bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Histone Acetylation Modification on Biosynthesis of Secondary Metabolites in Fungi
Authors: Hou Xuwen , Liu Liyao , Li Yu , Wang Pengfei , Pan Xiaoqian , Xu Dan , Lai Daowan , Zhou Ligang
Published: December 2024

The histone acetylation modification is a conservative post-translational epigenetic regulation in fungi. It includes acetylation and deacetylation at the lysine residues of histone, which are catalyzed by histone acetyltransferase (HAT) and deacetylase (HDAC), respectively. The histone acetylation modification plays crucial roles in fungal growth and development, environmental stress response, secondary metabolite (SM) biosynthesis, and pathogenicity. One of the most important roles is to regulate the gene expression that is responsible for SM biosynthesis in fungi. This mini-review summarized the regulation of histone acetylation modification by HATs and HDACs on the biosynthesis of SMs in fungi. In most cases, histone acetylation by HATs positively regulated the biosynthesis of fungal SMs, while HDACs had their negative regulations. Some HATs and HDACs were revealed to regulate fungal SM biosynthesis. Hda1 was found to be the most efficient regulator to affect the biosynthesis of SMs in fungi. The regulated fungal species were mainly from the genera of Aspergillus, Calcarisporium, Cladosporium, Fusarium, Monascus, Penicillium, and Pestalotiopsis. With the strategy of histone acetylation modification, the biosynthesis of some harmful SMs will be inhibited, while the production of useful bioactive SMs will be promoted in fungi. The subsequent research should focus on the study of regulatory mechanisms.
Autoimmune Thyroid Disease in Patients with Down Syndrome—Review
Authors: Szybiak-Skora Weronika , Cyna Wojciech , Lacka Katarzyna
Published: December 2024

Down syndrome develops due to the presence of supernumerary chromosome 21. This diagnosis is made in approximately 1:800 live births. The tendency to develop autoimmune disorders like idiopathic arthritis, celiac disease, diabetes mellitus type 1, vitiligo and autoimmune thyroid disease is strongly expressed in patients with Down syndrome. Autoimmune thyroid diseases consisting of Hashimoto’s thyroiditis and Graves’ disease are specifically prevalent in patients with Down syndrome. The aim of our study is to collect available data connecting the pathogenesis and clinical course of autoimmune thyroid diseases in patients with Down syndrome of different ages and compare them to control groups. According to published data, the incidence ratio of Hashimoto’s thyroiditis diagnosis in patients with Down syndrome is elevated compared to in age-matched controls without this chromosomal aberration, similarly to Graves’ disease risk, which is also increased in a group of patients with Down syndrome. What is more, both Hashimoto’s thyroiditis and Graves’ disease are diagnosed at an earlier age than in the healthy population and are not correlated with gender or a family history of autoimmune diseases.
How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism
Authors: Nicholls Robert A. , Morgan Harry , Warren Anna J. , Ward Simon E. , Long Fei , Murshudov Garib N. , Sutormin Dmitry , Bax Benjamin D.
Published: December 2024

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water–metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks. Gepotidacin has been observed to sit on the twofold axis of the complex, midway between the two four-base-pair separated DNA-cleavage sites and has been observed to stabilize singe-stranded DNA breaks. Here, we use information from three crystal structures of complexes of Staphlococcus aureus DNA gyrase (one with a precursor of gepotidacin and one with the progenitor of zoliflodacin) to propose a simple single moving metal-ion-catalyzed DNA-cleavage mechanism. Our model explains why the catalytic tyrosine is in the tyrosinate (negatively charged) form for DNA cleavage. Movement of a single catalytic metal-ion (Mg2+ or Mn2+) guides water-mediated protonation and cleavage of the scissile phosphate, which is then accepted by the catalytic tyrosinate. Type IIA topoisomerases need to be able to rapidly cut the DNA when it becomes positively supercoiled (in front of replication forks and transcription bubbles) and we propose that the original purpose of the small Greek Key domain, common to all type IIA topoisomerases, was to allow access of the catalytic metal to the DNA-cleavage site. Although the proposed mechanism is consistent with published data, it is not proven and other mechanisms have been proposed. Finally, how such mechanisms can be experimentally distinguished is considered.
Plant Nuclear Factor Y (NF-Y) Transcription Factors: Evolving Insights into Biological Functions and Gene Expansion
Authors: Siriwardana Chamindika L.
Published: December 2024

Gene expansion is a common phenomenon in plant transcription factor families; however, the underlying molecular mechanisms remain elusive. Examples of gene expansion in transcription factors are found in all eukaryotes. One example is plant nuclear factor Y (NF-Y) transcription factors. NF-Y is ubiquitous to eukaryotes and comprises three independent protein families: NF-YA, NF-YB, and NF-YC. While animals and fungi mostly have one of each NF-Y subunit, NF-Y is greatly expanded in plants. For example, humans have one each of NF-YA, NF-YB, and NF-YC, while the model plant Arabidopsis has ten each of NF-YA, NF-YB, and NF-YC. Our understanding of the plant NF-Y, including its biological roles, molecular mechanisms, and gene expansion, has improved over the past few years. Here we will review its biological roles and focus on studies demonstrating that NF-Y can serve as a model for plant gene expansion. These studies show that NF-Y can be classified into ancestrally related subclasses. Further, the primary structure of each NF-Y contains a conserved core domain flanked by non-conserved N- and C-termini. The non-conserved N- and C-termini, under pressure for diversifying selection, may provide clues to this gene family’s retention and functional diversification following gene duplication. In summary, this review demonstrates that NF-Y expansion has the potential to be used as a model to study the gene expansion and retention of transcription factor families.
Compare Analysis of Codon Usage Bias of Nuclear Genome in Eight Sapindaceae Species
Authors: Song Yuxuan , Shen Meng , Cao Fuliang , Yang Xiaoming
Published: December 2024

