bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary Aspergillosis in Critically Ill COVID-19 Patients Admitted to the Intensive Care Unit: A Retrospective Cohort Study
Authors: Bergmann Felix , Jorda Anselm , Blaschke Amelie , Gabler Cornelia , Bohdan Serhii , Nussbaumer-Pröll Alina , Radtke Christine , Zeitlinger Markus
Published: March 2023

COVID-19-associated pulmonary aspergillosis (CAPA) is a life-threatening fungal infection that mainly affects critically ill patients. The aim of this study was to assess the incidence and clinical outcomes of putative CAPA in critically ill COVID-19 patients. This retrospective observational cohort study included 181 cases from 5 ICUs at Vienna General Hospital between January 2020 and April 2022. Patients were diagnosed with putative CAPA according to the AspICU classification, which included a positive Aspergillus culture in a bronchoalveolar lavage sample, compatible signs and symptoms, and abnormal medical imaging. The primary outcome was adjusted 60-day all-cause mortality from ICU admission in patients with vs. without putative CAPA. Secondary outcomes included time from ICU admission to CAPA diagnosis and pathogen prevalence and distribution. Putative CAPA was identified in 35 (19.3%) of 181 COVID-19 patients. The mean time to diagnosis was 9 days. Death at 60 days occurred in 18 of 35 (51.4%) patients with CAPA and in 43 of 146 (29.5%) patients without CAPA (adjusted HR (95%CI) = 2.15 (1.20–3.86, p = 0.002). The most frequently isolated Aspergillus species was Aspergillus fumigatus. The prevalence of putative pulmonary aspergillosis in critically ill COVID-19 patients was high and was associated with significantly higher mortality.
Cost-Effectiveness of Nature-Based Solutions under Different Implementation Scenarios: A National Perspective for Italian Urban Areas
Authors: Di Pirro Elena , Roebeling Peter , Sallustio Lorenzo , Marchetti Marco , Lasserre Bruno
Published: March 2023

Worldwide, national governments and private organizations are increasingly investing in Nature-Based Solutions (NBS) to foster both human well-being and biodiversity while achieving climate and environmental targets. Yet, investments in NBS remain uncoordinated among planning levels, their co-benefits underestimated, and their effectiveness undermined. This study aims to provide a spatially explicit approach to optimize the budget allocation for NBS implementation across Italian urban areas while maximizing their effectiveness in terms of environmental health. We explored three different NBS implementation scenarios oriented to (i) maximize the Ecosystem Services supply of NBS (Scenario BP), (ii) minimize costs of NBS (Scenario LC), and (iii) maximize Ecosystem Services supply of NBS at the lowest cost (Scenario CP). Once selected, we prioritized their allocation through the territory following an environmental risk index for population, and we explored the relationship between costs and effectiveness for the three scenarios. The implementation of Scenario BP costs EUR 777 billion while showing 31 billion of effectiveness. Scenario LC costs 70% less than scenario BP (EUR 206 billion) while losing 70% of its effectiveness. Scenario CP costs 60% less than Scenario BP (EUR 301 billion), offering just 20% less effectiveness. Our results show that employing the risk index for NBS allocation would allow for reducing the surface of interventions by saving 67% of the budget in the three scenarios with a negligible loss in terms of return for human health. The here-proposed approach can guide the national funds’ allocation system, improving its cost-effectiveness and equitableness.
Vowel Quality in Xiang Non-Lexical Hesitation Markers: New Forms of Typological Evidence?
Authors: Sevilla Robert Marcelo
Published: March 2023

Xiang (hsn) remains a poorly understood grouping within Sinitic, with no satisfactory conclusions on how to demarcate its boundaries or define its subgroupings. One general observation is that there is a rough typological split between the Northeast and Southwest related to contact from northern- and southern-type Sinitic varieties, respectively, which can be supported with phonological, lexical, and syntactic evidence. It is predicted here that an additional source of evidence can be found in the phonetic features of hesitation markers (HMs; ‘fillers’, ‘speech disfluencies’, etc.), which tend towards the central area of the vowel space (approaching [ə], [ɤ], [e], etc.) but still conform to the phonologies of the languages in which they occur. This study introduces a novel three-way division of Xiang in terms of phonemic central vowels found in open syllables (either [ə/ɤ], [e/ɛ], or both) which is then evaluated against the vocalic quality found in HMs to determine whether they can be used as evidence for Xiang internal typology. Data are gathered from 47 speakers representing 16 Xiang localities, distributed across Hunan province, recorded performing the Pear Stories paradigm, with 304 hesitation markers extracted. Features reported on include vowel quality (F1-F2), tonal contour (F0), and duration (ms). It is found that Xiang HMs demonstrate four distinct vowel qualities, but that their distribution does not neatly fit established taxonomic schemes; however, the evidence does support the transitional status of Xiang varieties as a site of mixture of northern and southern Sinitic features.
Effect of Carbon Nanotubes on the Na+ Intercalation Capacity of Binder Free Mn2V2O7-CNTs Electrode: A Structural Investigation
Authors: Parmar Rahul , Rezvani Javad , Amati Matteo , Gregoratti Luca , Neto Decio Batista de Freitas , Rosolen Jose Mauricio , Gunnella Roberto
Published: March 2023

