bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs
Authors: Zhang Cang , Zhang Xiaolan , Wang Guangji , Peng Ying , Zhang Xueyuan , Wu Hui , Yu Boyang , Sun Jianguo
Published: November 2018

C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC0-inf) and C30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, suggested nonlinear pharmacokinetic occurred at high dose. As a prodrug, C118P can be quickly hydrolyzed into C118 after an intravenous administration. The unbound C118 in plasma is slightly higher than C118P. C118P can hardly penetrate the tissue, while C118 can distribute widely into tissues. In tumor-bearing nude mice, the concentration of C118 is high in lung, ovary, and tumor, with an extended half-life in tumor. C118P is a promising candidate prodrug for further clinical development.
Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis
Authors: In Eun-Jung , Lee Yuno , Koppula Sushruta , Kim Tae-Yeon , Han Jun-Hyuk , Lee Kwang-Ho , Kang Tae-Bong
Published: November 2018

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.
Effect of Conductive Material Morphology on Spherical Lithium Iron Phosphate
Authors: Wen Lizhi , Sun Jiachen , An Liwei , Wang Xiaoyan , Ren Xin , Liang Guangchuan
Published: November 2018

As an integral part of a lithium-ion battery, carbonaceous conductive agents have an important impact on the performance of the battery. Carbon sources (e.g., granular Super-P and KS-15, linear carbon nanotube, layered graphene) with different morphologies were added into the battery as conductive agents, and the effects of their morphologies on the electrochemical performance and processability of spherical lithium iron phosphate were investigated. The results show that the linear carbon nanotube and layered graphene enable conductive agents to efficiently connect to the cathode materials, which contribute to improving the stability of the electrode-slurry and reducing the internal resistance of cells. The batteries using nanotubes and graphene as conductive agents showed weaker battery internal resistance, excellent electrochemical performance and low-temperature dischargeability. The battery using carbon nanotube as the conductive agent had the best overall performance with an internal resistance of 30 mΩ. The battery using a carbon nanotube as the conductive agent exhibited better low-temperature performance, whose discharge capacity at −20 °C can reach 343 mAh, corresponding to 65.0% of that at 25 °C.
Three-Dimensional Hierarchical Reticular Nanostructure of Fulfora candelaria Wing Decorated by Ag Nanoislands as Practical SERS-Active Substrates
Authors: Wang Mingli , Wang Yuhong , Yan Xiaoya , Sun Xin , Shi Guochao , Zhang Keqin , Ren Lijian , Ma Wanli
Published: November 2018

Although surface-enhanced Raman scattering (SERS) technology has been widely explored nowadays in various fields, the fabrication of practical SERS-active substrates with prominent recognition ability for various analyte molecules is still defective. Natural Fulfora candelaria wing (FCW) with three-dimensional (3D) hierarchical reticular nanostructure was selected as a new bioscaffold for rough silver (Ag) nanoislands to be assembled on to prepare a practical SERS substrate (Ag/FCW substrate). By adjusting the sputtering time of metal Ag, the morphology of the substrates could be easily tuned to control the formation and distribution of “hot spots”. Three-dimensional finite-difference time-domain (3D-FDTD) simulation indicated that the excellent SERS performance under optimal morphology was ascribed to the local enhanced electric field in rough Ag surface and effective “hot spot” areas. The SERS measurement results show that the optimal Ag/FCW substrates had high SERS performance in terms of Raman signal sensitivity, reproducibility, uniformity and recognition ability for various analyte molecules. Coupled with flexibility of the biological substrates and the cost effectiveness, the sensitive SERS detection of varied analytes based on Ag/FCW substrates offered great potential for practical applications.
The Immunomodulatory and Anti-Inflammatory Role of Polyphenols
Authors: Yahfoufi Nour , Alsadi Nawal , Jambi Majed , Matar Chantal
Published: November 2018

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.
Crocin Ameliorates Atopic Dermatitis Symptoms by down Regulation of Th2 Response via Blocking of NF-κB/STAT6 Signaling Pathways in Mice
Authors: Sung Yoon-Young , Kim Ho Kyoung
Published: November 2018

