bluuebunny/crossref_metadata_2025 huggingface dataset:
VR-PEER: A Personalized Exer-Game Platform Based on Emotion Recognition
Authors: Izountar Yousra , Benbelkacem Samir , Otmane Samir , Khababa Abdallah , Masmoudi Mostefa , Zenati Nadia
Published: February 2022

Motor rehabilitation exercises require recurrent repetitions to enhance patients’ gestures. However, these repetitive gestures usually decrease the patients’ motivation and stress them. Virtual Reality (VR) exer-games (serious games in general) could be an alternative solution to address the problem. This innovative technology encourages patients to train different gestures with less effort since they are totally immersed in an easy to play exer-game. Despite this evolution, patients, with available exer-games, still suffer in performing their gestures correctly without pain. The developed applications do not consider the patients psychological states when playing an exer-game. Therefore, we believe that is necessary to develop personalized and adaptive exer-games that take into consideration the patients’ emotions during rehabilitation exercises. This paper proposed a VR-PEER adaptive exer-game system based on emotion recognition. The platform contain three main modules: (1) computing and interpretation module, (2) emotion recognition module, (3) adaptation module. Furthermore, a virtual reality-based serious game is developed as a case study, that uses updated facial expression data and provides dynamically the patient’s appropriate game to play during rehabilitation exercises. An experimental study has been conducted on fifteen subjects who expressed the usefulness of the proposed system in motor rehabilitation process.
Applying Data Mining and Artificial Intelligence Techniques for High Precision Measuring of the Two-Phase Flow’s Characteristics Independent of the Pipe’s Scale Layer
Authors: Mayet Abdulilah Mohammad , Salama Ahmed S. , Alizadeh Seyed Mehdi , Nesic Slavko , Guerrero John William Grimaldo , Eftekhari-Zadeh Ehsan , Nazemi Ehsan , Iliyasu Abdullah M.
Published: February 2022

Scale formation inside oil and gas pipelines is always one of the main threats to the efficiency of equipment and their depreciation. In this study, an artificial intelligence method method is presented to provide the flow regime and volume percentage of a two-phase flow while considering the presence of scale inside the test pipe. In this non-invasive method, a dual-energy source of barium-133 and cesium-137 isotopes is irradiated, and the photons are absorbed by a detector as they pass through the test pipe on the other side of the pipe. The Monte Carlo N Particle Code (MCNP) simulates the structure and frequency features, such as the amplitudes of the first, second, third, and fourth dominant frequencies, which are extracted from the data recorded by the detector. These features use radial basis function neural network (RBFNN) inputs, where two neural networks are also trained to accurately determine the volume percentage and correctly classify all flow patterns, independent of scale thickness in the pipe. The advantage of the proposed system in this study compared to the conventional systems is that it has a better measuring precision as well as a simpler structure (using one detector instead of two).
An Intelligent Coaching Prototype for Elderly Care
Authors: Martinho Diogo , Crista Vítor , Carneiro João , Corchado Juan Manuel , Marreiros Goreti
Published: February 2022

The world ageing problem is prompting new sustainable ways to support elderly people. As such, it is important to promote personalized and intelligent ways to assure the active and healthy ageing of the population. Technological breakthroughs have led to the development of personalized healthcare systems, capable of monitoring and providing feedback on different aspects that can improve the health of the elderly person. Furthermore, defining motivational strategies to persuade the elderly person to be healthier and stay connected to such systems is also fundamental. In this work, a coaching system is presented, especially designed to support elderly people and motivate them to pursue healthier ways of living. To do this, a coaching application is developed using both a cognitive virtual assistant to directly interact with the elderly person and provide feedback on his/her current health condition, and several gamification techniques to motivate the elderly person to stay engaged with the application. Additionally, a set of simulations were performed to validate the proposed system in terms of the support and feedback provided to the user according to his progress, and through interactions with the cognitive assistant.
Dynamic Simulation of Permanent Magnet Synchronous Motor (PMSM) Electric Vehicle Based on Simulink
Authors: Zhang Yunfei , Zhao Can , Dai Bin , Li Zhiheng
Published: February 2022

As an important component of vehicle design and energy conservation, electric vehicle dynamics simulation is essential, especially under complicated testing conditions. The current commercial vehicle simulation software is mostly used for fuel vehicle dynamics simulation, which lacks accurate electric powertrain parts and open sources. To address this problem, this paper proposes an open-source and flexible vehicle dynamics simulation platform that includes 27 degrees of freedom (DOFs) based on Simulink, which can compatibly support both traditional vehicle dynamics simulations and electric vehicle dynamics simulations. In addition, the platform can support module customization, which is convenient for researchers. Although this platform still needs some iterations to reach industrial and commercial standards, it can already achieve parameter consistency under the stability demands in general scenarios. We believe this work should receive research attention and participation to provide lower thresholds and more references to the dynamic simulation of electric vehicles to reduce vehicle energy consumption.
Optimization of the Adsorption/Desorption Contribution from Metal-Organic-Heat-Carrier Nanoparticles in Waste Heat Recovery Applications: R245fa/MIL101 in Organic Rankine Cycles
Authors: Cavazzini Giovanna , Bari Serena
Published: February 2022

