bluuebunny/crossref_metadata_2025 huggingface dataset:
Condition Maintenance Decision of Wind Turbine Gearbox Based on Stochastic Differential Equation
Authors: Su Hongsheng , Wang Dantong , Duan Xuping
Published: August 2020

Maintenance decision analysis is necessary to ensure the safe and stable operation of wind turbine equipment. To address gearboxes with a high failure rate in wind turbines, this paper establishes a new stochastic differential equation model of gearbox state transition to maximize the utilization of gearboxes. This model divides the state of the gearbox into two parts: internal degradation and external random interference. Weibull distribution and polynomial approximation were used to construct the internal degradation model of the gearbox. The external random interference is simulated by Brownian motion. On the basis of the analysis of monitoring data, the parameters of the gearbox state model were solved using the Newton–Raphson iterative method and entropy method. The state change of the gearbox was simulated in MATLAB, and the residual value between the predicted state and the real state was calculated. Compared with the state transformation model constructed by the traditional ordinary differential equation and the gamma distribution, the Weibull polynomial approximation stochastic model can better reflect the state of the device. With reliability set as the decision goal, the maintenance time of the gearbox is predicted, and the validity of the model is verified through case analysis.
Predicting Renewable Energy Investment Using Machine Learning
Authors: Hosein Govinda , Hosein Patrick , Bahadoorsingh Sanjay , Martinez Robert , Sharma Chandrabhan
Published: August 2020

In order to combat climate change, many countries have promised to bolster Renewable Energy (RE) production following the Paris Agreement with some countries even setting a goal of 100% by 2025. The reasons are twofold: capitalizing on carbon emissions whilst concomitantly benefiting from reduced fossil fuel dependence and the fluctuations associated with imported fuel prices. However, numerous countries have not yet made preparations to increase RE production and integration. In many instances, this reluctance seems to be predominant in energy-rich countries, which typically provide heavy subsidies on electricity prices. With such subsidies, there is no incentive to invest in RE since the time taken to recoup such investments would be significant. We develop a model using a Neural Network (NN) regression algorithm to quantitatively illustrate this conjecture and also use it to predict the reduction in electricity price subsidies required to achieve a specified RE production target. The model was trained using 10 leading metrics from 53 countries. It is envisaged that policymakers and researchers can use this model to plan future RE targets to satisfy the Nationally Determined Contributions (NDC) and determine the required electricity subsidy reductions. The model can easily be modified to predict what changes in other country factors can be made to stimulate growth in RE production. We illustrate this approach with a sample use case.
Genome-Wide DNA Methylation Signatures of Sea Cucumber Apostichopus japonicus during Environmental Induced Aestivation
Authors: Yang Yujia , Zheng Yingqiu , Sun Lina , Chen Muyan
Published: August 2020

Organisms respond to severe environmental changes by entering into hypometabolic states, minimizing their metabolic rates, suspending development and reproduction, and surviving critical ecological changes. They come back to an active lifestyle once the environmental conditions are conducive. Marine invertebrates live in the aquatic environment and adapt to environmental changes in their whole life. Sea cucumbers and sponges are only two recently known types of marine organisms that aestivate in response to temperature change. Sea cucumber has become an excellent model organism for studies of environmentally-induced aestivation by marine invertebrates. DNA methylation, the most widely considered epigenetic marks, has been reported to contribute to phenotypic plasticity in response to environmental stress in aquatic organisms. Most of methylation-related enzymes, including DNA methyltransferases, Methyl-CpG binding domain proteins, and DNA demethylases, were up-regulated during aestivation. We conducted high-resolution whole-genome bisulfite sequencing of the intestine from sea cucumber at non-aestivation and deep-aestivation stages. Further DNA methylation profile analysis was also conducted across the distinct genomic features and entire transcriptional units. A different elevation in methylation level at internal exons was observed with clear demarcation of intron/exon boundaries during transcriptional unit scanning. The lowest methylation level occurs in the first exons, followed by the last exons and the internal exons. A significant increase in non-CpG methylation (CHG and CHH) was observed within the intron and mRNA regions in aestivation groups. A total of 1393 genes were annotated within hypermethylated DMRs (differentially methylated regions), and 749 genes were annotated within hypomethylated DMRs. Differentially methylated genes were enriched in the mRNA surveillance pathway, metabolic pathway, and RNA transport. Then, 24 hypermethylated genes and 15 hypomethylated genes were Retrovirus-related Pol polyprotein from transposon (RPPT) genes. This study provides further understanding of epigenetic control on environmental induced hypometabolism in aquatic organisms.
Carex muskingumensis and Osmotic Stress: Identification of Reference Genes for Transcriptional Profiling by RT-qPCR
Authors: Sozoniuk Magdalena , Parzymies Marzena , Kozak Danuta , Ismael Bairam Solomon
Published: August 2020

