bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Printed Porous Titanium Screw with Bioactive Surface Modification for Bone–Tendon Healing: A Rabbit Animal Model
Authors: Huang Yu-Min , Huang Chih-Chieh , Tsai Pei-I , Yang Kuo-Yi , Huang Shin-I , Shen Hsin-Hsin , Lai Hong-Jen , Huang Shu-Wei , Chen San-Yuan , Lin Feng-Huei , Chen Chih-Yu
Published: May 2020

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.
Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole
Authors: Stryjska Karolina , Radko Lidia , Chęcińska Lilianna , Kusz Joachim , Posyniak Andrzej , Ochocki Justyn
Published: May 2020

Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = NO3− (1), ClO4− (2)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, 1H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.
FAK Family Kinases in Vascular Diseases
Authors: Murphy James M. , Jeong Kyuho , Lim Ssang-Taek Steve
Published: May 2020

In various vascular diseases, extracellular matrix (ECM) and integrin expression are frequently altered, leading to focal adhesion kinase (FAK) or proline-rich tyrosine kinase 2 (Pyk2) activation. In addition to the major roles of FAK and Pyk2 in regulating adhesion dynamics via integrins, recent studies have shown a new role for nuclear FAK in gene regulation in various vascular cells. In particular, FAK primarily localizes within the nuclei of vascular smooth muscle cells (VSMCs) of healthy arteries. However, vessel injury increased FAK localization back to adhesions and elevated FAK activity, leading to VSMC hyperplasia. The study suggested that abnormal FAK or Pyk2 activation in vascular cells may cause pathology in vascular diseases. Here we will review several studies of FAK and Pyk2 associated with integrin signaling in vascular diseases including restenosis, atherosclerosis, heart failure, pulmonary arterial hypertension, aneurysm, and thrombosis. Despite the importance of FAK family kinases in vascular diseases, comprehensive reviews are scarce. Therefore, we summarized animal models involving FAK family kinases in vascular diseases.
Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion
Authors: Boggia Raffaella , Turrini Federica , Roggeri Alessandra , Olivero Guendalina , Cisani Francesca , Bonfiglio Tommaso , Summa Maria , Grilli Massimo , Caviglioli Gabriele , Alfei Silvana , Zunin Paola , Bertorelli Rosalia , Pittaluga Anna
Published: May 2020

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.
The Role of High-Density Lipoproteins in Endothelial Cell Metabolism and Diabetes-Impaired Angiogenesis
Authors: Primer Khalia R. , Psaltis Peter J. , Tan Joanne T.M. , Bursill Christina A.
Published: May 2020

Diabetes mellitus affects millions of people worldwide and is associated with devastating vascular complications. A number of these complications, such as impaired wound healing and poor coronary collateral circulation, are characterised by impaired ischaemia-driven angiogenesis. There is increasing evidence that high-density lipoproteins (HDL) can rescue diabetes-impaired angiogenesis through a number of mechanisms, including the modulation of endothelial cell metabolic reprogramming. Endothelial cell metabolic reprogramming in response to tissue ischaemia is a driver of angiogenesis and is dysregulated by diabetes. Specifically, diabetes impairs pathways that allow endothelial cells to upregulate glycolysis in response to hypoxia adequately and impairs suppression of mitochondrial respiration. HDL rescues the impairment of the central hypoxia signalling pathway, which regulates these metabolic changes, and this may underpin several of its known pro-angiogenic effects. This review discusses the current understanding of endothelial cell metabolism and how diabetes leads to its dysregulation whilst examining the various positive effects of HDL on endothelial cell function.
KRAB-Induced Heterochromatin Effectively Silences PLOD2 Gene Expression in Somatic Cells and Is Resilient to TGFβ1 Activation
Authors: Gjaltema Rutger A. F. , Goubert Désirée , Huisman Christian , Pilar García Tobilla Consuelo del , Koncz Mihály , Jellema Pytrick G. , Wu Dandan , Brouwer Uilke , Kiss Antal , Verschure Pernette J. , Bank Ruud A. , Rots Marianne G.
Published: May 2020

