bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Harmonic Distortion Reduction in Multilevel Inverters through the Utilization of the Moth–Flame Optimization Algorithm
Authors: Lopez Adolfo R. , López-Núñez Oscar A. , Pérez-Zúñiga Ricardo , Gómez Radilla Jair , Martínez-García Mario , López-Osorio Maria A. , Ortiz-Torres Gerardo , Mena-Enriquez Mayra G. , Ramos-Martinez Moises , Mixteco-Sánchez Juan Carlos , Torres-Cantero Carlos Alberto , Sorcia-Vázquez Felipe D. J. , Rumbo-Morales Jesse Y.
Published: November 2023

This paper shows the implementation of the Moth–Flame Optimization algorithm in a Cascade-H multilevel inverter with five and seven levels to determine the optimal switching sequence of the inverter’s semiconductor devices. The algorithm was coded in Matlab software, and the obtained switching sequences were implemented in a Cascade-H multilevel inverter laboratory prototype, where the output voltage waveform was obtained using a digital oscilloscope. The experimental Total Harmonic Distortion was obtained using a power quality analyzer. The experimental results show the improvement of the Total Harmonic Distortion in the voltage output. These results were compared with other papers in the literature with different metaheuristic methods concerning the same modulation. These findings demonstrate the feasibility of employing the Moth–Flame Optimization Algorithm to significantly reduce the Total Harmonic Distortion, obtaining a lower value than most analyzed papers.
Research on New Greenable Class Gravity Retaining Wall Structure Technology Based on Video Monitoring
Authors: Li Zengle , Zhang Huimei , Zhi Bin , Li Xin , Chen Shiguan
Published: November 2023

As the most common geological disaster problem in mines, slope geological disasters have become a focus of research, along with the difficulty of mine safety and ecological environment protection together with the ecological restoration of open-pit mines. At present, a large number of slope-retaining wall structures lack research on safety monitoring, real-time acquisition, and intelligent early warning. Therefore, this paper combines cement-modified loess with gravity retaining wall structures and puts forward a new type of greening gravity retaining wall structure. From the perspective of “the Internet of Things + construction”, a video monitoring system is established to monitor the retaining wall structure in real time. Finally, based on video image processing technology, the deformation of the retaining wall surface is identified and the inclination angle of the wall surface is calculated, so as to improve the real-time and intelligent monitoring of the new greening gravity retaining wall. The results show that the new greening gravity retaining wall based on video monitoring proposed in this paper has the characteristics of a gravity retaining wall and ecological retaining wall, which are conducive to improving the real-time and intelligent monitoring of the new greening gravity retaining wall. Cement-modified loess is used as the planting matrix, and the cement mixing ratio should not exceed 10%. Considering the requirements of economy and shear strength, the cement mixing ratio should be selected from 5% to 12%.
The Vibration Analysis Based on Experimental and Finite Element Modeling for Investigating the Effect of a Multi-Notch Location of a Steel Plate
Authors: Charoensuk Kritchanan , Sethaput Thunyaseth
Published: November 2023

Vibration is challenging and significant in solving engineering problems. The issue of vibration in loaded objects by utilizing a three-dimensional model and experiments. Typically, an object is subjected to a random frequency, which changes the notch shape depending on the frequency model. The investigations determined the performance difference by conducting modal analysis with the finite element method and examining the various forms of each mode. We simulated metal plates with V notch and multiple notch locations on both sides and one side of the notch. The test kits included an accelerometer and a force sensor for correcting the national frequency via Simulink Matlab® and verifying the result from the finite element methods. The V-shaped vibration testing provided significant insights into its accuracy and potential for predicting damage and fracture through experimentation and the finite element method. The tested specimen analyzed the behavior of two models and found that the two V-shaped exhibited varying natural frequency values. Specifically, the double-sided V-shaped increased natural frequency, whereas the single-sided notched V-shaped cutting showed a significant decrease in natural frequency. Accordingly, this investigative approach, the result of the experiment, and the finite element shows that correlation disposition can be utilized to forecast various random frequencies for vibration analysis.
Pairing Hamiltonians of Nearest-Neighbor Interacting Superconducting Qubits on an IBM Quantum Computer
Authors: Chatterjee Shirshendu , Behera Bikash K. , Seo Felix J.
Published: November 2023

A quantum simulation experiment pairing Hamiltonians of nearest-neighbor interacting superconducting qubits was performed with a complete set of algorithms on an IBM Quantum Computer-IBMq Lima. The experiment revealed that the fidelity is a function of iteration using Suzuki–Trotter decomposition for four different types of nearest-neighbor Heisenberg, XY, transverse, and longitudinal Ising superconducting qubit couplings of Hamiltonians. The experiment displayed the models of how the experimental density matrices shift from the theoretical density matrices and how their behavior changes with different numbers of iterations. It also demonstrated the reconstruction of quantum states and how the states change as a function of iteration with the IBM Quantum Computer-IBMq Lima. The time evolutions of the states for different models were also shown to predict the dominance of each state.
TCCCD: Triplet-Based Cross-Language Code Clone Detection
Authors: Fang Yong , Zhou Fangzheng , Xu Yijia , Liu Zhonglin
Published: November 2023

