bluuebunny/crossref_metadata_2025 huggingface dataset:
Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in Neuropathic Rats after Chronic Constriction Injury
Authors: Wen Zhi-Hong , Huang Shi-Ying , Kuo Hsiao-Mei , Chen Chao-Ting , Chen Nan-Fu , Chen Wu-Fu , Tsui Kuan-Hao , Liu Hsin-Tzu , Sung Chun-Sung
Published: September 2021

Introduction: Angiogenesis in the central nervous system is visible in animal models of neuroinflammation and bone cancer pain. However, whether spinal angiogenesis exists and contributes to central sensitization in neuropathic pain remains unclear. This study analyzes the impact of angiogenesis on spinal neuroinflammation in neuropathic pain. Methods: Rats with chronic constriction injury (CCI) to the sciatic nerve underwent the implantation of an intrathecal catheter. Fumagillin or vascular endothelial growth factor-A antibody (anti-VEGF-A) was administered intrathecally. Nociceptive behaviors, cytokine immunoassay, Western blot, and immunohistochemical analysis assessed the effect of angiogenesis inhibition on CCI-induced neuropathic pain. Results: VEGF, cluster of differentiation 31 (CD31), and von Willebrand factor (vWF) expressions increased after CCI in the ipsilateral lumbar spinal cord compared to that in the contralateral side of CCI and control rats from post-operative day (POD) 7 to 28, with a peak at POD 14. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 concentrations, but not IL-10 levels, also increased in the ipsilateral spinal cord after CCI. Fumagillin and anti-VEGF-A reduced CCI-induced thermal hyperalgesia from POD 5 to 14 and mechanical allodynia from POD 3 to 14. Fumagillin reduced CCI-upregulated expressions of angiogenic factors and astrocytes. Furthermore, fumagillin decreased TNF-α and IL-6 amounts and increased IL-10 levels at POD 7 and 14, but not IL-1β concentrations. Conclusions: Fumagillin significantly ameliorates CCI-induced nociceptive sensitization, spinal angiogenesis, and astrocyte activation. Our results suggest that angiogenesis inhibitor treatment suppresses peripheral neuropathy-induced central angiogenesis, neuroinflammation, astrocyte activation, and neuropathic pain.
The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis
Authors: Chai Jian Yi , Sugumar Vaisnevee , Alshawsh Mohammed Abdullah , Wong Won Fen , Arya Aditya , Chong Pei Pei , Looi Chung Yeng
Published: September 2021

The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. Hence, this review describes the various SMO-dependent and SMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involving GLI regulation. An in-depth understanding of the complex interplay between GLI and various signaling elements could help inspire new therapeutic breakthroughs for the treatment of Hh-GLI-dependent cancers in the future. Lastly, we have presented an up-to-date summary of the latest findings concerning the use of Hh inhibitors in clinical developmental studies and discussed the challenges, perspectives, and possible directions regarding the use of SMO/GLI inhibitors in clinical settings.
Iron Replacement and Redox Balance in Non-Anemic and Mildly Anemic Iron Deficiency COPD Patients: Insights from a Clinical Trial
Authors: Pérez-Peiró Maria , Martín-Ontiyuelo Clara , Rodó-Pi Anna , Piccari Lucilla , Admetlló Mireia , Durán Xavier , Rodríguez-Chiaradía Diego A. , Barreiro Esther
Published: September 2021

In COPD patients, non-anemic iron deficiency (NAID) is a common systemic manifestation. We hypothesized that in COPD patients with NAID, iron therapy may improve systemic oxidative stress. The FACE (Ferinject assessment in patients with COPD and iron deficiency to improve exercise tolerance) study was a single-blind, unicentric, parallel-group, placebo-controlled clinical trial (trial registry: 2016-001238-89). Sixty-six patients were enrolled (randomization 2:1): iron arm, n = 44 and placebo arm, n = 22, with similar clinical characteristics. Serum levels of 3-nitrotyrosine, MDA-protein adducts, and reactive carbonyls, catalase, superoxide dismutase (SOD), glutathione, Trolox equivalent antioxidant capacity (TEAC), and iron metabolism biomarkers were quantified in both groups. In the iron-treated patients compared to placebo, MDA-protein adducts and 3-nitrotyrosine serum levels significantly declined, while those of GSH increased and iron metabolism parameters significantly improved. Hepcidin was associated with iron status parameters. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers along with an improvement in GSH levels in patients with stable severe COPD. Hepcidin may be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases. These findings have potential clinical implications in the management of patients with severe COPD.
Self-Organization Provides Cell Fate Commitment in MSC Sheet Condensed Areas via ROCK-Dependent Mechanism
Authors: Nimiritsky Peter , Novoseletskaya Ekaterina , Eremichev Roman , Alexandrushkina Natalia , Karagyaur Maxim , Vetrovoy Oleg , Basalova Nataliya , Khrustaleva Anastasia , Tyakht Alexander , Efimenko Anastasia , Tkachuk Vsevolod , Makarevich Pavel
Published: September 2021

