bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent Chemoradiation in Anal Cancer Patients Delivered with Bone Marrow-Sparing IMRT: Final Results of a Prospective Phase II Trial
Authors: Arcadipane Francesca , Silvetti Patrick , Olivero Francesco , Gastino Alessio , Carlevato Roberta , Chiovatero Ilaria , Spinelli Lavinia , Mistrangelo Massimiliano , Cassoni Paola , Ritorto Giuliana , Gallio Elena , Lesca Adriana , Faletti Riccardo , Giglioli Francesca Romana , Fiandra Christian , Ricardi Umberto , Franco Pierfrancesco
Published: May 2021

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon’s design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; β = 0.20). A minimum of 21/39 (54%) with G0–G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as ‘promising’. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0–G2 HT events were observed, above the threshold set. Hence, 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting.
Effectiveness of Cognitive Rehabilitation in Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Sanchez-Luengos Itsasne , Balboa-Bandeira Yolanda , Lucas-Jiménez Olaia , Ojeda Natalia , Peña Javier , Ibarretxe-Bilbao Naroa
Published: May 2021

Cognitive deficits influence the quality of life of Parkinson’s disease (PD) patients. In order to reduce the impact of cognitive impairment in PD, cognitive rehabilitation programs have been developed. This study presents a systematic review and meta-analysis regarding the effectiveness of cognitive rehabilitation in non-demented PD patients. Twelve articles were selected according to PRISMA guidelines. The systematic review showed that attention, working memory, verbal memory, executive functions and processing speed were the most frequently improved domains. Meta-analysis results showed moderate effects on global cognitive status (g = 0.55) and working memory (g = 0.50); small significant effects on verbal memory (g = 0.41), overall cognitive functions (g = 0.39) and executive functions (g = 0.30); small non-significant effects on attention (g = 0.36), visual memory (g = 0.29), verbal fluency (g = 0.27) and processing speed (g = 0.24); and no effect on visuospatial and visuoconstructive abilities (g = 0.17). Depressive symptoms showed small effect (g = 0.24) and quality of life showed no effect (g = −0.07). A meta-regression was performed to examine moderating variables of overall cognitive function effects, although moderators did not explain the heterogeneity of the improvement after cognitive rehabilitation. The findings suggest that cognitive rehabilitation may be beneficial in improving cognition in non-demented PD patients, although further studies are needed to obtain more robust effects.
Viability of Quercetin-Induced Dental Pulp Stem Cells in Forming Living Cellular Constructs for Soft Tissue Augmentation
Authors: Fageeh Hytham N. , Bhandi Shilpa , Mashyakhy Mohammed , Kahtani Ahmed Al , Badran Zahi , Mehta Deepak , Fageeh Hammam Ibrahim , Balaji Thodur Madapusi , Baeshen Hosam Ali , Varadarajan Saranya , Raj A. Thirumal , Patil Vikrant R. , Vyas Nishant , Zanza Alessio , Testarelli Luca , Patil Shankargouda
Published: May 2021

Autogenous gingival grafts used for root coverage or gingival augmentation procedures often result in donor site morbidity. Living cellular constructs as an exogenous alternative have been proven to be associated with lower morbidity. With the available background information, the present study aims to assess if quercetin-induced living cell constructs, derived from dental pulp stem cells, have the potential to be applied as a tool for soft tissue augmentation. The characterized dental pulp stem cells (positive for CD73, CD90, and negative for CD34, HLA-DR) were expanded in Dulbecco’s Modified Eagle’s medium (DMEM) supplemented with 10 mM quercetin. The handling properties of the quercetin-induced dental pulp stem cell constructs were assessed by visual, and tactile sensation. A microscopic characterization using hematoxylin and eosin staining, and qRT-PCR-based analysis for stemness-associated genes (OCT4, NANOG, SOX2, and cMyc) was also performed. Dental pulp stem cells without quercetin administration were used as the control. Dental pulp stem cell constructs induced by quercetin easily detached from the surface of the plate, whereas there was no formation in the control cells. It was also simple to transfer the induced cellular construct on the flattened surface. Microscopic characterization of the constructs showed cells embedded in a tissue matrix. Quercetin also increased the expression of stemness-related genes. The use of quercetin-induced DPSC living constructs for soft tissue augmentation could provide an alternative to autogenous soft tissue grafts to lower patient morbidity and improve esthetic outcomes.
Customization of Diet May Promote Exercise and Improve Mental Wellbeing in Mature Adults: The Role of Exercise as a Mediator
Authors: Begdache Lina , Patrissy Cara M.
Published: May 2021

