bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilayer Reflective Coatings for BEUV Lithography: A Review
Authors: Uzoma Paul C. , Shabbir Salman , Hu Huan , Okonkwo Paul C. , Penkov Oleksiy V.
Published: October 2021

The development of microelectronics is always driven by reducing transistor size and increasing integration, from the initial micron-scale to the current few nanometers. The photolithography technique for manufacturing the transistor needs to reduce the wavelength of the optical wave, from ultraviolet to the extreme ultraviolet radiation. One approach toward decreasing the working wavelength is using lithography based on beyond extreme ultraviolet radiation (BEUV) with a wavelength around 7 nm. The BEUV lithography relies on advanced reflective optics such as periodic multilayer film X-ray mirrors (PMMs). PMMs are artificial Bragg crystals having alternate layers of “light” and “heavy” materials. The periodicity of such a structure is relatively half of the working wavelength. Because a BEUV lithographical system contains at least 10 mirrors, the optics’ reflectivity becomes a crucial point. The increasing of a single mirror’s reflectivity by 10% will increase the system’s overall throughput six-fold. In this work, the properties and development status of PMMs, particularly for BEUV lithography, were reviewed to gain a better understanding of their advantages and limitations. Emphasis was given to materials, design concepts, structure, deposition method, and optical characteristics of these coatings.
On the Role of Matrix-Weights Elements in Consensus Algorithms for Multi-Agent Systems
Authors: Ogbebor Joshua , Meng Xiangyu
Published: October 2021

This paper examines the roles of the matrix weight elements in matrix-weighted consensus. The consensus algorithms dictate that all agents reach consensus when the weighted graph is connected. However, it is not always the case for matrix weighted graphs. The conditions leading to different types of consensus have been extensively analysed based on the properties of matrix-weighted Laplacians and graph theoretic methods. However, in practice, there is concern on how to pick matrix-weights to achieve some desired consensus, or how the change of elements in matrix weights affects the consensus algorithm. By selecting the elements in the matrix weights, different clusters may be possible. In this paper, we map the roles of the elements of the matrix weights in the systems consensus algorithm. We explore the choice of matrix weights to achieve different types of consensus and clustering. Our results are demonstrated on a network of three agents where each agent has three states.
Hydrocephalus and Cerebrospinal Fluid Analysis Following Severe Traumatic Brain Injury: Evaluation of a Prospective Cohort
Authors: Deng Hansen , Goldschmidt Ezequiel , Nwachuku Enyinna , Yue John K. , Angriman Federico , Wei Zhishuo , Agarwal Nitin , Puccio Ava M. , Okonkwo David O.
Published: October 2021

The development of hydrocephalus after severe traumatic brain injury (TBI) is an under-recognized healthcare phenomenon and can increase morbidity. The current study aims to characterize post-traumatic hydrocephalus (PTH) in a large cohort. Patients were prospectively enrolled age 16–80 years old with Glasgow Coma Scale (GCS) score ≤8. Demographics, GCS, Injury Severity Score (ISS), surgery, and cerebrospinal fluid (CSF) were analyzed. Outcomes were shunt failure and Glasgow Outcome Scale (GOS) at 6 and 12-months. Statistical significance was assessed at p < 0.05. In 402 patients, mean age was 38.0 ± 16.7 years and 315 (78.4%) were male. Forty (10.0%) patients developed PTH, with predominant injuries being subdural hemorrhage (36.4%) and diffuse axonal injury (36.4%). Decompressive hemicraniectomy (DHC) was associated with hydrocephalus (OR 3.62, 95% CI (1.62–8.07), p < 0.01). Eighteen (4.5%) patients had shunt failure and proximal obstruction was most common. Differences in baseline CSF cell count were associated with increased shunt failure. PTH was not associated with worse outcomes at 6 (p = 0.55) or 12 (p = 0.47) months. Hydrocephalus is a frequent sequela in 10.0% of patients, particularly after DHC. Shunt placement and revision procedures are common after severe TBI, within the first 4 months of injury and necessitates early recognition by the clinician.
Reduced Rank Regression-Derived Dietary Patterns Related to the Fatty Liver Index and Associations with Type 2 Diabetes Mellitus among Ghanaian Populations under Transition: The RODAM Study
Authors: Osei Tracy Bonsu , van Dijk Anne-Marieke , Dingerink Sjoerd , Chilunga Felix Patience , Beune Erik , Meeks Karlijn Anna Catharina , Bahendeka Silver , Schulze Matthias Bernd , Agyemang Charles , Nicolaou Mary , Holleboom Adriaan Georgius , Danquah Ina
Published: October 2021