Carex muskingumensis is a highly valued perennial ornamental grass cultivated worldwide. However, there is limited genetic data regarding this species. Selection of proper reference genes (RGs) for reverse transcription quantitative PCR (RT-qPCR) data normalization has become an essential step in gene expression analysis. In this study, we aimed to examine expression stability of nine candidate RGs in C. muskingumensis plants, subjected to osmotic stress, generated either by salinity or PEG treatment. The identification of genes exhibiting high expression stability was performed by four algorithms (geNorm, NormFinder, BestKeeper and deltaCt method). The results showed that the combination of two genes would be sufficient for reliable expression data normalization. ADP (ADP-ribosylation factor) and TBP (TATA-box-binding protein) were identified as the most stably expressed under salinity treatment, while eIF4A (eukaryotic initiation factor 4A) and TBP were found to show the highest stability under PEG-induced drought. A set of three genes (ADP, eIF4A and TBP) displayed the highest expression stability across all experimental samples tested in this study. To our best knowledge, this is the first report regarding RGs selection in C. muskingumensis. It will provide valuable starting point information for conducting further analyses in this and related species concerning their responses to water shortage and salinity stress.
Asceticism in Old English and Syriac Soul and Body Narratives
Authors: Torabi Katayoun
Published: August 2020

A great deal of scholarship on Old English soul-body poetry centers on whether or not the presence of dualist elements in the poems are unorthodox in their implication that the body, as a material object, is not only wicked but seems to possess more agency in the world than the soul. I argue that the Old English soul-body poetry is not heterodox or dualist, but is best understood, as Allen J. Frantzen suggests, within the “context of penitential practice.” The seemingly unorthodox elements are resolved when read against the backdrop of pre-Conquest English monastic reform culture, which was very much concerned with penance, asceticism, death, and judgment. Focusing especially on two anonymous 10th-century Old English poems, Soul and Body I in the Vercelli Book and Soul and Body II in the Exeter Book, I argue that that both body and soul bear equal responsibility in achieving salvation and that the work of salvation must be performed before death, a position that was reinforced in early English monastic literature that was inspired, at least in part, by Eastern ascetics such as fourth-century Syrian hymnologist and theologian, St. Ephraim.
The Association between Temporomandibular Disorder and Sleep Apnea—A Nationwide Population-Based Cohort Study
Authors: Wu Ju-Hui , Lee Kun-Tsung , Kuo Chia-Yu , Cheng Chih-Hung , Chiu Jih-Yu , Hung Jen-Yu , Hsu Chung-Yao , Tsai Ming-Ju
Published: August 2020

An increased incidence of temporomandibular disorders (TMD) among patients with sleep apnea (SA) has been reported. However, the association between TMD and SA has not been demonstrated in a large-scale study. This population-based cohort study with the Taiwan National Health Insurance (NHI) Research Database aimed to understand the association between SA and TMD. We identified adult patients with suspected SA (identified with diagnostic codes) and excluded those diagnosed with TMD prior to SA. Patients with SA diagnosis after polysomnography were also identified as probable SA patients. The index dates were the dates of their initial SA diagnosis. Ten control subjects were matched, by age and sex, to each SA patient, and were assigned the same index dates as the SA patients. In total, 10,408 suspected SA patients (including 4105 probable SA patients) matched to 104,080 control subjects (including 41,050 subjects matched to the probable SA patients) in this study. The TMD incidence rate was significantly higher in the SA patients than in the control subjects (2.8 vs. 1.0 per thousand-patient-year in probable SA patients vs. the corresponding control subjects, with an adjusted incidence rate ratio [95% confidence interval] = 2.5 [2.3–2.7], p < 0.0001). SA patients significantly showed a higher cumulative incidence of TMD than the corresponding control subjects (p < 0.0001). Multivariable Cox regression analysis revealed SA as an independent risk factor for the development of TMD (adjusted hazard ratio = 2.5 [1.7–3.7], p < 0.0001). In summary, this study confirmed an increased TMD incidence in the SA patients. While treating TMD patients, dentists should pay careful attention to the potential underlying SA.
Lateral Window Design for Maxillary Sinus Graft Based on the Implant Position
Authors: Cheon Kyeong-Jun , Yang Byoung-Eun , Cho Seoung-Won , Chung Sung-Min , Byun Soo-Hwan
Published: August 2020

The purpose of this study was to devise a classification and lateral window design method based on implants and to evaluate whether these classifications and methods are applicable to clinical practice. When applying the maxillary sinus elevation technique using the lateral window, possible situations were classified into four: (A) two or more sites for implants are required for maxillary sinus augmentation, (B) a single implant is required when there are no adjacent teeth, (C) a single implant is required when one adjacent tooth is present at the mesial or distal area, and (D) a single implant is required when both mesial and distal adjacent teeth are present. In order to verify whether this classification can be used in all situations, 76 patients who underwent maxillary sinus elevation with a lateral window were selected and investigated. Of them, 47 (62%) were included in Group A, 9 (12%) in Group B, 8 (11%) in Group C, and 12 (15%) in Group D. Lateral window designing in the lateral approach of sinus augmentation can be classified into four clinical situations. There were no unclassified cases. This classification and window positioning method can be applied to most cases.
Institutional Engagement Practices as Barriers to Public Health Capacity in Climate Change Policy Discourse: Lessons from the Canadian Province of Ontario
Authors: Awuor Luckrezia , Meldrum Richard , Liberda Eric N.
Published: August 2020

