bluuebunny/crossref_metadata_2025 huggingface dataset:
Envisioning the Future of European Food Systems: Approaches and Research Priorities After COVID-19
Authors: Vittuari Matteo , Bazzocchi Giovanni , Blasioli Sonia , Cirone Francesco , Maggio Albino , Orsini Francesco , Penca Jerneja , Petruzzelli Mara , Specht Kathrin , Amghar Samir , Atanasov Aleksandar-Mihail , Bastia Teresa , Bertocchi Inti , Coudard Antoine , Crepaldi Andrea , Curtis Adam , Fox-Kämper Runrid , Gheorghica Anca Elena , Lelièvre Agnès , Muñoz Pere , Nolde Erwin , Pascual-Fernández Josè , Pennisi Giuseppina , Pölling Bernd , Reynaud-Desmet Lèlia , Righini Isabella , Rouphael Youssef , Saint-Ges Vèronique , Samoggia Antonella , Shaystej Shima , da Silva Macu , Toboso Chavero Susana , Tonini Pietro , Trušnovec Gorazd , Vidmar Benjamin L. , Villalba Gara , De Menna Fabio
Published: March 2021

The COVID-19 pandemic unveiled the fragility of food sovereignty in cities and confirmed the close connection urban dwellers have with food. Although the pandemic was not responsible for a systemic failure, it suggested how citizens would accept and indeed support a transition toward more localized food production systems. As this attitudinal shift is aligned with the sustainability literature, this work aims to explore the tools and actions needed for a policy framework transformation that recognizes the multiple benefits of food systems, while considering local needs and circumstances. This perspective paper reviews the trends in production and consumption, and systematizes several impacts emerged across European food systems in response to the first wave of pandemic emergency, with the final aim of identifying challenges and future strategies for research and innovation toward the creation of resilient and sustainable city/region food systems. The proposal does not support a return to traditional small-scale economies that might not cope with the growing global population. It instead stands to reconstruct and upscale such connections using a “think globally act locally” mind-set, engaging local communities, and making existing and future citizen-led food system initiatives more sustainable. The work outlines a set of recommended actions for policy-makers: support innovative and localized food production, training and use of information and communication technology for food production and distribution; promote cross-pollination among city/region food systems; empower schools as agents of change in food provision and education about food systems; and support the development of assessment methodologies and the application of policy tools to ensure that the different sustainability dimensions of the food chain are considered.
Transformation of Uncertain Linear Systems with Real Eigenvalues into Cooperative Form: The Case of Constant and Time-Varying Bounded Parameters
Authors: Rauh Andreas , Kersten Julia
Published: March 2021

Continuous-time linear systems with uncertain parameters are widely used for modeling real-life processes. The uncertain parameters, contained in the system and input matrices, can be constant or time-varying. In the latter case, they may represent state dependencies of these matrices. Assuming bounded uncertainties, interval methods become applicable for a verified reachability analysis, for feasibility analysis of feedback controllers, or for the design of robust set-valued state estimators. The evaluation of these system models becomes computationally efficient after a transformation into a cooperative state-space representation, where the dynamics satisfy certain monotonicity properties with respect to the initial conditions. To obtain such representations, similarity transformations are required which are not trivial to find for sufficiently wide a-priori bounds of the uncertain parameters. This paper deals with the derivation and algorithmic comparison of two different transformation techniques for which their applicability to processes with constant and time-varying parameters has to be distinguished. An interval-based reachability analysis of the states of a simple electric step-down converter concludes this paper.
Phasing Maneuver Analysis from a Low Lunar Orbit to a Near Rectilinear Halo Orbit
Authors: Bucchioni Giordana , Innocenti Mario
Published: March 2021

The paper describes the preliminary design of a phasing trajectory in a cislunar environment, where the third body perturbation is considered non-negligible. The working framework is the one proposed by the ESA’s Heracles mission in which a passive target station is in a Near Rectilinear Halo Orbit and an active vehicle must reach that orbit to start a rendezvous procedure. In this scenario the authors examine three different ways to design such phasing maneuver under the circular restricted three-body problem hypotheses: Lambert/differential correction, Hohmann/differential correction and optimization. The three approaches are compared in terms of ΔV consumption, accuracy and time of flight. The selected solution is also validated under the more accurate restricted elliptic three-body problem hypothesis.
Single Nucleotide Polymorphism (SNP) Discovery and Association Study of Flowering Times, Crude Fat and Fatty Acid Composition in Rapeseed (Brassica napus L.) Mutant Lines Using Genotyping-by-Sequencing (GBS)
Authors: Ryu Jaihyunk , Lyu Jae Il , Kim Dong-Gun , Koo Kwang Min , Yang Baul , Jo Yeong Deuk , Kim Sang Hoon , Kwon Soon-Jae , Ha Bo-Keun , Kang Si-Yong , Kim Jin-Baek , Ahn Joon-Woo
Published: March 2021

