bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Homogeneous Markov Set Systems
Authors: Vassiliou P.-C.G.
Published: February 2021

A more realistic way to describe a model is the use of intervals which contain the required values of the parameters. In practice we estimate the parameters from a set of data and it is natural that they will be in confidence intervals. In the present study, we study Non-Homogeneous Markov Systems (NHMS) processes for which the required basic parameters are in intervals. We call such processes Non-Homogeneous Markov Set Systems (NHMSS). First we study the set of the relative expected population structure of memberships and we prove that under certain conditions of convexity of the intervals of the parameters the set is compact and convex. Next, we establish that if the NHMSS starts with two different initial distributions sets and allocation probability sets under certain conditions, asymptotically the two expected relative population structures coincide geometrically fast. We continue proving a series of theorems on the asymptotic behavior of the expected relative population structure of a NHMSS and the properties of their limit set. Finally, we present an application for geriatric and stroke patients in a hospital and through it we solve problems that surface in an application.
Stochastic Chebyshev Goal Programming Mixed Integer Linear Model for Sustainable Global Production Planning
Authors: Wang Chia-Nan , Nhieu Nhat-Luong , Tran Trang Thi Thu
Published: February 2021

Production planning is a necessary process that directly affects the efficiency of production systems in most industries. The complexity of the current production planning problem depends on increased options in production, uncertainties in demand and production resources. In this study, a stochastic multi-objective mixed-integer optimization model is developed to ensure production efficiency in uncertainty conditions and satisfy the requirements of sustainable development. The efficiency of the production system is ensured through objective functions that optimize backorder quantity, machine uptime and customer satisfaction. The other three objective functions of the proposed model are related to optimization of profits, emissions, and employment changing. The objective functions respectively represent the three elements of sustainable development: economy, environment, and sociality. The proposed model also assures the production manager’s discretion over whether or not to adopt production options such as backorder, overtime, and employment of temporary workers. At the same time, the resource limits of the above options can also be adjusted according to the situation of each production facility via the model’s parameters. The solutions that compromise the above objective functions are determined with the Chebyshev goal programming approach together with the weights of the goals. The model is applied to the multinational production system of a Southeast Asian supplier in the textile industry. The goal programming solution of the model shows an improvement in many aspects compared to this supplier’s manufacturing practices under the same production conditions. Last but not least, the study develops different scenarios based on different random distributions of uncertainty demand and different weights between the objective functions. The analysis and evaluation of these scenarios provide a reference basis for managers to adjust the production system in different situations. Analysis of uncertain demand with more complex random distributions as well as making predictions about the effectiveness of scenarios through the advantages of machine learning can be considered in future studies.
Comparison of One-Year Functional Outcomes and Quality of Life between Posterior Pelvic Ring Fixation and Combined Anterior-Posterior Pelvic Ring Fixation after Lateral Compression (B2 Type) Pelvic Fracture
Authors: Petryla Giedrius , Uvarovas Valentinas , Bobina Rokas , Kurtinaitis Jaunius , Puronaitė Roma , Kvederas Giedrius , Šatkauskas Igoris
Published: February 2021

Background and Objectives: The treatment algorithm of lateral compression B2 type pelvic fractures are still under debate. Some authors advocate conservative treatment, while others recommend surgical approach. The clear indications for isolated anterior or posterior ring fixation or combined anterior-posterior pelvic ring fixation of B2 type fractures remain unclear. The aim of this study was to compare the functional outcomes and quality of life after isolated posterior pelvic ring fixation and combined anterior-posterior pelvic ring fixation for the treatment of B2 pelvic fractures. Materials and Methods: Patients aged 18 to 65 years with B2 type pelvic fracture hospitalized in a single trauma centre over a period of 3 years were included in the research. Based on the attending surgeon’s preference, patients were treated with isolated posterior or combined anterior-posterior pelvic fixation. The quality of life and pelvic function were assessed using SF-36 and Majeed questionnaires, respectively. Patients filled in the questionnaires twice: during the first hospitalization (concerning their pre-trauma state—timepoint I) and one-year after the injury (timepoint II). Results: A cohort of 32 patients with B2 type pelvic fracture was enrolled in the analysis: 23 (72%) were female and 9 (28%) were male. The mean age was 35.3 ± 11.9 years. In this cohort 13 (41%) patients underwent isolated posterior pelvic ring fixation (group I) and 19 (59%) patients underwent combined anterior-posterior pelvic ring fixation (group II). No statistically significant differences were observed between the groups in both timepoints concerning Majeed, SF-36 PCS and MCS scores. However, in both groups Majeed and SF-36 PCS scores were statistically significantly lower one year after pelvic fracture compared with pre-trauma state, while SF-36 MCS scores did not differ. Conclusions: No differences were found in quality of life and functional outcomes between isolated posterior pelvic ring fixation and combined anterior-posterior fixation for the treatment of B2 type pelvic fractures.
First-Time Acute Lateral Patellar Dislocation in Children and Adolescents: What about Unaffected Knee Patellofemoral Joint Anatomic Abnormalities?
Authors: Simonaitytė Rasa , Rutkauskas Saulius , Čekanauskas Emilis , Labanauskas Liutauras , Barauskas Vidmantas
Published: February 2021