Epigenetic editing, an emerging technique used for the modulation of gene expression in mammalian cells, is a promising strategy to correct disease-related gene expression. Although epigenetic reprogramming results in sustained transcriptional modulation in several in vivo models, further studies are needed to develop this approach into a straightforward technology for effective and specific interventions. Important goals of current research efforts are understanding the context-dependency of successful epigenetic editing and finding the most effective epigenetic effector(s) for specific tasks. Here we tested whether the fibrosis- and cancer-associated PLOD2 gene can be repressed by the DNA methyltransferase M.SssI, or by the non-catalytic Krüppel associated box (KRAB) repressor directed to the PLOD2 promoter via zinc finger- or CRISPR-dCas9-mediated targeting. M.SssI fusions induced de novo DNA methylation, changed histone modifications in a context-dependent manner, and led to 50%–70% reduction in PLOD2 expression in fibrotic fibroblasts and in MDA-MB-231 cancer cells. Targeting KRAB to PLOD2 resulted in the deposition of repressive histone modifications without DNA methylation and in almost complete PLOD2 silencing. Interestingly, both long-term TGFβ1-induced, as well as unstimulated PLOD2 expression, was completely repressed by KRAB, while M.SssI only prevented the TGFβ1-induced PLOD2 expression. Targeting transiently expressed dCas9-KRAB resulted in sustained PLOD2 repression in HEK293T and MCF-7 cells. Together, these findings point to KRAB outperforming DNA methylation as a small potent targeting epigenetic effector for silencing TGFβ1-induced and uninduced PLOD2 expression.
Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts
Authors: Morabito Caterina , Guarnieri Simone , Cucina Alessandra , Bizzarri Mariano , Mariggiò Maria A.
Published: May 2020

The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant—the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis.
Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein but not α-fetoprotein as a Long-Term Hepatocellular Carcinoma Predictor
Authors: Osawa Leona , Tamaki Nobuharu , Kurosaki Masayuki , Kirino Sakura , Watakabe Keiya , Wang Wan , Okada Mao , Shimizu Takao , Higuchi Mayu , Takaura Kenta , Takada Hitomi , Kaneko Shun , Yasui Yutaka , Tsuchiya Kaoru , Nakanishi Hiroyuki , Itakura Jun , Takahashi Yuka , Enomoto Nobuyuki , Izumi Namiki
Published: May 2020

Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 ± 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA±M2BP) ≥ 1.85 and α-fetoprotein (AFP) ≥ 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA±M2BP ≥ 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68–205) but not AFP. Among patients with WFA±M2BP ≥ 1.85 at SVR24, 42% had WFA±M2BP < 1.85 at 1 year after SVR24 (WFA±M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA±M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC.
Structural Mechanisms of Store-Operated and Mitochondrial Calcium Regulation: Initiation Points for Drug Discovery
Authors: Noble Megan , Lin Qi-Tong , Sirko Christian , Houpt Jacob A. , Novello Matthew J. , Stathopulos Peter B.
Published: May 2020

Calcium (Ca2+) is a universal signaling ion that is essential for the life and death processes of all eukaryotes. In humans, numerous cell stimulation pathways lead to the mobilization of sarco/endoplasmic reticulum (S/ER) stored Ca2+, resulting in the propagation of Ca2+ signals through the activation of processes, such as store-operated Ca2+ entry (SOCE). SOCE provides a sustained Ca2+ entry into the cytosol; moreover, the uptake of SOCE-mediated Ca2+ by mitochondria can shape cytosolic Ca2+ signals, function as a feedback signal for the SOCE molecular machinery, and drive numerous mitochondrial processes, including adenosine triphosphate (ATP) production and distinct cell death pathways. In recent years, tremendous progress has been made in identifying the proteins mediating these signaling pathways and elucidating molecular structures, invaluable for understanding the underlying mechanisms of function. Nevertheless, there remains a disconnect between using this accumulating protein structural knowledge and the design of new research tools and therapies. In this review, we provide an overview of the Ca2+ signaling pathways that are involved in mediating S/ER stored Ca2+ release, SOCE, and mitochondrial Ca2+ uptake, as well as pinpoint multiple levels of crosstalk between these pathways. Further, we highlight the significant protein structures elucidated in recent years controlling these Ca2+ signaling pathways. Finally, we describe a simple strategy that aimed at applying the protein structural data to initiating drug design.
Development of 3D Hepatic Constructs Within Polysaccharide-Based Scaffolds with Tunable Properties
Authors: Labour Marie-Noëlle , Le Guilcher Camile , Aid-Launais Rachida , El Samad Nour , Lanouar Soraya , Simon-Yarza Teresa , Letourneur Didier
Published: May 2020

