bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Parcel Grouping Method Based on Urban Form and Functional Connectivity Characterisation
Authors: Wu Peng , Zhang Shuqing , Li Huapeng , Dale Patricia , Ding Xiaohui , Lu Yuanbing
Published: June 2019

The grouping of parcel data based on proximity is a pre-processing step of GIS and a key link of urban structure recognition for regional function discovery and urban planning. Currently, most literature abstracts parcels into points and clusters parcels based on their attribute similarity, which produces a large number of coarse granularity functional regions or discrete distribution of parcels that is inconsistent with human cognition. In this paper, we propose a novel parcel grouping method to optimise this issue, which considers both the urban morphology and the urban functional connectivity. Infiltration behaviours of urban components provide a basis for exploring the correlation between morphology mechanism and functional connectivity of urban areas. We measured the infiltration behaviours among adjacent parcels and concluded that the occurrence of infiltration behaviours often appears in the form of groups, which indicated the practical significance of parcel grouping. Our method employed two parcel morphology indicators: the similarity of the line segments and the compactness of the distribution. The line segment similarity was used to establish the adjacent relationship among parcels and the compactness was used to optimise the grouping result in obtain a satisfactory visual expression. In our study, constrained Delaunay triangulation, Hausdorff distance, and graph theory were employed to construct the proximity, delineate the parcel adjacency matrix, and implement the grouping of parcels. We applied this method for grouping urban parcel data of Beijing and verified the rationality of grouping results based on the quantified results of infiltration behaviours. Our method proved to take a good account of infiltration behaviours and satisfied human cognition, compared with a k-means++ method. We also presented a case using Xicheng District in Beijing to demonstrate the practicability of the method. The result showed that our method obtained fine-grained groups while ensuring functional regions-integrity.
Detecting Urban Polycentric Structure from POI Data
Authors: Deng Yue , Liu Jiping , Liu Yang , Luo An
Published: June 2019

It is meaningful to analyze urban spatial structure by identifying urban subcenters, and many methods of doing so have been proposed in the published literature. Although these methods are widely applied, they exhibit obvious shortcomings that limit their further application. Therefore, it is of great value to propose a new urban subcenter identification method that can overcome these shortcomings. In this paper, we propose the density contour tree (DCT) method for detecting urban polycentric structures and their spatial distributions. Conceptually, this method is based on an analogy between urban spatial structure and terrain. The point-of-interest (POI) density is visualized as a continuous mathematical surface representing the urban terrain. Peaks represent the regions of the most frequent human activity, valleys represent regions with small population densities in the city, and slopes represent spatial changes in urban land-use intensity. Using this method, we have detected the urban “polycentric” structure of Beijing and determined the corresponding spatial relationships. In addition, several important properties of the urban centers have been identified. For example, Beijing has a typical urban polycentric structure with an urban center area accounting for 5.9% of the total urban area, and most of the urban centers in Beijing serve comprehensive functions. In general, the method and the results can serve as references for the later research on analyzing urban structure.
Costunolide—A Bioactive Sesquiterpene Lactone with Diverse Therapeutic Potential
Authors: Kim Dae Yong , Choi Bu Young
Published: June 2019

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms.
Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women
Authors: Arpón Ana , Santos José L. , Milagro Fermín I. , Cataldo Luis Rodrigo , Bravo Carolina , Riezu-Boj José-Ignacio , Martínez J. Alfredo
Published: June 2019

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.
The Recretohalophyte Tamarix TrSOS1 Gene Confers Enhanced Salt Tolerance to Transgenic Hairy Root Composite Cotton Seedlings Exhibiting Virus-Induced Gene Silencing of GhSOS1
Authors: Che Benning , Cheng Cong , Fang Jiajia , Liu Yongmei , Jiang Li , Yu Bingjun
Published: June 2019

