bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Flexible Family of Continuous Distributions: The Additive Odd-G Family
Authors: Altun Emrah , Korkmaz Mustafa Ç. , El-Morshedy Mahmoud , Eliwa Mohamed S.
Published: August 2021

This paper introduces a new family of distributions based on the additive model structure. Three submodels of the proposed family are studied in detail. Two simulation studies were performed to discuss the maximum likelihood estimators of the model parameters. The log location-scale regression model based on a new generalization of the Weibull distribution is introduced. Three datasets were used to show the importance of the proposed family. Based on the empirical results, we concluded that the proposed family is quite competitive compared to other models.
Preserving Geo-Indistinguishability of the Emergency Scene to Predict Ambulance Response Time
Authors: Arcolezi Héber , Cerna Selene , Guyeux Christophe , Couchot Jean-François
Published: August 2021

Emergency medical services (EMS) provide crucial emergency assistance and ambulatory services. One key measurement of EMS’s quality of service is their ambulances’ response time (ART), which generally refers to the period between EMS notification and the moment an ambulance arrives on the scene. Due to many victims requiring care within adequate time (e.g., cardiac arrest), improving ARTs is vital. This paper proposes to predict ARTs using machine-learning (ML) techniques, which could be used as a decision-support system by EMS to allow a dynamic selection of ambulance dispatch centers. However, one well-known predictor of ART is the location of the emergency (e.g., if it is urban or rural areas), which is sensitive data because it can reveal who received care and for which reason. Thus, we considered the ‘input perturbation’ setting in the privacy-preserving ML literature, which allows EMS to sanitize each location data independently and, hence, ML models are trained only with sanitized data. In this paper, geo-indistinguishability was applied to sanitize each emergency location data, which is a state-of-the-art formal notion based on differential privacy. To validate our proposals, we used retrospective data of an EMS in France, namely Departmental Fire and Rescue Service of Doubs, and publicly available data (e.g., weather and traffic data). As shown in the results, the sanitization of location data and the perturbation of its associated features (e.g., city, distance) had no considerable impact on predicting ARTs. With these findings, EMSs may prefer using and/or sharing sanitized datasets to avoid possible data leakages, membership inference attacks, or data reconstructions, for example.
Functional Mitral Regurgitation in Patients with Preserved Ejection Fraction Qualified for Pulmonary Vein Isolation: A Negative Prognostic Factor for Catheter Ablation Efficacy
Authors: Cichoń Małgorzata , Wybraniec Maciej , Mizia-Szubryt Magdalena , Mizia-Stec Katarzyna
Published: August 2021

Background and Objectives: Functional mitral regurgitation (F-MR) observed in patients with atrial fibrillation could affect the effectiveness of the sinus rhythm restoring procedures. The aim of the study was to evaluate the impact of F-MR on pulmonary vein isolation (PVI) efficacy in patient with preserved ejection fraction (EF). Materials and Methods: One hundred and thirty-six patients with EF ≥ 50% (65.4% males; mean age 56 ± 11 years) with symptomatic paroxysmal or persistent AF qualified for PVI were enrolled into the study. F-MR assessment was performed in transthoracic (TTE) and transesophageal (TEE) echocardiography before the PVI procedure. PVI efficacy was evaluated in three-month and long-term follow-up. Results: F-MR was diagnosed in 74.3% patient in transthoracic echocardiography (TTE) (trace: 26.5%, mild: 43.4%, moderate: 3.7%, severe 0.7%) and 94.9% in transesophageal echocardiography (TEE) (trace: 17.6%, mild: 59.6%, moderate: 16.2%, severe: 1.5%). The PVI three-month efficacy was 75.7% in the three-month and 64% in the long-term observation. Severe F-MR in TEE at baseline was associated with lower three-month PVI efficacy (p = 0.012), while moderate to severe F-MR in TEE was related to inefficient PVI assessed in long-term follow-up (p = 0.041). Conclusions: Significant F-MR confirmed by TEE predicts three-month as well as long-term PVI efficacy.
Association between Advanced Lung Inflammation Index and 30-Day Mortality in Patients with Acute Respiratory Distress Syndrome
Authors: Heo Manbong , Jeong Jonghwan , Heo Ire , Ju Sunmi , Lee Seungjun , Jeong Yiyeong , Lee Jongdeog , Kim Hocheol , Yoo Jungwan
Published: August 2021

