bluuebunny/crossref_metadata_2025 huggingface dataset:
Xeno-Hybrid Composite Scaffold Manufactured with CAD/CAM Technology for Horizontal Bone-Augmentation in Edentulous Atrophic Maxilla: A Short Communication
Authors: Cristalli Maria Paola , La Monaca Gerardo , Pranno Nicola , Annibali Susanna , Iezzi Giovanna , Vozza Iole
Published: April 2020

The present short communication described a new procedure for the reconstruction of the horizontal severely resorbed edentulous maxilla with custom-made deproteinized bovine bone block, fabricated using three-dimensional imaging of the patient and computer-aided design/computer-aided manufacturing (CAD/CAM) technology. The protocol consisted of three phases. In the diagnosis and treatment planning, cone-beam computed tomographic scans of the patient were saved in DICOM (digital imaging and communication in medicine) format, anatomic and prosthetic data were imported into a dedicated diagnostic and medical imaging software, the prosthetic-driven position of the implants, and the graft blocks perfectly adapted to the residual bone structure were virtually planned. In the manufacturing of customized graft blocks, the CAD-CAM technology and the bovine-derived xenohybrid composite bone (SmartBone® on Demand - IBI SA - Industrie Biomediche Insubri SA Switzerland) were used to fabricate the grafts in the exact shape of the 3D planning virtual model. In the surgical and prosthetic procedure, the maxillary ridge augmentation with custom-made blocks and implant-supported full-arch screw-retained rehabilitation were performed. The described protocol offered some advantages when compared to conventional augmentation techniques. The use of deproteinized bovine bone did not require additional surgery for bone harvesting, avoided the risk of donor site morbidity, and provided unlimited biomaterial availability. The customization of the graft blocks reduced the surgical invasiveness, shorting operating times because the manual shaping of the blocks and its adaptation at recipient sites are not necessary and less dependent on the clinician’s skill and experience.
Enhanced Crystal Stabilities of ε-CL-20 via Core-Shell Structured Energetic Composites
Authors: Zhang Honglei , Jiao Qingjie , Zhao Wanjun , Guo Xueyong , Li Dayong , Sun Xiaole
Published: April 2020

2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is a widely used high-energy explosive for the application of energetic materials. However, the phase transformation from ε-CL-20 to γ-CL-20 restrains its further application in polymer bonded explosives (PBXs) and propellants. To inhibit the phase transition of CL-20, dopamine was first used in an efficient and facile method of in situ polymerization to passivate CL-20 crystals. The core-shell microcapsule particles were obtained, and the morphological characterization demonstrates the formation of a dense core-shell structure. The differential scanning calorimetry (DSC) and in situ X-ray diffraction (XRD) test results show that the compact and dense coating delays the ε-CL-20 crystal transformation temperature by about 30 °C, which enhances thermal stability. In addition, with the coating via polymers, the friction sensitivity of ε-CL-20 crystals decreases significantly. The findings indicate a successful application of dopamine chemistry in high-energy explosives, which provides an attractive method to modify the properties of CL-20 crystals.
Multi-Objective Design Optimization of the Reinforced Composite Roof in a Solar Vehicle
Authors: Pavlovic Ana , Sintoni Davide , Fragassa Cristiano , Minak Giangiacomo
Published: April 2020

A multi-step and -objective design approach was used to optimize the photovoltaic roof in a multi-occupant racing vehicle. It permitted to select the best combination of design features (as shapes, widths, angles) in composite structures simultaneously balancing opposite requirements as static strength and dynamic stiffness. An attention to functional requirements, as weight, solar cells cooling and solar energy conversion, was also essential. Alternative carbon fiber-reinforced plastic structures were investigated by finite elements using static and modal analyses in the way to compare several design configurations in terms of natural frequencies, deformations, flexural stiffness, torsional stiffness, and heat exchange surfaces. A representative roof section was manufactured and tested for model validation. A significant improvement respect to the pre-existing solar roof was detected. The final configuration was manufactured and installed on the vehicle.
Experimental Investigation on the Use of Waste Elastomeric Polymers for Bitumen Modification
Authors: Yeganeh Sadegh , Ameri Mahmoud , Dalmazzo Davide , Santagata Ezio
Published: April 2020

