bluuebunny/crossref_metadata_2025 huggingface dataset:
Dependence of Sensitivity Factors on Ratio of Traffic Load to Dead Load
Authors: Milutinovic Goran , Hajdin Rade
Published: January 2024

According to modern structural codes, a design is considered to be adequate if the limit states are not exceeded. For the ultimate limit state, the design value of action effect Ed is required to be less or equal than the design value of ultimate resistance Rd. This ensures, according to the Eurocode, a sufficiently low probability of failure expressed as the target reliability index β. Consequently, the distributions of action effect and of resistance need to satisfy the following conditions: PE>Ed≤Φ+αEβ and PR≤Rd≤Φ−αRβ, where αE and αR, with |α| ≤ 1, are the values of the FORM sensitivity factors. The values of the sensitivity factors αE and αR are suggested, according to EN1990, as −0.7 and 0.8, respectively; for the accompanying actions, the sensitivity factor is recommended as 0.28. In this paper, the dependence of the sensitivity factors for traffic live load, dead load, and resistance on the ratio of traffic load to dead load is studied (which is directly proportional to the maximum span of the bridge). Significantly different sensitivity factors for resistance, dead load, and traffic load, other than proposed by the Eurocode, has been calculated for typical ratio of traffic to dead load. It further showed that, if it is assumed that Ed = Rd and the Eurocode partial safety factors are used, a different design point than the starting point, i.e., Ed = Rd, is obtained.
Computational Fluid Dynamics-Aided Simulation of Twisted Wind Flows in Boundary Layer Wind Tunnel
Authors: Yi Zijing , Wang Lingjun , Li Xiao , Zhang Zhigang , Zhou Xu , Yan Bowen
Published: January 2024

The twisted wind flow (TWF), referring to the phenomenon of wind direction varying with height, is a common feature of atmospheric boundary layer (ABL) winds, noticeably affecting the wind-resistant structural design and the wind environment assessment. The TWF can be effectively simulated by a guide vane system in wind tunnel tests, but the proper design and configuration of the guide vanes pose a major challenge as practical experience in using such devices is still limited in the literature. To address this issue, this study aims to propose an approach to determining the optimal wind tunnel setup for TWF simulations using a numerical wind tunnel, which is a replica of its physical counterpart, using computational fluid dynamics (CFD) techniques. By analyzing the mechanisms behind guide vanes for generating TWF based on CFD results, it was found that the design must take into account three key parameters, namely, (1) the distance from the vane system to the side wall, (2) the distance from the vane system to the model test region, and (3) the separation between the vanes. Following the optimal setup obtained from the numerical wind tunnel, TWF profiles matching both the power-law and Ekman spiral models, which, respectively, reflect the ABL and wind twist characteristics, were successfully generated in the actual wind tunnel. The findings of this study provide useful information for wind tunnel tests as well as for wind-resistant structural designs and wind environment assessment.
A Methodology for Rating Electricity Transmission Lines to Assess the Most Important or Critical Lines
Authors: Trukšinas Artūras , Radziukynas Virginijus , Kairaitis Gediminas
Published: January 2024

The proposed method, based on three combined criteria—Sn—design capacity of the power line, LF, (line flow)—power flow in an electric transmission line, MVA, and the ratio of LF/Sn—allows for ranking electric transmission lines when calculations are performed in normal/pre-emergency modes. A combined set of criteria used to study critical/post-emergency N-k modes is developed. The simulations were performed on the real Baltic 330 kV electricity transmission system. The results reveal that when the power system operates in different load modes, most of the critical power lines determined by our method fall into the actual set of important/“critical” power transmission lines. This allows us to significantly reduce the number of simulated combinations and shorten the calculation time required for it. During the study of the Baltic electricity system, it was found that the developed method was accurate and efficient and suitable for the assessment of the reliability of real electricity transmission networks when planning operational and perspective work modes. The simulations results revealed the high reliability of the Baltic electricity system. The 330 kV electricity transmission network of the Baltic countries fully meets the N-2 criterion (usually, electricity transmission networks are designed to meet the N-1 criterion).
Quantitative Characterization and Disturbance Law of Key Parameters Influencing Deformation of Overlying Strata during Strip Filling in a Goaf
Authors: Zhao Zenghui , Meng Zhe , Li Longfei , Liu Hao , Du Jiaze , Li Tianyu
Published: January 2024

