bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feasibility of Using N-Of-1 Trials to Investigate Deprescribing in Older Adults with Dementia: A Pilot Study
Authors: Clough Alexander J. , Hilmer Sarah N. , Naismith Sharon L. , Gnjidic Danijela
Published: December 2019

N-of-1 trials may provide insights into the impact of deprescribing medications in populations where evidence is currently lacking, such as the effect of statins on cognition in people with dementia. For this pilot, N-of-1, double-blinded, deprescribing trial, adults over 80 years of age with dementia taking statins for at least 6-months were recruited from a hospital’s geriatric medicine outpatient clinic in Sydney, Australia. Participants discontinued and restarted statins over the study period. At enrolment, the hospital pharmacy—using a random number generator, randomised recruited participants to their usual statin or placebo regimen, with assessment and switching of treatment every 5 weeks from baseline (0-weeks) until Visit 4 (15-weeks). Primary outcome was measured using the rate of change in Alzheimer’s Disease Assessment Score-Cognitive Subscale (ADAS-CoG). Over 6-months, 81 participants were screened, 14 were eligible, and four were randomised. One participant (female, 88 years) completed all four assessments with no major harms reported. Cognitive impairment, as measured by ADAS-CoG score, was similar on placebo (15.5/70) compared to statin (15/70). This study suggests there are significant challenges in performing N-of-1 trials and recruiting people with dementia into deprescribing trials from outpatient settings.
A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS
Authors: Palmer Katie , Carfì Angelo , Angioletti Carmen , Di Paola Antonella , Navickas Rokas , Dambrauskas Laimis , Jureviciene Elena , João Forjaz Maria , Rodriguez-Blazquez Carmen , Prados-Torres Alexandra , Gimeno-Miguel Antonio , Cano-del Pozo Mabel , Bestué-Cardiel María , Leiva-Fernández Francisca , Poses Ferrer Elisa , Carriazo Ana M , Lama Carmen , Rodríguez-Acuña Rafael , Cosano Inmaculada , Bedoya-Belmonte Juan José , Liseckiene Ida , Barbolini Mirca , Txarramendieta Jon , de Manuel Keenoy Esteban , Fullaondo Ane , Rijken Mieke , Onder Graziano
Published: December 2019

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis—“strengths, weaknesses, opportunities, threats” (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.
The Temporal and Spatial Evolution of Marathons in China from 2010 to 2018
Authors: Zuo Yifan , Zou Liye , Zhang Mu , Smith Lee , Yang Lin , Loprinzi Paul D. , Ren Zhanbing
Published: December 2019

The purpose of this study is to explore the spatial distribution pattern and influencing factors of the Chinese marathon. Geographic Information System (GIS) related spatial analysis tools were used to calculate the following—averaged nearest neighbor index, nuclear density analysis and hot spot analysis among others. The spatial distribution evolution characteristics and the influencing factors of eighteen Chinese marathon events in 2010, 129 in 2015 and 342 in 2018 were analyzed. The results show that (a) in 2010 the nearest neighbor ratio was 1.164714, Moran’s I was −0.010165 (type: Random), in 2015 it was 0.502146, Moran’s I was 0.066267 (type: Clustered) and in 2018 it was 0.531149 and Moran’s I was 0.083485 (type: Clustered); (b) in 2010 there was a 333.6 km search radius; the core circle of the Yangtze River Delta was adopted. In 2015 and 2018, a search radius of 556 km was adopted, which was respectively obtained from the core circle of the Yangtze River Delta, the core circle of Beijing-Tianjin-Hebei and the core circle of East China; (c) according to the Z-value data, East China and North China in 2015 passed 95% confidence in five provinces and municipal hot spots, passed 90% confidence in three hot spots and passed 95% confidence in Chongqing Cold Point. In 2018, East China, North China, Central Region and eight other provinces and cities’ hot spots passed 95% confidence, four hot spots passed 90% confidence, the Tibet Autonomous Region cold spot passed 90% confidence. Conclusion: The overall distribution of marathon events is greater in the eastern region than the western region, greater in the southern region than the northern region and greater in coastal regions than the inland regions; the nuclear density distribution has spread from the Yangtze River Delta mononuclear circle in 2010 to the core circle of the entire East China region. Moreover, it spread to North China, Central China and South China; the distribution of hot spots spread from Shanghai, Jiangsu and Zhejiang to the entire North China and East China regions. During the past thirty-eight years of development of the Chinese marathon, it has been divided into three stages due to different political, economic and social environments.
The Dutch Comparative Scale for Assessing Volunteer Motivations among Volunteers and Non-Volunteers: An Adaptation of the Volunteer Functions Inventory
Authors: Niebuur Jacobien , Liefbroer Aart C. , Steverink Nardi , Smidt Nynke
Published: December 2019