The Fatty Liver Index (FLI) is a proxy for the steatotic component of non-alcoholic fatty liver disease (NAFLD). For sub-Saharan African populations, the contribution of dietary factors to the development of NAFLD in the etiology of type 2 diabetes mellitus (T2DM) remains to be clarified. We identified sex-specific dietary patterns (DPs) related to the FLI using reduced ranked regression (RRR) and evaluated the associations of these DPs with T2DM. This analysis used data from the RODAM, a multi-center cross-sectional study of Ghanaian populations living in Ghana and Europe. The daily intake frequencies of 30 food groups served as the predictor variables, while the FLI was the response variable. The odds ratios and 95% confidence intervals for T2DM were calculated per one standard deviation increase in the DP score using logistic regression. In males, the DP score explained 9.9% of the variation in their food intake and 16.0% of the variation in the FLI. This DP was characterized by high intakes of poultry, whole-grain cereals, coffee and tea, condiments, and potatoes, and the chance of T2DM was 45% higher per 1 DP score-SD (Model 2). Our results indicate that the intake of modernized foods was associated with proxies of NAFLD, possibly underlying the metabolic pathways to developing T2DM.
Effect of COVID-19 Pandemic-Induced Dietary and Lifestyle Changes and Their Associations with Perceived Health Status and Self-Reported Body Weight Changes in India: A Cross-Sectional Survey
Authors: Madan Jagmeet , Blonquist Traci , Rao Eram , Marwaha Ankita , Mehra Joshya , Bharti Richa , Sharma Nishi , Samaddar Ritika , Pandey Sandhya , Mah Eunice , Shete Varsha , Chu YiFang , Chen Oliver
Published: October 2021

Home confinement during the COVID-19 pandemic is accompanied by dramatic changes in lifestyle and dietary behaviors that can significantly influence health. We conducted an online cross-sectional survey to assess COVID-19 pandemic-induced dietary and lifestyle changes and their association with perceived health status and self-reported body weight changes among 1000 Indian adults in early 2021. Positive improvements in dietary habits, e.g., eating more nutritious (85% of participants) and home-cooked food (89%) and an increase in overall nutrition intake (79%), were observed. Sixty-five percent of participants self-reported increased oat consumption to support immunity. There were some negative changes, e.g., more binge eating (69%), eating more in between meals (67%), and increasing meal portion size (72%). Two-thirds of participants reported no change in lifestyles, whereas 21 and 23% reported an increase, and 13 and 10% reported a decrease in physical activity and sleep, respectively. Overall, 64 and 65% of participants reported an improvement in perceived health and an increase in body weight during the COVID-19 period compared to pre-COVID-19, respectively. The top motivations for improving dietary habits included improving physical and mental health and building immunity. In conclusion, the overall perceived health was improved and there was an increase in self-reported body weight in most participants during COVID-19. Diet emerged as the most crucial determinant for these changes.
A High-Sodium Diet Modulates the Immune Response of Food Allergy in a Murine Model
Authors: Liu Zheying , Li Shih-Kuan , Huang Chih-Kang , Huang Ching-Feng
Published: October 2021

Mounting evidence demonstrates that a high-salt diet (HSD) not only affects hemodynamic changes but also disrupts immune homeostasis. The T helper 17 (Th17) and regulatory T cells (Tregs) are susceptible to hypersalinity. However, research on the influence of sodium on Th2-mediated food allergies remains scarce. We aimed to investigate the effect of dietary sodium on the immune response to food allergies. Mice maintained on an HSD (4% NaCl), low-salt diet (LSD; 0.4% NaCl), or control diet (CTRL; 1.0% NaCl) were orally sensitized with ovalbumin (OVA) and a cholera toxin (CT) adjuvant, and then subjected to an intragastric OVA challenge. OVA-specific immunoglobulin G (IgG), IgG1, IgG2a, and IgE antibodies were significantly higher in the HSD group than in the CTRL group (p < 0.001, p < 0.05, p < 0.01, and p < 0.05, respectively). Mice on HSD had significantly higher interleukin (IL)-4 levels than the CTRL group (p < 0.01). The IL-10 levels were significantly lower in the HSD group than in the CTRL group (p < 0.05). The serum levels of interferon-γ (IFN-γ), sodium, and chloride did not differ among the three groups. This study indicates that excessive salt intake promotes Th2 responses in a mouse model of food allergy.
Insulin-Induced Cardiomyocytes Hypertrophy That Is Prevented by Taurine via β-alanine-Sensitive Na+-Taurine Symporter
Authors: Jazzar Ashley , Jacques Danielle , Bkaily Ghassan
Published: October 2021