Diet, dietary practices and exercise are modifiable risk factors for individuals living with mental distress. However, these relationships are intricate and multilayered in such a way that individual factors may influence mental health differently when combined within a pattern. Additionally, two important factors that need to be considered are gender and level of brain maturity. Therefore, it is essential to assess these modifiable risk factors based on gender and age group. The purpose of the study was to explore the combined and individual relationships between food groups, dietary practices and exercise to appreciate their association with mental distress in mature men and women. Adults 30 years and older were invited to complete the food–mood questionnaire. The anonymous questionnaire link was circulated on several social media platforms. A multi-analyses approach was used. A combination of data mining techniques, namely, a mediation regression analysis, the K-means clustering and principal component analysis as well as Spearman’s rank–order correlation were used to explore these research questions. The results suggest that women’s mental health has a higher association with dietary factors than men. Mental distress and exercise frequency were associated with different dietary and lifestyle patterns, which support the concept of customizing diet and lifestyle factors to improve mental wellbeing.
Risk Management: Exploring Emerging Human Resource Issues during the COVID-19 Pandemic
Authors: Zhong Yifan , Li Yameng , Ding Jian , Liao Yiyi
Published: May 2021

The unanticipated coronavirus disease 2019 (COVID-19) pandemic has hit global business heavily, disrupting the management of human resources across numerous industries. More than 500 articles (indexed in Scopus and the Web of Science) on the impact of the COVID-19 outbreak on emerging human resources issues and related practices were published from 1 January 2020 to 31 January 2021. In this study, we conduct a systematic literature review on emerging studies in the business and management field to explore what the emerging human resource issues are during the COVID-19 pandemic and propose related practices to solve these issues. The analysis of the published literature identifies nine main human resource issues across 13 industries. The findings of this study suggest that COVID-19 has enormous impact on conventional human resource management and requires the theoretical and empirical attention of researchers. The propositions nominate related human resource practices to deal with emerging human resources issues and identify several research venues for future studies in this field.
Prototyping a Methodology for Long-Term (1680–2100) Historical-to-Future Landscape Modeling for the Conterminous United States
Authors: Dornbierer Jordan , Wika Steve , Robison Charles , Rouze Gregory , Sohl Terry
Published: May 2021

Land system change has been identified as one of four major Earth system processes where change has passed a destabilizing threshold. A historical record of landscape change is required to understand the impacts change has had on human and natural systems, while scenarios of future landscape change are required to facilitate planning and mitigation efforts. A methodology for modeling long-term historical and future landscape change was applied in the Delaware River Basin of the United States. A parcel-based modeling framework was used to reconstruct historical landscapes back to 1680, parameterized with a variety of spatial and nonspatial historical datasets. Similarly, scenarios of future landscape change were modeled for multiple scenarios out to 2100. Results demonstrate the ability to represent historical land cover proportions and general patterns at broad spatial scales and model multiple potential future landscape trajectories. The resulting land cover collection provides consistent data from 1680 through 2100, at a 30-m spatial resolution, 10-year intervals, and high thematic resolution. The data are consistent with the spatial and thematic characteristics of widely used national-scale land cover datasets, facilitating use within existing land management and research workflows. The methodology demonstrated in the Delaware River Basin is extensible and scalable, with potential applications at national scales for the United States.
Transforming Land Administration Practices through the Application of Fit-For-Purpose Technologies: Country Case Studies in Africa
Authors: Antonio Danilo , Njogu Solomon , Nyamweru Hellen , Gitau John
Published: May 2021

Access to land for many people in Africa is insecure and continues to pose risks to poverty, hunger, forced evictions, and social conflicts. The delivery of land tenure in many cases has not been adequately addressed. Fit-for-purpose spatial frameworks need to be adapted to the context of a country based on simple, affordable, and incremental solutions toward addressing these challenges. This paper looked at three case studies on the use of the Social Tenure Domain Model (STDM) tool in promoting the development of a fit-for-purpose land administration spatial framework. Data gathering from primary and secondary sources was used to investigate the case studies. The empirical findings indicated that the use and application of the STDM in support of the fit-for-purpose land administration framework is quite effective and can facilitate the improvement in land tenure security. The findings also revealed that the tool, together with participatory and inclusive processes, has the potential to contribute to other frameworks of Fit-For-Purpose Land Administration (FFP LA) toward influencing changes in policy and institutional practices. Evidently, there was a remarkable improvement in the institutional arrangements and collaboration among different institutions, as well as a notable reduction in land conflicts or disputes in all three case studies.
Informed Geoheritage Conservation: Determinant Analysis Based on Bibliometric and Sustainability Indicators Using Ordination Techniques
Authors: Németh Boglárka , Németh Károly , Procter Jon N.
Published: May 2021

