bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Recognition Strategy for Epilepsy EEG Signals Based on Conditional Entropy of Ordinal Patterns
Authors: Liu Xian , Fu Zhuang
Published: September 2020

Epilepsy is one of the most ordinary neuropathic illnesses, and electroencephalogram (EEG) is the essential method for recording various brain rhythm activities due to its high temporal resolution. The conditional entropy of ordinal patterns (CEOP) is known to be fast and easy to implement, which can effectively measure the irregularity of the physiological signals. The present work aims to apply the CEOP to analyze the complexity characteristics of the EEG signals and recognize the epilepsy EEG signals. We discuss the parameter selection and the performance analysis of the CEOP based on the neural mass model. The CEOP is applied to the real EEG database of Bonn epilepsy for identification. The results show that the CEOP is an excellent metrics for the analysis and recognition of epileptic EEG signals. The differences of the CEOP in normal and epileptic brain states suggest that the CEOP could be a judgment tool for the diagnosis of the epileptic seizure.
A Multi-Scale Approach to Modeling E. coli Chemotaxis
Authors: Agmon Eran , Spangler Ryan K.
Published: September 2020

The degree to which we can understand the multi-scale organization of cellular life is tied to how well our models can represent this organization and the processes that drive its evolution. This paper uses Vivarium—an engine for composing heterogeneous computational biology models into integrated, multi-scale simulations. Vivarium’s approach is demonstrated by combining several sub-models of biophysical processes into a model of chemotactic E. coli that exchange molecules with their environment, express the genes required for chemotaxis, swim, grow, and divide. This model is developed incrementally, highlighting cross-compartment mechanisms that link E. coli to its environment, with models for: (1) metabolism and transport, with transport moving nutrients across the membrane boundary and metabolism converting them to useful metabolites, (2) transcription, translation, complexation, and degradation, with stochastic mechanisms that read real gene sequence data and consume base pairs and ATP to make proteins and complexes, and (3) the activity of flagella and chemoreceptors, which together support navigation in the environment.
Neuron Blockchain Algorithm for Legal Problems in Inheritance of Legacy
Authors: Kim Seong-Kyu , Huh Jun-Ho
Published: September 2020

This paper discusses the worldwide trend of aging as the lifespan of humans increases. Nonetheless, most people do not write wills, which results in many legal problems after their death. There are many reasons for this including the problem of the validity of their heritage possibly not being legally certified. Wills can be divided into two categories, i.e., testimony and documents. A lawyer in the middle should notarize them, however, instead of providing these notarized services, we propose more transparent algorithms, blockchain shading, and smart country functions. Architectures are designed based on a neural network, the blockchain deep neural network (DNN), and deep neural network-based units are built with a necessary artificial neural network (ANN) base. A heritage inherited blockchain architecture is designed to communicate between nodes based on the minimum distance algorithm and multichannel protocol. In addition, neurons refer to the nerve cells that make up the nervous system of an organism, and artificial neurons are an abstraction of the functions of dendrite, soma, and axon that constitute the neurons of an organism. Similar to the neurons in organisms, artificial neural algorithms such as the depth-first search (DFS) algorithm are expressed in pseudocode. In addition, all blockchain nodes are equipped with verified nodes. A research model is proposed for an artificial network blockchain that is needed for this purpose. The experimental environment builds the server and network environments based on deep neural networks that require verification. Weights are also set for the required verification and performance. This paper verifies the blockchain algorithm equipped with this non-fiction preprocessor function. We also study the blockchain neuron engine that can safely construct a block node for a suicide blockchain. After empirical testing of the will system with artificial intelligence and blockchain, the values are close to 2 and 10 and the distribution is good. The blockchain node also tested 50 nodes more than 150 times, and we concluded that it was suitable for actual testing by completing a demonstration test with 4500 TPS.
Real-time Neural Networks Implementation Proposal for Microcontrollers
Authors: Guimarães Caio José B. V. , Fernandes Marcelo A. C.
Published: September 2020

The adoption of intelligent systems with Artificial Neural Networks (ANNs) embedded in hardware for real-time applications currently faces a growing demand in fields such as the Internet of Things (IoT) and Machine to Machine (M2M). However, the application of ANNs in this type of system poses a significant challenge due to the high computational power required to process its basic operations. This paper aims to show an implementation strategy of a Multilayer Perceptron (MLP)-type neural network, in a microcontroller (a low-cost, low-power platform). A modular matrix-based MLP with the full classification process was implemented as was the backpropagation training in the microcontroller. The testing and validation were performed through Hardware-In-the-Loop (HIL) of the Mean Squared Error (MSE) of the training process, classification results, and the processing time of each implementation module. The results revealed a linear relationship between the values of the hyperparameters and the processing time required for classification, also the processing time concurs with the required time for many applications in the fields mentioned above. These findings show that this implementation strategy and this platform can be applied successfully in real-time applications that require the capabilities of ANNs.
Valorization of Cynara Cardunculus L. Oil as the Basis of a Biorefinery for Biodiesel and Biolubricant Production
Authors: Nogales-Delgado Sergio , Sánchez Nuria , Encinar José María
Published: September 2020

