bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I
Authors: Åberg N. David , Gadd Gustaf , Åberg Daniel , Hällgren Peter , Blomstrand Christian , Jood Katarina , Nilsson Michael , Walker Fredrick R. , Svensson Johan , Jern Christina , Isgaard Jörgen
Published: March 2020

Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (ΔIGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1–4, with PA1 representing sedentary and PA2–4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and ΔIGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (ΔIGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, ΔIGF-I increased by 9.7 (95% CI 1,1−18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to ΔIGF-I.
Outer Nuclear Layer Damage for Detection of Early Retinal Toxicity of Hydroxychloroquine
Authors: Casado Alfonso , López-de-Eguileta Alicia , Fonseca Soraya , Muñoz Pedro , Demetrio Rosalía , Gordo-Vega Miguel A. , Cerveró Andrea
Published: March 2020

In hydroxychloroquine (HCQ) retinopathy, early detection of asymptomatic retinal changes and the interruption of the drug are essential to prevent permanent vision loss. Our purpose was to investigate the roles of ganglion cell layer (GCL) and outer nuclear layer (ONL) thicknesses measured by optical coherence tomography (OCT) in the early diagnosis of retinopathy. One hundred and fourteen eyes of 76 individuals with HCQ treatment were enrolled in the study (42 eyes with impaired visual field (VF) and 72 eyes with nondamaged VF). We found that ONL was significantly decreased in the HCQ retinopathy group compared with the control group in the nasal macula (p = 0.032) as well as in four sectors (p < 0.044), whereas no significant differences were found comparing GCL in both groups. If VF were altered superiorly or temporarily, ONL was significantly thinned inferiorly (p = 0.029) and nasally (p = 0.008), respectively. Duration of HCQ treatment was significantly related with ONL in seven sectors of ONL (p < 0.047). We suggest that ONL measured with OCT might be used to assess early HCQ retinal toxicity.
The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review
Authors: Brahm Cyrillo G. , van Linde Myra E. , Enting Roelien H. , Schuur Maaike , Otten René H.J. , Heymans Martijn W. , Verheul Henk M.W. , Walenkamp Annemiek M.E.
Published: March 2020

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.
Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways
Authors: Santos Jerran , Hubert Thibaut , Milthorpe Bruce K
Published: March 2020

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.
Easy and Fast Fabrication of Self-Cleaning and Anti-Icing Perfluoroalkyl Silane Film on Aluminium
Authors: Rodič Peter , Kapun Barbara , Panjan Matjaž , Milošev Ingrid
Published: March 2020

A combination of the chemical etching process in FeCl3 solution and chemical surface grafting by immersion in ethanol solution containing 1H,1H,2H,2H-perfluorodecyltriethoxysilane is a viable route to achieve a hierarchical surface topography and chemical bonding of silane molecules on an aluminium surface leading to (super)hydrophobic characteristics. Characterisation of untreated and treated aluminium surfaces was carried out using contact profilometry, optical tensiometry, scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray photoelectron spectroscopy to define the surface topography, wettability, morphology and surface composition. Additionally, the dynamic characteristics were evaluated to define bouncing and the self-cleaning effect. A thermal infrared camera was employed to evaluate anti-icing properties. The micro/nano-structured etched aluminium surface grafted with perfluoroalkyl silane film showed excellent superhydrophobicity and bounce dynamics in water droplet tests. The superhydrophobic aluminium surface exhibited the efficient self-cleaning ability of solid pollutants as well as improved anti-icing performance with melting delay.
Cu–MoS2 Superhydrophobic Coating by Composite Electrodeposition
Authors: Prado Lucia Helena , Virtanen Sannakaisa
Published: March 2020

In this work, a superhydrophobic coating was developed by composite electrodeposition of MoS2 particles in a copper matrix. AISI 316L stainless steel and N80 carbon steel, with a thin electrodeposited Ni layer to improve adherence of the coating, were used as substrates. Different operational parameters of electrodeposition were studied in order to produce the highest possible contact angle. We demonstrate that, using this method, a coating with a hierarchical structure with feature dimensions in the range of µm to nm is obtained, with advancing contact angle values up to 158.2° and a contact angle hysteresis equal to 1.8°. To study the coating composition energy dispersive X-ray, X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry were performed. Moreover, potentiodynamic polarizations were performed in H2SO4, NaCl and NaOH solutions to study the corrosion behavior of the coating. As a control, a sample coated only with MoS2 particles by means of electrophoretic deposition was produced. The results show that the composite coating can be used in applications where copper is used for corrosion protection, with the addition of the desirable effects of its superhydrophobicity.
Antioxidant, Antimicrobial and Antibiofilm Activity of Coriander (Coriandrum sativum L.) Essential Oil for Its Application in Foods
Authors: Kačániová Miroslava , Galovičová Lucia , Ivanišová Eva , Vukovic Nenad L. , Štefániková Jana , Valková Veronika , Borotová Petra , Žiarovská Jana , Terentjeva Margarita , Felšöciová Soňa , Tvrdá Eva
Published: March 2020

