bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hybrid Deep Learning Model for Air Quality Prediction Based on the Time–Frequency Domain Relationship
Authors: Xu Rui , Wang Deke , Li Jian , Wan Hang , Shen Shiming , Guo Xin
Published: February 2023

Deep learning models have been widely used in time-series numerical prediction of atmospheric environmental quality. The fundamental feature of this application is to discover the correlation between influencing factors and target parameters through a deep network structure. These relationships in original data are affected by several different frequency factors. If the deep network is adopted without guidance, these correlations may be masked by entangled multifrequency data, which will cause the problem of insufficient correlation feature extraction and difficult model interpretation. Because the wavelet transform has the ability to separate these entangled multifrequency data, and these correlations can be extracted by deep learning methods, a hybrid model combining wavelet transform and transformer-like (WTformer) was designed to extract time–frequency domain features and prediction of air quality. The 2018–2021 hourly data in Guilin was used as the benchmark training dataset. Pollutants and meteorological variables in the local dataset are decomposed into five frequency bands by wavelet. The analysis of the WTformer model showed that particulate matter (PM2.5 and PM10) had an obvious correlation in the low-frequency band and a low correlation in the high-frequency band. PM2.5 and temperature had a negative correlation in the high-frequency band and an obvious positive correlation in the low-frequency band. PM2.5 and wind speed had a low correlation in the high-frequency band and an obvious negative correlation in the low-frequency band. These results showed that the laws of variables in the time–frequency domain could be found by the model, which made it possible to explain the model. The experimental results show that the prediction performance of the established model was better than that of multilayer perceptron (MLP), one-dimensional convolutional neural network (1D-CNN), gate recurrent unit (GRU), long short-term memory (LSTM) and Transformer, in all time steps (1, 4, 8, 24 and 48 h).
Research on Temporal and Spatial Distribution of Carbon Emissions from Urban Buses Based on Big Data Analysis
Authors: Long Yan , Zhu Changzheng , Zhang Cong , Pan Renjie
Published: February 2023

In recent years, global warming has become increasingly severe, and the ecological and environmental problems facing mankind have become increasingly serious. As the main areas of transportation activities, cities are also the main places of carbon emissions. As a necessary condition for human’s daily-life travel, it is particularly important to calculate the carbon emissions from urban transportation. Due to the different characteristics of economy and population in different regions of a city, the carbon emissions of urban buses show different characteristics in terms of temporal and spatial distribution. The developments of science and technology promote the application of big data analysis to specific practical life, enabling people to research and solve problems from a new perspective. This paper uses the GPS data of urban buses in Sanya City, China, to identify operation conditions from urban buses, and calculates the distance and time under different conditions. Based on the measured data of carbon emissions, this paper visualizes the distribution characteristics of carbon emissions by density analysis; explains the time distribution characteristics by the visual analysis of carbon emissions in different time periods, working days and rest days, and different energy types; and illustrates the spatial distribution characteristics by the spatial distributions of carbon emissions from Sanya’s buses on working days and rest days, as well as in different routes, providing reference for a low-carbon development of urban green transport.
Analysis of Gravity Wave Characteristics during a Hailstone Event in the Cold Vortex of Northeast China
Authors: Wang Xiujuan , Ran Lingkun , Qi Yanbin , Jiang Zhongbao , Yun Tian , Jiao Baofeng
Published: February 2023

Based on high-resolution pressure data collected by a microbarograph and Fourier transform (FFT) data processing, a detailed analysis of the frequency spectra characteristics of gravity waves during a hailstone event in the cold vortex of Northeast China (NECV) on 9 September 2021 is presented. The results show that the deep NECV served as the large-scale circulation background for the hailstone event. The development of hailstones was closely related to gravity waves. In different hail stages, the frequency spectra characteristics of gravity waves were obviously different. One and a half hours before hailfall, there were gravity wave precursors with periods of 50–180 min and corresponding amplitudes ranging from 30 to 60 Pa. During hailfall, the center amplitudes of the gravity waves were approximately 50 Pa and 60 Pa, with the corresponding period ranges expanding to 60–70 min and 160–240 min. Simultaneously, hailstones initiated shorter periods (26–34 min) of gravity waves, with the amplitudes increasing to approximately 12–18 Pa. The relationship between hailstones and gravity waves was positive. After hailfall, gravity waves weakened and dissipated rapidly. As shown by the reconstructed gravity waves, key periods of gravity wave precursors ranged from 50–180 min, which preceded hailstones by several hours. When convection developed, there was thunderstorm high pressure and an outflow boundary. The airflow converged and diverged downstream, resulting in the formation of gravity waves and finally triggering hailfall. Gravity wave predecessors are significant for hail warnings and artificial hail suppression.
Parameter Estimation Analysis in a Model of Honey Production
Authors: Atanasov Atanas Z. , Georgiev Slavi G. , Vulkov Lubin G.
Published: February 2023