Ordination methods are used in ecological multivariate statistics in order to reduce the number of dimensions and arrange individual variables along environmental variables. Geoheritage designation is a new challenge for conservation planning. Quantification of geoheritage to date is used explicitly for site selection, however, it also carries significant potential to be one of the indicators of sustainable development that is delivered through geosystem services. In order to achieve such a dominant position, geoheritage needs to be included in the business as usual model of conservation planning. Questions about the quantification process that have typically been addressed in geoheritage studies can be answered more directly by their relationships to world development indicators. We aim to relate the major informative geoheritage practices to underlying trends of successful geoheritage implementation through statistical analysis of countries with the highest trackable geoheritage interest. Correspondence analysis (CA) was used to obtain information on how certain indicators bundle together. Multiple correspondence analysis (MCA) was used to detect sets of factors to determine positive geoheritage conservation outcomes. The analysis resulted in ordination diagrams that visualize correlations among determinant variables translated to links between socio-economic background and geoheritage conservation outcomes. Indicators derived from geoheritage-related academic activity and world development metrics show a shift from significant Earth science output toward disciplines of strong international agreement such as tourism, sustainability and biodiversity. Identifying contributing factors to conservation-related decisions helps experts to tailor their proposals for required evidence-based quantification reports and reinforce the scientific significance of geoheritage.
Accessory Subunits of the Matrix Arm of Mitochondrial Complex I with a Focus on Subunit NDUFS4 and Its Role in Complex I Function and Assembly
Authors: Kahlhöfer Flora , Gansen Max , Zickermann Volker
Published: May 2021

NADH:ubiquinone-oxidoreductase (complex I) is the largest membrane protein complex of the respiratory chain. Complex I couples electron transfer to vectorial proton translocation across the inner mitochondrial membrane. The L shaped structure of complex I is divided into a membrane arm and a matrix arm. Fourteen central subunits are conserved throughout species, while some 30 accessory subunits are typically found in eukaryotes. Complex I dysfunction is associated with mutations in the nuclear and mitochondrial genome, resulting in a broad spectrum of neuromuscular and neurodegenerative diseases. Accessory subunit NDUFS4 in the matrix arm is a hot spot for mutations causing Leigh or Leigh-like syndrome. In this review, we focus on accessory subunits of the matrix arm and discuss recent reports on the function of accessory subunit NDUFS4 and its interplay with NDUFS6, NDUFA12, and assembly factor NDUFAF2 in complex I assembly.
The Geographical Distance between Producers and Consumers of the Organic Street Markets: The Case of Belo Horizonte, Brazil
Authors: Oliveira Isabela Kopperschmidt de , Oliveira Leise Kelli de , Lisboa Maria Rosa Amorim Faria , Madalon Ellen Caroline Nunes , Freitas Luiza Fleury de , Peres Filho Augusto Cezar
Published: May 2021

The organic street markets are considered a short food supply chain, and their importance gained new proportions since COVID-19 brought difficulties to the traditional supply chain. The organic street markets represent a place to sell the product for organic family farmers and an opportunity to obtain better quality and variety of organic products at a lower price. This work aimed to analyze the geographical distance from producers and consumers of organic street markets in Belo Horizonte, Brazil, identifying the organic street market characteristics that influence the organic consumers. The research methods used descriptive statistics, a chi-squared test, and the measurement of the geographical distance. Results allowed us to conclude the organic street markets with more producers attract more consumers and consumers willing to travel long distances. Additionally, the factors related to a street market location, product, and consumer behavior are associated. Finally, results indicated the location of organic street markets contributes to displacements by non-motorized modes. The results indicated that the organic street market characteristics can contribute to a sustainable, short, organic food supply chain in Belo Horizonte.
Comparison of the Effects of a Bioceramic and Conventional Resin-Based Sealers on Postoperative Pain after Nonsurgical Root Canal Treatment: A Randomized Controlled Clinical Study
Authors: Shim Kiche , Jang Young-Eun , Kim Yemi
Published: May 2021

Background: This clinical trial aimed to compare the effects of bioceramic sealer and resin-based sealer on the incidence and intensity of postoperative pain. Methods: Patients with anterior teeth or premolars requiring root canal treatment were assigned to group 1 (n = 51). Those with molars requiring treatment were assigned to group 2 (n = 57). In groups 1En and 2En, root canals were obturated with Endoseal MTA using the single-cone technique. In groups 1AH and 2AH, the sealer used was AH Plus with the continuous wave technique. On the day of canal filling, each patient was instructed to indicate their pain intensity over the 7 day postoperative period, at rest and, while biting, using a visual analog scale. Results: There was no significant difference in the incidence or intensity of postoperative pain between the Endoseal MTA and AH Plus groups during the 7 day postoperative period (p > 0.05). Less time was needed to seal the root canals with Endoseal MTA, especially in group 2 (p < 0.05). Conclusions: Endoseal MTA and AH Plus had similar effects on the incidence and intensity of postoperative pain. The obturation time was shorter when using Endoseal MTA compared to AH Plus.
The Optimal Mechanism Design of Retail Prices in the Electricity Market for Several Types of Consumers
Authors: Aizenberg Natalia , Voropai Nikolai
Published: May 2021