The aim of this study was to assess the chemical composition, antioxidant, antimicrobial and antibiofilm activity of the Coriandrum sativum essential oil. Changes in the biofilm profile of Stenotropomonas maltophilia and Bacillus subtilis were studied using MALDI-TOF MS Biotyper on glass and wooden surfaces. The molecular differences of biofilms in different days were observed as well. The major volatile compounds of the coriander essential oil in the present study were β-linalool 66.07%. Coriander essential oil radical scavenging activity was 51.05% of inhibition. Coriander essential oil expressed the strongest antibacterial activity against B. subtilis followed by S. maltophilia and Penicillium expansum. The strongest antibiofilm activity of the coriander essential oil was found against S. maltophilia. A clearly differentiated branch was obtained for early growth variants of S. maltophilia in case of planktonic cells and all experimental groups and time span can be reported for the grouping pattern of B. subtilis preferentially when comparing to the media matrix, but without clear differences among variants. The results indicate that coriander was effective against the tested Penicillium expansum in the vapor phase after 14 days with MID50 367.19 and MID90 445.92 µL/L of air.
A Real-Time PCR Method for the Authentication of Common Cuttlefish (Sepia officinalis) in Food Products
Authors: Velasco Amaya , Ramilo-Fernández Graciela , Sotelo Carmen G.
Published: March 2020

Cephalopods are very relevant food resources. The common cuttlefish (Sepia officinalis) is highly appreciated by consumers and there is a lack of rapid methods for its authentication in food products. We introduce a new minor groove binding (MGB) TaqMan real-time PCR (Polymerase Chain Reaction) method for the authentication of S. officinalis in food products to amplify a 122 base pairs (bp) fragment of the mitochondrial COI (Cytochrome Oxidase I) region. Reference and commercial samples of S. officinalis showed a threshold cycle (Ct) mean of 14.40, while the rest of the species examined did not amplify, or showed a significantly different Ct (p < 0.001). The calculated efficiency of the system was 101%, and the minimum DNA quantity detected was 10−4 ng. No cross-reactivity was detected with any other species, thus, the designed method differentiates S. officinalis from other species of the genus Sepia and other cephalopod species and works for fresh, frozen, grilled, cooked and canned samples of Sepia spp. The method has proved to be reliable and rapid, and it may prove to be a useful tool for the control of fraud in cuttlefish products.
Effect of Innovative Food Processing Technologies on the Physicochemical and Nutritional Properties and Quality of Non-Dairy Plant-Based Beverages
Authors: Munekata Paulo E. S. , Domínguez Rubén , Budaraju Sravanthi , Roselló-Soto Elena , Barba Francisco J. , Mallikarjunan Kumar , Roohinejad Shahin , Lorenzo José M.
Published: March 2020

Increase in allergenicity towards cow’s milk, lactose intolerance, the prevalence of hypercholesterolemia, and flexitarian choice of food consumption have increased the market for cow’s milk alternatives. Non-dairy plant-based beverages are useful alternatives because of the presence of bioactive components with health-promoting properties, which attract health-conscious consumers. However, the reduced nutritional value and sensory acceptability of the plant-based beverages (such as flavor, taste, and solubility) compared to cow’s milk pose a big threat to its place in the market. Thermal treatments are commonly used to ensure the quality of plant-based beverages during storage. However, the application of high temperatures can promote the degradation of thermolabile compounds and some detrimental reactions, thus reducing protein digestibility and amino acid availability of non-dairy plant-based beverages substitutes. New and advanced food processing technologies, such as high-pressure processing, high-pressure homogenization, pulsed electric fields, and ultrasound, are being researched for addressing the issues related to shelf life increase, emulsion stability, preservation of nutritional content and sensorial acceptability of the final product. However, the literature available on the application of non-thermal processing technologies on the physicochemical and nutritional properties of plant-based beverages is scarce. Concerted research efforts are required in the coming years in the functional plant-based beverages sector to prepare newer, tailor-made products which are palatable as well as nutritionally adequate.
High Contiguity de novo Genome Sequence Assembly of Trifoliate Yam (Dioscorea dumetorum) Using Long Read Sequencing
Authors: Siadjeu Christian , Pucker Boas , Viehöver Prisca , Albach Dirk C. , Weisshaar Bernd
Published: March 2020

