bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the JAK/STAT Inhibitor Tofacitinib on Macrophage Cholesterol Metabolism
Authors: Adorni Maria Pia , Papotti Bianca , Borghi Maria Orietta , Raschi Elena , Zimetti Francesca , Bernini Franco , Meroni Pier Luigi , Ronda Nicoletta
Published: August 2023

The impact of JAK/STAT inhibitors, which are used in various inflammatory diseases, on cardiovascular risk is controversial and has recently raised safety concerns. Our study investigates the direct effects of tofacitinib on macrophage cholesterol metabolism, which is crucial for atherosclerosis plaque development and stability. Cultured human macrophages THP-1 were used to assess the impact of tofacitinib on cell cholesterol efflux and synthesis via radioisotopic methods, and on cholesterol uptake by measuring the cell cholesterol content with a fluorometric assay. The cholesterol acceptors and donors were either standard lipoproteins or sera from patients with juvenile idiopathic arthritis (JIA) and from control subjects. Tofacitinib significantly increased the macrophage cholesterol efflux to all acceptors; it reduced cholesterol uptake from both the normal and hypercholesterolemic sera; and it reduced cholesterol synthesis. The treatment of macrophages with tofacitinib was able to increase the cholesterol efflux and decrease cholesterol uptake when using sera from untreated JIA patients with active disease as cholesterol acceptors and donors, respectively. In conclusion, our in vitro data support the concept that tofacitinib has a favorable impact on macrophage cholesterol metabolism, even in the presence of sera from rheumatologic patients, and suggest that other mechanisms may be responsible for the cardiovascular risk associated with tofacitinib use in selected patient populations.
Catalyst Design through Grafting of Diazonium Salts—A Critical Review on Catalyst Stability
Authors: Smołka Szymon , Krukiewicz Katarzyna
Published: August 2023

In the pursuit of designing a reusable catalyst with enhanced catalytic activity, recent studies indicate that electrochemical grafting of diazonium salts is an efficient method of forming heterogeneous catalysts. The aim of this review is to assess the industrial applicability of diazonium-based catalysts with particular emphasis on their mechanical, chemical, and thermal stability. To this end, different approaches to catalyst production via diazonium salt chemistry have been compared, including the immobilization of catalysts by a chemical reaction with a diazonium moiety, the direct use of diazonium salts and nanoparticles as catalysts, the use of diazonium layers to modulate wettability of a carrier, as well as the possibility of transforming the catalyst into the corresponding diazonium salt. After providing descriptions of the most suitable carriers, the most common deactivation routes of catalysts have been discussed. Although diazonium-based catalysts are expected to exhibit good stability owing to the covalent bond created between a catalyst and a post-diazonium layer, this review indicates the paucity of studies that experimentally verify this hypothesis. Therefore, use of diazonium salts appears a promising approach in catalysts formation if more research efforts can focus on assessing their stability and long-term catalytic performance.
Tools for Etiologic Diagnosis of Drug-Induced Allergic Conditions
Authors: Rodríguez-Pérez Rosa , de las Vecillas Leticia , Cabañas Rosario , Bellón Teresa
Published: August 2023

Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice.
Depletion of SNORA33 Abolishes ψ of 28S-U4966 and Affects the Ribosome Translational Apparatus
Authors: Chabronova Alzbeta , van den Akker Guus , Housmans Bas A. C. , Caron Marjolein M. J. , Cremers Andy , Surtel Don A. M. , Peffers Mandy J. , van Rhijn Lodewijk W. , Marchand Virginie , Motorin Yuri , Welting Tim J. M.
Published: August 2023

Eukaryotic ribosomes are complex molecular nanomachines translating genetic information from mRNAs into proteins. There is natural heterogeneity in ribosome composition. The pseudouridylation (ψ) of ribosomal RNAs (rRNAs) is one of the key sources of ribosome heterogeneity. Nevertheless, the functional consequences of ψ-based ribosome heterogeneity and its relevance for human disease are yet to be understood. Using HydraPsiSeq and a chronic disease model of non-osteoarthritic primary human articular chondrocytes exposed to osteoarthritic synovial fluid, we demonstrated that the disease microenvironment is capable of instigating site-specific changes in rRNA ψ profiles. To investigate one of the identified differential rRNA ψ sites (28S-ψ4966), we generated SNORA22 and SNORA33 KO SW1353 cell pools using LentiCRISPRv2/Cas9 and evaluated the ribosome translational capacity by 35S-Met/Cys incorporation, assessed the mode of translation initiation and ribosomal fidelity using dual luciferase reporters, and assessed cellular and ribosomal proteomes by LC-MS/MS. We uncovered that the depletion of SNORA33, but not SNORA22, reduced 28S-ψ4966 levels. The resulting loss of 28S-ψ4966 affected ribosomal protein composition and function and led to specific changes in the cellular proteome. Overall, our pioneering findings demonstrate that cells dynamically respond to disease-relevant changes in their environment by altering their rRNA pseudouridylation profiles, with consequences for ribosome function and the cellular proteome relevant to human disease.
Impact of Obesity on Atrial Electrophysiological Substrate
Authors: Schram Serban Corina , de Groot Natasja M. S.
Published: August 2023

