including the blood–testis barrier (BTB) and Leydig cells (LC). We compared three populations: 35 KS 47,XXY non-mosaic patients, 28 Sertoli-cell-only (SCO) syndrome patients and 9 patients with normal spermatogenesis. In KS patients the expression of BTB proteins connexin-43 and claudin-11 assessed with a semi-quantitative scoring system appeared significantly reduced with a disorganised pattern. A significant reduction in seminiferous tubules expressing androgen receptors (AR) was observed in KS compared to normal spermatogenesis controls. INSL3 expression, a marker of LC maturation, was also significantly reduced in KS compared to patients with normal spermatogenesis or SCO. Hence, the somatic compartment impairment in KS could be involved in degeneration of seminiferous tubules.
A Gene Signature of Survival Prediction for Kidney Renal Cell Carcinoma by Multi-Omic Data Analysis
Authors: Hu Fuyan , Zeng Wenying , Liu Xiaoping
Published: November 2019

Kidney renal cell carcinoma (KIRC), which is the most common subtype of kidney cancer, has a poor prognosis and a high mortality rate. In this study, a multi-omics analysis is performed to build a multi-gene prognosis signature for KIRC. A combination of a DNA methylation analysis and a gene expression data analysis revealed 863 methylated differentially expressed genes (MDEGs). Seven MDEGs (BID, CCNF, DLX4, FAM72D, PYCR1, RUNX1, and TRIP13) were further screened using LASSO Cox regression and integrated into a prognostic risk score model. Then, KIRC patients were divided into high- and low-risk groups. A univariate cox regression analysis revealed a significant association between the high-risk group and a poor prognosis. The time-dependent receiver operating characteristic (ROC) curve shows that the risk group performs well in predicting overall survival. Furthermore, the risk group is contained in the best multivariate model that was obtained by a multivariate stepwise analysis, which further confirms that the risk group can be used as a potential prognostic biomarker. In addition, a nomogram was established for the best multivariate model and shown to perform well in predicting the survival of KIRC patients. In summary, a seven-MDEG signature is a powerful prognosis factor for KIRC patients and may provide useful suggestions for their personalized therapy.
Evaluating Museum Virtual Tours: The Case Study of Italy
Authors: Kabassi Katerina , Amelio Alessia , Komianos Vasileios , Oikonomou Konstantinos
Published: November 2019

Virtual tours in museums are an ideal solution for those that are not able to visit a museum or those who want to have a small taste of what is presented in the museum before their visit. However, these tours often encounter severe problems while users interact with them. In order to check the status of virtual tours of museums, we present the implementation of an evaluation experiment that uses a combination of two multi-criteria decision making theories, namely the analytic hierarchy process (AHP) and the fuzzy technique for order of preference by similarity to ideal solution (TOPSIS). AHP has been used for the estimation of the weights of the heuristics and fuzzy TOPSIS has been used for the evaluation of virtual tours of museums. This paper presents the exact steps that have to be followed in order to implement such an experiment and run an example experiment for virtual tours of Italian museums.
The Scope for Thalassemia Gene Therapy by Disruption of Aberrant Regulatory Elements
Authors: Patsali Petros , Mussolino Claudio , Ladas Petros , Floga Argyro , Kolnagou Annita , Christou Soteroula , Sitarou Maria , Antoniou Michael N. , Cathomen Toni , Lederer Carsten Werner , Kleanthous Marina
Published: November 2019