Crocin, a major constituent of Gardenia jasminoides, is a natural colorant carotenoid compound that has been reported to have anti-inflammatory effects. This study investigated the therapeutic effects of crocin on mice with atopic dermatitis induced by Dermatophagoides farinae crude extract, which is a common environmental allergen in house dust that causes atopic dermatitis in humans. Crocin application ameliorated Dermatophagoides farinae crude extract-induced atopic dermatitis symptoms by inhibiting the dermatitis severity score, ear thickness, and serum immunoglobulin E levels in NC/Nga mice. The increases in epidermal thickness and dermal inflammatory cells (eosinophil and mast cells) infiltrations observed on the dorsal back skin of atopic dermatitis control mice were inhibited in a dose-dependent manner by topical application of crocin in atopic dermatitis treatment mice. Crocin inhibited the Dermatophagoides farinae crude extract-induced increase of thymus and activation-regulated chemokines, interleukin (IL)-4, and IL-13 on the dorsal skin of mice. Crocin also inhibited Dermatophagoides farinae crude extract-induced activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT) 6. These results show that crocin ameliorates atopic dermatitis symptoms by down regulation of the Th2 cells-mediated immune response via blocking of NF-κB/STAT6 signaling pathways.
Transcription Factor Eb Is Required for Macropinocytosis-Mediated Growth Recovery of Nutrient-Deprived Kras-Mutant Cells
Authors: Jeong Seokmin , Byun Jun-Kyu , Cho Sung Jin , Chin Jungwook , Lee In-Kyu , Choi Yeon-Kyung , Park Keun-Gyu
Published: November 2018

Macropinocytosis is a regulated form of endocytosis that mediates the nonselective uptake of nutrients to support growth under nutrient-deprived conditions. KRAS-mutant cancer cells upregulate macropinocytosis to import extracellular proteins, which subsequently undergo proteolytic degradation in the lysosome. Although transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and function, its role in the degradation of extracellular protein from macropinocytosis in KRAS-mutant cells has not previously been elucidated. In this study, we investigated the role of TFEB in the recovery of macropinocytosis-mediated mTORC1 activity and cell growth under nutrient depletion. Mouse embryonic fibroblasts (MEFs) expressing KrasG12D and KRAS-mutant human cancer cells took up markedly higher levels of tetramethylrhodamine (TMR)-dextran than the corresponding wild-type cells. siRNA-mediated inhibition of TFEB did not influence extracellular TMR-dextran uptake, but significantly attenuated lysosomal degradation of extracellular protein. Bovine serum albumin (BSA) treatment restored p-S6K levels and cell proliferation suppressed by leucine deprivation, and these effects were blocked by siTFEB. Collectively, our results show that TFEB plays a role in macropinocytosis-mediated KRAS-mutant cell growth under nutrient deprivation by promoting lysosomal degradation of extracellular proteins.
Human Breast Milk Bacteriome in Health and Disease
Authors: Ojo-Okunola Anna , Nicol Mark , Du Toit Elloise
Published: November 2018

It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant’s mucosal system, including that of the gut. They also have a role in priming the infant’s immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.
Substitution of Fish for Red Meat or Poultry and Risk of Ischemic Stroke
Authors: Venø Stine K. , Bork Christian S. , Jakobsen Marianne U. , Lundbye-Christensen Søren , Bach Flemming W. , McLennan Peter L. , Tjønneland Anne , Schmidt Erik B. , Overvad Kim
Published: November 2018

We investigated the risk of ischemic stroke and its subtypes when red meat or poultry was substituted with fish. A total of 57,053 participants aged 50–65 years at baseline were included in the Danish Diet, Cancer and Health study. All participants filled in a food-frequency questionnaire at recruitment. Potential ischemic stroke cases were identified by linkage to the Danish National Patient Register, and all cases were validated and subclassified. Substitutions were investigated as 150 g/week of fish for 150 g/week of red meat or of poultry using multivariable Cox proportional hazard regression models. During 13.5 years of follow-up, 1879 participants developed an ischemic stroke. Replacing red meat or poultry with fish was not associated with the rate of total ischemic stroke, but there was a statistically significant lower rate of large artery atherosclerosis when fish replaced processed (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.67; 0.90) and unprocessed (HR: 0.87; 95% CI: 0.75; 0.99) red meat. A statistically significant higher rate of cardioembolism was found when poultry was replaced by total fish (HR: 1.42; 95% CI: 1.04; 1.93). When fatty fish replaced unprocessed red meat, a statistically significant lower rate of small-vessel occlusion was found (HR: 0.88; 95% CI: 0.77; 0.99). In conclusion, replacing red meat with fish was not associated with risk of total ischemic stroke but was associated with a lower risk of subtypes of ischemic stroke.
Carotenoid Content in Human Colostrum is Associated to Preterm/Full-Term Birth Condition
Authors: Xavier Ana A. O. , Díaz-Salido Elena , Arenilla-Vélez Isabel , Aguayo-Maldonado Josefa , Garrido-Fernández Juan , Fontecha Javier , Sánchez-García Alicia , Pérez-Gálvez Antonio
Published: November 2018