Strip filling mining in a goaf is of great significance for solving the ‘three under’ coal-pressure and mining-area ecological environment problems in Central and Eastern China, but the disturbance characteristics of filling parameters on overlying rock are not clear at present. Taking the geological conditions of the CT30101 working face in Mahuangliang coal mine and the short-wall interval strip filling as a background, the strength parameters (cohesion and friction angle), deformation parameters (elastic modulus and Poisson’s ratio), and structural parameters (strip width and spacing) of the filling body were selected as experimental factors, and the maximum settlement of the direct roof and the ground surface was taken as the evaluation index. The influence degree of each factor was quantitatively characterized via a variance analysis and an F test, and the main control factors of the strip filling overburden settlement were proposed. The roof and surface displacement, the stress evolution law of the filling body, and the shape change of the surrounding rock plastic zone under different levels of main control factors in the entire process of mining filling coupling were analyzed in detail. The results showed that the cohesion of the backfill had a highly significant impact on the direct roof settlement, the strip spacing and the friction angle of backfill had a significant impact on it, the cohesion of the backfill and the strip spacing had a certain impact on the surface settlement, and the two had a cross-coupling effect. In the process of mining and filling, the stress evolution of the filling body was extremely complex, and it finally presented a saddle shape that was high on both sides and low in the middle; the majority of the strata and the filling body primarily exhibited shear damage, with a small amount of tensile failure zones appearing only in the direct roof and mid-section of the filling body. The above conclusions have a certain guiding significance for the optimal design of strip filling in a goaf.
A Novel Hybrid Spatiotemporal Missing Value Imputation Approach for Rainfall Data: An Application to the Ratnapura Area, Sri Lanka
Authors: Saubhagya Shanthi , Tilakaratne Chandima , Lakraj Pemantha , Mammadov Musa
Published: January 2024

Meteorological time series, such as rainfall data, show spatiotemporal characteristics and are often faced with the problem of containing missing values. Discarding missing values or modeling data with missing values causes negative impacts on the accuracy of the final predictions. Hence, accurately estimating missing values by considering the spatiotemporal variations in data has become a crucial step in eco-hydrological modeling. The multi-layer perceptron (MLP) is a promising tool for modeling temporal variation, while spatial kriging (SK) is a promising tool for capturing spatial variations. Therefore, in this study, we propose a novel hybrid approach combining the multi-layer perceptron method and spatial kriging to impute missing values in rainfall data. The proposed approach was tested using spatiotemporal data collected from a set of nearby rainfall gauging stations in the Ratnapura area, Sri Lanka. Missing values are present in collected rainfall data consecutively for a considerably longer period. This pattern has scattered among stations discontinuously over five years. The proposed hybrid model captures the temporal variability and spatial variability of the rainfall data through MLP and SK, respectively. It integrates predictions obtained through both MLP and SK with a novel optimal weight allocation method. The performance of the model was compared with individual approaches, MLP, SK, and spatiotemporal kriging. The results indicate that the novel hybrid approach outperforms spatiotemporal kriging and the other two pure approaches.
Examining Modulations of Internal Tides within An Anticyclonic Eddy Using a Wavelet-Coherence Network Approach
Authors: Lim Gyuchang , Park Jong-Jin
Published: January 2024

Interactions between internal tides and mesoscale eddies are an important topic. However, examining modulations of internal tides inside a mesoscale eddy based on observations is difficult due to limited observation duration and inaccurate positioning within the eddy. In order to overcome these two practical limitations, we use the active navigation capability of underwater gliders to conduct measurements inside the targeted eddy and utilize the wavelet approach to investigate modulations of internal tides with diurnal and semidiurnal periods inside the eddy. Based on the wavelet’s frequency–time locality, we construct scale-specific networks via wavelet coherence (WC) from multivariate timeseries with a small sample size. The modulation of internal tides is then examined in terms of temporal evolutionary characteristics of the WC network’s topological structure. Our findings are as follows: (1) the studied eddy is vertically separated into two layers, the upper (<400 m) and lower (>400 m) layers, indicating that the eddy is surface intensified; (2) the eddy is also horizontally divided into two domains, the inner and outer centers, where the modulation of internal tides seems to actively occur in the inner center; and (3) diurnal internal tides are more strongly modulated compared to semidiurnal ones, indicating the influence of spatial scales on the strength of interactions between internal tides and eddies.
Potential Application of Natural Fibres for the Reinforcement of Unpaved Forest Roads—Response after RL-CBR Tests
Authors: Carlos David Miranda , Rodrigues Daniela , Martins Catarina , Macedo Joaquim , Pinho-Lopes Margarida
Published: January 2024

Unpaved roads are essential as transportation infrastructure. These roads are traditionally built utilizing local soils and aggregates. The application of different materials to improve the strength and the overall performance of these road solutions has been investigated. This study focuses on the assessment of the suitability of reinforcing a fine soil using natural fibres from the forest value chain—specifically, pine needles—for unpaved forest roads. The resilient response of both unreinforced and reinforced soils was assessed with RL-CBR tests (California Bearing tests with repeated load) for different percentages of natural fibres incorporated into the soil. The force–penetration response, CBR value, recoverable and permanent displacements, and equivalent modulus were estimated. The effect of different load stages on the elastic response of both unreinforced and reinforced soils was also evaluated. The CBR values improved with the addition of pine needles; the best response was observed for specimens reinforced with 1% (mass) of these natural fibres (the CBR value increased by 45%). The equivalent modulus also was improved, showing that the stiffness of the soil increased with the inclusion of reinforcement. The findings imply that RL-CBR studies offer a promising method for obtaining important design parameters, especially for unpaved forest roads where investments in soil characterization are frequently limited.
Radiative Regime According to the New RAD-MSU(BSRN) Complex in Moscow: The Roles of Aerosol, Surface Albedo, and Sunshine Duration
Authors: Piskunova Daria , Chubarova Natalia , Poliukhov Aleksei , Zhdanova Ekaterina
Published: January 2024

The radiative budget is one of the key factors that influences climate change. The aim of this study was to analyze the radiative regime in Moscow using the RAD-MSU(BSRN) complex and to estimate the radiative effects of the main geophysical factors during the 2021–2023 period. This complex is equipped and maintained according to the recommendations of the Baseline Surface Radiation Network; however, it is not a part of this network. In cloudless conditions, the decrease in global shortwave irradiance (Q) is about 18–22% due to the aerosol content with a pronounced change in the direct to diffuse ratio. In winter, the increase in Q is about 45 W/m2 (or 9%) at h = 30° due to a high surface albedo and reduced aerosol and water vapor contents, while the net shortwave irradiance (Bsh) demonstrates a significant decrease due to the prevailing effects of snow albedo. In cloudy conditions, a nonlinear dependence of Q and Bsh cloud transmittance on the relative sunshine duration is observed. The mean changes in Q for the 2021–2023 against the 1955–2020 period are characterized by negative anomalies (−22%) in winter and positive anomalies in summer (+3%) due to the changes in cloudiness. This is in line with the global tendencies in the long-term changes in shortwave irradiance in moderate climates in Europe in recent years.
Boolean Subtypes of the U4 Hexagon of Opposition
Authors: Demey Lorenz , Erbas Atahan
Published: January 2024

This paper investigates the so-called ‘unconnectedness-4 (U4) hexagons of opposition’, which have various applications across the broad field of philosophical logic. We first study the oldest known U4 hexagon, the conversion closure of the square of opposition for categorical statements. In particular, we show that this U4 hexagon has a Boolean complexity of 5, and discuss its connection with the so-called ‘Gergonne relations’. Next, we study a simple U4 hexagon of Boolean complexity 4, in the context of propositional logic. We then return to the categorical square and show that another (quite subtle) closure operation yields another U4 hexagon of Boolean complexity 4. Finally, we prove that the Aristotelian family of U4 hexagons has no other Boolean subtypes, i.e., every U4 hexagon has a Boolean complexity of either 4 or 5. These results contribute to the overarching goal of developing a comprehensive typology of Aristotelian diagrams, which will allow us to systematically classify these diagrams into various Aristotelian families and Boolean subfamilies.
Bayesian Sensitivity Analysis for VaR and CVaR Employing Distorted Band Priors
Authors: Arias-Nicolás José Pablo , Parra María Isabel , Pizarro Mario M. , Sanjuán Eva L.
Published: January 2024

In the context of robust Bayesian analysis, studies mainly focus on computing the range of some quantities of interest when the prior distribution varies in a class. We use the concept of distorted bands to introduce a family of priors on the shape parameter of the Generalized Pareto distribution. We show how certain properties of the likelihood ratio order allow us to propose novel sensitivity measures for Value at Risk and Conditional Value at Risk, which are the most useful and reliable risk measures. Although we focus on the Generalized Pareto distribution, which is essential in Extreme Value Theory, the new sensitivity measures could be employed for all the distributions that verify certain conditions related to likelihood ratio order. A thorough simulation study was carried out to perform a sensitivity analysis, and two illustrative examples are also provided.
Investigation of Xinomavro Red Wine Aging with Various Wood Chips Using Pulsed Electric Field
Authors: Toulaki Artemis K. , Athanasiadis Vassilis , Chatzimitakos Theodoros , Kalompatsios Dimitrios , Bozinou Eleni , Roufas Kosmas , Mantanis George I. , Dourtoglou Vassilis G. , Lalas Stavros I.
Published: January 2024

This study explored the potential of pulsed electric field (PEF) as an alternative wine-aging method in four Xinomavro red wines with the implementation of several wood chips (apricot, peach, apple, cherry, acacia, and oak trees). The evolution of total polyphenol content (TPC) and sensory properties of the wines were investigated. Sensory evaluation revealed that PEF treatment increased volatile compound extraction from each wood chip, thereby enhancing the overall quality of the wines. The utilization of acacia tree wood chips in Goumenissa wine led to a notable increase of 10.84% in TPC from the control sample, reaching 2334.74 mg gallic acid equivalents/L. A notable outcome was that PEF decreased TPC, a trend that was also verified through correlation analyses. The highest positive impact of PEF was observed in peach tree wood chips in Goumenissa wine, with a significant increase of 11.05% in TPC. The results from the volatile compound analysis revealed an increase in alcohols and esters from 0.24% to 23.82%, with the highest proportion found in 2-phenylethanol (16.92 mg/L) when utilizing peach tree wood chips in the production of Amyndeo wine. This study could provide a benchmark for rapid, efficient, and cost-effective wine aging through the implementation of the PEF process.
Enzyme-Mediated Exponential Glucose Release: A Model-Based Strategy for Continuous Defined Fed-Batch in Small-Scale Cultivations
Authors: Kemmer Annina , Cai Linda , Born Stefan , Cruz Bournazou M. Nicolas , Neubauer Peter
Published: January 2024