The study described in this paper focused on the possible use of waste products coming from the production of styrene–butadiene rubber (SBR) and polybutadiene rubber (PBR), as bitumen modifiers. Modified binders containing these products were prepared in the laboratory with different polymer dosages and were thereafter subjected to the evaluation of empirical and rheological properties. For comparative purposes, the study also considered SBR and PBR products of premium quality. Ageing effects were also taken into account by means of proper laboratory simulations. Obtained results indicated that the two types of polymer (SBR and PBR) have completely different effects on the rheology and expected performance of the resulting modified binders. In particular, while the two polymers showed similar effects in terms of resistance to permanent deformation, the SBR products proved to be superior from the viewpoint of fatigue resistance. However, only minor differences were found when comparing the effects produced by premium quality and waste polymers. As a result of the experimental findings, it was concluded that the use of waste SBR polymers can be an attractive solution for the production of affordable modified binders.
Simultaneous Nano-Texturing onto a CVD-Diamond Coated Piercing Punch with Femtosecond Laser Trimming
Authors: Aizawa Tatsuhiko , Shiratori Tomomi , Kira Yoshihiro , Inohara Tadahiko
Published: April 2020

In this study, a CVD (Chemical Vapor Deposition)-diamond coated tungsten carbide cobalt (WC (Co)) punch was trimmed to adjust its surface roughness and to significantly reduce its edge curvature for fine piercing by femtosecond laser processing. Through this laser trimming, the surface quality of the diamond coating and the punch edge profile were improved to less than 0.5 μm at the maximum roughness and 2 μm in the edge width, respectively. In parallel with this improvement of surface quality, the side surface of the diamond coating was modified to include nano-textures via the LIPSS (Laser Induced Periodic Surface Structuring) process. Through the fine piercing process, this nanotexture was transcribed onto the pierced hole surface together with fine shearing of the hole by piercing. WLI (White-Light Interferometry) and SEM (Scanning Electron Microscopy) were utilized to describe this transcription of nanotextures during the piercing process. These semiregular nanotextures with an LIPSS period of 300 nm on the pierced hole surface induced a blue colored surface plasmon.
A Survey of Optimal Hardware and Software Mapping for Distributed Integrated Modular Avionics Systems
Authors: Zhang Weiwen , Liu Jianqi , Cheng Lianglun , Filho Ricardo Shirota , Gao Fei
Published: April 2020

With an increasing number of aircraft systems, a fully manual developmental approach is impractical for finding optimal hardware and software mapping from overwhelming configurations for Distributed Integrated Modular Avionics (DIMA) systems. The automation of finding such optimized mapping should be available and thoroughly understood. This paper is an investigation on the foundations of optimal hardware and software mapping for DIMA. We begin by reviewing the DIMA system architecture. Following that, we present the problem statement of hardware and software mapping and its ensuring mathematical optimization models. A set of primary architectural quality metrics (e.g., reliability and scalability) and aircraft constraints (e.g., segregation and resource constraints) are identified, which can be used to compose an objective function or compare and trade alternatives. Based on the quality metrics and aircraft constraints, we synthesize an encompassing formulation by means of multi-objective optimization. Various optimization approaches for hardware and software mapping are then reviewed and compared. Case studies of DIMA optimization are presented for avionics systems, in which running time is reported for different optimization problems with different objectives and constraints. In addition, we present and discuss open issues and future trends, from which future developments may draw upon.
Indoor Air Quality: A Focus on the European Legislation and State-of-the-Art Research in Italy
Authors: Settimo Gaetano , Manigrasso Maurizio , Avino Pasquale
Published: April 2020

The World Health Organization (WHO) has always stressed the importance of indoor air quality (IAQ) and the potential danger of pollutants emitted from indoor sources; thus, it has become one of the main determinants for health. In recent years, reference documents and guidelines have been produced on many pollutants in order to: i) decrease their impact on human health (as well as the number of pollutants present in indoor environments), and ii) regulate the relevant levels of chemicals that can be emitted from the various materials. The aim of this paper is to discuss and compare the different legislations present in the European Union (EU). Furthermore, a focus of this paper will be dedicated at Italian legislation, where there is currently no specific reference to IAQ. Although initiatives in the pre-regulatory sector have multiplied, a comprehensive and integrated policy on the issue is lacking. Pending framework law for indoor air quality, which takes into account WHO indications, the National Study Group (GdS) on Indoor Air Pollution by the Italian Institute of Health (IIS) is committed to providing shared technical-scientific documents in order to allow actions harmonized at a national level. An outlook of the main Italian papers published during these last five years will be reported and discussed.
Clear Night Sky Polarization Patterns Under the Super Blue Blood Moon
Authors: Yang Yueting , Hu Pengwei , Yang Jian , Wang Shanpeng , Zhang Qingyun , Wang Yan
Published: April 2020

