bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Analysis of the Stress Field in Peri-Implant Bone: A Parametric Study of Influencing Parameters and Their Interactions for Multi-Objective Optimization
Authors: Didier Paul , Piotrowski Boris , Le Coz Gael , Joseph David , Bravetti Pierre , Laheurte Pascal
Published: August 2020

The present work proposes a parametric finite element model of the general case of a single loaded dental implant. The objective is to estimate and quantify the main effects of several parameters on stress distribution and load transfer between a loaded dental implant and its surrounding bone. The interactions between them are particularly investigated. Seven parameters (implant design and material) were considered as input variables to build the parametric finite element model: the implant diameter, length, taper and angle of inclination, Young’s modulus, the thickness of the cortical bone and Young’s modulus of the cancellous bone. All parameter combinations were tested with a full factorial design for a total of 512 models. Two biomechanical responses were identified to highlight the main effects of the full factorial design and first-order interaction between parameters: peri-implant bone stress and load transfer between bones and implants. The description of the two responses using the identified coefficients then makes it possible to optimize the implant configuration in a case study with type IV. The influence of the seven considered parameters was quantified, and objective information was given to support surgeon choices for implant design and placement. The implant diameter and Young’s modulus and the cortical thickness were the most influential parameters on the two responses. The importance of a low Young’s modulus alloy was highlighted to reduce the stress shielding between implants and the surrounding bone. This method allows obtaining optimized configurations for several case studies with a custom-made design implant.
Automatic Chinese Font Generation System Reflecting Emotions Based on Generative Adversarial Network
Authors: Chen Lu , Lee Feifei , Chen Hanqing , Yao Wei , Cai Jiawei , Chen Qiu
Published: August 2020

Manual font design is difficult and requires professional knowledge and skills to perform. Therefore, how to automatically generate the required fonts is a very challenging research task. On the other hand, there are few people who have studied the relationship between fonts and emotions, and common fonts generally cannot reflect emotional information. This paper proposes an Emotional Guidance GAN: an automatic Chinese font generation framework based on Generative Adversarial Network (GAN), which enables the generated fonts to reflect human emotional information. First, an elaborated questionnaire system was developed from Tencent company, which aims to quantitatively figure out the relationship between fonts and emotions. A visual expression recognition part is designed based on the trained model to provide a font generation module with conditional information. Moreover, the Emotional Guidance GAN (EG-GAN) with EM Distance and Gradient Penalty, as well as classification strategies, is proposed to generate new fonts with combined multiple styles that infer by an expression recognition module. The results of the evaluation experiments and the resolution of the synthesized font characters show the credibility of our model.
Seasonal Variability of Lightning Activity in Yakutia in 2009–2019
Authors: Tarabukina Lena , Kozlov Vladimir
Published: August 2020

The instrumental continuous monitoring of lightning activity in Yakutia has been carried by the lightning direction finder since the 2000s. Devices for detection of sferic (very low frequency radio pulses emitted by lightning discharges) in Yakutia were supplemented in 2009 with relatively short-range (effective detection radius up to 480 km) single-point Stormtracker and LD-250 direction finders from Boltek Corporation (Welland, ON, Canada). The Stormtracker gives a slightly overestimated ratio of CG strokes due to the amplitude threshold of a single-point direction finder, but the device has not changed over the years, which allows for the consideration of the annual dynamics of parameters. In 2009, a sensor in Yakutsk was included in the World Wide Lightning Location Network (WWLLN). The seasonal and diurnal variations of the total lightning stroke number in the central part and the entire area of Yakutia were obtained (up to 1200 km in radius and limited by latitude–longitude boundaries of 105–150° E, 55–75° N). The longest thunderstorm seasons are often observed in the southern part of Yakutia. There was a slight increase in the duration of the thunderstorm season until 2015 in the central part of Yakutia. The interannual variations in the total number of lightning strokes showed periodic fluctuations (with a period of about three years) over the whole area of Yakutia. The periods of high lightning activity shifted within a season from year to year, as revealed by the monthly stroke number variation. Thus, the maximum lightning rate occurred at the beginning of summer, in the middle or at the beginning of August, and had a period of about three years. Every summer, there were 2–3 periods of high lightning activity, resulting from the moving average with a two-week window (according to the longest duration of cyclones). If the periods of high lightning activity shifted toward the beginning of summer, a decrease in the number of days between seasonal peaks was observed. If the maximum shifted to the beginning of August, the number of days between peaks increased. The ratio of cloud-to-ground (CG) lightning strokes and the ratio of negative CG strokes was slightly decreasing by 2015 in the central part of Yakutia.
Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
Authors: Brito Leonardo Miranda , Ribeiro-dos-Santos Ândrea , Vidal Amanda Ferreira , de Araújo Gilderlanio Santana
Published: August 2020

Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. APOE, Amyloid Beta Precursor Protein (APP), and Presenilin-1 (PSEN1) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with limma package on ADNI Cohort data highlighted eight differential expressed (DE) genes (AGER, LINC00483, MMP19, CATSPER1, ARFGAP1, GPER1, PHLPP2, TRPM2) (false discovery rate (FDR) p-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and edgeR (FDR p-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA–gene interactions that may be involved in cognitive and neurodegeneration processes.
Bioactive Compounds in Anti-Diabetic Plants: From Herbal Medicine to Modern Drug Discovery
Authors: Tran Ngan , Pham Bao , Le Ly
Published: August 2020

Natural products, including organisms (plants, animals, or microorganisms) have been shown to possess health benefits for animals and humans. According to the estimation of the World Health Organization, in developing countries, 80% of the population has still depended on traditional medicines or folk medicines which are mostly prepared from the plant for prevention or treatment diseases. Traditional medicine from plant extracts has proved to be more affordable, clinically effective and relatively less adverse effects than modern drugs. Literature shows that the attention on the application of phytochemical constituents of medicinal plants in the pharmaceutical industry has increased significantly. Plant-derived secondary metabolites are small molecules or macromolecules biosynthesized in plants including steroids, alkaloids, phenolic, lignans, carbohydrates and glycosides, etc. that possess a diversity of biological properties beneficial to humans, such as their antiallergic, anticancer, antimicrobial, anti-inflammatory, antidiabetic and antioxidant activities Diabetes mellitus is a chronic disease result of metabolic disorders in pancreas β-cells that have hyperglycemia. Hyperglycemia can be caused by a deficiency of insulin production by pancreatic (Type 1 diabetes mellitus) or insufficiency of insulin production in the face of insulin resistance (Type 2 diabetes mellitus). The current medications of diabetes mellitus focus on controlling and lowering blood glucose levels in the vessel to a normal level. However, most modern drugs have many side effects causing some serious medical problems during a period of treating. Therefore, traditional medicines have been used for a long time and play an important role as alternative medicines. Moreover, during the past few years, some of the new bioactive drugs isolated from plants showed antidiabetic activity with more efficacy than oral hypoglycemic agents used in clinical therapy. Traditional medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus. World Health Organization has pointed out this prevention of diabetes and its complications is not only a major challenge for the future, but essential if health for all is to be attained. Therefore, this paper briefly reviews active compounds, and pharmacological effects of some popular plants which have been widely used in diabetic treatment. Morphological data from V-herb database of each species was also included for plant identification.
Enhancing Sustainability by Improving Plant Salt Tolerance through Macro- and Micro-Algal Biostimulants
Authors: Carillo Petronia , Ciarmiello Loredana F. , Woodrow Pasqualina , Corrado Giandomenico , Chiaiese Pasquale , Rouphael Youssef
Published: August 2020

Algal biomass, extracts, or derivatives have long been considered a valuable material to bring benefits to humans and cultivated plants. In the last decades, it became evident that algal formulations can induce multiple effects on crops (including an increase in biomass, yield, and quality), and that algal extracts contain a series of bioactive compounds and signaling molecules, in addition to mineral and organic nutrients. The need to reduce the non-renewable chemical input in agriculture has recently prompted an increase in the use of algal extracts as a plant biostimulant, also because of their ability to promote plant growth in suboptimal conditions such as saline environments is beneficial. In this article, we discuss some research areas that are critical for the implementation in agriculture of macro- and microalgae extracts as plant biostimulants. Specifically, we provide an overview of current knowledge and achievements about extraction methods, compositions, and action mechanisms of algal extracts, focusing on salt-stress tolerance. We also outline current limitations and possible research avenues. We conclude that the comparison and the integration of knowledge on the molecular and physiological response of plants to salt and to algal extracts should also guide the extraction procedures and application methods. The effects of algal biostimulants have been mainly investigated from an applied perspective, and the exploitation of different scientific disciplines is still much needed for the development of new sustainable strategies to increase crop tolerance to salt stress.
Fully-Connected Neural Networks with Reduced Parameterization for Predicting Histological Types of Lung Cancer from Somatic Mutations
Authors: Kobayashi Kazuma , Bolatkan Amina , Shiina Shuichiro , Hamamoto Ryuji
Published: August 2020