In this paper, we discuss the demand side management (DSM) problem: how to incentivize a consumer to equalize the load during the day through price-dependent demand. Traditionally, the retail market offers several electricity payment schemes. A scheme is effective when the different tariffs satisfy different consumers. At the same time, the existing and generally accepted retail pricing schemes can lead to an "adverse selection" problem when all consumers choose the same price, thereby, reducing the possible general welfare. We propose an optimal design of pricing mechanisms, taking into account the interests of the electricity supplier and different types of consumers. The results of our work are that the optimal mechanism is implemented simultaneously for several periods, including the case when the ratio of types of consumers in periods changes. In addition, the mechanism proposed by us, in contrast to the studies of other researchers, provides an equilibrium close to the socially optimal maximum. We describe the implementation algorithm of the mechanism and provide examples of its action in the electric power system with different types and numbers of consumers.
Combined Effect of Activated Carbon Particles and Non-Adsorptive Spherical Beads as Fluidized Media on Fouling, Organic Removal and Microbial Communities in Anaerobic Membrane Bioreactor
Authors: Kwon Daeeun , Lam Theo Y.C. , Kim Minseok , Tan Giin-Yu Amy , Lee Po-Heng , Kim Jeonghwan
Published: May 2021

The combined effect of acrylonitrile butadiene styrene (ABS) spherical beads and granular activated carbon (GAC) particles as fluidized media on the performance of anaerobic fluidized bed membrane bioreactor (AFMBR) was investigated. GAC particles and ABS beads were fluidized together in a single AFMBR to investigate membrane fouling and organic removal efficiency as well as energy consumption. The density difference between these two similarly sized media caused the stratified bed layer where ABS beads are fluidized above the GAC along the membrane. Membrane relaxation was effective to reduce the fouling and trans-membrane pressure (TMP) below 0.25 bar could be achieved at 6 h of hydraulic retention time (HRT). More than 90% of soluble chemical oxygen demand (SCOD) was removed after 80 d operation. Biogas consisting of 65% of methane was produced by AFMBR, suggesting that combined use of GAC and ABS beads did not have any adverse effect on methane production during the operational period. Scanning Electron Microscope (SEM) examinations showed the adherence of microbes to both media. However, 16S rRNA results revealed that fewer microbes attached to ABS beads than GAC. There were also compositional differences between the ABS and GAC microbial communities. The abundance of the syntrophs and exoelectrogens population on ABS beads was relatively low compared to that of GAC. Our result implied that syntrophic synergy and possible occurrence of direct interspecies electron transfer (DIET) might be facilitated in AFMBR by GAC, while traditional methanogenic pathways were dominant in ABS beads. The electrical energy required was 0.02 kWh/m3, and it was only about 13% of that produced by AFMBR.
Thermophysical Properties of the Fe48Cr15Mo14C15B6Y2 Alloy in Liquid State
Authors: Kozak Dmytro , Tsepelev Vladimir , Konaskov Viktor , Vyukhin Viktor , Zadorozhnyy Vladislav , Bazlov Andrey , Kvaratskheliya Askar , Tsarkov Andrey , Van Impe Jan
Published: May 2021

In this work, the physical properties of Fe48Cr15Mo14C15B6Y2 alloy in liquid state at high temperature are studied. It was observed that the basic physical characteristics of the alloy, such as viscosity, electrical resistivity, and density, decrease with an increase of the temperature to 1700 °C. An abnormal increasing rate of viscosity for Fe48Cr15Mo14C15B6Y2 alloy in the temperature range from 1360 to 1550 °C was noted. The measurement of the electrical resistivity and density did not reveal any anomalies in the same temperature range.
Effects of Weight Loss and Moderate-Protein, High-Fiber Diet Consumption on the Fasted Serum Metabolome of Cats
Authors: Pallotto Marissa R. , Oba Patrícia M. , de Godoy Maria R. C. , Pappan Kirk L. , Buff Preston R. , Swanson Kelly S.
Published: May 2021