Trifoliate yam (Dioscorea dumetorum) is one example of an orphan crop, not traded internationally. Post-harvest hardening of the tubers of this species starts within 24 h after harvesting and renders the tubers inedible. Genomic resources are required for D. dumetorum to improve breeding for non-hardening varieties as well as for other traits. We sequenced the D. dumetorum genome and generated the corresponding annotation. The two haplophases of this highly heterozygous genome were separated to a large extent. The assembly represents 485 Mbp of the genome with an N50 of over 3.2 Mbp. A total of 35,269 protein-encoding gene models as well as 9941 non-coding RNA genes were predicted, and functional annotations were assigned.
First-Hand Experience of Severe Dysphagia Following Brainstem Stroke: Two Qualitative Cases
Authors: Kjaersgaard Annette , Pallesen Hanne
Published: March 2020

Background: Dysphagia has profound effects on individuals, and living with dysphagia is a complex phenomenon that touches essential areas of life. Dysphagia following a brainstem stroke is often more severe and the chances of spontaneous recovery are less likely as compared with dysphagia following a hemispheric stroke. Objective: To explore how two individuals with brainstem stroke experienced severe dysphagia during their inpatient neurorehabilitation and how they experienced their recovery approximately one month following discharge. Methods: An explorative study was conducted to evaluate the first-hand perspective on severe eating difficulties. A qualitative case study was chosen to collect data during two face-to-face semi-structured interviews. Phenomenological perspectives shaped the interview-process and the processing of data. Results: Analysis of the empirical data generated the following main themes regarding experiences of: (i) the mouth and throat; (ii) shared dining; and (iii) recovery and regression related to swallowing-eating-drinking. Conclusion: Participants expressed altered sensations of the mouth and throat, which affected their oral intake and social participation in meals. Good support for managing and adapting their problems of swallowing, eating, and drinking in daily activities is essential. Knowledge and skills of professionals in relation to dysphagia is a significant requirement for recovery progress in settings within the municipality.
Investigating the Qualities of a Recreational Forest: Findings from the Cross-Sectional Hallerwald Case Study
Authors: Cervinka Renate , Schwab Markus , Haluza Daniela
Published: March 2020

Prior research shows that forests contribute to human health and well-being. In this sense, this cross-sectional case study, adopting the principles of citizen science, assessed the restorative potential of places in the Hallerwald, an Austrian community forest. A convenience sample of adult forest visitors (n = 99, 64% females) completed a survey during a guided 2.5 h forest tour. The German questionnaire assessed the qualities of defined places in the forest. We also investigated changes in mood states, perceived stress, restoration, connectedness, and mindfulness before and after visiting the forest. In cooperation with a local working group, we developed the new Widen One’s Mind (WOM) scale, which showed good scale characteristics. All places received high scores in their potential to increase restoration and vitality and to widen one’s mind. Positive affect, restoration, connectedness with nature and the forest, and mindfulness increased pre- versus post-visits, whereas negative affect and perceived stress decreased. The findings of this study suggest that in recreational forests, visitors experience beneficial mental effects such as stress reduction in addition to physical exercise. To facilitate regional development goals, we recommend evaluating places in forests regarding the potential effects on the health and well-being as well as citizen participation before initiating extensive remodeling.
The Respiratory Metabolism of Polistes biglumis, a Paper Wasp from Mountainous Regions
Authors: Kovac Helmut , Käfer Helmut , Stabentheiner Anton
Published: March 2020

European Polistine wasps inhabit mainly temperate and warm climate regions. However, the paper wasp Polistes biglumis represents an exception; it resides in mountainous areas, e.g., in the Alps and in the Apennines. In these habitats, the wasps are exposed to a broad temperature range during their lifetime. We investigated whether they developed adaptations in their metabolism to their special climate conditions by measuring their CO2 production. The standard or resting metabolic rate and the metabolism of active wasps was measured in the temperature range which they are exposed to in their habitat in summer. The standard metabolic rate increased in a typical exponential progression with ambient temperature, like in other wasps. The active metabolism also increased with temperature, but not in a simple exponential course. Some exceptionally high values were presumed to originate from endothermy. The simultaneous measurement of body temperature and metabolic rate revealed a strong correlation between these two parameters. The comparison of the standard metabolic rate of Polistes biglumis with that of Polistes dominula revealed a significantly lower metabolism of the alpine wasps. This energy saving metabolic strategy could be an adaptation to the harsh climate conditions, which restricts foraging flights and energy recruitment.
The Predictability of the Exchange Rate When Combining Machine Learning and Fundamental Models
Authors: Zhang Yuchen , Hamori Shigeyuki
Published: March 2020