Currently, no valid scales exist to compare volunteer motivations between volunteers and non-volunteers. We aimed to adapt the Dutch version of the Volunteer Functions Inventory (VFI) in order to make it applicable for the comparison of volunteer motivations between Dutch older volunteers and non-volunteers. The Dutch version of the VFI was included in the Lifelines ‘Daily Activities and Leisure Activities add on Study’, which was distributed among participants aged 60 to 80. Confirmatory factor analysis (CFA) models were estimated for volunteers and non-volunteers separately, and subsequently a CFA model was created based on all observations irrespective of volunteer status. Finally, group-based CFA models were estimated to assess measurement invariance. The resulting measurement instrument (6 factors, 18 items), containing both a volunteer version and a non-volunteer version, indicated an acceptable model fit for the separate and the combined CFA models (root mean square error of approximation (RMSEA) = 0.06, comparative fit index (CFI) = 0.95). Group-based models demonstrated strong invariance between the samples. The current study provides support for the validity of the Dutch Comparative Scale for Assessing Volunteer Motivations among Volunteers and Non-Volunteers, among Dutch older adults.
Quantification of Similarity Relationships According to Parameters of Day Surgery System
Authors: Gavurova Beata , Kovac Viliam , Bejtkovsky Jiri
Published: December 2019

Performing day surgery should minimise a number of hospitalisation cases, but its use is determined by many factors. It takes advantage of the latest advances in surgical care, enabling better use of highly costly specialised operating room equipment. This analysis of the day surgery system of the Slovak Republic stands on an examination of the five specialised fields—surgery, gynaecology, ophthalmology, otorhinolaryngology, and urology. The explored period covers the years 2009 to 2017. The whole analysis is divided into the two sections—the youth category and for the adult category. For each case, a hospitalisation ratio is computed. A map visualisation supports the analysis outcome. A quantification of the similarity relationships between the regions is done according to a Euclidean distance approach and it is illustrated through the heat map. The centremost region is the Žilina Region with distance at a level of 1.9821, meaning that it performs as the most similar region to a development of a hospitalisation ratio in the whole Slovak Republic regarding all the examined aspects. The findings introduce an important platform for a creation of regional and national health plans in the area of healthcare provision for the population of the country.
Highs and Lows of Lambing Time: Sheep Farmers’ Perceptions of the First Outbreak of Schmallenberg Disease in South West England on Their Well-Being
Authors: Phythian Clare J. , Glover Mike J.
Published: December 2019

The outbreak of a previously unknown and new disease in the United Kingdom, known as ‘Schmallenberg disease’, a disease associated with abortions, stillbirths and fetal deformities in naïve ewes, was reported for the first time in South West England during the 2012/13 early lambing season. Epidemiological studies confirmed that the Schmallenberg virus (SBV) had a severe negative impact upon animal welfare and the productivity of affected flocks. By contrast, there was a specific lack of research on the impact of SBV on sheep farmer well-being. This study aimed to improve our understanding of sheep farmers’ experiences of Schmallenberg disease, and the impact of the first outbreak on sheep farmer well-being during the 2012/13 early lambing season in South West England. Face-to-face, semi-structured interviews with six farmers with small flocks of pedigree and purebred sheep in South West England were conducted in 2013. The data were analysed via thematic analysis. The main themes regarding the impact of disease on farmer well-being included: (i) emotional highs and lows are part of a normal lambing season; (ii) negative emotions and memories associated with the Schmallenberg disease outbreak; and (iii) resilience and coping with the unexpected disease outbreak. These novel data present preliminary findings from a small number of sheep farmers, and indicate that for some farmers, an unexpected outbreak of a new and emerging disease for the first time during lambing, and dealing with high levels of dystocia, deformities and deaths in their animals, had a negative impact on their emotional well-being during the peak period of the sheep production cycle.
Vulnerability and Adaptation to Extreme Heat in Odisha, India: A Community Based Comparative Study
Authors: Swain Subhashisa , Bhattacharya Shreeporna , Dutta Ambarish , Pati Sanghamitra , Nanda Lipika
Published: December 2019

Background: Extreme heat and heat illness are becoming very frequent in India. We aimed to identify the factors associated with heat illness and the coping practices among city dwellers of Odisha, India during the summer. Methods: A cross-sectional study included 766 households (HHs) in twin cities of Odisha covering a population of 1099 (slum: 404 and non-slum: 695) in the year 2017. We collected information on sociodemographic, household characteristics, coping practices to heat and the heat illness history reported during the summer. Multivariate logistic regression accounting for clustering effects at the household and slum levels was used to identify the associated factors of heat illness after adjustment of other variables. Result: Nearly, 49% of the study participants were female and the mean age was 38.36 years (95% confidence interval (CI): 37.33–39.39 years). A significant difference of living environment was seen across the groups. More than two-thirds of the study participants at least once had heat illness. In the non-slum population, males (adjusted odds ratio (aOR): 3.56; 95% CI: 2.39–5.29), persons under medication (aOR: 3.09; 95% CI: 1.15–8.29), and chronic conditions had higher association with heat illness. Whereas, in the slum population, having a kitchen outside the home (aOR: 1.63; 95% CI: 1.02–3.96) and persons with chronic conditions were positively associated with heat illness. Use of cooling practices in slum areas reduced the risk of heat illness by 60%. Conclusion: Heat illness is associated with the living environment and physical health of the individuals. Identifying the vulnerable population and scaling up adaptive practices can strengthen the public health preparedness.
Do Mutations Turn p53 into an Oncogene?
Authors: Pitolli Consuelo , Wang Ying , Mancini Mara , Shi Yufang , Melino Gerry , Amelio Ivano
Published: December 2019