Honeybee losses are an extensive global problem. In this study, a new compartment model of honeybee population that mainly concerns honey production is developed. The model describes the interaction of the food stock with the brood (immature bees), adult bees and produced honey. In the present paper, the issue of an adequate model recovery is addressed and the parameter identification inverse problem is solved. An adjoint equation procedure to obtain the unknown parameter values by minimizing the functional error during a period of time is proposed. Numerical simulations with realistic data are discussed.
Pseudo-Quasi Overlap Functions and Related Fuzzy Inference Methods
Authors: Jing Mei , Zhang Xiaohong
Published: February 2023

The overlap function, a particular kind of binary aggregate function, has been extensively utilized in decision-making, image manipulation, classification, and other fields. With regard to overlap function theory, many scholars have also obtained many achievements, such as pseudo-overlap function, quasi-overlap function, semi-overlap function, etc. The above generalized overlap functions contain commutativity and continuity, which makes them have some limitations in practical applications. In this essay, we give the definition of pseudo-quasi overlap functions by removing the commutativity and continuity of overlap functions, and analyze the relationship of pseudo-t-norms and pseudo-quasi overlap functions. Moreover, we present a structure method for pseudo-quasi overlap functions. Then, we extend additive generators to pseudo-quasi overlap functions, and we discuss additive generators of pseudo-quasi overlap functions. The results show that, compared with the additive generators generated by overlap functions, the additive generators generated by pseudo-quasi overlap functions have fewer restraint conditions. In addition, we also provide a method for creating quasi-overlap functions by utilizing pseudo-t-norms and pseudo automorphisms. Finally, we introduce the idea of left-continuous pseudo-quasi overlap functions, and we study fuzzy inference triple I methods of residual implication operators induced by left-continuous pseudo-quasi overlap functions. On the basis of the above, we give solutions of pseudo-quasi overlap function fuzzy inference triple I methods based on FMP (fuzzy modus ponens) and FMT (fuzzy modus tollens) problems.
Quadratic-Phase Hilbert Transform and the Associated Bedrosian Theorem
Authors: Srivastava Hari M. , Shah Firdous A. , Qadri Huzaifa L. , Lone Waseem Z. , Gojree Musadiq S.
Published: February 2023

The Hilbert transform is a commonly used linear operator that separates the real and imaginary parts of an analytic signal and is employed in various fields, such as filter design, signal processing, and communication theory. However, it falls short in representing signals in generalized domains. To address this limitation, we propose a novel integral transform, coined the quadratic-phase Hilbert transform. The preliminary study encompasses the formulation of all the fundamental properties of the generalized Hilbert transform. Additionally, we examine the relationship between the quadratic-phase Fourier transform and the proposed transform, and delve into the convolution theorem for the quadratic-phase Hilbert transform. The Bedrosian theorem associated with the quadratic-phase Hilbert transform is explored in detail. The validity and accuracy of the obtained results were verified through simulations.
New Conditions for Testing the Asymptotic and Oscillatory Behavior of Solutions of Neutral Differential Equations of the Fourth Order
Authors: Nabih Amany , Moaaz Osama , AlNemer Ghada , Elabbasy Elmetwally M.
Published: February 2023

In this work, in the noncanonical case, we find new properties for a class of positive solutions of fourth-order differential equations. These properties allow us to obtain iterative criteria that exclude positive decreasing solutions, and we then establish sufficient conditions to guarantee that all solutions to the examined equation oscillate. The importance of applying the results to a special case of the investigated equation is demonstrated.
A New Framework for Numerical Techniques for Fuzzy Nonlinear Equations
Authors: Abbasi Fazlollah , Allahviranloo Tofigh , Akram Muhammad
Published: February 2023