Although insulin-induced cardiac hypertrophy is reported, very little information is available on the hypertrophic effect of insulin on ventricular cardiomyocytes and the regulation of sodium and calcium homeostasis. Taurine is a non-essential amino acid synthesized by cardiomyocytes and the brain and is present in low quantities in many foods, particularly seafood. The purpose of this study was to investigate whether chronic exposure to insulin induces hypertrophy of ventricular cardiomyocytes that are associated with changes in Na+ and Ca2+ homeostasis and whether taurine pre-treatment prevents these effects. Our results showed that chronic treatment with insulin leads to cardiomyocyte hypertrophy that is associated with an increase in basal intracellular Na+ and Ca2+ levels. Furthermore, long-term taurine treatment prevents morphological and ionic remodeling induced by insulin. In addition, blocking the Na+-taurine co-transporter prevented the taurine antihypertrophic effect. Finally, the insulin-induced remodeling of cardiomyocytes was associated with a decrease in the ratio of phospho-CREB (pCREB) to total cAMP response element binding protein (CREB); taurine prevented this effect. In conclusion, our results show that insulin induces ventricular cardiomyocyte hypertrophy via downregulation of the pCREB/tCREB level and that chronic taurine treatment prevents this effect.
Utility of Geriatric Nutritional Risk Index in Patients with Chronic Kidney Disease: A Mini-Review
Authors: Nakagawa Naoki , Maruyama Keisuke , Hasebe Naoyuki
Published: October 2021

Chronic kidney disease (CKD) is one of the most significant risk factors for cardiovasculardisese. Malnutrition has been recognized as a significant risk factor for cardiovascular disease in patients with CKD, including those on chronic dialysis. Current studies showed higher all-cause and cardiovascular mortality rates in patients with CKD and malnutrition. Geriatric nutritional risk index (GNRI), a simple and validated nutritional screening measure for both elderly people and patients on dialysis, is based only on three objective parameters: body weight, height, and serum albumin level. Recently, we demonstrated that the cutoff GNRI for predicting all-cause and cardiovascular mortality was 96 in patients on hemodialysis. Moreover, together with left ventricular hypertrophy and low estimated glomerular filtration rate, the utility of GNRI as a significant determinant of cardiovascular events was demonstrated in non-dialysis-dependent patients with CKD. In the present review, we summarize available evidence regarding the relationship of GNRI with all-cause and cardiovascular mortality in patients with CKD including those on dialysis.
Evaluation of 5-Aminolevulenic Acid Plus Ferrous Ion for Its Potential to Improve Symptoms of Bovine Babesiosis
Authors: Elata Afraa , Suganuma Keisuke , Mossaad Ehab , Zafar Iqra , Galon Eloiza May , Yoshimoto Keiichiro , Tanaka Tohru , Xuenan Xuan , Kawazu Shin-Ichiro
Published: October 2021

5-aminolevulenic acid (ALA), an endogenous, non-proteinogenic, naturally occurring amino acid found in diverse organisms, is a precursor of heme biosynthesis. For apicomplexan protozoan parasites, an ALA and sodium ferrous citrate (SFC) combination was previously evaluated and suggested as a potential drug candidate for Plasmodium falciparum malaria. This study aimed to evaluate the potential of this combination against bovine babesiosis. ALA administration at 100 and 500 µM coupled with 10 µM SFC in culture medium significantly inhibited intraerythrocytic development and growth of Babesia bovis, which causes cerebral babesiosis in cattle, under in vitro culture. However, administration of 10 µM SFC only in the medium did not inhibit parasite growth. ALA/SFC was efficacious in treating babesiosis in an experimental animal model with B. microti, which causes debilitating babesiosis in mice. Female BALB/c mice were infected with B. microti and administered a single oral dose of ALA/SFC combination daily in different concentrations for 30 days. Treatment with ALA/SFC at 4/0.4 mg/kg body weight significantly suppressed parasite development in the mice blood circulation and resulted in significantly lower parasitemia. Moreover, body weight loss in the mice has been improved significantly compared with the control group at the peak of parasitemia. Treated mice showed moderate decreases in red blood cell count, hemoglobin value, and hematocrit compared with those observed in the control group, indicating an effect in moderating progressive anemia. These findings suggested the potential of ALA/SFC to achieve symptomatic improvement against bovine babesiosis.
Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools
Authors: Nasrolahi Shirazi Amir , Sajid Muhammad Imran , Mandal Dindyal , Stickley David , Nagasawa Stephanie , Long Joshua , Lohan Sandeep , Parang Keykavous , Tiwari Rakesh Kumar
Published: October 2021

