bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in a Large Independent Cohort
Authors: Melloni Giulia , Eoli Marica , Cesaretti Claudia , Bianchessi Donatella , Ibba Maria Cristina , Esposito Silvia , Scuvera Giulietta , Morcaldi Guido , Micheli Roberto , Piozzi Elena , Avignone Sabrina , Chiapparini Luisa , Pantaleoni Chiara , Natacci Federica , Finocchiaro Gaetano , Saletti Veronica
Published: November 2019

The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring NF1 mutations in the 5’ tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of NF1 mutation with the development of OPG was analysed using the χ2 test and Fisher’s exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni’s correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype–phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions.
ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data
Authors: Wu Sheng , Nitschke Katja , Heinkele Jakob , Weis Cleo-Aron , Worst Thomas Stefan , Eckstein Markus , Porubsky Stefan , Erben Philipp
Published: November 2019

Anilin actin binding protein (ANLN) and transducing-like enhancer protein 2 (TLE2) are associated with cancer patient survival and progression. The impact of their gene expression on progression-free survival (PFS) of patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) and subtype association has not yet been investigated. qRT-PCR was used to measure the transcript levels of ANLN and TLE2 in the Mannheim cohort, and validated in silico by The Cancer Genome Atlas (TCGA) cohort. Uni- and multivariate Cox regression analyses identified predictors for disease-specific survival (DSS) and overall survival (OS). In the Mannheim cohort, tumors with high ANLN expression were associated with lower OS and DSS, while high TLE2 expression was associated with a favorable OS. The TCGA cohort confirmed that high ANLN and low TLE2 expression was associated with shorter OS and disease-free survival (DFS). In both cohorts, multivariate analyses showed ANLN and TLE2 expression as independent outcome predictors. Furthermore, ANLN was more highly expressed in cell lines and patients with the basal subtype, while TLE2 expression was higher in cell lines and patients with the luminal subtype. ANLN and TLE2 are promising biomarkers for individualized bladder cancer therapy including cancer subclassification and informed MIBC prognosis.
Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis
Authors: Al Kafri Nour , Hafizi Sassan
Published: November 2019

The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including its ligand selectivity and signalling in cancer cells. Tyro3 showed widespread protein and mRNA expression in a variety of human cancer cell lines. In SCC-25 head and neck cancer cells expressing both Tyro3 and Axl, Western blotting showed that both natural TAM ligands ProS1 and Gas6 rapidly stimulated Tyro3 and Erk kinase phosphorylation, with ProS1 eliciting a greater effect. In contrast, Gas6 was the sole stimulator of Axl and Akt kinase phosphorylation. In MGH-U3 bladder cancer cells, which express Tyro3 alone, ProS1 was again the stronger stimulator of Tyro3 and Erk stimulation but additionally stimulated Akt phosphorylation. Conditioned medium from ProS1-secreting 786-0 kidney cancer cells replicated the kinase activation effects of recombinant ProS1 in SCC-25 cells, with specificity confirmed by ProS1 ligand traps and warfarin. In addition, ProS1 protected cancer cells from acute apoptosis induced by staurosporine, as well as additionally, long-term serum starvation-induced apoptosis in MGH-U3 cells (Tyro3 only), which reflects its additional coupling to Akt signalling in these cells. In conclusion, we have shown that ProS1 is a tumour-derived functional ligand for Tyro3 that supports cancer cell survival. Furthermore, the ProS1-Tyro3 interaction is primarily coupled to Erk signalling although it displays signalling diversity dependent upon its representative expression as a TAM receptor in tumour cells.
Synthesis of Stilbene and Chalcone Inhibitors of Influenza A Virus by SBA-15 Supported Hoveyda-Grubbs Metathesis
Authors: Bizzarri Bruno Mattia , Fanelli Angelica , Piccinino Davide , De Angelis Marta , Dolfa Camilla , Palamara Anna Teresa , Nencioni Lucia , Zippilli Claudio , Crucianelli Marcello , Saladino Raffaele
Published: November 2019

Stilbene and chalcone derivatives with biological activity against influenza A virus have been synthesized by self-, cross-, and ring-closing metathesis procedures. The reactions were performed under environmentally friendly conditions using the second generation Hoveyda-Grubbs catalyst Aquamet SiPr after immobilization on Santa Barbara Amorphous mesoporous silicate SBA-15. Irrespective from the experimental conditions, the heterogeneous catalyst showed activity and selectivity comparable than the homogeneous counterpart for at least six successive runs without appreciable leaching of the active species. An appreciable antiviral activity against influenza A virus for some of the novel derivatives were observed, mainly involving the early stage of the virus-replication life-cycle.
Mitochondrial MiRNA in Cardiovascular Function and Disease
Authors: Song Rui , Hu Xiang-Qun , Zhang Lubo
Published: November 2019