Multipotent mesenchymal stem/stromal cells (MSC) are one of the crucial regulators of regeneration and tissue repair and possess an intrinsic program from self-organization mediated by condensation, migration and self-patterning. The ability to self-organize has been successfully exploited in tissue engineering approaches using cell sheets (CS) and their modifications. In this study, we used CS as a model of human MSC spontaneous self-organization to demonstrate its structural, transcriptomic impact and multipotent stromal cell commitment. We used CS formation to visualize MSC self-organization and evaluated the role of the Rho-GTPase pathway in spontaneous condensation, resulting in a significant anisotropy of the cell density within the construct. Differentiation assays were carried out using conventional protocols, and microdissection and RNA-sequencing were applied to establish putative targets behind the observed phenomena. The differentiation of MSC to bone and cartilage, but not to adipocytes in CS, occurred more effectively than in the monolayer. RNA-sequencing indicated transcriptional shifts involving the activation of the Rho-GTPase pathway and repression of SREBP, which was concordant with the lack of adipogenesis in CS. Eventually, we used an inhibitory analysis to validate our findings and suggested a model where the self-organization of MSC defined their commitment and cell fate via ROCK1/2 and SREBP as major effectors under the putative switching control of AMP kinase.
Cortical Thinning of Motor and Non-Motor Brain Regions Enables Diagnosis of Amyotrophic Lateral Sclerosis and Supports Distinction between Upper- and Lower-Motoneuron Phenotypes
Authors: Ferrea Stefano , Junker Frederick , Korth Mira , Gruhn Kai , Grehl Torsten , Schmidt-Wilcke Tobias
Published: September 2021

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. In addition to the classical ALS affecting both the upper and lower motoneurons (UMN and LMN), other subtypes with the predominant (or even exclusive) affection of the UMN or LMN have been identified. This work sought to detect specific patterns of cortical brain atrophy in the UMN and LMN phenotypes to distinguish these two forms from the healthy state. Methods: Using high-resolution structural MRI and cortical thickness analysis, 38 patients with a diagnosis of ALS and predominance of either the UMN (n = 20) or the LMN (n = 18) phenotype were investigated. Results: Significant cortical thinning in the temporal lobe was found in both the ALS groups. Additionally, UMN patients displayed a significant thinning of the cortical thickness in the pre- and postcentral gyrus, as well as the paracentral lobule. By applying multivariate analyses based on the cortical thicknesses of 34 brain regions, ALS patients with either a predominant UMN or LMN phenotype were distinguished from healthy controls with an accuracy of 94% and UMN from LMN patients with an accuracy of 75%. Conclusions: These findings support previous hypothesis that neural degeneration in ALS is not confined to the sole motor regions. In addition, the amount of cortical thinning in the temporal lobe helps to distinguish ALS patients from healthy controls, that is, to support or discourage the diagnosis of ALS, while the cortical thickness of the precentral gyrus specifically helps to distinguish the UMN from the LMN phenotype.
Influence of Habitat and Food Resource Availability on Common Raven Nest Site Selection and Reproductive Success in Mediterranean Forests
Authors: Segura Amalia , Acevedo Pelayo
Published: September 2021

Bird nest selection in forests can be influenced by the composition of key structural elements and resources. This has important consequences in terms of species population dynamics since it can determine reproduction success. Here, we assessed Common raven nest-site selection and reproductive success, and how these might be determined by foraging behavior and habitat structure. A previously documented breeding raven population that exerts high predation pressure on young Spur-thighed tortoises (Testudo graeca) in a Mediterranean forest was monitored. Generalized linear mixed models were performed to determine the singularities of the trees with nests and the drivers of reproductive success of breeding pairs of ravens. The results showed a high density of breeding pairs in the study area (0.8 pairs/km2), which selected taller trees in areas with higher bare ground cover and a high density of tortoises for nesting. Nests were spatially aggregated; breeding pairs occupied smaller territories and intraspecific competition seemed relaxed, reflecting the abundance of food resources. Most breeding pairs occasionally predated on young tortoises. Tortoises seem to play a part in raven reproductive success in our study area, which might be associated with the availability/catchability of young tortoises. The study illustrates that Spur-thighed tortoise distribution and abundance plays a role in the breeding behavior of ravens and is mediated by habitat structure. Understanding the drivers of nest-site selection and the breeding behavior of ravens is pivotal to implementing appropriate habitat management and conservation strategies across their distribution range, particularly in areas where ravens potentially affect threatened species.
Atypical Pupil Reactions in Brain Dead Patients
Authors: Sołek-Pastuszka Joanna , Zegan-Barańska Małgorzata , Biernawska Jowita , Sawicki Marcin , Iwańczuk Waldemar , Chełstowski Kornel , Bohatyrewicz Romuald , Dąbrowski Wojciech , Kojder Klaudyna
Published: September 2021

