bluuebunny/crossref_metadata_2025 huggingface dataset:
A Probabilistic Matrix Factorization Method for Identifying lncRNA-Disease Associations
Authors: Xuan Zhanwei , Li Jiechen , Yu Jingwen , Feng Xiang , Zhao Bihai , Wang Lei
Published: February 2019

Recently, an increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) can participate in various crucial biological processes and can also be used as the most promising biomarkers for the treatment of certain diseases such as coronary artery disease and various cancers. Due to costs and time complexity, the number of possible disease-related lncRNAs that can be verified by traditional biological experiments is very limited. Therefore, in recent years, it has been very popular to use computational models to predict potential disease-lncRNA associations. In this study, we constructed three kinds of association networks, namely the lncRNA-miRNA association network, the miRNA-disease association network, and the lncRNA-disease correlation network firstly. Then, through integrating these three newly constructed association networks, we constructed an lncRNA-disease weighted association network, which would be further updated by adopting the KNN algorithm based on the semantic similarity of diseases and the similarity of lncRNA functions. Thereafter, according to the updated lncRNA-disease weighted association network, a novel computational model called PMFILDA was proposed to infer potential lncRNA-disease associations based on the probability matrix decomposition. Finally, to evaluate the superiority of the new prediction model PMFILDA, we performed Leave One Out Cross-Validation (LOOCV) based on strongly validated data filtered from MNDR and the simulation results indicated that the performance of PMFILDA was better than some state-of-the-art methods. Moreover, case studies of breast cancer, lung cancer, and colorectal cancer were implemented to further estimate the performance of PMFILDA, and simulation results illustrated that PMFILDA could achieve satisfying prediction performance as well.
Dual Oncogenic/Anti-Oncogenic Role of PATZ1 in FRTL5 Rat Thyroid Cells Transformed by the Ha-RasV12 Oncogene
Authors: Vitiello Michela , Palma Giuseppe , Monaco Mario , Bello Anna Maria , Camorani Simona , Francesca Paola , Rea Domenica , Barbieri Antonio , Chiappetta Gennaro , Vita Gabriella De , Cerchia Laura , Arra Claudio , Fedele Monica
Published: February 2019

PATZ1 is a transcriptional factor downregulated in thyroid cancer whose re-expression in thyroid cancer cells leads to a partial reversion of the malignant phenotype, including the capacity to proliferate, migrate, and undergo epithelial-to-mesenchymal transition. We have recently shown that PATZ1 is specifically downregulated downstream of the Ras oncogenic signaling through miR-29b, and that restoration of PATZ1 in Ha-Ras transformed FRTL5 rat thyroid cells is able to inhibit their capacities to proliferate and migrate in vitro. Here, we analyzed the impact of PATZ1 expression on the in vivo tumorigenesis of these cells. Surprisingly, FRTL5-Ras-PATZ1 cells showed enhanced tumor initiation when engrafted in nude mice, even if their tumor growth rate was reduced compared to that of FRTL5-Ras control cells. To further investigate the cause of the enhanced tumor engraftment of FRTL5-Ras-PATZ1 cells, we analyzed the stem-like potential of these cells through their capacity to grow as thyrospheres. The results showed that restoration of PATZ1 expression in these cells increases stem cell markers’ expression and self-renewal ability of the thyrospheres while limiting their growth capacity. Therefore, we suggest that PATZ1 may play a role in enhancing the stem cell potential of thyroid cancer cells, but, at the same time, it impairs the proliferation of non-stem cells.
Estimating the Spatial Distribution of Soil Properties Using Environmental Variables at a Catchment Scale in the Loess Hilly Area, China
Authors: Hu Chenxia , Wright Alan L , Lian Gang
Published: February 2019

A comprehensive understanding of the spatial distribution and dynamic changes of soil properties are the basis for sustainable land management. Topography and land use types are key factors affecting soil property variability. This study analyzed the effects of land use types and landscape locations on soil properties, based on data from 111 points of surface soil (0–20 cm) in the Zhujiagou catchment on the Loess Plateau of Northwest China. Soil properties include clay, silt, bulk density (BD), soil organic matter (SOM), total nitrogen (TN) and total phosphorus (TP). Land use types include slope farmland (SFL), terrace farmland (TFL), check-dam farmland (CDL), woodland (WL), shrub land (SL) and grassland (GL). Landscape locations include crest (CT), upper slope (US), middle slope (MS), lower slope (LS) and flat valley (FV). Topographical attributes were divided into primary and secondary (or compound) attributes. Correlation analyses were carried out between soil properties and terrain attribute, and multiple-linear regression models were established to estimate soil properties using land use types and topographic attributes as independents. Results indicated that significant differences in soil properties existed between six land use types, except for bulk density. Higher values of clay, silt, SOM and TN occurred in soils from check-dam farmland, but lower values in soils from shrub land. Significant differences among landscape positions were observed for clay, BD, SOM and TN. Clay, SOM and TN contents on flat valley (FV) positions were higher than those of other positions. Different correlations were found between soil properties and terrain attributes. The regression models explained 13% to 63% of the variability of the measured soil properties, and the model for Clay had the highest R2 value, followed by TN, silt, BD, SOM and TP. Validation results of the regression models showed that the model was precise for soil bulk density, but the variation was large and a high smoothing effect existed for predicted values of other soil properties. For TP, the predicted result was poor. Further observations suggested that land use was the dominant factor affecting soil chemical properties. But for soil physical properties, especially for BD, topography was the dominant factor.
The Effect of Cross-Level Interaction between Community Factors and Social Capital among Individuals on Physical Activity: Considering Gender Difference
Authors: Jun Hee-Jung , Park Seoyeon
Published: February 2019

