bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Knee Injury Landscape: A Comprehensive Study of Youth Male Football Players in the Central Region of Saudi Arabia
Authors: Almansour Latifah , Mohammad Walaa Sayed , Elsais Walaa , Alonazi Asma , Alyahya Danah
Published: May 2024

Knee injuries represent a significant health concern for young male football players in Saudi Arabia. Despite global research on football-related injuries, there is a distinct lack of studies focusing on this demographic in the Saudi context. This research aims to fill this gap, offering insights into injury prevalence and risk factors, thereby contributing to athlete well-being and informing tailored interventions. This study aimed to investigate the prevalence of knee injuries among youth male football players in Saudi Arabia, with a focus on injury patterns, risk factors, and associated factors. A cross-sectional study was conducted, involving 104 male football players who represent five Saudi clubs and are aged 18.82 ± 0.68 years. Injury data, including severity, timing, and mechanisms, were collected. Logistic regression analyses were performed to assess the impact of various factors on the likelihood of knee injuries. The study revealed that 37.5% of participants reported prior knee injuries, predominantly muscle injuries (61.5%) occurring during training. Ligamentous injuries, particularly anterior cruciate ligament injuries, were also notable (25.6%). Logistic regression analyses indicated that factors such as age, weight, height, body mass index, playing position, duration of playing football, and playing surface significantly influenced the odds of sustaining a knee injury. This study provides insights into the prevalence and patterns of knee injuries among youth male football players in the central region of Saudi Arabia. Muscle injuries are common. Factors such as age, weight, and playing position contribute to the risk of knee injuries. The findings underscore the need for targeted injury prevention strategies and player education programs.
Virtual Simulation Design and Debugging of Lift-and-Transverse Stereo Garage Based on the Digital Twin
Authors: Zhang Ke , Ding Ziyang
Published: May 2024

In the face of the challenges of limited urban space and the continuous increase of vehicles, stereo garages have been widely used as a solution in cities. In order to improve the automation and intelligence level of the stereo garage, this paper applies the digital twin technology to the lift-and-transverse stereo garage. A five-dimensional model of a digital twin has been developed based on an actual stereo garage. Combined with S7-PLCSIM Advanced, Botu TIA Portal, and NX MCD to build a virtual simulation platform, realizing the virtual simulation design and debugging of the digital twin-based stereo garage. This approach allows to test and optimize operational processes without relying on physical equipment, reducing labor and field debugging costs, shortening deployment cycles, and significantly reducing development costs. In addition, MCD allows real-time monitoring and control of security risks and failures detected. Finally, the feasibility of the virtual simulation and debugging scheme based on digital twin is verified by comparing the operation data of the virtual model and the actual stereo garage, which provides new ideas for the intelligent development of stereo garage but also can be used as an important reference for the development of equipment in other areas.
Terpenes as Potential Anti-Alzheimer’s Disease Agents
Authors: Lima Elisabete , Medeiros Jorge
Published: May 2024

Alzheimer’s disease (AD), a slowly progressive neurodegenerative disorder, is the main cause of dementia worldwide. However, currently, the approved drugs to combat AD are effective only in treating its symptoms. In fact, an efficacious treatment for this complex and multifactorial disorder remains to be discovered, demanding the urgent development of new therapeutic approaches for the disease, such as the use of bioactive secondary metabolites (SMs) from natural sources. Sessile organisms, like plants, are unable to escape from adverse environmental conditions and must therefore create their own defense. Their main defense strategy is chemical defense that includes the production of an enormously diverse array of bioactive SMs, such as terpenes and their derivatives. This largest and most diverse group of plant SMs also provide the treatment of several diseases due to their broad-spectrum bioactivities, for example, anticancer, antioxidant, and anti-inflammatory properties. Thus, the evaluation of the neuroprotective potential of terpenes is imperative. It is known that the major AD clinical indications (CIs) are extracellular senile plaques of amyloid-β (Aβ) protein, intracellular hyperphosphorylated tau (τ) neurofibrillary tangles (NFTs), uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. Therefore, terpenes that may decrease these CIs might be used for AD treatment. Surely, terpenes targeting more than one AD pathogenic mechanism, multi-target drug ligands (MTDLs), have the potential to become a leading AD treatment. Thus, this review analyzes, for each CI, the scaffolds of the selected terpenes leading to the highest activity.
Bioferments and Biosurfactants as New Products with Potential Use in the Cosmetic Industry
Authors: Klimek-Szczykutowicz Marta , Błońska-Sikora Ewelina Maria , Kulik-Siarek Katarzyna , Zhussupova Aizhan , Wrzosek Małgorzata
Published: May 2024

