bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydria: An Online Data Lake for Multi-Faceted Analytics in the Cultural Heritage Domain
Authors: Deligiannis Kimon , Raftopoulou Paraskevi , Tryfonopoulos Christos , Platis Nikos , Vassilakis Costas
Published: April 2020

Advancements in cultural informatics have significantly influenced the way we perceive, analyze, communicate and understand culture. New data sources, such as social media, digitized cultural content, and Internet of Things (IoT) devices, have allowed us to enrich and customize the cultural experience, but at the same time have created an avalanche of new data that needs to be stored and appropriately managed in order to be of value. Although data management plays a central role in driving forward the cultural heritage domain, the solutions applied so far are fragmented, physically distributed, require specialized IT knowledge to deploy, and entail significant IT experience to operate even for trivial tasks. In this work, we present Hydria, an online data lake that allows users without any IT background to harvest, store, organize, analyze and share heterogeneous, multi-faceted cultural heritage data. Hydria provides a zero-administration, zero-cost, integrated framework that enables researchers, museum curators and other stakeholders within the cultural heritage domain to easily (i) deploy data acquisition services (like social media scrapers, focused web crawlers, dataset imports, questionnaire forms), (ii) design and manage versatile customizable data stores, (iii) share whole datasets or horizontal/vertical data shards with other stakeholders, (iv) search, filter and analyze data via an expressive yet simple-to-use graphical query engine and visualization tools, and (v) perform user management and access control operations on the stored data. To the best of our knowledge, this is the first solution in the literature that focuses on collecting, managing, analyzing, and sharing diverse, multi-faceted data in the cultural heritage domain and targets users without an IT background.
High-Density Lipoprotein Cholesterol in Age-Related Ocular Diseases
Authors: Betzler Bjorn Kaijun , Rim Tyler Hyungtaek , Sabanayagam Charumathi , Cheung Chui Ming Gemmy , Cheng Ching-Yu
Published: April 2020

There is limited understanding of the specific role of high-density lipoprotein cholesterol (HDL-C) in the development of various age-related ocular diseases, despite it being a common measurable biomarker in lipid profiles. This literature review summarizes current knowledge of the role of HDL-C, if any, in pathogenesis and progression of four age-related ocular diseases, namely age-related macular degeneration (AMD), age-related cataract, glaucoma, and diabetic retinopathy (DR), and will primarily discuss epidemiological and genetic evidence.
The Supplementary Motor Area Responsible for Word Retrieval Decline After Acute Thalamic Stroke Revealed by Coupled SPECT and Near-Infrared Spectroscopy
Authors: Obayashi Shigeru
Published: April 2020

Damage to the thalamus may affect cognition and language, but the underlying mechanism remains unknown. In particular, it remains a riddle why thalamic aphasia occasionally occurs and then mostly recovers to some degree. To explore the mechanism of the affected cognition and language, we used two neuroimaging techniques—single-photon emission computed tomography (SPECT), suitable for viewing the affected brain distribution after acute thalamic stroke, and functional near-infrared spectroscopy (f-NIRS), focusing on hemodynamic responses of the supplementary motor area (SMA) responsible for speech production in conjunction with the frontal aslant tract (FAT) pathway. SPECT yielded common perfusion abnormalities not only in the fronto–parieto–cerebellar loop, but also in the SMA, IFG and surrounding language-relevant regions. In NIRS sessions during a phonemic verbal fluency task, we found significant word retrieval decline in acute thalamic patients relative to age-matched healthy volunteers. Further, NIRS showed strong correlation between word retrieval and posterior SMA responses. In addition, follow-up NIRS exhibited increased bilateral SMA responses linked to improving word retrieval ability. The findings suggest that cognitive dysfunction may be related to the fronto–parieto–cerebellar loop, while language dysfunction is attributed to the SMA, IFG and language-related brain areas. SMA may contribute to the recovery of word retrieval difficulty and aphasia after thalamic stroke.
Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome
Authors: Cordeiro Lisa , Braden Marcia , Coan Elizabeth , Welnick Nanastasia , Tanda Tanea , Tartaglia Nicole
Published: April 2020