Several challenges appear in the application of deep learning to genomic data. First, the dimensionality of input can be orders of magnitude greater than the number of samples, forcing the model to be prone to overfitting the training dataset. Second, each input variable’s contribution to the prediction is usually difficult to interpret, owing to multiple nonlinear operations. Third, genetic data features sometimes have no innate structure. To alleviate these problems, we propose a modification to Diet Networks by adding element-wise input scaling. The original Diet Networks concept can considerably reduce the number of parameters of the fully-connected layers by taking the transposed data matrix as an input to its auxiliary network. The efficacy of the proposed architecture was evaluated on a binary classification task for lung cancer histology, that is, adenocarcinoma or squamous cell carcinoma, from a somatic mutation profile. The dataset consisted of 950 cases, and 5-fold cross-validation was performed for evaluating the model performance. The model achieved a prediction accuracy of around 80% and showed that our modification markedly stabilized the learning process. Also, latent representations acquired inside the model allowed us to interpret the relationship between somatic mutation sites for the prediction.
Simultaneous Blockade of Histamine H3 Receptors and Inhibition of Acetylcholine Esterase Alleviate Autistic-Like Behaviors in BTBR T+ tf/J Mouse Model of Autism
Authors: Eissa Nermin , Jayaprakash Petrilla , Stark Holger , Łażewska Dorota , Kieć-Kononowicz Katarzyna , Sadek Bassem
Published: August 2020

Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder defined by persistent deficits in social interaction and the presence of patterns of repetitive and restricted behaviors. The central neurotransmitters histamine (HA) and acetylcholine (ACh) play pleiotropic roles in physiological brain functions that include the maintenance of wakefulness, depression, schizophrenia, epilepsy, anxiety and narcolepsy, all of which are found to be comorbid with ASD. Therefore, the palliative effects of subchronic systemic treatment using the multiple-active test compound E100 with high H3R antagonist affinity and AChE inhibitory effect on ASD-like behaviors in male BTBR T+tf/J (BTBR) mice as an idiopathic ASD model were assessed. E100 (5, 10 and 15 mg/kg, i.p.) dose-dependently palliated social deficits of BTBR mice and significantly alleviated the repetitive/compulsive behaviors of tested animals. Moreover, E100 modulated disturbed anxiety levels, but failed to modulate hyperactivity parameters, whereas the reference AChE inhibitor donepezil (DOZ, one milligram per kilogram) significantly obliterated the increased hyperactivity measures of tested mice. Furthermore, E100 mitigated the increased levels of AChE activity in BTBR mice with observed effects comparable to that of DOZ and significantly reduced the number of activated microglial cells compared to the saline-treated BTBR mice. In addition, the E100-provided effects on ASD-like parameters, AChE activity, and activated microglial cells were entirely reversed by co-administration of the H3R agonist (R)-α-methylhistamine (RAM). These initial overall results observed in an idiopathic ASD mice model show that E100 (5 mg/kg) alleviated the assessed behavioral deficits and demonstrate that simultaneous targeting of brain histaminergic and cholinergic neurotransmissions is crucial for palliation of ASD-like features, albeit further in vivo assessments on its effects on brain levels of ACh as well as HA are still needed.
Computational Methods and Software Tools for Functional Analysis of miRNA Data
Authors: Garcia-Moreno Adrian , Carmona-Saez Pedro
Published: August 2020

miRNAs are important regulators of gene expression that play a key role in many biological processes. High-throughput techniques allow researchers to discover and characterize large sets of miRNAs, and enrichment analysis tools are becoming increasingly important in decoding which miRNAs are implicated in biological processes. Enrichment analysis of miRNA targets is the standard technique for functional analysis, but this approach carries limitations and bias; alternatives are currently being proposed, based on direct and curated annotations. In this review, we describe the two workflows of miRNAs enrichment analysis, based on target gene or miRNA annotations, highlighting statistical tests, software tools, up-to-date databases, and functional annotations resources in the study of metazoan miRNAs.
The Morphoregulatory Role of Thidiazuron: Metabolomics-Guided Hypothesis Generation for Mechanisms of Activity
Authors: Erland Lauren A. E. , Giebelhaus Ryland T. , Victor Jerrin M. R. , Murch Susan J. , Saxena Praveen K.
Published: August 2020

Thidiazuron (TDZ) is a diphenylurea synthetic herbicide and plant growth regulator used to defoliate cotton crops and to induce regeneration of recalcitrant species in plant tissue culture. In vitro cultures of African violet thin petiole sections are an ideal model system for studies of TDZ-induced morphogenesis. TDZ induces de novo shoot organogenesis at low concentrations and somatic embryogenesis at higher concentrations of exposure. We used an untargeted metabolomics approach to identify metabolites in control and TDZ-treated tissues. Statistical analysis including metabolite clustering, pattern and pathway tools, logical algorithms, synthetic biotransformations and hormonomics identified TDZ-induced changes in metabolism. A total of 18,602 putative metabolites with extracted masses and predicted formulae were identified with 1412 features that were found only in TDZ-treated tissues and 312 that increased in response to TDZ. The monomer of TDZ was not detected intact in the tissues but putative oligomers were found in the database and we hypothesize that these may form by a Diels–Alder reaction. Accumulation oligomers in the tissue may act as a reservoir, slowly releasing the active TDZ monomer over time. Cleavage of the amide bridge released TDZ-metabolites into the tissues including organic nitrogen and sulfur containing compounds. Metabolomics data analysis generated six novel hypotheses that can be summarized as an overall increase in uptake of sugars from the culture media, increase in primary metabolism, redirection of terpene metabolism and mediation of stress metabolism via indoleamine and phenylpropanoid metabolism. Further research into the specific mechanisms hypothesized is likely to unravel the mode of action of TDZ and to provide new insights into the control of plant morphogenesis.
Evidence of Altered Peripheral Nerve Function in a Rodent Model of Diet-Induced Prediabetes
Authors: Hossain Md Jakir , Kendig Michael D. , Wild Brandon M. , Issar Tushar , Krishnan Arun V. , Morris Margaret J. , Arnold Ria
Published: August 2020