The key role of p53 as a tumor suppressor became clear when it was realized that this gene is mutated in 50% of human sporadic cancers, and germline mutations expose carriers to cancer risk throughout their lifespan. Mutations in this gene not only abolish the tumor suppressive functions of p53, but also equip the protein with new pro-oncogenic functions. Here, we review the mechanisms by which these new functions gained by p53 mutants promote tumorigenesis.
The Eighth ECS Workshop on “Calcium Signaling in Aging and Neurodegenerative Diseases”
Authors: Parys Jan B. , Pereira Cláudia F. , Villalobos Carlos
Published: December 2019

The European Calcium Society (ECS) is very glad to present the realization of a special issue of the International Journal of Molecular Sciences (IJMS) related to the eighth ECS workshop organized this year around the theme of “Calcium Signaling in Aging and Neurodegenerative Diseases” [...]
Novel Insights into the Role of HDL-Associated Sphingosine-1-Phosphate in Cardiometabolic Diseases
Authors: Diarte-Añazco Elena M. G. , Méndez-Lara Karen Alejandra , Pérez Antonio , Alonso Núria , Blanco-Vaca Francisco , Julve Josep
Published: December 2019

Sphingolipids are key signaling molecules involved in the regulation of cell physiology. These species are found in tissues and in circulation. Although they only constitute a small fraction in lipid composition of circulating lipoproteins, their concentration in plasma and distribution among plasma lipoproteins appears distorted under adverse cardiometabolic conditions such as diabetes mellitus. Sphingosine-1-phosphate (S1P), one of their main representatives, is involved in regulating cardiomyocyte homeostasis in different models of experimental cardiomyopathy. Cardiomyopathy is a common complication of diabetes mellitus and represents a main risk factor for heart failure. Notably, plasma concentration of S1P, particularly high-density lipoprotein (HDL)-bound S1P, may be decreased in patients with diabetes mellitus, and hence, inversely related to cardiac alterations. Despite this, little attention has been given to the circulating levels of either total S1P or HDL-bound S1P as potential biomarkers of diabetic cardiomyopathy. Thus, this review will focus on the potential role of HDL-bound S1P as a circulating biomarker in the diagnosis of main cardiometabolic complications frequently associated with systemic metabolic syndromes with impaired insulin signaling. Given the bioactive nature of these molecules, we also evaluated its potential of HDL-bound S1P-raising strategies for the treatment of cardiometabolic disease.
Ataluren for the Treatment of Usher Syndrome 2A Caused by Nonsense Mutations
Authors: Samanta Ananya , Stingl Katarina , Kohl Susanne , Ries Jessica , Linnert Joshua , Nagel-Wolfrum Kerstin
Published: December 2019

The identification of genetic defects that underlie inherited retinal diseases (IRDs) paves the way for the development of therapeutic strategies. Nonsense mutations caused approximately 12% of all IRD cases, resulting in a premature termination codon (PTC). Therefore, an approach that targets nonsense mutations could be a promising pharmacogenetic strategy for the treatment of IRDs. Small molecules (translational read-through inducing drugs; TRIDs) have the potential to mediate the read-through of nonsense mutations by inducing expression of the full-length protein. We provide novel data on the read-through efficacy of Ataluren on a nonsense mutation in the Usher syndrome gene USH2A that causes deaf-blindness in humans. We demonstrate Ataluren´s efficacy in both transiently USH2AG3142*-transfected HEK293T cells and patient-derived fibroblasts by restoring USH2A protein expression. Furthermore, we observed enhanced ciliogenesis in patient-derived fibroblasts after treatment with TRIDs, thereby restoring a phenotype that is similar to that found in healthy donors. In light of recent findings, we validated Ataluren´s efficacy to induce read-through on a nonsense mutation in USH2A-related IRD. In line with published data, our findings support the use of patient-derived fibroblasts as a platform for the validation of preclinical therapies. The excellent biocompatibility combined with sustained read-through efficacy makes Ataluren an ideal TRID for treating nonsense mutations based IRDs.
Technetium Nitrido-Peroxo Complexes: An Unexplored Class of Coordination Compounds
Authors: Pasquali Micol , Janevik-Ivanovska Emilija , Duatti Adriano
Published: December 2019