Rapeseed is the most important oil crop used in the food and biodiesel industries. In this study, based on single nucleotide polymorphism (SNP) identified from genotyping-by-sequencing (GBS), and an association study of flowering time, crude fat and fatty acid contents were investigated in 46 rapeseed mutant lines derived from gamma rays. A total of 623,026,394 clean data reads were generated with 6.6 million reads on average. A set of 37,721 filtered SNPs was used to perform gene ontology and phylogenetic analysis. Hierarchical cluster analysis of the rapeseed mutant lines gave eight groups based on flowering time and fatty acid compositions. Gene ontological analysis of the mutant lines showed that many genes displaying SNPs are involved in cellular processes, cellular anatomy, and binding. A total of 40 SNPs were significantly associated with flowering time (1 SNP), crude fat content (2 SNPs), and fatty acid content (37 SNPs). A total of 21 genes were annotated from fatty acid content SNPs; among them, nine genes were significantly enriched in reproductive processes, such as embryonic development, fruit development, and seed development. This study demonstrated that SNPs are efficient tools for mutant screening and it provides a basis that the improving the oil qualities of rapeseed.
Effect of Bacillus megaterium var. phosphaticum Bacteria and L-Alpha Proline Amino Acid on Iron Content in Soil and Triticum aestivum L. Plants in Sustainable Agriculture System
Authors: Płaza Anna , Rzążewska Emilia , Gąsiorowska Barbara
Published: March 2021

Research was conducted in Poland in 2017–2019 at Siedlce University of Natural Sciences and Humanities in Siedlce. It aimed at determining the effect of the bacteria Bacillus megaterium var. phosphaticum, the amino acid L-alpha proline, and the mineral nitrogen fertiliser regime on iron content in soil during the period of rapid growth of spring wheat plants, as well as in spring wheat grain and straw. The following two factors were examined: (I) biological products: untreated control, Bacillus megaterium var. phosphaticum, L-alpha proline, Bacillus megaterium var. phosphaticum + L-alpha proline; (II) mineral nitrogen fertiliser regime: nonfertilised control, 60 kg N·ha−1, 90 kg N·ha−1, 90 kg N·ha−1 + foliar fertilisation. The study demonstrated that, during the period of rapid spring wheat plant growth, Fe content was the highest in the soil following an application of Bacillus megaterium var. phosphaticum + L-alpha proline + mineral nitrogen fertiliser applied at the rate of 90 kg N·ha−1. This combination resulted in the highest concentration and uptake of iron by spring wheat grain, whereas for straw, the same result was also achieved following mineral nitrogen fertiliser at a rate of 90 kg N·ha−1 + foliar fertilisation.
The Development of an Abattoir-Based Surveillance System in Lao PDR for the Detection of Zoonoses in Large Ruminants: Q Fever and Brucellosis Seroepidemiology as a Pilot Study
Authors: Siengsanan-Lamont Jarunee , Douangngeun Bounlom , Theppangna Watthana , Khounsy Syseng , Phommachanh Phouvong , Selleck Paul W. , Matsumoto Nina , Gleeson Laurence J. , Blacksell Stuart D.
Published: March 2021

Although animal health surveillance programmes are useful for gaining information to help improve global health and food security, these programmes can be challenging to establish in developing economies with a low-resource base. This study focused on establishing a national surveillance system initiated by the Lao PDR government using a passive surveillance system of abattoir samples as a pilot model, and to gain information on contagious zoonoses, particularly Q fever and brucellosis, in the large ruminant population. A total of 683 cattle and buffalo samples were collected from six selected provinces of Lao PDR between March–December 2019. Out of 271 samples tested, six samples (2.2%, 95% confidence interval (CI) of 1.0, 4.8) were positive in the Q fever antibody ELISA test. Only one sample (out of 683; 0.2%, 95% CI 0.0, 0.8) tested positive to the Brucella antibody ELISA test. Seroprevalence of these important zoonoses in Lao PDR were relatively low in cattle and buffaloes; however, extensive animal movement within the country was identified which could increase risks of spreading transboundary diseases. The study highlights the importance of ongoing animal health surveillance and the need to find cost-effective approaches for its long-term sustainability.
Aflatoxicosis Dysregulates the Physiological Responses to Crowding Densities in the Marine Teleost Gilthead Seabream (Sparus aurata)
Authors: Barany Andre , Fuentes Juan , Martínez-Rodríguez Gonzalo , Mancera Juan Miguel
Published: March 2021