Background and objectives: The advanced lung inflammation index (ALI) was developed to assess the degree of systemic inflammation and has an association with prognosis in patients with lung malignancy. The prognostic value of ALI has not yet been evaluated in patients with acute respiratory distress syndrome (ARDS). Materials and Methods: Between January 2014 and May 2018, patients with ARDS in the medical intensive care unit (ICU) were reviewed retrospectively. The ALI value was calculated as the (body mass index × serum albumin level)/neutrophil-lymphocyte ratio. The cut-off value for distinguishing low from high ALI was defined according to receiver-operating characteristic curve analysis. Results: A total of 164 patients were analyzed. Their median age was 73 years, and 73% was male. The main cause of ARDS was pneumonia (95.7%, 157/164). ICU and in-hospital mortality rates were 59.8% (98/164) and 64% (105/164), respectively. The 30 day mortality was 60.9% (100/164). The median ALI value in non-survivors was lower than that in survivors at 30 day (3.81 vs. 7.39, p = 0.005). In multivariate analysis, low ALI value (≤5.38) was associated with increased 30 day mortality (odds ratio, 2.944, confidence interval 1.178–7.355, p = 0.021). Conclusions: A low ALI value was associated with increased 30 day mortality in patients with ARDS.
Microstructural Characterization and Crack Propagation Behavior of a Novel β-Solidifying TiAl Alloy
Authors: Zhang Shuling , Cui Ning , Sun Wei , Li Qiucheng
Published: August 2021

Novel β-solidifying TiAl alloys have great potential for engineering applications in the aerospace and automotive industries. The introduction of the β0 phase will inevitably affect crack propagation. However, the related mechanism is unclear. In this study, the crack propagation behavior of different β0-containing microstructures was systematically investigated by three-point bending tests. The results show that the coarse γ/α2 lamellar microstructure exhibits better fracture toughness than the fine-grain microstructure because large numbers of γ/α2 lamellar boundaries can effectively hinder crack propagation. The propagation direction depends largely on the orientation of the γ/α2 lamellae. When the angle between the crack propagation direction and the γ/α2 lamellar boundary is small, the crack tends to propagate along γ/α2 lamellae. When the angle is close to 90°, the crack generally propagates by the trans-lamellar mode. Moreover, the crack tends to traverse across the fine β0/γ duplex region due to the low resistance of fine grains in the crack propagation. The transgranular and intergranular modes are the main fracture mechanisms in the microstructure of the fine β0/γ grains. Some shear ligaments can also be identified in the lamellar microstructure and these can consume propagation energy. The enlarged image shows that the crack propagation direction can be changed by the β0 phase, owing to its high hardness. The crack tends to stop at the β0 phase region.
Influence of Segmented Rolls on Homogeneity of Cooling in Continuous Casting
Authors: Kominek Jan , Luks Tomas , Pohanka Michal , Hwang Jong-Yeon
Published: August 2021

This paper deals with secondary cooling in a continuous caster. In particular, it deals with cooling inhomogeneity caused by spray arrangement and segmented rolls used for leading the strand. The cooling section is placed under the mold. Segmented rolls are supported by bearings in several places across the strand. Sprayed water can flow in the gaps between rolls where the bearing pocket is located. The main question that was experimentally studied is how this geometry with segmented rolls can influence homogeneity of cooling. Two experimental approaches developed for this study were applied, and both used full-scale geometrical configuration. The first one was a cold test where water flow and water distribution were observed using a transparent board with the studied surface structures (rollers and bearing pockets) and four spraying nozzles. The second one was a cooling test using a heated steel plate with rolls and bearing pockets. Cooling homogeneity was studied based on the temperature distribution on the rear side of the sample, which was recorded using an infrared camera. Homogeneity of cooling distribution was experimentally studied for three levels of cooling intensity that are used in typical cooling sections in plants. The hot tests showed that the bearing pockets do not provide significant cooling inhomogeneity despite the fact that a large amount of water flows through the gap between the rollers (which has been observed in cold tests).
Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans
Authors: Valente-Silva Paula , Cervenka Igor , Ferreira Duarte M. S. , Correia Jorge C. , Edman Sebastian , Horwath Oscar , Heng Benjamin , Chow Sharron , Jacobs Kelly R. , Guillemin Gilles J. , Blomstrand Eva , Ruas Jorge L.
Published: August 2021

The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.
Serum Retinal and Retinoic Acid Predict the Development of Type 2 Diabetes Mellitus in Korean Subjects with Impaired Fasting Glucose from the KCPS-II Cohort
Authors: Han Youngmin , Yang Yeunsoo , Kim Minjoo , Jee Sun Ha , Yoo Hye Jin , Lee Jong Ho
Published: August 2021

We aimed to investigate whether retinal and retinoic acid (RA), which are newly discovered biomarkers from our previous research, reliably predict type 2 diabetes mellitus (T2DM) development in subjects with impaired fasting glucose (IFG). Among the Korean Cancer Prevention Study (KCPS)-II cohort, subjects were selected and matched by age and sex (IFG-IFG group, n = 100 vs. IFG-DM group, n = 100) for study 1. For real-world validation of two biomarkers (study 2), other participants in the KCPS-II cohort who had IFG at baseline (n = 500) were selected. Targeted LC/MS was used to analyze the baseline serum samples; retinal and RA levels were quantified. In study 1, we revealed that both biomarkers were significantly decreased in the IFG-DM group (retinal, p = 0.017; RA, p < 0.001). The obese subjects in the IFG-DM group showed markedly lower retinal (p = 0.030) and RA (p = 0.003) levels than those in the IFG-IFG group. In study 2, the results for the two metabolites tended to be similar to those of study 1, but no significant difference was observed. Notably, the predictive ability for T2DM was enhanced when the metabolites were added to conventional risk factors for T2DM in both studies (study 1, AUC 0.682 → 0.775; study 2, AUC 0.734 → 0.786). The results suggest that retinal- and RA-related metabolic pathways are altered before the onset of T2DM.
Proline as a Sparker Metabolite of Oxidative Metabolism during the Flight of the Bumblebee, Bombus impatiens
Authors: Stec Nadia , Saleem Ammar , Darveau Charles-A.
Published: August 2021