Codon usage bias (CUB) refers to the different frequencies with which various codons are utilized within a genome. Examining CUB is essential for understanding genome structure, function, and evolution. However, little was known about codon usage patterns and the factors influencing the nuclear genomes of eight ecologically significant Sapindaceae species widely utilized for food and medicine. In this study, an analysis of nucleotide composition revealed a higher A/T content and showed a preference for A/T at the third codon position in the eight species of Sapindaceae. A correspondence analysis of relative synonymous codon usage explained only part of the variation, suggesting that not only natural selection but also various other factors contribute to selective constraints on codon bias in the nuclear genomes of the eight Sapindaceae species. Additionally, ENC-GC3 plot, PR2-Bias, and neutrality plot analyses indicated that natural selection exerted a greater influence than mutation pressure across these eight species. Among the eight Sapindaceae species, 16 to 26 optimal codons were identified, with two common high-frequency codons: AGA (encoding Arg) and GCU (encoding Ala). The clustering heat map, which included the 8 Sapindaceae species and 13 other species, revealed two distinct clusters corresponding to monocots and dicots. This finding suggested that CUB analysis was particularly effective in elucidating evolutionary relationships at the family level. Collectively, our results emphasized the distinct codon usage characteristics and unique evolutionary traits of the eight Sapindaceae species.
Evaluation of Selected Pro- and Anti-Inflammatory Adipokines in Colostrum from Mothers with Gestational Diabetes Mellitus
Authors: Lis-Kuberka Jolanta , Berghausen-Mazur Marta , Orczyk-Pawiłowicz Magdalena
Published: December 2024

Adipokines related to gestational diabetes mellitus (GDM) are an emerging area of interest. The aim of this study was to evaluate the associations between GDM and adipokine levels in human milk. This was an observational cohort study targeting mothers with gestational diabetes, which evaluated the association of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment), with colostral adipokines involved in pro- and anti-inflammatory processes. Colostrum was collected from hyperglycemic (N = 34) and normoglycemic (N = 26) mothers, and adipokine levels were determined by immunoenzymatic assay. Among anti-inflammatory adipokines, only for irisin and vaspin, but not for obestatin and adropin, were significantly different levels noted between the GDM-G1, GDM-G2 and non-GDM cohorts. Colostrum of the GDM-G2 subgroup contained more vaspin (4.77 ng/mL) than that of normoglycemic mothers (3.12 ng/mL) and more irisin (26.95 μg/mL) than in the GDM-G1 subgroup (17.59 μg/mL). The levels of pro-inflammatory adipokines, namely, dermcidin, chemerin and visfatin, were at similar levels irrespective of maternal glycemia. Moreover, irisin showed a negative correlation with dermcidin in GDM-G2 and non-GDM cohorts. Associations were observed between colostral irisin and maternal preconception BMI, dermcidin and gestational age, and vaspin and maternal age. This study provides evidence that the way of restoring glucose homeostasis in pregnant women has an impact on the anti-inflammatory adipokines irisin and vaspin, but not on obestatin and adropin. GDM, regardless of severity, did not influence the colostral pro-inflammatory adipokines visfatin, chemerin and dermcidin.
Biogenesis of Extracellular Vesicles (EVs) and the Potential Use of Embryo-Derived EVs in Medically Assisted Reproduction
Authors: Ovčar Andreja , Kovačič Borut
Published: December 2024

Extracellular vesicles (EVs) are lipid bilayer-bound particles released from cells that cannot replicate on their own, play a crucial role in intercellular communication, and are implicated in various physiological and pathological processes. Within the domain of embryo culture media research, extensive studies have been conducted to evaluate embryo viability by analyzing spent culture medium. Advanced methodologies such as metabolomic profiling, proteomic and genomic analyses, transcriptomic profiling, non-coding RNA assessments, and oxidative status measurements have been employed to further understand the molecular characteristics of embryos and improve selection criteria for successful implantation. In the field of EVs, only a limited number of studies have been conducted on embryo-conditioned medium, indicating a significant gap in knowledge regarding the potential role of EVs in embryo development and implantation. Therefore, this review aims to evaluate current research findings on EVs enriched from animal and human embryo spent medium. By unraveling the potential link between embryo-derived EVs and embryo selection in clinical settings, such research might enhance embryo-selection methods in assisted reproductive technologies, eventually increasing the success rates of fertility treatments and advancing our understanding of mechanisms underlying successful embryo development and implantation in humans.
Chloroquine Affects Presynaptic Membrane Retrieval in Diaphragm Neuromuscular Junctions of Old Mice
Authors: Jahanian Sepideh , Gulbronson Chloe I. , Gransee Heather M. , Millesi Elena , Sieck Gary C. , Mantilla Carlos B.
Published: December 2024

Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes. Diaphragm-phrenic nerve preparations from 24-month-old male and female C57BL/6 × 129 J mice were incubated with FM 4-64 (5 µM) and either chloroquine (50 µM) or vehicle during 80 Hz phrenic nerve stimulation. Acute chloroquine treatment significantly decreased FM 4-64 intensity at diaphragm neuromuscular junctions following 80 Hz phrenic nerve stimulation, consistent with disrupted synaptic vesicle recycling. A similar reduction was evident in regions with the greatest FM 4-64 fluorescence intensity, which most likely surround synaptic vesicle release sites. In the absence of nerve stimulation, chloroquine treatment significantly increased FM 4-64 intensity at diaphragm neuromuscular junctions. These findings highlight the importance of autophagy in regulating presynaptic vesicle retrieval (including vesicle recycling and endosomal processing) and support the role of autophagy impairments in age-related neuromuscular dysfunction.
ATAD1 Regulates Neuronal Development and Synapse Formation Through Tuning Mitochondrial Function
Authors: Yan Hao-Hao , He Jia-Jia , Fu Chuanhai , Chen Jia-Hui , Tang Ai-Hui
Published: December 2024

Mitochondrial function is essential for synaptic function. ATAD1, an AAA+ protease involved in mitochondrial quality control, governs fission–fusion dynamics within the organelle. However, the distribution and functional role of ATAD1 in neurons remain poorly understood. In this study, we demonstrate that ATAD1 is primarily localized to mitochondria in dendrites and, to a lesser extent, in spines in cultured hippocampal neurons. We found that ATAD1 deficiency disrupts the mitochondrial fission–fusion balance, resulting in mitochondrial fragmentation. This deficiency also impairs dendritic branching, hinders dendritic spine maturation, and reduces glutamatergic synaptic transmission in hippocampal neuron. To further investigate the underlying mechanism, we employed an ATP hydrolysis-deficient mutant of ATAD1 to rescue the neuronal deficits associated with ATAD1 loss. We discovered that the synaptic deficits are independent of the mitochondrial morphology changes but rely on its ATP hydrolysis. Furthermore, we show that ATAD1 loss leads to impaired mitochondrial function, including decreased ATP production, impaired membrane potential, and elevated oxidative stress. In conclusion, our results provide evidence that ATAD1 is crucial for maintaining mitochondrial function and regulating neurodevelopment and synaptic function.
The Immunophenotype and the Odontogenic Commitment of Dental Pulp Stem Cells Co-Cultured with Macrophages Under Inflammatory Conditions Is Modulated by Complex Magnetic Fields
Authors: Gallorini Marialucia , Mencarelli Noemi , Di Pietro Natalia , di Giacomo Viviana , Zara Susi , Ricci Alessia , Rapino Monica , Piattelli Adriano , Cipollina Alessandro , Cataldi Amelia
Published: December 2024

Dental inflammatory diseases remain a challenging clinical issue, whose causes and development are still not fully understood. During dental caries, bacteria penetrate the tooth pulp, causing pulpitis. To prevent pulp necrosis, it is crucial to promote tissue repair by recruiting immune cells, such as macrophages, able to secrete signal molecules for the pulp microenvironment and thus to recruit dental pulp stem cells (DPSCs) in the damaged site. To date, root canal therapy is the standard for dental caries, but alternative regenerative treatments are gaining attention. Complex Multifrequency Magnetoelectric Fields (CMFs) represent an interesting tool due to their potential anti-inflammatory activity. Against this background, the present work aims at investigating whether the CMF treatment might restore redox balance in a co-culture model of DPSCs and inflamed macrophages mimicking an inflammatory condition, like pulpitis. Results show that superoxide anion levels and markers related to the polarization of macrophages are modulated by the CMF treatment. In parallel, the use of CMFs discloses an impact on the odontogenic commitment of DPSCs, their immunophenotype being considerably modified. In conclusion, CMFs, by modulating the odontogenic commitment and the anti-inflammatory response of DPSCs, might represent a suitable therapeutic tool against pulpitis and, in general, towards dental inflammatory diseases.
Beyond Misfolding: A New Paradigm for the Relationship Between Protein Folding and Aggregation
Authors: Choi Seong Il , Jin Yoontae , Choi Yura , Seong Baik L.
Published: December 2024