The efficient recovery of low temperature waste heat, representing from 25% up to 55% of the energy losses in industrial processes, still remains a challenge and even Organic Rankine Cycles (ORCs) experience a strong efficiency decay in such a low temperature operating range (T < 150 °C). In similar heat transfer processes, several nanofluids have been proposed as a solution for increasing heat transfer efficiency, but they produced only moderate enhancements of the heat transfer efficiency in comparison with pure fluids. This paper aims at numerically assessing the potential gain in efficiency deriving from the application of an unconventional type of nanoparticles, the metal-organic heat carriers (MOHCs), in the ORC field. In comparison with standard nanoparticles, these MOHCs make it possible to extract additional heat from the endothermic enthalpy of desorption, with a theoretically high potential for boosting the heat transfer capacity of ORC systems. In this paper a numerical model was developed and customized for considering the adsorption/desorption processes of the pure fluid R245fa (pentafluoropropane) combined with a crystal structure for porous chromium terephthalate (MIL101). The R245fa/MIL101 nanofluid behavior was experimentally characterized, defining proper semi-emipirical correlations. Then, an optimization procedure was developed, combining the numerical model with a PSO algorithm, to optimize the thermodynamic conditions in the ORC so as to maximize the contribution of desorption/absorption processes. The results confirm the increase in net power output (+2.9% for 100 °C) and in expander efficiency (+2.4% for 100 °C) at very low heat source temperature. The relevance of tuning the operating cycle and the nanofluid properties is also demonstrated.
Modelling of Liquid Hydrogen Boil-Off
Authors: Al Ghafri Saif Z. S. , Swanger Adam , Jusko Vincent , Siahvashi Arman , Perez Fernando , Johns Michael L. , May Eric F.
Published: February 2022

A model has been developed and implemented in the software package BoilFAST that allows for reliable calculations of the self-pressurization and boil-off losses for liquid hydrogen in different tank geometries and thermal insulation systems. The model accounts for the heat transfer from the vapor to the liquid phase, incorporates realistic heat transfer mechanisms, and uses reference equations of state to calculate thermodynamic properties. The model is validated by testing against a variety of scenarios using multiple sets of industrially relevant data for liquid hydrogen (LH2), including self-pressurization and densification data obtained from an LH2 storage tank at NASA’s Kennedy Space Centre. The model exhibits excellent agreement with experimental and industrial data across a range of simulated conditions, including zero boil-off in microgravity environments, self-pressurization of a stored mass of LH2, and boil-off from a previously pressurized tank as it is being relieved of vapor.
Simulation of 15% and 50% Thermal Power Dispatch to an Industrial Facility Using a Flexible Generic Full-Scope Pressurized Water Reactor Plant Simulator
Authors: Hancock Stephen , Westover Tyler
Published: February 2022

Nuclear power plants in the United States are increasingly challenged to compete in wholesale electricity markets due to the low electricity costs and increasingly dynamic grid conditions from competing generation sources. An alternative market for nuclear power is industrial facilities that can use the thermal and/or electrical power generated by a nuclear power plant to offset the economic losses incurred by electricity market challenges. A generic pressurized water reactor (PWR) simulator was used to show the results of a basic design for a generic thermal power extraction system and tests were run using a set of procedures to show what happens when a nuclear power plant transitions from full electrical power dispatch to 15% and 50% thermal power dispatch. This type of operation leads to losses in turbine performance efficiency due to the deviation from the design operating point, but because the thermal power is also used by the industry load without conversion losses, the combined thermal efficiency of the PWR increases. For the 15% case, the thermal efficiency increased from 32% to 41.9%, while for the 50% case, the efficiency increased up to 60.1%. In addition, for 50% thermal power dispatch, the power dissipated by the condenser decreased from approximately 2000 to approximately 1300 MW (thermal), indicating a substantially diminished impact on the environment in terms of releasing heat into the cooling water reservoir.
Breakdown Initiation and Electrical Strength of a Vacuum Insulating System in the Environment of Selected Noble Gases at AC Voltage
Authors: Lech Michał , Węgierek Paweł
Published: February 2022