The production of sustainable and biodegradable products, for energy or material use, is becoming important for local economies. Thus, biorefineries can play an important role in sustainable development at regional levels and therefore the search for feedstocks with multiple uses is vital. The goal of this research was to assess the implementation of Cynara Cardunculus L. oil as the basis of a biorefinery for biodiesel and biolubricant production, proposing the main steps for this purpose. The chemical reaction selected for biodiesel and biolubricant production was transesterification, using methanol and other more complex alcohols. The optimization of each step was carried out, assessing the yield by gas chromatography. Once the optimum conditions were selected, the main characteristics of the biofuel or biolubricant were measured, paying attention to viscosity and oxidative stability. As a result, Cynara Cardunculus L. oil could be a suitable feedstock for a biorefinery, as long as some antioxidants are added in final products, especially to increase its oxidative stability in biodiesel (whose value was 1.35 h). Concerning biolubricant production, the yields were acceptable (exceeding 92%) and the products showed variable viscosity values (from 8.6 to 18.85 cSt), implying a desirable diversification of production depending on demand.
Differential Regulation of Telomeric Complex by BCR-ABL1 Kinase in Human Cellular Models of Chronic Myeloid Leukemia—From Single Cell Analysis to Next-Generation Sequencing
Authors: Deregowska Anna , Pepek Monika , Pruszczyk Katarzyna , Machnicki Marcin M. , Wnuk Maciej , Stoklosa Tomasz
Published: September 2020

Telomeres are specialized nucleoprotein complexes, localized at the physical ends of chromosomes, that contribute to the maintenance of genome stability. One of the features of chronic myeloid leukemia (CML) cells is a reduction in telomere length which may result in increased genomic instability and progression of the disease. Aberrant telomere maintenance in CML is not fully understood and other mechanisms such as the alternative lengthening of telomeres (ALT) are involved. In this work, we employed five BCR-ABL1-positive cell lines, namely K562, KU-812, LAMA-84, MEG-A2, and MOLM-1, commonly used in the laboratories to study the link between mutation, copy number, and expression of telomere maintenance genes with the expression, copy number, and activity of BCR-ABL1. Our results demonstrated that the copy number and expression of BCR-ABL1 are crucial for telomere lengthening. We observed a correlation between BCR-ABL1 expression and telomere length as well as shelterins upregulation. Next-generation sequencing revealed pathogenic variants and copy number alterations in major tumor suppressors, such as TP53 and CDKN2A, but not in telomere-associated genes. Taken together, we showed that BCR-ABL1 kinase expression and activity play a crucial role in the maintenance of telomeres in CML cell lines. Our results may help to validate and properly interpret results obtained by many laboratories employing these in vitro models of CML.
Deleterious AGXT Missense Variant Associated with Type 1 Primary Hyperoxaluria (PH1) in Zwartbles Sheep
Authors: Letko Anna , Dijkman Reinie , Strugnell Ben , Häfliger Irene M. , Paris Julia M. , Henderson Katrina , Geraghty Tim , Orr Hannah , Scholes Sandra , Drögemüller Cord
Published: September 2020

Severe oxalate nephropathy has been previously reported in sheep and is mostly associated with excessive oxalate in the diet. However, a rare native Dutch breed (Zwartbles) seems to be predisposed to an inherited juvenile form of primary hyperoxaluria and no causative genetic variant has been described so far. This study aims to characterize the phenotype and genetic etiology of the inherited metabolic disease observed in several purebred Zwartbles sheep. Affected animals present with a wide range of clinical signs including condition loss, inappetence, malaise, and, occasionally, respiratory signs, as well as an apparent sudden unexpected death. Histopathology revealed widespread oxalate crystal deposition in kidneys of the cases. Whole-genome sequencing of two affected sheep identified a missense variant in the ovine AGXT gene (c.584G>A; p.Cys195Tyr). Variants in AGXT are known to cause type I primary hyperoxaluria in dogs and humans. Herein, we present evidence that the observed clinicopathological phenotype can be described as a form of ovine type I primary hyperoxaluria. This disorder is explained by a breed-specific recessively inherited pathogenic AGXT variant. Genetic testing enables selection against this fatal disorder in Zwartbles sheep as well as more precise diagnosis in animals with similar clinical phenotype. Our results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 001672-9940).
Relations of Bedtime Mobile Phone Use to Cognitive Functioning, Academic Performance, and Sleep Quality in Undergraduate Students
Authors: Ragupathi Darnisha , Ibrahim Normala , Tan Kit-Aun , Andrew Beatrice Ng
Published: September 2020