The salt overly sensitive 1 (SOS1) gene encodes the plasma membrane Na+/H+ antiporter, SOS1, that is mainly responsible for extruding Na+ from the cytoplasm and reducing the Na+ content in plants under salt stress and is considered a vital determinant in conferring salt tolerance to the plant. However, studies on the salt tolerance function of the TrSOS1 gene of recretohalophytes, such as Tamarix, are limited. In this work, the effects of salt stress on cotton seedlings transformed with tobacco-rattle-virus-based virus-induced gene silencing (VIGS) of the endogenous GhSOS1 gene, or Agrobacterium rhizogenes strain K599-mediated TrSOS1-transgenic hairy root composite cotton plants exhibiting VIGS of GhSOS1 were first investigated. Then, with Arabidopsis thaliana AtSOS1 as a reference, differences in the complementation effect of TrSOS1 or GhSOS1 in a yeast mutant were compared under salt treatment. Results showed that compared to empty-vector-transformed plants, GhSOS1-VIGS-transformed cotton plants were more sensitive to salt stress and had reduced growth, insufficient root vigor, and increased Na+ content and Na+/K+ ratio in roots, stems, and leaves. Overexpression of TrSOS1 enhanced the salt tolerance of hairy root composite cotton seedlings exhibiting GhSOS1-VIGS by maintaining higher root vigor and leaf relative water content (RWC), and lower Na+ content and Na+/K+ ratio in roots, stems, and leaves. Transformations of TrSOS1, GhSOS1, or AtSOS1 into yeast NHA1 (Na+/H+ antiporter 1) mutant reduced cellular Na+ content and Na+/K+ ratio, increased K+ level under salt stress, and had good growth complementation in saline conditions. In particular, the ability of TrSOS1 or GhSOS1 to complement the yeast mutant was better than that of AtSOS1. This may indicate that TrSOS1 is an effective substitute and confers enhanced salt tolerance to transgenic hairy root composite cotton seedlings, and even the SOS1 gene from salt-tolerant Tamarix or cotton may have higher efficiency than salt-sensitive Arabidopsis in regulating Na+ efflux, maintaining Na+ and K+ homeostasis, and therefore contributing to stronger salt tolerance.
The Association of Periodontitis and Peripheral Arterial Occlusive Disease—A Systematic Review
Authors: Kaschwich Mark , Behrendt Christian-Alexander , Heydecke Guido , Bayer Andreas , Debus Eike Sebastian , Seedorf Udo , Aarabi Ghazal
Published: June 2019

Background: Observational studies support an association between periodontitis (PD) and atherosclerotic vascular disease, but little is known specifically about peripheral arterial occlusive disease (PAOD). Objectives: To systematically review the evidence for an association between PD and PAOD. Data Sources: Medline via PubMed. Review Methods: We searched the Pubmed database for original studies, case reports, case series, meta-analyses and systematic reviews that assessed whether there is an association between PD (all degrees of severity) and PAOD (all degrees of severity). The reporting of this systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement following the Population, Intervention, Control, and Outcome (PICO) format. Results: 17 out of 755 detected studies were included in the qualitative synthesis. Nine studies demonstrated associations between PD and PAOD, and two studies reported associations between tooth loss and PAOD. Six studies addressed the pathomechanism regarding PD as a possible trigger for PAOD. No study that dismissed an association could be detected. Odds ratios or hazard ratios ranged from 1.3 to 3.9 in four large cohort studies after adjusting for established cardiovascular risk factors. Conclusions: The presented evidence supports a link between PD and PAOD. Further studies which address the temporality of PD and PAOD and randomized controlled intervention trials examining the causal impact of PD on PAOD are needed. Although our results cannot confirm a causal role of PD in the development of PAOD, it is likely that PD is associated with PAOD and plays a contributing role.
Epigenetics: A Potential Mechanism Involved in the Pathogenesis of Various Adverse Consequences of Obstructive Sleep Apnea
Authors: Chen Yung-Che , Hsu Po-Yuan , Hsiao Chang-Chun , Lin Meng-Chih
Published: June 2019

Epigenetics is defined as the heritable phenotypic changes which do not involve alterations in the DNA sequence, including histone modifications, non-coding RNAs, and DNA methylation. Recently, much attention has been paid to the role of hypoxia-mediated epigenetic regulation in cancer, pulmonary hypertension, adaptation to high altitude, and cardiorenal disease. In contrast to sustained hypoxia, chronic intermittent hypoxia with re-oxygenation (IHR) plays a major role in the pathogenesis of various adverse consequences of obstructive sleep apnea (OSA), resembling ischemia re-perfusion injury. Nevertheless, the role of epigenetics in the pathogenesis of OSA is currently underexplored. This review proposes that epigenetic processes are involved in the development of various adverse consequences of OSA by influencing adaptive potential and phenotypic variability under conditions of chronic IHR. Improved understanding of the interaction between genetic and environmental factors through epigenetic regulations holds great value to give deeper insight into the mechanisms underlying IHR-related low-grade inflammation, oxidative stress, and sympathetic hyperactivity, and clarify their implications for biomedical research.
Novel Bioactive and Antibacterial Acrylic Bone Cement Nanocomposites Modified with Graphene Oxide and Chitosan
Authors: Valencia Zapata Mayra Eliana , Mina Hernandez José Herminsul , Grande Tovar Carlos David , Valencia Llano Carlos Humberto , Diaz Escobar José Alfredo , Vázquez-Lasa Blanca , San Román Julio , Rojo Luis
Published: June 2019

