bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Coastal Walking Outdoors and Virtual Reality Indoor Walking on Heart Rate, Enjoyment Levels and Mindfulness Experiences in Healthy Adults
Authors: Greco Gianpiero , Centrone Claudio , Poli Luca , Silva Ana Filipa , Russo Luca , Cataldi Stefania , Giustino Valerio , Fischetti Francesco
Published: December 2023

Outdoor exercise is beneficial for psychophysical well-being. Limited studies have compared outdoor and virtual reality (VR) indoor physical activities, especially in coastal settings. Therefore, this study aimed to assess the impact of outdoor coastal walking and indoor walking in a VR simulation with a similar environment on physiological and psychological variables in healthy adults. A total of 26 subjects (14 M and 12 F, age 25.2 ± 2.5 years) voluntarily participated in this crossover randomized controlled and counterbalanced study and were allocated under three conditions: VR indoor walking (INVR), outdoor walking (OUT) and standard indoor walking (IN). IN and INVR conditions were performed on a treadmill (speed 4.5 km/h) and the OUT was performed on a seaside pedestrian road. The same outdoor environment was displayed in the visor during the INVR. Heart rate (HRmean/max), physical activity enjoyment (PACES-It) and state of mindfulness for physical activity (SMS-PA) were assessed at the end of each condition. The OUT condition showed significantly greater PACES-It scores and HRmean than IN and INVR (p < 0.001) and greater SMS-PA scores and HRmax than IN (p < 0.01 and p < 0.05, respectively). No significant differences were found between OUT and INVR regarding HRmax and SMS-PA scores (p > 0.05). Findings suggest that physical activity in an immersive technology may lead to physiological loads comparable to the outdoor environment. OUT is more enjoyable than IN and INVR but exhibits a mindfulness response comparable to INVR. Therefore, INVR could be an alternative to OUT for those who cannot engage in outdoor activities for various reasons.
Visually Significant Dimensions and Parameters for Gloss
Authors: Šarić Donatela , Sole Aditya Suneel
Published: December 2023

The appearance of a surface depends on four main appearance attributes, namely color, gloss, texture, and translucency. Gloss is an important attribute that people use to understand surface appearance, right after color. In the past decades, extensive research has been conducted in the field of gloss and gloss perception, with different aims to understand the complex nature of gloss appearance. This paper reviews the research conducted on the topic of gloss and gloss perception and discusses the results and potential future research on gloss and gloss perception. Our primary focus in this review is on research in the field of gloss and the setup of associated psychophysical experiments. However, due to the industrial and application-oriented nature of this review, the primary focus is the gloss of dielectric materials, a critical aspect in various industries. This review not only summarizes the existing research but also highlights potential avenues for future research in the pursuit of a more comprehensive understanding of gloss perception.
Application of a Microeconomic Approach for Explanation of Citizen Participation in Open Government
Authors: Alderete María Verónica
Published: December 2023

The digital economy and the sharing economy have changed the role citizens may acquire in society. Citizens can perform at least two roles from the open government perspective: on the one hand, they can be passive users/demanders of information and, on the other hand, they can provide or produce the information in an active manner. The objective of this paper is to offer a theoretical model to explain citizens’ incentives to participate in open government projects. Which is the opportunity cost of participation for the citizen? Which are the drivers of the preferences for the social good? This model is based on the utility function and consumption theory. We complement the theoretical framework with an exploratory–descriptive analysis based on a case study’s primary data about citizen participation. In democracy projects where citizens actively collaborate and could earn monetary gains or become entrepreneurs, the opportunity cost of participation is lower than in a passive type and the amount of the social good depends on the preferences. Preferences for social goods are related to community experiences and e-government and they also affect the decision to participate. Very few studies in the field of open government have pretended to explain citizens’ participation by using microeconomic foundations.
In Vitro Effects of Cypermethrin and Glyphosate on LPS-Induced Immune Cell Activation
Authors: El Mabrouk Narjesse , Iulini Martina , Maddalon Ambra , Galbiati Valentina , Harizi Hedi , Mastouri Maha , Corsini Emanuela
Published: December 2023

