bluuebunny/crossref_metadata_2025 huggingface dataset:
The Golden Fig: A Plasmonic Effect Study of Organic-Based Solar Cells
Authors: Barichello Jessica , Mariani Paolo , Matteocci Fabio , Vesce Luigi , Reale Andrea , Di Carlo Aldo , Lanza Maurizio , Di Marco Gaetano , Polizzi Stefano , Calogero Giuseppe
Published: January 2022

An optimization work on dye-sensitized solar cells (DSSCs) based on both artificial and natural dyes was carried out by a fine synthesis work embedding gold nanoparticles in a TiO2 semiconductor and perfecting the TiO2 particle sizes of the scattering layer. Noble metal nanostructures are known for the surface plasmon resonance peculiarity that reveals unique properties and has been implemented in several fields such as sensing, photocatalysis, optical antennas and PV devices. By embedding gold nanoparticles in the mesoporous TiO2 layer and adding a scattering layer, we were able to boost the power conversion efficiency (PCE) to 10.8%, using an organic ruthenium complex. The same implementation was carried out using a natural dye, betalains, extracted from Sicilian prickly pear. In this case, the conversion efficiency doubled from 1 to 2% (measured at 1 SUN illumination, 100 mW/cm2 under solar simulation irradiation). Moreover, we obtained (measured at 0.1 SUN, 10 mW/cm2 under blue light LED irradiation) a record efficiency of 15% with the betalain-based dye, paving the way for indoor applications in organic natural devices. Finally, an attempt to scale up the system is shown, and a betalain-based- dye-sensitized solar module (DSSM), with an active area of 43.2 cm2 and a PCE of 1.02%, was fabricated for the first time.
Electronic Structure of Monolayer FeSe on Si(001) from First Principles
Authors: Carva Karel , Vlaic Petru , Honolka Jan
Published: January 2022

The huge increase in the superconducting transition temperature of FeSe induced by an interface to SrTiO3 remains unexplained to date. However, there are numerous indications of the critical importance of specific features of the FeSe band topology in the vicinity of the Fermi surface. Here, we explore how the electronic structure of FeSe changes when located on another lattice matched substrate, namely a Si(001) surface, by first-principles calculations based on the density functional theory. We study non-magnetic (NM) and checkerboard anti-ferromagnetic (AFM) magnetic orders in FeSe and determine which interface arrangement is preferred. Our calculations reveal interesting effects of Si proximity on the FeSe band structure. Bands corresponding to hole pockets at the Γ point in NM FeSe are generally pushed down below the Fermi level, except for one band responsible for a small remaining hole pocket. Bands forming electron pockets centered at the M point of the Brillouin zone become less dispersive, and one of them is strongly hybridized with Si. We explain these changes by a redistribution of electrons between different Fe 3d orbitals rather than charge transfer to/from Si, and we also notice an associated loss of degeneracy between dxz and dyz orbitals.
Impact of Smoluchowski Temperature and Maxwell Velocity Slip Conditions on Axisymmetric Rotated Flow of Hybrid Nanofluid past a Porous Moving Rotating Disk
Authors: Khan Umair , Zaib Aurang , Waini Iskandar , Ishak Anuar , Sherif El-Sayed M. , Xia Wei-Feng , Muhammad Noor
Published: January 2022

Colloidal suspensions of regular fluids and nanoparticles are known as nanofluids. They have a variety of applications in the medical field, including cell separation, drug targeting, destruction of tumor tissue, and so on. On the other hand, the dispersion of multiple nanoparticles into a regular fluid is referred to as a hybrid nanofluid. It has a variety of innovative applications such as microfluidics, heat dissipation, dynamic sealing, damping, and so on. Because of these numerous applications of nanofluids in minds, therefore, the objective of the current exploration divulged the axisymmetric radiative flow and heat transfer induced by hybrid nanofluid impinging on a porous stretchable/shrinkable rotating disc. In addition, the impact of Smoluchowski temperature and Maxwell velocity slip boundary conditions are also invoked. The hybrid nanofluid was formed by mixing the copper (Cu) and alumina (Al2O3) nanoparticles scattered in the regular (viscous) base fluid (H2O). Similarity variables are used to procure the similarity equations, and the numerical outcomes are achieved using bvp4c in MATLAB software. According to the findings, double solutions are feasible for stretching (λ>0) and shrinking cases (λ<0). The heat transfer rate is accelerated as the hybrid nanoparticles increases. The suction parameter enhances the friction factors as well as heat transfer rate. Moreover, the friction factor in the radial direction and heat transfer enrich for the first solution and moderate for the second outcome due to the augmentation δ1, while the trend of the friction factor in the radial direction is changed only in the case of stretching for both branches.
A Retrospective Study of the Effects of Traumatic Brain Injury on Auditory Function: From a Clinical Perspective
Authors: White Mira , Duquette-Laplante Fauve , Jutras Benoît , Bursch Caryn , Koravand Amineh
Published: January 2022