Acrylic bone cements (ABCs) have played a key role in orthopedic surgery mainly in arthroplasties, but their use is increasingly extending to other applications, such as remodeling of cancerous bones, cranioplasties, and vertebroplasties. However, these materials present some limitations related to their inert behavior and the risk of infection after implantation, which leads to a lack of attachment and makes necessary new surgical interventions. In this research, the physicochemical, thermal, mechanical, and biological properties of ABCs modified with chitosan (CS) and graphene oxide (GO) were studied. Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) scanning electron microscopy (SEM), Raman mapping, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), compression resistance, mechanical dynamic analysis (DMA), hydrolytic degradation, cell viability, alkaline phosphatase (ALP) activity with human osteoblasts (HOb), and antibacterial activity against Gram-negative bacteria Escherichia coli were used to characterize the ABCs. The results revealed good dispersion of GO nanosheets in the ABCs. GO provided an increase in antibacterial activity, roughness, and flexural behavior, while CS generated porosity, increased the rate of degradation, and decreased compression properties. All ABCs were not cytotoxic and support good cell viability of HOb. The novel formulation of ABCs containing GO and CS simultaneously, increased the thermal stability, flexural modulus, antibacterial behavior, and osteogenic activity, which gives it a high potential for its uses in orthopedic applications.
Phytochemicals as Modulators of Long Non-Coding RNAs and Inhibitors of Cancer-Related Carbonic Anhydrases
Authors: Saghafi Tayebeh , Taheri Ramezan Ali , Parkkila Seppo , Zolfaghari Emameh Reza
Published: June 2019

Long non-coding RNAs (lncRNAs) are classified as a group of transcripts which regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition, but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothcin, and 3,3′-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy. In this review, we describe the state-of-the-art and potential of phytochemicals as modulators of lncRNAs in different types of cancers.
MtBZR1 Plays an Important Role in Nodule Development in Medicago truncatula
Authors: Cui Can , Wang Hongfeng , Hong Limei , Xu Yiteng , Zhao Yang , Zhou Chuanen
Published: June 2019

Brassinosteroid (BR) is an essential hormone in plant growth and development. The BR signaling pathway was extensively studied, in which BRASSINAZOLE RESISTANT 1 (BZR1) functions as a key regulator. Here, we carried out a functional study of the homolog of BZR1 in Medicago truncatula R108, whose expression was induced in nodules upon Sinorhizobium meliloti 1021 inoculation. We identified a loss-of-function mutant mtbzr1-1 and generated 35S:MtBZR1 transgenic lines for further analysis at the genetic level. Both the mutant and the overexpression lines of MtBZR1 showed no obvious phenotypic changes under normal growth conditions. After S. meliloti 1021 inoculation, however, the shoot and root dry mass was reduced in mtbzr1-1 compared with the wild type, caused by partially impaired nodule development. The transcriptomic analysis identified 1319 differentially expressed genes in mtbzr1-1 compared with wild type, many of which are involved in nodule development and secondary metabolite biosynthesis. Our results demonstrate the role of MtBZR1 in nodule development in M. truncatula, shedding light on the potential role of BR in legume–rhizobium symbiosis.
Transformation of Construction Cement to a Self-Healing Hybrid Binder
Authors: Müller Werner E.G. , Tolba Emad , Wang Shunfeng , Li Qiang , Neufurth Meik , Ackermann Maximilian , Muñoz-Espí Rafael , Schröder Heinz C. , Wang Xiaohong
Published: June 2019

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with an average chain length of 40, as well as natural long-chain polyP isolated from soil bacteria, has the ability to support self-healing of this construction material. Furthermore, polyP, used as a water-soluble Na-salt, is subject to Na+/Ca2+ exchange by the Ca2+ from the cement, resulting in the formation of a water-rich coacervate when added to the cement surface, especially to the surface of bacteria-containing cement/concrete samples. The addition of polyP in low concentrations (<1% on weight basis for the solids) not only accelerated the hardening of cement/concrete but also the healing of microcracks present in the material. The results suggest that long-chain polyP is a promising additive that increases the self-healing capacity of cement by mimicking a bacteria-mediated natural mechanism.
Phenolic Compounds and Ginsenosides in Ginseng Shoots and Their Antioxidant and Anti-Inflammatory Capacities in LPS-Induced RAW264.7 Mouse Macrophages
Authors: Yao Fan , Xue Qiang , Li Ke , Cao Xinxin , Sun Liwei , Liu Yujun
Published: June 2019