Improvements in sodium intercalation in sodium cathodes have been debated in recent years. In the present work, we delineate the significant effect of the carbon nanotubes (CNTs) and their weight percent in the intercalation capacity of the binder-free manganese vanadium oxide (MVO)-CNTs composite electrodes. The performance modification of the electrode is discussed taking into account the cathode electrolyte interphase (CEI) layer under optimal performance. We observe an intermittent distribution of the chemical phases on the CEI, formed on these electrodes after several cycles. The bulk and superficial structure of pristine and Na+ cycled electrodes were identified via micro-Raman scattering and Scanning X-ray Photoelectron Microscopy. We show that the inhomogeneous CEI layer distribution strongly depends on the CNTs weight percentage ratio in an electrode nano-composite. The capacity fading of MVO-CNTs appears to be associated with the dissolution of the Mn2O3 phase, leading to electrode deterioration. This effect is particularly observed in electrodes with low weight percentage of the CNTs in which the tubular topology of the CNTs are distorted due to the MVO decoration. These results can deepen the understanding of the CNTs role on the intercalation mechanism and capacity of the electrode, where there are variations in the mass ratio of CNTs and the active material.
The Impact of Nutshell Biochar on the Environment as an Alternative Fuel or as a Soil Amendment
Authors: Jeníček Lukáš , Tunklová Barbora , Malaťák Jan , Velebil Jan , Malaťáková Jitka , Neškudla Michal , Hnilička František
Published: March 2023

Walnut, pistachio, and peanut nutshells were treated by pyrolysis to biochar and analyzed for their possible usage as fuels or soil fertilizers. All the samples were pyrolyzed to five different temperatures, i.e., 250 °C, 300 °C, 350 °C, 450 °C, and 550 °C. Proximate and elemental analyses were carried out for all the samples, as well as calorific value and stoichiometric analysis. For sample usage as a soil amendment, phytotoxicity testing was performed and the content of phenolics, flavonoids, tannin, juglone, and antioxidant activity were determined. To characterize the chemical composition of walnut, pistachio, and peanut shells, lignin, cellulose, holocellulose, hemicellulose, and extractives were determined. As a result, it was found that walnut shells and pistachio shells are best pyrolyzed at the temperature of 300 °C and peanut shells at the temperature of 550 °C for their use as alternative fuels. The highest measured net calorific value was in pistachio shells, which were biochar pyrolyzed at 550 °C, of 31.35 MJ kg−1. On the other hand, walnut biochar pyrolyzed at 550 °C had the highest ash share of 10.12% wt. For their use as soil fertilizers, peanut shells were the most suitable when pyrolyzed at 300 °C, walnut shells at 300 and 350 °C, and pistachio shells at 350 °C.
Design to Reduce Cogging Torque and Irreversible Demagnetization in Traction Hybrid Motor Using Dy-free Magnet
Authors: Song Si-Woo , Kim Won-Ho , Lee Ju , Jung Dong-Hoon
Published: March 2023

The PMSM (Permanent Magnet Synchronous Motor) is being studied a lot in traction motors for high efficiency and high performance. Usually, magnets containing rare earth elements are used. However, since rare earth elements are not suitable for future industries due to their limited reserves, many studies on magnets excluding rare earth elements are being conducted. Magnets excluding rare earth elements have a low coercive force and are vulnerable to irreversible demagnetization, so their design must be robust. Additionally, the design used for reducing the cogging torque, which is a major variable of traction motors, is also important. Therefore, in this study, a design process for reducing irreversible demagnetization and cogging torque is proposed. There are three methods for this process. The first one is the application of the tapering structure, and the second one is the tapering skew structure. The third one is the application of an asymmetric air hole. As a result of these methods, the target irreversible demagnetization ratio was satisfied and the cogging torque was reduced. This was proven through FEA (Finite Element Analysis) and verified by comparing and analyzing the experimental results and simulation results of actual manufacturing.
Performance Investigation of a Large Turning Blade for Marine Gas Turbine Based on Experimental and Numerical Methods
Authors: Qi Mengyao , Ren Xiaodong , Li Xuesong , Xiao Yaobin , Li Yuhong
Published: March 2023

