bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Warming Potential (GWP) for Methane: Monte Carlo Analysis of the Uncertainties in Global Tropospheric Model Predictions
Authors: Derwent Richard G.
Published: May 2020

Estimates of the global warming potential (GWP) of methane rely on the predictions from global chemistry-transport models. These models employ many uncertain input parameters representing the sources and sinks for methane and those for the tropospheric ozone, which is formed as a by-product of the methane sink process. Five thousand quasi-randomly Monte Carlo sampled model runs employing a zonally averaged global model were completed, each with a base case and a pulse case that differed from the base case only in having an additional 149 Tg (1Tg = 109 kg) emission pulse of methane. Each of the five thousand pulse case experiments had a small excess of methane that decayed away throughout the twenty-year model experiment. The radiative forcing consequences of this excess methane, and the excess tropospheric ozone formed from it, were integrated over a 100-year time horizon. The GWP was calculated in each of the five thousand model experiments from the sum of the radiative forcing consequences of methane and tropospheric ozone, by expressing them relative to the radiative forcing consequences of an identical emission pulse of carbon dioxide. The 2-sigma confidence range surrounding the methane atmospheric lifetime estimated in the Monte Carlo analysis was considerably wider than that derived from observations, suggesting that some of the input parameter combinations may have been unrealistic. The rejection of the unrealistic Monte Carlo replicates increased the mean methane GWP and narrowed its 2-sigma confidence interval to 37 ± 10 over a 100-year time horizon for emission pulses of the order of 1 Tg. Multiple linear regression was used to attribute the uncertainty in the output GWPs to each of the 183 uncertain input parameters, which represented emission source sectors, chemical kinetic rate coefficients, dry deposition velocities and biases in temperature and water vapour concentrations. Overall, the only significant contributions to the uncertainty in the methane GWP came from the chemical kinetic parameters representing the CH4 + OH, CH3O2 + HO2, CH3O2 + NO and the terpene + O3 reaction rate coefficients.
Frequency-Agile FFT Spectrometer for Microwave Remote Sensing Applications
Authors: Hagen Jonas , Luder Andres , Murk Axel , Kämpfer Niklaus
Published: May 2020

We report on a Fast Fourier Transform Spectrometer (FFTS) that provides larger bandwidth by fast local oscillator switching of the base-band converter. We demonstrate that this frequency scanning technique is suited for atmospheric remote sensing and conduct measurements of atmospheric ozone using the WIRA-C (WInd RAdiometer for Campaigns) Doppler wind radiometer. The comparison of our measurements to an adjusted atmospheric and instrumental model exposes no systematic biases due to the switching procedure in the measured spectra. It further shows that the combination of high spectral resolution with large bandwidth yields good measurement response to stratospheric and mesospheric ozone from approximately a 20 km to 70 km altitude with a resolution of 7 km in the lower stratosphere to 20 km in the mesosphere. We conclude that low-cost, low-power software-defined radio hardware designed for communications applications is very well suited for a variety of spectroscopic applications, including ozone monitoring. This allows the design of low-cost, multi-purpose instruments for atmospheric remote sensing and thus has a direct impact on future radiometer developments and their adoption in remote sensing campaigns and networks.
Molecular Markers in Ambient Air Associated with Biomass Burning in Morelos, México
Authors: Arias-Montoya Mónica Ivonne , López-Márquez Rebecca , Murillo-Tovar Mario Alfonso , Guerrero-Alvarez Jorge Antonio , Vergara-Sánchez Josefina , Reyes Pedro Guillermo , Ramos-Quintana Fernando , Montiel-Palma Silvia , Saldarriaga-Noreña Hugo
Published: May 2020