Background: During routine diagnosis of brain death, changes in pupil diameter in response to the stimulation of peripheral nerves are sometimes observed. For example, pupillary dilation after diagnosed brain death is described in the literature as the ciliospinal reflex. However, pupil constriction creates diagnostic doubts. Objective: The pupillometric analysis of pupil response to stimulation of the cervicothoracic spinal cord in patients with diagnosed brain death. Methods: Instrumental tests to confirm the arrest of cerebral circulation were performed in 30 adult subjects (mean age 53.5 years, range 26–75 years) with diagnosed brain death. In addition, a pupillometer was used to measure the change in pupil diameter in response to neck flexion. Intervention: Flexion of the neck and measuring the response in change of the pupil with the use of the pupillometer. Results: The change in the pupil was observed in the examined group of patients. Difference in pupil size ≥ 0.2 mm was observed in 14 cases (46%). In five cases (17%), pupil constriction was found (from 0.2 to 0.7 mm). Measurement error was +/− 0.1 mm. Conclusions: Both pupillary constriction and dilatation may occur due to a ciliospinal reflex in patients with brain death. This phenomenon needs further research in order to establish its pathophysiology.
Considering Hemispheric Specialization in Emotional Face Processing: An Eye Tracking Study in Left- and Right-Lateralised Semantic Dementia
Authors: Hutchings Rosalind , Palermo Romina , Hazelton Jessica L. , Piguet Olivier , Kumfor Fiona
Published: September 2021

Face processing relies on a network of occipito-temporal and frontal brain regions. Temporal regions are heavily involved in looking at and processing emotional faces; however, the contribution of each hemisphere to this process remains under debate. Semantic dementia (SD) is a rare neurodegenerative brain condition characterized by anterior temporal lobe atrophy, which is either predominantly left- (left-SD) or right-lateralised (right-SD). This syndrome therefore provides a unique lesion model to understand the role of laterality in emotional face processing. Here, we investigated facial scanning patterns in 10 left-SD and 6 right-SD patients, compared to 22 healthy controls. Eye tracking was recorded via a remote EyeLink 1000 system, while participants passively viewed fearful, happy, and neutral faces over 72 trials. Analyses revealed that right-SD patients had more fixations to the eyes than controls in the Fear (p = 0.04) condition only. Right-SD patients also showed more fixations to the eyes than left-SD patients in all conditions: Fear (p = 0.01), Happy (p = 0.008), and Neutral (p = 0.04). In contrast, no differences between controls and left-SD patients were observed for any emotion. No group differences were observed for fixations to the mouth, or the whole face. This study is the first to examine patterns of facial scanning in left- versus right- SD, demonstrating more of a focus on the eyes in right-SD. Neuroimaging analyses showed that degradation of the right superior temporal sulcus was associated with increased fixations to the eyes. Together these results suggest that right lateralised brain regions of the face processing network are involved in the ability to efficiently utilise changeable cues from the face.
Tumor-Derived Exosomes: Hidden Players in PD-1/PD-L1 Resistance
Authors: Vautrot Valentin , Bentayeb Hafidha , Causse Sébastien , Garrido Carmen , Gobbo Jessica
Published: September 2021

Recently, immunotherapy has garnered increasing importance in cancer therapy, leading to substantial improvements in patient care and survival. By blocking the immune checkpoints—protein regulators of the immune system—immunotherapy prevents immune tolerance toward tumors and reactivates the immune system, prompting it to fight cancer cell growth and diffusion. A widespread strategy for this is the blockade of the interaction between PD-L1 and PD-1. However, while patients generally respond well to immunotherapy, a certain proportion of patients present tumors that resist these treatments. This portion can be very high in some cancers and hinders cancer curability. For this reason, current efforts are focusing on combining PD-1/PD-L1 immunotherapy with the targeting of other immune checkpoints to counter resistance and achieve better results. Exosomes, small vesicles secreted by almost any cell, including tumor cells, have proven to be key actors in this resistance. The exosomes released by tumor cells spread the immune-suppressive properties of the tumor throughout the tumor microenvironment and participate in establishing metastatic niches. In this review, we will describe immune checkpoints and immune modulators whose presence in tumor-derived exosomes (TEXs) has been established. We will focus on the most promising proteins under scrutiny for use in combination with PD-1 blockade therapy in a clinical setting, such as PD-L1, CTLA-4, TIM-3, CD73/39, LAG-3, and TIGIT. We will explore the immunosuppressive impact of these exosomal proteins on a variety of immune cells. Finally, we will discuss how they can change the game in immunotherapy and guide therapeutic decisions, as well as the current limits of this approach. Depending on the viewpoint, these exosomal proteins may either provide key missing information on tumor growth and resistance mechanisms or they may be the next big challenge to overcome in improving cancer treatment.
Histological and Somatic Mutational Profiles of Mismatch Repair Deficient Endometrial Tumours of Different Aetiologies
Authors: Ryan Neil A. J. , Walker Thomas D. J. , Bolton James , ter Haar Natalja , Van Wezel Tom , Glaire Mark A. , Church David N. , Evans D. Gareth , Bosse Tjalling , Crosbie Emma J.
Published: September 2021