The cosmetics industry is one of the fastest growing markets in terms of searching for new ingredients. Recently, there has been a growing interest in products made during fermentation, which are being introduced into cosmetics with increasing frequency, creating a market that emphasizes the positive image of healthy, environmentally friendly components with a positive effect on skin. Scientists mainly focus on examining biological activity as well as the impact on changes in the production of bioactive ingredients in various plant species undergoing fermentation. The studies show that bioferments have scientifically proven anti-aging and anti-inflammatory effects, among other skin benefits. Due to the increasing emphasis on environmental protection, ecofriendly compounds are being sought. This group includes surfactants, which are also obtained by fermentation. Plant-based and microbial biosurfactants, due to their multifunctional properties, such as detergency, emulsifying, foaming, moisturizing, and antibacterial activity, can replace chemical surfactants in many skincare formulations. This review focuses especially on elucidating the importance of the bioferments and biosurfactants and their potential in the cosmetic industry.
Real-Time Navigation Roads: Lightweight and Efficient Convolutional Neural Network (LE-CNN) for Arabic Traffic Sign Recognition in Intelligent Transportation Systems (ITS)
Authors: Khalifa Alaa A. , Alayed Walaa M. , Elbadawy Hesham M. , Sadek Rowayda A.
Published: May 2024

Smart cities are now embracing the new frontier of urban living, with advanced technology being used to enhance the quality of life for residents. Many of these cities have developed transportation systems that improve efficiency and sustainability, as well as quality. Integrating cutting-edge transportation technology and data-driven solutions improves safety, reduces environmental impact, optimizes traffic flow during peak hours, and reduces congestion. Intelligent transportation systems consist of many systems, one of which is traffic sign detection. This type of system utilizes many advanced techniques and technologies, such as machine learning and computer vision techniques. A variety of traffic signs, such as yield signs, stop signs, speed limits, and pedestrian crossings, are among those that the traffic sign detection system is trained to recognize and interpret. Ensuring accurate and robust traffic sign recognition is paramount for the safe deployment of self-driving cars in diverse and challenging environments like the Arab world. However, existing methods often face many challenges, such as variability in the appearance of signs, real-time processing, occlusions that can block signs, low-quality images, and others. This paper introduces an advanced Lightweight and Efficient Convolutional Neural Network (LE-CNN) architecture specifically designed for accurate and real-time Arabic traffic sign classification. The proposed LE-CNN architecture leverages the efficacy of depth-wise separable convolutions and channel pruning to achieve significant performance improvements in both speed and accuracy compared to existing models. An extensive evaluation of the LE-CNN on the Arabic traffic sign dataset that was carried out demonstrates an impressive accuracy of 96.5% while maintaining superior performance with a remarkably low inference time of 1.65 s, crucial for real-time applications in self-driving cars. It achieves high accuracy with low false positive and false negative rates, demonstrating its potential for real-world applications like autonomous driving and advanced driver-assistance systems.
Modeling the Impact of Misinformation on the Transmission Dynamics of COVID-19
Authors: Su Ziyi , Agyingi Ephraim
Published: May 2024