An efficient and direct measure of social interactions and autism symptoms is needed for fragile X syndrome (FXS) research and clinical care. The Autism Screening Instrument for Educational Planning-Third Edition (ASIEP-3) Interaction assessment is a brief standardized measure that quantifies social responses under different conditions. The feasibility and validity of the ASIEP-3 was evaluated in 26 males and 13 females with FXS, along with cognitive testing and behavior questionnaires. The videos were scored at 10-second intervals, and the observed behaviors were scored as an interaction, independent play, no response, or aggression. In total, 39/41 participants successfully completed the ASIEP-3 (age M = 14.4 ± 10.2), with a range of cognitive abilities (abbreviated IQ (ABIQ) M = 58.9 ± 17.3, median = 50), behaviors (Aberrant Behavior Checklist (ABC) Total M = 37.00 ± 27.3), and autism diagnoses (N = 22/39). Reliable administration was demonstrated by all team members. The mean coded behaviors included interaction (40.6%), independent play (36.8%), no response (21.1%), and aggressive behavior (<10%). The interaction score was negatively correlated with the Social Communication Questionnaire (SCQ) score (p = 0.037), and the profiles differed by autism spectrum disorder (ASD) diagnosis. The intraclass correlation coefficients (ICCs) ranged from 0.79 to 0.93 for master’s level and above. Administration of the ASIEP-3 was feasible for FXS across sex, age, ability, and behavior ratings by a trained research team. Reliable scoring required advanced training in the assessment of social development and FXS experience. The scores correlated to ratings and diagnoses of ASD. The ASIEP-3 shows promise to reliably index social interactions in FXS.
Self-Concept and Inattention or Hyperactivity–Impulsivity Symptomatology: The Role of Anxiety
Authors: Cueli Marisol , Rodríguez Celestino , Cañamero Laura , Núñez José , González-Castro Paloma
Published: April 2020

Attention-deficit/hyperactivity disorder (ADHD) has been associated with low levels of self-concept (academic, emotional, social or physical), although this association can differ in the function of the inattention or hyperactivity–impulsivity symptomatology. Furthermore, the relation between ADHD and self-concept can be mediated or moderated by the levels of anxiety. This work is aimed to examine the differential effect of inattention symptomatology and hyperactivity–impulsivity symptomatology on academic, emotional, social and physical self-concept and the mediating or moderating role of anxiety in this relationship. A total of 167 students (70.7% boys and 29.3% girls) aged between 11 and 16 participated in this study. Students’ ADHD symptomatology, self-concept in four areas (academic, emotional, social and physical self-concept) and trait anxiety were measured with the State-Trait Anxiety Inventory for Children. The results indicate that trait anxiety mediates the relationship between inattention and emotional, social and physical self-concept but does not moderate this relationship. Trait anxiety does not mediate or moderate the relationship between hyperactivity–impulsivity symptoms and self-concept. When inattention symptomatology increases, academic self-concept decreases directly, but students’ emotional, social and physical self-concept decreases indirectly through trait anxiety.
Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors
Authors: Idilli Aurora Irene , Pagani Francesca , Kerschbamer Emanuela , Berardinelli Francesco , Bernabé Manuel , Cayuela María Luisa , Piazza Silvano , Poliani Pietro Luigi , Cusanelli Emilio , Mione Maria Caterina
Published: April 2020

Background: The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative lengthening of telomeres (ALT) is found in a subset of sarcomas and malignant brain tumors. ALT is a non-canonical mechanism of telomere maintenance developed by cancer cells with no-functional telomerase. Methods: To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent. Results: Comparative analysis of gene expression identified five genes of the pre-replicative complex, ORC4, ORC6, MCM2, CDC45 and RPA3 as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9me3 localization at telomeres. Conclusions: Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes.
The Mitochondrial Protein VDAC1 at the Crossroads of Cancer Cell Metabolism: The Epigenetic Link
Authors: Amsalem Zohar , Arif Tasleem , Shteinfer-Kuzmine Anna , Chalifa-Caspi Vered , Shoshan-Barmatz Varda
Published: April 2020