Background and Objectives: Acute lateral patellar dislocation (LPD) is the most common acute knee disorder in children and adolescents, and may lead to functional disability. The purpose of this study was to identify key differences and correlations of the patellofemoral joint (PFJ) morphology between intact and contralateral injured knees in a first-time traumatic LPD population aged under 18 years. Materials and Methods: The data were gathered prospectively from a cohort of 58 patients (35 girls and 23 boys). The prevalence and combined prevalence of patella alta (PA) and trochlear dysplasia (TD) in both knees of patients were evaluated using X-ray by two radiologists. Results: The PFJ of patients’ intact knees had a lower rate of TD (1.72% vs. 5.2%) and a less common combination of PA with shallow femoral sulcus (SFS) (22.4% vs. 44.8%) but more frequent PA (62.1% vs. 41.4%) compared with their injured knees. We noted statistically significant positive correlations (SSPCs) between the femoral sulcus angle (FSA) and PA in patients with intact (r = 0.37; p < 0.005) and contralateral injured knees (r = 0.33; p < 0.05). Conclusion: There were SSPCs between the FSA and PA in both gender and age groups of patients with intact and contralateral injured knees. The SSPCs between the FSA and PA of intact knees were higher in the patients with a more dysplastic PFJ anatomy (PA and TD) of the injured knees as compared to patients with only PA of the injured knees.
Perceptions of European ME/CFS Experts Concerning Knowledge and Understanding of ME/CFS among Primary Care Physicians in Europe: A Report from the European ME/CFS Research Network (EUROMENE)
Authors: Cullinan John , Pheby Derek F. H. , Araja Diana , Berkis Uldis , Brenna Elenka , de Korwin Jean-Dominique , Gitto Lara , Hughes Dyfrig A. , Hunter Rachael M. , Trepel Dominic , Wang-Steverding Xia
Published: February 2021

Background and Objectives: We have conducted a survey of academic and clinical experts who are participants in the European ME/CFS Research Network (EUROMENE) to elicit perceptions of general practitioner (GP) knowledge and understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and suggestions as to how this could be improved. Materials and Methods: A questionnaire was sent to all national representatives and members of the EUROMENE Core Group and Management Committee. Survey responses were collated and then summarized based on the numbers and percentages of respondents selecting each response option, while weighted average responses were calculated for questions with numerical value response options. Free text responses were analysed using thematic analysis. Results: Overall there were 23 responses to the survey from participants across 19 different European countries, with a 95% country-level response rate. Serious concerns were expressed about GPs’ knowledge and understanding of ME/CFS, and, it was felt, about 60% of patients with ME/CFS went undiagnosed as a result. The vast majority of GPs were perceived to lack confidence in either diagnosing or managing the condition. Disbelief, and misleading illness attributions, were perceived to be widespread, and the unavailability of specialist centres to which GPs could refer patients and seek advice and support was frequently commented upon. There was widespread support for more training on ME/CFS at both undergraduate and postgraduate levels. Conclusion: The results of this survey are consistent with the existing scientific literature. ME/CFS experts report that lack of knowledge and understanding of ME/CFS among GPs is a major cause of missed and delayed diagnoses, which renders problematic attempts to determine the incidence and prevalence of the disease, and to measure its economic impact. It also contributes to the burden of disease through mismanagement in its early stages.
Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs
Authors: Ridziauskas Martynas , Zablockienė Birutė , Jančorienė Ligita , Samuilis Artūras , Zablockis Rolandas , Jackevičiūtė Aušrinė
Published: February 2021

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.
A Novel Moderately Thermophilic Facultative Methylotroph within the Class Alphaproteobacteria
Authors: Islam Tajul , Hernández Marcela , Gessesse Amare , Murrell J. Colin , Øvreås Lise
Published: February 2021