Factors such as lactation stage and premature and small-for-gestational conditions could lead to great inter-individual variability in the carotenoid content of human milk. The aim was to analyze the carotenoid content in colostrum and mature milk of preterm (PT) and full-term (FT) mothers to establish whether they are significantly different and, if so, the stage of lactation when the differences are established. Samples of blood, colostrum, and mature milk were collected from Spanish donating mothers who gave birth to PT or FT infants. Carotenoids from serum and milk samples were analyzed by HPLC-atmospheric pressure chemical ionization (APCI)-MS. Quantitatively, colostrum from PT mothers presented lower total carotenoid content when compared to that from FT mothers. The only exception was lutein, where levels were not different. The transition from colostrum to mature milk makes observed differences in the carotenoid content disappear, since there were no variances between PT and FT groups for both individual and total carotenoid content. The premature birth condition affects the quantitative carotenoid composition of the colostrum but has no effect on the lutein content. This fact could be related to the significant role of this xanthophyll in the development of infant retina and feasibly to cognitive function.
Carbohydrate Intake Does Not Counter the Post-Exercise Decrease in Natural Killer Cell Cytotoxicity
Authors: Wentz Laurel M. , Nieman David C. , McBride Jennifer E. , Gillitt Nicholas D. , Williams Leonard L. , Warin Renaud F.
Published: November 2018

In a study using a randomized crossover approach, cyclists (n = 20, overnight fasted) engaged in three 75 km time trials while ingesting water (WAT) or carbohydrate (0.2 g/kg every 15 min) from bananas (BAN) or a 6% sugar beverage (SUG). Blood samples were collected pre-exercise and 0 h, 1.5 h, and 21 h post-exercise and analyzed for natural killer (NK) cytotoxicity activity (NKCA) using pure NK cell populations. The two carbohydrate trials (BAN, SUG) compared to WAT were associated with higher post-exercise glucose and lower cortisol, total blood leukocyte, neutrophil, and NK cell counts (interaction effects, p < 0.001). The immediate post-exercise increase in NK cell counts was higher in WAT (78%) compared to BAN (32%) and SUG (15%) trials (p ≤ 0.017). The 1.5 h post-exercise decrease in NK cell counts did not differ after WAT (−46%), BAN (−46%), and SUG (−51%) trials. The pattern of change in post-exercise NKCA differed between trials (p < 0.001). The 1.5 h post-exercise decreases in NKCA were 23%, 29%, and 33% in the WAT, BAN, and SUG trials, respectively, but trial contrasts did not differ significantly. Carbohydrate ingestion from BAN or SUG attenuated immediate post-exercise increases in leukocyte, neutrophil, and NK cell counts, but did not counter the 1.5 h decreases in NK cell counts and NKCA.
A Comprehensive Review of Chemistry, Sources and Bioavailability of Omega-3 Fatty Acids
Authors: Cholewski Mateusz , Tomczykowa Monika , Tomczyk Michał
Published: November 2018