We conducted this study for the first time to evaluate changes in the composition and contents of phenolic compounds and ginsenosides in ginseng shoot extracts (GSEs) prepared with different steaming times (2, 4, and 6 h) at 120 °C, as well as their antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages (RAW264.7 cells). The results show that total phenol and flavonoid contents were both significantly higher in steamed versus raw GSEs, and the same trend was found for 2,2′-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) scavenging capacities. Among the 18 ginsenosides quantified using high-performance liquid chromatography (HPLC) with the aid of pure standards, polar ginsenosides were abundant in raw GSEs, whereas less-polar or rare ginsenosides appeared after steaming at 120 °C and increased with steaming time. Furthermore, steamed GSEs exhibited a greater ability to inhibit the production of inflammatory mediators and pro-inflammatory cytokines, such as nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in LPS-induced RAW264.7 cells at the same concentration. Relative expression levels of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNAs were attenuated by the GSEs, probably due to the enrichment of less-polar ginsenosides and enhanced antioxidant activity in steamed GSEs. These findings, combined with correlation analysis, showed that less-polar ginsenosides were major contributors to the inhibition of the overproduction of various inflammatory factors, while the inhibitory effects of total phenols and total flavonoids, and their antioxidant abilities, are also important.
Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach
Authors: Jangphattananont Nawaphat , Sato Hiroki , Imamura Ryu , Sakai Katsuya , Terakado Yumi , Murakami Kazuhiro , Barker Nick , Oshima Hiroko , Oshima Masanobu , Takagi Junichi , Kato Yukinari , Yano Seiji , Matsumoto Kunio
Published: June 2019

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain HGF (tcHGF) can activate the MET receptor. We investigated the localization of tcHGF and activated/phosphorylated MET (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total HGF (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial cells in endodermal organs, including the stomach. In the adult stomach, total HGF was localized in smooth muscle cells, and tcHGF was mainly localized in the glandular base region. Immunostaining for pMET and Lgr5-driven green fluorescent protein (GFP) indicated that pMET localization overlapped with Lgr5+ gastric stem cells. HGF promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. pMET and tcHGF localizations changed during regeneration following gastric injury. These results indicate that MET is constantly activated in gastric stem cells and that the localization of pMET differs from the primary localization of precursor HGF but has a close relationship to tcHGF. Our results suggest the importance of the microenvironmental generation of tcHGF in the regulation of development, regeneration, and stem cell behavior.
Melatonin Abrogates the Anti-Developmental Effect of the AKT Inhibitor SH6 in Bovine Oocytes and Embryos
Authors: El Sheikh Marwa , Mesalam Ayman , Mesalam Ahmed Atef , Idrees Muhammad , Lee Kyeong-Lim , Kong Il-Keun
Published: June 2019

Melatonin, a nighttime-secreted antioxidant hormone produced by the pineal gland, and AKT, a serine/threonine-specific protein kinase, have been identified as regulators for several cellular processes essential for reproduction. The current study aimed to investigate the potential interplay between melatonin and AKT in bovine oocytes in the context of embryo development. Results showed that the inclusion of SH6, a specific AKT inhibitor, during in vitro maturation (IVM) significantly reduced oocyte maturation, cumulus cell expansion, cleavage, and blastocyst development that were rescued upon addition of melatonin. Oocytes treated with SH6 in the presence of melatonin showed lower levels of reactive oxygen species (ROS) and blastocysts developed exhibited low apoptosis while the mitochondrial profile was significantly improved compared to the SH6-treated group. The RT-qPCR results showed up-regulation of the mRNA of maturation-, mitochondrial-, and cumulus expansion-related genes including GDF-9, BMP-15, MARF1, ATPase, ATP5F1E, POLG2, HAS2, TNFAIP6, and PTGS2 and down-regulation of Bcl-2 associated X apoptosis regulator (BAX), caspase 3, and p21 involved in apoptosis and cell cycle arrest in melatonin-SH6 co-treated group compared to SH6 sole treatment. The immunofluorescence showed high levels of caspase 3 and caspase 9, and low AKT phosphorylation in the SH6-treated group compared to the control and melatonin-SH6 co-treatment. Taken together, our results showed the importance of both melatonin and AKT for overall embryonic developmental processes and, for the first time, we report that melatonin could neutralize the deleterious consequences of AKT inhibition, suggesting a potential role in regulation of AKT signaling in bovine oocytes.
Luminescence- and Fluorescence-Based Complementation Assays to Screen for GPCR Oligomerization: Current State of the Art
Authors: Wouters Elise , Vasudevan Lakshmi , Crans René A. J. , Saini Deepak K. , Stove Christophe P.
Published: June 2019