(1) Background: The insecticide cypermethrin (Cypm) and the herbicide glyphosate (Glyp) are among the most widely used pesticides. While the two pesticides have been considered to have low toxicity in mammals, some indication of potential immunotoxicity has emerged. The aim of this work was to investigate in vitro the effects of Cypm and Glyp on bacteria lipopolysaccharide (LPS)-induced immune cell activation and of Cypm on 2-mercaptobenzothiazole (MBT)-induced maturation of dendritic cells (DCs). (2) Methods: The release of the inflammatory cytokines TNF-α and IL-8, the expression of the surface markers CD54 and CD86 in human primary peripheral blood mononuclear cells (PBMC), and THP-1 cells were investigated together with CD83, HLA-DR, IL-6, and IL-18 in DCs. (3) Results: While no significant modulation on LPS-induced immune cell activation was observed following Glyp exposure, with only a trend toward an increase at the highest concentration tested, Cypm reduced the responses to LPS and to MBT, supporting a direct immunosuppressive effect. Overall, the present study contributes to our understanding of pesticide-induced immunotoxicity, and the results obtained support evidence showing the immunosuppressive effects of Cypm.
Time-Frequency Fusion Features-Based GSWOA-KELM Model for Gear Fault Diagnosis
Authors: Hu Qin , Zhou Haiting , Wang Chengcheng , Zhu Chenxi , Shen Jiaping , He Peng
Published: December 2023

To improve the accuracy of gear fault diagnosis and overcome the low diagnostic accuracy of the model caused by manual parameter selection, a combined diagnostic model based on time-frequency fusion features is combined with the improved global search whale optimization algorithm (GSWOA) to optimize the fault diagnosis capability of the kernel extreme learning machine (KELM). First, the time-domain and frequency-domain features of the gear fault state are extracted separately, and feature vectors are constructed through feature fusion, which overcomes the limitations of single features. Second, the GSWOA based on three strategies is used to optimize the regularization coefficient C and kernel function parameter γ of KELM, and a GSWOA-KELM fault diagnosis model is built to avoid the problem of low fault diagnosis accuracy caused by the manual selection of KELM parameters. Finally, the public dataset from Southeast University is taken to verify the performance of the proposed model by comparing it with KELM, SSA-KELM, and WOA-KELM models. The experimental results demonstrate that the improved time-frequency fusion features-based GSWOA-KELM model shows faster convergence speed and stronger global search ability. Compared with KELM, SSA-KELM, and WOA-KELM models, the performance of the proposed model has been improved by 11.33%, 8.67%, and 1.33%, respectively.
State of the Art in Wearable Wrist Exoskeletons Part II: A Review of Commercial and Research Devices
Authors: Pitzalis Roberto Francesco , Park Daegeun , Caldwell Darwin G. , Berselli Giovanni , Ortiz Jesús
Published: December 2023

Manual handling tasks, both in daily activities and at work, require high dexterity and the ability to move objects of different shapes and sizes. However, musculoskeletal disorders that can arise due to aging, disabilities, overloading, or strenuous work can impact the natural capabilities of the hand with serious repercussions both in working and daily activities. To address this, researchers have been developing and proving the benefits of wrist exoskeletons. This paper, which is Part II of a study on wrist exoskeletons, presents and summarizes wearable wrist exoskeleton devices intended for use in rehabilitation, assistance, and occupational fields. Exoskeletons considered within the study are those available either in a prototyping phase or on the market. These devices can support the human wrist by relieving pain or mitigating fatigue while allowing for at least one movement. Most of them have been designed to be active (80%) for higher force/torque transmission, and soft for better kinematic compliance, ergonomics, and safety (13 devices out of 24, more than 50%). Electric motors and cable transmission (respectively 11 and 9 devices, out of 24, i.e., almost 50% and 40%) are the most common due to their simplicity, controllability, safety, power-to-weight ratio, and the possibility of remote actuation. As sensing technologies, position and force sensors are widely used in all devices (almost 90%). The control strategy depends mainly on the application domain: for rehabilitation, CPM (control passive motion) is preferred (35% of devices), while for assistance and occupational purposes, AAN (assistance-as-needed) is more suitable (38% of the devices). What emerges from this analysis is that, while rehabilitation and training are fields in which exoskeletons have grown more easily and gained some user acceptance (almost 18 devices, of which 4 are available on the market), relatively few devices have been designed for occupational purposes (5, with only 2 available on the market) due to difficulties in meeting the acceptance and needs of users. In this perspective, as a result of the state-of-the-art analysis, the authors propose a conceptual idea for a portable soft wrist exoskeleton for occupational assistance.
Design and Control of Autonomous Flying Excavator
Authors: Zaman Arif , Seo Jaho
Published: December 2023