Purpose: The main purpose of this retrospective study was to identify auditory dysfunctions related to traumatic brain injury (TBI) in individuals evaluated in an Audiology clinic. Method: Peripheral and central auditory evaluations were performed from March 2014 to June 2018 in 26 patients (14 males) with TBI. The age of the participants ranged from 9 to 59 years old (34.24 ± 15.21). Six participants had blast-related TBI and 20 had blunt force TBI. Sixteen experienced a single TBI event whereas ten experienced several. Correlation analyses were performed to verify the relationship, if any, between the number of auditory tests failed and the number, type, and severity of TBIs. Result: All participants failed at least one auditory test. Nearly 60% had abnormal results on degraded speech tests (compressed and echoed, filtered or in background noise) and 25% had a high frequency hearing loss. There was no statistically significant correlation between the number of auditory tests failed and the number, type, and severity of TBIs. Conclusion: Results indicated negative and heterogenous effects of TBI on peripheral and central auditory function and highlighted the need for a more extensive auditory assessment in individuals with TBI.
Nutrient Availability for Lactuca sativa Cultivated in an Amended Peatland: An Ionic Exchange Study
Authors: Dessureault-Rompré Jacynthe , Gloutney Alexis , Caron Jean
Published: January 2022

Few conservation strategies have been applied to cultivated peatland. This field study over one growth cycle of Lactuca sativa examined the effect of plant-based, high-C/N-ratio amendments in a real farming situation on peatland. Plant Root Simulator (PRS®) probes were used directly in the field to assess the impacts of incorporating Miscanthus x giganteus straw and Salix miyabeana chips on nutrient availability for lettuce. The results showed that lettuce yield decreased by 35% in the miscanthus straw treatment and by 14% in the willow chip treatment. In addition, the nitrogen flux rate was severely reduced during crop growth (75% reduction) and the plant N uptake index was much lower in the amended treatments than in the control. The phosphorus supply rate was also significantly lower (24% reduction) in the willow treatment. The influence of sampling zone was significant as well, with most macro-nutrients being depleted in the root zone and most micro-nutrients being mobilized. Additional work is needed to optimize the proposed conservation strategy and investigate the effects of consecutive years of soil amendment on different vegetable crops and in different types of cultivated peatlands to confirm and generalize the findings of this study. Future field studies should also explore the long-term carbon dynamics under plant-based, high-C/N-ratio amendments to determine if they can offset annual C losses.
The Impact of Selenium Supplementation on Trauma Patients—Systematic Review and Meta-Analysis
Authors: Huang Jen-Fu , Hsu Chih-Po , Ouyang Chun-Hsiang , Cheng Chi-Tung , Wang Chia-Cheng , Liao Chien-Hung , Wu Yu-Tung , Hsieh Chi-Hsun
Published: January 2022

This study aimed to assess current evidence regarding the effect of selenium (Se) supplementation on the prognosis in patients sustaining trauma. MEDLINE, Embase, and Web of Science databases were searched with the following terms: “trace element”, “selenium”, “copper”, “zinc”, “injury”, and “trauma”. Seven studies were included in the meta-analysis. The pooled results showed that Se supplementation was associated with a lower mortality rate (OR 0.733, 95% CI: 0.586, 0.918, p = 0.007; heterogeneity, I2 = 0%). Regarding the incidence of infectious complications, there was no statistically significant benefit after analyzing the four studies (OR 0.942, 95% CI: 0.695, 1.277, p = 0.702; heterogeneity, I2 = 14.343%). The patients with Se supplementation had a reduced ICU length of stay (standard difference in means (SMD): −0.324, 95% CI: −0.382, −0.265, p < 0.001; heterogeneity, I2 = 0%) and lesser hospital length of stay (SMD: −0.243, 95% CI: −0.474, −0.012, p < 0.001; heterogeneity, I2 = 45.496%). Se supplementation after trauma confers positive effects in decreasing the mortality and length of ICU and hospital stay.
Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians
Authors: Tanaka Kotone , Nakamura Sho , Narimatsu Hiroto
Published: January 2022

Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.
Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects
Authors: De Matteis Carlo , Crudele Lucilla , Cariello Marica , Battaglia Stefano , Piazzolla Giuseppina , Suppressa Patrizia , Sabbà Carlo , Piccinin Elena , Moschetta Antonio
Published: January 2022

Vitamin D deficiency is often linked with Metabolic Syndrome, both being more frequent with ageing and associated with an increase inflammatory state. Recently, monocytes-to-high density lipoprotein (HDL) ratio (MHR) has emerged as a powerful index to predict systemic inflammation. In this cross-sectional study, we investigated the association between circulating vitamin D level (25-OH vitamin D) and inflammatory status in a population of 1048 adult individuals. Our study reveals an inverse association between 25-OH vitamin D levels and MHR in the overall population. When the population is stratified by gender, waist circumference, and body mass index (BMI), we observed that while in men this relation is strongly significative only in condition of central obesity, in women a lifelong negative correlation exists between circulating 25-OH vitamin D and MHR and it is independent of the metabolic status. These observations underscore the relevance of circulating biomarkers such as MHR in the prediction of systemic inflammatory conditions sustained by vitamin D deficiency also in healthy and young women.
Food Insecurity and Associated Factors in Brazilian Undergraduates during the COVID-19 Pandemic
Authors: Maciel Bruna Leal Lima , Lyra Clélia de Oliveira , Gomes Jéssica Raissa Carlos , Rolim Priscilla Moura , Gorgulho Bartira Mendes , Nogueira Patrícia Simone , Rodrigues Paulo Rogério Melo , da Silva Tiago Feitosa , Martins Fernanda Andrade , Dalamaria Tatiane , Santos Thanise Sabrina Souza , Höfelmann Doroteia Aparecida , Crispim Sandra Patricia , Slater Betzabeth , Ramalho Alanderson Alves , Marchioni Dirce Maria
Published: January 2022

Undergraduates may face challenges to assure food security, related to economic and mental distress, especially during the COVID-19 pandemic. This study aimed to assess food insecurity and its associated factors in undergraduates during the COVID-19 pandemic. An online cross-sectional study was conducted from August 2020 to February 2021 with 4775 undergraduates from all Brazilian regions. The questionnaire contained socio-economic variables, the validated Brazilian food insecurity scale, and the ESQUADA scale to assess diet quality. The median age of the students was 22.0 years, and 48.0% reported income decreasing with the pandemic. Food insecurity was present in 38.6% of the students, 4.5% with severe food insecurity and 7.7% moderate. Logistic regressions showed students with brown and black skin color/race presented the highest OR for food insecurity; both income and weight increase or reduction during the pandemic was also associated with a higher OR for food insecurity, and better diet quality was associated with decreased OR for food insecurity. Our study showed a considerable presence of food insecurity in undergraduates. Policy for this population must be directed to the most vulnerable: those with brown and black skin color/race, who changed income during the pandemic, and those presented with difficulties maintaining weight and with poor diet quality.
Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults
Authors: Lu Xiaoting , Huang Rongzhu , Li Shuyi , Fang Aiping , Chen Yuming , Chen Si , Wang Fan , Lin Xinlei , Liu Zhaoyan , Zhu Huilian
Published: January 2022

Previous studies have explored associations between betaine and diabetes, but few have considered the effects of genes on them. We aimed to examine associations between serum betaine, methyl-metabolizing genetic polymorphisms and the risk of type 2 diabetes in Chinese adults. This prospective study comprised 1565 subjects aged 40–75 without type 2 diabetes at baseline. Serum betaine was measured by high-performance liquid chromatography tandem mass spectrometry. Genotyping of methyl-metabolizing genes was detected by Illumina ASA-750K arrays. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 8.9 years of follow-up, 213 participants developed type 2 diabetes. Compared with participants in the lowest quartile of serum betaine, those in the highest quartile had lower risk of type 2 diabetes, adjusted HRs (95%CIs) was 0.46 (0.31, 0.69). For methylenetetrahydrofolate reductase (MTHFR) G1793A (rs2274976) and MTHFR A1298C (rs1801131), participants carrying 1793GA + AA and 1298AC + CC had lower risk of type 2 diabetes. Interactions of serum betaine and genotype of MTHFR G1793A and MTHFR A1298C could be found influencing type 2 diabetes risk. Our findings indicate that higher serum betaine, mutations of MTHFR G1793A and A1298C, as well as the joint effects of them, are associated with lower risk of type 2 diabetes.
Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review
Authors: Rees Gail , Brough Louise , Orsatti Gustavo Moya , Lodge Anna , Walker Steven
Published: January 2022