This paper presents the results of testing the electrical strength of an insulating system in a vacuum obtained from three noble gases: argon, neon, helium, and air. The breakdown voltages were measured for contact gaps of 1 mm and 2 mm. A difference was observed in the pressure range where the electrical strength was kept constant. The chamber filled with helium residual gases lost its insulating properties at the highest pressure among the tested gases (2.00 × 100 Pa at contact gap d = 2 mm), while the chamber filled with argon gas lost its insulating properties at the lowest pressure among the tested gases (2.00 × 10−1 Pa at contact gap d = 2 mm). After a decrease in electrical strength, an intense glow discharge was observed. A theoretical description related to the initiation of an electrical breakdown in vacuum insulating systems is also presented. The situation in which the discharge chamber with a contact system was filled with the mentioned gases was analyzed. The mean free paths of the electrons and molecules as well as the velocities and energies of the electrons accelerated by the voltage applied to electrodes were calculated. The obtained results were related to the measurement parameters and analyzed in terms of the discharge development. The results of the research suggest alternatives for the further development of vacuum-extinguishing chambers used in environmentally-friendly electrical switchgear by increasing the rated operating pressure, maintaining the required electrical strength values, and thus facilitating the operation due to greater certainty in regard tomaintaining the integrity of such a vacuum interrupter.
Natural ‘Green’ Sugar-Based Treatment for Hair Styling
Authors: Patil Namrata V. , Netravali Anil N.
Published: February 2022

A major drawback of current hair styling treatments is their use of toxic chemicals, such as thioglycolates, sulfites, formaldehyde, and others. Exposure to such chemicals is not only harmful to hairstylists but also to the millions who routinely receive hair treatments. The present research discusses the development of a benign sucrose-based crosslinker consisting of aldehyde groups to stabilize hair via crosslinking amine groups in keratin. ATR-FTIR and 1H-NMR were used to confirm functional groups on sucrose. Hair straightening was carried out by crosslinking via flat ironing. Crosslinked hair swatches were hung in a high humidity environment and subjected to repeated washings with shampoo to characterize the permanency of the treatment. Hair straightening through crosslinking was found to be durable to high humidity and repeat shampoo washings. The tensile characteristics of hair, such as fracture stress, strain, and Young’s modulus, were unaffected by the treatment. SEM images showed no damage to surface scales. The sucrose-based crosslinker could be used to create curls in straight hair as well.
Development of a 3D Printer for the Manufacture of Functional Food Protein Gels
Authors: Portanguen Stéphane , Tournayre Pascal , Gibert Paul , Leonardi Selma , Astruc Thierry , Mirade Pierre-Sylvain
Published: February 2022

The use of additive manufacturing is growing in multiple sectors, including food, and its scientific and technological challenges form the subject of much ongoing research. One current hurdle is the implementation of the 3D printing process for meat protein matrices. This article gives an overview of the various 3D printers used to study the printability properties of foods and presents the development of a 3D printer designed to print food protein gels. Printhead development (flow rate and temperature control) and the modifications made to the printing plate (temperature control) are described and discussed in relation to the constraints highlighted in a first prototype. A second, developed prototype was characterized and validated. This last phase showed perfect control of the prototype in the purging of the extrusion system, the flow rate, the calibration and the displacement of the printhead, along with the temperatures at both printhead and plate. A study of the printed gels also revealed good repeatability of the printed gel geometry and pointed to new ways to improve the process. In the near future, the protein gels that will be printed from this prototype will serve as a base for texturizer-free functional foods for people with chewing difficulties.
Plant and Dairy-Based Yogurts: A Comparison of Consumer Sensory Acceptability Linked to Textural Analysis
Authors: Gupta Mitali K. , Torrico Damir D. , Ong Lydia , Gras Sally L. , Dunshea Frank R. , Cottrell Jeremy J.
Published: February 2022

Yogurt, readily available in plant and dairy-based formulations, is widely consumed and linked with health benefits. This research is aimed to understand the sensory and textural spectrum of commercially available dairy and plant-based yogurts. In a preliminary study, qualitative focus group discussions (4 groups; n = 32) were used to determine perceptions of 28 dairy and plant-based yogurts, identifying positive consumer perceptions of plant-based yogurts. A smaller subset of five spoonable and one drinkable yogurts—(Reference, Soy, Coconut, Cookies, Berry, and Drinkable) was subsequently selected for rheological and structural measurements, showing wide variations in the microstructure and rheology of selected yogurt samples. A quantitative blind sensory tasting (n = 117) showed varying yogurt acceptability, with Berry being the least-liked and Cookies being the most-liked yogurt, in terms of overall liking. The multi-factor analysis confirmed that compositional and textural elements, including protein content, gel firmness, and consistency coefficient, displayed a positive relationship with overall liking. In contrast, fat, sugar, and calories were negatively correlated to the overall liking. This research showed that texture and other compositional factors are significant determinants of the consumer acceptability of yogurt products and are essential properties to consider in product development.
A Conceptual Framework to Improve Cyber Forensic Administration in Industry 5.0: Qualitative Study Approach
Authors: Adel Amr
Published: February 2022

