bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatically Injecting Robustness Statements into Distributed Applications
Authors: Marletta Daniele , Midolo Alessandro , Tramontana Emiliano
Published: November 2024

When developing a distributed application, several issues need to be handled, and software components should include some mechanisms to make their execution resilient when network faults, delays, or tampering occur. For example, synchronous calls represent a too-tight connection between a client requesting a service and the service itself, whereby potential network delays or temporary server overloads would keep the client side hanging, exposing it to a domino effect. The proposed approach assists developers in dealing with such issues by providing an automatic tool that enhances a distributed application using simple blocking calls and makes it robust in the face of adverse events. The proposed devised solution consists in automatically identifying the parts of the application that connect to remote services using simple synchronous calls and substituting them with a generated customized snippet of code that handles potential network delays or faults. To accurately perform the proposed transformation, the devised tool finds application code statements that are data-dependent on the results of the original synchronous calls. Then, for the dependent statements, a solution involving guarding code, proper synchronization, and timeouts is injected. We experimented with the analysis and transformation of several applications and report a meaningful example, together with the analysis of the results achieved.
Method for Non-Contact Measuring the Weight of Sturgeon in Intensive Aquaculture
Authors: Hu Junjie , Lin Kai , Zhang Shiyu , Zhang Rui , Li Hongsong , Xia Runqiu
Published: November 2024

Weight information plays a pivotal role in sturgeon breeding and production management. However, manual measurement is time consuming and labor intensive due to the immense size of the sturgeon. Due to the unique body shape of the sturgeon, traditional image segmentation algorithms struggle to extract the necessary features from sturgeon images, which makes them unsuitable for this particular species. Moreover, accurately measuring weight in an occlusion environment is difficult. To address these challenges, an improved YOLOv5s model with a context augmentation module, focal-efficient intersection over union, and soft non-maximum suppression was proposed in this paper. To validate the model’s feasibility, the improved YOLOv5s model was first pre-trained using the sturgeon dataset, followed by further training on the occlusion dataset for segmentation tasks. Based on the phenotypic data obtained from the improved model, a multilayer perceptron method was used to estimate the sturgeon’s weight accurately. Experimental results demonstrated that the average precision of the improved YOLOv5s model reached 89.80% under occlusion conditions, and the correlation coefficient of noncontact weight measurement results reached 89.80%. The experimental results showed that the improved algorithm effectively performs segmentation of sturgeon in occlusion conditions and can accurately estimate the mass.
Influence of Self-Heating on Landfill Leachate Migration
Authors: Parshakova Yanina , Kataev Ruslan , Kartavykh Natalya , Viskov Mikhail , Ivantsov Andrey
Published: November 2024

The hydrodynamic processes of landfill leachate migration in the base of a solid waste landfill can have a critical impact on the natural environment. In the case of improper operation of municipal solid waste placement facilities, highly contaminated leachate may penetrate into groundwater and subsequently into surface water. This work addresses fundamental issues of multicomponent fluid propagation in a multilayer porous medium, taking into account temperature inhomogeneities caused by waste decomposition with heat release. The regimes of diffusion and convection of leachate water penetrating into soil layers in the base of municipal solid waste facilities are numerically studied. Archival data from a set of field and laboratory measurements in the area of the operating landfill are used to model the features of pollutant propagation and determine migration parameters. The process of pollutant propagation and migration is described by quantitative values of dry residue content in leachate. Factors that have a significant impact on the migration of leachate are considered. The main ones are convective transfer, diffusion, and properties of the geological composition of the landfill base, which are taken into account in the mathematical formulation of the problem. The calculations show that leachate self-heating can substantially intensify leachate filtration and has to be taken into account in the assessment of leachate migration rate.
Tea Quality: An Overview of the Analytical Methods and Sensory Analyses Used in the Most Recent Studies
Authors: Moreira Juan , Aryal Jyoti , Guidry Luca , Adhikari Achyut , Chen Yan , Sriwattana Sujinda , Prinyawiwatkul Witoon
Published: November 2024

Tea, one of the world’s most consumed beverages, has a rich variety of sensory qualities such as appearance, aroma, mouthfeel and flavor. This review paper summarizes the chemical and volatile compositions and sensory qualities of different tea infusions including black, green, oolong, dark, yellow, and white teas based on published data over the past 4 years (between 2021 and 2024), largely focusing on the methodologies. This review highlights the relationships among the different processing methods of tea and their resulting chemical and sensory profiles. Environmental and handling factors during processing, such as fermentation, roasting, and drying are known to play pivotal roles in shaping the unique flavors and aromas of different types of tea, each containing a wide variety of compounds enhancing specific sensory characteristics like umami, astringency, sweetness, and fruity or floral notes, which may correlate with certain groups of chemical compositions. The integration of advanced analytical methods, such as high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC–MS), with traditional sensory analysis techniques was found to be essential in the evaluation of the chemical composition and sensory attributes of teas. Additionally, emerging approaches like near-infrared spectroscopy (NIRS) and electronic sensory methods show potential in modern tea evaluation. The complexity of tea sensory characteristics necessitates the development of combined approaches using both analytical methods and human sensory analysis for a comprehensive and better understanding of tea quality.
Water-Soluble Intracellular Polysaccharides (IPSW-2 to 4) from Phellinus igniarius Mycelia: Fractionation, Structural Elucidation, and Antioxidant Activity
Authors: Boateng Isaac Duah , Yang Xiaoming
Published: November 2024