(1) Background. Obesity is a well-established worldwide recognised risk factor for atrial fibrillation (AF). Prior review papers reported on the associations between obesity and AF development, but not on the relation between obesity and atrial electrophysiology. We therefore conducted a systematic review to describe the current knowledge of the characteristics of the atrial electrophysiological substrate in obese individuals and how they relate to the development of AF. (2) Methods. A search was conducted in Pubmed, Embase, and the Cochrane Library for publications evaluating the impact of obesity on atrial electrophysiology, electrical substrates, and their relation to the development of AF. (3) Results. A systematic literature search retrieved 477 potential publications based on the inclusion criteria; 76 full-text articles were selected for the present systematic review. The literature demonstrated that obesity predisposes to not only a higher AF incidence but also to more extensive atrial electrophysiological abnormalities increasing susceptibility to AF development. (4) Conclusion. Obesity may predispose to an overall increase in atrial electropathology, consisting of an increase in the slowing of the conduction, conduction block, low-voltage areas, and complex fractionated electrograms. To determine the impact of obesity-induced atrial electrical abnormalities on the long-term clinical outcome, further prospective studies are mandatory.
Does Screening for Bipolar Disorders Identify a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS)? A Heuristic Working Hypothesis
Authors: Carta Mauro Giovanni , Kalcev Goce , Fornaro Michele , Pinna Samantha , Gonzalez Cesar Ivan Aviles , Nardi Antonio Egidio , Primavera Diego
Published: August 2023

The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, identifying a specific syndrome. This is a case-control study based on a database from a community survey. Cases: MDQ-positive without mood disorders; Controls: MDQ negatives matched by sex, age, and psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Tools: MDQ, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) semi-structured interview for psychiatric diagnosis, and the Health Survey Short Form (SF-12) for measuring HRQol. People scoring positive on the MDQ without a diagnosis of mood disorders showed significantly lower scores on the SF-12 compared to people of the same age and of the same sex with an equal diagnosis of psychiatric disorders not related to mood disorders (35.21 ± 6.30 vs. 41.48 ± 3.39, p < 0.0001). In the debate whether a positive score on the MDQ selects an area of “malaise” due to the presence of disorders differing from Bipolar Disorders, or if a positive score on the MDQ may be considered a “subthreshold” form of bipolar disorder in people who may later develop bipolar disorder, a third hypothesis can be advanced, i.e., that a positive score on the MDQ identifies a specific “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS), characterized by a considerable amount of suffering and not attributable to other disorders, and which might represent a trigger for the previously mentioned disorders with which a positive score on the MDQ is associated, probably including, in severe conditions, bipolar disorder.
Association between Serum Varicella-Zoster Virus IgM and IgG and Prognosis of Ramsay Hunt Syndrome
Authors: Chung Seok Hwan , Kim Jung Min , Rim Hwa Sung , Yeo Seung Geun , Kim Sang Hoon
Published: August 2023

Ramsay Hunt syndrome (RHS) has a poor prognosis because of varicella-zoster virus (VZV) infection. This is most closely related to severe inflammation in the geniculate ganglion of the facial nerve due to VZV infection or reactivation. This study investigated whether there were differences in the prognosis and accompanying symptoms of facial paralysis based on the presence or absence of VZV IgM and IgG antibodies. This study was conducted as a retrospective chart analysis of 105 patients with RHS who were admitted to our hospital between 2015 and 2021. The House–Brackmann (HB) grade and electroneurography (ENoG) was used to evaluate the degree of facial paralysis. Patients’ subjective symptoms were evaluated by dividing them into dizziness, tinnitus, hyperacusis, and hearing loss. No difference was observed in the initial HB grade with or without IgM; however, the final HB grade was significantly higher in IgM-positive patients than in IgM-negative patients (p < 0.05). Further, when IgM was positive, the value of the orbicularis oculi muscle in the ENoG test results was significantly higher (p < 0.05), and symptoms of tinnitus and hyperacusis occurred more frequently (p < 0.05). The initial and final HB grades were significantly higher in IgG-positive patients than in IgG-negative patients (p < 0.05). When IgG was positive, the values of nasalis and oris muscles in the ENoG test results were significantly higher (p < 0.05), and symptoms of dizziness occurred more frequently (p < 0.05). This study confirmed that the more active the immunological action of the VZV in the body, the greater the damage to the facial and vestibulocochlear nerves, which are associated with the degree of facial paralysis and the accompanying otologic symptoms.
Position of the ISTENT Inject® Trabecular Micro-Bypass System Visualized with the NIDEK GS-1 Gonioscope—A Postoperative Analysis
Authors: Zimmermann Julian Alexander , Storp Jens Julian , Merté Ralph-Laurent , Heiduschka Peter , Eter Nicole , Brücher Viktoria Constanze
Published: August 2023