The threat posed by the COVID-19 pandemic has been accompanied by an epidemic of misinformation, causing confusion and mistrust among the public. Misinformation about COVID-19 whether intentional or unintentional takes many forms, including conspiracy theories, false treatments, and inaccurate information about the origins and spread of the virus. Though the pandemic has brought to light the significant impact of misinformation on public health, mathematical modeling emerged as a valuable tool for understanding the spread of COVID-19 and the impact of public health interventions. However, there has been limited research on the mathematical modeling of the spread of misinformation related to COVID-19. In this paper, we present a mathematical model of the spread of misinformation related to COVID-19. The model highlights the challenges posed by misinformation, in that rather than focusing only on the reproduction number that drives new infections, there is an additional threshold parameter that drives the spread of misinformation. The equilibria of the model are analyzed for both local and global stability, and numerical simulations are presented. We also discuss the model’s potential to develop effective strategies for combating misinformation related to COVID-19.
Approximating a Function with a Jump Discontinuity—The High-Noise Case
Authors: Muzaffar Qusay , Levin David , Werman Michael
Published: May 2024

This paper presents a novel deep-learning network designed to detect intervals of jump discontinuities in single-variable piecewise smooth functions from their noisy samples. Enhancing the accuracy of jump discontinuity estimations can be used to find a more precise overall approximation of the function, as traditional approximation methods often produce significant errors near discontinuities. Detecting intervals of discontinuities is relatively straightforward when working with exact function data, as finite differences in the data can serve as indicators of smoothness. However, these smoothness indicators become unreliable when dealing with highly noisy data. In this paper, we propose a deep-learning network to pinpoint the location of a jump discontinuity even in the presence of substantial noise.
A Sublethal Concentration of Chlorine Induces Antibiotic Resistance in Salmonella via Production of Reactive Oxygen Species
Authors: Aljuwayd Mohammed , Malli Israa Abdullah , Ricke Steven C. , Kwon Young Min
Published: May 2024

Studies have shown that the production of reactive oxygen species (ROS) is triggered by bactericidal antibiotics, which contributes significantly to the killing of bacterial cells and increasing mutations in surviving cells. In this study, we hypothesized that exposure of Salmonella to sublethal concentrations of hypochlorite (NaOCl), a commonly used sanitizer in household and food industries increases mutation rates, leading to the development of antibiotic resistance. We found that a sublethal concentration (20 ppm) of NaOCl increased the mutation rates of S. typhimurium 14028s significantly (p < 0.05), which was prevented by the ROS scavenger thiourea, supporting that the increased mutation was due to NaOCl-triggered ROS production. We further found that the exposure of S. typhimurium 14028s to the same sublethal concentration of NaOCl increases resistance to kanamycin among the 3 antibiotics evaluated. The results of this study suggest that when NaOCl applied as a sanitizer fails to kill Salmonella due to diluted local concentrations or presence of organic materials, it can cause an adverse outcome of developing antibiotic resistance of the pathogen.
Nurses’ Role in the Control and Treatment of Asthma in Adults: A Systematic Literature Review
Authors: Alexandre-Sousa Pedro , Sousa Nuno , Bento Joana , Azevedo Filipa , Assis Maíra , Mendes José
Published: May 2024

Bronchial asthma is a chronic pathology and a global public health problem. However, asthma can be controlled and treated for the most part by patients, so the Portuguese General Directorate of Health recommends shared medical appointments in primary health care (PHC). The present study aims to identify the role of PHC nurses in the control and treatment of asthma in adults. Using the MeSH platform, the following descriptors were validated: asthma, nurses, adults. An individual search was carried out in the following databases: CINAHL (ESBSCO host), MEDLINE (Pubmed host), Web of Science, and Scopus. Out of a total of 280 publications, 79 of which were duplicates and 185 publications which did not meet the inclusion criteria, 16 publications remained readable. Of the eligible articles, there were 13 specialist reports, one mixed study, one quasi-experimental study, and one randomized trial. Education was the intervention most identified in the scientific evidence analyzed, and patient assessment, application of an asthma control questionnaire, verification and training of inhalation technique, empowerment for self-management of the disease, support, promotion of seasonal influenza vaccination, and use of written action plans were also identified. The results reveal that, although the scientific evidence on the intervention of these professionals is poorly developed, nurses play a crucial role in the control and treatment of asthma. The scientific evidence analyzed allowed the identification of interventions that can help the organization of a nursing health appointment, providing nurses with a crucial role in the control and treatment of asthma in adults in the context of PHC.
Was Shostakovich’s Second Cello Concerto a Hidden Homage?
Authors: Ritzarev Marina
Published: May 2024