G protein-coupled receptors (GPCRs) have the propensity to form homo- and heterodimers. Dysfunction of these dimers has been associated with multiple diseases, e.g., pre-eclampsia, schizophrenia, and depression, among others. Over the past two decades, considerable efforts have been made towards the development of screening assays for studying these GPCR dimer complexes in living cells. As a first step, a robust in vitro assay in an overexpression system is essential to identify and characterize specific GPCR–GPCR interactions, followed by methodologies to demonstrate association at endogenous levels and eventually in vivo. This review focuses on protein complementation assays (PCAs) which have been utilized to study GPCR oligomerization. These approaches are typically fluorescence- and luminescence-based, making identification and localization of protein–protein interactions feasible. The GPCRs of interest are fused to complementary fluorescent or luminescent fragments that, upon GPCR di- or oligomerization, may reconstitute to a functional reporter, of which the activity can be measured. Various protein complementation assays have the disadvantage that the interaction between the reconstituted split fragments is irreversible, which can lead to false positive read-outs. Reversible systems offer several advantages, as they do not only allow to follow the kinetics of GPCR–GPCR interactions, but also allow evaluation of receptor complex modulation by ligands (either agonists or antagonists). Protein complementation assays may be used for high throughput screenings as well, which is highly relevant given the growing interest and effort to identify small molecule drugs that could potentially target disease-relevant dimers. In addition to providing an overview on how PCAs have allowed to gain better insights into GPCR–GPCR interactions, this review also aims at providing practical guidance on how to perform PCA-based assays.
Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs
Authors: Lee Min-Woo , Lee Mihye , Oh Kyoung-Jin
Published: June 2019

Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site for initiation and aggravation of obesity and T2DM. As a key endocrine organ, the adipose tissue communicates with other organs, such as the brain, liver, muscle, and pancreas, for the maintenance of energy homeostasis. Two different types of adipose tissues—the white adipose tissue (WAT) and brown adipose tissue (BAT)—secrete bioactive peptides and proteins, known as “adipokines” and “batokines,” respectively. Some of them have beneficial anti-inflammatory effects, while others have harmful inflammatory effects. Recently, “exosomal microRNAs (miRNAs)” were identified as novel adipokines, as adipose tissue-derived exosomal miRNAs can affect other organs. In the present review, we discuss the role of adipose-derived secretory factors—adipokines, batokines, and exosomal miRNA—in obesity and T2DM. It will provide new insights into the pathophysiological mechanisms involved in disturbances of adipose-derived factors and will support the development of adipose-derived factors as potential therapeutic targets for obesity and T2DM.
The Impact of Cytokines on the Health-Related Quality of Life in Patients with Systemic Lupus Erythematosus
Authors: Raymond Warren David , Eilertsen Gro Østli , Shanmugakumar Sharanyaa , Nossent Johannes Cornelis
Published: June 2019