Aggregation is intricately linked to protein folding, necessitating a precise understanding of their relationship. Traditionally, aggregation has been viewed primarily as a sequential consequence of protein folding and misfolding. However, this conventional paradigm is inherently incomplete and can be deeply misleading. Remarkably, it fails to adequately explain how intrinsic and extrinsic factors, such as charges and cellular macromolecules, prevent intermolecular aggregation independently of intramolecular protein folding and structure. The pervasive inconsistencies between protein folding and aggregation call for a new framework. In all combined reactions of molecules, both intramolecular and intermolecular rate (or equilibrium) constants are mutually independent; accordingly, intrinsic and extrinsic factors independently affect both rate constants. This universal principle, when applied to protein folding and aggregation, indicates that they should be treated as two independent yet interconnected processes. Based on this principle, a new framework provides groundbreaking insights into misfolding, Anfinsen’s thermodynamic hypothesis, molecular chaperones, intrinsic chaperone-like activities of cellular macromolecules, intermolecular repulsive force-driven aggregation inhibition, proteome solubility maintenance, and proteinopathies. Consequently, this paradigm shift not only refines our current understanding but also offers a more comprehensive view of how aggregation is coupled to protein folding in the complex cellular milieu.
Tetramethylpyrazine Protects Against Chronic Hypobaric Hypoxia-Induced Cardiac Dysfunction by Inhibiting CaMKII Activation in a Mouse Model Study
Authors: Zhang Pengfei , Deng Huifang , Lan Xiong , Shen Pan , Bai Zhijie , Huangfu Chaoji , Wang Ningning , Xiao Chengrong , Gao Yehui , Sun Yue , Li Jiamiao , Guo Jie , Zhou Wei , Gao Yue
Published: December 2024

Chronic exposure to high altitudes causes pathophysiological cardiac changes that are characterized by cardiac dysfunction, cardiac hypertrophy, and decreased energy reserves. However, finding specific pharmacological interventions for these pathophysiological changes is challenging. In this study, we identified tetramethylpyrazine (TMP) as a promising drug candidate for cardiac dysfunction caused by simulated high-altitude exposure. By utilizing hypobaric chambers to simulate high-altitude environments, we found that TMP improved cardiac function, alleviated cardiac hypertrophy, and reduced myocardial injury in hypobaric hypoxic mice. RNA sequencing showed that TMP also upregulated heart-contraction-related genes that were suppressed by hypobaric hypoxia exposure. Mechanistically, TMP inhibited hypobaric hypoxia-induced cardiac Ca2+/calmodulin-dependent kinase II (CaMKII) activation and exerted cardioprotective effects by inhibiting CaMKII. Our data suggest that TMP application may be a promising approach for treating high-altitude-induced cardiac dysfunction, and they highlight the crucial role of CaMKII in hypobaric hypoxia-induced cardiac pathophysiology.
The Role of Different Rhizobacteria in Mitigating Aluminum Stress in Rice (Oriza sativa L.)
Authors: Carranza-Patiño Mercedes Susana , Torres-Rodriguez Juan Antonio , Reyes-Pérez Juan José , Herrera-Feijoo Robinson J. , Cedeño-Moreira Ángel Virgilio , Coello Mieles Alejandro Jair , Macías Holguín Cristhian John , Chicaiza-Ortiz Cristhian
Published: December 2024

Aluminum toxicity in acidic soils threatens rice (Oryza sativa L.) cultivation, hindering agricultural productivity. This study explores the potential of plant growth-promoting rhizobacteria (PGPR) as a novel and sustainable approach to mitigate aluminum stress in rice. Two rice varieties, INIAP-4M and SUPREMA I-1480, were selected for controlled laboratory experiments. Seedlings were exposed to varying aluminum concentrations (0, 2, 4, 8, and 16 mM) in the presence of four PGPR strains: Serratia marcescens (MO4), Enterobacter asburiae (MO5), Pseudomonas veronii (R4), and Pseudomonas protegens (CHAO). The INIAP-4M variety exhibited greater tolerance to aluminum than SUPREMA I-1480, maintaining 100% germination up to 4 mM and higher vigor index values. The study revealed that rhizobacteria exhibited different responses to aluminum concentrations. P. protegens and S. marcescens showed the highest viability at 0 mM (2.65 × 1010 and 1.71 × 1010 CFU mL−1, respectively). However, P. veronii and S. marcescens exhibited the highest viability at aluminum concentrations of 2 and 4 mM, indicating their superior tolerance and adaptability under moderate aluminum stress. At 16 mM, all strains experienced a decrease, with P. protegens and E. asburiae being the most sensitive. The application of a microbial consortium significantly enhanced plant growth, increasing plant height to 73.75 cm, root fresh weight to 2.50 g, and leaf fresh weight to 6 g compared to the control (42.75 cm, 0.88 g, and 3.63 g, respectively). These findings suggest that PGPR offer a promising and sustainable strategy to bolster rice resilience against aluminum stress and potentially improve crop productivity in heavy metal-contaminated soils.
Leveraging Social Media Data for Enhanced Forecasting of International Student Arrivals in Australia
Authors: Abdul Karim Ali , Pardede Eric , Mann Scott
Published: December 2024