Several insect species use the amino acid proline as a major energy substrate. Although initially thought to be limited to blood-feeding dipterans, studies have revealed this capability is more widespread. Recent work with isolated flight muscle showed that the bumblebee Bombus impatiens can oxidize proline at a high rate. However, its role as a metabolic fuel to power flight is unclear. To elucidate the extent to which proline is oxidized to power flight and how its contribution changes during flight, we profiled 14 metabolites central to energy and proline metabolism at key time points in flight muscle and abdominal tissues. Ultra-high performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF MS) analysis revealed that proline is likely used as a sparker metabolite of the tricarboxylic acid cycle at the onset of flight, whereby it supplements the intermediates of the cycle. Carbohydrates are the major energy substrates, which is evidenced by marked decreases in abdominal glycogen stores and a lack of alanine accumulation to replenish flight muscle proline. The time course of fuel stores and metabolites changes during flight highlights homeostatic regulation of energy substrates and patterns of changes in metabolic intermediates within pathways. This study clarifies the role of proline and carbohydrate metabolism during flight in hymenopterans, such as B. impatiens.
Taxogenomic and Metabolic Insights into Marinobacterium ramblicola sp. nov., a New Slightly Halophilic Bacterium Isolated from Rambla Salada, Murcia
Authors: Durán-Viseras Ana , Castro David J. , Reina José Carlos , Béjar Victoria , Martínez-Checa Fernando
Published: August 2021

A Gram-negative, motile, rod-shaped bacteria, designated D7T, was isolated by using the dilution-to-extinction method, from a soil sample taken from Rambla Salada (Murcia, Spain). Growth of strain D7T was observed at 15–40 °C (optimum, 37 °C), pH 5–9 (optimum, 7) and 0–7.5% (w/v) NaCl (optimum, 3%). It is facultatively anaerobic. Phylogenetic analysis based on 16S rRNA gene sequence showed it belongs to the genus Marinobacterium. The in silico DDH and ANI against closest Marinobacterium relatives support its placement as a new species within this genus. The major fatty acids of strain D7T were C16:0, summed feature 3 (C16:1 ω7c/C16:1 ω6c) and summed feature 8 (C18:1 ω7c/C18:1 ω6c). The polar lipid profile consists of phosphatidylethanolamine, phosphatidylglycerol and two uncharacterized lipids. Ubiquinone 8 was the unique isoprenoid quinone detected. The DNA G + C content was 59.2 mol%. On the basis of the phylogenetic, phenotypic, chemotaxonomic and genomic characterization, strain D7T (= CECT 9818T = LMG 31312T) represents a novel species of the genus Marinobacterium for which the name Marinobacterium ramblicola sp. nov. is proposed. Genome-based metabolic reconstructions of strain D7T suggested a heterotrophic and chemolitotrophic lifestyle, as well as the capacity to biosynthetize and catabolize compatible solutes, and to degrade hydrocarbon aromatic compounds.
Isolation and Biochemical Characterization of Six Anaerobic Fungal Strains from Zoo Animal Feces
Authors: Stabel Marcus , Schweitzer Tabea , Haack Karoline , Gorenflo Pascal , Aliyu Habibu , Ochsenreither Katrin
Published: August 2021

Anaerobic fungi are prime candidates for the conversion of agricultural waste products to biofuels. Despite the increasing interest in these organisms, their growth requirements and metabolism remain largely unknown. The isolation of five strains of anaerobic fungi and their identification as Neocallimastix cameroonii, Caecomyces spec., Orpinomyces joyonii, Pecoramyces ruminantium, and Khoyollomyces ramosus, is described. The phylogeny supports the reassignment of Neocallimastix californiae and Neocallimastix lanati to Neocallimastix cameroonii and points towards the redesignation of Cyllamyces as a species of Caecomyces. All isolated strains including strain A252, which was described previously as Aestipascuomyces dubliciliberans, were further grown on different carbon sources and the produced metabolites were analyzed; hydrogen, acetate, formate, lactate, and succinate were the main products. Orpinomyces joyonii was lacking succinate production and Khoyollomyces ramosus was not able to produce lactate under the studied conditions. The results further suggested a sequential production of metabolites with a preference for hydrogen, acetate, and formate. By comparing fungal growth on monosaccharides or on the straw, a higher hydrogen production was noticed on the latter. Possible reactions to elevated sugar concentrations by anaerobic fungi are discussed.
Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis
Authors: Esberg Anders , Johansson Linda , Johansson Ingegerd , Dahlqvist Solbritt Rantapää
Published: August 2021