Code cloning is a common practice in software development, where developers reuse existing code to accelerate programming speed and enhance work efficiency. Existing clone-detection methods mainly focus on code clones within a single programming language. To address the challenge of code clone instances in cross-platform development, we propose a novel method called TCCCD, which stands for Triplet-Based Cross-Language Code Clone Detection. Our approach is based on machine learning and can accurately detect code clone instances between different programming languages. We used the pre-trained model UniXcoder to map programs written in different languages into the same vector space and learn their code representations. Then, we fine-tuned TCCCD using triplet learning to improve its effectiveness in cross-language clone detection. To assess the effectiveness of our proposed approach, we conducted thorough comparative experiments using the dataset provided by the paper titled CLCDSA (Cross Language Code Clone Detection using Syntactical Features and API Documentation). The experimental results demonstrated a significant improvement of our approach over the state-of-the-art baselines, with precision, recall, and F1-measure scores of 0.96, 0.91, and 0.93, respectively. In summary, we propose a novel cross-language code-clone-detection method called TCCCD. TCCCD leverages the pre-trained model UniXcode for source code representation and fine-tunes the model using triplet learning. In the experimental results, TCCCD outperformed the state-of-the-art baselines in terms of the precision, recall, and F1-measure.
On Unique Determination of Polyhedral Sets
Authors: Rondi Luca
Published: November 2023

In this paper, we develop in detail the geometric constructions that lead to many uniqueness results for the determination of polyhedral sets, typically scatterers, by a finite minimal number of measurements. We highlight how unique continuation and a suitable reflection principle are enough to proceed with the constructions without any other assumption on the underlying partial differential equation or the boundary condition. We also aim to keep the geometric constructions and their proofs as simple as possible. To illustrate the applicability of this theory, we show how several uniqueness results present in the literature immediately follow from our arguments. Indeed, we believe that this theory may serve as a roadmap for establishing similar uniqueness results for other partial differential equations or boundary conditions.
Elevated Levels of Mislocalised, Constitutive Ras Signalling Can Drive Quiescence by Uncoupling Cell-Cycle Regulation from Metabolic Homeostasis
Authors: Piper-Brown Elliot , Dresel Fiona , Badr Eman , Gourlay Campbell W.
Published: November 2023

The small GTPase Ras plays an important role in connecting external and internal signalling cues to cell fate in eukaryotic cells. As such, the loss of RAS regulation, localisation, or expression level can drive changes in cell behaviour and fate. Post-translational modifications and expression levels are crucial to ensure Ras localisation, regulation, function, and cell fate, exemplified by RAS mutations and gene duplications that are common in many cancers. Here, we reveal that excessive production of yeast Ras2, in which the phosphorylation-regulated serine at position 225 is replaced with alanine or glutamate, leads to its mislocalisation and constitutive activation. Rather than inducing cell death, as has been widely reported to be a consequence of constitutive Ras2 signalling in yeast, the overexpression of RAS2S225A or RAS2S225E alleles leads to slow growth, a loss of respiration, reduced stress response, and a state of quiescence. These effects are mediated via cAMP/PKA signalling and transcriptional changes, suggesting that quiescence is promoted by an uncoupling of cell-cycle regulation from metabolic homeostasis. The quiescent cell fate induced by the overexpression of RAS2S225A or RAS2S225E could be rescued by the deletion of CUP9, a suppressor of the dipeptide transporter Ptr2, or the addition of peptone, implying that a loss of metabolic control, or a failure to pass a metabolic checkpoint, is central to this altered cell fate. Our data suggest that the combination of an increased RAS2 copy number and a dominant active mutation that leads to its mislocalisation can result in growth arrest and add weight to the possibility that approaches to retarget RAS signalling could be employed to develop new therapies.
Kinase Signaling in Colitis-Associated Colon Cancer and Inflammatory Bowel Disease
Authors: Temby Michelle , Boye Theresa L. , Hoang Jacqueline , Nielsen Ole H. , Gubatan John
Published: November 2023

Colorectal cancer is a known complication of chronic inflammation of the colon (“colitis-associated colon cancer”). Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Patients with IBD are at increased risk of colon cancer compared to the general population. Kinase signaling pathways play critical roles in both the inflammation and regulating cellular processes such as proliferation and survival that contribute to cancer development. Here we review the interplay of kinase signaling pathways (mitogen-activated protein kinases, cyclin-dependent kinases, autophagy-activated kinases, JAK-STAT, and other kinases) and their effects on colitis-associated colon cancer. We also discuss the role of JAK-STAT signaling in the pathogenesis of IBD and the therapeutic landscape of JAK inhibitors for the treatment of IBD.
Three Diseases Mediated by Different Immunopathologic Mechanisms—ANCA-Associated Vasculitis, Anti-Glomerular Basement Membrane Disease, and Immune Complex-Mediated Glomerulonephritis—A Common Clinical and Histopathologic Picture: Rapidly Progressive Crescentic Glomerulonephritis
Authors: Gluhovschi Cristina , Gadalean Florica , Velciov Silvia , Nistor Mirabela , Petrica Ligia
Published: November 2023

