bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Heuristic Evaluation in Immersive Virtual Reality—A Case Study on Future Guidance Systems
Authors: Stadler Sebastian , Cornet Henriette , Frenkler Fritz
Published: February 2023

A variety of evaluation methods for user interfaces (UI) exist such as usability testing, cognitive walkthrough, and heuristic evaluation. However, UIs such as guidance systems at transit hubs must be evaluated in their intended application field to allow the effective and valid identification of usability flaws. However, what if evaluations are not feasible in real environments, or laboratorial conditions cannot be ensured? Based on adapted heuristics, in the present study, the method of heuristic evaluation is combined with immersive Virtual Reality (VR) for the identification of usability flaws of dynamic guidance systems (DGS) at transit hubs. The study involved usability evaluations of nine DGS concepts using the newly proposed method. The results show that compared to computer-based heuristic evaluations, the use of immersive VR led to the identification of an increased amount of “severe” usability flaws as well as overall usability flaws. Within a qualitative assessment, immersive VR is validated as a suitable tool for conducting heuristic evaluations involving significant advantages such as the creation of realistic experiences in laboratorial conditions. Future work seeks to further prove the suitability of using immersive VR for heuristic evaluations and compare the proposed method to other evaluative methods.
Electronic and Spintronic Properties of Armchair MoSi2N4 Nanoribbons Doped by 3D Transition Metals
Authors: Su Xiao-Qian , Wang Xue-Feng
Published: February 2023

Structural and physical properties of armchair MoSi2N4 nanoribbons substitutionally doped by 3d transition metals (TM) at Mo sites are investigated using the density functional theory combined with the non-equilibrium Green’s function method. TM doping can convert the nonmagnetic direct semiconductor into device materials of a broad variety, including indirect semiconductors, half semiconductors, metals, and half metals. Furthermore the 100% spin filtering behavior in spin-up and spin-down half metals, a negative differential resistance with peak-to-valley ratio over 140 and a rectification effect with ratio over 130 are predicted, as well as semiconductor behavior with high spin polarization.
Methanol and Ethanol Electrooxidation on ZrO2/NiO/rGO
Authors: Askari Mohammad Bagher , Beitollahi Hadi , Di Bartolomeo Antonio
Published: February 2023

Recently, transition metal oxides have been considered for various applications due to their unique properties. We present the synthesis of a three-component catalyst consisting of zirconium oxide (ZrO2), nickel oxide (NiO), and reduced graphene oxide (rGO) in the form of ZrO2/NiO/rGO by a simple one-step hydrothermal method. X-ray powder diffraction (XRD), scanning electron microscope (SEM), and bright-field transmission electron microscopy (BF-TEM) analyses were performed to accurately characterize the catalysts. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and linear sweep voltammetry (LSV) analyses were also carried out to investigate the methanol and ethanol alcohol electrooxidation ability of the synthesized nanocatalysts. Inspired by the good potential of metal oxides in the field of catalysts, especially in fuel-cell anodes, we investigated the capability of this catalyst in the methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR). After proving the successful synthesis and examining the surface morphology of these materials, detailed electrochemical tests were performed to show the outstanding capability of this new nanocatalyst for use in the anode of alcohol fuel cells. ZrO2/NiO/rGO indicated a current density of 26.6 mA/cm2 at a peak potential of 0.52 V and 99.5% cyclic stability in the MOR and a current density of 17.3 mA/cm2 at a peak potential of 0.52 V and 98.5% cyclic stability in the EOR (at optimal concentration/scan rate 20 mV/s), representing an attractive option for use in the anode of alcoholic fuel cells.
Nanoneedles of Mixed Transition Metal Phosphides as Bifunctional Catalysts for Electrocatalytic Water Splitting in Alkaline Media
Authors: Salvò Davide , Mosconi Dario , Neyman Alevtina , Bar-Sadan Maya , Calvillo Laura , Granozzi Gaetano , Cattelan Mattia , Agnoli Stefano
Published: February 2023

In this work, mixed Ni/Co and Ni/Fe metal phosphides with different metal ratios were synthesized through the phosphidization of high-surface-area hydroxides grown hydrothermally on carbon cloth. The materials were characterized by means of X-ray photoemission spectroscopy, X-ray diffraction, energy dispersive X-ray analysis, and electron microscopies. The electrocatalytic performance in the electrochemical water splitting was tested in alkaline media. With the aim of determining the chemical stability of the mixed phosphides and the possible changes undergone under catalytic conditions, the materials were characterized before and after the electrochemical tests. The best performances in the hydrogen evolution reaction were achieved when synergic interactions are established among the metal centers, as suggested by the outstanding performances (50 mV to achieve 10 mA/cm2) of materials containing the highest amount of ternary compounds, i.e., NiCoP and NiFeP. The best performances in the oxygen evolution reaction were reached by the Ni-Fe materials. Under these conditions, it was demonstrated that a strong oxidation of the surface and the dissolution of the phosphide/phosphate component takes place, with the consequent formation of the corresponding metal oxides and hydroxides.
Nanotechnology and Wood Science
Authors: Papadopoulos Antonios N.
Published: February 2023