Miniaturized cultivation systems offer the potential to enhance experimental throughput in bioprocess development. However, they usually lack the miniaturized pumps necessary for fed-batch mode, which is commonly employed in industrial bioprocesses. An alternative are enzyme-mediated glucose release systems from starch-derived polymers, facilitating continuous glucose supply. Nevertheless, while the glucose release, and thus the feed rate, is controlled by the enzyme concentration, it also strongly depends on the type of starch derivative, and the culture conditions as well as pH and temperature. So far it was not possible to implement controlled feeding strategies (e.g., exponential feeding). In this context, we propose a model-based approach to achieve precise control over enzyme-mediated glucose release in cultivations. To this aim, an existing mathematical model was integrated into a computational framework to calculate setpoints for enzyme additions. We demonstrate the ability of the tool to maintain different pre-defined exponential growth rates during Escherichia coli cultivations in parallel mini-bioreactors integrated into a robotic facility. Although in this case study, the intermittent additions of enzyme and dextrin were performed by a liquid handler, the approach is adaptable to manual applications. Thus, we present a straightforward and robust approach for implementing defined continuous fed-batch processes in small-scale systems, where continuous feeding was only possible with low accuracy or high technical efforts until now.
A Deep Learning Approach for Improving Two-Photon Vascular Imaging Speeds
Authors: Zhou Annie , Mihelic Samuel A. , Engelmann Shaun A. , Tomar Alankrit , Dunn Andrew K. , Narasimhan Vagheesh M.
Published: January 2024

A potential method for tracking neurovascular disease progression over time in preclinical models is multiphoton fluorescence microscopy (MPM), which can image cerebral vasculature with capillary-level resolution. However, obtaining high-quality, three-dimensional images with traditional point scanning MPM is time-consuming and limits sample sizes for chronic studies. Here, we present a convolutional neural network-based (PSSR Res-U-Net architecture) algorithm for fast upscaling of low-resolution or sparsely sampled images and combine it with a segmentation-less vectorization process for 3D reconstruction and statistical analysis of vascular network structure. In doing so, we also demonstrate that the use of semi-synthetic training data can replace the expensive and arduous process of acquiring low- and high-resolution training pairs without compromising vectorization outcomes, and thus open the possibility of utilizing such approaches for other MPM tasks where collecting training data is challenging. We applied our approach to images with large fields of view from a mouse model and show that our method generalizes across imaging depths, disease states and other differences in neurovasculature. Our pretrained models and lightweight architecture can be used to reduce MPM imaging time by up to fourfold without any changes in underlying hardware, thereby enabling deployability across a range of settings.
Ovine Mesenchymal Stem Cell Chondrogenesis on a Novel 3D-Printed Hybrid Scaffold In Vitro
Authors: De Mori Arianna , Heyraud Agathe , Tallia Francesca , Blunn Gordon , Jones Julian R. , Roncada Tosca , Cobb Justin , Al-Jabri Talal
Published: January 2024

This study evaluated the use of silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) 3D-printed scaffolds, with channel sizes of either 200 (SC-200) or 500 (SC-500) µm, as biomaterials to support the chondrogenesis of sheep bone marrow stem cells (oBMSC), under in vitro conditions. The objective was to validate the potential use of SiO2/PTHF/PCL-diCOOH for prospective in vivo ovine studies. The behaviour of oBMSC, with and without the use of exogenous growth factors, on SiO2/PTHF/PCL-diCOOH scaffolds was investigated by analysing cell attachment, viability, proliferation, morphology, expression of chondrogenic genes (RT-qPCR), deposition of aggrecan, collagen II, and collagen I (immunohistochemistry), and quantification of sulphated glycosaminoglycans (GAGs). The results showed that all the scaffolds supported cell attachment and proliferation with upregulation of chondrogenic markers and the deposition of a cartilage extracellular matrix (collagen II and aggrecan). Notably, SC-200 showed superior performance in terms of cartilage gene expression. These findings demonstrated that SiO2/PTHF/PCL-diCOOH with 200 µm pore size are optimal for promoting chondrogenic differentiation of oBMSC, even without the use of growth factors.
Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations
Authors: Al-Ansari Nojoud , Samuel Samson Mathews , Büsselberg Dietrich
Published: January 2024

Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep–wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as inflammation. Additionally, melatonin has demonstrated promising potential as an anti-cancer agent as its function includes inhibition of tumorigenesis, induction of apoptosis, and regulation of anti-tumor immune response. Although a precise pathophysiological mechanism is yet to be established, several pathways related to the regulation of cell cycle progression, DNA repair mechanisms, and antioxidant activity have been implicated in the anti-neoplastic potential of melatonin. In the current manuscript, we focus on the potential anti-cancer properties of melatonin and its use in treating and managing pediatric osteosarcoma. This aggressive bone tumor primarily affects children and adolescents and is treated mainly by surgical and radio-oncological interventions, which has improved survival rates among affected individuals. Significant disadvantages to these interventions include disease recurrence, therapy-related toxicity, and severe/debilitating side effects that the patients have to endure, significantly affecting their quality of life. Melatonin has therapeutic effects when used for treating osteosarcoma, attributed to its ability to halt cancer cell proliferation and trigger apoptotic cell death, thereby enhancing chemotherapeutic efficacy. Furthermore, the antioxidative function of melatonin alleviates harmful side effects of chemotherapy-induced oxidative damage, aiding in decreasing therapeutic toxicities. The review concisely explains the many mechanisms by which melatonin targets osteosarcoma, as evidenced by significant results from several in vitro and animal models. Nevertheless, if further explored, human trials remain a challenge that could shed light and support its utility as an adjunctive therapeutic modality for treating osteosarcoma.
The HIF-1α and mTOR Pathways Amplify Heterotopic Ossification
Authors: Wang Haitao , Kaplan Frederick S. , Pignolo Robert J.
Published: January 2024