Replacing the last-stage stator and the outlet guide vane of the low-pressure compressor of the marine gas turbine with a large turning blade can reduce the number of compressor blades and reduce the size and weight of marine gas turbines. At present, there are few studies on similar profiles, and it is necessary to verify the feasibility of this type of compressor profile with a large turning angle. The performance of this profile is investigated by combining experimental measurement with numerical simulation calculation. The analysis of the experimental and numerical results reveals that this profile has a large flow turning angle, a wide operating range, and low overall total pressure losses. The loss of the profile only suddenly increases at some large positive angles of attack due to the large separation of the suction surface. The results show that this profile can compress air and increase the turning ability at a low loss, and can play the role of both the original last-stage stator and the outlet guide vane. This research provides a reference for the design and analysis of marine gas turbines and guidance for the application of the blade to gas turbines in other fields.
Research on Braking Energy Regeneration for Hybrid Electric Vehicles
Authors: Xu Mengtian , Peng Jianxin , Ren Xiaochen , Yang Xuekun , Hu Yuhui
Published: March 2023

In recent years, there has been a significant increase in braking energy regeneration for hybrid electric vehicles. To improve performance and reduce fuel consumption, a better control strategy composed of braking regeneration and gear shifting is needed. This work presents a braking energy regeneration control strategy for a hybrid electric vehicle (HEV). The mathematical model for the vehicle dynamic system is established, and the objective function of braking energy regeneration is presented based on system analysis. Taking the increased electric energy of a battery as the objective function of the economic downshift law, the multi-island genetic algorithm (MIGA) is used to solve the shifting condition factors corresponding to different deceleration speeds and motor torques and the optimal downshifting speed. The presented control strategy of braking energy regeneration is validated in a typical city cycle form in China, and the results show better energy efficiency.
Probabilistic Classification Method of Spiking Neural Network Based on Multi-Labeling of Neurons
Authors: Sung Mingyu , Kim Jaesoo , Kang Jae-Mo
Published: March 2023

Recently, deep learning has exhibited outstanding performance in various fields. Even though artificial intelligence achieves excellent performance, the amount of energy required for computations has increased with its development. Hence, the need for a new energy-efficient computer architecture has emerged, which further leads us to the neuromorphic computer. Although neuromorphic computing exhibits several advantages, such as low-power parallelism, it exhibits lower accuracy than deep learning. Therefore, the major challenge is to improve the accuracy while maintaining the neuromorphic computing-specific energy efficiency. In this paper, we propose a novel method of the inference process that considers the probability that after completing the learning process, a neuron can react to multiple target labels. Our proposed method can achieve improved accuracy while maintaining the hardware-friendly, low-power-parallel processing characteristics of a neuromorphic processor. Furthermore, this method converts the spike counts occurring in the learning process into probabilities. The inference process is conducted to implement the interaction between neurons by considering all the spikes that occur. The inferring circuit is expected to show a significant reduction in hardware cost and can afford an algorithm exhibiting a competitive computing performance.
The Fourth-Linear aff(1)-Invariant Differential Operators and the First Cohomology of the Lie Algebra of Vector Fields on RP1
Authors: Almoneef Areej A. , Abdaoui Meher , Ghallabi Abderraouf
Published: March 2023

In this paper, we denote the Lie algebra of smooth vector fields on RP1 by V(RP1). This paper focuses on two parts. In the beginning, we determine the cohomology space of aff(1) with coefficients in Dτ,λ,μ;ν. Afterward, we classify aff(1)-invariant fourth-linear differential operators from V(RP1) to Dτ,λ,μ;ν vanishing on aff(1). This result enables us to compute the aff(1)-relative cohomology of V(RP1) with coefficients in Dτ,λ,μ;ν.
Comprehensive Analysis of Learning Cases in an Autonomous Navigation Task for the Evolution of General Controllers
Authors: Naredo Enrique , Sansores Candelaria , Godinez Flaviano , López Francisco , Urbano Paulo , Trujillo Leonardo , Ryan Conor
Published: March 2023

Robotics technology has made significant advancements in various fields in industry and society. It is clear how robotics has transformed manufacturing processes and increased productivity. Additionally, navigation robotics has also been impacted by these advancements, with investors now investing in autonomous transportation for both public and private use. This research aims to explore how training scenarios affect the learning process for autonomous navigation tasks. The primary objective is to address whether the initial conditions (learning cases) have a positive or negative impact on the ability to develop general controllers. By examining this research question, the study seeks to provide insights into how to optimize the training process for autonomous navigation tasks, ultimately improving the quality of the controllers that are developed. Through this investigation, the study aims to contribute to the broader goal of advancing the field of autonomous navigation and developing more sophisticated and effective autonomous systems. Specifically, we conducted a comprehensive analysis of a particular navigation environment using evolutionary computing to develop controllers for a robot starting from different locations and aiming to reach a specific target. The final controller was then tested on a large number of unseen test cases. Experimental results provide strong evidence that the initial selection of the learning cases plays a role in evolving general controllers. This work includes a preliminary analysis of a specific set of small learning cases chosen manually, provides an in-depth analysis of learning cases in a particular navigation task, and develops a tool that shows the impact of the selected learning cases on the overall behavior of a robot’s controller.
Estimation of the Equivalent Circuit Parameters in Transformers Using Evolutionary Algorithms
Authors: Ascencion-Mestiza Hector , Maximov Serguei , Mezura-Montes Efrén , Olivares-Galvan Juan Carlos , Ocon-Valdez Rodrigo , Escarela-Perez Rafael
Published: March 2023