This study examines the extent to which incorporating social media data enhances the predictive accuracy of models forecasting international students’ arrivals. Private social media data collected from a public university, along with collected web traffic data and Google Trend data, were used in the forecasting models. Initially, a correlation analysis was conducted, revealing a strong relationship between the institution’s international student enrolment and the social media activity, as well as with the overall number of international students arriving in Australia. Building on these insights, features were derived from the collected data for use in the development of the forecasting models. Two XGBoost models were developed: one excluding social media’s features and one including them. The model incorporating social media data outperformed the one without it. Furthermore, a feature selection process was applied, resulting in even more accurate forecasts. These findings suggest that integrating social media data can significantly enhance the accuracy of forecasting models for international student arrivals.
An Approach for Detecting Parkinson’s Disease by Integrating Optimal Feature Selection Strategies with Dense Multiscale Sample Entropy
Authors: Nguyen Minh Tai Pham , Tran Minh Khue Phan , Nakano Tadashi , Tran Thi Hong , Nguyen Quoc Duy Nam
Published: December 2024

Parkinson’s disease (PD) is a neurological disorder that severely affects motor function, especially gait, requiring accurate diagnosis and assessment instruments. This study presents Dense Multiscale Sample Entropy (DM-SamEn) as an innovative method for diminishing feature dimensions while maintaining the uniqueness of signal features. DM-SamEn employs a weighting mechanism that considers the dynamic properties of the signal, thereby reducing redundancy and improving the distinctiveness of features extracted from vertical ground reaction force (VGRF) signals in patients with Parkinson’s disease. Subsequent to the extraction process, correlation-based feature selection (CFS) and sequential backward selection (SBS) refine feature sets, improving algorithmic accuracy. To validate the feature extraction and selection stage, three classifiers—Adaptive Weighted K-Nearest Neighbors (AW-KNN), Radial Basis Function Support Vector Machine (RBF-SVM), and Multilayer Perceptron (MLP)—were employed to evaluate classification efficacy and ascertain optimal performance across selection strategies, including CFS, SBS, and the hybrid SBS-CFS approach. K-fold cross-validation was employed to provide improved evaluation of model performance by assessing the model on various data subsets, thereby mitigating the risk of overfitting and augmenting the robustness of the results. As a result, the model demonstrated a significant ability to differentiate between PD patients and healthy controls, with classification accuracy reported as ACC [CI 95%: 97.82–98.5%] for disease identification and ACC [CI 95%: 96.3–97.3%] for severity assessment. Optimal performance was primarily achieved through feature sets chosen using SBS and the integrated SBS-CFS methods. The findings highlight the model’s potential as an effective instrument for diagnosing PD and assessing its severity, contributing to advancements in clinical management of the condition.
Flexural and Shear Strengthening of High-Strength Concrete Beams Using near Surface Basalt Fiber Bars
Authors: Ashteyat Ahmed , Obaidat Ala’ Taleb , Al-Khreisat Ahmad , Abdel-Jaber Mu’tasime
Published: December 2024

Strengthening of reinforced concrete (RC) structures has become a primary challenge in civil engineering. Different materials and procedures have been used in order to repair or strengthen RC structures. In this research, the NSM-Basalt Bar (NSM-BFRP) technique was used to strengthen high-strength reinforced concrete beams in flexure and shear. Twelve beams were designed, constructed, and tested under four-point loads. Six of them were designed to have insufficient longitudinal steel reinforcement to make sure that the failure would be a flexural failure in the control beam. Whereas, the other six specimens were designed to have insufficient transverse steel reinforcement to make sure that the failure will be a shear failure in the control beam. All RC beams were strengthened using NSM-BFRP with different configurations except control specimens. The load deflection curve, the cracking pattern and the failure mode were evaluated. The experimental results reveal that NSM-BFRP bars significantly enhance the ultimate load capacity of high-strength concrete beams, with flexural capacity improvements of up to 33.33% and shear capacity enhancements of up to 63.5%. However, the use of BFRP bars also led to a shift in failure modes from flexural to shear, particularly in specimens with increased flexural reinforcement. The findings suggest that while NSM-BFRP bars are highly effective in strengthening concrete beams, careful consideration of the reinforcement configuration is necessary to avoid premature shear failure and ensure balanced structural performance.
An Analytical Method for Determining the Stress–Strain State of a Subgrade with Combined Reinforcement
Authors: Alkhdour Ahmad , Tiutkin Oleksii , Fischer Szabolcs , Kurhan Dmytro
Published: December 2024

This article presents the fundamentals of an analytical method for determining the stress–strain state of a railway subgrade reinforced with geosynthetic material. The reinforcement described is a combined system where the geosynthetic material forms an open shell containing a layer of compacted crushed stone. The overall stress–strain state is proposed to be viewed as a superposition of two states of the subgrade. The stresses and displacements in the first state refer to the unreinforced subgrade (matrix), while the stress–strain state of the reinforcement element is determined using analytical constructs from composite theory. The dependencies of the overall stress–strain state are applied in a numerical analysis, which confirms the positive effect of reduced subgrade deformations. A small-scale experimental model further validates the accuracy of the analytical approach.
Management of Non-A Non-B Aortic Dissection: A Narrative Review
Authors: Kletzer Joseph , Kondov Stoyan , Dimov Aleksandar , Werdecker Victoria , Czerny Martin , Kreibich Maximilian , Berger Tim
Published: December 2024