Atmospheric particles with an aerodynamic diameter less than or equal to 2.5 micrometers (PM2.5) were collected at two sites located in the urban area of the city of Cuernavaca (Morelos) during a season when a large number of forest fires occurred. Three dicarboxylic acids (malonic, glutaric and succinic) and levoglucosan were analyzed by liquid chromatography coupled with mass spectrometry (ESI-Q-TOF) and soluble potassium (K+) was analyzed by ion chromatography. The concentration of PM2.5 increased on the days when the highest number of forest fires occurred. A strong correlation was observed between levoglucosan and K+, confirming the hypothesis that both are tracers of biomass burning (r = 0.57, p < 0.05). Levoglucosan (average 367.6 ng m−3, Site 2) was the most abundant compound, followed by succinic acid (average 101.7 ng m−3, Site 2), glutaric acid (average 63.2 ng m−3, Site 2), and malonic acid (average 46.9 ng m−3, Site 2), respectively. The ratio of C3/C4 concentrations ranged from 0.5 to 1.2, with an average of 0.8, which suggests great photochemical activity in the Cuernavaca atmosphere. The ratio of K+/levoglucosan concentrations (0.44) indicates that open fires are the main source of these tracers. The positive correlations between PM2.5 and levoglucosan and succinic and malonic acids suggest that such compounds are contributing to secondary organic aerosol particle formation.
Low-Cost Air Quality Sensors: One-Year Field Comparative Measurement of Different Gas Sensors and Particle Counters with Reference Monitors at Tušimice Observatory
Authors: Bauerová Petra , Šindelářová Adriana , Rychlík Štěpán , Novák Zbyněk , Keder Josef
Published: May 2020

With attention increasing regarding the level of air pollution in different metropolitan and industrial areas worldwide, interest in expanding the monitoring networks by low-cost air quality sensors is also increasing. Although the role of these small and affordable sensors is rather supplementary, determination of the measurement uncertainty is one of the main questions of their applicability because there is no certificate for quality assurance of these non-reference technologies. This paper presents the results of almost one-year field testing measurements, when the data from different low-cost sensors (for SO2, NO2, O3, and CO: Cairclip, Envea, FR; for PM1, PM2.5, and PM10: PMS7003, Plantower, CHN, and OPC-N2, Alphasense, UK) were compared with co-located reference monitors used within the Czech national ambient air quality monitoring network. The results showed that in addition to the given reduced measurement accuracy of the sensors, the data quality depends on the early detection of defective units and changes caused by the effect of meteorological conditions (effect of air temperature and humidity on gas sensors and effect of air humidity with condensation conditions on particle counters), or by the interference of different pollutants (especially in gas sensors). Comparative measurement is necessary prior to each sensor’s field applications.
Inertial Subgradient Extragradient Methods for Solving Variational Inequality Problems and Fixed Point Problems
Authors: Okeke Godwin Amechi , Abbas Mujahid , de la Sen Manuel
Published: May 2020

We propose two new iterative algorithms for solving K-pseudomonotone variational inequality problems in the framework of real Hilbert spaces. These newly proposed methods are obtained by combining the viscosity approximation algorithm, the Picard Mann algorithm and the inertial subgradient extragradient method. We establish some strong convergence theorems for our newly developed methods under certain restriction. Our results extend and improve several recently announced results. Furthermore, we give several numerical experiments to show that our proposed algorithms performs better in comparison with several existing methods.
Improved Adhesion of Nafion™-Coated Separator to Water-Processable LiNi0.5Mn1.5O4 Electrodes
Authors: Malavolta Laura , Terella Antonio , De Giorgio Francesca , Arbizzani Catia
Published: May 2020

The adhesion between electrode and separator is a key feature in cell assembly. Nafion™-coated separators for water-processed LiNi0.5Mn1.5O4 (LNMO) electrodes are here proposed as an alternative to the polyolefin separators. Specifically, polyolefin separators are modified with Nafion™ solutions and their adhesion to high-potential LNMO electrodes is investigated. The physicochemical properties of the Nafion™-coated separator and its electrochemical performance in Li/LNMO cells are discussed and compared to those obtained with polyolefin Celgard® (Charlotte, NC, USA) PP2075 separator. Improved adhesion and cycling stability, which could be further enhanced by a mild lamination process, were demonstrated with a thin layer of Nafion™ (0.1 mg cm−2).
Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates
Authors: Turkez Hasan , Cacciatore Ivana , Arslan Mehmet Enes , Fornasari Erika , Marinelli Lisa , Di Stefano Antonio , Mardinoglu Adil
Published: May 2020

Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer’s disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (Aβ1-42) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), α- and β-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against Aβ1-42-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by Aβ1-42 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.
Chemoenzymatic Synthesis and Biological Evaluation for Bioactive Molecules Derived from Bacterial Benzoyl Coenzyme A Ligase and Plant Type III Polyketide Synthase
Authors: Adhikari Kamal , Lo I-Wen , Chen Chun-Liang , Wang Yung-Lin , Lin Kuan-Hung , Zadeh Saeid Malek , Rattinam Rajesh , Li Yi-Shan , Wu Chang-Jer , Li Tsung-Lin
Published: May 2020