Shostakovich’s direct quotation from the Odessan street song “Bagels, Buy My Bagels!” (Bubliki, kupite bubliki!) in his Second Cello Concerto Op. 126 (1966) featured an unusual style, even in relation to some of his other compositions referencing popular and Jewish music. The song is widely known as one of the icons of the Odessa underworld. Shostakovich’s use of this melody as one of the main leit-themes of the Concerto can be compared to the use by the non-Jewish Andrei Sinyavsky of the Jewish pseudonym Abram Tertz, a bandit from the Odessa underworld—the only locus of freedom to tell the truth in a totalitarian society. The time of Shostakovich’s address to this song remarkably coincided with the famous Soviet trial of Andrei Sinyavsky and Yuly Daniel in the fall of 1965 and their final sentencing (February 1966) to years in a Gulag camp. The dramaturgy of Shostakovich’s Concerto, written in the same spring of 1966, demonstrates the transformation of the theme of “Bagels” into a tragic image. The totality of circumstantial evidence suggests that this opus could be the composer’s hidden tribute to the feats of Russian heroic writers.
OCT Intensity of the Region between Outer Retina Band 2 and Band 3 as a Biomarker for Retinal Degeneration and Therapy
Authors: Zeng Yong , Gao Shasha , Li Yichao , Marangoni Dario , De Silva Tharindu , Wong Wai T. , Chew Emily Y. , Sun Xun , Li Tiansen , Sieving Paul A. , Qian Haohua
Published: May 2024

Optical coherence tomography (OCT) is widely used to probe retinal structure and function. This study investigated the outer retina band (ORB) pattern and reflective intensity for the region between bands 2 and 3 (Dip) in three mouse models of inherited retinal degeneration (Rs1KO, TTLL5KO, RPE65KO) and in human AMD patients from the A2A database. OCT images were manually graded, and reflectivity signals were used to calculate the Dip ratio. Qualitative analyses demonstrated the progressive merging band 2 and band 3 in all three mouse models, leading to a reduction in the Dip ratio compared to wildtype (WT) controls. Gene replacement therapy in Rs1KO mice reverted the ORB pattern to one resembling WT and increased the Dip ratio. The degree of anatomical rescue in these mice was highly correlated with level of transgenic RS1 expression and with the restoration of ERG b-wave amplitudes. While the inner retinal cavity was significantly enlarged in dark-adapted Rs1KO mice, the Dip ratio was not altered. A reduction of the Dip ratio was also detected in AMD patients compared with healthy controls and was also positively correlated with AMD severity on the AMD score. We propose that the ORB and Dip ratio can be used as non-invasive early biomarkers for retina health, which can be used to probe therapeutic gene expression and to evaluate the effectiveness of therapy.
Lysophosphatidylcholine Acetyltransferase 2 (LPCAT2) Influences the Gene Expression of the Lipopolysaccharide Receptor Complex in Infected RAW264.7 Macrophages, Depending on the E. coli Lipopolysaccharide Serotype
Authors: Poloamina Victory Ibigo , Alrammah Hanaa , Abate Wondwossen , Avent Neil D. , Fejer Gyorgy , Jackson Simon K.
Published: May 2024