Introduction: Systemic lupus erythematosus (SLE) reduces the health-related quality of life (HRQoL), even during periods of disease quiescence. We investigated whether subclinical inflammation as reflected by cytokine levels is linked with reduced HRQoL. Methods: A cross-sectional study of SLE patients (n = 52, mean age 47.3, 86.5% female) who completed a Short Form Health Survey-36 (SF-36) questionnaire. The clinical and demographic data, scores for the disease activity (SLEDAI-2K), organ damage (SDI), and laboratory data were collected simultaneously. The autoantibody and cytokine levels (IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-17, BAFF, TNF-α, TGF-β1, MIP-1α, MIP-1β and MCP-1 (levels in pg/mL) were quantified by sandwich ELISA. The comparisons and associations were assessed non-parametrically, and a multiple regression determined the effect sizes (ES) of the variables on the SF-36 domain and summary scores. Results: The SF-36 summary and domain scores for SLE patients were significantly (20–40%) lower than in a comparable control group, with the exception of the Mental Health scores (p = 0.06). SLE patients had a normal body mass index (BMI) (median, 24.2 kg/m2), a high rate of smoking (69.2%), and usage of social security benefits (90.4%). TGF-β1 (ES 0.06), IL-12 (ES −0.11), IFN-γ (ES 0.07) and MCP-1 (ES 0.06) influenced the SF-36 domain scores; and MCP-1 (ES 0.04) influenced the Mental Health Summary Score (MCS). Obvious manifestations, including patient visual analogue scale (VAS) (ES −2.84 to −6.29), alopecia (ES −14.89), malar rash (ES −14.26), and analgesic requirement (ES −19.38), independently influenced the SF-36 items; however, the SF-36 scores were not reflected by the physician VAS or disease activity (SLEDAI-2K). Conclusions: Cytokines had a minimal impact on HRQoL in SLE patients, especially compared to visible skin manifestations, central nervous system (CNS) damage, and pain. Better tools are needed to capture HRQoL in measures of disease activity.
Effects of a High Fat Meal Associated with Water, Juice, or Champagne Consumption on Endothelial Function and Markers of Oxidative Stress and Inflammation in Young, Healthy Subjects
Authors: Rouyer Olivier , Auger Cyril , Charles Anne-Laure , Talha Samy , Meyer Alain , Piquard Francois , Andres Emmanuel , Schini-Kerth Valerie , Geny Bernard
Published: June 2019

Endothelial dysfunction (ED), often linked to hypertriglyceridemia, is an early step of atherosclerosis. We investigated, in a randomized cross-over study, whether high-fat meal (HFM)-induced ED might be reduced by fruit juice or champagne containing polyphenols. Flow-mediated dilatation (FMD) and biological parameters (lipid profile, glycemia, inflammation, and oxidative stress markers) were determined before and two and three hours after the HFM in 17 healthy young subjects (24.6 ± 0.9 years) drinking water, juice, or champagne. Considering the entire group, despite significant hypertriglyceridemia (from 0.77 ± 0.07 to 1.41 ± 0.18 mmol/L, p < 0.001) and a decrease in Low Density Lipoprotein (LDL), the FMD was not impaired. However, the FMD decreased in 10 subjects (from 10.73 ± 0.95 to 8.13 ± 0.86 and 8.07 ± 1.16%; p < 0.05 and p < 0.01; 2 and 3 h, respectively, after the HFM), without concomitant change in concentration reactive protein or reactive oxygen species, but with an increase in glycemia. In the same subjects, the FMD did not decrease when drinking juice or champagne. In conclusion, HFM can impair the endothelial function in healthy young subjects. Fruit juice, rich in anthocyanins and procyanidins, or champagne, rich in simple phenolic acids, might reduce such alterations, but further studies are needed to determine the underlying mechanisms, likely involving polyphenols.
Bacterial Colonization in Patients with Chronic Lymphocytic Leukemia and Factors Associated with Infections and Colonization
Authors: Korona-Glowniak Izabela , Grywalska Ewelina , Grzegorczyk Agnieszka , Roliński Jacek , Glowniak Andrzej , Malm Anna
Published: June 2019

Patients with chronic lymphocytic leukemia (CLL) have defects in both humoral and cellular immunity as a result of their underlying malignancy, as well as chemotherapy-related immune suppression. Upper respiratory tract (URT) colonization can be regarded as a major contributor to infection, so the relationship between carriage rates, disease incidence, or antibiotic resistance should be monitored. This prospective study included 50 newly diagnosed, previously untreated patients with CLL and 38 healthy volunteers. A total of 264 samples obtained from anterior nares and oropharynx were microbiologically examined. A significantly higher frequency of S. aureus and Gram-negative bacilli (GNB) colonization in CLL patients was observed in comparison to healthy volunteers. Information regarding baseline characteristics; the Rai staging system; hematological tests results; immunophenotype of basic lymphocyte subsets, including the expression of programmed cell death-1 protein (PD-1) and its ligand (PD-L1); as well as Epstein-Barr virus (EBV) status were determined to analyze risk factors for infections and bacterial colonization. The data represent the basic information for identification of further risk factors of infection and bacterial oropharyngeal colonization in CLL patients. The rate of disease progression within the time from the CLL diagnosis was significantly higher in patients colonized by GNB. This study highlights EBV infection and frequencies of PD-1 positive T CD3+ cells and B cells as risk factors in CLL patients.
Treatment Expectations, Convenience, and Satisfaction with Anticoagulant Treatment: Perceptions of Patients in South-East Queensland, Australia
Authors: Gospos Jonathan , Bernaitis Nijole
Published: June 2019