This study presents a drone-based excavation platform prototype with the key objectives of balancing stability during excavation, sensing, and digging the soil pile autonomously without human intervention. The whole platform was first designed in CAD software, and then each part of the excavator assembly was 3D printed by using PLA filament. The physical system was then combined with numerous electronic components and linked to various software applications for a drone to perform autonomous excavations. Pixhawk Orange Cube served as the main controller for the drone, while Nvidia Jetson Nano was used for processing data and controlling the tip of the bucket at a specified location for the autonomous excavator. Two scenarios were considered to validate the functionality of the developed platform. In the first scenario, the drone flies independently to a construction site, lands, senses the soil, excavates it, and then travels to another location specified by the mission to deposit the soil.
An Optimization Method of Flexible Manufacturing System Reliability Allocation Based on Two Dimension-Reduction Strategies
Authors: Xu Jingjing , Tao Long , Pei Yanhu , Liu Zhifeng , Yan Qiaobin , Cheng Qiang
Published: December 2023

As increasingly extensive applications of flexible manufacturing systems (FMSs) arise, their reliability allocation has been a research hot spot. But, since FMSs are always composed of transfer and buffer devices, production machines, and complex control systems, the large number of basic elements makes the number of variables and constraints of reliability-allocation optimization increase greatly, which leads to the difficulty and inefficiency of optimization. To solve the above problem, two dimension-reduction strategies are proposed for the FMS reliability optimization with low cost and a high level of reliability as the objectives, and they are the reliability-weight double-threshold qualification strategy (RWTS) and the bi-level optimization strategy (BLOS), respectively. Based on these two strategies, an overall reliability-allocation optimization model and a bi-level reliability-allocation optimization model are established based on the FMS reliability evaluation presented in our previous work, and their algorithms based on particle swarm optimization (PSO) are presented. In terms of their contributions, for the RWTS, thresholds of reliability and the weight index of each basic element are set to dynamically reduce the number of variables in each iteration of the optimization; for the BLOS, the overall reliability-allocation optimization problem for transitioning from the FMS to basic elements can be transformed into simpler allocation optimizations from the FMS to subsystems and from subsystems to basic elements, which have fewer variables, and this can largely improve the optimization convergence performance. Through applying this to a box-parts finishing FMS, compared with the traditional optimization method, the high efficiency and the good allocation effect of the optimization based on these two strategies for improving convergence speed are verified by the simulation results. The proposed method has great significance for FMS design due to its limited cost but high-reliability requirement.
Advancing Disability Management in Information Systems: A Novel Approach through Bidirectional Federated Learning-Based Gradient Optimization
Authors: Khan Surbhi Bhatia , Alojail Mohammed , Al Moteri Moteeb
Published: December 2023

Disability management in information systems refers to the process of ensuring that digital technologies and applications are designed to be accessible and usable by individuals with disabilities. Traditional methods face several challenges such as privacy concerns, high cost, and accessibility issues. To overcome these issues, this paper proposed a novel method named bidirectional federated learning-based Gradient Optimization (BFL-GO) for disability management in information systems. In this study, bidirectional long short-term memory (Bi-LSTM) was utilized to capture sequential disability data, and federated learning was employed to enable training in the BFL-GO method. Also, gradient-based optimization was used to adjust the proposed BFL-GO method’s parameters during the process of hyperparameter tuning. In this work, the experiments were conducted on the Disability Statistics United States 2018 dataset. The performance evaluation of the BFL-GO method involves analyzing its effectiveness based on evaluation metrics, namely, specificity, F1-score, recall, precision, AUC-ROC, computational time, and accuracy and comparing its performance against existing methods to assess its effectiveness. The experimental results illustrate the effectiveness of the BFL-GO method for disability management in information systems.
A Task Orchestration Strategy in a Cloud-Edge Environment Based on Intuitionistic Fuzzy Sets
Authors: Huang Chunmei , Fan Bingbing , Jiang Chunmao
Published: December 2023

In the context of the burgeoning cloud-edge collaboration paradigm, powered by advancements in the Internet of Things (IoT), cloud computing, and 5G technology, this paper proposes a task orchestrating strategy for cloud-edge collaborative environments based on intuitionistic fuzzy sets. The proposed strategy prioritizes efficient resource utilization, minimizes task failures, and reduces service time. First, WAN bandwidth, edge server virtual machine utilization, delay sensitivity of the task, and task length are used to determine whether the task should be executed on the cloud or edge device. Then, the cloud-edge collaborative decision-making algorithm is used to select the task’s target edge servers (either the local edge servers or the neighboring edge servers). Finally, simulation experiments are conducted to demonstrate the effectiveness and efficacy of the proposed algorithm.
Periodic Behaviour of HIV Dynamics with Three Infection Routes
Authors: El Hajji Miled , Alnjrani Rahmah Mohammed
Published: December 2023