Nanotechnology, in a sense, is not entirely a new concept [...]
Machine Learning Applied to LoRaWAN Network for Improving Fingerprint Localization Accuracy in Dense Urban Areas
Authors: Piroddi Andrea , Torregiani Maurizio
Published: February 2023

In the area of low-power wireless networks, one technology that many researchers are focusing on relates to positioning methods such as fingerprinting in densely populated urban areas. This work presents an experimental study aimed at quantifying mean location estimation error in populated areas. Using a dataset provided by the University of Antwerp, a neural network was implemented with the aim of providing end-device location. In this way, we were able to measure the mean localization error in areas of high urban density. The results obtained show a deviation of less than 150 m in locating the end device. This offset can be decreased up to a few meters, provided that there is a greater density of nodes per square meter. This result could enable Internet of Things (IoT) applications to use fingerprinting in place of energy-consuming alternatives.
Nuts in the Prevention and Management of Type 2 Diabetes
Authors: Nishi Stephanie K. , Viguiliouk Effie , Kendall Cyril W. C. , Jenkins David J. A. , Hu Frank B. , Sievenpiper John L. , Atzeni Alessandro , Misra Anoop , Salas-Salvadó Jordi
Published: February 2023

Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.
Molecular Targets and Mechanisms of 6,7-Dihydroxy-2,4-dimethoxyphenanthrene from Chinese Yam Modulating NF-κB/COX-2 Signaling Pathway: The Application of Molecular Docking and Gene Silencing
Authors: Nie Congyi , Zou Yuxiao , Liao Sentai , Gao Qunyu , Li Qian
Published: February 2023

Chinese yam (Dioscorea opposita) tuber has a significant effect of invigorating the intestine and improving the symptoms of long-term diarrhea according to the records of the Chinese Pharmacopoeia. Phenanthrene polyphenols from Chinese yam, with higher inhibition of cyclooxygenase-2 (COX-2) than anti-inflammatory drugs, are an important material basis in alleviating ulcerative colitis via nuclear factor kappa-B (NF-κB)/COX-2 pathway, based on our previous research. The present study further explored the target and molecular mechanisms of phenanthrenes’ modulation of the NF-κB/COX-2 signaling pathway by means of molecular docking and gene silencing. Firstly, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) expression of 6-hydroxy-2,4,7-trimethoxyphenanthrene (PC2)/6,7-dihydroxy-2,4-dimethoxyphe-nanthrene (PC4) were compared on TNF-α induced human colon adenocarcinoma (Caco-2) cells. Secondly, molecular docking and dynamics simulation were implemented for PC2/PC4 and COX-2. Finally, COX-2 silencing was performed on TNF-α induced Caco-2 cells to confirm the target of PC4 on NF-κB/COX-2 pathway. Lower expression of IL-8 and TNF-α in PC4 treated Caco-2 cells indicated that PC4 had stronger anti-inflammatory activity than PC2. The binding of PC4 and COX-2 was stronger due to the hydrogen bond between hydroxyl group and Tyr385. No significant differences were found in phosphorylation nuclear factor kappa-B inhibitor alpha (pIkBα), phosphorylation NF-κB (pNF-κB) and phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2) expression between control and PC4 group after silencing, while these protein expressions significantly decreased in PC4 group without silencing, which confirmed that COX-2 was the important target for PC4 in alleviating ulcerative colitis. These findings indicate that PC4 was supposed to have inhibited NF-κB pathway mediated inflammation via suppression of positive feedback targeting COX-2.
Socioeconomic and Demographic Factors Associated with the Influence of the Food Traffic Light Labeling on the Decision of the Adult Population of Ecuador to Purchase Processed Foods, 2018
Authors: Bobbio Gonzáles Paolo Alfredo , Azañedo Diego , Hernández-Vásquez Akram
Published: February 2023