Background: Warfarin has long been the only oral anticoagulant (OAC) available, but options now include non-vitamin K antagonists. Prescribing an OAC may be influenced by patient factors and preferences influenced by dosing, monitoring, and adverse effects, which may ultimately impact patient satisfaction and convenience. The aim of this study was to explore the perception of OAC treatment by Australian patients in terms of treatment expectations, convenience, and satisfaction. Methods: The Perception of Anticoagulant Treatment Questionnaire was distributed to patients dispensed OAC medication from three pharmacies in South-East Queensland. Responses to questions using a five-point Likert scale were collated and mean results utilised to assess expectations, convenience, and satisfaction, including an analysis across demographic groups. Results: A total of 56 (26.8%) surveys were returned, with the majority of respondent’s male (58.2%). Highest mean scores for treatment expectation were for an OAC that was easy to take (4.85 ± 0.79) and that could be taken care of by the respondents themselves (4.11 ± 1.14). The mean overall score for convenience was 68.90 ± 11.44% and for satisfaction 69.43 ± 16.58%. Significantly higher mean convenience scores were found in females and patients with atrial fibrillation. Conclusions: Patients’ highest expectations were for an OAC that would be easy to take, and overall satisfaction and convenience was around 69%. Factors including demographics can influence perceptions of therapy, and addressing individual preferences for OAC therapy may increase ratings of satisfaction and convenience.
The New Era for Reno-Cardiovascular Treatment in Type 2 Diabetes
Authors: García-Carro Clara , Vergara Ander , Agraz Irene , Jacobs-Cachá Conxita , Espinel Eugenia , Seron Daniel , Soler María
Published: June 2019

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in the developed world. Until 2016, the only treatment that was clearly demonstrated to delay the DKD was the renin-angiotensin system blockade, either by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, this strategy only partially covered the DKD progression. Thus, new strategies for reno-cardiovascular protection in type 2 diabetic patients are urgently needed. In the last few years, hypoglycaemic drugs, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, demonstrated a cardioprotective effect, mainly in terms of decreasing hospitalization for heart failure and cardiovascular death in type 2 diabetic patients. In addition, these drugs also demonstrated a clear renoprotective effect by delaying DKD progression and decreasing albuminuria. Another hypoglycaemic drug class, dipeptidyl peptidase 4 inhibitors, has been approved for its use in patients with advanced chronic kidney disease, avoiding, in part, the need for insulinization in this group of DKD patients. Studies in diabetic and non-diabetic experimental models suggest that these drugs may exert their reno-cardiovascular protective effect by glucose and non-glucose dependent mechanisms. This review focuses on newly demonstrated strategies that have shown reno-cardiovascular benefits in type 2 diabetes and that may change diabetes management algorithms.
A Systematic Review of NAFLD-Associated Extrahepatic Disorders in Youths
Authors: Pacifico Lucia , Perla Francesco Massimo , Roggini Mario , Andreoli Gianmarco , D’Avanzo Miriam , Chiesa Claudio
Published: June 2019

Background: There is growing evidence that non-alcoholic fatty liver disease (NAFLD) is a disease affecting not only the liver but also extrahepatic organs. Aim: To investigate whether in youths NAFLD is associated with extrahepatic complications such as subclinical atherosclerosis, cardiac abnormalities, hypertension, type 2 diabetes, decreased bone mineral density, renal dysfunction, obstructive sleep apnea, and polycystic ovary syndrome. Methods: We systematically reviewed PubMed; Scopus; Embase; and the Cochrane Library databases up to 28 February 2019 and assessed the quality of studies using the Newcastle-Ottawa Scale. Results: Thirty-five articles were selected for this systematic review: fifteen (4627 participants) evaluated the association of NAFLD with subclinical atherosclerosis; four (969 participants) with cardiac abnormalities; two (550 participants) with hypertension; four (1328 participants) with diabetes; six (523 participants) with low bone mineral density; two (865 participants) with renal dysfunction; one with obstructive sleep apnea; and one with polycystic ovary syndrome. Most studies found that youths with NAFLD have increased features of subclinical atherosclerosis; as well as of cardiac alterations. Limited data were available to endorse a solid estimate of the prevalence of diabetes; low mineral density and renal dysfunction in the pediatric NAFLD population. Conclusion: NAFLD-related intermediate CVD outcomes can occur and be detected early in young populations.
The Potential of Optical Profilometry in the Study of Cultural Stone Weathering
Authors: Ambrosini Dario , de Rubeis Tullio , Nardi Iole , Paoletti Domenica
Published: June 2019