In 1983, Meese and Rogoff showed that traditional economic models developed since the 1970s do not perform better than the random walk in predicting out-of-sample exchange rates when using data obtained after the beginning of the floating rate system. Subsequently, whether traditional economical models can ever outperform the random walk in forecasting out-of-sample exchange rates has received scholarly attention. Recently, a combination of fundamental models with machine learning methodologies was found to outcompete the predictability of random walk (Amat et al. 2018). This paper focuses on combining modern machine learning methodologies with traditional economic models and examines whether such combinations can outperform the prediction performance of random walk without drift. More specifically, this paper applies the random forest, support vector machine, and neural network models to four fundamental theories (uncovered interest rate parity, purchase power parity, the monetary model, and the Taylor rule models). We performed a thorough robustness check using six government bonds with different maturities and four price indexes, which demonstrated the superior performance of fundamental models combined with modern machine learning in predicting future exchange rates in comparison with the results of random walk. These results were examined using a root mean squared error (RMSE) and a Diebold–Mariano (DM) test. The main findings are as follows. First, when comparing the performance of fundamental models combined with machine learning with the performance of random walk, the RMSE results show that the fundamental models with machine learning outperform the random walk. In the DM test, the results are mixed as most of the results show significantly different predictive accuracies compared with the random walk. Second, when comparing the performance of fundamental models combined with machine learning, the models using the producer price index (PPI) consistently show good predictability. Meanwhile, the consumer price index (CPI) appears to be comparatively poor in predicting exchange rate, based on its poor results in the RMSE test and the DM test.
Digital k-Contractibility of an n-Times Iterated Connected Sum of Simple Closed k-Surfaces and Almost Fixed Point Property
Authors: Han Sang-Eon
Published: March 2020

The paper firstly establishes the so-called n-times iterated connected sum of a simple closed k-surface in Z 3 , denoted by C k n , k ∈ { 6 , 18 , 26 } . Secondly, for a simple closed 18-surface M S S 18 , we prove that there are only two types of connected sums of it up to 18-isomorphism. Besides, given a simple closed 6-surface M S S 6 , we prove that only one type of M S S 6 ♯ M S S 6 exists up to 6-isomorphism, where ♯ means the digital connected sum operator. Thirdly, we prove the digital k-contractibility of C k n : = M S S k ♯ ⋯ ♯ M S S k ︷ n - times , k ∈ { 18 , 26 } , which leads to the simply k-connectedness of C k n , k ∈ { 18 , 26 } , n ∈ N . Fourthly, we prove that C 6 2 and C k n do not have the almost fixed point property (AFPP, for short), k ∈ { 18 , 26 } . Finally, assume a closed k-surface S k ( ⊂ Z 3 ) which is ( k , k ¯ ) -isomorphic to ( X , k ) in the picture ( Z 3 , k , k ¯ , X ) and the set X is symmetric according to each of x y -, y z -, and x z -planes of R 3 . Then we prove that S k does not have the AFPP. In this paper given a digital image ( X , k ) is assumed to be k-connected and its cardinality | X | ≥ 2 .
3D Mineral Prospectivity Modeling for the Low-Sulfidation Epithermal Gold Deposit: A Case Study of the Axi Gold Deposit, Western Tianshan, NW China
Authors: Mao Xiancheng , Zhang Wei , Liu Zhankun , Ren Jia , Bayless Richard C. , Deng Hao
Published: March 2020

The Axi low-sulfidation (LS) epithermal deposit in northwestern China is the result of geological controls on hydrothermal fluid flow through strike-slip faults. Such controls occur commonly in LS epithermal deposits worldwide, but unfortunately, these have not been quantitatively analyzed to determine their spatial relationships with gold distribution and further guide mineral prospecting. In this study, we conduct a 3D mineral prospectivity modeling approach for the Axi deposit involving 3D geological modeling, 3D spatial analysis, and prospectivity modeling. The spatial analysis of geometric features revealed the gold mineralization trends in convex segments (0–20 m) with a specific distance from fault 2, the lower interface of late volcanic phase, and the upper interface of phyllic alteration with steep slopes (>65°), implying that gold deposition was significantly controlled by the morphological characteristics and distance fields of geologic features. The present alteration–mineralization zone at Axi has a larger width in bending sites (sections No. 35–15 and No. 40–56) than elsewhere, indicating the location of two fluid conduits extending to depth. The prediction-area plots and receiver operating characteristic curves demonstrated that (genetic algorithm optimized support vector regression (GA-SVR)) outperformed multiple nonlinear regression and fuzzy weights-of-evidence, which was proposed as a robust method to solve complicated nonlinear and high-dimensional issues in prospectivity modeling. Our study manifests spatial controls of structure, host rock, and alteration on LS epithermal gold deposition, and highlights the capability of GA-SVR for identifying deposit-scale potential epithermal gold mineralization.
Influence of Pre-Existing Nuclei on the Crystallization Kinetics of Primitive Alkaline Magmas: Insights on the Deep Feeding System of the Campi Flegrei Volcanic District
Authors: Bonechi Barbara
Published: March 2020