Non-A non-B aortic dissection remains a complex and controversial topic in cardiovascular management, eliciting varied approaches among cardiologists and surgeons. Due to the limited evidence surrounding this condition, existing guidelines are limited in the complexity of their recommendations. While most patients are initially managed medically, invasive treatment becomes necessary in a large proportion of patients. When surgery is considered, the most utilized techniques include the frozen elephant trunk procedure and endovascular repair strategies targeting the arch and descending thoracic aorta. This narrative review aims to synthesize current knowledge and clinical experiences, highlighting the challenges and evolving practices related to non-A non-B dissection management.
Distribution of Pathogens in Early- and Late-Onset Sepsis Among Preterm Infants: A Decade-Long Study in a Tertiary Referral Neonatal Intensive Care Unit
Authors: Muszyńska-Radska Katarzyna , Szwed Krzysztof , Falkowski Adrian , Sadowska-Krawczenko Iwona
Published: December 2024

Background: Neonatal sepsis, a severe infection in newborns, remains one of the leading causes of morbidity and mortality among preterm infants. This study aimed to investigate the distribution of pathogens responsible for early-onset sepsis (EOS) and late-onset sepsis (LOS), the annual variability of pathogens responsible for each type of infection, and potential trends in their profiles in preterm infants from a tertiary care neonatal intensive care unit over a ten-year period. Methods: We analyzed 177 episodes of confirmed bloodstream infection between 1 January 2014 and 31 December 2023. An episode of confirmed bloodstream infection was defined by the growth of a single potential pathogen in the blood of an infant who met four criteria: showing clinical symptoms of infection, having abnormal hematologic parameters, receiving appropriate antibiotics for less than 5 days, and being born before 37 weeks of gestation. Pathogens were isolated from aseptically collected blood samples, processed within 2 h, incubated using the BACTEC system, and identified by Gram stains and selective media cultures. Pathogen identification was performed using standardized biochemical tests or MALDI-TOF MS. Sepsis was classified as EOS if it occurred within the first 72 h of life and as LOS if it occurred after 72 h. Results: Among the confirmed bloodstream infections, EOS accounted for 31 cases, while LOS accounted for 146 cases. Escherichia coli was identified as the primary pathogen responsible for early-onset sepsis (EOS), while Coagulase-negative Staphylococcus (CoNS) was most commonly associated with late-onset sepsis (LOS). The differences in the prevalence of these bacteria between EOS and LOS were statistically significant. However, no significant differences were found in the distribution of pathogens across different years, nor were there significant trends in their frequency over the study period. Our results demonstrate significant stability in the distribution of pathogens causing sepsis over the ten-year observation period, even during the COVID-19 pandemic. Conclusions: Understanding the temporal distribution of pathogens in neonatal sepsis can help prevent the overuse of antibiotics and support the implementation of screening programs, empiric therapy, and strategies to prevent healthcare-associated infections.
The “11 to Perf Score”, a Test for Professional Players Returning to Soccer After Anterior Cruciate Ligament Reconstruction
Authors: Disegni Elio , Memain Geoffrey , Bouvet Jean , Gaspar Maxime , Maille Romain , Tamalet Bertrand , Orhant Emmanuel , Maille Pascal , Bohu Yoann , Hardy Alexandre
Published: December 2024

Rupture of the anterior cruciate ligament (ACL) is common among soccer players. Although there are no strict recommendations for the return to sport, more and more practitioners are having their patients perform isokinetic and even composite tests. However, these tests have not yet been shown to be predictive of re-injury, and are not specific to professional footballers. Objectives: The “11 to Perf” is a test designed to help professional footballers return to sport after ACL reconstruction. Its originality lies in its integration of soccer practice with specific tests. The aim of this article is to present the “11 to Perf” evaluation method. Methods: A prospective cohort study was conducted at the Centre National du Football (FIFA center) in Clairefontaine, including professional footballers who have undergone anterior cruciate ligament surgery and rehabilitation. Tests include clinical assessments, jumping, agility, psychological and isokinetic tests and match simulation. Conclusions: The “11 to Perf” is a composite test designed to assess the return to sport of professional footballers after ACL reconstruction. Its predictive capacity for recurrence should be assessed in the future.
Recent Advances and Future Directions in Extracorporeal Carbon Dioxide Removal
Authors: Lamas Tomás , Fernandes Susana M. , Vasques Francesco , Karagiannidis Christian , Camporota Luigi , Barrett Nicholas
Published: December 2024

Extracorporeal carbon dioxide removal (ECCO2R) is an emerging technique designed to reduce carbon dioxide (CO2) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCO2R operates at lower blood flows (0.4–1.5 L/min), making it less invasive, with smaller cannulas and simpler devices. Despite encouraging results in controlling respiratory acidosis, its broader adoption is hindered by complications, including haemolysis, thrombosis, and bleeding. Technological advances, including enhanced membrane design, gas exchange efficiency, and anticoagulation strategies, are essential to improving safety and efficacy. Innovations such as wearable prototypes that adapt CO2 removal to patient activity and catheter-based systems for lower blood flow are expanding the potential applications of ECCO2R, including as a bridge-to-lung transplantation and in outpatient settings. Promising experimental approaches include respiratory dialysis, carbonic anhydrase-coated membranes, and electrodialysis to maximise CO2 removal. Further research is needed to optimise device performance, develop cost-effective systems, and establish standardised protocols for safe clinical implementation. As the technology matures, integration with artificial intelligence (AI) and machine learning may personalise therapy, improving outcomes. Ongoing clinical trials will be pivotal in addressing these challenges, ultimately enhancing the role of ECCO2R in critical care and its accessibility across healthcare settings.
Laboratory Assessment of Factor VIII Inhibitors: When Is It Required? A Perspective Informed by Local Practice
Authors: Favaloro Emmanuel J. , Curnow Jennifer , Pasalic Leonardo
Published: December 2024