The problem of deterioration of marble or stone monuments on display in the open air was raised in scientific terms around the mid-nineteenth century, correctly sensing the close dependence between the increased speed of surfaces alteration and air pollution. However, only more recently, around the years 1980–1990, emerged a need for quantitative data to assess the degree of degradation and the relative danger in the future projections. Non-destructive techniques can be an important aid in assessing the state of degradation and, above all, its speed, directly on the most important monuments exposed to the urban environment. In this work we discuss some non-destructive techniques able to evaluate the alteration of the surface shape of artefacts exposed to the environment through a non-contact survey of their surface shape. Advantages and disadvantages will be highlighted, as well as the problems still open.
Image-Based RCS Estimation from Near-Field Data
Authors: Rajvanshi Tushar , Maisto Maria Antonia , Dell’Aversano Angela , Solimene Raffaele
Published: June 2019

This paper deals with the problem of estimating the RCS from near-field data by image-based approaches. In particular, a rigorous focusing procedure based on a weighted adjoint scheme, which is also applicable to an arbitrary measurement curve, is developed. The developed formalism allows us to address the important question concerning the need to employ a multi-frequency configuration to estimate the RCS. Accordingly, it is shown that if RCS is required at a given frequency, then the target image obtained solely at such a frequency can be exploited provided that the spatial truncation arising from the size of the investigated area is properly taken into account.
The Fight against HIV-Associated Disseminated Histoplasmosis in the Americas: Unfolding the Different Stories of Four Centers
Authors: Nacher Mathieu , Leitao Terezinha Silva , Gómez Beatriz L. , Couppié Pierre , Adenis Antoine , Damasceno Lisandra , Demar Magalie , Samayoa Blanca , Cáceres Diego H. , Pradinaud Roger , Sousa Anastacio de Queiroz , Arathoon Eduardo , Restrepo Angela
Published: June 2019

Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical “awakening” to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths.
Mass Spectrometry-Based Proteomics of Fungal Pathogenesis, Host–Fungal Interactions, and Antifungal Development
Authors: Ball Brianna , Bermas Arianne , Carruthers-Lay Duncan , Geddes-McAlister Jennifer
Published: June 2019

The prevalence of fungal diseases is increasing on a global scale, ranging from acute to systemic infections caused by commensal or pathogenic microorganisms, often associated with the immune status of the host. Morbidity and mortality rates remain high and our ability to treat fungal infections is challenged by a limited arsenal of antifungal agents and the emergence of drug resistant pathogens. There is a high demand for new approaches to elucidate the fungal mechanisms of pathogenesis and the interplay between host and pathogen to discover novel treatment options. Moreover, the need for improved drug efficacy and reduced host toxicity requires the identification and characterization of antifungal biological targets and molecular mechanisms of action. Mass spectrometry (MS)-based proteomics is a rapidly advancing field capable of addressing these priorities by providing comprehensive information on the dynamics of cellular processes, modifications, and interactions. In this Review, we focus on applications of MS-based proteomics in a diverse array of fungal pathogens and host systems to define and distinguish the molecular details of fungal pathogenesis and host–fungal interactions. We also explore the emerging role of MS-based proteomics in the discovery and development of novel antifungal therapies and provide insight into the future of MS-based proteomics in fungal biology.
Mutual Effects of Land Distribution and Economic Development: Evidence from Asia, Africa, and Latin America
Authors: Azadi Hossein , Vanhaute Eric
Published: June 2019

Land plays an important role in the economies of developing countries, and many theories connecting land inequality with different dimensions of economic development already exist. Even though efficacious land distribution allows societies to transition from poverty to a human capital-based developed economy, ongoing issues related to property rights, inequality, and the political economy of land distribution are unavoidable. The general objective of this paper is to explore the nexus between land distribution and economic development. The specific objectives are to: (i) identify which land distribution programs/activities contribute to economic development; (ii) investigate the role of stakeholders in land distribution programs that affect the growth of productivity; and (iii) assess the deficiencies of current land distribution policies in Asia, Africa, and Latin America to explore how economic development theories contribute to decreasing income inequality. This paper provides an overview of land distribution history and the main economic development theories. It also highlights the links between land distribution and the main elements of economic development. Finally, it provides a comparative review of the most recent empirical works regarding the characteristics, limitations, and potential (mutual) effects of land distribution and economic development settings on developing countries worldwide.