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.
Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy
Authors: Sun Xuechun , Sun Xiaodan , Meng Huali , Wu Junduo , Guo Xin , Du Lei , Wu Hao
Published: January 2022

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.
Characterizing Individual Differences in Sweet Taste Hedonics: Test Methods, Locations, and Stimuli
Authors: Cheung May M. , Kramer Matthew , Beauchamp Gary K. , Puputti Sari , Wise Paul M.
Published: January 2022

Sweetness drives the consumption of added sugars, so understanding how to best measure sweet hedonics is important for developing strategies to lower sugar intake. However, methods to assess hedonic response to sweetness vary, making results across studies difficult to integrate. We compared methods to measure optimal sucrose concentration in 21 healthy adults (1) using paired-comparison preference tracking vs. ratings of liking, (2) with participants in the laboratory vs. at home, and (3) using aqueous solutions vs. vanilla milk. Tests were replicated on separate days to assess test-retest reliability. Test-retest reliability was similar between laboratory and home testing, but tended to be better for vanilla milk and preference tracking. Optimal sucrose concentration was virtually identical between laboratory and home, slightly lower when estimated via preference tracking, and about 50% lower in vanilla milk. However, optimal sucrose concentration correlated strongly between methods, locations, and stimuli. More than 50% of the variability in optimal sucrose concentration could be attributed to consistent differences among individuals, while much less variability was attributable to differences between methods. These results demonstrate convergent validity between methods, support testing at home, and suggest that aqueous solutions can be useful proxies for some commonly consumed beverages for measuring individual differences.
Whole Grain Consumption and Inflammatory Markers: A Systematic Literature Review of Randomized Control Trials
Authors: Milesi Genevieve , Rangan Anna , Grafenauer Sara
Published: January 2022

Whole grain foods are rich in nutrients, dietary fibre, a range of antioxidants, and phytochemicals, and may have potential to act in an anti-inflammatory manner, which could help impact chronic disease risk. This systematic literature review aimed to examine the specific effects of whole grains on selected inflammatory markers from human clinical trials in adults. As per the Preferred Reporting Items for Systematic Reviews (PRISMA) protocol, the online databases MEDLINE, Embase, Cochrane, CINAHL, and Scopus were searched from inception through to 31 August 2021. Randomized control trials (RCTs) ≥ 4 weeks in duration, reporting ≥1 of the following: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF), were included. A total of 31 RCTs were included, of which 16 studies recruited overweight/obese individuals, 12 had pre-existing conditions, two were in a healthy population, and one study included participants with prostate cancer. Of these 31 RCTs, three included studies with two intervention arms. A total of 32 individual studies measured CRP (10/32 were significant), 18 individual studies measured IL-6 (2/18 were significant), and 13 individual studies measured TNF (5/13 were significant). Most often, the overweight/obese population and those with pre-existing conditions showed significant reductions in inflammatory markers, mainly CRP (34% of studies). Overall, consumption of whole grain foods had a significant effect in reducing at least one inflammatory marker as demonstrated in 12/31 RCTs.
Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients
Authors: Göbl Christian , Morettini Micaela , Salvatori Benedetta , Alsalim Wathik , Kahleova Hana , Ahrén Bo , Tura Andrea
Published: January 2022

Background: glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. Methods: thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants’ cohort. Results: in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. Conclusions: glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.
Dietary Intakes of Traditional Foods for Dene/Métis in the Dehcho and Sahtú Regions of the Northwest Territories
Authors: Ramirez Prieto Maria , Ratelle Mylène , Laird Brian Douglas , Skinner Kelly
Published: January 2022