MicroRNAs (miRNAs) are small noncoding RNAs functioning as crucial post-transcriptional regulators of gene expression involved in cardiovascular development and health. Recently, mitochondrial miRNAs (mitomiRs) have been shown to modulate the translational activity of the mitochondrial genome and regulating mitochondrial protein expression and function. Although mitochondria have been verified to be essential for the development and as a therapeutic target for cardiovascular diseases, we are just beginning to understand the roles of mitomiRs in the regulation of crucial biological processes, including energy metabolism, oxidative stress, inflammation, and apoptosis. In this review, we summarize recent findings regarding how mitomiRs impact on mitochondrial gene expression and mitochondrial function, which may help us better understand the contribution of mitomiRs to both the regulation of cardiovascular function under physiological conditions and the pathogenesis of cardiovascular diseases.
Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases
Authors: Olayioye Monilola A. , Noll Bettina , Hausser Angelika
Published: November 2019

As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo- and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.
Adjuvant Epigenetic Therapy of Decitabine and Suberoylanilide Hydroxamic Acid Exerts Anti-Neoplastic Effects in Acute Myeloid Leukemia Cells
Authors: Abou Najem Sonia , Khawaja Ghada , Hodroj Mohammad Hassan , Babikian Patil , Rizk Sandra
Published: November 2019

Atypical epigenetic processes including histone acetylation and DNA methylation have been identified as a fundamental theme in hematologic malignancies. Such mechanisms modify gene expression and prompt, in part at least, the initiation and progression of several malignancies including acute myeloid leukemia. In the current study we determined the effects of treating KG-1 and U937 acute myeloid leukemia (AML) cells, in vitro, with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), or with a DNMT inhibitor, decitabine (DAC), or their combination, on cell proliferation, cell cycle progression, apoptosis, and expression of apoptosis-related proteins. Each of SAHA and DAC attenuated cell proliferation and induced cell cycle arrest and apoptotic cell death of KG-1 and U937 cell lines. Besides, their sequential combination improved the obtained anti-neoplastic effect: significant augmentation of growth inhibition and apoptosis induction as compared to cells treated with either drug alone. This effect was featured by the upregulated expression of Bax, cytochrome c1, p21, and cleaved caspases 8, 9, and 3, signifying the activation of both the intrinsic and extrinsic pathways of apoptosis. The sequential combination of SAHA and DAC causes a profound antitumorigenic effect in AML cell lines by inducing the expression of tumor suppressor genes.
RITA Is Expressed in Trophoblastic Cells and Is Involved in Differentiation Processes of the Placenta
Authors: Wildner Julia Maria , Friemel Alexandra , Jennewein Lukas , Roth Susanne , Ritter Andreas , Schüttler Cornelia , Chen Qi , Louwen Frank , Yuan Juping , Kreis Nina-Naomi
Published: November 2019

Preeclampsia (PE) remains a leading cause of maternal and perinatal mortality and morbidity worldwide. Its pathogenesis has not been fully elucidated and no causal therapy is currently available. It is of clinical relevance to decipher novel molecular biomarkers. RITA (RBP-J (recombination signal binding protein J)-interacting and tubulin-associated protein) has been identified as a negative modulator of the Notch pathway and as a microtubule-associated protein important for cell migration and invasion. In the present work, we have systematically studied RITA’s expression in primary placental tissues from patients with early- and late-onset PE as well as in various trophoblastic cell lines. RITA is expressed in primary placental tissues throughout gestation, especially in proliferative villous cytotrophoblasts, in the terminally differentiated syncytiotrophoblast, and in migrating extravillous trophoblasts. RITA’s messenger RNA (mRNA) level is decreased in primary tissue samples from early-onset PE patients. The deficiency of RITA impairs the motility and invasion capacity of trophoblastic cell lines, and compromises the fusion ability of trophoblast-derived choriocarcinoma cells. These data suggest that RITA may play important roles in the development of the placenta and possibly in the pathogenesis of PE.
MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer
Authors: Ding Lei , Gu Huan , Xiong Xianhui , Ao Hongshun , Cao Jiaqi , Lin Wen , Yu Min , Lin Jie , Cui Qinghua
Published: November 2019

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3′-untranslated region (3′-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial–mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.
A Microlens Super-Surface Film with Regular Graded Circular Hole-Like Subwavelength Structures for Highly Focusing Strength
Authors: Wu Jinshuang , Zhang Leimengting , Li Yahong , Zhang Yixin , Yang Bowei , Fu Yuegang
Published: November 2019