This paper describes a computational method for solving the nonlinear equations with fuzzy input parameters that we encounter in engineering system analysis. In addition to discussing the existence of solutions, the definition and formalization of numerical solutions is based on a new fuzzy computation operation as a transmission average. Error analysis in numerical solutions is described. Finally, some examples are presented to implement the proposed method and its effectiveness compared to other previous methods.
Impact of Goodwill on Consumer Buying through Advertising in a Segmented Market: An Optimal Control Theoretic Approach
Authors: Kumar Pradeep , Chaudhary Kuldeep , Kumar Vijay , Chauhan Sudipa
Published: February 2023

Market segmentation is one of the key marketing activities to target the potential market for a product, which allows the firm to have a better understanding of their customers. This paper considers an optimal control problem to determine the dynamic price and advertising policies of a new product introduction in a segment-specific market incorporating advertising-based goodwill. Under differentiated advertising and single-channel advertising, advertising efforts increase the stock of goodwill in each segment. Single-channel advertising starts in all segments with a fixed segment spectrum, while the differentiated advertising process deals with each segment independently. The explicit optimal dynamic advertising effort and price strategies are obtained by applying Pontryagin’s maximum principle, and local stability of equilibria have also been examined. The effectiveness of the proposed method is validated through numerical examples, and a local sensitivity analysis is performed to find the sensitive parameters that can affect the optimal values of price and advertising effort rates.
Influence of Switching on the Aging of High Energy Lithium-Ion Cells
Authors: Straßer Xenia , Ngaleu Guy Williams , Hanzl Christian , Azzam Mohamed , Endisch Christian , Lewerenz Meinert
Published: February 2023

An AC-battery or multilevel inverter used to increase safety and flexibility is realizable by switching the cells and modules on and off in a defined way and thus can replace the bidirectional converter. Assessing possible additional aging due to switching, the results of a previous study for a high-power optimized cell showed no influence on the current rates or the switching. In this paper, a highly energy-optimized LG 18650-cell is investigated to discuss the influence of switching during the charge and discharge process, respectively, as well as combining both processes together with clear performance differences when applying higher charge and discharge currents. Moreover, the influence of switching is discussed for the two frequencies (50 Hz and 10 kHz) and different duty cycles. The aging is analyzed by capacity loss and resistance increase, by dV/dQ analysis, and by electrochemical impedance spectroscopy. We found no clear negative influence of switching but a positive effect if the cells are switched during charge. The best performance is found for switching during charge as well as during discharge. The cell aging during switching is clearly determined by the average and not the maximum current applied. This work shows no negative effects of multilevel inverter applications on the tested cells.
Investigation of Genome Biology by Synthetic Genome Engineering
Authors: Zhang Hui , Xiong Yao , Xiao Wenhai , Wu Yi
Published: February 2023

Synthetic genomes were designed based on an understanding of natural genomic information, offering an opportunity to engineer and investigate biological systems on a genome-wide scale. Currently, the designer version of the M. mycoides genome and the E. coli genome, as well as most of the S. cerevisiae genome, have been synthesized, and through the cycles of design–build–test and the following engineering of synthetic genomes, many fundamental questions of genome biology have been investigated. In this review, we summarize the use of synthetic genome engineering to explore the structure and function of genomes, and highlight the unique values of synthetic genomics.
Influence of Inlet Boundary Conditions on the Prediction of Flow Field and Hemolysis in Blood Pumps Using Large-Eddy Simulation
Authors: Xiang Wen-Jing , Huo Jia-Dong , Wu Wei-Tao , Wu Peng
Published: February 2023

Inlet boundary conditions (BC) are one of the uncertainties which may influence the prediction of flow field and hemolysis in blood pumps. This study investigated the influence of inlet BC, including the length of inlet pipe, type of inlet BC (mass flow rate or experimental velocity profile) and turbulent intensity (no perturbation, 5%, 10%, 20%) on the prediction of flow field and hemolysis of a benchmark centrifugal blood pump (the FDA blood pump) and a commercial axial blood pump (Heartmate II), using large-eddy simulation. The results show that the influence of boundary conditions on integral pump performance metrics, including pressure head and hemolysis, is negligible. The influence on local flow structures, such as velocity distributions, mainly existed in the inlet. For the centrifugal FDA blood pump, the influence of type of inlet BC and inlet position on velocity distributions can also be observed at the diffuser. Overall, the effects of position of inlet and type of inlet BC need to be considered if local flow structures are the focus, while the influence of turbulent intensity is negligible and need not be accounted for during numerical simulations of blood pumps.
Renal Microcirculation Injury as the Main Cause of Ischemic Acute Kidney Injury Development
Authors: Kwiatkowska Ewa , Kwiatkowski Sebastian , Dziedziejko Violetta , Tomasiewicz Izabela , Domański Leszek
Published: February 2023

Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules–peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5–10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin–angiotensin–aldosterone system.
Alleviation of Hyperuricemia by Strictinin in AML12 Mouse Hepatocytes Treated with Xanthine and in Mice Treated with Potassium Oxonate
Authors: Huang Kuo-Ching , Chang Yu-Ting , Pranata Rosita , Cheng Yung-Hsuan , Chen Yu-Chi , Kuo Ping-Chung , Huang Yi-Hsuan , Tzen Jason T. C. , Chen Rong-Jane
Published: February 2023

Hyperuricemia, an abnormally high level of blood uric acid, is a major risk factor for gout. Although xanthine oxidase inhibitors were clinically used to lower blood uric acid level, the concerned side effects restricted their utilization. In this study, strictinin, an abundant polyphenol in Pu’er tea, was evaluated for its preventive effects on hyperuricemia. The results showed that the xanthine oxidase activity, uric acid production, and inflammation in AML12 mouse hepatocytes treated with xanthine were significantly reduced by the supplementation of strictinin. Detailed analyses revealed that strictinin inhibited xanthine-induced NLRP3 inflammasome activation. Consistently, the elevated blood uric acid level and the enhanced xanthine oxidase activity in mice treated with potassium oxonate were effectively diminished by strictinin supplementation. Moreover, for the first time, strictinin was found to promote healthy gut microbiota. Overall, strictinin possesses a great potential to be utilized as a functional ingredient for the prevention of hyperuricemia.
DnFCA Isoforms Cooperatively Regulate Temperature-Related Flowering in Dendrobium nobile
Authors: Pan Ting , Deng Ning-Meng , Guo Wu-Xia , Wan Min-Zhen , Zheng Yan-Tong , Chen Song-Yi , Liu Chuan-Liang , Li Hong-Bo , Liang Shan
Published: February 2023

Timely flowering is a determinative trait for many economically valuable species in the Dendrobium genus of the Orchidaceae family, some of which are used for ornamental and medicinal purposes. D. nobile, a representative species of nobile-type Dendrobium, normally flowers in spring after exposure to sufficient low temperatures in winter. However, flowering can be stopped or disrupted by the untimely application of high temperatures. Little is known about the regulation and the mechanisms behind this switch. In this study, we report two isoforms from the KFK09_017173 locus of the D. nobile genome, named DnFCAγ and DnFCAβ, respectively, that cooperatively regulate flowering in D. nobile. These two isoforms are generated by alternative 3′ polyadenylation of DnFCA (FLOWERING CONTROL LOCUS C in D. nobile) pre-mRNA and contain a distinct 3′-terminus. Both can partially rescue late flowering in the Arabidopsis fca-1 mutant, while in wild-type Arabidopsis, they tend to delay the flowering time. When introduced into the detached axillary buds or young seedlings of D. nobile, both were able to induce the transcription of DnAGL19 (AGAMOUS LIKE 19 in D. nobile) in seedlings, whereas only DnFCAγ was able to suppress the transcription of DnAPL1 (AP1-LIKE 1 in D. nobile) in axillary buds. Furthermore, the time-course change of DnFCAγ accumulation was opposite to that of DnAPL1 in axillary buds, which was remarkable under low temperatures and within a short time after the application of high temperatures, supporting the suggestion that the expression of DnAPL1 can be inhibited by a high accumulation of DnFCAγ in floral buds. In leaves, the accumulation of DnFCAβ was in accordance with that of DnAGL19 and DnFT (FLOWERING LOCUS T in D. nobile) to a large extent, suggesting the activation of the DnAGL19–DnFT pathway by DnFCAβ. Taken together, these results suggest that the DnFCAγ–DnAPL1 pathway in axillary buds and the DnFCAβ–DnAGL19 pathway in the leaves cooperatively promote flowering under low temperatures. The long-term and constant, or untimely, application of high temperatures leads to the constitutive suppression of DnAPL1 by a high level of DnFCAγ in axillary buds, which consequently delays floral development.
A Vegetarian Diet Significantly Changes Plasma Kynurenine Concentrations
Authors: Bjørke-Monsen Anne-Lise , Varsi Kristin , Ulvik Arve , Sakkestad Sunniva Todnem , Ueland Per Magne
Published: February 2023