The conventional methods of parameter estimation in transformers, such as the open-circuit and short-circuit tests, are not always available, especially when the transformer is already in operation and its disconnection is impossible. Therefore, alternative (non-interruptive) methods of parameter estimation have become of great importance. In this work, no-interruption, transformer equivalent circuit parameter estimation is presented using the following metaheuristic optimization methods: the genetic algorithm (GA), particle swarm optimization (PSO) and the gravitational search algorithm (GSA). These algorithms provide a maximum average error of 12%, which is twice as better as results found in the literature for estimation of the equivalent circuit parameters in transformers at a frequency of 50 Hz. This demonstrates that the proposed GA, PSO and GSA metaheuristic optimization methods can be applied to estimate the equivalent circuit parameters of single-phase distribution and power transformers with a reasonable degree of accuracy.
Regeneration of Horizontal Bone Defect in Edentulous Maxilla Using the Allogenic Bone-Plate Shell Technique and a Composite Bone Graft—A Case Report
Authors: Kovac Zoran , Cabov Tomislav , Blaskovic Marko , Morelato Luka
Published: March 2023

An insufficient volume of the alveolar bone may prevent implants from being placed in the prosthetically optimal position. Complex restoration of bony structures is required to achieve long-term peri-implant bone stability and represents an adequate prosthetic solution. Background and Objectives: The shell technique has become a widespread and important method for guided bone regeneration in dentistry. Allogeneic bone materials appear to be the most similar substitution for autogenous bone transplants. However, there are few studies using cortical bone allografts in combination with a mix of autogenous and xenograft materials for the augmentation of horizontal ridge defects. This combination offers the advantage of reduced patient morbidity while adding adequate volume and contour to the alveolar ridge. Case report: The present case study aimed to clinically and radiographically evaluate the efficacy of allogenic cortical bone lamina combined with a composite bone graft in the augmentation of a horizontal bone defect in the edentulous maxilla during a 6-year follow-up period. Three CB CT scans taken before treatment, 6 months after the augmentation period/before implant placement, and after a 6-year follow-up period, were analyzed using stable referent points. After the 6 -year follow-up period, the average resorption rate was 21.65% on the augmented buccal side, with no implant exposure being observed. Conclusions: The bone shell technique used in conjunction with allogenic bone plates combined with autogenous bone, xenografts, and collagen membranes is an effective technique to manage horizontal ridge defects.
Effects of Natural Aging and Discontinuous Cyclic Loading on High Cycle Fatigue Behavior of Steels
Authors: Li Gen , Liu Jiajun , Sun Jian , Sun Chengqi
Published: March 2023

Metallic components may not be used immediately and are stored for several months or years after fabrication in some cases, which experience long-term natural aging. Moreover, the fatigue-beared components commonly suffer discontinuous cyclic loadings in service. In this paper, the effects of natural aging and discontinuous loading on high cycle fatigue life and failure mechanism were investigated through rotating bending fatigue tests. The long-term natural aging (e.g., more than 20,000 h) reduced the fatigue life of both 25CrMo4 and 30CrMnSiA steels, and this effect was irrespective of the roughness of the specimen surface. The effect of natural aging on the failure mechanism was related to the microstructure of materials. The natural aging promoted the probability of multi-site crack initiation for 25CrMo4 steel, but had no influence on the crack initiation mode of 30CrMnSiA steel. The discontinuous cyclic loading had no harmful influence on the fatigue life of 25CrMo4 steel, and it had no influence on the failure mechanism. The specimens under continuous and discontinuous cyclic loadings both failed from single-site crack initiation or multi-site crack initiation at the specimen surface.
Structure and Mechanical Properties of Ti-Al-Ta-N Coatings Deposited by Direct Current and Middle-Frequency Magnetron Sputtering
Authors: Shugurov Artur R. , Kuzminov Evgenii D. , Garanin Yuriy A.
Published: March 2023