Phellinus igniarius is a medicinal fungus. Nonetheless, research on its water-soluble intracellular polysaccharides (IPSW-2 to 4) fractionation, structural elucidation, and antioxidant activity is limited. In this study, water-soluble intracellular polysaccharides (IPSW-2 to 4) were extracted and fractionated from P. igniarius mycelia, and their antioxidant and structural properties were assessed using GC-FID, GC-MS, FTIR, and NMR spectroscopy (1H and 13C). In the water-eluted P. igniarius polysaccharide fractions (IPS30W, IPS60W, and IPS80W) of anion-exchange chromatography, the polysaccharide content was 79.05%, 68.25%, and 62.06%, with higher yields of 25.07%, 21.38%, and 20.34%, respectively. In contrast, the salt (NaCl) elution fractions (IPS30S1, IPS60S1, IPS60S2, and IPS80S1) of anion-exchange chromatography had lower polysaccharide content and yield. Hence, water elution fractions (IPS30W, IPS60W, and IPS80W) were selected for further purification. After repeated purification using size-exclusion chromatography, IPSW-2 to 4 were obtained with a yield of 8% to 15.83%. The IPSW-2 to IPSW-4 structures were elucidated, and they showed no triple helical conformation. Based on periodate oxidation, Smith degradation, methylation analysis, and 1H and 13C NMR spectroscopy, the primary structures of IPSW-2, IPSW-3, and IPSW-4 were all glucan, with the main chain consisting of (1→6)-α-D-Glcp, (1→3,4)-α-D-Glcp, and (1→3, 6)-α-D-Glcp, with α-D-Glcp as a side chain. Finally, antioxidant analysis showed that IPS30W, IPS60W, and IPS80W were all more capable of scavenging superoxide anions than the polysaccharides of Phyllostachys (13.8%) and floribunda (15.1%) at the same concentration (0.40 mg/mL). This will serve as a guide for the development of functional foods.
Development of Plant-Based Burgers with Partial Replacement of Texturized Soy Protein by Agaricus bisporus: Effects on Physicochemical and Sensory Properties
Authors: Hollweg Géssica , Trindade Pamela Cristiele Oliveira , dos Santos Bibiana Alves , Padilha Milena , Fracari Priscila Rossato , Rosa Sarita Correa , Cichoski Alexandre José , Campagnol Paulo Cezar Bastianello
Published: November 2024

This study aims to develop plant-based burgers with partial replacement of texturized soy protein (TSP) by Agaricus bisporus mushrooms at proportions of 5%, 10%, 15%, and 20%. The substitution was evaluated regarding its impact on the burgers’ chemical composition, texture, color, cooking performance, and sensory properties. Chemical analyses showed a significant increase in moisture content starting from the 10% substitution level, contributing to improved juiciness. Protein content remained similar to the control until the 15% substitution level, while the fat content showed no significant variation among treatments. The texture profile indicated reduced hardness in burgers with mushroom enrichment, particularly at 5% and 10%, leading to a more tender product. Color analysis revealed a reduction in lightness (L*) and red intensity (a*) with increased mushroom levels. Sensory analysis showed that burgers with up to a 15% substitution level maintained consumer acceptance comparable to the control, with attributes such as “softness”, “pleasant color”, and “good appearance” positively correlated with consumer acceptance. The findings indicate that Agaricus bisporus mushrooms can be effectively used as a partial substitute for TSP in plant-based burgers, enhancing sensory properties without compromising quality. This substitution offers a promising approach to diversifying ingredients in plant-based products while maintaining desirable characteristics for consumers.
Comparative Characterization of Three Homologous Glutathione Transferases from the Weed Lolium perenne
Authors: Kontouri Annie , Ataya Farid Shokry , Madesis Panagiotis , Labrou Nikolaos
Published: November 2024

The comparative analysis of homologous enzymes is a valuable approach for elucidating enzymes’ structure–function relationships. Glutathione transferases (GSTs, EC. 2.5.1.18) are crucial enzymes in maintaining the homeostatic stability of plant cells by performing various metabolic, regulatory, and detoxifying functions. They are promiscuous enzymes that catalyze a broad range of reactions that involve the nucleophilic attack of the activated thiolate of glutathione (GSH) to electrophilic compounds. In the present work, three highly homologous (96–98%) GSTs from ryegrass Lolium perenne (LpGSTs) were identified by in silico homology searches and their full-length cDNAs were isolated, cloned, and expressed in E. coli cells. The recombinant enzymes were purified by affinity chromatography and their substrate specificity and kinetic parameters were determined. LpGSTs belong to the tau class of the GST superfamily, and despite their high sequence homology, their substrate specificity displays remarkable differences. High catalytic activity was determined towards hydroxyperoxides and alkenals, suggesting a detoxification role towards oxidative stress metabolites. The prediction of the structure of the most active LpGST by molecular modeling allowed the identification of a non-conserved residue (Phe215) with key structural and functional roles. Site-saturation mutagenesis at position 215 and the characterization of eight mutant enzymes revealed that this site plays pleiotropic roles, affecting the affinity of the enzyme for the substrates, catalytic constant, and structural stability. The results of the work have improved our understanding of the GST family in L. perenne, a significant threat to agriculture, sustainable food production, and safety worldwide.
Proto-DS: A Self-Supervised Learning-Based Nondestructive Testing Approach for Food Adulteration with Imbalanced Hyperspectral Data
Authors: Pang Kunkun , Liu Yisen , Zhou Songbin , Liao Yixiao , Yin Zexuan , Zhao Lulu , Chen Hong
Published: November 2024