Plant type III polyketide synthases produce diverse bioactive molecules with a great medicinal significance to human diseases. Here, we demonstrated versatility of a stilbene synthase (STS) from Pinus Sylvestris, which can accept various non-physiological substrates to form unnatural polyketide products. Three enzymes (4-coumarate CoA ligase, malonyl-CoA synthetase and engineered benzoate CoA ligase) along with synthetic chemistry was practiced to synthesize starter and extender substrates for STS. Of these, the crystal structures of benzoate CoA ligase (BadA) from Rhodopseudomonas palustris in an apo form or in complex with a 2-chloro-1,3-thiazole-5-carboxyl-AMP or 2-methylthiazole-5-carboxyl-AMP intermediate were determined at resolutions of 1.57 Å, 1.7 Å, and 2.13 Å, respectively, which reinforces its capacity in production of unusual CoA starters. STS exhibits broad substrate promiscuity effectively affording structurally diverse polyketide products. Seven novel products showed desired cytotoxicity against a panel of cancer cell lines (A549, HCT116, Cal27). With the treatment of two selected compounds, the cancer cells underwent cell apoptosis in a dose-dependent manner. The precursor-directed biosynthesis alongside structure-guided enzyme engineering greatly expands the pharmaceutical repertoire of lead compounds with promising/enhanced biological activities.
Sorbaria kirilowii Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB
Authors: Jang Jiwon , Lee Jong Sub , Jang Young-Jin , Choung Eui Su , Li Wan Yi , Lee Sang Woo , Kim Eunji , Kim Jong-Hoon , Cho Jae Youl
Published: May 2020

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.
Blueberry-Derived Exosome-Like Nanoparticles Counter the Response to TNF-α-Induced Change on Gene Expression in EA.hy926 Cells
Authors: De Robertis Mariangela , Sarra Angelo , D’Oria Valentina , Mura Francesco , Bordi Federico , Postorino Paolo , Fratantonio Deborah
Published: May 2020

Exosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change > 1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes, such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors.
Targeting Intrinsically Disordered Proteins through Dynamic Interactions
Authors: Chen Jianlin , Liu Xiaorong , Chen Jianhan
Published: May 2020

Intrinsically disordered proteins (IDPs) are over-represented in major disease pathways and have attracted significant interest in understanding if and how they may be targeted using small molecules for therapeutic purposes. While most existing studies have focused on extending the traditional structure-centric drug design strategies and emphasized exploring pre-existing structure features of IDPs for specific binding, several examples have also emerged to suggest that small molecules could achieve specificity in binding IDPs and affect their function through dynamic and transient interactions. These dynamic interactions can modulate the disordered conformational ensemble and often lead to modest compaction to shield functionally important interaction sites. Much work remains to be done on further elucidation of the molecular basis of the dynamic small molecule–IDP interaction and determining how it can be exploited for targeting IDPs in practice. These efforts will rely critically on an integrated experimental and computational framework for disordered protein ensemble characterization. In particular, exciting advances have been made in recent years in enhanced sampling techniques, Graphic Processing Unit (GPU)-computing, and protein force field optimization, which have now allowed rigorous physics-based atomistic simulations to generate reliable structure ensembles for nontrivial IDPs of modest sizes. Such de novo atomistic simulations will play crucial roles in exploring the exciting opportunity of targeting IDPs through dynamic interactions.
Structure–Activity Relationship Study Reveals the Molecular Basis for Specific Sensing of Hydrophobic Amino Acids by the Campylobacter jejuni Chemoreceptor Tlp3
Authors: Khan Mohammad F. , Machuca Mayra A. , Rahman Mohammad M. , Koç Cengiz , Norton Raymond S. , Smith Brian J. , Roujeinikova Anna
Published: May 2020