Methylotrophic bacteria (non-methanotrophic methanol oxidizers) consuming reduced carbon compounds containing no carbon–carbon bonds as their sole carbon and energy source have been found in a great variety of environments. Here, we report a unique moderately thermophilic methanol-oxidising bacterium (strain LS7-MT) that grows optimally at 55 °C (with a growth range spanning 30 to 60 °C). The pure isolate was recovered from a methane-utilizing mixed culture enrichment from an alkaline thermal spring in the Ethiopia Rift Valley, and utilized methanol, methylamine, glucose and a variety of multi-carbon compounds. Phylogenetic analysis of the 16S rRNA gene sequences demonstrated that strain LS7-MT represented a new facultatively methylotrophic bacterium within the order Hyphomicrobiales of the class Alphaproteobacteria. This new strain showed 94 to 96% 16S rRNA gene identity to the two methylotroph genera, Methyloceanibacter and Methyloligella. Analysis of the draft genome of strain LS7-MT revealed genes for methanol dehydrogenase, essential for methanol oxidation. Functional and comparative genomics of this new isolate revealed genomic and physiological divergence from extant methylotrophs. Strain LS7-MT contained a complete mxaF gene cluster and xoxF1 encoding the lanthanide-dependent methanol dehydrogenase (XoxF). This is the first report of methanol oxidation at 55 °C by a moderately thermophilic bacterium within the class Alphaproteobacteria. These findings expand our knowledge of methylotrophy by the phylum Proteobacteria in thermal ecosystems and their contribution to global carbon and nitrogen cycles.
Clonal Diversity and Antimicrobial Resistance of Methicillin-Resistant Staphylococcus pseudintermedius Isolated from Canine Pyoderma
Authors: Silva Vanessa , Oliveira Ana , Manageiro Vera , Caniça Manuela , Contente Diogo , Capita Rosa , Alonso-Calleja Carlos , Carvalho Isabel , Capelo José L. , Igrejas Gilberto , Poeta Patrícia
Published: February 2021

The emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) antimicrobial resistance and epidemic genetic lineages is posing a challenge in veterinary medicine due to the limited therapeutical options. MRSP has been identified as an important canine pyoderma pathogen. Thus, we aimed to characterize the antimicrobial resistance and clonal lineages of MRSP isolated from canine cutaneous pyoderma. Thirty-one MRSP isolates recovered from pyoderma were further characterized. The antimicrobial susceptibility testing of the isolates was performed by the Kirby-Bauer disc diffusion method against 14 antimicrobial agents. The presence of antimicrobial and virulence genes was carried out by PCR. Multilocus sequence typing was performed in all isolates. All strains had a multidrug-resistant profile showing resistance mainly to penicillin, macrolides and lincosamides, aminoglycosides, tetracycline and trimethoprim-sulfamethoxazole, which was encoded by the blaZ, ermB, msr(A/B), aac(6′)-Ie-aph(2′′)-Ia, aph(3′)-IIIa, ant(4′)-Ia, tetM, tetK and dfrG genes. All isolates harbored the lukS-I/lukF-I virulence factors. Isolates were ascribed to nine previously described sequence types (STs): ST123, ST339, ST727, ST71, ST537, ST45, ST1029, ST118 and ST1468; and to five STs first described in this study: ST2024, ST2025, ST2026, ST2027 and ST2028. In this study, most isolates belonged to ST123 (n = 16), which belongs to CC71 and is the most common clone in Europe. All isolates were multidrug-resistant, which may impose a serious threat to animal health.
Predictive Modeling for the Growth of Salmonella spp. in Liquid Egg White and Application of Scenario-Based Risk Estimation
Authors: Kang Mi Seon , Park Jin Hwa , Kim Hyun Jung
Published: February 2021

The objective of the study was to develop a predictive model of Salmonella spp. growth in pasteurized liquid egg white (LEW) and to estimate the salmonellosis risk using the baseline model and scenario analysis. Samples were inoculated with six strains of Salmonella, and bacterial growth was observed during storage at 10–37 °C. The primary models were developed using the Baranyi model for LEW. For the secondary models, the obtained specific growth rate (μmax) and lag phase duration were fitted to a square root model and Davey model, respectively, as functions of temperature (R2 ≥ 0.98). For μmax, the values were satisfied within an acceptable range (Af, Bf: 0.70–1.15). The probability of infection (Pinf) due to the consumption of LEW was zero in the baseline model. However, scenario analysis suggested possible salmonellosis for the consumption of LEW. Because Salmonella spp. proliferated much faster in LEW than in egg white (EW) during storage at 20 and 30 °C (p < 0.01), greater Pinf may be obtained for LEW when these products are stored at the same conditions. The developed predictive model can be applied to the risk management of Salmonella spp. along the food chain, including during product storage and distribution.
Interconnections between the Oral and Gut Microbiomes: Reversal of Microbial Dysbiosis and the Balance between Systemic Health and Disease
Authors: Khor Brandon , Snow Michael , Herrman Elisa , Ray Nicholas , Mansukhani Kunal , Patel Karan A. , Said-Al-Naief Nasser , Maier Tom , Machida Curtis A.
Published: February 2021