Several studies in fish have shown that aflatoxin B1 (AFB1) causes a disparity of species-dependent physiological disorders without compromising survival. We studied the effect of dietary administration of AFB1 (2 mg AFB1 kg−1 diet) in gilthead seabream (Sparus aurata) juveniles in combination with a challenge by stocking density (4 vs. 40 g L−1). The experimental period duration was ten days, and the diet with AFB1 was administered to the fish for 85 days prior to the stocking density challenge. Our results indicated an alteration in the carbohydrate and lipid metabolites mobilization in the AFB1 fed group, which was intensified at high stocking density (HSD). The CT group at HSD increased plasma cortisol levels, as expected, whereas the AFB1-HSD group did not. The star mRNA expression, an enzyme involved in cortisol synthesis in the head kidney, presented a ninefold increase in the AFB1 group at low stocking density (LSD) compared to the CT-LSD group. Adenohypophyseal gh mRNA expression increased in the AFB1-HSD but not in the CT-HSD group. Overall, these results confirmed that chronic AFB1 dietary exposure alters the adequate endocrinological physiological cascade response in S. aurata, compromising the expected stress response to an additional stressor, such as overcrowding.
Influence of Human Eating Habits on Antimicrobial Resistance Phenomenon: Aspects of Clinical Resistome of Gut Microbiota in Omnivores, Ovolactovegetarians, and Strict Vegetarians
Authors: da Silva Suzane Fernandes , Reis Isabela Brito , Monteiro Melina Gabriela , Dias Vanessa Cordeiro , Machado Alessandra Barbosa Ferreira , da Silva Vânia Lúcia , Diniz Cláudio Galuppo
Published: March 2021

The use of xenobiotics in food production and how food intake is carried out in different cultures, along with different eating habits (omnivorism (ON), ovolactovegetarianism (VT), and strict vegetarianism (VG)) seem to have implications for antimicrobial resistance, especially in the human gut microbiota. Thus, the aim of this study was to evaluate aspects of the clinical resistome of the human gut microbiota among healthy individuals with different eating habits. Volunteers were divided into 3 groups: n = 19 omnivores (ON), n = 20 ovolactovegetarians (VT), and n = 19 strict vegetarians (VG), and nutritional and anthropometric parameters were measured. Metagenomic DNA from fecal samples was used as a template for PCR screening of 37 antimicrobial resistance genes (ARG) representative of commonly used agents in human medicine. The correlation between eating habits and ARG was evaluated. There were no significant differences in mean caloric intake. Mean protein intake was significantly higher in ON, and fiber and carbohydrate consumption was higher in VG. From the screened ARG, 22 were detected. No clear relationship between diets and the occurrence of ARG was observed. Resistance genes against tetracyclines, β-lactams, and the MLS group (macrolides, lincosamides, and streptogramins) were the most frequent, followed by resistance genes against sulfonamides and aminoglycosides. Vegetables and minimally processed foods seem to be the main source of ARG for the human gut microbiota. Although eating habits vary among individuals, the open environment and the widespread ARG from different human activities draw attention to the complexity of the antimicrobial resistance phenomenon which should be addressed by a One Health approach.
Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection
Authors: Garcia-Mesa Yoelvis , Xu He N. , Vance Patricia , Gruenewald Analise L. , Garza Rolando , Midkiff Cecily , Alvarez-Hernandez Xavier , Irwin David J. , Gill Alexander J. , Kolson Dennis L.
Published: March 2021

Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8+-T-lymphocyte-depleted rhesus macaques were studied. Five received oral DMF prior to the SIV infection and through to the necropsy day. Protein expression was analyzed in 11 brain regions, as well as the thymus, liver, and spleen, using Western blot and immunohistochemistry for antioxidant, inflammatory, and neuronal proteins. Additionally, oxidative stress was determined in brain sections using immunohistochemistry (8-OHdG, 3NT) and optical redox imaging of oxidized flavoproteins containing flavin adenine dinucleotide (Fp) and reduced nicotinamide adenine dinucleotide (NADH). The DMF treatment was associated with no changes in virus replication; higher expressions of the antioxidant enzymes NQO1, GPX1, and HO-1 in the brain and PRDX1 and HO-2 in the spleen; lower levels of 8-OHdG and 3NT; a lower optical redox ratio. The DMF treatment was also associated with increased expressions of cell-adhesion molecules (VCAM-1, ICAM-1) and no changes in HLA-DR, CD68, GFAP, NFL, or synaptic proteins. The concordantly increased brain antioxidant enzyme expressions and reduced oxidative stress in DMF-treated SIV-infected macaques suggest that DMF could limit oxidative stress throughout the brain through effective induction of the endogenous antioxidant response. We propose that DMF could potentially induce neuroprotective brain responses in persons living with HIV.
Improvement on Flux Weakening Control Strategy for Electric Vehicle Applications
Authors: Bianchini Claudio , Franceschini Giovanni , Torreggiani Ambra
Published: March 2021

This paper proposes an optimized flux weakening (FW) control strategy for interior permanent-magnet synchronous electric motor to address the critical issues that could occur under torque setpoint transition in flux weakening region, due, for example, to an emergency braking. This situation is typical in electric vehicles where the electrical machines operate over a wide speed range to reach high power density and avoid gearboxes. Two modified traditional flux weakening strategies are proposed in this paper to improve torque control quality during high speed torque transition. The proposed modified control strategies were validated both by Matlab/Simulink simulations, modeling the power train of a light vehicle application, and extensive experimental tests on a dedicated test bench.
Optimal Planning Method for Large-Scale Historical Exhibits in the Taiwan Railway Museum
Authors: Fan Lin Pey , Chu Tzu How
Published: March 2021