Chemotaxis is an important virulence factor of the foodborne pathogen Campylobacter jejuni. Inactivation of chemoreceptor Tlp3 reduces the ability of C. jejuni to invade human and chicken cells and to colonise the jejunal mucosa of mice. Knowledge of the structure of the ligand-binding domain (LBD) of Tlp3 in complex with its ligands is essential for a full understanding of the molecular recognition underpinning chemotaxis. To date, the only structure in complex with a signal molecule is Tlp3 LBD bound to isoleucine. Here, we used in vitro and in silico screening to identify eight additional small molecules that signal through Tlp3 as attractants by directly binding to its LBD, and determined the crystal structures of their complexes. All new ligands (leucine, valine, α-amino-N-valeric acid, 4-methylisoleucine, β-methylnorleucine, 3-methylisoleucine, alanine, and phenylalanine) are nonpolar amino acids chemically and structurally similar to isoleucine. X-ray crystallographic analysis revealed the hydrophobic side-chain binding pocket and conserved protein residues that interact with the ammonium and carboxylate groups of the ligands determine the specificity of this chemoreceptor. The uptake of hydrophobic amino acids plays an important role in intestinal colonisation by C. jejuni, and our study suggests that C. jejuni seeks out hydrophobic amino acids using chemotaxis.
A Novel Lysophosphatidic Acid Acyltransferase of Escherichia coli Produces Membrane Phospholipids with a cis-vaccenoyl Group and Is Related to Flagellar Formation
Authors: Toyotake Yosuke , Nishiyama Masayoshi , Yokoyama Fumiaki , Ogawa Takuya , Kawamoto Jun , Kurihara Tatsuo
Published: May 2020

Lysophosphatidic acid acyltransferase (LPAAT) introduces fatty acyl groups into the sn-2 position of membrane phospholipids (PLs). Various bacteria produce multiple LPAATs, whereas it is believed that Escherichia coli produces only one essential LPAAT homolog, PlsC—the deletion of which is lethal. However, we found that E. coli possesses another LPAAT homolog named YihG. Here, we show that overexpression of YihG in E. coli carrying a temperature-sensitive mutation in plsC allowed its growth at non-permissive temperatures. Analysis of the fatty acyl composition of PLs from the yihG-deletion mutant (∆yihG) revealed that endogenous YihG introduces the cis-vaccenoyl group into the sn-2 position of PLs. Loss of YihG did not affect cell growth or morphology, but ∆yihG cells swam well in liquid medium in contrast to wild-type cells. Immunoblot analysis showed that FliC was highly expressed in ∆yihG cells, and this phenotype was suppressed by expression of recombinant YihG in ∆yihG cells. Transmission electron microscopy confirmed that the flagellar structure was observed only in ∆yihG cells. These results suggest that YihG has specific functions related to flagellar formation through modulation of the fatty acyl composition of membrane PLs.
Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways
Authors: Ferrigno Andrea , Di Pasqua Laura G. , Palladini Giuseppina , Berardo Clarissa , Verta Roberta , Richelmi Plinio , Perlini Stefano , Collotta Debora , Collino Massimo , Vairetti Mariapia
Published: May 2020

In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK). Male Wistar rats were either subjected to 60 min partial-hepatic ischemia or sham-operated. After a 60 min or 120 min reperfusion, liver samples were collected for analysis of MMP-2 and MMP-9 by zymography and RECK, TIMP-1, and TIMP-2 content, MAPKs activation (ERK1/2, JNK1/2, and p38), as well as iNOS and eNOS by Western blot. Serum enzymes AST, ALT, and alkaline-phosphatase were quantified. A transitory decrease in hepatic RECK and TIMPs was associated with a transitory increase in both MMP-2 and MMP-9 activity and a robust activation of ERK1/2, JNK1/2, and p38 were detected at 60 min reperfusion. Hepatic expression of iNOS was maximally upregulated at 120 min reperfusion. An increase in eNOS was detected at 120 min reperfusion. I/R evoked significant hepatic injury in a time-dependent manner. These findings provide new insights into the underlying molecular mechanisms of reperfusion in inducing hepatic injury: a transitory decrease in RECK and TIMPs and increases in both MAPK and MMP activity suggest their role as triggering factors of the organ dysfunction.
Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects
Authors: Molina-Vega María , Castellano-Castillo Daniel , Sánchez-Alcoholado Lidia , Plaza-Andrade Isaac , Perera-Martin Gabriel , Cabrera-Mulero Amanda , Fernández-García Jose Carlos , Ramos-Molina Bruno , Cardona Fernando , Tinahones Francisco J.
Published: May 2020

Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist.
Chronic Periodontitis and Immunity, Towards the Implementation of a Personalized Medicine: A Translational Research on Gene Single Nucleotide Polymorphisms (SNPs) Linked to Chronic Oral Dysbiosis in 96 Caucasian Patients
Authors: Inchingolo Francesco , Martelli Francesco Saverio , Gargiulo Isacco Ciro , Borsani Elisa , Cantore Stefania , Corcioli Fabiana , Boddi Anna , Nguyễn Kieu C.D. , De Vito Danila , Aityan Sergey K. , Pham Van Hung , Dipalma Gianna , Ballini Andrea
Published: May 2020

