bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Ang-2/VEGF-A Inhibiting Antibodies in Combination with Radio- or Chemotherapy in Glioma
Authors: Solecki Gergely , Osswald Matthias , Weber Daniel , Glock Malte , Ratliff Miriam , Müller Hans-Joachim , Krieter Oliver , Kienast Yvonne , Wick Wolfgang , Winkler Frank
Published: March 2019

Antiangiogenic strategies have not shown striking antitumor activities in the majority of glioma patients so far. It is unclear which antiangiogenic combination regimen with standard therapy is most effective. Therefore, we compared anti-VEGF-A, anti-Ang2, and bispecific anti-Ang-2/VEGF-A antibody treatments, alone and in combination with radio- or temozolomide (TMZ) chemotherapy, in a malignant glioma model using multiparameter two-photon in vivo microscopy in mice. We demonstrate that anti-Ang-2/VEGF-A lead to the strongest vascular changes, including vascular normalization, both as monotherapy and when combined with chemotherapy. The latter was accompanied by the most effective chemotherapy-induced death of cancer cells and diminished tumor growth. This was most probably due to a better tumor distribution of the drug, decreased tumor cell motility, and decreased formation of resistance-associated tumor microtubes. Remarkably, all these parameters where reverted when radiotherapy was chosen as combination partner for anti-Ang-2/VEGF-A. In contrast, the best combination partner for radiotherapy was anti-VEGF-A. In conclusion, while TMZ chemotherapy benefits most from combination with anti-Ang-2/VEGF-A, radiotherapy does from anti-VEGF-A. The findings imply that uninformed combination regimens of antiangiogenic and cytotoxic therapies should be avoided.
Tumor Neovascularization and Developments in Therapeutics
Authors: Katayama Yuki , Uchino Junji , Chihara Yusuke , Tamiya Nobuyo , Kaneko Yoshiko , Yamada Tadaaki , Takayama Koichi
Published: March 2019

Tumors undergo fast neovascularization to support the rapid proliferation of cancer cells. Vasculature in tumors, unlike that in wound healing, is immature and affects the tumor microenvironment, resulting in hypoxia, acidosis, glucose starvation, immune cell infiltration, and decreased activity, all of which promote cancer progression, metastasis, and drug resistance. This innate defect of tumor vasculature can however represent a useful therapeutic target. Angiogenesis inhibitors targeting tumor vascular endothelial cells important for angiogenesis have attracted attention as cancer therapy agents that utilize features of the tumor microenvironment. While angiogenesis inhibitors have the advantage of targeting neovascularization factors common to all cancer types, some limitations to their deployment have emerged. Further understanding of the mechanism of tumor angiogenesis may contribute to the development of new antiangiogenic therapeutic approaches to control tumor invasion and metastasis. This review discusses the mechanism of tumor angiogenesis as well as angiogenesis inhibition therapy with antiangiogenic agents.
Catecholamines Induce Left Ventricular Subclinical Systolic Dysfunction: A Speckle-Tracking Echocardiography Study
Authors: Kvasnička Jan , Zelinka Tomáš , Petrák Ondřej , Rosa Ján , Štrauch Branislav , Krátká Zuzana , Indra Tomáš , Markvartová Alice , Widimský Jiří , Holaj Robert
Published: March 2019

Background: Pheochromocytomas (PHEO) are tumors arising from chromaffin cells from the adrenal medulla, having the ability to produce, metabolize and secrete catecholamines. The overproduction of catecholamines leads by many mechanisms to the impairment in the left ventricle (LV) function, however, endocardial measurement of systolic function did not find any differences between patients with PHEO and essential hypertension (EH). The aim of the study was to investigate whether global longitudinal strain (GLS) derived from speckle-tracking echocardiography can detect catecholamine-induced subclinical impairments in systolic function. Methods: We analyzed 17 patients (10 females and seven males) with PHEO and 18 patients (nine females and nine males) with EH. The groups did not differ in age or in 24-h blood pressure values. Results: The patients with PHEO did not differ in echocardiographic parameters including LV ejection fraction compared to the EH patients (0.69 ± 0.04 vs. 0.71 ± 0.05; NS), nevertheless, in spackle-tracking analysis, the patients with PHEO displayed significantly lower GLS than the EH patients (−14.8 ± 1.5 vs. −17.8 ± 1.7; p < 0.001). Conclusions: Patients with PHEO have a lower magnitude of GLS than the patients with EH, suggesting that catecholamines induce a subclinical decline in LV systolic function.
Insight into the Role and Regulation of Gap Junction Genes in Lung Cancer and Identification of Nuclear Cx43 as a Putative Biomarker of Poor Prognosis
Authors: Aasen Trond , Sansano Irene , Montero Maria Ángeles , Romagosa Cleofé , Temprana-Salvador Jordi , Martínez-Marti Alexandre , Moliné Teresa , Hernández-Losa Javier , Ramón y Cajal Santiago
Published: March 2019

Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 73 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p = 0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p = 0.002) but not in the squamous carcinoma subtype (p = 0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.
Bone Marrow CX3CL1/Fractalkine is a New Player of the Pro-Angiogenic Microenvironment in Multiple Myeloma Patients
Authors: Marchica Valentina , Toscani Denise , Corcione Anna , Bolzoni Marina , Storti Paola , Vescovini Rosanna , Ferretti Elisa , Dalla Palma Benedetta , Vicario Emanuela , Accardi Fabrizio , Mancini Cristina , Martella Eugenia , Ribatti Domenico , Vacca Angelo , Pistoia Vito , Giuliani Nicola
Published: March 2019

C-X3-C motif chemokine ligand 1 (CX3CL1)/fractalkine is a chemokine released after cleavage by two metalloproteases, ADAM metallopeptidase domain 10 (ADAM10) and ADAM metallopeptidase domain 17 (ADAM17), involved in inflammation and angiogenesis in the cancer microenvironment. The role of the CX3CL1/ C-X3-C motif chemokine receptor 1(CX3CR1) axis in the multiple myeloma (MM) microenvironment is still unknown. Firstly, we analyzed bone marrow (BM) plasma levels of CX3CL1 in 111 patients with plasma cell disorders including 70 with active MM, 25 with smoldering myeloma (SMM), and 16 with monoclonal gammopathy of undetermined significance (MGUS). We found that BM CX3CL1 levels were significantly increased in MM patients compared to SMM and MGUS and correlated with BM microvessel density. Secondly, we explored the source of CX3CL1 in MM and BM microenvironment cells. Primary CD138+ cells did not express CXC3L1 but up-regulated its production by endothelial cells (ECs) through the involvement of tumor necrosis factor alpha (TNFα). Lastly, we demonstrated the presence of CX3CR1 on BM CD14+CD16+ monocytes of MM patients and on ECs, but not on MM cells. The role of CX3CL1 in MM-induced angiogenesis was finally demonstrated in both in vivo chick embryo chorioallantoic membrane and in vitro angiogenesis assays. Our data indicate that CX3CL1, present at a high level in the BM of MM patients, is a new player of the MM microenvironment involved in MM-induced angiogenesis.
Phase Behavior and DFT Calculations of Laterally Methyl Supramolecular Hydrogen-Bonding Complexes
Authors: Ahmed Hoda A. , Hagar Mohamed , Alhaddad Omaima A.
Published: March 2019

Four new series of laterally methyl-substituted hydrogen-bonded supramolecular complexes were prepared. The prepared complexes were thermally investigated by differential scanning calorimetry (DSC) and phases identified by polarized light microscopy (PLM). Supramolecular hydrogen-bonded complexes formed from a 1:1 mixture of any two derivatives, bearing different alkoxy chains, of 4-alkoxyphenylazobenzoic acid and 4-(2-(pyridin-4-yl)diazenyl-(2-(or 3-)methylphenyl) 4-alkoxybenzoate. The investigated 1:1 mixture made by introducing a lateral methyl group by different spatial orientation angles into pyridine-based components. All new complexes were confirmed by Fourier-transform infrared spectroscopy (FTIR) and computational calculations used to study their stabilities. It is found that the prepared complexes are dimorphic, exhibiting smectic C and enhanced nematic phases. A comparison was made between the new series and previously investigated simpler complexes, revealed that the incorporation of the phenylazo group elongate the mesogenic part and hence broad nematic phases were obtained with high stability.
Optimal Sr-Doped Free TiO2@SrTiO3 Heterostructured Nanowire Arrays for High-Efficiency Self-Powered Photoelectrochemical UV Photodetector Applications
Authors: Ni Shiming , Guo Fengyun , Wang Dongbo , Jiao Shujie , Wang Jinzhong , Zhang Yong , Wang Bao , Zhao Liancheng
Published: March 2019

Due to their high performance, photoelectrochemical ultraviolet (UV) photodetectors have attracted much attention, but the recombination of photogenerated electrons at the interface of photoanode/electrolyte limited further improvement of photoelectrochemical UV photodetectors (PEC UVPDs). Modification of TiO2 photoanode by SrTiO3 could improve the performance of UVPD, because the energy barrier that is established at the TiO2–SrTiO3 interface could accelerate the separation of the photogenerated electrons-holes pair. However, the recombination center that is caused by the preparation of TiO2@SrTiO3 core-shell heterostructured nanostructure decreases the performance of PEC UVPDs, which is still an important problem that hindered its application in PEC UVPDs. In this paper, we presented a Sr-doped free TiO2@SrTiO3 core-shell heterostructured nanowire arrays as a photoanode for the self-powered PEC UVPD. This will not only accelerate the separation of the photogenerated electrons-holes pair, but it will also reduce the recombination of photogenerated electron-hole pairs in the photoanode. The intrinsic effect of SrTiO3 reaction time on the J variations of UVPDs is investigated in detail. An impressive responsivity of 0.358 A·W−1 was achieved at 360 nm for the UVPD based on TiO2@SrTiO3 core-shell heterostructured nanowire arrays, which heretofore is a considerably high photoresponsivity for self-powered photoelectrochemical UVPDs. Additionally, this UVPD also exhibits a high on/off ratio, fast response time, excellent visible-blind characteristic, and linear optical signal response.
4-Pyridoxic Acid/Pyridoxine Ratio in Patients with Type 2 Diabetes is Related to Global Cardiovascular Risk Scores
Authors: Obeid Rima , Geisel Juergen , Nix Wilfred A.
Published: March 2019

Background: Vascular diseases are multifactorial and several risk factors may have synergetic effect on the global vascular risk. Among patients with diabetes, we investigated whether vitamin B6 species differ according to global cardiovascular risk. Methods: The present observational study included 122 patients with type 2 diabetes (mean (SD) age = 69.9 (9.1) years; 50% men). Concentrations of vitamin B6 vitamers were measured. Classical blood biomarkers and risk factors were used to compute a multivariate risk score. Results: Plasma concentrations of 4-pyridoxic acid were higher in patients with high risk versus those with low risk scores (48.2 (63.7) vs. 31.9 (15.0) nmol/L; p = 0.031). Plasma pyridoxine was significantly lowered in patients at high risk (2.8 (28.4) vs. 38.1 (127.8) nmol/L; p = 0.003). PAr index (4-pyridoxic acid/pyridoxal + pyridoxal 5′-phosphate) (1.05 (0.07) vs. 0.84 (0.06); p = 0.017) and the ratio of 4-pyridoxic acid/pyridoxine (7.0 (4.8) vs. 3.9 (3.2); p < 0.001) were higher in patients at high risk. After adjustment for cystatin C and C-reactive protein, only pyridoxine and 4-pyridoxic acid/pyridoxine ratio remained significantly different according to vascular risk scores. 4-Pyridoxic acid/pyridoxine ratio was the best marker to discriminate between patients according to their risk scores—area under the curve (AUC) (95% confidence intervals (CI)) = 0.72 (0.62–0.81). 4-Pyridoxic acid/pyridoxine ratio was directly related to plasma levels of soluble vascular cell adhesion molecule 1. Conclusion: Vitamin B6 metabolism was shifted in patients with multiple vascular risk factors. The catabolism to 4-pyridoxic acid was enhanced, whereas the catabolism to pyridoxine was lowered. High 4-Pyridoxic acid/pyridoxine ratio is independently associated with global cardiovascular risk.
Effects of Endodontic Irrigants on Material and Surface Properties of Biocompatible Thermoplastics
Authors: Kucher Michael , Dannemann Martin , Modler Niels , Hannig Christian , Weber Marie-Theres
Published: March 2019

Passive irrigation is an efficient method for a successful endodontic treatment. During sonic activation biocompatible polymer tips are used to activate irrigants. Compared to ultrasonic activation with metallic tips, polymer tips have the advantage of a reduced risk of fracture and minimise dentine damage. Hence, two polymers, polyether ether ketones (PEEK) and polyamide (PA6), were identified for the manufacturing of novel irrigation tips. The chemical resistance against the irrigants ethylenediaminetetraacetic acid (EDTA) 20%, chlorhexidine gluconate (CHX) 2% and sodium hypochlorite (NaOCl) 5.25% was analysed. Using microindentation, the change of hardness, elasticity, surface roughness and appearance of the polymers was determined. PA6 had a high absorption of irrigant compared to PEEK. PEEK was resistant to the investigated irrigants and showed no significant alteration of surface and mechanical properties, whereas PA6 slightly increased its hardness, elastic modulus and surface roughness during long-term exposure at 37 °C. However, PA6 tips seem to be a promising disposable product due to the material’s high deformability and low manufacturing costs. Particularly with regard to structural-dynamic properties and high chemical resistance, PEEK can be considered as a material for reusable irrigation tips.
On Structural Entropy and Spatial Filling Factor Analysis of Colonoscopy Pictures
Authors: Nagy Szilvia , Sziová Brigita , Pipek János
Published: March 2019

Colonoscopy is the standard device for diagnosing colorectal cancer, which develops from little lesions on the bowel wall called polyps. The Rényi entropies-based structural entropy and spatial filling factor are two scale- and resolution-independent quantities that characterize the shape of a probability distribution with the help of characteristic curves of the structural entropy–spatial filling factor map. This alternative definition of structural entropy is easy to calculate, independent of the image resolution, and does not require the calculation of neighbor statistics, unlike the other graph-based structural entropies.The distant goal of this study was to help computer aided diagnosis in finding colorectal polyps by making the Rényi entropy based structural entropy more understood. The direct goal was to determine characteristic curves that can differentiate between polyps and other structure on the picture. After analyzing the distribution of colonoscopy picture color channels, the typical structures were modeled with simple geometrical functions and the structural entropy–spatial filling factor characteristic curves were determined for these model structures for various parameter sets. A colonoscopy image analying method, i.e., the line- or column-wise scanning of the picture, was also tested, with satisfactory matching of the characteristic curve and the image.
Optimized Compression for Implementing Convolutional Neural Networks on FPGA
Authors: Zhang Min , Li Linpeng , Wang Hai , Liu Yan , Qin Hongbo , Zhao Wei
Published: March 2019