The present cross-sectional study examined the relations of bedtime mobile phone use to cognitive functioning, academic performance, and sleep quality in a sample of undergraduate students. Three hundred eighty-five undergraduate students completed a self-administered questionnaire containing sociodemographic variables, bedtime mobile phone use, the Pittsburgh Sleep Quality Index, and the Cambridge Neuropsychological Test Automated Battery (attention and verbal memory). At bivariate level, increased scores in bedtime mobile phone use were significantly correlated with decreased scores in academic performance and sleep quality. Our multivariate findings show that increased scores in bedtime mobile phone use uniquely predicted decreased scores in academic performance and sleep quality, while controlling for gender, age, and ethnicity. Further untangling the relations of bedtime mobile phone use to academic performance and sleep quality may prove complex. Future studies with longitudinal data are needed to examine the bidirectional effect that bedtime mobile phone use may have on academic performance and sleep quality.
Acculturation Associated with Sleep Duration, Sleep Quality, and Sleep Disorders at the US–Mexico Border
Authors: Ghani Sadia B. , Delgadillo Marcos E. , Granados Karla , Okuagu Ashley C. , Alfonso-Miller Pamela , Buxton Orfeu M. , Patel Sanjay R. , Ruiz John , Parthasarathy Sairam , Haynes Patricia L. , Molina Patricia , Seixas Azizi , Williams Natasha , Jean-Louis Girardin , Grandner Michael A.
Published: September 2020

Sleep disparities exist among Hispanics/Latinos, although little work has characterized individuals at the United States (US)–Mexico border, particularly as it relates to acculturation. This study examined the association of Anglo and Mexican acculturation to various facets of sleep health among those of Mexican descent at the US–Mexico border. Data were collected from N = 100 adults of Mexican descent in the city of Nogales, Arizona (AZ). Surveys were presented in English or Spanish. Acculturation was assessed with the Acculturation Scale for Mexican-Americans (ARSMA-II). Insomnia was assessed with the Insomnia Severity Index (ISI), sleepiness was assessed with the Epworth Sleepiness Scale (ESS), sleep apnea risk was assessed with the Multivariable Apnea Prediction (MAP) index, weekday and weekend sleep duration and efficiency were assessed with the Sleep Timing Questionnaire, sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and sleep duration and sleep medication use were assessed with PSQI items. No associations were found between Mexican acculturation and any sleep outcomes in adjusted analyses. Anglo acculturation was associated with less weekend sleep duration and efficiency, worse insomnia severity and sleep quality, and more sleep apnea risk and sleep medication use. These results support the idea that sleep disparities may depend on the degree of acculturation, which should be considered in risk screening and interventions.
The Interplay between Transcriptional Factors and MicroRNAs as an Important Factor for Th17/Treg Balance in RA Patients
Authors: Kmiołek Tomasz , Rzeszotarska Ewa , Wajda Anna , Walczuk Ewa , Kuca-Warnawin Ewa , Romanowska-Próchnicka Katarzyna , Stypinska Barbara , Majewski Dominik , Jagodzinski Pawel Piotr , Pawlik Andrzej , Paradowska-Gorycka Agnieszka
Published: September 2020

MicroRNAs regulate gene expression of transcriptional factors, which influence Th17/Treg (regulatory T cells) balance, establishing the molecular mechanism of genetic and epigenetic regulation of Treg and Th17 cells is crucial for understanding rheumatoid arthritis (RA) pathogenesis. The study goal was to understand the potential impact of the selected microRNAs expression profiles on Treg/Th17 cells frequency, RA phenotype, the expression profile of selected microRNAs, and their correlation with the expression profiles of selected transcriptional factors: SOCS1, SMAD3, SMAD4, STAT3, STAT5 in RA; we used osteoarthritis (OA) and healthy controls (HCs) as controls. The study was conducted on 14 RA and 11 OA patients, and 15 HCs. Treg/Th17 frequency was established by flow cytometry. Gene expression analysis was estimated by qPCR. We noticed correlations in RA Th17 cells between miR-26 and SMAD3, STAT3, SOCS1; and miR-155 and STAT3—and in RA Treg cells between miR-26 and SOCS1; miR-31, -155 and SMAD3; and miR-155 and SMAD4. In RA Tregs, we found a negative correlation between miR-26, -126 and STAT5a. The expression level of miR-31 in Th17 cells from RA patients with DAS28 ≤ 5.1 is higher and that for miR-24 is greater in Tregs from patients with DAS28 > 5.1. MiR-146a in Tregs is higher in rheumatoid factor (RF) positive RA patients.
Oxidative Stress and Microglial Response in Retinitis Pigmentosa
Authors: Murakami Yusuke , Nakabeppu Yusaku , Sonoda Koh-Hei
Published: September 2020