In this study, we consider a system of nonlinear differential equations modeling the human immunodeficiency virus type-1 (HIV-1) in a variable environment. Infected cells were subdivided into two compartments describing both latently and productively infected cells. Thus, three routes of infection were considered including the HIV-to-cell contact, latently infected cell-to-cell contact, and actively infected cell-to-cell contact. The nonnegativity and boundedness of the trajectories of the dynamics were proved. The basic reproduction number was determined through an integral operator. The global stability of steady states is then analyzed using the Lyapunov theory together with LaSalle’s invariance principle for the case of a fixed environment. Similarly, for the case of a variable environment, we showed that the virus-free periodic solution is globally asymptotically stable once R0≤1, while the virus will persist once R0>1. Finally, some numerical examples are provided illustrating the theoretical investigations.
Machine Learning-Based Predictive Model of Aortic Valve Replacement Modality Selection in Severe Aortic Stenosis Patients
Authors: Chokesuwattanaskul Ronpichai , Petchlorlian Aisawan , Lertsanguansinchai Piyoros , Suttirut Paramaporn , Prasitlumkum Narut , Srimahachota Suphot , Buddhari Wacin
Published: December 2023

The current recommendation for bioprosthetic valve replacement in severe aortic stenosis (AS) is either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). We evaluated the performance of a machine learning-based predictive model using existing periprocedural variables for valve replacement modality selection. We analyzed 415 patients in a retrospective longitudinal cohort of adult patients undergoing aortic valve replacement for aortic stenosis. A total of 72 clinical variables including demographic data, patient comorbidities, and preoperative investigation characteristics were collected on each patient. We fit models using LASSO (least absolute shrinkage and selection operator) and decision tree techniques. The accuracy of the prediction on confusion matrix was used to assess model performance. The most predictive independent variable for valve selection by LASSO regression was frailty score. Variables that predict SAVR consisted of low frailty score (value at or below 2) and complex coronary artery diseases (DVD/TVD). Variables that predicted TAVR consisted of high frailty score (at or greater than 6), history of coronary artery bypass surgery (CABG), calcified aorta, and chronic kidney disease (CKD). The LASSO-generated predictive model achieved 98% accuracy on valve replacement modality selection from testing data. The decision tree model consisted of fewer important parameters, namely frailty score, CKD, STS score, age, and history of PCI. The most predictive factor for valve replacement selection was frailty score. The predictive models using different statistical learning methods achieved an excellent concordance predictive accuracy rate of between 93% and 98%.
Bayesian 13C-Metabolic Flux Analysis of Parallel Tracer Experiments in Granulocytes: A Directional Shift within the Non-Oxidative Pentose Phosphate Pathway Supports Phagocytosis
Authors: Hogg Melanie , Wolfschmitt Eva-Maria , Wachter Ulrich , Zink Fabian , Radermacher Peter , Vogt Josef Albert
Published: December 2023

The pentose phosphate pathway (PPP) plays a key role in the cellular regulation of immune function; however, little is known about the interplay of metabolic adjustments in granulocytes, especially regarding the non-oxidative PPP. For the determination of metabolic mechanisms within glucose metabolism, we propose a novel set of measures for 13C-metabolic flux analysis based on ex vivo parallel tracer experiments ([1,2-13C]glucose, [U-13C]glucose, [4,5,6-13C]glucose) and gas chromatography–mass spectrometry labeling measurements of intracellular metabolites, such as sugar phosphates and their fragments. A detailed constraint analysis showed that the permission range for net and irreversible fluxes was limited to a three-dimensional space. The overall workflow, including its Bayesian flux estimation, resulted in precise flux distributions and pairwise confidence intervals, some of which could be represented as a line due to the strength of their correlation. The principal component analysis that was enabled by these behaviors comprised three components that explained 99.6% of the data variance. It showed that phagocytic stimulation reversed the direction of non-oxidative PPP net fluxes from ribose-5-phosphate biosynthesis toward glycolytic pathways. This process was closely associated with the up-regulation of the oxidative PPP to promote the oxidative burst.
Miniature Ultrasonic Spatial Localization Module in the Lightweight Interactive
Authors: Li Lieguang , Xiu Xueying , Lyu Haochen , Yang Haolin , Safari Ahmad , Zhang Songsong
Published: December 2023