The purpose of this work was to further expand the chemistry of mixed technetium nitrido-peroxo complexes, a still poorly explored class of compounds containing the Tc(VII) moiety, [99gTc][Tc(N)(O2)2]. A number of novel complexes of the formula [99gTc][Tc(N)(O2)2(L)] with bidentate ligands (L) (where L = deprotonated alanine, glycine, proline) were prepared by reacting a solution of nitrido-technetic(VI) acid with L in the presence of a source of H2O2. Alternatively, the complex [99gTc][Tc(N)(O2)2X]− (X = Cl, Br) was used as a precursor for substitution reactions where the halogenide ion was replaced by the bidentate ligand. The new complexes were characterized by elemental analysis and mass spectroscopy. The preparation of the analogous [99mTc][Tc(N)(O2)2] moiety, radiolabeled with the metastable isomer Tc-99m, was also studied at a no-carrier-added level, using S-methyl-N-methyl-dithiocarbazate as the donor of the nitrido nitrogen atoms.
Characterization of a Vitellogenin Receptor in the Bumblebee, Bombus lantschouensis (Hymenoptera, Apidae)
Authors: Du Lin , Wang Mingming , Li Jilian , He Shaoyu , Huang Jiaxing , Wu Jie
Published: December 2019

The vitellogenin receptor (VgR) belongs to the low-density lipoprotein receptor (LDLR) family, responsible for mediating the endocytosis of vitellogenin (Vg) into the ovaries to promote ovarian growth and oviposition. Here, we cloned and measured VgR gene expression characteristics in the bumblebee Bombus lantschouensis. RNA interference was used to validate VgR function. The results showed that the full length of the BLVgR cDNA was 5519 bp, which included a 5280 bp open reading frame encoding 1759 amino acids (AAs). Sequence alignment revealed that the protein contained 12 LDLa, 5 EGF, 2 EGF-CA and 10 LY domains. Phylogenetic analysis showed that BLVgR and the VgR of Bombus terrestris clustered together and the tree of bumblebees (Bombus) appeared as one clade next to honeybees (Apis). Transcript expression analysis showed that BLVgR was expressed in all tested tissues and showed the highest abundance in the ovaries. BLVgR expression was present in all developmental stages. However, the expression level in larvae was extremely low. In addition, the expression of BLVgR was significantly upregulated after egg laying in both workers and queens. In new emerging workers injected with 5 µg of VgR dsRNA, the expression level of BLVgR was 4-fold lower than that in the GFP dsRNA-injected group after 72 h. Furthermore, BLVgR silencing significantly reduced the number of eggs laid (3.67 ± 1.96 eggs) and delayed the first egg-laying time (16.31 ± 2.07 days) in worker microcolonies when compared to dsGFP (37.31 ± 4.09 eggs, 8.15 ± 0.22 days) and DEPC-treated water injected controls (16.42 ± 2.24 eggs, 10.00 ± 0.37 days). In conclusion, the BLVgR gene and its reproductive function were explored in the bumblebee B. lantschouensis. This gene plays an important role in egg laying time and egg number.
The Response of Neotropical Dragonflies (Insecta: Odonata) to Local and Regional Abiotic Factors in Small Streams of the Amazon
Authors: Oliveira-Junior José Max Barbosa , Dias-Silva Karina , Teodósio Maria Alexandra , Juen Leandro
Published: December 2019

Since the relative role of local and regional abiotic factors on the Odonata diversity in rainforest streams is still poorly understood, we evaluated the effects of these factors on adult Odonata (Insecta) from preserved and altered streams in the Amazonian region. Adult Odonata were sampled in 98 streams in the Eastern Amazon, Pará, Brazil. Six variables were used to measure local environmental factors: habitat integrity index; mean canopy over the channel; and four physical and chemical descriptors of the water. To measure regional environmental factors, six variables were also used: altitude gradient, three bioclimatic variables and two percentage forest variables. In partial redundancy analysis, both abiotic factors (local and regional) were important to explain the variation in the Odonata community. The Odonata community can be influenced by regional and local factors. The relationship between Odonata and the local (e.g., integrity, canopy cover, and physical and chemical descriptors of the water) and regional (e.g., bioclimatic and forest cover variables) environmental variables recorded in this study has important implications for the use of these organisms to monitor small streams of the Eastern Amazon. The scale at which habitat is measured is an important issue in community structuring studies considering the rapid environmental changes. It is of great importance to consider the different scales in studies assessing community structure, once an adequate habitat must meet the ecological needs of all stages of the life of the Odonata.
Effect of Antibacterial Silver-Releasing Filler on the Physicochemical Properties of Poly(Methyl Methacrylate) Denture Base Material
Authors: Chladek Grzegorz , Pakieła Katarzyna , Pakieła Wojciech , Żmudzki Jarosław , Adamiak Marcin , Krawczyk Cezary
Published: December 2019

Colonization of polymeric dental prosthetic materials by yeast-like fungi and the association of these microorganisms with complications occurring during prosthetic treatment are important clinical problems. In previously presented research, submicron inorganic particles of silver sodium hydrogen zirconium phosphate (S–P) were introduced into poly(methyl methacrylate) (PMMA) denture base material which allowed for obtaining the antimicrobial effect during a 90 day experiment. The aim of the present study was to investigate the flexural strength, impact strength, hardness, wear resistance, sorption, and solubility during three months of storage in distilled water. With increasing S–P concentration after 2 days of conditioning in distilled water, reduced values of flexural strength (107–72 MPa), impact strength (18.4–5.5 MPa) as well as enhanced solubility (0.95–1.49 µg/mm3) were registered, but they were at acceptable levels, and the sorption was stable. Favorable changes included increased hardness (198–238 MPa), flexural modulus (2.9–3.3 GPa), and decreased volume loss during wear test (2.9–0.2 mm3). The percentage changes of the analyzed properties during the 90 days of storage in distilled water were similar for all materials.
2D–3D Digital Image Correlation Comparative Analysis for Indentation Process
Authors: Bermudo Gamboa Carolina , Martín-Béjar Sergio , Trujillo Vilches F. Javier , Castillo López G. , Sevilla Hurtado Lorenzo
Published: December 2019