As organizations strive to be compliant in a digitally evolving world, they need to ensure that they are forensically ready. Digital forensic readiness ensures compliance in legal, regulatory, functional, and operational structures. A literature review revealed a gap in detailed and comprehensive guidance on how such readiness ought to be accomplished. This is as a result of unfamiliar concepts and terms that revolve around digital forensic readiness. This research paper highlights and elaborates on a framework that can be achieved from research within focus groups. The insights drawn from the focus groups are used to critically assess the issues affecting practitioners in achieving complete digital forensic readiness.
Asymptotic Behavior of Solutions of Even-Order Differential Equations with Several Delays
Authors: Moaaz Osama , Albalawi Wedad
Published: February 2022

The higher-order delay differential equations are used in the describing of many natural phenomena. This work investigates the asymptotic properties of the class of even-order differential equations with several delays. Our main concern revolves around how to simplify and improve the oscillation parameters of the studied equation. For this, we use an improved approach to obtain new properties of the positive solutions of these equations.
Risk Factors, Manifestation, and Awareness of Osteoporosis among Patients of Various Specialists in Switzerland: Results of a National Survey
Authors: Jehle-Kunz Sigrid , Häuselmann Hans-Jörg , Keschawarzi Mitra , Lamy Olivier , Luzuy Franck , Marcoli Natalie , Meier Christian , Uebelhart Brigitte , Wiedersheim Peter
Published: February 2022

Osteoporosis is the most common chronic metabolic bone disease, known to be underdiagnosed and undertreated in parts of the Swiss population. Due to expected rise in new fragility fractures, adequate awareness of associated risk factors and diagnostic and therapeutic options will be essential for the management of osteoporosis. We therefore explored these aspects in a nationwide survey of Swiss specialists and their patients. A total of 262 physician questionnaires and 9065 patient questionnaires were analyzed, mainly from general practitioners (64.9%), followed by rheumatologists (16.8%), gynecologists (12.2%), and endocrinologists (6.1%). Around 20% of patients were under medication and/or had a medical condition increasing the risk of osteoporosis. Further risk factors, such as low consumption of calcium-rich foods, smoking, elevated alcohol intake, and insufficient physical activity, were present across regions and medical fields. 53.9% of patients did not take calcium/vitamin D supplements; 3.5% reported having fragility fractures, and 7.3% received treatment for osteoporosis. Only 38.5% of surveyed patients knew of the chronic nature of osteoporosis, indicating rather low awareness in this population. Despite generally perceived relevance of osteoporosis for daily practice, aspects of its prevention and management varied across regions and medical fields. Raising awareness among patients and physicians will be vital for addressing osteoporosis on a national scale.
The Public Health Governance of the COVID-19 Pandemic: A Bibliometric Analysis
Authors: Yang Keng , Qi Hanying
Published: February 2022

The 2019 global outbreak of COVID-19 has had a huge impact on public health governance systems around the world. In response, numerous scholars have conducted research on public health governance in the context of the COVID-19 pandemic. This paper provides a bibliometric analysis of 1437 documents retrieved from the Web of Science (WoS) core collection database, with 49,695 references. It analyses the research directions, countries of publications, core journals, leading authors and institutions and important publications. The paper also summarises research trends by analysing the co-occurrence of keywords, frequently cited documents and co-cited references. It summarises the global responses to COVID-19, including public health interventions and a range of supporting policies based on the features and impacts of the COVID-19 pandemic. The paper provides comprehensive literary support and clear lines of research for future studies on the governance or regulation of public health emergencies.
Adolescents’ Sexual and Reproductive Healthcare-Seeking Behaviour and Service Utilisation in Plateau State, Nigeria
Authors: Envuladu Esther Awazzi , Massar Karlijn , de Wit John
Published: February 2022

The high rate of sexual and reproductive health (SRH) challenges among adolescents in Nigeria has been linked with the poor access to and utilisation of health facilities. This study explores the factors that influence the actual use and willingness to use SRH services among adolescents. Survey questionnaires were administered to 428 adolescents aged 18 to 19 years in six local government areas (LGAs) in Plateau State. The results showed that more than one-third of the participating adolescents were currently sexually active, slightly more than three-quarters (76.6%) had never visited health facilities for SRH issues, and more than half (56.0%) were not willing to visit a health facility if they ever had any SRH issues. The most frequent reason for the non-use of health care facilities for SRH issues by adolescents was a perceived lack of privacy and confidentiality (66.1%), followed by the perceived negative attitude of health care providers (68.2%). However, being sexually active was the only independent covariate of seeking SRH care from health facility (AOR = 005; CI = 0.01–0.49; p = 0.011), while awareness of HIV was a significant covariate of willingness to seek SRH care in a health facility in the future (AOR = 3.17, 95% CI = 1.50–6.70; p = 0.002). We concluded that the utilisation of SRH services and willingness to do so in the future was fairly limited among adolescents in this study. Therefore, there is a need to address the challenges of privacy and confidentiality and commencement of the health promotion of SRH for adolescents ahead of sexual initiation to alleviate the SRH challenges adolescents encounter when sexually active.
Hydrology in the Caribbean Basin
Authors: Piasecki Michael , Harmsen Eric
Published: February 2022