Immune mechanisms play an important role in the pathogenesis of glomerulonephritis (GN), with autoimmunity being the main underlying pathogenetic process of both primary and secondary GN. We present three autoimmune diseases mediated by different autoimmune mechanisms: glomerulonephritis in vasculitis mediated by anti-neutrophil cytoplasmic antibodies (ANCAs), glomerulonephritis mediated by anti-glomerular basement membrane antibodies (anti-GBM antibodies), and immune complex-mediated glomerulonephritis. Some of these diseases represent a common clinical and histopathologic scenario, namely rapidly progressive crescentic glomerulonephritis. This is a severe illness requiring complex therapy, with the main role being played by therapy aimed at targeting immune mechanisms. In the absence of immune therapy, the crescents, the characteristic histopathologic lesions of this common presentation, progress toward fibrosis, which is accompanied by end-stage renal disease (ESRD). The fact that three diseases mediated by different immunopathologic mechanisms have a common clinical and histopathologic picture reveals the complexity of the relationship between immunopathologic mechanisms and their clinical expression. Whereas most glomerular diseases progress by a slow process of sclerosis and fibrosis, the glomerular diseases accompanied by glomerular crescent formation can progress, if untreated, in a couple of months into whole-nephron glomerulosclerosis and fibrosis. The outcome of different immune processes in a common clinical and histopathologic phenotype reveals the complexity of the relationship of the kidney with the immune system. The aim of this review is to present different immune processes that lead to a common clinical and histopathologic phenotype, such as rapidly progressive crescentic glomerulonephritis.
Homozygous Duplication in the CHRNE in a Family with Congenital Myasthenic Syndrome 4C: 18-Year Follow Up
Authors: Almatrafi Ahmad M. , Alluqmani Majed M. , Basit Sulman
Published: November 2023

Background and objectives: Congenital myasthenic syndromes (CMSs) are rare inherited diseases characterized by muscle weakness and fatigability on exertion resulting from defects in the neuromuscular junctions. Mutations in 32 genes have been reported as the underlying causes of CMS, with mutations in the cholinergic receptor nicotinic epsilon subunit (CHRNE) being the most common cause of the disease. Methodology and Materials: This study investigated a large consanguineous family with multiple individuals suffering from abnormal fatigue and muscle weakness in the ocular and limb regions. Moreover, the affected individuals were followed up for 18 years to observe the clinical course of the disease. Results: High-quality exome sequencing followed by bidirectional Sanger sequencing revealed a homozygous duplication variant (NM_000080.4: c.1220-8_1227dup) in the splice acceptor site of exon 11 of the CHRNE gene. This variant is predicted to cause frameshift and premature termination (p.Cys410ProfsTer51). Both parents had heterozygous duplication variants with no clinical symptoms. The personalized treatment of the affected individuals resulted in a marked improvement in the clinical symptoms. More than 80% of the disease symptoms in the affected individuals subsided after the use of pyridostigmine and salbutamol (4 mg). Conclusions: This is the first report of long-term follow up of cases with homozygous insertion (c.1220-8_1227dup) in the CHRNE gene. Furthermore, this report expands the phenotypic symptoms associated with the CHRNE mutation.
Propane Dehydrogenation over Cobalt Aluminates: Evaluation of Potential Catalytic Active Sites
Authors: Chernov Aleksey N. , Cherepanova Svetlana V. , Gerasimov Evgeny Yu. , Prosvirin Igor P. , Zenkovets Galina A. , Shutilov Alexei A. , Gorbunova Anna S. , Koltunov Konstantin Yu. , Sobolev Vladimir I.
Published: November 2023

Non-oxidative propane dehydrogenation (PDH) is becoming an increasingly important approach to propylene production, while cobalt-containing catalysts have recently demonstrated great potential for use in this reaction, providing efficiencies comparable to those of industrially employed Pt- and Cr-based catalytic systems. It is therefore essential to clarify the nature of their active sites, especially since contradictory opinions on this issue are expressed in the literature. In this study, efforts were made to determine the state of Co in cobalt aluminates (CoAl2O4-Al2O3) responsible for PDH under typical operating conditions (600 °C, 1 atm). It is shown that the catalyst with a low cobalt content (Co/Al = 0.1) ensured the highest selectivity to propylene, ca. 95%, while maintaining significant propylene conversion. The structural motifs such as cobalt oxide and metallic cobalt nanoparticles, in addition to tetrahedral Co2+ species in the CoAl2O4 spinel system, were evaluated as potential active-site ensembles based on the obtained catalytic performance data in combination with the XRD, H2-TPR, TEM and XPS characteristics of as-synthesized, spent and spent–regenerated catalysts. It is revealed that the most likely catalytic sites linked to PDH are the Co-oxide forms tightly covering alumina or embedded in the spinel structure. However, additional in situ tuning is certainly needed, probably through the formation of surface oxygen vacancies rather than through a deeper reduction in Co0 as previously thought.
Examining the Spatiotemporal Changes in the Annual, Seasonal, and Daily Rainfall Climatology of Puerto Rico
Authors: Hernández Ayala José Javier , Méndez Tejeda Rafael
Published: November 2023