Public health engagement in the communication, discussion, and development of climate change policies is essential for climate change policy decisions and discourse. This study examines how the existing governance approaches impact, enable, or constrain the inclusion, participation, and deliberation of public health stakeholders in the climate change policy discourse. Using the case study of the Canadian Province of Ontario, we conducted semi-structured, key informant interviews of public health (11) and non-public health (13) participants engaged in climate change policies in the province. The study results reveal that engagement and partnerships on climate change policies occurred within and across public health and non-public health organizations in Ontario. These engagements impacted public health’s roles, decisions, mandate, and capacities beyond the climate change discourse; enabled access to funds, expertise, and new stakeholders; built relationships for future engagements; supported knowledge sharing, generation, and creation; and advanced public health interests in political platforms and decision making. However, public health’s participation and deliberation were constrained by a fragmented sectoral approach, a lack of holistic inter-organizational structures and process, political and bureaucratic influences, irregular and unestablished communication channels for public health integration, and identities and culture focused on functions, mandates, biased ideologies, and a lack of clear commitment to engage public health. We conclude by providing practical approaches for integrating public health into climate change discourse and policymaking processes and advancing public health partnerships and collaborative opportunities.
Stigma and Discrimination (SAD) at the Time of the SARS-CoV-2 Pandemic
Authors: Baldassarre Antonio , Giorgi Gabriele , Alessio Federico , Lulli Lucrezia , Arcangeli Giulio , Mucci Nicola
Published: August 2020

Infectious disease control is a crucial public health issue. Although it is important to urgently perform public health measures in order to reduce the risk of spread, it could end up stigmatizing entire groups of people rather than offering control measures based on sound scientific principles. This “us” versus “them” dynamic is common in stigmatization, in general, and indicates a way in which disease stigma can be viewed as a proxy for other types of fears, especially xenophobia and general fear of outsiders. The pandemic risk associated with SARS-CoV-2 infection led us to consider, among other related issues, how stigma and discrimination remain serious barriers to care for people suspected of being infected, even more if they are assisting professions, such as health workers, employed in emergency response. The purpose of this review is to evaluate and promote the importance of psychological aspects of the stigma and social discrimination (SAD) in pandemic realities and, more specifically, nowadays, in the context of SARS-CoV-2/COVID-19. Just as it happened with HIV, HCV, tuberculosis, and Zika, stigma and discrimination undermine the social fabric compromising the ethics and principles of civilization to which each individual in entitled. Recognizing disease stigma history can give us insight into how, exactly, stigmatizing attitudes are formed, and how they are disbanded. Instead of simply blaming the ignorance of people espousing stigmatizing attitudes about certain diseases, we should try to understand precisely how these attitudes are formed so that we can intervene in their dissemination. We should also look at history to see what sorts of interventions against stigma may have worked in the past. Ongoing research into stigma should evaluate what has worked in the past, as above-mentioned, providing us with some clues as to what might work in the current pandemic emergency, to reduce devastating discrimination that keeps people from getting the care they need. We propose a systematic and historical review, in order to create a scientific and solid base for the following SAD analysis. The aim is to propose a coping strategy to face stigma and discrimination (SAD) related to SARS-CoV-2/COVID-19 pandemic outbreak, borrowing coping strategy tools and solutions from other common contagious diseases. Furthermore, our study observes how knowledge, education level, and socioeconomic status (SES) can influence perception of SARS-CoV-2/ COVID-19 risk in a digital world, based on previous research, best practices, and evidence-based research.
Physical Fitness, Exercise Self-Efficacy, and Quality of Life in Adulthood: A Systematic Review
Authors: Medrano-Ureña María del Rocio , Ortega-Ruiz Rosario , Benítez-Sillero Juan de Dios
Published: August 2020

Background: The aim of the present work is the elaboration of a systematic review of existing research on physical fitness, self-efficacy for physical exercise, and quality of life in adulthood. Method: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, and based on the findings in 493 articles, the final sample was composed of 37 articles, which were reviewed to show whether self-efficacy has previously been studied as a mediator in the relationship between physical fitness and quality of life in adulthood. Results: The results indicate that little research exists in relation to healthy, populations with the majority being people with pathology. Physical fitness should be considered as a fundamental aspect in determining the functional capacity of the person. Aerobic capacity was the most evaluated and the 6-min walk test was the most used. Only one article shows the joint relationship between the three variables. Conclusions: We discuss the need to investigate the mediation of self-efficacy in relation to the value of physical activity on quality of life and well-being in the healthy adult population in adult life.
Physical Activity, Sedentary Behaviour and Sleep, and Their Association with BMI in a Sample of Adolescent Females in New Zealand
Authors: Tye Lauren S. , Scott Tessa , Haszard Jillian J. , Peddie Meredith C.
Published: August 2020