Ti-Al-Ta-N coatings are characterized by attractive mechanical properties, thermal stability and oxidation resistance, which are superior to ternary compositions, such as Ti-Al-N. However, because of their open columnar microstructure, the Ti-Al-Ta-N coatings deposited by conventional direct current magnetron sputtering (DCMS) exhibit insufficient wear resistance. This work is focused on obtaining the Ti-Al-Ta-N coatings with improved microstructure and mechanical and tribological properties by middle-frequency magnetron sputtering (MFMS). The coatings are deposited by the co-sputtering of two separate targets (Ti-Al and Ta) using pure DCMS and MFMS modes as well as hybrid modes. It is found that the MFMS coating has a denser microstructure consisting of fragmented columnar grains interspersed with equiaxed grains and a smaller grain size than the DCMS coating, which is characterized by a fully columnar microstructure. The modification of the microstructure of the MFMS coating results in the simultaneous enhancement of its hardness, toughness and adhesion. As a result, the wear rate of the MFMS coating is less than half of that of the DCMS coating.
Effect of Al2O3 and ZrO2 Filler Material on the Microstructural, Thermal and Dielectric Properties of Borosilicate Glass-Ceramics
Authors: Arıbuğa Dilara , Karaahmet Oğuz , Balcı-Çağıran Özge , Çiçek Buğra
Published: March 2023

Various glass-ceramics are widely used or considered for use as components of microelectronic materials due to their promising properties. In this study, borosilicate glass was prepared using the powder metallurgical route and then mixed with different amounts of Al2O3 and ZrO2 filler materials. Glass-ceramics are produced by high-energy ball milling and conventional sintering process under Ar or air. In this study, the effects of different filler materials and different atmospheres on the microstructural, thermal and dielectric properties were investigated. The data showed that ZrO2 filler material led to better results than Al2O3 under identical working conditions and similar composite structures. ZrO2 filler material significantly enhanced the densification process of glass-ceramics (100% relative density) and led to a thermal conductivity of 2.904 W/K.m, a dielectric constant of 3.97 (at 5 MHz) and a dielectric loss of 0.0340 (at 5 MHz) for the glass with 30 wt.% ZrO2 sample. This paper suggests that prepared borosilicate glass-ceramics have strong sinterability, high thermal conductivity, and low dielectric constants, making them promising candidates for microelectronic devices.
The Importance of Biofilms on Microplastic Particles in Their Sinking Behavior and the Transfer of Invasive Organisms between Ecosystems
Authors: Gaylarde Christine C. , de Almeida Marcelo P. , Neves Charles V. , Neto José Antônio Baptista , da Fonseca Estefan M.
Published: March 2023

Although plastic is ubiquitous in marine systems, our current knowledge of its transport is limited. Recent studies suggest size-selective removal of small plastic particles (<5 mm) from the ocean surface as a result of the formation of a biofilm (the “plastisphere”) on the microplastic particle (MP) surface. This localized microenvironment can isolate the microcosm from the adjacent aqueous medium, and thus protect component alien species from the surrounding physico-chemical conditions. Apart from resulting in specific conditions for the transfer of alien species through the environment, the plastisphere can impact MP hydrodynamics and cause MPs to move through the water column, initially sinking. The importance of this phenomenon has not been previously considered for these particles. The size-dependent vertical movement of MPs through the water column determines their distribution, which will vary with time of exposure and colonization. Some plastisphere organisms have plastic-degrading activities, which could be harnessed in marine depollution strategies. This article seeks to increase our understanding of the role of biofilms in the biological dynamics and diffusion of plastic microparticles.
A Guide to Molecular Characterization of Genotype II African Swine Fever Virus: Essential and Alternative Genome Markers
Authors: Mazloum Ali , van Schalkwyk Antoinette , Chernyshev Roman , Igolkin Alexey , Heath Livio , Sprygin Alexander
Published: March 2023

African swine fever is a contagious viral disease that has been spreading through Europe and Asia since its initial report from Georgia in 2007. Due to the large genome size of the causative agent, the African swine fever virus (ASFV), the molecular epidemiology, and virus evolution are analyzed by employing different markers. Most of these markers originate from single nucleotide polymorphisms or disparities in the copy number of tandem repeat sequences observed during the comparisons of full genome sequences produced from ASFVs isolated during different outbreaks. Therefore, consistent complete genome sequencing and comparative analysis of the sequence data are important to add innovative genomic markers that contribute to the delineation of ASFV phylogeny and molecular epidemiology during active circulation in the field. In this study, the molecular markers currently employed to assess the genotype II ASFVs circulating in Europe and Asia have been outlined. The application of each of these markers to differentiate between ASFVs from related outbreaks is described to implement a guideline to their suitability for analyzing new outbreaks. These markers do not signify the complete repertoire of genomic differences between ASFVs, but will be beneficial when analyzing the first outbreaks in a new region or a large number of samples. Furthermore, new markers must be determined via complete genome sequence analyses for enabling in-depth insights into the molecular epidemiology of ASFV.
Novel Functional Grape Juices Fortified with Free or Immobilized Lacticaseibacillus rhamnosus OLXAL-1
Authors: Nikolaou Anastasios , Mitropoulou Gregoria , Nelios Grigorios , Kourkoutas Yiannis
Published: March 2023