Carcinogenesis is a complicated process that involves the deregulation of epigenetics, resulting in cellular transformational events, such as proliferation, differentiation, and metastasis. Most chromatin-modifying enzymes utilize metabolites as co-factors or substrates and thus are directly dependent on such metabolites as acetyl-coenzyme A, S-adenosylmethionine, and NAD+. Here, we show that using specific siRNA to deplete a tumor of VDAC1 not only led to reprograming of the cancer cell metabolism but also altered several epigenetic-related enzymes and factors. VDAC1, in the outer mitochondrial membrane, controls metabolic cross-talk between the mitochondria and the rest of the cell, thus regulating the metabolic and energetic functions of mitochondria, and has been implicated in apoptotic-relevant events. We previously demonstrated that silencing VDAC1 expression in glioblastoma (GBM) U-87MG cell-derived tumors, resulted in reprogramed metabolism leading to inhibited tumor growth, angiogenesis, epithelial–mesenchymal transition and invasiveness, and elimination of cancer stem cells, while promoting the differentiation of residual tumor cells into neuronal-like cells. These VDAC1 depletion-mediated effects involved alterations in transcription factors regulating signaling pathways associated with cancer hallmarks. As the epigenome is sensitive to cellular metabolism, this study was designed to assess whether depleting VDAC1 affects the metabolism–epigenetics axis. Using DNA microarrays, q-PCR, and specific antibodies, we analyzed the effects of si-VDAC1 treatment of U-87MG-derived tumors on histone modifications and epigenetic-related enzyme expression levels, as well as the methylation and acetylation state, to uncover any alterations in epigenetic properties. Our results demonstrate that metabolic rewiring of GBM via VDAC1 depletion affects epigenetic modifications, and strongly support the presence of an interplay between metabolism and epigenetics.
Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer
Authors: Afrin Farjana , Chi Mengna , Eamens Andrew L. , Duchatel Ryan J. , Douglas Alicia M. , Schneider Jennifer , Gedye Craig , Woldu Ameha S. , Dun Matthew D.
Published: April 2020

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆9-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.
β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells
Authors: Irrera Natasha , D’Ascola Angela , Pallio Giovanni , Bitto Alessandra , Mannino Federica , Arcoraci Vincenzo , Rottura Michelangelo , Ieni Antonio , Minutoli Letteria , Metro Daniela , Vaccaro Mario , Altavilla Domenica , Squadrito Francesco
Published: April 2020

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK.
Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation
Authors: Nair Mitra , Khosla Maninder , Otani Yoshihiro , Yeh Margaret , Park Flora , Shimizu Toshihiko , Kang Jin Muk , Bolyard Chelsea , Yu Jun-Ge , Kumar Banasavadi-Siddegowda Yeshavanth , Lopez Gonzalo , Kaur Balveen , Pollock Raphael E. , Lee Tae Jin , Old Matthew , Yoo Ji Young
Published: April 2020

Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including ImlygicTM, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angiogenesis inhibition on endothelial cell activation has not been previously described. Here, we tested the effects of Rapid Antiangiogenesis Mediated By Oncolytic Virus (RAMBO), an oHSV which expresses a potent anti-angiogenic gene Vasculostatin on endothelial cell activation in heavily vascularized solid tumors. oHSV treatment induces endothelial cell activation, which inhibits virus propagation and oncolysis in adjacent tumor cells in vitro. Consistently, this was also observed in intravital imaging of intracranial tumor-bearing mice in vivo where infected tumor endothelial cells could efficiently clear the virus without cell lysis. Quantitative real-time PCR (Q-PCR), leukocyte adhesion assay, and fluorescent microscopy imaging data, however, revealed that RAMBO virus significantly decreased expression of endothelial cell activation markers and leukocyte adhesion, which in turn increased virus replication and cytotoxicity in endothelial cells. In vivo RAMBO treatment of subcutaneously implanted sarcoma tumors significantly reduced tumor growth in mice bearing sarcoma compared to rHSVQ. In addition, histological analysis of RAMBO-treated tumor tissues revealed large areas of necrosis and a statistically significant reduction in microvessel density (MVD). This study provides strong preclinical evidence of the therapeutic benefit for the use of RAMBO virus as a treatment option for highly vascularized tumors.
Functional and Clinical Impact of CircRNAs in Oral Cancer
Authors: Cristóbal Ion , Caramés Cristina , Rubio Jaime , Sanz-Alvarez Marta , Luque Melani , Madoz-Gúrpide Juan , Rojo Federico , García-Foncillas Jesús
Published: April 2020

The increasing number of recently published works regarding the role of circular RNAs (circRNAs) in oral cancer highlights the key contribution of this novel class of endogenous noncoding RNAs as regulators of critical signaling pathways and their clinical value as novel biomarkers. This review summarizes and puts into context the existing literature in order to clarify the relevance of circRNAs as novel mediators of oral cancer pathogenesis as well as their potential usefulness as predictors of clinical outcome and response to therapy in this disease.
18F-FDG and 11C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers
Authors: Morales-Lozano Maria I , Viering Oliver , Samnick Samuel , Rodriguez-Otero Paula , Buck Andreas K , Marcos-Jubilar Maria , Rasche Leo , Prieto Elena , Kortüm K Martin , San-Miguel Jesus , Garcia-Velloso Maria J. , Lapa Constantin
Published: April 2020