Nowadays, localized forming operations, such as incremental forming processes, are being developed as an alternative to conventional machining or forming techniques. An indentation process is the main action that takes places in these forming activities, allowing small, localized deformations. It is essential to have the knowledge of the material behavior under the punch and the transmitted forces to achieve correct control of the entire procedure. This paper presents the work carried out with the digital image correlation (DIC) technique applied to the study of the material flow that takes place under an indentation process. The material flow analysis is performed under 2D and 3D conditions, establishing the methodology for the calibration and implementation for each alternative. Two-dimensional DIC has been proven to be a satisfactory technique compared with the 3D method, showing results in good agreement with experimental tests and models developed by the finite element method. Notwithstanding, part of the indented material flows under the punch, emerging on the front surface and generating a dead zone that can only be addressed with a 3D technique. So, the main objective is to carry out a comparison between the 2D and 3D techniques to identify if the 3D application could be mandatory for this type of process. Also, a 2D–3D mix analysis is proposed for study cases in which it is necessary to know the material flow in that specific area of the workpiece.
Environmental and Economic Analysis of FDM, SLS and MJF Additive Manufacturing Technologies
Authors: Tagliaferri Vincenzo , Trovalusci Federica , Guarino Stefano , Venettacci Simone
Published: December 2019

In this study, the authors present a comparative analysis of different additive manufacturing (AM) technologies for high-performance components. Four 3D printers, currently available on the Italian national manufacturing market and belonging to three different AM technologies, were considered. The analysis focused on technical aspects to highlight the characteristics and performance limits of each technology, economic aspects to allow for an assessment of the costs associated with the different processes, and environmental aspects to focus on the impact of the production cycles associated with these technologies on the ecosystem, resources and human health. This study highlighted the current limits of additive manufacturing technologies in terms of production capacity in the case of large-scale production of plastic components, especially large ones. At the same time, this study highlights how the geometry of the object to be developed greatly influences the optimal choice between the various AM technologies, in both technological and economic terms. Fused deposition modeling (FDM) is the technology that exhibits the greatest limitations hindering mass production due to production times and costs, but also due to the associated environmental impact.
High Strength X3NiCoMoTi 18-9-5 Maraging Steel Prepared by Selective Laser Melting from Atomized Powder
Authors: Strakosova Angelina , Kubásek Jiří , Michalcová Alena , Průša Filip , Vojtěch Dalibor , Dvorský Drahomír
Published: December 2019

Maraging steels are generally characterized by excellent mechanical properties, which make them ideal for various industrial applications. The application field can be further extended by using selective laser melting (SLM) for additive manufacturing of shape complicated products. However, the final mechanical properties are strongly related to the microstructure conditions. The present work studies the effect of heat treatment on the microstructure and mechanical properties of 3D printed samples prepared from powder of high-strength X3NiCoMoTi 18-9-5 maraging steel. It was found that the as-printed material had quite low mechanical properties. After sufficient heat treatment, the hardness of the material increased from 350 to 620 HV0.1 and the tensile yield strength increased from 1000 MPa up to 2000 MPa. In addition, 3% ductility was maintained. This behavior was primarily affected by strong precipitation during processing.
Chemical and Rheological Evaluation of Aged Lignin-Modified Bitumen
Authors: Zhang Yi , Liu Xueyan , Apostolidis Panos , Gard Wolfgang , van de Ven Martin , Erkens Sandra , Jing Ruxin
Published: December 2019

As bitumen oxidizes, material stiffening and embrittlement occur, and bitumen eventually cracks. The use of anti-oxidants, such as lignin, could be used to delay oxidative aging and to extend the lifetime of asphalt pavements. In this study, the chemical and rheological effect of lignin on bitumen was evaluated by using a single dosage organsolv lignin (10 wt.% dosage). A pressure aging vessel (PAV) was used to simulate the long-term aging process after performing the standard short-term aging procedure, and the lignin-modified bituminous binders were characterized by an environmental scanning electron microscope (ESEM), Fourier-transform infrared (FTIR) spectroscopy, and a dynamic shear rheometer (DSR). From the ESEM results, the uniform microstructure was observed, indicating that the addition of lignin did not affect the worm structure of bitumen. Based on the FTIR test results, lignin-modified bitumen showed that a lower number of carbonyl and sulfoxide compounds were generated after aging than for neat bitumen. Based on the linear amplitude sweep (LAS) results, the addition of lignin slightly reduced the fatigue life of bitumen. From the frequency sweep results, it showed that lignin in bitumen acts as a modifier since the physical interaction between lignin and bitumen predominantly affects the material rheology. Overall, lignin could be a promising anti-oxidant due to its economic and environmental benefits.
Explorative Study on the Use of Curauá Reinforced Polypropylene Composites for the Automotive Industry
Authors: Delgado-Aguilar Marc , Tarrés Quim , Marques María de Fátima V. , Espinach Francesc X. , Julián Fernando , Mutjé Pere , Vilaseca Fabiola
Published: December 2019