A dietary transition away from traditional foods and toward a diet of the predominantly unhealthy market is a public health and sociocultural concern throughout Indigenous communities in Canada, including those in the sub-Arctic and remote regions of Dehcho and Sahtú of the Northwest Territories, Canada. The main aim of the present study is to describe dietary intakes for macronutrients and micronutrients in traditional and market food from the Mackenzie Valley study. We also show the trends of contributions and differences of dietary intakes over time from 1994 data collected and reported by the Centre for Indigenous People’s Nutrition and Environment (CINE) in 1996. Based on 24-h dietary recall data, the study uses descriptive statistics to describe the observed dietary intake of the Dene First Nations communities in the Dehcho and Sahtú regions of the NWT. Indigenous people in Canada, like the sub-Arctic regions of Dehcho and Sahtú of the NWT, continue to consume traditional foods, although as a small percentage of their total dietary intake. The observed dietary intake calls for action to ensure that traditional food remains a staple as it is critical for the wellbeing of Dene in the Dehcho and Sahtú regions and across the territory.
Avian Bornaviruses in Wild Aquatic Birds of the Anseriformes Order in Poland
Authors: Świętoń Edyta , Dziadek Kamila , Śmietanka Krzysztof
Published: January 2022

Bornaviruses are a diverse family of viruses infecting various hosts, including birds. Aquatic bird bornavirus 1 (ABBV-1) and aquatic bird bornavirus 2 (ABBV-2) have been found in wild waterfowl but data on their prevalence are scarce. To gain knowledge on the occurrence of ABBVs in Poland, samples originating from dead birds of the Anseriformes order collected in 2016–2021 were tested with a real time RT-PCR method targeting the ABBVs genome. A total of 514 birds were examined, including 401 swans, 96 ducks and 17 geese. The presence of ABBV-1 RNA was detected in 52 swans (10.1% of all tested birds) from 40 different locations. No positive results were obtained for ducks and geese. Sequences of about 2300 bases were generated for 18 viruses and phylogenetic analysis was performed. A relatively low genetic diversity of the examined ABBV-1 strains was observed as all were gathered in a single cluster in the phylogenetic tree and the minimum nucleotide identity was 99.14%. The Polish strains were closely related to ABBV-1 identified previously in Denmark and Germany, but a limited number of sequences from Europe hinders the drawing of conclusions about interconnections between Polish and other European ABBVs. The results of the present study provide new insights into the distribution and genetic characteristics of ABBVs in wild birds in Europe.
Endothelium Activation during Severe Yellow Fever Triggers an Intense Cytokine-Mediated Inflammatory Response in the Liver Parenchyma
Authors: Olímpio Fábio Alves , Falcão Luiz Fábio Magno , Carvalho Marcos Luiz Gaia , da Costa Lopes Jeferson , Mendes Caio Cesar Henriques , Filho Arnaldo Jorge Martins , da Silva Carlos Augusto Moreira , Miranda Vanessa do Socorro Cabral , Santos Lais Carneiro dos , da Silva Vilacoert Fellipe Souza , Cruz Ana Cecília Ribeiro , Galúcio Vanessa Costa Alves , da Silva Azevedo Raimunda do Socorro , Martins Lívia Caricio , Duarte Maria Irma Seixas , de Sousa Jorge Rodrigues , da Costa Vasconcelos Pedro Fernando , Quaresma Juarez Antônio Simões
Published: January 2022

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.
Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes
Authors: Lohr Chaelynne E. , Sporer Kelly R. B. , Brigham Kelsey A. , Pavliscak Laura A. , Mason Matelyn M. , Borgman Andrew , Ruggiero Vickie J. , Taxis Tasia M. , Bartlett Paul C. , Droscha Casey J.
Published: January 2022

