bluuebunny/crossref_metadata_2025 huggingface dataset:
High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome
Authors: Pietrobono Deborah , Giacomelli Chiara , Marchetti Laura , Martini Claudia , Trincavelli Maria Letizia
Published: October 2020

Glioblastoma is an aggressive, fast-growing brain tumor influenced by the composition of the tumor microenvironment (TME) in which mesenchymal stromal cell (MSCs) play a pivotal role. Adenosine (ADO), a purinergic signal molecule, can reach up to high micromolar concentrations in TME. The activity of specific adenosine receptor subtypes on glioma cells has been widely explored, as have the effects of MSCs on tumor progression. However, the effects of high levels of ADO on glioma aggressive traits are still unclear as is its role in cancer cells-MSC cross-talk. Herein, we first studied the role of extracellular Adenosine (ADO) on isolated human U343MG cells as a glioblastoma cellular model, finding that at high concentrations it was able to prompt the gene expression of Snail and ZEB1, which regulate the epithelial–mesenchymal transition (EMT) process, even if a complete transition was not reached. These effects were mediated by the induction of ERK1/2 phosphorylation. Additionally, ADO affected isolated bone marrow derived MSCs (BM-MSCs) by modifying the pattern of secreted inflammatory cytokines. Then, the conditioned medium (CM) of BM-MSCs stimulated with ADO and a co-culture system were used to investigate the role of extracellular ADO in GBM–MSC cross-talk. The CM promoted the increase of glioma motility and induced a partial phenotypic change of glioblastoma cells. These effects were maintained when U343MG cells and BM-MSCs were co-cultured. In conclusion, ADO may affect glioma biology directly and through the modulation of the paracrine factors released by MSCs overall promoting a more aggressive phenotype. These results point out the importance to deeply investigate the role of extracellular soluble factors in the glioma cross-talk with other cell types of the TME to better understand its pathological mechanisms.
First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
Authors: Diociaiuti Andrea , Castiglia Daniele , Corbeddu Marialuisa , Rotunno Roberta , Rossi Sabrina , Pisaneschi Elisa , Cesario Claudia , Condorelli Angelo Giuseppe , Zambruno Giovanna , El Hachem May
Published: October 2020

Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.
Impact of the Stroma on the Biological Characteristics of the Parenchyma in Oral Squamous Cell Carcinoma
Authors: Takabatake Kiyofumi , Kawai Hotaka , Omori Haruka , Qiusheng Shan , Oo May Wathone , Sukegawa Shintaro , Nakano Keisuke , Tsujigiwa Hidetsugu , Nagatsuka Hitoshi
Published: October 2020

Solid tumors consist of the tumor parenchyma and stroma. The standard concept of oncology is that the tumor parenchyma regulates the tumor stroma and promotes tumor progression, and that the tumor parenchyma represents the tumor itself and defines the biological characteristics of the tumor tissue. Thus, the tumor stroma plays a pivotal role in assisting tumor parenchymal growth and invasiveness and is regarded as a supporter of the tumor parenchyma. The tumor parenchyma and stroma interact with each other. However, the influence of the stroma on the parenchyma is not clear. Therefore, in this study, we investigated the effect of the stroma on the parenchyma in oral squamous cell carcinoma (OSCC). We isolated tumor stroma from two types of OSCCs with different invasiveness (endophytic type OSCC (ED-st) and exophytic type OSCC (EX-st)) and examined the effect of the stroma on the parenchyma in terms of proliferation, invasion, and morphology by co-culturing and co-transplanting the OSCC cell line (HSC-2) with the two types of stroma. Both types of stroma were partially positive for alpha-smooth muscle actin. The tumor stroma increased the proliferation and invasion of tumor cells and altered the morphology of tumor cells in vitro and in vivo. ED-st exerted a greater effect on the tumor parenchyma in proliferation and invasion than EX-st. Morphological analysis showed that ED-st changed the morphology of HSC-2 cells to the invasive type of OSCC, and EX-st altered the morphology of HSC-2 cells to verrucous OSCC. This study suggests that the tumor stroma influences the biological characteristics of the parenchyma and that the origin of the stroma is strongly associated with the biological characteristics of the tumor.
Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity—Potential Implications for Drug Sensitivity
Authors: Søe Kent
Published: October 2020

Classically, osteoclast fusion consists of four basic steps: (1) attraction/migration, (2) recognition, (3) cell–cell adhesion, and (4) membrane fusion. In theory, this sounds like a straightforward simple linear process. However, it is not. Osteoclast fusion has to take place in a well-coordinated manner—something that is not simple. In vivo, the complex regulation of osteoclast formation takes place within the bone marrow—in time and space. The present review will focus on considering osteoclast fusion in the context of physiology and pathology. Special attention is given to: (1) regulation of osteoclast fusion in vivo, (2) heterogeneity of osteoclast fusion partners, (3) regulation of multi-nucleation, (4) implications for physiology and pathology, and (5) implications for drug sensitivity and side effects. The review will emphasize that more attention should be given to the human in vivo reality when interpreting the impact of in vitro and animal studies. This should be done in order to improve our understanding of human physiology and pathology, as well as to improve anti-resorptive treatment and reduce side effects.
RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
Authors: Swami Priyanka , Thiyagarajan Swetha , Vidger Arianna , Indurthi Venkata S. K. , Vetter Stefan W. , Leclerc Estelle
Published: October 2020