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.
Microbial L-asparaginase for Application in Acrylamide Mitigation from Food: Current Research Status and Future Perspectives
Authors: Jia Ruiying , Wan Xiao , Geng Xu , Xue Deming , Xie Zhenxing , Chen Chaoran
Published: August 2021

L-asparaginase (E.C.3.5.1.1) hydrolyzes L-asparagine to L-aspartic acid and ammonia, which has been widely applied in the pharmaceutical and food industries. Microbes have advantages for L-asparaginase production, and there are several commercially available forms of L-asparaginase, all of which are derived from microbes. Generally, L-asparaginase has an optimum pH range of 5.0–9.0 and an optimum temperature of between 30 and 60 °C. However, the optimum temperature of L-asparaginase from hyperthermophilic archaea is considerable higher (between 85 and 100 °C). The native properties of the enzymes can be enhanced by using immobilization techniques. The stability and recyclability of immobilized enzymes makes them more suitable for food applications. This current work describes the classification, catalytic mechanism, production, purification, and immobilization of microbial L-asparaginase, focusing on its application as an effective reducer of acrylamide in fried potato products, bakery products, and coffee. This highlights the prospects of cost-effective L-asparaginase, thermostable L-asparaginase, and immobilized L-asparaginase as good candidates for food application in the future.
Phylogeny of Nitrogenase Structural and Assembly Components Reveals New Insights into the Origin and Distribution of Nitrogen Fixation across Bacteria and Archaea
Authors: Koirala Amrit , Brözel Volker S.
Published: August 2021

The phylogeny of nitrogenase has only been analyzed using the structural proteins NifHDK. As nifHDKENB has been established as the minimum number of genes necessary for in silico prediction of diazotrophy, we present an updated phylogeny of diazotrophs using both structural (NifHDK) and cofactor assembly proteins (NifENB). Annotated Nif sequences were obtained from InterPro from 963 culture-derived genomes. Nif sequences were aligned individually and concatenated to form one NifHDKENB sequence. Phylogenies obtained using PhyML, FastTree, RapidNJ, and ASTRAL from individuals and concatenated protein sequences were compared and analyzed. All six genes were found across the Actinobacteria, Aquificae, Bacteroidetes, Chlorobi, Chloroflexi, Cyanobacteria, Deferribacteres, Firmicutes, Fusobacteria, Nitrospira, Proteobacteria, PVC group, and Spirochaetes, as well as the Euryarchaeota. The phylogenies of individual Nif proteins were very similar to the overall NifHDKENB phylogeny, indicating the assembly proteins have evolved together. Our higher resolution database upheld the three cluster phylogeny, but revealed undocumented horizontal gene transfers across phyla. Only 48% of the 325 genera containing all six nif genes are currently supported by biochemical evidence of diazotrophy. In addition, this work provides reference for any inter-phyla comparison of Nif sequences and a quality database of Nif proteins that can be used for identifying new Nif sequences.
Comparison of Direct and Indirect Toxoplasma gondii Detection and Genotyping in Game: Relationship and Challenges
Authors: Stollberg Kaya C. , Schares Gereon , Mayer-Scholl Anne , Hrushetska Iryna , Diescher Susanne , Johne Annette , Richter Martin H. , Bier Nadja S.
Published: August 2021

The importance of game as a source of Toxoplasma gondii (T. gondii) infection in humans is largely unknown. New data on the presence of T. gondii in game hunted in the Federal State of Brandenburg, Germany, were obtained by direct and indirect detection (ELISA). DNA extracted either directly (5 g heart or foreleg muscle, DE) or after acid pepsin digestion (50 g heart, PD) or enriched by magnetic capture (50 g heart, MC) was examined by real-time PCR (qPCR). ELISA revealed seroprevalences of 20% in wild boar (Sus scrofa), 11% in roe deer (Capreolus capreolus) and 6% in red deer (Cervus elaphus). T. gondii DNA was detected by at least one direct detection method in 12% of wild boar, 6% of roe deer, 2% of fallow deer (Dama dama) and 2% of red deer. In both, positive wild boar and roe deer, T. gondii type II specific alleles were the most prevalent, as assessed by PCR-restriction fragment length polymorphism. The highest proportion of positive animals was detected by MC qPCR, followed by PD qPCR with a similar proportion of positive findings. Investigation of 50 g of heart muscle revealed a significantly higher proportion of positive qPCR results than analysis of 5 g (p = 0.048). An association between seropositivity and direct detection was evident in wild boar and roe deer (p < 0.001). Infectivity of T. gondii DNA–positive samples was confirmed by bioassay (4/4), providing evidence that game could represent a relevant source of viable T. gondii posing a risk for human infection.
Development of a Novel Method for Identification of Alaria alata Mesocercariae by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
Authors: Kästner Carolyn , Bahn Peter , Schönfelder Ralph , Ozoliņa Zanda , Alksne Laura , Richter Martin Heinrich , Deksne Gunita , Mayer-Scholl Anne , Johne Annette
Published: August 2021