This study examines the effect of cross-level interaction between community physical environment and social capital among individuals on physical activity by considering gender difference. In this regard, we ask two research questions: (1) What is the effect of cross-level interaction between community factors and social capital among individuals on physical activity? (2) Is there gender difference in the effect of the cross-level interaction? To examine the research questions, this study used the 2015 Korea Community Health Survey and used multi-level analyses. The empirical analyses show that while there are both positive and negative cross-level interaction effects between physical activity-supportive community environment and social capital among individuals on physical activity, the positive cross-level interaction effect is more pronounced for women than for men. These findings suggest that local efforts to improve public health should take into account the cross-level interaction effect between community physical environment and social capital among individuals as well as gender difference.
3D Printed Temporary Veneer Restoring Autotransplanted Teeth in Children: Design and Concept Validation Ex Vivo
Authors: Al-Rimawi Ali , EzEldeen Mostafa , Schneider Danilo , Politis Constantinus , Jacobs Reinhilde
Published: February 2019

(1) Background: Three-dimensional printing is progressing rapidly and is applied in many fields of dentistry. Tooth autotransplantation offers a viable biological approach to tooth replacement in children and adolescents. Restoring or reshaping the transplanted tooth to the anterior maxilla should be done as soon as possible for psychological and aesthetic reasons. However, to avoid interfering with the natural healing process, reshaping of transplanted teeth is usually delayed three to four months after transplantation. This delay creates a need for simple indirect temporary aesthetic restoration for autotransplanted teeth. The aim of this study was to develop and validate a digital solution for temporary restoration of autotransplanted teeth using 3D printing. (2) Methods: Four dry human skulls and four dry human mandibles were scanned using cone beam computed tomography to create 3D models for 15 premolars. Digital impression of the maxillary arch of one of the skulls was captured by intra oral scanner. The digital work flow for the design and fabrication of temporary veneers is presented. The seating and adaptation of the 3D printed veneers were evaluated using stereomicroscopy and micro-computed tomography. (3) Results: Evaluation of the veneer seating using stereomicroscopy showed that the mean marginal gap at all of the sides was below the cut-off value of 200 µm. The overall mean marginal gap was 99.9 ± 50.7 µm (median: 87.8 (IQR 64.2–133 µm)). The internal adaptation evaluation using micro-computed tomography showed an average median gap thickness of 152.5 ± 47.7 (IQR 129–149.3 µm). (4) Conclusions: The present concept of using temporary veneers that are designed and fabricated with CAD/CAM (computer-aided design/computer-aided manufacturing) technology using a DLP (digital light processing) printer may present a viable treatment option for restoration of autotransplanted teeth.
Spatiotemporal Prediction of Increasing Winter Perceived Temperature across a Sub-Tropical City for Sustainable Planning and Climate Change Mitigation
Authors: Ho Hung Chak , Abbas Sawaid , Yang Jinxin , Zhu Rui , Wong Man Sing
Published: February 2019

Climate variability has been documented as being key to influencing human wellbeing across cities as it is linked to mortality and illness due to changes in the perceived weather cycle. Many studies have investigated the impact of summer temperature on human health and have proposed mitigation strategies for summer heat waves. However, sub-tropical cities are still experiencing winter temperature variations. Increasing winter perceived temperature through the decades may soon affect city wellbeing, due to a larger temperature change between normal winter days and extreme cold events, which may cause higher health risk due to lack of adaptation and self-preparedness. Therefore, winter perceived temperature should also be considered and integrated in urban sustainable planning. This study has integrated the increasing winter perceived temperature as a factor for developing spatiotemporal protocols for mitigating the adverse impact of climate change. Land surface temperature (LST) derived from satellite images and building data extracted from aerial photographs were used to simulate the adjusted wind chill equivalent temperature (AWCET) particularly for sub-tropical scenarios between 1990 and 2010 of the Kowloon Peninsula, Hong Kong. Compared with perceived temperature based on the representative station located at the headquarters of the Hong Kong Observatory, the temperature of half the study area in the Kowloon Peninsula has raised by 1.5 °C. The areas with less green space and less public open space in 2010 show higher relative temperatures. Socioeconomically deprived areas (e.g., areas with lower median monthly income) may suffer more from this scenario, but not all types of socioeconomic disparities are associated with poor sustainable planning. Based on our results and the “no-one left behind” guideline from the United Nations, climate change mitigation should be conducted by targeting socioeconomic neighborhoods more than just aging communities.
Exploring Drug-Related Problems in Diabetic Patients during Ramadan Fasting in Saudi Arabia: A Mixed-Methods Study
Authors: Alluqmani Waleed Saleh , Alotaibi Mohammed Misri , Almalki Waleed Jamal , Althaqafi Abdulrahman , Alawi Hamed Abdullah , Althobiani Fahad , Albishi Amjad Abdullah , Madkhali Amjad Ahmad , Baunes Layal Yahia , Alhazmi Razan Ibrahim , Doman Elaf Mohammed , Alhazmi Anwar Hussain , Ali Majid , Cheema Ejaz
Published: February 2019