This study explores spatial and temporal changes in the rainfall climatology of Puerto Rico in order to identify areas where annual, seasonal or daily precipitation is increasing, decreasing, or remaining normal. Total annual, seasonal, and daily rainfall were retrieved from 23 historical rain gauges with consistent data for the 1956–2021 period. Mann–Kendall trend tests were done on the annual and seasonal rainfall series, and percentage change differences between two different climatologies (1956–1987 and 1988–2021) were calculated. Most of the stations did not exhibit statistically significant annual or seasonal trends in average rainfall. However, of the sites that did experience changes, most of them had statistically significant decreasing trends in mean precipitation. The annual, dry, and early wet season had more sites with negative trends when compared with positive trends, especially in the northwestern and southeastern region of the island. The late wet season was the only period with more sites showing statistically significant trends when compared with negative trends, specifically in the northern region of the island. Results for daily events show that extreme rainfall occurrences have generally decreased, especially in the western region of the island. When the 1955–1987 and 1988–2022 climatologies are compared, the results for annual average rainfall show two main regions with mean precipitation reductions, and those are the northwestern and southeastern areas of the island. The dry season was the only period with more areas exhibiting percentage increases in mean rainfall when the two climatologies were analyzed. The early and late wet season months exhibited similar patterns, with more areas on the island showing negative percentage decreases in average seasonal precipitation. The best predictor for the decreasing annual and seasonal trend in the northwest was a higher sea level pressure, and the variable that best explained the increasing trend in the northeast was total precipitable water.
Representation Learning Method for Circular Seal Based on Modified MLP-Mixer
Authors: Cao Yuan , Zhou You , Zhang Zhiwen , Yao Enyi
Published: November 2023

This study proposes Stamp-MLP, an enhanced seal impression representation learning technique based on MLP-Mixer. Instead of using the patch linear mapping preprocessing method, this technique uses circular seal remapping, which reserves the seals’ underlying pixel-level information. In the proposed Stamp-MLP, the average pooling is replaced by a global pooling of attention to extract the information more comprehensively. There were three classification tasks in our proposed method: categorizing the seal surface, identifying the product type, and distinguishing individual seals. The three tasks shared an identical dataset comprising 81 seals, encompassing 16 distinct seal surfaces, with each surface featuring six diverse product types. The experiment results showed that, in comparison to MLP-Mixer, VGG16, and ResNet50, the proposed Stamp-MLP achieved the highest classification accuracy (89.61%) in seal surface classification tasks with fewer training samples. Meanwhile, Stamp-MLP outperformed the others with accuracy rates of 90.68% and 91.96% in the product type and seal impression classification tasks, respectively. Moreover, Stamp-MLP had the fewest model parameters (2.67 M).
A Recombinant Alginate Lyase Algt1 with Potential in Preparing Alginate Oligosaccharides at High-Concentration Substrate
Authors: Liang Qingping , Huang Youtao , Liu Zhemin , Xiao Mengshi , Ren Xinmiao , Liu Tianhong , Li Hongyan , Yu Dongxing , Wang Ying , Zhu Changliang
Published: November 2023

Alginate lyase has been demonstrated as an efficient tool in the preparation of functional oligosaccharides (AOS) from alginate. The high viscosity resulting from the high concentration of alginate poses a limiting factor affecting enzymatic hydrolysis, particularly in the preparation of the fragments with low degrees of polymerization (DP). Herein, a PL7 family alginate lyase Algt from Microbulbifer thermotolerans DSM 19189 was developed and expressed in Pichia pastoris. The recombinant alginate lyase Algt1 was constructed by adopting the structural domain truncation strategy, and the enzymatic activity towards the alginate was improved from 53.9 U/mg to 212.86 U/mg compared to Algt. Algt1 was stable when incubated at 40 °C for 90 min, remaining with approximately 80.9% of initial activity. The analyses of thin-layer chromatography (TLC), fast protein liquid chromatography (FPLC), and electrospray ionization mass spectrometry (ESI-MS) demonstrated that the DP of the minimum identifiable substrate of Algt1 was five, and the main hydrolysis products were AOS with DP 1–4. Additionally, 1-L the enzymatic hydrolysis system demonstrated that Algt1 exhibited an effective degradation at alginate concentrations of up to 20%, with the resulting products of monosaccharides (14.02%), disaccharides (21.10%), trisaccharides (37.08%), and tetrasaccharides (27.80%). These superior properties of Algt1 make it possible to efficiently generate functional AOS with low DP in industrial processing.
The Petrology and Geochemistry of REE-Enriched, Alkaline Volcanic Rocks of Ambitle Island, Feni Island Group, Papua New Guinea
Authors: Ponyalou Olive L. , Petterson Michael G. , Espi Joseph O.
Published: November 2023