Glaucoma is one of the leading causes of irreversible blindness globally and is characterized by the gradual loss of retinal ganglion cells. The primary risk factor for the development and progression of glaucoma is increased intraocular pressure (IOP). Numerous surgical interventions exist to lower IOP should conservative therapy fail. One trend in recent years has been minimally invasive glaucoma surgery (MIGS) as an alternative to traditional methods. The ISTENT inject® is an ab interno trabecular micro-bypass implant designed to be implanted through the trabecular meshwork into the Schlemm’s canal to lower IOP. The aim of the study was the postoperative visualization and description of the positioning of the ISTENT inject® using automated circumferential goniophotography. Patients with symptomatic cataracts and mild to moderate primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEX), and pigment-dispersion glaucoma were included who underwent combined cataract surgery with the ISTENT inject® and received postoperative automated gonioscopy with the NIDEK Gonioscope GS-1 to visualize the location of the implant. Twenty-four implants of 14 eyes in 11 patients could be visualized. Out of the implants, 14.3% were in the trabecular meshwork, 46.4% were at the border between the trabecular meshwork and scleral spur, 25% were below the trabecular meshwork, and 14.3% of the implants were not detectable in the gonioscopy. In the overall cohort, a statistically significant IOP reduction was found over the 12-month postoperative observation period. Even in three eyes, in each of which both stents were located below the trabecular meshwork, an IOP reduction over 12 months was observed compared to the baseline IOP. In this study, vertical two-dimensional positioning of the ISTENT inject® was performed for the first time using NIDKE GS-1 automated 360° goniophotography. The method is suitable for postoperative visualization, control, and documentation of positioning after ISTENT inject® implantation. Further studies are needed to analyze the correlation between positioning of the ISTENT inject® in the chamber angle and postoperative IOP reduction.
Transvenous Lead Extraction during Cardiac Implantable Device Upgrade: Results from the Multicenter Swiss Lead Extraction Registry
Authors: Haeberlin Andreas , Noti Fabian , Breitenstein Alexander , Auricchio Angelo , Reichlin Tobias , Conte Giulio , Klersy Catherine , Curti Moreno , Pruvot Etienne , Domenichini Giulia , Schaer Beat , Kühne Michael , Gruszczynski Michal , Burri Haran , Kobza Richard , Grebmer Christian , Regoli François D.
Published: August 2023

Background: Device patients may require upgrade interventions from simpler to more complex cardiac implantable electronic devices. Prior to upgrading interventions, clinicians need to balance the risks and benefits of transvenous lead extraction (TLE), additional lead implantation or lead abandonment. However, evidence on procedural outcomes of TLE at the time of device upgrade is scarce. Methods: This is a post hoc analysis of the investigator-initiated multicenter Swiss TLE registry. The objectives were to assess patient and procedural factors influencing TLE outcomes at the time of device upgrades. Results: 941 patients were included, whereof 83 (8.8%) had TLE due to a device upgrade. Rotational mechanical sheaths were more often used in upgraded patients (59% vs. 42.7%, p = 0.015) and total median procedure time was longer in these patients (160 min vs. 105 min, p < 0.001). Clinical success rates of upgraded patients compared to those who received TLE due to other reasons were not different (97.6% vs. 93.0%, p = 0.569). Moreover, multivariable analysis showed that upgrade procedures were not associated with a greater risk for complications (HR 0.48, 95% confidence interval 0.14–1.57, p = 0.224; intraprocedural complication rate of upgraded patients 7.2% vs. 5.5%). Intraprocedural complications of upgraded patients were mostly associated with the implantation and not the extraction procedure (67% vs. 33% of complications). Conclusions: TLE during device upgrade is effective and does not attribute a disproportionate risk to the upgrade procedure.
Experimental Analysis and Spatial Component Impact of the Inert Cross Flow in Open-Architecture Laser Powder Bed Fusion
Authors: Kjer Magnus Bolt , Pan Zhihao , Nadimpalli Venkata Karthik , Pedersen David Bue
Published: August 2023

Laser-based powder bed fusion is an additive manufacturing process in which a high-power laser melts a thin layer of metal powder layer by layer to yield a three-dimensional object. An inert gas must remove process byproducts formed during laser processing to ensure a stable and consistent process. The process byproducts include a plasma plume and spatter particles. An NC sensor gantry is installed inside a bespoke open-architecture laser-based powder bed fusion system to experimentally characterize the gas velocity throughout the processing area. The flow maps are compared to manufactured samples, where the relative density and melt pools are analyzed, seeking a potential correlation between local gas flow conditions and the components. The results show a correlation between low gas flow velocities and increased porosity, leading to lower part quality. Local flow conditions across the build plate also directly impact components, highlighting the importance of optimizing the gas flow subsystem. The experimental flow analysis method enables optimization of the gas flow inlet geometry, and the data may be used to calibrate the computational modeling of the process.
Determination of the Influence of the Tool Side Stress Superposition and Tool Geometry on the Cut Surface Quality during Precision Shear Cutting
Authors: Graf Alexander , Kräusel Verena , Weise Dieter , Petrů Jana , Koziorek Jiří , Bhandari Pravishan
Published: August 2023