The human microbiota represents a complex array of microbial species that influence the balance between the health and pathology of their surrounding environment. These microorganisms impart important biological benefits to their host, such as immune regulation and resistance to pathogen colonization. Dysbiosis of microbial communities in the gut and mouth precede many oral and systemic diseases such as cancer, autoimmune-related conditions, and inflammatory states, and can involve the breakdown of innate barriers, immune dysregulation, pro-inflammatory signaling, and molecular mimicry. Emerging evidence suggests that periodontitis-associated pathogens can translocate to distant sites to elicit severe local and systemic pathologies, which necessitates research into future therapies. Fecal microbiota transplantation, probiotics, prebiotics, and synbiotics represent current modes of treatment to reverse microbial dysbiosis through the introduction of health-related bacterial species and substrates. Furthermore, the emerging field of precision medicine has been shown to be an effective method in modulating host immune response through targeting molecular biomarkers and inflammatory mediators. Although connections between the human microbiome, immune system, and systemic disease are becoming more apparent, the complex interplay and future innovations in treatment modalities will become elucidated through continued research and cross-disciplinary collaboration.
Fusarium Species in Mangrove Soil in Northern Peninsular Malaysia and the Soil Physico-Chemical Properties
Authors: Mohamed Zubi Wafa S. , Mohd Masratul Hawa , Mohamed Nor Nik Mohd Izham , Zakaria Latiffah
Published: February 2021

Fusarium genus comprises important saprophytic and phytopathogenic fungi and is widespread in nature. The present study reports the occurrence of Fusarium spp. in soils from two mangrove forests in northern Peninsular Malaysia and analyzed physico-chemical properties of the mangrove soil. Based on TEF-1α sequences, nine Fusarium species were identified: Fusarium solani species complex (FSSC) (n = 77), Fusarium verticillioides (n = 20), Fusarium incarnatum (n = 10), Fusarium proliferatum (n = 7), Fusarium lateritium (n = 4), Fusarium oxysporum (n = 3), Fusarium rigidiuscula (n = 2), Fusarium chlamydosporum (n = 1), and Fusarium camptoceras (n = 1); FSSC isolates were the most prevalent. Phylogenetic analysis of the combined TEF-1α and ITS sequences revealed diverse phylogenetic affinities among the FSSC isolates and potentially new phylogenetic clades of FSSC. Soil analysis showed varied carbon content, pH, soil moisture, and salinity, but not nitrogen content, between sampling locations. Regardless of the physico-chemical properties, various Fusarium species were recovered from the mangrove soils. These were likely saprophytes; however, some were well-known plant pathogens and opportunistic human pathogens. Thus, mangrove soils might serve as inoculum sources for plant and human pathogenic Fusarium species. The present study demonstrates the occurrence of various Fusarium species in the extreme environment of mangrove soil, thereby contributing to the knowledge on species diversity in Fusarium.
Improving Blind Docking in DOCK6 through an Automated Preliminary Fragment Probing Strategy
Authors: Jofily Paula , Pascutti Pedro G. , Torres Pedro H. M.
Published: February 2021

Probing protein surfaces to accurately predict the binding site and conformation of a small molecule is a challenge currently addressed through mainly two different approaches: blind docking and cavity detection-guided docking. Although cavity detection-guided blind docking has yielded high success rates, it is less practical when a large number of molecules must be screened against many detected binding sites. On the other hand, blind docking allows for simultaneous search of the whole protein surface, which however entails the loss of accuracy and speed. To bridge this gap, in this study, we developed and tested BLinDPyPr, an automated pipeline which uses FTMap and DOCK6 to perform a hybrid blind docking strategy. Through our algorithm, FTMap docked probe clusters are converted into DOCK6 spheres for determining binding regions. Because these spheres are solely derived from FTMap probes, their locations are contained in and specific to multiple potential binding pockets, which become the regions that are simultaneously probed and chosen by the search algorithm based on the properties of each candidate ligand. This method yields pose prediction results (45.2–54.3% success rates) comparable to those of site-specific docking with the classic DOCK6 workflow (49.7–54.3%) and is half as time-consuming as the conventional blind docking method with DOCK6.
Determination of Pharmaceuticals, Heavy Metals, and Oxysterols in Fish Muscle
Authors: Bobrowska-Korczak Barbara , Stawarska Agnieszka , Szterk Arkadiusz , Ofiara Karol , Czerwonka Małgorzata , Giebułtowicz Joanna
Published: February 2021