Tryptophan is an essential amino acid and a precursor of a number of physiologically important metabolites, including serotonin, melatonin, tryptamine, and kynurenines. We assessed tryptophan, kynurenines, and vitamin B2 and B6, as well as biomarkers of liver function and inflammation, in a group of 158 female omnivores and vegetarians aged 18–40 years. The majority of women were omnivores, and 22% were vegetarians. Vegetarians had 25% lower serum ALT, significantly higher pyridoxal concentrations, and significantly lower plasma concentrations of most kynurenines, varying from 8% lower concentrations of median plasma kynurenine to 42% lower concentrations of plasma xanthurenic acid, compared to omnivores. No significant differences were observed in vitamin B2 status or in inflammation markers, C-reactive protein and neopterin between the groups. Vegetarians had lower levels of several plasma kynurenines compared to omnivores. The reason for this is unknown; however, lower ALT concentrations, suggesting a better liver status, and a more favourable vitamin B6 status might be contributing factors.
Predicting Potent Compounds Using a Conditional Variational Autoencoder Based upon a New Structure–Potency Fingerprint
Authors: Janela Tiago , Takeuchi Kosuke , Bajorath Jürgen
Published: February 2023

Prediction of the potency of bioactive compounds generally relies on linear or nonlinear quantitative structure–activity relationship (QSAR) models. Nonlinear models are generated using machine learning methods. We introduce a novel approach for potency prediction that depends on a newly designed molecular fingerprint (FP) representation. This structure–potency fingerprint (SPFP) combines different modules accounting for the structural features of active compounds and their potency values in a single bit string, hence unifying structure and potency representation. This encoding enables the derivation of a conditional variational autoencoder (CVAE) using SPFPs of training compounds and apply the model to predict the SPFP potency module of test compounds using only their structure module as input. The SPFP–CVAE approach correctly predicts the potency values of compounds belonging to different activity classes with an accuracy comparable to support vector regression (SVR), representing the state-of-the-art in the field. In addition, highly potent compounds are predicted with very similar accuracy as SVR and deep neural networks.
Cellular Pathogenesis of Hepatic Encephalopathy: An Update
Authors: Lu Kaihui
Published: February 2023

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome derived from metabolic disorders due to various liver failures. Clinically, HE is characterized by hyperammonemia, EEG abnormalities, and different degrees of disturbance in sensory, motor, and cognitive functions. The molecular mechanism of HE has not been fully elucidated, although it is generally accepted that HE occurs under the influence of miscellaneous factors, especially the synergistic effect of toxin accumulation and severe metabolism disturbance. This review summarizes the recently discovered cellular mechanisms involved in the pathogenesis of HE. Among the existing hypotheses, ammonia poisoning and the subsequent oxidative/nitrosative stress remain the mainstream theories, and reducing blood ammonia is thus the main strategy for the treatment of HE. Other pathological mechanisms mainly include manganese toxicity, autophagy inhibition, mitochondrial damage, inflammation, and senescence, proposing new avenues for future therapeutic interventions.
Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma
Authors: Hinton Kristin , Kirk Andrew , Paul Paulose , Persad Sujata
Published: February 2023

The epithelial to mesenchymal transition (EMT) is a cellular process that has been linked to the promotion of aggressive cellular features in many cancer types. It is characterized by the loss of the epithelial cell phenotype and a shift to a more mesenchymal phenotype and is accompanied by an associated change in cell markers. EMT is highly complex and regulated via multiple signaling pathways. While the importance of EMT is classically described for carcinomas—cancers of epithelial origin—it has also been clearly demonstrated in non-epithelial cancers, including osteosarcoma (OS), a primary bone cancer predominantly affecting children and young adults. Recent studies examining EMT in OS have highlighted regulatory roles for multiple proteins, non-coding nucleic acids, and components of the tumor micro-environment. This review serves to summarize these experimental findings, identify key families of regulatory molecules, and identify potential therapeutic targets specific to the EMT process in OS.
The Role of Pericytes in Regulation of Innate and Adaptive Immunity
Authors: Dabravolski Siarhei A. , Andreeva Elena R. , Eremin Ilya I. , Markin Alexander M. , Nadelyaeva Irina I. , Orekhov Alexander N. , Melnichenko Alexandra A.
Published: February 2023