Omega-3 fatty acids, one of the key building blocks of cell membranes, have been of particular interest to scientists for many years. However, only a small group of the most important omega-3 polyunsaturated fatty acids are considered. This full-length review presents a broad and relatively complete cross-section of knowledge about omega-3 monounsaturated fatty acids, polyunsaturates, and an outline of their modifications. This is important because all these subgroups undoubtedly play an important role in the function of organisms. Some monounsaturated omega-3s are pheromone precursors in insects. Polyunsaturates with a very long chain are commonly found in the central nervous system and mammalian testes, in sponge organisms, and are also immunomodulating agents. Numerous modifications of omega-3 acids are plant hormones. Their chemical structure, chemical binding (in triacylglycerols, phospholipids, and ethyl esters) and bioavailability have been widely discussed indicating a correlation between the last two. Particular attention is paid to the effective methods of supplementation, and a detailed list of sources of omega-3 acids is presented, with meticulous reference to the generally available food. Both the oral and parenteral routes of administration are taken into account, and the omega-3 transport through the blood-brain barrier is mentioned. Having different eating habits in mind, the interactions between food fatty acids intake are discussed. Omega-3 acids are very susceptible to oxidation, and storage conditions often lead to a dramatic increase in this exposure. Therefore, the effect of oxidation on their bioavailability is briefly outlined.
The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut–Retina Axis
Authors: Rinninella Emanuele , Mele Maria Cristina , Merendino Nicolò , Cintoni Marco , Anselmi Gaia , Caporossi Aldo , Gasbarrini Antonio , Minnella Angelo Maria
Published: November 2018

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30–50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.
Isolation and Characterization of Potentially Probiotic Bacterial Strains from Mice: Proof of Concept for Personalized Probiotics
Authors: Celiberto Larissa S. , Pinto Roseli Aparecida , Rossi Elizeu Antonio , Vallance Bruce A. , Cavallini Daniela C. U.
Published: November 2018

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.
Antioxidant Status, Antidiabetic Properties and Effects on Caco-2 Cells of Colored and Non-Colored Enriched Extracts of Sweet Cherry Fruits
Authors: Gonçalves Ana C. , Rodrigues Márcio , Santos Adriana O. , Alves Gilberto , Silva Luís R.
Published: November 2018

This study aimed to compare three different extracts of Saco sweet cherry, namely the non-colored fraction, colored fraction, and total extract concerning phenolic composition, antioxidant and antidiabetic potential, and erythrocytes’ protection and effects on Caco-2 cells. Twenty-two phenolic compounds were identified using high-performance liquid chromatography with diode-array detection. Hydroxycinnamic acids were the most predominant in both the non-colored fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the colored fraction. The total extract was the most effective against 1,1-diphenyl-2-picrylhydrazyl, nitric oxide, and superoxide radicals, and in the inhibition of α-glucosidase enzyme. The colored fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the colored extract exhibited the highest cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by tert-butyl hydroperoxide.
Self-Dissolving Microneedle Arrays for Transdermal Absorption Enhancement of Human Parathyroid Hormone (1-34)
Authors: Naito Chihiro , Katsumi Hidemasa , Suzuki Tomoko , Quan Ying-shu , Kamiyama Fumio , Sakane Toshiyasu , Yamamoto Akira
Published: November 2018

Human parathyroid hormone (1-34) (PTH) has been widely used as the subcutaneous injection formulation for the treatment of osteoporosis. In the present study, we developed an efficient transdermal delivery system of PTH by using dissolving microneedle arrays (MNs) composed of hyaluronic acid (HA) for the treatment of osteoporosis. PTH-loaded MNs, with needle length 800 µm, were fabricated via a micro-molding method. The stability of PTH in MNs was found to be 6-fold higher than that of PTH solution when stored at room temperature (15–20 °C) for one month. Micron-scale pores were clearly visible in rat skin following application of PTH-loaded MNs. PTH-loaded MNs were completely dissolved by 60 min following application to rat skin. The bioavailability (BA) of PTH relative to subcutaneous injection was 100 ± 4% following application of PTH-loaded MNs in rats. In addition, PTH-loaded MNs were found to effectively suppress decreases in bone density in a rat model of osteoporosis. Furthermore, no skin irritation was observed at the site of application in rats. These findings indicate that our dissolving MNs have a potential use in formulations for the transdermal delivery of PTH and for the treatment of osteoporosis.
Exploration of Nurses’ Knowledge, Attitudes, and Perceived Barriers towards Medication Error Reporting in a Tertiary Health Care Facility: A Qualitative Approach
Authors: Dyab Eman Ali , Elkalmi Ramadan Mohamed , Bux Siti Halimah , Jamshed Shazia Qasim
Published: November 2018