Characterization of the bovine leukocyte antigen (BoLA) DRB3 gene has shown that specific alleles associate with susceptibility or resilience to the progression of bovine leukemia virus (BLV), measured by proviral load (PVL). Through surveillance of multi-farm BLV eradication field trials, we observed differential phenotypes within seropositive cows that persist from months to years. We sought to develop a multiplex next-generation sequencing workflow (NGS-SBT) capable of genotyping 384 samples per run to assess the relationship between BLV phenotype and two BoLA genes. We utilized longitudinal results from milk ELISA screening and subsequent blood collections on seropositive cows for PVL determination using a novel BLV proviral load multiplex qPCR assay to phenotype the cows. Repeated diagnostic observations defined two distinct phenotypes in our study population, ELISA-positive cows that do not harbor detectable levels of provirus and those who do have persistent proviral loads. In total, 565 cows from nine Midwest dairy farms were selected for NGS-SBT, with 558 cows: 168 BLV susceptible (ELISA-positive/PVL-positive) and 390 BLV resilient (ELISA-positive/PVL-negative) successfully genotyped. Three BoLA-DRB3 alleles, including one novel allele, were shown to associate with disease resilience, *009:02, *044:01, and *048:02 were found at rates of 97.5%, 86.5%, and 90.3%, respectively, within the phenotypically resilient population. Alternatively, DRB3*015:01 and *027:03, both known to associate with disease progression, were found at rates of 81.1% and 92.3%, respectively, within the susceptible population. This study helps solidify the immunogenetic relationship between BoLA-DRB3 alleles and BLV infection status of these two phenotypic groupings of US dairy cattle.
Giardia duodenalis in Wildlife: Exploring Genotype Diversity in Italy and across Europe
Authors: Guadano Procesi Isabel , Montalbano Di Filippo Margherita , De Liberato Claudio , Lombardo Andrea , Brocherel Giuseppina , Perrucci Stefania , Di Cave David , Berrilli Federica
Published: January 2022

Fragmented data are so far available on genotype diversity of G. duodenalis in wildlife in different countries in Europe, in particular, in Italy. In the present study, G. duodenalis sequences obtained from different Italian wild animals [12 porcupines (Hystrix cristata), 4 wild boars (Sus scrofa), 1 wolf (Canis lupus italicus), 6 Alpine chamois (Rupicapra rupicapra rupicapra)] were compared with those available from wild host species in Europe to add new data on the geographic distribution of Giardia assemblages/sub-assemblages and their transmission patterns among natural hosts. Thirty-eight sequences were obtained by MLG analysis (SSU-rRNA, bg, gdh, and tpi genes) and subsequently compared by phylogenetic and network analyses with those from wild species monitored in the last decades in Europe. The results revealed the presence of potentially zoonotic (A-AI, A-AII from wild boar; B from porcupine) and host-adapted (D from wolf; E, A-AIII from chamois) assemblages and sub-assemblages and represent the first report for Italian wild boar. The analysis did not find any evidence of spatial or host segregation for specific genetic variants, mostly shared between different hosts from different European countries. However, conflicting evidence was found in genotypic assignment, advocating for data improvement and new genomic approaches.
How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease
Authors: Galvez-Llompart Maria , Zanni Riccardo , Garcia-Domenech Ramon , Galvez Jorge
Published: January 2022

Even if amyotrophic lateral sclerosis is still considered an orphan disease to date, its prevalence among the population is growing fast. Despite the efforts made by researchers and pharmaceutical companies, the cryptic information related to the biological and physiological onset mechanisms, as well as the complexity in identifying specific pharmacological targets, make it almost impossible to find effective treatments. Furthermore, because of complex ethical and economic aspects, it is usually hard to find all the necessary resources when searching for drugs for new orphan diseases. In this context, computational methods, based either on receptors or ligands, share the capability to improve the success rate when searching and selecting potential candidates for further experimentation and, consequently, reduce the number of resources and time taken when delivering a new drug to the market. In the present work, a computational strategy based on Molecular Topology, a mathematical paradigm capable of relating the chemical structure of a molecule to a specific biological or pharmacological property by means of numbers, is presented. The result was the creation of a reliable and accessible tool to help during the early in silico stages in the identification and repositioning of potential hits for ALS treatment, which can also apply to other orphan diseases. Considering that further computational and experimental results will be required for the final identification of viable hits, three linear discriminant equations combined with molecular docking simulations on specific proteins involved in ALS are reported, along with virtual screening of the Drugbank database as a practical example. In this particular case, as reported, a clinical trial has been already started for one of the drugs proposed in the present study.
Inclusion Scenarios and Conformational Flexibility of the SSRI Paroxetine as Perceived from Polymorphism of β-Cyclodextrin–Paroxetine Complex
Authors: Aree Thammarat
Published: January 2022