Organoids production is a key tool for in vitro studies of physiopathological conditions, drug-induced toxicity assays, and for a potential use in regenerative medicine. Hence, it prompted studies on hepatic organoids and liver regeneration. Numerous attempts to produce hepatic constructs had often limited success due to a lack of viability or functionality. Moreover, most products could not be translated for clinical studies. The aim of this study was to develop functional and viable hepatic constructs using a 3D porous scaffold with an adjustable structure, devoid of any animal component, that could also be used as an in vivo implantable system. We used a combination of pharmaceutical grade pullulan and dextran with different porogen formulations to form crosslinked scaffolds with macroporosity ranging from 30 µm to several hundreds of microns. Polysaccharide scaffolds were easy to prepare and to handle, and allowed confocal observations thanks to their transparency. A simple seeding method allowed a rapid impregnation of the scaffolds with HepG2 cells and a homogeneous cell distribution within the scaffolds. Cells were viable over seven days and form spheroids of various geometries and sizes. Cells in 3D express hepatic markers albumin, HNF4α and CYP3A4, start to polarize and were sensitive to acetaminophen in a concentration-dependant manner. Therefore, this study depicts a proof of concept for organoid production in 3D scaffolds that could be prepared under GMP conditions for reliable drug-induced toxicity studies and for liver tissue engineering.
Roles of Actin in the Morphogenesis of the Early Caenorhabditis elegans Embryo
Authors: Samandar Eweis Dureen , Plastino Julie
Published: May 2020

The cell shape changes that ensure asymmetric cell divisions are crucial for correct development, as asymmetric divisions allow for the formation of different cell types and therefore different tissues. The first division of the Caenorhabditis elegans embryo has emerged as a powerful model for understanding asymmetric cell division. The dynamics of microtubules, polarity proteins, and the actin cytoskeleton are all key for this process. In this review, we highlight studies from the last five years revealing new insights about the role of actin dynamics in the first asymmetric cell division of the early C. elegans embryo. Recent results concerning the roles of actin and actin binding proteins in symmetry breaking, cortical flows, cortical integrity, and cleavage furrow formation are described.
Differential ESR1 Promoter Methylation in the Peripheral Blood—Findings from the Women 40+ Healthy Aging Study
Authors: Gardini Elena S. , Chen Gary G. , Fiacco Serena , Mernone Laura , Willi Jasmine , Turecki Gustavo , Ehlert Ulrike
Published: May 2020

Background Estrogen receptor α (ERα) contributes to maintaining biological processes preserving health during aging. DNA methylation changes of ERα gene (ESR1) were established as playing a direct role in the regulation of ERα levels. In this study, we hypothesized decreased DNA methylation of ESR1 associated with postmenopause, lower estradiol (E2) levels, and increased age among healthy middle-aged and older women. Methods We assessed DNA methylation of ESR1 promoter region from dried blood spots (DBSs) and E2 from saliva samples in 130 healthy women aged 40–73 years. Results We found that postmenopause and lower E2 levels were associated with lower DNA methylation of a distal regulatory region, but not with DNA methylation of proximal promoters. Conclusion Our results indicate that decreased methylation of ESR1 cytosine-phosphate-guanine island (CpGI) shore may be associated with conditions of lower E2 in older healthy women.
Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy
Authors: Cecconi Maurizio , Piovani Daniele , Brunetta Enrico , Aghemo Alessio , Greco Massimiliano , Ciccarelli Michele , Angelini Claudio , Voza Antonio , Omodei Paolo , Vespa Edoardo , Pugliese Nicola , Parigi Tommaso Lorenzo , Folci Marco , Danese Silvio , Bonovas Stefanos
Published: May 2020

We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802–0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.
Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis
Authors: Na Hee Sam , Kim Si Yeong , Han Hyejung , Kim Hyun-Joo , Lee Ju-Youn , Lee Jae-Hyung , Chung Jin
Published: May 2020