Pericytes are perivascular multipotent cells wrapping microvascular capillaries, where they support vasculature functioning, participate in tissue regeneration, and regulate blood flow. However, recent evidence suggests that in addition to traditionally credited structural function, pericytes also manifest immune properties. In this review, we summarise recent data regarding pericytes’ response to different pro-inflammatory stimuli and their involvement in innate immune responses through expression of pattern-recognition receptors. Moreover, pericytes express various adhesion molecules, thus regulating trafficking of immune cells across vessel walls. Additionally, the role of pericytes in modulation of adaptive immunity is discussed. Finally, recent reports have suggested that the interaction with cancer cells evokes immunosuppression function in pericytes, thus facilitating immune evasion and facilitating cancer proliferation and metastasis. However, such complex and multi-faceted cross-talks of pericytes with immune cells also suggest a number of potential pericyte-based therapeutic methods and techniques for cancer immunotherapy and treatment of autoimmune and auto-inflammatory disorders.
An Array SPRi Biosensor for the Determination on PARP-1 in Blood Plasma
Authors: Zielinska Zuzanna , Oldak Lukasz , Kacperczyk-Bartnik Joanna , Koc-Żórawska Ewa , Żórawski Marcin , Laudanski Piotr , Gorodkiewicz Ewa
Published: February 2023

A biosensor was developed for the quantification of poly(ADP-ribose) polymerase-1 (PARP-1) in body fluids. An antibody specific for PARP-1 was placed on a chip with cysteamine (linker) and a gold layer. This biosensor has a linear response range (10–1000 pg∙mL−1) under appropriate pH conditions and with an antibody ligand concentration of 5 ng∙mL−1. Plasma samples were diluted with PBS buffer in appropriate quantities so that they fell within the linear range of the calibration curve. The biosensor exhibited suitable precision and accuracy, and good recovery (at levels from 95% to 105%). The method was validated by means of PARP-1 determinations in plasma samples from patients with endometriosis and a control group, using surface plasmon resonance imaging (SPRi) biosensors and an enzyme-linked immunosorbent assay (ELISA) test. The Spearman correlation coefficient was close to 1. PARP-1 may be a marker providing information about pathological changes in the body during endometriosis.
High-Dose Intravenous Steroid Treatment Seems to Have No Long-Term Negative Effect on Bone Mineral Density of Young and Newly Diagnosed Multiple Sclerosis Patients: A Pilot Study
Authors: Simeakis George , Anagnostouli Maria , Fakas Nikolaos , Koutsikos John , Papatheodorou Athanasios , Chanopoulos Konstantinos , Athanasiou Kwnstantinos , Papatheodorou George , Zapanti Evangelia , Alevizaki Maria , Kaltsas Gregory , Terpos Evangelos
Published: February 2023

High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.
Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis
Authors: Tiu Vlad Eugen , Popescu Bogdan Ovidiu , Enache Iulian Ion , Tiu Cristina , Cherecheanu Alina Popa , Panea Cristina Aura
Published: February 2023

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-ups. Disability progression was measured using the EDSS-plus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.
Transcriptomic Analysis of Macrophage Polarization Protocols: Vitamin D3 or IL-4 and IL-13 Do Not Polarize THP-1 Monocytes into Reliable M2 Macrophages
Authors: Rynikova Maria , Adamkova Petra , Hradicka Petra , Stofilova Jana , Harvanova Denisa , Matejova Jana , Demeckova Vlasta
Published: February 2023

