bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology and Physiology Response to Stratification during Seeds Epicotyl Dormancy Breaking of Paeonia emodi Wall. ex Royle
Authors: Wan Yingling , Zhang Min , Liu Aiqing , Yuan Qiuping , Liu Yan
Published: July 2022

Paeonia emodi is a type of wild herbaceous peony with high ornamental and breeding value. Cold stratification is the only method to break its seed epicotyl dormancy to date, however, the key physiological factors during this process are not clear. In this study, rooted seeds of P. emodi were treated with 4 °C stratification, and the changes of the embryo, four nutrients, and two endogenous hormones in the seeds were investigated. The results showed that the plumule elongated at S6 (i.e., ten weeks of cold stratification), and grew to nearly the same length as the cotyledon at S9. Cold stratification increased starch consumption, significantly decreased soluble sugar content in the later stages, and decreased soluble protein content at S9, but it did not influence crude fat content. The activities of α-amylase and β-amylase increased significantly at S4 and S4 to S6, respectively. At S8 and S9, acid protease activity increased, and the increase in lipase activity continued throughout the whole process. At the same time, the ABA content decreased significantly after S6; from this stage, the ABA/GA3 ratio gradually decreased compared with that of the control, and the difference was significant at S9. Correlation analysis showed that the ABA/GA3 ratio was significantly correlated with starch content and α-amylase activity. It can be concluded that both carbohydrates and proteins were the energy supply for the epicotyl dormancy breaking of P. emodi seeds, rather than crude fat. Cold stratification promoted substance transformation by increasing the corresponding enzyme activities. The balance of ABA and GA3 suggested the key stage for the release of dormancy.
Presence of Methicillin Resistant Staphylococcus aureus (MRSA) in Feces of the Small Indian Mongooses (Urva auropunctata) on Saint Kitts and Nevis, West Indies
Authors: Hoefer Andreas , Becker Anne A. M. J. , Moodley Arshnee , Boyen Filip , Butaye Patrick
Published: July 2022

Although, historically, Methicillin-Resistant Staphylococcus aureus (MRSA) was restricted to humans, since 2005 these strains emerged in livestock and wildlife. Therefore, a One Health approach was applied to analyze the diversity and characteristics of S. aureus strains isolated from the invasive species of mongoose (Urva auropunctata) in St. Kitts. Fecal samples collected from these animals (n = 81) were cultured on selective agar. The isolated S. aureus strains were identified using MALDI-TOF and further characterized by whole genome sequence analysis. The fecal microbiome study identified the presence of S. aureus in 5 animals. Both MSSA (n = 3) and MRSA (n = 2) strains were identified. The two MRSA isolated were nearly identical ST5 SCCmec IVa (2B) strains. The two MSSA isolated were a new ST7434, pertaining to clonal complex 30, and the other belonged to ST5, but unrelated to the MRSA ST5. The SCCmec IVa (2B) is, however, the main SCCmec in human MRSA of different STs identified in St Kitts, indicating potential horizontal transmission events. In conclusion, a new type of MSSA, ST7434, was found and MRSA ST5 t002 SCCmec IVa (2B) found its way into wildlife on a small Caribbean Island. Further One Health studies are necessary to determine the role of MRSA in wildlife.
Anti-Biofilm and Antibacterial Activities of Cycas media R. Br Secondary Metabolites: In Silico, In Vitro, and In Vivo Approaches
Authors: Attallah Nashwah G. M. , Al-Fakhrany Omnia Momtaz , Elekhnawy Engy , Hussein Ismail A. , Shaldam Moataz A. , Altwaijry Najla , Alqahtani Moneerah J. , Negm Walaa A.
Published: July 2022

Enterococcus species possess many virulence factors that have an essential role in exacerbating the infections caused by them. The current study aimed to evaluate the effect of the secondary metabolites ginkgetin (GINK) and sotetsuflavone (SOTE), isolated from Cycas media R. Br dichloromethane fraction, on Enterococcus faecalis (E. faecalis) isolates for the first time. The antibacterial and antivirulence activities of the isolated compounds were investigated using docking studies and in vitro by determination of the minimum inhibitory concentrations (MICs). Additionally, flow cytometry and scanning electron microscope (SEM) were utilized to assess the effect of SOTE on the tested bacteria. Moreover, crystal violet assay and qRT-PCR were used to test the effect of SOTE on the biofilm-forming ability of E. faecalis isolates. In addition, a systemic infection model was utilized in vivo to investigate the antibacterial activity of SOTE. We found that both GINK and SOTE showed a good affinity for the five proteins enrolled in the virulence of E. faecalis, with SOTE being the highest, suggesting the possible mechanisms for the antivirulence activity of both ligands. In addition, SOTE exhibited a higher antibacterial activity than GINK, as the values of the MICs of SOTE were lower than those of GINK. Thus, we performed the in vitro and in vivo assays on SOTE. However, they did not exhibit any significant variations (p > 0.05) in the membrane depolarization of E. faecalis isolates. Moreover, as evaluated by SEM, SOTE caused distortion and deformation in the treated cells. Regarding its impact on the biofilm formation, it inhibited the biofilm-forming ability of the tested isolates, as determined by crystal violet assay and qRT-PCR. The in vivo experiment revealed that SOTE resulted in a reduction of the inflammation of the liver and spleen with an increase in the survival rate. SOTE also improved the liver-function tests and decreased tumor necrosis factor-alpha using immunostaining and the inflammation markers, interleukins (IL-1β and IL-6), using ELISA. Thus, we can conclude that SOTE could be a promising compound that should be investigated in future preclinical and clinical studies.
Oxidative Stress: What Is It? Can It Be Measured? Where Is It Located? Can It Be Good or Bad? Can It Be Prevented? Can It Be Cured?
Authors: Azzi Angelo
Published: July 2022