Conventional food fraud detection using hyperspectral imaging (HSI) relies on the discriminative power of machine learning. However, these approaches often assume a balanced class distribution in an ideal laboratory environment, which is impractical in real-world scenarios with diverse label distributions. This results in suboptimal performance when less frequent classes are overshadowed by the majority class during training. Thus, the critical research challenge emerges of how to develop an effective classifier on a small-scale imbalanced dataset without significant bias from the dominant class. In this paper, we propose a novel nondestructive detection approach, which we call the Dice Loss Improved Self-Supervised Learning-Based Prototypical Network (Proto-DS), designed to address this imbalanced learning challenge. The proposed amalgamation mitigates the label bias on the most frequent class, further improving robustness. We validate our proposed method on three collected hyperspectral food image datasets with varying degrees of data imbalance: Citri Reticulatae Pericarpium (Chenpi), Chinese herbs, and coffee beans. Comparisons with state-of-the-art imbalanced learning techniques, including the Synthetic Minority Oversampling Technique (SMOTE) and class-importance reweighting, reveal our method’s superiority. Notably, our experiments demonstrate that Proto-DS consistently outperforms conventional approaches, achieving the best average balanced accuracy of 88.18% across various training sample sizes, whereas the Logistic Model Tree (LMT), Multi-Layer Perceptron (MLP), and Convolutional Neural Network (CNN) approaches attain only 59.42%, 60.38%, and 66.34%, respectively. Overall, self-supervised learning is key to improving imbalanced learning performance and outperforms related approaches, while both prototypical networks and the Dice loss can further enhance classification performance. Intriguingly, self-supervised learning can provide complementary information to existing imbalanced learning approaches. Combining these approaches may serve as a potential solution for building effective models with limited training data.
Some Insights into the Sierpiński Triangle Paradox
Authors: Martínez-Cruz Miguel-Ángel , Patiño-Ortiz Julián , Patiño-Ortiz Miguel , Balankin Alexander S.
Published: November 2024

We realize that a Sierpiński arrowhead curve (SAC) fills a Sierpiński gasket (SG) in the same manner as a Peano curve fills a square. Namely, in the limit of an infinite number of iterations, the fractal SAC remains self-avoiding, such that SAC⊂SG. Therefore, SAC differs from SG in the same sense as the self-avoiding Peano curve PC⊂0,12 differs from the square. In particular, the SG has three-line segments constituting a regular triangle as its border, whereas the border of SAC has the structure of a totally disconnected fat Cantor set. Thus, in contrast to the SG, which has loops at all scales, the SAC is loopless. Consequently, although both patterns have the same similarity dimension D=ln⁡3/ln⁡2, their connectivity dimensions are different. Specifically, the connectivity dimension of the self-avoiding SAC is equal to its topological dimension dlSAC=d=1, whereas the connectivity dimension of the SG is equal to its similarity dimension, that is, dlSG=D. Therefore, the dynamic properties of SG and SAC are also different. Some other noteworthy features of the Sierpiński triangle are also highlighted.
Exposure to High Concentrations of Tetrabromobisphenol A Slows the Process of Tissue Regeneration and Induces an Imbalance of Metabolic Homeostasis in the Regenerated Intestines of Apostichopus japonicus
Authors: Wang Zi , Song Xiaojun , Yin Wenhui , Shi Kuntao , Lin Ying , Liu Jixiang , Li Xiaohan , Tan Jiabo , Rong Junjie , Xu Kefeng , Wang Guodong
Published: November 2024

Background: Tissue regenerative capacity following evisceration, potentially influenced by environmental contaminants and intestinal microflora, is essential for the financial success of Apostichopus japonicus farming. However, the morphological structure, gut microbiome composition, and genes expression pattern of the regenerated gut after exposure to high levels of TBBPA remain poorly unclear. Methods: In this research, the effect of TBBPA exposure on tissue regeneration in A. japonicus was investigated through a comprehensive multi-omics approach. Results: Our results showed that the integrity, the intestinal wall thickness, and the villi length of the regenerated intestines in A. japonicus decreased after treatment with high levels of TBBPA. The findings from PCoA and NMDS analyses revealed that the microbial community composition was significantly altered following exposure to high concentrations of TBBPA in the regenerated intestines of A. japonicus. The KEGG pathway enrichment analysis indicated that the DEGs (differentially expressed genes) were predominantly enriched on metabolism and immunity-related signaling pathways after exposure to high levels of TBBPA. These included pathways involved in the PPAR signaling pathway, ECM receptor interaction, glycerolipid metabolism, and fatty acid degradation. Interestingly, the results have demonstrated that there are 77 transcript factors that were significantly different after exposure to TBBPA. Conclusions: These results suggested that high levels of exposure to TBBPA induces an imbalance of the metabolic homeostasis by regulating the expression levels of transcription factors in the regenerated intestines of A. japonicus.
Durability of Two-Component Grout in Tunneling Applications: A Laboratory Test Campaign
Authors: Todaro Carmine , Carigi Andrea , Peila Daniele
Published: November 2024