To determine the socioeconomic and demographic factors associated with the influence of the nutritional traffic light (NTL) on the decision to purchase processed foods using information from the National Health and Nutrition Survey (ENSANUT) 2018 of Ecuador, a cross-sectional and analytical study based on a secondary analysis of the information from the ENSANUT 2018 was performed. We collected data from 25,932 participants 18 years of age or older who knew or had seen the NTL, and for whom complete information on the variables of interest for the study was available. The “Influence of the NTL on the purchase decision of processed foods” was the outcome variable of the study. Generalized linear models of the Poisson family, with log link, were used to assess the association between socioeconomic factors and outcome, using crude (PR) and adjusted (aPR) prevalence ratios, with 95% confidence intervals (CI) and a p-value < 0.05. Participants who understood the NTL (aPR: 2.49; 95% CI: 2.19–2.83), with a higher educational level (aPR: 1.33; 95% CI: 1.09–1.61), women (aPR 1.06; 95% CI: 1.01–1.10), and who had a partner (aPR 1.09; 95% CI: 1.04–1.14) were more likely to be influenced by the NTL when deciding to purchase processed foods, compared to people who did not understand the NTL, who had no educational level or who only attended a literacy center, were men, and those without a partner. The inhabitants of the coastal region (aPR: 0.92; 95% CI: 0.88–0.97), the Amazon (aPR 0.93; 95% CI: 0.88–0.98), and the insular region (aPR 0.76; 95% CI: 0.68–0.84) had few probabilities of being influenced by the NTL in the decision to purchase processed foods, in comparison with the residents of the highlands. Similarly, compared to non-poor people, poor people had a lower probability of being influenced by the NTL (aPR 0.89; 95% CI: 0.82–0.97). Factors associated with the influence of NTL on the decision to purchase processed foods were identified. It is recommended to reformulate and focus awareness strategies for using the NTL to purchase processed foods by taking into account the associated factors.
Iodide Excess Inhibits Thyroid Hormone Synthesis Pathway Involving XBP1-Mediated Regulation
Authors: Yu Jing , Shen Siyi , Yan Ying , Liu Lingxiao , Luo Rongkui , Liu Shengnan , Wu Yuting , Li Yuying , Jiang Jingjing , Ying Hao
Published: February 2023

Iodine is an essential micronutrient for producing thyroid hormone (TH); however, iodide excess can lead to adverse thyroidal effects. Unfortunately, the lack of a proper in vitro model system hampered the studies of the effect of iodide excess on thyroid physiology and pathology. Here, we demonstrated that excessive iodide intake downregulated the genes related to TH synthesis in the thyroids of mice. Since sodium iodide has no effect on these genes in cultured cell lines, we developed a three-dimensional (3D) culture system to enable the murine thyrocytes to form organoids in vitro with thyroid follicle-like structures and function and found that the in vivo effect of iodide excess could be mimicked in these thyroid organoids. Our data indicate that iodide excess mainly activated the XBP1-mediated unfolded protein response in both murine thyroid and thyroid organoids, while activation of XBP1 was able to mimic the sodium iodide effect on genes for the synthesis of TH in murine thyroid organoids. Lastly, our results suggest that XBP1 might transcriptionally repress the genes involved in the synthesis of TH. Based on these findings, we propose that iodide excess inhibits the transcription of genes related to TH synthesis through a mechanism involving XBP1-mediated action.
The Impact of Free Sugar on Human Health—A Narrative Review
Authors: Gillespie Kerri M. , Kemps Eva , White Melanie J. , Bartlett Selena E.
Published: February 2023

The importance of nutrition in human health has been understood for over a century. However, debate is ongoing regarding the role of added and free sugars in physiological and neurological health. In this narrative review, we have addressed several key issues around this debate and the major health conditions previously associated with sugar. We aim to determine the current evidence regarding the role of free sugars in human health, specifically obesity, diabetes, cardiovascular diseases, cognition, and mood. We also present some predominant theories on mechanisms of action. The findings suggest a negative effect of excessive added sugar consumption on human health and wellbeing. Specific class and source of carbohydrate appears to greatly influence the impact of these macronutrients on health. Further research into individual effects of carbohydrate forms in diverse populations is needed to understand the complex relationship between sugar and health.
Does Aging Affect Vitamin C Status Relative to Intake? Findings from NHANES 2017–2018
Authors: Carr Anitra C. , Lykkesfeldt Jens
Published: February 2023

The aging population is growing and fueling a global increase in chronic diseases and healthcare expenditure. In this study, we examine vitamin C dose–concentration relationships based on data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 to identify a possible age-dependent change in intake vs. concentration relationship among non-supplemented individuals (n = 2828). The vitamin C intake was similar between the younger (18–36 years), middle (37–58 years) and older (59–80+ years) age groups; however, circulating vitamin C concentrations were significantly lower in the middle and older age groups (p < 0.001). For intakes above 75 mg/day, no significant difference in the intake vs. serum concentration relationship was identified between younger and older individuals. However, for intakes below 75 mg/day, we found significantly lower serum concentrations relative to intake for the older compared to younger individuals, despite smoking being more prevalent in the younger compared to older adults (p < 0.001). This effect persisted among non-smokers and was further exacerbated by smoking in older people. Collectively, the present study suggests that healthy aging in non-institutionalized individuals does not increase requirements for vitamin C. In contrast, the lower serum concentrations relative to intake observed in older individuals at intakes < 75 mg/day may suggest that older individuals are more sensitive to a low vitamin C intake, perhaps due to the increased impact of long-term smoking and increased chronic disease prevalence in older adults. This finding may have implications for future intake guidelines in countries with low RDAs and for WHO/FAO, but requires further investigation.
Effect of Gestational Weight Gain during the First Half of Pregnancy on the Incidence of GDM, Results from a Pregnant Cohort in Northern Greece
Authors: Tranidou Antigoni , Magriplis Emmanuela , Tsakiridis Ioannis , Pazaras Nikolaos , Apostolopoulou Aikaterini , Chourdakis Michail , Dagklis Themistoklis
Published: February 2023

