bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Analysis of RNA-Seq Data Identifies Key Gene Signatures and Pathways in Mpox Virus-Induced Gastrointestinal Complications Using Colon Organoid Models
Authors: Rezapour Mostafa , Narayanan Aarthi , Gurcan Metin Nafi
Published: October 2024

Mpox, caused by the Mpox virus (MPXV), emerged globally in 2022 with the Clade IIb strain, presenting a critical public health challenge. While MPXV is primarily characterized by fever and rash, gastrointestinal (GI) complications, such as diarrhea and proctitis, have also been observed. This study is a reanalysis of GSE219036 without own data and focuses on the impact of MPXV infection on the colon, using human-induced pluripotent stem cell-derived colon organoids as a model. We applied a tailored statistical framework for RNA-seq data, Generalized Linear Models with Quasi-Likelihood F-tests and Relaxed Magnitude–Altitude Scoring (GLMQL-RMAS), to identify differentially expressed genes (DEGs) across MPXV clades: MPXV I (Zr-599 Congo Basin), MPXV IIa (Liberia), and MPXV IIb (2022 MPXV). Through a novel methodology called Cross-RMAS, we ranked genes by integrating statistical significance and biological relevance across all clades. Machine learning analysis using the genes identified by Cross-RMAS, demonstrated 100% accuracy in differentiating between the different MPXV strains and mock samples. Furthermore, our findings reveal that MPXV Clade I induces the most extensive alterations in gene expression, with significant upregulation of stress response genes, such as HSPA6 and FOS, and downregulation of genes involved in cytoskeletal organization and vesicular trafficking, such as PSAP and CFL1. In contrast, Clade IIb shows the least impact on gene expression. Through Gene Ontology (GO) analysis, we identified pathways involved in protein folding, immune response, and epithelial integrity that are disrupted in infected cells, suggesting mechanisms by which MPXV may contribute to GI symptoms.
Loureirin B Reduces Insulin Resistance and Chronic Inflammation in a Rat Model of Polycystic Ovary Syndrome by Upregulating GPR120 and Activating the LKB1/AMPK Signaling Pathway
Authors: Wang Jing , Huang Zheng , Cao Zhiyong , Luo Yehao , Liu Yueting , Cao Huilu , Tang Xiusong , Fang Gang
Published: October 2024

Polycystic ovary yndrome (PCOS) is a common metabolic disorder in women, which is usually associated with insulin resistance (IR) and chronic inflammation. Loureirin B (LrB) can effectively improve insulin resistance and alleviate chronic inflammation, and in order to investigate the therapeutic effect of LrB on polycystic ovary syndrome with insulin resistance (PCOS-IR), we conducted animal experiments. A PCOS-IR rat model was established by feeding a high-fat diet combined with letrozole (1 mg/kg·d for 21 days). The rats were treated with the GPR120 agonists TUG-891 and LrB for 4 weeks. Biochemical parameters (fasting blood glucose, total cholesterol, triglycerides, high- and low-density lipoprotein), hormone levels (serum insulin, E2, T, LH, and FSH), and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) were analyzed. Histopathological analyses of ovaries were performed using hematoxylin/eosin (H&E) staining. Real-time PCR and western blotting were used to assess GPR120, NLRP3, and caspase-1 expression in ovaries, and immunohistochemistry was used to evaluate LKB1 and AMPK protein expression. LrB reduced body weight, Lee’s index, ovarian index, ovarian area, and volume in PCOS-IR rats. It lowered fasting blood glucose, serum insulin, and HOMA-IR. LrB decreased total serum cholesterol, triglyceride, and LDL levels and increased HDL levels. It reduced serum T, LH, and LH/FSH and raised serum E2 and FSH levels. LrB downregulated the mRNA and protein expression levels of NLRP3 and Caspase-1, increased the protein and mRNA expression levels of GPR120 in rat ovaries, and increased LKB1 and AMPK protein expression in ovaries, ameliorating ovarian histopathological changes in PCOS-IR rats. Taken together, LrB upregulated GPR120, LKB1, and AMPK protein expression, downregulated NLRP3 and Caspase-1 protein expression, reduced insulin resistance and chronic inflammation, and ameliorated histopathological changes in ovarian tissues in PCOS rats, suggesting its potential as a treatment for PCOS.
Rheumatoid Arthritis and COVID-19 at the Intersection of Immunology and Infectious Diseases: A Related PRISMA Systematic Literature Review
Authors: Vlădulescu-Trandafir Andreea-Iulia , Bojincă Violeta-Claudia , Munteanu Constantin , Anghelescu Aurelian , Popescu Cristina , Stoica Simona-Isabelle , Aurelian Sorina , Bălănescu Andra , Băetu Cristina , Ciobanu Vlad , Onose Gelu
Published: October 2024