Fibrodysplasia ossificans progressiva (FOP; MIM# 135100) is an ultra-rare congenital disorder caused by gain-of-function point mutations in the Activin receptor A type I (ACVR1, also known as ALK2) gene. FOP is characterized by episodic heterotopic ossification (HO) in skeletal muscles, tendons, ligaments, or other soft tissues that progressively causes irreversible loss of mobility. FOP mutations cause mild ligand-independent constitutive activation as well as ligand-dependent bone morphogenetic protein (BMP) pathway hypersensitivity of mutant ACVR1. BMP signaling is also a key pathway for mediating acquired HO. However, HO is a highly complex biological process involving multiple interacting signaling pathways. Among them, the hypoxia-inducible factor (HIF) and mechanistic target of rapamycin (mTOR) pathways are intimately involved in both genetic and acquired HO formation. HIF-1α inhibition or mTOR inhibition reduces HO formation in mouse models of FOP or acquired HO in part by de-amplifying the BMP pathway signaling. Here, we review the recent progress on the mechanisms of the HIF-1α and mTOR pathways in the amplification of HO lesions and discuss the future directions and strategies to translate the targeting of HIF-1α and the mTOR pathways into clinical interventions for FOP and other forms of HO.
Biological Effects of Small Sized Graphene Oxide Nanosheets on Human Leukocytes
Authors: Aventaggiato Michele , Valentini Federica , Caissutti Daniela , Relucenti Michela , Tafani Marco , Misasi Roberta , Zicari Alessandra , Di Martino Sara , Virtuoso Sara , Neri Anna , Mardente Stefania
Published: January 2024

Since the discovery of graphene, there has been a wide range of the literature dealing with its versatile structure and easy binding of biomolecules as well as its large loading capacity. In the emerging field of immunotherapy, graphene and its derivatives have potential uses as drug delivery platforms directly into tumour sites or as adjuvants in cancer vaccines, as they are internalized by monocytes which in turn may activate adaptive anti-tumoral immune responses. In this study, we expose cells of the innate immune system and a human acute monocytic leukemia cell line (THP-1) to low doses of small-sized GO nanosheets functionalized with bovine serum albumin (BSA) and fluorescein isothiocyanate (FITC), to study their acute response after internalization. We show by flow cytometry, uptake in cells of GO-BSA-FITC reaches 80% and cell viability and ROS production are both unaffected by exposure to nanoparticles. On the contrary, GO-BSA nanosheets seem to have an inhibitory effect on ROS production, probably due to their antioxidant properties. We also provided results on chemotaxis of macrophages derived from peripheral blood monocytes treated with GO-BSA. In conclusion, we showed the size of nanosheets, the concentration used and the degree of functionalization were important factors for biocompatibility of GO in immune cells. Its low cytotoxicity and high adaptability to the cells of the innate immune system make it a good candidate for deployment in immunotherapy, in particular for delivering protein antigens to monocytes which activate adaptive immunity.
The Role of Chaperone-Mediated Autophagy in Tissue Homeostasis and Disease Pathogenesis
Authors: Valdor Rut , Martinez-Vicente Marta
Published: January 2024

Chaperone-mediated autophagy (CMA) is a selective proteolytic pathway in the lysosomes. Proteins are recognized one by one through the detection of a KFERQ motif or, at least, a KFERQ-like motif, by a heat shock cognate protein 70 (Hsc70), a molecular chaperone. CMA substrates are recognized and delivered to a lysosomal CMA receptor, lysosome-associated membrane protein 2A (LAMP-2A), the only limiting component of this pathway, and transported to the lysosomal lumen with the help of another resident chaperone HSp90. Since approximately 75% of proteins are reported to have canonical, phosphorylation-generated, or acetylation-generated KFERQ motifs, CMA maintains intracellular protein homeostasis and regulates specific functions in the cells in different tissues. CMA also regulates physiologic functions in different organs, and is then implicated in disease pathogenesis related to aging, cancer, and the central nervous and immune systems. In this minireview, we have summarized the most important findings on the role of CMA in tissue homeostasis and disease pathogenesis, updating the recent advances for this Special Issue.
The Neutrophil/Lymphocyte Ratio and Outcomes in Hospitalized Patients with Community-Acquired Pneumonia: A Retrospective Cohort Study
Authors: Tekin Aysun , Wireko Felix W. , Gajic Ognjen , Odeyemi Yewande E.
Published: January 2024

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome was mortality. ICU admission and hospital- and ICU-free days were secondary outcomes. The pneumonia severity index (PSI) and the NLR’s ability to predict outcomes was also tested. An NLR ≤12 was observed in 2513 (62.2%) patients and >12 in 1526 (37.8%). After adjusting for PSI, the NLR was not associated with hospital mortality (odds ratio [OR] 1.115; 95% confidence interval [CI] 0.774, 1.606; p = 0.559), but it was associated with a higher risk of ICU admission (OR 1.405; 95% CI 1.216, 1.624; p < 0.001). The PSI demonstrated acceptable discrimination for mortality (area under the receiver operating characteristic curve [AUC] 0.78; 95% CI 0.75, 0.82) which was not improved by adding the NLR (AUC 0.78; 95% CI 0.75, 0.82, p = 0.4476). The PSI’s performance in predicting ICU admission was also acceptable (AUC 0.75; 95% CI 0.74, 0.77) and improved by including the NLR (AUC 0.76, 95% CI 0.74, 0.77, p = 0.008), although with limited clinical significance. The NLR was not superior to the PSI for predicting mortality in hospitalized CAP patients.
Gender Medicine and Pharmacology
Authors: Allegra Sarah , Chiara Francesco , De Francia Silvia
Published: January 2024

Gender-specific medicine consists of a transversal methodological approach that aims to study the influence of sex and gender on diseases [...]
Ventricular Tachycardia Catheter Ablation: Retrospective Analysis and Prospective Outlooks—A Comprehensive Review
Authors: Stanciulescu Laura Adina , Vatasescu Radu
Published: January 2024

Ventricular tachycardia is a potentially life-threatening arrhythmia associated with an overall high morbi-mortality, particularly in patients with structural heart disease. Despite their pivotal role in preventing sudden cardiac death, implantable cardioverter-defibrillators, although a guideline-based class I recommendation, are unable to prevent arrhythmic episodes and significantly alter the quality of life by delivering recurrent therapies. From open-heart surgical ablation to the currently widely used percutaneous approach, catheter ablation is a safe and effective procedure able to target the responsible re-entry myocardial circuit from both the endocardium and the epicardium. There are four main mapping strategies, activation, entrainment, pace, and substrate mapping, each of them with their own advantages and limitations. The contemporary guideline-based recommendations for VT ablation primarily apply to patients experiencing antiarrhythmic drug ineffectiveness or those intolerant to the pharmacological treatment. Although highly effective in most cases of scar-related VTs, the traditional approach may sometimes be insufficient, especially in patients with nonischemic cardiomyopathies, where circuits may be unmappable using the classic techniques. Alternative methods have been proposed, such as stereotactic arrhythmia radioablation or radiotherapy ablation, surgical ablation, needle ablation, transarterial coronary ethanol ablation, and retrograde coronary venous ethanol ablation, with promising results. Further studies are needed in order to prove the overall efficacy of these methods in comparison to standard radiofrequency delivery. Nevertheless, as the field of cardiac electrophysiology continues to evolve, it is important to acknowledge the role of artificial intelligence in both the pre-procedural planning and the intervention itself.
Pan-Cancer Analysis Reveals Disulfidoptosis-Associated Genes as Promising Immunotherapeutic Targets: Insights Gained from Bulk Omics and Single-Cell Sequencing Validation
Authors: Xu Borui , Li Minghao , Weng Nuoqing , Zhou Chuzhou , Chen Yinghui , Wei Jinhuan , Fu Liangmin
Published: January 2024

Disulfidoptosis, a novel form of cell death, is distinct from other well-known cell death mechanisms. Consequently, a profound investigation into disulfidoptosis elucidates the fundamental mechanisms underlying tumorigenesis, presenting promising avenues for therapeutic intervention. Comprehensive analysis of disulfidoptosis-associated gene (DRG) expression in pan cancer utilized TCGA, GEO, and ICGC datasets, including survival and Cox-regression analyses for prognostic evaluation. We analyzed the association between DRG expression and both immune cell infiltration and immune-related gene expression using the ESTIMATE and TISDIB datasets. We obtained our single-cell RNA sequencing (scRNA-seq) data from the GEO repository. Subsequently, we assessed disulfidoptosis activity in various cell types. Evaluation of immune cell infiltration and biological functions was analyzed via single-sample gene set enrichment (ssGSEA) and gene set variation analysis (GSVA). For in vitro validation experiments, the results from real-time PCR (RT-qPCR) and Western blot were used to explore the expression of SLC7A11 in hepatocellular carcinoma (HCC) tissues and different cancer cell lines, while siRNA-mediated SLC7A11 knockdown effects on HCC cell proliferation and migration were examined. Expression levels of DRGs, especially SLC7A11, were significantly elevated in tumor samples compared to normal samples, which was associated with poorer outcomes. Except for SLC7A11, DRGs consistently exhibited high CNV and SNV rates, particularly in HCC. In various tumors, DRGs were negatively associated with DNA promoter methylation. TME analyses further illustrated a negative correlation of DRG expression with ImmuneScore and StromalScore and a positive correlation with tumor purity. Our analysis unveiled diverse cellular subgroups within HCC, particularly focusing on Treg cell populations, providing insights into the intricate interplay of immune activation and suppression within the tumor microenvironment (TME). These findings were further validated through RT-qPCR, Western blot analyses, and immunohistochemical analyses. Additionally, the knockdown of SLC7A11 induced a suppression of proliferation and migration in HCC cell lines. In conclusion, our comprehensive pan-cancer analysis research has demonstrated the significant prognostic and immunological role of disulfidoptosis across a spectrum of tumors, notably HCC, and identified SLC7A11 as a promising therapeutic target.
Role of BAL and Serum Krebs von den Lungen-6 (KL-6) in Patients with Pulmonary Fibrosis
Authors: Soccio Piera , Moriondo Giorgia , d’Alessandro Miriana , Scioscia Giulia , Bergantini Laura , Gangi Sara , Tondo Pasquale , Foschino Barbaro Maria Pia , Cameli Paolo , Bargagli Elena , Lacedonia Donato
Published: January 2024