The meaning, the appropriate usage and the misusage of the terms oxidative stress, oxidative eustress, and oxidative distress have been evaluated. It has been realized that the terms oxidative stress and oxidative damage are often used inappropriately as synonyms. The usage of the term eustress (intended as good stress) is unsuitable to indicate signaling by reactive molecular an event that can be finalistically considered either good or bad, depending on the circumstances. The so defined oxidative distress is an oxidative damage but not an oxidative stress. What is measured and defined as oxidative stress is in fact an oxidative damage. Damaging oxidations and signaling oxidant events (good or bad) can be present, also simultaneously, in different and multiple location of a cell, tissue or body and the measure of an oxidant event in body fluids or tissue specimen can only be the sum of non-separatable events, sometimes of opposite sign. There is no officially approved therapy to prevent or cure oxidative stress or oxidative damage.
Characterization and Encapsulation of Natural Antioxidants: Interaction, Protection, and Delivery
Authors: Cheng Hao , Liang Li
Published: July 2022

Natural antioxidants (e [...]
Leukocyte Telomere Length Variability as a Potential Biomarker in Patients with PolyQ Diseases
Authors: Scarabino Daniela , Veneziano Liana , Fiore Alessia , Nethisinghe Suran , Mantuano Elide , Garcia-Moreno Hector , Bellucci Gianmarco , Solanky Nita , Morello Maria , Zanni Ginevra , Corbo Rosa Maria , Giunti Paola
Published: July 2022

SCA1, SCA2, and SCA3 are the most common forms of SCAs among the polyglutamine disorders, which include Huntington’s Disease (HD). We investigated the relationship between leukocyte telomere length (LTL) and the phenotype of SCA1, SCA2, and SCA3, comparing them with HD. The results showed that LTL was significantly reduced in SCA1 and SCA3 patients, while LTL was significantly longer in SCA2 patients. A significant negative relationship between LTL and age was observed in SCA1 but not in SCA2 subjects. LTL of SCA3 patients depend on both patient’s age and disease duration. The number of CAG repeats did not affect LTL in the three SCAs. Since LTL is considered an indirect marker of an inflammatory response and oxidative damage, our data suggest that in SCA1 inflammation is present already at an early stage of disease similar to in HD, while in SCA3 inflammation and impaired antioxidative processes are associated with disease progression. Interestingly, in SCA2, contrary to SCA1 and SCA3, the length of leukocyte telomeres does not reduce with age. We have observed that SCAs and HD show a differing behavior in LTL for each subtype, which could constitute relevant biomarkers if confirmed in larger cohorts and longitudinal studies.
Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases
Authors: Jang Eungyeong
Published: July 2022

Hyperoside (Hyp), also known as quercetin-3-O-galactoside or 3-O-β-D-galactopyranosyl, is a well-known flavonol glycoside that is abundant in various fruits, vegetables, and medicinal plants. Hyp has been suggested to exhibit a wide range of biological actions, including cardiovascular, renal, neuroprotective, antifungal, antifibrotic, and anticancer effects. Accumulating evidence supports the pharmacological activities of Hyp in improving liver pathophysiology. Hence, the present literature review aims to summarize preclinical data suggesting the beneficial effects and underlying mechanisms of Hyp. In addition, our study focuses on hepatic antioxidant defense signaling to assess the underlying mechanisms of the biological actions of Hyp that are closely associated with liver diseases. Experimental findings from an up-to-date search showed that Hyp possesses hepatoprotective, antiviral, antisteatotic, anti-inflammatory, antifibrotic, and anticancer activities in cellular and animal models related to liver dysfunction by enhancing antioxidant responses. In particular, hepatocellular antioxidant defense via activation of erythroid-related nuclear factor 2 by Hyp chiefly explains how this compound acts as a therapeutic agent in liver diseases. Thus, this review emphasizes the therapeutic potential of Hyp as a strong antioxidative substance that plays a crucial role in the regulation of various liver disorders during their pathogenesis.
An Electrochemical Determination of the Total Reducing Capacity of Wheat, Spelt, and Rye Breads
Authors: Zielińska Danuta , Zieliński Henryk , Piskuła Mariusz Konrad
Published: July 2022