An imbalance between the production of reactive oxygen species (ROS) and anti-oxidant capacity results in oxidative injury to cellular components and molecules, which in turn disturbs the homeostasis of cells and organs. Although retinitis pigmentosa (RP) is a hereditary disease, non-genetic biological factors including oxidative stress also modulate or contribute to the disease progression. In animal models of RP, the degenerating retina exhibits marked oxidative damage in the nucleic acids, proteins, and lipids, and anti-oxidant treatments substantially suppress photoreceptor cell death and microgliosis. Although the mechanisms by which oxidative stress mediates retinal degeneration have not been fully elucidated, our group has shown that oxidative DNA damage and its defense system are key regulators of microglial activation and photoreceptor degeneration in RP. In this review, we summarize the current evidence regarding oxidative stress in animal models and patients with RP. The clinical efficacy of anti-oxidant treatments for RP has not been fully established. Nevertheless, elucidating key biological processes that underlie oxidative damage in RP will be pivotal to understanding the pathology and developing a potent anti-oxidant strategy that targets specific cell types or molecules under oxidative stress.
Folate-Targeted Transgenic Activity of Dendrimer Functionalized Selenium Nanoparticles In Vitro
Authors: Pillay Nikita Simone , Daniels Aliscia , Singh Moganavelli
Published: September 2020

Current chemotherapeutic drugs, although effective, lack cell-specific targeting, instigate adverse side effects in healthy tissue, exhibit unfavourable bio-circulation and can generate drug-resistant cancers. The synergistic use of nanotechnology and gene therapy, using nanoparticles (NPs) for therapeutic gene delivery to cancer cells is hereby proposed. This includes the benefit of cell-specific targeting and exploitation of receptors overexpressed in specific cancer types. The aim of this study was to formulate dendrimer-functionalized selenium nanoparticles (PAMAM-SeNPs) containing the targeting moiety, folic acid (FA), for delivery of pCMV-Luc-DNA (pDNA) in vitro. These NPs and their gene-loaded nanocomplexes were physicochemically and morphologically characterized. Nucleic acid-binding, compaction and pDNA protection were assessed, followed by cell-based in vitro cytotoxicity, transgene expression and apoptotic assays. Nanocomplexes possessed favourable sizes (<150 nm) and ζ-potentials (>25 mV), crucial for cellular interaction, and protected the pDNA from degradation in an in vivo simulation. PAMAM-SeNP nanocomplexes exhibited higher cell viability (>85%) compared to selenium-free nanocomplexes (approximately 75%), confirming the important role of selenium in these nanocomplexes. FA-conjugated PAMAM-SeNPs displayed higher overall transgene expression (HeLa cells) compared to their non-targeting counterparts, suggesting enhanced receptor-mediated cellular uptake. Overall, our results bode well for the use of these nano-delivery vehicles in future in vivo studies.
Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes
Authors: Heimes Anne-Sophie , Härtner Franziska , Almstedt Katrin , Krajnak Slavomir , Lebrecht Antje , Battista Marco J. , Edlund Karolina , Brenner Walburgis , Hasenburg Annette , Sahin Ugur , Gehrmann Mathias , Hengstler Jan G. , Schmidt Marcus
Published: September 2020

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ, as well as the IFN-γ signature for metastasis-free survival (MFS), were examined using Kaplan–Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. The independent prognostic significance of IFN-γ as a single gene was limited to basal-like breast cancer (hazard ratio (HR) 2.779, 95% confidence interval (95% CI) 1.117–6.919, p = 0.028). In contrast, the IFN-γ-associated gene signature was an independent prognostic factor in the whole cohort (HR 2.287, 95% CI 1.410–3.633, p < 0.001) as well as in the basal-like (HR 3.458, 95% CI 1.154–10.359, p = 0.027) and luminal B (HR 2.690, 95% CI 1.416–5.112, p = 0.003) molecular subtypes. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.
Bioactive Ent-Kaurane Diterpenes Oridonin and Irudonin Prevent Cancer Cells Migration by Interacting with the Actin Cytoskeleton Controller Ezrin
Authors: Pagliara Valentina , Donadio Giuliana , De Tommasi Nunziatina , Amodio Giuseppina , Remondelli Paolo , Moltedo Ornella , Dal Piaz Fabrizio
Published: September 2020

The ent-kaurane diterpene oridonin was reported to inhibit cell migration and invasion in several experimental models. However, the process by which this molecule exerts its anti-metastatic action has not been yet elucidated. In this article, we have investigated the anti-metastatic activity of Oridonin and of one homolog, Irudonin, with the aim to shed light on the molecular mechanisms underlying the biological activity of these ent-kaurane diterpenes. Cell-based experiments revealed that both compounds are able to affect differentiation and cytoskeleton organization in mouse differentiating myoblasts, but also to impair migration, invasion and colony formation ability of two different metastatic cell lines. Using a compound-centric proteomic approach, we identified some potential targets of the two bioactive compounds among cytoskeletal proteins. Among them, Ezrin, a protein involved in the actin cytoskeleton organization, was further investigated. Our results confirmed the pivotal role of Ezrin in regulating cell migration and invasion, and indicate this protein as a potential target for new anti-cancer therapeutic approaches. The interesting activity profile, the good selectivity towards cancer cells, and the lower toxicity with respect to Oridonin, all suggest that Irudonin is a very promising anti-metastatic agent.
The Class III Peroxidase Encoding Gene AtPrx62 Positively and Spatiotemporally Regulates the Low pH-Induced Cell Death in Arabidopsis thaliana Roots
Authors: Graças Jonathas Pereira , Ranocha Philippe , Vitorello Victor Alexandre , Savelli Bruno , Jamet Elisabeth , Dunand Christophe , Burlat Vincent
Published: September 2020