Despite activity guidelines moving towards a 24-h focus, we have a poor understanding of the 24-h activity patterns of adolescents. Therefore, this study aims to describe the 24-h activity patterns of a sample of adolescent females and investigate the association with body mass index (BMI). Adolescent females aged 15–18 years (n = 119) were recruited across 13 schools in 8 locations throughout New Zealand. Actigraph GT3X+ accelerometers were worn 24-h a day for seven days and the output was used to identify time spent in each 24-h component (sleep, sedentary, light-intensity physical activity and moderate-to-vigorous intensity physical activity). In a 24-h period, adolescent females spent approximately half their time sedentary, one third sleeping and the remainder in light-intensity physical activity (15%) and moderate-to-vigorous intensity physical activity (5%). Higher BMI z-scores were associated with 16 min more time spent in light-intensity physical activity. Additionally, those with higher BMI were less likely to meet the sleep and physical activity guidelines for this age group. Compliance with the moderate-to-vigorous intensity physical activity guidelines, sleep guidelines, or both, was low, especially in those classified as overweight or obese. The association between BMI and light activity warrants further investigation.
The Key Role of MicroRNAs in Self-Renewal and Differentiation of Embryonic Stem Cells
Authors: Divisato Giuseppina , Passaro Fabiana , Russo Tommaso , Parisi Silvia
Published: August 2020

Naïve pluripotent embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent distinctive developmental stages, mimicking the pre- and the post-implantation events during the embryo development, respectively. The complex molecular mechanisms governing the transition from ESCs into EpiSCs are orchestrated by fluctuating levels of pluripotency transcription factors (Nanog, Oct4, etc.) and wide-ranging remodeling of the epigenetic landscape. Recent studies highlighted the pivotal role of microRNAs (miRNAs) in balancing the switch from self-renewal to differentiation of ESCs. Of note, evidence deriving from miRNA-based reprogramming strategies underscores the role of the non-coding RNAs in the induction and maintenance of the stemness properties. In this review, we revised recent studies concerning the functions mediated by miRNAs in ESCs, with the aim of giving a comprehensive view of the highly dynamic miRNA-mediated tuning, essential to guarantee cell cycle progression, pluripotency maintenance and the proper commitment of ESCs.
Classification of Thyroid Tumors Based on Mass Spectrometry Imaging of Tissue Microarrays; a Single-Pixel Approach
Authors: Kurczyk Agata , Gawin Marta , Chekan Mykola , Wilk Agata , Łakomiec Krzysztof , Mrukwa Grzegorz , Frątczak Katarzyna , Polanska Joanna , Fujarewicz Krzysztof , Pietrowska Monika , Widlak Piotr
Published: August 2020

The primary diagnosis of thyroid tumors based on histopathological patterns can be ambiguous in some cases, so proper classification of thyroid diseases might be improved if molecular biomarkers support cytological and histological assessment. In this work, tissue microarrays representative for major types of thyroid malignancies—papillary thyroid cancer (classical and follicular variant), follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer—and benign thyroid follicular adenoma and normal thyroid were analyzed by mass spectrometry imaging (MSI), and then different computation approaches were implemented to test the suitability of the registered profiles of tryptic peptides for tumor classification. Molecular similarity among all seven types of thyroid specimens was estimated, and multicomponent classifiers were built for sample classification using individual MSI spectra that corresponded to small clusters of cells. Moreover, MSI components showing the most significant differences in abundance between the compared types of tissues detected and their putative identity were established by annotation with fragments of proteins identified by liquid chromatography-tandem mass spectrometry in corresponding tissue lysates. In general, high accuracy of sample classification was associated with low inter-tissue similarity index and a high number of components with significant differences in abundance between the tissues. Particularly, high molecular similarity was noted between three types of tumors with follicular morphology (adenoma, follicular cancer, and follicular variant of papillary cancer), whose differentiation represented the major classification problem in our dataset. However, low level of the intra-tissue heterogeneity increased the accuracy of classification despite high inter-tissue similarity (which was exemplified by normal thyroid and benign adenoma). We compared classifiers based on all detected MSI components (n = 1536) and the subset of the most abundant components (n = 147). Despite relatively higher contribution of components with significantly different abundance and lower overall inter-tissue similarity in the latter case, the precision of classification was generally higher using all MSI components. Moreover, the classification model based on individual spectra (a single-pixel approach) outperformed the model based on mean spectra of tissue cores. Our result confirmed the high feasibility of MSI-based approaches to multi-class detection of cancer types and proved the good performance of sample classification based on individual spectra (molecular image pixels) that overcame problems related to small amounts of heterogeneous material, which limit the applicability of classical proteomics.
Immune Modulation of Platelet-Derived Mitochondria on Memory CD4+ T Cells in Humans
Authors: Yu Haibo , Hu Wei , Song Xiang , Zhao Yong
Published: August 2020