The common IVSI-110 (G>A) β-thalassemia mutation is a paradigm for intronic disease-causing mutations and their functional repair by non-homologous end joining-mediated disruption. Such mutation-specific repair by disruption of aberrant regulatory elements (DARE) is highly efficient, but to date, no systematic analysis has been performed to evaluate disease-causing mutations as therapeutic targets. Here, DARE was performed in highly characterized erythroid IVSI-110(G>A) transgenic cells and the disruption events were compared with published observations in primary CD34+ cells. DARE achieved the functional correction of β-globin expression equally through the removal of causative mutations and through the removal of context sequences, with disruption events and the restriction of indel events close to the cut site closely resembling those seen in primary cells. Correlation of DNA-, RNA-, and protein-level findings then allowed the extrapolation of findings to other mutations by in silico analyses for potential repair based on the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9, Cas12a, and transcription activator-like effector nuclease (TALEN) platforms. The high efficiency of DARE and unexpected freedom of target design render the approach potentially suitable for 14 known thalassemia mutations besides IVSI-110(G>A) and put it forward for several prominent mutations causing other inherited diseases. The application of DARE, therefore, has a wide scope for sustainable personalized advanced therapy medicinal product development for thalassemia and beyond.
Interaction of the p.Q141K Variant of the ABCG2 Gene with Clinical Data and Cytokine Levels in Primary Hyperuricemia and Gout
Authors: Horváthová Veronika , Bohatá Jana , Pavlíková Markéta , Pavelcová Kateřina , Pavelka Karel , Šenolt Ladislav , Stibůrková Blanka
Published: November 2019

Gout is an inflammatory arthritis influenced by environmental risk factors and genetic variants. The common dysfunctional p.Q141K allele of the ABCG2 gene affects gout development. We sought after the possible association between the p.Q141K variant and gout risk factors, biochemical, and clinical determinants in hyperuricemic, gouty, and acute gouty arthritis cohorts. Further, we studied the correlation of p.Q141K allele and levels of pro-/anti-inflammatory cytokines. Coding regions of the ABCG2 gene were analyzed in 70 primary hyperuricemic, 182 gout patients, and 132 normouricemic individuals. Their genotypes were compared with demographic and clinical parameters. Plasma levels of 27 cytokines were determined using a human multiplex cytokine assay. The p.Q141K variant was observed in younger hyperuricemic/gout individuals (p = 0.0003), which was associated with earlier disease onset (p = 0.004), trend toward lower BMI (p = 0.056), and C-reactive protein (CRP, p = 0.007) but a higher glomerular filtration rate (GFR, p = 0.035). Levels of 19 cytokines were higher, mainly in patients with acute gouty arthritis (p < 0.001), irrespective of the presence of the p.Q141K variant. The p.Q141K variant influences the age of onset of primary hyperuricemia or gout and other disease-linked risk factors and symptoms. There was no association with cytokine levels in the circulation.
Lung Microbiome in Asthma: Current Perspectives
Authors: Loverdos Konstantinos , Bellos Georgios , Kokolatou Louiza , Vasileiadis Ioannis , Giamarellos Evangelos , Pecchiari Matteo , Koulouris Nikolaos , Koutsoukou Antonia , Rovina Nikoletta
Published: November 2019

A growing body of evidence implicates the human microbiome as a potentially influential player actively engaged in shaping the pathogenetic processes underlying the endotypes and phenotypes of chronic respiratory diseases, particularly of the airways. In this article, we specifically review current evidence on the characteristics of lung microbiome, and specifically the bacteriome, the modes of interaction between lung microbiota and host immune system, the role of the “lung–gut axis”, and the functional effects thereof on asthma pathogenesis. We also attempt to explore the possibilities of therapeutic manipulation of the microbiome, aiming at the establishment of asthma prevention strategies and the optimization of asthma treatment.
Coping Strategies in Male Patients under Treatment for Substance Use Disorders and/or Severe Mental Illness: Influence in Clinical Course at One-Year Follow-Up
Authors: Marquez-Arrico Julia , Río-Martínez Laura , Navarro José , Prat Gemma , Forero Diego , Adan Ana
Published: November 2019

Coping strategies have an impact on substance use disorders (SUD), relapses, and clinical variables, but knowledge on this area is scarce. We explored the coping strategies used during treatment in patients with dual diagnosis (DD), SUD, and severe mental illness (SMI), and the relation with clinical course and relapses at one-year follow-up. A sample of 223 patients was divided into three groups depending on diagnosis: DD (N = 80; SUD with comorbid schizophrenia or major depressive disorder), SUD only (N = 80), and SMI only (N = 63; schizophrenia or major depressive disorder). MANCOVA analyses reflected differences in self-criticism and problem avoidance, with a higher use of these in the DD and SUD groups. The coping strategies used differed depending on the presence/absence of a SUD, but not depending on psychiatric diagnosis. At one-year follow-up, social support was the only strategy that predicted the presence of relapses in DD patients with schizophrenia (positively), and in SMI patients with major depressive disorder (negatively). Thus, social support was associated with relapses, but the relationship was different depending on psychiatric diagnosis. Further studies should analyze the implications of social support as a coping strategy in different mental disorders, as well as its usefulness in individualized interventions.
Microbiota Dysbiosis in Fungal Rhinosinusitis
Authors: Lu Yen-Ting , Wang Shao-Hung , Liou Ming-Li , Shen Ting-An , Lu Ying-Chou , Hsin Chung-Han , Yang Shun-Fa , Chen Yih-Yuan , Chang Tzu-Hao
Published: November 2019