Shearing high-strength steels often leads to a subpar cut quality and excessive stress on the tool components. To enhance the quality of the cut surface, intricate techniques like fine blanking are commonly employed. However, for applications with lower quality requirements, precision shear cutting offers an alternative solution. This research paper introduces a novel approach to directly superimpose radial stress on a workpiece during the precision shear cutting process and showcases for the first time how the application of direct stress superimposition can impact the cut surface by concurrently modifying the shear cutting edge and punch surface. A statistical experimental design is employed to investigate the interrelationships between the parameters and their effects. The results indicate that the overall cut quality, including cylindricity, clean-cut angle, rollover height, and tool stress, defined by punch force and retraction force, is influenced by the superimposed stress. Regarding the clean-cut zone, the statistical significance of direct radially superimposed stress was not observed, except when interacting with sheet thickness and clearance. Additionally, the sheet thickness and cutting gap emerged as significant parameters affecting the overall quality of the cut surface.
Projected Changes in Spawning Ground Distribution of Mature Albacore Tuna in the Indian Ocean under Various Global Climate Change Scenarios
Authors: Mondal Sandipan , Ray Aratrika , Lee Ming-An , Boas Malagat
Published: August 2023

The present study utilised a geometric mean model in which sea surface temperature, oxygen, and sea surface salinity were used to predict the effects of climate change on the habitats of mature albacore tuna in the Indian Ocean under multiple representative concentration pathway (RCP) scenarios. Data pertaining to the albacore tuna fishing conducted by Taiwanese longline fisheries during the October–March period in 1998–2016 were analysed. The fishery data comprised fishing location (latitude and longitude), fishing effort (number of hooks used), number of catches, fishing time (month and year), and fish weight. Nominal catch per unit effort data were standardised to mitigate the potential effects of temporal and spatial factors in causing bias and overestimation. The Habitat Suitability Index (HSI) scores of potential habitats for mature albacore in the Indian Ocean are predicted to change considerably in response to varying levels of predicted climate change. Under projected warm climate conditions (RCP 8.5), the stratification of water is predicted to cause low HSI areas to expand and potential habitats for mature albacore to shift southward by 2100. The findings derived from these mature albacore habitat forecasts can contribute to the evaluation of potential hazards and feasible adaptation measures for albacore fishery resources in the context of climate change. The distribution trends pertaining to potential habitats for mature albacore should be used with caution and can provide resource stakeholders with guidance for decision-making.
Sensitivity Baselines, Resistance Monitoring, and Molecular Mechanisms of the Rice False Smut Pathogen Ustilaginoidea virens to Prochloraz and Azoxystrobin in Four Regions of Southern China
Authors: Fang Anfei , Zhang Ruixuan , Qiao Wei , Peng Tao , Qin Yubao , Wang Jing , Tian Binnian , Yu Yang , Sun Wenxian , Yang Yuheng , Bi Chaowei
Published: August 2023

Rice false smut caused by Ustilaginoidea virens is one of the most devastating fungal diseases of rice (Oryza sativa) worldwide. Prochloraz and azoxystrobin belong to the groups of demethylation inhibitors and quinone outside inhibitors, respectively, and are commonly used for controlling this disease. In this study, we analyzed the sensitivities of 100 U. virens isolates from Yunnan, Sichuan, Chongqing, and Zhejiang in Southern China to prochloraz and azoxystrobin. The ranges of EC50 for prochloraz and azoxystrobin were 0.004−0.536 and 0.020−0.510 μg/mL, with means and standard errors of 0.062 ± 0.008 and 0.120 ± 0.007 μg/mL, respectively. However, the sensitivity frequency distributions of U. virens to prochloraz and azoxystrobin indicated the emergence of subpopulations with decreased sensitivity. Therefore, the mean EC50 values of 74% and 68% of the isolates at the main peak, 0.031 ± 0.001 and 0.078 ± 0.004 μg/mL, were used as the sensitivity baselines of U. virens to prochloraz and azoxystrobin, respectively. We found significant sensitivity differences to azoxystrobin among different geographical populations and no correlation between the sensitivities of U. virens to prochloraz and azoxystrobin. Among 887 U. virens isolates, the isolate 5-3-1 from Zhejiang showed moderate resistance to prochloraz, with a resistance factor of 22.45, while no nucleotide variation in the 1986-bp upstream or 1827-bp gene regions of CYP51 from 5-3-1 was detected. Overexpression of CYP51 is probably responsible for its resistance to prochloraz. Finally, artificial inoculation showed that 5-3-1 was highly pathogenic to rice, suggesting that the resistance of U. virens to prochloraz must be monitored and managed in Zhejiang.
Strategies for the Development of Industrial Fungal Producing Strains
Authors: Salazar-Cerezo Sonia , de Vries Ronald P. , Garrigues Sandra
Published: August 2023