Ambitle in the Feni Island Group is located within the NW trending Tabar–Lihir–Tanga–Feni (TLTF) volcanic island chain, Melanesian Arc, northeastern Papua New Guinea. The TLTF chain is renowned for its alkaline magmatism, geothermal activity, copper–gold mineralization, and world-class gold mining. Although its geochemical patterns indicate island arc signatures (i.e., high LILE and depleted HFSE), TLTF volcanism is not directly related to the older Melanesian Arc subduction system. However, it may have been influenced by source mantle metasomatism linked to the older subduction. The purpose of this study is to (1) present and interpret the petrographic, mineralogical, and geochemical data from Feni within the context of the tectonic evolution of the TLTF and (2) propose a geodynamic, petrogenetic model for the Feni volcanic rocks. The key methodologies used in this study are field mapping and sampling, petrographic analysis using the optical microscope, whole-rock geochemical analysis via XRF and ICP MS, and mineralogical analysis using an electron microprobe. The main rock types sampled in this study include feldspathoid-bearing basalt, trachybasalt, phonotephrite, trachyandesite, and trachydacite. Minerals identified include forsteritic olivine, diopside, augite, labradorite, andesine, anorthitic plagioclase, nepheline, and leucite in the primitive mafic suites, whereas the more evolved intermediate and felsic hypabyssal suites contain amphibole, albite, orthoclase, biotite, and either rare quartz or feldspathoids. Amphibole composition is primarily magnesiohastingsite with minor pargasite formed under polybaric conditions. Accessory minerals include apatite, titanite, and Ti-magnetite. We propose that limestone assimilation followed by fractional crystallization are plausible dominant processes in the geochemical evolution of the Ambitle volcanics. Clinopyroxene fractionation is dominant in the mafic volcanics whereas hornblende fractionation is a major petrologic process within the intermediate suites proven by the enrichment of LREE and depletions in MREE and HREE. Feni magmas are also highly enriched in REEs relative to neighboring arcs. This study is globally significant as alkaline magmas are important sources of Cu, Au, and REE as critical elements for green energy and modern technology.
VEPL-Net: A Deep Learning Ensemble for Automatic Segmentation of Vegetation Encroachment in Power Line Corridors Using UAV Imagery
Authors: Cano-Solis Mateo , Ballesteros John R. , Sanchez-Torres German
Published: November 2023

Vegetation encroachment in power line corridors remains a major challenge for modern energy-dependent societies, as it can cause power outages and lead to significant financial losses. Unmanned Aerial Vehicles (UAVs) have emerged as a promising solution for monitoring infrastructure, owing to their ability to acquire high-resolution overhead images of these areas quickly and affordably. However, accurate segmentation of the vegetation encroachment in this imagery is a challenging task, due to the complexity of the scene and the high pixel imbalance between the power lines, the vegetation and the background classes. In this paper, we propose a deep learning-based approach to tackle this problem caused by the original and different geometry of the objects. Specifically, we use DeepLabV3, U-Net and a modified version of the U-Net architecture with VGG-16 weights to train two separate models. One of them segments the dominant classes, the vegetation from the background, achieving an IoU of 0.77. The other one segments power line corridors from the background, obtaining an IoU of 0.64. Finally, ensembling both models into one creates an “encroachment” zone, where power lines and vegetation are intersected. We train our models using the Vegetation Encroachment in Power Line Corridors dataset (VEPL), which includes RGB orthomosaics and multi-label masks for segmentation. Experimental results demonstrate that our approach outperforms individual networks and original prominent architectures when applied to this specific problem. This approach has the potential to significantly improve the efficiency and accuracy of vegetation encroachment monitoring using UAV, thus helping to ensure the reliability and sustainability of power supply.
“Alphabet” Selenoproteins: Their Characteristics and Physiological Roles
Authors: Dogaru Carmen Beatrice , Muscurel Corina , Duță Carmen , Stoian Irina
Published: November 2023

Selenium (Se) is a metalloid that is recognized as one of the vital trace elements in our body and plays multiple biological roles, largely mediated by proteins containing selenium—selenoproteins. Selenoproteins mainly have oxidoreductase functions but are also involved in many different molecular signaling pathways, physiological roles, and complex pathogenic processes (including, for example, teratogenesis, neurodegenerative, immuno-inflammatory, and obesity development). All of the selenoproteins contain one selenocysteine (Sec) residue, with only one notable exception, the selenoprotein P (SELENOP), which has 10 Sec residues. Although these mechanisms have been studied intensely and in detail, the characteristics and functions of many selenoproteins remain unknown. This review is dedicated to the recent data describing the identity and the functions of several selenoproteins that are less known than glutathione peroxidases (Gpxs), iodothyronine deiodinases (DIO), thioredoxin reductases (TRxRs), and methionine sulfoxide reductases (Msrs) and which are named after alphabetical letters (i.e., F, H, I, K, M, N, O, P, R, S, T, V, W). These “alphabet” selenoproteins are involved in a wide range of physiological and pathogenetic processes such as antioxidant defense, anti-inflammation, anti-apoptosis, regulation of immune response, regulation of oxidative stress, endoplasmic reticulum (ER) stress, immune and inflammatory response, and toxin antagonism. In selenium deficiency, the “alphabet” selenoproteins are affected hierarchically, both with respect to the particular selenoprotein and the tissue of expression, as the brain or endocrine glands are hardly affected by Se deficiency due to their equipment with LRP2 or LRP8.
Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing
Authors: Green Macauley J. , Murray Ewan J. , Williams Paul , Ghaemmaghami Amir M. , Aylott Jonathan W. , Williams Philip M.
Published: November 2023

Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. Staphylococcus aureus is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes acute and chronic infections. Virulence and colonization factors are positively and negatively regulated, respectively, by bacterial cell-to-cell communication (quorum sensing) via the agr (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), S. aureus has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of agr expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the S. aureus strains JE2 (methicillin-resistant) and SH1000 (methicillin-sensitive) both exhibited reduced cytotoxicity towards the human leukemia monocytic cell line (THP-1) and increased fibronectin binding. Using S. aureus agrP3::lux reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of agr, which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible agr system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, S. aureus agrP3::lux reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to S. aureus USA300 during microgravity culture restored the cytotoxicity of culture supernatants for the THP-1 cells. These data suggest that microgravity does not affect AgrC-AIP interactions but more likely the generation of AIPs.
Measurement of Cardiac-Specific Biomarkers in the Emergency Department: New Insight in Risk Evaluation
Authors: Aspromonte Nadia , Zaninotto Martina , Aimo Alberto , Fumarulo Isabella , Plebani Mario , Clerico Aldo
Published: November 2023

The aim of this article review is to analyze some models and clinical issues related to the implementation of accelerated diagnostic protocols based on specific cardiac biomarkers in patients admitted to the emergency department (ED) with symptoms compatible with acute cardiac disorders. Four specific clinical issues will be discussed in detail: (a) pathophysiological and clinical interpretations of circulating hs-cTnI and hs-cTnT levels; (b) the clinical relevance and estimation of the biological variation of biomarkers in patients admitted to the ED with acute and severe diseases; (c) the role and advantages of the point-of-care testing (POCT) methods for cardiac-specific biomarkers in pre-hospital and hospital clinical practice; and (d) the clinical role of specific cardiac biomarkers in patients with acute heart failure (AHF). In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the measurement of specific cardiac biomarkers is essential for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the length and costs of hospitalization. Moreover, specific cardiac biomarkers (especially hs-cTnI and hs-cTnT) are useful predictors of mortality and major adverse cardiovascular events (MACE) in patients admitted to the ED with suspected acute cardiovascular disease. To guide the implementation of the most rapid algorithms for the diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of these clinical protocols and POCT methods in the ED clinical practice.
Targeting NADPH Oxidase and Integrin α5β1 to Inhibit Neutrophil Extracellular Traps-Mediated Metastasis in Colorectal Cancer
Authors: Zhu Wenyuan , Yang Siqi , Meng Delan , Wang Qingsong , Ji Jianguo
Published: November 2023

Metastasis leads to a high mortality rate in colorectal cancer (CRC). Increased neutrophil extracellular traps (NETs) formation is one of the main causes of metastasis. However, the mechanism of NETs-mediated metastasis remains unclear and effective treatments are lacking. In this study, we found neutrophils from CRC patients have enhanced NETs formation capacity and increased NETs positively correlate with CRC progression. By quantitative proteomic analysis of clinical samples and cell lines, we found that decreased secreted protein acidic and rich in cysteine (SPARC) results in massive NETs formation and integrin α5β1 is the hub protein of NETs-tumor cell interaction. Mechanistically, SPARC regulates the activation of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) pathway by interacting with the receptor for activated C kinase 1 (RACK1). Over-activated NADPH oxidase generates more reactive oxygen species (ROS), leading to the release of NETs. Then, NETs upregulate the expression of integrin α5β1 in tumor cells, which enhances adhesion and activates the downstream signaling pathways to promote proliferation and migration. The combination of NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) and integrin α5β1 inhibitor ATN-161 (Ac-PHSCN-NH2) effectively suppresses tumor progression in vivo. Our work reveals the mechanistic link between NETs and tumor progression and suggests a combination therapy against NETs-mediated metastasis for CRC.
An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development
Authors: Choi Kyudam , Lee Yurim , Kim Cheongwon
Published: November 2023

Cannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer’s disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a genetic algorithm combined with a molecular docking system. As a result, we identified six targets associated with AD: Endothelial NOS (ENOS), Myeloperoxidase (MPO), Apolipoprotein E (APOE), Amyloid-beta precursor protein (APP), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and Presenilin-1 (PSEN1). Furthermore, we generated CBD analogs for each target that optimize for all desired drug-likeness properties and physicochemical property filters, resulting in improved pIC50 values and docking scores compared to CBD. Molecular dynamics (MD) simulations were applied to analyze each target’s CBD and highest-scoring CBD analogs. The MD simulations revealed that the complexes of ENOS, MPO, and ADAM10 with CBD exhibited high conformational stability, and the APP and PSEN1 complexes with CBD analogs demonstrated even higher conformational stability and lower interaction energy compared to APP and PSEN1 complexes with CBD. These findings demonstrated the capable binding of the six identified targets with CBD and the enhanced binding stability achieved with the developed CBD analogs for each target.
Cellular and Molecular Mechanisms in Oxidative Stress-Related Diseases 2.0/3.0
Authors: Remigante Alessia , Morabito Rossana
Published: November 2023