During the last decade, a rising interest in novel functional products containing probiotic microorganisms has been witnessed. As food processing and storage usually lead to a reduction of cell viability, freeze-dried cultures and immobilization are usually recommended in order to maintain adequate loads and deliver health benefits. In this study, freeze-dried (free and immobilized on apple pieces) Lacticaseibacillus rhamnosus OLXAL-1 cells were used to fortify grape juice. Juice storage at ambient temperature resulted in significantly higher (>7 log cfu/g) levels of immobilized L. rhamnosus cells compared to free cells after 4 days. On the other hand, refrigerated storage resulted in cell loads > 7 log cfu/g for both free and immobilized cells for up to 10 days, achieving populations > 109 cfu per share, with no spoilage noticed. The possible resistance of the novel fortified juice products to microbial spoilage (after deliberate spiking with Saccharomyces cerevisiae or Aspergillus niger) was also investigated. Significant growth limitation of both food-spoilage microorganisms was observed (both at 20 and 4 °C) when immobilized cells were contained compared to the unfortified juice. Keynote volatile compounds derived from the juice and the immobilization carrier were detected in all products by HS-SPME GC/MS analysis. PCA revealed that both the nature of the freeze-dried cells (free or immobilized), as well as storage temperature affected significantly the content of minor volatiles detected and resulted in significant differences in the total volatile concentration. Juices with freeze-dried immobilized cells were distinguished by the tasters and perceived as highly novel. Notably, all fortified juice products were accepted during the preliminary sensory evaluation.
Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil
Authors: da Matta Vania Lucia R. , Gonçalves André N. , Gomes Cláudia Maria C. , Chouman Islam H. , Ferreira Frederico M. , Campos Marliane B. , Lima Luciana V. , Vasconcelos dos Santos Thiago , Ramos Patrícia Karla , Furtado Rodrigo R. , Laurenti Marcia D. , Corbett Carlos Eduardo P. , Nakaya Helder I. , Silveira Fernando T.
Published: March 2023

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.
Significance of Secondary Fe-Oxide and Fe-Sulfide Minerals in Upper Peak Ring Suevite from the Chicxulub Impact Structure
Authors: Verhagen Christina M. , Jung Ji-In , Tikoo Sonia M. , Wittmann Axel , Kring David A. , Brachfeld Stefanie , Wu Laying , Burns Dale H. , Gulick Sean P. S.
Published: March 2023

The suevite (polymict melt rock-bearing breccia) composing the upper peak ring of the Chicxulub impact crater is extremely heterogeneous, containing a combination of relict clasts and secondary minerals. Using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM/EDS) and electron probe microanalysis (EPMA), we investigated the nature and occurrence of primary and secondary Fe-oxide and Fe-sulfide minerals to better understand hydrothermal trends such as mineral precipitation and dissolution, and to document the remobilization of Fe and associated siderophile elements within suevites. Large primary Fe-oxides (~20–100 µm) reveal decomposition and dissolution patterns, forming sub-micrometer to micrometer Fe-oxide phases. Secondary sub-micrometer Fe-oxide crystals are also visibly concentrated within clay. The occurrence of Fe-oxide crystals within clay suggests that these likely formed at temperatures ≤100 °C, near the formation temperature of smectite. The formation of Fe-oxide minerals on clay surfaces is of interest as it may form a micro-setting, where free electrons (from the oxidation of Fe2+) and the adsorption of simple organic molecules on the surface of clay could generate reactive conditions favorable to microbial communities. Primary and secondary Fe-sulfide minerals exhibiting a variety of morphologies are present within samples, representing different formation mechanisms. Secondary Fe-sulfide minerals occur within rims of clasts and vesicles and in fractures and voids. Some secondary Fe-sulfide grains are associated with Ni- and Co-rich phases, potentially reflecting the post-impact migration of siderophile elements within the suevite of the Chicxulub crater.
Studies on the Prediction and Extraction of Methanol and Dimethyl Carbonate by Hydroxyl Ammonium Ionic Liquids
Authors: Wang Xiaokang , Cui Yuanyuan , Song Yingying , Liu Yifan , Zhang Junping , Chen Songsong , Dong Li , Zhang Xiangping
Published: March 2023

The separation of dimethyl carbonate (DMC) and methanol is of great significance in industry. In this study, ionic liquids (ILs) were employed as extractants for the efficient separation of methanol from DMC. Using the COSMO-RS model, the extraction performance of ILs consisting of 22 anions and 15 cations was calculated, and the results showed that the extraction performance of ILs with hydroxylamine as the cation was much better. The extraction mechanism of these functionalized ILs was analyzed by molecular interaction and the σ-profile method. The results showed that the hydrogen bonding energy dominated the interaction force between the IL and methanol, and the molecular interaction between the IL and DMC was mainly Van der Waals force. The molecular interaction changes with the type of anion and cation, which in turn affects the extraction performance of ILs. Five hydroxyl ammonium ILs were screened and synthesized for extraction experiments to verify the reliability of the COSMO-RS model. The results showed that the order of selectivity of ILs predicted by the COSMO-RS model was consistent with the experimental results, and ethanolamine acetate ([MEA][Ac]) had the best extraction performance. After four regeneration and reuse cycles, the extraction performance of [MEA][Ac] was not notably reduced, and it is expected to have industrial applications in the separation of methanol and DMC.
Design and Synthesis of New Acyl Urea Analogs as Potential σ1R Ligands
Authors: Thapa Rajesh , Flores Rafael , Cheng Kwan H. , Mochona Bereket , Sikazwe Donald
Published: March 2023