Periodontitis is a chronic and multifactorial inflammatory disease that can lead to tooth loss. At present, the diagnosis for periodontitis is primarily based on clinical examination and radiographic parameters. Detecting the periodontal pathogens at the subgingival plaque requires skilled professionals to collect samples. Periodontal pathogens are also detected on various mucous membranes in patients with periodontitis. In this study, we characterized the oral microbiome profiles from buccal mucosa and supragingival space in a total of 272 healthy subjects as a control group, and periodontitis patients as a disease group. We identified 13 phyla, 193 genera, and 527 species and determined periodontitis-associated taxa. Porphyromonas gingivalis, Tannerella forsythia, Treponema denticolar, Filifactor alocis, Porphyromonas endodontalis, Fretibacterium fastiosum and Peptostreptococcus species were significantly increased in both the buccal mucosa and the supragingival space in periodontitis patients. The identified eight periodontitis-associated bacterial species were clinically validated in an independent cohort. We generated the prediction model based on the oral microbiome profiles using five machine learning algorithms, and validated its capability in predicting the status of patients with periodontitis. The results showed that the oral microbiome profiles from buccal mucosa and supragingival space can represent the microbial composition of subgingival plaque and further be utilized to identify potential microbial biomarkers for the diagnosis of periodontitis. Besides, bacterial community interaction network analysis found distinct patterns associated with dysbiosis in periodontitis. In summary, we have identified oral bacterial species from buccal and supragingival sites which can predict subgingival bacterial composition and can be used for early diagnosis of periodontitis. Therefore, our study provides an important basis for developing easy and noninvasive methods to diagnose and monitor periodontitis.
Analgesic Efficacy of Melatonin: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials
Authors: Oh Si Nae , Myung Seung-Kwon , Jho Hyun Jung
Published: May 2020

Previous systematic reviews and meta-analyses of randomized controlled trials have reported controversial findings regarding the effects of melatonin on pain reduction. The aim of this study was to evaluate the efficacy of melatonin on pain among adults using a meta-analysis of randomized, double-blind, placebo-controlled trials (RDBPCTs). PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles were searched up to February 2020. Two of the authors independently evaluated eligibility of the studies based on the pre-determined criteria and extracted data. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) for the pain score change were calculated using a random-effects meta-analysis. Out of 463 that met the initial criteria, a total of 30 trials, which involved 1967 participants with 983 in an intervention group and 984 in a control group, were included in the final analysis. In a random-effects meta-analysis, the use of melatonin reduced chronic pain in all the trials (5 studies, SMD −0.65, 95% CI −0.96 to −0.34, I2 = 57.2%) and high-quality trials (4 studies, SMD −0.62, 95% CI −1.01 to −0.23, I2 = 49.3%). Moreover, the use of melatonin significantly reduced acute postoperative pain (11 studies, SMD −0.82, 95% CI −1.40 to −0.25, I2 = 93.0%). However, the subgroup meta-analysis of high-quality RDBPCTs showed no significant association between them (6 studies, SMD −0.21, 95 % CI −0.66 to 0.24, I2 = 82.4%). The current study suggests that melatonin might be used in treatment of chronic pain, while there is no sufficient evidence for acute postoperative or procedural pain. Further trials are warranted to confirm its analgesic effect.
Interleukin-15 as a Biomarker Candidate of Rheumatoid Arthritis Development
Authors: Kurowska Weronika , Przygodzka Malgorzata , Jakubaszek Michal , Kwiatkowska Brygida , Maslinski Wlodzimierz
Published: May 2020