This perspective discusses the critical role of laboratory assessments in assessing factor VIII (FVIII) inhibitors. These are auto- and alloantibodies that can develop against both endogenous and exogenous FVIII, respectively. Assessment for inhibitors represents a key part of the management of both congenital hemophilia A (CHA), an inherited deficiency, and acquired hemophilia A (AHA), an autoimmune condition. Both conditions pose significant bleeding risks, necessitating careful monitoring of FVIII levels and inhibitor presence and level. Laboratory assays, particularly the Bethesda assay, are essential for detecting these inhibitors and assessing their levels. The complexities of FVIII inhibitor kinetics may pose challenges to interpretation of assay results, such that even normal FVIII levels do not always exclude inhibitor presence. Clinical practice guidelines recommend ongoing monitoring of AHA/CHA patients until inhibitors are no longer detectable. Overall, timely laboratory evaluations are essential to optimizing treatment strategies for patients with hemophilia, aiming to improve patient outcomes and quality of life. We summarize our approach to the laboratory assessment of FVIII inhibitors, as reflecting our perspective and as informed by local practice.
Gut Dysbiosis and Adult Atopic Dermatitis: A Systematic Review
Authors: Díez-Madueño Kevin , de la Cueva Dobao Pablo , Torres-Rojas Isabel , Fernández-Gosende Marta , Hidalgo-Cantabrana Claudio , Coto-Segura Pablo
Published: December 2024

Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.
Impact of Uric Acid Levels on Mortality and Cardiovascular Outcomes in Relation to Kidney Function
Authors: Kwon Young-Eun , Ahn Shin-Young , Ko Gang-Jee , Kwon Young-Joo , Kim Ji-Eun
Published: December 2024

Background: Uric acid levels are linked to cardiovascular outcomes and mortality, especially in chronic kidney disease (CKD). However, their impact across varying kidney function remains unclear. Methods: We conducted a retrospective cohort study using the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database from a single center. Adult patients with at least one serum uric acid measurement between 2002 and 2021 were included and categorized by estimated glomerular filtration rate (eGFR): normal kidney function (≥90 mL/min/1.73 m2), mild dysfunction (60–89 mL/min/1.73 m2), moderate dysfunction (30–59 mL/min/1.73 m2), and advanced dysfunction (<30 mL/min/1.73 m2). The primary outcome was all-cause mortality with secondary outcomes being myocardial infarction (MI) and heart failure (HF). Results: A total of 242,793 participants were analyzed. Uric acid levels showed a U-shaped association with all-cause mortality in advanced kidney dysfunction, where both low (<3 mg/dL) and high (>10 mg/dL) levels increased mortality risk. In mild kidney dysfunction, lower uric acid levels were linked to better survival. HF risk increased linearly with higher uric acid, particularly in normal kidney function, while no significant association was found between uric acid and MI in any group. Conclusions: Uric acid levels are associated with mortality in a U-shaped pattern for advanced kidney dysfunction, while lower levels appear protective in mild dysfunction. These findings suggest the need for personalized uric acid management in CKD patients based on their kidney function.
Customized 3D Allogenic Bone Blocks for Mandibular Buccal-Bone Reconstruction Increase Resistance to Tongue-Protrusion Forces: A Finite Element Analysis
Authors: Dominiak Sebastian , Majer Jennifer , Bourauel Christoph , Keilig Ludger , Gedrange Tomasz
Published: December 2024

Background. The impact of tongue protrusion forces on the formation of malocclusions is well documented in academic literature. In the case of bone dehiscence of the buccal wall in front of the lower frontal teeth, this process may be even more pronounced. Augmentation with 3D customized allogenic bone blocks (CABB) has been proposed as a potential solution for treating such defects. The objective was to assess the impact of bone block adjustment accuracy on the resistance of teeth to protrusion forces at various stages of alveolar bone loss. Methods: A finite element analysis (FEM) was conducted to ascertain whether augmentation with a CABB will result in increased resilience to tongue protrusion forces. Three-dimensional models of the mandible with dehiscenses were created, based on the dehiscences classification and modification proposed in the journal by the authors of regenerative method. The models feature a CABB positioned at three different distances: 0.1 mm, 0.4 mm, and 1.0 mm. The material parameters were as follows: bone (homogenous, isotropic, E = 2 GPa), teeth (E = 20 GPa), periodontal ligament (E = 0.44 MPa), and membrane between bones (E = 3.4 MPa). A tongue protrusion force within the range of 0–5 N was applied to each individual frontal tooth. Results: The use of an CABB has been shown to positively impact the stability of the teeth. The closer the bone block was placed to the alveolar bone, the more stable was the result. The best results were obtained with a ¼ dehiscence and 0.1 mm distance. Conclusions: The protrusive forces produced by the tongue might not be the biggest one, but in a presence of the bone loss they might have serious results. Even shortly after the surgery, CABB has a positive impact on the incisor resilience.
Enhancing Digestibility and Intestinal Peptide Release of Pleurotus eryngii Protein: An Enzymatic Approach
Authors: Wang Dandan , Zhang Meng , Wan Jianing , Liu Haiquan , Wang Ying , Yang Ruiheng , Wu Yingying , Bao Dapeng , Chen Hongyu , Zou Gen , Zhao Yong
Published: December 2024