Escherichia coli (E. coli) is a frequent gram-negative bacterium that causes nosocomial infections, affecting more than 100 million patients annually worldwide. Bacterial lipopolysaccharide (LPS) from E. coli binds to toll-like receptor 4 (TLR4) and its co-receptor’s cluster of differentiation protein 14 (CD14) and myeloid differentiation factor 2 (MD2), collectively known as the LPS receptor complex. LPCAT2 participates in lipid-raft assembly by phospholipid remodelling. Previous research has proven that LPCAT2 co-localises in lipid rafts with TLR4 and regulates macrophage inflammatory response. However, no published evidence exists of the influence of LPCAT2 on the gene expression of the LPS receptor complex induced by smooth or rough bacterial serotypes. We used RAW264.7—a commonly used experimental murine macrophage model—to study the effects of LPCAT2 on the LPS receptor complex by transiently silencing the LPCAT2 gene, infecting the macrophages with either smooth or rough LPS, and quantifying gene expression. LPCAT2 only significantly affected the gene expression of the LPS receptor complex in macrophages infected with smooth LPS. This study provides novel evidence that the influence of LPCAT2 on macrophage inflammatory response to bacterial infection depends on the LPS serotype, and it supports previous evidence that LPCAT2 regulates inflammatory response by modulating protein translocation to lipid rafts.
The First Records of Trissolcus japonicus (Ashmead) and Trissolcus mitsukurii (Ashmead) (Hymenoptera, Scelionidae), Alien Egg Parasitoids of Halyomorpha halys (Stål) (Hemiptera, Pentatomidae) in Serbia
Authors: Konjević Aleksandra , Tavella Luciana , Tortorici Francesco
Published: May 2024

Serbia has recently begun facing a serious problem with the Brown Marmorated Stink Bug, Halyomorpha halys (Stål), which was first recorded in October 2015. This species belongs to the Pentomidae family and is notorious for causing extensive damage to plants. During the winter, it tends to gather in urban areas, such as houses and different man-made facilities, which has raised concerns among producers and citizens. The population of this species has rapidly increased, causing significant economic damage to cultivated plants. However, despite the alarming situation no natural enemies have yet been identified in Serbia. Therefore, research in 2022 was focused on collecting stink bug eggs to investigate the presence of egg parasitoids. The study identified two foreign Hymenoptera species for the European region, Trissolcus japonicus (Ashmead) and Tr. mitsukurii (Ashmead) (Scelionidae), recorded for the first time in Serbia. Additionally, the list of egg parasitoid species belonging to the Hymenoptera order includes seven local species: Anastatus bifasciatus (Geoffroy), from the Eupelmidae family; Ooencyrtus sp., from the Encyrtidae family; and Telenomus turesis (Walker), Tr. basalis (Wollaston), Tr. belenus (Walker), Tr. colemani (Crawford), and Tr. semistriatus (Nees von Esenbeck), from the Scelionidae family. In total, nine egg parasitoid species were, for the first time, reported as parasitizing H. halys and related species in Serbia.
The New Buffer Salt-Protected Sodium Butyrate Promotes Growth Performance by Improving Intestinal Histomorphology, Barrier Function, Antioxidative Capacity, and Microbiota Community of Broilers
Authors: Melaku Mebratu , Su Dan , Zhao Huaibao , Zhong Ruqing , Ma Teng , Yi Bao , Chen Liang , Zhang Hongfu
Published: May 2024

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. A total of 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs’ content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI and ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and the VH/CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum were significantly up-regulated in the NSB group. Additionally, SOD (p < 0.05) and the T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05), showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, and serum anti-inflammatory cytokines, and by regulating the intestinal barrier function and antioxidant capacity, SCFAs’ content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.
The First Defined Null Allele of the Notch Regulator, a Suppressor of Deltex: Uncovering Its Novel Roles in Drosophila melanogaster Oogenesis
Authors: Wilkin Marian B. , Whiteford Rory , Akbar Tanveer , Hosseini-Alghaderi Samira , Revici Raluca , Carbery Ann-Marie , Baron Martin
Published: May 2024