Peripheral neuropathy (PN) is a debilitating complication of diabetes that affects >50% of patients. Recent evidence suggests that obesity and metabolic disease, which often precede diabetes diagnosis, may influence PN onset and severity. We examined this in a translationally relevant model of prediabetes induced by a cafeteria (CAF) diet in Sprague–Dawley rats (n = 15 CAF versus n = 15 control). Neuropathy phenotyping included nerve conduction, tactile sensitivity, intraepidermal nerve fiber density (IENFD) and nerve excitability testing, an in vivo measure of ion channel function and membrane potential. Metabolic phenotyping included body composition, blood glucose and lipids, plasma hormones and inflammatory cytokines. After 13 weeks diet, CAF-fed rats demonstrated prediabetes with significantly elevated fasting blood glucose, insulin and impaired glucose tolerance as well as obesity and dyslipidemia. Nerve conduction, tactile sensitivity and IENFD did not differ; however, superexcitability was significantly increased in CAF-fed rats. Mathematical modeling demonstrated this was consistent with a reduction in sodium–potassium pump current. Moreover, superexcitability correlated positively with insulin resistance and adiposity, and negatively with fasting high-density lipoprotein cholesterol. In conclusion, prediabetic rats over-consuming processed, palatable foods demonstrated altered nerve function that preceded overt PN. This work provides a relevant model for pathophysiological investigation of diabetic complications.
Selective Nonenzymatic Amperometric Detection of Lactic Acid in Human Sweat Utilizing a Multi-Walled Carbon Nanotube (MWCNT)-Polypyrrole Core-Shell Nanowire
Authors: Choi Young Min , Lim Hana , Lee Ho-Nyun , Park Young Min , Park Jin-Seong , Kim Hyun-Jong
Published: August 2020

Lactic acid plays an important role as a biochemical indicator for sports medicine and clinical diagnosis. The detection of lactic acid in sweat is a promising technique without any intrusive inconvenience or risk of infection. In this study, we present a selective nonenzymatic amperometric detection method for lactic acid in human sweat utilizing a multi-wall carbon nanotube (MWCNT)-polypyrrole core-shell nanowire. Because polypyrrole is a p-type conducting polymer, onto which anions are exclusively doped, leading to charge transfer, it offers selective detection for lactate anions at a specific potential, while being inert to the neutral and cationic species contained in human sweat. A chronoamperometric study reveals good sensing performance for lactic acid with a high sensitivity of 2.9 μA mM−1 cm−2 and detection limit of 51 μM. Furthermore, the MWCNT-polypyrrole nanowire exhibits excellent selectivity for lactic acid over interfering species, such as sodium chloride, glucose, urea, and riboflavin, which coexist with lactic acid in sweat. Finally, a nonenzymatic amperometric sensor for the selective detection of lactic acid in human sweat is demonstrated on commercial flexible electrodes. The results demonstrate the potential applications of the MWCNT-polypyrrole core-shell nanowire as a nonenzymatic amperometric lactate sensor.
Objective Evaluation of Risk Factors for Radiation Dermatitis in Whole-Breast Irradiation Using the Spectrophotometric L*a*b Color-Space
Authors: Böhner Alexander M. C. , Koch David , Schmeel Frederic Carsten , Röhner Fred , Schoroth Felix , Sarria Gustavo R. , Abramian Alina-Valik , Baumert Brigitta Gertrud , Giordano Frank Anton , Schmeel Leonard Christopher
Published: August 2020