The advancement of spatial interaction technology has greatly enriched the domain of consumer electronics. Traditional solutions based on optical technologies suffers high power consumption and significant costs, making them less ideal in lightweight implementations. In contrast, ultrasonic solutions stand out due to their lower power consumption and cost-effectiveness, capturing widespread attention and interest. This paper addresses the challenges associated with the application of ultrasound sensors in spatial localization. Traditional ultrasound systems are hindered by blind spots, large physical dimensions, and constrained measurement ranges, limiting their practical applicability. To overcome these limitations, this paper proposes a miniature ultrasonic spatial localization module employing piezoelectric micromechanical ultrasonic transducers (PMUTs). The module is comprised of three devices each with dimension of 1.2 mm × 1.2 mm × 0.5 mm, operating at a frequency of around 180 kHz. This configuration facilitates a comprehensive distance detection range of 0–800 mm within 80° directivity, devoid of blind spot. The error rate and failure range of measurement as well as their relationship with the SNR (signal-to-noise ratio) are also thoroughly investigated. This work heralds a significant enhancement in hand spatial localization capabilities, propelling advancements in acoustic sensor applications of the meta-universe.
Design and Investigation of Superatoms for Redox Applications: First-Principles Studies
Authors: Sikorska Celina
Published: December 2023

A superatom is a cluster of atoms that acts like a single atom. Two main groups of superatoms are superalkalis and superhalogens, which mimic the chemistry of alkali and halogen atoms, respectively. The ionization energies of superalkalis are smaller than those of alkalis (<3.89 eV for cesium atom), and the electron affinities of superhalogens are larger than that of halogens (>3.61 eV for chlorine atom). Exploring new superalkali/superhalogen aims to provide reliable data and predictions of the use of such compounds as redox agents in the reduction/oxidation of counterpart systems, as well as the role they can play more generally in materials science. The low ionization energies of superalkalis make them candidates for catalysts for CO2 conversion into renewable fuels and value-added chemicals. The large electron affinity of superhalogens makes them strong oxidizing agents for bonding and removing toxic molecules from the environment. By using the superatoms as building blocks of cluster-assembled materials, we can achieve the functional features of atom-based materials (like conductivity or catalytic potential) while having more flexibility to achieve higher performance. This feature paper covers the issues of designing such compounds and demonstrates how modifications of the superatoms (superhalogens and superalkalis) allow for the tuning of the electronic structure and might be used to create unique functional materials. The designed superatoms can form stable perovskites for solar cells, electrolytes for Li-ion batteries of electric vehicles, superatomic solids, and semiconducting materials. The designed superatoms and their redox potential evaluation could help experimentalists create new materials for use in fields such as energy storage and climate change.
Recent Records on Bacterial Opportunistic Infections via the Dietary Route
Authors: Rossi Franca , Santonicola Serena , Amadoro Carmela , Marino Lucio , Colavita Giampaolo
Published: December 2023

This narrative review was aimed at identifying the opportunistic bacterial pathogens that can be transmitted by contaminated food and represent a current threat for patients particularly susceptible to infections because of underlying conditions or predisposing factors. The analysis was focused on recent case or outbreak reports and systematic reviews published in the years 2019 to 2023 and resulted in sorting 24 bacterial groups comprising the genera or species able to cause a variety of systemic or invasive infections if ingested with food or drinking water. These included both bacteria known to cause mild infections in immunocompetent persons and bacteria considered to be innocuous, which are used in food fermentation or as probiotics. No recent cases of infections transmitted through dietary routes were reported for the critical nosocomial pathogens widely found in food products, primarily Acinetobacter baumannii and Klebsiella pneumoniae. However, the very first sources of their introduction into the clinical environment still need to be established. In many instances, risky dietary habits, such as eating raw fish, seafood, raw meat, unpasteurized milk, and their derived products or the lack of control in fermentation processes, has led to the reported illnesses, pointing out the necessity to improve the hygiene of production and consumer awareness of the risks.
Coinfection with Leishmania infantum and Toxoplasma gondii in Domestic Cats from a Region with a High Prevalence of Feline Immunodeficiency Virus
Authors: Bezerra José Artur Brilhante , Haisi Amanda , Rocha Gabrielle dos Santos , Lima Suellen Gonçalves , Brasil Arthur Willian de Lima , Tomaz Klívio Loreno Raulino , Fornazari Felipe , Langoni Helio , Araújo Junior João Pessoa , Antunes João Marcelo Azevedo de Paula , Azevedo Sérgio Santos de
Published: December 2023