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)5C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)5C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl3. Herein, we report [(WR)5C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated that the cellular uptakes of Alexa-488-labeled siRNA were found to be enhanced by more than 10 folds in the presence of [(WR)5C]-GdNPs compared with siRNA alone in CCRF-CEM and MDA-MB-231 cells after 6 h of incubation at 37 °C. The gene silencing efficacy of the nanoparticles was determined via the western blot technique using an over-expressed gene, STAT-3 protein, in MDA-MB-231 cells. The results showed ~62% reduction of STAT-3 was observed in MDA-MB-231 with [(WR)5C]-GdNPs at N/P 40. The integrity of the cellular membrane of CCRF-CEM cells was found to be intact when incubated with [(WR)5C]-Gd nanoparticles (50 µM) for 2 h. Confocal microscopy reveals higher internalization of siRNA in MDA-MB-231 cells using [(WR)5C]-GdNPs at N/P 40. These results provided insight about the use of the [(WR)5C]-GdNPs complex as a potent intracellular siRNA transporter that could be a nontoxic choice to be used as a transfection agent for nucleic-acid-based therapeutics.
Green Metallic Nanoparticles for Cancer Therapy: Evaluation Models and Cancer Applications
Authors: Tinajero-Díaz Ernesto , Salado-Leza Daniela , Gonzalez Carmen , Martínez Velázquez Moisés , López Zaira , Bravo-Madrigal Jorge , Knauth Peter , Flores-Hernández Flor Y. , Herrera-Rodríguez Sara Elisa , Navarro Rosa E. , Cabrera-Wrooman Alejandro , Krötzsch Edgar , Carvajal Zaira Y. García , Hernández-Gutiérrez Rodolfo
Published: October 2021

Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.
Exploring Acceptability Drivers of Oral Antibiotics in Children: Findings from an International Observational Study
Authors: Vallet Thibault , Bensouda Yahya , Saito Jumpei , Mathiesen Liv , Pokharkar Varsha , Klingmann Viviane , Peak Matthew , Elhamdaoui Omar , Yamatani Akimasa , Ivanovic Ivana , Sajith Manjusha , Münch Juliane , Bracken Louise , Duncan Jennifer Claire , Salunke Smita , Wang Siri , Ruiz Fabrice
Published: October 2021

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population.
Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System
Authors: Han Jiawei , Li Luyuan , Su Meiling , Heng Weili , Wei Yuanfeng , Gao Yuan , Qian Shuai
Published: October 2021

Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the Tg of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.
Gold-Decorated Platinum and Palladium Nanoparticles as Modern Nanocomplexes to Improve the Effectiveness of Simulated Anticancer Proton Therapy
Authors: Klebowski Bartosz , Stec Malgorzata , Depciuch Joanna , Gałuszka Adrianna , Pajor-Swierzy Anna , Baran Jarek , Parlinska-Wojtan Magdalena
Published: October 2021

Noble metal nanoparticles, such as gold (Au NPs), platinum (Pt NPs), or palladium (Pd NPs), due to their highly developed surface, stability, and radiosensitizing properties, can be applied to support proton therapy (PT) of cancer. In this paper, we investigated the potential of bimetallic, c.a. 30 nm PtAu and PdAu nanocomplexes, synthesized by the green chemistry method and not used previously as radiosensitizers, to enhance the effect of colorectal cancer PT in vitro. The obtained nanomaterials were characterized by scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), UV-Vis spectroscopy, and zeta potential measurements. The effect of PtAu and PdAu NPs in PT was investigated on colon cancer cell lines (SW480, SW620, and HCT116), as well as normal colon epithelium cell line (FHC). These cells were cultured with both types of NPs and then irradiated by proton beam with a total dose of 15 Gy. The results of the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) test showed that the NPs-assisted PT resulted in a better anticancer effect than PT used alone; however, there was no significant difference in the radiosensitizing properties between tested nanocomplexes. The MTS results were further verified by defining the cell death as apoptosis (Annexin V binding assay). Furthermore, the data showed that such a treatment was more selective for cancer cells, as normal cell viability was only slightly affected.
Cellular Toxicity Mechanisms and the Role of Autophagy in Pt(IV) Prodrug-Loaded Ultrasmall Iron Oxide Nanoparticles Used for Enhanced Drug Delivery
Authors: Gutiérrez-Romero L. , Rivas-García L. , Sánchez-González C. , Llopis J. , Blanco E. , Montes-Bayón M.
Published: October 2021