The aim of this study was to evaluate the effect of gestational weight gain (GWG) up to 23+6 weeks of gestation on the incidence of Gestational Diabetes Mellitus (GDM). A pregnant cohort of 5948 women in Northern Greece was recruited. Anthropometric features before and during pregnancy were recorded, the GWG by 23+6 weeks was calculated and a Generalized Linear Regression Model (GLM) with subgroup analyses based on weight status were computed. GDM was diagnosed in 5.5% of women. GLM results showed that GDM likelihood increased with maternal age (MA) and pre-pregnancy BMI (aOR: 1.08, 95%CI: [1.06, 1.11] and aOR: 1.09, 95%CI: [1.09, 1.11], respectively). Ιn the normal pre-pregnancy weight group, when the extra weight gain was >8 kgs, the odds of GDM increased (OR: 2.13, 95%CI: [0.98, 4.21], p = 0.03). Women with pre-pregnancy level 2 clinical obesity (OB2 pre) (BMI > 35 and <40 kg/m2) that shifted to OB3 category (BMI ≥ 40 kg/m2) had an increased GDM likelihood (OR: 4.85, 95%CI: [1.50, 15.95]). Women of higher MA may require stricter monitoring for GDM from early pregnancy, while in obese women, recommended GWG may need to be re-evaluated, since refraining from any weight gain may have a preventive effect for GDM.
Sonographic Markers Are Useful for Detection of Early Vascular Deterioration in Children with Overweight/Obesity: Effect of a 1-Year Combined Nutritional Education and Physical Exercise Program
Authors: Abellaneda Millán María , Morillas-Ruiz Juan María , Ballester Sajardo Raúl , Guillén Martínez Daniel , Morales Moreno Isabel , Hernández Morante Juan José
Published: February 2023

As in adults, childhood obesity is associated with several metabolic disorders; however, there is little information regarding complex obesity-derived complications such as hepatic steatosis or endothelial dysfunction at early ages. Therefore, the objective of the present study was to analyze the effect of a nutritional and physical exercise program on obesity comorbidities in the form of subclinical atherosclerosis and non-alcoholic fatty liver in young children. A total of 148 children completed the study. For nine months (one academic year), children carried out a nutritional and physical activity program of 3 h/week. Anthropometric, clinical, liver ultrasound and carotid intima-media thickness (cIMT) parameters were evaluated. Our results showed that the program significantly improved anthropometrical parameters, especially regarding BMI and body fat (p < 0.001 and p = 0.004, respectively). The effect on metabolic parameters was limited, although a significant reduction on triglycerides was observed (p = 0.009). The education program had a great influence on the echogenic parameters, since the percentage of children with light steatosis decreased from 35% to 4% at the end of the study. In addition, cIMT also decreased significantly in both groups, although there was no statistically significant differences between groups. In conclusion, detection of early complications of obesity through sonographic parameters may allow early intervention, as in the present study, to prevent obesity co-morbidities in children.
What Should I Eat? Dietary Recommendations for Patients with Inflammatory Bowel Disease
Authors: Saha Srishti , Patel Neha
Published: February 2023

Inflammatory bowel disease (IBD) is a chronic disorder thought to be caused by enteric inflammation in a genetically susceptible host. Although the pathogenesis of IBD is largely unknown, it is widely accepted that dietary components play an important role. Human and animal-based studies have explored the role of various dietary components such as meat, artificial sweeteners and food additives in causing enteric inflammation. Several diets have also been studied in patients with IBD, specifically their role in the induction or maintenance of remission. The most well-studied of these include exclusive enteral nutrition and specific carbohydrate diet. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), typically prescribed for patients with irritable bowel syndrome, has also been studied in a specific subgroup of patients with IBD. In this review, we describe the current evidence on how various dietary components can induce enteric and colonic inflammation, and the clinical–epidemiological evidence exploring their role in predisposing to or protecting against the development of IBD. We also discuss several special diets and how they affect clinical outcomes in IBD patients. Based on the available evidence, we provide guidance for patients and clinicians managing IBD regarding the best practice in dietary modifications.
GLIM Criteria for Assessment of Malnutrition in Saudi Patients with Type 2 Diabetes
Authors: Albukhari Sondos , Abulmeaty Mahmoud M. A. , Alguwaihes Abdullah M. , Shoqeair Mustafa , Aldisi Dara , Alhamdan Adel
Published: February 2023