Investigating celestial polarization patterns in the case of different environments is important for exploring the atmospheric radiative transfer mechanism. Although intensive studies on clear sky, foggy sky, and even total solar eclipse sky have been conducted, the polarization distribution generated by the moonlight has not been well investigated. This study analyzes celestial polarization patterns generated by the Super Blue Blood Moon (SBBM) through several comparative studies. The polarization patterns under the SBBM are collected, analyzed, and compared with both those generated by the ideal single-scattering Rayleigh model and those in the normal sky. From the analysis of the relative variation of the celestial polarization characteristics including the Degree of Polarization (DoP) and Angle of Polarization (AoP), the changes of the extremum, frequency, symmetric line, and neutral points are discussed. As a result, SBBM polarization patterns change at the beginning of the partial eclipse, and the neutral points vary from traditional neutral points. The value of DoP gradually decreases as the obscuration ratio of the Moon increases. The AoP is no longer symmetrical about the celestial meridian. As a conclusion, it is suggested that the variation of the polarized skylight during the SBBM should be considered in atmospheric model calculation for nocturnal biological activity and navigation information computation.
Chemical Characterization of Electronic Cigarette (e-cigs) Refill Liquids Prior to EU Tobacco Product Directive Adoption: Evaluation of BTEX Contamination by HS-SPME-GC-MS and Identification of Flavoring Additives by GC-MS-O
Authors: Palmisani Jolanda , Abenavoli Carmelo , Famele Marco , Di Gilio Alessia , Palmieri Laura , de Gennaro Gianluigi , Draisci Rosa
Published: April 2020

The present study focused on the determination of benzene, toluene, ethylbenzene and xylenes (BTEX) concentration levels in 97 refill liquids for e-cigs selected by the Italian National Institute of Health as representative of the EU market between 2013 and 2015 prior to the implementation of the European Union (EU) Tobacco Product Directive (TPD). Most of the e-liquids investigated (85/97) were affected by BTEX contamination, with few exceptions observed (levels below the limit of quantification (LOQ) of headspace-solid phase micro extraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) methodology). Across brands, concentration levels ranged from 2.7 to 30,200.0 µg/L for benzene, from 1.9 to 447.8 µg/L for ethylbenzene, from 1.9 to 1,648.4 µg/L for toluene and from 1.7 to 574.2 µg/L for m,p,o-xylenes. The variability observed in BTEX levels is likely to be related to the variability in contamination level of both propylene glycol and glycerol and flavoring additives included. No correlation was found with nicotine content. Moreover, on a limited number of e-liquids, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) analysis was performed, allowing the identification of key flavoring additives responsible of specific flavor notes. Among them, diacetyl is a flavoring additive of concern for potential toxicity when directly inhaled into human airways. The data reported are eligible to be included in the pre-TPD database and may represent a reference for the ongoing evaluation on e-liquids safety and quality under the current EU Legislation.
Vision-Based Contactless Pose Estimation for Human Thermal Discomfort
Authors: Qian Junpeng , Cheng Xiaogang , Yang Bin , Li Zhe , Ren Junchi , Olofsson Thomas , Li Haibo
Published: April 2020

Real-time and effective human thermal discomfort detection plays a critical role in achieving energy efficient control of human centered intelligent buildings because estimation results can provide effective feedback signals to heating, ventilation and air conditioning (HVAC) systems. How to detect occupant thermal discomfort is a challenge. Unfortunately, contact or semi-contact perception methods are inconvenient in practical application. From the contactless perspective, a kind of vision-based contactless human discomfort pose estimation method was proposed in this paper. Firstly, human pose data were captured from a vision-based sensor, and corresponding human skeleton information was extracted. Five thermal discomfort-related human poses were analyzed, and corresponding algorithms were constructed. To verify the effectiveness of the algorithms, 16 subjects were invited for physiological experiments. The validation results show that the proposed algorithms can recognize the five human poses of thermal discomfort.
Does Air Pollution Influence COVID-19 Outbreaks?
Authors: Contini Daniele , Costabile Francesca
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [...]
Climate Change and the Pattern of the Hot Spots of War in Ancient China
Authors: Zhang Shengda , Zhang David Dian , Li Jinbao
Published: April 2020

Quantitative research on climate change and war hot spots throughout history is lacking. In this study, the spatial distribution and dynamic process of war hot spots under different climatic phases in imperial China (1–1911 CE) are revealed using Emerging Hot Spot Analysis (EHSA), based on the Global Moran’s Index for testing the degree of spatial autocorrelation or dependency. The results show that: (1) Battles were significantly clustered regardless of any climatic mode or war category. (2) Hot spots for all war were generally located in the Loess Plateau and the North China Plain during warm and wet periods, but in the Central Plain, the Jianghuai region, and the lower reaches of the Yangtze River/Yangtze River Delta during cold and dry conditions. (3) Hot spots for agri-nomadic conflict have similar patterns as those for all war, whereas rebellion hot spots expanded outward during warm and wet intervals yet contracted inward during cold and dry stages. These findings, by providing insightful evidence into the spatiotemporal patterns of war under the movements of climatic-ecological zones and geopolitical variations in ancient China, can be a starting point for future exploration of the long-term relationship between climate change and social security.
A Preliminary Evaluation to Establish Bath Pasteurization Guidelines for Hard Cider
Authors: Valliere Brianna , Harkins Sarah
Published: April 2020

Though in-package water bath heat pasteurization for hard cider production is commonly employed to improve product safety and stability, there is a considerable lack of research-based guidelines to inform industry practices. In this study, fermented cider was bottled and inoculated with high populations of Saccharomyces cerevisiae and Zygosaccharomyces rouxii yeast. The bottles were then subjected to water bath pasteurization 60 °C at varying lengths of time. For both yeast species, populations were reduced to undetectable levels after just 1 min of processing time. Though validation of each individual process is recommended, cider producers may be able to sufficiently reduce the risks of spoilage organisms with minimal water bath pasteurization, especially when combined with other methods to reduce the presence of spoilage organisms.
Application of Zebrafish Model in the Suppression of Drug-Induced Cardiac Hypertrophy by Traditional Indian Medicine Yogendra Ras
Authors: Balkrishna Acharya , Rustagi Yashika , Bhattacharya Kunal , Varshney Anurag
Published: April 2020

Zebrafish is an elegant vertebrate employed to model the pathological etiologies of human maladies such as cardiac diseases. Persistent physiological stresses can induce abnormalities in heart functions such as cardiac hypertrophy (CH), which can lead to morbidity and mortality. In the present study, using zebrafish as a study model, efficacy of the traditional Indian Ayurveda medicine “Yogendra Ras” (YDR) was validated in ameliorating drug-induced cardiac hypertrophy. YDR was prepared using traditionally described methods and composed of nano- and micron-sized metal particles. Elemental composition analysis of YDR showed the presence of mainly Au, Sn, and Hg. Cardiac hypertrophy was induced in the zebrafish following a pretreatment with erythromycin (ERY), and the onset and reconciliation of disease by YDR were determined using a treadmill electrocardiogram, heart anatomy analysis, C-reactive protein release, and platelet aggregation time-analysis. YDR treatment of CH-induced zebrafish showed comparable results with the Standard-of-care drug, verapamil, tested in parallel. Under in-vitro conditions, treatment of isoproterenol (ISP)-stimulated murine cardiomyocytes (H9C2) with YDR resulted in the suppression of drug-stimulated biomarkers of oxidative stress: COX-2, NOX-2, NOX-4, ANF, troponin-I, -T, and cardiolipin. Taken together, zebrafish showed a strong disposition as a model for studying the efficacy of Ayurvedic medicines towards drug-induced cardiopathies. YDR provided strong evidence for its capability in modulating drug-induced CH through the restoration of redox homeostasis and exhibited potential as a viable complementary therapy.
PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels
Authors: De Rasmo Domenico , Ferretta Anna , Russo Silvia , Ruggieri Maddalena , Lasorella Piergiorgio , Paolicelli Damiano , Trojano Maria , Signorile Anna
Published: April 2020