Oxidative stress is frequently described as the balance between the production of reactive species (including oxygen and nitrogen) in biological systems and the ability of the latter to defend itself through the sophisticated antioxidant machinery [...]
Comparison of the Clinical Effectiveness of Correcting Different Types of Astigmatism with Small Incision Lenticule Extraction
Authors: Igras Estera , Czarnota-Nowakowska Barbara , O’Caoimh Rónán
Published: November 2023

Few studies have reported the differential outcomes of Small Incision Lenticule Extraction (SMILE) on myopic astigmatism. Given this, we examined the effectiveness of SMILE for up to one year, comparing with-the-rule (WTR), against-the-rule (ATR), and oblique astigmatism, conducting a retrospective review of patients who underwent correction of myopic astigmatism using the 500-kHz VisuMax femtosecond laser (Carl Zeiss Meditec) at two refractive clinics in Poland between 2016–2017. Patients were aged ≥21 with stable refractive errors between −0.5 and −10.0 diopter (D) with astigmatism up to 5D. The mean age of the 209 patients (355 eyes) available was 32 years; 58.4% were female. Of these, 247 had WTR, 62 oblique, and 46 ATR astigmatism. The mean pre-operative spherical equivalent (SE) was −5.4 ± 2.57D and the cylinder −1.7 ± 1.0D. The mean SE for WTR reduced from −5.60 ± 2.37D to −0.31 ± 0.67D at 2 months and −0.38 ± 0.70D at 12 months; the mean cylinder improved from −1.90 ± 1.10D to −0.31 ± 0.39D and −0.36 ± 0.43D, respectively. Eyes with oblique astigmatism also improved from a mean SE of −5.8 ± 3.4 D to −0.82 ± 1.50D and −0.69 ± 1.15D and a cylinder of −1.4 ± 0.73D to −0.17 ± 0.33D at 2 months and −0.1 ± 0.32D at 12. For ATR, the mean SE improved from −4.0 ± 1.8D to −0.08 ± 0.22D and −0.04 ± 0.12D; and the mean cylinder from −1.25 ± 0.53 to −0.02 ± 0.09D −0.08 ± 0.21D at 2 and 12 months, respectively. There were statistically significant improvements in SE, manifest sphere and cylinder refraction, and UDVA and CDVA scores for each cylinder type at 2 months with ATR cylinders having better outcomes. Although missing data limited interpretation at one year, differences were maintained. The magnitude of error calculations suggests that WTR was more prone to under-correction, particularly for high astigmatism (>1.5D). SMILE for myopic astigmatism reliably corrects SE, irrespective of the subtype of astigmatism.
Prevalence of Cardiovascular Risk Factors in Spain: A Systematic Review
Authors: Sacramento-Pacheco Jennifer , Sánchez-Gómez María Begoña , Gómez-Salgado Juan , Novo-Muñoz María Mercedes , Duarte-Clíments Gonzalo
Published: November 2023

Cardiovascular diseases are the leading cause of death in Spain, according to data from the National Institute of Statistics, with the lack of control of cardiovascular risk factors (CVRF) being the main contributing factor. The CVRFs of greatest clinical interest are high blood pressure (HBP), smoking, diabetes mellitus (DM2), overweight, obesity, hypercholesterolaemia, and sedentary lifestyle. The main objective of this review was to compare the prevalence of the different CVRFs according to population-based studies carried out in Spain. For this, a systematic review based on publications assessing CVRFs in the adult population and estimating their national prevalence was conducted. Pubmed and Dialnet databases were consulted, and the selected articles were analysed using the Critical Appraisal Skills Programme Español (CASPe) tool for cohort studies and the Berra et al. tool for cross-sectional studies. A total of 33 studies were obtained from the autonomous regions of Andalusia, the Canary Islands, Castilla-Leon, Castilla-La Mancha, Catalonia, Extremadura, the Balearic Islands, Madrid, Murcia, and Navarra. In all the population-based studies, there was a greater representation of women in the sample. The most prevalent CVRFs differed across the studies according to the autonomous region targeted, with dyslipidaemia, sedentary lifestyle, high blood pressure, hypercholesterolaemia, overweight, and obesity standing out. Numerous differences exist between the studies included in this review, such as the age range, the CVRFs analysed and their prevalence, and remarkable aspects such as the over-representation of the female sex in all cases. It can be concluded that, based on the presented results, the prevalence of CVRFs in Spain varies according to the autonomous region, the sex of the individual, and the studied age range.
Exploring the Potential of the Corpus Callosum Area as a Predictive Marker for Impaired Information Processing in Multiple Sclerosis
Authors: Akaike Shun , Okamoto Tomoko , Kurosawa Ryoji , Onodera Nozomi , Lin Youwei , Sato Wakiro , Yamamura Takashi , Takahashi Yuji
Published: November 2023