There is a need for definite diagnosis of rheumatoid arthritis (RA) at its earliest stages of development in order to introduce early and effective treatment. Here we assessed whether serum interleukin-15 (IL-15) can serve as a new biomarker of RA development in patients with undifferentiated arthritis (UA). Interleukin-15, IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) were measured in UA patients at inclusion. Six months later, the diagnosis was re-evaluated, and statistical analysis was performed. We found that at the UA stage, IL-15 was more prevalent in patients who progressed to RA than RF or anti-CCP Abs (83.3% vs. 61.1% and 66.7%, respectively). Interleukin-15 showed higher sensitivity (77.8%) than both autoantibodies and higher specificity (80.9%) than anti-CCP Abs in identification of UA patients who developed RA. The diagnostic utility of IL-15 was comparable to that of RF (AUC: 0.814 vs. 0.750, p > 0.05), but higher than that of anti-CCP Abs (AUC: 0.814 vs. 0.684, p = 0.04). The combined use of IL-15, RF and anti-CCP Abs yielded higher diagnostic accuracy for RA than autoantibodies determination only. Our results indicate that IL-15 can be used as a biomarker of RA development in patients with UA.
Heme Oxygenase-1 in Central Nervous System Malignancies
Authors: Sferrazzo Giuseppe , Di Rosa Michelino , Barone Eugenio , Li Volti Giovanni , Musso Nicolò , Tibullo Daniele , Barbagallo Ignazio
Published: May 2020

Central nervous system tumors are the most common pediatric solid tumors and account for 20–25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas.
Do Centenarians Die Healthier than Younger Elders? A Comparative Epidemiological Study in Spain
Authors: Clerencia-Sierra Mercedes , Ioakeim-Skoufa Ignatios , Poblador-Plou Beatriz , González-Rubio Francisca , Aza-Pascual-Salcedo Mercedes , Machón Mónica , Gimeno-Miguel Antonio , Prados-Torres Alexandra
Published: May 2020

This study aims to describe the clinical course, drug use, and health services use characteristics during the last year of life of elders who die being centenarians and to identify key aspects differentiating them from elders who die at an earlier age, with a particular focus on sex differences. We conducted an observational, population-based study in the EpiChron Cohort (Aragón, Spain). The population was stratified by sex and into three age sub-populations (80–89, 90–99, and ≥100 years), and their characteristics were described and compared. Multimorbidity was the rule in our elders, affecting up to 3 in 4 centenarians and 9 in 10 octogenarians and nonagenarians. Polypharmacy was also observed in half of the centenarian population and in most of the younger elders. Risk factors for cardiovascular disease (i.e., hypertension, dyslipidaemia, diabetes), cerebrovascular disease and dementia were amongst the most common chronic conditions in all age groups, whereas the gastroprotective drugs and antithrombotic agents were the most dispensed drugs. Centenarians presented in general lower morbidity and treatment burden and lower use of both primary and hospital healthcare services than octogenarians and nonagenarians, suggesting a better health status. Sex-differences in their clinical characteristics were more striking in octogenarians and tended to decrease with age.
Experimental Investigation on Small-Strain Stiffness of Marine Silty Sand
Authors: Wu Qi , Lu Qingrui , Guo Qizhou , Zhao Kai , Chen Pen , Chen Guoxing
Published: May 2020

The significance of small-strain stiffness (Gmax) of saturated composite soils are still of great concern in practice, due to the complex influence of fines on soil fabric. This paper presents an experimental investigation conducted through comprehensive bender element tests on Gmax of marine silty sand. Special attention is paid to the influence of initial effective confining pressure ( σ c 0 ′ ), global void ratio (e) and fines content (FC) on Gmax of a marine silty sand. The results indicate that under otherwise similar conditions, Gmax decreases with decreasing e or FC, but decreases with increasing FC. In addition, the reduction rate of Gmax with e increasing is not sensitive to σ c 0 ′ , but obviously sensitive to changes in FC. The equivalent skeleton void ratio (e*) is introduced as an alternative state index for silty sand with various FC, based on the concept of binary packing material. Remarkably, the Hardin model is modified with the new state index e*, allowing unified characterization of Gmax values for silty sand with various FC, e, and σ c 0 ′ . Independent test data for different silty sand published in the literature calibrate the applicability of this proposed model.
A UAV-Based Dye-Tracking Technique to Measure Surface Velocities over Tidal Channels and Salt Marshes
Authors: Pinton Daniele , Canestrelli Alberto , Fantuzzi Luca
Published: May 2020