Feline obesity elicits a plethora of metabolic responses leading to comorbidities, with potential reversal during weight loss. The specific metabolic alterations and biomarkers of organ dysfunction are not entirely understood. Untargeted, high-throughput metabolomic technologies may allow the identification of biological components that change with weight status in cats, increasing our understanding of feline metabolism. The objective of this study was to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite changes associated with reduced food intake and weight loss in overweight cats. During a four-wk baseline period, cats were fed to maintain body weight. For 18 wk following baseline, cats were fed to lose weight at a rate of ~1.5% body weight/wk. Blood serum metabolites were measured at wk 0, 1, 2, 4, 8, 12, and 16. A total of 535 named metabolites were identified, with up to 269 of them being altered (p- and q-values < 0.05) at any time point. A principal component analysis showed a continual shift in metabolite profile as weight loss progressed, with early changes being distinct from those over the long term. The majority of lipid metabolites decreased with weight loss; however, ketone bodies and small lipid particles increased with weight loss. The majority of carbohydrate metabolites decreased with weight loss. Protein metabolites had a variable result, with some increasing, but others decreasing with weight loss. Metabolic mediators of inflammation, oxidative stress, xenobiotics, and insulin resistance decreased with weight loss. In conclusion, global metabolomics identified biomarkers of reduced food intake and weight loss in cats, including decreased markers of inflammation and/or altered macronutrient metabolism.
Uranium Deposits of Erlian Basin (China): Role of Carbonaceous Debris Organic Matter and Hydrocarbon Fluids on Uranium Mineralization
Authors: Qiu Lin-Fei , Li Xi-De , Liu Wu-Sheng , Hu Bao-Qun , Gao Long , He Zhong-Bo
Published: May 2021

The relationship of sedimentary organic matter, oil-gas and sandstone-type uranium (U) deposits is the key problem of U-mineralization. Whether migrate hydrocarbons participate in U-mineralization is still a controversy. Typical U deposits of the Erlian Basin in northeast China have been investigated through detailed petrography, mineralogical, micro spectroscopic, organic geochemical and C-isotope studies. Petrographic observations, Microscopic Laser Raman Spectroscopic, Infrared Spectroscopic and Scanning Electron Microscope analyses indicated there are three types of organic matter (including carbonaceous debris and migrated hydrocarbons). A significant amount of uranium was associated with pyrites, clay minerals and carbonaceous debris organic matter, either coexisted with hydrocarbon fluids. There are at least two stages mineralization events, stage I is related to sedimentary organic matter (syngenetic pre-enrichment stage), and stage II is related to mobile hydrocarbon fluids (main mineralization stage). Therefore, our results support that migrated hydrocarbons were involved as a reducing agent for the main uranium mineralization after synsedimentary mineralization.
The Neglected Nuclei
Authors: Politzer Peter , Murray Jane S.
Published: May 2021

Since the nuclei in a molecule are treated as stationary, it is perhaps natural that interpretations of molecular properties and reactivity have focused primarily upon the electronic density distribution. The role of the nuclei has generally received little explicit consideration. Our objective has been to at least partially redress this imbalance in emphasis. We discuss a number of examples in which the nuclei play the determining role with respect to molecular properties and reactive behavior. It follows that conventional interpretations based solely upon electronic densities and donating or withdrawing tendencies should be made with caution.
Changes in Light Energy Utilization in Photosystem II and Reactive Oxygen Species Generation in Potato Leaves by the Pinworm Tuta absoluta
Authors: Sperdouli Ilektra , Andreadis Stefanos , Moustaka Julietta , Panteris Emmanuel , Tsaballa Aphrodite , Moustakas Michael
Published: May 2021

We evaluated photosystem II (PSII) functionality in potato plants (Solanum tuberosum L.) before and after a 15 min feeding by the leaf miner Tuta absoluta using chlorophyll a fluorescence imaging analysis combined with reactive oxygen species (ROS) detection. Fifteen minutes after feeding, we observed at the feeding zone and at the whole leaf a decrease in the effective quantum yield of photosystem II (PSII) photochemistry (ΦPSII). While at the feeding zone the quantum yield of regulated non-photochemical energy loss in PSII (ΦNPQ) did not change, at the whole leaf level there was a significant increase. As a result, at the feeding zone a significant increase in the quantum yield of non-regulated energy loss in PSII (ΦNO) occurred, but there was no change at the whole leaf level compared to that before feeding, indicating no change in singlet oxygen (1O2) formation. The decreased ΦPSII after feeding was due to a decreased fraction of open reaction centers (qp), since the efficiency of open PSII reaction centers to utilize the light energy (Fv′/Fm′) did not differ before and after feeding. The decreased fraction of open reaction centers resulted in increased excess excitation energy (EXC) at the feeding zone and at the whole leaf level, while hydrogen peroxide (H2O2) production was detected only at the feeding zone. Although the whole leaf PSII efficiency decreased compared to that before feeding, the maximum efficiency of PSII photochemistry (Fv/Fm), and the efficiency of the water-splitting complex on the donor side of PSII (Fv/Fo), did not differ to that before feeding, thus they cannot be considered as sensitive parameters to monitor biotic stress effects. Chlorophyll fluorescence imaging analysis proved to be a good indicator to monitor even short-term impacts of insect herbivory on photosynthetic function, and among the studied parameters, the reduction status of the plastoquinone pool (qp) was the most sensitive and suitable indicator to probe photosynthetic function under biotic stress.
Supported Biofilms on Carbon–Oxide Composites for Nitrate Reduction in Agricultural Waste Water
Authors: Bautista-Toledo M. Isidora , Maldonado-Hódar Francisco J. , Morales-Torres Sergio , Pastrana-Martínez Luisa M.
Published: May 2021

Escherichia coli colonies were grown on different supports for the removal of nitrates from water. A carbon material and different commercial metal oxides, such as SiO2, TiO2 and Al2O3, and their corresponding carbon–metal oxide composites were studied. The physicochemical properties were analyzed by different techniques and the results were correlated with their performance in the denitrification process. Developed biofilms effectively adhere to the supports and always reach the complete reduction of nitrates to gaseous products. Nevertheless, faster processes occur when the biofilm is supported on mesoporous and non-acid materials (carbon and silica).
Comparative Studies of Selected Criteria Enabling Optimization of the Extraction of Polar Biologically Active Compounds from Alfalfa with Supercritical Carbon Dioxide
Authors: Wrona Olga , Rafińska Katarzyna , Krakowska-Sieprawska Aneta , Buszewski Bogusław
Published: May 2021

The aim of this research was to provide crucial and useful data about the selection of the optimization criteria of supercritical carbon dioxide extraction of alfalfa at a quarter-technical plant. The correlation between more general output, including total phenolics and flavonoids content, and a more specified composition of polar constituents was extensively studied. In all alfalfa extracts, polar bioactive constituents were analyzed by both spectrometric (general output) and chromatographic (detailed output) analyses. Eight specific phenolic acids and nine flavonoids were determined. The most dominant were salicylic acid (221.41 µg g−1), ferulic acid (119.73 µg g−1), quercetin (2.23 µg g−1), and apigenin (2.60 µg g−1). For all seventeen analyzed compounds, response surface methodology and analysis of variance were used to provide the optimal conditions of supercritical fluid extraction for each individual constituent. The obtained data have shown that eight of those compounds have a similar range of optimal process parameters, being significantly analogous for optimization based on total flavonoid content.
Direct Visualization of Amlodipine Intervention into Living Cells by Means of Fluorescence Microscopy
Authors: Quentin Christine , Gerasimaitė Rūta , Freidzon Alexandra , Atabekyan Levon S. , Lukinavičius Gražvydas , Belov Vladimir N. , Mitronova Gyuzel Y.
Published: May 2021

Amlodipine, a unique long-lasting calcium channel antagonist and antihypertensive drug, has weak fluorescence in aqueous solutions. In the current paper, we show that direct visualization of amlodipine in live cells is possible due to the enhanced emission in cellular environment. We examined the impact of pH, polarity and viscosity of the environment as well as protein binding on the spectral properties of amlodipine in vitro, and used quantum chemical calculations for assessing the mechanism of fluorescence quenching in aqueous solutions. The confocal fluorescence microscopy shows that the drug readily penetrates the plasma membrane and accumulates in the intracellular vesicles. Visible emission and photostability of amlodipine allow confocal time-lapse imaging and the drug uptake monitoring.
New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles
Authors: Vlad Ilinca Margareta , Nuță Diana Camelia , Ancuceanu Robert Viorel , Caproiou Miron Teodor , Dumitrascu Florea , Marinas Ioana Cristina , Chifiriuc Mariana Carmen , Măruţescu Luminita Gabriela , Zarafu Irina , Papacocea Ioana Raluca , Vasile Bogdan Ștefan , Nicoară Adrian Ionuț , Ilie Cornelia-Ioana , Ficai Anton , Limban Carmen
Published: May 2021

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.
Prioritisation of Compounds for 3CLpro Inhibitor Development on SARS-CoV-2 Variants
Authors: Jukič Marko , Škrlj Blaž , Tomšič Gašper , Pleško Sebastian , Podlipnik Črtomir , Bren Urban
Published: May 2021