The Global Leadership Initiative on Malnutrition (GLIM) is a new approach established for the assessment of malnutrition. This study aimed to validate the GLIM for the diagnosis of malnutrition in patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia, using the Subjective Global Assessment (SGA) as a reference. In addition, the association between the GLIM criteria and vascular complications in those patients was examined. A cross-sectional study was conducted on 101 patients with T2DM. The level of agreement between the GLIM and SGA tools was calculated using the kappa coefficient (κ). A receiver operating characteristic curve was used to determine the sensitivity and specificity of the GLIM. In addition, binary logistic regression was performed to investigate the association between each GLIM criterion and T2DM vascular complications. According to both the GLIM and the SGA, malnutrition was found in 15.8% and 17.8% of patients, respectively. The GLIM criteria achieved a very good level of accuracy (AUC = 0.877). The agreement between the tools was substantial (κ = 0.778). The ‘disease/inflammation’ criterion of the GLIM was significantly associated with macrovascular complications. To conclude, the GLIM criteria for diagnosis of malnutrition presented satisfactory levels of validity, and as such are acceptable for assessing the nutritional status of patients with T2DM.
Understanding the Role of CalFresh Participation and Food Insecurity on Academic Outcomes among College Students during the COVID-19 Pandemic
Authors: Loofbourrow Brittany M. , Jones Anna M. , Martinez Suzanna M. , Kemp Leslie C. , George Gretchen L. , Scherr Rachel E.
Published: February 2023

Food insecurity (FI) is associated with many adverse outcomes in college students. The Supplemental Nutrition Assistance Program (SNAP, known as CalFresh in California) has been observed to alleviate FI; however, on college campuses, the benefits of food assistance programs are not well understood. This study investigated whether college students benefit from CalFresh participation. It was hypothesized that students would experience increased FI over time and that CalFresh participation would moderate the effect of FI on grade point average (GPA). A comprehensive FI and CalFresh questionnaires were distributed during the 2020–2021 academic year to 849 students. The chi-square test of independence assessed differences between FI and student factors. A Friedman test assessed differences in FI during the three quarters. Moderation analysis assessed whether CalFresh participation moderated FI’s effect on GPA. Differences were observed among food security scores in Winter 2021 (median = 1.69) and Fall 2020 (median = 2.14; p = 0.013) and Spring 2020 (median = 2.17; p = 0.009). In the moderation model, the interaction of FI score and CalFresh participation was positively correlated with GPA (B = 0.11; p = 0.002). These results indicate that SNAP/CalFresh participation was particularly beneficial for mitigating the negative effects of FI on GPA. Given these benefits, encouraging SNAP/CalFresh enrollment should be a priority for university administrators.
Identification of a Major QTL-Controlling Resistance to the Subtropical Race 4 of Fusarium oxysporum f. sp. cubense in Musa acuminata ssp. malaccensis
Authors: Chen Andrew , Sun Jiaman , Martin Guillaume , Gray Lesley-Ann , Hřibová Eva , Christelová Pavla , Yahiaoui Nabila , Rounsley Steve , Lyons Rebecca , Batley Jacqueline , Chen Ning , Hamill Sharon , Rai Subash K. , Coin Lachlan , Uwimana Brigitte , D’Hont Angelique , Doležel Jaroslav , Edwards David , Swennen Rony , Aitken Elizabeth A. B.
Published: February 2023

Vascular wilt caused by the ascomycete fungal pathogen Fusarium oxysporum f. sp. cubense (Foc) is a major constraint of banana production around the world. The virulent race, namely Tropical Race 4, can infect all Cavendish-type banana plants and is now widespread across the globe, causing devastating losses to global banana production. In this study, we characterized Foc Subtropical Race 4 (STR4) resistance in a wild banana relative which, through estimated genome size and ancestry analysis, was confirmed to be Musa acuminata ssp. malaccensis. Using a self-derived F2 population segregating for STR4 resistance, quantitative trait loci sequencing (QTL-seq) was performed on bulks consisting of resistant and susceptible individuals. Changes in SNP index between the bulks revealed a major QTL located on the distal end of the long arm of chromosome 3. Multiple resistance genes are present in this region. Identification of chromosome regions conferring resistance to Foc can facilitate marker assisted selection in breeding programs and paves the way towards identifying genes underpinning resistance.
Novel Scaffold Based on Chitosan Hydrogels/Phthalated Cashew Gum for Supporting Human Dental Pulp Stem Cells
Authors: Leite Yulla Klinger de Carvalho , Oliveira Antônia Carla de Jesus , Quelemes Patrick Veras , Neto Napoleão Martins Argolo , Carvalho Camila Ernanda Sousa de , Soares Rodrigues Huanna Waleska , Alves Michel Muálem de Moraes , Carvalho Fernando Aécio de Amorim , Arcanjo Daniel Dias Rufino , Silva-Filho Edson Cavalcanti da , Durazzo Alessandra , Lucarini Massimo , Carvalho Maria Acelina Martins de , Silva Durcilene Alves da , Leite José Roberto de Souza de Almeida
Published: February 2023