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA.
Probiotics as Potential Tool to Mitigate Nucleotide Metabolism Alterations Induced by DiNP Dietary Exposure in Danio rerio
Authors: Giommi Christian , Maradonna Francesca , Ladisa Claudia , Habibi Hamid R. , Carnevali Oliana
Published: October 2024

Diisononyl phthalate, classified as endocrine disruptor, has been investigate to trigger lipid biosynthesis in both mammalian and teleostean animal models. Despite this, little is known about the effects of DiNP exposure at tolerable daily intake level and the possible mechanisms of its toxicity. Probiotics, on the other hand, were demonstrated to have beneficial effects on the organism’s metabolism and recently emerged as a possible tool to mitigate the EDC toxicity. In the present study, using a metabolomic approach, the potential hepatic sex-related toxicity of DiNP was investigated in adult zebrafish together with the mitigating action of the probiotic formulation SLAB51, which has already demonstrated its ability to ameliorate gastrointestinal pathologies in animals including humans. Zebrafish were exposed for 28 days to 50 µg/kg body weight (bw)/day of DiNP (DiNP) through their diet and treated with 109 CFU/g bw of SLAB51 (P) and the combination of DiNP and SLAB51 (DiNP + P), and the results were compared to those of an untreated control group (C). DiNP reduced AMP, IMP, and GMP in the purine metabolism, while such alterations were not observed in the DiNP + P group, for which the phenotype overlapped that of C fish. In addition, in male, DiNP reduced UMP and CMP levels in the pyrimidine metabolism, while the co-administration of probiotic shifted the DiNP + P metabolic phenotype toward that of P male and closed to C male, suggesting the beneficial effects of probiotics also in male fish. Overall, these results provide the first evidence of the disruptive actions of DiNP on hepatic nucleotide metabolism and mitigating action of the probiotic to reduce a DiNP-induced response in a sex-related manner.
Assessing the Potential of 1,2,3-Triazole-Dihydropyrimidinone Hybrids Against Cholinesterases: In Silico, In Vitro, and In Vivo Studies
Authors: Gastalho Carlos M. , Sena Ana M. , López Óscar , Fernández-Bolaños José G. , García-Sosa Alfonso T. , Pereira Florbela , Antunes Célia M. , Costa Ana R. , Burke Anthony J. , Carreiro Elisabete P.
Published: October 2024

Combining the pharmacological properties of the 1,2,3-triazole and dihydropyrimidinone classes of compounds, two small families of mono- and di(1,2,3-triazole)-dihydropyrimidinone hybrids, A and B, were previously synthesized. The main objective of this work was to investigate the potential anti-Alzheimer effects of these hybrids. The inhibitory activities of cholinesterases (AChE and BuChE), antioxidant activity, and the inhibitory mechanism through in silico (molecular docking) and in solution (STD-NMR) experiments were evaluated. The 1,2,3-triazole-dihydropyrimidinone hybrids (A and B) showed moderate in vitro inhibitory activity on eqBuChE (IC50 values between 1 and 58.4 μM). The best inhibitor was the hybrid B4, featuring two 1,2,3-triazole cores, which exhibited stronger inhibition than galantamine, with an IC50 of 1 ± 0.1 μM for eqBuChE, through a mixed inhibition mechanism. Among the hybrids A, the most promising inhibitor was A1, exhibiting an IC50 of 12 ± 2 µM, similar to that of galantamine. Molecular docking and STD-NMR experiments revealed the key binding interactions of these promising inhibitors with BuChE. Hybrids A and B did not display Artemia salina toxicity below 100 μM.
Eutopic and Ectopic Endometrial Interleukin-17 and Interleukin-17 Receptor Expression at the Endometrial—Myometrial Interface in Women with Adenomyosis: Possible Pathophysiology Implications
Authors: Hsu Le-Tien , Lu Pei-Chen , Wang Yi-Wen , Wu Hsien-Ming , Chen I-Ju , Huang Hong-Yuan
Published: October 2024

Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial–myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to investigate the expression of IL-17 in eutopic and ectopic endometrium (adenomyosis) of individuals with adenomyosis at the level of EMI. Paired tissues of eutopic endometrium and adenomyoma were collected from 16 premenopausal women undergoing hysterectomy due to adenomyosis. The IL-17 system was demonstrated in paired tissue samples at the level of EMI by the immunochemistry study. Gene expression levels of IL-17A and IL-17 receptor (IL-17R) were assessed through quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Comparative gene transcript amounts were calculated using the delta-delta Ct method. By immunohistochemical staining, CD4, IL-17A, and IL-17R proteins were detected in both eutopic endometrium and adenomyosis at the level of EMI. IL-17A and IL-17R were expressed mainly in the glandular cells, and the expression of both IL-17A and IL-17R was found to be stronger in adenomyosis than in endometrium. 3-Diaminobenzidine (DAB) staining revealed greater IL-17A expression in adenomyosis compared to eutopic endometrium. Quantitative RT-PCR showed 7.28-fold change of IL-17A and 1.99-fold change of IL-17R, and the fold change level of both IL-17A and IL-17R is significantly higher in adenomyosis (IL-17A: p = 0.047, IL-17R: p = 0.027) versus eutopic endometrium. We found significantly higher IL-17 levels in adenomyosis compared to eutopic endometrium at the level of EMI. The results showed that the IL-17 system may play a role in adenomyosis.
Differential Urinary Microbiome and Its Metabolic Footprint in Bladder Cancer Patients Following BCG Treatment
Authors: Min Kyungchan , Zheng Chuang-Ming , Kim Sujeong , Kim Hyun , Lee Minji , Piao Xuan-Mei , Byun Young Joon , Kim Yunjae , Joo Yanghyun , Cho Beomki , Moon Seongmin , Kim Won Tae , Kang Ho Won , Park Hansoo , Yun Seok Joong
Published: October 2024

Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette–Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30–50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses.
Progress in the Stereoselective Synthesis Methods of Pyrrolidine-Containing Drugs and Their Precursors
Authors: Smolobochkin Andrey , Gazizov Almir , Appazov Nurbol , Sinyashin Oleg , Burilov Alexander
Published: October 2024

The presented review systematizes and summarizes the data on the synthesis of pyrrolidine derivatives, which are precursors for obtaining drugs. Based on the analysis of published data, the most promising directions in the synthesis of biologically active compounds containing a pyrrolidine ring are identified. Stereoselective synthesis methods are classified based on the source of the pyrrolidine ring. The first group includes methods that use a pyrrolidine ring as the starting compound. The second group combines stereoselective methods of cyclization of acyclic starting compounds, which lead to optically pure pyrrolidine derivatives.
The Knowns and Unknowns of Membrane Features and Changes During Autophagosome–Lysosome/Vacuole Fusion
Authors: Liu Jinmeng , Ma Hanyu , Wu Zulin , Ji Yanling , Liang Yongheng
Published: October 2024

Autophagosome (AP)–lysosome/vacuole fusion is one of the hallmarks of macroautophagy. Membrane features and changes during the fusion process have mostly been described using two-dimensional (2D) models with one AP and one lysosome/vacuole. The outer membrane (OM) of a closed mature AP has been suggested to fuse with the lysosomal/vacuolar membrane. However, the descriptions in some studies for fusion-related issues are questionable or incomplete. The correct membrane features of APs and lysosomes/vacuoles are the prerequisite for describing the fusion process. We searched the literature for representative membrane features of AP-related structures based on electron microscopy (EM) graphs of both animal and yeast cells and re-evaluated the findings. We also summarized the main 2D models describing the membrane changes during AP–lysosome/vacuole fusion in the literature. We used three-dimensional (3D) models to characterize the known and unknown membrane changes during and after fusion of the most plausible 2D models. The actual situation is more complex, since multiple lysosomes may fuse with the same AP in mammalian cells, multiple APs may fuse with the same vacuole in yeast cells, and in some mutant cells, phagophores (unclosed APs) fuse with lysosomes/vacuoles. This review discusses the membrane features and highly dynamic changes during AP (phagophore)–lysosome/vacuole fusion. The resulting information will improve the understanding of AP–lysosome/vacuole fusion and direct the future research on AP–lysosome/vacuole fusion and regeneration.
Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review
Authors: Kitamura Eiji , Imai Noboru
Published: October 2024

Migraine is a prevalent neurological disorder, particularly among individuals aged 20–50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies.
Examining Carotenoid Metabolism Regulation and Its Role in Flower Color Variation in Brassica rapa L.
Authors: Liu Guomei , Luo Liuyan , Yao Lin , Wang Chen , Sun Xuan , Du Chunfang
Published: October 2024

Carotenoids are vital organic pigments that determine the color of flowers, roots, and fruits in plants, imparting them yellow, orange, and red hues. This study comprehensively analyzes carotenoid accumulation in different tissues of the Brassica rapa mutant “YB1”, which exhibits altered flower and root colors. Integrating physiological and biochemical assessments, transcriptome profiling, and quantitative metabolomics, we examined carotenoid accumulation in the flowers, roots, stems, and seeds of YB1 throughout its growth and development. The results indicated that carotenoids continued to accumulate in the roots and stems of YBI, especially in its cortex, throughout plant growth and development; however, the carotenoid levels in the petals decreased with progression of the flowering stage. In total, 54 carotenoid compounds were identified across tissues, with 30 being unique metabolites. Their levels correlated with the expression pattern of 22 differentially expressed genes related to carotenoid biosynthesis and degradation. Tissue-specific genes, including CCD8 and NCED in flowers and ZEP in the roots and stems, were identified as key regulators of color variations in different plant parts. Additionally, we identified genes in the seeds that regulated the conversion of carotenoids to abscisic acid. In conclusion, this study offers valuable insights into the regulation of carotenoid metabolism in B. rapa, which can guide the selection and breeding of carotenoid-rich varieties.
Phase-Sensitive Fluorescence Image Correlation Spectroscopy
Authors: Clayton Andrew H. A.
Published: October 2024