Aiming to evaluate the influence of pre-existing nuclei on the clinopyroxene crystallization kinetics, time-series experiments were performed using both natural and vitrified starting materials. Experiments were carried out at pressure of 0.8 GPa, temperatures between 1220 and 1250 °C, and dwell times ranging from 0.16 to 12 h. Clinopyroxene growth rates of the runs performed using the natural starting material containing pre-existing nuclei (~2 × 10−7 to ~6 × 10−8 cm∙s−1) are higher than those of the runs performed using the vitrified one (~3 × 10−7 to ~2 × 10−8 cm∙s−1). In both cases the growth rates decrease with increasing time. Conversely, clinopyroxene nucleation rates are lower in the experiments performed using the natural powder (102 and 10 mm−3∙s−1) compared to those performed with the glassy starting material (105 and 103 mm−3∙s−1). The nucleation rates tend to decrease increasing dwell time in all the series up to ~3 h, after which it remains nearly constant. Finally, the combination of the obtained clinopyroxene growth rates with the crystal size analysis of natural clinopyroxenes, allowed to estimate the magma ascent rate and the recharge rate of the Campi Flegrei Volcanic District deep reservoir.
Encapsulation of Black Seed Oil in Alginate Beads as a pH-Sensitive Carrier for Intestine-Targeted Drug Delivery: In Vitro, In Vivo and Ex Vivo Study
Authors: Azad Abul Kalam , Al-Mahmood Sinan Mohammed Abdullah , Chatterjee Bappaditya , Wan Sulaiman Wan Mohd Azizi , Elsayed Tarek Mohamed , Doolaanea Abd Almonem
Published: March 2020

Black seed oil (BSO) has been used for various therapeutic purposes around the world since ancient eras. It is one of the most prominent oils used in nutraceutical formulations and daily consumption for its significant therapeutic value is common phenomena. The main aim of this study was to develop alginate-BSO beads as a controlled release system designed to control drug release in the gastrointestinal tract (GIT). Electrospray technology facilitates formulation of small and uniform beads with higher diffusion and swelling rates resulting in process performance improvement. The effect of different formulation and process variables was evaluated on the internal and external bead morphology, size, shape, encapsulation efficiency, swelling rate, in vitro drug release, release mechanism, ex vivo mucoadhesive strength and gastrointestinal tract qualitative and quantitative distribution. All the formulated beads showed small sizes of 0.58 ± 0.01 mm (F8) and spherical shape of 0.03 ± 0.00 mm. The coefficient of weight variation (%) ranged from 1.37 (F8) to 3.93 (F5) ng. All formulations (F1–F9) were studied in vitro for release characteristics and swelling behaviour, then the release data were fitted to various equations to determine the exponent (ns), swelling kinetic constant (ks), swelling rate (%/h), correlation coefficient (r2) and release kinetic mechanism. The oil encapsulation efficiency was almost complete at 90.13% ± 0.93% in dried beads. The maximum bead swelling rate showed 982.23 (F8, r2 = 0.996) in pH 6.8 and the drug release exceeded 90% in simulated gastrointestinal fluid (pH 6.8). Moreover, the beads were well distributed throughout various parts of the intestine. This designed formulation could possibly be advantageous in terms of increased bioavailability and targeted drug delivery to the intestine region and thus may find applications in some diseases like irritable bowel syndrome.
Mertansine Inhibits mRNA Expression and Enzyme Activities of Cytochrome P450s and Uridine 5′-Diphospho-Glucuronosyltransferases in Human Hepatocytes and Liver Microsomes
Authors: Choi Won-Gu , Park Ria , Kim Dong Kyun , Shin Yongho , Cho Yong-Yeon , Lee Hye Suk
Published: March 2020

Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody–drug conjugates (ADCs) for cancer therapy. The effects of mertansine on uridine 5′-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes and its effects on the mRNA expression of cytochrome P450s (CYPs) and UGTs in human hepatocytes were evaluated to assess the potential for drug–drug interactions (DDIs). Mertansine potently inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-β-glucuronidation, and UGT1A4-catalyzed trifluoperazine N-β-d-glucuronidation, with Ki values of 13.5 µM, 4.3 µM, and 21.2 µM, respectively, but no inhibition of UGT1A6, UGT1A9, and UGT2B7 enzyme activities was observed in human liver microsomes. A 48 h treatment of mertansine (1.25–2500 nM) in human hepatocytes resulted in the dose-dependent suppression of mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, and UGT1A9, with IC50 values of 93.7 ± 109.1, 36.8 ± 18.3, 160.6 ± 167.4, 32.1 ± 14.9, 578.4 ± 452.0, 539.5 ± 233.4, 856.7 ± 781.9, and 54.1 ± 29.1 nM, respectively, and decreased the activities of CYP1A2-mediated phenacetin O-deethylase, CYP2B6-mediated bupropion hydroxylase, and CYP3A4-mediated midazolam 1′-hydroxylase. These in vitro DDI potentials of mertansine with CYP1A2, CYP2B6, CYP2C8/9/19, CYP3A4, UGT1A1, and UGT1A9 substrates suggest that it is necessary to carefully characterize the DDI potentials of ADC candidates with mertansine as a payload in the clinic.
Safety and Efficacy of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Renal Impairment
Authors: Jang Soo Min , Bahjri Khaled , Tran Huyentran
Published: March 2020

Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to warfarin. However, safety and efficacy data of DOACs in patients with chronic kidney disease (CKD) are limited. This is a retrospective study to evaluate thromboembolic and bleeding events in patients with AF (with/without CKD) in October 2010 and July 2017. A total of 495 patients were included and only 150 patients had CKD. Our study found that patients with renal impairment on a DOAC do not have a higher incidence of bleeding events. It showed significant increase in thromboembolic events in CKD patients with dabigatran compared to CKD patients with apixaban with odds ratio of 6.58 (95%CI 1.35–32.02, p = 0.02).
Bio-Based Epoxy Shape-Memory Thermosets from Triglycidyl Phloroglucinol
Authors: Santiago David , Guzmán Dailyn , Ferrando Francesc , Serra Àngels , De la Flor Silvia
Published: March 2020

A series of bio-based epoxy shape-memory thermosetting polymers were synthesized starting from a triglycidyl phloroglucinol (3EPOPh) and trimethylolpropane triglycidyl ether (TPTE) as epoxy monomers and a polyetheramine (JEF) as crosslinking agent. The evolution of the curing process was studied by differential scanning calorimetry (DSC) and the materials obtained were characterized by means of DSC, thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), stress-strain tests, and microindentation. Shape-memory properties were evaluated under free and totally constrained conditions. All results were compared with an industrial epoxy thermoset prepared from standard diglycidyl ether of Bisphenol A (DGEBA). Results revealed that materials prepared from 3EPOPh were more reactive and showed a tighter network with higher crosslinking density and glass transition temperatures than the prepared from DGEBA. The partial substitution of 3EPOPh by TPTE as epoxy comonomer caused an increase in the molecular mobility of the materials but without worsening the thermal stability. The shape-memory polymers (SMPs) prepared from 3EPOPh showed good mechanical properties as well as an excellent shape-memory performance. They showed almost complete shape-recovery and shape-fixation, fast shape-recovery rates, and recovery stress up to 7 MPa. The results obtained in this study allow us to conclude that the triglycidyl phloroglucinol derivative of eugenol is a safe and environmentally friendly alternative to DGEBA for preparing thermosetting shape-memory polymers.
Direct Conjugation of Streptavidin to Encoded Hydrogel Microparticles for Multiplex Biomolecule Detection with Rapid Probe-Set Modification
Authors: Roh Yoon Ho , Kim Ju Yeon , Mun Seok Joon , Lee Hye Sun , Hwang Changhyun , Park Kyong Hwa , Bong Ki Wan
Published: March 2020

Encoded hydrogel microparticles synthesized via flow lithography have drawn attention for multiplex biomarker detection due to their high multiplex capability and solution-like hybridization kinetics. However, the current methods for preparing particles cannot achieve a flexible, rapid probe-set modification, which is necessary for the production of various combinations of target panels in clinical diagnosis. In order to accomplish the unmet needs, streptavidin was incorporated into the encoded hydrogel microparticles to take advantage of the rapid streptavidin–biotin interactions that can be used in probe-set modification. However, the existing methods suffer from low efficiency of streptavidin conjugation, cause undesirable deformation of particles, and impair the assay capability. Here, we present a simple and powerful method to conjugate streptavidin to the encoded hydrogel microparticles for better assay performance and rapid probe-set modification. Streptavidin was directly conjugated to the encoded hydrogel microparticles using the aza-Michael addition click reaction, which can proceed in mild, aqueous condition without catalysts. A highly flexible and sensitive assay was developed to quantify DNA and proteins using streptavidin-conjugated encoded hydrogel microparticles. We also validated the potential applications of our particles conducting multiplex detection of cancer-related miRNAs.
Thermosensitive Hydrogel for Encapsulation and Controlled Release of Biocontrol Agents to Prevent Peanut Aflatoxin Contamination
Authors: Feng Jiachang , Dou Jianpeng , Zhang Youzhen , Wu Zidan , Yin Dongxue , Wu Wenfu
Published: March 2020