Today, two-component grout is the most widely used backfilling technology in shielded mechanized tunneling. Despite its intensive use, however, very scant information pertaining to the durability of this material is available in the scientific literature. In this work, the aging of two-component grout is studied by curing grout samples using three different modalities. Furthermore, the action of air on two-component grout is studied by assessing the dehydration process, which is a phenomenon that occurs when the material is cured without being completely embedded in soil/rock. Uniaxial compression tests and three-point flexural tests have been carried out for mechanical characterization. The results reveal that in a curing environment made of sand, a moisture of 5% is sufficient to guarantee correct curing of the grout and extend the mechanical performance to three years, whereas the action of air is potentially dangerous, since the grout suffers strongly from dehydration. Despite this dehydration process, however, the mechanical performance of the grout also tends to increase for samples cured under the action of air until a very high level of cracking and shrinkage is reached. A discussion of the limitations on the uniaxial compression strength as the main mechanical parameter for the characterization of two-component grout concludes the work.
Bypassing Emergency Service: Decoding the Drivers of Self-Referral During Acute Myocardial Infarction on Rural Areas in Sachsen-Anhalt, Germany
Authors: Holland Karen , Lueckmann Sara L. , Assaf Mohamad , Mikolajczyk Rafael
Published: November 2024

Background/Objectives: the timely and effective management of acute myocardial infarction (AMI) is crucial to improve patient outcomes. ‘Self-Referral’ is defined as instances either where patients arrive at the hospital by their own means or are transported by someone else, rather than through professional emergency medical services. This approach can lead to treatment delays and potentially worsen outcomes. This study aims to identify the factors associated with the choice of self-referral among patients with AMI in Saxony-Anhalt, Germany. Methods: We used the data from the Regional Myocardial Infarction Registry of Saxony-Anhalt (RHESA), which included 4044 patients with confirmed acute myocardial infarction (AMI), including 48.7% from urban areas (city of Halle) and 51.3% from rural areas (Altmark). The gender distribution was 65% male and 35% female, covering an age range from 25 to over 80 years. Multivariable logistic regression identified factors associated with self-referral and its impact on reaching a hospital with percutaneous coronary intervention (PCI) capability. Results: Rural residents were more likely to self-refer compared to those in urban settings (adjusted odds ratio 2.43 [95% CI: 2.00–2.94]). Odds of self-referral decreased with age, while metabolic factors, including hypertension, high body mass index (BMI), and diabetes, as well as sex were not associated with self-referral. Self-referral did not increase the odds of arriving in a hospital without PCI capability. (Adjusted odds ratio 1.12 [95% CI: 0.85–1.47]). Furthermore, in cases of self-referral, women did not have a disadvantage in reaching a hospital with PCI (0.91; 0.59–1.41) compared to men. However, in medically attended transports, women were at a disadvantage (odds ratio: 1.33; 95% CI: 1.06–1.67). Conclusions: These findings highlight the need for public education on self-referral and for medical personnel training to prevent gender bias in AMI transport to PCI-capable hospitals.
Studying the Combined Impact of Salinity and Drought Stress-Simulated Conditions on Physio-Biochemical Characteristics of Lettuce Plant
Authors: Abdelkader Mostafa , Suliman Ahmad A. , Salem Salem S. , Assiya Ansabayeva , Voronina Luidmila , Puchkov Mikhail , Loktionova Elena , Bhuker Axay , Ataya Farid Shokry , Mahmoud Mohamed H. , Abdelkader Mohamed F. M.
Published: November 2024

Water scarcity and increasing salinity stress are significant challenges in the farming sector as they often exacerbate each other, as limited water availability can concentrate salts in the soil, further hindering plant growth. Lettuce, a crucial leafy vegetable with high nutritional value, is susceptible to water availability and quality. This study investigates the growth and development of lettuce plants under water scarcity and varying levels of salinity stress to identify effective strategies for reducing water consumption while maintaining or improving plant productivity. Field experiments were designed to simulate three drought levels (50, 75, and 100% of class A pan evaporation) and three salinity stress levels (control, 1500, and 3000 ppm NaCl), assessing their impact on lettuce’s morphological and biochemical parameters. The combination of reduced water supply and high salinity significantly hindered growth, underscoring the detrimental effects of simultaneous water deficit and salinity stress on plant development. Non-stressed treatment enhanced nitrogen, phosphorus, and potassium contents and progressively decreased with the reduction in water supply from 100% to 50%. Interestingly, higher salinity levels increased total phenolic, flavonoid, and antioxidant activity, suggesting an adaptive stress response. Moreover, antioxidant activity, evaluated through DPPH and ABTS assays, peaked in plants irrigated with 75% ETo, whether under control or 1500 ppm salinity conditions. The Yield Stability Index was highest at 75% ETo (0.95), indicating robust stability under stress. The results indicated that lettuce could be cultivated with up to 75% of the water requirement without significantly impacting plant development or quality. Furthermore, the investigation demonstrated that lettuce could thrive when irrigated with water of moderate salinity (1500 ppm). These findings highlight the potential for reducing water quantities and saline water in lettuce production, offering practical solutions for sustainable farming in water-scarce regions.
Epidemiology of Traditional Cigarette and E-Cigarette Use Among Adolescents in Poland: Analysis of Sociodemographic Risk Factors
Authors: Kurdyś-Bykowska Paulina , Kośmider Leon , Bykowski Wojciech , Konwant Dawid , Stencel-Gabriel Krystyna
Published: November 2024