The most interesting activities associated with bread components such as phenolic compounds, fibre, tocols, or newly formed compounds in the Maillard reaction, are their reducing properties responsible for the formation of the overall reducing capacity of bread. Among the electrochemical methods, the cyclic voltammetry (CV) technique has been recently adapted for this purpose. In this study, the application of the CV assay for the determination of the total reducing capacity of flours, doughs, and breads as well as their crumbs and crusts, originated from wheat, spelt, and rye formulated on white flours (extraction rate of 70%) and dark flours (extraction rate of 100%) and baked at 200 °C for 35 min and at 240 °C for 30 min was addressed. The reducing capacity of hydrophilic extracts from white flours and breads as well as their crumbs and crusts showed double values when compared to that of lipophilic ones whilst hydrophilic and lipophilic extracts from dark breads and their parts revealed comparable levels. The dark wheat, spelt, and rye breads showed an approximately threefold higher total reducing capacity than white breads. Baking at higher temperature slightly increased the total reducing capacity of breads and the highest value was found for dark rye bread as well as its crust baked at 240 °C for 30 min. The cyclic voltammetry methodology showed to be especially suitable for screening the bread technology and allows for obtaining rapid electrochemical profiles of bread samples.
Human-Assisted vs. Deep Learning Feature Extraction: An Evaluation of ECG Features Extraction Methods for Arrhythmia Classification Using Machine Learning
Authors: Montenegro Larissa , Abreu Mariana , Fred Ana , Machado Jose M.
Published: July 2022

The success of arrhythmia classification tasks with Machine Learning (ML) algorithms is based on the handcrafting extraction of features from Electrocardiography (ECG) signals. However, feature extraction is a time-consuming trial-and-error approach. Deep Neural Network (DNN) algorithms bypass the process of handcrafting feature extraction since the algorithm extracts the features automatically in their hidden layers. However, it is important to have access to a balanced dataset for algorithm training. In this exploratory research study, we will compare the evaluation metrics among Convolutional Neural Networks (1D-CNN) and Support Vector Machines (SVM) using a dataset based on the merged public ECG signals database TNMG and CINC17 databases. Results: Both algorithms showed good performance using the new, merged ECG database. For evaluation metrics, the 1D-CNN algorithm has a precision of 93.04%, an accuracy of 93.07%, a recall of 93.20%, and an F1-score of 93.05%. The SVM classifier (λ = 10, C = 10 × 109) achieved the best classification metrics with two combined, handcrafted feature extraction methods: Wavelet transforms and R-peak Interval features, which achieved an overall precision of 89.04%, accuracy of 92.00%, recall of 94.20%, and F1-score of 91.54%. As an unique input feature and SVM (λ=10,C=100), wavelet transforms achieved precision, accuracy, recall, and F1-score metrics of 86.15%, 85.33%, 81.16%, and 83.58%. Conclusion: Researchers face a challenge in finding a broad dataset to evaluate ML models. One way to solve this problem, especially for deep learning models, is to combine several public datasets to increase the amount of data. The SVM and 1D-CNN algorithms showed positive results with the merge of databases, showing similar F1-score, precision, and recall during arrhythmia classification. Despite the favorable results for both of them, it should be considered that in the SVM, feature selection is a time-consuming trial-and-error process; meanwhile, CNN algorithms can reduce the workload significantly. The disadvantage of CNN algorithms is that it has a higher computational processing cost; moreover, in the absence of access to powerful computational processing, the SVM can be a reliable solution.
Singing Voice Detection in Electronic Music with a Long-Term Recurrent Convolutional Network
Authors: Romero-Arenas Raymundo , Gómez-Espinosa Alfonso , Valdés-Aguirre Benjamín
Published: July 2022

Singing Voice Detection (SVD) is a classification task that determines whether there is a singing voice in a given audio segment. While current systems produce high-quality results on this task, the reported experiments are usually limited to popular music. A Long-Term Recurrent Convolutional Network (LRCN) was adapted to detect vocals in a new dataset of electronic music to evaluate its performance in a different music genre and compare its results against those in other state-of-the-art experiments in pop music to prove its effectiveness across a different genre. Experiments on two datasets studied the impacts of different audio features and block size on LRCN temporal relationship learning, and the benefits of preprocessing on performance, and the results generate a benchmark to evaluate electronic music and its intricacies.
Ultraviolet-Assisted Modified Delignified Wood with High Transparency
Authors: Chen Xiaoli , Ge-Zhang Shangjie , Han Yu , Yang Hong , Ou-Yang Wenao , Zhu Haotong , Hao Junyi , Wang Jinxin
Published: July 2022

The substrate of solar cells with high haze, transparent, flexible, green and low coatings will be needed in the future. This paper reports a method for ultraviolet-assisted delignification of wood in an alkaline solution environment to improve the transmittance of “transparent wood”. Scanning electron microscope (SEM), X-ray diffraction image (XRD), Fourier transform infrared (FTIR) spectroscopy and transmittance-haze and chemical composition analysis were used to explore the mechanisms underlying the effect of ultraviolet-assisted lignin modification on the optical properties of “transparent wood”. The results show that UV-assisted delignification accelerates the rate of removal of lignin and chromogenic groups, which in turn improves the optical properties of the “transparent wood”, with UV-assisted lignin modification for 2 h increasing the light transmission of the “transparent wood” by 20%. UV-assisted delignification for 4 h and impregnation resulted in “transparent wood” with a transparency of 71% and a haze of 90%. This report provides a rapid and easy method to prepare high-quality “transparent wood”. The “transparent wood” with high transmittance and high haze is a potential candidate for transparent solar substrates. Meanwhile, this method is enlightening for high quality, fast and green preparation of other derived functional materials based on lignin wood.
Subduction Evolution Controlled Himalayan Orogenesis: Implications from 3-D Subduction Modeling
Authors: Zhu Weiling , Ding Lin , Ji Yingfeng , Qu Rui , Zhu Ye , Xie Chaodi , Zeng Deng
Published: July 2022

Himalayan orogenesis remains enigmatic in terms of Tibetan Plateau geodynamics originating from the Cenozoic India–Eurasian continental collision. India underthrusts below Tibet to the Yarlung–Tsangpo suture, which has been identified as the northernmost boundary for underplating. However, the way in which the historical evolution of continental subduction induces plateau uplift and the way it controls the variation in uplift between outboard and inboard areas is still unclear. To interpret the evolutionary mechanisms involved in the Himalayan growth history, we constructed different 3-D dynamic models at important stages to address these questions related to the formation of the Himalayas on the basis of paleoenthalpy evidence encoded in fossil leaves from recently documented assemblages in southern Tibet. The results show that (1) the effect of crustal thickening was the predominant factor in the early evolution from the Paleocene to the early Eocene, which resulted in a moderate growth rate. (2) The consecutive slab break-off eastward from the western syntaxis and the associated slab rebound significantly accelerated orogenesis from the late Eocene to the Oligocene. The upwelling asthenospheric flow was a key control of increasing crustal buoyancy, which resulted in the fastest growth of the Himalayas during the early Miocene. (3) Thereafter, the gradually enhanced monsoon and surface erosion during accompanying the increasing mountain height resulted in a slowdown of the orogenic rate, which counterbalanced the buoyant force produced by asthenospheric flow driving continuous Himalayan growth.
An Innovative, Green Cascade Protocol for Grape Stalk Valorization with Process Intensification Technologies
Authors: Salgado-Ramos Manuel , Tabasso Silvia , Calcio Gaudino Emanuela , Moreno Andrés , Mariatti Francesco , Cravotto Giancarlo
Published: July 2022

Valorization of agri-food residues to produce bio-based platform chemicals will enhance the transition to the bio-economy era. To this end, a sustainable process has been developed for the overall valorization of grape stalks (GS) according to a circular approach, starting from the lignin fraction to further deal with the cellulose-rich residue. This non-conventional protocol fully adheres to green chemistry principles, exploiting the so-called enabling technologies—mainly ultrasound and microwaves—for energy-saving innovative processes. Firstly, ultrasound-assisted extraction (UAE, 40 kHz, 200 W) demonstrated to be an excellent technique for GS delignification combined with natural deep eutectic solvents (NaDESs). Delignification enables isolation of the pertinent lignin framework and the potential to obtain a polyphenol-rich liquid fraction, focusing on the valorization of GS as source of bioactive compounds (BACs). Among the NaDESs employed, the combination of choline chloride (ChCl) and levulinic acid (LevA) (ChLevA) presented noteworthy results, enabling a delignification higher than 70%. LevA is one of the top-value biobased platform chemicals. In this work, a flash microwave (MW)-assisted process was subsequently applied to the cellulose-rich fraction remained after delignification, yielding 85% LevA. The regeneration of this starting compound to produce ChLevA can lead to a further biomass delignification cycle, thus developing a new cascade protocol for a full valorization of GS.
HTTP Adaptive Streaming Framework with Online Reinforcement Learning
Authors: Kang Jeongho , Chung Kwangsue
Published: July 2022

Dynamic adaptive streaming over HTTP (DASH) is an effective method for improving video streaming’s quality of experience (QoE). However, the majority of existing schemes rely on heuristic algorithms, and the learning-based schemes that have recently emerged also have a problem in that their performance deteriorates in a specific environment. In this study, we propose an adaptive streaming scheme that applies online reinforcement learning. When QoE degradation is confirmed, the proposed scheme adapts to changes in the client’s environment by upgrading the ABR model while performing video streaming. In order to adapt the adaptive bitrate (ABR) model to a changing network environment while performing video streaming, the neural network model is trained with a state-of-the-art reinforcement learning algorithm. The proposed scheme’s performance was evaluated using simulation-based experiments under various network conditions. The experimental results confirmed that the proposed scheme performed better than the existing schemes.
A Study of a Ride Comfort Control System for Ultra-Compact Vehicles Using Biometric Information
Authors: Ikeda Keigo , Kuroda Jyunpei , Uchino Daigo , Ogawa Kazuki , Endo Ayato , Kato Taro , Kato Hideaki , Narita Takayoshi
Published: July 2022