The idea for this Special Issue emerged from the recognition that the Caribbean Basin is fascinatingly diverse (26 countries border it), and a vast majority of its population are under threat from the intense pressures of climate change and human impacts [...]
Variability of Performance and Kinematics of Different Shot Put Techniques in Elite and Sub-Elite Athletes–A Preliminary Study
Authors: Mastalerz Andrzej , Sadowski Jerzy
Published: February 2022

The purpose of the study was to analyze the variability of performance and kinematics of different shot put techniques in elite athletes (group A: 5 athletes using the rotational technique and 3 athletes using the glide technique) and sub-elite athletes (group B: 3 athletes using the rotational technique and 3 athletes using the glide technique). Each athlete performed 6 trials. Only 34 trials in group A and 27 trials in group B were analyzed. Two high-speed digital cameras were positioned 8 m from the center of the shot put throwing circle. All throws performed during international and national competitions were analyzed using the Ariel Performance Analysis System. To estimate variability of kinematic parameters, the value of relative error was calculated. The average relative error generally showed low variability for the analyzed indicators. In only 4 analyzed cases, variability was high (>20%). Statistical analysis was used to find indicators which have a significant influence on the distance of the throw (according to the sports level and technique). Significant inverse correlations (at p < 0.05) between the distance and the average relative error of the selected indicators were mainly obtained, which meant that the distance was longer when the value of variability (average relative error) was low. The research results show that greater repeatability of the technique (lower RE) has a significant impact on the length of the shot put.
Electrospun Fiber-Coated Human Amniotic Membrane: A Potential Angioinductive Scaffold for Ischemic Tissue Repair
Authors: Hasmad Hanis Nazihah , Bt Hj Idrus Ruszymah , Sulaiman Nadiah , Lokanathan Yogeswaran
Published: February 2022

Cardiac patch implantation helps maximize the paracrine function of grafted cells and serves as a reservoir of soluble proangiogenic factors required for the neovascularization of infarcted hearts. We have previously fabricated a cardiac patch, EF-HAM, composed of a human amniotic membrane (HAM) coated with aligned PLGA electrospun fibers (EF). In this study, we aimed to evaluate the biocompatibility and angiogenic effects of EF-HAM scaffolds with varying fiber thicknesses on the paracrine behavior of skeletal muscle cells (SkM). Conditioned media (CM) obtained from SkM-seeded HAM and EF-HAM scaffolds were subjected to multiplex analysis of angiogenic factors and tested on HUVECs for endothelial cell viability, migration, and tube formation analyses. All three different groups of EF-HAM scaffolds demonstrated excellent biocompatibility with SkM. CM derived from SkM-seeded EF-HAM 7 min scaffolds contained significantly elevated levels of proangiogenic factors, including angiopoietin-1, IL-8, and VEGF-C compared to plain CM, which was obtained from SkM cultured on the plain surface. CM obtained from all SkM-seeded EF-HAM scaffolds significantly increased the viability of HUVECs compared to plain CM after five days of culture. However, only EF-HAM 7 min CM induced a higher migration capacity in HUVECs and formed a longer and more elaborate capillary-like network on Matrigel compared with plain CM. Surface roughness and wettability of EF-HAM 7 min scaffolds might have influenced the proportion of skeletal myoblasts and fibroblasts growing on the scaffolds and subsequently potentiated the angiogenic paracrine function of SkM. This study demonstrated the angioinductive properties of EF-HAM composite scaffold and its potential applications in the repair and regeneration of ischemic tissues.
Immature Vascular Smooth Muscle Cells in Healthy Murine Arteries and Atherosclerotic Plaques: Localization and Activity
Authors: Balatskiy Alexander , Ozhimalov Ilia , Balatskaya Maria , Savina Alexandra , Filatova Julia , Kalinina Natalia , Popov Vladimir , Tkachuk Vsevolod
Published: February 2022

The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis.
Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations
Authors: Ghoula Mariem , Janel Nathalie , Camproux Anne-Claude , Moroy Gautier
Published: February 2022