Starch, alginate, and poly(N-isopropylacrylamide) (PNIPAAm) were combined to prepare a semi-interpenetrating network (IPN) hydrogel with temperature sensitivity. Calcium chloride was used as cross-linking agent, the non-toxigenic Aspergillus flavus spores were successfully encapsulated as biocontrol agents by the method of ionic gelation. Characterization of the hydrogel was performed by Fourier-transform infrared spectroscopy (FTIR), scanning electron micrograph (SEM), and thermogravimetry analysis (TGA). Formulation characteristics, such as entrapment efficiency, beads size, swelling behavior, and rheological properties were evaluated. The optical and rheological measurements indicated that the lower critical solution temperature (LCST) of the samples was about 29–30 °C. TGA results demonstrated that the addition of kaolin could improve the thermal stability of the semi-IPN hydrogel. Morphological analysis showed a porous honeycomb structure on the surface of the beads. According to the release properties of the beads, the semi-IPN hydrogel beads containing kaolin not only have the effect of slow release before peanut flowering, but they also can rapidly release biocontrol agents after flowering begins. The early flowering stage of the peanut is the critical moment to apply biocontrol agents. Temperature-sensitive hydrogel beads containing kaolin could be considered as carriers of biocontrol agents for the control of aflatoxin in peanuts.
Development and Characterization of Hemicellulose-Based Films for Antibacterial Wound-Dressing Application
Authors: Ahmad Naveed , Tayyeb Danial , Ali Imran , K. Alruwaili Nabil , Ahmad Waqas , ur Rehman Atta , Khan Abdul Haleem , Iqbal Mohammad Saeed
Published: March 2020

Hemicelluloses are biopolymers with versatile properties for biomedical applications. Herein, hemicellulose (arabinoxylan)-based antibacterial film dressings were prepared and characterized. Arabinoxylan was isolated from psyllium husk. Blank and gentamicin-loaded films were prepared by the solvent cast method using glycerol as the plasticizer. The appropriate composition of the films was obtained by varying the amounts of arabinoxylan, glycerol, and gentamicin. The films were found to be transparent, smooth, bubble-free, flexible, and easily peelable with 2% to 3% arabinoxylan. They had uniform thickness and swelled up to 60% of their initial size. The mechanical properties and water vapor transmission rate through the films were found to be suitable for wound-dressing application. Fourier transform infrared spectroscopy (FTIR) analysis confirmed drug–film compatibility. In an in vitro release study, more than 85% of the gentamicin was released from the films in 12 h. The antibacterial activities of the gentamicin-loaded films were found to be close to the standard gentamicin solution. The films were found to be cytocompatible in cell viability assay. These results suggested that hemicellulose-based films are promising materials for the dressing of infected wounds.
Novel AIEgen-Functionalized Diselenide-Crosslinked Polymer Gels as Fluorescent Probes and Drug Release Carriers
Authors: Zhao Jie , Pan Xiangqiang , Zhu Jian , Zhu Xiulin
Published: March 2020

Stimuli-responsive functional gels have shown significant potential for application in biosensing and drug release systems. In this study, aggregation-induced emission luminogen (AIEgen)-functionalized, diselenide-crosslinked polymer gels were synthesized via free radical copolymerization. A series of polymer gels with different crosslink densities or tetraphenylethylene (TPE) contents were synthesized. The diselenide crosslinker in the gels could be fragmented in the presence of H2O2 or dithiothreitol (DTT) due to its redox-responsive property. Thus, the TPE-containing polymer chains were released into the aqueous solution. As a result, the aqueous solution exhibited enhanced fluorescence emission due to the strong hydrophobicity of TPE. The degradation of polymer gels and fluorescence enhancement in an aqueous solution under different H2O2 or DTT concentrations were studied. Furthermore, the polymer gels could be used as drug carriers, suggesting a visual drug release process under the action of external redox agents. The AIEgen-functionalized, diselenide-crosslinked polymer gels hold great potential in the biomedical area for biosensing and controlled drug delivery.
Experimental and Numerical Assessment of Fibre Bridging Toughening Effects on the Compressive Behaviour of Delaminated Composite Plates
Authors: Riccio Aniello , Russo Angela , Sellitto Andrea , Toscano Cinzia , Alfano Davide , Zarrelli Mauro
Published: March 2020

Increasing the Mode I inter-laminar fracture toughness of composite laminates can contribute to slowing down delamination growth phenomena, which can be considered one of the most critical damage mechanisms in composite structures. Actually, the Mode I interlaminar fracture toughness (GIc) in fibre-reinforced composite materials has been found to considerably increase with the crack length when the fibre bridging phenomenon takes place. Hence, in this paper, the fibre bridging phenomenon has been considered as a natural toughening mechanism able to replace embedded metallic or composite reinforcements, currently used to increase tolerance to inter-laminar damage. An experimental/numerical study on the influence of delamination growth on the compressive behaviour of fibre-reinforced composites characterised by high sensitivity to the fibre bridging phenomenon has been performed. Coupons, made of material systems characterised by a variable toughness related to a high sensitivity to the fibre bridging phenomenon and containing artificial through-the-width delaminations, were subjected to a compressive mechanical test and compared to coupons made of standard material system with constant toughness. Out-of-plane displacements and strains were monitored during the compression test by means of strain gauges and digital image correlation to assess the influence of fibre bridging on delamination buckling, delamination growth and on the global buckling of the specimens, including buckling shape changes. Experimental data were combined with a numerical study, performed by means of a virtual crack closure technique based procedure, named SMart Time XB – Fibre Bridging (SMXB-FB), able to mimic the crack bridging effect on the toughness properties of the material system. The combination of numerical results and experimental data has allowed the deformations and the buckling shape changes to be correlated to the onset and evolution of damage and, hence, contributes to improving the knowledge on the interaction of the failure mechanisms in the investigated composite specimens.
Enhanced Electrical Conductivity and Seebeck Coefficient in PEDOT:PSS via a Two-Step Ionic liquid and NaBH4 Treatment for Organic Thermoelectrics
Authors: Atoyo Jonathan , Burton Matthew R. , McGettrick James , Carnie Matthew J.
Published: March 2020