We investigated whether there is a correlation between the comfort felt by occupants and the comfort estimated from biological information obtained by experiments to improve the ride quality of an ultra-compact vehicle. A single frequency in the vertical direction can help to estimate occupant comfort. However, we hypothesized that the study of a single frequency was insufficient. We oscillated the occupants with vibrations containing multiple vibration frequencies and obtained biometric information. The vibration frequency was set based on the difference in ride quality felt by humans. Biometric information was obtained using a cerebral hemodynamic meter and electrocardiogram. Acquiring multiple types of biometric information helps to more accurately estimate the psychological state. After the experiment, we obtained a subjective evaluation of comfort against vibrations using the visual analog scale (VAS). The biometric information obtained by the experiment was cluster-analyzed, and experimental participants with similar characteristics of the biometric information were grouped. Multiple regression analysis was performed based on the values of the typical biometric information of the cluster. Comfort was estimated from biometric information using multiple regression analysis. A correlation was confirmed between measured and estimated VAS scores.
Differential Sensitivity of Two Leukemia Cell Lines towards Two Major Gas Plasma Products Hydrogen Peroxide and Hypochlorous Acid
Authors: Singer Debora , Miebach Lea , Bekeschus Sander
Published: July 2022

Oxidative stress has major implications for health and disease. At the same time, the term collectively describes the reactions to different types of reactive oxygen species (ROS) and oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). However, how both compare in terms of cytotoxicity and mechanism of action is less known. Using two leukemia cell lines, Jurkat and THP-1, as model systems at similar cell concentrations, we found an 8-fold greater sensitivity of the former over the latter for H2O2 exposure. Unexpectantly, this was not the case with HOCl exposure. Jurkat cells were 2-fold more resistant to HOCl-induced cytotoxicity than THP-1 cells. In each cell type, the relatively more toxic oxidant also induced activation of caspases 3 and 7 at earlier time points, as time-lapse fluorescence microscopy revealed. The effects observed did not markedly correlate with changes in intracellular GSH and GSSG levels. In addition, siRNA-mediated knockdown of the Nrf2 target HMOX-1 encoding for HO-1 protein and the growth and survival factor IL-8 revealed Jurkat cells to become more sensitive to HOCl, while HO-1 and IL-8 siRNA-mediated knockdown in THP-1 cells produced greater sensitivity towards H2O2. siRNA-mediated knockdown of catalase increased oxidant sensitivity only negligibly. Collectively, the data suggest striking HOCl-resistance of Jurkat and H2O2 resistance of THP-1 cells, showing similar protective roles of HO-1 and IL-8, while caspase activation kinetics differ.
Comparison of Ambient Air Quality among Industrial and Residential Areas of a Typical South Asian City
Authors: Zahra Syeda Iram , Iqbal Muhammad Javid , Ashraf Sobia , Aslam Afifa , Ibrahim Muhammad , Yamin Muhammad , Vithanage Meththika
Published: July 2022

The rapid increase in population growth due to industrialization and urbanization has resulted in air quality deterioration in Pakistan. Consequently, a considerable increase has been seen in the types of sources of air pollutants. However, the air quality of the country has deteriorated in the absence of management capabilities against air quality. Evidence from numerous governmental organizations and international bodies has specified that the environment, health, and quality of life are at high risk due to air pollution. Although the government of Pakistan established the Pakistan Clean Air Program, along with continuous monitoring stations to manage the quality of ambient air, air quality values have not yet been achieved. The present investigations were made in the city of Faisalabad in selected locations. Sampling of a 24 h average was done for selected sites. The air quality parameters such as NO2, SO2, COx, O2, noise level, and suspended particulate matter (SPM) were measured at two locations, i.e., Khurrianwala and Liaqatabad in the Faisalabad District. The measured values of air quality parameters were compared with national environmental quality standards (NEQS). Air pollutants such as SPM, SO2, and noise levels were found to be significantly higher than the 24-h standards of NEQS, which poses harmful effects on the quality of air and health, whereas the O2 concentration was found to be lower than the normal values, and NO2 and COx values were normal. The SO2, CO2, noise level, SPM, and O2 values ranged from 418–652 and 423–661 µg/m3, 3.03–3.44 and 3.08–3.51 mg/m3, 68–73 and 69–75 dB, 555–667 and 581–682 µg/m3, and 19.5–20 and 19.5–20.3 % for summer and winter season, respectively, as compared to standard values (150 µg/m3, 10 mg/m3, 65 dB, 550 µg/m3 and 21%). After the complete analysis of the selected locations, it was concluded that the ambient air quality of this area is severely degraded due to industrial as well as other commercial activities. These significant variations in air quality parameters suggest that there is a need to check the air quality regularly to take appropriate measures for reducing ambient air pollutants, especially in industrial areas as well as commercial areas.
Combining Students’ Grades and Achievements on the National Assessment of Knowledge: A Fuzzy Logic Approach
Authors: Doz Daniel , Felda Darjo , Cotič Mara
Published: July 2022

Although the idea of evaluating students’ mathematical knowledge with fuzzy logic is not new in the literature, few studies have explored the possibility of assessing students’ mathematical knowledge by combining teacher-assigned grades (i.e., school grades) with students’ achievements on standardized tests (e.g., national assessments). Thus, the present study aims to investigate the use of fuzzy logic to generate a novel assessment model, which combines teacher-assigned mathematics grades with students’ results on the Italian National Assessment of Mathematical Knowledge (INVALSI). We expanded the findings from previous works by considering a larger sample, which included more than 90,000 students attending grades 8, 10, and 13. The results showed that the tested model led to a lower assessment score compared to the traditional grading method based on teacher’s evaluation. Additionally, the use of fuzzy logic across the examined school levels yielded similar results, suggesting that the model is adequate among different educational levels.
Numerical Parametric Investigation of Nonaqueous Vanadium Redox Flow Batteries
Authors: Huang Shaopei , Lu Yujuan
Published: July 2022

Nonaqueous redox flow batteries are promising candidates for large-scale energy storage technologies. However, the effect of structural design and key factors limiting the performance are still not thoroughly understood. In this work, we constructed a physical model to study the effect of various design parameters on the performance of such a battery. It was found that the kinetics of redox reaction was improved with active material concentration and electrode surface area. The modeling results also showed that the local current density was much higher in the vicinity of membrane than near the current collector due to relatively low ionic conductivity of electrolytes. Furthermore, decreasing the electrode thickness and increasing the membrane conductivity both reduced the voltage loss associated with ohmic resistance, thereby resulting in improved battery performance. The obtained numerical simulation results would be helpful not only for understanding the physicochemical process in nonaqueous vanadium flow batteries but also for future structural optimization of these batteries.
Molecular Biomarkers in Cancer
Authors: Sarhadi Virinder Kaur , Armengol Gemma
Published: July 2022

Molecular cancer biomarkers are any measurable molecular indicator of risk of cancer, occurrence of cancer, or patient outcome. They may include germline or somatic genetic variants, epigenetic signatures, transcriptional changes, and proteomic signatures. These indicators are based on biomolecules, such as nucleic acids and proteins, that can be detected in samples obtained from tissues through tumor biopsy or, more easily and non-invasively, from blood (or serum or plasma), saliva, buccal swabs, stool, urine, etc. Detection technologies have advanced tremendously over the last decades, including techniques such as next-generation sequencing, nanotechnology, or methods to study circulating tumor DNA/RNA or exosomes. Clinical applications of biomarkers are extensive. They can be used as tools for cancer risk assessment, screening and early detection of cancer, accurate diagnosis, patient prognosis, prediction of response to therapy, and cancer surveillance and monitoring response. Therefore, they can help to optimize making decisions in clinical practice. Moreover, precision oncology is needed for newly developed targeted therapies, as they are functional only in patients with specific cancer genetic mutations, and biomarkers are the tools used for the identification of these subsets of patients. Improvement in the field of cancer biomarkers is, however, needed to overcome the scientific challenge of developing new biomarkers with greater sensitivity, specificity, and positive predictive value.
Structures and Biological Activities of Alkaloids Produced by Mushrooms, a Fungal Subgroup
Authors: Zorrilla Jesús G. , Evidente Antonio
Published: July 2022

Alkaloids are a wide family of basic N-containing natural products, whose research has revealed bioactive compounds of pharmacological interest. Studies on these compounds have focused more attention on those produced by plants, although other types of organisms have also been proven to synthesize bioactive alkaloids, such as animals, marine organisms, bacteria, and fungi. This review covers the findings of the last 20 years (2002–2022) related to the isolation, structures, and biological activities of the alkaloids produced by mushrooms, a fungal subgroup, and their potential to develop drugs and agrochemicals. In some cases, the synthesis of the reviewed compounds and structure−activity relationship studies have been described.
Association between Height and Hypertension: A Retrospective Study
Authors: Shimizu Yuji , Hayakawa Hidenobu , Sasaki Nagisa , Takada Midori , Okada Takeo , Kiyama Masahiko
Published: July 2022

Height loss starting in middle age is reported to be an independent risk factor for cardiovascular mortality. Recent studies have revealed an inverse association between height and hypertension, but the influence of hypertension on height loss is unknown. Since hypertension is an established cardiovascular risk factor, clarifying the association between baseline hypertension and height loss could lead to an efficient tool to estimate the risk of mortality. A retrospective study of 11,154 Japanese aged 40–74 years was conducted. Height loss was defined as being in the highest quintile of annual height decrease (≥2.015 mm/year for men and ≥1.756 mm/year). Baseline height was significantly inversely associated with incident hypertension for men only. The adjusted odds ratio (OR) and 95% confidence interval (CI) for incident hypertension for each 1 standard deviation increment of height (5.9 cm for men and 5.6 cm for women) was 0.90 (0.84, 0.97) for men and 1.07 (0.91, 1.26) for women, respectively. We also found that baseline hypertension is independently positively associated with height loss for men only. The adjusted OR was 1.25 (1.11, 1.42) for men and 0.93 (0.71, 1.21) for women. These results might lead to an efficient tool for estimating the risk of height loss, which has been reported to be associated with a higher risk of mortality in adults.
VEGF-A and FGF4 Engineered C2C12 Myoblasts and Angiogenesis in the Chick Chorioallantoic Membrane
Authors: Kennedy Donna C. , Wheatley Antony M. , McCullagh Karl J. A.
Published: July 2022

Angiogenesis is the formation of new blood vessels from pre-existing vessels. Adequate oxygen transport and waste removal are necessary for tissue homeostasis. Restrictions in blood supply can lead to ischaemia which can contribute to disease pathology. Vascular endothelial growth factor (VEGF) is essential in angiogenesis and myogenesis, making it an ideal candidate for angiogenic and myogenic stimulation in muscle. We established C2C12 mouse myoblast cell lines which stably express elevated levels of (i) human VEGF-A and (ii) dual human FGF4-VEGF-A. Both stably transfected cells secreted increased amounts of human VEGF-A compared to non-transfected cells, with the latter greater than the former. In vitro, conditioned media from engineered cells resulted in a significant increase in endothelial cell proliferation, migration, and tube formation. In vivo, this conditioned media produced a 1.5-fold increase in angiogenesis in the chick chorioallantoic membrane (CAM) assay. Delivery of the engineered myoblasts on Matrigel demonstrated continued biological activity by eliciting an almost 2-fold increase in angiogenic response when applied directly to the CAM assay. These studies qualify the use of genetically modified myoblasts in therapeutic angiogenesis for the treatment of muscle diseases associated with vascular defects.
Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma
Authors: Sundqvist Benjamin , Kilpinen Sami , Böhling Tom , Koljonen Virve , Sihto Harri
Published: July 2022

Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. Methods: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. Results: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response. Conclusion: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.
A Pilot Study: Favorable Effects of Clostridium butyricum on Intestinal Microbiota for Adjuvant Therapy of Lung Cancer
Authors: Cong Jing , Zhang Chuantao , Zhou Siyu , Zhu Jingjuan , Liang Chengwei
Published: July 2022

Probiotics as medications have previously been shown to change intestinal microbial characteristics, potentially influencing cancer therapy efficacy. Patients with non-squamous non-small cell lung cancer (NS-NSCLC) treated by bevacizumab plus platinum-based chemotherapy were randomized to obtain Clostridium butyricum supplement (CBS) or receive a placebo as adjuvant therapy. Clinical efficacy and safety were assessed using progression-free survival (PFS), overall survival (OS), and adverse events (AE). Intestinal microbiota was longitudinally explored between CBS and placebo groups over time. Patients who took CBS had significantly decreased bacterial richness and abundance, as well as increased the total richness of the genus Clostridium, Bifidobacterium, and Lactobacillus compared to the placebo group (p < 0.05). Beta diversity and the interactional network of intestinal microbiota were distinctly different between CBS and placebo group. However, there were no significant variations between them in terms of microbial taxonomical taxa and alpha diversity. The potential opportunistic pathogen Shewanella was still detectable after treatment in the placebo group, while no distinguishing microbial markers were found in the CBS group. In terms of clinical efficacy, the CBS group had a significantly reduced AE compare to the placebo group (p < 0.05), although no significantly longer PFS and OS. Therefore, favorable modifications in intestinal microbiota and significant improvements in drug safety make probiotics be promising adjunctive therapeutic avenues for lung cancer treatment.
Update in Pathogenesis, Diagnosis, and Therapy of Prolactinoma
Authors: Fukuhara Noriaki , Nishiyama Mitsuru , Iwasaki Yasumasa
Published: July 2022

Prolactinomas comprise 30–50% of all pituitary neuroendocrine tumors, frequently occur in females aged 20 to 50, and cause hypogonadism and infertility. In typical cases, female patients exhibit galactorrhea and amenorrhea due to serum prolactin (PRL) elevation, and patients during pregnancy should be carefully treated. During diagnosis, other causes of hyperprolactinemia must be excluded, and an MRI is useful for detecting pituitary neuroendocrine tumors. For treating prolactinoma, dopamine agonists (DAs) are effective for decreasing PRL levels and shrinking tumor size in most patients. Some DA-resistant cases and the molecular mechanisms of resistance to a DA are partially clarified. The side effects of a DA include cardiac valve alterations and impulse control disorders. Although surgical therapies are invasive, recent analysis shows that long-term remission rates are higher than from medical therapies. The treatments for giant or malignant prolactinomas are challenging, and the combination of medication, surgery, and radiation therapy should be considered. Regarding pathogenesis, somatic SF3B1 mutations were recently identified even though molecular mechanisms in most cases of prolactinoma have not been elucidated. To understand the pathogenesis of prolactinomas, the development of new therapeutic approaches for treatment-resistant patients is expected. This review updates the recent advances in understanding the pathogenesis, diagnosis, and therapy of prolactinoma.
Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Arshad Haroon , Siokis Anastasios , Franke Raimo , Habib Aamna , Alfonso Juan Carlos López , Poliakova Yuliya , Lücke Eva , Michaelis Katina , Brönstrup Mark , Meyer-Hermann Michael , Bilitewski Ursula , Vila Jordi , Abel Laurent , Illig Thomas , Schreiber Jens , Pessler Frank
Published: July 2022

Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD.
The Challenge of Risk Assessment of Tetrahydrocannabinol (THC) in Cannabidiol (CBD) Oils and Food Supplements: An Approach for Deriving Maximum Limits
Authors: Schweikle Sandra , Golombek Patricia , Sproll Constanze , Walch Stephan G. , Lachenmeier Dirk W.
Published: July 2022

Information about unsafe foods or feeds must be exchanged between European Union (EU) member states as quickly as possible. This is why the EU’s Rapid Alert System for Food and Feed (RASFF) exists. It helps to ensure that products that may be harmful to health do not enter the market or can be specifically withdrawn from the market. Different notifications are used depending on the risk and urgency. This article provides an overview of the 61 notifications in the RASFF between 2020 and 2022 on the Δ9-tetrahydrocannabinol (Δ9-THC) content in cannabidiol (CBD) oils and CBD food supplements. These products are available on the EU market despite the lack of novel food approval. Δ9-THC is a naturally occurring psychotropic compound extracted from the hemp plant Cannabis sativa that can have adverse effects on consumers (such as drowsiness, dizziness, tachycardia, or changes in blood pressure). In a previous German national survey, 23 of the 125 products tested (18%) exceeded the lowest observed adverse effect level (LOAEL) of Δ9-THC. In comparison, for products identified as a serious risk in the RASFF, the Δ9-THC concentrations were generally higher (up to 2410 mg/kg) and 14 of 34 products (41%) exceeded the LOAEL. Considering these data, a threshold of 500 mg/kg (0.05%) may be proposed to define a serious risk, as the LOAEL would not be exceeded in typical consumption scenarios below this level and serious risks, as well as narcotic effects in the product group of food supplements, could be excluded. This threshold could be used in the interim until the full toxicological assessment is available within the novel food approval procedure.
Review of Helical Magnetic Structures in Magnetic Microwires
Authors: Chizhik Alexander , Gonzalez Julian , Zhukov Arcady , Gawronski Przemyslaw
Published: July 2022

We provide an overview of the helical magnetic structures in magnetic microwires. Having analyzed the experimental data describing the magnetic behavior of magnetic microwires since the 1990s, we found indirect evidence of the existence of various types of helical magnetic structures. Purposeful research has allowed us to discover the spiral magnetic structure as one of the most unusual helical structures. A comparison of the spiral structure with another type of helical structure—elliptical—was carried out. In the analysis, emphasis was placed on the length of the domain wall as one of the most important parameters. The difference in the dynamic properties of the spiral and elliptical domain walls has been demonstrated.
Heat Vulnerability Index Mapping: A Case Study of a Medium-Sized City (Amiens)
Authors: Qureshi Aiman Mazhar , Rachid Ahmed
Published: July 2022

Urbanization, anthropogenic activities, and social determinants such as poverty and literacy rate greatly contribute to heat-related mortalities. The 2003 strong heat wave (Lucifer) in France resulted in catastrophic health consequences in the region that may be attributed to urbanization and other anthropogenic activities. Amiens is a medium-sized French city, where the average temperature has increased since the year 2000. In this study, we evaluated the Heat Vulnerability Index (HVI) in Amiens for extreme heat days recorded during three years (2018–2020). We used the principal component analysis (PCA) technique for fine-scale vulnerability mapping. The main types of considered data included (a) socioeconomic and demographic data, (b) air pollution, (c) land use and cover, (d) elderly heat illness, (e) social vulnerability, and (f) remote sensing data (land surface temperature (LST), mean elevation, normalized difference vegetation index (NDVI), and normalized difference water index (NDWI)). The output maps identified the hot zones through comprehensive GIS analysis. The resultant maps showed that high HVI exists in three typical areas: (1) areas with dense population and low vegetation, (2) areas with artificial surfaces (built-up areas), and (3) industrial zones. Low-HVI areas are in natural landscapes such as rivers and grasslands. Our analysis can be implemented in other cities to highlight areas at high risk of extreme heat and air pollution.