Insulin-degrading enzyme (IDE) is a ubiquitously expressed metallopeptidase that degrades insulin and a large panel of amyloidogenic peptides. IDE is thought to be a potential therapeutic target for type-2 diabetes and neurodegenerative diseases, such as Alzheimer’s disease. IDE catalytic chamber, known as a crypt, is formed, so that peptides can be enclosed and degraded. However, the molecular mechanism of the IDE function and peptide recognition, as well as its conformation changes, remains elusive. Our study elucidates IDE structural changes and explains how IDE conformational dynamics is important to modulate the catalytic cycle of IDE. In this aim, a free-substrate IDE crystallographic structure (PDB ID: 2JG4) was used to model a complete structure of IDE. IDE stability and flexibility were studied through molecular dynamics (MD) simulations to witness IDE conformational dynamics switching from a closed to an open state. The description of IDE structural changes was achieved by analysis of the cavity and its expansion over time. Moreover, the quasi-harmonic analysis of the hinge connecting IDE domains and the angles formed over the simulations gave more insights into IDE shifts. Overall, our results could guide toward the use of different approaches to study IDE with different substrates and inhibitors, while taking into account the conformational states resolved in our study.
PCD Genes—From Patients to Model Organisms and Back to Humans
Authors: Niziolek Michal , Bicka Marta , Osinka Anna , Samsel Zuzanna , Sekretarska Justyna , Poprzeczko Martyna , Bazan Rafal , Fabczak Hanna , Joachimiak Ewa , Wloga Dorota
Published: February 2022

Primary ciliary dyskinesia (PCD) is a hereditary genetic disorder caused by the lack of motile cilia or the assembxly of dysfunctional ones. This rare human disease affects 1 out of 10,000–20,000 individuals and is caused by mutations in at least 50 genes. The past twenty years brought significant progress in the identification of PCD-causative genes and in our understanding of the connections between causative mutations and ciliary defects observed in affected individuals. These scientific advances have been achieved, among others, due to the extensive motile cilia-related research conducted using several model organisms, ranging from protists to mammals. These are unicellular organisms such as the green alga Chlamydomonas, the parasitic protist Trypanosoma, and free-living ciliates, Tetrahymena and Paramecium, the invertebrate Schmidtea, and vertebrates such as zebrafish, Xenopus, and mouse. Establishing such evolutionarily distant experimental models with different levels of cell or body complexity was possible because both basic motile cilia ultrastructure and protein composition are highly conserved throughout evolution. Here, we characterize model organisms commonly used to study PCD-related genes, highlight their pros and cons, and summarize experimental data collected using these models.
Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil
Authors: Liberi Stefano , Linciano Sara , Moro Giulia , De Toni Luca , Cendron Laura , Angelini Alessandro
Published: February 2022

Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow’s binding sites I (FA7) and II (FA3–FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA–drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies.
Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2
Authors: Rampogu Shailima , Lee Gihwan , Park Jun Sung , Lee Keun Woo , Kim Myeong Ok
Published: February 2022

Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be a major disease claiming many lives. The natural compound curcumin is bestowed with multiple medicinal applications in addition to demonstrating antiviral and anticancer activities. In order to elucidate the impact of curcumin on COVID-19 and cancer, the current investigation has adapted several computational techniques to unfold its possible inhibitory activity. Accordingly, curcumin and similar compounds and analogues were retrieved and assessed for their binding affinities at the binding pocket of SARS-CoV-2 main protease and DDX3. The best binding pose was escalated to molecular dynamics simulation (MDS) studies to assess the time dependent stability. Our findings have rendered one compound that has demonstrated good molecular dock score complemented by key residue interactions and have shown stable MDS results inferred by root mean square deviation (RMSD), radius of gyration (Rg), binding mode, hydrogen bond interactions, and interaction energy. Essential dynamics results have shown that the systemadapts minimum energy conformation to attain a stable state. The discovered compound (curA) could act as plausible inhibitor against SARS-CoV-2 and DDX3. Furthermore, curA could serve as a chemical scaffold for designing and developing new compounds.
Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers
Authors: Bryniarski Paweł , Nazimek Katarzyna , Marcinkiewicz Janusz
Published: February 2022

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.
Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins
Authors: Rikken Gijs , van den Brink Noa J. M. , van Vlijmen-Willems Ivonne M. J. J. , van Erp Piet E. J. , Pettersson Lars , Smits Jos P. H. , van den Bogaard Ellen H.
Published: February 2022