The automotive industry is under a growing volume of regulations regarding environmental impact and component recycling. Nowadays, glass fiber-based composites are commodities in the automotive industry, but show limitations when recycled. Thus, attention is being devoted to alternative reinforcements like natural fibers. Curauá (Curacao, Ananas erectifolius) is reported in the literature as a promising source of natural fiber prone to be used as composite reinforcement. Nonetheless, one important challenge is to obtain properly dispersed materials, especially when the percentages of reinforcements are higher than 30 wt %. In this work, composite materials with curauá fiber contents ranging from 20 wt % to 50 wt % showed a linear positive evolution of its tensile strength and Young’s modulus against reinforcement content. This is an indication of good reinforcement dispersion and of favorable stress transfer at the fiber-matrix interphase. A car door handle was used as a test case to assess the suitability of curauá-based composites to replace glass fiber-reinforced composites. The mechanical analysis and a preliminary lifecycle analysis are performed to prove such ability.
Inequalities by Means of Generalized Proportional Fractional Integral Operators with Respect to Another Function
Authors: Rashid Saima , Jarad Fahd , Noor Muhammad Aslam , Kalsoom Humaira , Chu Yu-Ming
Published: December 2019

In this article, we define a new fractional technique which is known as generalized proportional fractional (GPF) integral in the sense of another function Ψ . The authors prove several inequalities for newly defined GPF-integral with respect to another function Ψ . Our consequences will give noted outcomes for a suitable variation to the GPF-integral in the sense of another function Ψ and the proportionality index ς . Furthermore, we present the application of the novel operator with several integral inequalities. A few new properties are exhibited, and the numerical approximation of these new operators is introduced with certain utilities to real-world problems.
Effect of Oral Administration of Active Peptides of Pinctada Martensii on the Repair of Skin Wounds
Authors: Yang Faming , Qin Xiaoming , Zhang Ting , Zhang Chaohua , Lin Haisheng
Published: December 2019

Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of APs, the effect of APs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that APs consisted of polypeptides with molecular weights in the range 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that mice in APs-L group which were fed a low dose of APs (0.5 g/kg bw) had a shortened epithelialization time due to a shortening inflammatory period (p < 0.05). Mechanistically, this relied on its specific ability to promote the proliferation of CD31, FGF and EGF which accelerated the percentage of wound closure. Moreover, the APs-L group mice had enhanced collagen synthesis and increased type III collagen content in their wounds through a TGF-β/Smad signaling pathway (p > 0.05). Consequently, scar formation was inhibited and wound healing efficiency was significantly improved. These results show that the APs of Pinctada martensii promote dermal wound healing in mice and have tremendous potential for development and utilization in skin wound healing.
Enhypyrazinones A and B, Pyrazinone Natural Products from a Marine-Derived Myxobacterium Enhygromyxa sp.
Authors: Zhang Fan , Braun Doug R. , Rajski Scott R. , DeMaria Don , Bugni Tim S.
Published: December 2019

To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of biological activities. Marine-derived myxobacteria are especially attractive due to their unique biosynthetic gene clusters, although they are more difficult to handle than terrestrial myxobacteria. Here, we report the discovery of two new pyrazinone-type molecules, enhypyrazinones A and B, from a marine-derived myxobacterium Enhygromyxa sp. Their structures were elucidated by HRESIMS and comprehensive NMR data analyses. Compounds 1 and 2, which contain a rare trisubstituted-pyrazinone core, represent a unique class of molecules from Enhygromyxa sp.
A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa
Authors: Chen Xingchen , Leahy Darren , Van Haeften Jessica , Hartfield Perry , Prentis Peter J. , van der Burg Chloé A. , Surm Joachim M. , Pavasovic Ana , Madio Bruno , Hamilton Brett R. , King Glenn F. , Undheim Eivind A. B. , Brattsand Maria , Harris Jonathan M.
Published: December 2019

Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular scaffolds for inhibitor design. This investigation is a bioprospecting study that aims to isolate and identify protease inhibitors from the cnidarian Actinia tenebrosa. The study isolated two Kunitz-type protease inhibitors with very similar sequences but quite divergent inhibitory potencies when assayed against bovine trypsin, chymostrypsin, and a selection of human sequence-related peptidases. Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. Thermal denaturation studies showed that the inhibitors were remarkably robust. To gain a fine-grained map of the residues responsible for this stability, we conducted in silico alanine scanning and quantified individual residue contributions to the inhibitor’s stability. Sequences of these inhibitors were then used to search for Kunitz homologs in an A. tenebrosa transcriptome library, resulting in the discovery of a further 14 related sequences. Consensus analysis of these variants identified a rich molecular diversity of Kunitz domains and expanded the palette of potential residue substitutions for rational inhibitor design using this domain.
A Microfluidic Detection System for Bladder Cancer Tumor Cells
Authors: Lv Shuxing , Yu Jinwei , Zhao Yan , Li Hongxiang , Zheng Fang , Liu Ning , Li Dahua , Sun Xuguo
Published: December 2019