Alaria (A.) alata mesocercariae (AM) have increasingly appeared as incidental findings during the mandatory inspection of wild boars for Trichinella in many European countries. An Alaria spp.-specific PCR is available for the identification of AM; however, it is time- and cost-intensive. Therefore, we propose a rapid and cost-efficient MALDI-TOF assay for the identification of AM in wild boar meat that can be applied in routine diagnostics. In this study, a fast and methodologically simple protocol for the protein extraction of AM from different host species in different countries was established, and an AM-specific reference spectra database was created as part of the ongoing development of an existing Trichinella spp. database. A formic acid protein extraction was performed after pooling 10 AM from the same host individual. In total, 61 main spectra profiles (MSPs) from different host individuals were stored in an AM-specific MSP library. The cluster analysis of these 61 MSPs indicated a possible variation within the A. alata species with a tentative association with the geographical origin of the host, but not the host species. This MALDI-TOF assay allows for a fast verification of the AM isolates, which is the next step in the development of a universal database for the identification of several parasites isolated from meat.
Rheological Contrast between Quartz and Coesite Generates Strain Localization in Deeply Subducted Continental Crust
Authors: Asano Kouhei , Michibayashi Katsuyoshi , Takebayashi Tomohiro
Published: August 2021

Deformation microstructures of peak metamorphic conditions in ultrahigh-pressure (UHP) metamorphic rocks constrain the rheological behavior of deeply subducted crustal material within a subduction channel. However, studies of such rocks are limited by the overprinting effects of retrograde metamorphism during exhumation. Here, we present the deformation microstructures and crystallographic-preferred orientation data of minerals in UHP rocks from the Dabie–Shan to study the rheological behavior of deeply subducted continental material under UHP conditions. The studied samples preserve deformation microstructures that formed under UHP conditions and can be distinguished into two types: high-strain mafic–ultramafic samples (eclogite and garnet-clinopyroxenite) and low-strain felsic samples (jadeite quartzite). This distinction suggests that felsic rocks are less strained than mafic–ultramafic rocks under UHP conditions. We argue that the phase transition from quartz to coesite in the felsic rocks may explain the microstructural differences between the studied mafic–ultramafic and felsic rock samples. The presence of coesite, which has a higher strength than quartz, may result in an increase in the bulk strength of felsic rocks, leading to strain localization in nearby mafic–ultramafic rocks. The formation of shear zones associated with strain localization under HP/UHP conditions can induce the detachment of subducted crustal material from subducting lithosphere, which is a prerequisite for the exhumation of UHP rocks. These findings suggest that coesite has an important influence on the rheological behavior of crustal material that is subducted to coesite-stable depths.
CYPstrate: A Set of Machine Learning Models for the Accurate Classification of Cytochrome P450 Enzyme Substrates and Non-Substrates
Authors: Holmer Malte , de Bruyn Kops Christina , Stork Conrad , Kirchmair Johannes
Published: August 2021

The interaction of small organic molecules such as drugs, agrochemicals, and cosmetics with cytochrome P450 enzymes (CYPs) can lead to substantial changes in the bioavailability of active substances and hence consequences with respect to pharmacological efficacy and toxicity. Therefore, efficient means of predicting the interactions of small organic molecules with CYPs are of high importance to a host of different industries. In this work, we present a new set of machine learning models for the classification of xenobiotics into substrates and non-substrates of nine human CYP isozymes: CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. The models are trained on an extended, high-quality collection of known substrates and non-substrates and have been subjected to thorough validation. Our results show that the models yield competitive performance and are favorable for the detection of CYP substrates. In particular, a new consensus model reached high performance, with Matthews correlation coefficients (MCCs) between 0.45 (CYP2C8) and 0.85 (CYP3A4), although at the cost of coverage. The best models presented in this work are accessible free of charge via the “CYPstrate” module of the New E-Resource for Drug Discovery (NERDD).
Magnetless Optical Circulator Based on an Iron Garnet with Reduced Magnetization Saturation
Authors: Portela Gianni , Levy Miguel , Hernandez-Figueroa Hugo E.
Published: August 2021