Hydrogels are structures that have value for application in the area of tissue engineering because they mimic the extracellular matrix. Naturally obtained polysaccharides, such as chitosan (CH) and cashew gum, are materials with the ability to form polymeric networks due to their physicochemical properties. This research aimed to develop a scaffold based on chitosan and phthalated cashew tree gum and test it as a support for the growth of human mesenchymal stem cells. In this study, phthalation in cashew gum (PCG) was performed by using a solvent-free route. PCG-CH scaffold was developed by polyelectrolyte complexation, and its ability to support adherent stem cell growth was evaluated. The scaffold showed a high swelling rate. The pore sizes of the scaffold were analyzed by scanning electron microscopy. Human dental pulp stem cells (hDPSCs) were isolated, expanded, and characterized for their potential to differentiate into mesenchymal lineages and for their immunophenotypic profile. Isolated mesenchymal stem cells presented fibroblastoid morphology, plastic adhesion capacity, and differentiation in osteogenic, adipogenic, and chondrogenic lineages. Mesenchymal stem cells were cultured in scaffolds to assess cell adhesion and growth. The cells seeded on the scaffold showed typical morphology, attachment, and adequate distribution inside the matrix pores. Thus, cells seeded in the scaffold may improve the osteoinductive and osteoconductive properties of these biomaterials.
Comparative Analysis of Physical and Chemical Properties of Differently Obtained Zn—Methionine Chelate with Proved Antibiofilm Properties (Part II)
Authors: Marukhlenko Alla V. , Tumasov Vladimir N. , Butusov Leonid A. , Shandryuk Georgy A. , Morozova Mariya A.
Published: February 2023

The previously demonstrated activity of aqueous solutions of methionine and zinc salts against biofilms of uropathogenic bacteria prompted us to investigate the structure and properties of zinc methionine complex obtained from such solutions. The paper presents the analysis results of zinc coordination complexes with methionine obtained by synthesis (0.034 mol of L-methionine, 0.034 mol of NaOH, 40 mL of H2O, 0.017 mol ZnSO4, 60 °C) and simple crystallization from water solution (25 mL of a solution containing 134 mmol/L L-methionine, 67 mmol/L ZnSO4, pH = 5.74, I = 0.37 mmol/L, crystallization at room temperature during more than two weeks). IR spectral analysis and X-ray diffraction showed the structural similarity of the substances to each other, in agreement with the data described in the literature. DSC confirmed the formation of a thermally stable (in the range from −30 °C to 180 °C) chelate compound in both cases and indicated the possible retention of the polymorphic two-dimensional structure inherent in L-methionine with the temperature of phase transition 320 K. The crystallized complex had better solubility in water (100 to 1000 mL per 1.0 g) contra the synthesized analog, which was practically insoluble (more than 10 000 mL per 1.0 g). The results of the solubility assessment, supplemented by the results of the dispersion analysis of solutions by the dynamic light scattering method indicated the formation of zinc-containing nanoparticles (80 nm) in a saturated water solution of a crystallized substance, suggesting the crystallized substance may have higher bioavailability. We predicted a possibility of the equivalent existence of optically active cis and trans isomers in methionine-zinc solutions by the close values of formation enthalpy (−655 kJ/mol and −657 kJ/mol for cis and trans forms, respectively) and also illustrated by the polarimetry measurement results (∆α = 0.4°, pH = 5.74, C(Met) = 134 mmol/L; the concentration of metal ion gradually increased from 0 to 134 mmol/L). The obtained results allowed us to conclude that the compound isolated from the solution is a zinc-methionine chelate with the presence of sulfate groups and underline the role of the synthesis route for the biopharmaceutical characteristics of the resulting substance. We provided some quality indicators that it may be possible to include in the pharmacopeia monographs.
Safety in Rats of a Novel Nasal Spray Formulation for the Prevention of Airborne Viral Infections
Authors: Tanori Mirella , Pitaro Michele , Fratini Emiliano , Colantoni Eleonora , Amoresano Angela , Celentano Simona , Chiaramonte Barbara , Mancuso Mariateresa
Published: February 2023