The use of microorganisms in industry has enabled the (over)production of various compounds (e.g., primary and secondary metabolites, proteins and enzymes) that are relevant for the production of antibiotics, food, beverages, cosmetics, chemicals and biofuels, among others. Industrial strains are commonly obtained by conventional (non-GMO) strain improvement strategies and random screening and selection. However, recombinant DNA technology has made it possible to improve microbial strains by adding, deleting or modifying specific genes. Techniques such as genetic engineering and genome editing are contributing to the development of industrial production strains. Nevertheless, there is still significant room for further strain improvement. In this review, we will focus on classical and recent methods, tools and technologies used for the development of fungal production strains with the potential to be applied at an industrial scale. Additionally, the use of functional genomics, transcriptomics, proteomics and metabolomics together with the implementation of genetic manipulation techniques and expression tools will be discussed.
Quantifying Damages to Soil Health and Emissions from Land Development in the State of Illinois (USA)
Authors: Mikhailova Elena A. , Zurqani Hamdi A. , Lin Lili , Hao Zhenbang , Post Christopher J. , Schlautman Mark A. , Post Gregory C. , Shepherd George B. , Dixon Renee M.
Published: August 2023

The concept of soil health is increasingly being used as an indicator for sustainable soil management and even includes legislative actions. Current applications of soil health often lack geospatial and monetary analyses of damages (e.g., land development), which can degrade soil health through loss of carbon (C) and productive soils. This study aims to evaluate the damages to soil health (e.g., soil C, the primary soil health indicator) attributed to land developments within the state of Illinois (IL) in the United States of America (USA). All land developments in IL can be associated with damages to soil health, with 13,361.0 km2 developed, resulting in midpoint losses of 2.5 × 1011 of total soil carbon (TSC) and a midpoint social cost of carbon dioxide emissions (SC-CO2) of $41.8B (where B = billion = 109, USD). More recently developed land area (721.8 km2) between 2001 and 2016 likely caused the midpoint loss of 1.6 × 1010 kg of TSC and a corresponding midpoint of $2.7B in SC-CO2. New developments occurred adjacent to current urban areas near the capital cities of Springfield, Chicago, and St. Louis (the border city between the states of Missouri and IL). Results of this study reveal several types of damage to soil health from developments: soil C loss, associated “realized” soil C social costs (SC-CO2), and loss of soil C sequestration potential from developments. The innovation of this study has several aspects. Geospatial analysis of land cover combined with corresponding soil types can identify changes in the soil health continuum at the landscape level. Because soil C is a primary soil health indicator, land conversions caused by developments reduce soil health and the availability of productive soils for agriculture, forestry, and C sequestration. Current IL soil health legislation can benefit from this landscape level data on soil C loss with GHG emissions and associated SC-CO2 costs by providing insight into the soil health continuum and its dynamics. These techniques and data can also be used to expand IL’s GHG emissions reduction efforts from being solely focused on the energy sector to include soil-based emissions from developments. Current soil health legislation does not recognize that soil’s health is harmed by disturbance from land developments and that this disturbance results in GHG emissions. Soil health programs could be broadened to encourage less disturbance of soil types that release high levels of GHG and set binding targets based on losses in the soil health continuum.
How Does Smart City Construction Affect Urban–Rural Collaborative Development? A Quasi-Natural Experiment from Chinese Cities
Authors: Gong Daxin , Shan Xiaofan
Published: August 2023

In recent years, smart city construction has brought significant social and economic impacts to emerging economies, especially in narrowing the urban–rural gap. However, there is relatively little empirical research on this aspect. We take China as an example for research. This study uses a Spatial Multi-period Difference-in-Differences (DID) approach to investigate the relationship between smart city construction and urban–rural collaborative development in Chinese cities, taking digital infrastructure as the mechanism variable. Our findings reveal that smart city construction significantly promotes urban–rural collaborative development and exhibits positive spatial externalities. These results remain robust after parallel trend tests, placebo checks, and controlling for other policy interferences. Further analysis suggests that this effect operates largely through the reinforcement of digital infrastructure, whereby the smart city initiatives enhance connectivity and interaction between urban and rural areas, fostering collaborative development. Moreover, the efficacy of smart city policies is found to be particularly prominent in cities with strong economic development, weak levels of urban–rural collaborative development, and high degrees of digitization. By illuminating the role of smart city construction in propelling urban–rural collaborative development, this study provides valuable insights for policymakers.
Optimization of a 6-DOF Platform for Simulators Based on an Analysis of Structural and Force Parameters
Authors: Duyun Tatiana , Duyun Ivan , Kabalyants Petr , Rybak Larisa
Published: August 2023

Automotive driving simulators are widely used in driving schools and training centers, where they help students acquire the necessary skills without risk to life and health. This paper presents modern research in the field of creating a model and a real prototype of an automotive driving simulator based on the Gough–Stewart platform. This investigation presents optimized geometric parameters using the PSO algorithm. Virtual prototypes of the robotic platform were created by MSC Adams. In turn, this made it possible to conduct the simulation of kinematic and dynamic parameters. They represent operating conditions when exposed to workloads. This paper shows a prototype of an automotive driving simulator and special equipment with an integrated system of virtual 3D models of real terrain.
Properties of Multivariate Hermite Polynomials in Correlation with Frobenius–Euler Polynomials
Authors: Zayed Mohra , Wani Shahid Ahmad , Quintana Yamilet
Published: August 2023