The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine interferes with the recognition of tumor cells. In this paper, a technique for detecting cancer cells in urine based on microfluidics provides a novel approach to bladder cancer diagnosis. The bladder cancer cell line (T24) and MeT-5A were used as positive bladder tumor cells and non-tumor cells, respectively. The practicality of the tumor cell detection system based on microfluidic cell chip detection technology is discussed. The tumor cell (T24) concentration was around 1 × 104 to 300 × 104 cells/mL. When phosphate buffer saline (PBS) was the diluted solution, the tumor cell detected rate was 63–71% and the detection of tumor cell number stability (coefficient of variation, CV%) was 6.7–4.1%, while when urine was the diluted solution, the tumor cell detected rate was 64–72% and the detection of tumor cell number stability (CV%) was 6.3–3.9%. In addition, both PBS and urine are tumor cell dilution fluid solutions. The sample was analyzed at a speed of 750 microns per hour. Based on the above experiments, a system for detecting bladder cancer cells in urine by microfluidic analysis chip technology was reported. The rate of recognizing bladder cancer cells reached 68.4%, and the speed reached 2 mL/h.
Pathogenesis and Immune Response Caused by Vector-Borne and Other Viral Infections in a Tupaia Model
Authors: Kayesh Mohammad Enamul Hoque , Hashem Md Abul , Kitab Bouchra , Tsukiyama-Kohara Kyoko
Published: December 2019

The Tupaia or tree shrew (Tupaia belangeri), a small mammal of the Tupaiidae family, is an increasingly used and promising infection model for virological and immunological research. Recently, sequencing of the Tupaia whole genome revealed that it is more homologous to the genome of humans than of rodents. Viral infections are a global threat to human health, and a complex series of events are involved in the interactions between a virus and the host immune system, which play important roles in the activation of an immune response and the outcome of an infection. Majority of immune response data in viral infections are obtained from studies using animal models that enhance the understanding of host-virus interactions; a proper understanding of these interactions is very important for the development of effective antivirals and prophylactics. Therefore, animal models that are permissive to infection and that recapitulate human disease pathogenesis and immune responses to viral infections are essential. Several studies have shown the permissiveness of Tupaia to a number of important human viral infections in vitro and in vivo without prior adaptation of the viruses; the immune responses and clinical manifestations were comparable to those observed in human infections. Thus, the Tupaia is being utilized and developed as a promising immunocompetent small animal model for viral infection studies. In this review, we focused on the immune responses, mostly innate, during viral infection and pathogenesis in the Tupaia model; we evaluated the interaction between the virus and the components of host resistance, the usefulness of this model for immunopathogenesis studies, and the vaccines and antivirals available.
Activation of a Bovine Mammary Epithelial Cell Line by Ruminant-Associated Staphylococcus aureus is Lineage Dependent
Authors: Hoekstra Jurriaan , Rutten Victor P. M. G. , Lam Theo J. G. M. , Van Kessel Kok P. M. , Spaninks Mirlin P. , Stegeman J. Arjan , Benedictus Lindert , Koop Gerrit
Published: December 2019

Bovine mastitis is a costly disease to the dairy industry and intramammary infections (IMI) with Staphylococcus aureus are a major cause of mastitis. Staphylococcus aureus strains responsible for mastitis in cattle predominantly belong to ruminant-associated clonal complexes (CCs). Recognition of pathogens by bovine mammary epithelial cells (bMEC) plays a key role in activation of immune responsiveness during IMI. However, it is still largely unknown to what extent the bMEC response differs according to S. aureus CC. The aim of this study was to determine whether ruminant-associated S. aureus CCs differentially activate bMEC. For this purpose, the immortalized bMEC line PS was stimulated with S. aureus mastitis isolates belonging to four different clonal complexes (CCs; CC133, CC479, CC151 and CC425) and interleukin 8 (IL-8) release was measured as indicator of activation. To validate our bMEC model, we first stimulated PS cells with genetically modified S. aureus strains lacking (protein A, wall teichoic acid (WTA) synthesis) or expressing (capsular polysaccharide (CP) type 5 or type 8) factors expected to affect S. aureus recognition by bMEC. The absence of functional WTA synthesis increased IL-8 release by bMEC in response to bacterial stimulation compared to wildtype. In addition, bMEC released more IL-8 after stimulation with S. aureus expressing CP type 5 compared to CP type 8 or a strain lacking CP expression. Among the S. aureus lineages, isolates belonging to CC133 induced a significantly stronger IL-8 release from bMEC than isolates from the other CCs, and the IL-8 response to CC479 was higher compared to CC151 and CC425. Transcription levels of IL-8, tumor necrosis factor alpha (TNFα), serum amyloid A3 (SAA3), Toll-like receptor (TLR)-2 and nuclear factor κB (NF-κB) in bMEC after bacterial stimulation tended to follow a similar pattern as IL-8 release, but there were no significant differences between the CCs. This study demonstrates a differential activation of bMEC by ruminant-associated CCs of S. aureus, which may have implications for the severity of mastitis during IMI by S. aureus belonging to these lineages.
Geochemical Study of Weathered Coal, a Co-Substrate for Bioremediation of South African Coal Discard Dumps
Authors: van Breugel Yvonne , Cowan Ashton Keith , Tsikos Harilaos
Published: December 2019