Atopic dermatitis (AD) is a common T-helper 2 (Th2) lymphocyte-mediated chronic inflammatory skin disease characterized by disturbed epidermal differentiation (e.g., filaggrin (FLG) expression) and diminished skin barrier function. Therapeutics targeting the aryl hydrocarbon receptor (AHR), such as coal tar and tapinarof, are effective in AD, yet new receptor ligands with improved potency or bioavailability are in demand to expand the AHR-targeting therapeutic arsenal. We found that carboxamide derivatives from laquinimod, tasquinimod, and roquinimex can activate AHR signaling at low nanomolar concentrations. Tasquinimod derivative (IMA-06504) and its prodrug (IMA-07101) provided full agonist activity and were most effective to induce FLG and other epidermal differentiation proteins, and counteracted IL-4 mediated repression of terminal differentiation. Partial agonist activity by other derivatives was less efficacious. The previously reported beneficial safety profile of these novel small molecules, and the herein reported therapeutic potential of specific carboxamide derivatives, provides a solid rationale for further preclinical assertation.
Role of Combined Na2HPO4 and ZnCl2 in the Unprecedented Catalysis of the Sequential Pretreatment of Sustainable Agricultural and Agro-Industrial Wastes in Boosting Bioethanol Production
Authors: Elyamny Shaimaa , Hamdy Ali , Ali Rehab , Hamad Hesham
Published: February 2022

Improper lignocellulosic waste disposal causes severe environmental pollution and health damage. Corn Stover (CS), agricultural, and aseptic packaging, Tetra Pak (TP) cartons, agro-industrial, are two examples of sustainable wastes that are rich in carbohydrate materials and may be used to produce valuable by-products. In addition, attempts were made to enhance cellulose fractionation and improve enzymatic saccharification. In this regard, these two wastes were efficiently employed as substrates for bioethanol production. This research demonstrates the effect of disodium hydrogen phosphate (Na2HPO4) and zinc chloride (ZnCl2) (NZ) as a new catalyst on the development of the sequential pretreatment strategy in the noticeable enzymatic hydrolysis. Physico-chemical changes of the native and the pretreated sustainable wastes were evaluated by compositional analysis, scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). These investigations showed major structural changes after the optimized sequential pretreatment. This pretreatment not only influences the delignification process, but also affects the functionalization of cellulose chemical structure. NZ released a higher glucose concentration (328.8 and 996.8 mg/dl) than that of ZnCl2 (Z), which released 203.8 and 846.8 mg/dl from CS and TP, respectively. This work led to the production of about 500 mg/dl of ethanol, which is promising and a competitor to other studies. These findings contribute to increasing the versatility in the reuse of agricultural and agro-industrial wastes to promote interaction areas of pollution prevention, industrialization, and clean energy production, to attain the keys of sustainable development goals.
Reactivity Studies of Phosphinines: The Selenation of Diphenyl-Phosphine Substituents and Formation of a Chelating Bis(Phosphinine) Palladium(II) Complex
Authors: Cleaves Peter A. , Gourlay Ben , Newland Robert J. , Westgate Robert , Mansell Stephen M.
Published: February 2022

Phosphinines and donor-substituted phosphinines are of recent interest due to their use in homogeneous catalysis. In this article, a Pd(II) bis(phosphinine) complex was characterised and phosphorus–selenium coupling constants were used to assess the donor properties of the diphenylphosphine substituents of phosphinine ligands to promote their further use in catalysis. The selenation of 2,5-bis(diphenylphosphino)-3,6-dimethylphosphinine (5) and 2-diphenylphosphino-3-methyl-6-trimethylsilylphosphinine (6) gave the corresponding phosphine selenides 8 and 9, respectively, leaving the phosphinine ring intact. Multinuclear NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction confirmed the oxidation of all the diphenylphosphine substituents with 1JP-Se coupling constants determined to be similar to SePPh3, indicating that the phosphinine rings were electronically similar to phenyl substituents. Solutions of 6 were found to react with oxygen slowly to produce the phosphine oxide 10 along with other by-products. The reaction of [bis{3-methyl-6-(trimethylsilyl)phosphinine-2-yl}dimethylsilane] (4) with [PdCl2(COD)] gave the chelating dichloropalladium(II) complex, as determined by multinuclear NMR spectroscopy, mass spectrometry and an elemental analysis. The molecular structure of the intermediate 2 in the formation of 4,6-di(tert-butyl)-1,3,2-diazaphosphinine (3) was also determined, which confirmed the structure of the diazaphosphacycle P(Cl){N=C(tBu)CH=C(tBu)-N(H)}.
An Investigation on the Vortex Effect of a CALM Buoy under Water Waves Using Computational Fluid Dynamics (CFD)
Authors: Amaechi Chiemela Victor , Ye Jianqiao
Published: February 2022