This study aimed to identify any drug-related problems (DRPs) in diabetic patients during Ramadan fasting in Saudi Arabia. The study used a mixed-methods approach consisting of two phases and was conducted in Makkah, Saudi Arabia from December 2017 to March 2018. The first phase of the study involved qualitative semi-structured individual interviews with diabetic patients. A 13-item questionnaire was used in the second phase to further identify DRPs in the wider population. The data was mainly presented as frequencies and percentages. Inferential statistics was performed using Statistical Package for Social Sciences (SPSS) version 21 to compare relevant variables/questions using the chi-square test. Twenty patients (10 male, 10 female) attended face-to-face interviews during the first phase of the study while 95 (40 male, 55 female) completed the questionnaire in the second phase of the study. Two possible risk factors for DRPs were identified from the qualitative data: patient-related factors, including changes in their medicine intake during fasting, and healthcare professionals-related factors, including lack of advice from healthcare professionals regarding fasting. The quantitative results indicated that 52 (54%) of the 95 participants who observed fasting reported to have changed the way they were taking their medicines. Furthermore, 41% of the participants experienced general healthcare problems such as hypoglycemia, hyperglycemia, fatigue, excessive sweating, and gastrointestinal disturbances. Healthcare professionals need to educate patients who are at risk of DRPs by providing structured education and counseling.
Prevalence of Dietary Behavior and Determinants of Quality of Diet among Beneficiaries of Government Welfare Assistance in Poland
Authors: Kałucka Sylwia , Kaleta Dorota , Makowiec-Dabrowska Teresa
Published: February 2019

Diet, as a modifiable factor for good health maintenance, reduces the risk of numerous non-communicable chronic diseases and prevents premature death. The aim of the study was to examine the prevalence of a dietary behavior and to find out what the determinants of diet quality among the low socio-economic status population are. The studied sample consisted of 1710 respondents. Only 3% of the beneficiaries had healthy dietary habits. Unhealthy dietary habits dominated in all the study group regardless of the subjects’ level of education (p < 0.001). Higher odds of unhealthy dietary habits were reported among the respondents with primary, vocational, and secondary education than among the respondents with high education (for the primary education OR = 11.10; 95% CI: 5.86–21.01; p ≤ 0.001; for vocational education OR = 10.54; 95% CI: 5.79–19.18; p ≤ 0.001 and for secondary education OR = 5.83; 95% CI: 3.48–9.79; p ≤ 0.001). The unhealthy dietary behavior prevalence among beneficiaries of government welfare assistance in Poland is much higher than in the general population. Since only educational level is a determinant which is significantly correlated with the unhealthy dietary behavior, promotion of a healthy diet among disadvantaged individuals should be focused on this factor.
V-Factor Indicator in the Assessment of the Change in the Attractiveness of View as a Result of the Implementation of a Specific Planning Scenario
Authors: Pluta Magda , Mitka Bartosz
Published: February 2019

This paper describes the algorithm of the view factor (V-factor). It is based on an analysis of visibility, taking into account the attractiveness of the observed elements in a three-dimensional space. The results of the V-factor analysis provide input for the decision-making process when selecting the most advantageous planning scenario so that the harmony of landscape and ecological balance can be maintained. The V-factor indicator can be successfully used in the process of spatial planning, in particular, at the stage of determining the parameters of new buildings and lines of sight between planned buildings. The purpose of the indicator is to determine the numerical values for observation points, thus facilitating a comparative assessment of the attractiveness of view available from the special points in space. The analysis uses a 3D space model that includes an integrated existing and planning state designed on the basis of planning scenarios. The V-factor analysis takes into account the distance of the observation point from the observed object, vertical and horizontal angles of observation, and the aesthetic value of the observed object. As a result, an average value of the V-factor indicator was obtained for each planning scenario, which facilitated the determination of the more beneficial one in terms of the attractiveness of view.
Plasma Dimethylarginine Levels and Carotid Intima–Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke
Authors: Grosse Gerrit M. , Biber Saskia , Sieweke Jan-Thorben , Martens-Lobenhoffer Jens , Gabriel Maria M. , Putzer Anne-Sophie , Hasse Isabel , van Gemmeren Till , Schuppner Ramona , Worthmann Hans , Lichtinghagen Ralf , Bode-Böger Stefanie M. , Bavendiek Udo , Weissenborn Karin
Published: February 2019