A two-step approach of improving the thermoelectric properties of Poly(3,4-ethylenedioxythiophene)poly(4-styrenesulfonate) (PEDOT:PSS) via the addition of the ionic liquid, 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM:TFSI) and subsequent reduction with NaBH4 is presented. The addition of 2.5 v/v% of EMIM:TFSI to PEDOT:PSS increases the electrical conductivity from 3 S·cm−1 to 1439 S·cm−1 at 40 °C. An additional post treatment using the reducing agent, NaBH4, increases the Seebeck coefficient of the film from 11 µV·K−1 to 30 µV·K−1 at 40 °C. The combined treatment gives an overall improvement in power factor increase from 0.04 µW·m−1·K−2 to 33 µW·m−1·K−2 below 140 °C. Raman and XPS measurements show that the increase in PEDOT:PSS conductivity is due to PSS separation from PEDOT and a conformational change of the PEDOT chains from the benzoid to quinoid molecular orientation. The improved Seebeck coefficient is due to a reduction of charge carriers which is evidenced from the UV–VIS depicting the emergence of polarons.
Malus baccata var. gracilis and Malus toringoides Bark Polyphenol Studies and Antioxidant, Antimicrobial and Anticancer Activities
Authors: Elansary Hosam O. , Szopa Agnieszka , Kubica Paweł , O. El-Ansary Diaa , Ekiert Halina , A. Al-Mana Fahed
Published: March 2020

Exploring new sources of polyphenols with biological activities that work against human diseases is the target of natural product studies. This study determined the polyphenol composition of the bark of Malus species M. baccata var. gracilis (Rehder) T.C.Ku and M. toringoides (Rehder) Hughes, using high-performance liquid chromatography with a diode-array detector (HPLC-DAD) analysis. The antiproliferative, cytotoxic, antioxidant and antimicrobial applications of these extracts, as well as the identified phenol, were studied. The HPLC-DAD analysis confirmed three polyphenols in the extracts out of the 21 screened compounds: protocatechuic acid, gallic acid, and catechin. The major constituents in M. baccata and M. toringoides were protocatechuic acid, at 3.16 and 7.15 mg 100 g−1 dry weight (DW), respectively, and catechin, at 5.55 and 6.80 mg 100 g−1 DW, respectively. M. baccata and M. toringoides bark extracts showed antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), β-carotene bleaching, and ferric-reducing antioxidant power (FRAP) assays, which were attributed to the dominance of protocatechuic acid. The highest antiproliferative and cytotoxic effects were against Jurkat cells. Against MCF-7 and Hela cells, there was necrotic cell accumulation in the early apoptotic as well as the late apoptotic phase. The bark extracts showed noticeable antibacterial effects against Listeria monocytogenes, Bacillus cereus, and Escherichia coli. Protocatechuic acid showed comparable results to bark extracts. There were antifungal effects against Aspergillus ochraceus, A. niger, and Candida albicans, and the activities were higher than the commercial reagent. M. baccata and M. toringoides could be considered as a new source of phenolic acids, including protocatechuic acid with anticancer, antibacterial antifungal, and antioxidant-promising effects.
Maleated Natural Rubber/Halloysite Nanotubes Composites
Authors: Hayeemasae Nabil , Sensem Zareedan , Sahakaro Kannika , Ismail Hanafi
Published: March 2020

In this study, maleic anhydride (MA) grafted natural rubber (NR), known as maleated natural rubber (MNR), was melt-prepared with the MA content varied within 1–8 phr. MNR was used as the main matrix, with Halloysite Nanotubes (HNT) as a filler, in order to obtain composites with improved performance. The compounds were investigated for their filler–filler interactions by considering their Payne effect. On increasing the MA content, scorch and cure times increased along with maximum torque and torque difference. The MNR with 4 phr of MA exhibited the least filler–filler interactions, as indicated by the retention of the storage modulus after applying a large strain to the filled compound. This MNR compound also provided the highest tensile strength among the cases tested. It is interesting to highlight that MNR, with an appropriate MA content, reduces filler–filler interactions, and, thereby, enhances the HNT filler dispersion, as verified by SEM images, leading to improved mechanical and dynamical properties.