Background: E-cigarettes are electronic nicotine-dispensing systems in the form of an aerosol. Their popularity among adolescents is growing at an exceedingly fast pace. Methods: This study aimed to determine the prevalence of the use of traditional cigarettes and e-cigarettes and identify demographic risk factors for the use of these products by adolescents in large and small cities and rural areas in Poland. This cross-sectional study conducted in 2021 aimed to assess the prevalence of traditional cigarette and e-cigarette use among adolescents aged 12–18 in Poland, while identifying demographic risk factors associated with their usage. A total of 10,388 adolescents participated, predominantly from rural areas. Results: Findings revealed that 12.3% were traditional cigarette smokers, with 90% smoking in the past month, while 14.9% were e-cigarette users, with 84.7% using them in the past month. Dual users accounted for 6.4% of respondents. Non-smokers were younger, and e-cigarette users were more likely to be boys from larger cities. Moreover, mothers of non-smokers tended to have higher education levels than those of traditional cigarette smokers. Conclusions: This study provides important new insights into demographic predictors associated with the use of specific devices, which can help inform targeted interventions to reduce e-cigarette use.
Importance of Return to Usual and School Activities After Social Isolation in Recovering Vitamin D Concentrations, Physical Fitness, and Motor Performance in Adolescents
Authors: Moraes Frederico Bento de , Tadiotto Maiara Cristina , Lenardt Brenda , Mota Jorge , Matos Oslei de , Leite Neiva
Published: November 2024

This study aimed to observe adolescents’ changes and individual responses regarding the anthropometry, cardiometabolic profile, vitamin D concentrations, physical fitness, and motor competence upon immediate return and three months of school activities after lockdown. Methods: The study included 28 adolescents (14.8 ± 0.8 years) of both sexes. Anthropometric measures, body composition, cardiometabolic parameters, physical fitness, and motor competence were assessed. A paired t-test was used to compare the frequencies of respondents and the effect size of the results, considering significant p < 0.05. Results: After three months of school activities, adolescents changed their body composition, reducing % fat mass (p = 0.008) and increasing fat-free mass (p = 0.008). In terms of physical fitness, there was increased abdominal resistance (p < 0.001; ES = −0.42) and motor performance, with reduction in supine-to-stand test time (p < 0.001; ES = 0.53). There were very beneficial effects in reducing resting heart rate (p ≤ 0.001; ES = 0.61) and increasing vitamin D concentrations (p < 0.001; ES = −0.61). After three months of a school routine, the proportions of change in respondents were similar between girls and boys and eutrophic individuals and overweight individuals. Conclusions: Returning to school activities after lockdown was important for the recovery of vitamin D concentrations, physical fitness, and motor competence, whose responses were independent of the level of adiposity and sex of the adolescents.
Stress and Self-Efficacy in Parents/Caregivers and Oral Health of Individuals with Down Syndrome During the COVID-19 Pandemic: A Cross-Sectional Study
Authors: Campos Julya Ribeiro , Costa Fernando Oliveira , Borges-Oliveira Ana Cristina , Cota Luís Otávio Miranda
Published: November 2024

The family of individuals living with Down Syndrome (DS) often demonstrate high levels of stress associated with the demand for care and difficulties experienced in everyday life. The aim of this cross-sectional study was to assess perceived stress by parents/caregivers of individuals with DS and its association with general perceived self-efficacy and dental outcomes, considering the COVID-19 pandemic’s impacts on family’s daily activities and finances. A sample of 257 parents/caregivers answered a questionnaire with socioeconomic, dental, and behavioral variables and the short version of the Perceived Stress Scale and the General Perceived Self-Efficacy Scale. The sample was divided into three groups based on perceived stress levels. Associated variables were evaluated using multinomial logistic regression (level of significance 5%), adjusting for socioeconomic factors. The mean perceived stress score was 17.84 ± 5.75 (0–39). Medium stress (second tertile) was associated with finger/nail biting in individuals with DS (OR = 2.05; 95%CI 1.04–4.03; p = 0.038), difficulty in performing oral hygiene (OR = 2.39; 95%CI 1.23–4.65; p = 0.011) and medium and high self-efficacy (OR = 0.12; 95%CI 0.05–0.31; p < 0.001 and OR = 0.38; 95%CI 0.15–0.98; p = 0.046, respectively); high stress (third tertile) was associated with medium and high self-efficacy (OR = 0.25; 95%CI 0.09–0.67; p = 0.006 and OR = 0.05; 95%CI 0.02–0.15; p < 0.001, respectively) and negative impact of COVID-19 in family finances (OR = 3.00; 95%CI 1.39–6.44; p = 0.005). It was concluded that parents/caregivers’ perceived stress was averaged and associated with self-efficacy, finger/nail biting, oral hygiene demands, and the financial impact of COVID-19.
The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies
Authors: Begovic Merima , Schneider Luca , Zhou Xiaobo , Hamdani Nazha , Akin Ibrahim , El-Battrawy Ibrahim
Published: November 2024

Cardiac channelopathies are inherited diseases that increase the risk of sudden cardiac death. While different genes have been associated with inherited channelopathies, there are still subtypes, e.g., catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome, where the genetic cause remains unknown. Various models, including animal models, heterologous expression systems, and the human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSCs-CMs) model, have been used to study the pathophysiological mechanisms of channelopathies. Recently, researchers have focused on using hiPSCs-CMs to understand the genotype–phenotype correlation and screen drugs. By combining innovative techniques such as Clustered Regularly Interspaced Short Palindromic Repeats/Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR/Cas9)-mediated genome editing, and three-dimensional (3D) engineered heart tissues, we can gain new insights into the pathophysiological mechanisms of channelopathies. This approach holds promise for improving personalized drug treatment. This review highlights the role of hiPSCs-CMs in understanding the pathomechanism of Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia and how these models can be utilized for drug screening.
Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction
Authors: Shen Yanjia , Zhao Jiaying , Yang Ran , Yang Huilin , Guo Minmin , Ji Baixi , Du Guanhua , Li Li
Published: November 2024

Multiple sclerosis (MS) is an autoimmune disease mediated by T helper cells, which is characterized by neuroinflammation, axonal or neuronal loss, demyelination, and astrocytic gliosis. Histone deacetylase inhibitors (HDACis) are noted for their roles in easing inflammatory conditions and suppressing the immune response. Panobinostat, an HDACi, is now being used in treating multiple myeloma. Nevertheless, the effect of panobinostat on autoimmune diseases remains largely unclear. Thus, our research endeavored to determine if the administration of panobinostat could prevent experimental autoimmune encephalomyelitis (EAE) in mice, one of the most commonly used animal models of MS, and further explored the underlying mechanisms. The EAE mice were generated and then administered continuously with panobinostat at a dosage of 30 mg/kg for 16 days. The results indicated that panobinostat markedly alleviated the clinical symptoms of EAE mice, inhibiting demyelination and loss of oligodendrocytes in the central nervous system (CNS). Moreover, panobinostat decreased inflammation and the activation of microglia and astrocytes in the spinal cords of EAE mice. Mechanistically, treatment with panobinosat significantly suppressed M1 microglial polarization by blocking the activation of toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/interferon regulatory factor 5 (IRF5) pathway. Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.
Synovial Fluid Immune Cell Composition Following Intraarticular Fracture May Contribute to Posttraumatic Osteoarthritis
Authors: Aitchison Alexandra Hunter , Allen Nicholas B. , O’Neill Conor N. , Droz Lindsey G. , Patel Prekshaben , Anastasio Albert T. , Reilly Rachel M. , Pean Christian A. , DeBaun Malcolm R. , Nunley James A. , Adams Samuel B.
Published: November 2024

Intra-articular ankle fracture (IAF) often leads to post-traumatic osteoarthritis (PTOA), resulting in significant long-term morbidity. While previous research has focused on the inflammatory cytokines and matrix metalloproteinases within the synovial fluid fracture hematoma (SFFH), the immune cell populations within SFFH that contribute to PTOA development remain underexplored. This study aimed to characterize the immune cell populations in SFFH to better understand their role in the inflammatory response and potential for inducing lasting cartilage damage. Twenty-four patients with IAF underwent surgical ankle aspiration to collect SFFH, which was analyzed using polychromatic flow cytometry. The analysis revealed that 72.8% of the CD45+ cells were lymphocytes, predominantly CD3+ T cells (76.5%), with 42.1% being CD4+ and 39.2% CD8+ T cells. Additionally, monocytes accounted for 21.2% of CD45+ cells, with small populations of natural killer cells and myeloid-derived suppressor cells also present. These findings emphasize the predominance of T cells, particularly CD4+ subsets, in the immune response following IAF. Understanding these dynamics is essential for developing targeted interventions to prevent PTOA. Future research should focus on elucidating the specific roles of these immune cell populations in PTOA progression and exploring potential therapeutic strategies.
Vine Tea Extract (VTE) Inhibits High-Fat Diet-Induced Adiposity: Evidence of VTE’s Anti-Obesity Effects In Vitro and In Vivo
Authors: Lim Wonchul , Choi Seongmin , Kim Jinhak , Baek Kwang-Soo , Park Minkuk , Lee Gakyung , Lim Tae-Gyu
Published: November 2024

This study focused on evaluating the anti-obesity effects of an extract from Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang, also known as vine tea, in mature adipocytes and high-fat diet-induced obese mice. Vine tea extract (VTE) effectively decreased lipid accumulation in mature adipocytes without cytotoxicity, as confirmed by the regulation of several factors associated with adipogenesis, lipogenesis, or lipolysis. Subsequently, in a 12-week experiment with obese mice, oral VTE administration significantly reduced body weight gain induced with high-fat diet intake. Au-topsy findings showed reduced fat accumulation in various areas without liver damage. The VTE-administered group showed lower serum LDL levels, while increasing HDL, than the high-fat diet-administered group. Analysis of adipose tissue biomarkers indicated VTE’s ability to inhibit adipogenesis and lipogenesis, promote lipolysis, and regulate energy metabolism, contributing to reduced adiposity induced by the consumption of a high-fat diet.
Forced Overexpression and Knockout Analysis of SLC30A and SLC39A Family Genes Suggests Their Involvement in Establishing Resistance to Cisplatin in Human Cancer Cells
Authors: Kamynina Margarita , Rozenberg Julian M. , Kushchenko Artem S. , Dmitriev Sergey E. , Modestov Aleksander , Kamashev Dmitry , Gaifullin Nurshat , Shaban Nina , Suntsova Maria , Emelianova Anna , Buzdin Anton A.
Published: November 2024

Abstract: The metabolism of zinc and manganese plays a pivotal role in cancer progression by mediating cancer cell growth and metastasis. The SLC30A family proteins SLC30A3 and SLC30A10 mediate the efflux of zinc, manganese, and probably other transition element ions outside the cytoplasm to the extracellular space or into intracellular membrane compartments. The SLC39A family members SLC39A8 and SLC39A14 are their functional antagonists that transfer these ions into the cytoplasm. Recently, the SLC30A10 gene was suggested as a promising methylation biomarker of colorectal cancer. Here, we investigated whether forced overexpression or inactivation of SLC30A and SLC39A family genes has an impact on the phenotype of cancer cells and their sensitivity to cancer therapeutics. In the human colon adenocarcinoma HCT-15 and duodenal adenocarcinoma HuTu80 cell lines, we generated clones with knockouts of the SLC39A8 and SLC39A14 genes and forced overexpression of the SLC30A3, SLC30A10, and SLC39A8 genes. Gene expression in the mutant and control cells was assessed by RNA sequencing. The cell growth rate, mitochondrial activity, zinc accumulation, and sensitivity to the drugs cetuximab and cisplatin were investigated in functional tests. Overexpression or depletion of SLC30A or SLC39A family genes resulted in the deep reshaping of intracellular signaling and provoked hyperactivation of mitochondrial respiration. Variation in the expression of the SLC30A/SLC39A genes did not increase the sensitivity to cetuximab but significantly altered the sensitivity to cisplatin: overexpression of SLC30A10 resulted in an ~2.7–4 times increased IC50 of cisplatin, and overexpression of SLC30A3 resulted in an ~3.3 times decreased IC50 of cisplatin. The SLC30A/SLC39A genes should be considered as potential cancer drug resistance biomarkers and putative therapeutic targets.
Emerging Functions of Protein Tyrosine Phosphatases in Plants
Authors: Xin Jing , Li Chuanling , Liu Xiaoqian , Shi Xueke , Sun Yu , Shang Jian-Xiu
Published: November 2024

Reversible protein phosphorylation, known as the “switch” of the cell, is controlled by protein kinases (PKs) and protein phosphatases (PPs). Based on substrate specificity, PPs are classified into protein serine/threonine phosphatases and protein tyrosine phosphatases (PTPs). PTPs can dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine. In plants, PTPs monitor plant physiology, growth, and development. This review summarizes an overview of the PTPs’ classification and describes how PTPs regulate various plant processes, including plant growth and development, plant hormone responses, and responses to abiotic and biotic stresses. Then, future research directions on the PTP family in plants are discussed. This summary will serve as a reference for researchers studying PTPs in plants.
The Transcriptomic Response of Cells of the Thermophilic Bacterium Geobacillus icigianus to Terahertz Irradiation
Authors: Peltek Sergey , Bannikova Svetlana , Khlebodarova Tamara M. , Uvarova Yulia , Mukhin Aleksey M. , Vasiliev Gennady , Scheglov Mikhail , Shipova Aleksandra , Vasilieva Asya , Oshchepkov Dmitry , Bryanskaya Alla , Popik Vasily
Published: November 2024

As areas of application of terahertz (THz) radiation expand in science and practice, evidence is accumulating that this type of radiation can affect not only biological molecules directly, but also cellular processes as a whole. In this study, the transcriptome in cells of the thermophilic bacterium Geobacillus icigianus was analyzed immediately after THz irradiation (0.23 W/cm2, 130 μm, 15 min) and at 10 min after its completion. THz irradiation does not affect the activity of heat shock protein genes and diminishes the activity of genes whose products are involved in peptidoglycan recycling, participate in redox reactions, and protect DNA and proteins from damage, including genes of chaperone protein ClpB and of DNA repair protein RadA, as well as genes of catalase and kinase McsB. Gene systems responsible for the homeostasis of transition metals (copper, iron, and zinc) proved to be the most sensitive to THz irradiation; downregulation of these systems increased significantly 10 min after the end of the irradiation. It was also hypothesized that some negative effects of THz radiation on metabolism in G. icigianus cells are related to disturbances in activities of gene systems controlled by metal-sensitive transcription factors.
Genomic and Bioinformatics Analysis of Familial Partial Lipodystrophy Type 3 Identified in a Patient with Novel PPARγ Mutation and Robust Response to Pioglitazone
Authors: Hummadi Abdulrahman , Yafei Saeed , Mutawwam Dhayf Alrahman , Abutaleb Raed , Solan Yahia , Khawaji Abdullah , Alhagawy Ali Jaber , Algohani Turki , Khardali Mamdouh , Hakami Mohammed , Daghriri Abdulrraheem , Hezam Wegdan , Kariri Nourah
Published: November 2024