Chronic periodontitis (CP) is a complex pathology with a significant impact worldwide causing bone loss. Oral dysbiosis is a highly inflammatory condition associated to a long-term insulting infection and represents an underestimated CP key factor associated with an imbalance of pro-inflammatory and anti-inflammatory gene responses. The presence of a single nucleotide polymorphisms (SNPs) in the promoter region of interleukin 10 (IL-10) gene −1082, −819, and −592 was a possible determinant cause. This translational research aimed to provide outcomes on the role of IL-10 gene expression in bone loss diseases in patients affected by CP. Caucasian patients (n = 96) affected by CP were recruited from the Italian population. The subgingival samples were collected using the Bacterial Periodontal Assessment by Biomolecular Diagnostic® and the characterization of a set of 15 bacterial DNA responsible of periodontitis was performed by real-time multiplex PCR. In addition, two viruses, Epstein–Barr Virus (EBV) and Herpes Simplex Virus 1 (HSV-1), and a pathogenic fungi (Candida albicans) were included as a part of our panel. Our results confirmed an existing association between IL-10 gene polymorphisms and polymorphism of tumor necrosis factor alpha (TNFα), interleukin 1α-β-RN (IL-1α-β-RN), collagen type-l alpha (COLIA1), and vitamin D receptor (VDRs) genes in CP. Further studies are needed to improve diagnosis and endorse more effective therapeutic procedures for periodontal disease.
Fecal Volatile Organic Compound Profiles are Not Influenced by Gestational Age and Mode of Delivery: A Longitudinal Multicenter Cohort Study
Authors: Deianova Nancy , el Manouni el Hassani Sofia , Niemarkt Hendrik J. , Cossey Veerle , van Kaam Anton H. , Jenken Floor , van Weissenbruch Mirjam M. , Doedes Esmee M. , Baelde Kyra , Menezes Renee , Benninga Marc A. , de Jonge Wouter J. , de Boer Nanne K. , de Meij Tim G.
Published: May 2020

Fecal volatile organic compounds (VOC) reflect human and gut microbiota metabolic pathways and their interaction. VOC behold potential as non-invasive preclinical diagnostic biomarkers in various diseases, e.g., necrotizing enterocolitis and late onset sepsis. There is a need for standardization and assessment of the influence of clinical and environmental factors on the VOC outcome before this technique can be applied in clinical practice. The aim of this study was to investigate the influence of gestational age (GA) and mode of delivery on the fecal VOC pattern in preterm infants born below 30 weeks of gestation. Longitudinal fecal samples, collected on days 7, 14, and 21 postnatally, were analyzed by an electronic nose device (Cyranose 320®). In total, 58 preterm infants were included (29 infants born at GA 24–26 weeks vs. 29 at 27–29 completed weeks, 24 vaginally born vs. 34 via C-section). No differences were identified at any predefined time point in terms of GA and delivery mode (p > 0.05). We, therefore, concluded that correction for these factors in this population is not warranted when performing fecal VOC analysis in the first three weeks of life.
Persistent Roseoloviruses Infection in Adult Patients with Epilepsy
Authors: Rasa-Dzelzkaleja Santa , Gravelsina Sabine , Chapenko Svetlana , Krukle Zaiga-Nora , Svirskis Simons , Suna Normunds , Kashuba Elena , Karelis Guntis , Murovska Modra
Published: May 2020

Background: Human herpesviruses (HHV)-6A, HHV-6B and HHV-7 are considered to be involved in the pathogenesis of epilepsy, a common neurological disorder. The objective of this study was to determine the association of roseoloviruses infection with epilepsy. Methods: 53 epilepsy patients and 104 ordinary blood donors were analyzed to determine presence of virus-specific antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), genomic sequences, viral load and gene expression by polymerase chain reactions (PCRs) and restriction analysis, HHV-6 protein expression by IFA and level of cytokines by ELISA. Results: Roseoloviruses genomic sequences in DNA samples from whole blood were found in 86.8% of patients versus 54.8% of controls and active infection was revealed only in patients with epilepsy (19.6% of roseolovirus-positive patients). Significantly higher viral load and more frequent gene expression was detected in patients compared to the controls. HHV-6-encoded protein expression was demonstrated in 53.3% of patients with previously detected HHV-6 DNA. Changes in level of cytokines were determined in patients with elevated viral load compared to the patients without elevated viral loads and to the controls. Conclusions: Results on frequent active HHV-6 and HHV-7 infection in epilepsy patient’ peripheral blood indicate on possible involvement of these viruses in the disease development.
The Long Road of Immunotherapeutics against Multiple Sclerosis
Authors: Apostolopoulos Vasso , Rostami Abdolmohamad , Matsoukas John
Published: May 2020