CD4+ T cells are one of the key immune cells contributing to the immunopathogenesis of type 1 diabetes (T1D). Previous studies have reported that platelet-derived mitochondria suppress the proliferation of peripheral blood mononuclear cells (PBMC). To further characterize the immune modulation of platelet-derived mitochondria, the purified CD4+ T cells were treated, respectively, with platelet-derived mitochondria. The data demonstrated that MitoTracker Deep Red-labeled platelet-derived mitochondria could directly target CD4+ T cells through C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1), regulating the anti-CD3/CD28 bead-activated CD4+ T cells. The result was an up-regulation of Naïve and central memory (TCM) CD4+ T cells, the down-regulation of effector memory (TEM) CD4+ T cells, and modulations of cytokine productions and gene expressions. Thus, platelet-derived mitochondria have a translational potential as novel immune modulators to treat T1D and other autoimmune diseases.
Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells
Authors: Zhao Yurong , Tang Shulin , Lin Ruqin , Zheng Ting , Li Danyang , Chen Xiaoxuan , Zhu Jiahui , Wen Jikai , Deng Yiqun
Published: August 2020

Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.
Elastic Modulus of ECM Hydrogels Derived from Decellularized Tissue Affects Capillary Network Formation in Endothelial Cells
Authors: Kobayashi Mako , Kadota Junpei , Hashimoto Yoshihide , Fujisato Toshiya , Nakamura Naoko , Kimura Tsuyoshi , Kishida Akio
Published: August 2020

Recent applications of decellularized tissue have included the use of hydrogels for injectable materials and three-dimensional (3D) bioprinting bioink for tissue regeneration. Microvascular formation is required for the delivery of oxygen and nutrients to support cell growth and regeneration in tissues and organs. The aim of the present study was to evaluate the formation of capillary networks in decellularized extracellular matrix (d-ECM) hydrogels. The d-ECM hydrogels were obtained from the small intestine submucosa (SIS) and the urinary bladder matrix (UBM) after decellularizing with sodium deoxycholate (SDC) and high hydrostatic pressure (HHP). The SDC d-ECM hydrogel gradually gelated, while the HHP d-ECM hydrogel immediately gelated. All d-ECM hydrogels had low matrix stiffness compared to that of the collagen hydrogel, according to a compression test. D-ECM hydrogels with various elastic moduli were obtained, irrespective of the decellularization method or tissue source. Microvascular-derived endothelial cells were seeded on d-ECM hydrogels. Few cells attached to the SDC d-ECM hydrogel with no network formation, while on the HHP d-ECM hydrogel, a capillary network structure formed between elongated cells. Long, branched networks formed on d-ECM hydrogels with lower matrix stiffness. This suggests that the capillary network structure that forms on d-ECM hydrogels is closely related to the matrix stiffness of the hydrogel.
Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation
Authors: Kulkarni Nishant S. , Vaidya Bhuvaneshwar , Parvathaneni Vineela , Bhanja Debarati , Gupta Vivek
Published: August 2020

Malignant mesothelioma (MM) is a rare type of cancer primarily affecting mesothelial cells lining the pleural cavity. In this study, we propose to repurpose quinacrine (QA), a widely approved anti-malarial drug, for Malignant Pleural Mesothelioma (MPM) treatment. QA demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC50) values ranging from 1.2 µM (H2452) to 5.03 µM (H28). Further, QA also inhibited cellular migration and colony formation in MPM cells, demonstrated using scratch and clonogenic assays, respectively. A 3D-spheroid cell culture experiment was performed to mimic in-vivo tumor conditions, and QA was reported to be highly effective in this simulated cellular model. Anti-angiogenic properties were also discovered for QA. Autophagy inhibition assay was performed, and results revealed that QA successfully inhibited autophagy process in MPM cells, which has been cited to be one of the survival pathways for MPM. Annexin V real-time apoptosis study revealed significant apoptotic induction in MPM cells following QA treatment. Western blots confirmed inhibition of autophagy and induction of apoptosis. These studies highlight anti-mesothelioma efficacy of QA at low doses, which can be instrumental in developing it as a stand-alone treatment strategy for MPM.
The Salt Sensitivity Induced by Disruption of Cell Wall-Associated Kinase 1 (SlWAK1) Tomato Gene Is Linked to Altered Osmotic and Metabolic Homeostasis
Authors: Meco Victoriano , Egea Isabel , Ortíz-Atienza Ana , Drevensek Stéphanie , Esch Elisabeth , Yuste-Lisbona Fernando J. , Barneche Fredy , Vriezen Wim , Bolarin María C. , Lozano Rafael , Flores Francisco B.
Published: August 2020

Tomato cell wall-associated kinase 1 (SlWAK1) has only been studied in biotic stress response and hence its function in abiotic stress remains unknown. In a screening under salinity of an insertional mutant collection of tomato (Solanum lycopersicum L.), a mutant exhibiting lower degree of leaf chlorosis than wild type (WT) together with reduced leaf Na+ accumulation was selected. Genetic analysis of the mutation revealed that a single T-DNA insertion in the SlWAK1 gene was responsible of the mutant phenotype. Slwak1 null mutant reduced its shoot growth compared with WT, despite its improved Na+ homeostasis. SlWAK1 disruption affected osmotic homeostasis, as leaf water content was lower in mutant than in WT under salt stress. In addition, Slwak1 altered the source-sink balance under salinity, by increasing sucrose content in roots. Finally, a significant fruit yield reduction was found in Slwak1 vs. WT under long-term salt stress, mainly due to lower fruit weight. Our results show that disruption of SlWAK1 induces a higher sucrose transport from source leaf to sink root, negatively affecting fruit, the main sink at adult stage.
Established and Emerging Mechanisms in the Pathogenesis of Arrhythmogenic Cardiomyopathy: A Multifaceted Disease
Authors: Gao Shanshan , Puthenvedu Deepa , Lombardi Raffaella , Chen Suet Nee
Published: August 2020

Arrhythmogenic cardiomyopathy (ACM) is a heritable myocardial disease that manifests with cardiac arrhythmias, syncope, sudden cardiac death, and heart failure in the advanced stages. The pathological hallmark of ACM is a gradual replacement of the myocardium by fibroadiposis, which typically starts from the epicardium. Molecular genetic studies have identified causal mutations predominantly in genes encoding for desmosomal proteins; however, non-desmosomal causal mutations have also been described, including genes coding for nuclear proteins, cytoskeleton componentsand proteins involved in excitation-contraction coupling. Despite the poor prognosis, currently available treatments can only partially control symptoms and to date there is no effective therapy for ACM. Inhibition of the canonical Wnt/β-catenin pathway and activation of the Hippo and the TGF-β pathways have been implicated in the pathogenesis of ACM. Yet, our understanding of the molecular mechanisms involved in the development of the disease and the cell source of fibroadiposis remains incomplete. Elucidation of the pathogenesis of the disease could facilitate targeted approaches for treatment. In this manuscript we will provide a comprehensive review of the proposed molecular and cellular mechanisms of the pathogenesis of ACM, including the emerging evidence on abnormal calcium homeostasis and inflammatory/autoimmune response. Moreover, we will propose novel hypothesis about the role of epicardial cells and paracrine factors in the development of the phenotype. Finally, we will discuss potential innovative therapeutic approaches based on the growing knowledge in the field.
Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments
Authors: Sandomenico Annamaria , Sivaccumar Jwala P. , Ruvo Menotti
Published: August 2020

Antibodies and antibody-derived molecules are continuously developed as both therapeutic agents and key reagents for advanced diagnostic investigations. Their application in these fields has indeed greatly expanded the demand of these molecules and the need for their production in high yield and purity. While full-length antibodies require mammalian expression systems due to the occurrence of functionally and structurally important glycosylations, most antibody fragments and antibody-like molecules are non-glycosylated and can be more conveniently prepared in E. coli-based expression platforms. We propose here an updated survey of the most effective and appropriate methods of preparation of antibody fragments that exploit E. coli as an expression background and review the pros and cons of the different platforms available today. Around 250 references accompany and complete the review together with some lists of the most important new antibody-like molecules that are on the market or are being developed as new biotherapeutics or diagnostic agents.
Learning a Convolutional Autoencoder for Nighttime Image Dehazing
Authors: Feng Mengyao , Yu Teng , Jing Mingtao , Yang Guowei
Published: August 2020

Currently, haze removal of images captured at night for foggy scenes rely on the traditional, prior-based methods, but these methods are frequently ineffective at dealing with night hazy images. In addition, the light sources at night are complicated and there is a problem of inconsistent brightness. This makes the estimation of the transmission map complicated in the night scene. Based on the above analysis, we propose an autoencoder method to solve the problem of overestimation or underestimation of transmission captured by the traditional, prior-based methods. For nighttime hazy images, we first remove the color effect of the haze image with an edge-preserving maximum reflectance prior (MRP) method. Then, the hazy image without color influence is input into the self-encoder network with skip connections to obtain the transmission map. Moreover, instead of using the local maximum method, we estimate the ambient illumination through a guiding image filtering. In order to highlight the effectiveness of our experiments, a large number of comparison experiments were conducted between our method and the state-of-the-art methods. The results show that our method can effectively suppress the halo effect and reduce the effectiveness of glow. In the experimental part, we calculate that the average Peak Signal to Noise Ratio (PSNR) is 21.0968 and the average Structural Similarity (SSIM) is 0.6802.
The Microbiome of Neotropical Water Striders and Its Potential Role in Codiversification
Authors: Castillo Anakena M. , Saltonstall Kristin , Arias Carlos F. , Chavarria Karina A. , Ramírez-Camejo Luis A. , Mejía Luis C. , De León Luis F.
Published: August 2020

Insects host a highly diverse microbiome, which plays a crucial role in insect life. However, the composition and diversity of microbiomes associated with Neotropical freshwater insects is virtually unknown. In addition, the extent to which diversification of this microbiome is associated with host phylogenetic divergence remains to be determined. Here, we present the first comprehensive analysis of bacterial communities associated with six closely related species of Neotropical water striders in Panama. We used comparative phylogenetic analyses to assess associations between dominant bacterial linages and phylogenetic divergence among species of water striders. We found a total of 806 16S rRNA amplicon sequence variants (ASVs), with dominant bacterial taxa belonging to the phyla Proteobacteria (76.87%) and Tenericutes (19.51%). Members of the α- (e.g., Wolbachia) and γ- (e.g., Acinetobacter, Serratia) Proteobacteria, and Mollicutes (e.g., Spiroplasma) were predominantly shared across species, suggesting the presence of a core microbiome in water striders. However, some bacterial lineages (e.g., Fructobacillus, Fluviicola and Chryseobacterium) were uniquely associated with different water strider species, likely representing a distinctive feature of each species’ microbiome. These findings indicate that both host identity and environmental context are important drivers of microbiome diversity in water striders. In addition, they suggest that diversification of the microbiome is associated with diversification in water striders. Although more research is needed to establish the evolutionary consequences of host-microbiome interaction in water striders, our findings support recent work highlighting the role of bacterial community host-microbiome codiversification.
EMG, Rate of Perceived Exertion, Pain, Tolerability and Possible Adverse Effects of a Knee Extensor Exercise with Progressive Elastic Resistance in Patients with Severe Haemophilia
Authors: Calatayud Joaquín , Navarro-Navarro Jonás , Carrasco Juan J. , Pérez-Alenda Sofía , Cruz-Montecinos Carlos , Andersen Lars L. , Querol-Giner Felipe , Casaña José
Published: August 2020

In people with haemophilia (PWH), elastic band training is considered an optimal option, even though the literature is scarce. The aim was to evaluate normalized electromyographic amplitude (nEMG), rate of perceived exertion (RPE), pain, tolerability, and possible adverse effects during the knee extension exercise using multiple elastic resistance intensities in PWH. During a single session, 14 severe PWH undergoing prophylactic treatment performed knee extensions without resistance and with different intensity levels of elastic resistance. nEMG was measured for the knee extensors and participants rated their RPE, tolerability and pain intensity after each condition. Patients had to report the possible adverse effects after the session. In most of the cases, an nEMG increase is only evidenced after increasing the resistance by two to three levels. Significant associations were found between RPE and the nEMG (ρ = 0.61), as well as between the elastic resistance level and nEMG (ρ = 0.69) and RPE (ρ = 0.71). All conditions were generally tolerated, without increased pain, and no adverse effects were reported. A wide variety of elastic resistance intensities during the knee extension are safe, tolerated, and do not increase knee pain in the majority of severe PWH undergoing prophylactic treatment.
Efficacy and Safety of Cystatin C-Guided Renal Dose Adjustment of Cefepime Treatment in Hospitalized Patients with Pneumonia
Authors: Kim Min-Chul , Kim Seon Ok , Kim Su-Hyun , Shin Jung-ho , Choi Seong-Ho , Chung Jin-Won , Hwang Jin Ho
Published: August 2020

Cystatin C (CysC) may estimate renal function more accurately than serum creatinine (SCr). The clinical impact of renal dose adjustment of cefepime according to CysC rather than SCr has remained uncertain. We investigated the efficacy and safety of CysC-guided cefepime dosing compared with SCr-guided dosing in hospitalized patients with pneumonia. All adults hospitalized with pneumonia between July 2016 and December 2018 who used cefepime for at least 3 days were enrolled. Mortality, acute kidney injury (AKI), cefepime-induced encephalopathy (CIE), and Clostridium difficile infection were compared between the CysC-guided and SCr-guided groups. One hundred and ninety patients were divided into two groups: 129 and 61 received cefepime based on CysC and SCr, respectively. In-hospital mortality did not significantly differ between the groups (12% versus 31%; hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.31–1.77; p = 0.50). CysC-guided cefepime dosing decreased the risk of AKI (13% versus 61%; HR 0.18; 95% CI, 0.07–0.44; p < 0.001) and CIE (2% versus 11%; HR 0.11; 95% CI, 0.03–0.47; p = 0.003) compared with SCr-guided dosing. There was no significant difference in the risk of Clostridium difficile infection. CysC-guided dosing of cefepime was associated with decreased risk of the cefepime-associated morbidities including AKI and CIE without increasing mortality among the hospitalized patients with pneumonia.
Sub-Perception and Supra-Perception Spinal Cord Stimulation in Chronic Pain Syndrome: A Randomized, Semi-Double-Blind, Crossover, Placebo-Controlled Trial
Authors: Sokal Paweł , Malukiewicz Agnieszka , Kierońska Sara , Murawska Joanna , Guzowski Cezary , Rudaś Marcin , Paczkowski Dariusz , Rusinek Marcin , Krakowiak Mateusz
Published: August 2020

Background: The introduction of modern sub-perception modalities has improved the efficacy of spinal cord stimulation (SCS) in refractory pain syndromes of the trunk and lower limbs. The objective of this study was to evaluate the effectiveness of low and high frequency SCS among patients with chronic pain. Material and methods: A randomised, semi-double-blind, placebo controlled, four period (4 × 2 weeks) crossover trial was conducted from August 2018 to January 2020. Eighteen patients with SCS due to failed back surgery syndrome and/or complex regional pain syndrome were randomised to four treatment arms without washout periods: (1) low frequency (40-60 Hz), (2) 1 kHz, (3) clustered tonic, and (4) sham SCS (i.e., placebo). The primary outcome was pain scores measured by visual analogue scale (VAS) preoperatively and during subsequent treatment arms. Results: Pain scores (VAS) reported during the preoperative period was M (SD) = 8.13 (0.99). There was a 50% reduction in pain reported in the low frequency tonic treatment group (M (SD) = 4.18 (1.76)), a 37% reduction in the 1 kHz treatment group (M (SD) = 5.17 (1.4)), a 34% reduction in the clustered tonic settings group (M (SD) = 5.27 (1.33)), and a 34% reduction in the sham stimulation group (M (SD) = 5.42 (1.22)). The reduction in pain from the preoperative period to the treatment period was significant in each treatment group (p < 0.001). Overall, these reductions were of comparable magnitude between treatments. However, the modality most preferred by patients was low frequency (55% or 10 patients). Conclusions: The pain-relieving effects of SCS reached significance and were comparable across all modes of stimulation including sham. Sub-perception stimulation was not superior to supra-perception. SCS was characterised by a high degree of placebo effect. No evidence of carryover effect was observed between subsequent treatments. Contemporary neuromodulation procedures should be tailored to the individual preferences of patients.
NGAL Correlates with Femoral and Carotid Plaque Volume Assessed by Sonographic 3D Plaque Volumetry
Authors: Schreinlechner Michael , Noflatscher Maria , Lener Daniela , Bauer Axel , Kirchmair Rudolf , Marschang Peter , Theurl Markus
Published: August 2020

Background/Objectives: Inflammation represents a cornerstone in the development of atherosclerosis and early detection is essential to avoid cardiovascular events. Biomarkers like interleukin-1 beta, interleukin-6, or high sensitivity CRP (hs-CRP) have been investigated intensively in this field. Since they have several limitations, additional biomarkers are needed for cardiovascular risk stratification. The acute phase protein, neutrophil gelatinase-associated lipocalin (NGAL), modulates inflammation and is elevated in cardiovascular disease (CVD). Moreover, it contributes to plaque destabilization. Methods: In this prospective, single-center study, we included 323 asymptomatic patients with at least one cardiovascular risk factor or established CVD. NGAL levels were measured in plasma samples using a commercially available ELISA. Carotid, femoral, and total atherosclerotic plaque volumes (PV) were measured using a 3D ultrasound system (Philips iU22). Patients were separated into a low (n = 243) and high (n = 80) total PV group. Results: NGAL was significantly higher in patients with high total PV versus patients with low total PV. The NGAL amplitude for the prediction of high total PV was significantly higher when compared with hs-CRP. A high predictive value could also be observed for patients without established CVD. Conclusion: NGAL seems to be a promising biomarker for the identification of asymptomatic patients with atherosclerotic disease.
Investigation of Meibomian Gland Function and Dry Eye Disease in Patients with Graves’ Ophthalmopathy
Authors: Inoue Sachiko , Kawashima Motoko , Arita Reiko , Kozaki Ai , Tsubota Kazuo
Published: August 2020

We prospectively evaluated the relationship between meibomian gland dysfunction (MGD) and Graves’ ophthalmopathy (GO) in 19 patients (38 eyes) with subjective dry eye symptoms, compared to 14 age-matched normal participants (14 eyes). Extraocular muscle and lacrimal gland enlargement were evaluated by magnetic resonance imaging (MRI). Ocular surface examinations included fluorescein staining for keratoconjunctival epithelial damage, tear breakup time (TBUT) evaluation, and Schirmer’s test. Dry eye symptoms were evaluated with the Dry Eye-related Quality-of-Life Score (DEQS) questionnaire. Lid-margin abnormalities, meibum grade, and meiboscores were assessed using meibography. Clinical activity scores and T2 signal intensity ratios were used to define GO activity. All GO patients had obstructive MGD and 79% exhibited levator muscle enlargement. Ocular surface parameters of TBUT (p = 0.000), meibum score (p = 0.000), eyelid vasculitis (p = 0.000), meiboscore of the upper lid (p = 0.002), total meiboscores (p = 0.001), and DEQS (p = 0.000) significantly differed between GO patients and normal subjects. In addition, GO patients had significantly more abnormalities of the central region of the upper eyelid than normal subjects (p = 0.000). Thus, MGD might be related to eye discomfort and deterioration of the ocular surface in GO patients. Inflammation and morphological meibomian gland changes might be characteristic of GO.