In search of synthetically accessible open-ring analogs of PD144418 or 5-(1-propyl-1,2,5,6-tetrahydropyridin-3-yl)-3-(p-tolyl)isoxazole, a highly potent sigma-1 receptor (σ1R) ligand, we herein report the design and synthesis of sixteen arylated acyl urea derivatives. Design aspects included modeling the target compounds for drug-likeness, docking at σ1R crystal structure 5HK1, and contrasting the lower energy molecular conformers with that of the receptor-embedded PD144418—a molecule we opined that our compounds could mimic pharmacologically. Synthesis of our acyl urea target compounds was achieved in two facile steps which involved first generating the N-(phenoxycarbonyl) benzamide intermediate and then coupling it with the appropriate amines weakly to strongly nucleophilic amines. Two potential leads (compounds 10 and 12, with respective in vitro σ1R binding affinities of 2.18 and 9.54 μM) emerged from this series. These leads will undergo further structure optimization with the ultimate goal of developing novel σ1R ligands for testing in neurodegeneration models of Alzheimer’s disease (AD).
Sweetener System Intervention Shifted Neutrophils from Homeostasis to Priming
Authors: Skurk Thomas , Krämer Tamara , Marcinek Patrick , Malki Agne , Lang Roman , Dunkel Andreas , Krautwurst Tiffany , Hofmann Thomas F. , Krautwurst Dietmar
Published: March 2023

Background: Non-nutritive sweeteners (NNS) are part of personalized nutrition strategies supporting healthy glycemic control. In contrast, the consumption of non-nutritive sweeteners has been related to person-specific and microbiome-dependent glycemic impairments. Reports on the effects of NNS on our highly individual cellular immune system are sparse. The recent identification of taste receptor expression in a variety of immune cells, however, suggested their immune-modulatory relevance. Methods: We studied the influence of a beverage-typical NNS system on the transcriptional profiling of sweetener-cognate taste receptors, selected cytokines and their receptors, and on Ca2+ signaling in isolated blood neutrophils. We determined plasma concentrations of saccharin, acesulfame-K, and cyclamate by HPLC-MS/MS, upon ingestion of a soft drink-typical sweetener surrogate. In an open-labeled, randomized intervention study, we determined pre- versus post-intervention transcript levels by RT-qPCR of sweetener-cognate taste receptors and immune factors. Results: Here we show that the consumption of a food-typical sweetener system modulated the gene expression of cognate taste receptors and induced the transcriptional regulation signatures of early homeostasis- and late receptor/signaling- and inflammation-related genes in blood neutrophils, shifting their transcriptional profile from homeostasis to priming. Notably, sweeteners at postprandial plasma concentrations facilitated fMLF (N-formyl-Met-Leu-Phe)-induced Ca2+ signaling. Conclusions: Our results support the notion of sweeteners priming neutrophils to higher alertness towards their adequate stimuli.
Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome
Authors: Chojnacki Cezary , Błońska Aleksandra , Konrad Paulina , Chojnacki Marcin , Podogrocki Marcin , Poplawski Tomasz
Published: March 2023

(1) Background: L-tryptophan is a substrate for the synthesis of many biological compounds through the serotonin and kynurenine pathways. These compounds have a significant influence on gastrointestinal functions and mental processes. The aim of the study was to evaluate the urinary excretion of selected tryptophan metabolites in patients with constipation-predominant and diarrhoea-predominant irritable bowel syndrome (IBS-C and IBS-D, respectively), related to somatic and mental symptoms. (2) Methods: 120 people were included in the study and three groups were distinguished, with 40 individuals each, including healthy subjects (controls), patients with IBS-C and patients with IBS-D. The Gastrointestinal Symptoms Rating Scale (GSRS-IBS) was used to assess the severity of abdominal symptoms. The Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were used to evaluate the mental state of patients. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), L-tryptophan and the following metabolites in urine, related to the creatinine level, were measured: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA). (3) Results: In both groups of patients with IBS, changes in tryptophan metabolism were found as compared to the control group. We observed an increase in the activity of the serotonin pathway and a positive correlation between the 5-HIAA level and the GSRS score (p < 0.01) and HAM-A score (p < 0.001) in IBS-D patients. The IBS-C group was characterized by a higher concentration of kynurenines (KYN, QA) in urine. Moreover, the QA (p < 0.001) and KYNA (p < 0.05) levels were correlated with the HAM-D score among IBS-C patients. (4) Conclusions: Various changes in the tryptophan metabolism pathway can determine the differences in the clinical picture of irritable bowel syndrome. These results should be included in the nutritional and pharmacological treatment of this syndrome.
Challenges Regarding Transition from Case-Based Learning to Problem-Based Learning: A Qualitative Study with Student Nurses
Authors: Phage Ramoipei J. , Molato Boitumelo J. , Matsipane Molekodi J.
Published: March 2023

Background: The transition from case-based learning to problem-based learning can be challenging and may have negative effects on the academic, psychological, emotional, or social well-being of student nurses. As a result, this exposes student nurses to high failure rates, anxiety disorders, a loss of uniqueness, and fear of the unknown. However, student nurses employ different strategies aimed at overcoming challenges faced during this transition period. Methods: An exploratory, and descriptive research approach was used. A purposive non-probability sampling technique was used to select participants. Focus group discussions via Zoom video communication were used to collect data, which were analysed using Braun and Clarke’s six steps of thematic analysis. Results: The following three themes emerged: challenges regarding facilitation, challenges regarding assessment, and strategies to overcome challenges. Conclusions: The study established that student nurses are faced with different challenges during the transition from one teaching strategy to another. Student nurses suggested strategies that could be used to overcome these challenges. However, these strategies are not enough and therefore more needs to be done to support and empower student nurses.
Prospects for the (Hyper)Nuclei Study in the Nica Energy Range
Authors: Kireyeu Viktar , Kolesnikov Vadim , Zinchenko Alexander , Vasendina Veronika , Mudrokh Alexander
Published: March 2023

The production of nuclei and hypernuclei is of interest for experimental and theoretical studies: it is a big question how such weakly bound objects survive in a hot, dense environment and which new insights on the heavy-ion collisions dynamics they can bring us. We present the results on the hypernuclei feasibility study for the flagship Nuclotron-based Ion Collider fAcility (NICA)/Multi-Purpose Detector (MPD) experiment at the Joint Institute for Nuclear Research (JINR) in Dubna using the Parton-Hadron-Quantum-Molecular Dynamics (PHQMD) transport approach and a realistic reconstruction chain.
Preparation and Characterization of Amorphous Solid Dispersions for the Solubilization of Fenretinide
Authors: Zuccari Guendalina , Russo Eleonora , Villa Carla , Zorzoli Alessia , Marimpietri Danilo , Marchitto Leonardo , Alfei Silvana
Published: March 2023

Fenretinide (4-HPR), a retinoid derivative, has shown high antitumor activity, a low toxicological profile, and no induction of resistance. Despite these favorable features, the variability in oral absorption due to its low solubility combined with the high hepatic first pass effect strongly reduce clinical outcomes. To overcome the solubility and dissolution challenges of poorly water-soluble 4-HPR, we prepared a solid dispersion of the drug (4-HPR-P5) using a hydrophilic copolymer (P5) previously synthesized by our team as the solubilizing agent. The molecularly dispersed drug was obtained by antisolvent co-precipitation, an easy and up-scalable technique. A higher drug apparent solubility (1134-fold increase) and a markedly faster dissolution were obtained. In water, the colloidal dispersion showed a mean hydrodynamic diameter of 249 nm and positive zeta potential (+41.3 mV), confirming the suitability of the formulation for intravenous administration. The solid nanoparticles were also characterized by a high drug payload (37%), as was also evidenced by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. The 4-HPR-P5 exhibited antiproliferative activity, with IC50 values of 1.25 and 1.93 µM on IMR-32 and SH-SY5Y neuroblastoma cells, respectively. Our data confirmed that the 4-HPR-P5 formulation developed herein was able to increase drug apparent aqueous solubility and provide an extended release over time, thus suggesting that it represents an efficient approach to improve 4-HPR bioavailability.
A Validated Chiral LC–MS/MS Method for the Enantioselective Determination of (S)-(+)- and (R)-(-)-Ibuprofen in Dog Plasma: Its Application to a Pharmacokinetic Study
Authors: Choi Sanghee , Shim Wang-Seob , Yoon Jiyoung , Choi Doowon , Lee Jinseong , Paik Soo-Heui , Chung Eun-Kyoung , Lee Kyung-Tae
Published: March 2023

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC–MS/MS). LC–MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid–liquid extraction, 10 μL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water–methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs.
CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization
Authors: Sebastião Ana Isabel , Mateus Daniela , Carrascal Mylène A. , Sousa Cátia , Cortes Luísa , Bachmann Martin F. , do Carmo Anália , Matos Ana Miguel , Sales Maria Goreti F. , Cruz Maria Teresa
Published: March 2023

Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs’ interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2.