This commentary highlights novel immunomodulation and vaccine-based research against multiple sclerosis (MS) and reveals the amazing story that triggered this cutting-edge MS research in Greece and worldwide. It further reveals the interest and solid support of some of the world’s leading scientists, including sixteen Nobel Laureates who requested from European leadership to take action in supporting Greece and its universities in the biggest ever financial crisis the country has encountered in the last decades. This support endorsed vaccine-based research on MS, initiated in Greece and Australia, leading to a worldwide network aiming to treat or manage disease outcomes. Initiatives by bright and determined researchers can result in frontiers science. We shed light on a unique story behind great research on MS which is a step forward in our efforts to develop effective treatments for MS.
Lack of Truth-Telling in Palliative Care and Its Effects among Nurses and Nursing Students
Authors: Testoni Ines , Wieser Michael Alexander , Kapelis Dafni , Pompele Sara , Bonaventura Marino , Crupi Robert
Published: May 2020

Unclear communication of inauspicious prognoses may disorientate both patients and their relatives, drastically jeopardizing the planning of palliative care. This paper considers the issue of truth-telling in the communicative problems of nurses and students of nursing with terminally ill patients. The fundamental objective is the analysis of the difficulties related to the lack of truth-telling and how it might impact their professional and personal lives. A qualitative study was realized, involving 47 participants, both nurses (25) and nursing students (22), working in palliative care units or in associations of volunteers for the assistance of oncological patients. The exploration was focused on the way they relate to patients who are not aware of their real health conditions and their consequences. Particular attention was paid to their opinions concerning what could be done in order to manage such problematic situations in the near future.
Correction: Emami, N., et al. A Life Cycle Assessment of Two Residential Buildings Using Two Different LCA Database-Software Combinations: Recognizing Uniformities and Inconsistencies. Buildings, 2019, 9, 20
Authors: Emami Nargessadat , Heinonen Jukka , Marteinsson Björn , Säynäjoki Antti , Junnonen Juha-Matti , Laine Jani , Junnila Seppo
Published: May 2020

We noticed that the Figures 2 and 3 have become the same in the final version of this paper [...]
Predicting Maximum and Cumulative Response of A Base-isolated Building Using Pushover Analysis
Authors: Fujii Kenji , Mogi Yoshiyuki , Noguchi Takumi
Published: May 2020

The evaluation of the maximum and cumulative response is an important issue for the seismic design of new base-isolated buildings. This study predicts the maximum and cumulative response of a 14-story reinforced concrete base-isolated building using a set of pushover analyses. In the proposed pushover analysis method, the maximum and cumulative responses of the first and higher modes are evaluated from the nonlinear analysis of equivalent single-degree-of-freedom (SDOF) models. Then, the maximum local responses are predicted by enveloping the two pushover analysis results by referring to the contribution of the first and higher modal responses, while the cumulative strain energies of the lead-rubber bearings and steel dampers are predicted from the cumulative response of the first mode. The results reveal that the responses predicted by the proposed set of pushover analyses have satisfactory accuracy.
Graphene-Quantum-Dot-Mediated Semiconductor Bonding: A Route to Optoelectronic Double Heterostructures and Wavelength-Converting Interfaces
Authors: Nishigaya Kosuke , Kishibe Kodai , Tanabe Katsuaki
Published: May 2020

A semiconductor bonding technique that is mediated by graphene quantum dots is proposed and demonstrated. The mechanical stability, electrical conductivity, and optical activity in the bonded interfaces are experimentally verified. First, the bonding scheme can be used for the formation of double heterostructures with a core material of graphene quantum dots. The Si/graphene quantum dots/Si double heterostructures fabricated in this study can constitute a new basis for next-generation nanophotonic devices with high photon and carrier confinements, earth abundance, environmental friendliness, and excellent optical and electrical controllability via silicon clads. Second, the bonding mediated by the graphene quantum dots can be used as an optical-wavelength-converting semiconductor interface, as experimentally demonstrated in this study. The proposed fabrication method simultaneously realizes bond formation and interfacial function generation and, thereby, can lead to efficient device production. Our bonding scheme might improve the performance of optoelectronic devices, for example, by allowing spectral light incidence suitable for each photovoltaic material in multijunction solar cells and by delivering preferred frequencies to the optical transceiver components in photonic integrated circuits.
Long Non-Coding RNA HOTAIR in Breast Cancer Therapy
Authors: Cantile Monica , Di Bonito Maurizio , Cerrone Margherita , Collina Francesca , De Laurentiis Michelino , Botti Gerardo
Published: May 2020

Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC. In the present review, we summarize the role of HOTAIR in cancer progression and drug resistance, in particular in BC, and we illustrate the main approaches for silencing it.
Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment
Authors: Dianzani Chiara , Monge Chiara , Miglio Gianluca , Serpe Loredana , Martina Katia , Cangemi Luigi , Ferraris Chiara , Mioletti Silvia , Osella Sara , Gigliotti Casimiro Luca , Boggio Elena , Clemente Nausicaa , Dianzani Umberto , Battaglia Luigi
Published: May 2020

Aims: Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. Methods: a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid®), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. Results: Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid®, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid®-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. Conclusions: In these preliminary studies, Intralipid® proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.
Clinical Theragnostic Potential of Diverse miRNA Expressions in Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Jayaraj Rama , Raymond Greg , Krishnan Sunil , Tzou Katherine S. , Baxi Siddhartha , Ram M. Ravishankar , Govind Suresh Kumar , Chandramoorthy Harish C. , Abu-Khzam Faisal N. , Shaw Peter
Published: May 2020

Background: Prostate cancer (PrC) is the second-most frequent cancer in men, its incidence is emerging globally and is the fifth leading cause of death worldwide. While diagnosis and prognosis of PrC have been studied well, the associated therapeutic biomarkers have not yet been investigated comprehensively. This systematic review and meta-analysis aim to evaluate the theragnostic effects of microRNA expressions on chemoresistance in prostate cancer and to analyse the utility of miRNAs as clinical theragnostic biomarkers. Methods: A systematic literature search for studies reporting miRNA expressions and their role in chemoresistance in PrC published until 2018 was collected from bibliographic databases. The evaluation of data was performed as per PRISMA guidelines for systematic review and meta-analysis. Meta-analysis was performed using a random-effects model using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between studies was analysed using Cochran’s Q test, I2 and the Tau statistic. Quality assessment of the studies was performed using the Newcastle–Ottawa Scale (NOS) for the methodological assessment of cohort studies. Publication bias was assessed using Egger’s bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill methods. Findings: Out of 2909 studies retrieved, 79 studies were shortlisted and reviewed. A total of 17 studies met our eligibility criteria, from which 779 PrC patients and 17 chemotherapy drugs were examined, including docetaxel and paclitaxel. The majority of the drug regulatory genes reported were involved in cell survival, angiogenesis and cell proliferation pathways. We studied 42 miRNAs across all studies, out of which two miRNAs were found to be influencing chemosensitivity, while 21 were involved in chemoresistance. However, the remaining 19 miRNAs did not appear to have any theragnostic effects. Besides, the prognostic impact of the miRNAs was evaluated and had a pooled HR value of 1.960 with 95% CI (1.377–2.791). Interpretation: The observation of the current study depicts the significance of miRNA expression as a theragnostic biomarker in medical oncology. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in PrC. Hence, the current systematic review and meta-analysis provide insight on the use of miRNA as PrC biomarkers, which can be harnessed as molecular candidates for therapeutic targeting.
Applications of Artificial Intelligence to Prostate Multiparametric MRI (mpMRI): Current and Emerging Trends
Authors: Bardis Michelle D. , Houshyar Roozbeh , Chang Peter D. , Ushinsky Alexander , Glavis-Bloom Justin , Chahine Chantal , Bui Thanh-Lan , Rupasinghe Mark , Filippi Christopher G. , Chow Daniel S.
Published: May 2020