A three-port circulator for optical communication systems comprising a photonic crystal slab made of a magneto-optical material in which an magnetizing element is not required to keep its magnetic domains aligned is suggested for the first time. By maximizing the incorporation of europium to its molecular formula, the magneto-optical material can remain in the saturated magnetic state even in the absence of an external DC magnetic field. Two- and three-dimensional simulations of the device performed with full-wave electromagnetic solvers based on the finite element method demonstrate that, at the 1550 nm wavelength, the insertion loss, isolation, and reflection levels are equal to or better than −1 dB, −14 dB, and −20 dB, respectively. Since its operation does not require an electromagnet or a permanent magnet, the suggested circulator is much more compact, being able to reach footprints in the range of three orders of magnitude smaller, when compared to other circulator designs referred to in the literature and the presented results can be useful for the design of other nonreciprocal devices with reduced dimensions for optical communication systems.
Modeling Chemical Reactivity at the Interfaces of Emulsions: Effects of Partitioning and Temperature
Authors: Costa Marlene , Paiva-Martins Fátima , Losada-Barreiro Sonia , Bravo-Díaz Carlos
Published: August 2021

Bulk phase chemistry is hardly ever a reasonable approximation to interpret chemical reactivity in compartmentalized systems, because multiphasic systems may alter the course of chemical reactions by modifying the local concentrations and orientations of reactants and by modifying their physical properties (acid-base equilibria, redox potentials, etc.), making them—or inducing them—to react in a selective manner. Exploiting multiphasic systems as beneficial reaction media requires an understanding of their effects on chemical reactivity. Chemical reactions in multiphasic systems follow the same laws as in bulk solution, and the measured or observed rate constant of bimolecular reactions can be expressed, under dynamic equilibrium conditions, in terms of the product of the rate constant and of the concentrations of reactants. In emulsions, reactants distribute between the oil, water, and interfacial regions according to their polarity. However, determining the distributions of reactive components in intact emulsions is arduous because it is physically impossible to separate the interfacial region from the oil and aqueous ones without disrupting the existing equilibria and, therefore, need to be determined in the intact emulsions. The challenge is, thus, to develop models to correctly interpret chemical reactivity. Here, we will review the application of the pseudophase kinetic model to emulsions, which allows us to model chemical reactivity under a variety of experimental conditions and, by carrying out an appropriate kinetic analysis, will provide important kineticparameters.
Formulation of Environmentally Safe Graffiti Remover Containing Esterified Plant Oils and Sugar Surfactant
Authors: Bartman Marcin , Balicki Sebastian , Wilk Kazimiera A.
Published: August 2021

The removal of graffiti or over-painting requires special attention in order to not induce the surface destruction but to also address all of the important eco-compatibility concerns. Because of the necessity to avoid the use of volatile and toxic petroleum-based solvents that are common in cleaning formulations, much attention has recently been paid to the design of a variety of sustainable formulations that are based on biodegradable raw materials. In the present contribution we propose a new approach to graffiti cleaning formulations that are composed of newly synthesized green solvents such as esterified plant oils, i.e., rapeseed oil (RO), sunflower oil (SO), or used cooking oil (UCO), ethyl lactate (EL), and alkylpolyglucosides (APGs) as surfactants. Oil PEG-8 ester solvents were synthesized through the direct esterification/transesterification of these oils using monobutyltin(IV) tris(2-ethylhexanoate) and titanium(IV) butoxide catalysts under mild process conditions. The most efficient formulations, determined by optimization through the response surface methodology (RSM) was more effective in comparison to the reference solvents such as the so-called Nitro solvent (denoting a mixture of toluene and acetone) and petroleum ether. Additionally, the optimal product was found to be effective in removing graffiti from glass, metal, or sandstone surfaces under open-field conditions in the city of Wrocław. The performed studies could be an invaluable tool for developing future green formulations for graffiti removal.
The Effects of Photosensitizing Dyes Fagopyrin and Hypericin on Planktonic Growth and Multicellular Life in Budding Yeast
Authors: Sytar Oksana , Kotta Konstantia , Valasiadis Dimitrios , Kosyan Anatoliy , Brestic Marian , Koidou Venetia , Papadopoulou Eleftheria , Kroustalaki Maria , Emmanouilidou Christina , Pashalidis Alexandros , Avdikos Ilias , Hilioti Zoe
Published: August 2021

Naphthodianthrones such as fagopyrin and hypericin found mainly in buckwheat (Fagopyrum spp.) and St. John’s wort (SJW) (Hypericum perforatum L.) are natural photosensitizers inside the cell. The effect of photosensitizers was studied under dark conditions on growth, morphogenesis and induction of death in Saccharomyces cerevisiae. Fagopyrin and hypericin induced a biphasic and triphasic dose response in cellular growth, respectively, over a 10-fold concentration change. In fagopyrin-treated cells, disruptions in the normal cell cycle progression were evident by microscopy. DAPI staining revealed several cells that underwent premature mitosis without budding, a striking morphological abnormality. Flow Cytometric (FC) analysis using a concentration of 100 µM showed reduced cell viability by 41% in fagopyrin-treated cells and by 15% in hypericin-treated cells. FC revealed the development of a secondary population of G1 cells in photosensitizer-treated cultures characterized by small size and dense structures. Further, we show that fagopyrin and the closely related hypericin altered the shape and the associated fluorescence of biofilm-like structures. Colonies grown on solid medium containing photosensitizer had restricted growth, while cell-to-cell adherence within the colony was also affected. In conclusion, the photosensitizers under dark conditions affected culture growth, caused toxicity, and disrupted multicellular growth, albeit with different efficiencies.
Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies
Authors: Alogna Andrea , Gentili Valentina , Trapella Claudio , Hallan Supandeep Singh , Sguizzato Maddalena , Strazzabosco Giovanni , Fernández Mercedes , Cortesi Rita , Rizzo Roberta , Bortolotti Daria
Published: August 2021