Ultrasmall iron oxide nanoparticles (<10 nm) were loaded with cis-diamminetetrachloroplatinum (IV), a cisplatin (II) prodrug, and used as an efficient nanodelivery system in cell models. To gain further insight into their behavior in ovarian cancer cells, the level of cellular incorporation as well as the platination of mitochondrial and nuclear DNA were measured using inductively coupled plasma mass spectrometry (ICP-MS) strategies. Quantitative Pt results revealed that after 24 h exposure to 20 µM Pt in the form of the Pt(IV)-loaded nanoparticles, approximately 10% of the incorporated Pt was associated with nuclear DNA. This concentration increased up to 60% when cells were left to stand in drug-free media for 3 h. These results indicated that the intracellular reducing conditions permitted the slow release of cisplatin (II) from the cisplatin (IV)-loaded nanoparticles. Similar results were obtained for the platination of mitochondrial DNA, which reached levels up to 17,400 ± 75 ng Pt/ mg DNA when cells were left in drug-free media for 3 h, proving that this organelle was also a target for the action of the released cisplatin (II). The time-dependent formation of Pt-DNA adducts could be correlated with the time-dependent decrease in cell viability. Such a decrease in cell viability was correlated with the induction of apoptosis as the main route of cell death. The formation of autophagosomes, although observed upon exposure in treated cells, does not seem to have played an important role as a means for cells to overcome nanoparticles’ toxicity. Thus, the designed nanosystem demonstrated high cellular penetration and the “in situ” production of the intracellularly active cisplatin (II), which is able to induce cell death, in a sustained manner.
On the Biocompatibility and Teat Retention of In Situ Gelling Intramammary Formulations: Cattle Mastitis Prevention and Treatment
Authors: Bhattarai Sushila , Perumal Dhayaneethie , Rathbone Michael J. , Bunt Craig R. , Alany Raid G.
Published: October 2021

Treatment and prevention of cattle mastitis remains a formidable challenge due to the anatomical and physiological constraints of the cow udder. In this study, we investigated polymeric excipients and solvents that can form, (when combined) novel, non-toxic and biocompatible in situ gelling formulations in the mammary gland of bovine cattle. We also report on a new approach to screen intramammary formulations using fresh excised cow teats. Fourteen hydrophilic polymers and six solvents were evaluated for in vitro cytotoxicity and biocompatibility towards cultured bovine mammary epithelial cells (MAC-T), microscopic and macroscopic examination upon contact with excised cow teats. No significant cytotoxicity (p > 0.05) was observed with polyethylene oxides, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium alginate and xanthan gum. Polycarbophil and carbopol polymers showed significantly higher cytotoxicity (p < 0.05). Concentration-dependent cytotoxicity was observed for glycerin, propylene glycol, polyethylene glycol 400, ethanol, N-methyl-2-pyrrolidone and 2-pyrrolidone, with the 2-pyrrolidone solvents showing higher cytotoxic effects (p < 0.05). In situ gelling formulations comprising hydroxypropyl methylcellulose or carboxymethyl cellulose and solvents in specific ratios were biocompatible at higher concentrations with MAC-T cells compared to alginates. All investigated formulations could undergo in situ sol-to-gel phase transformation, forming non-toxic gels with good biocompatibility in excised cow teats hence, showing potential for use as intramammary carriers for sustained drug delivery.
Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine
Authors: Ahmed Tarek A. , Felimban Raed I. , Tayeb Hossam H. , Rizg Waleed Y. , Alnadwi Fuad H. , Alotaibi Hanadi A. , Alhakamy Nabil A. , Abd-Allah Fathy I. , Mohamed Gamal A. , Zidan Ahmed S. , El-Say Khalid M.
Published: October 2021

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6–11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.
In Vitro Cellular and Molecular Interplay between Human Foreskin-Derived Mesenchymal Stromal/Stem Cells and the Th17 Cell Pathway
Authors: Najar Mehdi , Merimi Makram , Faour Wissam H. , Lombard Catherine A. , Moussa Agha Douâa , Ouhaddi Yassine , Sokal Etienne M. , Lagneaux Laurence , Fahmi Hassan
Published: October 2021

Foreskin, considered a biological waste material, has been shown to be a reservoir of therapeutic cells. The immunomodulatory properties of mesenchymal stromal/stem cells (MSCs) from the foreskin (FSK-MSCs) are being evaluated in cell-based therapy for degenerative, inflammatory and autoimmune disorders. Within the injured/inflamed tissue, proinflammatory lymphocytes such as IL-17-producing T helper cells (Th17) may interact with the stromal microenvironment, including MSCs. In this context, MSCs may encounter different levels of T cells as well as specific inflammatory signals. Uncovering the cellular and molecular changes during this interplay is central for developing an efficient and safe immunotherapeutic tool. To this end, an in vitro human model of cocultures of FSK-MSCs and T cells was established. These cocultures were performed at different cell ratios in the presence of an inflammatory setting. After confirming that FSK-MSCs respond to ISCT criteria by showing a typical phenotype and multilineage potential, we evaluated by flow cytometry the expression of Th17 cell markers IL-17A, IL23 receptor and RORγt within the lymphocyte population. We also measured 15 human Th17 pathway-related cytokines. Regardless of the T cell/MSC ratio, we observed a significant increase in IL-17A expression associated with an increase in IL-23 receptor expression. Furthermore, we observed substantial modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α secretion. These findings suggest that FSK-MSCs are receptive to their environment and modulate the T cell response accordingly. The changes within the secretome of the stromal and immune environment are likely relevant for the therapeutic effect of MSCs. FSK-MSCs represent a valuable cellular product for immunotherapeutic purposes that needs to be further clarified and developed.
Investigation of the Transport Pathways Associated with Enhanced Brain Delivery of Peptide Drugs by Intranasal Coadministration with Penetratin
Authors: Kamei Noriyasu , Suwabe Susumu , Arime Kenji , Bando Hidemi , Murata Kaho , Yamaguchi Maika , Yokoyama Natsuki , Tanaka Erina , Hashimoto Ayaka , Kanazawa Takanori , Ago Yukio , Takeda-Morishita Mariko
Published: October 2021