Fungal rhinosinusitis is a unique phenotype of chronic rhinosinusitis with unique clinical and histological characteristics. The role of bacterial microbiota in various phenotypes chronic rhinosinusitis is not thoroughly understood. Therefore, we conducted 16s rRNA amplification sequencing to determine differences in bacterial communities between phenotypes (fungal vs. non- fungal) and anatomical sites (middle meatus vs. nasopharynx). Endoscope-guided swabs were used to collect samples from the middle meatus and nasopharynx of seven consecutive patients with fungal and 18 consecutive patients with non-fungal rhinosinusitis. DNA was extracted and investigated through 16S rRNA amplification. Among samples from the middle meatus, Shannon diversity was significantly lower in those from the fungal rhinosinusitis group (p = 0.029). However, no significant differences in diversity were noted between nasopharynx samples (p = 0.85). Fungal rhinosinusitis samples exhibited a distinct distribution of taxon relative abundance, which involved not only the absence of rhinosinusitis-associated commensal Corynebacterium and Fusobacterium in the middle meatus but also a significant increase in Haemophilus prevalence and abundance. This is the first study to compare bacterial communities in fungal and non-fungal rhinosinusitis samples. Our findings demonstrated that bacterial community dysbiosis was more apparent in fungal rhinosinusitis samples and was limited to the middle meatus.
Adipose-Derived Stem Cells from Systemic Sclerosis Patients Maintain Pro-Angiogenic and Antifibrotic Paracrine Effects In Vitro
Authors: VELIER Mélanie , SIMONCINI Stéphanie , ABELLAN Maxime , FRANCOIS Pauline , EAP Sandy , LAGRANGE Anaïs , BERTRAND Baptiste , DAUMAS Aurélie , GRANEL Brigitte , DELORME Bruno , DIGNAT GEORGE Françoise , MAGALON Jérémy , SABATIER Florence
Published: November 2019

Innovative therapies based on autologous adipose-derived stem/stromal cells (ASC) are currently being evaluated for treatment of systemic sclerosis (SSc). Although paracrine angiogenic and antifibrotic effects are considered the predominant mechanisms of ASC therapeutic potential, the impact of SSc on ASC paracrine functions remains controversial. In this study, phenotype, senescence, differentiation potential, and molecular profile were determined in ASC from SSc patients (SSc-ASC) (n = 7) and healthy donors (HD-ASC) (n = 7). ASC were co-cultured in indirect models with dermal fibroblasts (DF) from SSc patients or endothelial cells to assess their pro-angiogenic and antifibrotic paracrine effects. The angiogenic activity of endothelial cells was measured in vitro using tube formation and spheroid assays. DF collagen and alpha smooth muscle actin (αSMA) content were quantified after five days of co-culture with ASC. Differentiation capacity, senescence, and mRNA profiles did not differ significantly between SSc-ASC and HD-ASC. SSc-ASC retained the ability to stimulate angiogenesis through paracrine mechanisms; however, functional assays revealed reduced potential compared to HD-ASC. DF fibrosis markers were significantly decreased after co-culture with SSc-ASC. Together, these results indicate that SSc effects do not significantly compromise the angiogenic and the antifibrotic paracrine properties of ASC, thereby supporting further development of ASC-based autologous therapies for SSc treatment.
In Situ Crosslinking Bionanocomposite Hydrogels with Potential for Wound Healing Applications
Authors: Leone Federica , Firlak Melike , Challen Kirsty , Bonnefin Wayne , Onida Barbara , Wright Karen L. , Hardy John G.
Published: November 2019

In situ forming hydrogels are a class of biomaterials that can fulfil a variety of important biomedically relevant functions and hold promise for the emerging field of patient-specific treatments (e.g., cell therapy, drug delivery). Here we report the results of our investigations on the generation of in situ forming hydrogels with potential for wound healing applications (e.g., complex blast injuries). The combination of polysaccharides that were oxidized to display aldehydes, amine displaying chitosan and nanostructured ZnO yields in situ forming bionanocomposite hydrogels. The physicochemical properties of the components, their cytotoxicity towards HaCat cells and the in vitro release of zinc ions on synthetic skin were studied. The in situ gel formation process was complete within minutes, the components were non-toxic towards HaCat cells at functional levels, Zn2+ was released from the gels, and such materials may facilitate wound healing.
A Sensor Web Prototype for Cabled Seafloor Observatories in the East China Sea
Authors: Yu Yang , Xu Huiping , Xu Changwei
Published: November 2019

Seafloor observatories enable continuous power supply and real-time bidirectional data transmission, which marks a new way for marine environment monitoring. As in situ observation produces massive data in a constant way, the research involved with data acquisition, data transmission, data analysis, and user-oriented data application is vital to the close-loop operations of seafloor observatories. In this paper, we design and implement a sensor web prototype (ESOSW) to resolve seafloor observatory information processing in a plug-and-play way. A sensor web architecture is first introduced, which is information-oriented and structured into four layers enabling bidirectional information flow of observation data and control commands. Based on the layered architecture, the GOE Control Method and the Hot Swapping Interpretation Method are proposed as the plug-and-play mechanism for sensor control and data processing of seafloor observatory networks. ESOSW was thus implemented with the remote-control system, the data management system, and the real-time monitoring system, supporting managed sensor control and on-demand measurement. ESOSW was tested for plug-and-play enablement through a series of trials and was put into service for the East China Sea Seafloor Observation System. The experiment shows that the sensor web prototype design and implementation are feasible and could be a general reference to related seafloor observatory networks.
Analysis of Offshore Structures Based on Response Spectrum of Ice Force
Authors: Liu Yingzhou , Li Xin , Zhang Youwei
Published: November 2019

With the development of large-scale offshore projects, sea ice is a potential threat to the safety of offshore structures. The main forms of damage to bottom-fixed offshore structures under sea ice are crushing failure and bending failure. Referred to as the concept of seismic response spectrums, the design response spectrum of offshore structures induced by the crushing and bending ice failure is presented. Selecting the Bohai Sea in China as an example, the sea areas were divided into different ice zones due to the different sea ice parameters. Based on the crushing and bending failure power spectral densities of ice force, a large amount of ice force time-history samples are firstly generated for each ice zone. The time-history of the maximum responses of a series of single degree of freedom systems with different natural frequencies under the ice force are calculated and subsequently, a response spectrum curve is obtained. Finally, by fitting all the response spectrum curves from different samples, the design response spectrum is generated for each ice zone. The ice force influence coefficients for crushing and bending failure are obtained, which can be used to estimate the stochastic sea ice force acting on a structure conveniently in a static way. A comparison of the proposed response spectrum method with the Monte Carlo method by a numerical example shows good agreement.
Law, Violence, and Property Expropriation in Syria: Impediments to Restitution and Return
Authors: Stubblefield Emily , Joireman Sandra
Published: November 2019

After eight years of civil war, parts of Syria are now free from conflict. In recognition of the return to peace, the government officially welcomes back all who fled the country to escape violence. Yet, a pattern of property expropriation supported by the government during the war limits the ability of some to return and reclaim their homes and businesses. We argue here that intentional changes to law and policy regarding property rights during the war has led to asset losses for members of groups opposed to the government and created a barrier to property restitution and the return of these groups. We examine legal documents and secondary sources identifying government actions and their impact, noting the proliferation of laws that systematically erode the property rights of people who lack proximity, legal status, and regime allies. As the results of these laws manifest after the war, a disproportionate number of Syrians who opposed the government will find themselves without the houses, land, and property they held before the war began.