Exogenous low pH stress causes cell death in root cells, limiting root development, and agricultural production. Different lines of evidence suggested a relationship with cell wall (CW) remodeling players. We investigated whether class III peroxidase (CIII Prx) total activity, CIII Prx candidate gene expression, and reactive oxygen species (ROS) could modify CW structure during low pH-induced cell death in Arabidopsis thaliana roots. Wild-type roots displayed a good spatio-temporal correlation between the low pH-induced cell death and total CIII Prx activity in the early elongation (EZs), transition (TZs), and meristematic (MZs) zones. In situ mRNA hybridization showed that AtPrx62 transcripts accumulated only in roots treated at pH 4.6 in the same zones where cell death was induced. Furthermore, roots of the atprx62-1 knockout mutant showed decreased cell mortality under low pH compared to wild-type roots. Among the ROS, there was a drastic decrease in O2●− levels in the MZs of wild-type and atprx62-1 roots upon low pH stress. Together, our data demonstrate that AtPrx62 expression is induced by low pH and that the produced protein could positively regulate cell death. Whether the decrease in O2●− level is related to cell death induced upon low pH treatment remains to be elucidated.
Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review
Authors: Sławiński Grzegorz , Wrona Anna , Dąbrowska-Kugacka Alicja , Raczak Grzegorz , Lewicka Ewa
Published: September 2020

Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80–85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.
Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase
Authors: Barchetta Ilaria , Chiappetta Caterina , Ceccarelli Valentina , Cimini Flavia Agata , Bertoccini Laura , Gaggini Melania , Cristofano Claudio Di , Silecchia Gianfranco , Lenzi Andrea , Leonetti Frida , Baroni Marco Giorgio , Gastaldelli Amalia , Cavallo Maria Gisella
Published: September 2020

Angiopoietin-like protein 4 (ANGPTL4) regulates lipid partitioning by inhibiting circulating and tissue lipoprotein lipase (LPL); ANGPTL4 loss-of-function variants improve insulin sensitivity and reduce type 2 diabetes (T2D) risk with mechanisms partially unknown. This study was designed to explore metabolic implications of differential ANGPTL4 and LPL expression in human adipose tissue (AT). We recruited eighty-eight obese individuals, with and without abnormal glucose metabolism (AGM), undergoing bariatric surgery; visceral AT (VAT) fragments were obtained intra-operatively and analyzed by immunohistochemistry and mRNA by rt-PCR. Data on hepatic ANGPTL4 mRNA were available for 40 participants. VAT ANGPTL4 expression was higher in AGM individuals than in those with normal glucose tolerance (NGT) and associated with VAT inflammation, insulin resistance, and presence of adipocyte size heterogeneity. Increased ANGPTL4 was associated with AGM with OR = 5.1 (95% C.I.: 1.2–23; p = 0.02) and AUROC = 0.76 (95% C.I.: 1.2–23; p < 0.001). High LPL was associated with the detection of homogeneous adipocyte size, reduced microvessel density, and higher HIF-1α levels and inversely correlated to blood transaminases. In conclusion, in obese individuals, VAT ANGPTL4 levels are increased in the presence of local inflammation and AGM. Conversely, higher LPL expression describes a condition of increased lipid storage in adipocytes, which may serve as a protective mechanism against ectopic fat accumulation and related metabolic disease in obesity.
Inositol Polyphosphate-Based Compounds as Inhibitors of Phosphoinositide 3-Kinase-Dependent Signaling
Authors: Maffucci Tania , Falasca Marco
Published: September 2020