An accurate description of hydrodynamic processes in coastal wetlands is needed to improve their management and conservation. As a consequence, higher knowledge of the connected morphological and ecologic processes is achievable. However, it is very costly to collect spatially distributed values of flow velocities over tidal channels and intertidal areas by means of in situ sensors. Also, when deploying sensors, humans perturb the ecosystem, which takes time to recover. In this study, a new low-cost unmanned aerial vehicle (UAV)-based method to measure surface velocities is proposed and validated. The study area is a salt marsh system on the southeast coast of Little Sapelo Island, Georgia, USA. Two unmanned aerial vehicles were used in the survey. A first UAV released a fluorescent dye tracer on marshes and tidal creeks, while a second one tracked its movement by collecting RGB images. Flow direction and magnitude were calculated from the images using a newly developed algorithm. A comparison with velocities measured with an acoustic Doppler current profiler confirmed the effectiveness of the method. Our results indicate that the calculated flow field is affected by vegetation, marsh morphology, and marsh width. In particular, a non-negligible velocity component perpendicular to the creek axes is detected both in ebb and in flood. Our technique proves to be an effective, non-intrusive, low-cost way to survey the two-dimensional hydrodynamics on salt marsh environments at a km scale. Collected data would be beneficial for calibrating and validating numerical models with accurate water flux information.
Historical-Genetic Features in Rural Settlement System: A Case Study from Mogilev District (Mogilev Oblast, Belarus)
Authors: Gorbenkova Elena , Shcherbina Elena
Published: May 2020

Settlement system development is currently one of the basic objectives in land use planning, which is significant for Belarus, as it is the most urbanized country in the European region. Historical-genetic analysis is the most effective approach for studying the transformational changes in settlement systems. The research was aimed at analyzing the transformation peculiarities in the rural settlement system of Belarus. The core of the methodological basis lies in general scientific methods (systematic approach, historicism approach, historical-genetic method) and special interdisciplinary methods (cartographic analysis using GIS software). Historical-genetic analysis made it possible to identify the most significant historical periods in the formation of the rural settlement system in Belarus: pre-revolutionary, Soviet and recent. For each period, the pattern and spatial configuration of the rural settlement system were analyzed. Spatial changes in settlement pattern were highlighted: polarization, increasing the share and the population number of the “largest” settlements, the decreasing of “large” and “medium-sized” settlements and the degradation of “small” settlements. As a result, two types of rural settlement transformation were identified: “development” and “degradation”. Three ways of spatial configuration of the rural settlement system were identified: “relocation to city”, “relocation to the center of the settlement system” and “relocation to settlement”. Directions for future research are linked with conceptualizing the model of the spatial–territorial organizing of the rural settlement system.
Land Cover and Land Use Change in the US Prairie Pothole Region Using the USDA Cropland Data Layer
Authors: Alemu Woubet G. , Henebry Geoffrey M. , Melesse Assefa M.
Published: May 2020

The Prairie Pothole Region (PPR) is a biotically important region of grassland, wetland, and cropland that traverses the Canada-US border. Significant amounts of grasslands and wetlands within the PPR have been converted to croplands in recent years due to increasing demand for biofuels. We characterized land dynamics across the US portion of the PPR (US–PPR) using the USDA Crop Data Layer (CDL) for 2006–2018. We also conducted a comparative analysis between two epochs (1998–2007 & 2008–2017) of the CDL data time series in the North Dakotan portion of the US–PPR. The CDL revealed the western parts of the US–PPR have been dominated by grass/pasture, to the north it was spring wheat, to the east and southern half, soybeans dominated, and to the south it was corn (maize). Nonparametric trend analysis on the major crop and land cover types revealed statistically significant net decreases in the grass/pasture class between 2006 and 2018, which accounts for more than a quarter of grass/pasture area within the US–PPR. Other crops experiencing significant decreases included sunflower (-5%), winter wheat (-3%), spring wheat (-2%), and durum wheat (-1%). The combined coverage of corn and soybeans exhibited significant net increases in 23.5% of its cover; whereas, the individual significant net increases were 5% for corn and 11% for soybeans. Hotspots of increase in corn and soybeans were distributed across North and South Dakota. Other crop/land covers with huge significant increases include other hay/non-alfalfa (15%), and alfalfa (11%), which appear to be associated with the sharp increase in larger dairy operations, mostly in Minnesota. Wetland area increased 5% in the US–PPR, due to increased precipitation as well as inundation associated with Devils Lake in North Dakota. Hotspots of decreasing grass/pasture area were evident across the study area. Comparative trend analysis of two epochs (1998–2007 vs. 2008–2017) in North Dakota revealed that grass/pasture cover showed a negligible net trend (-0.3 %) between 1998 and 2007; whereas, there was a statistically significant decrease of more than 30% between 2008 and 2017. Combined coverage of corn and soybeans experienced statistically significant net increases in both epochs: 11% greater during 1998–2007 and 17% greater during 2008–2017. Recent sharp losses of grasslands and smaller wetlands combined the expansion of corn, soybeans, and alfalfa bode ill for wildlife habitat and require a re-examination of agricultural and energy policies that have encouraged these land transitions.
Exercise Training, Intermittent Fasting and Alkaline Supplementation as an Effective Strategy for Body Weight Loss: A 12-Week Placebo-Controlled Double-Blind Intervention with Overweight Subjects
Authors: Hottenrott Kuno , Werner Tanja , Hottenrott Laura , Meyer Till P. , Vormann Jürgen
Published: May 2020