Multiple sclerosis (MS) is an autoimmune disease in which activated lymphocytes affect the central nervous system. Increase of reactive oxygen species (ROS), impairment of mitochondria-mediated apoptosis and mitochondrial alterations have been reported in peripheral lymphocytes of MS patients. Mitochondria-mediated apoptosis is regulated by several mechanisms and proteins. Among others, optic atrophy 1 (OPA1) protein plays a key role in the regulating mitochondrial dynamics, cristae architecture and release of pro-apoptotic factors. Very interesting, mutations in OPA1 gene, have been associated with multiple sclerosis-like disorder. We have analyzed OPA1 and some factors involved in its regulation. Fifteen patients with MS and fifteen healthy control subjects (HC) were enrolled into the study and peripheral blood mononuclear cells (PBMCs) were isolated. H2O2 level was measured spectrofluorimetrically, OPA1, PHB2, SIRT3, and OMA1 were analyzed by western blotting. Statistical analysis was performed using Student’s t-test. The results showed that PBMC of MS patients were characterized by a deregulation of OPA1 processing associated with increased H2O2 production, inactivation of OMA1 and increase of PHB2 protein level. The presented data suggest that the alteration of PHB2, OMA1, and OPA1 processing could be involved in resistance towards apoptosis. These molecular parameters could also be useful to assess disease activity.
Enhancement of Amyloid β1–43 Production in the Lens Epithelium of Japanese Type 2 Diabetic Patients
Authors: Mano Yu , Otake Hiroko , Shibata Teppei , Kubo Eri , Sasaki Hiroshi , Nagai Noriaki
Published: April 2020

We investigated whether the accumulation of amyloid β-protein (Aβ) is enhanced in the lenses of diabetic patients. Lens epithelium samples were collected from Japanese patients during cataract surgery, and the Aβ levels and gene expression of Aβ-producing and -degrading enzymes in the samples were measured by ELISA and real-time RT-PCR, respectively. The Aβ1–43 levels in lenses of non-diabetic patients were low (0.11 pmol/g protein), while the levels in lenses of diabetic patients were significantly (6-fold) higher. Moreover, the Aβ1–43/total-Aβ ratio in the lenses of diabetic patients was also significantly higher than non-diabetic patients (p < 0.05). In addition, the mRNA levels for Aβ-producing enzymes were also enhanced in the lenses of diabetic patients. In contrast to the results for Aβ-producing enzymes, the mRNAs for the Aβ-degrading enzymes in the lenses of diabetic patients were significantly lower than in non-diabetic patients (p < 0.05). Furthermore, Aβ1–43/total-Aβ ratio in lenses was found to increase with plasma glucose level. In conclusion, these results suggest that high glucose levels cause both an increase in Aβ production and a decrease in Aβ degradation, and these changes lead to the enhancement in Aβ1–43 accumulation in the lenses of diabetic patients. These findings are useful for developing therapies for diabetic cataracts and for developing anti-cataract drugs.
A Non-Coding RNA Landscape of Bronchial Epitheliums of Lung Cancer Patients
Authors: Lin Yanli , Holden Van , Dhilipkannah Pushpawallie , Deepak Janaki , Todd Nevins W. , Jiang Feng
Published: April 2020

We propose to systematically identify a non-coding RNA (ncRNA) profile of exfoliated bronchial epitheliums of sputum from lung cancer patients. Bronchial epithelial cells enriched from sputum of 32 lung cancer patients and 33 cancer-free smokers were analyzed by next-generation sequencing to comprehensively characterize the ncRNA profiles. In addition, 108 miRNAs, 88 small nucleolar RNAs, 13 piwi-interacting RNAs, 6 transfer RNAs, 4 ribosomal RNAs, 19 small nuclear RNAs, and 25 long-noncoding (lnc) RNAs displayed a significantly different level in bronchial epitheliums of sputum of lung cancer patients versus cancer-free smokers (all <0.001). PCR analysis confirmed their different expression levels in the sputum specimens. A high expression of SNHG9, an lncRNA, was validated in 78 lung tumor tissues, and the expression was inversely associated with overall survival of lung cancer patients (p = 0.002). Knockdown of SNHG9 in cancer cells reduced the cell growth, proliferation, and invasion in vitro and tumorigenesis in vivo. The multiple differentially expressed ncRNAs in bronchial epitheliums may contribute to the development and progression of lung cancer and provide potential biomarkers and therapeutic targets for the disease.
Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review
Authors: Schaffert Larissa-Nele , Carter Wayne G.
Published: April 2020