Background: Radiation-induced dermatitis (RID) is frequent in breast cancer patients undergoing radiotherapy (RT). Spectrophotometry (SP) is an objective and reliable tool for assessing RID severity. Despite intensive research efforts during the past decades, no sustainable prophylactic and treatment strategies have been found. Estimation of new and reevaluation of established risk factors leading to severe RID is therefore of major importance. Methods: 142 early breast cancer patients underwent whole-breast irradiation following breast-conserving surgery. RID was evaluated by physician-assessed Common Terminology Criteria of Adverse Events (CTCAE v4.03). Spectrophotometers provided additional semi quantification of RID using the L*a*b color-space. A total of 24 patient- and treatment-related parameters as well as subjective patient-assessed symptoms were analyzed. Results: Values for a*max strongly correlated with the assessment of RID severity by physicians. Breast volume, initial darker skin, boost administration, and treatment technique were identified as risk factors for severe RID. RID severity positively correlated with the patients’ perception of pain, burning, and reduction of everyday activities. Conclusions: Physician-assessed RID gradings correlate with objective SP skin measurements. Treatment technique and high breast volumes were identified as objective and significant predictors of RID. Our data provide a solid benchmark for future studies on RID with objective SP.
Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice
Authors: Liu Yu-Ming , Wu Tsung-Han , Chiu Yi-Han , Wang Hang , Li Tsung-Lin , Hsia Simon , Chan Yi-Lin , Wu Chang-Jer
Published: August 2020

(1) Background: Radiotherapy (RT) is one of the major treatments for non-small cell lung cancer, but RT-associated toxicities usually impede its anticancer effect. Nutrient supplementation has been applied for cancer prevention or a complementary measure to anticancer therapy. Here, we explored the influence of total nutrition supplementation before and after cancer occurrence on the anticancer benefit and side effects of RT. (2) Methods: C57BL/6JNarl mice were inoculated with Lewis lung carcinoma cells and then treated with radiotherapy. TNuF, a total nutrition formula, was prescribed by oral gavage. In the preventive groups, TNuF supplementation started from seven days before tumor inoculation. In the complementary groups, TNuF supplementation began after tumor inoculation. (3) Results: TNuF successfully enhanced the anticancer effect of RT against primary tumor and lung metastasis. Additionally, the complementary supplement improved the high serum TNF-α level and the wasting of sartorius muscle in mice receiving RT. In histologic and molecular analysis, TNuF was observed to modulate EGFR, apoptosis, and VEGF and PD-1/PD-L1 pathways. Furthermore, the anticancer benefit of the preventive supplement was comparable to that of the complementary administration. (4) Conclusions: Our results demonstrated that the prescription of the TNuF total nutrition formula before and after cancer diagnosis attains similar benefits in testing subjects with typical anticancer RT. TNuF is also a potential sensitizer to anti-PD-1 immune therapy.
The DNA Glycosylase NEIL2 Suppresses Fusobacterium-Infection-Induced Inflammation and DNA Damage in Colonic Epithelial Cells
Authors: Sayed Ibrahim M. , Chakraborty Anirban , Abd El-Hafeez Amer Ali , Sharma Aditi , Sahan Ayse Z. , Huang Wendy Jia Men , Sahoo Debashis , Ghosh Pradipta , Hazra Tapas K. , Das Soumita
Published: August 2020

Colorectal cancer (CRC) is the third most prevalent cancer, while the majority (80–85%) of CRCs are sporadic and are microsatellite stable (MSS), and approximately 15–20% of them display microsatellite instability (MSI). Infection and chronic inflammation are known to induce DNA damage in host tissues and can lead to oncogenic transformation of cells, but the role of DNA repair proteins in microbe-associated CRCs remains unknown. Using CRC-associated microbes such as Fusobacterium nucleatum (Fn) in a coculture with murine and human enteroid-derived monolayers (EDMs), here, we show that, among all the key DNA repair proteins, NEIL2, an oxidized base-specific DNA glycosylase, is significantly downregulated after Fn infection. Fn infection of NEIL2-null mouse-derived EDMs showed a significantly higher level of DNA damage, including double-strand breaks and inflammatory cytokines. Several CRC-associated microbes, but not the commensal bacteria, induced the accumulation of DNA damage in EDMs derived from a murine CRC model, and Fn had the most pronounced effect. An analysis of publicly available transcriptomic datasets showed that the downregulation of NEIL2 is often encountered in MSS compared to MSI CRCs. We conclude that the CRC-associated microbe Fn induced the downregulation of NEIL2 and consequent accumulation of DNA damage and played critical roles in the progression of CRCs.
Endothelial Dysfunction Following Enhanced TMEM16A Activity in Human Pulmonary Arteries
Authors: Skofic Maurer Davor , Zabini Diana , Nagaraj Chandran , Sharma Neha , Lengyel Miklós , Nagy Bence M. , Frank Saša , Klepetko Walter , Gschwandtner Elisabeth , Enyedi Péter , Kwapiszewska Grazyna , Olschewski Horst , Olschewski Andrea
Published: August 2020