We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas.
Formulation, Optimization and Evaluation of Luteolin-Loaded Topical Nanoparticulate Delivery System for the Skin Cancer
Authors: Kazmi Imran , Al-Abbasi Fahad A. , Nadeem Muhammad Shahid , Altayb Hisham N. , Alshehri Sultan , Imam Syed Sarim
Published: October 2021

In the present study, luteolin (LT)-loaded nanosized vesicles (LT-NVs) were prepared by a solvent evaporation–hydration method using phospholipid and edge activator. The formulation was optimized using three factors at a three-level Box–Behnken design. The formulated LT-NVs were prepared using the three independent variables phospholipid (A), edge activator (B) and sonication time (C). The effect of used variables was assessed on the vesicle size (Y1) and encapsulation efficiency (Y2). The selection of optimum composition (LT-NVopt) was based on the point prediction method of the software. The prepared LT-NVopt showed the particle size of 189.92 ± 3.25 nm with an encapsulation efficiency of 92.43 ± 4.12% with PDI and zeta potential value of 0.32 and −21 mV, respectively. The formulation LT-NVopt was further converted into Carbopol 934 gel (1% w/v) to enhance skin retention. LT-NVoptG was further characterized for viscosity, spreadability, drug content, drug release, drug permeation and antioxidant, antimicrobial and cytotoxicity assessment. The evaluation result revealed optimum pH, viscosity, spreadability and good drug content. There was enhanced LT release (60.81 ± 2.87%), as well as LT permeation (128.21 ± 3.56 µg/cm2/h), which was found in comparison to the pure LT. The antioxidant and antimicrobial study results revealed significantly (p ˂ 0.05) better antioxidant potential and antimicrobial activity against the tested organisms. Finally, the samples were evaluated for cytotoxicity assessment using skin cancer cell line and results revealed a significant difference in the viability % at the tested concentration. LT-NVoptG showed a significantly lower IC50 value than the pure LT. From the study, it can be concluded that the prepared LT-NVoptG was found to be an alternative to the synthetic drug as well as conventional delivery systems.
In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies
Authors: Tratnjek Larisa , Sibinovska Nadica , Kristan Katja , Kreft Mateja Erdani
Published: October 2021

Certain active drugs and excipients of nasal formulations may impair ciliary function and mucociliary clearance. The ciliary beat frequency (CBF) is a key parameter for determining mucociliary clearance rate, and in vitro assessments of CBF have proven to be accurate and reproducible. Since topical nasal formulations are applied with repeated doses, it is essential to elucidate their chronic, as opposed to acute, effect on mucociliary clearance and nasal mucosa. The aim of this study was to assess for the first time the ciliotoxicity and cytotoxicity of nasal sprays intended for chronic treatment (with repeated doses) using a previously designed set-up for CBF measurements. For 2 weeks, the 3D nasal MucilAir™ in vitro models were treated daily with undiluted or clinically relevant doses of mometasone nasal spray, placebo nasal spray, culture medium, or they were untreated. We demonstrated a dose-dependent and time-dependent (cumulative) effect of the nasal sprays on ciliary activity and cytotoxicity using CBF measurements and ultrastructural analysis, respectively. Our results indicate that repeated administration of clinically relevant doses of mometasone nasal spray is safe for in vivo use, which is in good agreement with a previous clinical study. Overall, our study suggests that such in vitro assays have great potential for topical nasal drug screening.
Stabilization by Nano Spray Dryer of Pioglitazone Polymeric Nanosystems: Development, In Vivo, Ex Vivo and Synchrotron Analysis
Authors: Silva-Abreu Marcelle , Miralles Esther , Kamma-Lorger Christina S. , Espina Marta , García María Luisa , Calpena Ana Cristina
Published: October 2021