Coal mining creates large volumes of waste in the form of discard coal that is stockpiled. In South Africa, rehabilitation of coal discard dumps remains a challenge due to reliance on topsoil for establishment of vegetation. Exploitation of fungal bio liquefaction/degradation of coal resulted in the emergence of Fungcoal as a bioprocess for the rehabilitation of coal discard dumps and opencast spoils. In this process, a suite of fungi is used to bio liquefy/degrade recalcitrant waste coal to form a soil-like material which promotes reinvigoration of the microbial component, grass growth, and re-vegetation. Here, the role of outcrop weathered coal as a mineral/carbon source to ensure biologically induced humic acid-like substance enrichment of discard and spoil to increase efficacy of fungi-plant mutualism and stimulate revegetation without the need for topsoil was investigated. Mineralogical, elemental, and pyrolysis gas chromatography-mass spectroscopic analyses show that outcrop weathered coal has decreased volatile material and increased humics, ash, and mineral bound water in comparison to bituminous coal. These changes occur coincidently with decreased C, N, and H contents, and a substantial increase in O concentration. No apparent stoichiometric relationship between sulphur and iron oxide content of weathered coal could be discerned suggesting little residual pyrite in this material and a dominance of oxy-hydroxides of Fe. Organic analysis showed weathered coal to be enriched in C-16 and C-18 fatty acids and the presence of the indicator, 17α(H),21β(H)-homohopane but not the β,β-stereoisomer, was interpreted to indicate that bacteria may only have been active prior to transformation of hard coal into weathered coal.
Carbon Nanotubes Incorporated Z-Scheme Assembly of AgBr/TiO2 for Photocatalytic Hydrogen Production under Visible Light Irradiations
Authors: Shezad Nasir , Maafa Ibrahim M. , Johari Khairiraihanna , Hafeez Ainy , Akhter Parveen , Shabir Maira , Raza Ali , Anjum Hirra , Hussain Murid , Tahir Muhammad
Published: December 2019

Photocatalytic H2 production is a promising strategy toward green energy and alternative to carbon-based fuels which are the root cause of global warming and pollution. In this study, carbon nanotubes (CNTs) incorporated Z-scheme assembly of AgBr/TiO2 was developed for photocatalytic H2 production under visible light irradiations. Synthesized photocatalysts were characterized through transmission electron microscope (TEM), X-ray photoelectron spectra (XPS), X-ray diffractometer (XRD), Fourier transform infrared (FTIR), photoluminescence spectra (PL), Brunauer Emmet-Teller(BET), and UV-vis spectroscopy analysis techniques. The composite photocatalysts exhibited a H2 production of 477 ppm which was three-folds higher than that produced by TiO2. The good performance was attributed to the strong interaction of three components and the reduced charge recombination, which was 89 and 56.3 times lower than the TiO2 and AgBr/TiO2. Furthermore, the role of surface acidic and basic groups was assessed and the photocatalytic results demonstrated the importance of surface functional groups. In addition, the composites exhibited stability and reusability for five consecutive cycles of reaction. Thus, improved performance of the photocatalyst was credited to the CNTs as an electron mediator, surface functional groups, higher surface area, enhanced charge separation and extended visible light absorption edge. This work provides new development of Z-scheme photocatalysts for sustainable H2 production.
Self-Filtering Monochromatic Infrared Detectors Based on Bi2Se3 (Sb2Te3)/Silicon Heterojunctions
Authors: Pan Xujie , He Jing , Gao Lei , Li Handong
Published: December 2019

This paper focuses on the photoelectric properties of heterostructures formed by surface-modified Si (111) and hexagonal, quintuple-layered selenides (Bi2Se3 and Sb2Te3). It was shown that H-passivated Si (111) can form robust Schottky junctions with either Bi2Se3 or Sb2Te3. When back illuminated (i.e., light incident towards the Si side of the junction), both the Bi2Se3/Si and Sb2Te3/Si junctions exhibited significant photovoltaic response at 1030 nm, which is right within the near-infrared (NIR) light wavelength range. A maximum external quantum efficiency of 14.7% with a detection response time of 2 ms for Bi2Se3/Si junction, and of 15.5% with a 0.8 ms response time for the Sb2Te3/Si junction, were achieved. Therefore, utilizing Si constituents as high-pass filters, the Bi2Se3 (Sb2Te3)/Si heterojunctions can serve as monochromatic NIR photodetectors.