Two main types of macrophages (Mφ) include inflammatory (M1) and anti-inflammatory (M2) macrophages. These cells can be obtained in vitro by polarization of monocytic cell lines using various stimuli. Since there is currently no consensus on the best method for the acquisition of reliable M1 and M2 macrophages from the THP-1 cell line, we decided to compare three different polarization protocols at the transcriptomic level. Whole transcriptomes of Mφ polarized according to the chosen protocols were analyzed using RNA-seq. Differential expression of genes and functional enrichment for gene ontology terms were assessed. Compared with other protocols, M1 macrophages polarized using PMA (61.3 ng/mL) and IFN-γ along with LPS had the highest expression of M1-associated regulatory genes and genes for M1 cytokines and chemokines. According to the GO enrichment analysis, genes involved in defensive and inflammatory processes were differentially expressed in these Mφ. However, all three chosen protocols which use Vit D3, IL-13/IL-4, and IL-4, respectively, failed to promote the polarization of macrophages with a reliable M2 phenotype. Therefore, optimization or development of a new M2 polarization protocol is needed to achieve macrophages with a reliable anti-inflammatory phenotype.
New Monoclonal Antibodies Specific for Different Epitopes of the Spike Protein of SARS-CoV-2 and Its Major Variants: Additional Tools for a More Specific COVID-19 Diagnosis
Authors: Mariotti Sabrina , Chiantore Maria Vincenza , Teloni Raffaela , Iacobino Angelo , Capocefalo Antonio , Michelini Zuleika , Borghi Martina , Baggieri Melissa , Marchi Antonella , Bucci Paola , Gioacchini Silvia , D’Amelio Raffaele , Brouwer Philip J. M. , Sandini Silvia , Acchioni Chiara , Sgarbanti Marco , Di Virgilio Antonio , Grasso Felicia , Cara Andrea , Negri Donatella , Magurano Fabio , Di Bonito Paola , Nisini Roberto
Published: February 2023

The emergence of the new pathogen SARS-CoV-2 determined a rapid need for monoclonal antibodies (mAbs) to detect the virus in biological fluids as a rapid tool to identify infected individuals to be treated or quarantined. The majority of commercially available antigenic tests for SARS-CoV-2 rely on the detection of N antigen in biologic fluid using anti-N antibodies, and their capacity to specifically identify subjects infected by SARS-CoV-2 is questionable due to several structural analogies among the N proteins of different coronaviruses. In order to produce new specific antibodies, BALB/c mice were immunized three times at 20-day intervals with a recombinant spike (S) protein. The procedure used was highly efficient, and 40 different specific mAbs were isolated, purified and characterized, with 13 ultimately being selected for their specificity and lack of cross reactivity with other human coronaviruses. The specific epitopes recognized by the selected mAbs were identified through a peptide library and/or by recombinant fragments of the S protein. In particular, the selected mAbs recognized different linear epitopes along the S1, excluding the receptor binding domain, and along the S2 subunits of the S protein of SARS-CoV-2 and its major variants of concern. We identified combinations of anti-S mAbs suitable for use in ELISA or rapid diagnostic tests, with the highest sensitivity and specificity coming from proof-of-concept tests using recombinant antigens, SARS-CoV-2 or biological fluids from infected individuals, that represent important additional tools for the diagnosis of COVID-19.
The Influence of SARS-CoV-2 Infection on the Thyroid Gland
Authors: Piekarska Aleksandra , Góral Marta , Kozula Marta , Jawiarczyk-Przybyłowska Aleksandra , Zawadzka Katarzyna , Bolanowski Marek
Published: February 2023

It is important to acknowledge the impact that COVID-19 has on the thyroid gland and how the thyroid gland status before and during infection affects SARS-CoV-2 severity. To this day those dependencies are not fully understood. It is known that the virus uses angiotensin-converting enzyme-2 as the receptor for cellular entry and it can lead to multiple organ failures due to a cytokine storm. Levels of proinflammatory molecules (such as cytokines and chemokines) which are commonly elevated during infection were significantly higher in observed SARS-CoV-2-positive patients. In terms of hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases, there is no proof that those dysfunctions have a direct impact on the more severe courses of COVID-19. Regarding hyper- and hypothyroidism there was no consequential dependency between the frequency of SARS-CoV-2 infection morbidity and more severe post-infectious complications. When it comes to autoimmune thyroid diseases, more evaluation has to be performed due to the unclear relation with the level of antibodies commonly checked in those illnesses and its binding with the mentioned before virus. Nonetheless, based on analyzed works we found that COVID-19 can trigger the immune system and cause its hyperactivity, sometimes leading to the new onset of autoimmune disorders. We also noticed more acute SARS-CoV-2 courses in patients with mainly reduced free triiodothyronine serum levels, which in the future, might be used as a mortality indicating factor regarding SARS-CoV-2-positive patients. Considering subacute thyroiditis (SAT), no statistically important data proving its direct correlation with COVID-19 infection has been found. Nevertheless, taking into account the fact that SAT is triggered by respiratory tract viral infections, it might be that SARS-CoV-2 can cause it too. There are many heterogenous figures in the symptoms, annual morbidity distribution, and frequency of new cases, so this topic requires further evaluation.
Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment
Authors: Mucci Viviana , Demori Ilaria , Browne Cherylea J. , Deblieck Choi , Burlando Bruno
Published: February 2023

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic “weakening” in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients.
Allergic Reactions to Vaccines in Children: From Constituents to Specific Vaccines
Authors: Tsai Ming-Han , Chiu Chih-Yung
Published: February 2023

Vaccination is an essential public health measure that helps to reduce the burden of infectious diseases in children. Although vaccines have an excellent safety record and the association of severe allergic reactions is rare, public concerns about vaccine safety can lead to incomplete vaccination coverage in children with or without allergies. Therefore, it is important to understand the mechanisms and implications of allergic reactions to vaccines and define strategies to manage them to provide the safest care for vaccine recipients. In this review, we provide an overview on the types of allergic reactions that can occur after vaccination, including those caused by various vaccine constituents. We also discuss the mechanisms underlying these allergic reactions and the recommended diagnosis and management strategies for children with a history of suspected allergic reactions to vaccines. An improved understanding of allergic reactions to vaccines can aid in the enhancement of the safety and effectiveness of vaccination.
Evaluation of CAR-T Cells’ Cytotoxicity against Modified Solid Tumor Cell Lines
Authors: Valiullina Aigul Kh. , Zmievskaya Ekaterina A. , Ganeeva Irina A. , Zhuravleva Margarita N. , Garanina Ekaterina E. , Rizvanov Albert A. , Petukhov Alexey V. , Bulatov Emil R.
Published: February 2023

In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines—lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells’ monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome.
Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial
Authors: Yeh Ta-Chuan , Huang Cathy Chia-Yu , Chung Yong-An , Park Sonya Youngju , Im Jooyeon Jamie , Lin Yen-Yue , Ma Chin-Chao , Tzeng Nian-Sheng , Chang Hsin-An
Published: February 2023

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5–7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.
Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma
Authors: Petrogiannis-Haliotis Tina , Pehr Kevin , Roberge David , Rys Ryan N. , Monczak Yury , Popradi Gizelle , Ajjamada Lissa , Benlimame Naciba , Querfeld Christiane , Johnson Nathalie , Knecht Hans
Published: February 2023

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/− PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1−, CD4+/PD1+, CD8+/PD1− and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL.
Phenotypic Characterization of Male Tafazzin-Knockout Mice at 3, 6, and 12 Months of Age
Authors: Tomczewski Michelle V. , Chan John Z. , Campbell Zurie E. , Strathdee Douglas , Duncan Robin E.
Published: February 2023

Barth syndrome (BTHS) is an X-linked mitochondrial disease caused by mutations in the gene encoding for tafazzin (TAZ), a key enzyme in the remodeling of cardiolipin. Mice with a germline deficiency in Taz have been generated (Taz-KO) but not yet fully characterized. We performed physiological assessments of 3-, 6-, and 12-month-old male Taz-KO mice, including measures of perinatal survival, growth, lifespan, gross anatomy, whole-body energy and substrate metabolism, glucose homeostasis, and exercise capacity. Taz-KO mice displayed reduced viability, with lower-than-expected numbers of mice recorded at 4 weeks of age, and a shortened lifespan due to disease progression. At all ages, Taz-KO mice had lower body weights compared with wild-type (Wt) littermates despite similar absolute food intakes. This finding was attributed to reduced adiposity and diminutive organs and tissues, including heart and skeletal muscles. Although there were no differences in basal levels of locomotion between age-matched genotypes, indirect calorimetry studies showed higher energy expenditure measures and respiratory exchange ratios in Taz-KO mice. At the youngest age, Taz-KO mice had comparable glucose tolerance and insulin action to Wt mice, but while these measures indicated metabolic impairments in Wt mice with advancing age that were likely associated with increasing adiposity, Taz-KO mice were protected. Comparisons across the three age-cohorts revealed a significant and more severe deterioration of exercise capacity in Taz-KO mice than in their Wt littermate controls. The Taz-KO mouse model faithfully recapitulates important aspects of BTHS, and thus provides an important new tool to investigate pathophysiological mechanisms and potential therapies.