Signaling pathways regulated by the phosphoinositide 3-kinase (PI3K) enzymes have a well-established role in cancer development and progression. Over the past 30 years, the therapeutic potential of targeting this pathway has been well recognized, and this has led to the development of a multitude of drugs, some of which have progressed into clinical trials, with few of them currently approved for use in specific cancer settings. While many inhibitors compete with ATP, hence preventing the catalytic activity of the kinases directly, a deep understanding of the mechanisms of PI3K-dependent activation of its downstream effectors led to the development of additional strategies to prevent the initiation of this signaling pathway. This review summarizes previously published studies that led to the identification of inositol polyphosphates as promising parent molecules to design novel inhibitors of PI3K-dependent signals. We focus our attention on the inhibition of protein–membrane interactions mediated by binding of pleckstrin homology domains and phosphoinositides that we proposed 20 years ago as a novel therapeutic strategy.
Transcriptional and Metabolic Profiling of Potato Plants Expressing a Plastid-Targeted Electron Shuttle Reveal Modulation of Genes Associated to Drought Tolerance by Chloroplast Redox Poise
Authors: Karlusich Juan J. Pierella , Arce Rocío C. , Shahinnia Fahimeh , Sonnewald Sophia , Sonnewald Uwe , Zurbriggen Matias D. , Hajirezaei Mohammad-Reza , Carrillo Néstor
Published: September 2020

Water limitation represents the main environmental constraint affecting crop yield worldwide. Photosynthesis is a primary drought target, resulting in over-reduction of the photosynthetic electron transport chain and increased production of reactive oxygen species in plastids. Manipulation of chloroplast electron distribution by introducing alternative electron transport sinks has been shown to increase plant tolerance to multiple environmental challenges including hydric stress, suggesting that a similar strategy could be used to improve drought tolerance in crops. We show herein that the expression of the cyanobacterial electron shuttle flavodoxin in potato chloroplasts protected photosynthetic activities even at a pre-symptomatic stage of drought. Transcriptional and metabolic profiling revealed an attenuated response to the adverse condition in flavodoxin-expressing plants, correlating with their increased stress tolerance. Interestingly, 5–6% of leaf-expressed genes were affected by flavodoxin in the absence of drought, representing pathways modulated by chloroplast redox status during normal growth. About 300 of these genes potentially contribute to stress acclimation as their modulation by flavodoxin proceeds in the same direction as their drought response in wild-type plants. Tuber yield losses under chronic water limitation were mitigated in flavodoxin-expressing plants, indicating that the flavoprotein has the potential to improve major agronomic traits in potato.
Ceramide-Enriched Membrane Domains Contribute to Targeted and Nontargeted Effects of Radiation through Modulation of PI3K/AKT Signaling in HNSCC Cells
Authors: Ladjohounlou Riad , Louati Safa , Lauret Alexandra , Gauthier Arnaud , Ardail Dominique , Magne Nicolas , Alphonse Gersende , Rodriguez-Lafrasse Claire
Published: September 2020

We investigated the potential involvement of ceramide-enriched membrane domains in radiation-induced targeted and nontargeted effects using head and neck squamous cell carcinoma with opposite radiosensitivities. In radiosensitive SCC61 cells, the proportion of targeted effects was 34% and nontargeted effects killed 32% of cells. In contrast, only targeted effects (30%) are involved in the overall death of radioresistant SQ20B cells. We then demonstrated in SCC61 cells that nontargeted cell response was driven by the formation of the radiation-induced ceramide-enriched domain. By contrast, the existence of these platforms in SQ20B cells confers a permissive region for phosphatidylinositol-3-kinase (PI3K)/AKT activation. The disruption of lipid raft results in strong inhibition of PI3K/AKT signaling, leading to radiosensitization and apparition of nontargeted effects. These results suggest that ceramide-enriched platforms play a significant role in targeted and nontargeted effects during radiotherapy and that drugs modulating cholesterol levels may be a good alternative for improving radiotherapy effectiveness.
Age-Related Hearing Loss in C57BL/6J Mice Is Associated with Mitophagy Impairment in the Central Auditory System
Authors: Youn Cha Kyung , Jun Yonghyun , Jo Eu-Ri , Cho Sung Il
Published: September 2020

Aging is associated with functional and morphological changes in the sensory organs, including the auditory system. Mitophagy, a process that regulates the turnover of dysfunctional mitochondria, is impaired with aging. This study aimed to investigate the effect of aging on mitophagy in the central auditory system using an age-related hearing loss mouse model. C57BL/6J mice were divided into the following four groups based on age: 1-, 6-, 12-, and 18-month groups. The hearing ability was evaluated by measuring the auditory brainstem response (ABR) thresholds. The mitochondrial DNA damage level and the expression of mitophagy-related genes, and proteins were investigated by real-time polymerase chain reaction and Western blot analyses. The colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus was analyzed by immunofluorescence analysis. The expression of genes involved in mitophagy, such as PINK1, Parkin, and BNIP3 in the mouse auditory cortex and inferior colliculus, was investigated by immunohistochemical staining. The ABR threshold increased with aging. In addition to the mitochondrial DNA integrity, the mRNA levels of PINK1, Parkin, NIX, and BNIP3, as well as the protein levels of PINK1, Parkin, BNIP3, COX4, LC3B, mitochondrial oxidative phosphorylation (OXPHOS) subunits I–IV in the mouse auditory cortex significantly decreased with aging. The immunofluorescence analysis revealed that the colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus decreased with aging. The immunohistochemical analysis revealed that the expression of PINK1, Parkin, and BNIP3 decreased in the mouse auditory cortex and inferior colliculus with aging. These findings indicate that aging-associated impaired mitophagy may contribute to the cellular changes observed in an aged central auditory system, which result in age-related hearing loss. Thus, the induction of mitophagy can be a potential therapeutic strategy for age-related hearing loss.
Information and Communication Technology (ICT) Governance Processes: A Case Study
Authors: Dias Canedo Edna , Morais do Vale Ana Paula , Patrão Rafael Leite , Camargo de Souza Leomar , Machado Gravina Rogério , Eloy dos Reis Vinicius , Lúcio Lopes Mendonça Fábio , T. de Sousa Rafael
Published: September 2020