11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.
Nicotine in Senescence and Atherosclerosis
Authors: Centner Ann Marie , Bhide Pradeep G. , Salazar Gloria
Published: April 2020

Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the role of nicotine and its major metabolite cotinine is yet to be elucidated. Considering the growing amount of nicotine-containing aerosol use in recent years, the role of nicotine is a relevant public health concern. A number of recent studies and health education sites have focused on nicotine aerosol-induced adverse lung function, and neglected cardiovascular (CV) impairments and diseases. A critical review of the present scientific literature leads to the hypothesis that nicotine mediates the effects of cigarette smoke in the CV system by increasing MAPK signaling, inflammation, and oxidative stress through NADPH oxidase 1 (Nox1), to induce vascular smooth muscle cell (VSMC) senescence. The accumulation of senescent VSMCs in the lesion cap is detrimental as it increases the pathogenesis of atherosclerosis by promoting an unstable plaque phenotype. Therefore, nicotine, and most likely its metabolite cotinine, adversely influence atherosclerosis.
E-Cadherin in Pancreatic Ductal Adenocarcinoma: A Multifaceted Actor during EMT
Authors: Sommariva Michele , Gagliano Nicoletta
Published: April 2020

Epithelial-to-mesenchymal transition (EMT) is a step-wise process observed in normal and tumor cells leading to a switch from epithelial to mesenchymal phenotype. In tumors, EMT provides cancer cells with a metastatic phenotype characterized by E-cadherin down-regulation, cytoskeleton reorganization, motile and invasive potential. E-cadherin down-regulation is known as a key event during EMT. However, E-cadherin expression can be influenced by the different experimental settings and environmental stimuli so that the paradigm of EMT based on the loss of E-cadherin determining tumor cell behavior and fate often becomes an open question. In this review, we aimed at focusing on some critical points in order to improve the knowledge of the dynamic role of epithelial cells plasticity in EMT and, specifically, address the role of E-cadherin as a marker for the EMT axis.
Molecular Regulation of the RhoGAP GRAF3 and Its Capacity to Limit Blood Pressure In Vivo
Authors: Dee Rachel A. , Bai Xue , Mack Christopher P. , Taylor Joan M.
Published: April 2020

Anti-hypertensive therapies are usually prescribed empirically and are often ineffective. Given the prevalence and deleterious outcomes of hypertension (HTN), improved strategies are needed. We reported that the Rho-GAP GRAF3 is selectively expressed in smooth muscle cells (SMC) and controls blood pressure (BP) by limiting the RhoA-dependent contractility of resistance arterioles. Importantly, genetic variants at the GRAF3 locus controls BP in patients. The goal of this study was to validate GRAF3 as a druggable candidate for future anti-HTN therapies. Importantly, using a novel mouse model, we found that modest induction of GRAF3 in SMC significantly decreased basal and vasoconstrictor-induced BP. Moreover, we found that GRAF3 protein toggles between inactive and active states by processes controlled by the mechano-sensing kinase, focal adhesion kinase (FAK). Using resonance energy transfer methods, we showed that agonist-induced FAK-dependent phosphorylation at Y376GRAF3 reverses an auto-inhibitory interaction between the GAP and BAR-PH domains. Y376 is located in a linker between the PH and GAP domains and is invariant in GRAF3 homologues and a phosphomimetic E376GRAF3 variant exhibited elevated GAP activity. Collectively, these data provide strong support for the future identification of allosteric activators of GRAF3 for targeted anti-hypertensive therapies.
A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment
Authors: Kadye Rose , Stoffels Mihlali , Fanucci Sidne , Mbanxa Siso , Prinsloo Earl
Published: April 2020

Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.
Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases
Authors: Groot Michael , Lee Heedoo
Published: April 2020

Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.
Satellite Cells in Skeletal Muscle of the Hibernating Dormouse, a Natural Model of Quiescence and Re-Activation: Focus on the Cell Nucleus
Authors: Malatesta Manuela , Costanzo Manuela , Cisterna Barbara , Zancanaro Carlo
Published: April 2020