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch (Perca fluviatilis); flounder (Platichthys flesus); turbot (Scophthalmus maximus); plaice (Pleuronectes platessa); cod (Gadus morhua callarias); bream (Abramis brama); crucian (Carassius carassius). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7β-hydroxycholesterol; 5β,6β-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) μg/g–4.18 μg/g (perch), which corresponded to 0.7–1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14–1.79 ± 0.06 μg/g), 7β-hydroxycholesterol (0.50 ± 0.04–3.20 ± 2.95 μg/g) and 5β,6β-epoxycholesterol (0.66 ± 0.03–1.53 ± 0.66 μg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.
A Review on Stems Composition and Their Impact on Wine Quality
Authors: Blackford Marie , Comby Montaine , Zeng Liming , Dienes-Nagy Ágnes , Bourdin Gilles , Lorenzini Fabrice , Bach Benoit
Published: February 2021

Often blamed for bringing green aromas and astringency to wines, the use of stems is also empirically known to improve the aromatic complexity and freshness of some wines. Although applied in different wine-growing regions, stems use remains mainly experimental at a cellar level. Few studies have specifically focused on the compounds extracted from stems during fermentation and maceration and their potential impact on the must and wine matrices. We identified current knowledge on stem chemical composition and inventoried the compounds likely to be released during maceration to consider their theoretical impact. In addition, we investigated existing studies that examined the impact of either single stems or whole clusters on the wine quality. Many parameters influence stems’ effect on the wine, especially grape variety, stem state, how stems are incorporated, when they are added, and contact duration. Other rarely considered factors may also have an impact, including vintage and ripening conditions, which could affect the lignification of the stem.
The Impact of Formulation on the Content of Phenolic Compounds in Snacks Enriched with Dracocephalum moldavica L. Seeds: Introduction to Receiving a New Functional Food Product
Authors: Oniszczuk Tomasz , Kasprzak-Drozd Kamila , Olech Marta , Wójtowicz Agnieszka , Nowak Renata , Rusinek Robert , Szponar Jarosław , Combrzyński Maciej , Oniszczuk Anna
Published: February 2021

A new type of multigrain snack has been designed containing varied additions of Moldavian dragonhead (Dracocephalum moldavica L.) seeds. The antioxidant properties and the general health benefits of this plant material have already been widely acknowledged. The research discussed herein aimed to investigate the influence of the formulation and expansion method (frying) on the content of polyphenolic compounds, individual phenolic acids, and antiradical properties of innovative snacks enriched with dragonhead seeds. The highest content of polyphenols (0.685 mg GAE/mL), free phenolic acids (47.052 µg/g of dry matter), and highest radical scavenging activity (96.23% towards DPPH) were found in the fried snacks enriched with 22% of seeds. In these samples, 11 phenolic acids were detected. Strong positive correlations were seen between the addition of dragonhead and the polyphenol content (r = 0.989) and between the quantity of the enriching additive and the content of free phenolic acids (r = 0.953). The research has shown that such innovative snacks have the potential to supply health-benefiting free phenolic acids, e.g., salicylic, isoferulic, ferulic, p-coumaric, vanillic. Our studies provide an introduction to the development of a new range of functional foods.
Key Factor Study for Generic Long-Acting PLGA Microspheres Based on a Reverse Engineering of Vivitrol®
Authors: Hua Yabing , Wang Zengming , Wang Dan , Lin Xiaoming , Liu Boshi , Zhang Hui , Gao Jing , Zheng Aiping
Published: February 2021

The FDA (U.S. Food and Drug Administration) has approved only a negligible number of poly(lactide-co-glycolide) (PLGA)-based microsphere formulations, indicating the difficulty in developing a PLGA microsphere. A thorough understanding of microsphere formulations is essential to meet the challenge of developing innovative or generic microspheres. In this study, the key factors, especially the key process factors of the marketed PLGA microspheres, were revealed for the first time via a reverse engineering study on Vivitrol® and verified by the development of a generic naltrexone-loaded microsphere (GNM). Qualitative and quantitative similarity with Vivitrol®, in terms of inactive ingredients, was accomplished by the determination of PLGA. Physicochemical characterization of Vivitrol® helped to identify the critical process parameters in each manufacturing step. After being prepared according to the process parameters revealed by reverse engineering, the GNM demonstrated similarity to Vivitrol® in terms of quality attributes and in vitro release (f2 = 65.3). The research on the development of bioequivalent microspheres based on the similar technology of Vivitrol® will benefit the development of other generic or innovative microspheres.
Probiotics in Cosmetic and Personal Care Products: Trends and Challenges
Authors: Puebla-Barragan Scarlett , Reid Gregor
Published: February 2021