Hexedra+® is a nasal spray containing hydroxypropyl methylcellulose, beta-cyclodextrin, and usnic acid. It has been developed with the aim of reducing the risk of transmission of airborne viral infections, with particular reference to influenza and COVID-19. As part of the preclinical development of the product, we carried out a study on thirty male Wistar rats divided into three study groups and treated with Hexedra+, an alternative formulation containing a double concentration of usnic acid (0.015% instead of 0.0075%) or saline solution. Products were administered at the dose of 30 μL into each nostril, three times a day for seven consecutive days by means of a micropipette. By the end of the treatment period, no significant changes were observed in body weight. Histological examination of nasal mucosa and soft organs did not show any significant difference in the three study groups. Serum transaminase level remained in the normal limit in all the animals treated. The serum level of usnic acid was measured in order to assess the absorption of the molecule through the nasal mucosa. By the end of the study period, the usnic acid serum level was negligible in all the animals treated. In conclusion, the safety profile of Hexedra+ appears favorable in the animal model studied.
Commercially Available Cell-Free Permeability Tests for Industrial Drug Development: Increased Sustainability through Reduction of In Vivo Studies
Authors: Jacobsen Ann-Christin , Visentin Sonja , Butnarasu Cosmin , Stein Paul C. , di Cagno Massimiliano Pio
Published: February 2023

Replacing in vivo with in vitro studies can increase sustainability in the development of medicines. This principle has already been applied in the biowaiver approach based on the biopharmaceutical classification system, BCS. A biowaiver is a regulatory process in which a drug is approved based on evidence of in vitro equivalence, i.e., a dissolution test, rather than on in vivo bioequivalence. Currently biowaivers can only be granted for highly water-soluble drugs, i.e., BCS class I/III drugs. When evaluating poorly soluble drugs, i.e., BCS class II/IV drugs, in vitro dissolution testing has proved to be inadequate for predicting in vivo drug performance due to the lack of permeability interpretation. The aim of this review was to provide solid proofs that at least two commercially available cell-free in vitro assays, namely, the parallel artificial membrane permeability assay, PAMPA, and the PermeaPad® assay, PermeaPad, in different formats and set-ups, have the potential to reduce and replace in vivo testing to some extent, thus increasing sustainability in drug development. Based on the literature review presented here, we suggest that these assays should be implemented as alternatives to (1) more energy-intense in vitro methods, e.g., refining/replacing cell-based permeability assays, and (2) in vivo studies, e.g., reducing the number of pharmacokinetic studies conducted on animals and humans. For this to happen, a new and modern legislative framework for drug approval is required.
Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
Authors: Jermy B. Rabindran , Salahuddin Mohammed , Tanimu Gazali , Dafalla Hatim , Almofty Sarah , Ravinayagam Vijaya
Published: February 2023

An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe3+ species were identified using diffuse reflectance spectroscopy. The large surface area (804 m2/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug’s release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08–1 h), insulin/ferrisilicate ratios (0.125–1.0) and drug release rates at different pH were examined using the Korsmeyer–Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.
Quantitative Assessment of Low-Dose Photodynamic Therapy Effects on Diabetic Wound Healing Using Raman Spectroscopy
Authors: Zuhayri Hala , Samarinova Alice A. , Borisov Alexey V. , Guardado David A. Lopez , Baalbaki Houssain , Krivova Natalya A. , Kistenev Yury V.
Published: February 2023

One of challenges that faces diabetes is the wound healing process. The delayed diabetic wound healing is caused by a complicated molecular mechanism involving numerous physiological variables. Low-dose photodynamic therapy (LDPDT) provides excellent results in rejuvenation and wound healing. In this study, the LDPDT effect on diabetic wounds in mice was studied using two photosensitizers, 5-aminolevulinic acid and methylene blue, and two laser dose expositions of 1 J/cm2 and 4 J/cm2 by Raman spectroscopy (RS). The latter was used as a noninvasive method, providing specific information about tissue state based on the fundamental vibrational modes of its molecular components. RS allows high spatial resolution acquisition of biochemical and structural information through the generation of point spectra or spectral images. An approach to in vivo quantitative assessment of diabetic wound healing state was developed. This approach is based on an application of the principal component analysis combined with the Mahalanobis metrics to skin Raman spectra, in particular, intensities of the amide I and CH2 bands.
Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery
Authors: Adekeye Adenike O. , Needham David , Rahman Ruman
Published: February 2023

Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL receptor (LDLR) expression in HGGs using immunohistochemistry on tissue microarrays from intra- and inter tumour regions of 36 adult and 133 paediatric patients to confirm LDLR as a therapeutic target. Additionally, we analysed expression levels in three representative cell line models to confirm their future utility to test LDLR-targeted nanoparticle uptake, retention, and cytotoxicity. Our data show widespread LDLR expression in adult and paediatric cohorts, but with significant intra-tumour variation observed between the core and either rim or invasive regions of adult HGG. Expression was independent of paediatric tumour grade or identified clinicopathological factors. LDLR-expressing tumour cells localized preferentially within perivascular niches, also with significant adult intra-tumour variation. We demonstrated variable levels of LDLR expression in all cell lines, confirming their suitability as models to test LDLR-targeted nanotherapy delivery. Overall, our study reveals the LDLR pathway as a ubiquitous metabolic vulnerability in high grade gliomas across all ages, amenable to future consideration of LDL-mediated nanoparticle/drug delivery to potentially circumvent tumour heterogeneity.
Screening of Fenofibrate-Simvastatin Solid Dispersions in the Development of Fixed-Dose Formulations for the Treatment of Lipid Disorders
Authors: Górniak Agata , Czapor-Irzabek Hanna , Złocińska Adrianna , Gawin-Mikołajewicz Agnieszka , Karolewicz Bożena
Published: February 2023