Floating offshore structures (FOS) must be designed to be stable, to float, and to be able to support other structures for which they were designed. These FOS are needed for different transfer operations in oil terminals. However, water waves affect the motion response of floating buoys. Under normal sea states, the free-floating buoy presents stable periodic responses. However, when moored, they are kept in position. Mooring configurations used to moor buoys in single point mooring (SPM) terminals could require systems such as Catenary Anchor Leg Moorings (CALM) and Single Anchor Leg Moorings (SALM). The CALM buoys are one of the most commonly-utilised type of offshore loading terminal. Due to the wider application of CALM buoy systems, it is necessary to investigate the fluid structure interaction (FSI) and vortex effect on the buoy. In this study, a numerical investigation is presented on a CALM buoy model conducted using Computational Fluid Dynamics (CFD) in ANSYS Fluent version R2 2020. Some hydrodynamic definitions and governing equations were presented to introduce the model. The results presented visualize and evaluate specific motion characteristics of the CALM buoy with emphasis on the vortex effect. The results of the CFD study present a better understanding of the hydrodynamic parameters, reaction characteristics and fluid-structure interaction under random waves.
An Evaluation of the Role of Oxidative Stress in Non-Obstructive Coronary Artery Disease
Authors: Pahimi Nurnajwa , Rasool Aida Hanum Ghulam , Sanip Zulkefli , Bokti Nur Adilah , Yusof Zurkurnai , W. Isa W. Yus Haniff
Published: February 2022

Approximately half of all women presenting to the emergency department with angina chest pain do not have obstructive coronary artery disease (CAD) on coronary angiography. This condition is termed non-obstructive coronary artery disease (NOCAD), and includes ischemia with no obstructive coronary artery disease (INOCA) and myocardial infarction with non-obstructive coronary arteries (MINOCA). Oxidative stress has been reported to be involved in the development and progression of CAD. However, a scarcity of studies has assessed a correlation between oxidative stress and NOCAD. Thus, a literature review was performed of available reports on the role of oxidative stress in NOCAD. Possible mechanisms involved in oxidative stress that may contribute to NOCAD were identified and evaluated. A key finding of this literature review was that oxidative stress caused vasoconstriction and endothelial damage, and this results in coronary microvascular dysfunction and vasospasm, which, in turn, lead to the pathogenesis of NOCAD.
Circulating Small Extracellular Vesicles May Contribute to Vaso-Occlusive Crises in Sickle Cell Disease
Authors: Gemel Joanna , Zhang Jared , Mao Yifan , Lapping-Carr Gabrielle , Beyer Eric C.
Published: February 2022

We previously found that the plasma of patients with sickle cell disease (SCD) contains large numbers of small extracellular vesicles (EVs) and that the EVs disrupt the integrity of endothelial cell monolayers (especially if obtained during episodes of acute chest syndrome, ACS). The present study was designed to test the generality of this finding to other complications of SCD, specifically to evaluate the possibility that circulating EVs isolated during a vaso-occlusive crises (VOC) also cause damage to the intercellular connections between endothelial cells. Plasma was obtained from nine pediatric subjects at baseline and during VOC episodes. EVs isolated from these samples were added to cultures of microvascular endothelial cells. Immunofluorescence microscopy was employed to assess monolayer integrity and to localize two intercellular junction proteins (VE-cadherin and connexin43). The EVs isolated during VOC caused significantly greater monolayer disruption than those isolated at baseline. The extent of disruption varied between different episodes of VOC or ACS in the same patient. The VOC EVs disrupted the integrity of both junction proteins at appositional membranes. These results suggest that circulating EVs may be involved in modulating endothelial integrity contributing to the pathogenesis of different complications of SCD.
Human Tissue Analysis of Left Atrial Adipose Tissue and Atrial Fibrillation after Cox Maze Procedure
Authors: Kim Jung-Hwan , Song Joon-Young , Shim Hyo-Sup , Lee Sak , Youn Young-Nam , Joo Hyun-Chel , Yoo Kyung-Jong , Lee Seung-Hyun
Published: February 2022

Cardiac adipose tissue is a well-known risk factor for the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation, but its correlation with maze surgery remains unknown. The aim of this study was to investigate the correlation between the recurrence of AF and the adipose component of the left atrium (LA) in patients who underwent a modified Cox maze (CM) III procedure. We reviewed the pathology data of resected LA tissues from 115 patients, including the adipose tissue from CM-III procedures. The mean follow-up duration was 30.05 ± 23.96 months. The mean adipose tissue component in the AF recurrence group was 16.17% ± 14.32%, while in the non-recurrence group, it was 9.48% ± 10.79% (p = 0.021), and the cut-off value for the adipose component for AF recurrence was 10% (p = 0.010). The rates of freedom from AF recurrence at 1, 3, and 5 years were 84.8%, 68.8%, and 38.6%, respectively, in the high-adipose group (≥10%), and 96.3%, 89.7%, and 80.3%, respectively, in the low-adipose group (<10%; p = 0.002). A high adipose component (≥10%) in the LA is a significant risk factor for AF recurrence after CM-III procedures. Thus, it may be necessary to attempt to reduce the perioperative adipose portion of the cardiac tissue using a statin in a randomized study.