Probiotics, defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host,” are becoming increasingly popular and marketable. However, too many of the products currently labelled as probiotics fail to comply with the defining characteristics. In recent years, the cosmetic industry has increased the number of products classified as probiotics. While there are several potential applications for probiotics in personal care products, specifically for oral, skin, and intimate care, proper regulation of the labelling and marketing standards is still required to guarantee that consumers are indeed purchasing a probiotic product. This review explores the current market, regulatory aspects, and potential applications of probiotics in the personal care industry.
The Interplay of Cholesterol and Ligand Binding in hTSPO from Classical Molecular Dynamics Simulations
Authors: Lai Hien T. T. , Giorgetti Alejandro , Rossetti Giulia , Nguyen Toan T. , Carloni Paolo , Kranjc Agata
Published: February 2021

The translocator protein (TSPO) is a 18kDa transmembrane protein, ubiquitously present in human mitochondria. It is overexpressed in tumor cells and at the sites of neuroinflammation, thus representing an important biomarker, as well as a promising drug target. In mammalian TSPO, there are cholesterol–binding motifs, as well as a binding cavity able to accommodate different chemical compounds. Given the lack of structural information for the human protein, we built a model of human (h) TSPO in the apo state and in complex with PK11195, a molecule routinely used in positron emission tomography (PET) for imaging of neuroinflammatory sites. To better understand the interactions of PK11195 and cholesterol with this pharmacologically relevant protein, we ran molecular dynamics simulations of the apo and holo proteins embedded in a model membrane. We found that: (i) PK11195 stabilizes hTSPO structural fold; (ii) PK11195 might enter in the binding site through transmembrane helices I and II of hTSPO; (iii) PK11195 reduces the frequency of cholesterol binding to the lower, N–terminal part of hTSPO in the inner membrane leaflet, while this impact is less pronounced for the upper, C–terminal part in the outer membrane leaflet, where the ligand binding site is located; (iv) very interestingly, cholesterol most frequently binds simultaneously to the so-called CRAC and CARC regions in TM V in the free form (residues L150–X–Y152–X(3)–R156 and R135–X(2)–Y138–X(2)–L141, respectively). However, when the protein is in complex with PK11195, cholesterol binds equally frequently to the CRAC–resembling motif that we observed in TM I (residues L17–X(2)–F20–X(3)–R24) and to CRAC in TM V. We expect that the CRAC–like motif in TM I will be of interest in future experimental investigations. Thus, our MD simulations provide insight into the structural features of hTSPO and the previously unknown interplay between PK11195 and cholesterol interactions with this pharmacologically relevant protein.
pH-Sensitive Glycyrrhizin Based Vesicles for Nifedipine Delivery
Authors: Selyutina Olga Yu. , Mastova Anna V. , Shelepova Ekaterina A. , Polyakov Nikolay E.
Published: February 2021

Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stability and solubility at pH > 6 when the GA molecule is fully deprotonated. It means the higher release rate of the drug in a neutral and basic environment compared with acid media. These results could form the basis of follow-up studies of GA self-associates as pH-controlled drug delivery systems.
Evaluation of Fused Pyrrolothiazole Systems as Correctors of Mutant CFTR Protein
Authors: Spanò Virginia , Barreca Marilia , Cilibrasi Vincenzo , Genovese Michele , Renda Mario , Montalbano Alessandra , Galietta Luis Juan Vicente , Barraja Paola
Published: February 2021

Cystic fibrosis (CF) is a genetic disease caused by mutations that impair the function of the CFTR chloride channel. The most frequent mutation, F508del, causes misfolding and premature degradation of CFTR protein. This defect can be overcome with pharmacological agents named “correctors”. So far, at least three different classes of correctors have been identified based on the additive/synergistic effects that are obtained when compounds of different classes are combined together. The development of class 2 correctors has lagged behind that of compounds belonging to the other classes. It was shown that the efficacy of the prototypical class 2 corrector, the bithiazole corr-4a, could be improved by generating conformationally-locked bithiazoles. In the present study, we investigated the effect of tricyclic pyrrolothiazoles as analogues of constrained bithiazoles. Thirty-five compounds were tested using the functional assay based on the halide-sensitive yellow fluorescent protein (HS-YFP) that measured CFTR activity. One compound, having a six atom carbocyle central ring in the tricyclic pyrrolothiazole system and bearing a pivalamide group at the thiazole moiety and a 5-chloro-2-methoxyphenyl carboxamide at the pyrrole ring, significantly increased F508del-CFTR activity. This compound could lead to the synthesis of a novel class of CFTR correctors.
Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia
Authors: Kudryavtsev Denis , Isaeva Anastasia , Barkova Daria , Spirova Ekaterina , Mukhutdinova Renata , Kasheverov Igor , Tsetlin Victor
Published: February 2021

Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, α1(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca2+ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC50 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca2+ rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.
Synthesis of Super-Oscillatory Point-Spread Functions with Taylor-Like Tapered Sidelobes for Advanced Optical Super-Resolution Imaging
Authors: Yang Haitang , Eleftheriades George V.
Published: February 2021

Recently, the super-oscillation phenomenon has attracted attention because of its ability to super-resolve unlabelled objects in the far-field. Previous synthesis of super-oscillatory point-spread functions used the Chebyshev patterns where all sidelobes are equal. In this work, an approach is introduced to generate super-oscillatory Taylor-like point-spread functions that have tapered sidelobes. The proposed method is based on the Schelkunoff’s super-directive antenna theory. This approach enables the super-resolution, the first sidelobe level and the tapering rate of the sidelobes to be controlled. Finally, we present the design of several imaging experiments using a spatial light modulator as an advanced programmable grating to form the Taylor-like super-oscillatory point-spread functions and demonstrate their superiority over the Chebyshev ones in resolving the objects of two apertures and of a mask with the letter E.
Removal of Chromium(VI) from Contaminated Water Using Untreated Moringa Leaves as Biosorbent
Authors: Madhuranthakam Chandra Mouli R. , Thomas Archana , Akhter Zhainab , Fernandes Shannon Q. , Elkamel Ali
Published: February 2021

Biosorption of chromium (Cr(VI)) is studied by using raw (chemically not modified) Moringa (Moringa Oleifera) leaf powder without any pretreatment. Cr(VI) is one of the potentially harmful heavy metals found in industrial wastewater. In the Moringa leaf powder, the presence of a significant amount of organic acids form the source for the biosorption of Cr(VI). The concentration of Cr(VI) in the feed solution is varied and different dosages of the proposed biosorbent are used to study its efficiency in the removal of Cr(VI). The concentration of Cr(VI) is varied from 1 ppm to 20 ppm while the amount of biosorbent is varied from 0.5 g to 2.5 g. The equilibrium time for adsorption of Cr(VI) is observed to vary between half an hour and 90 min. The metal removal efficiency varied from 30% to 90% which is a significant achievement compared to other conventional methods which are either energy-intensive or not cost effective. The experimental results are modeled using Langmuir, Freundlich and Redlich–Peterson isotherms. The metal removal efficiency is attributed to the chelating effect of carboxylate and hydroxyl groups present in the moringa leaves and is confirmed from the FTIR analysis. Further molecular docking simulations are performed to confirm the binding of the metal to the speculated sites within the different acids present in the moringa leaves. Untreated green moringa leaf powder used as a biosorbent in this study leads to a sustainable and cheaper option for treating wastewater containing Cr(VI).
A Modified 2-DOF Control Framework and GA Based Intelligent Tuning of PID Controllers
Authors: So Gun-Baek
Published: February 2021

Although a controller is well-tuned for set-point tracking, it shows poor control results for load disturbance rejection and vice versa. In this paper, a modified two-degree-of-freedom (2-DOF) control framework to solve this problem is proposed, and an optimal tuning method for the pa-rameters of each proportional integral derivative (PID) controller is discussed. The unique feature of the proposed scheme is that a feedforward controller is embedded in the parallel control structure to improve set-point tracking performance. This feedforward controller and the standard PID con-troller are combined to create a new set-point weighted PID controller with a set-point weighting function. Therefore, in this study, two controllers are used: a set-point weighted PID controller for set-point tracking and a conventional PID controller for load disturbance rejection. The parameters included in the two controllers are tuned separately to improve set-point tracking and load dis-turbance rejection performances, respectively. Each controller is optimally tuned by genetic algo-rithm (GA) in terms of minimizing the IAE performance index, and what is special at this time is that it also tunes the set-point weighting parameter simultaneously. The simulation results performed on four virtual processes verify that the proposed method shows better performance in set-point tracking and load disturbance rejection than those of the other methods.
Mechanical Property Assessment of Interlocking Plastic Pavers Manufactured from Electronic Industry Waste in Brazil
Authors: Gabriel Luiz , Bianchi Rodrigo , Bernardes Américo
Published: February 2021