Background: Interstitial lung diseases (ILDs) encompass a diverse group of disorders affecting the lung interstitium, leading to inflammation, fibrosis, and impaired respiratory function. Currently, the identification of new diagnostic and prognostic biomarkers for ILDs turns out to be necessary. Several studies show the role of KL-6 in various types of interstitial lung disease and suggest that serum KL-6 levels can be used as a prognostic marker of disease. The aim of this study was to analyze KL-6 expression either in serum or bronchoalveolar lavage samples in order to: (i) make a serum vs. BAL comparison; (ii) better understand the local behavior of fibrosis vs. the systemic one; and (iii) evaluate any differences in patients with progressive fibrosis (PPF) versus patients with non-progressive fibrosis (nPPF). Methods: We used qRT-PCR to detect KL-6 expression both in serum and BAL samples. Mann–Whitney’s U test was used to compare the differential expression between groups. Results: In serum, KL-6 is more highly expressed in PPF than in non-progressive fibrosis (p = 0.0295). This difference is even more significant in BAL (p < 0.001). Therefore, it is clear that KL-6 values are related to disease progression. Significant differences were found by making a comparison between BAL and serum. KL-6 was markedly higher in serum than BAL (p = 0.0146). Conclusions: This study identifies KL-6 as a promising biomarker for the severity of the fibrosing process and disease progression in ILDs, with significantly higher levels observed in PPF compared to nPPF. Moreover, the marked difference in KL-6 levels between serum and BAL emphasizes its potential diagnostic and prognostic relevance, providing enlightening insights into both the local and systemic aspects of ILDs.
A Multienzyme Reaction-Mediated Electrochemical Biosensor for Sensitive Detection of Organophosphorus Pesticides
Authors: Ji Chengzhen , Tang Xuemei , Wen Ruiming , Xu Chengdong , Wei Jing , Han Bingjun , Wu Long
Published: January 2024

Ethephon (ETH), a commonly employed growth regulator, poses potential health risks due to its residue in fruits and vegetables, leading to both acute and subchronic toxicity. However, the detection accuracy of ETH is compromised by the color effects of the samples during the detection process. In this work, a multienzyme reaction-mediated electrochemical biosensor (MRMEC) was developed for the sensitive, rapid, and color-interference-resistant determination of ETH. Nanozymes Fe3O4@Au–Pt and graphene nanocomplexes (GN–Au NPs) were prepared as catalysts and signal amplifiers for MRMEC. Acetylcholinesterase (AChE), acetylcholine (ACh), and choline oxidase (CHOx) form a cascade enzyme reaction to produce H2O2 in an electrolytic cell. Fe3O4@Au–Pt has excellent peroxidase-like activity and can catalyze the oxidation of 3,3′,5,5′-tetramethvlbenzidine (TMB) in the presence of H2O2, resulting in a decrease in the characteristic peak current of TMB. Based on the inhibitory effect of ETH on AChE, the differential pulse voltammetry (DPV) current signal of TMB was used to detect ETH, offering the limit of detection (LOD) of 2.01 nmol L−1. The MRMEC method effectively analyzed ETH levels in mangoes, showing satisfactory precision (coefficient of variations, 2.88–15.97%) and recovery rate (92.18–110.72%). This biosensor holds promise for detecting various organophosphorus pesticides in food samples.
A Ratiometric Biosensor Containing Manganese Dioxide Nanosheets and Nitrogen-Doped Quantum Dots for 2,4-Dichlorophenoxyacetic Acid Monitoring
Authors: Guo Yang , Sun Jingran , Liu Mingzhu , Wu Jin , Zhao Zunquan , Ma Ting , Fang Yanjun
Published: January 2024

Nanomaterials are desirable for sensing applications. Therefore, MnO2 nanosheets and nitrogen-doped carbon dots (NCDs) were used to construct a ratiometric biosensor for quantification of 2,4-dichlorophenoxyacetic acid. The MnO2 nanosheets drove the oxidation of colorless o-phenylenediamine to OPDox, which exhibits fluorescence emission peaks at 556 nm. The fluorescence of OPDox was efficiently quenched and the NCDs were recovered as the ascorbic acid produced by the hydrolyzed alkaline phosphatase (ALP) substrate increased. Owing to the selective inhibition of ALP activity by 2,4-D and the inner filter effect, the fluorescence intensity of the NCDs at 430 nm was suppressed, whereas that at 556 nm was maintained. The fluorescence intensity ratio was used for quantitative detection. The linear equation was F = 0.138 + 3.863·C 2,4-D (correlation coefficient R2 = 0.9904), whereas the limits of detection (LOD) and quantification (LOQ) were 0.013 and 0.040 μg/mL. The method was successfully employed for the determination of 2,4-D in different vegetables with recoveries of 79%~105%. The fluorescent color change in the 2,4-D sensing system can also be captured by a smartphone to achieve colorimetric detection by homemade portable test kit.
The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review
Authors: Salvagno Michele , Geraldini Federico , Coppalini Giacomo , Robba Chiara , Gouvea Bogossian Elisa , Annoni Filippo , Vitali Eva , Sterchele Elda Diletta , Balestra Costantino , Taccone Fabio Silvio
Published: January 2024

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting.
Sensory Stimulation of the Triceps Surae Muscle Complex Modulates Spinal Reflex Responses—A Comparison between Tapotement Massage and Repetitive Peripheral Magnetic Stimulation (rPMS)
Authors: Zschorlich Volker R. , Qi Fengxue , Schorer Jörg , Büsch Dirk
Published: January 2024

Background: The reduction of muscular hypertonia is important in the treatment of various diseases or rehabilitation. This study aims to test the efficacy of a 5 Hz mechanical muscle stimulation (tapotement massage) in comparison to a 5 Hz repetitive peripheral magnetic stimulation (rPMS) on the neuromuscular reflex response. Methods: In a randomized control trial, 15 healthy volunteers were administered with either 5 Hz rPMS, tapotement massage, or rPMS sham stimulation. The posterior tibial nerve was stimulated with rPMS and sham stimulation. The Achilles tendon was exposed to a mechanically applied high-amplitude 5 Hz repetitive tendon tapotement massage (rTTM). The tendon reflex (TR) was measured for the spinal response of the soleus muscle. Results: After rPMS, there was a reduction of the TR response (−9.8%, p ≤ 0.034) with no significant changes after sham stimulation. Likewise, TR decreased significantly (−17.4%, p ≤ 0.002) after Achilles tendon tapotement intervention. Conclusions: These findings support the hypothesis that both afferent 5 Hz sensory stimulations contributed to a modulation within the spinal and/or supraspinal circuits, which resulted in a reduction of the spinal reflex excitability. The effects could be beneficial for patients with muscle hypertonia and could improve the functional results of rehabilitation programs.
Associations between Gross and Fine Motor Skills, Physical Activity, Executive Function, and Academic Achievement: Longitudinal Findings from the UK Millennium Cohort Study
Authors: Zhou Yuxi , Tolmie Andrew
Published: January 2024

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The sample was 3188 children from the United Kingdom Millennium Cohort Study, followed at 9 months and 5, 7, and 11 years. Early motor skills were examined at 9 months. Children’s daily physical activity level was measured using accelerometers at 7 years and a questionnaire was conducted at 11 years. Cognitive skills, including executive function and academic achievement, were measured at age 11. The results suggest that gross motor skills were positively associated with spatial working memory, whereas fine motor skills were predictive of good English and science outcomes. Moderate-to-vigorous activity was found to be negatively associated with English performance, although self-reported activity frequency was positively linked to math. Our results highlight the significant role of both gross and fine motor skills in cognitive development. This study also elucidates the limitations of using activity intensity to assess the impact of motor activity on children’s cognitive development, suggesting that attention to the effects of specific types of physical activity would better elucidate the motor/cognition link.
Working Memory Maintenance of Visual and Auditory Spatial Information Relies on Supramodal Neural Codes in the Dorsal Frontoparietal Cortex
Authors: Rizza Aurora , Pedale Tiziana , Mastroberardino Serena , Olivetti Belardinelli Marta , Van der Lubbe Rob H. J. , Spence Charles , Santangelo Valerio
Published: January 2024

The frontoparietal attention network plays a pivotal role during working memory (WM) maintenance, especially under high-load conditions. Nevertheless, there is ongoing debate regarding whether this network relies on supramodal or modality-specific neural signatures. In this study, we used multi-voxel pattern analysis (MVPA) to evaluate the neural representation of visual versus auditory information during WM maintenance. During fMRI scanning, participants maintained small or large spatial configurations (low- or high-load trials) of either colour shades or sound pitches in WM for later retrieval. Participants were less accurate in retrieving high- vs. low-load trials, demonstrating an effective manipulation of WM load, irrespective of the sensory modality. The frontoparietal regions involved in maintaining high- vs. low-load spatial maps in either sensory modality were highlighted using a conjunction analysis. Widespread activity was found across the dorsal frontoparietal network, peaking on the frontal eye fields and the superior parietal lobule, bilaterally. Within these regions, MVPAs were performed to quantify the pattern of distinctness of visual vs. auditory neural codes during WM maintenance. These analyses failed to reveal distinguishable patterns in the dorsal frontoparietal regions, thus providing support for a common, supramodal neural code associated with the retention of either visual or auditory spatial configurations.