COVID-19 represents a new potentially life-threatening illness caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pathogen. In 2021, new variants of the virus with multiple key mutations have emerged, such as B.1.1.7, B.1.351, P.1 and B.1.617, and are threatening to render available vaccines or potential drugs ineffective. In this regard, we highlight 3CLpro, the main viral protease, as a valuable therapeutic target that possesses no mutations in the described pandemically relevant variants. 3CLpro could therefore provide trans-variant effectiveness that is supported by structural studies and possesses readily available biological evaluation experiments. With this in mind, we performed a high throughput virtual screening experiment using CmDock and the “In-Stock” chemical library to prepare prioritisation lists of compounds for further studies. We coupled the virtual screening experiment to a machine learning-supported classification and activity regression study to bring maximal enrichment and available structural data on known 3CLpro inhibitors to the prepared focused libraries. All virtual screening hits are classified according to 3CLpro inhibitor, viral cysteine protease or remaining chemical space based on the calculated set of 208 chemical descriptors. Last but not least, we analysed if the current set of 3CLpro inhibitors could be used in activity prediction and observed that the field of 3CLpro inhibitors is drastically under-represented compared to the chemical space of viral cysteine protease inhibitors. We postulate that this methodology of 3CLpro inhibitor library preparation and compound prioritisation far surpass the selection of compounds from available commercial “corona focused libraries”.
Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach
Authors: Zhang Yumeng , Shi Guohui , Luo Zhonghua , Wang Jiewen , Wu Shao , Zhang Xiaoshu , Zhao Yuqing
Published: May 2021

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 μM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K–Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.
Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments
Authors: Zhao Rusin , Yang Ruijia , Cooper Paul R. , Khurshid Zohaib , Shavandi Amin , Ratnayake Jithendra
Published: May 2021

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.
Effects of Functionalization in Different Conditions and Ball Milling on the Dispersion and Thermal and Electrical Conductivity of MWCNTs in Aqueous Solution
Authors: Tserengombo Baasandulam , Jeong Hyomin , Dolgor Erdenechimeg , Delgado Antonio , Kim Sedong
Published: May 2021

In this work, the effects of a functionalization method involving different conditions and milling processes on the dispersion and thermal and electrical conductivity of multiwalled carbon nanotubes were studied. The surfaces of MWCNTs were modified using a mixture of sulfuric and nitric acid as an acid treatment and potassium persulfate and sodium hydroxide as an alkaline treatment to achieve more hydrophilic MWCNTs. The morphological and structural investigations were carried out using transmission electron microscopy and Fourier transform infrared spectroscopy. Furthermore, the dispersion characteristics and thermal and electrical conductivity of the as-prepared water-based nanofluids were measured. As a result, the dispersion characteristics revealed that the best dispersion and stability results were obtained for alkaline-treated MWCNTs using potassium persulfate and sodium hydroxide. The thermophysical study using a thermal conductivity analyzer exhibited that the thermal conductivity of the pristine MWCNT nanofluid (0.1 wt%) was enhanced from 603.5 to 610.4 mW/m·K and the electrical conductivity of the raw MWCNT nanofluid was increased from 16.2 to 125.8 μS/cm at 25 °C after alkaline treatment and milling processes, which were performed using planetary ball milling. Regarding the overall results, the milling process and mild alkaline oxidation process are more environmentally friendly, effective, and convenient for the functionalization of CNTs, without requiring any organic solvents or strong acids.
An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection
Authors: Harrell Jaikin E. , Kurtz Jonathan R. , Bauer David L. , Prior J. Timothy , Gellings Patrick S. , Morici Lisa A. , McLachlan James B.
Published: May 2021

Non-typhoidal salmonellosis, caused by Salmonella enterica serovar Typhimurium is a common fecal-oral disease characterized by mild gastrointestinal distress resulting in diarrhea, chills, fever, abdominal cramps, head and body aches, nausea, and vomiting. Increasing incidences of antibiotic resistant invasive non-typhoidal Salmonella infections makes this a global threat requiring novel treatment strategies including next-generation vaccines. The goal of the current study was to formulate a novel vaccine platform against Salmonella infection that could be delivered orally. To accomplish this, we created a Salmonella-specific vaccine adjuvanted with Burkholderia pseudomallei outer membrane vesicles (OMVs). We show that adding OMVs to a heat-killed oral Salmonella vaccine (HKST + OMVs) protects against a lethal, oral challenge with Salmonella. Further, we show that opsonizing anti-Salmonella antibodies are induced in response to immunization and that CD4 T cells and B cells can be induced when OMVs are used as the oral adjuvant. This study represents a novel oral vaccine approach to combatting the increasing problem of invasive Salmonella infections.
Serosurvey and Risk Factors Associated with Brucella Infection in High Risk Occupations from District Lahore and Kasur of Punjab, Pakistan
Authors: Ali Shahzad , Saeed Usama , Rizwan Muhammad , Hassan Laiba , Syed Muhammad Ali , Melzer Falk , El-Adawy Hosny , Neubauer Heinrich
Published: May 2021

Brucellosis is a neglected zoonotic disease, and occupations with a high risk of infection exist. Limited information is available on brucellosis for these employees at high risk in Pakistan. A total of 459 persons with high-risk occupations, i.e., 211 abattoir workers, 63 milkers, 52 dung cake makers, 44 veterinarians, 44 shepherds, and 45 veterinary students of the districts Kasur and Lahore, Pakistan, were tested in this study. Blood samples and information on place of residence, gender, age, urbanicity, type of occupation, socioeconomic status, contact with animals, consumption of raw milk, contact to women who had a miscarriage, contact to aborted animal fetus or abortion material, pregnancy, miscarriage history, or intrauterine fetal death were collected. Serum samples were examined using Rose Bengal tests for anti-Brucella antibodies and seropositive samples were subjected to genus-specific qPCR for the detection of DNA. Data were analyzed using chi-squared and binary regression. Twenty (4.35%) persons were seropositive for anti-Brucella antibodies. Out of these, 18 (90%) were tested positive by Brucella genus-specific qPCR. Positive sera were more often found in Lahore district (8.3%) than in Kasur district (3.1%). Persons older than 36 years were more often seropositive. Persons involved in the handing of milk and in contact with animals were more often seropositive. Contact with women who had had a miscarriage was also a significant factor for seropositivity for brucellosis. Place of residence, gender, age, urbanicity, and contact with animals were identified as potential risk factors in the present study. The present study confirmed that brucellosis is an occupation hazard for abattoir workers, milkers, dung cake makers, and veterinarians in the districts of Lahore and Kasur of Punjab, Pakistan. The study shows the need for strategies for safety at work to minimize the risk of infection. Raising awareness for the prevention and use of proper personal protection equipment during the slaughtering and treatment of animal is highly needed.
Chitosan from Crabs (Scylla serrata) Represses Hyperlipidemia-Induced Hepato-Renal Dysfunctions in Rats: Modulation of CD43 and p53 Expression
Authors: Ugbaja Regina Ngozi , Ogungbemi Kunle , James Adewale Segun , Peter Folorunsho Ayodele , Abolade Samuel Olanrewaju , Ajamikoko Stella Onajite , Atayese Eniola Olapeju , Adedeji Omowunmi Victoria
Published: May 2021

Hepato-renal dysfunctions associated with hyperlipidemia necessitates a continuous search for natural remedies. This study thus evaluated the effect of dietary chitosan on diet-induced hyperlipidemia in rats. A total of 30 male Wistar rats (90 ± 10) g were randomly allotted into six (6) groups (n = 5): Normal diet, High-fat diet (HFD), and Normal diet + 5% chitosan. The three other groups received HFD, supplemented with 1%, 3%, and 5% of chitosan. The feeding lasted for 6 weeks, after which the rats were sacrificed. The liver and kidneys were harvested for analyses. Hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity, and renal biomarkers (ALT, AST, urea, and creatinine) were assayed spectrophotometrically. Additionally, expression of hepatic and renal CD43 and p53 was estimated immunohistochemically. The HFD group had elevated bodyweight compared to normal which was reversed in the chitosan-supplemented groups. Hyperlipidemia caused a significant (p < 0.05) decrease in the hepatic (AST, ALT, and ALP) and renal (AST and ALT) activities, while renal urea and creatinine increased. Furthermore, the HFD group showed an elevated level of hepatic and renal CD43 while p53 expression decreased. However, groups supplemented with chitosan showed improved hepatic and renal biomarkers, as well as corrected the aberrations in the expressions of p53 and CD43. Conclusively, dietary chitosan inclusion in the diet (between 3% and 5%) could effectively improve kidney and liver functionality via abatement of inflammatory responses.
Current and Future Therapeutic Strategies for Limb Girdle Muscular Dystrophy Type R1: Clinical and Experimental Approaches
Authors: Şahin İzem Olcay , Özkul Yusuf , Dündar Munis
Published: May 2021

Limb girdle muscular dystrophy type R1 disease is a progressive disease that is caused by mutations in the CAPN3 gene and involves the extremity muscles of the hip and shoulder girdle. The CAPN3 protein has proteolytic and non-proteolytic properties. The functions of the CAPN3 protein that have been determined so far can be listed as remodeling and combining contractile proteins in the sarcomere with the substrates with which it interacts, controlling the Ca2+ flow in and out through the sarcoplasmic reticulum, and regulation of membrane repair and muscle regeneration. Even though there are several gene therapies, cellular therapies, and drug therapies, such as glucocorticoid treatment, AAV- mediated therapy, CRISPR-Cas9, induced pluripotent stem cells, MYO-029, and AMBMP, which are either in preclinical or clinical phases, or have been completed, there is no final cure. Inhibitors and small molecules (tauroursodeoxycholic acid, salubrinal, rapamycin, CDN1163, dwarf open reading frame) targeting ER stress factors that are thought to be effective in muscle loss can be considered potential therapy strategies. At present, little can be done to treat the progressive muscle wasting, loss of function, and premature mortality of patients with LGMDR1, and there is a pressing need for more research to develop potential therapies.