The estimated production of world electronic waste until 2017 is approximately 6 Gt. Despite this enormous problem, there are no clear regulations regarding the orientation for disposal or treatment of this type of residuals in many countries. There is a federal public policy in Brazil that supports a network of Computer Reconditioning Centers—CRCs. These CRCs train young people and recover or recycle electronic equipment. Through this work, CRCs produce interlocking plastic pavers for application on pavements from recycled electronic industry waste. This article presents the characterization of these interlocking paver’s mechanical properties when applied on the pavement. This characterization is a necessary step to show the effectiveness of this product. We show that the plastic pavers behave similarly to the artifacts manufactured in concrete, thus creating commercial opportunities for this initiative, and contributing to the Brazilian Solid Waste Policy.
Immobilized TiO2/ZnO Sensitized Copper (II) Phthalocyanine Heterostructure for the Degradation of Ibuprofen under UV Irradiation
Authors: BethelAnucha Chukwuka , Altin IIknur , Bacaksiz Emin , Degirmencioglu Ismail , Kucukomeroglu Tayfur , Yılmaz Salih , Stathopoulos Vassilis N.
Published: February 2021

Photocatalytic coatings of TiO2/ZnO/CuPc were developed on stainless steel substrates by subsequent sol gel dip coating for TiO2, spray pyrolysis for ZnO, and spin coating for copper (ii) phthalocyanine (CuPc) deposition. The latter compound was successfully prepared using a Schiff-based process. The materials and coatings developed were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy with attached energy dispersive spectroscopy (SEM-EDS), UV-Vis spectroscopy, room temperature photoluminescence (RTPL) spectroscopy, H1-nuclear magnetic resonance (1H-NMR) spectroscopy, C13-nuclear magnetic resonance (13C-NMR) spectroscopy, and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The as-deposited TiO2/ZnO/CuPc on stainless steel retained in pristine state the structural and morphological/spectroscopic characteristics of its respective components. Estimated energy band gap values were 3.22 eV, 3.19 eV, 3.19 eV for TiO2, ZnO, TiO2/ZnO respectively and 1.60 eV, 2.44 eV, and 2.92 eV for CuPc. The photocatalytic efficiency of the fabricated TiO2/ZnO/CuPc coatings was tested toward ibuprofen (IBF). After 4 h irradiation under 365 nm UV, an increased degradation of about 80% was achieved over an initial 5 mg/L ibuprofen (IBF). This was much higher compared to about 42% and 18% IBF degradation by TiO2/ZnO and TiO2 thin film, respectively. In all cases, the stability of the best-performing photocatalyst was investigated showing a small decline to 77% of IBF degradation after the 5th cycle run. The effect of pH, reactive oxygen species (ROS) probe, shed light on a possible catalytic mechanism that was suggested.
Undisturbed Soil Pedon under Birch Forest: Characterization of Microbiome in Genetic Horizons
Authors: Naumova Natalia B. , Belanov Ivan P. , Alikina Tatiana Y. , Kabilov Marsel R.
Published: February 2021

Vast areas of land in the forest-steppe of West Siberia are occupied by birch forests, the most common ecosystems there. However, currently, little is known about the microbiome composition in the underlying soil, especially along a sequence of soil genetic horizons. The study aimed at inventorying microbiome in genetic horizons of a typical Phaeozem under undisturbed birch forest in West Siberia. Bacteria and fungi were studied using 16S rRNA genes’ and ITS2 amplicon sequencing with Illumina MiSeq. Proteobacteria and Acidobacteria together accounted for two-thirds of the operational taxonomic units (OTUs) numbers and half of the sequences in each genetic horizon. Acidobacteria predominated in eluvial environments, whereas Proteobacteria, preferred topsoil. The fungal sequences were dominated by Ascomycota and Basidiomycota phyla. Basidiomycota was the most abundant in the topsoil, whereas Ascomycota increased down the soil profile. Thelephoraceae family was the most abundant in the A horizon, whereas the Pyronemataceae family dominants in the AEl horizon, ultimately prevailing in the subsoil. We conclude that soil genetic horizons shape distinct microbiomes, therefore soil horizontation should be accounted for while studying undisturbed soils. This study, representing the first description of bacterio- and mycobiomes in genetic horizons of the Phaeozem profile, provides a reference for future research.
A new football hooliganism act necessary?
Authors: Mihaylova Ekaterina , Mihaylov Boris
Published: February 2021

This article examines the term “football hooliganism” and its legal regulation. It analyses Bulgarian and European legislation on football hooliganism. It further discusses in details the 2018 amendments of the Protection of Public Order at Sports Events Act that employs new methods for tackling with this negative phenomenon.