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima–media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.
Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus
Authors: Dullaart Robin P. F. , Pagano Sabrina , Perton Frank G. , Vuilleumier Nicolas
Published: February 2019

Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). Methods: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [3H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. Results: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear regression models, CEC, EST and CET were inversely associated with Ac-terAA1 levels independently of age, sex, T2D and drug use (β = −0.186, p = 0.026; β = −0.261, p < 0.001; and β = −0.321, p < 0.001; respectively). These associations were lost after additional adjustment for non-HDL cholesterol and triglycerides. No associations were observed for AAA1. Conclusions: CEC, plasma EST and CET are inversely associated with Ac-terAA1 autoantibodies, conceivably attributable to an inverse relationship of these autoantibodies with apolipoprotein B-containing lipoproteins.
Deregulation of Biologically Significant Genes and Associated Molecular Pathways in the Oral Epithelium of Electronic Cigarette Users
Authors: Tommasi Stella , Caliri Andrew W. , Caceres Amanda , Moreno Debra E. , Li Meng , Chen Yibu , Siegmund Kimberly D. , Besaratinia Ahmad
Published: February 2019

We have investigated the regulation of genes and associated molecular pathways, genome-wide, in oral cells of electronic cigarette (e-cigs) users and cigarette smokers as compared to non-smokers. Interrogation of the oral transcriptome by RNA-sequencing (RNA-seq) analysis showed significant number of aberrantly expressed transcripts in both e-cig users (vapers) and smokers relative to non-smokers; however, smokers had ~50% more differentially expressed transcripts than vapers (1726 versus 1152). Whereas the deregulated transcripts in smokers were predominately from protein-coding genes (79% versus 53% in vapers), nearly 28% of the aberrantly expressed transcripts in vapers (versus 8% in smokers) belonged to regulatory non-coding RNAs, including long intergenic non-coding, antisense, small nucleolar and misc RNA (P < 0.0001). Molecular pathway and functional network analyses revealed that “cancer” was the top disease associated with the deregulated genes in both e-cig users and smokers (~62% versus 79%). Examination of the canonical pathways and networks modulated in either e-cig users or smokers identified the “Wnt/Ca+ pathway” in vapers and the “integrin signaling pathway” in smokers as the most affected pathways. Amongst the overlapping functional pathways impacted in both e-cig users and smokers, the “Rho family GTPases signaling pathway” was the top disrupted pathway, although the number of affected targets was three times higher in smokers than vapers. In conclusion, we observed deregulation of critically important genes and associated molecular pathways in the oral epithelium of vapers that bears both resemblances and differences with that of smokers. Our findings have significant implications for public health and tobacco regulatory science.
Synthesis of Fe3C@C from Pyrolysis of Fe3O4-Lignin Clusters and Its Application for Quick and Sensitive Detection of PrPSc through a Sandwich SPR Detection Assay
Authors: Yuan Chenglong , Lou Zhichao , Wang Weikai , Yang Lintian , Li Yanjun
Published: February 2019

The prion protein (PrPSc) has drawn widespread attention due to its pathological potential to cause prion diseases. Herein, we successfully synthesized Fe3C@C by carbonizing Fe3O4-lignin clusters, which were prepared through a facile hydrogen bonding interaction between ≡Fe-OH and hydroxyl groups of lignin. Our in-depth investigation confirmed that the composites were Fe3C@C core/shell particles. We constructed a novel sandwich surface plasmon resonance (SPR) detection assay for sensitive PrPSc detection, utilizing bare gold surface and aptamer-modified Fe3C@C (Fe3C@C-aptamer). Due to the highly specific affinity of Fe3C@C-aptamer towards PrPSc, the sandwich type SPR sensor exhibited excellent analytical performance towards the discrimination and quantitation of PrPSc. A good linear relationship was obtained between the SPR responses and the logarithm of PrPSc concentrations over a range of 0.1–200 ng/mL. The detection sensitivity for PrPSc was improved by ~10 fold compared with the SPR direct detection format. The required detection time was only 20 min. The specificity of the present biosensor was also confirmed by PrPC and other reagents as controls. This proposed approach could also be used to isolate and detect other highly pathogenic biomolecules with similar structural characteristics by altering the corresponding aptamer in the Fe3C@C conjugates.
Heterogeneous Nuclear Ribonucleoproteins Involved in the Functioning of Telomeres in Malignant Cells
Authors: Shishkin Sergey S. , Kovalev Leonid I. , Pashintseva Natalya V. , Kovaleva Marina A. , Lisitskaya Ksenia
Published: February 2019