The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and β1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT.
Internalization of the Aspergillus nidulans AstA Transporter into Mitochondria Depends on Growth Conditions, and Affects ATP Levels and Sulfite Oxidase Activity
Authors: Piłsyk Sebastian , Mieczkowski Adam , Golan Maciej P. , Wawrzyniak Agata , Kruszewska Joanna S.
Published: October 2020

The astA gene encoding an alternative sulfate transporter was originally cloned from the genome of the Japanese Aspergillus nidulans isolate as a suppressor of sulfate permease-deficient strains. Expression of the astA gene is under the control of the sulfur metabolite repression system. The encoded protein transports sulfate across the cell membrane. In this study we show that AstA, having orthologs in numerous pathogenic or endophytic fungi, has a second function and, depending on growth conditions, can be translocated into mitochondria. This effect is especially pronounced when an astA-overexpressing strain grows on solid medium at 37 °C. AstA is also recruited to the mitochondria in the presence of mitochondria-affecting compounds such as menadione or antimycin A, which are also detrimental to the growth of the astA-overexpressing strain. Disruption of the Hsp70–Porin1 mitochondrial import system either by methylene blue, an Hsp70 inhibitor, or by deletion of the porin1-encoding gene abolishes AstA translocation into the mitochondria. Furthermore, we observed altered ATP levels and sulfite oxidase activity in the astA-overexpressing strain in a manner dependent on sulfur sources. The presented data indicate that AstA is also involved in the mitochondrial sulfur metabolism in some fungi, and thereby indirectly manages redox potential and energy state.
Dietary Energy Partition: The Central Role of Glucose
Authors: Remesar Xavier , Alemany Marià
Published: October 2020

Humans have developed effective survival mechanisms under conditions of nutrient (and energy) scarcity. Nevertheless, today, most humans face a quite different situation: excess of nutrients, especially those high in amino-nitrogen and energy (largely fat). The lack of mechanisms to prevent energy overload and the effective persistence of the mechanisms hoarding key nutrients such as amino acids has resulted in deep disorders of substrate handling. There is too often a massive untreatable accumulation of body fat in the presence of severe metabolic disorders of energy utilization and disposal, which become chronic and go much beyond the most obvious problems: diabetes, circulatory, renal and nervous disorders included loosely within the metabolic syndrome. We lack basic knowledge on diet nutrient dynamics at the tissue-cell metabolism level, and this adds to widely used medical procedures lacking sufficient scientific support, with limited or nil success. In the present longitudinal analysis of the fate of dietary nutrients, we have focused on glucose as an example of a largely unknown entity. Even most studies on hyper-energetic diets or their later consequences tend to ignore the critical role of carbohydrate (and nitrogen disposal) as (probably) the two main factors affecting the substrate partition and metabolism.
Discrete and Distributed Error Assessment of UAS-SfM Point Clouds of Roadways
Authors: Liao Yijun , Wood Richard L.
Published: October 2020

Perishable surveying, mapping, and post-disaster damage data typically require efficient and rapid field collection techniques. Such datasets permit highly detailed site investigation and characterization of civil infrastructure systems. One of the more common methods to collect, preserve, and reconstruct three-dimensional scenes digitally, is the use of an unpiloted aerial system (UAS), commonly known as a drone. Onboard photographic payloads permit scene reconstruction via structure-from-motion (SfM); however, such approaches often require direct site access and survey points for accurate and verified results, which may limit its efficiency. In this paper, the impact of the number and distribution of ground control points within a UAS SfM point cloud is evaluated in terms of error. This study is primarily motivated by the need to understand how the accuracy would vary if site access is not possible or limited. In this paper, the focus is on two remote sensing case studies, including a 0.75 by 0.50-km region of interest that contains a bridge structure, paved and gravel roadways, vegetation with a moderate elevation range of 24 m, and a low-volume gravel road of 1.0 km in length with a modest elevation range of 9 m, which represent two different site geometries. While other studies have focused primarily on the accuracy at discrete locations via checkpoints, this study examines the distributed errors throughout the region of interest via complementary light detection and ranging (lidar) datasets collected at the same time. Moreover, the international roughness index (IRI), a professional roadway surface standard, is quantified to demonstrate the impact of errors on roadway quality parameters. Via quantification and comparison of the differences, guidance is provided on the optimal number of ground control points required for a time-efficient remote UAS survey.
Effect of Evolocumab on Vulnerable Coronary Plaques: A Serial Coronary Computed Tomography Angiography Study
Authors: Hirai Keiji , Imamura Shigeki , Hirai Aizan , Ookawara Susumu , Morishita Yoshiyuki
Published: October 2020

This study investigated the effects of evolocumab on vulnerable coronary plaques and factors associated with the change in stability and size of plaques in patients taking statins. Vulnerable coronary plaques were defined using coronary computed tomography (CT) angiography as having a density of <50 HU within the region of interest and a remodeling index ≥1.1. The changes in minimum CT density, remodeling index, and percent stenosis of vulnerable coronary plaques after six months of evolocumab administration were retrospectively analyzed in 136 vulnerable coronary plaques from 98 patients (68 men and 30 women; mean age: 72.9 ± 8.7 years) treated with a statin. The administration of evolocumab significantly increased the minimum CT density (39.1 ± 8.1 HU to 84.9 ± 31.4 HU, p < 0.001), reduced the remodeling index (1.29 ± 0.11 to 1.19 ± 0.10, p < 0.001), and decreased the percent stenosis (27.0 ± 10.4% to 21.2 ± 9.8%, p < 0.001). Multiple linear regression analysis revealed that baseline percent stenosis (standard coefficient (β) = −0.391, p = 0.002) independently correlated with the change in minimum CT density, whereas the baseline remodeling index (β = −0.368, p < 0.001) independently correlated with a change in the remodeling index. Evolocumab stabilized vulnerable coronary plaques and reduced their size. These results suggest that evolocumab protects against coronary artery disease progression in patients taking statins.
Cardiac Complications Following Cardiac Surgery Procedures
Authors: Udzik Jakub , Sienkiewicz Sandra , Biskupski Andrzej , Szylińska Aleksandra , Kowalska Zuzanna , Biskupski Patrick
Published: October 2020

Background: Elderly patients and those with multiple concomitant disorders are nowadays qualified for cardiac surgery procedures, which is related to higher incidence of the postoperative complications. Aim: The aim of this study was a retrospective analysis of the perioperative factors potentially contributing to occurrence of cardiac incidents after cardiac surgery procedures. Methods: Data of 552 patients of the cardiac surgery clinic were collected and analyzed. Data concerning medical history, previous treatment, laboratory results, additional tests results, operation and hospitalization period were examined. Results: In the study population of 552 patients, cardiac complications were observed in 49.5% of them. Among cardiac complications, the most frequent were supraventricular tachycardia (30.1%) and atrial fibrillation (27.4%). Postoperative bradycardia occurred in 5.25% patients, half of whom required temporary cardiac pacing. Conclusions: The risk of incidence of cardiac complications after cardiac surgery procedures depends mostly on patient’s age, EuroSCORE Logistic (ESL) score, left ventricular ejection fraction, myocardial hypertrophy, presence of paroxysmal AF and coincidence of nephrological complications. The necessity of performing more than one heart defibrillation after removing aortic cross-clamp favors early postoperative bradycardia. Considering the outcomes of this study, continuing reperfusion at least until 1/3 of the aortic cross-clamp time brings no additional benefits to the patients.
Recent Advances in Porous 3D Cellulose Aerogels for Tissue Engineering Applications: A Review
Authors: Mirtaghavi Ali , Luo Jikui , Muthuraj Rajendran
Published: October 2020

Current approaches in developing porous 3D scaffolds face various challenges, such as failure of mimicking extracellular matrix (ECM) native building blocks, non-sustainable scaffold fabrication techniques, and lack of functionality. Polysaccharides and proteins are sustainable, inexpensive, biodegradable, and biocompatible, with structural similarities to the ECM. As a result, 3D-structured cellulose (e.g., cellulose nanofibrils, nanocrystals and bacterial nanocellulose)-based aerogels with high porosity and interconnected pores are ideal materials for biomedical applications. Such 3D scaffolds can be prepared using a green, scalable, and cost-effective freeze-drying technique. The physicochemical, mechanical, and biological characteristics of the cellulose can be improved by incorporation of proteins and other polysaccharides. This review will focus on recent developments related to the cellulose-based 3D aerogels prepared by sustainable freeze-drying methods for tissue engineering applications. We will also provide an overview of the scaffold development criteria; parameters that influenced the aerogel production by freeze-drying; and in vitro and in vivo studies of the cellulose-based porous 3D aerogel scaffolds. These efforts could potentially help to expand the role of cellulose-based 3D scaffolds as next-generation biomaterials.
Investigating the Effect of Stepped Scarf Repair Ratio in Repaired CFRP Laminates under Compressive Loading
Authors: Psarras Spyridon , Loutas Theodoros , Papanaoum Magdalini , Triantopoulos Orestis Konstantinos , Kostopoulos Vasilis
Published: October 2020

In this work the effectiveness of stepped repairs to damaged fiber reinforced composite materials is investigated by using previously validated numerical models which were compared with tested repaired composite plates. Parametric studies were carried out in order to assess the scarf ratio (i.e., step length to ply thickness ratio) influence on ultimate forces, displacements, stresses and stiffnesses. FE models with repair scarf ratios varying from the value of 20 to the value 60 with a step increase of 10 were developed. The numerical models allowed a direct comparison of the influence that the scarf ratio had to the strength and stiffness restoration of the repaired composite structure. The study verifies that the restoration of the strength of a damaged laminate depends largely on the size of the repair patch. Generally, the bigger the size of a patch, the stronger the repaired structure is, up to a critical threshold size. To maximize the strength restoration, it is advised that the number of steps in each patch are no less than the number of plies on the base laminate.
The Influence of Situational Cues on Children’s Creativity in an Alternative Uses Task and the Moderating Effect of Selective Attention
Authors: van Dijk Marloes , Blom Elma , Kroesbergen Evelyn H. , Leseman Paul P. M.
Published: October 2020

Taking a perception-action perspective, we investigated how the presence of different real objects in children’s immediate situation affected their creativity and whether this effect was moderated by their selective attention. Seventy children between ages 9 and 12 years old participated. Verbal responses on a visual Alternative Uses Task with a low stimulus and high stimulus condition were coded on fluency, flexibility, and originality. Selective attention was measured with a visual search task. Results showed that fluency was not affected by stimulus condition and was unrelated to selective attention. Flexibility was positively associated with selective attention. Originality, net of fluency and flexibility, showed a main effect of stimulus condition in an unexpected direction, as children gave more original responses in the low stimulus condition compared to the high stimulus condition. A significant moderation effect revealed that children with better selective attention skills benefitted from a low stimulus environment, whereas children with weaker selective attention performed better in a high stimulus environment. The findings demonstrate differential effects of the immediate situation and selective attention, and support the hypothesis that creativity is impacted by immediate situation and selective attention, yet in unexpected ways.
Evidences of CTLA-4 and PD-1 Blocking Agents-Induced Cardiotoxicity in Cellular and Preclinical Models
Authors: Quagliariello Vincenzo , Passariello Margherita , Rea Domenica , Barbieri Antonio , Iovine Martina , Bonelli Annamaria , Caronna Antonietta , Botti Gerardo , De Lorenzo Claudia , Maurea Nicola
Published: October 2020

Background: Several strategies based on immune checkpoint inhibitors (ICIs) have been developed for cancer therapy, opening to advantages in cancer outcomes. However, several ICI-induced side effects have emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We studied the cytotoxic and pro-inflammatory properties of Ipilimumab and Nivolumab, the underlying pathways and cytokine storm involved. Methods: Co-cultures of human cardiomyocytes and lymphocytes were exposed to Ipilimumab or Nivolumab; cell viability and expression of leukotrienes, NLRP3, MyD88, and p65/NF-kB were performed. C57 mice were treated with Ipilimumab (15 mg/kg); analysis of fractional shortening, ejection fraction, radial and longitudinal strain were made before and after treatments through 2D-echocardiography. Expression of NLRP3, MyD88, p65/NF-kB, and 12 cytokines were analyzed in murine myocardium. Results: Nivolumab and Ipilimumab exert effective anticancer, but also significant cardiotoxic effects in co-cultures of lymphocytes and tumor or cardiac cells. Both ICIs increased NLRP3, MyD88, and p65/NF-kB expression compared to untreated cells, however, the most pro-inflammatory and cardiotoxic effects were seen after exposure to Ipilimumab. Mice treated with Ipilimumab showed a significant decrease in fractional shortening and radial strain with respect to untreated mice, coupled with a significant increase in myocardial expression of NLRP3, MyD88, and several interleukins. Conclusions: Nivolumab and Ipilimumab exert cytotoxic effects mediated by the NLRP3/IL-1β and MyD88 pathways, leading to pro-inflammatory cytokine storm in heart tissue.
Systems Biology and Experimental Model Systems of Cancer
Authors: Yalcin Gizem Damla , Danisik Nurseda , Baygin Rana Can , Acar Ahmet
Published: October 2020

Over the past decade, we have witnessed an increasing number of large-scale studies that have provided multi-omics data by high-throughput sequencing approaches. This has particularly helped with identifying key (epi)genetic alterations in cancers. Importantly, aberrations that lead to the activation of signaling networks through the disruption of normal cellular homeostasis is seen both in cancer cells and also in the neighboring tumor microenvironment. Cancer systems biology approaches have enabled the efficient integration of experimental data with computational algorithms and the implementation of actionable targeted therapies, as the exceptions, for the treatment of cancer. Comprehensive multi-omics data obtained through the sequencing of tumor samples and experimental model systems will be important in implementing novel cancer systems biology approaches and increasing their efficacy for tailoring novel personalized treatment modalities in cancer. In this review, we discuss emerging cancer systems biology approaches based on multi-omics data derived from bulk and single-cell genomics studies in addition to existing experimental model systems that play a critical role in understanding (epi)genetic heterogeneity and therapy resistance in cancer.
Impacts of Future Crop Tree Release Treatments on Forest Carbon as REDD+ Mitigation Benefits
Authors: Gräfe Sebastian , Köhl Michael
Published: October 2020

Sustainable forest management activities, such as future crop tree (FCT) release treatments, became part of the REDD+ strategy to avoid carbon emissions from forests. FCT release treatments are intended to achieve increased growth of FCTs by removing competitor trees. This initially leads to a reduction of the forest carbon pool and represents a carbon debt. We estimated that the time it takes for FCTs to offset the carbon debt through increased growth on experimental sites of 10 km² in Belize, Guyana, Suriname, and Trinidad and Tobago. We further investigated whether the costs of treatment can be compensated by the generated financial carbon benefits. An average of 2.3 FCT per hectare were released through the removal of an average of 3.3 competitors per hectare. This corresponds to an average above ground biomass (AGB) deficit of 2.3 Mg FCT−1. Assuming a 30% increase in growth, the FCT would need on average 130 years to offset the carbon loss. For carbon prices from US$ 5 to 100 Mg CO2e−1 an additional increment between 0.6 and 22.7 Mg tree−1 would be required to cover the treatment costs of US$ 4.2 to 8.4 FCT−1. Assuming a carbon price of US$ 10 Mg CO2e−1, the additional increment required would be between 5.8 and 11.4 Mg tree−1, thus exceeding the biological growth potential of most individual trees. The release of FCTs does not ensure an increase in forest carbon stocks, and refinancing of treatment costs is problematic.
Automatic Judgement of Online Video Watching: I Know Whether or Not You Watched
Authors: Yi Eunseon , Lim Heuiseok , Jo Jaechoon
Published: October 2020

Videos have long been viewed through the free choice of customers, but in some cases currently, watching them is absolutely required, for example, in institutions, companies, and education, even if the viewers prefer otherwise. In such cases, the video provider wants to determine whether the viewer has honestly been watching, but the current video viewing judging system has many loopholes; thus, it is hard to distinguish between honest viewers and false viewers. Time interval different answer popup quiz (TIDAPQ) was developed to judge honest watching. In this study, TIDAPQ randomly inserts specially developed popup quizzes in the video. Viewers must solve time interval pass (RESULT 1) and individually different correct answers (RESULT 2) while they watch. Then, using these two factors, TIDAPQ immediately performs a comprehensive judgement on whether the viewer honestly watched the video. To measure the performance of TIDAPQ, 100 experimental subjects were recruited to participate in the model verification experiment. The judgement performance on normal watching was 93.31%, and the judgement performance on unusual watching was 85.71%. We hope this study will be useful in many areas where watching judgements are needed.
An Efficient Design and Implementation of a Quadrotor Unmanned Aerial Vehicle Using Quaternion-Based Estimator
Authors: Dulf Eva H. , Saila Mihnea , Muresan Cristina I. , Miclea Liviu C.
Published: October 2020

The main goal of the research is to design a low-cost, performing quadrotor unmaned aerial vehicle (UAV) system. Because of low cost limits, the performance must be ensured by other ways. The present proposal is a quaternion-based estimator used in the control loop. In order to make the proposed solution easy to be reproduced by the reader, step-by-step instructions are given, including component choices, design, and implementation. Throughout the article, detailed description of the system model is given. The efficacy of the suggested quaternion-based predictive control is evaluated by extended experimental results.
Extreme Value Index Estimation by Means of an Inequality Curve
Authors: Taufer Emanuele , Santi Flavio , Novi Inverardi Pier Luigi , Espa Giuseppe , Dickson Maria Michela
Published: October 2020

A characterizing property of Zenga (1984) inequality curve is exploited in order to develop an estimator for the extreme value index of a distribution with regularly varying tail. The approach proposed here has a nice graphical interpretation which provides a powerful method for the analysis of the tail of a distribution. The properties of the proposed estimation strategy are analysed theoretically and by means of simulations. The usefulness of the method will be tested also on real data sets.
Design, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpenes
Authors: Mazzotta Sarah , Carullo Gabriele , Schiano Moriello Aniello , Amodeo Pietro , Di Marzo Vincenzo , Vega-Holm Margarita , Vitale Rosa Maria , Aiello Francesca , Brizzi Antonella , De Petrocellis Luciano
Published: October 2020

Labdane diterpenes are widespread classes of natural compounds present in variety of marine and terrestrial organisms and plants. Many of them represents “natural libraries” of compounds with interesting biological activities due to differently functionalized drimane nucleus exploitable for potential pharmacological applications. The transient receptor potential channel subfamily V member 4 (TRPV4) channel has recently emerged as a pharmacological target for several respiratory diseases, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inspired by the labdane-like bicyclic core, a series of homodrimane-derived esters and amides was designed and synthesized by modifying the flexible tail in position 1 of (+)-sclareolide, an oxidized derivative of the bioactive labdane-type diterpene sclareol. The potency and selectivity towards rTRPV4 and hTRPV1 receptors were assessed by calcium influx cellular assays. Molecular determinants critical for eliciting TRPV4 antagonism were identified by structure-activity relationships. Among the selective TRPV4 antagonists identified, compound 6 was the most active with an IC50 of 5.3 μM. This study represents the first report of semisynthetic homodrimane TRPV4 antagonists, selective over TRPV1, and potentially useful as pharmacological tools for the development of novel TRPV4 channel modulators.
Induction of Natural Defenses in Tomato Seedlings by Using Alginate and Oligoalginates Derivatives Extracted from Moroccan Brown Algae
Authors: Aitouguinane Meriem , Bouissil Soukaina , Mouhoub Anouar , Rchid Halima , Fendri Imen , Abdelkafi Slim , Ould El-Hadj Mohamed Didi , Boual Zakaria , Dubessay Pascal , Gardarin Christine , Michaud Philippe , El Alaoui-Talibi Zainab , El Modafar Cherkaoui , Pierre Guillaume , Delattre Cédric
Published: October 2020

Polysaccharides extracted from marine algae have attracted much attention due to their biotechnological applications, including therapeutics, cosmetics, and mainly in agriculture and horticulture as biostimulants, biofertilizers, and stimulators of the natural defenses of plants. This study aimed to evaluate the ability of alginate isolated from Bifurcaria bifurcata from the Moroccan coast and oligoalginates derivatives to stimulate the natural defenses of tomato seedlings. Elicitation was carried out by the internodal injection of bioelicitor solutions. The elicitor capacities were evaluated by monitoring the activity of phenylalanine ammonia-lyase (PAL) as well as polyphenols content in the leaves located above the elicitation site for 5 days. Alginate and oligoalginates treatments triggered plant defense responses, which showed their capacity to significantly induce the PAL activity and phenolic compounds accumulation in the leaves of tomato seedlings. Elicitation by alginates and oligoalginates showed an intensive induction of PAL activity, increasing from 12 h of treatment and remaining at high levels throughout the period of treatment. The amount of polyphenols in the leaves was increased rapidly and strongly from 12 h of elicitation by both saccharide solutions, representing peaks value after 24 h of application. Oligoalginates exhibited an effective elicitor capacity in polyphenols accumulation compared to alginate polymers. The alginate and oligosaccharides derivatives revealed a similar elicitor capacity in PAL activity whereas the accumulation of phenolic compounds showed a differential effect. Polysaccharides extracted from the brown seaweed Bifurcaria bifurcate and oligosaccharides derivatives induced significantly the phenylpropanoid metabolism in tomato seedlings. These results contribute to the valorization of marine biomass as a potential bioresource for plant protection against phytopathogens in the context of eco-sustainable green technology.
Slow-Freezing Cryopreservation Ensures High Ovarian Tissue Quality Followed by In Vivo and In Vitro Methods and Is Safe for Fertility Preservation
Authors: Gudlevičienė Živilė , Žilinskas Kastytis , Kundrotas Gabrielis , Grubliauskaitė Monika , Baltriukienė Daiva , Bukelskienė Virginija
Published: October 2020

Background and objectives: Cancer incidence is growing with younger patients diagnosed with this disease every year. Improved cancer diagnostics and treatment lead to better survival of cancer patients. However, after aggressive chemo- or radiotherapy, cancer survivors suffer from various degrees of subfertility or infertility. Several fertility preservation technologies have been developed for young cancer patients: cryopreservation of germ cells, embryos, or reproductive tissues. The best results have been shown by cryopreservation of sperm and embryos. Yet the success of using cryopreserved oocytes or reproductive tissues (ovarian and testicular) is still insufficient. Therefore, this study was designed to assess the vitality, viability, general quality, and safety of frozen–thawed human ovarian tissue for retransplantation using modern molecular tests. Materials and Methods: The new miRNA array test was used to evaluate miRNA expression in thawed ovarian tissue in combination with standard xenotransplantation and pathological examination of microslides. Results: Our results demonstrated that slow freezing is an efficient way (80%) to cryopreserve ovarian tissue with no structural damage afterwards. We have shown that xenotransplantation into immunodeficient mice, histology, and immunohistochemistry could be potentially replaced by more recent molecular methods. Conclusions: The latter method has shown that altered expression of miRNAs might be used as identifiers of normal/damaged tissue after further analysis. Newer, safer, and more specific approaches need to be developed in order to eliminate the risk of disease reoccurrence.
Effect of Mucosal Brushing on the Serum Levels of C-Reactive Protein for Patients Hospitalized with Acute Symptoms
Authors: Nakahodo Naoko , Nomura Yoshiaki , Oshiro Takumi , Otsuka Ryoko , Kakuta Erika , Okada Ayako , Inai Yuko , Takei Noriko , Hanada Nobuhiro
Published: October 2020

This study was based in a hospital setting. Patients with acute symptoms face a life-threatening crisis and often have systemic complications during the convalescence stage. During the acute stage, oral function does not work and oral hygiene status deteriorates. A gauze or sponge brush is generally used to wipe the oral cavity; however, this process does not clean the oral cavity enough. Effective oral care requires better methods. Patients participating in this study were all hospitalized by ambulance and with acute symptoms. During the convalescence stage, patients were assigned application of mucosal brushing or wiping by gauze or sponge brush by order of hospitalization. The effects were evaluated by the number of bacteria on the tongue surface, serum C-reactive protein (CRP) and body temperature. Changes in bacterial count, body temperature, and CRP were effectively reduced in the mucosal brushing group compared to the wiping by gauze or sponge brush group. Based on mixed effect modeling, the coefficient of mucosal brushing for CRP was −2.296 and for body temperature was −0.067 and statistically significant. This simple method can effectively prevent systemic complication of inpatients with deteriorated oral conditions. This method may also be effective for the elderly in nursing homes or perioperative oral-care management.
Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
Authors: Sessa Lucia , Concilio Simona , Walde Peter , Robinson Tom , Dittrich Petra S. , Porta Amalia , Panunzi Barbara , Caruso Ugo , Piotto Stefano
Published: October 2020

Most linear peptides directly interact with membranes, but the mechanisms of interaction are far from being completely understood. Here, we present an investigation of the membrane interactions of a designed peptide containing a non-natural, synthetic amino acid. We selected a nonapeptide that is reported to interact with phospholipid membranes, ALYLAIRKR, abbreviated as ALY. We designed a modified peptide (azoALY) by substituting the tyrosine residue of ALY with an antimicrobial azobenzene-bearing amino acid. Both of the peptides were examined for their ability to interact with model membranes, assessing the penetration of phospholipid monolayers, and leakage across the bilayer of large unilamellar vesicles (LUVs) and giant unilamellar vesicles (GUVs). The latter was performed in a microfluidic device in order to study the kinetics of leakage of entrapped calcein from the vesicles at the single vesicle level. Both types of vesicles were prepared from a 9:1 (mol/mol) mixture of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(1′-rac-glycerol). Calcein leakage from the vesicles was more pronounced at a low concentration in the case of azoALY than for ALY. Increased vesicle membrane disturbance in the presence of azoALY was also evident from an enzymatic assay with LUVs and entrapped horseradish peroxidase. Molecular dynamics simulations of ALY and azoALY in an anionic POPC/POPG model bilayer showed that ALY peptide only interacts with the lipid head groups. In contrast, azoALY penetrates the hydrophobic core of the bilayers causing a stronger membrane perturbation as compared to ALY, in qualitative agreement with the experimental results from the leakage assays.
Bacterial Community Dynamics Distinguish Poultry Compost from Dairy Compost and Non-Amended Soils Planted with Spinach
Authors: Neher Deborah A. , Limoges Marie A. , Weicht Thomas R. , Sharma Manan , Millner Patricia D. , Donnelly Catherine
Published: October 2020

The aim of this study was to determine whether and how poultry litter compost and dairy manure compost alter the microbial communities within field soils planted with spinach. In three successive years, separate experimental plots on two fields received randomly assigned compost treatments varying in animal origin: dairy manure (DMC), poultry litter (PLC), or neither (NoC). The composition and function of bacterial and fungal communities were characterized by the amplicon sequencing of marker genes and by the ecoenzyme activity, respectively. The temporal autocorrelation within and among years was adjusted by principal response curves (PRC) to analyze the effect of compost on community composition among treatments. Bacteria in the phylum Bacteriodetes, classes Flavobacteriia and Spingobacteriales (Fluviicola, Flavobacteriia, and Pedobacter), were two to four times more abundant in soils amended with PLC than DMC or NoC consistently among fields and years. Fungi in the phylum Ascomycota were relatively abundant, but their composition was field-specific and without treatment differences. The ecoenzyme data verify that the effects of PLC and DMC on soil communities are based on their microbial composition and not a response to the C source or nutrient content of the compost.
Concordance between Histology, Immunohistochemistry, and RT-PCR in the Diagnosis of Feline Infectious Peritonitis
Authors: Stranieri Angelica , Scavone Donatella , Paltrinieri Saverio , Giordano Alessia , Bonsembiante Federico , Ferro Silvia , Gelain Maria Elena , Meazzi Sara , Lauzi Stefania
Published: October 2020

Histology, immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) have been used to diagnose feline infectious peritonitis (FIP), but no information regarding the comparison of their diagnostic performances on the same organ is available. The aims of this study were to determine the concordance among these tests and to evaluate which combination of tests and organs can be used in vivo. Histology, IHC, and nested RT-PCR (RT-nPCR) for feline coronavirus (FCoV) were performed on spleen, liver, mesenteric lymph node, kidney, large and small intestine, and lung from 14 FIP and 12 non-FIP cats. Sensitivity, specificity, predictive values, likelihood ratios, and concordance were calculated. IHC and RT-nPCR had the highest concordance in lung and liver, histology and IHC in the other organs. The sensitivity of histology, IHC, and RT-nPCR on the different organs ranged from 41.7 to 76.9%, 46.2 to 76.9%, and 64.3 to 85.7%, respectively, and their specificity ranged from 83.3 to 100.0%, 100% and 83.3 to 100.0%. Therefore, IHC is recommended when histology is consistent with FIP. If RT-nPCR is performed as the first diagnostic approach, results should always be confirmed with IHC. Lung or liver provide accurate information regardless of the method, while IHC is preferred to RT-nPCR to confirm FIP in the kidney or intestine.
An Abattoir-Based Study on the Prevalence of Salmonella Fecal Carriage and ESBL Related Antimicrobial Resistance from Culled Adult Dairy Cows in Wuhan, China
Authors: Wang Jie , Xue Kaili , Yi Ping , Zhu Xiaojie , Peng Qingjie , Wang Zijian , Peng Yongchong , Chen Yingyu , Robertson Ian D. , Li Xiang , Guo Aizhen , Aleri Joshua W.
Published: October 2020

The objective of this study was to estimate the fecal carriage of Salmonella spp. among culled adult dairy cows presented to an abattoir in Wuhan, China and to evaluate their antimicrobial resistance profiles. Rectal swabs from 138 culled cows were cultured. Laboratory analysis involved the identification of Salmonella, the susceptibility assessment and the presence of Extended Spectrum β-lactamases and mcr genes in the isolates. An overall prevalence of Salmonella of 29.0% was recorded with 63.4% (26/41) and 2.4% (1/41) of the isolates identified as S. Typhimurium and S. Dublin, respectively. The occurrence of Salmonella was higher (odd ratios: 3.3) in culled cows originating from the northeast zone of China than cows originating from the central and north zones. Twenty multi-drug resistant strains (resistant to three or more antimicrobial agents) were detected (48.8%) and overall, a high resistance to ampicillin (36/41) and tetracycline (15/41) was observed. Extended Spectrum β-lactamases phenotypes were found in 7/41 isolates, of which all contained the blaCTX-M resistance gene, and no mcr genes were found by polymerase chain reaction. The high prevalence of Salmonella fecal carriage and antimicrobial resistance may contribute to an increased risk of Salmonella transmission to food.
Effects of Land Cover Changes on Sediment and Nutrient Balance in the Catchment with Cascade-Dammed Waters
Authors: Szatten Dawid , Habel Michał
Published: October 2020

It is commonly believed that changes in the use of the catchment area have a direct impact on the quality of the water environment. Rivers with dams and reservoirs are characterized by a disturbed outflow of sediments and nutrients from the catchment area. The research was based on indicating the variation in time and space of loads of selected parameters of the water quality of the Brda River (Northern Poland) against the land cover changes based on the CORINE Land Cover (CLC) data for the 1990–2018 period. In the lower part of the Brda catchment area, there are three hydropower dams with reservoirs in the form of a cascade, whose work clearly affects the hydrological regime of the river. The analysis of the dependence of the dynamics of water quality changes on the usage of CLC was based on indicators such as sediments (suspended sediment load) and nutrients (total phosphorus load and total nitrogen load). The use of hydrological data on the Brda discharge above and below the reservoirs made it possible to calculate sediment and nutrient trapping efficiency. Linking the CLC data with the indices responsible for the mechanical denudation of the catchment area made it possible to show the strength of changes taking place in the catchment area. The results of the research do not indicate any direct correlation between land cover changes and the dynamics of the denudation process and matter transport in the Brda catchment area. As our research shows, the strong influence on the hydrological regime of the catchment points out the necessity to search for still other research methods supporting the decision-making cycle in the field of water management in the face of climate change.
Impact of Acoustic and Interactive Disruptive Factors during Robot-Assisted Surgery—A Virtual Surgical Training Model
Authors: Krüger Magret , Ackermann Johannes , Osmonov Daniar , Günther Veronika , Bauerschlag Dirk , Hensler Johannes , Egberts Jan-Hendrik , Lippross Sebastian , Gitas Georgios , Becker Thomas , Maass Nicolai , Jünemann Klaus-Peter , Alkatout Ibrahim
Published: October 2020

The use of virtual reality trainers for teaching minimally invasive surgical techniques has been established for a long time in conventional laparoscopy as well as robotic surgery. The aim of the present study was to evaluate the impact of reproducible disruptive factors on the surgeon’s work. In a cross-sectional investigation, surgeons were tested with regard to the impact of different disruptive factors when doing exercises on a robotic-surgery simulator (Mimic Flex VRTM). Additionally, we collected data about the participants’ professional experience, gender, age, expertise in playing an instrument, and expertise in playing video games. The data were collected during DRUS 2019 (Symposium of the German Society for Robot-assisted Urology). Forty-two surgeons attending DRUS 2019 were asked to participate in a virtual robotic stress training unit. The surgeons worked in various specialties (visceral surgery, gynecology, and urology) and had different levels of expertise. The time taken to complete the exercise (TTCE), the final score (FSC), and blood loss (BL) were measured. In the basic exercise with an interactive disruption, TTCE was significantly longer (p < 0.01) and FSC significantly lower (p < 0.05). No significant difference in TTCE, FSC, or BL was noted in the advanced exercise with acoustic disruption. Performance during disruption was not dependent on the level of surgical experience, gender, age, expertise in playing an instrument, or playing video games. A positive correlation was registered between self-estimation and surgical experience. Interactive disruptions have a greater impact on the performance of a surgeon than acoustic ones. Disruption affects the performance of experienced as well as inexperienced surgeons. Disruption in daily surgery should be evaluated and minimized in the interest of the patient’s safety.