Suppressor of deltex (Su(dx)) is a Drosophila melanogaster member of the NEDD4 family of the HECT domain E3 ubiquitin ligases. Su(dx) acts as a regulator of Notch endocytic trafficking, promoting Notch lysosomal degradation and the down-regulation of both ligand-dependent and ligand-independent signalling, the latter involving trafficking through the endocytic pathway and activation of the endo/lysosomal membrane. Mutations of Su(dx) result in developmental phenotypes in the Drosophila wing that reflect increased Notch signalling, leading to gaps in the specification of the wing veins, and Su(dx) functions to provide the developmental robustness of Notch activity to environmental temperature shifts. The full developmental functions of Su(dx) are unclear; however, this is due to a lack of a clearly defined null allele. Here we report the first defined null mutation of Su(dx), generated by P-element excision, which removes the complete open reading frame. We show that the mutation is recessive-viable, with the Notch gain of function phenotypes affecting wing vein and leg development. We further uncover new roles for Su(dx) in Drosophila oogenesis, where it regulates interfollicular stalk formation, egg chamber separation and germline cyst enwrapment by the follicle stem cells. Interestingly, while the null allele exhibited a gain in Notch activity during oogenesis, the previously described Su(dx)SP allele, which carries a seven amino acid in-frame deletion, displayed a Notch loss of function phenotypes and an increase in follicle stem cell turnover. This is despite both alleles displaying similar Notch gain of function in wing development. We attribute this unexpected context-dependent outcome of Su(dx)sp being due to the partial retention of function by the intact C2 and WW domain regions of the protein. Our results extend our understanding of the developmental role of Su(dx) in the tissue renewal and homeostasis of the Drosophila ovary and illustrate the importance of examining an allelic series of mutations to fully understand developmental functions.
Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia
Authors: Basingab Fatemah S. , Alzahrani Reem A. , Alrofaidi Aisha A. , Barefah Ahmed S. , Hammad Rawan M. , Alahdal Hadil M. , Alrahimi Jehan S. , Zaher Kawther A. , Algiraigri Ali H. , El-Daly Mai M. , Alkarim Saleh A. , Aldahlawi Alia M.
Published: May 2024

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.
Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction
Authors: Zhou Jie , Hou Hai-Tao , Song Yu , Zhou Xiao-Lin , Chen Huan-Xin , Zhang Li-Li , Xue Hong-Mei , Yang Qin , He Guo-Wei
Published: May 2024

Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.
Virtual Screening of Small Molecules Targeting BCL2 with Machine Learning, Molecular Docking, and MD Simulation
Authors: Tondar Abtin , Sánchez-Herrero Sergio , Bepari Asim Kumar , Bahmani Amir , Calvet Liñán Laura , Hervás-Marín David
Published: May 2024

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. The RF model classified 61% (2355/3867) of molecules as ‘Active’. Further analysis through molecular docking with Vina identified CHEMBL3940231, CHEMBL3938023, and CHEMBL3947358 as top-scored small molecules with docking scores of −11, −10.9, and 10.8 kcal/mol, respectively. MD simulations validated these compounds’ stability and binding affinity to the BCL2 protein.
SNP-Associated Substitutions of Amino Acid Residues in the dNTP Selection Subdomain Decrease Polβ Polymerase Activity
Authors: Kladova Olga A. , Tyugashev Timofey E. , Miroshnikov Aleksandr A. , Novopashina Daria S. , Kuznetsov Nikita A. , Kuznetsova Aleksandra A.
Published: May 2024

In the cell, DNA polymerase β (Polβ) is involved in many processes aimed at maintaining genome stability and is considered the main repair DNA polymerase participating in base excision repair (BER). Polβ can fill DNA gaps formed by other DNA repair enzymes. Single-nucleotide polymorphisms (SNPs) in the POLB gene can affect the enzymatic properties of the resulting protein, owing to possible amino acid substitutions. For many SNP-associated Polβ variants, an association with cancer, owing to changes in polymerase activity and fidelity, has been shown. In this work, kinetic analyses and molecular dynamics simulations were used to examine the activity of naturally occurring polymorphic variants G274R, G290C, and R333W. Previously, the amino acid substitutions at these positions have been found in various types of tumors, implying a specific role of Gly-274, Gly-290, and Arg-333 in Polβ functioning. All three polymorphic variants had reduced polymerase activity. Two substitutions—G274R and R333W—led to the almost complete disappearance of gap-filling and primer elongation activities, a decrease in the deoxynucleotide triphosphate–binding ability, and a lower polymerization constant, due to alterations of local contacts near the replaced amino acid residues. Thus, variants G274R, G290C, and R333W may be implicated in an elevated level of unrepaired DNA damage.
Test–Retest Reliability of a Motorized Resistance Device for Measuring Throwing Performance in Volleyball Athletes
Authors: Paraskevopoulos Eleftherios , Christakou Anna , Plakoutsis George , Pamboris George M. , Papandreou Maria
Published: May 2024

Throwing performance is a critical aspect of sports, particularly in overhead activities, necessitating reliable assessment methods. This study explores the test–retest reliability of throwing performance metrics measured by the 1080 Sprint, a robotic device integrating linear position technology and an electric motor. Specifically focusing on professional volleyball athletes with scapular dyskinesis, the study draws data from a previously published investigation on the impact of mirror cross exercise. Thirty-nine athletes were recruited, aged 21.9 ± 3.6 years, height 1.79 ± 0.3 m weight 68.5 ± 19.8 kg, and body mass index 21.3 ± 3.2 kg/m2, meeting stringent inclusion criteria. One-sample t-tests indicated no statistically significant differences between test–retest trials. The study revealed excellent reliability of the 1080 Sprint, with intraclass correlation coefficient (ICC) values exceeding 0.99 for all metrics, including speed, force, and power. The standard error of measurement (SEM) calculation revealed that the Sprint 1080 motorized resistance device demonstrates high precision in measuring throwing performance. Bland and Altman plots indicated minimal systematic bias across all metrics, encompassing speed, force, and power. The provision of the minimum detectable change (MDC) for each variable of the Sprint 1080 motorized resistance device offers coaches a valuable tool to identify performance improvements in volleyball athletes. In conclusion, the present study shows that the 1080 Sprint is valid and reliable for measuring throwing performance in volleyball athletes for monitoring purposes.
Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome
Authors: Boruga Madalina , Septimiu-Radu Susa , Nandarge Prashant Sunil , Elagez Ahmed , Doros Gabriela , Lazureanu Voichita Elena , Stoicescu Emil Robert , Tanase Elena , Iacob Roxana , Dumitrescu Andreea , Bota Adrian Vasile , Cotoraci Coralia , Bratu Melania Lavinia
Published: May 2024

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the “Victor Babes” Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study’s findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.
Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab
Authors: Bagnasco Diego , Bondi Benedetta , Caminati Marco , Nicola Stefania , Pini Laura , Milanese Manlio , Brussino Luisa , Senna Gianenrico , Canonica Giorgio Walter , Braido Fulvio
Published: May 2024

Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. Objective: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. Methods: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. Results: According to the criteria, 39–52% of patients experienced complete remission in the first year, increasing to 51–73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Conclusions: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.
Relationship between Non-Invasive Brain Stimulation and Autonomic Nervous System
Authors: Messina Giovanni , Monda Antonietta , Messina Antonietta , Di Maio Girolamo , Monda Vincenzo , Limone Pierpaolo , Dipace Anna , Monda Marcellino , Polito Rita , Moscatelli Fiorenzo
Published: May 2024

Non-invasive brain stimulation (NIBS) approaches have seen a rise in utilization in both clinical and basic neuroscience in recent years. Here, we concentrate on the two methods that have received the greatest research: transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). Both approaches have yielded pertinent data regarding the cortical excitability in subjects in good health as well as pertinent advancements in the management of various clinical disorders. NIBS is a helpful method for comprehending the cortical control of the ANS. Previous research has shown that there are notable changes in muscular sympathetic nerve activity when the motor cortex is modulated. Furthermore, in NIBS investigations, the ANS has been employed more frequently as an outcome measure to comprehend the overall impacts of these methods, including their safety profile. Though there is ample proof that brain stimulation has autonomic effects on animals, new research on the connection between NIBS and the ANS has produced contradictory findings. In order to better understand NIBS processes and ANS function, it is crucial to take into account the reciprocal relationship that exists between central modulation and ANS function.
Lipid Toxicity in the Cardiovascular-Kidney-Metabolic Syndrome (CKMS)
Authors: D’Elia John A. , Weinrauch Larry A.
Published: May 2024

Recent studies of Cardiovascular-Kidney-Metabolic Syndrome (CKMS) indicate that elevated concentrations of derivatives of phospholipids (ceramide, sphingosine), oxidized LDL, and lipoproteins (a, b) are toxic to kidney and heart function. Energy production for renal proximal tubule resorption of critical fuels and electrolytes is required for homeostasis. Cardiac energy for ventricular contraction/relaxation is preferentially supplied by long chain fatty acids. Metabolism of long chain fatty acids is accomplished within the cardiomyocyte cytoplasm and mitochondria by means of the glycolytic, tricarboxylic acid, and electron transport cycles. Toxic lipids and excessive lipid concentrations may inhibit cardiac function. Cardiac contraction requires calcium movement from the sarcoplasmic reticulum from a high to a low concentration at relatively low energy cost. Cardiac relaxation involves calcium return to the sarcoplasmic reticulum from a lower to a higher concentration and requires more energy consumption. Diastolic cardiac dysfunction occurs when cardiomyocyte energy conversion is inadequate. Diastolic dysfunction from diminished ATP availability occurs in the presence of inadequate blood pressure, glycemia, or lipid control and may lead to heart failure. Similar disruption of renal proximal tubular resorption of fuels/electrolytes has been found to be associated with phospholipid (sphingolipid) accumulation. Elevated concentrations of tissue oxidized low-density lipoprotein cholesterols are associated with loss of filtration efficiency at the level of the renal glomerular podocyte. Macroscopically excessive deposits of epicardial and intra-nephric adipose are associated with vascular pathology, fibrosis, and inhibition of essential functions in both heart and kidney. Chronic triglyceride accumulation is associated with fibrosis of the liver, cardiac and renal structures. Successful liver, kidney, or cardiac allograft of these vital organs does not eliminate the risk of lipid toxicity. Lipid lowering therapy may assist in protecting vital organ function before and after allograft transplantation.
High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma
Authors: Cheng Yu-Wen , Lee Jia-Hau , Chang Chih-Hui , Tseng Tzu-Ting , Chai Chee-Yin , Lieu Ann-Shung , Kwan Aij-Lie
Published: May 2024

Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.
Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease
Authors: Bonacchi Giacomo , Rossi Valentina Alice , Garofalo Manuel , Mollace Rocco , Uccello Giuseppe , Pieragnoli Paolo , Checchi Luca , Perrotta Laura , Voltolini Luca , Ricciardi Giuseppe , Beltrami Matteo
Published: May 2024

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called “kidney tamponade”, explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium–glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.
Endurance Training Provokes Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Heterozygous Desmoglein-2 Mutants: Alleviation by Preload Reduction
Authors: Fabritz Larissa , Fortmueller Lisa , Gehmlich Katja , Kant Sebastian , Kemper Marcel , Kucerova Dana , Syeda Fahima , Faber Cornelius , Leube Rudolf E. , Kirchhof Paulus , Krusche Claudia A.
Published: May 2024

Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients.