bluuebunny/crossref_metadata_2025 huggingface dataset:
Ascorbic Acid Enhances the Inhibitory Effect of Theasaponins against Candida albicans
Authors: Chen Yuhong , Gao Ying , Yin Junfeng
Published: October 2024

Candida albicans (C. albicans) is a main cause of hospital-acquired fungal infections. Combination therapy is promising as a novel anti-C. albicans strategy because of its better efficacy. Theasaponins are pentacyclic triterpenes in the Camellia genus with multiple biological activities. Our previous studies prove that theasaponins display inhibitory activity against C. albicans. Ascorbic acid (VC) is a vitamin found in many plants that shows potential in combination therapy. However, whether VC enhances the activity of theasaponins remains unclear. In this study, the checkerboard micro-dilution method was used to assess the effect of VC (0–80 mmol/L) on the anti-C. albicans effect of theasaponins (0–1000 μg/mL). Then, the effects of theasaponins (31.25 μg/mL), VC (80 mmol/L), and theasaponins (31.25 μg/mL) + VC (80 mmol/L) on C. albicans planktonic cells and different stages of biofilm formation were assessed. Transcriptomic analysis was conducted to investigate the molecular mechanisms. According to the results, VC enhanced the anti-planktonic and anti-biofilm effect of theasaponins against C. albicans. The minimum inhibitory concentration of theasaponins was significantly decreased and the fungicidal efficiency was increased with the addition of VC. VC remarkably aggravated the suppression of theasaponins with regard to various virulence factors of C. albicans, including adhesion, early biofilm formation, mature biofilm, cell surface hydrophobicity, and phospholipase activity. Compared with the theasaponins or VC groups, the level of intracellular reactive oxygen species was higher, while the levels of mitochondrial membrane potential and adenosine triphosphate were lower in the combination group, suggesting more severe oxidative stress, mitochondrial injury, and energy deficiency. Transcriptomic analysis revealed that the combination predominantly suppressed the pathways of glycolysis, glycerophospholipid metabolism, glutathione metabolism, and cysteine and methionine metabolism. This implied that energy deficiency and redox imbalance were associated with the anti-C. albicans activity of the combination. These results prove that VC enhances the inhibitory effect of theasaponins against C. albicans and that the combination has the potential to be used as a topical antifungal therapy or disinfectant.
Radiofrequency Currents Modulate Inflammatory Processes in Keratinocytes
Authors: Toledano-Macías Elena , Martínez-Pascual María Antonia , Cecilia-Matilla Almudena , Bermejo-Martínez Mariano , Pérez-González Alfonso , Jara Rosa Cristina , Sacristán Silvia , Hernández-Bule María Luisa
Published: October 2024

Keratinocytes play an essential role in the inflammatory phase of wound regeneration. In addition to migrating and proliferating for tissue regeneration, they produce a large amount of cytokines that modulate the inflammatory process. Previous studies have shown that subthermal treatment with radiofrequency (RF) currents used in capacitive resistive electric transfer (CRET) therapy promotes the proliferation of HaCat keratinocytes and modulates their cytokine production. Although physical therapies have been shown to have anti-inflammatory effects in a variety of experimental models and in patients, knowledge of the biological basis of these effects is still limited. The aim of this study was to investigate the effect of CRET on keratinocyte proliferation, cytokine production (IL-8, MCP-1, RANTES, IL-6, IL-11), TNF-α secretion, and the expression of MMP9, MMP1, NF-κB, ERK1/2, and EGFR. Human keratinocytes (HaCat) were treated with an intermittent 448 kHz electric current (CRET signal) in subthermal conditions and for different periods of time. Cell proliferation was analyzed by XTT assay, cytokine and TNF-α production by ELISA, NF-κB expression and activation by immunofluorescence, and MMP9, MMP1, ERK1/2, and EGF receptor expression and activation by immunoblot. Compared to a control, CRET increases keratinocyte proliferation, increases the transient release of MCP-1, TNF-α, and IL-6 while decreasing IL-8. In addition, it modifies the expression of MMPs and activates EGFR, NF-κB, and ERK1/2 proteins. Our results indicate that CRET reasonably modifies cytokine production through the EGF receptor and the ERK1/2/NF-κB pathway, ultimately modulating the inflammatory response of human keratinocytes.
Syntaxin 3B: A SNARE Protein Required for Vision
Authors: Dey Himani , Perez-Hurtado Mariajose , Heidelberger Ruth
Published: October 2024

Syntaxin 3 is a member of a large protein family of syntaxin proteins that mediate fusion between vesicles and their target membranes. Mutations in the ubiquitously expressed syntaxin 3A splice form give rise to a serious gastrointestinal disorder in humans called microvillus inclusion disorder, while mutations that additionally involve syntaxin 3B, a splice form that is expressed primarily in retinal photoreceptors and bipolar cells, additionally give rise to an early onset severe retinal dystrophy. In this review, we discuss recent studies elucidating the roles of syntaxin 3B and the regulation of syntaxin 3B functionality in membrane fusion and neurotransmitter release in the vertebrate retina.
Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways
Authors: Zhang Ting , Liu Chang , Zhong Ning , Wang Yichen , Huang Yiyun , Zhang Xiaoqin
Published: October 2024

Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in the pathogenesis and prognosis of this disorder. Cognitive impairment in schizophrenia encompasses a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcomes and quality of life. Therefore, it is imperative to identify the biological basis of cognitive deficits in schizophrenia and develop effective treatments. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptors, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia.
The Impact of Disease Severity on the Serum Levels of Significant Neutrophil Extracellular Trap (NET) Proteins in Patients with Psoriasis
Authors: Czerwińska Joanna , Owczarczyk-Saczonek Agnieszka
Published: October 2024

Psoriasis is an inflammatory skin disease with various symptoms of differing severities and with the reported prominent involvement of neutrophil extracellular traps (NETs). The excitation of neutrophils, e.g., by interleukin 8 (IL-8) or lipopolysaccharide (LPS), leads to the citrullination of histones and the release of protein–DNA complexes into the extracellular space, where they are digested by DNases. Our aim was to explore data on the levels of protein-complexed DNAs neutrophil elastase–DNA (NE-DNA) and myeloperoxidase–DNA (MPO-DNA), citrullinated histones (citH2, citH3, citH4), and NET-degrading enzyme DNase I in the serum of psoriatic patients with varying severities of clinical symptoms assessed with the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores. The levels of factors were detected in 52 patients with psoriasis and 22 healthy volunteers by the enzyme-linked immunosorbent assay (ELISA). The results showed the elevated levels of NE-DNA, MPO-DNA, citH3, and DNase I in the patients with psoriasis compared to healthy volunteers (p < 0.05). Additionally, changes were noticed in the levels of NE-DNA, citH3, and DNase I, depending on the severity of symptoms (p < 0.05). In mild psoriasis (PASI < 10, BSA < 10, DLQI < 10), the suppressing activity of the enzyme caused the impaired ability to remove the physiological level of NETs, whereas in moderate to severe psoriasis (PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10), the enhanced activity of DNase I failed to remove NETs due to the observed overexpression. It may, thus, be concluded that the mechanism of action of NETs, which play an undeniable role in psoriatic diseases, seem to follow two different paths depending on the severity of disease, which may be crucial in selecting potential anti-NET treatment methods.
Modulation of the Oncogenic LINE-1 Regulatory Network in Non-Small Cell Lung Cancer by Exosomal miRNAs
Authors: Hassanin Abeer A. I. , Ramos Kenneth S.
Published: October 2024

Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate the expression of genes within the oncogenic LINE-1 regulatory network. To test this hypothesis, plasma exosomes from controls, early, and late-stage NSCLC patients were co-cultured with non-tumorigenic lung epithelial cells for 72 h and processed for measurements of gene expression. Exosomes from late-stage NSCLC patients markedly increased the mRNA levels of LINE-1 ORF1 and ORF2, as well as the levels of target miRNAs in naïve recipient cells compared to saline or control exosomes. Late-stage exosomes also modulated the expression of oncogenic targets within the LINE-1 regulatory network, namely, ICAM1, AGL, RGS3, RGS13, VCAM1, and TGFβ1. In sharp contrast, exosomes from controls or early-stage NSCLC patients inhibited LINE-1 expression, along with many of the genetic targets within the LINE-1 regulatory network. Thus, late-stage NSCLC exosomes activate LINE-1 and miRNA-regulated oncogenic signaling in non-tumorigenic, recipient lung bronchial epithelial cells. These findings raise important questions regarding lung cancer progression and metastasis and open the door for the exploration of new therapeutic interventions.
Epigenetic Reprogramming and Inheritance of the Cellular Differentiation Status Following Transient Expression of a Nonfunctional Dominant-Negative Retinoblastoma Mutant in Murine Mesenchymal Stem Cells
Authors: Baryshev Mikhail , Maksimova Irina , Sasoveca Ilona
Published: October 2024

The retinoblastoma gene product (Rb1), a master regulator of the cell cycle, plays a prominent role in cell differentiation. Previously, by analyzing the differentiation of cells transiently overexpressing the ΔS/N DN Rb1 mutant, we demonstrated that these cells fail to differentiate into mature adipocytes and that they constitutively silence Pparγ2 through CpG methylation. Here, we demonstrate that the consequences of the transient expression of ΔS/N DN Rb1 are accompanied by the retention of Cebpa promoter methylation near the TSS under adipogenic differentiation, thereby preventing its expression. The CGIs of the promoters of the Rb1, Ezh2, Mll4, Utx, and Tet2 genes, which are essential for adipogenic differentiation, have an unmethylated status regardless of the cell differentiation state. Moreover, Dnmt3a, a de novo DNA methyltransferase, is overexpressed in undifferentiated ΔS/N cells compared with wild-type cells and, in addition to Dnmt1, Dnmt3a is significantly upregulated by adipogenic stimuli in both wild-type and ΔS/N cells. Notably, the chromatin modifier Ezh2, which is also involved in epigenetic reprogramming, is highly induced in ΔS/N cells. Overall, we demonstrate that two major genes, Pparγ2 and Cebpa, which are responsible for terminal adipocyte differentiation, are selectively epigenetically reprogrammed to constitutively silent states. We hypothesize that the activation of Dnmt3a, Rb1, and Ezh2 observed in ΔS/N cells may be a consequence of a stress response caused by the accumulation and malfunctioning of Rb1-interacting complexes for the epigenetic reprogramming of Pparγ2/Cebpa and prevention of adipogenesis in an inappropriate cellular context. The failure of ΔS/N cells to differentiate and express Pparγ2 and Cebpa in culture following the expression of the DN Rb1 mutant may indicate the creation of epigenetic memory for new reprogrammed epigenetic states of genes.
Utilizing Adenovirus Knob Proteins as Carriers in Cancer Gene Therapy Amidst the Presence of Anti-Knob Antibodies
Authors: Koizumi Naoya , Hirai Takamasa , Kano Junpei , Sato Anna , Suzuki Yurika , Sasaki Arisa , Nomura Tetsuya , Utoguchi Naoki
Published: October 2024

Numerous gene therapy drugs for cancer have received global approval, yet their efficacy against solid tumors remains inadequate. Our previous research indicated that the fiber protein, a component of the adenovirus capsid, can propagate from infected cells to neighboring cells that express the adenovirus receptor. We hypothesize that merging this fiber protein with an anti-cancer protein could enable the anti-cancer protein to disseminate around the transfected cells, presenting a novel approach to cancer gene therapy. In our study, we discovered that the knob region of the adenovirus type 5 fiber protein is the smallest unit capable of spreading to adjacent cells in a receptor-specific manner. We also showed that the recombinant knob protein infiltrates cells after dispersing to surrounding cells. To assess the potential of the knob protein to augment gene therapy for solid tumors in mice, we expressed a fusion gene of the A subunit of cytotoxic cholera toxin and the knob region in mouse tumors. We found that this fusion protein only inhibited tumor growth in receptor-expressing mouse melanomas, and this inhibitory effect persisted even in mice with anti-knob antibodies. Our study’s findings propose a novel cancer gene therapy strategy that enhances therapeutic effects by specifically delivering therapeutic proteins, expressed from in vivo administered genes, to target molecules. This outcome offers a fresh perspective on gene therapy for solid cancers, and we anticipate that knob proteins will serve as a platform for this method.
Aclarubicin Reduces the Nuclear Mobility of Human DNA Topoisomerase IIβ
Authors: Morotomi-Yano Keiko , Yano Ken-ichi
Published: October 2024

DNA topoisomerase II (TOP2) is an enzyme that resolves DNA topological problems arising in various nuclear processes, such as transcription. Aclarubicin, a member of the anthracyclines, is known to prevent the association of TOP2 with DNA, inhibiting the early step of TOP2 catalytic reactions. During our research on the subnuclear distribution of human TOP2B, we found that aclarubicin affects the mobility of TOP2B in the nucleus. FRAP analysis demonstrated that aclarubicin decreased the nuclear mobility of EGFP-tagged TOP2B in a concentration-dependent manner. Aclarubicin exerted its inhibitory effects independently of TOP2B enzymatic activities: TOP2B mutants defective for either ATPase or topoisomerase activity also exhibited reduced nuclear mobility in the presence of aclarubicin. Immunofluorescence analysis showed that aclarubicin antagonized the induction of DNA damage by etoposide. Although the prevention of the TOP2-DNA association is generally considered a primary action of aclarubicin in TOP2 inhibition, our findings highlight a previously unanticipated effect of aclarubicin on TOP2B in the cellular environment.
Prediction of Fan Array Performance with Polynomial and Support Vector Regression Models
Authors: Ostmann Philipp , Rätz Martin , Kremer Martin , Müller Dirk
Published: October 2024

The increasing utilisation of demand-controlled ventilation strategies leads to the frequent operation of fans under part-load conditions. To accurately predict the energy demand of a ventilation system with a fan array in the early design stages, models that calculate reliable results across the whole operating range are required. We present the comparison of a polynomial and a machine learning approach through support vector regression (SVR) to predict the fan performance over a wide range of typical operating points. For fitting and validation, we use experimental data. We investigate the extrapolation performance of both approaches. The SVR model achieves a slightly better representation of the experimental data with a lower error, especially when only sparse data are available. Both approaches yield similar results when the evaluation is conducted within the experimentally captured domain but deviates outside the domain. At operating points that are far from the experimentally captured domain, the polynomial models yield fan efficiencies that are physically plausible, while the SVR models drastically overpredict the fan efficiency. To rate the influence of such deviations towards modelling the actual energy demand, both approaches are applied to an operation simulation of a simplified office building. Both approaches yield similar results despite differing extrapolation capabilities.
Predictive Modeling of NOx Emissions from Lean Direct Injection of Hydrogen and Hydrogen/Natural Gas Blends Using Flame Imaging and Machine Learning
Authors: Gomez Escudero Iker , McDonell Vincent
Published: October 2024

This research paper explores the use of machine learning to relate images of flame structure and luminosity to measured NOx emissions. Images of reactions produced by 16 aero-engine derived injectors for a ground-based turbine operated on a range of fuel compositions, air pressure drops, preheat temperatures and adiabatic flame temperatures were captured and postprocessed. The experimental investigations were conducted under atmospheric conditions, capturing CO, NO and NOx emissions data and OH* chemiluminescence images from 27 test conditions. The injector geometry and test conditions were based on a statistically designed test plan. These results were first analyzed using the traditional analysis approach of analysis of variance (ANOVA). The statistically based test plan yielded 432 data points, leading to a correlation for NOx emissions as a function of injector geometry, test conditions and imaging responses, with 70.2% accuracy. As an alternative approach to predicting emissions using imaging diagnostics as well as injector geometry and test conditions, a random forest machine learning algorithm was also applied to the data and was able to achieve an accuracy of 82.6%. This study offers insights into the factors influencing emissions in ground-based turbines while emphasizing the potential of machine learning algorithms in constructing predictive models for complex systems.
Short-Term Water Demand Forecasting from Univariate Time Series of Water Reservoir Stations
Authors: Myllis Georgios , Tsimpiris Alkiviadis , Vrana Vasiliki
Published: October 2024

This study presents an improved data-centric approach to short-term water demand forecasting using univariate time series from water reservoir levels. The dataset comprises water level recordings from 21 reservoirs in Eastern Thessaloniki collected over 15 months via a SCADA system provided by the water company EYATH S.A. The methodology involves data preprocessing, anomaly detection, data imputation, and the application of predictive models. Techniques such as the Interquartile Range method and moving standard deviation are employed to identify and handle anomalies. Missing values are imputed using LSTM networks optimized through the Optuna framework. This study emphasizes a data-centric approach in deep learning, focusing on improving data quality before model application, which has proven to enhance prediction accuracy. This strategy is crucial, especially in regions where reservoirs are the primary water source, and demand distribution cannot be solely determined by flow meter readings. LSTM, Random Forest Regressor, ARIMA, and SARIMA models are utilized to extract and analyze water level trends, enabling more accurate future water demand predictions. Results indicate that combining deep learning techniques with traditional statistical models significantly improves the accuracy and reliability of water demand predictions, providing a robust framework for optimizing water resource management.
Fall Detection Based on Data-Adaptive Gaussian Average Filtering Decomposition and Machine Learning
Authors: Lin Yue-Der , Lu Chi-Jen , Sun Ming-Hsuan , Hung Ju-Hsuan
Published: October 2024

Falls are a significant health concern leading to increased morbidity and healthcare costs, especially for the elderly. Early and accurate detection of fall events is critical for timely intervention and preventing severe complications. This study presents a novel approach to triaxial accelerometer signals by employing data-adaptive Gaussian average filtering (DAGAF) decomposition in conjunction with machine learning techniques for fall detection. The triaxial accelerometer signals from the FallAllD dataset were decomposed into intrinsic mode functions (IMFs) and a residual component, from which feature vectors were extracted to train support vector machine (SVM) and k-nearest neighbor (kNN) classifiers. Experimental results demonstrate that the combination of the first and the third IMFs with the residual component yields the highest classification accuracy of 96.34%, with SVM outperforming kNN across all performance metrics. This approach significantly improves fall detection accuracy compared to using raw accelerometer signals, highlighting its potential in enhancing wearable fall detection systems. The proposed DAGAF decomposition method not only enhances feature extraction but also provides a promising advancement in the field, suggesting its potential to increase the reliability and accuracy of fall detection in practical applications.
The Impact of Attitude on High-Speed Rail Technology Acceptance among Elderly Passengers in Urban and Rural Areas: A Multigroup SEM Analysis
Authors: Dangbut Adisorn , Watcharamaisakul Fareeda , Champahom Thanapong , Jomnonkwao Sajjakaj , Wisutwattanasak Panuwat , Phojaem Thanakorn , Ratanavaraha Vatanavongs
Published: October 2024

This study investigates the impact of the attitudes of the elderly on the acceptance of Thailand’s high-speed rail technology according to the technology readiness index (TRI) and technology acceptance model (TAM) theories as guidelines for policies or strategies to enhance passengers’ intentions to use high-speed rail. A self-administered questionnaire was used to collect data from 3200 elderly people aged over 60 years in the surveyed areas along high-speed rail routes in Thailand, before the use of statistical analysis and multigroup structural equation modeling (SEM) to analyze variations in the participants’ attitudes toward urban and rural areas. The results that were thus obtained from both groups showed their differing attitudes toward the acceptance of technology. The TAM theory considers the attitude toward high-speed rail use in urban areas to be important, while, in rural areas, attitudes and perceived usefulness are important. With respect to the ease of use of high-speed rail, the most important factors were attitudes toward use and perceived usefulness. For the TRI theory, innovativeness features as the most positive influence on the perceived ease of high-speed rail use in both groups. Optimism and innovativeness were positive influences, but discomfort and insecurity carried a negative influence with respect to the perceived ease of use and usefulness.
The Role of Nuclear Medicine in the Diagnostic Work-Up of Athletes: An Essential Guide for the Sports Cardiologist
Authors: Zorzi Alessandro , Bondarev Sergei , Graziano Francesca , Cecere Annagrazia , Giordani Andrea , Turk Luka , Corrado Domenico , Zucchetta Pietro , Cecchin Diego
Published: October 2024

Athletes with heart disease are at increased risk of malignant ventricular arrhythmias and sudden cardiac death compared to their sedentary counterparts. When athletes have symptoms or abnormal findings at preparticipation screenings, a precise diagnosis by differentiating physiological features of the athlete’s heart from pathological signs of cardiac disease is as important as it is challenging. While traditional imaging methods such as echocardiography, cardiac magnetic resonance, and computed tomography are commonly employed, nuclear medicine offers unique advantages, especially in scenarios requiring stress-based functional evaluation. This article reviews the use of nuclear medicine techniques in the diagnostic work-up of athletes with suspected cardiac diseases by highlighting their ability to investigate myocardial perfusion, metabolism, and innervation. The article discusses the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiotracers such as [99mTc]MIBI, [99mTc]HDP, [18F]FDG, and [123I]MIBG. Several clinical scenarios are explored, including athletes with coronary atherosclerosis, congenital coronary anomalies, ventricular arrhythmias, and non-ischemic myocardial scars. Radiation concerns are addressed, highlighting that modern SPECT and PET equipment significantly reduces radiation doses, making these techniques safer for young athletes. We conclude that, despite being underutilized, nuclear medicine provides unique opportunities for accurate diagnosis and effective management of cardiac diseases in athletes.
Effect of Prior Moderate Aerobic Exercise to Prolonged Sitting on Peripheral and Central Cardiovascular Measures in Young Women
Authors: Alansare Abdullah Bandar , Alotaibi Rawan Tuayes , Albarrati Ali Mufrih , Stoner Lee , Gibbs Bethany Barone
Published: October 2024

Background: Prolonged sitting is a risk factor for cardiovascular disease (CVD). We examined whether moderate aerobic exercise prior to prolonged sitting (EX + SIT) has protective effects on peripheral and central cardiovascular and autonomic measures. Methods: Young women (n = 26; 23.4 ± 4.3 years old; BMI = 23.1 ± 4.3) completed two sessions in random order: (1) EX + SIT, which consisted of 25 min of moderate aerobic exercise followed by a 3 h prolonged sitting bout, and (2) a 3 h prolonged sitting bout only (SIT-only). Seated peripheral and central blood pressure (BP), pulse wave velocity (PWV), and heart rate variability (HRV) were measured at baseline and after 1 h, 2 h, and 3 h of sitting. Generalized linear mixed models with random effects examined the effects of conditions (i.e., EX + SIT vs. SIT) on BP, PWV, and HRV while adjusting for baseline values. Results: Only peripheral and central diastolic BP (β = 2.18; p = 0.016 and β = 1.99; p = 0.034, respectively) were significantly lower in the EX + SIT condition compared to the SIT-only condition. No differences were detected in other BP, PWV, or HRV variables between the two conditions (p > 0.05 for all). Conclusions: Performing moderate aerobic exercise in the morning before engaging in prolonged sitting bouts may reduce some of the prolonged-sitting-induced cardiovascular impairments in young women. Further research is needed to confirm these findings in males and middle-aged/older adults.
Psychometric Properties of the Serbian Version of the Arm, Shoulder, and Hand Disability Self-Assessment Questionnaire: Criterion Validity, Construct Validity, and Internal Consistency
Authors: Vucetic Milos , Pavlovic Vedrana , Milutinovic Suzana , Stojicic Milan , Milic Natasa , Aleksandric Dejan , Miceta Lazar , Petrovic Bojan , Matejic Aleksandar , Rajovic Nina , Stanisic Vladislav , Tasic Ana , Dubravac Milena , Masic Srdjan , Stanisavljevic Dejana
Published: October 2024

Background/Objectives: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a widely employed self-report tool for assessing upper extremity function. The aim of this study was to assess the psychometric properties of the Serbian version of the DASH by determining its criterion and construct validity, as well as internal consistency. Methods: This cross-sectional study was conducted among patients with hand and wrist disabilities at the Institute for Orthopedics “Banjica”, Serbia. The psychometric properties of the Serbian version of the DASH were analyzed through an examination of its factorial structure and internal consistency. The DASH consists of 30 items, 24 of which assess function, 21 of which focus on physical function and three on social/role function. The remaining six items evaluate symptoms related to pain, tingling/numbness, weakness, and stiffness. Results: A total of 297 patients were included in the study. The mean age was 47.4 ± 16.8 years, with 50.5% males. Three models were assessed to determine the reliability and validity of the questionnaire across different domains. Model 1 examined a single-factor structure. In Model 2, the items were divided into two domains: Physical Function and Psychosocial/Symptoms. In Model 3, items were subdivided into three domains: Physical Function, Symptoms, and Psychosocial. All models demonstrated an excellent internal consistency with a Cronbach’s alpha > 0.9 for most domains. The values for the fit indices Tucker–Lewis index (TLI) and Comparative-Fit Index (CFI) were above their cut-off criteria of 0.9, while the Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) were below the suggested value of 0.06, indicating an excellent level of models fit. Standardized factor loadings were statistically significant (p < 0.05). Conclusions: The present study provided the evidence for the appropriate metric properties of the Serbian version of the DASH. Results support both the unidimensional and multidimensional structures of the DASH.
Electrocardiogram Features of Left Ventricular Excessive Trabeculation with Preserved Cardiac Function in Light of Cardiac Magnetic Resonance and Genetics
Authors: Farkas-Sütő Kristóf Attila , Grebur Kinga , Mester Balázs , Gyulánczi Flóra Klára , Bödör Csaba , Vágó Hajnalka , Merkely Béla , Szűcs Andrea
Published: October 2024

Background and Objectives: Although left ventricular excessive trabeculation (LVET) can cause heart failure, arrhythmia and thromboembolism, limited literature is available on the ECG characteristics of primary LVET with preserved left ventricular function (EF). We aimed to compare the ECG characteristics and cardiac MR (CMR) parameters of LVET individuals with preserved left ventricular EF to a control (C) group, to identify sex-specific differences, and to compare the genetic subgroups of LVET with each other and with a C population. Methods: In our study, we selected 69 LVET individuals (EF > 50%) without any comorbidities and compared them to 69 sex- and age-matched control subjects (42% females in both groups, p = 1.000; mean age LVET-vs-C: 38 ± 14 vs. 38 ± 14 years p = 0.814). We analyzed the pattern and notable parameters of the 12-lead ECG recordings. We determined the volumetric and functional parameters, as well as the muscle mass values of the left and right ventricles (LV, RV) based on the CMR recordings. Based on the genotype, three subgroups were established: pathogenic, variant of uncertain significance and benign. Results: In the LVET group, we found normal but elevated volumetric and muscle mass values and a decreased LV_EF, wider QRS, prolonged QTc, higher RV Sokolow index values and lower T wave amplitude compared to the C. When comparing MR and ECG parameters between genetic subgroups, only the QTc showed a significant difference. Over one-third of the LVET population had arrhythmic episodes and a positive family history. Conclusions: The subclinical morphological and ECG changes and the clinical background of the LVET group indicate the need for follow-up of this population, even with preserved EF.
Effects of Iron, Copper, Zinc, and Magnesium on Chronic Widespread Pain: A Two-Sample Mendelian Randomization
Authors: Kim Hyunjik , Ko Dai Sik
Published: October 2024

Background: Chronic widespread pain (CWP) affects approximately 10% of the adult population globally, causing significant physical and psychological distress. Micronutrients, such as iron, copper, zinc, and magnesium, are essential in various physiological functions, and their imbalances may impact pain perception and chronic pain conditions. Methods: This study used Mendelian randomization (MR) to investigate the causal relationships between micronutrient levels and CWP. Data were obtained from genome-wide association studies (GWASs) for iron, copper, zinc, and magnesium, and CWP data were sourced from large-scale GWASs with 461,857 European participants. Genetic variants were used as instrumental variables to infer causal relationships, minimizing confounding factors. Results: MR analysis revealed a significant association between higher iron levels and an increased risk of CWP (IVW, OR 1.01, 95% CI: 1.00–1.01, p = 0.029). This finding was supported by the weighted median and MR-Egger methods. No significant associations were found for copper, zinc, and magnesium levels. Conclusions: These results suggest that iron levels may influence pain perception and chronic pain conditions. Balanced iron levels are crucial for managing chronic pain. Regular monitoring and personalized treatment plans could benefit individuals with CWP. Further research is needed to understand the mechanisms linking micronutrient levels to chronic pain and to develop targeted therapeutic interventions.
Sera from Rheumatoid Arthritis Patients Induce Oxidative Stress and Pro-Angiogenic and Profibrotic Phenotypes in Human Endothelial Cells
Authors: Giordo Roberta , Posadino Anna Maria , Maccioccu Paola , Capobianco Giampiero , Zinellu Angelo , Erre Gian Luca , Pintus Gianfranco
Published: October 2024

Background: Rheumatoid arthritis (RA) is a long-term autoimmune condition marked by persistent inflammation of the joints and various systemic complications, including endothelial dysfunction, atherosclerosis, and pulmonary fibrosis. Oxidative stress is a key contributor to the pathogenesis of RA, potentially exacerbating vascular damage and promoting pro-angiogenic and profibrotic processes. Objective: This study aims to investigate the effects of sera from RA patients on human umbilical vein endothelial cells (HUVECs), focusing on the induction of oxidative stress, endothelial cell proliferation, migration, and collagen type I synthesis. Methods: Twenty-eight serum samples were collected from RA patients and healthy donors (HDs). HUVECs were exposed to these sera, and intracellular reactive oxygen species (ROS) levels were fluorescently detected using H2DCF-DA. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was evaluated through a scratch wound assay, and collagen type I synthesis was measured using a lentiviral vector expressing the green fluorescent protein (GFP) under the control of the human COL1A1 gene promoter. Results: Exposure to RA sera resulted in a significant increase in intracellular ROS levels in HUVECs compared to HD sera, indicating an elevated state of oxidative stress. RA sera also promoted endothelial cell proliferation and migration, suggesting a pro-angiogenic stimulus. Additionally, RA sera significantly increased collagen type I synthesis in HUVECs, implicating a potential role in profibrotic processes associated with RA. Conclusion: The results of this study emphasize the importance of circulating factors in RA sera in promoting oxidative stress, endothelial dysfunction, and pro-angiogenic and profibrotic phenotypes in endothelial cells. These processes may contribute to the vascular and fibrotic complications observed in RA, highlighting the necessity for additional research into focused therapeutic approaches to alleviate these effects.
Discogenic Low Back Pain: Anatomic and Pathophysiologic Characterization, Clinical Evaluation, Biomarkers, AI, and Treatment Options
Authors: De Simone Matteo , Choucha Anis , Ciaglia Elena , Conti Valeria , Pecoraro Giuseppina , Santurro Alessandro , Puca Annibale Alessandro , Cascella Marco , Iaconetta Giorgio
Published: October 2024

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes.
Improving Stroke Outcome Prediction Using Molecular and Machine Learning Approaches in Large Vessel Occlusion
Authors: Rout Madhusmita , Vaughan April , Sidorov Evgeny V. , Sanghera Dharambir K.
Published: October 2024

Introduction: Predicting stroke outcomes in acute ischemic stroke (AIS) can be challenging, especially for patients with large vessel occlusion (LVO). Available tools such as infarct volume and the National Institute of Health Stroke Scale (NIHSS) have shown limited accuracy in predicting outcomes for this specific patient population. The present study aimed to confirm whether sudden metabolic changes due to blood-brain barrier (BBB) disruption during LVO reflect differences in circulating metabolites and RNA between small and large core strokes. The second objective was to evaluate whether integrating molecular markers with existing neurological and imaging tools can enhance outcome predictions in LVO strokes. Methods: The infarction volume in patients was measured using magnetic resonance diffusion-weighted images, and the 90-day stroke outcome was defined by a modified Rankin Scale (mRS). Differential expression patterns of miRNAs were identified by RNA sequencing of serum-driven exosomes. Nuclear magnetic resonance (NMR) spectroscopy was used to identify metabolites associated with AIS with small and large infarctions. Results: We identified 41 miRNAs and 11 metabolites to be significantly associated with infarct volume in a multivariate regression analysis after adjusting for the confounders. Eight miRNAs and ketone bodies correlated significantly with infarct volume, NIHSS (severity), and mRS (outcome). Through integrative analysis of clinical, radiological, and omics data using machine learning, our study identified 11 top features for predicting stroke outcomes with an accuracy of 0.81 and AUC of 0.91. Conclusions: Our study provides a future framework for advancing stroke therapeutics by incorporating molecular markers into the existing neurological and imaging tools to improve predictive efficacy and enhance patient outcomes.
A Numerical Framework of Simulating Flow-Induced Deformation during Liquid Composite Moulding
Authors: Alotaibi Hatim , Soutis Constantinos , Zhang Dianyun , Jabbari Masoud
Published: October 2024

Fibre deformation (or shearing of yarns) can develop during the liquid moulding of composites due to injection pressures or polymerisation (cross-linking) reactions (e.g., chemical shrinkage). On that premise, this may also induce potential residual stress–strain, warpage, and design defects in the composite part. In this paper, a developed numerical framework is customised to analyse deformations and the residual stress–strain of fibre (at a micro-scale) and yarns (at a meso-scale) during a liquid composite moulding (LCM) process cycle (fill and cure stages). This is achieved by linking flow simulations (coupled filling–curing simulation) to a transient structural model using ANSYS software. This work develops advanced User-Defined Functions (UDFs) and User-Defined Scalers (UDSs) to enhance the commercial CFD code with extra models for chemorheology, cure kinetics, heat generation, and permeability. Such models will be hooked within the conservation equations in the thermo-chemo-flow model and hence reflected by the structural model. In doing so, the knowledge of permeability, polymerisation, rheology, and mechanical response can be digitally obtained for more coherent and optimised manufacturing processes of advanced composites.
Processing Influence on the Properties of Injection-Molded Wood Plastic Composites
Authors: Burgstaller Christoph , Renner Károly
Published: October 2024

Wood–plastic composites (WPCs) utilize wood particles as the reinforcing phase. These particles are susceptible to thermal degradation, which can happen while processing the WPCs in usual thermoplastic processes. In this work, we investigated the influence of different processing parameters in injection molding and their influence on WPC properties. To achieve that, WPCs with wood contents ranging from 10 to 50 wt% were processed using different process settings, and then characterized using mechanical testing and appearance changes. We found that the melt temperature showed a major influence, due to degrading the interface between the wood and the polymer matrix, while other parameters, like mold temperature and dwell pressure, showed only minor influence. Overall, the WPCs exhibited good process stability and, with proper process settings, their performance can be improved.
Mechanical Analysis of Corrugated Cardboard Subjected to Shear Stresses
Authors: Boaca Florin Ionut , Cananau Sorin , Calin Andrei , Bucur Mihai , Prisecaru Delia Alexandra , Stoica Marilena
Published: October 2024

Corrugated cardboard is widely used for packaging due to its sturdiness and lightweight properties. However, its ability to withstand lateral forces during handling, transportation, and storage is critical for maintaining its structural integrity. In this study, the problem of understanding and quantifying the strain experienced by corrugated cardboard boxes under shear stresses at various points in their lifecycle is addressed. Specifically, a precise methodology for testing shear stresses was developed and validated, enhancing the understanding of the material’s behaviour. Several key problems are addressed in this research, including the quantification of the amount of strain experienced by cardboard boxes from a warehouse to the final delivery, the development of a reliable testing methodology to measure shear stresses, and the understanding of the mechanical behaviour and structural integrity of corrugated cardboard under these conditions. It is anticipated that the findings will improve the design and durability of corrugated cardboard packaging, ensuring better performance during transportation and storage. This research contributes to the optimisation of logistics, the improvement of packaging quality, and the support of sustainable development by enhancing the reuse and recyclability of corrugated cardboard.
Fire Safety and Impact and Frost Resistance of Basalt Fiber-Reinforced Polysiloxane Matrix Composite Processed under Partial Pyrolysis Conditions
Authors: Černý Martin , Chlup Zdeněk , Kužma Ján , Růžička Milan , Ševčík Libor , Kácha Petr , Schweigstillová Jana , Svítilová Jaroslava , Strachota Adam
Published: October 2024

The study focuses on developing a fiber-reinforced composite that would exhibit good mechanical properties and climate resistance, and fire safety parameters would surpass commonly used fiber-reinforced polymers. The subject of development is a polysiloxane thermoset matrix reinforced with basalt fibers, which is processed by partial pyrolysis at 650 °C after curing. The heat release rate test showed virtually zero heat released, and the toxicity test showed only a very low amount of carbon monoxide. The flammability test showed no ignition, no radiation, and no glow. Composites for mechanical tests were prepared in three variants differing in the distribution of reinforcement. Due to the intended use of the composite for thin-walled panels or shells of buildings, the mechanical properties were compared in identical tests with fiber cement plates. The flexural strength of the composites was 3 to 10 times, and the impact energy was 10 to 100 times higher than the values measured on fiber cement, depending on the type and orientation of the composite. The flexural strength measured after 240 freeze–thaw conditioning cycles is higher than fiber cement by 1.3 to 2 times. The climate resistance of the composite should be the subject of further development.
Nanofat Improves Vascularization and Tissue Integration of Dermal Substitutes without Affecting Their Biocompatibility
Authors: Bonomi Francesca , Limido Ettore , Weinzierl Andrea , Ampofo Emmanuel , Harder Yves , Menger Michael D. , Laschke Matthias W.
Published: October 2024

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.