Information and Communication Technology (ICT) Governance is increasingly necessary and present in organizations aiming to improve the maturity of their ICT processes. This paper presents an analysis of the ICT Governance processes of a Brazilian Federal Public Administration agency. To assess the maturity of the ICT Governance processes, we surveyed and diagnosed the processes performed by the agency and organized a series of meetings/discussions to assist in the improvement and modeling of the processes related to the ICT Contract Planning process. As a result, we proposed improvements and identified the maturity level of the existing ICT processes, also assessing the awareness of employees of the General Coordination of Information Technology regarding these processes. Our findings reveal that the agency still needs to implement the following processes: (1) ICT People Management; (2) Business Process Modeling (Automated/to Automate); (3) Change Management; (4) Execution Monitoring of the ICT Projects and Services Portfolio; and (5) ICT Service Continuity Management. We also identified several artifacts that need to be implemented by the agency in different processes and collected survey participants’ suggestions about new processes to improve the maturity in ICT Governance.
Recent Advancements in the Control of Cat Fleas
Authors: Rust Michael K.
Published: September 2020

With the advent of imidacloprid and fipronil spot-on treatments and the oral ingestion of lufenuron, the strategies and methods to control cat fleas dramatically changed during the last 25 years. New innovations and new chemistries have highlighted this progress. Control strategies are no longer based on the tripartite approach of treating the pet, the indoor environment, and outdoors. The ability of modern therapies to break the cat flea life cycle and prevent reproduction has allowed for the stand-alone treatments that are applied or given to the pet. In doing so, we have not only controlled the cat flea, but we have prevented or reduced the impact of many of the diseases associated with ectoparasites and endoparasites of cats and dogs. This review provides an update of newer and non-conventional approaches to control cat fleas.
Evaluation of the Performance of Algorithm-Based Methods for Subjective Refraction
Authors: Venkataraman Abinaya Priya , Sirak Delila , Brautaset Rune , Dominguez-Vicent Alberto
Published: September 2020

Objective: To evaluate the performance of two subjective refraction measurement algorithms by comparing the refraction values, visual acuity, and the time taken by the algorithms with the standard subjective refraction (SSR). Methods: The SSR and two semi-automated algorithm-based subjective refraction (SR1 and SR2) in-built in the Vision-R 800 phoropter were performed in 68 subjects. In SR1 and SR2, the subject’s responses were recorded in the algorithm which continuously modified the spherical and cylindrical component accordingly. The main difference between SR1 and SR2 is the use of an initial fogging step in SR1. Results: The average difference and agreement limits intervals in the spherical equivalent between each refraction method were smaller than 0.25 D, and 2.00 D, respectively. For the cylindrical components, the average difference was almost zero and the agreement limits interval was less than 0.50 D. The visual acuities were not significantly different among the methods. The times taken for SR1 and SR2 were significantly shorter, and SR2 was on average was three times faster than SSR. Conclusions: The refraction values and the visual acuity obtained with the standard subjective refraction and algorithm-based methods were similar on average. The algorithm-based methods were significantly faster than the standard method.
The Effect of Anti-TNF Therapy on Cardiac Function in Rheumatoid Arthritis: An Observational Study
Authors: Baniaamam Milad , Handoko M. Louis , Agca Rabia , Heslinga Sjoerd C. , Konings Thelma C. , van Halm Vokko P. , Nurmohamed Mike T.
Published: September 2020

Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might improve the cardiac function by lowering the overall inflammatory state. This study investigated the effect of anti-TNF on the cardiac function in RA patients. Fifty one RA patients were included, of which thirty three completed follow-up. Included patients were >18 years, had moderate–high disease activity and no history of cardiac disease. Patients were assessed at baseline and after six months of anti-TNF treatment. Patients underwent conventional Speckle tracking and tissue Doppler echocardiography in combination with clinical and laboratory assessments at baseline and follow-up. The left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed no changes during follow-up, LVEF 63% (±9) to 62% (±8) p = 0.097 and GLS −20 (±4) to −20 (±3) p = 0.79, respectively. Furthermore, E/e’ nor E/A changed significantly between baseline and follow-up, respectively 8 (7–9) and 8 (7–9) p = 0.17 and 1.1 (±0.4) and 1.1 (±0.4) p = 0.94. Follow-up NT-proBNP decreased with 23%, from 89 ng/L (47–142) to 69 ng/L (42–155), p = 0.10. Regression analysis revealed no association between change in inflammatory variables and cardiac function. Echocardiography showed no effect of anti-TNF treatment on the cardiac function in RA patients with low prevalence of cardiac dysfunction. Moreover, NT-proBNP decreased, possibly indicating (subtle) improvement of the cardiac function.
Prognostic Relevance of the Eighth Edition of TNM Classification for Resected Perihilar Cholangiocarcinoma
Authors: Hau Hans-Michael , Meyer Felix , Jahn Nora , Rademacher Sebastian , Sucher Robert , Seehofer Daniel
Published: September 2020

Objectives: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). Conclusions: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC—for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient’s outcome.
A Deep Brain Stimulation Trial Period for Treating Chronic Pain
Authors: Shirvalkar Prasad , Sellers Kristin K. , Schmitgen Ashlyn , Prosky Jordan , Joseph Isabella , Starr Philip A. , Chang Edward F.
Published: September 2020

Early studies of deep brain stimulation (DBS) for various neurological disorders involved a temporary trial period where implanted electrodes were externalized, in which the electrical contacts exiting the patient’s brain are connected to external stimulation equipment, so that stimulation efficacy could be determined before permanent implant. As the optimal brain target sites for various diseases (i.e., Parkinson’s disease, essential tremor) became better established, such trial periods have fallen out of favor. However, deep brain stimulation trial periods are experiencing a modern resurgence for at least two reasons: (1) studies of newer indications such as depression or chronic pain aim to identify new targets and (2) a growing interest in adaptive DBS tools necessitates neurophysiological recordings, which are often done in the peri-surgical period. In this review, we consider the possible approaches, benefits, and risks of such inpatient trial periods with a specific focus on developing new DBS therapies for chronic pain.
Does Social Capital Help to Reduce Farmland Abandonment? Evidence from Big Survey Data in Rural China
Authors: Deng Xin , Zeng Miao , Xu Dingde , Qi Yanbin
Published: September 2020

At a time when COVID-19 is sweeping the world, farmland abandonment is obviously not conducive to solving food security problems. Since the formal institutions of local government in China have not been effective in the reduction of farmland abandonment, this study aims to explore whether informal institutions can help mitigate this problem. Based on big survey data from 8031 farmer households in 27 provinces in mainland China, this study uses an econometric model to investigate the quantitative impact of social capital on farmland abandonment, and to analyze the channels through which that impact manifests itself. The empirical results point to the following conclusions: (i) Social capital, as a key informal institution, can help reduce farmland abandonment. More specifically, after controlling for other variables, for every unit increase in social capital, the proportion of farmland abandonment can be predicted to drop by 7.17 percentage points. (ii) Both off-farm employment and farmland rent are channels for the impact of social capital on farmland abandonment. However, social capital’s effect on increasing farmland abandonment via the promotion of off-farm employment is small when compared with its effect on reducing farmland abandonment via the promotion of farmland rent. This study’s conclusions may help generate new ideas for reducing farmland abandonment. At the same time, the study may provide a sound, empirical basis for policies aimed at reducing the negative impact of COVID-19 on food security while also revitalizing rural areas.
Enhancement of Titania Photoanode Performance by Sandwiching Copper between Two Titania Layers
Authors: Yang Fan , Yang Ruizhuang , Yan Lin , Wu Jiankun , Liu Xiaolin , Yang Lirong , Zhong Minglong , Luo Xuan , Zhang Lin
Published: September 2020

Vacancies in semiconductors can play a versatile role in boosting their photocatalytic activity. In this work, a novel TiO2/Cu/TiO2 sandwich structure is designed and constructed. Abundant vacancies were introduced in TiO2 lattice by Cu reduction under heat treatment. Meanwhile, Cu atom could diffuse into TiO2 to form Cu-doped TiO2. The synergistic effect between oxygen vacancies and Cu atoms achieved about 2.4 times improved photocurrent of TiO2/Cu/TiO2 sandwich structure compared to bare TiO2 thin film. The enhanced photoactivity may be attributed to regulated electron structure of TiO2 by oxygen vacancies and Cu dopant from experimental results and density functional theory calculations. Oxygen vacancies and Cu dopant in TiO2 formed through copper metal reduction can introduce impurity levels and narrow the band gap of TiO2, thus improve the visible light response. More importantly, the Cu2+ and oxygen vacancies in TiO2 lattice can dramatically increase the charge density around conduction band and promote separation of photo-induced charge carriers. Furthermore, the oxygen vacancies on the surface may serve as active site for sufficient chemical reaction. This work presents a novel method to prepare doped metal oxides catalysts with abundant vacancies for improving photocatalytic activity.