Background: Mismatch repair deficient (MMRd) tumours may arise from somatic events acquired during carcinogenesis or in the context of Lynch syndrome (LS), an inherited cancer predisposition condition caused by germline MMR pathogenic variants. Our aim was to explore whether sporadic and hereditary MMRd endometrial cancers (EC) display distinctive tumour biology. Methods: Clinically annotated LS-EC were collected. Histological slide review was performed centrally by two specialist gynaecological pathologists. Mutational analysis was by a bespoke 75- gene next-generation sequencing panel. Comparisons were made with sporadic MMRd EC. Multiple correspondence analysis was used to explore similarities and differences between the cohorts. Results: After exclusions, 135 LS-EC underwent independent histological review, and 64 underwent mutational analysis. Comparisons were made with 59 sporadic MMRd EC. Most tumours were of endometrioid histological subtype (92% LS-EC and 100% sporadic MMRd EC, respectively, p = NS). Sporadic MMRd tumours had significantly fewer tumour infiltrating lymphocytes (p ≤ 0.0001) and showed more squamous/mucinous differentiation than LS-EC (p = 0.04/p = 0.05). PTEN mutations were found in 88% sporadic MMRd and 61% LS-EC, respectively (p < 0.001). Sporadic MMRd tumours had significantly more mutations in PDGFRA, ALK, IDH1, CARD11, CIC, MED12, CCND1, PTPN11, RB1 and KRAS, while LS-EC showed more mutations affecting SMAD4 and ARAF. LS-EC showed a propensity for TGF-β signalling disruption. Cluster analysis found that wild type PTEN associates predominantly with LS-EC, whilst co-occurring mutations in PTEN, PIK3CA and KRAS predict sporadic MMRd EC. Conclusions: Whilst MMRd EC of hereditary and sporadic aetiology may be difficult to distinguish by histology alone, differences in infiltrating immune cell counts and mutational profile may predict heterogenous responses to novel targeted therapies and warrant further study.
Metallothionein 2A Expression in Cancer-Associated Fibroblasts and Cancer Cells Promotes Esophageal Squamous Cell Carcinoma Progression
Authors: Shimizu Masaki , Koma Yu-ichiro , Sakamoto Hiroki , Tsukamoto Shuichi , Kitamura Yu , Urakami Satoshi , Tanigawa Kohei , Kodama Takayuki , Higashino Nobuhide , Nishio Mari , Shigeoka Manabu , Kakeji Yoshihiro , Yokozaki Hiroshi
Published: September 2021

Esophageal cancer has the sixth highest mortality rate worldwide. Cancer-associated fibroblasts (CAFs) are involved in the progression of various cancers. Previously, we demonstrated an association between high expression of the CAF marker, fibroblast activation protein, and poor prognosis of esophageal squamous cell carcinoma (ESCC). We also established CAF-like cells by indirect co-culture of bone marrow-derived mesenchymal stem cells with ESCC cell lines and found metallothionein 2A (MT2A) to be highly expressed in them. Here, to explore the function of MT2A in CAFs, we silenced MT2A in the CAF-like cells and ESCC cell lines using small interfering RNA. MT2A knockdown in the CAF-like cells suppressed expression and secretion of insulin-like growth factor binding protein 2 (IGFBP2); recombinant IGFBP2 promoted migration and invasiveness of ESCC cells via NFκB, Akt, and Erk signaling pathways. Furthermore, MT2A knockdown in the ESCC cell lines inhibited their growth, migration, and invasiveness. Immunohistochemistry demonstrated that high MT2A expression in the cancer stroma and cancer nest of ESCC tissues correlated with poor prognosis of ESCC patients. Hence, we report that MT2A in CAFs and cancer cells contributes to ESCC progression. MT2A and IGFBP2 are potential novel therapeutic targets in ESCC.
The Antimicrobial Mode of Action of Maltol and Its Synergistic Efficacy with Selected Cationic Surfactants
Authors: Ziklo Noa , Bibi Maayan , Salama Paul
Published: September 2021

Maltol, mostly used as a flavoring molecule, also has various potential applications as a biomedical compound. Despite its extensive use in the food industry, maltol’s antimicrobial activity was evaluated only briefly, and was suggested to be insufficient on its own. Recently, we have shown that maltol can be used in conjunction with cationic surfactant species to receive higher activity against contaminant microorganisms. In this paper, we have broadened the antimicrobial efficacy studies and evidenced maltol’s mode of action against Gram-negative, Gram-positive bacteria, and fungi. In addition, to increase its efficacy, blends of maltol and two selected cationic surfactants, dodecyl-dimethyl-ammonium chloride (DDAC) and polyquaternium 80 (P-80), were appraised for their activity. Broad efficacy studies revealed synergistic interactions between maltol and both cationic surfactants against most of the tested microorganisms. Electron microscopy images were used to evaluate the microorganisms’ morphology following treatment, pinpointing the specific cell wall damage caused by each of the compounds. Our findings indicate that maltol’s effect on the microbial cell wall can be complemented by catalytic amounts of selected cationic surfactants to enhance and extend its activity. Such a solution can be used as a broad-spectrum preservative for personal care products in cosmetic applications.
Nematode Parasites of Rockfish (Sebastes spp.) and Cod (Gadus spp.) from Waters near Kodiak Island Alaska, USA
Authors: Oğuz Mehmet Cemal , Campbell Andrea McRae , Bennett Samuel P. , Belk Mark C.
Published: September 2021

Distribution and abundance of common parasitic nematodes in marine fishes is not well documented in many geographic regions. Understanding the influence of large-scale environmental changes on infection rates of fish by nematodes requires quantitative assessments of parasite abundance for multiple host species. We collected samples of two species of cod and eight species of rockfish (total of 232 specimens) from waters near Kodiak Island, Alaska, USA during Spring and Summer of 2015, and dissected and recorded all internal nematode parasites. We quantified the prevalence and intensity of nematode parasites in the ten host species, and tested for differences in prevalence among host species. We found three species of nematode: Anisakis simplex, sensu lato (Van Thiel), Pseudoterranova decipiens, sensu lato (Krabbe), and Hysterothylacium sp. (Ward and Magath). Eighty-two percent of the examined fish were infected with at least one parasitic nematode. The overall prevalence of P. decipiens, A. simplex, and Hysterothylacium sp. was 56%, 62%, and 2%, respectively. Anisakis simplex and P. decipiens were abundant and present in all ten species of host fish examined, whereas Hysterothylacium sp. was rare and found in only five of the host fish species. Prevalence and mean intensity of P. decipiens and A. simplex varied across the ten host species, and the number of parasites varied substantially among individual hosts within host species. The mean intensity of P. terranova and A. simplex in our study was substantially higher than the mean intensity for these same species from multiple other locations in a recent meta-analysis. This study provides a baseline of nematode parasite abundance in long-lived fish in waters near Kodiak Island, AK, and fills an important gap in our quantitative understanding of patterns of occurrence and abundance of these common and widespread parasites of marine fish.
Coleopteran Pollinators of Annonaceae in the Brazilian Cerrado—A Review
Authors: Saravy Fábio Pinheiro , Marques Marinez Isaac , Schuchmann Karl-L.
Published: September 2021

The evolutionary trajectories of insects and angiosperms appear to be intimately interconnected. Increases in the diversity of phytophagous beetles and angiosperms co-occur in the Mesozoic fossil record, and there is fossil evidence of pollinivory and pollination by insects, both in flowering plants and in gymnosperms. The oldest records of angiosperm pollination indicate flies as pollen vectors. A basal group of angiosperms, the order Magnoliales, has retained plesiomorphic characters such as dozens of pistils and stamens spiraling around the receptacle. In a family of this order, Annonaceae, over 90% of species are pollinated by beetles. In many Annonaceae species, flowers display wide spaces, referred to as floral chambers, where beetles can find shelter from weather conditions and predators, food in the form of pollen and tissues, and a mating site. Two basic types of floral chambers can be distinguished: small chambers visited by small beetles (Nitidulidae, Staphylinidae, Chrysomelidae, and Curculionidae) with diurnal and/or nocturnal activity and large and thermogenic floral chambers visited by beetles of the tribe Cyclocephalini (Scarabaeoidea, Melolonthidae). In the latter case, the heat that the flowers produce may serve as a resource for the beetles that visit them, resulting in smaller endothermy costs for the scarabs. This study reviewed the literature including PhD and MSc theses on cantharophilous Annonaceae in the Cerrado. In this biome, both types of associations are found, although cantharophilous Annonaceae represent a small portion of the plant species (<5%). Cantharophilous Annonaceae in the Cerrado share attributes according to the beetles that pollinate them: species pollinated by small beetles, for instance, may flower throughout the year, whereas Annonaceae pollinated by Cyclocephalini normally flower in the beginning of the rainy season (October/November), in synchrony with the phenological patterns of their pollinators. Cantharophilous Annonaceae flowers, regardless of their size, tend to have light colors and sweet and fruity odors. In addition to the lack of studies on the attraction of beetles by these floral characters, the taxonomic composition of the beetles that pollinate Annonaceae in the Cerrado is poorly known. This review attempts to discuss, in light of what has already been published, potential fields of investigation concerning pollinating beetles’ behavior and evolution.
The Current and Potential Application of Medicinal Cannabis Products in Dentistry
Authors: Lowe Henry , Toyang Ngeh , Steele Blair , Bryant Joseph , Ngwa Wilfred , Nedamat Kaveh
Published: September 2021

Oral and dental diseases are a major global burden, the most common non-communicable diseases (NCDs), and may even affect an individual’s general quality of life and health. The most prevalent dental and oral health conditions are tooth decay (otherwise referred to as dental caries/cavities), oral cancers, gingivitis, periodontitis, periodontal (gum) disease, Noma, oro-dental trauma, oral manifestations of HIV, sensitive teeth, cracked teeth, broken teeth, and congenital anomalies such as cleft lip and palate. Herbs have been utilized for hundreds of years in traditional Chinese, African and Indian medicine and even in some Western countries, for the treatment of oral and dental conditions including but not limited to dental caries, gingivitis and toothaches, dental pulpitis, halitosis (bad breath), mucositis, sore throat, oral wound infections, and periodontal abscesses. Herbs have also been used as plaque removers (chew sticks), antimicrobials, analgesics, anti-inflammatory agents, and antiseptics. Cannabis sativa L. in particular has been utilized in traditional Asian medicine for tooth-pain management, prevention of dental caries and reduction in gum inflammation. The distribution of cannabinoid (CB) receptors in the mouth suggest that the endocannabinoid system may be a target for the treatment of oral and dental diseases. Most recently, interest has been geared toward the use of Cannabidiol (CBD), one of several secondary metabolites produced by C. sativa L. CBD is a known anti-inflammatory, analgesic, anxiolytic, anti-microbial and anti-cancer agent, and as a result, may have therapeutic potential against conditions such burning mouth syndrome, dental anxiety, gingivitis, and possible oral cancer. Other major secondary metabolites of C. sativa L. such as terpenes and flavonoids also share anti-inflammatory, analgesic, anxiolytic and anti-microbial properties and may also have dental and oral applications. This review will investigate the potential of secondary metabolites of C. sativa L. in the treatment of dental and oral diseases.
Economic Evaluation of the Management of Municipal Firms at the Level of Rural Local Self-Governments (Case Study)
Authors: Ágh Peter , Vavrek Roman , Dvořák Marek , Papcunová Viera
Published: September 2021

The municipality generally uses its property to perform self-governing functions, and public or business activities. In the conditions of the Slovak Republic, the municipality operates either as a legal entity in its own name or carries out business activities with the help of a contributory and budgetary organization or business firm established by the municipality. Revenues from business activities form an important part of the revenue of local self-government budgets. The aim of this paper was an economic evaluation of the management of municipal firms at the level of rural local self-governments in the conditions of the Slovak Republic on the basis of selected economic indicators. At the same time, we analyzed the relationship between selected economic indicators in relation to the size, lifespan and number of employees of the firm. The analysis was performed in the time period 2015–2019 on a sample of municipal firms at the level of rural local self-governments. For the analysis, we used selected mathematical–statistical methods (Shapiro–Wilk test, Kruskal–Wallis test, and regression analysis). The analysis showed that the differences in the profitability of municipal firms from the point of view of the region in which they operate as well as from the point of view of the number of employees is not statistically significant. Statistical significance was not demonstrated even within the volume of revenue of municipal firms from the point of view of the region in which the municipal firm operates. The volume of revenues of municipal enterprises with the population of the municipality as well as the length of time of operation on the market is growing, but these are not the only factors on which these results depend.
Perceptual and Semantic Processing in Cognitive Robots
Authors: Bukhari Syed Tanweer Shah , Qazi Wajahat Mahmood
Published: September 2021

The challenge in human–robot interaction is to build an agent that can act upon human implicit statements, where the agent is instructed to execute tasks without explicit utterance. Understanding what to do under such scenarios requires the agent to have the capability to process object grounding and affordance learning from acquired knowledge. Affordance has been the driving force for agents to construct relationships between objects, their effects, and actions, whereas grounding is effective in the understanding of spatial maps of objects present in the environment. The main contribution of this paper is to propose a methodology for the extension of object affordance and grounding, the Bloom-based cognitive cycle, and the formulation of perceptual semantics for the context-based human–robot interaction. In this study, we implemented YOLOv3 to formulate visual perception and LSTM to identify the level of the cognitive cycle, as cognitive processes synchronized in the cognitive cycle. In addition, we used semantic networks and conceptual graphs as a method to represent knowledge in various dimensions related to the cognitive cycle. The visual perception showed average precision of 0.78, an average recall of 0.87, and an average F1 score of 0.80, indicating an improvement in the generation of semantic networks and conceptual graphs. The similarity index used for the lingual and visual association showed promising results and improves the overall experience of human–robot interaction.
Multi-Level Control of Resistive RAM (RRAM) Using a Write Termination to Achieve 4 Bits/Cell in High Resistance State
Authors: Aziza Hassan , Hamdioui Said , Fieback Moritz , Taouil Mottaqiallah , Moreau Mathieu , Girard Patrick , Virazel Arnaud , Coulié Karine
Published: September 2021

RRAM density enhancement is essential not only to gain market share in the highly competitive emerging memory sector but also to enable future high-capacity and power-efficient brain-inspired systems, beyond the capabilities of today’s hardware. In this paper, a novel design scheme is proposed to realize reliable and uniform multi-level cell (MLC) RRAM operation without the need of any read verification. RRAM quad-level cell (QLC) capability with 4 bits/cell is demonstrated for the first time. QLC is implemented based on a strict control of the cell programming current of 1T-1R HfO2-based RRAM cells. From a design standpoint, a self-adaptive write termination circuit is proposed to control the RESET operation and provide an accurate tuning of the analog resistance value of each cell of a memory array. The different resistance levels are obtained by varying the compliance current in the RESET direction. Impact of variability on resistance margins is simulated and analyzed quantitatively at the circuit level to guarantee the robustness of the proposed MLC scheme. The minimal resistance margin reported between two consecutive states is 2.1 kΩ along with an average energy consumption and latency of 25 pJ/cell and 1.65 μs, respectively.
Mathematical Modelling of Transient Processes in an Asynchronous Drive with a Long Shaft Including Cardan Joints
Authors: Chaban Andriy , Łukasik Zbigniew , Popenda Andrzej , Szafraniec Andrzej
Published: September 2021

Beginning with the classic methods, a mathematical model of an electromechanical system is developed that consists of a deep bar cage induction motor that, via a complex motion transmission with distributed mechanical parameters, drives a working machine, loading the drive system with a constant torque. The electromagnetic field theory serves to create the motor model, which allows addressing the displacement of current in the rotor cage bars. Ordinary and partial differential equations are used to describe the electromechanical processes of energy conversion in the motor. The complex transmission of the drive motion consists of a long shaft with variable geometry cardan joints mounted on its ends. Non-linear electromechanical differential equations are presented as a system of ordinary differential equations combined with a mixed problem of Dirichlet first-type and Poincaré third-type boundary conditions. This system of equations is integrated by discretising partial derivatives by means of the straight-line methods and successive integration as a function of time using the Runge–Kutta fourth-order method. Starting from there, complicated transient processes in the drive system are analysed. Results of computer simulations are presented in the graphic form, which is analysed.
Two-Stage Stochastic Model to Invest in Distributed Generation Considering the Long-Term Uncertainties
Authors: Angarita-Márquez Jorge Luis , Mokryani Geev , Martínez-Crespo Jorge
Published: September 2021

This paper used different risk management indicators applied to the investment optimization performed by consumers in Distributed Generation (DG). The objective function is the total cost incurred by the consumer including the energy and capacity payments, the savings, and the revenues from the installation of DG, alongside the operation and maintenance (O&M) and investment costs. Probability density function (PDF) was used to model the price volatility in the long-term. The mathematical model uses a two-stage stochastic approach: investment and operational stages. The investment decisions are included in the first stage and which do not change with the scenarios of the uncertainty. The operation variables are in the second stage and, therefore, take different values with every realization. Three risk indicators were used to assess the uncertainty risk: Value-at-Risk (VaR), Conditional Value-at-Risk (CVaR), and Expected Value (EV). The results showed the importance of migration from deterministic models to stochastic ones and, most importantly, the understanding of the ramifications of every risk indicator.
An Assessment Framework for Solar Cell Material Based on a Modified Fuzzy DEMATEL Approach
Authors: Sun Chia-Chi , Chang Shih-Chi
Published: September 2021

We propose an evaluation system to choose appropriate materials for solar cells. A fuzzy DEMATEL information procedure was used for decision-making to gather information and analyze the casual relationship. These data acquired were partitioned into causal and impact bunches, empowering users to gather an improved understanding of the intelligent relationship among them, as well as making recommendations for changes to upgrade their general execution. The proposed approach can deliver a compelling fabric choice assessment with satisfactory criteria that fit the respondent’s discernment designs; particularly, these evaluation dimensions are interlaced. Recommendations are given to assist government authorities to plan a Taiwan solar cell industry approach and for industries to develop commerce techniques for improvement in the solar cell field.
The Ability of a Soil Temperature Gradient-Based Methodology to Detect Leaks from Pipelines in Buried District Heating Channels
Authors: Perpar Matjaž , Rek Zlatko
Published: September 2021

We carried out several numerical experiments to analyze how different boundary conditions affect the ability to detect small pipeline leaks. Our method is based on determining the soil temperature gradient above a buried district heating channel. The equivalent thermal conductivity of a wet insulation (λeq) value of 0.5 W/(m·K) was used to mimic a small water leakage. To evaluate the heat loss through the channel cross section, the heat conduction model was used for the pipe insulation, the concrete, and the soil, while the convection model was considered within the channel. The following effects were used to simulate different operating conditions: heat convection at the soil surface, leakage only from the supply or return pipe, soil height above the channel, soil thermal conductivity, and pipe diameter. With the exception of leakage only from the return pipe and low soil thermal conductivity 0.4 W/(m·K), the results showed a doubling of the soil temperature gradient when compared with the no-leakage case. This fact undoubtedly confirms the potential of the method, which is particularly suitable for leak detection in old pipelines that have priority for renovation. A key added value of this research is that the soil temperature gradient-based leak detection technique was found useful in most foreseeable DH operating situations.
Deep Heat: A Comparison of Water Temperature, Anemone Bleaching, Anemonefish Density and Reproduction between Shallow and Mesophotic Reefs
Authors: Haguenauer Anne , Zuberer Frédéric , Siu Gilles , Cortese Daphne , Beldade Ricardo , Mills Suzanne C.
Published: September 2021