Pleurotus eryngii is a tasty and low-calorie mushroom containing abundant high-quality protein. This study aims to improve the digestibility of P. eryngii protein (PEP) and hence to facilitate its development as a healthy alternative protein. The extracted PEP was pretreated with 1000–5000 U of papain, neutral protease and alkaline protease. The Chyme collected from in vitro simulated gastrointestinal digestion was analyzed by fluorescence microscopy and protein particle analyzer, and the endpoint profiles of peptides and amino acids were determined by UHPLC-MS/MS and NanoLC-MS/MS. The particle size curve and fluorescence microscopy images jointly supported that protease hydrolysis improved decomposition and dispersion of PEP during digestion, particularly in the gastric phase. The impact on Zeta potential was minimal. Proteases effectively increased the abundance of amino acids after digestion, particularly L-isomer Lys and Arg Maximum release was achieved when pretreated with 5000 U of alkaline protease, reaching 7.54 times that of control. Pretreatments by proteases also notably increased digestive yields of 16,736–19,870 peptides, with the maximum reaching 1.70 times that of the control, which mainly consisted of small peptides composed of 7–15 amino acids with molecular weight below 800 Da. The findings indicated that protease hydrolysis, especially pretreatment with 5000 U of alkaline protease, effectively enhanced the digestibility of PEP, which shed light on providing enzymatic approaches for improving bioavailability and developing healthy fungal proteins.
From Random Perturbation to Precise Targeting: A Comprehensive Review of Methods for Studying Gene Function in Monascus Species
Authors: Gong Yunxia , Li Shengfa , Zhao Deqing , Yuan Xi , Zhou Yin , Chen Fusheng , Shao Yanchun
Published: December 2024

Monascus, a genus of fungi known for its fermentation capability and production of bioactive compounds, such as Monascus azaphilone pigments and Monacolin K, have received considerable attention because of their potential in biotechnological applications. Understanding the genetic basis of these metabolic pathways is crucial for optimizing the fermentation and enhancing the yield and quality of these products. However, Monascus spp. are not model fungi, and knowledge of their genetics is limited, which is a great challenge in understanding physiological and biochemical phenomena at the genetic level. Since the first application of particle bombardment to explore gene function, it has become feasible to link the phenotypic variation and genomic information on Monascus strains. In recent decades, accurate gene editing assisted by genomic information has provided a solution to analyze the functions of genes involved in the metabolism and development of Monascus spp. at the molecular level. This review summarizes most of the genetic manipulation tools used in Monascus spp. and emphasizes Agrobacterium tumefaciens-mediated transformation and nuclease-guided gene editing, providing comprehensive references for scholars to select suitable genetic manipulation tools to investigate the functions of genes of interest in Monascus spp.
Recticladiella inexpectata gen. et sp. nov. (Nectriaceae) Pathogenic to Native Cinnamomum camphora (Lauraceae) Trees in Southeastern China
Authors: Han Fangying , Chen Shuaifei
Published: December 2024

The ascomycete family Nectriaceae includes soil-borne saprobes, plant pathogens and human pathogens, biodegraders, and biocontrol agents for industrial and commercial applications. Cinnamomum camphora is a native tree species that is widely planted in southern China for landscaping purposes. During a routine survey of Eucalyptus diseases in southern China, disease spots were frequently observed on the leaves of Ci. camphora trees planted close to Eucalyptus. The asexual fungal structures on the leaf spots presented morphological characteristics typical of the Nectriaceae. The aim of this study is to identify these fungi and determine their pathogenic effect on Ci. camphora. Of the isolates obtained from 13 sites in the Fujian and Guangdong Provinces, 54 isolates were identified based on the DNA phylogeny of the tef1, tub2, cmdA, and his3 regions and morphological features. Two isolates were identified as Calonectria crousiana, and fifty-two isolates were described as a new genus, including a single species. These fungi were named Recticladiella inexpectata gen. et sp. nov. The identification of the new genus was based on strong DNA base differences in each of the four sequenced gene regions. The conidiophores of this fungus had several avesiculate stipe extensions tapering toward a straight, occasionally slightly curved terminal cell, distinguishing it from other phylogenetically close Nectriaceae genera. The results indicate that R. inexpectata is distributed in wide geographic regions in southern China. Inoculation showed that R. inexpectata and Ca. crousiana caused lesions on the leaves of Ci. camphora seedlings within 6 days of inoculation, indicating that they are pathogenic to native Ci. camphora in China.