bluuebunny/crossref_metadata_2025 huggingface dataset:
Metacognitive Labeling of Contentious Claims: Facts, Opinions, and Conspiracy Theories
Authors: Brotherton Robert , Son Lisa K.
Published: March 2021

Congenial information is often judged to be more valid than uncongenial (but otherwise equivalent) information. The present research explores a related possibility concerning the process by which people label a claim as fundamentally factual (open to proof or disproof) or opinion (a matter of personal preference not amenable to falsification). Rather than merely being more skeptical of uncongenial claims, uncongenial claims may be metacognitively categorized as more opinion than factual, while congenial claims may be more likely to be categorized as factual. The two studies reported here attempt to trace a preliminary outline of how claims are categorized as fact, opinion, or some mix of the two in the context of mundane claims, contentious political issues, and conspiracy theories. The findings suggest that claims are more likely to be labeled factual (and, to a lesser extent, are less likely to be labeled opinion) to the extent that one subjectively agrees with the content of the claim. Conspiracy theories appear to occupy a middle-ground between fact and opinion. This metacognitive approach may help shed light on popular debate about conspiracy theories, as well as seemingly intractable political disagreements more generally, which may reflect fundamental differences in the perceived epistemic foundations of claims rather than simple disagreement over the facts of the matter. Given limitations of the stimuli and participant samples, however, it remains to be seen how generalizable these findings are.
Covid, AI, and Robotics—A Neurologist's Perspective
Authors: Ahmed Syed Nizamuddin
Published: March 2021

Two of the major revolutions of this century are the Artificial Intelligence and Robotics. These technologies are penetrating through all disciplines and faculties at a very rapid pace. The application of these technologies in medicine, specifically in the context of Covid 19 is paramount. This article briefly reviews the commonly applied protocols in the Health Care System and provides a perspective in improving the efficiency and effectiveness of the current system. This article is not meant to provide a literature review of the current technology but rather provides a personal perspective of the author regarding what could happen in the ideal situation.
Case Report: Positive Pressure Therapy Combined With Endolymphatic sac Surgery in a Patient With Ménière's Disease
Authors: Fukushima Munehisa , Akahani Shiro , Inohara Hidenori , Takeda Noriaki
Published: March 2021

Positive pressure therapy (PPT) is applied for medically-intractable vertigo in Ménière's disease (MD); however, it remains unknown whether PPT affects in vivo endolymphatic hydrops (EH). In this case report, we describe a 5-year course of MD in a patient in which EH was repeatedly observed. As the patient experienced recurrent vertigo attacks after endolymphatic sac surgery, he began to use the PPT device additionally and vertiginous episodes decreased in accordance with a decrease in the EH volume. The mechanism of PPT is suggested that the pressure increase in the middle ear inhibits EH development. PPT, if added after surgery, might be more effective to reduce EH volume compared with surgery alone. A larger study group size is required to test these preliminary data concerning EH changes.
Alterations in CD8+ Tregs, CD56+ Natural Killer Cells and IL-10 Are Associated With Invasiveness of Nonfunctioning Pituitary Adenomas (NFPAs)
Authors: Huang Xinmei , Xu Jiong , Wu Yueyue , Sheng Li , Li Yue , Zha Bingbing , Sun Tiange , Yang Ju , Zang Shufei , Liu Jun
Published: March 2021

Invasive nonfunctioning pituitary adenomas (NFPAs) grow rapidly and the mechanisms are unclear. Among many complex mechanisms, the role of immunity in the development of NFPAs has not been fully explored. Here, we analyzed the clinical features 146 NFPA patients who underwent trans-sphenoidal surgery or craniotomy and examined the effects of immune tolerance in invasiveness of NFPA patients using fluorescence-activated cell sorting and immunohistochemical methods. We found patients with invasive NFPAs had more visual deficits and defective fields, higher tumor size, and lower white blood cell count compared with patients with noninvasive NFPAs. Additionally, compared with patients with noninvasive NFPAs, patients with invasive NFPAs had conspicuously lower CD3−CD56+ natural killer (NK) cells and significantly higher levels of CD3+CD8+CD28-T cells (CD8+ Tregs) and interleukin-10 (IL-10) in peripheral blood. Moreover, patients with invasive NFPAs had lower infiltrated CD56+ cells, less infiltrated CD28+ cells, and significantly greater IL-10 expression. These results demonstrated that low CD56+ cells infiltration and CD28+ cells infiltration, as well as high IL-10 expression in pituitary tumor tissues, were related with increased invasiveness of NFPAs. Levels of CD3−CD56+ NK cells, CD8+ Tregs and IL-10 in the peripheral blood could be feasible diagnostic markers for invasive NFPAs.
An Origami Flexiball-Inspired Metamaterial Actuator and Its In-Pipe Robot Prototype
Authors: Hu Fuwen , Li Tian
Published: March 2021

Usually, polyhedra are viewed as the underlying constructive cells of packing or tiling in many disciplines, including crystallography, protein folding, viruses structure, building architecture, etc. Here, inspired by the flexible origami polyhedra (commonly called origami flexiballs), we initially probe into their intrinsic metamaterial properties and robotized methods from fabrication to actuation. Firstly, the topology, geometries and elastic energies of shape shifting are analyzed for the three kinds of origami flexiballs with extruded outward rhombic faces. Provably, they meet the definitions of reconfigurable and transformable metamaterials with switchable stiffness and multiple degrees of freedom. Secondly, a new type of soft actuator with rhombic deformations is successfully put forward, different from soft bionic deformations like elongating, contracting, bending, twisting, spiraling, etc. Further, we redesign and fabricate the three-dimensional (3D) printable structures of origami flexiballs considering their 3D printability and foldability, and magnetically actuated them through the attachment of magnetoactive elastomer. Lastly, a fully soft in-pipe robot prototype is presented using the origami flexiball as an applicable attempt. Experimental work clearly suggests that the presented origami flexiball robot has good adaptability to various pipe sizes, and also can be easily expanded to different scales, or reconfigured into more complex metastructures by assembly. In conclusion, this research provides a newly interesting and illuminating member for the emerging families of mechanical metamaterials, soft actuators and soft robots.
Recycled Wastewater and Reverse Osmosis Brine Use for Halophytes Irrigation: Differences in Physiological, Nutritional and Hormonal Responses of Crithmum maritimum and Atriplex halimus Plants
Authors: Gómez-Bellot María José , Lorente Beatriz , Ortuño María Fernanda , Medina Sonia , Gil-Izquierdo Ángel , Bañón Sebastián , Sánchez-Blanco María Jesús
Published: March 2021

Halophytes are capable of coping with excessive NaCl in their tissues, although some species may differ in their degree of salt tolerance. In addition, it is not clear whether they can tolerate other confounding factors and impurities associated with non-conventional waters. The experiment was performed in a greenhouse with Crithmum maritimum and Atriplex halimus plants, growing on soil and irrigated with two different water types: reclaimed wastewater (RWW) (EC: 0.8–1.2 dS m−1) and reverse osmosis brine (ROB) (EC: 4.7–7.9 dS m−1). Both species showed different physiological and nutritional responses, when they were irrigated with ROB. Atriplex plants reduced leaf water potential and maintained leaf turgor as consequence of an osmotic adjustment process. Atriplex showed higher intrinsic water use efficiency than Crithmum, regardless of the type of water used. In Crithmum, the water status and photosynthetic efficiency were similar in both treatments. Crithmum presented a higher leaf accumulation of B and Ca ions, while Atriplex a higher amount of K, Mg, Na and Zn. Crithmum plants irrigated with ROB presented higher concentrations of 1-aminocyclopropane-1-carboxylic acid and trans-zeatin-glucoside, whereas abscisic acid concentration was lower. Atriplex showed a lower concentration of trans-zeatin-riboside and scopoletin. The characteristics associated to water irrigation did not influence negatively the development of any of these species, which confirms the use of brine as an alternative to irrigate them with conventional waters.
Glucose-6-Phosphate Dehydrogenase Is Involved in the Tolerance of Soybean Seedlings to Low Nitrogen Stress
Authors: Jin Jie , Wang Xiaomin , Wang Jianfeng , Li Keke , Wang Shengwang , Zhang Wenya , Zhang Guohong , Bi Yurong
Published: March 2021

Nitrogen (N) deficiency affects plant growth and crop yield. In this study, we investigated the role of glucose-6-phosphate dehydrogenase (G6PDH) in response to N availability in three soybean cultivars, JINDOU 19 (JD19), LONGHUANG 3 (LH3), and LONGDOU 2 (LD2), that have different tolerances to low-N stress. The results showed that the leaf area and primary root length of JD19 and LH3 were greater than that of LD2 under low-N stress, suggesting that the growth of JD19 and LH3 were impaired less than LD2, and thus are more tolerant to low-N stress than LD2 is. Interestingly, the G6PDH expression showed different degrees of change in these soybean cultivars under low-N conditions, and the G6PDH activity in JD19 and LH3 was higher than that in LD2. When G6PDH was inhibited by glucosamine (GlcN), the contents of malondialdehyde (MDA) and H2O2 were dramatically increased under low-N stress. Meanwhile, the activities of N metabolism-related enzymes were inhibited. These results indicate that G6PDH is involved in the tolerance of soybean cultivars to low-N stress through affecting the N metabolism. Furthermore, under low-N conditions, the contents of NADP+ and reduced glutathione (GSH) in JD19 and LH3 were increased more than that in LD2. In contrast, the activity of the plasma membrane (PM), NADPH oxidase, and the NADPH content in JD19 and LH3 were lower than that in LD2. In conclusion, G6PDH reduces the accumulation of ROS in plant cells by modulating NADPH/NADP+ and GSH levels to maintain the growth of soybeans under low-N conditions.
A Mixture of Green Waste Compost and Biomass Combustion Ash for Recycled Nutrient Delivery to Soil
Authors: Buneviciene Kristina , Drapanauskaite Donata , Mazeika Romas , Baltrusaitis Jonas
Published: March 2021

The use of major nutrient-containing solid residuals, such as recycled solid waste materials, has a strong potential in closing the broken nutrient cycles. In this work, biofuel ash (BA) combined with green waste compost (GWC) was used as a nutrient source to improve soil properties and enhance wheat and triticale yields. The main goal was to obtain the nutrient and heavy metal release dynamics and ascertain whether GWC together with BA can potentially be used for concurrent bioremediation to mitigate any negative solid waste effects on the environment. Both BA and GWC were applied in the first year of study. No fertilization was performed in the second year of the study. The results obtained in this work showed the highest spring wheat yield when the GWC (20 t ha−1) and BA (4.5 t ha−1) mixture was used. After the first harvest, the increase in the mobile forms of all measured nutrients was detected in the soil with complex composted materials (GWC + BA). The content of heavy metals (Cd, Zn, and Cr) in the soil increased significantly with BA and all GWC + BA mixtures. In both experiment years, the application of BA together with GWC resulted in fewer heavy metals transferred to the crops than with BA alone.
Antimicrobial Resistance Profile and ExPEC Virulence Potential in Commensal Escherichia coli of Multiple Sources
Authors: Massella Elisa , Giacometti Federica , Bonilauri Paolo , Reid Cameron J. , Djordjevic Steven P. , Merialdi Giuseppe , Bacci Cristina , Fiorentini Laura , Massi Paola , Bardasi Lia , Rubini Silva , Savini Federica , Serraino Andrea , Piva Silvia
Published: March 2021

We recently described the genetic antimicrobial resistance and virulence profile of a collection of 279 commensal E. coli of food-producing animal (FPA), pet, wildlife and human origin. Phenotypic antimicrobial resistance (AMR) and the role of commensal E. coli as reservoir of extra-intestinal pathogenic Escherichia coli (ExPEC) virulence-associated genes (VAGs) or as potential ExPEC pathogens were evaluated. The most common phenotypic resistance was to tetracycline (76/279, 27.24%), sulfamethoxazole/trimethoprim (73/279, 26.16%), streptomycin and sulfisoxazole (71/279, 25.45% both) among the overall collection. Poultry and rabbit were the sources mostly associated to AMR, with a significant resistance rate (p > 0.01) to quinolones, streptomycin, sulphonamides, tetracycline and, only for poultry, to ampicillin and chloramphenicol. Finally, rabbit was the source mostly associated to colistin resistance. Different pandemic (ST69/69*, ST95, ST131) and emerging (ST10/ST10*, ST23, ST58, ST117, ST405, ST648) ExPEC sequence types (STs) were identified among the collection, especially in poultry source. Both ST groups carried high number of ExPEC VAGs (pandemic ExPEC STs, mean = 8.92; emerging ExPEC STs, mean = 6.43) and showed phenotypic resistance to different antimicrobials (pandemic ExPEC STs, mean = 2.23; emerging ExPEC STs, mean = 2.43), suggesting their role as potential ExPEC pathogens. Variable phenotypic resistance and ExPEC VAG distribution was also observed in uncommon ExPEC lineages, suggesting commensal flora as a potential reservoir of virulence (mean = 3.80) and antimicrobial resistance (mean = 1.69) determinants.
Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections
Authors: Bonetti Justine , Corti Alessandro , Lerouge Lucie , Pompella Alfonso , Gaucher Caroline
Published: March 2021

Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of “foam cells” within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs.
Metabolic Targets of Coenzyme Q10 in Mitochondria
Authors: Hidalgo-Gutiérrez Agustín , González-García Pilar , Díaz-Casado María Elena , Barriocanal-Casado Eliana , López-Herrador Sergio , Quinzii Catarina M. , López Luis C.
Published: March 2021

Coenzyme Q10 (CoQ10) is classically viewed as an important endogenous antioxidant and key component of the mitochondrial respiratory chain. For this second function, CoQ molecules seem to be dynamically segmented in a pool attached and engulfed by the super-complexes I + III, and a free pool available for complex II or any other mitochondrial enzyme that uses CoQ as a cofactor. This CoQ-free pool is, therefore, used by enzymes that link the mitochondrial respiratory chain to other pathways, such as the pyrimidine de novo biosynthesis, fatty acid β-oxidation and amino acid catabolism, glycine metabolism, proline, glyoxylate and arginine metabolism, and sulfide oxidation metabolism. Some of these mitochondrial pathways are also connected to metabolic pathways in other compartments of the cell and, consequently, CoQ could indirectly modulate metabolic pathways located outside the mitochondria. Thus, we review the most relevant findings in all these metabolic functions of CoQ and their relations with the pathomechanisms of some metabolic diseases, highlighting some future perspectives and potential therapeutic implications.
Principles of Different X-ray Phase-Contrast Imaging: A Review
Authors: Tao Siwei , He Congxiao , Hao Xiang , Kuang Cuifang , Liu Xu
Published: March 2021

Numerous advances have been made in X-ray technology in recent years. X-ray imaging plays an important role in the nondestructive exploration of the internal structures of objects. However, the contrast of X-ray absorption images remains low, especially for materials with low atomic numbers, such as biological samples. X-ray phase-contrast images have an intrinsically higher contrast than absorption images. In this review, the principles, milestones, and recent progress of X-ray phase-contrast imaging methods are demonstrated. In addition, prospective applications are presented.
Integrating Gear Shifting Preference into Personalized Shift-Scheduling Calibration
Authors: He Xin , Lin Mingming , Xu Li
Published: March 2021

Shift-scheduling calibration of automatic transmission (AT) vehicles is vital for both driving experience and automobile industry. Shifting schedules are usually calibrated with the consideration of fuel economy and drivability while neglecting the individual driving preference. In this work, we propose to exemplify the individual shifting preference by integrating the manual transmission (MT) shifting habit into the AT shift-scheduling calibration, where the habit is reflected as the shifting points and is available in most automated manual transmission (AMT) vehicles. The automated calibration of AT shifting schedules is directed by using the particle swarm optimization (PSO), during the virtual automobile cycle test, i.e., FTP-72. Candidate shifting-schedules are generated in the overlapped zone of MT shifting points and the space around the base map, and are evaluated on both shifting quality and fuel economy. Through iterations, the generated candidate shift schedules are tested and assessed until the overall performance reach the optimum. Experimental results are presented to show the effectiveness of the proposed method, which retains the shifting preferences as well as enhances the performance index by about 5%, 4%, and 2% for the drivers with aggressive, moderate, and mild styles, respectively.
Regression Diagnostics with Predicted Residuals of Linear Model with Improved Singular Value Classification Applied to Forecast the Hydrodynamic Efficiency of Wave Energy Converters
Authors: Tenekedjiev Kiril , Abdussamie Nagi , An Hyunbin , Nikolova Natalia
Published: March 2021

In the preliminary stages of design of the oscillating water column (OWC) type of wave energy converters (WECs), we need a reliable cost- and time-effective method to predict the hydrodynamic efficiency as a function of the design parameters. One of the cheapest approaches is to create a multiple linear regression (MLR) model using an existing data set. The problem with this approach is that the reliability of the MLR predictions depend on the validity of the regression assumptions, which are either rarely tested or tested using sub-optimal procedures. We offer a series of novel methods for assumption diagnostics that we apply in our case study for MLR prediction of the hydrodynamics efficiency of OWC WECs. Namely, we propose: a novel procedure for reliable identification of the zero singular values of a matrix; a modified algorithm for stepwise regression; a modified algorithm to detect heteroskedasticity and identify statistically significant but practically insignificant heteroscedasticity in the original model; a novel test of the validity of the nullity assumption; a modified Jarque–Bera Monte Carlo error normality test. In our case study, the deviations from the assumptions of the classical normal linear regression model were fully diagnosed and dealt with. The newly proposed algorithms based on improved singular value decomposition (SVD) of the design matrix and on predicted residuals were successfully tested with a new family of goodness-of-fit measures. We empirically investigated the correct placement of an elaborate outlier detection procedure in the overall diagnostic sequence. As a result, we constructed a reliable MLR model to predict the hydrodynamic efficiency in the preliminary stages of design. MLR is a useful tool at the preliminary stages of design and can produce highly reliable and time-effective predictions of the OWC WEC performance provided that the constructing and diagnostic procedures are modified to reflect the latest advances in statistics. The main advantage of MLR models compared to other modern black box models is that their assumptions are known and can be tested in practice, which increases the reliability of the model predictions.
Bio-Based Polyester Fiber Substitutes: From GWP to a More Comprehensive Environmental Analysis
Authors: Ivanović Tijana , Hischier Roland , Som Claudia
Published: March 2021

The textile industry has lately started exploring the possibility of bio-sourcing for synthetics, notably polyester fiber, in the effort to break from the proven fossil-fuel dependency and decrease the environmental impacts. Traditionally made out of fossil-based polyethylene terephthalate polymer, polyester can be functionally substituted with three bio-based alternatives: bio-polyester, polytrimethylene terephthalate, and polylactic acid fibers. At present, however, there is a lack of studies on the environmental effects of such substitution. We, therefore, performed a comparative, cradle-to-gate life cycle assessment of conventional polyester and those substitutes featuring varying levels of bio-content. The impact assessment was performed with the most recent version of the Environmental Footprint method including some adaptations—using carbon crediting and a different, distance-to-target weighting approach. Bio-sourced fibers are found to cause higher environmental burdens than polyester. Acidification, eutrophication, ecotoxicity, water, and land use increase with the bio-content and are predominantly linked to the first generation feedstock (agriculture and transport). The results on climate change vary with the impact method adaptations, yet do not manage to offset the aforementioned deteriorations. In single scores, only three out of nine substitutes are found to perform comparably, while the rest perform significantly worse than the incumbent fiber.
Fitness Shifts the Balance of BDNF and IL-6 from Inflammation to Repair among People with Progressive Multiple Sclerosis
Authors: Devasahayam Augustine Joshua , Kelly Liam Patrick , Williams John Bradley , Moore Craig Stephen , Ploughman Michelle
Published: March 2021

Physical sedentarism is linked to elevated levels of circulating cytokines, whereas exercise upregulates growth-promoting proteins such as brain-derived neurotrophic factor (BDNF). The shift towards a ‘repair’ phenotype could protect against neurodegeneration, especially in diseases such as multiple sclerosis (MS). We investigated whether having higher fitness or participating in an acute bout of maximal exercise would shift the balance of BDNF and interleukin-6 (IL-6) in serum samples of people with progressive MS (n = 14), compared to matched controls (n = 8). Participants performed a maximal graded exercise test on a recumbent stepper, and blood samples were collected at rest and after the test. We assessed walking speed, fatigue, and maximal oxygen consumption (V·O2max). People with MS achieved about 50% lower V·O2max (p = 0.003) than controls. At rest, there were no differences in BDNF between MS and controls; however, IL-6 was significantly higher in MS. Higher V·O2max was associated with a shift in BDNF/IL-6 ratio from inflammation to repair (R = 0.7, p = 0.001) when considering both groups together. In the MS group, greater ability to upregulate BDNF was associated with faster walking speed and lower vitality. We present evidence that higher fitness indicates a shift in the balance of blood biomarkers towards a repair phenotype in progressive MS.
The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas
Authors: Artemaki Pinelopi I. , Letsos Petros A. , Zoupa Ioanna C. , Katsaraki Katerina , Karousi Paraskevi , Papageorgiou Sotirios G. , Pappa Vasiliki , Scorilas Andreas , Kontos Christos K.
Published: March 2021

Normal B-cell development is a tightly regulated complex procedure, the deregulation of which can lead to lymphomagenesis. One common group of blood cancers is the B-cell non-Hodgkin lymphomas (NHLs), which can be categorized according to the proliferation and spread rate of cancer cells into indolent and aggressive ones. The most frequent indolent B-cell NHLs are follicular lymphoma and marginal zone lymphoma. MicroRNAs (miRNAs) are small non-coding RNAs that can greatly influence protein expression. Based on the multiple interactions among miRNAs and their targets, complex networks of gene expression regulation emerge, which normally are essential for proper B-cell development. Multiple miRNAs have been associated with B-cell lymphomas, as the deregulation of these complex networks can lead to such pathological states. The aim of the present review is to summarize the existing information regarding the multifaceted role of miRNAs in indolent B-cell NHLs, affecting the main B-cell subpopulations. We attempt to provide insight into their biological function, the complex miRNA-mRNA interactions, and their biomarker utility in these malignancies. Lastly, we address the limitations that hinder the investigation of the role of miRNAs in these lymphomas and discuss ways that these problems could be overcome in the future.
Applications of Microwave Energy in Medicine
Authors: Gartshore Alexandra , Kidd Matt , Joshi Lovleen Tina
Published: March 2021

Microwaves are a highly utilized electromagnetic wave, used across a range of industries including food processing, communications, in the development of novel medical treatments and biosensor diagnostics. Microwaves have known thermal interactions and theorized non-thermal interactions with living matter; however, there is significant debate as to the mechanisms of action behind these interactions and the potential benefits and limitations of their use. This review summarizes the current knowledge surrounding the implementation of microwave technologies within the medical industry.
High Expression of Solute Carrier Family 2 Member 1 (SLC2A1) in Cancer Cells Is an Independent Unfavorable Prognostic Factor in Pediatric Malignant Peripheral Nerve Sheath Tumor
Authors: Krawczyk Malgorzata A. , Kunc Michal , Styczewska Malgorzata , Gabrych Anna , Karpinsky Gabrielle , Izycka-Swieszewska Ewa , Bien Ewa
Published: March 2021

Malignant peripheral nerve sheath tumor (MPNST) in children is a rare mesenchymal malignancy developing predominantly in the setting of neurofibromatosis type 1. The prognosis in advanced MPNST is poor therefore new prognostic markers are highly needed for optimal therapeutic decisions. In many solid tumors, the bidirectional interactions between hypoxia and inflammation in the tumor microenvironment via functions of tumor-associated cells, like neutrophils, lymphocytes and macrophages, have been investigated recently. There is no data whether in MPNST hypoxic microenvironment may translate into systemic inflammation, which is a well-established factor for worse prognosis in cancer patients. Therefore, we investigated the prognostic significance of markers of tumor hypoxia and systemic inflammation in 26 pediatric malignant peripheral nerve sheath tumors (MPNST). Tumor tissue microarrays were stained for hypoxia-inducible factor-1α (HIF1A), solute carrier family 2 member 1 (SLC2A1, also known as glucose transporter 1 (GLUT1)), carbonic anhydrase 9 (CA9), and vascular endothelial growth factor A (VEGFA) and classified into low- or high-expression groups. Baseline complete blood counts and C-reactive protein (CRP) levels were collected for all cases. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated from age-adjusted complete blood count parameters. Both 10-year RFS and OS were significantly lower in patients with high NLR values (17% vs. 75%, p = 0.009, q = 0.018; and 31% vs. 100%, p = 0.0077, q = 0.014; respectively). Ten-year-OS was significantly lower in patients with high expression of SLC2A1 (20.00% vs. 94%, p < 0.001, log-rank), high expression of HIF1A (23% vs. 79%, p = 0.016, log-rank), and CRP higher than 31 mg/L (11% vs. 82%, p = 0.003, q = 0.009). Cox’s proportional hazard regression analysis revealed that high expression of SLC2A1 (HR = 3.31, 95% CI = 1.08–10.09, p = 0.036) and VEGFA (HR = 4.40, 95% CI = 0.95–20.34, p = 0.058) were the independent factors predicting relapse, whereas high SLC2A1 was identified as the independent risk factor for death (HR = 12.20, 95% CI = 2.55–58.33, p = 0.002). Patients with high expression of hypoxic markers and low or high NLR/CRP values had the highest events rate, patients with low hypoxic markers and high NLR/CRP had intermediate events rate, while patients with low hypoxic markers and low NLR/CRP had the lowest events rate. SLC2A1 and VEGFA are promising novel prognostic factors in pediatric MPNST. Correlations between hypoxic and systemic inflammatory markers suggest the interplay between local tumor hypoxia and systemic inflammation.
Entropy and the Direction of Time
Authors: Gołosz Jerzy
Published: March 2021

The paper tries to demonstrate that the process of the increase of entropy does not explain the asymmetry of time itself because it is unable to account for its fundamental asymmetries, that is, the asymmetry of traces (we have traces of the past and no traces of the future), the asymmetry of causation (we have an impact on future events with no possibility of having an impact on the past), and the asymmetry between the fixed past and the open future, To this end, the approaches of Boltzmann, Reichenbach (and his followers), and Albert are analysed. It is argued that we should look for alternative approaches instead of this, namely we should consider a temporally asymmetrical physical theory or seek a source of the asymmetry of time in metaphysics. This second approach may even turn out to be complementary if only we accept that metaphysics can complement scientific research programmes.
Dynamic Robustness of Semantic-Based Collaborative Knowledge Network of Open Source Project
Authors: Lei Shaojuan , Zhang Xiaodong , Xie Shilin , Zheng Xin
Published: March 2021

Robustness of the collaborative knowledge network (CKN) is critical to the success of open source projects. To study this robustness more comprehensively and accurately, we constructed a weighted CKN based on the semantic analysis of collaborative behavior, where (a) open source designers were the network nodes, (b) collaborative behavior among designers was the edges, and (c) collaborative text content intensity and collaborative frequency intensity were the edge weights. To study the robustness from a dynamic viewpoint, we constructed three CKNs from different stages of the project life cycle: the start-up, growth and maturation stages. The connectivity and collaboration efficiency of the weighted network were then used as robustness evaluation indexes. Further, we designed four edge failure modes based on the behavioral characteristics of open source designers. Finally, we carried out dynamic robustness analysis experiments based on the empirical data of a Local Motors open source car design project. Our results showed that the CKN performed differently at different stages of the project life cycle, and our specific findings could help community managers of open source projects to formulate different network protection strategies at different stages of their projects.
Power Management Strategy of a Parallel Hybrid Three-Wheeler for Fuel and Emission Reduction
Authors: Maddumage Waruna , Perera Malika , Attalage Rahula , Kelly Patrick
Published: March 2021

Millions of three-wheelers in large cities of Asia and Africa contribute to the already increasing urban air pollutants. An emerging method to reduce adverse effects of the growing three-wheeler fleet is hybrid-electric technology. The overall efficiency of a hybrid electric vehicle heavily depends on the power management strategy used in controlling the main powertrain components of the vehicle. Recent studies highlight the need for a comprehensive report on developing an easy-to-implement and efficient control strategy for hybrid electric three-wheelers. Thus, in the present study, a design methodology for a rule-based supervisory controller of a pre-transmission parallel hybrid three-wheeler based on an optimal control strategy (i.e., dynamic programming) is proposed. The optimal control problem for minimizing fuel, emissions (i.e., HC, CO and NOx) and gear shift frequency are solved using dynamic programming (DP). Numerical issues of DP are analyzed and trade-offs between optimizing objectives are presented. Since DP strategy cannot be implemented as a real-time controller, useful strategies are extracted to develop the proposed rule-based strategy. The developed rule-based strategy show performance within 10% of the DP results on WLTC and UDC-NEDC drive cycles and has the clear advantage of being near-optimal, easy-to-implement and computationally less demanding.
Assessment of Concentration of Mineral Oil in Synthetic Ester Based on the Density of the Mixture and the Capacitance of the Capacitor Immersed in It
Authors: Moranda Hubert , Gielniak Jaroslaw , Kownacki Ireneusz
Published: March 2021

This research was carried out during the realization of a project with the aim of developing a method of drying cellulose insulation in power transformers by using synthetic ester. Unfortunately, during the drying process, the ester is systematically contaminated with mineral oil, which reduces its water absorption. Information on the oil concentration in the mixture is needed in two cases: when deciding how to treat the mixture, and during the treatment. The article presents two methods: (1) based on the measurement of the mixture density, and (2) based on the measurement of a capacitor immersed in the mixture. The most important scientific achievement of the work is the proof, by way of experiment, of the existence of a relationship between the concentration of mineral oil and (1) the density of the mixture, and (2) the capacity of the capacitor immersed in it. These relations are presented in the form of equations for which the error calculus showed that the uncertainty of measurement for both methods did not exceed 3 p. %. Due to the similar measurement error of both methods, the authors recommend the capacitance method as easier to use, especially online.
Plasma Membrane H+-ATPase SmPHA4 Negatively Regulates the Biosynthesis of Tanshinones in Salvia miltiorrhiza
Authors: Li Xiuhong , Zhang Bin , Ma Pengda , Cao Ruizhi , Yang Xiaobing , Dong Juane
Published: March 2021

Salvia miltiorrhiza Bunge has been widely used in the treatment of cardiovascular and cerebrovascular diseases, due to the pharmacological action of its active components such as the tanshinones. Plasma membrane (PM) H+-ATPase plays key roles in numerous physiological processes in plants. However, little is known about the PM H+-ATPase gene family in S. miltiorrhiza (Sm). Here, nine PM H+-ATPase isoforms were identified and named SmPHA1–SmPHA9. Phylogenetic tree analysis showed that the genetic distance of SmPHAs was relatively far in the S. miltiorrhiza PM H+-ATPase family. Moreover, the transmembrane structures were rich in SmPHA protein. In addition, SmPHA4 was found to be highly expressed in roots and flowers. HPLC revealed that accumulation of dihydrotanshinone (DT), cryptotanshinone (CT), and tanshinone I (TI) was significantly reduced in the SmPHA4-OE lines but was increased in the SmPHA4-RNAi lines, ranging from 2.54 to 3.52, 3.77 to 6.33, and 0.35 to 0.74 mg/g, respectively, suggesting that SmPHA4 is a candidate regulator of tanshinone metabolites. Moreover, qRT-PCR confirmed that the expression of tanshinone biosynthetic-related key enzymes was also upregulated in the SmPHA4-RNAi lines. In summary, this study highlighted PM H+-ATPase function and provided new insights into regulatory candidate genes for modulating secondary metabolism biosynthesis in S. miltiorrhiza.
Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past, Present and Future Applications
Authors: van den Kerkhof Danique L. , van der Meijden Paola E.J. , Hackeng Tilman M. , Dijkgraaf Ingrid
Published: March 2021

The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.
The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation
Authors: Startek Justyna B. , Milici Alina , Naert Robbe , Segal Andrei , Alpizar Yeranddy A. , Voets Thomas , Talavera Karel
Published: March 2021

The Transient Receptor Potential Ankyrin 1 cation channel (TRPA1) is a broadly-tuned chemosensor expressed in nociceptive neurons. Multiple TRPA1 agonists are chemically unrelated non-electrophilic compounds, for which the mechanisms of channel activation remain unknown. Here, we assess the hypothesis that such chemicals activate TRPA1 by inducing mechanical perturbations in the plasma membrane. We characterized the activation of mouse TRPA1 by non-electrophilic alkylphenols (APs) of different carbon chain lengths in the para position of the aromatic ring. Having discarded oxidative stress and the action of electrophilic mediators as activation mechanisms, we determined whether APs induce mechanical perturbations in the plasma membrane using dyes whose fluorescence properties change upon alteration of the lipid environment. APs activated TRPA1, with potency increasing with their lipophilicity. APs increased the generalized polarization of Laurdan fluorescence and the anisotropy of the fluorescence of 1,6-diphenyl-1,3,5-hexatriene (DPH), also according to their lipophilicity. Thus, the potency of APs for TRPA1 activation is an increasing function of their ability to induce lipid order and membrane rigidity. These results support the hypothesis that TRPA1 senses non-electrophilic compounds by detecting the mechanical alterations they produce in the plasma membrane. This may explain how structurally unrelated non-reactive compounds induce TRPA1 activation and support the role of TRPA1 as an unspecific sensor of potentially noxious compounds.
The Winged Helix Domain of CSB Regulates RNAPII Occupancy at Promoter Proximal Pause Sites
Authors: Batenburg Nicole L. , Cui Shixin , Walker John R. , Schellhorn Herb E. , Zhu Xu-Dong
Published: March 2021

Cockayne syndrome group B protein (CSB), a member of the SWI/SNF superfamily, resides in an elongating RNA polymerase II (RNAPII) complex and regulates transcription elongation. CSB contains a C-terminal winged helix domain (WHD) that binds to ubiquitin and plays an important role in DNA repair. However, little is known about the role of the CSB-WHD in transcription regulation. Here, we report that CSB is dependent upon its WHD to regulate RNAPII abundance at promoter proximal pause (PPP) sites of several actively transcribed genes, a key step in the regulation of transcription elongation. We show that two ubiquitin binding-defective mutations in the CSB-WHD, which impair CSB’s ability to promote cell survival in response to treatment with cisplatin, have little impact on its ability to stimulate RNAPII occupancy at PPP sites. In addition, we demonstrate that two cancer-associated CSB mutations, which are located on the opposite side of the CSB-WHD away from its ubiquitin-binding pocket, impair CSB’s ability to promote RNAPII occupancy at PPP sites. Taken together, these results suggest that CSB promotes RNAPII association with PPP sites in a manner requiring the CSB-WHD but independent of its ubiquitin-binding activity. These results further imply that CSB-mediated RNAPII occupancy at PPP sites is mechanistically separable from CSB-mediated repair of cisplatin-induced DNA damage.
The Effect of the 2019 Novel Coronavirus Pandemic on Stroke and TIA Patient Admissions: Perspectives and Risk Factors
Authors: Carson Luke , Kui Christopher , Smith Gemma , Dixit Anand K.
Published: March 2021

Background: The 2019 novel coronavirus pandemic has generated concern from stroke specialist centres across the globe. Reductions in stroke admissions have been reported, despite many expecting an increase due to the pro-thrombotic nature of 2019 novel coronavirus. Aims: To assess the impact of the pandemic and subsequent lockdown on stroke admissions and transient ischaemic attack referrals at the Royal Victoria Infirmary, Newcastle-Upon-Tyne, and additionally on patient behaviours affecting modifiable risk factors or perspectives related to accessing healthcare. Methods: A single-centre retrospective data analysis was carried out on a “lockdown” cohort of suspected stroke patients admitted between 11 March to 26 May 2020 and a “pre-lockdown” cohort admitted in 2019. Differences in weekly admissions, weekly referrals, onset-to-presentation time and weekly thrombolysis cases were examined. Further analysis interrogated these cohorts separated by Bamford classification and stroke mimics (such as seizure/hemiplegic migraine/functional neurology). A binary-format questionnaire was separately administered to admitted patients from 15 April to 5 June 2020. Results: Significant reductions in weekly posterior circulation infarct (−43%, p = 0.017) and stroke-mimic (−47%, p < 0.001) admissions and weekly referrals diagnosed as non-transient ischaemic attack (−55%, p = 0.002) were observed in the lockdown cohort, with no differences in onset-to-presentation time. Over 25% of questionnaire respondents reported less physical activity, increased isolation and delaying their presentation due to the pandemic. Conclusions: This study provides evidence of reduced stroke-mimic and posterior circulation infarct admissions. Questionnaire findings suggest that patients need to be informed to ensure they appropriately seek medical advice. Significant communication at the stroke-primary care interface is needed to support referral pathways and management of modifiable risk factors.
High Incidence of Adverse Outcomes in Haemodialysis Patients with Diabetes with or without Diabetic Foot Syndrome: A 5-Year Observational Study in Lleida, Spain
Authors: Dòria Montserrat , Betriu Àngels , Belart Montserrat , Rosado Verónica , Hernández Marta , Sarro Felipe , Real Jordi , Castelblanco Esmeralda , Pacheco Linda , Fernández Elvira , Franch-Nadal Josep , Gratacòs Mònica , Mauricio Dídac
Published: March 2021

Background: We evaluated whether, in subjects receiving haemodialysis (HD), the presence of diabetic foot syndrome (DFS) was associated with increased mortality compared with subjects with diabetes mellitus (DM) without DFS and with non-diabetic subjects. Methods: Retrospective, observational study in 220 subjects followed for six years. We calculated and compared the frequency and 5-year cumulative incidence of all-cause mortality, cardiovascular (CV) mortality, CV events, major adverse CV events (MACE), and new foot ulcer (FU) or amputation. We also examined prognostic factors of all-cause and CV mortality based on baseline characteristics. Results: DM patients had a 1.98 times higher probability of all-cause mortality than those without DM (p = 0.001) and 2.42 times higher likelihood of CV mortality and new FU or amputation (p = 0.002 and p = 0.008, respectively). In the DM cohort, only the risk of a new FU or amputation was 2.69 times higher among those with previous DFS (p = 0.021). In patients with DM, older age was the only predictor of all-cause and CV mortality (p = 0.001 and p = 0.014, respectively). Conclusions: Although all-cause and CV mortality were increased on HD subjects with DM, the presence of DFS did not modify the excess risk. Additional studies are warranted to further explore the impact of DFS in subjects with DM undergoing HD.
Epigenetic Characteristics of Human Subtelomeres Vary in Cells Utilizing the Alternative Lengthening of Telomeres (ALT) Pathway
Authors: Toubiana Shir , Tzur-Gilat Aya , Selig Sara
Published: March 2021

Most human cancers circumvent senescence by activating a telomere length maintenance mechanism, most commonly involving telomerase activation. A minority of cancers utilize the recombination-based alternative lengthening of telomeres (ALT) pathway. The exact requirements for unleashing normally repressed recombination at telomeres are yet unclear. Epigenetic modifications at telomeric regions were suggested to be pivotal for activating ALT; however, conflicting data exist regarding their exact nature and necessity. To uncover common ALT-positive epigenetic characteristics, we performed a comprehensive analysis of subtelomeric DNA methylation, histone modifications, and TERRA expression in several ALT-positive and ALT-negative cell lines. We found that subtelomeric DNA methylation does not differentiate between the ALT-positive and ALT-negative groups, and most of the analyzed subtelomeres within each group do not share common DNA methylation patterns. Additionally, similar TERRA levels were measured in the ALT-positive and ALT-negative groups, and TERRA levels varied significantly among the members of the ALT-positive group. Subtelomeric H3K4 and H3K9 trimethylation also differed significantly between samples in the ALT-positive group. Our findings do not support a common route by which epigenetic modifications activate telomeric recombination in ALT-positive cells, and thus, different therapeutic approaches will be necessary to overcome ALT-dependent cellular immortalization.