Fluorescence lifetime imaging microscopy is sensitive to molecular interactions and environments. In homo-dyne frequency-domain fluorescence lifetime imaging microscopy, images of fluorescence objects are acquired at different phase settings of the detector. The detected intensity as a function of detector phase is a sinusoidal function that is sensitive to the lifetime of the fluorescent species. In this paper, the theory of phase-sensitive fluorescence image correlation spectroscopy is described. In this version of lifetime imaging, image correlation spectroscopy analysis (i.e., spatial autocorrelation) is applied to successive fluorescence images acquired at different phase settings of the detector. Simulations of different types of lifetime distributions reveal that the phase-dependent density of fluorescent objects is dependent on the heterogeneity of lifetimes present in the objects. We provide an example of this analysis workflow to a cervical cancer cell stained with a fluorescent membrane probe.
HIV-Associated Neurocognitive Disorder (HAND) and Alzheimer’s Disease Pathogenesis: Future Directions for Diagnosis and Treatment
Authors: Mustafa Mohammed , Musselman Dominique , Jayaweera Dushyantha , da Fonseca Ferreira Andrea , Marzouka George , Dong Chunming
Published: October 2024

HIV-associated neurocognitive disorder (HAND) and Alzheimer’s disease (AD) are two neurocognitive disorders with overlapping clinical presentations and pathophysiology. The two have been thought to be two separate entities. However, the introduction and widespread use of antiretroviral therapy (ART) has altered the clinical manifestations of HAND, shifting from a pattern of subcortical dementia to one more akin to cortical dementia, resembling AD. Thus, the line between the two disease entities is not clear-cut. In this review, we discuss the concept of Alzheimer’s disease-like dementia (ADLD) in HIV, which describes this phenomenon. While the mechanisms of HIV-associated ADLD remain to be elucidated, potential mechanisms include HIV-specific pathways, including epigenetic imprinting from initial viral infection, persistent and low viral load (which can only be detected by ultra-sensitive PCR), HIV-related inflammation, and putative pathways underlying traditional AD risk factors. Importantly, we have shown that HIV-specific microRNAs (miRs) encapsulated in extracellular vesicles (EV-miRs) play an important role in mediating the detrimental effects in the cardiovascular system. A useful preclinical model to study ADLD would be to expose AD mice to HIV-positive EVs to identify candidate EV-miRs that mediate the HIV-specific effects underlying ADLD. Characterization of the candidate EV-miRs may provide novel therapeutic armamentaria for ADLD.
Identification of Genetic Variants Associated with Hereditary Thoracic Aortic Diseases (HTADs) Using Next Generation Sequencing (NGS) Technology and Genotype–Phenotype Correlations
Authors: Butnariu Lăcrămioara Ionela , Russu Georgiana , Luca Alina-Costina , Sandu Constantin , Trandafir Laura Mihaela , Vasiliu Ioana , Popa Setalia , Ghiga Gabriela , Bălănescu Laura , Țarcă Elena
Published: October 2024

Hereditary thoracic aorta diseases (HTADs) are a heterogeneous group of rare disorders whose major manifestation is represented by aneurysm and/or dissection frequently located at the level of the ascending thoracic aorta. The diseases have an insidious evolution and can be encountered as an isolated manifestation or can also be associated with systemic, extra-aortic manifestations (syndromic HTADs). Along with the development of molecular testing technologies, important progress has been made in deciphering the heterogeneous etiology of HTADs. The aim of this study is to identify the genetic variants associated with a group of patients who presented clinical signs suggestive of a syndromic form of HTAD. Genetic testing based on next-generation sequencing (NGS) technology was performed using a gene panel (Illumina TruSight Cardio Sequencing Panel) or whole exome sequencing (WES). In the majority of cases (8/10), de novo mutations in the FBN1 gene were detected and correlated with the Marfan syndrome phenotype. In another case, a known mutation in the TGFBR2 gene associated with Loeys–Dietz syndrome was detected. Two other pathogenic heterozygous variants (one de novo and the other a known mutation) in the SLC2A10 gene (compound heterozygous genotype) were identified in a patient diagnosed with arterial tortuosity syndrome (ATORS). We presented the genotype–phenotype correlations, especially related to the clinical evolution, highlighting the particularities of each patient in a family context. We also emphasized the importance of genetic testing and patient monitoring to avoid acute aortic events.
Computational Approach to Identifying New Chemical Entities as Elastase Inhibitors with Potential Antiaging Effects
Authors: Pitasi Giovanna , Brancale Andrea , Floris Sonia , Fais Antonella , Gitto Rosaria , De Luca Laura
Published: October 2024