The aim of this study was to investigate the coinfection of feline retroviruses (feline immunodeficiency virus—FIV, and the feline leukemia virus—FeLV) with Leishmania infantum and Toxoplasma gondii and the factors associated with these pathogens in domestic cats from Mossoró, a city endemic for canine and human leishmaniasis situated in the semiarid region of Northeast Brazil. Blood samples from 120 cats were collected, and an epidemiological questionnaire was applied to investigate the risk factors associated with the infections. Retroviruses, L. infantum, and T. gondii infections were assessed using a point-of-care ELISA and quantitative PCR (qPCR), indirect fluorescent antibody test (IFAT) and qPCR, and IFAT, respectively. The overall seroprevalences observed were 35% (95% CI = 27.0–43.8%) for FIV, 0.8% (95% CI = 0.1–4.5%) for FeLV, 25.8% (95% CI = 18.8–34.3%) for T. gondii, and 4.2% (95% CI = 1.7–9.3%) for L. infantum. Coinfection with FIV and L. infantum was observed in 2.5% (3/120) of the assessed cats, while 12.5% (15/120) were coinfected with FIV and T. gondii. No significant association was found among the investigated agents (p > 0.05). The factors associated with FIV infection in the multivariable analysis were male sex and age above 78 months. The findings of this study demonstrated a high rate of FIV infection in cats from the Brazilian semiarid region and the exposure of these animals to zoonotic and opportunistic agents. Due to the immunosuppressive potential of FIV, cats infected with this retrovirus should be screened for coinfections with L. infantum and T. gondii, and preventative measures should be adopted.
In Silico and In Vitro Identification of 1,8-Dihydroxy-4,5-dinitroanthraquinone as a New Antibacterial Agent against Staphylococcus aureus and Enterococcus faecalis
Authors: Amorim Juliana , Vásquez Viviana , Cabrera Andrea , Martínez Maritza , Carpio Juan
Published: December 2023

Increasing rates of bacterial resistance to antibiotics are a growing concern worldwide. The search for potential new antibiotics has included several natural products such as anthraquinones. However, comparatively less attention has been given to anthraquinones that exhibit functional groups that are uncommon in nature. In this work, 114 anthraquinones were evaluated using in silico methods to identify inhibitors of the enzyme phosphopantetheine adenylyltransferase (PPAT) of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. Virtual screenings based on molecular docking and the pharmacophore model, molecular dynamics simulations, and free energy calculations pointed to 1,8-dihydroxy-4,5-dinitroanthraquinone (DHDNA) as the most promising inhibitor. In addition, these analyses highlighted the contribution of the nitro group to the affinity of this anthraquinone for the nucleotide-binding site of PPAT. Furthermore, DHDNA was active in vitro towards Gram-positive bacteria with minimum inhibitory concentration (MIC) values of 31.25 µg/mL for S. aureus and 62.5 µg/mL for E. faecalis against both antibiotic-resistant isolates and reference strains but was ineffective against E. coli. Experiments on kill-time kinetics indicated that, at the tested concentrations, DHDNA produced bacteriostatic effects on both Gram-positive bacteria. Overall, our results present DHDNA as a potential PPAT inhibitor, showing antibacterial activity against antibiotic-resistant isolates of S. aureus and E. faecalis, findings that point to nitro groups as key to explaining these results.
A Comprehensive Phytochemical Analysis of Sideritis scardica Infusion Using Orbitrap UHPLC-HRMS
Authors: Zheleva-Dimitrova Dimitrina , Voynikov Yulian , Gevrenova Reneta , Balabanova Vessela
Published: December 2023

Sideritis scardica Griseb, also known as “mountain tea” and “Olympus tea” (Lamiaceae family) is an endemic plant from the mountainous regions of the Balkan Peninsula. In this study, we focused on an in-depth phytochemical analysis of S. scardica infusion using ultra-high-performance liquid chromatography hyphenated with high-resolution mass spectrometry (UHPLC–HRMS). Quantitative determination of the main secondary metabolites was carried out by UHPLC–HRMS analyses using the external standard method. The results revealed more than 100 metabolites, including five sugar acids and saccharides, 21 carboxylic, hydroxybenzoic, hydroxycinnamic acids, and derivatives, 15 acylquinic acids, 10 phenylpropanoid glycosides, four iridoid glycosides, 28 flavonoids, seven fatty acids, and four organosulfur compounds. Furthermore, a dereplication and fragmentation patterns of five caffeic acids oligomers and four acylhexaric acids was performed for the first time in S. scardica. Regarding the quantitative analysis, the phenylethanoid verbascoside (53) (151.54 ± 10.86 mg/g lyophilized infusion, li), the glycosides of isoscutellarein (78) (151.70 ± 14.78 mg/g li), methylisoscutelarein (82) (107.4 ± 9.07 mg/g li), and hypolaetin (79) (78.33 ± 3.29 mg/g li), as well as caffeic acid (20) (87.25 ± 6.54 mg/g li), were found to be the major compounds in S. scardica infusion. The performed state-of-the-art phytochemical analysis of S. scardica provides additional knowledge for the chemical constituents and usage of this valuable medicinal plant.
Preparations of trans- and cis-μ-1,2-Peroxodiiron(III) Complexes
Authors: Kajita Yuji , Kubo Masaki , Arii Hidekazu , Ishikawa Shinya , Saito Yamato , Wasada-Tsutsui Yuko , Funahashi Yasuhiro , Ozawa Tomohiro , Masuda Hideki
Published: December 2023