French Polynesia is experiencing increasing coral bleaching events in shallow waters triggered by thermal anomalies and marine heatwaves linked to climate change, a trend that is replicated worldwide. As sea surface thermal anomalies are assumed to lessen with depth, mesophotic deep reefs have been hypothesized to act as refuges from anthropogenic and natural disturbances, the ‘deep reef refugia hypothesis’ (DRRH). However, evidence supporting the DRRH is either inconclusive or conflicting. We address this by investigating four assumptions of the DRRH focusing on the symbiotic association between anemones and anemonefish. First, we compare long-term temperature conditions between shallow (8 m) and mesophotic sites (50 m) on the island of Moorea from 2011–2020. Second, we compare the densities of the orange-fin anemonefish, Amphiprion chrysopterus between shallow and mesophotic (down to 60 m) reefs across three archipelagos in French Polynesia. Finally, we compare the percentage of anemone bleaching, as well as anemonefish reproduction, between shallow and mesophotic reefs. We found that the water column was well mixed in the cooler austral winter months with only a 0.19 °C difference in temperature between depths, but in the warmer summer months mixing was reduced resulting in a 0.71–1.03 °C temperature difference. However, during thermal anomalies, despite a time lag in warm surface waters reaching mesophotic reefs, there was ultimately a 1.0 °C increase in water temperature at both 8 and 50 m, pushing temperatures over bleaching thresholds at both depths. As such, anemone bleaching was observed in mesophotic reefs during these thermal anomalies, but was buffered compared to the percentage of bleaching in shallower waters, which was nearly five times greater. Our large-scale sampling across French Polynesia found orange-fin anemonefish, A. chrysopterus, in mesophotic zones in two high islands and one atoll across two archipelagos, extending its bathymetric limit to 60 m; however, orange-fin anemonefish densities were either similar to, or 25–92 times lower than in shallower zones. Three spawning events were observed at 50 m, which occurred at a similar frequency to spawning on shallower reefs at the same date. Our findings of thermal anomalies and bleaching in mesophotic reefs, coupled with mainly lower densities of anemonefish in mesophotic populations, suggest that mesophotic reefs show only a limited ability to provide refugia from anthropogenic and natural disturbances.
Comparative Analysis of the Chemical Composition and Physicochemical Properties of the Mucilage Extracted from Fresh and Dehydrated Opuntia ficus indica Cladodes
Authors: Quintero-García Michelle , Gutiérrez-Cortez Elsa , Bah Moustapha , Rojas-Molina Alejandra , Cornejo-Villegas María de los Angeles , Del Real Alicia , Rojas-Molina Isela
Published: September 2021

The development of sustainable extraction methods to obtain natural products constitutes a challenge for the food industry. The aim of this work was to compare yield, separation efficiency, chemical composition, and physicochemical properties of the mucilage extracted from fresh cladodes (FNM) and mucilage extracted from dehydrated cladodes (DNM) of O. ficus indica. Suspensions of fresh and dehydrated cladodes (4% w/w) were prepared for mucilage extraction by using a mechanical separation process. Subsequently, the separated mucilage was precipitated with ethyl alcohol (1:2 v/v) then, yield and separation efficiency were determined. The mucilage was characterized by measuring Z potential, viscosity, color, and texture attributes. Additionally, chemical proximate analysis, scanning electron microscopy, and thermogravimetric analysis (TGA) were conducted. No significant differences (p < 0.05) were detected in the yield and separation efficiencies between samples. Nevertheless, the dehydration process of cladodes prior to mucilage extraction increased protein, ashes, nitrogen free extract, and calcium content. The viscosity was higher in DNM than in FNM. The TGA revealed a different thermal behavior between samples. In addition, the DNM showed lower L (darkness/lightness), cohesiveness, adhesiveness, and springiness values than those of FNM. These results support that differences found between the chemical and physicochemical properties of DNM and those of FNM will determine the applications of the mucilage obtained from the O. ficus indica cladodes in the food, pharmaceutical, and cosmetic industries.
Competition between Starter Cultures and Wild Microbial Population in Sausage Fermentation: A Case Study Regarding a Typical Italian Salami (Ventricina)
Authors: Montanari Chiara , Barbieri Federica , Gardini Fausto , Tabanelli Giulia
Published: September 2021

The work reports a case study describing how the competition wild microflora vs. starter cultures affects the final product characteristics. This study regards an industrial lot of Ventricina, an Italian long-ripened traditional fermented sausages, produced using starter cultures. After ripening, some relevant organoleptic defects (off-odour, crust formation) were observed. Therefore, analyses were carried out in the inner and outer sausage section to explain this phenomenon. Microbiological analyses indicated a high meat batter contamination and metagenomic analyses evidenced the inability of LAB starter cultures to lead the fermentation process. The results of this not controlled fermentation were the accumulation of high levels of biogenic amines (including histamine) and the formation of a volatile profile different if compared with similar products. Indeed, the volatilome analysis revealed unusually high amounts of molecules such as isovaleric acid, propanoic acid, 1-propanol, which can be responsible for off-odours. This study demonstrated that starter culture use needs to be modulated in relation to production parameters to avoid safety and organoleptic concerns.
Drought and Heat Stress Impacts on Phenolic Acids Accumulation in Durum Wheat Cultivars
Authors: Laddomada Barbara , Blanco Antonio , Mita Giovanni , D’Amico Leone , Singh Ravi P. , Ammar Karim , Crossa Jose , Guzmán Carlos
Published: September 2021

Droughts and high temperatures are the main abiotic constraints hampering durum wheat production. This study investigated the accumulation of phenolic acids (PAs) in the wholemeal flour of six durum wheat cultivars under drought and heat stress. Phenolic acids were extracted from wholemeals and analysed through HPLC-DAD analysis. Ferulic acid was the most represented PA, varying from 390.1 to 785.6 µg/g dry matter across all cultivars and growth conditions, followed by sinapic acids, p-coumaric, vanillic, syringic, and p-hydroxybenzoic acids. Among the cultivars, Cirno had the highest PAs content, especially under severe drought conditions. Heat stress enhanced the accumulation of minor individual PAs, whereas severe drought increased ferulic acid and total PAs. Broad-sense heritability was low (0.23) for p-coumaric acid but ≥0.69 for all other components. Positive correlations occurred between PA content and grain morphology and between test weight and grain yield. Durum wheat genotypes with good yields and high accumulation of PAs across different growing conditions could be significant for durum wheat resilience and health-promoting value.