Familial partial lipodystrophies (FPLDs) are very rare inherited disorders characterized by partial loss of adipose tissue from the upper and lower extremities. At least seven subtypes of FPLD have been identified and are mostly dominantly inherited. FPLD type 3 is caused by mutations in the PPARγ gene, which encodes for the protein peroxisome proliferator-activated receptor gamma (PPARγ). We identified a Saudi female with PFLD3 presented with partial lipoatrophy, uncontrolled diabetes, severe hypertriglyceridemia, and recurrent pancreatitis. The clinical and biochemical findings in this proband were described before and after treatment with Pioglitazone in addition to the conventional treatment. DNA extraction and whole exome sequencing (WES) were performed to detect the variant. The mutant gene was subjected to Sanger analysis to confirm the results. We applied five specific computational prediction tools to assess the pathogenicity of variation, namely the MT, DANN, CADD, BayesDel, and fitCons tools. We assessed protein modeling and stability with the AlphaFold-generated structures for both wild-type and mutant proteins. Finally, we conducted molecular docking using the AutoDock Vina virtual docking. Upon whole exome sequencing, a c.1024C>T p.(Gln342Ter) missense mutation was detected in the PPARγ gene associated with FPLD3. This variant is a novel mutation that has not been described in all genome databases. Sanger analysis confirmed the heterogenicity and pathogenicity of this variant. All five computational prediction tools indicate that this variant is considered highly pathogenic. Our patient showed a dramatic response to Pioglitazone, a synthetic PPARγ agonist. From structural modeling, we found that the enhanced binding affinity of the mutant PPARγ protein to Pioglitazone likely improves the activation of PPARγ, enhancing its transcriptional activity and resulting in better clinical outcomes. These findings extend the spectrum of PPARγ mutations responsible for FPLD3 and highlight the potential for personalized treatment strategies based on genetic mutations.
Efficient Production of Chondrocyte Particles from Human iPSC-Derived Chondroprogenitors Using a Plate-Based Cell Self-Aggregation Technique
Authors: Hanaki Shojiro , Yamada Daisuke , Takao Tomoka , Iwai Ryosuke , Takarada Takeshi
Published: November 2024

The limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT®), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects.
Human-Brain-Derived Ischemia-Induced Stem Cell Transplantation Is Associated with a Greater Neurological Functional Improvement Compared with Human-Bone Marrow-Derived Mesenchymal Stem Cell Transplantation in Mice After Stroke
Authors: Tanada Shuichi , Nakagomi Takayuki , Nakano-Doi Akiko , Sawano Toshinori , Kubo Shuji , Kuramoto Yoji , Uchida Kazutaka , Yamahara Kenichi , Doe Nobutaka , Yoshimura Shinichi
Published: November 2024

The transplantation of injury/ischemia-induced stem cells (iSCs) extracted from post-stroke human brains can improve the neurological functions of mice after stroke. However, the usefulness of iSCs as an alternative stem cell source remains unclear. The current study aimed to assess the efficacy of iSC and mesenchymal stem cell (MSC) transplantation. In this experiment, equal numbers of human brain-derived iSCs (h-iSCs) (5.0 × 104 cells/μL) and human bone marrow-derived MSCs (h-MSCs) (5.0 × 104 cells/μL) were intracranially transplanted into post-stroke mouse brains after middle cerebral artery occlusion. Results showed that not only h-iSC transplantation but also h-MSC transplantation activated endogenous neural stem/progenitor cells (NSPCs) around the grafted sites and promoted neurological functional improvement. However, mice that received h-iSC transplantation experienced improvement in a higher number of behavioral tasks compared with those that received h-MSC transplantation. To investigate the underlying mechanism, NSPCs extracted from the ischemic areas of post-stroke mouse brains were cocultured with h-iSCs or h-MSCs. After coincubation, NSPCs, h-iSCs, and h-MSCs were selectively collected via fluorescence-activated cell sorting. Next, their traits were analyzed via microarray analysis. The genes related to various neuronal lineages in NSPCs after coincubation with h-iSCs were enriched compared with those in NSPCs after coincubation with h-MSCs. In addition, the gene expression patterns of h-iSCs relative to those of h-MSCs showed that the expression of genes related to synapse formation and neurotransmitter-producing neurons increased more after coincubation with NSPCs. Hence, cell–cell interactions with NSPCs promoted transdifferentiation toward functional neurons predominantly in h-iSCs. In accordance with these findings, immunohistochemistry showed that the number of neuronal networks between NSPCs and h-iSCs was higher than that between NSPCs and h-MSCs. Therefore, compared with h-MSC transplantation, h-iSC transplantation is associated with a higher neurological functional improvement, presumably by more effectively modulating the fates of endogenous NSPCs and grafted h-iSCs themselves.