The curation design of cultural heritage sites, such as museums, influence the level of visitor satisfaction and the possibility of revisitation; therefore, an efficient exhibit layout is critical. The difficulty of determining the behavior of visitors and the layout of galleries means that exhibition layout is a knowledge-intensive, time-consuming process. The progressive development of machine learning provides a low-cost and highly flexible workflow in the management of museums, compared to traditional curation design. For example, the facility’s optimal layout, floor, and furniture arrangement can be obtained through the repeated adjustment of artificial intelligence algorithms within a relatively short time. In particular, an optimal planning method is indispensable for the immense and heavy trains in the railway museum. In this study, we created an innovative strategy to integrate the domain knowledge of exhibit displaying, spatial planning, and machine learning to establish a customized recommendation scheme. Guided by an interactive experience model and the morphology of point–line–plane–stereo, we obtained three aspects (visitors, objects, and space), 12 dimensions (orientation, visiting time, visual distance, centrality, main path, district, capacity, etc.), 30 physical principles, 24 suggestions, and five main procedures to implement layout patterns and templates to create an exhibit layout guide for the National Railway Museum of Taiwan, which is currently being transferred from the railway workshop for the sake of preserving the rail culture heritage. Our results are suitable and extendible to different museums by adjusting the criteria used to establish a new recommendation scheme.
AraSenCorpus: A Semi-Supervised Approach for Sentiment Annotation of a Large Arabic Text Corpus
Authors: Al-Laith Ali , Shahbaz Muhammad , Alaskar Hind F. , Rehmat Asim
Published: March 2021

At a time when research in the field of sentiment analysis tends to study advanced topics in languages, such as English, other languages such as Arabic still suffer from basic problems and challenges, most notably the availability of large corpora. Furthermore, manual annotation is time-consuming and difficult when the corpus is too large. This paper presents a semi-supervised self-learning technique, to extend an Arabic sentiment annotated corpus with unlabeled data, named AraSenCorpus. We use a neural network to train a set of models on a manually labeled dataset containing 15,000 tweets. We used these models to extend the corpus to a large Arabic sentiment corpus called “AraSenCorpus”. AraSenCorpus contains 4.5 million tweets and covers both modern standard Arabic and some of the Arabic dialects. The long-short term memory (LSTM) deep learning classifier is used to train and test the final corpus. We evaluate our proposed framework on two external benchmark datasets to ensure the improvement of the Arabic sentiment classification. The experimental results show that our corpus outperforms the existing state-of-the-art systems.
Histological and Histomorphometric Effectiveness of the Barrier Membranes for Jawbone Regeneration: An Overview of More Than 30 Years’ Experience of Research Results of the Italian Implant Retrieval Center (1988–2020)
Authors: Tumedei Margherita , Mourão Carlos Fernando , D’Agostino Silvia , Dolci Marco , Di Cosola Michele , Piattelli Adriano , Lucchese Alessandra
Published: March 2021

With the advent of implant dentistry, height and width of the bone site are fundamental to perform implant placements. There are several techniques to restore the amount of bone loss and one of them is guided bone regeneration, which is based on the employment of a membrane in order to bypass non-osteogenic cell invasion in the bone healing area, dispersing every interference with bone regeneration. Two expert reviewers performed a retrospective evaluation of all scientific papers published by the Implant Retrieval Center Laboratory of University “G. D’Annunzio” of Chieti-Pescara in the last three decades, and they implemented it by also similar conducting research on the main scientific databases, i.e., PubMed, Scopus, and EMBASE. The search was conducted up to December 2020, and a total of 843 articles published by the Implant Retrieval Center Laboratory of University “G.D’Annunzio” of Chieti-Pescara were identified and evaluated. After the application of inclusion and exclusion criteria, a total of 27 manuscripts were included for the qualitative synthesis: 8 animal studies, 17 human studies, and 2 in vitro articles. The present overview shows the importance of translational research for barrier membranes for bone regeneration, and additionally, the need for experts in different fields and research centers to produce high quality data in future research.
Steel Reinforcing Bar and Steel Fibers Content Effect on Tensile and Electrical Behaviors of Strain-Hardening Cement Composite (SHCC) with MWCNTs in Direct Tension
Authors: Kim Dong-Hui , Park Wan-Shin , Kim Sun-Woo , Lee Moon-Sung , Seo Soo-Yeon , Yun Hyun-Do
Published: March 2021

This research examines the influence of an embedded steel reinforcing bar and micro steel fibers on the tensile and electrical properties of polyethylene (PE) fibers reinforced cement composite dumbbell-shaped specimens with multi-walled carbon nanotubes (MWCNTs) in direct tension. The cement composites are reinforced with 0.75 vol.% PE fibers to achieve a strain-hardening performance in direct tension and 1.0 wt % MWCNTs are incorporated to give the electrical conductivity into the cement composites. To investigate the steel bar and steel fibers effect on the electrical behavior of synthetic PE fiber reinforced strain-hardening cement composites (PE-SHCCs), a round bar with a diameter of 4 or 7 mm is placed at the center of specimen’s cross-section. Additionally, steel fibers’ content of 0, 0.5 and 1.0 vol.% are added into the PE-SHCC mixtures. The test result indicates that the addition of steel fibers improves the tensile strength and electrical behavior of synthetic PE fiber reinforced SHCC. The self-sensing ability of PE-SHCC with 1.0% steel fibers is improved by the presence of the embedded steel bar before an initial crack while the reinforced PE-SHCC specimens were less sensitive as the tensile strain increased after the initial crack. The optimal linear regressions between fractional changes in resistivity (FCR) and tensile strain were achieved for PE-SHCC containing 1.0% steel fibers.
Quality Properties of Execution Tracing, an Empirical Study
Authors: Galli Tamas , Chiclana Francisco , Siewe Francois
Published: March 2021