Early cognitive impairment (CI) detection is crucial in multiple sclerosis (MS). However, it can progress silently regardless of relapse activity and reach an advanced stage. We aimed to determine whether the corpus callosum area (CCA) is a sensitive and feasible marker for CI in MS compared to other neuroimaging markers. We assessed cognitive function in 77 MS patients using the Symbol Digit Modalities Test, Paced Auditory Serial Additions Task, Wechsler Adult Intelligence Scale-IV, and Wechsler Memory Scale-Revised. The neuroimaging markers included manually measured CCA, two diffusion tensor imaging markers, and nine volumetric measurements. Apart from volumes of the hippocampus and cerebellum, ten markers showed a significant correlation with all neuropsychological tests and significant differences between the groups. The normalized CCA demonstrated a moderate-to-strong correlation with all neuropsychological tests and successfully differentiated between the CI and cognitively normal groups with 80% sensitivity and 83% specificity. The marker had a large area under the curve and a high Youden index (0.82 and 0.63, respectively) and comparability with established cognitive markers. Therefore, the normalized CCA may serve as a reliable marker for CI in MS and can be easily implemented in clinical practice, providing a supportive diagnostic tool for CI in MS.
Real-World Efficacy and Safety of an 8-Week Glecaprevir/Pibrentasvir Regimen in Children and Adolescents with Chronic Hepatitis C—Results of a Multicenter EpiTer-2 Study
Authors: Pawlowska Malgorzata , Dobrowolska Krystyna , Moppert Justyna , Pokorska-Śpiewak Maria , Purzynska Mariola , Marczynska Magdalena , Zarebska-Michaluk Dorota , Flisiak Robert
Published: November 2023

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3–12 years and the first in Europe for adolescents aged 12–17.
Application of Electrophysiology in Non-Macular Inherited Retinal Dystrophies
Authors: Haraguchi Yulia , Chiang Tsun-Kang , Yu Minzhong
Published: November 2023

Inherited retinal dystrophies encompass a diverse group of disorders affecting the structure and function of the retina, leading to progressive visual impairment and, in severe cases, blindness. Electrophysiology testing has emerged as a valuable tool in assessing and diagnosing those conditions, offering insights into the function of different parts of the visual pathway from retina to visual cortex and aiding in disease classification. This review provides an overview of the application of electrophysiology testing in the non-macular inherited retinal dystrophies focusing on both common and rare variants, including retinitis pigmentosa, progressive cone and cone-rod dystrophy, bradyopsia, Bietti crystalline dystrophy, late-onset retinal degeneration, and fundus albipunctatus. The different applications and limitations of electrophysiology techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP), in the diagnosis and management of these distinctive phenotypes are discussed. The potential for electrophysiology testing to allow for further understanding of these diseases and the possibility of using these tests for early detection, prognosis prediction, and therapeutic monitoring in the future is reviewed.
Propofol-Based Anesthesia Maintenance and/or Volatile Anesthetics during Intracranial Aneurysm Repair: A Comparative Analysis of Neurological Outcomes
Authors: Esmaeeli Shooka , Motayagheni Negar , Brenes Bastos Andres , Ogilvy Christopher , Thomas Ajith , Pollard Richard , Buhl Lauren , Baker Maxwell , Phan Sheshanna , Hassan Omron , Fehnel Corey , Eikermann Matthias , Shaefi Shahzad , Nozari Ala
Published: November 2023

Background: Volatile and intravenous anesthetics have substantial effects on physiological functions, notably influencing neurological function and susceptibility to injury. Despite the importance of the anesthetic approach, data on its relative risks or benefits during surgical clipping or endovascular treatments for unruptured intracranial aneurysms (UIAs) remains scant. We investigated whether using volatile anesthetics alone or in combination with propofol infusion yields superior neurological outcomes following UIA obliteration. Methods: We retrospectively reviewed 1001 patients who underwent open or endovascular treatment for UIA, of whom 596 had short- and long-term neurological outcome data (modified Rankin Scale) recorded. Multivariable ordinal regression analysis was performed to examine the association between the anesthetic approach and outcomes. Results: Of 1001 patients, 765 received volatile anesthetics alone, while 236 received propofol infusion and volatile anesthetics (combined anesthetic group). Short-term neurological outcome data were available for 619 patients and long-term data for 596. No significant correlation was found between the anesthetic approach and neurologic outcomes, irrespective of the type of procedure (open craniotomy or endovascular treatment). The combined anesthetic group had a higher rate of ICU admission (p < 0.001) and longer ICU and hospital length of stay (LOS, p < 0.001). Similarly, a subgroup analysis revealed longer ICU and hospital LOS (p < 0.0001 and p < 0.001, respectively) in patients who underwent endovascular UIA obliteration under a combined anesthetic approach (n = 678). Conclusions: The addition of propofol to volatile anesthetics during UIA obliteration does not provide short- or long-term benefits to neurologic outcomes. Compared to volatile anesthetics alone, the combination of propofol and volatile anesthetics may be associated with an increased rate of ICU admission, as well as longer ICU and hospital LOS.