bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Conversion of Furoic Acid Derivatives to Multi‐Substituted Furanacrylate by a Ruthenium Catalyst
Authors: Li Feng , Li Xinglong , Gong Tianjun , Fu Yao
Published: August 2019

Furanacrylate derivatives, as a class of multi‐substituted furan compounds, have been widely used in drug synthesis, organic functional materials, novel polymer monomers, etc. In this paper, direct alkenylation and decarboxylation‐alkenylation of furoic acid derivatives to furanacrylate were carried out by efficient [Ru(p‐cymene)Cl2]2 catalyst. The effects of reaction parameters on product distribution were investigated and discussed in detail. Up to 76 % and 80 % isolated yield of furanacrylate by direct alkenylation and decarboxylation‐alkenylation of furoic acid derivatives were obtained at 80 °C and 125 °C, respectively. A good substrate compatibility was disclosed through the screening of substrate scope. Meanwhile, Ru(II) or Cu(II) was essential for decarboxylation according to the control experiments. This opened a new general route from biomass‐derived compounds to functionalized multi‐substituted furan compounds.
Constrained sintering of Bi2O3‐doped ZnO
Authors: Wu Cheng‐Feng , Jean Jau‐Ho
Published: August 2019

Effects of Bi2O3 on densification kinetics and mechanism of a polycrystalline ZnO ceramics under free and constrained sintering have been investigated. With the presence of 1‐5 wt% Bi2O3, the densification temperature of ZnO is reduced from 1200°C to 850°C under free sintering. Although the densification kinetics of ZnO + 1 wt% Bi2O3 is slowed down due to the presence of in‐plain tensile stress generated during constrained sintering, a high degree of densification of >95% at 950°C is still obtained. The above phenomena are attributed to the formation of Bi2O3‐rich intergranular glassy film at the grain boundaries, yielding a decrease in the grain boundary energy and an increase in the grain boundary migration kinetics of ZnO. Results of molecular dynamics simulation confirm the above observations, at which the ratio of grain boundary energy of ZnO between with and without 1 wt% Bi2O3 is consistent with that obtained experimentally.
Magnetic‐Field‐Manipulated Growth of Flow‐Driven Precipitate Membrane Tubes
Authors: Takács Dóra , Schuszter Gábor , Sebők Dániel , Kukovecz Ákos , Horváth Dezső , Tóth Ágota
Published: August 2019

Chemobrionics is an emerging scientific field focusing on the coupling of chemical reactions and different forms of motion, that is, transport processes. Numerous phenomena appearing in various gradient fields, for example, pH, concentration, temperature, and so on, are thoroughly investigated to mimic living systems in which spatial separation plays a major role in proper functioning. In this context, chemical garden experiments have received increased attention because they inherently involve membrane formation and various transport processes. In this work, a noninvasive external magnetic field was applied to gain control over the directionality of membrane structures obtained by injecting one reactant solution into the other in a three‐dimensional domain. The geometry of the resulted patterns was quantitatively characterized as a function of the injection rate and the magnitude of magnetic induction. The magnetic field was proven to influence the microstructure of precipitate tubes by diminishing spatial defects.
Optimization methodology for the material assignation in bioprinted scaffolds to achieve the desired stiffness over time
Authors: Paz Rubén , Monzón Mario D.
Published: August 2019

The optimum scaffold for tissue engineering must guarantee the mechanical integrity in the damaged zone and ensure an appropriate stiffness to regulate the cellular function. For this to happen, scaffolds must be designed to match the stiffness of the native tissue. Moreover, the degradation rate in the case of bioresorbable materials must also be considered to fit the tissue regeneration rate. This paper presents a methodology based on design of experiments, finite element analysis, metamodels, and genetic algorithms to optimize the assignation of material in different sections of the scaffold to obtain the desired stiffness over time and comply with the constraints needed. The method applies an initial sampling focused on a modified Latin Hypercube strategy to obtain data from the simulations. These data are used in the next stages to generate the metamodels by using kriging. The predictions of the metamodels are used by the genetic algorithms to find the best estimated solutions. Different runs of the genetic algorithm drive the sampling, improving the accuracy of the surrogate models over the optimization process. Once the accuracy of the metamodels estimates is sufficient, a final genetic algorithm is applied to obtain the optimum design. This approach guarantees a low sampling effort and convergence to carry out the optimization process. The method allows the combination of discrete and continuous design variables in the optimization problem, and it can be applied both in solid and in hierarchical‐based geometries.
Synthesis and evaluation of several high absorbance black pigments for spacecraft thermal control coatings
Authors: Kiomarsipour Narges , Ghasemi Mohsen , Ghani Kamal
Published: August 2019

Using black coatings and materials with high light absorbance that are capable of absorbing photons at visible and longer wavelengths is a very effective way to reduce unwanted stray light, also known as optical noise, within optical equipment. These lights can be greatly reduced to a reasonable level by functional and performable black coatings that are modified to absorb incident light as much as possible by their specific pigments. In the present work, several carbonaceous pigments were synthesized for the first time from wasteful materials and their optical properties in the visible and near‐infrared ranges studied. First, MCM‐48 and SBA‐15 were synthesized at different conditions and were then used as templates for carbonaceous products. SSS‐1 (the carbonic pigment synthesized by the mixture of sucrose and sodium silicate), SSS‐2 (the carbonic pigment synthesized by the mixture of sawdust and sodium silicate), and mesoporous carbon pigments (CMK‐3 and CMK‐1 with different levels of saturations) were synthesized. Finally, their structure, morphology, and optical properties were investigated by X‐ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FE‐SEM), and Diffuse Reflectance Spectroscopy (DRS). The results indicated that the SSS‐1 pigment had a lower reflectance (below 1%) than carbon black (about 2.5%) in the visible region despite it being more cost‐effective than carbon black. The mesoporous pigments showed very high light absorbance in the visible region (about 2.5%). Compared with other black pigments, the CMK‐1 was the blackest synthesized material with a very low reflectance (about 0.05% in visible region), making it an ideal candidate as a super black pigment for reducing unwanted stray light within optical equipment.
Coloured shadows—Why they can be photographed
Authors: Sik‐Lanyi Cecilia , Szücs Veronika , Hirschler Robert
Published: August 2019

Coloured shadows have been observed, studied, and described for centuries, raising heated debates on whether they were objective or subjective, real or imaginary, psychological or physiological. We can demonstrate this phenomenon by projecting coloured light from one and white light from the other projector on a screen, where an object casts two shadows: one (illuminated by coloured light) expectedly coloured and the other (illuminated by white light) unexpectedly coloured. One of the seemingly most solid arguments for the objectivity of the unexpected colour was the fact that it could be photographed. The aim of this work was to photograph the shadows both with conventional (colour slide film) and digital cameras and explain why the unexpected colour of the shadows appears in these photographs. With spectroradiometric measurements of the shadows themselves and also those of the photographs, it may be proven that this is simply a spectacular case of adaptation and simultaneous contrast. Digital rendering of the coloured shadow situation also supports this conclusion. Coloured shadows are excellent tools for the demonstration of adaptation and simultaneous contrast.
Improving unsupervised saliency detection by migrating from RGB to multispectral images
Authors: Martínez Miguel Á. , Etchebehere Sergi , Valero Eva M. , Nieves Juan L.
Published: August 2019

Saliency detection has been an important topic during the last decade. The main goal of saliency detection models is to detect the most relevant objects in a given scene. Most of these models use RGB (Red, Green, Blue) images as an input because they mainly focus on applications where features (eg, faces, textures, colors, or human silhouettes) are extracted from color images, and there are many labeled databases available for RGB‐based saliency data. Nevertheless, the use of RGB inputs clearly limits the amount of information from where to extract the salient regions as spectral information is lost during the color image recording. On the contrary, multispectral systems are able to capture more than three bands in a single capture and can retrieve information from the full spectrum at a pixel. The main aim of this study is to investigate the advantages of using multispectral images instead of RGB images for saliency detection within the framework of unsupervised models. We compare the performance of several unsupervised saliency models with both RGB and multispectral images using a specific dataset of multispectral images with ground‐truth data extracted from observers' fixation patterns. Our results show a general improvement when multispectral information is taken into account. The saliency maps estimated by using the multispectral features are closer to the ground‐truth data, with the simplest Graph‐based visual saliency and Boolean Map‐based models showing good relative gain compared with other approaches.
On‐Surface Synthesis of Porous Carbon Nanoribbons on Silver: Reaction Kinetics and the Influence of the Surface Structure
Authors: Ammon Maximilian , Haller Martin , Sorayya Shadi , Maier Sabine
Published: August 2019

We report on the influence of the surface structure and the reaction kinetics in the bottom‐up fabrication of porous nanoribbons on silver surfaces using low‐temperature scanning tunneling microscopy. The porous carbon nanoribbons are fabricated by the polymerization of 1,3,5‐tris(3‐bromophenyl)benzene directly on the Ag surface using an Ullmann‐type reaction in combination with dehydrogenative coupling reactions. We demonstrate the successful on‐surface synthesis of porous nanoribbons on Ag(111) and Ag(100) even though the self‐assemblies of the intermediate organometallic structures and covalently‐linked polymer chains are different on both surfaces. Furthermore, we present the formation of isolated porous nanoribbons by kinetic control. Our results give valuable insights into the role of substrate‐induced templating effects and the reaction kinetics in the on‐surface synthesis of conformationally flexible molecules.
Pleomorphic adenoma with bizarre myoepithelial cells: A diagnostic challenge on cytologic smear
Authors: Taweevisit Mana , Thorner Paul S.
Published: August 2019

The diagnosis on fine needle aspiration of salivary gland tumors with a myoepithelial component is challenging because myoepithelial cells can have a wide cytomorphologic spectrum. The authors report a case of a pleomorphic adenoma of the parotid gland that expands the spectrum of appearances that myoepithelial cells can show with this tumor. A 55‐year‐old female was found to have a right parotid gland mass. FNA showed hypercellularity, with loosely cohesive fragments of spindle‐shaped myoepithelial cells admixed with small nests of epithelial cells. Interspersed may occasional bizarre cells possessing severely pleomorphic nuclei with hyperchromasia. The cytologic diagnosis was “suspicious for carcinoma ex pleomorphic adenoma.” A total parotidectomy was performed with complete resection of the tumor that was confirmed to be a pleomorphic adenoma. The pleomorphic cells noted on FNA were scattered throughout the tumor, and were positive by immunostaining for keratin, S‐100 protein and p63, identifying them as myoepithelial cells. These cells did not show mitotic activity and were negative for Ki67. The pleomorphic adenoma showed extensive degenerative changes including central cyst formation, stromal hyalinization and hemosiderin deposition. On the basis of the combined light microscopic and immunohistochemical findings, there was no evidence to support a malignant change in the pleomorphic adenoma. It was concluded the pleomorphic myoepithelial cells were a degenerative change, reminiscent of what is seen in “ancient” schwannoma and some uterine leiomyomata. Our case expands the spectrum of appearances that can be seen in myoepithelial cells in the salivary gland.
Intranodal palisaded myofibroblastoma of para‐esophageal lymph node: Case report with cytologic and histologic findings
Authors: Hu Jingjing , Tipps Ann M. P. , Hasteh Farnaz , Lin Grace , Zare Somaye Y.
Published: August 2019

Intranodal palisaded myofibroblastoma is a rare lymph node mesenchymal neoplasm that most commonly arises in inguinal lymph nodes. There is limited data about cytologic features of this tumor and its diagnostic pitfalls. The combination of bland appearing spindle cells, fibrillary matrix, and hemosiderin pigments are the characteristic features of this neoplasm in cytologic specimens.
Cyp1B1 expression patterns in the developing chick inner ear
Authors: Cardeña‐Núñez Sheila , Sánchez‐Guardado Luis Ó. , Hidalgo‐Sánchez Matías
Published: August 2019

Background

Retinoic acid (RA) plays an important role in organogenesis as a paracrine signal through transcriptional regulation of an increasing number of known downstream target genes, regulating cell proliferation, and differentiation. During the development of the inner ear, RA directly governs the morphogenesis and specification processes mainly by means of RA‐synthesizing retinaldehyde dehydrogenase (RALDH) enzymes. Interestingly, CYP1B1, a cytochrome P450 enzyme, is able to mediate the oxidative metabolisms also leading to RA generation, its expression patterns being associated with many known sites of RA activity.

Results

This study describes for the first time the presence of CYP1B1 in the developing chick inner ear as a RALDH‐independent RA‐signaling mechanism. In our in situ hybridization analysis, Cyp1B1 expression was first observed in a domain located in the ventromedial wall of the otic anlagen, being included within the rostralmost aspect of an Fgf10‐positive pan‐sensory domain. As development proceeds, all identified Fgf10‐positive areas were Cyp1B1 stained, with all sensory patches being Cyp1B1 positive at stage HH34, except the macula neglecta.

Conclusions

Cyp1B1 expression suggested a possible contribution of CYP1B1 action in the specification of the lateral‐to‐medial and dorsal‐to‐ventral axes of the developing chick inner ear.
The failure of success: cyclic recurrences of a globally invasive pest
Authors: Zhao Zihua , Hui Cang , Plant Richard E. , Su Min , Papadopoulos Nikos T. , Carpenter Tim E. , Li Zhihong , Carey James R.
Published: August 2019

In the six decades since 1960, the oriental fruit fly, Bactrocera dorsalis (Hendel), has been announced successfully eradicated in California by the U.S. Department of Agriculture a total of 564 times. This includes eradication declarations in one city a total of 25 different years, in 12 cities 8–19 different years, and in 101 cities 2–7 different years. We here show that the false negatives in declaring elimination success hinge on the easily achieved regulatory criteria, which have virtually guaranteed the failure of complete extirpation of this pest. Analyses of the time series of fly detection over California placed on a grid of 100‐km2 cells revealed (1) partial success of the eradication program in controlling the invasion of the oriental fruit fly; (2) low prevalence of the initial detection in these cells is often followed by high prevalence of recurrences; (3) progressively shorter intervals between years of consecutive detections; and (4) high likelihood of early‐infested cells also experiencing the most frequent outbreaks. Facing the risk of recurrent invasions, such short‐term eradication programs have only succeeded annually according to the current regulatory criteria but have failed to achieve the larger goal of complete extirpation of the oriental fruit fly. Based on the components and running costs of the current programs, we further estimated the efficiency of eradication programs with different combinations of eradication radius, duration, and edge impermeability in reducing invasion recurrences and slowing the spread of the oriental fruit fly. We end with policy implications including the need for agricultural agencies worldwide to revisit eradication protocols in which monitoring and treatments are terminated when the regulatory criteria for declaring eradication are met. Our results also have direct implications to invasion biologists and agriculture policy makers regarding long‐term risks of short‐term expediency.
Will growing invasive arthropod biodiversity outpace our ability for eradication?
Authors: Suckling David M. , Stringer Lloyd D. , Baird David B. , Kean John M.
Published: August 2019

The Global Eradication Database documents 811 eradication attempts against invasive arthropods since 1890, in 104 countries. Eradication programs show a greater than exponential increase in the number of programs started in recent decades. In addition, there is a trend of a rapidly diversifying burden of the most severe threats. The species richness showed a three‐fold increase in number of species under eradication in the last 50 yr, and all taxonomic levels rose dramatically. The increase in number of eradication programs shows that current management measures for constraining the spread of invasive species are inadequate. A similar surge in the number of governments trying to prevent the establishment of new pests has occurred. Increased biodiversity of arthropod eradication targets includes new pest groups with fewer tools developed for management. We argue that a rapid increase in biodiversity of invasive and economically or environmentally damaging organisms represents a substantial and underestimated challenge for managers wanting to prevent their establishment, requiring a shift in research focus to accelerate delimitation and suppression options with less reliance on insecticides.
The effects of sodium‐glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions
Authors: Lan Nick S.R. , Fegan P. Gerry , Yeap Bu B. , Dwivedi Girish
Published: August 2019

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti‐hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo‐controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions.
Measuring the T‐cell down‐regulation of TCR‐zeta, ZAP‐70 and CD28 in arthritis patients: An old tool for new biomarkers
Authors: Zizzo Gaetano , De Santis Maria , Bosello Silvia , Tolusso Barbara , Alivernini Stefano , De Luca Giacomo , Gremese Elisa , Ferraccioli Gianfranco
Published: August 2019

Low T‐cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down‐expression of TCR‐related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR‐ZETA, ZAP‐70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)‐derived T cells. In PB, ZETA‐downregulation in CD4+CD28+ and consequent CD4+CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA‐downregulation extends to CD8+CD28null and/or CD8+CD28+ cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA‐downregulation in CD4+CD28+ may also lead to CD4+CD28+ZETAnull cell expansion, which strongly correlates with HAQ.

In SF, ZETA‐downregulation in CD8+CD28null and consequent CD8+CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP‐downregulation in CD8+CD28+ and consequent CD8+CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS.

ZETA‐downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down‐regulation in CD8+CD28null, and non‐rheumatoid arthritides showing significant down‐regulation in CD4+CD28+.

Altogether, we identified new molecular and cellular biomarkers of arthritis‐related T‐cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.
Electrochemical Study of Highly Substituted Titanocene Dihalides
Authors: Šimková Ludmila , Svoboda Jan , Pinkas Jiří , Skoupilová Hana , Hrstka Roman , Dunlop David , Lamač Martin , Gyepes Róbert , Ludvík Jiří
Published: August 2019

Titanocene dihalides are promising alternative to Cisplatin in cancer chemotherapy which should reduce negative side effects and overcome increasing resistance of cancer cells. Since the mechanism of anti‐cancer action is associated with generation of reactive oxygen species (ROS), hence with redox processes, electrochemical investigation of titanocene species would be an important issue, not applied up to now. In this article we report on the electrochemical reduction as well as oxidation of titanocene difluorides and dichlorides where unsubstituted as well as highly substituted titanocene dihalides are compared. The experiments were realized in acetonitrile using various electrode materials. The studied series was completed by a new dimethylsilylene bridged ansa‐titanocene difluoride which was characterized by NMR and x‐ray crystallography. The influence of structure and substitution on the redox properties was evaluated and, in addition to this, cytotoxicity of studied titanocene dihalides against human ovarian cancer cell lines A2780 and SK‐OV‐3, as well as against human embryonic kidney cell line HEK293 were screened. Two of highly substituted titanocenes exhibit cytotoxicity comparable with that of Cisplatin.
Monitoring bioactive and total antibody concentrations for continuous process control by surface plasmon resonance spectroscopy
Authors: Zschätzsch Marlen , Ritter Paul , Henseleit Anja , Wiehler Klaus , Malik Sven , Bley Thomas , Walther Thomas , Boschke Elke
Published: August 2019

Monoclonal antibodies have become an increasingly important part of fundamental research and medical applications. To meet the high market demand for monoclonal antibodies in the biopharmaceutical sector, industrial manufacturing needs to be achieved by large scale, highly productive and consistent production processes. These are subject to international guidelines and have to be monitored intensely due to high safety standards for medical applications. Surface plasmon resonance spectroscopy — a fast, real‐time, and label‐free bio‐sensing method — represents an interesting alternative to the quantification of monoclonal antibody concentrations by enzyme‐linked immunosorbent assay during monoclonal antibody production. For the application of monitoring bioactive and total monoclonal antibody concentrations in cell culture samples, a surface plasmon resonance assay using a target‐monoclonal antibody model system was developed. In order to ensure the subsequent detection of bioactive monoclonal antibody concentrations, suitable immobilization strategies of the target were identified. A significant decrease of the limit of detection was achieved by using an adapted affinity method compared to the commonly used amine coupling. Furthermore, the system showed limit of detection in the low ng/mL range similar to control quantifications by enzyme‐linked immunosorbent assay. Moreover, the comparison of total to bioactive monoclonal antibody concentrations allows analysis of antibody production efficiency. The development of an alternative quantification system to monitor monoclonal antibody production was accomplished using surface plasmon resonance with the advantage of low analyte volume, shorter assay time, and biosensor reusability by target‐layer regeneration. The established method provides the basis for the technical development of a surface plasmon resonance‐based system for continuous process monitoring.
Chemical characterization and antioxidant properties of products and by‐products from Olea europaea L.
Authors: Tamasi Gabriella , Baratto Maria Camilla , Bonechi Claudia , Byelyakova Anastasiya , Pardini Alessio , Donati Alessandro , Leone Gemma , Consumi Marco , Lamponi Stefania , Magnani Agnese , Rossi Claudio
Published: August 2019

The products and by‐products of Olea europaea L.: olive fruits (primary agricultural product), oils (primary agro‐industrial product), pomaces (agro‐industrial processing by‐product), and leaves (agricultural practices by‐product), are promising sources of bioactive compounds. In the present study, qualitative and quantitative analyses of selected bioactive components in olive fruits, oils, and pomaces were performed. Total polyphenol content and antioxidant activity were analyzed in all samples (humid pomaces 2015: TPP, 26.0 ± 1.5–43.7 ± 3.0 g(GAEq)/kg DW; TEAC/ABTS, 189.5 ± 3.7–388.1 ± 12.0 mmol(Trx)kg DW). Radical (DPPH) quenching potential was analyzed via photometric and EPR methods, obtaining Vis/EPR signal ratio by 1.05 ± 0.45 and 1.66 ± 0.39 for fruits and pomaces, respectively. Through HPLC‐UV and HPLC‐MS/MS techniques, oleuropein and hydroxytyrosol, as well as selected hydroxycinnamic acids and flavonoids, were identified and quantified in olive fruits and pomaces. The main components were rutin, luteolin, and chlorogenic acid. Cytotoxic assay on fibroblast cells revealed toxic effects for selected extracts at highest tested concentrations (5%).
Gene fusion analysis in renal cell carcinoma by FusionPlex RNA‐sequencing and correlations of molecular findings with clinicopathological features
Authors: Tretiakova Maria S. , Wang Wenjing , Wu Yu , Tykodi Scott S. , True Lawrence , Liu Yajuan J.
Published: August 2019

Translocation renal cell carcinoma (tRCC) affects younger patients and often presents as advanced disease. Accurate diagnosis is required to guide clinical management. Here we evaluate the RNA‐sequencing FusionPlex platform with a 115‐gene panel including TFE3 and TFEB for tRCC diagnosis and correlate molecular findings with clinicopathological features. We reviewed 996 consecutive RCC cases from our institution over the preceding 7 years and retrieved 17 cases with histological and immunohistochemical features highly suggestive of either TFE3 (n = 16) or TFEB (n = 1). Moderate to strong labeling for TFE3 was present in 15 cases; two cases with weak TFE3 expression were melan‐A or cathepsin‐K positive. RNA‐sequencing detected gene rearrangements in eight cases: PRCC‐TFE3 (3), ASPSCR1‐TFE3 (2), LUC7L3‐TFE3 (1), SFPQ‐TFE3 (1), and a novel SETD1B‐TFE3 (1). FISH assays of 11 tumors verified six positive cases concordant with FusionPlex analysis results. Two other cases were confirmed by RT‐PCR. FusionPlex was superior to FISH by providing precise breakpoints for tRCC‐related genes in a single assay and allowing identification of both known and novel fusion partners, thereby facilitating clinicopathological correlations as fusion partners can influence tumor appearance, immunophenotype, and behavior. Cases with partner genes PRCC and novel partner SETD1B were associated with prominent papillary architecture while cases with partner genes ASPSCR1 and LUC7L3 were associated with a predominantly nested/alveolar pattern. The case with SFPQ‐TFE3 fusion was characterized by biphasic morphology mimicking TFEB‐like translocation RCC. We recommend FusionPlex analysis of RCC in patients under age 50 or when the histologic appearance suggests tRCC.
Optogenetic manipulation of astrocytes from synapses to neuronal networks: A potential therapeutic strategy for neurodegenerative diseases
Authors: Xie Zhen , Yang Qinghu , Song Da , Quan Zhenzhen , Qing Hong
Published: August 2019

Astrocytes are the most widespread and heterogeneous glial cells in the central nervous system and key regulators for brain development. They are capable of receiving neurotransmitters produced by synaptic activities and regulating synaptic functions by releasing gliotransmitters as part of the tripartite synapse. In addition to communicating with neurons at synaptic levels, astrocytes can integrate into inhibitory neural networks to interact with neurons in neuronal circuits. Astrocytes are closely related to the pathogenesis and pathological processes of neurodegenerative diseases (NDs). Recently, optogenetics has now been applied to reveal the function of astrocytes in physiology and pathology. Herein, we discuss the possibility whether optogenetics could be used to control the release of gliotransmitters and regulate astrocytic membrane channels. Thus, the capability of modulating the bidirectional interactions between astrocytes and neurons in both synaptic and neuronal networks via optogenetics is evaluated. Furthermore, we discuss that manipulating astrocytes via optogenetics might be an effective way to investigate the potential therapeutic strategy for NDs.
Salomone et al did not induce PEG‐fusion repair of severed rat facial nerves
Authors: Bittner George , Ghergherehchi Cameron , Mikesh Michelle , Sengelaub Dale , Trevino Richard , Shores Jamie
Published: August 2019

See article on page 3740–3742, in this issue
Elective neck dissection in patients with radio‐recurrent and radio‐residual squamous cell carcinoma of the larynx undergoing salvage total laryngectomy: Systematic review and meta‐analysis
Authors: Lin Daniel J. , Lam Alyson , Warner Laura , Paleri Vinidh
Published: August 2019

Background

Approximately 30% of nonsurgically treated patients with laryngeal squamous cell carcinoma will suffer recurrence, and many will be clinically N0; the indication for elective neck dissection (END) remains uncertain. We aimed to determine whether END is indicated during salvage laryngectomy.

Methods

Systematic review and meta‐analysis.

Results

A total of 1141 patients were identified from 17 studies. Occult nodal positivity was 13.7% (106/775) confidence interval (CI) 11.3%‐16.1%; higher in supraglottic than glottic disease (17.8%, CI 10.3%‐25.3% vs 12%, CI 7.1%‐16.9%, P = .18). No significant difference existed between END vs observation in 5‐year disease free survival (odds ratio [OR] = 0.76, CI = 0.49‐1.17, P = .21, I2 = 10%) and overall survival (OS; OR = 0.96, CI = 0.65‐1.41, P = .82, I2 = 54%).

Conclusions

No significant survival advantage was found for END vs observation. Individual studies trended towards improved survival with END in supraglottic and locally advanced tumors. These factors should be considered when deciding on END in salvage laryngectomy.
Hepatitis C Virus Mediated Inhibition of miR‐181c Activates ATM Signaling and Promotes Hepatocyte Growth
Authors: Patra Tapas , Meyer Keith , Ray Ratna B. , Ray Ranjit
Published: August 2019

Background and Aims

Hepatitis C virus (HCV) infection promotes hepatocyte growth and progress to hepatocellular carcinoma. We previously observed that HCV infection of hepatocytes transcriptionally down‐regulates miR‐181c expression through CCAAT/enhancer binding protein β (C/EBP‐β). Here, we examined the role of miR‐181c in the regulation of cell cycle progression in relation to HCV infection. In silico analysis suggested that ataxia‐telangiectasia mutated (ATM) protein, a protein kinase, is a direct target of miR‐181c. ATM is a central mediator of response for cellular DNA double‐strand break.

Approach and Results

Our results demonstrated that ATM expression is higher in HCV‐infected hepatocytes and chronic HCV‐infected liver biopsy specimens. We have shown a direct interaction of miR‐181c with the 3′ untranslated region of ATM, and the presence of ATM in miR‐181c‐associated RNA‐induced silencing complex. Exogenous expression of miR‐181c inhibited ATM expression and activation of its downstream molecules, Chk2 and Akt. On the other hand, introduction of anti‐miR‐181c restored ATM and phosphorylated Akt. Furthermore, introduction of miR‐181c significantly inhibited phospho–cyclin‐dependent kinase 2 (CDK2) and cyclin‐A expression, arresting cell cycle progression, whereas overexpression of miR‐181c promoted apoptosis of HCV‐infected hepatocytes and can be inhibited by overexpression of ATM from a clone lacking miR‐181c binding sites. In addition, miR‐181c significantly regressed tumor growth in the xenograft human hepatocellular carcinoma mouse model.

Conclusions

Together, our results suggest that HCV infection suppresses miR‐181c in hepatocytes, resulting in ATM activation and apoptosis inhibition for promotion of cell cycle progression. The results provide mechanistic insight into understanding the role of miR‐181c in HCV‐associated hepatocyte growth promotion, and may have the potential for therapeutic intervention.
Use of an Outbred Rat Hepacivirus Challenge Model for Design and Evaluation of Efficacy of Different Immunization Strategies for Hepatitis C Virus
Authors: Atcheson Erwan , Li Wenqin , Bliss Carly M. , Chinnakannan Senthil , Heim Kathrin , Sharpe Hannah , Hutchings Claire , Dietrich Isabelle , Nguyen Dung , Kapoor Amit , Jarvis Michael A. , Klenerman Paul , Barnes Eleanor , Simmonds Peter
Published: August 2019

Background and Aims

The lack of immunocompetent small animal models for hepatitis C virus (HCV) has greatly hindered the development of effective vaccines. Using rodent hepacivirus (RHV), a homolog of HCV that shares many characteristics of HCV infection, we report the development and application of an RHV outbred rat model for HCV vaccine development.

Approach and Results

Simian adenovirus (ChAdOx1) encoding a genetic immune enhancer (truncated shark class II invariant chain) fused to the nonstructural (NS) proteins NS3‐NS5B from RHV (ChAd‐NS) was used to vaccinate Sprague‐Dawley rats, resulting in high levels of cluster of differentiation 8–positive (CD8+) T‐cell responses. Following RHV challenge (using 10 or 100 times the minimum infectious dose), 42% of vaccinated rats cleared infection within 6‐8 weeks, while all mock vaccinated controls became infected with high‐level viremia postchallenge. A single, 7‐fold higher dose of ChAd‐NS increased efficacy to 67%. Boosting with ChAd‐NS or with a plasmid encoding the same NS3‐NS5B antigens increased efficacy to 100% and 83%, respectively. A ChAdOx1 vector encoding structural antigens (ChAd‐S) was also constructed. ChAd‐S alone showed no efficacy. Strikingly, when combined with ChAd‐NS, ChAD‐S produced 83% efficacy. Protection was associated with a strong CD8+ interferon gamma–positive recall response against NS4. Next‐generation sequencing of a putative RHV escape mutant in a vaccinated rat identified mutations in both identified immunodominant CD8+ T‐cell epitopes.

Conclusions

A simian adenovirus vector vaccine strategy is effective at inducing complete protective immunity in the rat RHV model. The RHV Sprague‐Dawley rat challenge model enables comparative testing of vaccine platforms and antigens and identification of correlates of protection and thereby provides a small animal experimental framework to guide the development of an effective vaccine for HCV in humans.
An automated methodology for the classification of focal and nonfocal EEG signals using a hybrid classification approach
Authors: Mariam Bee Mohamed Kasim , Vidhya Krishnan
Published: August 2019

The uncertainty in human brain leads to the formation of epilepsy disease in human. The automatic detection and severity analysis of epilepsy disease is proposed in this article using a hybrid classification algorithm. The proposed method consists of decomposition stage, feature extraction, and classification stages. The electroencephalogram (EEG) signals are decomposed using dual‐tree complex wavelet transform and then features are extracted from these coefficients. These features are then classified using the neural network classification approach in order to classify the EEG signals into either focal or nonfocal EEG signals. Furthermore, severity of the focal EEG signal is analyzed using an adaptive neuro‐fuzzy inference system classification approach. The proposed hybrid classification method for the classification of focal signals and nonfocal signals achieved 98.6% of sensitivity, 99.1% of specificity, and 99.4% of accuracy. The average detection rate for both focal and nonfocal dataset is about 98.5%.
Removal of noise in MRI images using a block difference‐based filtering approach
Authors: Nagarajan I. , Lakshmi Priya G.G.
Published: August 2019

Magnetic resonance imaging (MRI) images are frequently sensitive to certain types of noises and artifacts. The denoising of MRI images is essential for improving visual quality and reliability of the quantitative analysis of diagnosis and treatment. In this article, a new block difference‐based filtering method is proposed to denoise the MRI images. First, the normal MRI image is degraded by a certain percentage of noise. The block difference between the intensity of the normal and noisy MRI is computed, and then it is compared with the intensity of the blocks of the normal MRI image. Based on the comparison, the pixel weights are updated to each block of the denoised MRI image. Observational results are brought out on the BrainWeb and BraTS datasets and evaluated by performance metrics such as peak signal‐to‐noise ratio, structural similarity index measures, universal quality index, and root mean square error. The proposed method outperforms the existing denoising filtering techniques.
Exogenous uncertainty and the identification of structural vector autoregressions with external instruments
Authors: Angelini Giovanni , Fanelli Luca
Published: August 2019

We provide necessary and sufficient conditions for the identification (point‐identification) of structural vector autoregressions (SVARs) with external instruments considering the case in which r instruments are used to identify g structural shocks of interest, r ≥ g ≥ 1. Novel frequentist estimation methods are discussed by considering both a “partial shocks” identification strategy, where only g structural shocks are of interest and are instrumented, and a “full shocks” identification strategy, where despite g structural shocks being instrumented, all n=g+(n−g) structural shocks of the system can be identified under certain conditions. The suggested approach is applied to investigate empirically whether financial and macroeconomic uncertainty can be approximated as exogenous drivers of US real economic activity, or rather as endogenous responses to first moment shocks, or both. We analyze whether the dynamic causal effects of nonuncertainty shocks on macroeconomic and financial uncertainty are significant in the period after the global financial crisis.
Characterization of the human myocardium by optical coherence tomography
Authors: Gan Yu , Lye Theresa H. , Marboe Charles C. , Hendon Christine P.
Published: August 2019

Imaging of cardiac tissue structure plays a critical role in the treatment and understanding of cardiovascular disease. Optical coherence tomography (OCT) offers the potential to provide valuable, high‐resolution imaging of cardiac tissue. However, there is a lack of comprehensive OCT imaging data of the human heart, which could improve identification of structural substrates underlying cardiac abnormalities. The objective of this study was to provide qualitative and quantitative analysis of OCT image features throughout the human heart. Fifty human hearts were acquired, and tissues from all chambers were imaged with OCT. Histology was obtained to verify tissue composition. Statistical differences between OCT image features corresponding to different tissue types and chambers were estimated using analysis of variance. OCT imaging provided features that were able to distinguish structures such as thickened collagen, as well as adipose tissue and fibrotic myocardium. Statistically significant differences were found between atria and ventricles in attenuation coefficient, and between adipose and all other tissue types. This study provides an overview of OCT image features throughout the human heart, which can be used for guiding future applications such as OCT‐integrated catheter‐based treatments or ex vivo investigation of structural substrates.
Bioengineered corneal epithelial cell sheet from mesenchymal stem cells—A functional alternative to limbal stem cells for ocular surface reconstruction
Authors: Venugopal Balu , Shenoy Sachin J. , Mohan Sumitha , Anil Kumar P. R. , Kumary T. V.
Published: August 2019

Limbal stem cell deficiency (LSCD) is the loss of limbal stem cells that reside in the corneoscleral junction resulting in vision loss or blindness. Bilateral LSCD is usually treated by allogeneic corneal transplantation, with instances of tissue rejection or failure in long‐term follow‐up. This study aims to use adipose mesenchymal stem cells (ASC) as an alternative autologous cell source for treating bilateral limbal deficiency conditions. ASCs derived from rabbit fat tissue were differentiated into corneal epithelial lineage using limbal explant condition media. Apart from transdifferentiation, ASC sheets were developed to facilitate effective delivery of these cells to the damage site. A thermoresponsive polymer N‐isopropylacrylamide‐co‐glycidylmethacrylate (NGMA) was synthesized and characterized to demonstrate ASC sheet formation. Transdifferentiated ASCs showed positive expression of corneal epithelial marker CK3/12 on immunostaining, supported by gene expression studies. in vivo studies by transplanting cell sheet in rabbit models of corneal injury showed clear and smooth cornea in comparison to the sham models. Histology revealed a sheet of cells aligned and integrated on to the injured corneal surface, 1 month posttransplantation. Identifying ASCs as an alternative cell source along with cell sheet technology will be a novel step in the field of corneal surface therapies.
Adipose tissue‐derived stem cells upon decellularized ovine small intestine submucosa for tissue regeneration: An optimization and comparison method
Authors: Ferdowsi Khosroshahi Ahad , Soleimani Rad Jafar , Kheirjou Razie , Roshangar Babak , Rashtbar Morteza , Salehi Roya , Ranjkesh Mohammad Reza , Roshangar Leila
Published: August 2019

The extracellular matrix of different mammalian tissues is commonly used as scaffolds in the field of tissue engineering. One of these tissues, which has frequently been studied due to its structural and biological features, is the small intestine submucosal membrane. These research are mainly done on the porcine small intestine. However, a report has recently been published about a scaffold produced from the submucosal layer of the ovine small intestine. In the present study, ovine small intestine submucosal (OSIS) was decellularized in a modified manner and its histological, morphological, and biomechanical properties were studied. Decellularization was performed in two phases: physical and chemical. In this method, a chloroform‐methanol mixture, enzymatic digestion, and a constant dose of sodium dodecyl sulfate (SDS) was used in the least agitation time and its histological property and biocompatibility were evaluated in the presence of adipose tissue‐derived stem cells (ADSCs); furthermore, ADSCs were isolated with a simple method (modified physical washing non‐enzymatic isolation). The results were showed that the use of OSIS could be effective and operative. Mechanical properties, histological structure and shape, and glycosaminoglycan content were preserved. In the SDS‐treated group, more than 90% of the native cells of tissue were deleted, and also in this group, no toxicity was observed and cell proliferation was supported, compared to the untreated group. Therefore, our results indicate that ADSCs seeded on OSIS scaffold could be used as a new approach in regenerative medicine as hybrid or hydrogel application.
Cell‐based aqueous two‐phase systems for therapeutics
Authors: González‐González Mirna , Rito‐Palomares Marco
Published: August 2019

Cell‐based aqueous two‐phase system technologies present an emerging and promising translational tool for the development of next‐generation therapeutic applications. Advantages such as biocompatibility, scalability and ease of implementation confirm this possibility. The aim of this perspective article is to present a brief, process‐oriented analysis of cell‐based aqueous two‐phase system strategies for therapeutic purposes, highlighting their potential advantages and limitations. These strategies include regenerative therapies, high‐throughput screening platforms and clinical diagnostics. Special attention is given to the implementation of polyethylene glycol and dextran aqueous two‐phase systems in the culture, expansion and separation of cells to accomplish novel diagnostic and therapeutic tasks for the healthcare, biotechnology and pharmaceutical industries. © 2019 Society of Chemical Industry