Background: Intermittent fasting (IF) combined with exercise has been suggested to enhance weight loss. However, both procedures might negatively influence acid–base status. The aim of this study was to determine the combined effects of IF, exercise training and alkaline supplementation in overweight subjects on body composition and running performance. Methods: 80 overweight subjects of age 45.5 ± 7.8 years were assigned to IF or non-intermittent fasting (nIF). Furthermore, subjects were randomly assigned to take either an alkaline supplement (IF-v, nIF-v) or a placebo (IF-p, nIF-p) twice a day. All subjects performed a personalized endurance exercise program (3–4 times/week for 12 weeks). Body weight, body composition, running performance and acid–base parameters were determined before (pre) and after the 12-week program (post). Results: 68 participants completed the study. There was a significant effect on body weight loss, body fat loss, visceral fat loss and running performance enhancement in all groups (p < 0.01) for pre and post measurements. Body weight decreased in all groups (IF-p: −5.80 ± 0.77 kg and nIF-p: −3.40 ± 0.58 kg; IF-v: −8.28 ± 0.75 kg and nIF-v: −5.59 ± 0.87 kg). In both dietary strategies, weight loss was significantly further enhanced by alkaline supplementation. The increase in running velocity was significantly higher in IF combined with alkaline supplementation (IF-v 1.73 ± 0.23 km/h and IF-p 0.97 ± 0.20 km/h). In addition, alkaline supplementation increased plasma HCO3− concentration and urinary pH. Conclusion: Exercise training in combination with IF and alkaline supplementation is an effective strategy to reduce body weight and improve running performance in a 12-week intervention.
Selecting the Low-Carbon Tourism Destination: Based on Pythagorean Fuzzy Taxonomy Method
Authors: Wei Guiwu , Tang Yanxin , Zhao Mengwei , Lin Rui , Wu Jiang
Published: May 2020

Low-carbon tourism plays the increasingly significant role in carbon emission reduction and natural environmental protection. The choice of low-carbon tourist destination (LCTD) often involves the multiple attributes or criteria and can be regarded as the corresponding multiple attribute group decision making (MAGDM) issues. Since the Pythagorean fuzzy sets (PFSs) could well depict uncertain information or fuzzy information and cope with the LCTD selection, thus this essay develops a framework to tackle such MAGDM issues under the Pythagorean fuzzy environment. In this essay, due to few methods can compare with different alternatives along with their advantages from designed attributes, therefore, to overcome this challenge, the taxonomy method is utilized to integrate with PFSs. What’s more, the entropy method is also utilized to determine the attribute weights. Eventually, an application related to LCTD selection and some comparative analysis have been given to demonstrate the superiority of the designed method. The results illustrate that the designed framework is useful for identifying optimal tourist destination among the potential tourist destinations.
Efficient Breadth-First Reduct Search
Authors: Boonjing Veera , Chanvarasuth Pisit
Published: May 2020