Satellite cells (SCs) participate in skeletal muscle plasticity/regeneration. Activation of SCs implies that nuclear changes underpin a new functional status. In hibernating mammals, periods of reduced metabolic activity alternate with arousals and resumption of bodily functions, thereby leading to repeated cell deactivation and reactivation. In hibernation, muscle fibers are preserved despite long periods of immobilization. The structural and functional characteristics of SC nuclei during hibernation have not been investigated yet. Using ultrastructural and immunocytochemical analysis, we found that the SCs of the hibernating edible dormouse, Glis glis, did not show apoptosis or necrosis. Moreover, their nuclei were typical of quiescent cells, showing similar amounts and distributions of heterochromatin, pre-mRNA transcription and processing factors, as well as paired box protein 7 (Pax7) and the myogenic differentiation transcription factor D (MyoD), as in euthermia. However, the finding of accumulated perichromatin granules (i.e., sites of storage/transport of spliced pre-mRNA) in SC nuclei of hibernating dormice suggested slowing down of the nucleus-to-cytoplasm transport. We conclude that during hibernation, SC nuclei maintain similar transcription and splicing activity as in euthermia, indicating an unmodified status during immobilization and hypometabolism. Skeletal muscle preservation during hibernation is presumably not due to SC activation, but rather to the maintenance of some functional activity in myofibers that is able to counteract muscle wasting.
Progenitor Cells Activated by Platelet Lysate in Human Articular Cartilage as a Tool for Future Cartilage Engineering and Reparative Strategies
Authors: Carluccio Simonetta , Martinelli Daniela , Palamà Maria Elisabetta Federica , Pereira Rui Cruz , Benelli Roberto , Guijarro Ana , Cancedda Ranieri , Gentili Chiara
Published: April 2020

Regenerative strategies for human articular cartilage are still challenging despite the presence of resident progenitor cell population. Today, many efforts in the field of regenerative medicine focus on the use of platelet derivatives due to their ability to reactivate endogenous mechanisms supporting tissue repair. While their use in orthopedics continues, mechanisms of action and efficacy need further characterization. We describe that the platelet lysate (PL) is able to activate chondro-progenitor cells in a terminally differentiated cartilage tissue. Primary cultures of human articular chondrocytes (ACs) and cartilage explants were set up from donor hip joint biopsies and were treated in vitro with PL. PL recruited a chondro-progenitors (CPCs)-enriched population from ex vivo cartilage culture, that showed high proliferation rate, clonogenicity and nestin expression. CPCs were positive for in vitro tri-lineage differentiation and formed hyaline cartilage-like tissue in vivo without hypertrophic fate. Moreover, the secretory profile of CPCs was analyzed, together with their migratory capabilities. Some CPC-features were also induced in PL-treated ACs compared to fetal bovine serum (FBS)-control ACs. PL treatment of human articular cartilage activates a stem cell niche responsive to injury. These facts can improve the PL therapeutic efficacy in cartilage applications.
Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer
Authors: Baj Jacek , Korona-Głowniak Izabela , Forma Alicja , Maani Amr , Sitarz Elżbieta , Rahnama-Hezavah Mansur , Radzikowska Elżbieta , Portincasa Piero
Published: April 2020

Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world’s population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial–mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial–mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.
Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile
Authors: Franco da Cunha Flavia , Andrade-Oliveira Vinicius , Candido de Almeida Danilo , Borges da Silva Tamiris , Naffah de Souza Breda Cristiane , Costa Cruz Mario , Faquim-Mauro Eliana L. , Antonio Cenedeze Marcos , Ioshie Hiyane Meire , Pacheco-Silva Alvaro , Aparecida Cavinato Regiane , Torrecilhas Ana Claudia , Olsen Saraiva Câmara Niels
Published: April 2020

Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. Extracellular vesicles (EVs) release is a pivotal mechanism by which MSCs exert their actions. In this study, we evaluate whether mesenchymal stromal cell extracellular vesicles (MSC-EVs) can modulate T cell response. MSCs were expanded and EVs were obtained by differential ultracentrifugation of the supernatant. The incorporation of MSC-EVs by T cells was detected by confocal microscopy. Expression of surface markers was detected by flow cytometry or CytoFLEX and cytokines were detected by RT-PCR, FACS and confocal microscopy and a miRNA PCR array was performed. We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. Interestingly, in Th1 polarization, MSC-EVs increased Foxp3 expression and generated a subpopulation of IFN-γ+/Foxp3+T cells with suppressive capacity. A differential expression profile of miRNAs in MSC-EVs-treated Th1 cells was seen, and also a modulation of one of their target genes, TGFbR2. MSC-EVs altered the metabolism of Th1-differentiated T cells, suggesting the involvement of the TGF-β pathway in this metabolic modulation. The addition of MSC-EVs in vivo, in an OVA immunization model, generated cells Foxp3+. Thus, our findings suggest that MSC-EVs are able to specifically modulate activated T cells at an alternative regulatory profile by miRNAs and metabolism shifting.
Compressive Creep Measurements of Fired Magnesia Bricks at Elevated Temperatures Including Creep Law Parameter Identification and Evaluation by Finite Element Analysis
Authors: Unterreiter Guenter , Kreuzer Daniel R. , Lorenzoni Bernd , Marschall Hans U. , Wagner Christoph , Machhammer Robert , Hackl Gernot
Published: April 2020

Creep behavior is very important for the selection of refractory materials. This paper presents a methodology to measure the compressive creep behavior of fired magnesia materials at elevated temperatures. The measurements were carried out at 1150–1500 °C and under compression loads from 1–8 MPa. Creep strain was calculated from the measured total strain data. The obtained creep deformations of the experimental investigations were subjected to detailed analysis to identify the Norton-Bailey creep law parameters. The modulus of elasticity was determined in advance to simplify the inverse estimation process for finding the Norton-Bailey creep parameters. In the next step; an extended material model including creep was used in a finite element analysis (FEA) and the creep testing procedure was reproduced numerically. Within the investigated temperature and load range; the creep deformations calculated by FEA demonstrated a good agreement with the results of the experimental investigations. Finally; a finite element unit cell model of a quarter brick representing a section of the lining of a ferrochrome (FeCr) electric arc furnace (direct current) was used to assess the thermo-mechanical stresses and strains including creep during a heat-up procedure. The implementation of the creep behavior into the design process led to an improved prediction of strains and stresses.
Pickett Equation for the Description of Adsorption on Arbitrary Surfaces
Authors: Kutarov Volodymyr V. , Schieferstein Eva , Jayaweera Shanath A. A.
Published: April 2020

The theory of multilayer adsorption of gases, namely the Pickett equation, has been developed to the case of adsorption on arbitrary surfaces in a molecular and a topological approach. We present the prediction of the fractal dimension for the surface of an adsorbent and for the set of interfaces generated by the growing of layers. The theoretical models correctly predict quantities and qualitative features of the experiment for two systems: adsorption of water vapor (T = 298 K) on the sample of lunar regolith and of nitrogen (T = 77 K) on a coal sample.
Optical and Thermoelectric Properties of Surface-Oxidation Sensitive Layered Zirconium Dichalcogenides ZrS2−xSex (x = 0, 1, 2) Crystals Grown by Chemical Vapor Transport
Authors: Herninda Thalita Maysha , Ho Ching-Hwa
Published: April 2020

In this work, structure, optical, and thermoelectric properties of layered ZrS2−xSex single crystals with selenium composition of x = 0, 1, and 2 were examined. Single crystals of zirconium dichalcogenides layer compounds were grown by chemical vapor transport method using I2 as the transport agent. X-ray diffraction (XRD) and high-resolution transmission electron microscope (HRTEM) results indicated that ZrS2−xSex (x = 0, 1, and 2) were crystalized in hexagonal CdI2 structure with one-layer trigonal (1T) stacking type. X-ray photoelectron and energy dispersive X-ray measurements revealed oxidation sensitive behavior of the chalcogenides series. Transmittance and optical absorption showed an indirect optical gap of about 1.78 eV, 1.32 eV, and 1.12 eV for the ZrS2−xSex with x = 0, 1, and 2, respectively. From the result of thermoelectric experiment, ZrSe2 owns the highest figure-of merit (ZT) of ~0.085 among the surface-oxidized ZrS2−xSex series layer crystals at 300 K. The ZT values of the ZrS2−xSex (x = 0, 1, and 2) series also reveal increase with the increase of Se content owing to the increase of carrier concentration and mobility in the highly Se-incorporated zirconium dichalcogenides with surface states.
Structural Dynamics of An ELM-11 Framework Transformation Accompanied with Double-Step CO2 Gate sorption: An NMR Spin Relaxation Study
Authors: Ohazama Kazuki , Ueda Takahiro , Ukai Kazuki , Ichikawa Manami , Masu Hyuma , Kajiro Hiroshi , Kanoh Hirofumi
Published: April 2020