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are structurally and functionally distinct proteins containing specific domains and motifs that enable the proteins to bind certain nucleotide sequences, particularly those found in human telomeres. In human malignant cells (HMCs), hnRNP-A1—the most studied hnRNP—is an abundant multifunctional protein that interacts with telomeric DNA and affects telomerase function. In addition, it is believed that other hnRNPs in HMCs may also be involved in the maintenance of telomere length. Accordingly, these proteins are considered possible participants in the processes associated with HMC immortalization. In our review, we discuss the results of studies on different hnRNPs that may be crucial to solving molecular oncological problems and relevant to further investigations of these proteins in HMCs.
Thermal Stability and Rheological Properties of Epoxidized Natural Rubber-Based Magnetorheological Elastomer
Authors: Yunus Nurul Azhani , Mazlan Saiful Amri , Ubaidillah  , Abdul Aziz Siti Aishah , Tan Shilan Salihah , Abdul Wahab Nurul Ain
Published: February 2019

Determination of the thermal characteristics and temperature-dependent rheological properties of the magnetorheological elastomers (MREs) is of paramount importance particularly with regards to MRE applications. Hitherto, a paucity of temperature dependent analysis has been conducted by MRE researchers. In this study, an investigation on the thermal and rheological properties of epoxidized natural rubber (ENR)-based MREs was performed. Various percentages of carbonyl iron particles (CIPs) were blended with the ENR compound using a two roll-mill for the preparation of the ENR-based MRE samples. The morphological, elemental, and thermal analyses were performed before the rheological test. Several characterizations, as well as the effects of the strain amplitude, temperature, and magnetic field on the rheological properties of ENR-based MRE samples, were evaluated. The micrographs and elemental results were well-correlated regarding the CIP and Fe contents, and a uniform distribution of CIPs was achieved. The results of the thermal test indicated that the incorporation of CIPs enhanced the thermal stability of the ENR-based MREs. Based on the rheological analysis, the storage modulus and loss factor were dependent on the CIP content and strain amplitude. The effect of temperature on the rheological properties revealed that the stiffness of the ENR-based MREs was considered stable, and they were appropriate to be employed in the MRE devices exposed to high temperatures above 45 °C.
Mitochondrial Genomes Provide Insights into the Phylogeny of Culicomorpha (Insecta: Diptera)
Authors: Zhang Xiao , Kang Zehui , Ding Shuangmei , Wang Yuyu , Borkent Chris , Saigusa Toyohei , Yang Ding
Published: February 2019

Culicomorpha is a monophyletic group containing most bloodsucking lower dipterans, including many important vectors of pathogens. However, the higher-level phylogenetic relationships within Culicomorpha are largely unresolved, with multiple competing hypotheses based on molecular sequence data. Here we sequenced four nearly complete mitochondrial (mt) genomes representing four culicomorph families, and combined these new data with published mt genomes to reconstruct the phylogenetic relationships of all eight extant culicomorph families. We estimated phylogenies using four datasets and three methods. We also used four-cluster likelihood mapping to study potential incongruent topologies supported by the different datasets and phylogenetic questions generated by the previous studies. The results showed that a clade containing Ceratopogonidae, Thaumaleidae and Simuliidae was the sister group to all other Culicomorpha; in another clade, the Dixidae was basal to the remaining four families; Chaoboridae, Corethrellidae and Culicidae formed a monophyletic group and the Chironomidae was the sister group to this clade; Culicidae and Corethrellidae were sister groups in all trees. Our study provides novel mt genome data in Culicomorpha for three new family representatives, and the resulting mt phylogenomic analysis helps to resolve the phylogeny and taxonomy of Culicomorpha.
Hypoxia Induced ER Stress Response as an Adaptive Mechanism in Cancer
Authors: Chipurupalli Sandhya , Kannan Elango , Tergaonkar Vinay , D’Andrea Richard , Robinson Nirmal
Published: February 2019

It is evident that regions within tumors are deprived of oxygen, which makes the microenvironment hypoxic. Cancer cells experiencing hypoxia undergo metabolic alterations and cytoprotective adaptive mechanisms to survive such stringent conditions. While such mechanisms provide potential therapeutic targets, the mechanisms by which hypoxia regulates adaptive responses—such as ER stress response, unfolded protein response (UPR), anti-oxidative responses, and autophagy—remain elusive. In this review, we summarize the complex interplay between hypoxia and the ER stress signaling pathways that are activated in the hypoxic microenvironment of the tumors.
Development of SNP, KASP, and SSR Markers by BSR-Seq Technology for Saturation of Genetic Linkage Map and Efficient Detection of Wheat Powdery Mildew Resistance Gene Pm61
Authors: Hu Jinghuang , Li Jingting , Wu Peipei , Li Yahui , Qiu Dan , Qu Yunfeng , Xie Jingzhong , Zhang Hongjun , Yang Li , Fu Tiantian , Yu Yawei , Li Mengjuan , Liu Hongwei , Zhu Tongquan , Zhou Yang , Liu Zhiyong , Li Hongjie
Published: February 2019

The gene Pm61 that confers powdery mildew resistance has been previously identified on chromosome arm 4AL in Chinese wheat landrace Xuxusanyuehuang (XXSYH). To facilitate the use of Pm61 in breeding practices, the bulked segregant analysis-RNA-Seq (BSR-Seq) analysis, in combination with the information on the Chinese Spring reference genome sequence, was performed in the F2:3 mapping population of XXSYH × Zhongzuo 9504. Two single nucleotide polymorphism (SNP), two Kompetitive Allele Specific PCR (KASP), and six simple sequence repeat (SSR) markers, together with previously identified polymorphic markers, saturated the genetic linkage map for Pm61, especially in the proximal side of the target gene that was short of gene-linked markers. In the newly established genetic linkage map, Pm61 was located in a 0.71 cM genetic interval and can be detected in a high throughput scale by the KASP markers Xicsk8 and Xicsk13 or by the standard PCR-based markers Xicscx497 and Xicsx538. The newly saturated genetic linkage map will be useful in molecular marker assisted-selection of Pm61 in breeding for disease resistant cultivar and in its map-based cloning.
Macroglossia, Motor Neuron Pathology, and Airway Malacia Contribute to Respiratory Insufficiency in Pompe Disease: A Commentary on Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases
Authors: McCall Angela L. , ElMallah Mai K.
Published: February 2019

The authors of the recently published, “Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases”, provide an important review of the various mechanisms of lysosomal storage diseases (LSD) and how they culminate in similar clinical pathologies [...]
A Novel Discovery: Holistic Efficacy at the Special Organ Level of Pungent Flavored Compounds from Pungent Traditional Chinese Medicine
Authors: Chen Zhao , Cao Yanfeng , Zhang Yanling , Qiao Yanjiang
Published: February 2019

Pungent traditional Chinese medicines (TCMs) play a vital role in the clinical treatment of hepatobiliary disease, gastrointestinal diseases, cardiovascular diseases, diabetes, skin diseases and so on. Pungent TCMs have a vastness of pungent flavored (with pungent taste or smell) compounds. To elucidate the molecular mechanism of pungent flavored compounds in treating cardiovascular diseases (CVDs) and liver diseases, five pungent TCMs with the action of blood-activating and stasis-resolving (BASR) were selected. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between pungent flavored compounds and their holistic efficacy at the special organ level. First, we identified target proteins that are associated with pungent flavored compounds and found that these targets were functionally related to CVDs and liver diseases. Then, based on the phenotype that directly links human genes to the body parts they affect, we clustered target modules associated with pungent flavored compounds into liver and heart organs. We applied systems-based analysis to introduce a pungent flavored compound-target-pathway-organ network that clarifies mechanisms of pungent substances treating cardiovascular diseases and liver diseases by acting on the heart/liver organ. The systems pharmacology also suggests a novel systematic strategy for rational drug development from pungent TCMs in treating cardiovascular disease and associated liver diseases.
mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy
Authors: Tian Tian , Li Xiaoyi , Zhang Jinhua
Published: February 2019

The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression. In addition, mTOR also negatively regulates autophagy via different ways. We discuss mTOR signaling and its key upstream and downstream factors, the specific genetic changes in the mTOR pathway and the inhibitors of mTOR applied as therapeutic strategies in eight solid tumors. Although monotherapy and combination therapy with mTOR inhibitors have been extensively applied in preclinical and clinical trials in various cancer types, innovative therapies with better efficacy and less drug resistance are still in great need, and new biomarkers and deep sequencing technologies will facilitate these mTOR targeting drugs benefit the cancer patients in personalized therapy.
Insulin and Insulin Receptors in Adipose Tissue Development
Authors: Cignarelli Angelo , Genchi Valentina Annamaria , Perrini Sebastio , Natalicchio Annalisa , Laviola Luigi , Giorgino Francesco
Published: February 2019

Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.
Transcriptome Analysis Reveals New Insights into the Bacterial Wilt Resistance Mechanism Mediated by Silicon in Tomato
Authors: Jiang Nihao , Fan Xueying , Lin Weipeng , Wang Guoping , Cai Kunzheng
Published: February 2019

Bacterial wilt is a devastating disease of tomato caused by soilborne pathogenic bacterium Ralstonia solanacearum. Previous studies found that silicon (Si) can increase tomato resistance against R. solanacearum, but the exact molecular mechanism remains unclear. RNA sequencing (RNA-Seq) technology was used to investigate the dynamic changes of root transcriptome profiles between Si-treated (+Si) and untreated (−Si) tomato plants at 1, 3, and 7 days post-inoculation with R. solanacearum. The contents of salicylic acid (SA), ethylene (ET), and jasmonic acid (JA) and the activity of defense-related enzymes in roots of tomato in different treatments were also determined. The burst of ET production in roots was delayed, and SA and JA contents were altered in Si treatment. The transcriptional response to R. solanacearum infection of the +Si plants was quicker than that of the untreated plants. The expression levels of differentially-expressed genes involved in pathogen-associated molecular pattern-triggered immunity (PTI), oxidation resistance, and water-deficit stress tolerance were upregulated in the Si-treated plants. Multiple hormone-related genes were differentially expressed in the Si-treated plants. Si-mediated resistance involves mechanisms other than SA- and JA/ET-mediated stress responses. We propose that Si-mediated tomato resistance to R. solanacearum is associated with activated PTI-related responses and enhanced disease resistance and tolerance via several signaling pathways. Such pathways are mediated by multiple hormones (e.g., SA, JA, ET, and auxin), leading to diminished adverse effects (e.g., senescence, water-deficit, salinity and oxidative stress) normally caused by R. solanacearum infection. This finding will provide an important basis to further characterize the role of Si in enhancing plant resistance against biotic stress.
Solid Target System with In-Situ Target Dissolution
Authors: Gelbart William Z. , Johnson Richard R.
Published: February 2019

A significant number of medical radioisotopes use solid, often metallic, parent materials. These materials are deposited on a substrate to facilitate the cooling and handling of the target during placing, irradiation, and processing. The processing requires the transfer of the target to a processing area outside the irradiation area. In this new approach the target is processed at the irradiation site for liquid only transport of the irradiated target material to the processing area. The design features common to higher energy production target systems are included in the target station. The target is inclined at 14 degrees to the beam direction. The system has been designed to accept an incident beam of 15 to 16 mm diameter and a beam power between 2 and 5 kW. Thermal modeling is presented for targets of metals and compounds. A cassette of five or 10 prepared targets is housed at the target station as well as a target dissolution assembly. Only the dissolved target material is transported to the chemistry laboratory so that the design does not require additional irradiation area penetrations. This work presents the design, construction, and modeling details of the assembly. A full performance characterization will be reported after the unit is moved to a cyclotron facility for beam related measurements.
Microfluidics and Nanofluidics
Authors: Yang Ruey-Jen
Published: February 2019

Microfluidics and nanofluidics deal with fluid flows in geometries of micro/nano scales [...]
The Benefice of Mobile Parts’ Exchange in the Management of Infected Total Joint Arthroplasties with Prosthesis Retention (DAIR Procedure)
Authors: Hirsiger Stefanie , Betz Michael , Stafylakis Dimitrios , Götschi Tobias , Lew Daniel , Uçkay Ilker
Published: February 2019

Background: The management of prosthetic joint infections (PJI) with debridement and retention of the implant (DAIR) has its rules. Some authors claim that lacking the exchange of mobile prosthetic parts is doomed to failure, while others regard it as optional. Methods: Single-center retrospective cohort in PJIs treated with DAIR. Results: We included 112 PJIs (69 total hip arthroplasties, 9 medullary hip prostheses, 41 total knee arthroplasties, and 1 total shoulder arthroplasty) in 112 patients (median age 75 years, 52 females (46%), 31 (28%) immune-suppressed) and performed a DAIR procedure in all cases—48 (43%) with exchange of mobile parts and 64 without. After a median follow-up of 3.3 years, 94 patients (84%) remained in remission. In multivariate Cox regression analysis, remission was unrelated to PJI localization, pathogens, number of surgical lavages, duration of total antibiotic treatment or intravenous therapy, choice of antibiotic agents, immune-suppression, or age. In contrast, the exchange of mobile parts was protective (hazard ratio 1.9; 95% confidence interval 1.2–2.9). Conclusions: In our retrospective single-center cohort, changing mobile parts of PJI during the DAIR approach almost doubled the probability for long-term remission.
Effects of Stepwise Lung Recruitment Maneuvers in Patients with Early Acute Respiratory Distress Syndrome: A Prospective, Randomized, Controlled Trial
Authors: Kung Shu-Chen , Hung Yi-Li , Chen Wan-Ling , Wang Ching-Min , Chang Hui-Chun , Liu Wei-Lun
Published: February 2019

Since the clinical benefit of lung recruitment maneuvers (LRMs) is still conflicting, we performed this prospective, randomized, controlled study to investigate whether LRMs should be used in the routine management of acute respiratory distress syndrome (ARDS). This trial was conducted in four intensive care units (ICUs) to compare application of a modified stepwise LRMs with solely lung-protective ventilation in patients with moderate to severe ARDS within 72 h from the onset. The primary outcome was 28-day mortality, and the secondary outcomes were ventilator-free days and ICU-free days. We collected data on 120 ARDS patients from 2009 to 2012, and there was no difference in 28-day mortality between the two groups (28.3% vs. 30.0%, p = 0.84). However, among survivors, patients in the LRM group had a significant longer median duration of ventilator-free days (18 vs. 13 days; p = 0.04) and ICU-free days (16 vs. 11 days; p = 0.03) at 28 days than in the control group. The respiratory system compliance was significantly higher in the LRM group from day 1 to day 7. The occurrence rate of barotrauma was similar in both groups. We concluded that LRMs combined with lung-protective ventilation in early ARDS may improve patient outcomes.
Trastuzumab Induced Chemobrain, Atorvastatin Rescued Chemobrain with Enhanced Anticancer Effect and without Hair Loss-Side Effect
Authors: Lee Seonhwa , Lee Hae-June , Kang Hyunji , Kim Eun-Ho , Lim Young-Cheol , Park Hyejin , Lim Sang Moo , Lee Yong Jin , Kim Jung Min , Kim Jin Su
Published: February 2019

The authors identified that chemo-brain was induced after trastuzumab (TZB) therapy. In addition, atorvastatin (ATV) could rescue chemo-brain during trastuzumab (TZB) therapy. Enhanced therapeutic effect of TZB was confirmed after ATV therapy. We also investigated that there was no hair loss side effect due to ATV therapy. In an animal model, 150 μg TZB and five serial doses of 20 mg/kg ATV were administered. 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data were acquired. Statistical parametric mapping analysis and voxel-based morphometry analysis were performed to identify differences in glucose metabolism and gray matter concentration. The enhanced therapeutic efficacy of TZB after ATV treatment was assessed using a human epidermal growth factor receptor 2-positive gastric cancer model. We found a decrease in cerebral glucose metabolism and gray matter concentration in the frontal lobe following TZB therapy (p < 0.005). After subsequent ATV administration, glucose metabolism and regional gray matter concentration were rescued (p < 0.005). Cognitive impairment due to TZB and the rescue effect of ATV were confirmed using a passive avoidance test and quantitative real-time reverse transcription PCR. Furthermore, the penetration and accumulation of TZB in tumors increased by 100% after ATV co-administration, which resulted in an enhanced anti-cancer effect. Our study collectively demonstrates that ATV co-administration with TZB rescued the TZB-induced chemo-brain and enhances the therapeutic efficacy of TZB in tumors. We also showed that there was no hair loss during ATV therapy.
Monitoring Effects of Land Cover Change on Biophysical Drivers in Rangelands Using Albedo
Authors: Münch Zahn , Gibson Lesley , Palmer Anthony
Published: February 2019

This paper explores the relationship between land cover change and albedo, recognized as a regulating ecosystems service. Trends and relationships between land cover change and surface albedo were quantified to characterise catchment water and carbon fluxes, through respectively evapotranspiration (ET) and net primary production (NPP). Moderate resolution imaging spectroradiometer (MODIS) and Landsat satellite data were used to describe trends at catchment and land cover change trajectory level. Peak season albedo was computed to reduce seasonal effects. Different trends were found depending on catchment land management practices, and satellite data used. Although not statistically significant, albedo, NPP, ET and normalised difference vegetation index (NDVI) were all correlated with rainfall. In both catchments, NPP, ET and NDVI showed a weak negative trend, while albedo showed a weak positive trend. Modelled land cover change was used to calculate future carbon storage and water use, with a decrease in catchment carbon storage and water use computed. Grassland, a dominant dormant land cover class, was targeted for land cover change by woody encroachment and afforestation, causing a decrease in albedo, while urbanisation and cultivation caused an increase in albedo. Land cover map error of fragmented transition classes and the mixed pixel effect, affected results, suggesting use of higher-resolution imagery for NPP and ET and albedo as a proxy for land cover.
Numerical Simulations of Laser and Hybrid S700MC T-Joint Welding
Authors: Kik Tomasz , Górka Jacek
Published: February 2019

This article presents examples of numerical simulations done based on the real experiments of S700MC steel T-joint laser and hybrid welding. Presented results of numerical analyses carried out using SYSWELD show the possibilities offered to contemporary engineers by modern software used to make numerical analyses of production processes. After calibration of a heat source models on the chosen examples of S700MC steel 10-mm-thick T-joint laser and hybrid welding, distributions of temperature fields, thermal cycles, distributions of individual metallurgical phases and hardness, and strains and plastic deformations in simulated processes were calculated for one selected joint from both mentioned methods. The results of the analysis allow determining both the differences in the stress distributions and their minimal and maximal values. This article also presents the benefits resulting from the use of such analyses, due to the significant savings in time and resources to be spent on the development of correct technologies for joining modern construction materials such as thermomechanically treated steels, especially given that some of the results are unavailable or very difficult to collect using conventional measurement methods.