A comprehensive framework has been developed to apply the monomiality principle from mathematical physics to various mathematical concepts from special functions. This paper presents research on a novel family of multivariate Hermite polynomials associated with Apostol-type Frobenius–Euler polynomials. The study derives the generating expression, operational rule, differential equation, and other defining characteristics for these polynomials. Additionally, the monomiality principle for these polynomials is verified. Moreover, the research establishes series representations, summation formulae, and operational and symmetric identities, as well as recurrence relations satisfied by these polynomials.
Black-Box Solver for Numerical Simulations and Mathematical Modelling in Engineering Physics
Authors: Martynenko Sergey I. , Varaksin Aleksey Yu.
Published: August 2023

This article presents a two-grid approach for developing a black-box iterative solver for a large class of real-life problems in continuum mechanics (heat and mass transfer, fluid dynamics, elasticity, electromagnetism, and others). The main requirements on this (non-)linear black-box solver are: (1) robustness (the lowest number of problem-dependent components), (2) efficiency (close-to-optimal algorithmic complexity), and (3) parallelism (a parallel robust algorithm should be faster than the fastest sequential one). The basic idea is to use the auxiliary structured grid for more computational work, where (non-)linear problems are simpler to solve and to parallelize, i.e., to combine the advantages of unstructured and structured grids: simplicity of generation in complex domain geometry and opportunity to solve (non-)linear (initial-)boundary value problems by using the Robust Multigrid Technique. Topics covered include the description of the two-grid algorithm and estimation of their robustness, convergence, algorithmic complexity, and parallelism. Further development of modern software for solving real-life problems justifies relevance of the research. The proposed two-grid algorithm can be used in black-box parallel software for the reduction in the execution time in solving (initial-)boundary value problems.
Teaching and Playing? A Survey on Young Musicians’ Well-Being and Motivations
Authors: Sacchetti Silvia , Salustri Andrea
Published: August 2023

The aim of this study is to analyze the well-being of young music teachers working in Trentino Music Schools (TMS). Specifically, we assess (i) the extent to which the interaction between teaching and playing affects the well-being of young musicians using a satisfaction measure for their overall professional path as teachers and musicians, and (ii) what extrinsic and intrinsic drivers may guide their involvement in teaching activities in the early stages of their careers. To this end, we analyze original survey data on young musicians teaching in TMS to estimate their relative satisfaction and identify their motivational drivers. Specifically, we estimate from elementary items six constructs concerning material work conditions, immaterial welfare (i.e., the capabilities activated by the schools), and initial monetary and non-monetary motivations to become a music teacher, then we run two ordered logit regressions to test whether a set of variables of interest and the estimated constructs contribute to explaining junior teachers’ satisfaction. Our findings highlight that junior teachers are satisfied if they can preserve the desired proportion of artistic activity and can teach a consistent number of hours so as to leave the desired space and time for making music independently of school activities. They consider teaching to be one of the components of their professional activities and can be expected to try to maintain sufficient space to be able to also develop the independent artistic sphere of their career as musicians.
The Unicellular, Parasitic Fungi, Sanchytriomycota, Possess a DNA Sequence Possibly Encoding a Long Tubulin Polymerization Promoting Protein (TPPP) but Not a Fungal-Type One
Authors: Orosz Ferenc
Published: August 2023

The unicellular, parasitic fungi of the phylum Sanchytriomycota (sanchytrids) were discovered a few years ago. These unusual chytrid-like fungi parasitize algae. The zoospores of the species of the phylum contain an extremely long kinetosome composed of microtubular singlets or doublets and a non-motile pseudocilium (i.e., a reduced posterior flagellum). Fungi provide an ideal opportunity to test and confirm the correlation between the occurrence of flagellar proteins (the ciliome) and that of the eukaryotic cilium/flagellum since the flagellum occurs in the early-branching phyla and not in terrestrial fungi. Tubulin polymerization promoting protein (TPPP)-like proteins, which contain a p25alpha domain, were also suggested to belong to the ciliome and are present in flagellated fungi. Although sanchytrids have lost many of the flagellar proteins, here it is shown that they possess a DNA sequence possibly encoding long (animal-type) TPPP, but not the fungal-type one characteristic of chytrid fungi. Phylogenetic analysis of p25alpha domains placed sanchytrids into a sister position to Blastocladiomycota, similarly to species phylogeny, with maximal support.
Characterization of the Pathogenic Potential of the Beach Sand Microbiome and Assessment of Quicklime as a Remediation Tool
Authors: Soffritti Irene , D’Accolti Maria , Bini Francesca , Mazziga Eleonora , Volta Antonella , Bisi Matteo , Rossi Silvia , Viroli Francesco , Balzani Marcello , Petitta Marco , Mazzacane Sante , Caselli Elisabetta
Published: August 2023