The quality of execution tracing impacts the time to a great extent to locate errors in software components; moreover, execution tracing is the most suitable tool, in the majority of the cases, for doing postmortem analysis of failures in the field. Nevertheless, software product quality models do not adequately consider execution tracing quality at present neither do they define the quality properties of this important entity in an acceptable manner. Defining these quality properties would be the first step towards creating a quality model for execution tracing. The current research fills this gap by identifying and defining the variables, i.e., the quality properties, on the basis of which the quality of execution tracing can be judged. The present study analyses the experiences of software professionals in focus groups at multinational companies, and also scrutinises the literature to elicit the mentioned quality properties. Moreover, the present study also contributes to knowledge with the combination of methods while computing the saturation point for determining the number of the necessary focus groups. Furthermore, to pay special attention to validity, in addition to the the indicators of qualitative research: credibility, transferability, dependability, and confirmability, the authors also considered content, construct, internal and external validity.
An Ontological Approach for Early Detection of Suspected COVID-19 among COPD Patients
Authors: Kouamé Konan-Marcelin , Mcheick Hamid
Published: March 2021

Recent studies on chronic obstructive pulmonary disease (COPD) patients in the context of the coronavirus 19 (COVID-19) pandemic have reported two important problems, i.e., high mortality and vulnerability among COPD patients vs. non-COPD patients. The high number of deaths are caused by exacerbations, COVID-19, and other comorbidities. Therefore, the purpose of this article is to reduce the risk factors of COPD in the COVID-19 context. In this article, we propose approaches based on adaptation mechanisms for detecting COVID-19 symptoms, to better provide appropriate care to COPD patients. To achieve this goal, an ontological model called SuspectedCOPDcoviDOlogy has been created, which consists of five ontologies for detecting suspect cases. These ontologies use vital sign parameters, symptom parameters, service management, and alerts. SuspectedCOPDcoviDOlogy enhances the COPDology proposed by a previous research project in the COPD domain. To validate the solution, an experimental study comparing the results of an existing test for the detection of COVID-19 with the results of the proposed detection system is conducted. Finally, with these results, we conclude that a rigorous combination of detection rules based on the vital sign and symptom parameters can greatly improve the dynamic detection rate of COPD patients suspected of having COVID-19, and therefore enable rapid medical assistance.
Polaron Problems in Ultracold Atoms: Role of a Fermi Sea across Different Spatial Dimensions and Quantum Fluctuations of a Bose Medium
Authors: Tajima Hiroyuki , Takahashi Junichi , Mistakidis Simeon , Nakano Eiji , Iida Kei
Published: March 2021

The notion of a polaron, originally introduced in the context of electrons in ionic lattices, helps us to understand how a quantum impurity behaves when being immersed in and interacting with a many-body background. We discuss the impact of the impurities on the medium particles by considering feedback effects from polarons that can be realized in ultracold quantum gas experiments. In particular, we exemplify the modifications of the medium in the presence of either Fermi or Bose polarons. Regarding Fermi polarons we present a corresponding many-body diagrammatic approach operating at finite temperatures and discuss how mediated two- and three-body interactions are implemented within this framework. Utilizing this approach, we analyze the behavior of the spectral function of Fermi polarons at finite temperature by varying impurity-medium interactions as well as spatial dimensions from three to one. Interestingly, we reveal that the spectral function of the medium atoms could be a useful quantity for analyzing the transition/crossover from attractive polarons to molecules in three-dimensions. As for the Bose polaron, we showcase the depletion of the background Bose-Einstein condensate in the vicinity of the impurity atom. Such spatial modulations would be important for future investigations regarding the quantification of interpolaron correlations in Bose polaron problems.
Piscirickettsia salmonis-Triggered Extracellular Traps Formation as an Innate Immune Response of Atlantic Salmon-Derived Polymorphonuclear Neutrophils
Authors: Alarcon Pablo , Espinosa Gabriel , Millan Catalina , Saravia Julia , Quinteros Vania , Enriquez Ricardo , Henriquez Claudio , Vargas-Chacoff Luis , Burgos Rafael A. , Taubert Anja , Hermosilla Carlos , Morera Francisco J.
Published: March 2021