Using the fact that a sub-wavelength structure exhibits the same thermal expansion coefficient as a micro-lens array, we design a micro-lens super-surface film with regular circular hole-like subwavelength structures to realize the high performances of central highly focusing strength and short focal length. In addition, based on the Fresnel—Kirchhoff diffraction theory, the influences of subwavelength structural period and height on the focusing performance of a micro-lens are analyzed. Furthermore, the finite-difference time-domain method is utilized to optimize the structural parameters. Via direct laser writing and an inductively coupled plasma process, we fabricated a square micro-lens array consisting of a 1000 × 1000 micro-lens unit with a sub-wavelength structure, and the optical focusing performance was measured in the visible light band. Finally, the experimental results indicate that the focal length is decreased to 15 μm, the focal spot central energy is increased by 7.3%, and the light transmission, enhanced via inserting sub-wavelength structures, corresponds to 3%. This proves that the designed micro-lens array with a regular-graded circular hole-like subwavelength structure can achieve central high focusing and a short focal length. This has applications in several fields of wavefront detection and light field imaging systems.
Extreme High-Speed Laser Material Deposition (EHLA) of AISI 4340 Steel
Authors: Li Tianci , Zhang Lele , Bultel Gregor Gilles Pierre , Schopphoven Thomas , Gasser Andres , Schleifenbaum Johannes Henrich , Poprawe Reinhart
Published: November 2019

A variant of conventional laser material deposition (LMD), extreme high-speed laser material deposition (German acronym: EHLA) is characterized by elevated process speeds of up to 200 m/min, increased cooling rates, and a significantly reduced heat affected zone. This study focuses on the feasibility of using EHLA to apply material onto Fe-based substrate materials with AISI 4340 as a filler material. We studied how three different build-up strategies—consisting of one, three, and five consecutive deposited layers and hence, different thermal evolutions of the build-up volume—influence the metallurgical characteristics such as microstructure, porosity, hardness, and static mechanical properties. We propose a thermo-metallurgical scheme to help understand the effects of the build-up strategy and the thermal evolution on the microstructure and hardness. The tensile strength of the build-up volume was determined and is higher than the ones of forged AISI 4340 material.
Influence of the Coupling between Two Qubits in an Open Coherent Cavity: Nonclassical Information via Quasi-Probability Distributions
Authors: Mohamed Abdel-Baset A. , Eleuch Hichem , Obada Abdel-Shafy F.
Published: November 2019

In this paper, we investigate the dynamics of two coupled two-level systems (or qubits) that are resonantly interacting with a microwave cavity. We examine the effects of the intrinsic decoherence rate and the coupling between the two qubits on the non-classicality of different system partitions via quasi-probability functions. New definitions for the partial Q-function and its Wehrl entropy are used to investigate the information and the quantum coherence of the phase space. The amount of the quantum coherence and non-classicality can be appropriately tuned by suitably adopting the rates of the intrinsic-decoherence and the coupling between the two qubits. The intrinsic decoherence has a pronounced effect on the negativity and the positivity of the Wigner function. The coupling between the two qubits can control the negativity and positivity of the quasi-probability functions.
“Food is Environmentally and Culturally Specific!”: A Preliminary Qualitative Study on U.S. Immigrant Parents’ Perceptions of School Lunch
Authors: Obeng-Gyasi Emmanuel , Antwi Godfred , Obeng Cecilia
Published: November 2019

Children spend most of their day hours in school, so the dietary choices they make during school days are important for their childhood development and later life. This research examined food choices among immigrant families with school-age children in Indiana, USA. Open-ended questions were answered by 52 immigrant parents in 2017. Parents who answered the questions had children in classes ranging from kindergarten to grade 12. NVivo 11 was used for the initial analysis of the dataset, and several themes were identified. After the initial analysis, the data were categorized into major themes to condense the themes. Thirty-eight (73%) of the respondents indicated that their children ate school lunch, 14 (27%) indicated that they prepared lunch for their children to eat at school, and 39 (75%), mostly from non-industrialized countries, indicated that their children ate their home-country staple foods for dinner and on non-school days. Parents indicated that schools are serving the needs of immigrant children by serving varieties of foods during lunchtime.
Generative Noise Reduction in Dental Cone-Beam CT by a Selective Anatomy Analytic Iteration Reconstruction Algorithm
Authors: Dao-Ngoc Lam , Du Yi-Chun
Published: November 2019

Dental cone-beam computed tomography (CBCT) is a powerful tool in clinical treatment planning, especially in a digital dentistry platform. Currently, the “as low as diagnostically acceptable” (ALADA) principle and diagnostic ability are a trade-off in most of the 3D integrated applications, especially in the low radio-opaque densified tissue structure. The CBCT benefits in comprehensive diagnosis and its treatment prognosis for post-operation predictability are clinically known in modern dentistry. In this paper, we propose a new algorithm called the selective anatomy analytic iteration reconstruction (SA2IR) algorithm for the sparse-projection set. The algorithm was simulated on a phantom structure analogous to a patient’s head for geometric similarity. The proposed algorithm is projection-based. Interpolated set enrichment and trio-subset enhancement were used to reduce the generative noise and maintain the scan’s clinical diagnostic ability. The results show that proposed method was highly applicable in medico-dental imaging diagnostics fusion for the computer-aided treatment planning, because it had significant generative noise reduction and lowered computational cost when compared to the other common contemporary algorithms for sparse projection, which generate a low-dosed CBCT reconstruction.
Experimental Validation of a Reliable Palmprint Recognition System Based on 2D Ultrasound Images
Authors: Iula Antonio , Micucci Monica
Published: November 2019

Ultrasound has been trialed in biometric recognition systems for many years, and at present different types of ultrasound fingerprint readers are being produced and integrated in portable devices. An important merit of the ultrasound is its ability to image the internal structure of the hand, which can guarantee improved recognition rates and resistance to spoofing attacks. In addition, ambient noise like changes of illumination, humidity, or temperature, as well as oil or ink stains on the skin do not affect the ultrasound image. In this work, a palmprint recognition system based on ultrasound images is proposed and experimentally validated. The system uses a gel pad to obtain acoustic coupling between the ultrasound probe and the user’s hand. The collected volumetric image is processed to extract 2D palmprints at various under-skin depths. Features are extracted from one of these 2D palmprints using a line-based procedure. Recognition performances of the proposed system were evaluated by performing both verification and identification experiments on a home-made database containing 281 samples collected from 32 different volunteers. An equal error rate of 0.38% and an identification rate of 100% were achieved. These results are very satisfactory, even if obtained with a relatively small database. A discussion on the causes of bad acquisitions is also presented, and a possible solution to further optimize the acquisition system is suggested.
Deformation Effect on Water Transport through Nanotubes
Authors: Robinson Ferlin , Shahbabaei Majid , Kim Daejoong
Published: November 2019

In this study, we used non-equilibrium molecular dynamics to study the transport of water through deformed (6,6) Carbon Nanotubes (CNTs) and Boron Nitride Nanotubes (BNNTs). The results were then compared with that of the perfect nanotubes. The main aim of this study was to get a better insight into the deformation effect on water transport through nanotubes rather than directly comparing the CNTs and BNNTs. As the diameters of both types of nanotubes differ from each other for the same chiral value, they are not directly comparable. We carried out our study on deformations such as screw distortion, XY-distortion, and Z-distortion. XY-distortion of value 2 shows a change from single-file water transport to near-Fickian diffusion. The XY-distortions of higher value shows a notable negative effect on water transport when their distortion values get larger. These suggest that the degree of deformation plays a crucial role in water transport through deformed nanotubes. The Z-distortion of 2 showed discontinuous single-file chain formation inside the nanotubes. Similar phenomena are observed in both nanotubes, irrespective of their type, while the magnitudes of their effects vary.
Understanding Community Assembly Based on Functional Traits, Ontogenetic Stages, Habitat Types and Spatial Scales in a Subtropical Forest
Authors: Li Yanpeng , Bin Yue , Xu Han , Ni Yunlong , Zhang Ruyun , Ye Wanhui , Lian Juyu
Published: November 2019

Community assembly in natural communities is commonly explained by stochastic and niche-based processes such as environmental filtering and biotic interactions. Many studies have inferred the importance of these processes using a trait-based approach, however, there are still unknowns around what factors affect the importance of different assembly processes in natural communities. In this study, the trait dispersion patterns of 134 species were examined across different functional traits, habitat types, ontogenetic stages and spatial scales from a 20-ha Dinghushan Forest Dynamic Plot in China. The results showed that (1) functional traits related to productivity such as specific leaf area and leaf area mainly showed functional clustering, indicating these two functional traits were more affected by environmental filtering. However, trait dispersion patterns depended on more than the ecological significances of functional traits. For example, trait dispersions of leaf dry matter content, leaf thickness and maximum height did not show consistent patterns across habitat types and ontogenetic stages, suggesting more complex mechanisms may operate on these traits; (2) the trait dispersion varied with the habitat types and ontogenetic stages. Specifically, we found that habitat types only affected the strength of trait dispersions for all the five traits, but ontogenetic stages influenced both the strength and direction of trait dispersions, which depended on the traits selected; (3) the relative importance of soil, topography and space to trait dispersion varied with ontogenetic stages. Topography and space were more important for trait dispersion of saplings but soil was more important for trait dispersion of adults; (4) biotic interactions dominated community assembly at smaller spatial scales but environmental filtering dominated community assembly at larger spatial scales. Overall, the results highlight the importance of functional traits, habitat types, ontogenetic stages and spatial scales to community assembly in natural communities.
A Fractional Measles Model Having Monotonic Real Statistical Data for Constant Transmission Rate of the Disease
Authors: Almeida Ricardo , Qureshi Sania
Published: November 2019

Non-Markovian effects have a vital role in modeling the processes related with natural phenomena such as epidemiology. Various infectious diseases have long-range memory characteristics and, thus, non-local operators are one of the best choices to be used to understand the transmission dynamics of such diseases and epidemics. In this paper, we study a fractional order epidemiological model of measles. Some relevant features, such as well-posedness and stability of the underlying Cauchy problem, are considered accompanying the proofs for a locally asymptotically stable equilibrium point for basic reproduction number R 0 < 1 , which is most sensitive to the fractional order parameter and to the percentage of vaccination. We show the efficiency of the model through a real life application of the spread of the epidemic in Pakistan, comparing the fractional and classical models, while assuming constant transmission rate of the epidemic with monotonically increasing and decreasing behavior of the infected population. Secondly, the fractional Caputo type model, based upon nonlinear least squares curve fitting technique, is found to have smaller residuals when compared with the classical model.
The Hearing Impairment Ontology: A Tool for Unifying Hearing Impairment Knowledge to Enhance Collaborative Research
Authors: Hotchkiss Jade , Manyisa Noluthando , Mawuli Adadey Samuel , Oluwole Oluwafemi Gabriel , Wonkam Edmond , Mnika Khuthala , Yalcouye Abdoulaye , Nembaware Victoria , Haendel Melissa , Vasilevsky Nicole , Mulder Nicola J. , Jupp Simon , Wonkam Ambroise , K. Mazandu Gaston
Published: November 2019

Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and can be non-syndromic or syndromic. HI can be caused by various genetic, environmental, and/or unknown factors. Some ontologies capture some HI forms, phenotypes, and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration, and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the ‘Hearing Impairment’ concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical, and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promotes collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic, and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology.
Computational Inference of Gene Co-Expression Networks for the identification of Lung Carcinoma Biomarkers: An Ensemble Approach
Authors: Delgado-Chaves Fernando M. , Gómez-Vela Francisco , García-Torres Miguel , Divina Federico , Vázquez Noguera José Luis
Published: November 2019

Gene Networks (GN), have emerged as an useful tool in recent years for the analysis of different diseases in the field of biomedicine. In particular, GNs have been widely applied for the study and analysis of different types of cancer. In this context, Lung carcinoma is among the most common cancer types and its short life expectancy is partly due to late diagnosis. For this reason, lung cancer biomarkers that can be easily measured are highly demanded in biomedical research. In this work, we present an application of gene co-expression networks in the modelling of lung cancer gene regulatory networks, which ultimately served to the discovery of new biomarkers. For this, a robust GN inference was performed from microarray data concomitantly using three different co-expression measures. Results identified a major cluster of genes involved in SRP-dependent co-translational protein target to membrane, as well as a set of 28 genes that were exclusively found in networks generated from cancer samples. Amongst potential biomarkers, genes N C K A P 1 L and D M D are highlighted due to their implications in a considerable portion of lung and bronchus primary carcinomas. These findings demonstrate the potential of GN reconstruction in the rational prediction of biomarkers.
Long Noncoding RNA from PVT1 Exon 9 Is Overexpressed in Prostate Cancer and Induces Malignant Transformation and Castration Resistance in Prostate Epithelial Cells
Authors: Pal Gargi , Huaman Jeannette , Levine Fayola , Orunmuyi Akintunde , Olapade-Olaopa E. Oluwabunmi , Onagoruwa Onayemi T. , Ogunwobi Olorunseun O.
Published: November 2019

Prostate cancer (PCa) is the most common non-cutaneous cancer and second leading cause of cancer-related death for men in the United States. The nonprotein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in different cancers. PVT1 gives rise to several alternatively spliced transcripts and microRNAs. There are at least twelve exons of PVT1, which make separate transcripts, and likely have different functions. Here, we demonstrate that PVT1 exon 9 is significantly overexpressed in PCa tissues in comparison to normal prostate tissues. Both transient and stable overexpression of PVT1 exon 9 significantly induced greater prostate epithelial cell migration, as well as increased proliferation and corresponding proliferating cell nuclear antigen (PCNA) expression. Notably, implantation into mice of a non-tumorigenic prostate epithelial cell line stably overexpressing PVT1 exon 9 resulted in the formation of malignant tumors. Furthermore, PVT1 exon 9 overexpression significantly induced castration resistance. Consequently, PVT1 exon 9 expression is important for PCa initiation and progression, and holds promise as a therapeutic target in PCa.
SXGBsite: Prediction of Protein–Ligand Binding Sites Using Sequence Information and Extreme Gradient Boosting
Authors: Zhao Ziqi , Xu Yonghong , Zhao Yong
Published: November 2019

The prediction of protein–ligand binding sites is important in drug discovery and drug design. Protein–ligand binding site prediction computational methods are inexpensive and fast compared with experimental methods. This paper proposes a new computational method, SXGBsite, which includes the synthetic minority over-sampling technique (SMOTE) and the Extreme Gradient Boosting (XGBoost). SXGBsite uses the position-specific scoring matrix discrete cosine transform (PSSM-DCT) and predicted solvent accessibility (PSA) to extract features containing sequence information. A new balanced dataset was generated by SMOTE to improve classifier performance, and a prediction model was constructed using XGBoost. The parallel computing and regularization techniques enabled high-quality and fast predictions and mitigated overfitting caused by SMOTE. An evaluation using 12 different types of ligand binding site independent test sets showed that SXGBsite performs similarly to the existing methods on eight of the independent test sets with a faster computation time. SXGBsite may be applied as a complement to biological experiments.
Comparison of Aluminum Alloys from Aircraft of Four Nations Involved in the WWII Conflict Using Multiscale Analyses and Archival Study
Authors: Ouissi Toufa , Collaveri Gilles , Sciau Philippe , Olivier Jean-Marc , Brunet Magali
Published: November 2019

Aluminum alloys are very interesting witnesses of industrial and technical development. The first ever developed was Duralumin, a light metal with good mechanical properties. In the 1930s, the rise of nationalism stimulated research and development, generating various aluminum alloys. This work reports the comparison of two versions of aluminum alloys, which were found in collected parts of WWII crashed aircraft from four nations: a Messerschmitt Bf 109 (DE), a Dewoitine D.520 (FR), and a P-51 Mustang (USA) and an Avro Lancaster (United Kingdom). The first version of alloy with magnesium content below or equal to 1 wt.% and the second version with higher magnesium content (1.5 wt.%), were identified as respectively AlCuMg1, AlCuMg2 in Germany; Duralumin, Duralumin F.R. in France; Hiduminium DU Brand, Hiduminium 72 in the UK and 17S, 24S in the USA. This study uses a multiscale approach based on historical research complimented by laboratory analyses of materials directly collected on the crashed aircraft. It allows a comparison and a better knowledge of the alloys used in each nations: their chemical composition, designations, microstructure, and mechanical properties are investigated.
Making a Difference in PE Lessons: Using a Low Organized Games Approach to Teach Fundamental Motor Skills in China
Authors: Zhang Li , Cheung Peggy
Published: November 2019

Background: Fundamental motor skills (FMS) is the foundational movement for children’s physical development. Physical Education (PE) lessons provide a unique opportunity for children to acquire these skills. The purposes of this study were to: (1) to describe the FMS performance of primary school children in China; and (2) to examine the effect of a PE-based intervention on children’s FMS. Methods: The 12-week PE-based intervention was conducted using a low organized games (LOG) approach. Children’s FMS was measured by the Test of Gross Motor Development-2 (TGMD-2). Participants were 560 children aged between 6–9 years old (grade one to three) from two primary schools in Chongqing, China. They were grouped into intervention group (with LOG program PE; n = 282) or control group (with regular PE; n = 278). Results: The results revealed significant interaction effect between group and grade on the locomotor skill score changes (F(1,554) = 22.31, p < 0.000), and object control score change (F(1,554) = 627.1, p < 0.000). There was no significant interaction effect between the intervention group and gender on locomotor skill (F(1,554) = 1.49, p = 0.223) and object control skill significant (F(1,554) = 743, p = 0.389). Conclusions: The present study supported the application of LOG approach in PE lesson as an effective intervention to enhance children’s FMS in China.
Gender Equality, Drinking Cultures and Second-Hand Harms from Alcohol in the 50 US States
Authors: Karriker-Jaffe Katherine J. , Tam Christina C. , Cook Won Kim , Greenfield Thomas K. , Roberts Sarah C.M.
Published: November 2019

Background: Gender inequality and cultures of binge drinking may increase the risk of second-hand harms from alcohol. Methods: Using the 2014–2015 National Alcohol Survey and 2015 National Alcohol’s Harm to Others Survey (N = 7792), we examine associations of state-level gender equality measures (contraceptive access, abortion rights, women’s economic equality) and binge drinking cultures (rates of men’s and women’s binge drinking) with individual-level indicators of second-hand harms by drinking strangers and partners/spouses. Results: In main effects models, only male binge drinking was associated with greater odds of harms from drinking strangers. There were significant interactions of gender equality with male binge drinking: High male binge drinking rates were more strongly associated with stranger-perpetrated harms in states low on contraceptive access or abortion rights compared to states high on these measures. Conversely, male binge drinking was more strongly associated with spouse/partner-perpetrated second-hand harms in states with more economic equality, compared to states lower on this measure. Conclusions: Detrimental effects of high male binge drinking rates may be modified by gender equality. Targeted interventions may reduce alcohol-related harms experienced by women in states with high rates of male binge drinking. Restrictions in access to contraception and abortion may exacerbate harms due to men’s drinking.
Putting Co-Exposures on Equal Footing: An Ecological Analysis of Same-Scale Measures of Air Pollution and Social Factors on Cardiovascular Disease in New York City
Authors: Humphrey Jamie L. , Reid Colleen E. , Kinnee Ellen J. , Kubzansky Laura D. , Robinson Lucy F. , Clougherty Jane E.
Published: November 2019

Epidemiologic evidence consistently links urban air pollution exposures to health, even after adjustment for potential spatial confounding by socioeconomic position (SEP), given concerns that air pollution sources may be clustered in and around lower-SEP communities. SEP, however, is often measured with less spatial and temporal resolution than are air pollution exposures (i.e., census-tract socio-demographics vs. fine-scale spatio-temporal air pollution models). Although many questions remain regarding the most appropriate, meaningful scales for the measurement and evaluation of each type of exposure, we aimed to compare associations for multiple air pollutants and social factors against cardiovascular disease (CVD) event rates, with each exposure measured at equal spatial and temporal resolution. We found that, in multivariable census-tract-level models including both types of exposures, most pollutant–CVD associations were non-significant, while most social factors retained significance. Similarly, the magnitude of association was higher for an IQR-range difference in the social factors than in pollutant concentrations. We found that when offered equal spatial and temporal resolution, CVD was more strongly associated with social factors than with air pollutant exposures in census-tract-level analyses in New York City.
A Case-Crossover Study to Investigate the Effects of Atmospheric Particulate Matter Concentrations, Season, and Air Temperature on Accident and Emergency Presentations for Cardiovascular Events in Northern Italy
Authors: Contiero Paolo , Boffi Roberto , Tagliabue Giovanna , Scaburri Alessandra , Tittarelli Andrea , Bertoldi Martina , Borgini Alessandro , Favia Immacolata , Ruprecht Ario Alberto , Maiorino Alfonso , Voza Antonio , Ripoll Pons Marta , Cau Alessandro , DeMarco Cinzia , Allegri Flavio , Tresoldi Claudio , Ciccarelli Michele
Published: November 2019

Atmospheric particulate matter (PM) has multiple adverse effects on human health, high temperatures are also associated with adverse health outcomes, and the frequency of cardiovascular events (CVEs) varies with season. We investigated a hypothesized increase in PM-related accident and emergency (A&E) presentations for CVE with high temperature, warm season, days of high influenza incidence, and in people with a cancer diagnosis, using a time-stratified case-crossover study design. Outcomes were associations of A&E presentation for CVE with atmospheric PM ≤ 10 μm (PM10), season, and air temperature. PM10 levels in the municipality of residence (exposure variable) were estimated by modeling data from local monitoring stations. Conditional logistic regression models estimated odds ratios (OR) with 95% confidence intervals (CI) for presentations in relation to supposed influencers, adjusting for confounders. Study participants were all who presented at the A&E of a large hospital near Milan, Italy, for a CVE (ICD-9: 390–459) from 1st January 2014 to 31st December 2015. There were 1349 A&E presentations for CVE in 2014–2015 and 5390 control days. Risk of A&E presentation was significantly increased on hot days with OR 1.34 (95%CI 1.05–1.71) per 10 μg/m3 PM10 increment (as mean PM10 on day of presentation, and 1 and 2 days before (lags 0–2)), and (for lag 0) in autumn (OR 1.23, 95%CI 1.09–1.37) and winter (OR 1.18, 95%CI 1.01–1.38). Risks were also significantly increased when PM10 was on lag 1, in people with a cancer diagnosis in the spring and summer months (1.88, 95%CI 1.05–3.37), and on days (lags 0–2) of high influenza incidence (OR 2.34, 95%CI 1.01–5.43). PM10 levels exceeded the 50 μg/m3 “safe” threshold recommended by the WHO and Italian legislation for only 3.8% of days during the warm periods of 2014–2015. Greater risk of A&E presentation for CVE in periods of high PM10 and high temperature suggests that “safe” thresholds for PM10 should be temperature-dependent and that the adverse effects of PM10 will increase as temperatures increase due to climate change.
Effects of a Risk-Based Licensing Scheme on the Incidence of Alcohol-Related Assault in Queensland, Australia: A Quasi-Experimental Evaluation
Authors: Nepal Smriti , Kypri Kypros , Attia John , Evans Tiffany-Jane , Chikritzhs Tanya , Miller Peter
Published: November 2019