This paper formulates the problem of determining all reducts of an information system as a graph search problem. The search space is represented in the form of a rooted graph. The proposed algorithm uses a breadth-first search strategy to search for all reducts starting from the graph root. It expands nodes in breadth-first order and uses a pruning rule to decrease the search space. It is mathematically shown that the proposed algorithm is both time and space efficient.
Market Volatility of the Three Most Powerful Military Countries during Their Intervention in the Syrian War
Authors: Naimy Viviane , Montero José-María , El Khoury Rim , Maalouf Nisrine
Published: May 2020

This paper analyzes the volatility dynamics in the financial markets of the (three) most powerful countries from a military perspective, namely, the U.S., Russia, and China, during the period 2015–2018 that corresponds to their intervention in the Syrian war. As far as we know, there is no literature studying this topic during such an important distress period, which has had very serious economic, social, and humanitarian consequences. The Generalized Autoregressive Conditional Heteroscedasticity (GARCH (1, 1)) model yielded the best volatility results for the in-sample period. The weighted historical simulation produced an accurate value at risk (VaR) for a period of one month at the three considered confidence levels. For the out-of-sample period, the Monte Carlo simulation method, based on student t-copula and peaks-over-threshold (POT) extreme value theory (EVT) under the Gaussian kernel and the generalized Pareto (GP) distribution, overstated the risk for the three countries. The comparison of the POT-EVT VaR of the three countries to a portfolio of stock indices pertaining to non-military countries, namely Finland, Sweden, and Ecuador, for the same out-of-sample period, revealed that the intervention in the Syrian war may be one of the pertinent reasons that significantly affected the volatility of the stock markets of the three most powerful military countries. This paper is of great interest for policy makers, central bank leaders, participants involved in these markets, and all practitioners given the economic and financial consequences derived from such dynamics.
Correction: Wang, B., et al. Pectin Degradation Is an Important Determinant for Alfalfa Silage Fermentation through the Rescheduling of the Bacterial Community. Microorganisms 2020, 8, 488
Authors: Wang Bing , Sun Zhiqiang , Yu Zhu
Published: May 2020

The authors wish to make the following correction to this paper [...]
Detection of Canine Vector-Borne Filariasis and Their Wolbachia Endosymbionts in French Guiana
Authors: Laidoudi Younes , Marié Jean-Lou , Tahir Djamel , Watier-Grillot Stéphanie , Mediannikov Oleg , Davoust Bernard
Published: May 2020

In French Guiana, canine heartworm disease is well known, but the diversity of filarial parasites of dogs remains largely unknown. A total of 98 canine blood samples from Cayenne and Kourou were assessed by a blood wet mount preparation, heartworm antigen test and molecular exploration of filarioid and Wolbachia DNAs, followed by a multiplex species-specific qPCR’s identification and a subsequent sequencing analysis. Thereafter, a phylogeny based on maximum likelihood was carried out to facilitate specific identification. Five dogs were microfilaremic. Heartworm antigens were detected in 15 (15.3%) dogs. Of these, six (6.1%) were considered as occult infections as neither microfilariae nor Dirofilaria immitis DNA were detected. The 11 (11.2%) D. immitis isolates corresponded to a low virulent strain. Six of the D. immitis isolates were positive for Wolbachia endosymbionts of D. immitis belonging to the clade C DNA. Acanthocheilonema reconditum DNA was detected in 3 (3.1%) samples. Of these latter, one was found co-infected with the Brugia sp. genotype and the DNA of the clade D of the Wolbachia endosymbiont of Brugia species. This latter was also detected in two filarioid DNA-free samples. Finally, two samples were positive for Cercopithifilaria bainae genotype, which is distinct from those identified in Europe. The present study highlights the urgent need to implement chemoprophylaxis associated with anti-Wolbachia drugs to control these potential zoonoses.
The Crimean-Congo Hemorrhagic Fever Virus NSm Protein Is Dispensable for Growth In Vitro and Disease in Ifnar-/- Mice
Authors: Welch Stephen R. , Scholte Florine E. M. , Spengler Jessica R. , Ritter Jana M. , Coleman-McCray JoAnn D. , Harmon Jessica R. , Nichol Stuart T. , Zaki Sherif R. , Spiropoulou Christina F. , Bergeron Eric
Published: May 2020

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200∆NSm) and observing CCHFV ∆NSm replication in cell lines and pathogenicity in Ifnar-/- mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice.