bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractSodium‐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

AbstractLow 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

AbstractTitanocene 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

AbstractMonoclonal 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

AbstractThe 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

AbstractTranslocation 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

AbstractAstrocytes 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.
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

AbstractBackgroundApproximately 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.MethodsSystematic review and meta‐analysis.ResultsA 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%).ConclusionsNo 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

AbstractThe 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

AbstractMagnetic 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

SummaryWe 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.