Amid concerns about increasing alcohol-related violence in licensed premises, Queensland introduced a system of risk-based licensing (RBL) in 2009, the first of five Australian jurisdictions to do so. Under RBL, annual license fees are supposed to reflect the risk of harm associated with the outlet’s trading hours and record of compliance with liquor laws. The objective is to improve service and management practices thereby reducing patron intoxication and related problems. Using police data, we defined cases as assaults that occurred during so-called ‘high-alcohol hours’, and compared a pre-intervention period of 2004–2008 with the post-intervention period 2009–2014. We employed segmented linear regression, adjusting for year and time of assault (high vs. low alcohol hours), to model the incidence of (1) all assaults and (2) a subset that police indicated were related to drinking in licensed premises. We found a small decrease in all assaults (β = −5 per 100,000 persons/year; 95% CI: 2, 9) but no significant change in the incidence of assault attributed to drinking in licensed premises (β = −8; 95% CI: −18, 2). Accordingly, we concluded that the results do not support a hypothesis that RBL is effective in the prevention of harm from licensed premises. There may be value in trialing regulatory schemes with meaningful contingencies for non-compliance, and, in the meantime, implementing demonstrably effective strategies, such as trading hour restrictions, if the aim is to reduce alcohol-related violence.
‘It Shouldn’t Be This Hard’: Exploring the Challenges of Rural Health Research
Authors: Greville Heath , Haynes Emma , Kagie Robin , Thompson Sandra C
Published: November 2019

Health research is important for innovation and assessment of health status and health interventions, and maintaining a strong, engaged cohort of rural health researchers is essential for the ongoing improvement of the health of rural populations. Ethical guidelines and processes ensure research is undertaken in a way that protects and, where possible, empowers participants. We set out to systematically examine and document the challenges posed by ethics and governance processes for rural health researchers in Western Australia (WA) and the impact on the research undertaken. In this qualitative study, fifteen WA-based rural health researchers were interviewed. The identified challenges included inefficient systems, gatekeeping, apparent resistance to research and the lack of research experience of those involved in approval processes. For researchers seeking to conduct studies to improve rural and Aboriginal health, extended delays in approvals can hold up and impede research, ultimately changing the nature of the research undertaken and constraining the willingness of practitioners and researchers to undertake health research. Unwieldy ethics processes were seen to have a particularly onerous impact on rural research pertaining to service delivery, multiple sites, and research involving Aboriginal people, impeding innovation and inquiry in areas where it is much needed.
Perceptions about the Self-Learning Methodology in Simulated Environments in Nursing Students: A Mixed Study
Authors: Díaz Agea José Luis , Ramos-Morcillo Antonio Jesús , Amo Setien Francisco José , Ruzafa-Martínez María , Hueso-Montoro César , Leal-Costa César
Published: November 2019

The self-learning methodology in simulated environments (MAES©) is an active method of education. The aim of this study was to analyze the perceptions and opinions of undergraduate and graduate nursing students about the self-learning methodology in simulated environments. A mixed, cross-sectional, descriptive study based on a survey tool made ad hoc (quantitative approach) and an open questionnaire (qualitative approach) was carried out. A sample of 149 undergraduate and 25 postgraduate nursing students were tested. The score was high for all the variables of the questionnaire analyzed: for perception of simulation performance, M = 73.5 (SD = 14.5), for motivation, M = 23.9 (SD = 5.9), for the opinion about facilitators, M = 25.9 (SD = 4.5), and for the promotion of team work, M = 16.9 (SD = 3.4). Five dimensions were identified and evaluated in the qualitative research. The students were pleased with MAES© and had a positive perception, since they considered that MAES© increased their learning.
Predicting Adolescent Adjustment and Well-Being: The Interplay between Socio-Emotional and Personal Factors
Authors: de la Barrera Usue , Schoeps Konstanze , Gil-Gómez José-Antonio , Montoya-Castilla Inmaculada
Published: November 2019

Social and emotional factors such as emotional competence and self-esteem are protective factors that promote adolescent mental health and well-being. In this paper, we will examine the combined contribution of these socio-emotional factors in addition to personal factors, in the prediction of psychological adjustment and subjective well-being in adolescence. The study included 840 adolescents aged between 12 and 16 years old (M = 13.37, SD = 1.16, 51.4% girls). We measured personal variables (sex, age, number of siblings), socio-emotional variables (emotional competence and self-esteem), psychological adjustment (emotional and behavioural problems) and subjective well-being (life satisfaction and affect balance). Besides descriptive analysis and Pearson bivariate correlations, two different methodologies were performed, including hierarchical regression models and a fuzzy-set qualitative comparative analysis (fsQCA). The results show that emotional competence is a protective factor for optimal adjustment and well-being, and suggest that self-esteem reinforces this relation. Different patterns were observed for female and male adolescents of different ages and with different family backgrounds. The practical implications of our findings for intervention programs have been discussed.