Pioglitazone-loaded PLGA-PEG nanoparticles (NPs) were stabilized by the spray drying technique as an alternative to the treatment of ocular inflammatory disorders. Pioglitazone-NPs were developed and characterized physiochemically. Interaction studies, biopharmaceutical behavior, ex vivo corneal and scleral permeation, and in vivo bioavailability evaluations were conducted. Fibrillar diameter and interfibrillar corneal spacing of collagen was analyzed by synchrotron X-ray scattering techniques and stability studies at 4 °C and was carried out before and after the spray drying process. NPs showed physicochemical characteristics suitable for ocular administration. The release was sustained up to 46 h after drying; ex vivo corneal and scleral permeation profiles of pioglitazone-NPs before and after drying demonstrated higher retention and permeation through cornea than sclera. These results were correlated with an in vivo bioavailability study. Small-angle X-ray scattering (SAXS) analysis did not show a significant difference in the organization of the corneal collagen after the treatment with pioglitazone-NPs before and after the drying process, regarding the negative control. The stabilization process by Nano Spray Dryer B-90 was shown to be useful in preserving the activity of pioglitazone inside the NPs, maintaining their physicochemical characteristics, in vivo bioavailability, and non-damage to corneal collagen function after SAXS analysis was observed.
[18F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound
Authors: Hugon Gaëlle , Goutal Sébastien , Dauba Ambre , Breuil Louise , Larrat Benoit , Winkeler Alexandra , Novell Anthony , Tournier Nicolas
Published: October 2021

Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood-brain barrier (BBB) permeability in vivo. Positron-emission tomography (PET) imaging using [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [18F]FDS was straightforwardly produced from chemical reduction of commercial [18F]2-deoxy-2-fluoro-D-glucose. [18F]FDS and the invasive BBB integrity marker Evan’s blue (EB) were i.v. injected in mice after an optimized FUS protocol designed to generate controlled hemispheric BBB disruption. Quantitative determination of the impact of FUS on the BBB permeability was determined using kinetic modeling. A 2.2 ± 0.5-fold higher PET signal (n = 5; p < 0.01) was obtained in the sonicated hemisphere and colocalized with EB staining observed post mortem. FUS significantly increased the blood-to-brain distribution of [18F]FDS by 2.4 ± 0.8-fold (VT; p < 0.01). Low variability (=10.1%) of VT values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [18F]FDS PET provides a readily available, sensitive and reproducible marker of BBB permeability to noninvasively monitor the extent of BBB disruption induced by FUS in vivo.
The Event Ontology of Nature
Authors: Mikki Said
Published: October 2021

We propose a new event ontology of the world, which is part of a general approach to philosophy based on combining ideas from science, ontology, and the philosophy of nature. While the position advocated here is grounded in science and philosophy, it attempts to move beyond each of them by devising and exploring a series of technical (naturalized or naturalistic) ontological concepts such as Interconnectedness, the Whole, the Global, Chaos, the event assemblage, and Nonspace. A central theme in our event ontology is the mapping out of a fundamental critique of the theory of the organism and organization, especially when the latter two are viewed as processes in spacetime. In particular, and following earlier leads, we criticize the spacetime doctrine by arguing that it is not ontologically fundamental, where we suggest its replacement by more primordial naturalized ontological concepts of space such as ontospace and Nonspace. The event ontology of nature can be considered a radical alternative attitude toward the relation between the human and nature, an attitude, in fact, that has been repeatedly explored, though under very different headings, by numerous scattered thinkers throughout the history of ideas. We examine some of the past thinkers who contributed to this general but still incoherent body of thought, including Leibniz, Heidegger, Simondon, Ruyer, Deleuze, Whitehead, and Guattari. The goal of this article is to provide a condensed high-level view on this very complex and still evolving subject intended for a large audience, not necessarily only philosophers, but also scientists, mathematicians, technologists, theologians, sociologists, artists, and psychologists.
Dielectric Barrier Discharge Plasma Jet (DBDjet) Processed Reduced Graphene Oxide/Polypyrrole/Chitosan Nanocomposite Supercapacitors
Authors: Liu Chen , Hung Cheng-Wei , Cheng I-Chung , Hsu Cheng-Che , Cheng I-Chun , Chen Jian-Zhang
Published: October 2021

Reduced graphene oxide (rGO) and/or polypyrrole (PPy) are mixed with chitosan (CS) binder materials for screen-printing supercapacitors (SCs) on arc atmospheric-pressure plasma jet (APPJ)-treated carbon cloth. The performance of gel-electrolyte rGO/CS, PPy/CS, and rGO/PPy/CS SCs processed by a dielectric barrier discharge plasma jet (DBDjet) was assessed and compared. DBDjet processing improved the hydrophilicity of these three nanocomposite electrode materials. Electrochemical measurements including electrical impedance spectroscopy (EIS), cyclic voltammetry (CV), and galvanostatic charging-discharging (GCD) were used to evaluate the performance of the three types of SCs. The Trasatti method was used to evaluate the electric-double layer capacitance (EDLC) and pseudocapacitance (PC) of the capacitance. The energy and power density of the three types of SCs were illustrated and compared using Ragone plots. Our experiments verify that, with the same weight of active materials, the combined use of rGO and PPy in SCs can significantly increase the capacitance and improve the operation stability.
Detection of Barely Visible Impact Damage in Polymeric Laminated Composites Using a Biomimetic Tactile Whisker
Authors: Fotouhi Sakineh , Khayatzadeh Saber , Pui Wei Xia , Damghani Mahdi , Bodaghi Mahdi , Fotouhi Mohamad
Published: October 2021

This is a novel investigation on the possibility of detecting barely visible impact damage (BVID) in composite materials by whisking across the surface via tactile whisker sensors that resemble rats’ whiskers. A series of drop tower low-velocity impact tests were performed on quasi-isotropic composite plates. The plates were made from unidirectional T800 carbon/MTM49-3 epoxy prepregs with the stacking sequence of [45/0/90/−45]4S. Investigating the specimens’ surface by the naked eye does not reveal any significant damage, rather than a small dent on the surface, with no tangible difference in the different impact energy levels. Ultrasonic C-scan observations showed the existence of BVID in all the impact energy levels, with an increasing trend in the damage size by increasing the impact energy level. The collected data from whisker sensors were analyzed using the support vector machine classifier, based on their vibrational properties, to identify the impacted region and classify the impact severity. It was observed that after training for 13 whisker contacts, the BVID severity can be classified with an accuracy of 100%. This is offering a new BVID detection technique, with a high potential for automation and high reliability that can be used as an alternative or combined with available inspection systems.
Experimental Investigation of the Wear Behaviour of Coated Polymer Gears
Authors: Polanec Brigita , Zupanič Franc , Bončina Tonica , Tašner Frančišek , Glodež Srečko
Published: October 2021

A comprehensive experimental investigation of the wear behaviour of coated spur polymer gears made of POM is performed in this study. The three physical vapour deposition (PVD) coatings investigated were aluminium (Al), chromium (Cr), and chromium nitrite (CrN). Al was deposited in three process steps: By plasma activation, metallisation of Al by the magnetron sputtering process, and by plasma polymerisation. Cr deposition was performed in only one step, namely, the metallization of Cr by the magnetron sputtering process. The deposition of CrN was carried out in two steps: the first involved the metallization of Cr by the magnetron sputtering process while the second step, vapour deposition, involved the reactive metallisation of Cr with nitrogen, also by the magnetron sputtering process. The gears were tested on an in-house developed testing rig for different torques (16, 20, 24 and 30 Nm) and rotational speed of 1000 rpm. The duration of the experiments was set to 13 h, when the tooth thickness, and, consequently, the wear of the tooth flank was recorded. The experimental results showed that the influence of metallisation with aluminium, chromium, and chromium nitrite surface coatings on the wear behaviour of the analysed polymer gear is not significant. This is probably due to the fact that the analysed coatings were, in all cases, very thin (less than 500 nm), and therefore did not influence the wear resistance significantly. In that respect, an additional testing using thicker coatings should be applied in the further research work.
Effect of Process Control Parameters on the Filtration Performance of PAN–CTAB Nanofiber/Nanonet Web Combined with Meltblown Nonwoven
Authors: Kang Hyo Kyoung , Oh Hyun Ju , Kim Jung Yeon , Kim Hak Yong , Choi Yeong Og
Published: October 2021

Nanofibers have potential applications as filters for particles with diameters <10 μm owing to their large specific surface area, macropores, and controllable geometry or diameter. The filtration efficiency can be increased by creating nanonets (<50 nm) whose diameter is smaller than that of nanofibers. This study investigates the effect of process conditions on the generation of nanonet structures from a polyacrylonitrile (PAN) solution containing cation surfactants; in addition, the filtration performance is analyzed. The applied electrospinning voltage and the electrostatic treatment of meltblown polypropylene (used as a substrate) are the most influential process parameters of nanonet formation. Electrospun polyacrylonitrile–cetylmethylammonium bromide (PAN–CTAB) showed a nanofiber/nanonet structure and improved thermal and mechanical properties compared with those of the electrospun PAN. The pore size distribution and filter efficiency of the PAN nanofiber web and PAN–CTAB nanofiber/nanonet web with meltblown were measured. The resulting PAN–CTAB nanofiber/nanonet air filter showed a high filtration efficiency of 99% and a low pressure drop of 7.7 mmH2O at an air flow rate of 80 L/min. The process control methods for the nanonet structures studied herein provide a new approach for developing functional materials for air-filtration applications.