In the aging process, skin morphology might be affected by wrinkle formation due to the loss of elasticity and resilience of connective tissues linked to the cleavage of elastin by the enzymatic activity of elastase. Little information is available about the structural requirements to efficiently inhibit elastase 1 (EC 3.4.21.36) expressed in skin keratinocytes. In this study, a structure-based approach led to the identification to the pharmacophoric hypotheses that described the main structural requirements for binding to porcine pancreatic elastase as a valuable tool for the development of skin therapeutic agents due to its similarity with human elastase 1. The obtained models were subsequently refined through the application of computational alanine-scanning mutagenesis to evaluate the effect of single residues on the binding affinity and protein stability; in turn, molecular dynamic simulations were carried out; these procedures led to a simplified model bearing few essential features, enabling a reliable collection of chemical features for their interactions with elastase. Then, a virtual screening campaign on the in-house library of synthetic compounds led to the identification of a nonpeptide-based inhibitor (IC50 = 60.4 µM) belonging to the class of N-substituted-1H-benzimidazol-2-yl]thio]acetamides, which might be further exploited to obtain more efficient ligands of elastase for therapeutic applications.
Torque teno virus (TTV) Infection in Patients with Encephalitis
Authors: Jurasz Henryk , Bukowska-Ośko Iwona , Rydzanicz Małgorzata , Popiel Marta , Dzieciątkowski Tomasz , Bakuła-Grządka Karolina , Paciorek Marcin , Makowiecki Michał , Horban Andrzej , Laskus Tomasz , Radkowski Marek , Perlejewski Karol
Published: October 2024

Torque teno virus (TTV) is a ssDNA orphan virus belonging to the Anelloviridae family, but some recent studies suggested its possible involvement in central nervous system (CNS) pathology. We analyzed serum and cerebrospinal fluid samples (CSF) from 109 patients with encephalitis for TTV infection using serological and molecular testing, virus quantitative measurement, and next-generation sequencing-based (NGS) phylogenetic analysis. TTV noncoding region (UTR) and/or open reading frame 1 (ORF-1) sequences were detected in serum of 86 (79%) patients and in nine (8%) patients in CSF. Five of the latter patients were coinfected with various entero- and herpesviruses. Anti-TTV-IgG were detected in 80 (73.4%) sera and in two (1.8%) CSF samples, while anti-TTV-IgM were present in three (2.8%) sera and in none of the CSFs. Phylogenic analysis of CSF-derived TTV ORF-1 sequences revealed the presence of three unique variants in one patient. TTV was quantified in five CSF-serum pairs: in two patients viral loads were similar, and in three serum TTV loads were approximately one log higher. Our results suggest at least an occasional replication of TTV in CNS. However, whether TTV could be the cause of encephalitis requires further studies.
Calcium ATPase (PMCA) and GLUT-4 Upregulation in the Transverse Tubule Membrane of Skeletal Muscle from a Rat Model of Chronic Heart Failure
Authors: Gitler Sofia , Ramirez-Soto Ibrahim , Jiménez-Graduño Aura , Ortega Alicia
Published: October 2024

Intolerance to exercise is a symptom associated with chronic heart failure (CHF) resulting in SM waste and weakness in humans. The effect of CHF on skeletal muscle (SM) arose from experimental evidence in rat models to explain the underlying mechanism. We investigated SM mechanical and metabolic properties in sham rats and with coronary ligation-induced CHF. After twelve weeks of CHF, rats were catheterized to measure right auricular pressure, SM mechanical properties, SERCA-ATPase activity and plasma membrane Ca2+-ATPase (PMCA) hydrolytic activity in isolated sarcoplasmic reticulum (SR) and transverse tubule (TT membrane), respectively, in the sham and CHF. The right auricular pressure and plasma nitrite concentration in CHF increased two-fold with respect to the sham. Pleural effusion and ascites were detected in CHF, confirming CHF. SERCA activity was conserved in CHF. In TT membranes from CHF, the glucose transporter GLUT4 increased seven-fold, and the PMCA hydrolytic activity increased five-fold, but in isolated muscle, the mechanical properties were unaffected. The absence of a deleterious effect of coronary ligation-induced CHF in the rat model on SM could be explained by the increased activity of PMCA and increased presence of GLUT-4 on the TT membrane, which may be involved in the mechanical outcome of the EDL.
Ribosome Structural Changes Dynamically Affect Ribosome Function
Authors: Lindahl Lasse
Published: October 2024