Depression, a global mental health problem, is prevalent during the coronavirus disease 2019 (COVID-19) pandemic and can be efficiently treated by selective serotonin reuptake inhibitors (SSRIs). Our study series aims at forwarding insights on the β-cyclodextrin (β-CD)–SSRI inclusion complexes by X-ray crystallography combined with density functional theory (DFT) calculation. Here, we report a new crystal form (II) of the 1:1 β-CD–paroxetine (PXT) complex, which is inspired by the reported 2:1 β-CD–PXT complex (crystal form I), reflecting an elusive phenomenon of the polymorphism in CD inclusion complexes. The β-CD–PXT polymorphism stems from the PXT conformational flexibility, which is defined by torsion angles κ, ε around the -CH2–O- group bridging the A- and C–D-rings, of which those of PXT in I and II are totally different. While PXT (II) in an open V-shaped conformation that has the B-ring shallowly inserted in the β-CD cavity, PXT (I) in a closed U-shaped structure is mostly entirely embedded in the β-CD dimeric cavity, of which the A-ring is deeply inserted in the main β-CD cavity. However, PXT molecules in both crystal forms are similarly maintained in the CD cavity via host–guest N–H···O5/O6 H-bonds and C/O–H···π(B/C) interactions and β-CDs have similar 3D arrangements, channel (II) vs. screw-channel (I). Further theoretical explorations on the β-CD–PXT thermodynamic stabilities and the PXT conformational stabilities based on their potential energy surfaces (PESs) have been completed by DFT calculations. The 2:1 β-CD–PXT complex with the greater presence of dispersion interactions is more energetically favorable than the unimolar complex. Conversely, whereas free PXT, PXT (II) and PXT in complex with serotonin transporter are more energetically stable, PXT (I) is least stable and stabilized in the β-CD cavity. As SSRIs could lessen the COVID-19 severity, the CD inclusion complexation not only helps to improve the drug bioavailability, but also promotes the use of antidepressants and COVID-19 medicines concurrently.
The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Bajtel Ákos , Kiss Tivadar , Tóth Barbara , Kiss Szabolcs , Hegyi Péter , Vörhendi Nóra , Csupor-Löffler Boglárka , Gede Noémi , Hohmann Judit , Csupor Dezső
Published: January 2022

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64–31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92–152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33–68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19–9.78), dizziness (OR: 4.60 95% CI: 2.39–8.83) and headache (OR: 2.90; 95% CI: 1.07–7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.
Towards Complete Tumor Resection: Novel Dual-Modality Probes for Improved Image-Guided Surgery of GRPR-Expressing Prostate Cancer
Authors: Handula Maryana , Verhoeven Marjolein , Chen Kuo-Ting , Haeck Joost , de Jong Marion , Dalm Simone , Seimbille Yann
Published: January 2022

Nuclear and optical dual-modality probes can be of great assistance in prostate cancer localization, providing the means for both preoperative nuclear imaging and intraoperative surgical guidance. We developed a series of probes based on the backbone of the established GRPR-targeting radiotracer NeoB. The inverse electron demand of the Diels–Alder reaction was used to integrate the sulfo-cyanine 5 dye. Indium-111 radiolabeling, stability studies and a competition binding assay were carried out. Pilot biodistribution and imaging studies were performed in PC-3 tumor-bearing mice, using the best two dual-labeled probes. The dual-modality probes were radiolabeled with a high yield (>92%), were proven to be hydrophilic and demonstrated high stability in mouse serum (>94% intact labeled ligand at 4 h). The binding affinity for the GRPR was in the nanomolar range (21.9–118.7 nM). SPECT/CT images at 2 h p.i. clearly visualized the tumor xenograft and biodistribution studies, after scanning confirmed the high tumor uptake (8.47 ± 0.46%ID/g and 6.90 ± 0.81%ID/g for probe [111In]In-12 and [111In]In-15, respectively). Receptor specificity was illustrated with blocking studies, and co-localization of the radioactive and fluorescent signal was verified by ex vivo fluorescent imaging. Although optimal tumor-to-blood and tumor-to-kidney ratios might not yet have been reached due to the prolonged blood circulation, our probes are promising candidates for the preoperative and intraoperative visualization of GRPR-positive prostate cancer.
Induction of Immunogenic Cell Death by Photodynamic Therapy Mediated by Aluminum-Phthalocyanine in Nanoemulsion
Authors: Rodrigues Mosar Corrêa , de Sousa Júnior Wellington Tavares , Mundim Thayná , Vale Camilla Lepesqueur Costa , de Oliveira Jaqueline Vaz , Ganassin Rayane , Pacheco Thyago José Arruda , Vasconcelos Morais José Athayde , Longo João Paulo Figueiró , Azevedo Ricardo Bentes , Muehlmann Luis Alexandre
Published: January 2022

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs–CRT, HSP70, HSP90, HMGB1, and IL-1β–were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.
Safe and Effective Cynomolgus Monkey GLP—Tox Study with Repetitive Intrathecal Application of a TGFBR2 Targeting LNA-Gapmer Antisense Oligonucleotide as Treatment Candidate for Neurodegenerative Disorders
Authors: Peters Sebastian , Wirkert Eva , Kuespert Sabrina , Heydn Rosmarie , Johannesen Siw , Friedrich Anita , Mailänder Susanne , Korte Sven , Mecklenburg Lars , Aigner Ludwig , Bruun Tim-Henrik , Bogdahn Ulrich
Published: January 2022

The capability of the adult central nervous system to self-repair/regenerate was demonstrated repeatedly throughout the last decades but remains in debate. Reduced neurogenic niche activity paralleled by a profound neuronal loss represents fundamental hallmarks in the disease course of neurodegenerative disorders. We and others have demonstrated the endogenous TGFβ system to represent a potential pathogenic participant in disease progression, of amyotrophic lateral sclerosis (ALS) in particular, by generating and promoting a disequilibrium of neurodegenerative and neuroregenerative processes. The novel human/primate specific LNA Gapmer Antisense Oligonucleotide “NVP-13”, targeting TGFBR2, effectively reduced its expression and lowered TGFβ signal transduction in vitro and in vivo, paralleled by boosting neurogenic niche activity in human neuronal progenitor cells and nonhuman primate central nervous system. Here, we investigated NVP-13 in vivo pharmacology, safety, and tolerability following repeated intrathecal injections in nonhuman primate cynomolgus monkeys for 13 weeks in a GLP-toxicology study approach. NVP-13 was administered intrathecally with 1, 2, or 4 mg NVP-13/animal within 3 months on days 1, 15, 29, 43, 57, 71, and 85 in the initial 13 weeks. We were able to demonstrate an excellent local and systemic tolerability, and no adverse events in physiological, hematological, clinical chemistry, and microscopic findings in female and male Cynomolgus Monkeys. Under the conditions of this study, the no observed adverse effect level (NOAEL) is at least 4 mg/animal NVP-13.
77Se-Enriched Selenoglycoside Enables Significant Enhancement in NMR Spectroscopic Monitoring of Glycan–Protein Interactions
Authors: Timári István , Balla Sára , Fehér Krisztina , Kövér Katalin E. , Szilágyi László
Published: January 2022

Detailed investigation of ligand–protein interactions is essential for better understanding of biological processes at the molecular level. Among these binding interactions, the recognition of glycans by lectins is of particular importance in several diseases, such as cancer; therefore, inhibition of glycan-lectin/galectin interactions represents a promising perspective towards developing therapeutics controlling cancer development. The recent introduction of 77Se NMR spectroscopy for monitoring the binding of a selenoglycoside to galectins prompted interest to optimize the sensitivity by increasing the 77Se content from the natural 7.63% abundance to 99%. Here, we report a convenient synthesis of 77Se-enriched selenodigalactoside (SeDG), which is a potent ligand of the medically relevant human galectin-3 protein, and proof of the expected sensitivity gain in 2D 1H, 77Se correlation NMR experiments. Our work opens perspectives for adding isotopically enriched selenoglycans for rapid monitoring of lectin-binding of selenated as well as non-selenated ligands and for ligand screening in competition experiments.
Mesoporous Bioglasses Enriched with Bioactive Agents for Bone Repair, with a Special Highlight of María Vallet-Regí’s Contribution
Authors: Salinas Antonio J. , Esbrit Pedro
Published: January 2022

Throughout her impressive scientific career, Prof. María Vallet-Regí opened various research lines aimed at designing new bioceramics, including mesoporous bioactive glasses for bone tissue engineering applications. These bioactive glasses can be considered a spin-off of silica mesoporous materials because they are designed with a similar technical approach. Mesoporous glasses in addition to SiO2 contain significant amounts of other oxides, particularly CaO and P2O5 and therefore, they exhibit quite different properties and clinical applications than mesoporous silica compounds. Both materials exhibit ordered mesoporous structures with a very narrow pore size distribution that are achieved by using surfactants during their synthesis. The characteristics of mesoporous glasses made them suitable to be enriched with various osteogenic agents, namely inorganic ions and biopeptides as well as mesenchymal cells. In the present review, we summarize the evolution of mesoporous bioactive glasses research for bone repair, with a special highlight on the impact of Prof. María Vallet-Regí´s contribution to the field.