Beach sand may act as a reservoir for potential human pathogens, posing a public health risk. Despite this, the microbiological monitoring of sand microbiome is rarely performed to determine beach quality. In this study, the sand microbial population of a Northern Adriatic Sea beach sand was profiled by microbiological (CFU counts) and molecular methods (WGS, microarray), showing significant presence of potential human pathogens including drug-resistant strains. Consistent with these results, the potential of quicklime as a restoring method was tested in vitro and on-field. Collected data showed that adding 1–3% quicklime (w/w) to sand provided an up to −99% of bacteria, fungi, and viruses, in a dose- and time-dependent manner, till 45 days post-treatment. In conclusion, data suggest that accurate monitoring of sand microbiome may be essential, besides water, to assess beach quality and safety. Moreover, first evidences of quicklime potential for sand decontamination are provided, suggesting its usage as a possible way to restore the microbiological quality of sand in highly contaminated areas.
Synthesis, Antioxidant, Molecular Docking and DNA Interaction Studies of Metal-Based Imine Derivatives
Authors: Ibrahim Mohammad , Nabi Hazrat Un , Muhammad Niaz , Ikram Muhammad , Khan Momin , Ibrahim Musadiq , AlAsmari Abdullah F. , Alharbi Metab , Alshammari Abdulrahman
Published: August 2023

Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. The metal complexes have shown significant dose-dependent antioxidant activities higher than those of the free ligand but lesser than those of the standard antioxidant, ascorbic acid. The DNA binding constants (Kb) were found in the order Zn(pimp)2 {9.118 × 105 M−1} > H-pimp {3.487 × 105 M−1} > Co(pimp)2 {3.090 × 105 M−1} > Ni(pimp)2 {1.858 × 105 M−1} > Cu(pimp)2 {1.367 × 105 M−1}. Binding constants (Kb) values calculated from the molecular docking analysis were found to be in close agreement with the experimental results. The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs.
Computer-Aided Designing Peptide Inhibitors of Human Hematopoietic Prostaglandin D2 Synthase Combined Molecular Docking and Molecular Dynamics Simulation
Authors: Cui Jing , Feng Yongwei , Yang Ting , Wang Xinglong , Tang Heng
Published: August 2023

Human hematopoietic prostaglandin D2 synthase (HPGDS) is involved in the production of prostaglandin D2, which participates in various physiological processes, including inflammation, allergic reactions, and sleep regulation. Inhibitors of HPGDS have been investigated as potential anti-inflammatory agents. For the investigation of potent HPGDS inhibitors, we carried out a computational modeling study combining molecular docking and molecular dynamics simulation for selecting and virtual confirming the designed binders. We selected the structure of HPGDS (PDB ID: 2CVD) carrying its native inhibitor compound HQL as our research target. The random 5-mer peptide library was created by building the 3-D structure of random peptides using Rosetta Buildpeptide and performing conformational optimization. Molecular docking was carried out by accommodating the peptides into the location of their native binder and then conducting docking using FlexPepDock. The two peptides RMYYY and VMYMI, which display the lowest binding energy against HPGDS, were selected to perform a comparative study. The interaction of RMYYY and VMYMI against HPGDS was further confirmed using molecular dynamics simulation and aligned with its native binder, HQL. We show the selected binders to have stronger binding energy and more frequent interactions against HPGDS than HQL. In addition, we analyzed the solubility, hydrophobicity, charge, and bioactivity of the generated peptides, and we show that the selected strong binder may be further used as therapeutic drugs.
Solvent-Free Determination of Selected Polycyclic Aromatic Hydrocarbons in Plant Material Used for Food Supplements Preparation: Optimization of a Solid Phase Microextraction Method
Authors: Benedetti Barbara , Di Carro Marina , Scapuzzi Chiara , Magi Emanuele
Published: August 2023

The exploitation of waste and by-products in various applications is becoming a cornerstone of the circular economy. A range of biomasses can be employed to produce food supplements. An example is a particular extract obtained from plant buds (rich in bioactive molecules), which can be easily retrieved from cities’ pruning. In order to safely use this material, its possible contamination by organic pollutants needs to be estimated. A green and simple method to detect priority polycyclic aromatic hydrocarbons (PAHs) in bud samples by head space solid phase microextraction coupled to GC-MS was developed. This strategy, optimized through experimental design and response surface methodology, requires a minimal sample pre-treatment and negligible solvent consumption. The final method was found to be accurate and sensitive for PAHs with mass up to 228 Da. For these analytes, satisfactory figures of merit were achieved, with detection limits in the range 1–4 ng g−1, good inter-day precision (relative standard deviation in the range 4–11%), and satisfactory accuracy (88–105%), along with specificity guaranteed by the selected ion monitoring detection. The method was applied to bud samples coming from differently polluted areas, thus helping in estimating the safety of their use for the production of food supplements.
Rapid and Low-Cost Quantification of Adulteration Content in Camellia Oil Utilizing UV-Vis-NIR Spectroscopy Combined with Feature Selection Methods
Authors: Liu Qiang , Gong Zhongliang , Li Dapeng , Wen Tao , Guan Jinwei , Zheng Wenfeng
Published: August 2023

This study aims to explore the potential use of low-cost ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy to quantify adulteration content of soybean, rapeseed, corn and peanut oils in Camellia oil. To attain this aim, test oil samples were firstly prepared with different adulterant ratios ranging from 1% to 90% at varying intervals, and their spectra were collected by an in-house built experimental platform. Next, the spectra were preprocessed using Savitzky–Golay (SG)–Continuous Wavelet Transform (CWT) and the feature wavelengths were extracted using four different algorithms. Finally, Support Vector Regression (SVR) and Random Forest (RF) models were developed to rapidly predict adulteration content. The results indicated that SG–CWT with decomposition scale of 25 and the Iterative Variable Subset Optimization (IVSO) algorithm can effectively improve the accuracy of the models. Furthermore, the SVR model performed best for predicting adulteration of camellia oil with soybean oil, while the RF models were optimal for camellia oil adulterated with rapeseed, corn, or peanut oil. Additionally, we verified the models’ robustness by examining the correlation between the absorbance and adulteration content at certain feature wavelengths screened by IVSO. This study demonstrates the feasibility of using low-cost UV-Vis-NIR spectroscopy for the authentication of Camellia oil.
Exploring Species-Specificity in TLR4/MD-2 Inhibition with Amphiphilic Lipid A Mimicking Glycolipids
Authors: Borio Alessio , Holgado Aurora , Passegger Christina , Strobl Herbert , Beyaert Rudi , Heine Holger , Zamyatina Alla
Published: August 2023

The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex is a key receptor of the innate immune system and a major driver of inflammation that is responsible for the multifaceted defense response to Gram-negative infections. However, dysfunction in the tightly regulated mechanisms of TLR4-mediated signaling leads to the uncontrolled upregulation of local and systemic inflammation, often resulting in acute or chronic disease. Therefore, the TLR4/MD-2 receptor complex is an attractive target for the design and development of anti-inflammatory therapies which aim to control the unrestrained activation of TLR4-mediated signaling. Complex structure–activity relationships and species-specificity behind ligand recognition by the TLR4/MD-2 complex complicate the development of MD-2-specific TLR4 antagonists. The restriction of the conformational flexibility of the disaccharide polar head group is one of the key structural features of the newly developed lipid A—mimicking glycophospholipids, which are potential inhibitors of TLR4-mediated inflammation. Since phosphorylation has a crucial influence on MD-2–ligand interaction, glycolipids with variable numbers and positioning of phosphate groups were synthesized and evaluated for their ability to inhibit TLR4-mediated pro-inflammatory signaling in human and murine immune cells. A bis-phosphorylated glycolipid was found to have nanomolar antagonist activity on human TLR4 while acting as a partial agonist on murine TLR4. The glycolipid inhibited mTLR4/MD-2-mediated cytokine release, acting as an antagonist in the presence of lipopolysaccharide (LPS), but at the same time induced low-level cytokine production.
Glucosinolates Extracts from Brassica juncea Ameliorate HFD-Induced Non-Alcoholic Steatohepatitis
Authors: Sheu Ming-Jen , Yeh Mei-Chen , Tsai Ming-Chang , Wang Chi-Chih , Chang Yen-Ling , Wang Chau-Jong , Huang Hui-Pei
Published: August 2023

Non-alcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver. It spans a spectrum of diseases from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Brassica juncea is rich in glucosinolates and has been proven to possess many potential pharmacological properties, including hypoglycemic, anti-oxidation, anti-inflammatory, and anti-carcinogenic activities. This study aims to investigate whether whole-plant Brassica juncea (WBJ) and its glucosinolates extracts (BGE) have hepatoprotective effects against a high-fat diet (HFD)-induced NAFLD and further explore the mechanism underlying this process in vivo and in vitro. WBJ treatment significantly reduced body fat, dyslipidemia, hepatic steatosis, liver injury, and inflammation; WBJ treatment also reversed the antioxidant enzyme activity to attenuate oxidative stress in HFD-fed rat liver. Moreover, WBJ and BGE enhanced the activation of AMPK to reduce SREBPs, fatty acid synthase, and HMG-CoA reductase but increased the expression of CPT-I and PPARα to improve hepatic steatosis. In addition, WBJ and BGE could ameliorate NAFLD by inhibiting TNF-α and NF-κB. Based on the above results, this study demonstrates that WBJ and BGE ameliorate HFD-induced hepatic steatosis and liver injury. Therefore, these treatments could represent an unprecedented hope toward improved strategies for NAFLD.
The Sophisticated and Naive View of Moral Experience
Authors: Mylonaki Evgenia
Published: August 2023

In this paper, I draw a contrast between two ways of posing the question of moral experience: the episodic and the contemplative. On the first, the episodic outlook, the question of moral experience is the question of specifying the workings of a capacity (or set of capacities) whose exercise may ground claims of moral knowledge. On the contemplative outlook, on the other hand, the question of understanding moral experience is the question of articulating a standpoint: the moral standpoint. On this view, philosophical reflection on moral experience aims to shed light on the human experiences that paradigmatically exemplify and, thus, best reveal the moral standpoint. In the tradition of contemplative accounts, I propose that some of the human experiences that paradigmatically exemplify and reveal the moral standpoint are experiences of “moral growth and change”. Finally, I argue that in “moral growth and change”, one is in view of the world as what is at stake. This leads to a different sense in which moral experience grounds knowledge claims.