Ribosomes were known to be multicomponent complexes as early as the 1960s. Nonetheless, the prevailing view for decades considered active ribosomes to be a monolithic population, in which all ribosomes are identical in composition and function. This implied that ribosomes themselves did not actively contribute to the regulation of protein synthesis. In this perspective, I review evidence for a different model, based on results showing that ribosomes can harbor different types of ribosomal RNA (rRNA) and ribosomal proteins (r-proteins) and, furthermore, need not contain a complete set of r-proteins. I also summarize recent results favoring the notion that such distinct types of ribosomes have different affinities for specific messenger RNAs and may execute the translation process differently. Thus, ribosomes should be considered active contributors to the regulation of protein synthesis.
Combined BSA-Seq and RNA-Seq Analysis to Identify Candidate Genes Associated with Aluminum Toxicity in Rapeseed (Brassica napus L.)
Authors: Zhou Huiwen , Yu Paolan , Wu Lanhua , Han Depeng , Wu Yang , Zheng Wei , Zhou Qinghong , Xiao Xiaojun
Published: October 2024

Exchangeable aluminum (Al) ions released from acidic soils with pH < 5.5 inhibit root elongation of crops, ultimately leading to yield reduced. It is necessary to identify the quantitative trait locus (QTLs) and candidate genes that confer toxicity resistance to understand the mechanism and improve tolerance of rapeseed. In this study, an F2 segregating population was derived from a cross between Al-tolerance inbred line FDH188 (R178) and -sensitive inbred line FDH152 (S169), and the F2:3 were used as materials to map QTLs associated with the relative elongation of taproot (RET) under Al toxicity stress. Based on bulked segregant analysis sequencing (BSA-seq), three QTLs (qAT-A07-1, qAT-A07-2, and qAT-A09-1) were detected as significantly associated with RET, and 656 candidate genes were screened. By combined BSA and RNA-seq analysis, 55 candidate genes showed differentially expressed, including genes encoding ABC transporter G (ABCG), zinc finger protein, NAC, ethylene-responsive transcription factor (ERF), etc. These genes were probably positive factors in coping with Al toxicity stress in rapeseed. This study provides new insight into exploring the QTLs and candidate genes’ response to Al toxicity stress by combined BSA-seq and RNA-seq and is helpful to further research on the mechanism of Al resistance in rapeseed.
Temperature Effects on Seed Germination and Seedling Biochemical Profile of Cannabis Landraces
Authors: Langa Sabeliwe , Magwaza Lembe Samukelo , Mditshwa Asanda , Tesfay Samson Zeray
Published: October 2024

This study investigated the effect of temperature on the germination and seedling biochemical profiles of eight cannabis landraces, namely Ladysmith Ugwayi wesiZulu (L1) and Iswazi (L2), Durban Poison (H1), Bergville Ugwayi wesiZulu (B1), Natal (B2), and Iswazi (B3), and Msinga Ugwayi wesiZulu (M1) and Iswazi (M2). Seed viability, germination rate, and germination percentage were evaluated along with seedling amino acids, carbohydrates, and fatty acids methyl esters (FAMEs) under day/night temperature regimes of 20/15 °C, 30/25 °C, and 40/35 °C. Results showed a significant effect (p < 0.001) of temperature on germination percentage, rate, and biochemical profiles of cannabis landraces. Landraces L1, B1, H1, B2, and M1 had higher germination at 20/15 °C, while B3, M2, and L2 performed better at 30/25 °C. Biochemical profiles varied with temperature and landraces. Amino acid content increased with temperature but did not correlate with germination indexes. Carbohydrates and FAMEs decreased with rising temperature, peaking at 30/25 °C. FAMEs strongly correlated with germination indexes, linking lipid composition to seed performance. Sorbitol positively correlated with germination, while glucose and fructose showed indirect correlations. This study underscores the impact of temperature on germination and the biochemical profiles of cannabis landraces, highlighting the importance of considering genotype-specific responses in varietal selection.
The Localization of Software and Video Games: Current State and Future Perspectives
Authors: Pirrone Marco , D’Ulizia Arianna
Published: October 2024

The study of linguistics applied to computer science is a much-discussed topic today. In this area, particularly relevant is the software localization process describing the linguistic and cultural adaptation of software products to a specific market scenario. Software localization is going through a phase of strong development due to the great market demand and the current trend of making the computer more human-like in the way it interacts with the user. This paper focuses on “linguistic” localization by addressing the language translation process from the perspective of translation studies. In particular, the process of translating the language assets in a game and making the game linguistically and culturally appropriate for the target market will be explored. The study provides a systematic literature review of the main localization methods developed over the last four decades, along with the major issues and challenges mainly related to the main linguistic and cultural aspects of videogames. The review results are integrated with the results of a qualitative analysis conducted through a focus group with the participation of both academic and professional experts in software and videogame localization. The results of this study are worthwhile for many academics and industry professionals as they provide an in-depth overview of the localization process in software and videogames as well as potential directions for future research.
A Method for Single-Phase Ground Fault Section Location in Distribution Networks Based on Improved Empirical Wavelet Transform and Graph Isomorphic Networks
Authors: Wang Chen , Feng Lijun , Hou Sizu , Ren Guohui , Wang Wenyao
Published: October 2024

When single-phase ground faults occur in distribution systems, the fault characteristics of zero-sequence current signals are not prominent. They are quickly submerged in noise, leading to difficulties in fault section location. This paper proposes a method for fault section location in distribution networks based on improved empirical wavelet transform (IEWT) and GINs to address this issue. Firstly, based on kurtosis, EWT is optimized using the N-point search method to decompose the zero-sequence current signal into modal components. Noise is filtered out through weighted permutation entropy (WPE), and signal reconstruction is performed to obtain the denoised zero-sequence current signal. Subsequently, GINs are employed for graph classification tasks. According to the topology of the distribution network, the corresponding graph is constructed as the input to the GIN. The denoised zero-sequence current signal is the node input for the GIN. The GIN autonomously explores the features of each graph structure to achieve fault section location. The experimental results demonstrate that this method has strong noise resistance, with a fault section location accuracy of up to 99.95%, effectively completing fault section location in distribution networks.
An Enhanced Learning with Error-Based Cryptosystem: A Lightweight Quantum-Secure Cryptography Method
Authors: Kara Mostefa , Karampidis Konstantinos , Papadourakis Giorgos , Hammoudeh Mohammad , AlShaikh Muath
Published: October 2024

Quantum-secure cryptography is a dynamic field due to its crucial role in various domains. This field aligns with the ongoing efforts in data security. Post-quantum encryption (PQE) aims to counter the threats posed by future quantum computers, highlighting the need for further improvement. Based on the learning with error (LWE) system, this paper introduces a novel asymmetric encryption technique that encrypts entire messages of n bits rather than just 1 bit. This technique offers several advantages including an additive homomorphic cryptosystem. The robustness of the proposed lightweight public key encryption method, which is based on a new version of LWE, ensures that private keys remain secure and that original data cannot be recovered by an attacker from the ciphertext. By improving encryption and decryption execution time—which achieve speeds of 0.0427 ms and 0.0320 ms, respectively—and decreasing ciphertext size to 708 bits for 128-bit security, the obtained results are very promising.
A 3D Statistical Shape Model of the Right Ventricular Outflow Tract in Pulmonary Valve Replacement Patients Post-Surgical Repair
Authors: Swanson Liam , Sivera Raphaël , Capelli Claudio , Alosaimi Abdulaziz , Mroczek Dariusz , Lam Christopher Z. , Cook Andrew , Chaturvedi Rajiv R. , Schievano Silvia
Published: October 2024

Assessment of the right ventricular outflow tract and pulmonary arteries (RVOT) for percutaneous pulmonary valve implantation (PPVI) uses discrete measurements (diameters and lengths) from medical images. This multi-centre study identified the 3D RVOT shape features prevalent in patients late after surgical repair of congenital heart disease (CHD). A 3D RVOT statistical shape model (SSM) was computed from 81 retrospectively selected CHD patients (14.7 ± 6.8 years) who required pulmonary valve replacement late after surgical repair. A principal component analysis identified prevalent shape features (modes) within the population which were compared with standard geometric measurements (diameter, length and surface area) and between sub-groups of diagnosis, RVOT type and dysfunction. Shape mode 1 and 2 represented RVOT size and curvature and tapering and length, respectively. Shape modes 3–5 related to branch pulmonary artery calibre, conical vs. bulbous RVOTs and RVOT curvature, respectively. Tetralogy of Fallot, transannular patch type and regurgitant RVOTs were larger and straighter while conduit and stenotic types were longer and more cylindrical than other subgroups. This SSM analysed the main 3D shape features present in a population of RVOTs, exploiting the wide 3D anatomical information provided by routine imaging. This morphological information may have implications for PPVI patient selection and device design.
Association of Cardiovascular Risk Factors and Coronary Calcium Burden with Epicardial Adipose Tissue Volume Obtained from PET–CT Imaging in Oncological Patients
Authors: Nappi Carmela , Ponsiglione Andrea , Vallone Carlo , Lepre Roberto , Basile Luigi , Green Roberta , Cantoni Valeria , Mainolfi Ciro Gabriele , Imbriaco Massimo , Petretta Mario , Cuocolo Alberto
Published: October 2024

Whole-body positron emission tomography (PET)–computed tomography (CT) imaging performed for oncological purposes may provide additional parameters such as the coronary artery calcium (CAC) and epicardial adipose tissue (EAT) volume with cost-effective prognostic information in asymptomatic people beyond traditional cardiovascular risk factors. We evaluated the feasibility of measuring the CAC score and EAT volume in cancer patients without known coronary artery disease (CAD) referred to whole-body 18F-FDG PET–CT imaging, regardless of the main clinical problem. We also investigated the potential relationships between traditional cardiovascular risk factors and CAC with EAT volume. A total of 109 oncological patients without overt CAD underwent whole-body PET–CT imaging with 18F-fluorodeoxyglucose (FDG). Unenhanced CT images were retrospectively viewed for CAC and EAT measurements on a dedicated platform. Overall, the mean EAT volume was 99 ± 49 cm3. Patients with a CAC score ≥ 1 were older than those with a CAC = 0 (p < 0.001) and the prevalence of hypertension was higher in patients with detectable CAC as compared to those without (p < 0.005). The EAT volume was higher in patients with CAC than in those without (p < 0.001). For univariable age, body mass index (BMI), hypertension, and CAC were associated with increasing EAT values (all p < 0.005). However, the correlation between the CAC score and EAT volume was weak, and in multivariable analysis only age and BMI were independently associated with increased EAT (both p < 0.001), suggesting that potential prognostic information on CAC and EAT is not redundant. This study demonstrates the feasibility of a cost-effective assessment of CAC scores and EAT volumes in oncological patients undergoing whole-body 18F-FDG PET–CT imaging, enabling staging cancer disease and atherosclerotic burden by a single test already included in the diagnostic work program, with optimization of the radiation dose and without additional costs.
Estimating Progression-Free Survival in Patients with Primary High-Grade Glioma Using Machine Learning
Authors: Kwiatkowska-Miernik Agnieszka , Wasilewski Piotr Gustaw , Mruk Bartosz , Sklinda Katarzyna , Bujko Maciej , Walecki Jerzy
Published: October 2024

Background/Objectives: High-grade gliomas are the most common primary malignant brain tumors in adults. These neoplasms remain predominantly incurable due to the genetic diversity within each tumor, leading to varied responses to specific drug therapies. With the advent of new targeted and immune therapies, which have demonstrated promising outcomes in clinical trials, there is a growing need for image-based techniques to enable early prediction of treatment response. This study aimed to evaluate the potential of radiomics and artificial intelligence implementation in predicting progression-free survival (PFS) in patients with highest-grade glioma (CNS WHO 4) undergoing a standard treatment plan. Methods: In this retrospective study, prediction models were developed in a cohort of 51 patients with pathologically confirmed highest-grade glioma (CNS WHO 4) from the authors’ institution and the repository of the Cancer Imaging Archive (TCIA). Only patients with confirmed recurrence after complete tumor resection with adjuvant radiotherapy and chemotherapy with temozolomide were included. For each patient, 109 radiomic features of the tumor were obtained from a preoperative magnetic resonance imaging (MRI) examination. Four clinical features were added manually—sex, weight, age at the time of diagnosis, and the lobe of the brain where the tumor was located. The data label was the time to recurrence, which was determined based on follow-up MRI scans. Artificial intelligence algorithms were built to predict PFS in the training set (n = 75%) and then validate it in the test set (n = 25%). The performance of each model in both the training and test datasets was assessed using mean absolute percentage error (MAPE). Results: In the test set, the random forest model showed the highest predictive performance with 1-MAPE = 92.27% and a C-index of 0.9544. The decision tree, gradient booster, and artificial neural network models showed slightly lower effectiveness with 1-MAPE of 88.31%, 80.21%, and 91.29%, respectively. Conclusions: Four of the six models built gave satisfactory results. These results show that artificial intelligence models combined with radiomic features could be useful for predicting the progression-free survival of high-grade glioma patients. This could be beneficial for risk stratification of patients, enhancing the potential for personalized treatment plans and improving overall survival. Further investigation is necessary with an expanded sample size and external multicenter validation.
Prevalence of Disordered Eating Risk Attitudes in Youth Elite Male and Female Football Players
Authors: Vásquez-Díaz Fernanda , Aguayo-Muela Álvaro Del Carmen , Radesca Krizia , Muñoz-Andradas Guillermo , Domínguez-Balmaseda Diego
Published: October 2024

Objectives: Examine the prevalence of risk behaviors for the development of eating disorders in academy footballers of the Liga MX, compare sociodemographic data and highlight the participants’ perceptions regarding the influence of the sports environment and external pressure on their relationship with food and their bodies. Methods: A cross-sectional study was carried out with 536 footballers (331 men and 205 women) in the categories U14, U16, U18 men and U15, U19 women of Liga MX with prior consent from their clubs and strict confidentiality measures. The data were collected via Google Forms using the Eating Attitudes Test (EAT-26). Results: Of the participants, 13.4% met or exceeded the cut-off point on the EAT-26. The highest prevalence was observed in the Female U19 category. The reflections indicated that the sports environment and external pressure affect the relationship with food and bodies in a significant proportion of participants. Conclusions: The study highlights a high prevalence of risk behaviors for eating disorders in Liga MX football players, with a higher incidence in the female categories, also evidencing a multifactorial etiology.