In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, p = 0.03 and p= 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, p = 0.006 and p = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.
Photodynamic Inactivation Using Natural Bioactive Compound Prevents and Disrupts the Biofilm Produced by Staphylococcus saprophyticus
Authors: Yang Wei , Wang Ziyuan , Li Qing , Jia Yating , Song Shuimiao , Ma Zichu , Liu Jie , Wang Jing
Published: August 2021

Staphylococcus saprophyticus, the food-borne bacteria present in dairy products, ready-to-eat food and environmental sources, has been reported with antibiotic resistance, raising concerns about food microbial safety. The antimicrobial resistance of S. saprophyticus requires the development of new strategies. Light- and photosensitizer-based antimicrobial photodynamic inactivation (PDI) is a promising approach to control microbial contamination, whereas there is limited information regarding the effectiveness of PDI on S. saprophyticus biofilm control. In this study, PDI mediated by natural bioactive compound (curcumin) associated with LED was evaluated for its potential to prevent and disrupt S. saprophyticus biofilms. Biofilms were treated with curcumin (50, 100, 200 µM) and LED fluence (4.32 J/cm2, 8.64 J/cm2, 17.28 J/cm2). Control groups included samples treated only with curcumin or light, and samples received neither curcumin nor light. The action was examined on biofilm mass, viability, cellular metabolic activity and cytoplasmic membrane integrity. PDI using curcumin associated with LED exhibited significant antibiofilm activities, inducing biofilm prevention and removal, metabolic inactivation, intracellular membrane damage and cell death. Likewise, scanning electronic microscopy observations demonstrated obvious structural injury and morphological alteration of S. saprophyticus biofilm after PDI application. In conclusion, curcumin is an effective photosensitizer for the photodynamic control of S. saprophyticus biofilm.
Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses
Authors: Cañas-Arranz Rodrigo , de León Patricia , Defaus Sira , Torres Elisa , Forner Mar , Bustos María J. , Andreu David , Blanco Esther , Sobrino Francisco
Published: August 2021

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.
Safety Assessment of Polypyrrole Nanoparticles and Spray-Coated Textiles
Authors: Bengalli Rossella , Fiandra Luisa , Vineis Claudia , Sanchez-Ramirez Diego Omar , Azoia Nuno G. , Varesano Alessio , Mantecca Paride
Published: August 2021

Polypyrrole (PPy) nanoparticles (NPs) are used for the coating of materials, such as textiles, with biomedical applications, including wound care and tissue engineering, but they are also promising antibacterial agents. In this work, PPy NPs were used for the spray-coating of textiles with antimicrobial properties. The functional properties of the materials were verified, and their safety was evaluated. Two main exposure scenarios for humans were identified: inhalation of PPy NPs during spray (manufacturing) and direct skin contact with NPs-coated fabrics (use). Thus, the toxicity properties of PPy NPs and PPy-coated textiles were assessed by using in vitro models representative of the lung and the skin. The results from the materials’ characterization showed the stability of both the PPy NP suspension and the textile coating, even after washing cycles and extraction in artificial sweat. Data from an in vitro model of the air–blood barrier showed the low toxicity of these NPs, with no alteration of cell viability and functionality observed. The skin toxicity of PPy NPs and the coated textiles was assessed on a reconstructed human epidermis model following OECD 431 and 439 guidelines. PPy NPs proved to be non-corrosive at the tested conditions, as well as non-irritant after extraction in artificial sweat at two different pH conditions. The obtained data suggest that PPy NPs are safe NMs in applications for textile coating.
Giant Photoluminescence Enhancement and Carrier Dynamics in MoS2 Bilayers with Anomalous Interlayer Coupling
Authors: Li Han , Ma Yating , Xu Zhongjie , Cheng Xiang’ai , Jiang Tian
Published: August 2021