[Cu(4,4'-bipyridine)2(BF4)2] (ELM-11), an elastic layer-structured MOF (metal-organic framework), is expected to be a sophisticated CO2 reservoir candidate because of its high capacity and recovery efficiency for CO2 sorption. While ELM-11 shows a unique double-step gate sorption for CO2 gas, the dynamics of the structural transition have not yet been clarified. In this study, the dynamics of the 4,4'-bipyridine linkers and the BF4- anions were studied by determining 1H spin-lattice relaxation times (T1). The ELM-11 structural transition accompanying CO2 sorption was also examined through the CO2 uptake dependence of the 1H spin–spin relaxation time (T2), in addition to T1. In its closed form, the temperature dependence of the 1H T1 of ELM-11 was analyzed by considering the contributions of both paramagnetic and dipolar relaxations, which revealed the isotropic reorientation of BF4- and the torsional flipping of the 4,4'-bipyridine moieties. The resultant activation energy of 32 kJ mol-1 for the isotropic BF4− reorientation is suggestive of strong (B-F...Cu2+) interactions between Cu(II) and the F atoms in BF4−. Furthermore, the CO2 uptake dependence of T1 was found to be dominated by competition between the increase in the longitudinal relaxation time of the electron spins and the decrease in the spin density in the unit cell.
Nano-Ridge Engineering of GaSb for the Integration of InAs/GaSb Heterostructures on 300 mm (001) Si
Authors: Baryshnikova Marina , Mols Yves , Ishii Yoshiyuki , Alcotte Reynald , Han Han , Hantschel Thomas , Richard Olivier , Pantouvaki Marianna , Van Campenhout Joris , Van Thourhout Dries , Langer Robert , Kunert Bernardette
Published: April 2020

Nano-ridge engineering (NRE) is a novel heteroepitaxial approach for the monolithic integration of lattice-mismatched III-V devices on Si substrates. It has been successfully applied to GaAs for the realization of nano-ridge (NR) laser diodes and heterojunction bipolar transistors on 300 mm Si wafers. In this report we extend NRE to GaSb for the integration of narrow bandgap heterostructures on Si. GaSb is deposited by selective area growth in narrow oxide trenches fabricated on 300 mm Si substrates to reduce the defect density by aspect ratio trapping. The GaSb growth is continued and the NR shape on top of the oxide pattern is manipulated via NRE to achieve a broad (001) NR surface. The impact of different seed layers (GaAs and InAs) on the threading dislocation and planar defect densities in the GaSb NRs is investigated as a function of trench width by using transmission electron microscopy (TEM) as well as electron channeling contrast imaging (ECCI), which provides significantly better defect statistics in comparison to TEM only. An InAs/GaSb multi-layer heterostructure is added on top of an optimized NR structure. The high crystal quality and low defect density emphasize the potential of this monolithic integration approach for infrared optoelectronic devices on 300 mm Si substrates.
Effects of Various Inhibitors on the Nucleation of Calcium Oxalate in Synthetic Urine
Authors: Hsu Yu-Chao , Lin Yi-Hsuan , Shiau Lie-Ding
Published: April 2020

A new synthetic urine was adopted in this work to study the nucleation kinetics of calcium oxalate using a batch crystallizer for various supersaturations at 37 °C. In the studied new synthetic urine, three additional components (urea, uric acid and creatinine) within the normal physiological ranges were added to the commonly-used synthetic urine to simulate human urine more closely. The interfacial energy for the nucleation of calcium oxalate was determined based on classical nucleation theory using the turbidity induction time measurements. The effects of various inhibitors, including magnesium, citrate, hydroxycitrate, chondroitin sulfate, and phytate, on the nucleation of calcium oxalate were investigated in detail. Scanning electron microscopy was used to examine the influences of these inhibitors on the preferential nucleation of the different hydrates of calcium oxalate crystals.
Changes in the Building Stock of Da Nang between 2015 and 2017
Authors: Braun Andreas , Warth Gebhard , Bachofer Felix , Quynh Bui Tram Thi , Tran Hao , Hochschild Volker
Published: April 2020

This descriptor introduces a novel dataset, which contains the number and types of buildings in the city of Da Nang in Central Vietnam. The buildings were classified into nine distinct types and initially extracted from a satellite image of the year 2015. Secondly, changes were identified based on a visual interpretation of an image of the year 2017, so that new buildings, demolished buildings and building upgrades can be quantitatively analyzed. The data was aggregated by administrative wards and a hexagonal grid with a diameter of 250 m to protect personal rights and to avoid the misuse of a single building’s information. The dataset shows an increase of 19,391 buildings between October 2015 and August 2017, with a variety of interesting spatial patterns. The center of the city is mostly dominated by building changes and upgrades, while most of the new buildings were constructed within a distance of five to six kilometers from the city center.
Mechanical Fault Diagnosis of a High Voltage Circuit Breaker Based on High-Efficiency Time-Domain Feature Extraction with Entropy Features
Authors: Qi Jiajin , Gao Xu , Huang Nantian
Published: April 2020

The fault samples of high voltage circuit breakers are few, the vibration signals are complex, the existing research methods cannot extract the effective information in the features, and it is easy to overfit, slow training, and other problems. To improve the efficiency of feature extraction of a circuit breaker vibration signal and the accuracy of circuit breaker state recognition, a Light Gradient Boosting Machine (LightGBM) method based on time-domain feature extraction with multi-type entropy features for mechanical fault diagnosis of the high voltage circuit breaker is proposed. First, the original vibration signal of the high voltage circuit breaker is segmented in the time domain; then, 16 features including 5 kinds of entropy features are extracted directly from each part of the original signal after time-domain segmentation, and the original feature set is constructed. Second, the Split importance value of each feature is calculated, and the optimal feature subset is determined by the forward feature selection, taking the classification accuracy of LightGBM as the decision variable. After that, the LightGBM classifier is constructed based on the feature vector of the optimal feature subset, which can accurately distinguish the mechanical fault state of the high voltage circuit breaker. The experimental results show that the new method has the advantages of high efficiency of feature extraction and high accuracy of fault identification.
On the Structure of the World Economy: An Absorbing Markov Chain Approach
Authors: Kostoska Olivera , Stojkoski Viktor , Kocarev Ljupco
Published: April 2020

The expansion of global production networks has raised many important questions about the interdependence among countries and how future changes in the world economy are likely to affect the countries’ positioning in global value chains. We are approaching the structure and lengths of value chains from a completely different perspective than has been available so far. By assigning a random endogenous variable to a network linkage representing the number of intermediate sales/purchases before absorption (final use or value added), the discrete-time absorbing Markov chains proposed here shed new light on the world input/output networks. The variance of this variable can help assess the risk when shaping the chain length and optimize the level of production. Contrary to what might be expected simply on the basis of comparative advantage, the results reveal that both the input and output chains exhibit the same quasi-stationary product distribution. Put differently, the expected proportion of time spent in a state before absorption is invariant to changes of the network type. Finally, the several global metrics proposed here, including the probability distribution of global value added/final output, provide guidance for policy makers when estimating the resilience of world trading system and forecasting the macroeconomic developments.
Melanoma and Nevus Skin Lesion Classification Using Handcraft and Deep Learning Feature Fusion via Mutual Information Measures
Authors: Almaraz-Damian Jose-Agustin , Ponomaryov Volodymyr , Sadovnychiy Sergiy , Castillejos-Fernandez Heydy
Published: April 2020

In this paper, a new Computer-Aided Detection (CAD) system for the detection and classification of dangerous skin lesions (melanoma type) is presented, through a fusion of handcraft features related to the medical algorithm ABCD rule (Asymmetry Borders-Colors-Dermatoscopic Structures) and deep learning features employing Mutual Information (MI) measurements. The steps of a CAD system can be summarized as preprocessing, feature extraction, feature fusion, and classification. During the preprocessing step, a lesion image is enhanced, filtered, and segmented, with the aim to obtain the Region of Interest (ROI); in the next step, the feature extraction is performed. Handcraft features such as shape, color, and texture are used as the representation of the ABCD rule, and deep learning features are extracted using a Convolutional Neural Network (CNN) architecture, which is pre-trained on Imagenet (an ILSVRC Imagenet task). MI measurement is used as a fusion rule, gathering the most important information from both types of features. Finally, at the Classification step, several methods are employed such as Linear Regression (LR), Support Vector Machines (SVMs), and Relevant Vector Machines (RVMs). The designed framework was tested using the ISIC 2018 public dataset. The proposed framework appears to demonstrate an improved performance in comparison with other state-of-the-art methods in terms of the accuracy, specificity, and sensibility obtained in the training and test stages. Additionally, we propose and justify a novel procedure that should be used in adjusting the evaluation metrics for imbalanced datasets that are common for different kinds of skin lesions.