Endothelial dysfunction is one of the hallmarks of different vascular diseases, including pulmonary arterial hypertension (PAH). Ion channelome changes have long been connected to vascular remodeling in PAH, yet only recently has the focus shifted towards Ca2+-activated Cl− channels (CaCC). The most prominent member of the CaCC TMEM16A has been shown to contribute to the pathogenesis of idiopathic PAH (IPAH) in pulmonary arterial smooth muscle cells, however its role in the homeostasis of healthy human pulmonary arterial endothelial cells (PAECs) and in the development of endothelial dysfunction remains underrepresented. Here we report enhanced TMEM16A activity in IPAH PAECs by whole-cell patch-clamp recordings. Using adenoviral-mediated TMEM16A increase in healthy primary human PAECs in vitro and in human pulmonary arteries ex vivo, we demonstrate the functional consequences of the augmented TMEM16A activity: alterations of Ca2+ dynamics and eNOS activity as well as decreased NO production, PAECs proliferation, wound healing, tube formation and acetylcholine-mediated relaxation of human pulmonary arteries. We propose that the ERK1/2 pathway is specifically affected by elevated TMEM16A activity, leading to these pathological changes. With this work we introduce increased TMEM16A activity in the cell membrane of human PAECs for the development of endothelial dysfunction in PAH.
Protein Glycosylation Investigated by Mass Spectrometry: An Overview
Authors: Illiano Anna , Pinto Gabriella , Melchiorre Chiara , Carpentieri Andrea , Faraco Vincenza , Amoresano Angela
Published: August 2020

The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.
Effects of Zirconium and Yttrium Oxide on Mechanical and Oxidation Properties of Mo–3Si–1B–1Zr–1Y2O3 (wt.%) Alloy
Authors: Guo Zhenping , Wang Lei , Wang Cheng , Li Qiuliang
Published: August 2020

Mo–3Si–1B alloys with zirconium (1 wt.%) and yttrium oxide (1 wt.%) additives were fabricated by vibrating sintering techniques. The doped Mo–3Si–1B alloys consisted mainly of α-Mo, Mo3Si, and Mo5SiB2 (T2) phases. It was found that the grains were reduced, and the intermetallics particles were dispersed more homogeneously after the addition of Zr and Y2O3. The optimization in microstructure induced corresponding improvements in both fracture toughness and oxidation resistance. The predominant strengthening mechanisms were fine-grain strengthening and particle dispersion strengthening. In addition, fracture toughness test showed that the additions could improve the toughness of Mo–3Si–1B alloys, for which the toughening mechanism involved a crack trapping by α-Mo phases and extensive small second phase particles in the alloys. What should be paid attention to is the satisfactory oxidation resistance, both at medium-low temperature (800 °C) and high temperature (1200 °C) with doped additives.
Polysialic Acid Modified Liposomes for Improving Pharmacokinetics and Overcoming Accelerated Blood Clearance Phenomenon
Authors: Han Xi , Zhang Ting , Liu Mengyang , Song Yanzhi , Liu Xinrong , Deng Yihui
Published: August 2020

Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and spleen. To avoid the unexpected phenomenon, polysialic acid (PSA) was selected to modify liposomes. PSA is a natural, highly hydrophilic polysaccharide polymer for which no receptors exists in the body. It is non-immunogenic, biodegradable and endows the conjugated bioactive macromolecule and drugs with increased circulation time in vivo. In the present study, the in vivo evaluation showed that PSA modified liposomes (PSA-Lip) afford extended blood circulation in wistar rats and beagle dogs. Moreover, the ABC phenomenon did not occur and the IgM antibody was not induced after repeated injections of PSA-Lip. These results strongly suggest that PSA modification represents a promising strategy to afford good stealth of the liposomes without evoking the ABC phenomenon.
The Mechanisms of Degradation of Titanium Dental Implants
Authors: Ossowska Agnieszka , Zieliński Andrzej
Published: August 2020

Titanium dental implants show very good properties, unfortunately there are still issues regarding material wear due to corrosion, implant loosening, as well as biological factors—allergic reactions and inflammation leading to rejection of the implanted material. In order to avoid performing reimplantation operations, changes in the chemical composition and/or modifications of the surface layer of the materials are used. This research is aimed at explaining the possible mechanisms of titanium dissolution and the role of oxide coating, and its damage, in the enhancement of the corrosion process. The studies of new and used implants were made by scanning electron microscopy and computer tomography. The long-term chemical dissolution of rutile was studied in Ringer’s solution and artificial saliva at various pH levels and room temperature. Inductively coupled plasma mass spectrometry (ICP-MS) conjugated plasma ion spectrometry was used to determine the number of dissolved titanium ions in the solutions. The obtained results demonstrated the extremely low dissolution rate of rutile, slightly increasing along with pH. The diffusion calculations showed that the diffusion of titanium through the oxide layer at human body temperature is negligible. The obtained results indicate that the surface damage followed by titanium dissolution is initiated at the defects caused by either the manufacturing process or implantation surgery. At a low thickness of titanium oxide coating, there is a stepwise appearance and development of cracks that forms corrosion tunnels within the oxide coating.
Steam Oxidation of Aluminide-Coated and Uncoated TP347HFG Stainless Steel under Atmospheric and Ultra-Supercritical Steam Conditions at 700 °C
Authors: Agüero Alina , Baráibar Ignacio , Gutiérrez Marcos , Tuurna Satu , Toivonen Aki , Penttilä Sami , Auerkari Pertti
Published: August 2020

The efficiency of ultra-supercritical (USC) steam power plants is limited by the materials properties, in particular, the steam oxidation resistance of the currently used steels at temperatures higher than 600 °C. Under these conditions, steam oxidation results in the development of thick oxide scales which spall and can accumulate in tube bends leading to blockage, overheating and premature creep rupture, as well as erosion of downstream components such as steam valves and turbine blades. Most published work related to oxidation testing is carried out at atmospheric pressure, with significantly less testing of austenitic steels in supercritical steam, and rarely including protective coatings. Indeed, the effect of high-pressure steam in the oxidation process is not quite understood at present. This paper covers a comparison of the behaviour of TP347HFG stainless steel at 700 °C under atmospheric pressure and 25 MPa, with and without slurry-applied diffusion aluminide coatings. The results show a very protective behaviour of the aluminide coatings, which develop a very thin Al-rich protective oxide, and no significant difference between the two environments. In contrast, the uncoated steel exhibited a different behaviour. Indeed, under atmospheric pressure after 3000 h, very thin scales, rich in Cr and not surpassing 5 to 10 µm in thickness, covered the samples along with some much thicker Fe-rich oxide nodules (up to 150 µm). However, under 25 MPa, a thick multilayer scale with a non-homogeneous thickness oscillating between 10 to 120 µm was present. A microstructural investigation was undertaken on the oxidised uncoated and coated substrates. The results suggest that pressure increases the oxidation rate of the chromia former steels but that the oxidation mechanism remains the same. A mechanism is proposed, including early detachment of the outer growing scales under supercritical pressure.
New Records of Heliopora hiberniana from SE Asia and the Central Indian Ocean
Authors: Richards Zoe , Haines Leon , Scaps Patrick , Ader Denis
Published: August 2020

Coral reefs are among the most diverse ecosystems on the planet [...]
An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials
Authors: Leow Wei-Qiang , Bedossa Pierre , Liu Feng , Wei Lai , Lim Kiat-Hon , Wan Wei-Keat , Ren Yayun , Chang Jason Pik-Eu , Tan Chee-Kiat , Wee Aileen , Goh George Boon-Bee
Published: August 2020

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.
Elaboration of Screening Scales for Mental Development Problems Detection in Russian Preschool Children: Psychometric Approach
Authors: Nasledov Andrey , Miroshnikov Sergey , Tkacheva Liubov , Goncharov Vadim
Published: August 2020

Background: computer-based screenings are usually used for early detection of a child’s mental development problems. However, there are no such screenings in Russia yet. This study aimed to elaborate scales for rapid monitoring of mental development of 3-year-olds. Methods: 863 children took part in the study, among them 814 children of the group Norm, 49 children with developmental delay (DD), including 23 children with symptoms of autistic spectrum disorder (ASD). The multifactor study of mental development tool was used as a part of a software complex for longitudinal research for data collection. This study used a set of 233 tasks that were adequate for 3-year-olds. Exploratory and confirmatory factor analysis was used for the elaboration and factor validation of the scales. The structure of the relationship between scales and age was refined using structural equation modeling. Results: as a result of the research, screening scales were elaborated: “Logical reasoning”, “Motor skills”, “General awareness”, “Executive functions”. The factor validity and reliability of scales were proved. The high discriminability of the scales in distinguishing the “Norm” and “DD” samples was revealed. The developed test norms take into account the child’s age in days and allow identifying a “risk group” with an expected forecast accuracy of at least 90%. The obtained scales meet psychometric requirements for their application and allow creating an online screening system for wide application.
Identification of Denatured Biological Tissues Based on Compressed Sensing and Improved Multiscale Dispersion Entropy during HIFU Treatment
Authors: Liu Bei , Wang Runmin , Peng Ziqi , Qin Lingjie
Published: August 2020

Identification of denatured biological tissue is crucial to high-intensity focused ultrasound (HIFU) treatment, which can monitor HIFU treatment and improve treatment efficiency. In this paper, a novel method based on compressed sensing (CS) and improved multiscale dispersion entropy (IMDE) is proposed to evaluate the complexity of ultrasonic scattered echo signals during HIFU treatment. In the analysis of CS, the method of orthogonal matching pursuit (OMP) is employed to reconstruct the denoised signal. CS-OMP can denoise the ultrasonic scattered echo signal effectively. Comparing with traditional multiscale dispersion entropy (MDE), IMDE improves the coarse-grained process in the multiscale analysis, which improves the stability of MDE. In the analysis of simulated signals, the entropy value of the IMDE method has less fluctuation compared with MDE, indicating that the IMDE method has better stability. In addition, MDE and IMDE are applied to the 300 cases of ultrasonic scattered echo signals after denoising (including 150 cases of normal tissues and 150 cases of denatured tissues). The experimental results show that the MDE and IMDE values of denatured tissues are higher than normal tissues. Both the MDE and IMDE method can be used to identify whether biological tissue is denatured. However, the multiscale entropy curve of IMDE is smoother and more stable than MDE. The interclass distance of IMDE is greater than MDE, and the intraclass distance of IMDE is less than MDE at different scale factors. This indicates that IMDE can better distinguish normal tissues and denatured tissues to obtain more accurate clinical diagnosis during HIFU treatment.
The Effect of Non-Intellective Competencies and Academic Performance on School Satisfaction
Authors: Magnano Paola , Boerchi Diego , Lodi Ernesto , Patrizi Patrizia
Published: August 2020

(1) Background: To improve academic performance and prevent dropouts, many studies have investigated the effects of non-intellective competencies on performance, and the effects of performance on school satisfaction. The aim of this study was to investigate the direct role of both non-intellective competencies and performance on school satisfaction at the same time. (2) Methods: The study involved 731 Italian students, attending three different high schools, who responded to the H-Comp Scale, a questionnaire assessing twelve different aspects of students’ skills, attitudes and motivations over the study, and the H-Sat Scale, a questionnaire assessing five different areas of school satisfaction. (3) Results: We found a strong role of non-intellective competencies on school satisfaction and a marginal role of academic performance, gender and the attended class, which reduced as students’ seniority increased. (4) Conclusions: This study showed that school satisfaction depends on students’ self-perception in terms of their study competencies and the motivations possessed more than their sole performance, suggesting that this helps students to improve their non-intellective competencies in order to increase their performance and reduce the risk of dropouts, both directly and indirectly, through increasing their school satisfaction.
Subjective Well-Being and Its Relation to Academic Performance among Students in Medicine, Dentistry, and Other Health Professions
Authors: Chattu Vijay Kumar , Sahu Pradeep Kumar , Seedial Neela , Seecharan Gerlisa , Seepersad Amanda , Seunarine Melina , Sieunarine Shivanna , Seymour Kahamaron , Simboo Samantha , Singh Arissa
Published: August 2020

Subjective well-being is defined as a person’s cognitive and affective evaluations of his or her life. This study aims to investigate the differences in the domains of subjective well-being based on gender, type of school, and academic performance. Additionally, the study aimed to determine the factors (socio-demographic variables, including the academic performance of the students) that are predictive of subjective well-being. Subjective well-being was assessed using a questionnaire which included the Satisfaction with Life Scale (SWLS), which measured the respondent’s life satisfaction, the Scale of Positive and Negative Experience (SPANE), which consisted of six positive and negative emotions, and, lastly, the Flourishing Scale (FS), which measured the respondents’ self-perceived success. Data were collected, transformed into a linear scale, and exported into SPSS version 24, where t-tests, one-way analysis of variance, Pearson correlation, and stepwise regression were performed. Of the total of 535 participants, the majority were females (383 = 71.6%) and studying in a school of medicine (31.8%). With respect to the SWLS and FS, a significant difference was reported among students based on the type of school and their academic performance (p < 0.05). While comparing the differences in the SPANE, a significant difference was recorded based on academic performance. Among the domains of subjective well-being, only the SPANE showed a significant association with academic performance. Greater subjective well-being correlates with higher academic performance, indicating that subjective well-being is an important aspect of a student’s academic life; provisions can be made by paying more attention to those who showed poor academic performance during and at the end of each semester.
Multi-Channel Transfer Learning of Chest X-ray Images for Screening of COVID-19
Authors: Misra Sampa , Jeon Seungwan , Lee Seiyon , Managuli Ravi , Jang In-Su , Kim Chulhong
Published: August 2020

The 2019 novel coronavirus (COVID-19) has spread rapidly all over the world. The standard test for screening COVID-19 patients is the polymerase chain reaction test. As this method is time consuming, as an alternative, chest X-rays may be considered for quick screening. However, specialization is required to read COVID-19 chest X-ray images as they vary in features. To address this, we present a multi-channel pre-trained ResNet architecture to facilitate the diagnosis of COVID-19 chest X-ray. Three ResNet-based models were retrained to classify X-rays in a one-against-all basis from (a) normal or diseased, (b) pneumonia or non-pneumonia, and (c) COVID-19 or non-COVID19 individuals. Finally, these three models were ensembled and fine-tuned using X-rays from 1579 normal, 4245 pneumonia, and 184 COVID-19 individuals to classify normal, pneumonia, and COVID-19 cases in a one-against-one framework. Our results show that the ensemble model is more accurate than the single model as it extracts more relevant semantic features for each class. The method provides a precision of 94% and a recall of 100%. It could potentially help clinicians in screening patients for COVID-19, thus facilitating immediate triaging and treatment for better outcomes.