The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs.
P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse
Authors: Pascucci Tiziana , Colamartino Marco , Fiori Elena , Sacco Roberto , Coviello Annalisa , Ventura Rossella , Puglisi-Allegra Stefano , Turriziani Laura , Persico Antonio M.
Published: April 2020

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction/communication, stereotypic behaviors, restricted interests, and abnormal sensory-processing. Several studies have reported significantly elevated urinary and foecal levels of p-cresol in ASD children, an aromatic compound either of environmental origin or produced by specific gut bacterial strains. Methods: Since p-cresol is a known uremic toxin, able to negatively affect multiple brain functions, the present study was undertaken to assess the effects of a single acute injection of low- or high-dose (1 or 10 mg/kg i.v. respectively) of p-cresol in behavioral and neurochemical phenotypes of BTBR mice, a reliable animal model of human ASD. Results: P-cresol significantly increased anxiety-like behaviors and hyperactivity in the open field, in addition to producing stereotypic behaviors and loss of social preference in BTBR mice. Tissue levels of monoaminergic neurotransmitters and their metabolites unveiled significantly activated dopamine turnover in amygdala as well as in dorsal and ventral striatum after p-cresol administration; no effect was recorded in medial-prefrontal cortex and hippocampus. Conclusion: Our study supports a gene x environment interaction model, whereby p-cresol, acting upon a susceptible genetic background, can acutely induce autism-like behaviors and produce abnormal dopamine metabolism in the reward circuitry.
Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer
Authors: Yoon Han Gyul , Oh Dongryul , Ahn Yong Chan , Noh Jae Myoung , Pyo Hongryull , Cho Won Kyung , Song Yun Mi , Park Minsu , Hwang Na Young , Sun Jong-Mu , Kim Hong Kwan , Zo Jae Ill , Shim Young Mog
Published: April 2020

Backgrounds: The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients. Methods: We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm2/m2, and excessive muscle loss was defined as SMI change <−10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected. Results: In the univariable Cox analysis, pre- (p = 0.689) and post-radiotherapy (RT) sarcopenia (p = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all p = 0.001). Excessive muscle loss was also related to RFS in both the univariable (p = 0.011) and multivariable (p = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin (p < 0.001) and PNI (p < 0.001), higher levels of post-RT NLR (p = 0.031) and PLR (p = 0.071), larger decrease in albumin (p < 0.001) and PNI (p < 0.001) after NACRT, and larger increase in NLR (p = 0.051) and PLR (p = 0.088) after NACRT than in those with non-excessive muscle loss. Conclusion: Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers.
Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
Authors: Segura-Díaz Adrián , Stuckey Ruth , Florido Yanira , González-Martín Jesús María , López-Rodríguez Juan Francisco , Sánchez-Sosa Santiago , González-Pérez Elena , Sáez Perdomo María Nieves Sáez , Perera María del Mar , de la Iglesia Silvia , Molero-Labarta Teresa , Gómez-Casares María Teresa , Bilbao-Sieyro Cristina
Published: April 2020

The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort (p = 0.025, OR: 1.047, 95% CI: 1.006–1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients (p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15–11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.
Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer
Authors: Yu Jeong Il , Park Hee Chul , Lee Jeeyun , Choi Changhoon , Kang Won Ki , Park Se Hoon , Kim Seung Tae , Sohn Tae Sung , Lee Jun Ho , An Ji Yeong , Choi Min Gew , Bae Jae Moon , Kim Kyoung-Mee , Han Heewon , Kim Kyunga , Kim Sung , Lim Do Hoon
Published: April 2020

Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21–3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31–3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.
The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications
Authors: Recagni Marta , Bidzinska Joanna , Zaffaroni Nadia , Folini Marco
Published: April 2020

Telomere maintenance mechanisms (i.e., telomerase activity (TA) and the alternative lengthening of telomere (ALT) mechanism) contribute to tumorigenesis by providing unlimited proliferative capacity to cancer cells. Although the role of either telomere maintenance mechanisms seems to be equivalent in providing a limitless proliferative ability to tumor cells, the contribution of TA and ALT to the clinical outcome of patients may differ prominently. In addition, several strategies have been developed to interfere with TA in cancer, including Imetelstat that has been the first telomerase inhibitor tested in clinical trials. Conversely, the limited information available on the molecular underpinnings of ALT has hindered thus far the development of genuine ALT-targeting agents. Moreover, whether anti-telomerase therapies may be hampered or not by possible adaptive responses is still debatable. Nonetheless, it is plausible hypothesizing that treatment with telomerase inhibitors may exert selective pressure for the emergence of cancer cells that become resistant to treatment by activating the ALT mechanism. This notion, together with the evidence that both telomere maintenance mechanisms may coexist within the same tumor and may distinctly impinge on patients’ outcomes, suggests that ALT may exert an unexpected role in tumor biology that still needs to be fully elucidated.
Validating the ACOSOG Z0011 Trial Result: A Population-Based Study Using the SEER Database
Authors: Jung Jiwoong , Kim Byoung Hyuck , Kim Jongjin , Oh Sohee , Kim Su-jin , Lim Chang-Sup , Choi In Sil , Hwang Ki-Tae
Published: April 2020

The Z0011 trial demonstrated that axillary lymph node dissection (ALND) could be omitted in spite of 1–2 metastatic sentinel lymph nodes. This study aimed to validate the results on a population-based database. The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients comparable to the Z0011 participants. The type of axillary surgery was estimated using the total number of examined axillary lymph nodes (ALNs). Breast cancer-specific mortality (BCSM) was compared between patients with ≥10 ALNs (the sentinel lymph node dissection (SLND) and ALND group, or “SLND + ALND group”) and patients with one or two ALNs (the “SLND group”). During 2010–2015, the SEER database included 7077 and 6620 patients categorized in the SLND group and the SLND + ALND group, respectively. Death was observed for 515 patients (7.3%) in the SLND group and 589 patients (8.9%) in the SLND + ALND group based on a median follow-up of 41 months. After propensity-score matching, the adjusted hazard ratio for BCSM in the SLND group (vs. the SLND + ALND group) was 1.038 (95% confidence interval: 0.798–1.350). Regardless of the SLND criteria, the outcomes were not significantly different between the two groups. This retrospective cohort study of Z0011-comparable patients revealed that ALND could be omitted based on the Z0011 strategy, even among patients with ≤2 dissected ALNs.
Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers
Authors: Wen Pengbo , Gao Yang , Chen Bin , Qi Xiaojing , Hu Guanshuo , Xu An , Xia Junfeng , Wu Lijun , Lu Huayi , Zhao Guoping
Published: April 2020

Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, we investigated the link between immune infiltration status and clinical RT outcome in order to identify certain leukocyte subsets that could potentially influence the clinical RT benefit across cancers. By integrally analyzing the TCGA data across seven cancers, we identified complex associations between immune infiltration and patients RT outcomes. Besides, immune cells showed large differences in their populations in various cancers, and the most abundant cells were resting memory CD4 T cells. Additionally, the proportion of activated CD4 memory T cells and activated mast cells, albeit at low number, were closely related to RT overall survival in multiple cancers. Furthermore, a prognostic model for RT outcomes was established with good performance based on the immune infiltration status. Summarized, immune infiltration was found to be of significant clinical relevance to RT outcomes. These findings may help to shed light on the impact of tumor-associated immune cell infiltration on cancer RT outcomes, and identify biomarkers and therapeutic targets.
Catalytic Activity of Hybrid Iron Oxide Silver Nanoparticles in Methyl Methacrylate Polymerization
Authors: Solyman Sanaa M. , Darwish Mohamed S.A. , Yoon Jungwon
Published: April 2020

One of the challenges in the preparation of poly(methyl methacrylate) (PMMA) is to develop new catalytic systems with improved efficiency. A hybrid iron oxide silver catalyst holds promise in solving this issue. Catalysts were prepared at room temperature by a two-step technique. First, iron oxide nanoparticles were prepared by the reduction of FeCl3 using sodium borohydride (NaBH4) at room temperature. Second, magnetic nanoparticles doped with a series of Ag nanoparticles (Ag, Ag/3 –amino propyltriethoxysilane (APTES) and Ag/poly(ethyleneimine) (PEI)). The prepared catalysts were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX), and Fourier-transform infrared spectroscopy (FTIR). The catalytic activity of Fe, Ag/Fe, PEI–Ag/Fe, and APTES–Ag/Fe in methyl methacrylate (MMA) polymerization was investigated in the presence of O2, N2, NaHSO3, and benzoyl peroxide in bulk or solution conditions. The produced polymer was characterized by gel permeation chromatography (GPC) and proton nuclear magnetic resonance spectroscopy (1HNMR). The structures of PEI–Ag/Fe and APTES–Ag/Fe are assumed. The conversion efficiency was 100%, 100%, 97.6%, and 99.1% using Fe, Ag/Fe, PEI–Ag/Fe, and APTES–Ag/Fe catalysts at the optimum conditions, respectively. Hybrid iron oxide silver nanoparticles are promising catalysts for PMMA preparation.
Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity
Authors: Luarte Alejandro , Henzi Roberto , Fernández Anllely , Gaete Diego , Cisternas Pablo , Pizarro Matias , Batiz Luis Federico , Villalobos Isabel , Masalleras Matias , Vergara Rodrigo , Varas-Godoy Manuel , Abarzua-Catalan Lorena , Herrera-Molina Rodrigo , Lafourcade Carlos , Wyneken Ursula
Published: April 2020

In the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e., GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation, but also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.
Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway
Authors: Lin Yi-Hsuan , Wang Yi-Hsun , Peng Yi-Jen , Liu Feng-Cheng , Lin Gu-Jiun , Huang Shing-Hwa , Sytwu Huey-Kang , Cheng Chia-Pi
Published: April 2020

Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.
Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model
Authors: Oliveira Fernando A. , Nucci Mariana P. , Filgueiras Igor S. , Ferreira João M. , Nucci Leopoldo P. , Mamani Javier B. , Alvieri Fernando , Souza Lucas E. B. , Rego Gabriel N. A. , Kondo Andrea T. , Hamerschlak Nelson , Gamarra Lionel F.
Published: April 2020

The hematopoietic stem cell engraftment depends on adequate cell numbers, their homing, and the subsequent short and long-term engraftment of these cells in the niche. We performed a systematic review of the methods employed to track hematopoietic reconstitution using molecular imaging. We searched articles indexed, published prior to January 2020, in PubMed, Cochrane, and Scopus with the following keyword sequences: (Hematopoietic Stem Cell OR Hematopoietic Progenitor Cell) AND (Tracking OR Homing) AND (Transplantation). Of 2191 articles identified, only 21 articles were included in this review, after screening and eligibility assessment. The cell source was in the majority of bone marrow from mice (43%), followed by the umbilical cord from humans (33%). The labeling agent had the follow distribution between the selected studies: 14% nanoparticle, 29% radioisotope, 19% fluorophore, 19% luciferase, and 19% animal transgenic. The type of graft used in the studies was 57% allogeneic, 38% xenogeneic, and 5% autologous, being the HSC receptor: 57% mice, 9% rat, 19% fish, 5% for dog, porcine and salamander. The imaging technique used in the HSC tracking had the following distribution between studies: Positron emission tomography/single-photon emission computed tomography 29%, bioluminescence 33%, fluorescence 19%, magnetic resonance imaging 14%, and near-infrared fluorescence imaging 5%. The efficiency of the graft was evaluated in 61% of the selected studies, and before one month of implantation, the cell renewal was very low (less than 20%), but after three months, the efficiency was more than 50%, mainly in the allogeneic graft. In conclusion, our review showed an increase in using noninvasive imaging techniques in HSC tracking using the bone marrow transplant model. However, successful transplantation depends on the formation of engraftment, and the functionality of cells after the graft, aspects that are poorly explored and that have high relevance for clinical analysis.