Medication error reporting (MER) is an effective way used to identify the causes of Medication Errors (MEs) and to prevent repeating them in future. The underreporting of MEs is a challenge generally in all MER systems. The current research aimed to explore nurses’ knowledge on MER by determining their attitudes towards reporting and studying the implicated barriers and facilitators. A total of 23 nurses were interviewed using a semi-structured interview guide. The saturation point was attained after 21 interviews. All the interviews were tape-recorded and transcribed verbatim, and analysed using inductive thematic analysis. Four major themes and 17 sub-themes were identified. Almost all the interviewees were aware about the existence of the MER system. They showed a positive attitude towards MER. The main barriers for MER were the impacts of time and workload, fear of investigation, impacts on the job, and negative reactions from the person in charge. The nurses were knowledgeable about MER but there was uncertainty towards reporting harmless MEs, thus indicating the need for an educational program to highlight the benefits of near-miss reporting. To improve participation strategies, a blameless reporting culture, reporting anonymously, and a simplified MER process should be considered.
Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems
Authors: Irimia Teodora , Ghica Mihaela , Popa Lăcrămioara , Anuţa Valentina , Arsene Andreea-Letiţia , Dinu-Pîrvu Cristina-Elena
Published: November 2018

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.
Effect of Non-Newtonian Flow on Polymer Flooding in Heavy Oil Reservoirs
Authors: Xin Xiankang , Yu Gaoming , Chen Zhangxin , Wu Keliu , Dong Xiaohu , Zhu Zhouyuan
Published: November 2018

The flow of polymer solution and heavy oil in porous media is critical for polymer flooding in heavy oil reservoirs because it significantly determines the polymer enhanced oil recovery (EOR) and polymer flooding efficiency in heavy oil reservoirs. In this paper, physical experiments and numerical simulations were both applied to investigate the flow of partially hydrolyzed polyacrylamide (HPAM) solution and heavy oil, and their effects on polymer flooding in heavy oil reservoirs. First, physical experiments determined the rheology of the polymer solution and heavy oil and their flow in porous media. Then, a new mathematical model was proposed, and an in-house three-dimensional (3D) two-phase polymer flooding simulator was designed considering the non-Newtonian flow. The designed simulator was validated by comparing its results with those obtained from commercial software and typical polymer flooding experiments. The developed simulator was further applied to investigate the non-Newtonian flow in polymer flooding. The experimental results demonstrated that the flow behavior index of the polymer solution is 0.3655, showing a shear thinning; and heavy oil is a type of Bingham fluid that overcomes a threshold pressure gradient (TPG) to flow in porous media. Furthermore, the validation of the designed simulator was confirmed to possess high accuracy and reliability. According to its simulation results, the decreases of 1.66% and 2.49% in oil recovery are caused by the difference between 0.18 and 1 in the polymer solution flow behavior indexes of the pure polymer flooding (PPF) and typical polymer flooding (TPF), respectively. Moreover, for heavy oil, considering a TPG of 20 times greater than its original value, the oil recoveries of PPF and TPF are reduced by 0.01% and 5.77%, respectively. Furthermore, the combined effect of shear thinning and a threshold pressure gradient results in a greater decrease in oil recovery, with 1.74% and 8.35% for PPF and TPF, respectively. Thus, the non-Newtonian flow has a hugely adverse impact on the performance of polymer flooding in heavy oil reservoirs.
A Hybrid Maximum Power Point Tracking Method for Photovoltaic Systems for Dynamic Weather Conditions
Authors: Bataineh Khaled , Eid Naser
Published: November 2018

A hybrid MPPT (maximum power point tracking) controller integrates FLC (fuzzy logic controller) and P&O (Perturbation and Observation) method for MMPT of PV (Photovoltaic) under dynamic weather conditions is proposed. An adaptive neuro-fuzzy inference system is used to optimize parameters and membership functions of FLC. FLC is used to find the region of MPP (maximum power point); then, P&O technique is employed to accurately track the MPP. MATLAB/Simulink models are built to evaluate the performance of the proposed hybrid algorithm. In order to validate the performance of the proposed algorithm, comparisons with standalone FLC and P&O are carried out. The performance of the proposed algorithm is tested against dynamic weather condition. The results showed that the proposed algorithm successfully improve the dynamic and steady state responses of PV under severe dynamic weather condition. More specifically, the proposed approach shows its capability to attain the MPP faster than P&O and provided higher power than the standalone FLC. Finally, the proposed algorithm overcomes the limitations associated with FLC and P&O.
Prediction of Forest Structural Parameters Using Airborne Full-Waveform LiDAR and Hyperspectral Data in Subtropical Forests
Authors: Shen Xin , Cao Lin , Chen Dong , Sun Yuan , Wang Guibin , Ruan Honghua
Published: November 2018

Accurate acquisition of forest structural parameters, which is essential for the parameterization of forest growth models and understanding forest ecosystems, is also crucial for forest inventories and sustainable forest management. In this study, simultaneously acquired airborne full-waveform (FWF) LiDAR and hyperspectral data were used to predict forest structural parameters in subtropical forests of southeast China. The pulse amplitude and waveform shape of airborne FWF LiDAR data were calibrated using a physical process-driven and a voxel-based approach, respectively. Different suites of FWF LiDAR and hyperspectral metrics, i.e., point cloud (derived from LiDAR-waveforms) metrics (DPC), full-waveform (geometric and radiometric features) metrics (FW) and hyperspectral (original reflectance bands, vegetation indices and statistical indices) metrics (HS), were extracted and assessed using correlation analysis and principal component analysis (PCA). The selected metrics of DPC, FW and HS were used to fit regression models individually and in combination to predict diameter at breast height (DBH), Lorey’s mean height (HL), stem number (N), basal area (G), volume (V) and above ground biomass (AGB), and the capability of the predictive models and synergetic effects of metrics were assessed using leave-one-out cross validation. The results showed that: among the metrics selected from three groups divided by the PCA analysis, twelve DPC, eight FW and ten HS were highly correlated with the first and second principal component (r > 0.7); most of the metrics selected from DPC, FW and HS had weak relationships between each other (r < 0.7); the prediction of HL had a relatively higher accuracy (Adjusted-R2 = 0.88, relative RMSE = 10.68%), followed by the prediction of AGB (Adjusted-R2 = 0.84, relative RMSE = 15.14%), and the prediction of V had a relatively lower accuracy (Adjusted-R2 = 0.81, relative RMSE = 16.37%); and the models including only DPC had the capability to predict forest structural parameters with relatively high accuracies (Adjusted-R2 = 0.52–0.81, relative RMSE = 15.70–40.87%) whereas the usage of DPC and FW resulted in higher accuracies (Adjusted-R2 = 0.62–0.87, relative RMSE = 11.01–31.30%). Moreover, the integration of DPC, FW and HS can further improve the accuracies of forest structural parameters prediction (Adjusted-R2 = 0.68–0.88, relative RMSE = 10.68–28.67%).
Pros and Cons of Structure for Motion Embarked on a Vehicle to Survey Slopes along Transportation Lines Using 3D Georeferenced and Coloured Point Clouds
Authors: Voumard Jérémie , Derron Marc-Henri , Jaboyedoff Michel , Bornemann Pierrick , Malet Jean-Philippe
Published: November 2018

We discuss the different challenges, pros and cons of the fairly new Structure for Motion (SfM) embarked on a vehicle (SfM-EV) technique for slope surveys along transportation network tracks using action cameras embarked on standard moving vehicles. This low-cost technique generates georeferenced and coloured 3D point clouds without using any ground control points. Four action cameras, two of which had an integrated GNSS chip, were used to collect a series of pictures of tracksides at a rate of two images per second each. The SfM-EV results were compared with the results of seven other 3D survey techniques to evaluate the precision and accuracy of this technique, demonstrating the ability of this simple setting to generate 3D scenes. Different platforms for the cameras were tested, such as a bike, car, train, funicular, helicopter and so on. The SfM-EV technique was also tested on several study sites to highlight its strengths and weaknesses and obtain data, such as the density of points, equations of errors, overlap ratios and image resolution. The precision of the SfM-EV results was sufficient for detecting topographical changes close to the track for a volume of ~1 dm3 and the absolute positioning obtained with a low sky obstruction was approximately 5 m. The precision of SfM-EV was of a similar order to the other techniques, with an order of magnitude of a few centimetres. This approach possesses a low price-result quality ratio and is very simple to use. The possibility of using any type of vehicle for surveying is an advantage, especially for transportation track embankments.
Identifying Tree-Related Microhabitats in TLS Point Clouds Using Machine Learning
Authors: Rehush Nataliia , Abegg Meinrad , Waser Lars T. , Brändli Urs-Beat
Published: November 2018

Tree-related microhabitats (TreMs) play an important role in maintaining forest biodiversity and have recently received more attention in ecosystem conservation, forest management and research. However, TreMs have until now only been assessed by experts during field surveys, which are time-consuming and difficult to reproduce. In this study, we evaluate the potential of close-range terrestrial laser scanning (TLS) for semi-automated identification of different TreMs (bark, bark pockets, cavities, fungi, ivy and mosses) in dense TLS point clouds using machine learning algorithms, including deep learning. To classify the TreMs, we applied: (1) the Random Forest (RF) classifier, incorporating frequently used local geometric features and two additional self-developed orientation features, and (2) a deep Convolutional Neural Network (CNN) trained using rasterized multiview orthographic projections (MVOPs) containing top view, front view and side view of the point’s local 3D neighborhood. The results confirmed that using local geometric features is beneficial for identifying the six groups of TreMs in dense tree-stem point clouds, but the rasterized MVOPs are even more suitable. Whereas the overall accuracy of the RF was 70%, that of the deep CNN was substantially higher (83%). This study reveals that close-range TLS is promising for the semi-automated identification of TreMs for forest monitoring purposes, in particular when applying deep learning techniques.
Mapping Urban Functional Zones by Integrating Very High Spatial Resolution Remote Sensing Imagery and Points of Interest: A Case Study of Xiamen, China
Authors: Song Jinchao , Lin Tao , Li Xinhu , Prishchepov Alexander V.
Published: November 2018

Fine-scale, accurate intra-urban functional zones (urban land use) are important for applications that rely on exploring urban dynamic and complexity. However, current methods of mapping functional zones in built-up areas with high spatial resolution remote sensing images are incomplete due to a lack of social attributes. To address this issue, this paper explores a novel approach to mapping urban functional zones by integrating points of interest (POIs) with social properties and very high spatial resolution remote sensing imagery with natural attributes, and classifying urban function as residence zones, transportation zones, convenience shops, shopping centers, factory zones, companies, and public service zones. First, non-built and built-up areas were classified using high spatial resolution remote sensing images. Second, the built-up areas were segmented using an object-based approach by utilizing building rooftop characteristics (reflectance and shapes). At the same time, the functional POIs of the segments were identified to determine the functional attributes of the segmented polygon. Third, the functional values—the mean priority of the functions in a road-based parcel—were calculated by functional segments and segmental weight coefficients. This method was demonstrated on Xiamen Island, China with an overall accuracy of 78.47% and with a kappa coefficient of 74.52%. The proposed approach could be easily applied in other parts of the world where social data and high spatial resolution imagery are available and improve accuracy when automatically mapping urban functional zones using remote sensing imagery. It will also potentially provide large-scale land-use information.
Vegetation Horizontal Occlusion Index (VHOI) from TLS and UAV Image to Better Measure Mangrove LAI
Authors: Guo Xianxian , Wang Le , Tian Jinyan , Yin Dameng , Shi Chen , Nie Sheng
Published: November 2018

Accurate measurement of the field leaf area index (LAI) is crucial for assessing forest growth and health status. Three-dimensional (3-D) structural information of trees from terrestrial laser scanning (TLS) have information loss to various extents because of the occlusion by canopy parts. The data with higher loss, regarded as poor-quality data, heavily hampers the estimation accuracy of LAI. Multi-location scanning, which proved effective in reducing the occlusion effects in other forests, is hard to carry out in the mangrove forest due to the difficulty of moving between mangrove trees. As a result, the quality of point cloud data (PCD) varies among plots in mangrove forests. To improve retrieval accuracy of mangrove LAI, it is essential to select only the high-quality data. Several previous studies have evaluated the regions of occlusion through the consideration of laser pulses trajectories. However, the model is highly susceptible to the indeterminate profile of complete vegetation object and computationally intensive. Therefore, this study developed a new index (vegetation horizontal occlusion index, VHOI) by combining unmanned aerial vehicle (UAV) imagery and TLS data to quantify TLS data quality. VHOI is asymptotic to 0.0 with increasing data quality. In order to test our new index, the VHOI values of 102 plots with a radius of 5 m were calculated with TLS data and UAV image. The results showed that VHOI had a strong linear relationship with estimation accuracy of LAI (R2 = 0.72, RMSE = 0.137). In addition, as TLS data were selected by VHOI less than different thresholds (1.0, 0.9, …, 0.1), the number of remaining plots decreased while the agreement between LAI derived from TLS and field-measured LAI was improved. When the VHOI threshold is 0.3, the optimal trade-off is reached between the number of plots and LAI measurement accuracy (R2 = 0.67). To sum up, VHOI can be used as an index to select high-quality data for accurately measuring mangrove LAI and the suggested threshold is 0.30.
Characterization of S-Band Dual-Polarized Radar Data for the Convective Rain Melting Layer Detection in A Tropical Region
Authors: Yuan Feng , Lee Yee Hui , Meng Yu Song , Ong Jin Teong
Published: November 2018

In the tropical region, convective rain is a dominant rain event. However, very little information is known about the convective rain melting layer. In this paper, S-band dual-polarized radar data is studied in order to identify both the stratiform and convective rain melting layers in the tropical region, with a focus on the convective events. By studying and analyzing the above-mentioned two types of rain events, amongst three radar measurements of reflectivity ( Z ), differential reflectivity ( Z DR ), and cross correlation coefficient ( ρ HV ), the latter one is the best indicator for convective rain melting layer detection. From two years (2014 and 2015) of radar and radiosonde observations, 13 convective rain melting layers are identified with available 0 °C isothermal heights which are derived from radiosonde vertical profiles. By comparing the melting layer top heights with the corresponding 0 °C isothermal heights, it is found that for convective rain events, the threshold to detect melting layer should be modified to ρ HV = 0.95 for the tropical region. The melting layer top and bottom heights are then estimated using the proposed threshold, and it is observed from this study that the thickness of convective rain melting layer is around 2 times that of stratiform rain melting layer which is detected by using the conventional ρ HV = 0.97 .
Assessment of Ground-Reference Data and Validation of the H-SAF Precipitation Products in Brazil
Authors: Martins Costa do Amaral Lia , Barbieri Stefano , Vila Daniel , Puca Silvia , Vulpiani Gianfranco , Panegrossi Giulia , Biscaro Thiago , Sanò Paolo , Petracca Marco , Marra Anna Cinzia , Gosset Marielle , Dietrich Stefano
Published: November 2018

The uncertainties associated with rainfall estimates comprise various measurement scales: from rain gauges and ground-based radars to the satellite rainfall retrievals. The quality of satellite rainfall products has improved significantly in recent decades; however, such algorithms require validation studies using observational rainfall data. For this reason, this study aims to apply the H-SAF consolidated radar data processing to the X-band radar used in the CHUVA campaigns and apply the well established H-SAF validation procedure to these data and verify the quality of EUMETSAT H-SAF operational passive microwave precipitation products in two regions of Brazil (Vale do Paraíba and Manaus). These products are based on two rainfall retrieval algorithms: the physically based Bayesian Cloud Dynamics and Radiation Database (CDRD algorithm) for SSMI/S sensors and the Passive microwave Neural network Precipitation Retrieval algorithm (PNPR) for cross-track scanning radiometers (AMSU-A/AMSU-B/MHS sensors) and for the ATMS sensor. These algorithms, optimized for Europe, Africa and the Southern Atlantic region, provide estimates for the MSG full disk area. Firstly, the radar data was treated with an overall quality index which includes corrections for different error sources like ground clutter, range distance, rain-induced attenuation, among others. Different polarimetric and non-polarimetric QPE algorithms have been tested and the Vulpiani algorithm (hereafter, R q 2 V u 15 ) presents the best precipitation retrievals when compared with independent rain gauges. Regarding the results from satellite-based algorithms, generally, all rainfall retrievals tend to detect a larger precipitation area than the ground-based radar and overestimate intense rain rates for the Manaus region. Such behavior is related to the fact that the environmental and meteorological conditions of the Amazon region are not well represented in the algorithms. Differently, for the Vale do Paraíba region, the precipitation patterns were well detected and the estimates are in accordance with the reference as indicated by the low mean bias values.