Prostate carcinoma is one of the most prevalent cancers worldwide. Multiparametric magnetic resonance imaging (mpMRI) is a non-invasive tool that can improve prostate lesion detection, classification, and volume quantification. Machine learning (ML), a branch of artificial intelligence, can rapidly and accurately analyze mpMRI images. ML could provide better standardization and consistency in identifying prostate lesions and enhance prostate carcinoma management. This review summarizes ML applications to prostate mpMRI and focuses on prostate organ segmentation, lesion detection and segmentation, and lesion characterization. A literature search was conducted to find studies that have applied ML methods to prostate mpMRI. To date, prostate organ segmentation and volume approximation have been well executed using various ML techniques. Prostate lesion detection and segmentation are much more challenging tasks for ML and were attempted in several studies. They largely remain unsolved problems due to data scarcity and the limitations of current ML algorithms. By contrast, prostate lesion characterization has been successfully completed in several studies because of better data availability. Overall, ML is well situated to become a tool that enhances radiologists’ accuracy and speed.
Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer
Authors: Bouberhan Sara , Philp Lauren , Hill Sarah , Al-Alem Linah F. , Rueda Bo
Published: May 2020

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance.
The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice
Authors: Harris Michael A. , Miles Mark A. , Shekhar Tanmay M. , Cerra Carmelo , Georgy Smitha R. , Ryan Stewart D. , Cannon Claire M. , Hawkins Christine J.
Published: May 2020

Osteosarcoma is the most common form of primary bone cancer. Over 20% of osteosarcoma patients present with pulmonary metastases at diagnosis, and nearly 70% of these patients fail to respond to treatment. Previous work revealed that human and canine osteosarcoma cell lines are extremely sensitive to the therapeutic proteasome inhibitor bortezomib in vitro. However, bortezomib has proven disappointingly ineffective against solid tumors including sarcomas in animal experiments and clinical trials. Poor tumor penetration has been speculated to account for the inconsistency between in vitro and in vivo responses of solid tumors to bortezomib. Here we show that the second-generation proteasome inhibitor ixazomib, which reportedly has enhanced solid tumor penetration compared to bortezomib, is toxic to human and canine osteosarcoma cells in vitro. We used experimental osteosarcoma metastasis models to compare the efficacies of ixazomib and bortezomib against primary tumors and metastases derived from luciferase-expressing KRIB or 143B human osteosarcoma cell lines in athymic mice. Neither proteasome inhibitor reduced the growth of primary intramuscular KRIB tumors, however both drugs inhibited the growth of established pulmonary metastases created via intravenous inoculation with KRIB cells, which were significantly better vascularized than the primary tumors. Only ixazomib slowed metastases from KRIB primary tumors and inhibited the growth of 143B pulmonary and abdominal metastases, significantly enhancing the survival of mice intravenously injected with 143B cells. Taken together, these results suggest ixazomib exerts better single agent activity against osteosarcoma metastases than bortezomib. These data provide hope that incorporation of ixazomib, or other proteasome inhibitors that penetrate efficiently into solid tumors, into current regimens may improve outcomes for patients diagnosed with metastatic osteosarcoma.
Enhanced Photoelectrochemical Water Splitting at Hematite Photoanodes by Effect of a NiFe-Oxide co-Catalyst
Authors: Lo Vecchio Carmelo , Trocino Stefano , Campagna Zignani Sabrina , Baglio Vincenzo , Carbone Alessandra , Díez García María Isabel , Contreras Maxime , Gómez Roberto , Aricò Antonino Salvatore
Published: May 2020

Tandem photoelectrochemical cells (PECs), made up of a solid electrolyte membrane between two low-cost photoelectrodes, were investigated to produce “green” hydrogen by exploiting renewable solar energy. The assembly of the PEC consisted of an anionic solid polymer electrolyte membrane (gas separator) clamped between an n-type Fe2O3 photoanode and a p-type CuO photocathode. The semiconductors were deposited on fluorine-doped tin oxide (FTO) transparent substrates and the cell was investigated with the hematite surface directly exposed to a solar simulator. Ionomer dispersions obtained from the dissolution of commercial polymers in the appropriate solvents were employed as an ionic interface with the photoelectrodes. Thus, the overall photoelectrochemical water splitting occurred in two membrane-separated compartments, i.e., the oxygen evolution reaction (OER) at the anode and the hydrogen evolution reaction (HER) at the cathode. A cost-effective NiFeOx co-catalyst was deposited on the hematite photoanode surface and investigated as a surface catalytic enhancer in order to improve the OER kinetics, this reaction being the rate-determining step of the entire process. The co-catalyst was compared with other well-known OER electrocatalysts such as La0.6Sr0.4Fe0.8CoO3 (LSFCO) perovskite and IrRuOx. The Ni-Fe oxide was the most promising co-catalyst for the oxygen evolution in the anionic environment in terms of an enhanced PEC photocurrent and efficiency. The materials were physico-chemically characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM).