bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Coronary Angiography Is Associated with Improved 30-Day Outcomes among Patients with Out-of-Hospital Cardiac Arrest
Authors: Lim Shir Lynn , Lau Yee How , Chan Mark Y. , Chua Terrance , Tan Huay Cheem , Foo David , Lim Zhan Yun , Liew Boon Wah , Shahidah Nur , Mao Desmond R. , Cheah Si Oon , Chia Michael Y. C. , Gan Han Nee , Leong Benjamin S. H. , Ng Yih Yng , Yeo Khung Keong , Ong Marcus E. H.
Published: November 2021

We evaluated the association between early coronary angiography (CAG) and outcomes in resuscitated out-of-hospital cardiac arrest (OHCA) patients, by linking data from the Singapore Pan-Asian Resuscitation Outcomes Study, with a national registry of cardiac procedures. The 30-day survival and neurological outcome were compared between patients undergoing early CAG (within 1-calender day), versus patients not undergoing early CAG. Inverse probability weighted estimates (IPWE) adjusted for non-randomized CAG. Of 976 resuscitated OHCA patients of cardiac etiology between 2011–2015 (mean(SD) age 64(13) years, 73.7% males), 337 (34.5%) underwent early CAG, of whom, 230 (68.2%) underwent PCI. Those who underwent early CAG were significantly younger (60(12) vs. 66(14) years old), healthier (42% vs. 59% with heart disease; 29% vs. 44% with diabetes), more likely males (86% vs. 67%), and presented with shockable rhythms (69% vs. 36%), compared with those who did not. Early CAG with PCI was associated with better survival and neurological outcome (adjusted odds ratio 1.91 and 1.82 respectively), findings robust to IPWE adjustment. The rates of bleeding and stroke were similar. CAG with PCI within 24 h was associated with improved clinical outcomes after OHCA, without increasing complications. Further studies are required to identify the characteristics of patients who would benefit most from this invasive strategy.
Dual-Energy Heart CT: Beyond Better Angiography—Review
Authors: Tarkowski Piotr , Czekajska-Chehab Elżbieta
Published: November 2021

Heart CT has undergone substantial development from the use of calcium scores performed on electron beam CT to modern 256+-row CT scanners. The latest big step in its evolution was the invention of dual-energy scanners with much greater capabilities than just performing better ECG-gated angio-CT. In this review, we present the unique features of dual-energy CT in heart diagnostics.
Associations of Obstructive Sleep Apnea, Obestatin, Leptin, and Ghrelin with Gastroesophageal Reflux
Authors: Pardak Piotr , Filip Rafał , Woliński Jarosław , Krzaczek Maciej
Published: November 2021

Gastroesophageal reflux disease (GERD) is commonly observed in patients with obstructive sleep apnea (OSA). Hormonal disorders observed in OSA may be relevant in the development of GERD. The aim of the study was to assess the correlations between ghrelin, obestatin, leptin, and the intensity of GERD in patients with OSA. The study included 58 patients hospitalized due to clinical suspicion of sleep disorders during sleep. All patients underwent a sleep study, and blood samples were collected overnight for hormonal tests. Survey data concerning symptoms of GERD, gastroscopy, and esophageal pH monitoring results were included in the study. In patients with OSA, GERD was twice as common when compared to the group without OSA. Among subjects with severe sleep apnea (AHI > 30; n = 31; 53%), we observed lower ghrelin levels, especially in the second half of the night and in the morning (p5.00 = 0.0207; p7.00 = 0.0344); the presence of OSA had no effect on obestatin and leptin levels. No significant differences in hormonal levels were observed between the groups depending on the diagnosis of GERD. However, correlations of ghrelin levels with the severity of esophagitis, leptin and ghrelin levels with the severity of GERD symptoms, and leptin levels with lower esophageal pH were found. GERD is more frequent among patients with OSA. In both GERD and OSA, deviations were observed in the levels of ghrelin and leptin. However, our analysis demonstrates that the relationship between OSA and GERD does not result from these disorders.
Cortisol as a Biomarker of Mental Disorder Severity
Authors: Dziurkowska Ewelina , Wesolowski Marek
Published: November 2021

Cortisol—the most important steroid hormone with a significant effect on body metabolism—strongly affects peripheral tissues and the central nervous system. Fluctuations in cortisol secretion often accompany psychiatric disorders, and normalization of its levels correlates with improvement in the patient’s health. This indicates that cortisol may be useful as a biological marker that can help determine the likelihood of mental illness, its impending onset, and the severity of symptoms, which is especially important in the face of the increasing prevalence of mental disorders, including those associated with social isolation and anxiety during the COVID-19 pandemic. This publication reviews recent reports on cortisol levels in healthy participants and shows the current state of knowledge on changes in the levels of this hormone in people at risk for depression, bipolar disorder, and psychosis. It shows how people with psychiatric disorders react to stressful situations and how the applied therapies affect cortisol secretion. The influence of antidepressants and antipsychotics on cortisol levels in healthy people and those with mental disorders is also described. Finally, it reviews publications on the patterns of cortisol secretion in patients in remission.
Measuring Equity through Spatial Variability of Infrastructure Systems across the Urban-Rural Gradient
Authors: Karkun Sen Shrobona , Pearsall Hamil , Gutierrez-Velez Victor Hugo , Gilbert Melissa R.
Published: November 2021

Recent regional research has taken an ‘infrastructure turn’ where scholars have called for examining the transformative ability of different infrastructures in causing systemic inequities beyond the spatial conception of ‘urban and the other’. This research examines the interconnected impact of infrastructure systems on existing spatial inequities through a study in metropolitan Philadelphia, Pennsylvania. This study investigates whether the urban-rural (U-R) gradient concept can enhance understanding of the spatial relationship between socioeconomic indicators and infrastructure systems. Indicators of spatial inequalities were regressed against infrastructure variables and imperviousness, as a proxy for the U-R gradient, using multivariate and spatial regression methods. The models show that imperviousness has a positive correlation with the concentration of racialized minorities and a negative correlation with access to health insurance. The study also shows that the predictive power of multiple infrastructures varies across space and does not adhere to urban boundaries or the U-R gradient. The complex interactions among different infrastructures shape inequities and require further inquiry in urban regions around the world.
Multi-Omics for the Understanding of Brain Diseases
Authors: Villa Chiara , Yoon Jong Hyuk
Published: November 2021

Brain diseases, including both neurodegenerative diseases and mental disorders, represent the third largest healthcare problem in developed countries, after cardiovascular disorders and cancer [...]
Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects
Authors: Sur Lucia M. , Armat Ionel , Duca Emanuela , Sur Genel , Lupan Iulia , Sur Daniel , Samasca Gabriel , Lazea Cecilia , Lazar Calin
Published: November 2021

Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.
Perna canaliculus as an Ecological Material in the Removal of o-Cresol Pollutants from Soil
Authors: Zaborowska Magdalena , Wyszkowska Jadwiga , Borowik Agata , Kucharski Jan
Published: November 2021

Soil contamination with cresol is a problem of the 21st century and poses a threat to soil microorganisms, humans, animals, and plants. The lack of precise data on the potential toxicity of o-cresol in soil microbiome and biochemical activity, as well as the search for effective remediation methods, inspired the aim of this study. Soil is subjected to four levels of contamination with o-cresol: 0, 0.1, 1, 10, and 50 mg o-cresol kg−1 dry matter (DM) of soil and the following are determined: the count of eight groups of microorganisms, colony development index (CD) and ecophysiological diversity index (EP) for organotrophic bacteria, actinobacteria and fungi, and the bacterial genetic diversity. Moreover, the responses of seven soil enzymes are investigated. Perna canaliculus is a recognized biosorbent of organic pollutants. Therefore, microbial biostimulation with Perna canaliculus shells is used to eliminate the negative effect of the phenolic compound on the soil microbiome. Fungi appears to be the microorganisms most sensitive to o-cresol, while Pseudomonas sp. is the least sensitive. In o-cresol-contaminated soils, the microbiome is represented mainly by the bacteria of the Proteobacteria and Firmicutes phyla. Acid phosphatase, alkaline phosphatase and urease can be regarded as sensitive indicators of soil disturbance. Perna canaliculus shells prove to be an effective biostimulator of soil under pressure with o-cresol.
Light-Driven Linear Inchworm Motor Based on Liquid Crystal Elastomer Actuators Fabricated with Rubbing Overwriting
Authors: Rogóż Mikołaj , Haberko Jakub , Wasylczyk Piotr
Published: November 2021

Linear displacement is used for positioning and scanning, e.g., in robotics at different scales or in scientific instrumentation. Most linear motors are either powered by rotary drives or are driven directly by pressure, electromagnetic forces or a shape change in a medium, such as piezoelectrics or shape-memory materials. Here, we present a centimeter-scale light-powered linear inchworm motor, driven by two liquid crystal elastomer (LCE) accordion-like actuators. The rubbing overwriting technique was used to fabricate the LCE actuators, made of elastomer film with patterned alignment. In the linear motor, a scanned green laser beam induces a sequence of travelling deformations in a pair of actuators that move a gripper, which couples to a shaft via friction moving it with an average speed in the order of millimeters per second. The prototype linear motor demonstrates how LCE light-driven actuators with a limited stroke can be used to drive more complex mechanisms, where large displacements can be achieved, defined only by the technical constrains (the shaft length in our case), and not by the limited strain of the material. Inchworm motors driven by LCE actuators may be scaled down to sub-millimeter size and can be used in applications where remote control and power supply with light, either delivered in free space beams or via fibers, is an advantage.
Surface Modification of Carbon Fiber-Polyetheretherketone Composite to Impart Bioactivity by Using Apatite Nuclei
Authors: Yamane Yuya , Yabutsuka Takeshi , Takaoka Yusuke , Ishizaki Chihiro , Takai Shigeomi , Fujibayashi Shunsuke
Published: November 2021

The authors aimed to impart the apatite-forming ability to 50 wt% carbon fiber-polyetheretherketone composite (50C-PEEK), which has more suitable mechanical properties as artificial bone materials than pure PEEK. First, the 50C-PEEK was treated with sulfuric acid in a short time to form pores on the surface. Second, the surface of the 50C-PEEK was treated with oxygen plasma to improve the hydrophilicity. Finally, fine particles of calcium phosphate, which the authors refer to as “apatite nuclei”, were precipitated on the surface of the 50C-PEEK by soaking in an aqueous solution containing multiple inorganic ions such as phosphate and calcium (modified-SBF) at pH 8.20, 25 °C. The 50C-PEEK without the modified-SBF treatment did not show the formation of apatitic phase even after immersion in simulated body fluid (SBF) for 7 days. The 50C-PEEK treated with the modified-SBF showed the formation of apatitic phase on the entire surface within 1 day in the SBF. The apatite nuclei-precipitated 50C-PEEK will be expected as a new artificial bone material with high bioactivity that is obtained without complicated fabrication processes.
Development of Machine Learning Models to Evaluate the Toughness of OPH Alloys
Authors: Khalaj Omid , Ghobadi Moslem , Saebnoori Ehsan , Zarezadeh Alireza , Shishesaz Mohammadreza , Mašek Bohuslav , Štadler Ctibor , Svoboda Jiří
Published: November 2021

Oxide Precipitation-Hardened (OPH) alloys are a new generation of Oxide Dispersion-Strengthened (ODS) alloys recently developed by the authors. The mechanical properties of this group of alloys are significantly influenced by the chemical composition and appropriate heat treatment (HT). The main steps in producing OPH alloys consist of mechanical alloying (MA) and consolidation, followed by hot rolling. Toughness was obtained from standard tensile test results for different variants of OPH alloy to understand their mechanical properties. Three machine learning techniques were developed using experimental data to simulate different outcomes. The effectivity of the impact of each parameter on the toughness of OPH alloys is discussed. By using the experimental results performed by the authors, the composition of OPH alloys (Al, Mo, Fe, Cr, Ta, Y, and O), HT conditions, and mechanical alloying (MA) were used to train the models as inputs and toughness was set as the output. The results demonstrated that all three models are suitable for predicting the toughness of OPH alloys, and the models fulfilled all the desired requirements. However, several criteria validated the fact that the adaptive neuro-fuzzy inference systems (ANFIS) model results in better conditions and has a better ability to simulate. The mean square error (MSE) for artificial neural networks (ANN), ANFIS, and support vector regression (SVR) models was 459.22, 0.0418, and 651.68 respectively. After performing the sensitivity analysis (SA) an optimized ANFIS model was achieved with a MSE value of 0.003 and demonstrated that HT temperature is the most significant of these parameters, and this acts as a critical rule in training the data sets.
Snow Melting Performance of Graphene Composite Conductive Concrete in Severe Cold Environment
Authors: Wang Xinjie , Wu Yongkang , Zhu Pinghua , Ning Tao
Published: November 2021

The use of conductive concrete is an effective way to address snow and ice accretion on roads in cold regions because of its energy saving and high efficiency without interruption of traffic. Composite conductive concrete was prepared using graphene, carbon fiber, and steel fiber, and the optimum dosage of graphene was explored with resistivity as the criterion. Subsequently, under the conditions of an initial temperature of −15 °C and a wind speed of 20 km/h, the extremely severe snow event environment in cold regions was simulated. The effects of electrode spacing and electric voltage on snow melting performance of conductive concrete slab were explored. Results showed that graphene can significantly improve the conductivity of conductive concrete; the optimal content of graphene was 0.4% of cement mass in terms of resistivity. The snow-melting power of conductive concrete slab decreased with increase in electrode spacing and increased with increase in on-voltage. For an optimal input voltage of 156 V and an optimal electrode spacing of 10 cm, the time required to melt a 24 h snow thickness (21 cm), accumulated during a simulated severe snow event, was only 2 h, which provides an empirical basis for the application of graphene composite conductive concrete to pavement snow melting in cold regions.
Study of Construction and Performance on Photoelectric Devices of Cs–Pb–Br Perovskite Quantum Dot
Authors: Ma Shiyu , Lu Yan , Wang Bo , Li Jinkai
Published: November 2021

White LEDs were encapsulated using Cs4PbBr6 quantum dots and Gd2O3:Eu red phosphor as lamp powder. Under the excitation of a GaN chip, the color coordinates of the W-LED were (0.33, 0.34), and the color temperature was 5752 K, which is close to the color coordinate and color temperature range of standard sunlight. The electric current stability was excellent with an increase in the electric current, voltage, and luminescence intensity of the quantum dots and phosphors by more than 10 times. However, the stability of the quantum dots was slightly insufficient over long working periods. The photocatalytic devices were constructed using TiO2, CsPbBr3, and NiO as an electron transport layer, light absorption layer, and catalyst, respectively. The Cs–Pb–Br-based perovskite quantum dot photocatalytic devices were constructed using a two-step spin coating method, one-step spin coating method, and full PLD technology. In order to improve the water stability of the device, a hydrophobic carbon paste and carbon film were selected as the hole transport layer. The TiO2 layer and perovskite layer with different thicknesses and film forming qualities were obtained by changing the spin coating speed. The influence of the spin coating speed on the device’s performance was explored through SEM and a J–V curve to find the best spin coating process. The device constructed by the two-step spin coating method had a higher current density but no obvious increase in the current density under light, while the other two methods could obtain a more obvious light response, but the current density was very low.
3D Printing in Alginic Acid Bath of In-Situ Crosslinked Collagen Composite Scaffolds
Authors: Melo Priscila , Montalbano Giorgia , Fiorilli Sonia , Vitale-Brovarone Chiara
Published: November 2021

Bone-tissue regeneration is a growing field, where nanostructured-bioactive materials are designed to replicate the natural properties of the target tissue, and then are processed with technologies such as 3D printing, into constructs that mimic its natural architecture. Type I bovine collagen formulations, containing functional nanoparticles (enriched with therapeutic ions or biomolecules) or nanohydroxyapatite, are considered highly promising, and can be printed using support baths. These baths ensure an accurate deposition of the material, nonetheless their full removal post-printing can be difficult, in addition to undesired reactions with the crosslinking agents often used to improve the final structural integrity of the scaffolds. Such issues lead to partial collapse of the printed constructs and loss of geometrical definition. To overcome these limitations, this work presents a new alternative approach, which consists of adding a suitable concentration of crosslinking agent to the printing formulations to promote the in-situ crosslinking of the constructs prior to the removal of the support bath. To this aim, genipin, chosen as crosslinking agent, was added (0.1 wt.%) to collagen-based biomaterial inks (containing either 38 wt.% mesoporous bioactive glasses or 65 wt.% nanohydroxyapatite), to trigger the crosslinking of collagen and improve the stability of the 3D printed scaffolds in the post-processing step. Moreover, to support the material deposition, a 15 wt.% alginic acid solution was used as a bath, which proved to sustain the printed structures and was also easily removable, allowing for the stable processing of high-resolution geometries.
Influence of CNT Incorporation on the Carbonation of Conductive Cement Mortar
Authors: Lee Gun-Cheol , Kim Youngmin , Seo Soo-Yeon , Yun Hyun-Do , Hong Seongwon
Published: November 2021

This study analyzed the influence of carbon nanotubes (CNTs) on the carbonation conductive cementitious composites. Two powder types of CNT, multi-walled and single-wall CNTs, were employed to give the cement mortar the conductivity, and four tests including the accelerated carbonation, compressive and flexural strength, electrical resistance, and porosity tests were carried out. To intentionally accelerate the carbonation, the prismatic specimens of conductive cement composites were fabricated and stored in the controlled environmental chamber at a constant temperature of 20 ± 2 °C, constant relative humidity of 60 ± 5%, and carbon dioxide (CO2) concentration of 5% for 12 weeks. It was observed that carbonation resulted in only chemical damage so that there was no change in the electrical resistance value of conductive cementitious mortar that had undergone a carbonation attack.
The Influence of Selected Meteorological Factors on the Prevalence and Course of Stroke
Authors: Zaręba Katarzyna , Lasek-Bal Anetta , Student Sebastian
Published: November 2021

Background: The objective of this study was to evaluate the impact of weather factors on stroke parameters. Methods: This retrospective study analyzed the records of stroke patients concerning the influence of meteorological conditions and moon phases on stroke parameters. Results: The study group consisted of 402 patients aged between 20 and 102; women constituted 49.8% of the subjects. Ischaemic stroke was diagnosed in 90.5% of patients and hemorrhagic stroke was diagnosed in 9.5% of patients. The highest number of hospitalizations due to stroke was observed in January (48 events); the lowest number was observed in July (23 events). There was no statistically significant correlation between the meteorological parameters on the day of onset and the preceding day of stroke and the neurological status (NIHSS) of patients. Mean air temperature on the day of stroke and the day preceding stroke was significantly lower in the group of patients discharged with a very good functional status (≤2 points in modified Rankin scale (mRS)) compared to the patients with a bad functional status (>2 points in mRS); respectively: 7.98 ± 8.01 vs. 9.63 ± 7.78; p = 0.041 and 8.13 ± 7.72 vs. 9.70 ± 7.50; p = 0.048). Humidity above 75% on the day of stroke was found to be a factor for excellent functional state (RR 1.61; p = 0.016). The total anterior circulation infarcts (in comparison with stroke in the other localization) were more frequent (70%) during a third quarter moon (p = 0.011). The following parameters had a significant influence on the number of stroke cases in relation to autumn having the lowest number of onsets: mean temperature (OR 1.019 95% CI 1.014–1.024, p < 0.000), humidity (OR 1.028, CI 1.023–1.034, p < 0.0001), wind speed (OR 0.923, 95% CI 0.909–0.937, p < 0.0001), insolation (OR 0.885, 95% CI 0.869–0.902, p < 0.0001), precipitation (OR 0.914, 95% CI 0.884–0.946, p < 0.0001). Conclusion: Air humidity and air temperature on the day of stroke onset as well as air temperature on the day preceding stroke are important for the functional status of patients in the acute disease period. A combination of the following meteorological parameters: lowered mean temperature and low sunshine, high humidity and high wind speed all increase the risk of stroke during the winter period. High humidity combined with high precipitation, low wind speed and low sunshine in the autumn period are associated with the lowest stroke incidence risk. A possible relationship between phases of the moon and the incidence requires further investigation.
Hybrid Feature Selection Framework for the Parkinson Imbalanced Dataset Prediction Problem
Authors: Qasim Hayder Mohammed , Ata Oguz , Ansari Mohammad Azam , Alomary Mohammad N. , Alghamdi Saad , Almehmadi Mazen
Published: November 2021

Background and Objectives: Recently, many studies have focused on the early detection of Parkinson’s disease (PD). This disease belongs to a group of neurological problems that immediately affect brain cells and influence the movement, hearing, and various cognitive functions. Medical data sets are often not equally distributed in their classes and this gives a bias in the classification of patients. We performed a Hybrid feature selection framework that can deal with imbalanced datasets like PD. Use the SOMTE algorithm to deal with unbalanced datasets. Removing the contradiction from the features in the dataset and decrease the processing time by using Recursive Feature Elimination (RFE), and Principle Component Analysis (PCA). Materials and Methods: PD acoustic datasets and the characteristics of control subjects were used to construct classification models such as Bagging, K-nearest neighbour (KNN), multilayer perceptron, and the support vector machine (SVM). In the prepressing stage, the synthetic minority over-sampling technique (SMOTE) with two-feature selection RFE and PCA were used. The PD dataset comprises a large difference between the numbers of the infected and uninfected patients, which causes the classification bias problem. Therefore, SMOTE was used to resolve this problem. Results: For model evaluation, the train–test split technique was used for the experiment. All the models were Grid-search tuned, the evaluation results of the SVM model showed the highest accuracy of 98.2%, and the KNN model exhibited the highest specificity of 99%. Conclusions: the proposed method is compared with the current modern methods of detecting Parkinson’s disease and other methods for medical diseases, it was noted that our developed system could treat data bias and reach a high prediction of PD and this can be beneficial for health organizations to properly prioritize assets.
Propagation Laws of Reclamation Risk in Tailings Ponds Using Complex Network Theory
Authors: Zhen Zhixin , Zhang Ying , Hu Mengrong
Published: November 2021

Accidents have occurred periodically in the tailings ponds where mine solid waste is stored in recent years, and thus their safety has become one of the constraints restricting the sustainable development of the mining industry. Reclamation is an important way to treat tailings ponds, but improper reclamation methods and measures not only cannot reduce the accident risk of tailings ponds, but will further increase the pollution to the surrounding environment. The influencing factors of reclamation accidents in tailings ponds are complex, and the existing models cannot characterize them. In order to study the propagation process of tailings pond reclamation risk, this paper proposes a three-dimensional identification framework for accident hazards based on evidence (TDIFAHE) to identify all potential hazards that may occur during the reclamation stage, and obtain a list of hazards. Based on the complex network theory, this paper uses identified hazards as network nodes and the correlation between hazards as the edges of the network. Based on the identified hazard data, the evolution network of reclamation risk in tailings ponds (ENRRTP) is constructed. By analyzing the statistical characteristics of ENRRTP, it can be found that ENRRTP has small world and scale-free characteristics. The above characteristics show that the reclamation risk of tailings ponds is coupled with multiple factors and the disaster path is short. Giving priority to those hub hazards that have a dominant impact on the reclamation risk can significantly reduce the reclamation risk of the tailings pond.
Generation of Custom Textual Model Editors
Authors: Syriani Eugene , Riegelhaupt Daniel , Barroca Bruno , David Istvan
Published: November 2021

Textual editors are omnipresent in all software tools. Editors provide basic features, such as copy-pasting and searching, or more advanced features, such as error checking and text completion. Current technologies in model-driven engineering can automatically generate textual editors to manipulate domain-specific languages (DSLs). However, the customization and addition of new features to these editors is often limited to changing the internal structure and behavior. In this paper, we explore a new generation of self-descriptive textual editors for DSLs, allowing full configuration of their structure and behavior in a convenient formalism, rather than in source code. We demonstrate the feasibility of the approach by providing a prototype implementation and applying it in two domain-specific modeling scenarios, including one in architecture modeling.
MAS-NMR of [Pyr13][Tf2N] and [Pyr16][Tf2N] Ionic Liquids Confined to Carbon Black: Insights and Pitfalls
Authors: Merz Steffen , Wang Jie , Galvosas Petrik , Granwehr Josef
Published: November 2021

Electrolytes based on ionic liquids (IL) are promising candidates to replace traditional liquid electrolytes in electrochemical systems, particularly in combination with carbon-based porous electrodes. Insight into the dynamics of such systems is imperative for tailoring electrochemical performance. In this work, 1-Methyl-1-propylpyrrolidinium bis(trifluoromethylsulfonyl)imide and 1-Hexyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide were studied in a carbon black (CB) host using spectrally resolved Carr-Purcell-Meiboom-Gill (CPMG) and 13-interval Pulsed Field Gradient Stimulated Echo (PFGSTE) Magic Angle Spinning Nuclear Magnetic Resonance (MAS-NMR). Data were processed using a sensitivity weighted Laplace inversion algorithm without non-negativity constraint. Previously found relations between the alkyl length and the aggregation behavior of pyrrolidinium-based cations were confirmed and characterized in more detail. For the IL in CB, a different aggregation behavior was found compared to the neat IL, adding the surface of a porous electrode as an additional parameter for the optimization of IL-based electrolytes. Finally, the suitability of MAS was assessed and critically discussed for investigations of this class of samples.
Discovery of Novel Delta Opioid Receptor (DOR) Inverse Agonist and Irreversible (Non-Competitive) Antagonists
Authors: Tanguturi Parthasaradhireddy , Pathak Vibha , Zhang Sixue , Moukha-Chafiq Omar , Augelli-Szafran Corinne , Streicher John
Published: November 2021

The delta opioid receptor (DOR) is a crucial receptor system that regulates pain, mood, anxiety, and similar mental states. DOR agonists, such as SNC80, and DOR-neutral antagonists, such as naltrindole, were developed to investigate the DOR in vivo and as potential therapeutics for pain and depression. However, few inverse agonists and non-competitive/irreversible antagonists have been developed, and none are widely available. This leaves a gap in our pharmacological toolbox and limits our ability to investigate the biology of this receptor. Thus, we designed and synthesized the novel compounds SRI-9342 as an irreversible antagonist and SRI-45128 as an inverse agonist. These compounds were then evaluated in vitro for their binding affinity by radioligand binding, their functional activity by 35S-GTPγS coupling, and their cAMP accumulation in cells expressing the human DOR. Both compounds demonstrated high binding affinity and selectivity at the DOR, and both displayed their hypothesized molecular pharmacology of irreversible antagonism (SRI-9342) or inverse agonism (SRI-45128). Together, these results demonstrate that we have successfully designed new inverse agonists and irreversible antagonists of the DOR based on a novel chemical scaffold. These new compounds will provide new tools to investigate the biology of the DOR or even new potential therapeutics.
First Immunoassay for Measuring Isoaspartate in Human Serum Albumin
Authors: Wang Jijing , Lundström Susanna L. , Seelow Sven , Rodin Sergey , Meng Zhaowei , Astorga-Wells Juan , Jia Qinyu , Zubarev Roman A.
Published: November 2021

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins mostly as a result of spontaneous deamidation of asparaginyl residues. An association has been found between isoAsp in human serum albumin (HSA) and Alzheimer’s disease (AD). Here we report on a novel monoclonal antibody (mAb) 1A3 with excellent specificity to isoAsp in the functionally important domain of HSA. Based on 1A3 mAb, an indirect enzyme-linked immunosorbent assay (ELISA) was developed, and the isoAsp occupancy in 100 healthy plasma samples was quantified for the first time, providing the average value of (0.74 ± 0.13)%. These results suggest potential of isoAsp measurements for supplementary AD diagnostics as well as for assessing the freshness of stored donor blood and its suitability for transfusion.
Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design
Authors: Rios-Soto Lluvia , Téllez-Valencia Alfredo , Sierra-Campos Erick , Valdez-Solana Mónica , Cisneros-Martínez Jorge , Gómez Palacio-Gastélum Marcelo , Castillo-Villanueva Adriana , Avitia-Domínguez Claudia
Published: November 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in the shikimate pathway, is considered a good target for developing antimicrobial drugs; this is given because of its pathway, which is essential in bacteria whereas it is absent in mammals. In this work, a computer-assisted drug design strategy was used to report the first potentials inhibitors for Shikimate kinase from methicillin-resistant Staphylococcus aureus (SaSK), employing approximately 5 million compounds from ZINC15 database. Diverse filtering criteria, related to druglike characteristics and virtual docking screening in the shikimate binding site, were performed to select structurally diverse potential inhibitors from SaSK. Molecular dynamics simulations were performed to elucidate the dynamic behavior of each SaSK–ligand complex. The potential inhibitors formed important interactions with residues that are crucial for enzyme catalysis, such as Asp37, Arg61, Gly82, and Arg138. Therefore, the compounds reported provide valuable information and can be seen as the first step toward developing SaSK inhibitors in the search of new drugs against MRSA.
Structural Optimization and Biological Activity of Pyrazole Derivatives: Virtual Computational Analysis, Recovery Assay and 3D Culture Model as Potential Predictive Tools of Effectiveness against Trypanosoma cruzi
Authors: Orlando Lorraine Martins Rocha , Lechuga Guilherme Curty , da Silva Lara Leonardo , Ferreira Byanca Silva , Pereira Cynthia Nathalia , Silva Rafaela Corrêa , dos Santos Maurício Silva , Pereira Mirian Claudia S.
Published: November 2021

Chagas disease, a chronic and silent disease caused by Trypanosoma cruzi, is currently a global public health problem. The treatment of this neglected disease relies on benznidazole and nifurtimox, two nitroheterocyclic drugs that show limited efficacy and severe side effects. The failure of potential drug candidates in Chagas disease clinical trials highlighted the urgent need to identify new effective chemical entities and more predictive tools to improve translational success in the drug development pipeline. In this study, we designed a small library of pyrazole derivatives (44 analogs) based on a hit compound, previously identified as a T. cruzi cysteine protease inhibitor. The in vitro phenotypic screening revealed compounds 3g, 3j, and 3m as promising candidates, with IC50 values of 6.09 ± 0.52, 2.75 ± 0.62, and 3.58 ± 0.25 µM, respectively, against intracellular amastigotes. All pyrazole derivatives have good oral bioavailability prediction. The structure–activity relationship (SAR) analysis revealed increased potency of 1-aryl-1H-pyrazole-imidazoline derivatives with the Br, Cl, and methyl substituents in the para-position. The 3m compound stands out for its trypanocidal efficacy in 3D microtissue, which mimics tissue microarchitecture and physiology, and abolishment of parasite recrudescence in vitro. Our findings encourage the progression of the promising candidate for preclinical in vivo studies.
Role of Partial Splenectomy in Hematologic Childhood Disorders
Authors: Attina’ Giorgio , Triarico Silvia , Romano Alberto , Maurizi Palma , Mastrangelo Stefano , Ruggiero Antonio
Published: November 2021

The spleen is a secondary lymphoid organ that belongs to the reticular-endothelial system, directly connected to blood circulation. The spleen is greatly involved in the immune response, especially against capsulated bacteria. Splenectomy plays a fundamental role in the treatment of numerous pediatric hematologic disorders. Taking into account all the possible complications (especially infections) linked to this procedure, alternatives to total splenectomy have been sought. Partial splenectomy has been proposed as a treatment that allows the reduction of infectious risk. This approach has proven safe and feasible in most patients, but multicentric and prospective studies are necessary to more accurately define the indications for performing partial splenectomy. However, vaccinations and antibiotic prophylaxis remain fundamental for preventing serious infections, even in the case of partial splenectomy. We review anatomical and functional properties of the spleen, with a focus on medical or surgical indications to splenectomy, aiming to give practical educational information to patients and their families after splenectomy. Furthermore, we discuss the feasibility of partial splenectomy in children with hematologic diseases who require splenectomy.
Effect of Two Kinds of Fertilizers on Growth and Rhizosphere Soil Properties of Bayberry with Decline Disease
Authors: Ren Haiying , Wang Hongyan , Yu Zheping , Zhang Shuwen , Qi Xingjiang , Sun Li , Wang Zhenshuo , Zhang Muchen , Ahmed Temoor , Li Bin
Published: November 2021

Decline disease causes severe damage to bayberry. However, the cause of this disease remains unclear. Interestingly, our previous studies found that the disease severity is related with the level of soil fertilizer. This study aims to explore the effect and mechanism of compound fertilizer (CF) and bio-organic fertilizer (OF) in this disease by investigating the vegetative growth, fruit characters, soil property, rhizosphere microflora and metabolites. Results indicated that compared with the disease control, CF and OF exhibited differential effect in plant healthy and soil quality, together with the increase in relative abundance of Burkholderia and Mortierella, and the reduction in that of Rhizomicrobium and Acidibacter, Trichoderma, and Cladophialophora reduced. The relative abundance of Geminibasidium were increased by CF (251.79%) but reduced by OF (13.99%). In general, the composition of bacterial and fungal communities in rhizosphere soil was affected significantly at genus level by exchangeable calcium, available phosphorus, and exchangeable magnesium, while the former two variables had a greater influence in bacterial communities than fungal communities. Analysis of GC-MS metabonomics indicated that compared to the disease control, CF and OF significantly changed the contents of 31 and 45 metabolites, respectively, while both fertilizers changed C5-branched dibasic acid, galactose, and pyrimidine metabolic pathway. Furthermore, a significant correlation was observed at the phylum, order and genus levels between microbial groups and secondary metabolites of bayberry rhizosphere soil. In summary, the results provide a new way for rejuvenation of this diseased bayberry trees.
Identification and Characterization of Citrus Concave Gum-Associated Virus Infecting Citrus and Apple Trees by Serological, Molecular and High-Throughput Sequencing Approaches
Authors: Minutolo Maria , Cinque Maria , Chiumenti Michela , Di Serio Francesco , Alioto Daniela , Navarro Beatriz
Published: November 2021

Citrus concave gum-associated virus (CCGaV) is a negative-stranded RNA virus, first reported a few years ago in citrus trees from Italy. It has been reported in apple trees in the USA and in Brazil, suggesting a wider host range and geographic distribution. Here, an anti-CCGaV polyclonal antiserum to specifically detect the virus has been developed and used in a standard double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) that has been validated as a sensitive and reliable method to detect this virus both in citrus and apple trees. In contrast, when the same antiserum was used in direct tissue-blot immunoassay, CCGaV was efficiently detected in citrus but not in apple. Using this antiserum, the first apple trees infected by CCGaV were identified in Italy and the presence of CCGaV in several apple cultivars in southern Italy was confirmed by field surveys. High-throughput sequencing (HTS) allowed for the assembling of the complete genome of one CCGaV Italian apple isolate (CE-c3). Phylogenetic analysis of Italian CCGaV isolates from apple and citrus and those available in the database showed close relationships between the isolates from the same genus (Citrus or Malus), regardless their geographical origin. This finding was further confirmed by the identification of amino acid signatures specific of isolates infecting citrus or apple hosts. Analysis of HTS reads also revealed that the CE-c3 Italian apple tree, besides CCGaV, was simultaneously infected by several viruses and one viroid, including apple rubbery wood virus 2 which is reported for the first time in Italy. The complete or almost complete genomic sequences of the coinfecting agents were determined.
Origin and Function of Structural Diversity in the Plant Specialized Metabolome
Authors: Desmet Sandrien , Morreel Kris , Dauwe Rebecca
Published: November 2021

The plant specialized metabolome consists of a multitude of structurally and functionally diverse metabolites, variable from species to species. The specialized metabolites play roles in the response to environmental changes and abiotic or biotic stresses, as well as in plant growth and development. At its basis, the specialized metabolism is built of four major pathways, each starting from a few distinct primary metabolism precursors, and leading to distinct basic carbon skeleton core structures: polyketides and fatty acid derivatives, terpenoids, alkaloids, and phenolics. Structural diversity in specialized metabolism, however, expands exponentially with each subsequent modification. We review here the major sources of structural variety and question if a specific role can be attributed to each distinct structure. We focus on the influences that various core structures and modifications have on flavonoid antioxidant activity and on the diversity generated by oxidative coupling reactions. We suggest that many oxidative coupling products, triggered by initial radical scavenging, may not have a function in se, but could potentially be enzymatically recycled to effective antioxidants. We further discuss the wide structural variety created by multiple decorations (glycosylations, acylations, prenylations), the formation of high-molecular weight conjugates and polyesters, and the plasticity of the specialized metabolism. We draw attention to the need for untargeted methods to identify the complex, multiply decorated and conjugated compounds, in order to study the functioning of the plant specialized metabolome.
Genetic Diversity, Pathogenicity and Pseudorecombination of Cucurbit-Infecting Begomoviruses in Malaysia
Authors: Chen Yu-Jeng , Lai Hsuan-Chun , Lin Chung-Cheng , Neoh Zhuan Yi , Tsai Wen-Shi
Published: November 2021

Cucurbits are important crops in the world. However, leaf curl disease constrains their production. Here, begomovirus diversity and pathogenicity associated with the disease in Malaysia were studied based on 49 begomovirus-detected out of 69 symptomatic plants from seven cucurbit crops in 15 locations during 2016 and 2017. The presence of Squash leaf curl China virus (SLCCNV) and Tomato leaf curl New Delhi virus (ToLCNDV) were confirmed by virus detection by polymerase chain reaction, viral DNA sequence analysis and specific detection of the viral components. ToLCNDV Malaysian isolates were further distinguished into strains A, B, C and D. Virus co-infection was detected in bitter gourd, bottle gourd and squash. Among them, eight bitter gourd samples were detected without SLCCNV DNA-A. However, one bottle gourd and five squash samples were without ToLCNDV DNA-B. Pseudorecombination of ToLCNDV DNA-A and SLCCNV DNA-B was detected in two bitter gourd samples. The pathogenic viruses and pseudorecombinants were confirmed by agroinoculation. The viral DNA-B influencing on symptomology and host range was also confirmed. The results strengthen the epidemic of cucurbit-infecting begomovirus in Malaysia as well as Southeast Asia. Especially, the natural pseudorecombinant of begomovirus that extends host range and causes severe symptom implies a threat to crops.
Foliar Sprayed Green Zinc Oxide Nanoparticles Mitigate Drought-Induced Oxidative Stress in Tomato
Authors: El-Zohri Manal , Al-Wadaani Naseem A. , Bafeel Sameera O.
Published: November 2021

This study explored the effectiveness of green zinc oxide nanoparticles (ZnO-NPs) foliar spray on tomato growth and oxidative stress relief under drought conditions. Tomato plant subjected to four water regimes (100, 75, 50, and 25% FC), and in the same while seedlings were sprayed with 25, 50, and 100 mg/L green ZnO-NPs. The results showed that tomato growth parameters reduced significantly by increasing drought stress levels, while ZnO-NPs enhanced plant growth under all studied drought levels. Out of three ZnO-NPs concentrations tested, 25 and 50 mg/L ZnO-NPs proved to be the optimum treatments for alleviating drought stress. They increased shoot and root biomass compared to untreated controls. Application of 25 and 50 mg/L ZnO-NPs enhanced shoot dry weight by about 2–2.5-fold, respectively, under severe drought conditions (25%) compared to ZnO-NPs untreated plants. The application of 25 and 50 mg/L green ZnO-NPs decreased the drought-induced oxidative stress as indicated by the reduction in malondialdehyde and hydrogen peroxide concentrations compared to untreated controls. While 100 mg/L ZnO-NPs further increased oxidative stress. The beneficial effects of ZnO-NPs were evident in the plants’ defensive state, in which the concentration of ascorbic acid, free phenols, and the activity of superoxide dismutase, catalase, and ascorbate peroxidase were maintained at higher levels compared to NPs-untreated plants. At severe drought conditions, 25 mg/L ZnO-NPs induced SOD, CAT, and APX activity by about 3.99-, 3.23-, and 2.82-fold of their corresponding controls, respectively. Likewise, at 25% FC, SOD, CAT, and APX activity increased with 50 mg/L ZnO-NPs by about 4.58-, 3.57-, and 3.25-fold consecutively compared with their respective controls. Therefore, foliar use of green ZnO-NPs at lower concentrations might be suggested as an efficient way for enhancing tomato tolerance to drought stress.