Extracellular traps (ETs) are webs of DNA, citrullinated histones, anti-microbial peptides, and proteins that were not previously reported in Atlantic salmon (Salmo salar). ETs are mainly released from polymorphonuclear neutrophils (PMN) and are considered a novel PMN-derived effector mechanism against different invasive pathogens. Here, we showed that Atlantic salmon-derived PMN released ETs-like structures in vitro in response to highly pathogenic facultative intracellular rickettsial bacteria Piscirickettsia salmonis. PMN were isolated from pre-smolt Atlantic salmon and stimulated in vitro with oleic acid and P. salmonis. Extracellular DNA was measured using the PicoGreen™ dye, while immunofluorescence image analysis was used to confirm the classical components of salmonid-extruded ETs. Future studies are required to better understand the role of Atlantic salmon-derived ETs orchestrating innate/adaptive immunity and the knowledge on regulation pathways involved in this cell death process. Thus, comprehension of salmonid-derived ETs against P. salmonis might represent novel alternative strategies to improve host innate defense mechanisms of farmed salmon against closely related rickettsial bacteria, as a complement to disease prevention and control strategies.
A New Rise of Non-Human Primate Models of Synucleinopathies
Authors: Teil Margaux , Arotcarena Marie-Laure , Dehay Benjamin
Published: March 2021

Synucleinopathies are neurodegenerative diseases characterized by the presence of α-synuclein-positive intracytoplasmic inclusions in the central nervous system. Multiple experimental models have been extensively used to understand better the mechanisms involved in the pathogenesis of synucleinopathy. Non-human primate (NHP) models are of interest in neurodegenerative diseases as they constitute the highest relevant preclinical model in translational research. They also contribute to bringing new insights into synucleinopathy’s pathogenicity and help in the quest and validation of therapeutical strategies. Here, we reviewed the different NHP models that have recapitulated key characteristics of synucleinopathy, and we aimed to highlight the contribution of NHP in mechanistic and translational approaches for synucleinopathies.
Exosomes as Pleiotropic Players in Pancreatic Cancer
Authors: De Lellis Laura , Florio Rosalba , Di Bella Maria Cristina , Brocco Davide , Guidotti Francesca , Tinari Nicola , Grassadonia Antonino , Lattanzio Rossano , Cama Alessandro , Veschi Serena
Published: March 2021

Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response to current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis is of paramount importance for rational diagnostic and therapeutic approaches. Multiple lines of evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos of bioactive molecules to recipient cells within the tumor microenvironment and systemically. Intriguingly, exosomes may exert both protumor and antitumor effects, supporting or hampering processes that play a role in the pathogenesis and progression of PC, including shifts in tumor metabolism, proliferation, invasion, metastasis, and chemoresistance. They also have a dual role in PC immunomodulation, exerting immunosuppressive or immune enhancement effects through several mechanisms. PC-derived exosomes also induce systemic metabolic alterations, leading to the onset of diabetes and weight loss. Moreover, exosomes have been described as promising diagnostic and prognostic biomarkers for PC. Their potential application in PC therapy as drug carriers and therapeutic targets is under investigation. In this review, we provide an overview of the multiple roles played by exosomes in PC biology through their specific cargo biomolecules and of their potential exploitation in early diagnosis and treatment of PC.
Pipeline Inspection Tests Using a Biomimetic Robot
Authors: Islas-García Elizabeth , Ceccarelli Marco , Tapia-Herrera Ricardo , Torres-SanMiguel Christopher R.
Published: March 2021

This paper presents a biomimetic prototype of a mobile robot that can be used to inspect the subdrainage conditions of pipelines located along different highways in Mexico. Computer-aided design tools have been used to size each of the prototype components as inspired by anatomical spider structure. Springs are integrated to generate proper contact pressure against the pipe walls. The robot locomotion system is implemented with adaptable behaviour for the irregularities of pipelines along its journey. The robot prototype is manufactured in 3D printing with the advantage of having its spare parts easily replaceable. Reported results show internal pipe status through a mini video camera on the top of the robot.
Preclinical Safety Evaluation of Intranasally Delivered Human Mesenchymal Stem Cells in Juvenile Mice
Authors: Aguilera Yolanda , Mellado-Damas Nuria , Olmedo-Moreno Laura , López Víctor , Panadero-Morón Concepción , Benito Marina , Guerrero-Cázares Hugo , Márquez-Vega Catalina , Martín-Montalvo Alejandro , Capilla-González Vivian
Published: March 2021

Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic approach in the management of several pathologies, including central nervous system diseases. Previously, we demonstrated the therapeutic potential of human adipose-derived MSCs for neurological sequelae of oncological radiotherapy using the intranasal route as a non-invasive delivery method. However, a comprehensive investigation of the safety of intranasal MSC treatment should be performed before clinical applications. Here, we cultured human MSCs in compliance with quality control standards and administrated repeated doses of cells into the nostrils of juvenile immunodeficient mice, mimicking the design of a subsequent clinical trial. Short- and long-term effects of cell administration were evaluated by in vivo and ex vivo studies. No serious adverse events were reported on mouse welfare, behavioral performances, and blood plasma analysis. Magnetic resonance study and histological analysis did not reveal tumor formation or other abnormalities in the examined organs of mice receiving MSCs. Biodistribution study reveals a progressive disappearance of transplanted cells that was further supported by an absent expression of human GAPDH gene in the major organs of transplanted mice. Our data indicate that the intranasal application of MSCs is a safe, simple and non-invasive strategy and encourage its use in future clinical trials.
Value of the Lung Immune Prognostic Index in Patients with Non-Small Cell Lung Cancer Initiating First-Line Atezolizumab Combination Therapy: Subgroup Analysis of the IMPOWER150 Trial
Authors: Hopkins Ashley , Kichenadasse Ganessan , Abuhelwa Ahmad , McKinnon Ross , Rowland Andrew , Sorich Michael
Published: March 2021

The lung immune prognostic index (LIPI) is proposed to differentiate prognosis and treatment benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC). There is minimal information on the predictive importance with first-line, combination ICI approaches. In post-hoc analysis of IMpower150, Cox-proportional hazard analysis assessed the association between LIPI groups and overall survival (OS)/progression free survival (PFS). IMpower150 involved chemotherapy-naïve, metastatic non-squamous NSCLC participants randomized atezolizumab-carboplatin-paclitaxel (ACP), bevacizumab-carboplatin-paclitaxel (BCP), or atezolizumab-BCP (ABCP). Good (0 factors), intermediate (1 factor), and poor LIPI (2 factors) were defined via derived neutrophil-to-lymphocyte ratio >3, and lactate dehydrogenase >upper limit of normal. Of 1148 participants, 548 had good, 479 intermediate, and 121 poor LIPI. In 385 participants randomised ABCP, a significant association between LIPI and OS (HR (95%CI): intermediate LIPI = 2.16 (1.47–3.18), poor LIPI = 5.28 (3.20–8.69), p < 0.001) and PFS (HR (95%CI): intermediate LIPI = 1.47 (1.11–1.95), poor LIPI = 3.02 (2.03–4.50), p < 0.001) was identified. Median OS was 24, 16, and 7 months for good, intermediate, and poor LIPI, respectively. ACP associations were similar. Relative OS treatment effect (HR 95%CI) of ABCP vs. BCP was 0.78 (0.53–1.15), 0.67 (0.49–0.91), and 0.87 (0.51–1.47) for the good, intermediate, and poor LIPI groups, respectively (P(interaction) = 0.66), with no benefit in median OS observed in the poor LIPI group. LIPI identified subgroups with significantly different survival following ABCP and ACP initiation for chemotherapy-naïve, metastatic non-squamous NSCLC. There was insufficient evidence that LIPI identifies patients unlikely to benefit from ABCP treatment.
Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study
Authors: Choi In Young , Chun Sohyun , Shin Dong Wook , Han Kyungdo , Jeon Keun Hye , Yu Jonghan , Chae Byung Joo , Suh Mina , Park Yong-Moon
Published: March 2021

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.
Combined De-Repression of Chemoresistance Associated Mitogen-Activated Protein Kinase 14 and Activating Transcription Factor 2 by Loss of microRNA-622 in Hepatocellular Carcinoma
Authors: Fritz Valerie , Malek Lara , Gaza Anne , Wormser Laura , Appel Majken , Kremer Andreas E. , Thasler Wolfgang E. , Siebler Jürgen , Neurath Markus F. , Hellerbrand Claus , Bosserhoff Anja K. , Dietrich Peter
Published: March 2021

Chemoresistance is a major hallmark driving the progression and poor prognosis of hepatocellular carcinoma (HCC). Limited chemoresponse of HCC was demonstrated to be mediated by mitogen-activated protein kinase 14 (MAPK14) and activating transcription factor 2 (ATF2). Recently, we have demonstrated loss of control of RAS-RAF-ERK-signaling as a consequence of miR-622 downregulation in HCC. However, the majority of target genes of this potent tumorsuppressive microRNA had remained elusive. The MAPK14-ATF2-axis represents a collateral pathway ensuring persisting ERK-activation in the presence of sorafenib-mediated RAF-inhibition. In contrast to the function of the MAPK14-ATF2-axis, both the expression and regulation of MAPK14 and ATF2 in human HCC remained to be clarified. We found combined overexpression of MAPK14 and ATF2 in human HCC cells, tissues and in sorafenib resistant cell lines. High expression of MAPK14 and ATF2 was associated with reduced overall survival in HCC patients. Deciphering the molecular mechanism promoting combined upregulation of MAPK14 and ATF2 in HCC, we revealed that miR-622 directly targets both genes, resulting in combined de-repression of the MAPK14-ATF2-axis. Together, miR-622 represents a superior regulator of both RAS-RAF-ERK as well as MAPK14-ATF2-signaling pathways in liver cancer.
New Insights into the Significance of PARP-1 Activation: Flow Cytometric Detection of Poly(ADP-Ribose) as a Marker of Bovine Intramammary Infection
Authors: De Matteis Giovanna , Grandoni Francesco , Zampieri Michele , Reale Anna , Scatà Maria Carmela
Published: March 2021

Bovine intramammary infections are common diseases affecting dairy cattle worldwide and represent a major focus of veterinary research due to financial losses and food safety concerns. The identification of new biomarkers of intramammary infection, useful for monitoring the health of dairy cows and wellness verification, represents a key advancement having potential beneficial effects on public health. In vitro experiments using bovine peripheral blood mononuclear cells (PBMC), stimulated with the bacterial endotoxin lipopolysaccharide (LPS) enabled a flow cytometric assay in order to evaluate in vivo poly-ADP-ribose (PAR) levels. Results showed a significant increase of PAR after 1 h of treatment, which is consistent with the involvement of PARP activity in the inflammatory response. This study investigated PARP-1 activation in leukocyte subpopulations from bovine milk samples during udder infection. A flow cytometric assay was, therefore, performed to evaluate the PAR content in milk leukocyte subsets of cows with and without intramammary infection (IMI). Results showed that milk lymphocytes and macrophages isolated from cows with IMI had a significant increase of PAR content compared to uninfected samples. These results suggest mastitis as a new model for the study of the role of PARP in zoonotic inflammatory diseases, opening a new perspective to the “One Health” approach.
The Role of IL-9 Polymorphisms and Serum IL-9 Levels in Carcinogenesis and Survival Rate for Laryngeal Squamous Cell Carcinoma
Authors: Pasvenskaite Agne , Liutkeviciene Rasa , Gedvilaite Greta , Vilkeviciute Alvita , Liutkevicius Vykintas , Uloza Virgilijus
Published: March 2021

Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients’ five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients’ survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.
Cytokine Profile in Plasma Extracellular Vesicles of Parkinson’s Disease and the Association with Cognitive Function
Authors: Chan Lung , Chung Chen-Chih , Chen Jia-Hung , Yu Ruan-Ching , Hong Chien-Tai
Published: March 2021

Plasma extracellular vesicles (EVs) containing various molecules, including cytokines, can reflect the intracellular condition and participate in cell-to-cell signaling, thus emerging as biomarkers for Parkinson’s disease (PD). Inflammation may be a crucial risk factor for PD development and progression. The present study investigated the role of plasma EV cytokines as the biomarkers of PD. This cross-sectional study recruited 113 patients with PD, with mild to moderate stage disease, and 48 controls. Plasma EVs were isolated, and the levels of cytokines, including pro-interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1β and TNF-α levels compared with controls after adjustment for age and sex. Despite the lack of a significant association between plasma EV cytokines and motor symptom severity in patients with PD, cognitive dysfunction severity, assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment, was significantly associated with plasma EV pro-IL-1β, IL-6, IL-10, and TNF-α levels. This association was PD specific and not found in controls. Furthermore, patients with PD cognitive deficit (MMSE < 26) exhibited a distinguished EV cytokine profile compared to those without cognitive deficit. The findings support the concept of inflammatory pathogenesis in the development and progression of PD and indicate that plasma EV cytokines may serve as PD biomarkers in future.
The Role of Cytokines and Chemokines in Shaping the Immune Microenvironment of Glioblastoma: Implications for Immunotherapy
Authors: Yeo Erica C. F. , Brown Michael P. , Gargett Tessa , Ebert Lisa M.
Published: March 2021

Glioblastoma is the most common form of primary brain tumour in adults. For more than a decade, conventional treatment has produced a relatively modest improvement in the overall survival of glioblastoma patients. The immunosuppressive mechanisms employed by neoplastic and non-neoplastic cells within the tumour can limit treatment efficacy, and this can include the secretion of immunosuppressive cytokines and chemokines. These factors can play a significant role in immune modulation, thus disabling anti-tumour responses and contributing to tumour progression. Here, we review the complex interplay between populations of immune and tumour cells together with defined contributions by key cytokines and chemokines to these intercellular interactions. Understanding how these tumour-derived factors facilitate the crosstalk between cells may identify molecular candidates for potential immunotherapeutic targeting, which may enable better tumour control and improved patient survival.
Adsorption of Polymer-Grafted Nanoparticles on Curved Surfaces
Authors: Ozmaian Aye , Coalson Rob D. , Ozmaian Masoumeh
Published: March 2021

Nanometer-curved surfaces are abundant in biological systems as well as in nano-sized technologies. Properly functionalized polymer-grafted nanoparticles (PGNs) adhere to surfaces with different geometries and curvatures. This work explores some of the energetic and mechanical characteristics of the adhesion of PGNs to surfaces with positive, negative and zero curvatures using Coarse-Grained Molecular Dynamics (CGMD) simulations. Our calculated free energies of binding of the PGN to the curved and flat surfaces as a function of separation distance show that curvature of the surface critically impacts the adhesion strength. We find that the flat surface is the most adhesive, and the concave surface is the least adhesive surface. This somewhat counterintuitive finding suggests that while a bare nanoparticle is more likely to adhere to a positively curved surface than a flat surface, grafting polymer chains to the nanoparticle surface inverts this behavior. Moreover, we studied the rheological behavior of PGN upon separation from the flat and curved surfaces under external pulling force. The results presented herein can be exploited in drug delivery and self-assembly applications.