The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.
Revisiting the Therapeutic Effects of Essential Oils on the Oral Microbiome
Authors: Radu Casandra-Maria , Radu Carmen Corina , Bochiș Sergiu-Alin , Arbănași Emil Marian , Lucan Alexandra Ioana , Murvai Viorela Romina , Zaha Dana Carmen
Published: February 2023

The extensive use of antibiotics has resulted in the development of drug-resistant bacteria, leading to a decline in the efficacy of traditional antibiotic treatments. Essential oils (EOs) are phytopharmaceuticals, or plant-derived compounds, that possess beneficial properties such as anti-inflammatory, antibacterial, antimicrobial, antiviral, bacteriostatic, and bactericidal effects. In this review, we present scientific findings on the activity of EOs as an alternative therapy for common oral diseases. This narrative review provides a deeper understanding of the medicinal properties of EOs and their application in dentistry. It not only evaluates the effectiveness of these oils as antibacterial agents against common oral bacteria but also covers general information such as composition, methods of extraction, and potential toxicity. Further nonclinical and clinical studies must be conducted to determine their potential use and safety for treating oral diseases.
Noise Considerations for Tomographic Reconstruction of Single-Projection Digital Holographic Interferometry-Based Radiation Dosimetry
Authors: Telford Tom , Roberts Jackson , Moggré Alicia , Meyer Juergen , Marsh Steven
Published: February 2023

Optical Calorimetry (OC) is a 2D Digital Holographic Interferometry (DHI)-based measurement technique with potential applications for the 3D dosimetry of ultra-high dose rate (FLASH) radiation therapy beams through tomographic reconstruction. This application requires accurate measurements of DHI signals in environments with low signal-to-noise ratios (SNRs) in order to accurately measure absorbed energy to a medium per unit mass (Dose). However, tomographic reconstruction accuracy is sensitive to noise in the measurements. In this study, a virtual model of an OC dosimeter was used to characterize and model major sources of noise within a DHI setup, allowing for the modelled noise sources to be selectively reduced. The tomographic reconstruction of the 3D dose distribution was achieved using the inverse Abel transform. Reducing the noise contribution from atmospheric turbulence and mechanical vibration by one half improved the central axis reconstruction error from 6.5% to 1.3% and 1.1%, respectively, and the mean dose difference from 2.9% to 0.4% and 0.3%, respectively. This indicates the potential of the tomographic DHI-based 3D OC dosimeter to reconstruct accurate 3D dose distributions from a single projection if the specified sources of noise can be reduced to acceptable levels. The used methodology is applicable to any application of tomographic DHI where reconstruction quality is highly sensitive to noise.
Inoculation with Oidiodendron maius BP Improves Nitrogen Absorption from Fertilizer and Growth of Vaccinium corymbosum during the Early Nursery Stage
Authors: Pescie María A. , Montecchia Marcela , Lavado Raul S. , Chiocchio Viviana M.
Published: February 2023

Blueberry roots are inefficient in taking up water and nutrients, a fact partially related to their scarcity of root hairs, but they improve nutrient uptake by associating with ericoid mycorrhizal and endophytic fungi. However, the benefits of this association are both cultivar- and fungus-dependent. Our objective was to assess the effect of inoculation with three native fungal strains (Oidiodendron maius A, O. maius BP, and Acanthomyces lecanii BC) on plantlet growth, plantlet survival, and nitrogen (N) absorption of the southern highbush blueberry (SHB) cultivars Biloxi and Misty. The fungal strains were inoculated into the peat-based substrate for growing blueberry cultivars, and plantlets produced by micropropagation were transplanted and grown for four months. The three inoculated strains positively affected the survival percentage in at least one of the cultivars tested, whereas O. maius BP positively affected plant biomass, N derived from fertilizer absorption, N content, and plant N recovery (%) in both Biloxi and Misty. Our results show that the O. maius BP strain may prove useful as a bio-inoculant to improve blueberry production during the nursery stage.
Advances in Alternative Measures in Plant Protection
Authors: Šunjka Dragana , Mechora Špela
Published: February 2023

Food production, along with the constant demand for higher yields, is an imperative of contemporary agricultural production [...]