Fundamental researches and explorations based on transition metal dichalcogenides (TMDCs) mainly focus on their monolayer counterparts, where optical densities are limited owing to the atomic monolayer thickness. Photoluminescence (PL) yield in bilayer TMDCs is much suppressed owing to indirect-bandgap properties. Here, optical properties are explored in artificially twisted bilayers of molybdenum disulfide (MoS2). Anomalous interlayer coupling and resultant giant PL enhancement are firstly observed in MoS2 bilayers, related to the suspension of the top layer material and independent of twisted angle. Moreover, carrier dynamics in MoS2 bilayers with anomalous interlayer coupling are revealed with pump-probe measurements, and the secondary rising behavior in pump-probe signal of B-exciton resonance, originating from valley depolarization of A-exciton, is firstly reported and discussed in this work. These results lay the groundwork for future advancement and applications beyond TMDCs monolayers.
Dispersion of Few-Layer Black Phosphorus in Binary Polymer Blend and Block Copolymer Matrices
Authors: Coiai Serena , Passaglia Elisa , Pinna Simone , Legnaioli Stefano , Borsacchi Silvia , Dinelli Franco , Ferretti Anna Maria , Caporali Maria , Serrano-Ruiz Manuel , Peruzzini Maurizio , Cicogna Francesca
Published: August 2021

Exfoliated black phosphorus (bP) embedded into a polymer is preserved from oxidation, is stable to air, light, and humidity, and can be further processed into devices without degrading its properties. Most of the examples of exfoliated bP/polymer composites involve a single polymer matrix. Herein, we report the preparation of biphasic polystyrene/poly(methyl methacrylate) (50/50 wt.%) composites containing few-layer black phosphorus (fl-bP) (0.6–1 wt.%) produced by sonicated-assisted liquid-phase exfoliation. Micro-Raman spectroscopy confirmed the integrity of fl-bP, while scanning electron microscopy evidenced the influence of fl-bP into the coalescence of polymeric phases. Furthermore, the topography of thin films analyzed by atomic force microscopy confirmed the effect of fl-bP into the PS dewetting, and the selective PS etching of thin films revealed the presence of fl-bP flakes. Finally, a block copolymer/fl-bP composite (1.2 wt.%) was prepared via in situ reversible addition–fragmentation chain transfer (RAFT) polymerization by sonication-assisted exfoliation of bP into styrene. For this sample, 31P solid-state NMR and Raman spectroscopy confirmed an excellent preservation of bP structure.
Poly(methacrylic Acid)-Cellulose Brushes as Anticancer Porphyrazine Carrier
Authors: Krasnopeeva Elena L. , Melenevskaya Elena Yu. , Klapshina Larisa G. , Shilyagina Natalia Yu. , Balalaeva Irina V. , Smirnov Nikolay N. , Smirnov Michael A. , Yakimansky Alexander V.
Published: August 2021

The prospective strategy for treatment of cancer is based on the application of nano-sized macromolecular carriers, which are able penetrate inside and can be accumulated within tumor tissue. In this work graft copolymers of cellulose and poly(methacrylic acid) has been prepared and tested as a nanocontainers for the delivery of drug to tumor. For this purpose, two derivatives of porphyrazine suitable for photodynamic cancer therapy were loaded into prepared polymer brush. Fluorescence imaging was applied for monitoring of accumulation of porphyrazine in the CT26 murine colon carcinoma. The selective accumulation of cellulose brush loaded with porphyrazine in tumor was demonstrated by fluorescence intensity contrast between the tumor area and normal tissues. The tumor growth rate after photodynamic therapy were assessed and inhibition of its growth was revealed.
Eating Behaviors of Children with Autism—Pilot Study
Authors: Brzóska Anna , Kazek Beata , Kozioł Karolina , Kapinos-Gorczyca Agnieszka , Ferlewicz Małgorzata , Babraj Agnieszka , Makosz-Raczek Anna , Likus Wirginia , Paprocka Justyna , Matusik Paweł , Emich-Widera Ewa
Published: August 2021

Autism Spectrum Disorder (ASD) is the most recognized neuropsychiatric disorder of childhood. Comorbid conditions (such as feeding disorders) are more common among people with autism than among the general population. The most frequent somatic disorders in autistic children include the gastrointestinal disorders observed in 46–91% of patients. The purpose of this study was the evaluation of the nutrition of children with autism, with particular emphasis placed on feeding in the first year of life, in comparison to the group of healthy peers. Participants included 75 Caucasian children (41 children diagnosed with pure autism, and the control group consisting of 34 children without autistic traits). The analysis was performed based on a questionnaire of own design with the first part devoted to the eating practices of the early infancy. Results: Autistic children, as compared to the healthy peers, presented a shortened time of breastfeeding (the children fell asleep at the breast) (p = 0.04), a delayed introduction of dairy products (p = 0.001), the need of more trials to introduce new foods (p = 0.006), a delayed introduction of foods with solid and lumpy structure (p = 0.004), a longer duration of bottle feeding (p = 0.005), delayed attempts to eating using own hands (p = 0.006) and needed a greater support of parents to divert their attention from food during eating (p = 0.05). Conclusions: 1. The dietary problems are more common among children with the autism spectrum disorder than among the population of healthy children, during the first year of life from the time of introducing the complementary foods. 2. The autistic children experience difficulties with eating and require their parents’ additional involvement significantly more often than their healthy peers.