The iron(II) complex with cis,cis-1,3,5-tris(benzylamino)cyclohexane (Bn3CY) (1) has been synthesized and characterized, which reacted with dioxygen to form the peroxo complex 2 in acetone at −60 °C. On the basis of spectroscopic measurements for 2, it was confirmed that the peroxo complex 2 has a trans-μ-1,2 fashion. Additionally, the peroxo complex 2 was reacted with benzoate anion as a bridging agent to give a peroxo complex 3. The results of resonance Raman and 1H-NMR studies supported that the peroxo complex 3 is a cis-μ-1,2-peroxodiiron(III) complex. These spectral features were interpreted by using DFT calculations.
Reaction of Picolinamides with Ketones Producing a New Type of Heterocyclic Salts with an Imidazolidin-4-One Ring
Authors: Kramarova Eugenia P. , Lyakhmun Dmitry N. , Tarasenko Dmitry V. , Borisevich Sophia S. , Khamitov Edward M. , Yusupova Alfia R. , Korlyukov Alexander A. , Romanenko Alexander R. , Shmigol Tatiana A. , Bylikin Sergey Yu. , Baukov Yuri I. , Negrebetsky Vadim V.
Published: December 2023

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a–f), with a protonated endocyclic nitrogen atom, and then heterocyclic salts (3a–j) containing an imidazolidin-4-one ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy, and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a–j towards hydrolysis and alcoholysis makes them excellent candidates for the search for new types of biologically active compounds.
Proteomics Applications in Toxoplasma gondii: Unveiling the Host–Parasite Interactions and Therapeutic Target Discovery
Authors: Deng Bin , Vanagas Laura , Alonso Andres M. , Angel Sergio O.
Published: December 2023

Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host–parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID (BirA*-mediated proximity-dependent biotin identification), APEX (ascorbate peroxidase-mediated proximity labeling), and Y2H (yeast two hybrid), as well as various proteomics approaches, including single-cell analysis, DIA (data-independent acquisition), targeted, top-down, and plasma proteomics. Furthermore, we discuss bioinformatics and the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.
A Structural Analysis of Host–Parasite Interactions in Achatina fulica (Giant African Snail) Infected with Angiostrongylus cantonensis
Authors: Lopes-Torres Eduardo J. , de Oliveira Simões Raquel , Mota Ester M. , Thiengo Silvana Carvalho
Published: December 2023

Angiostrongylus cantonensis is a nematode parasite that resides in the pulmonary arteries of rodents, serving as its definitive hosts. The life cycle involves several species of non-marine gastropods as intermediate hosts, and the African giant snail Achatina fulica is considered one of the most important around the world. Experimental data concerning A. cantonensis infection in the African giant snail remains notably limited. This helminth causes eosinophilic meningitis or meningoencephalitis in humans, representing an emergent zoonosis in Brazil. Understanding the host–parasite relationship through the application of new tools is crucial, given the complex interaction between zoonosis and the intricate mechanisms involving wild/human hosts, parasite adaptation, and dispersion. The objective of this study was to employ SEM as a novel methodology to understand the structural organization of the host tissue, particularly the granuloma formation. This sheds light on the complex balance between A. fulica and A. cantonensis. Nine three-month-old snails were randomly selected and exposed for 24 h to a concentration of 2000 L1/dose of A. cantonensis. A necropsy was performed 37 days after the infection, and the samples were examined using light and scanning electron microscopy (SEM). The histopathological results revealed third-stage larvae of A. cantonensis associated with granulomas distributed throughout the head-foot mass, mantle, and kidney. Scanning electron microscopy of the histological section surface showed that the granuloma is surrounded by a cluster of spherical particles, which are distributed in the region bordering the larvae. This reveal details of the nematode structure, demonstrating how this methodology can enhance our understanding of the role of granulomas in molluscan tissue. The structural characteristics of granuloma formation in A. fulica suggest it as an excellent invertebrate host for A. cantonensis. This relationship appears to provide protection to the parasite against the host’s immune defense system while isolating the snail’s tissue from potential exposure to nematode antigens.
Antipsychotics and Mortality in Adult and Geriatric Patients with Schizophrenia
Authors: Yeh Ling-Ling , Lee Wei-Chen , Kuo Kuei-Hong , Pan Yi-Ju
Published: December 2023

Patients with schizophrenia have a high mortality risk, and the role of antipsychotic medications remains inconclusive. In an aging society, older patients with schizophrenia warrant increased attention. This study investigated the association of antipsychotic medication dosages with mortality in patients with schizophrenia by using data from Taiwan’s National Health Insurance Research Database from 2010 to 2014. This study included 102,964 patients with schizophrenia and a subgroup of 6433 older patients in addition to an age- and sex-matched control group. The findings revealed that among patients with schizophrenia, the no antipsychotic exposure group had the highest mortality risk (3.61- and 3.37-fold higher risk for overall and cardiovascular mortality, respectively) in the age- and sex-adjusted model, followed by the high, low, and moderate exposure groups. A similar pattern was observed in the older patients with schizophrenia. High exposure to antipsychotics was associated with the highest risks of overall and cardiovascular mortality (3.01- and 2.95-fold higher risk, respectively). In conclusion, the use of antipsychotics can be beneficial for patients with schizophrenia with recommended exposure levels being low to moderate. In older patients, high antipsychotic exposure was associated with the highest mortality risk, indicating that clinicians should be cautious when administering antipsychotic medications to such patients.
Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era
Authors: Sánchez Suárez María Del Mar , Martín Roldán Alicia , Alarcón-Payer Carolina , Rodríguez-Gil Miguel Ángel , Poquet-Jornet Jaime Eduardo , Puerta Puerta José Manuel , Jiménez Morales Alberto
Published: December 2023

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon.
Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction
Authors: Pinto Bárbara , Silva João P. N. , Silva Patrícia M. A. , Barbosa Daniel José , Sarmento Bruno , Tavares Juliana Carvalho , Bousbaa Hassan
Published: December 2023

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness.
Microneedle-Assisted Transfersomes as a Transdermal Delivery System for Aspirin
Authors: Rahbari Raha , Francis Lewis , Guy Owen J. , Sharma Sanjiv , Von Ruhland Christopher , Xia Zhidao
Published: December 2023

Transdermal drug delivery systems offer several advantages over conventional oral or hypodermic administration due to the avoidance of first-pass drug metabolism and gastrointestinal degradation as well as patients’ convenience due to a minimally invasive and painless approach. A novel transdermal drug delivery system, comprising a combination of transfersomes with either solid silicon or solid polycarbonate microneedles has been developed for the transdermal delivery of aspirin. Aspirin was encapsulated inside transfersomes using a “thin-film hydration sonication” technique, yielding an encapsulation efficiency of approximately 67.5%. The fabricated transfersomes have been optimised and fully characterised in terms of average size distribution and uniformity, surface charge and stability (shelf-life). Transdermal delivery, enhanced by microneedle penetration, allows the superior permeation of transfersomes into perforated porcine skin and has been extensively characterised using optical coherence tomography (OCT) and transmission electron microscopy (TEM). In vitro permeation studies revealed that transfersomes enhanced the permeability of aspirin by more than four times in comparison to the delivery of unencapsulated “free” aspirin. The microneedle-assisted delivery of transfersomes encapsulating aspirin yielded 13-fold and 10-fold increases in permeation using silicon and polycarbonate microneedles, respectively, in comparison with delivery using only transfersomes. The cytotoxicity of different dose regimens of transfersomes encapsulating aspirin showed that encapsulated aspirin became cytotoxic at concentrations of ≥100 μg/mL. The results presented demonstrate that the transfersomes could resolve the solubility issues of low-water-soluble drugs and enable their slow and controlled release. Microneedles enhance the delivery of transfersomes into deeper skin layers, providing a very effective system for the systemic delivery of drugs. This combined drug delivery system can potentially be utilised for numerous drug treatments.
Monoclonal Antibody Therapy in Alzheimer’s Disease
Authors: Neațu Monica , Covaliu Anca , Ioniță Iulia , Jugurt Ana , Davidescu Eugenia Irene , Popescu Bogdan Ovidiu
Published: December 2023

Alzheimer’s disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer’s disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer’s disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer’s disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer’s disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer’s disease worldwide.
Mutual Flourishing: A Dialogical Approach to Environmental Virtue Ethics
Authors: Arcos Esteban
Published: December 2023

Environmental virtue ethics is about how things (nature) matter, and this is explicated through the virtues (character and dispositions of the agent). It has been suggested that human virtue should be informed by what constitutes our flourishing and by what constitutes nonhuman entities flourishing. Our flourishing, in other words, involves recognising their flourishing and autonomy. My purpose in this paper is to elucidate the notion of mutual flourishing through a study on the relational space that a recognising attitude or disposition of a loving and caring subject creates in its interactions with ‘earth others’.