Field programmable gate array (FPGA) is widely considered as a promising platform for convolutional neural network (CNN) acceleration. However, the large numbers of parameters of CNNs cause heavy computing and memory burdens for FPGA-based CNN implementation. To solve this problem, this paper proposes an optimized compression strategy, and realizes an accelerator based on FPGA for CNNs. Firstly, a reversed-pruning strategy is proposed which reduces the number of parameters of AlexNet by a factor of 13× without accuracy loss on the ImageNet dataset. Peak-pruning is further introduced to achieve better compressibility. Moreover, quantization gives another 4× with negligible loss of accuracy. Secondly, an efficient storage technique, which aims for the reduction of the whole overhead cache of the convolutional layer and the fully connected layer, is presented respectively. Finally, the effectiveness of the proposed strategy is verified by an accelerator implemented on a Xilinx ZCU104 evaluation board. By improving existing pruning techniques and the storage format of sparse data, we significantly reduce the size of AlexNet by 28×, from 243 MB to 8.7 MB. In addition, the overall performance of our accelerator achieves 9.73 fps for the compressed AlexNet. Compared with the central processing unit (CPU) and graphics processing unit (GPU) platforms, our implementation achieves 182.3× and 1.1× improvements in latency and throughput, respectively, on the convolutional (CONV) layers of AlexNet, with an 822.0× and 15.8× improvement for energy efficiency, separately. This novel compression strategy provides a reference for other neural network applications, including CNNs, long short-term memory (LSTM), and recurrent neural networks (RNNs).
Three-Phase Five-Level Cascade Quasi-Switched Boost Inverter
Authors: Tran Van-Thuan , Nguyen Minh-Khai , Ngo Cao-Cuong , Choi Youn-Ok
Published: March 2019

This paper presents a three-phase cascaded five-level H-bridge quasi-switched boost inverter (CHB-qSBI). The merits of the CHB-qSBI are as follows: single-stage conversion, shoot-through immunity, buck-boost voltage, and reduced passive components. Furthermore, a PWM control method is applied to the CHB-qSBI topology to improve the modulation index. The voltage stress across power semiconductor devices and the capacitor are significantly lower using improved pulse-width modulation (PWM) control. Additionally, by controlling individual shoot-through duty cycle, the DC-link voltage of each module can achieve the same values. As a result, the imbalance problem of the DC-link voltage can be solved. A detailed analysis and operating principle with the modulation scheme and comprehensive comparison for the CHB-qSBI are illustrated. The experimental and simulation results are presented to validate the operating principle of the three-phase CHB-qSBI.
Cooperative Carrying Control for Multi-Evolutionary Mobile Robots in Unknown Environments
Authors: Jhang Jyun-Yu , Lin Cheng-Jian , Young Kuu-Young
Published: March 2019

This study provides an effective cooperative carrying and navigation control method for mobile robots in an unknown environment. The manager mode switches between two behavioral control modes—wall-following mode (WFM) and toward-goal mode (TGM)—based on the relationship between the mobile robot and the unknown environment. An interval type-2 fuzzy neural controller (IT2FNC) based on a dynamic group differential evolution (DGDE) is proposed to realize the carrying control and WFM control for mobile robots. The proposed DGDE uses a hybrid method that involves a group concept and an improved differential evolution to overcome the drawbacks of the traditional differential evolution algorithm. A reinforcement learning strategy was adopted to develop an adaptive WFM control and achieve cooperative carrying control for mobile robots. The experimental results demonstrated that the proposed DGDE is superior to other algorithms at using WFM control. Moreover, the experimental results demonstrate that the proposed method can complete the task of cooperative carrying, and can realize navigation control to enable the robot to reach the target location.
Stabilization Method Considering Disturbance Mitigation for DC Microgrids with Constant Power Loads
Authors: Liang Haolan , Liu Zhangjie , Liu Hua
Published: March 2019

In this paper, the stability of direct current (DC) microgrids with a constant power load (CPL) and a non-ideal source is investigated. The CPL’s negative impedance will destabilize the system, and disturbances in the non-ideal source will degrade the load voltage quality. In this study, we aim to: (1) overcome the instability of the CPL; (2) mitigate disturbances from the non-ideal source; (3) prevent the discontinuous harmonic current of high-frequency switching regulator from interfering with the source. Then, a stabilization method based on active damping which can achieve the above three objectives simultaneously is proposed. To obtain the stability conditions, the small-signal model of the system near the high-voltage equilibrium is established. Then, stability conditions are derived by eigenvalue analysis, and the domain of attraction near equilibrium is also obtained using the quadratic Lyapunov function. For the second objective, the key is to choose the optimal parameters to achieve disturbance attenuation. For the third objective, the active damper can separate the source from the switching regulator, which can prevent the discontinuous harmonic current. Moreover, the proposed method can be extended to multiple cases, and simulation results verify the effectiveness of the proposed method.
A Comprehensive Methodology for the Integrated Optimal Sizing and Operation of Cogeneration Systems with Thermal Energy Storage
Authors: Urbanucci Luca , D’Ettorre Francesco , Testi Daniele
Published: March 2019

Cogeneration systems are widely acknowledged as a viable solution to reduce energy consumption and costs, and CO2 emissions. Nonetheless, their performance is highly dependent on their capacity and operational strategy, and optimization methods are required to fully exploit their potential. Among the available technical possibilities to maximize their performance, the integration of thermal energy storage is recognized as one of the most effective solutions. The introduction of a storage device further complicates the identification of the optimal equipment capacity and operation. This work presents a cutting-edge methodology for the optimal design and operation of cogeneration systems with thermal energy storage. A two-level algorithm is proposed to reap the benefits of the mixed integer linear programming formulation for the optimal operation problem, while overcoming its main drawbacks by means of a genetic algorithm at the design level. Part-load effects on nominal efficiency, variation of the unitary cost of the components in relation to their size, and the effect of the storage volume on its thermal losses are considered. Moreover, a novel formulation of the optimization problem is proposed to better characterize the heat losses and operation of the thermal energy storage. A rolling-horizon technique is implemented to reduce the computational time required for the optimization, without affecting the quality of the results. Furthermore, the proposed methodology is adopted to design a cogeneration system for a secondary school in San Francisco, California, which is optimized in terms of the equivalent annual cost. The results show that the optimally sized cogeneration unit directly meets around 70% of both the electric and thermal demands, while the thermal energy storage additionally covers 16% of the heat demands.
Origin Firing Regulations to Control Genome Replication Timing
Authors: Boos Dominik , Ferreira Pedro
Published: March 2019

Complete genome duplication is essential for genetic homeostasis over successive cell generations. Higher eukaryotes possess a complex genome replication program that involves replicating the genome in units of individual chromatin domains with a reproducible order or timing. Two types of replication origin firing regulations ensure complete and well-timed domain-wise genome replication: (1) the timing of origin firing within a domain must be determined and (2) enough origins must fire with appropriate positioning in a short time window to avoid inter-origin gaps too large to be fully copied. Fundamental principles of eukaryotic origin firing are known. We here discuss advances in understanding the regulation of origin firing to control firing time. Work with yeasts suggests that eukaryotes utilise distinct molecular pathways to determine firing time of distinct sets of origins, depending on the specific requirements of the genomic regions to be replicated. Although the exact nature of the timing control processes varies between eukaryotes, conserved aspects exist: (1) the first step of origin firing, pre-initiation complex (pre-IC formation), is the regulated step, (2) many regulation pathways control the firing kinase Dbf4-dependent kinase, (3) Rif1 is a conserved mediator of late origin firing and (4) competition between origins for limiting firing factors contributes to firing timing. Characterization of the molecular timing control pathways will enable us to manipulate them to address the biological role of replication timing, for example, in cell differentiation and genome instability.
Volcanic Tremor of Mt. Etna (Italy) Recorded by NEMO-SN1 Seafloor Observatory: A New Perspective on Volcanic Eruptions Monitoring
Authors: Sgroi Tiziana , Di Grazia Giuseppe , Favali Paolo
Published: March 2019

The NEMO-SN1 seafloor observatory, located 2100 m below sea level and about 40 km from Mt. Etna volcano, normally records a background seismic signal called oceanographic noise. This signal is characterized by high amplitude increases, lasting up to a few days, and by two typical 0.1 and 0.3 Hz frequencies in its spectrum. Particle motion analysis shows a strong E-W directivity, coinciding with the direction of sea waves; gravity waves induced by local winds are considered the main source of oceanographic noise. During the deployment of NEMO-SN1, the vigorous 2002–2003 Mt. Etna eruption occurred. High-amplitude background signals were recorded during the explosive episodes accompanying the eruption. The spectral content of this signal ranges from 0.1 to 4 Hz, with the most powerful signal in the 0.5–2 Hz band, typical of an Etna volcanic tremor. The tremor recorded by NEMO-SN1 shows a strong NW-SE directivity towards the volcano. Since the receiver is underwater, we inferred the presence of a circulation of magmatic fluids extended under the seafloor. This process is able to generate a signal strong enough to be recorded by the NEMO-SN1 seafloor observatory that hides frequencies linked to the oceanographic noise, permitting the offshore monitoring of the volcanic activity of Mt. Etna.
Neighborhood Greenness Attenuates the Adverse Effect of PM2.5 on Cardiovascular Mortality in Neighborhoods of Lower Socioeconomic Status
Authors: Yitshak-Sade Maayan , James Peter , Kloog Itai , Hart Jaime E. , Schwartz Joel D. , Laden Francine , Lane Kevin J. , Fabian M. Patricia , Fong Kelvin C. , Zanobetti Antonella
Published: March 2019

Features of the environment may modify the effect of particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) on health. Therefore, we investigated how neighborhood sociodemographic and land-use characteristics may modify the association between PM2.5 and cardiovascular mortality. We obtained residence-level geocoded cardiovascular mortality cases from the Massachusetts Department of Public Health (n = 179,986), and PM2.5 predictions from a satellite-based model (2001–2011). We appended census block group-level information on sociodemographic factors and walkability, and calculated neighborhood greenness within a 250 m buffer surrounding each residence. We found a 2.54% (1.34%; 3.74%) increase in cardiovascular mortality associated with a 10 µg/m3 increase in two-day average PM2.5. Walkability or greenness did not modify the association. However, when stratifying by neighborhood sociodemographic characteristics, smaller PM2.5 effects were observed in greener areas only among cases who resided in neighborhoods with a higher population density and lower percentages of white residents or residents with a high school diploma. In conclusion, the PM2.5 effects on cardiovascular mortality were attenuated by higher greenness only in areas with sociodemographic features that are highly correlated with lower socioeconomic status. Previous evidence suggests health benefits linked to neighborhood greenness may be stronger among lower socioeconomic groups. Attenuation of the PM2.5–mortality relationship due to greenness may explain some of this evidence.
Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers
Authors: Sunil Vasanthi R. , Radbel Jared , Hussain Sabiha , Vayas Kinal N. , Cervelli Jessica , Deen Malik , Kipen Howard , Udasin Iris , Laumbach Robert , Sunderram Jag , Laskin Jeffrey D. , Laskin Debra L.
Published: March 2019

Sarcoid-like granulomatous diseases (SGD) have been previously identified in cohorts of World Trade Center (WTC) dust-exposed individuals. In the present studies, we analyzed lung and/or lymph node biopsies from patients referred to our clinic with suspected WTC dust-induced lung disease to evaluate potential pathophysiologic mechanisms. Histologic sections of lung and/or lymph node samples were analyzed for markers of injury, oxidative stress, inflammation, fibrosis, and epigenetic modifications. Out of seven patients examined, we diagnosed four with SGD and two with pulmonary fibrosis; one was diagnosed later with SGD at another medical facility. Patients with SGD were predominantly white, obese men, who were less than 50 years old and never smoked. Cytochrome b5, cytokeratin 17, heme oxygenase-1, lipocalin-2, inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, ADP-ribosylation factor-like GTPase 11, mannose receptor-1, galectin-3, transforming growth factor β, histone-3 and methylated histone-3 were identified in lung and lymph nodes at varying levels in all samples examined. Three of the biopsy samples with granulomas displayed peri-granulomatous fibrosis. These findings are important and suggest the potential of WTC dust-induced fibrotic sarcoid. It is likely that patient demographics and/or genetic factors influence the response to WTC dust injury and that these contribute to different pathological outcomes.
Supervisor Support, Coworker Support and Presenteeism among Healthcare Workers in China: The Mediating Role of Distributive Justice
Authors: Yang Tianan , Lei Run , Jin Xuan , Li Yan , Sun Yangyang , Deng Jianwei
Published: March 2019

Healthcare workers in China are exposed to extremely high job stress and inequitable work conditions, and the Healthy China 2030 blueprint has made them an important focus of policymakers. To examine the importance of distributive justice in Chinese medical reform, we analyzed data from 1542 healthcare workers employed in 64 primary, secondary and tertiary hospitals in 28 Chinese cities in Western, Central and Eastern China in 2018. Supervisor support, coworker support, distributive justice, and presenteeism were assessed with the supervisor support scale, coworker support scale, distributive justice scale and perceived ability to work scale, respectively. Structural equation modeling was used to examine relationships among variables. The mediating effect of distributive justice on associations between supervisor support, coworker support, and presenteeism was examined with the Sobel test. The results revealed that significant indirect effects between supervisor support and presenteeism and between coworker support and presenteeism were significantly mediated by distributive justice. Better supervisor and coworker support might improve distributive justice among healthcare workers in Chinese hospitals, thereby increasing their performance.
Incorporating Participatory Action Research in Attention Bias Modification Interventions for Addictive Disorders: Perspectives
Authors: Zhang Melvyn W.B. , Ying Jiangbo
Published: March 2019

Participatory action research was introduced in the 1960s and early 1970s, but it has only been more widely adopted in the recent years. Such methodologies have since been applied to several web & mobile-based interventions in psychiatry. To date no prior review has scoped the extent of the application of such methodologies for web & mobile-based interventions in psychiatry. In this article, a scoping literature review was performed, and seven articles have been identified. The most common methodologies are that of co-design workshops; and increasingly service users and participants are included in these workshops. There remains a lack of application of such methodologies for addiction research. Increasingly, attention and cognitive bias modification interventions are more commonplace, given that they have been found to be effective in modifying underlying biases amongst individuals with addictive disorders. Unfortunately, there remains to be inherent limitations with web and mobile versions of attention and cognitive bias modification interventions. Participatory design research methods could help address these limitations and future research involving the conceptualization of new attention or cognitive bias modification applications ought to consider the incorporation of these research methods.
Targetoid Skin Lesions in a Child: Acute Hemorrhagic Oedema of Infancy and Its Differential Diagnosis
Authors: Miconi Francesco , Cassiani Lorenzo , Savarese Emanuela , Celi Federica , Papini Manuela , Principi Nicola , Esposito Susanna
Published: March 2019

Acute hemorrhagic oedema of infancy (AHEI) is a cutaneous leukocytoclastic small-vessel vasculitis presenting with localized purpuric large skin plaques that are frequently associated with fever and oedema. It must be promptly differentiated from a number of diseases with similar dermatologic manifestations with potentially severe clinical courses that require adequate monitoring and prompt therapy to avoid the risk of a negative evolution. A 15-month-old girl with a negative personal medical clinical history was admitted for the sudden appearance of petechiae on the soft palate. The patient was moderately febrile during the following two days, with a maximum ear temperature of 38.3 °C. The fever disappeared on the third day, whereas the hemorrhagic rash progressively increased and extended to the limbs, face and auricles associated with a strong oedematous component. Moreover, on the second day of hospitalization, bilateral oedema of the metacarpophalangeal joints with joint pain appeared. The blood and serological tests showed an increase in C-reactive protein concentration (3.58 mg/dL) in the absence of leukocytosis and with a normal platelet count (180,000/mm3). The examination of the peripheral smear showed the presence of some large mononuclear elements with hyperbasophile cytoplasm. No alterations in platelet morphology were evidenced. The skin manifestations progressively diminished and disappeared spontaneously within 3 weeks, leaving no sequelae. Conclusion: This case shows the classic skin lesions of AHEI that require differentiation from those of more severe diseases that need prompt recognition and therapy. In this case, the age of the patient, the lack of systemic involvement and the favorable clinical course without therapy were typical. However, as these patients may present to the emergency department with an impressive clinical picture, the condition must be promptly diagnosed to avoid unnecessary diagnostic procedures and to reassure parents.
Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators
Authors: Giménez-Mascarell Paula , González-Recio Irene , Fernández-Rodríguez Cármen , Oyenarte Iker , Müller Dominik , Martínez-Chantar María Luz , Martínez-Cruz Luis Alfonso
Published: March 2019

The cyclin and cystathionine β-synthase (CBS) domain magnesium transport mediators, CNNMs, are key players in maintaining the homeostasis of magnesium in different organs. The human family includes four members, whose impaired activity causes diseases such as Jalili Syndrome or Familial Hypomagnesemia, but is also linked to neuropathologic disorders, altered blood pressure, and infertility. Recent findings demonstrated that CNNMs are associated with the highly oncogenic phosphatases of the regenerating liver to promote tumor growth and metastasis, which has attracted renewed focus on their potential exploitation as targets for cancer treatment. However, the exact function of CNNMs remains unclear and is subject to debate, proposed as either direct transporters, sensors, or homeostatic factors. This review gathers the current structural knowledge on the CNNM family, highlighting similarities and differences with the closely related structural partners such as the bacterial Mg2+/Co2+ efflux protein CorC and the Mg2+ channel MgtE.
CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion
Authors: Cardoso Lais C. , Soares Roseli da S. , Laurentino Talita de S. , Lerario Antonio M. , Marie Suely K. N. , Oba-Shinjo Sueli Mieko
Published: March 2019

Glioblastoma (GBM) is the most aggressive type of brain tumor, with an overall survival of 17 months under the current standard of care therapy. CD99, an over-expressed transmembrane protein in several malignancies, has been considered a potential target for immunotherapy. To further understand this potentiality, we analyzed the differential expression of its two isoforms in human astrocytoma specimens, and the CD99 involved signaling pathways in glioma model U87MG cell line. CD99 was also analyzed in GBM molecular subtypes. Whole transcriptomes by RNA-Seq of CD99-siRNA, and functional in vitro assays in CD99-shRNA, that are found in U87MG cells, were performed. Astrocytoma of different malignant grades and U87MG cells only expressed CD99 isoform 1, which was higher in mesenchymal and classical than in proneural GBM subtypes. Genes related to actin dynamics, predominantly to focal adhesion, and lamellipodia/filopodia formation were down-regulated in the transcriptome analysis, when CD99 was silenced. A decrease in tumor cell migration/invasion, and dysfunction of focal adhesion, were observed in functional assays. In addition, a striking morphological change was detected in CD99-silenced U87MG cells, further corroborating CD99 involvement in actin cytoskeleton rearrangement. Inhibiting the overexpressed CD99 may improve resectability and decrease the recurrence rate of GBM by decreasing tumor cells migration and invasion.
Proteomics in Psoriasis
Authors: Chularojanamontri Leena , Charoenpipatsin Norramon , Silpa-Archa Narumol , Wongpraparut Chanisada , Thongboonkerd Visith
Published: March 2019

Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors. Complex interplay between inflammatory cytokines and T-cells, especially Th1 and Th17 cells, leads to abnormal cell proliferation and psoriatic skin lesions. Nevertheless, such mechanisms do not entirely represent the pathogenesis of psoriasis. Moreover, earlier and better biomarkers in diagnostics, prognostics, and monitoring therapeutic outcomes of psoriasis are still needed. During the last two decades, proteomics (a systematic analysis of proteins for their identities, quantities, and functions) has been widely employed to psoriatic research. This review summarizes and discusses all of the previous studies that applied various modalities of proteomics technologies to psoriatic skin disease. The data obtained from such studies have led to (i) novel mechanisms and new hypotheses of the disease pathogenesis; (ii) biomarker discovery for diagnostics and prognostics; and (iii) proteome profiling for monitoring treatment efficacy and drug-induced toxicities.
Evolution and Functional Analysis of orf1 Within nif Gene Cluster from Paenibacillus graminis RSA19
Authors: Li Qin , Liu Xiaomeng , Zhang Haowei , Chen Sanfeng
Published: March 2019

Paenibacillus is a genus of Gram-positive, facultative anaerobic and endospore-forming bacteria. Genomic sequence analysis has revealed that a compact nif (nitrogen fixation) gene cluster comprising 9–10 genes nifBHDKENX(orf1)hesAnifV is conserved in diazotrophic Paenibacillus species. The evolution and function of the orf1 gene within the nif gene cluster of Paenibacillus species is unknown. In this study, a careful comparison analysis of the compositions of the nif gene clusters from various diazotrophs revealed that orf1 located downstream of nifENX was identified in anaerobic Clostridium ultunense, the facultative anaerobic Paenibacillus species and aerobic diazotrophs (e.g., Azotobacter vinelandii and Azospirillum brasilense). The predicted amino acid sequences encoded by the orf1 gene, part of the nif gene cluster nifBHDKENXorf1hesAnifV in Paenibacillus graminis RSA19, showed 60–90% identity with those of the orf1 genes located downstream of nifENX from different diazotrophic Paenibacillus species, but shared no significant identity with those of the orf1 genes from different taxa of diazotrophic organisms. Transcriptional analysis showed that the orf1 gene was expressed under nitrogen fixation conditions from the promoter located upstream from nifB. Mutational analysis suggested that the orf1 gene functions in nitrogen fixation in the presence of a high concentration of O2.
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases
Authors: Law Shi-Hui , Chan Mei-Lin , Marathe Gopal K. , Parveen Farzana , Chen Chu-Huang , Ke Liang-Yin
Published: March 2019

Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.
Nanog Signaling Mediates Radioresistance in ALDH-Positive Breast Cancer Cells
Authors: Dehghan Harati Mozhgan , Rodemann H. Peter , Toulany Mahmoud
Published: March 2019

Recently, cancer stem cells (CSCs) have been identified as the major cause of both chemotherapy and radiotherapy resistance. Evidence from experimental studies applying both in vitro and in vivo preclinical models suggests that CSCs survive after conventional therapy protocols. Several mechanisms are proposed to be involved in CSC resistance to radiotherapy. Among them, stimulated DNA double-strand break (DSB) repair capacity in association with aldehyde dehydrogenase (ALDH) activity seems to be the most prominent mechanism. However, thus far, the pathway through which ALDH activity stimulates DSB repair is not known. Therefore, in the present study, we investigated the underlying signaling pathway by which ALDH activity stimulates DSB repair and can lead to radioresistance of breast cancer cell lines in vitro. When compared with ALDH-negative cells, ALDH-positive cells presented significantly enhanced cell survival after radiation exposure. This enhanced cell survival was associated with stimulated Nanog, BMI1 and Notch1 protein expression, as well as stimulated Akt activity. By applying overexpression and knockdown approaches, we clearly demonstrated that Nanog expression is associated with enhanced ALDH activity and cellular radioresistance, as well as stimulated DSB repair. Akt and Notch1 targeting abrogated the Nanog-mediated radioresistance and stimulated ALDH activity. Overall, we demonstrate that Nanog signaling induces tumor cell radioresistance and stimulates ALDH activity, most likely through activation of the Notch1 and Akt pathways.
Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis
Authors: Moya Leire , Meijer Jonelle , Schubert Sarah , Matin Farhana , Batra Jyotsna
Published: March 2019

Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low specificity and often associated with over-diagnosis. The dysregulation of miRNAs in cancer has been widely reported and it has often been shown to be specific, sensitive and stable, suggesting miRNAs could be a potential specific biomarker for the disease. Previously, we identified four miRNAs that are significantly upregulated in plasma from PCa patients when compared to healthy controls: miR-98-5p, miR-152-3p, miR-326 and miR-4289. This panel showed high specificity and sensitivity in detecting PCa (area under the curve (AUC) = 0.88). To investigate the specificity of these miRNAs as biomarkers for PCa, we undertook an in depth analysis on these miRNAs in cancer from the existing literature and data. Additionally, we explored their prognostic value found in the literature when available. Most studies showed these miRNAs are downregulated in cancer and this is often associated with cancer progression and poorer overall survival rate. These results suggest our four miRNA signatures could potentially become a specific PCa diagnostic tool of which prognostic potential should also be explored.