bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Socio-Demographic Profile of Non-Completion in Public Oral Healthcare Services: A Cross-Sectional Study in Melbourne, Victoria
Authors: Mariño Rodrigo , Price Kelsey , Shankumar Ramini
Published: December 2024

(1) Background: Completion of the full oral health course of care (CoC) is essential to prevent further deterioration of oral and overall health. Understanding these patterns, particularly in public oral healthcare services, is crucial for improving access to and the delivery of care. This study aims to identify the socio-demographic and clinical characteristics of adult patients who did not complete required dental treatments within a 12-month period at Monash Health Dental Services (MHDS), Melbourne, Victoria. (2) Methods: Data were collected on patients’ course of care (CoC), socio-demographic characteristics, and clinical information from the MHDS Titanium electronic database. This study represents a secondary data analysis from adult patients who attended MHDS between November 2022 and October 2023, excluding emergency dental care visits. Logistic regression analyzed the socio-demographic and clinical variables affecting CoC. (3) Results: Our findings identified several significant predictors of incomplete CoC; being a non-priority group, mental health clients, refugees, and identifying as Aboriginal or Torres Strait Islanders (OR = 1.41; 95% CI: 1.08–1.84). Conversely, speaking a language other than English increased the odds of completing treatment (OR = 0.85; 95% CI: 0.74–0.98). By age, patients in the 36-to-55- or the 56-to-75-year-old age groups were more likely to be in the incomplete group (OR = 1.65; 95% CI: 1.37–1.98; and OR = 1.43; 95% CI: 1.22–1.66, respectively). (4) Conclusions: This study identified predictors of discontinued care, emphasizing accessibility and equitable outcomes for users of public oral healthcare. The findings indicate that the predictors of course of care (CoC) completion differ from barriers to accessing care. This highlights key objectives in public health dentistry, focusing on improving accessibility and promoting equitable oral health outcomes for vulnerable populations.
A Set of Tools and Data Management Framework for the IoT–Edge–Cloud Continuum
Authors: Judvaitis Janis , Blumbergs Eduards , Arzovs Audris , Mackus Andris Ivars , Balass Rihards , Selavo Leo
Published: December 2024

Developing and managing complex IoT–Edge–Cloud Continuum (IECC) systems are challenging due to the system complexity and diversity. Internet of Things (IoT), Edge, and Cloud components combined with artificial intelligence (AI) in data processing systems must ensure strong security and privacy for data sources. The approach of the IECC Data Management Framework (DMF) introduces a novel combination of multiple easy-to-configure plugin environments using data visualization features. These contributions collectively address the critical challenges inherent in heterogeneous environments such as scalability, data privacy, and configuration management by standardizing data flow configurations and increasing stakeholder trust in sensitive applications, particularly in critical infrastructure monitoring.
Analysis of Long-Term Monitoring of Radon Levels in a Low-Ventilated, Semi-Underground Laboratory—Dose Estimation and Exploration of Potential Earthquake Precursors
Authors: Gulan Ljiljana
Published: December 2024

This study involves continuous radon monitoring during the academic year 2023/2024. An Airthings Corentium Home radon detector placed in the basement laboratory of a faculty building in Kosovska Mitrovica (N 42.897°, E 20.867°) was used for continuous measurements. The average radon concentration was 303 Bq/m3, and a seasonal pattern during the measuring period was observed. For the first time, the results were grouped by week, excluding non-working days, to present a real case scenario with the aim of assessing the radon exposure of students, teachers, and employed persons. The inhalation dose from radon (1.54 mSv) was very high considering that exposure occurred in both semesters. Another aspect of continuous radon monitoring was to explore the relationship between indoor radon measurements and the occurrences of earthquakes in the Balkan region. Daily variations in radon (peaks and differences) were analyzed at the monitoring site by using both empirical laws and taking into account the earthquake data set provided by the Seismological Survey of Serbia. The analysis revealed that the events chosen to confirm a clear association between earthquake occurrence and enhanced radon activities in the air(as a precursor of seismic activities) did not meet the required criteria but most likely reflected external meteorological conditions.
Estimation of Nitrous Oxide Emissions from Agricultural Sources and Characterization of Spatial and Temporal Changes in Anhui Province (China)
Authors: Ye Zhou , Sun Yujuan , Zhang Xianglin , Yao Youzhi
Published: December 2024

To evaluate the estimation and spatiotemporal variation characteristics of nitrous oxide emissions from agricultural sources in Anhui Province, the nitrous oxide emissions generated during crop cultivation and manure management were assessed based on the recommended methods in the “Guidelines for Provincial Greenhouse Gas Inventories” and official statistical data. The results showed that the overall emission of nitrous oxide from agricultural land showed a downward trend, reaching a valley value in 2019 with an emission of 2.83 × 104 tons. The annual average emissions of nitrous oxide from agricultural land and manure management account for 80.98% and 19.02% of the total annual average emissions of nitrous oxide from agricultural activities in Anhui Province, respectively. Both agricultural land emissions and livestock manure management show a trend of nitrous oxide emissions decreasing from the northern region of Anhui > central region of Anhui > southern region of Anhui. In this paper, we explored and discussed the intrinsic driving factors behind the spatiotemporal changes in nitrous oxide emissions, and analyzed the potential for future emission reductions. It is suggested that the emissions of nitrous oxide from agricultural sources can be reduced through measures such as reasonable nitrogen application, adjustment of aquaculture structures, and the improvement of manure treatment methods, providing a theoretical reference for the estimation of greenhouse gas emissions from agricultural sources.
Evaluation and Analysis of Next-Generation FY-4A LPW Products over Various Climatic Regions in China
Authors: Zhang Wenyuan , Xiao Xinyu , Peng Jinsong , Zhang Shubi , Shehaj Endrit , Moeller Gregor
Published: December 2024

Atmospheric water vapor, a significant constituent of the atmosphere, affects the energy balance between Earth’s atmosphere and space, and its changes play a crucial role in the greenhouse effect. Layer precipitable water (LPW), which represents the column-integral water vapor within a vertical range, is increasingly recognized as a key indicator of atmospheric water vapor distributions and variations. Due to its capability for layer-wise monitoring, LPW products have the potential to offer valuable insights into the characteristics and evolution of climatic regions through refined atmospheric spatiotemporal information. However, the observational quality and spatiotemporal variations of LPW products across different climate zones, e.g., the diverse climatic regions in China, have not been systematically assessed. In this paper, we aim to evaluate and analyze the climatic and seasonal variations of FY-4A LPW products across five climatic regions in China, contributing to a deeper understanding of water vapor variability and providing valuable data for climate change research. A surface pressure calibration algorithm for ERA5 data is developed to calculate accurate ERA5 LPW products. The results show that all four FY-4A LPWs are consistent with ERA5 LPWs, with an overall root mean square error (RMSE) of 2.58, 0.90, 1.30, and 1.01 mm, respectively. Furthermore, FY-4A LPWs are underestimated in the temperate monsoon area and overestimated in the subtropical and tropical monsoon regions, while FY-4A observations agree well with ERA5 reanalysis in temperate continental and plateau mountain zones. These analyses highlight the remarkable climate dependency of FY-4A LPWs and their potential for climate-related studies.
Optimizing CT Esophagography: Ex Vivo Study on Contrast Ratios, Image Quality, and Dual-Energy Benefits
Authors: Hao Luwen , Chen Xin , Jiang Yuchen , Wang Yufan , Hu Xuemei , Hu Daoyu , Li Zhen , Shen Yaqi
Published: December 2024

This study aimed to optimize CT esophagography by identifying effective oral contrast dilution ratios and exploring the advantages of dual-energy CT (DECT) over conventional CT for improving image quality. Ex vivo experiments using iodine contrast agents (320–400 mgI/mL) at 21 dilution ratios were scanned at three voltages, with additional dual-energy scans generating various reconstruction images. Image quality was assessed both objectively and subjectively. The study found significant variability in image quality across different dilution ratios. Specific dilution ratios that produced image quality comparable to the control group (a commercial oral contrast agent) and those meeting the standards for clinical diagnosis and high-quality images were identified based on image quality assessments. Recommendations for preparing 100 mL of oral contrast solution were provided, such as for achieving high-quality images at a scanning voltage of 100 kVp: the optimal dilution ratios are 1:6 to 1:19 for 320 mgI/mL, and 1:8 to 1:19 for 350 to 400 mgI/mL. Additionally, beam-hardening artifacts were significantly reduced in DECT images. These findings provide valuable guidance for improving CT esophagography protocols.
Assessment of the Active Sludge Microorganisms Population During Wastewater Treatment in a Micro-Pilot Plant
Authors: Popovici Daniela Roxana , Gheorghe Catalina Gabriela , Dușescu-Vasile Cristina Maria
Published: December 2024

Knowledge of the impact of chemicals on the environment is important for assessing the risks that chemicals can generate in ecosystems. With the help of pilot-scale micro-tests, it was possible to evaluate the biological sludge in terms of its chemical and biological composition, information that can be applied on an industrial scale in treatment plants. The important parameters analyzed in the evaluation of the biodegradability of wastewater were pH, chemical composition (NH4+, NO3−, NO2−, and PO43−), dry substance (DS), inorganic substance (IS), and organic substance (OS), and the biological oxygen demand (BOD)/chemical oxygen consumption (COD) ratio. The examination revealed the presence of free active ciliates Aspidisca polystyla, Lyndonotus setigerum, Vorticella microstoma, fixed by Zooglee, Paramecium sp., Opercularia, Colpoda colpidium, Euplotes, Didinum nasutum, Stentor, and Acineta tuberosa, metazoa Rotifers, filamentous algae, Nostoc and Anabena, and bacteria Bacillus subtilis, Nocardia, and Microccocus luteus. The novelty of this study lies in the fact that we carried out a study to evaluate the population of microorganisms starting from the premise that the probability of biodegradation of substances is directly proportional to the number of microorganisms existing in the environment and their enzymatic equipment.
RNA Sequencing Revealed a Weak Response of Gingival Fibroblasts Exposed to Hyaluronic Acid
Authors: Panahipour Layla , Imani Atefe , dos Santos Sanches Natália , Kühtreiber Hannes , Mildner Michael , Gruber Reinhard
Published: December 2024

Hyaluronic acid was proposed to support soft tissue recession surgery and guided tissue regeneration. The molecular mechanisms through which hyaluronic acid modulates the response of connective tissue cells remain elusive. To elucidate the impact of hyaluronic acid on the connective tissue cells, we used bulk RNA sequencing to determine the changes in the genetic signature of gingival fibroblasts exposed to 1.6% cross-linked hyaluronic acid and 0.2% natural hyaluronic acid. Transcriptome-wide changes were modest. Even when implementing a minimum of 1.5 log2 fold-change and a significance threshold of 1.0 −log10, only a dozenth of genes were differentially expressed. Upregulated genes were PLK3, SLC16A6, IL6, HBEGF, DGKE, DUSP4, PTGS2, FOXC2, ATAD2B, NFATC2, and downregulated genes were MMP24 and PLXNA2. RT-PCR analysis supported the impact of hyaluronic acid on increasing the expression of a selected gene panel. The findings from bulk RNA sequencing suggest that gingival fibroblasts experience weak changes in their transcriptome when exposed to hyaluronic acid.
A New Genus of Andean Katydid with Unusual Pronotal Structure for Enhancing Resonances
Authors: Sarria-Sarria Fabio A. , Morris Glenn K. , Montealegre-Z Fernando
Published: December 2024

Katydids employ acoustic signals to communicate with others of their species and have evolved to generate sounds by coupling the anatomical structures of their forewings. However, some species have evolved to implement an additional resonance mechanism that enhances the transmission and sound pressure of the acoustic signals produced by the primary resonators. Secondary resonators, such as burrow cavities or horn-shaped structures, are found in the surrounding environment but could also occur as anatomical modifications of their bodies. Chamber-like structures have been described in species of katydids with modified pronota or wings. It has been shown that these modified structures directly affect the transmission and filtering of acoustic signals and can function as a Helmholtz resonator that encapsulates the primary sound source. By morphological and acoustic analysis, we describe a new genus of Conocephalinae and investigate the physical properties of their sound production structures for three new species from the Andes of Colombia and Ecuador. Males of the new genus, here described as Tectucantus n. gen., have a characteristic inflated pronotum enclosing the reduced first pair of wings and extending rearward over the first abdominal segments. We test the hypothesis that the pronotal cavity volume correlates with the carrier frequency of specific calls. The cavity of the pronotal chamber acts as a Helmholtz resonator in all three Tectucantus species and, potentially, in other distantly related species, which use similar secondary body resonators.
Acephate Exposure Induces Transgenerational Ovarian Developmental Toxicity by Altering the Expression of Follicular Growth Markers in Female Rats
Authors: Alhazmi Abeer , Nahdi Saber , Alwasel Saleh , Harrath Abdel Halim
Published: December 2024

Acephate is an organophosphate foliar and soil insecticide that is used worldwide. In this study, the transgenerational ovarian developmental toxicity caused by acephate, along with its in utero reprogramming mechanisms, were explored. Thirty female virgin Wistar albino rats were randomly assigned to three groups: one control group and two acephate treatment groups. The treatment groups received daily low or high doses of acephate (34.2 mg/kg or 68.5 mg/kg body weight, respectively) from gestational day 6 until spontaneous labor, resulting in F1 offspring. At 28 days, a subgroup of F1 females were euthanized. The ovaries were extracted, thoroughly cleaned, and weighed before being fixed for further analysis. The remaining F1 females were mated with normal males to produce the F2 generation. The F1 female offspring presented reduced fertility and body weight, whereas the ovarian weight index and sex ratio increased in a dose-dependent manner. Structural analysis revealed altered follicular abnormalities with ovarian cells displaying pyknotic nuclei. Additionally, the gene and protein expression of Cyp19 decreased, whereas that of Gdf-9 increased in the high-dose treatment group (68.5 mg/kg). We also observed significantly increased expression levels of ovarian estrogen receptor 1 (Esr1) and insulin-like growth factor 1 (Igf1), whereas Insl3 expression was significantly decreased. The F2 female offspring presented reproductive phenotype alterations similar to those of F1 females including decreased fertility, reduced Cyp19 gene and protein expression, and structural ovarian abnormalities similar to those of polycystic ovary syndrome (PCOS). In conclusion, acephate induced ovarian developmental toxicity across two generations of rats, which may be linked to changes in the ovarian Cyp19, Gdf9, Insl3, and Igf1 levels.
Genes Associated with the Immune System Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model
Authors: Calaf Gloria M. , Roy Debasish , Jara Lilian , Romero Carmen , Crispin Leodan A.
Published: December 2024

Breast cancer is a global health issue that, when in the metastasis stage, is characterized by the lack of estrogen receptor-α, the progesterone receptor, and human epidermal growth receptor expressions. The present study analyzed the differential gene expression related to the immune system affected by ionizing radiation and estrogen in cell lines derived from an experimental breast cancer model that was previously developed; where the immortalized human breast epithelial cell line MCF-10F, a triple-negative breast cancer cell line, was exposed to low doses of high linear energy transfer α particle radiation (150 keV/μm), it subsequently grew in the presence or absence of 17β-estradiol. Results indicated that interferon-related developmental regulator 1 gene expression was affected in the estrogen-treated cell line; this interferon, as well as the Interferon-Induced Transmembrane protein 2, and the TNF alpha-induced Protein 6 gene expression levels were higher than the control in the Alpha3 cell line. Furthermore, the interferon-related developmental regulator 1, the Interferon-Induced Transmembrane protein 2, the TNF alpha-induced Protein 6, the Nuclear Factor Interleukin 3-regulated, and the Interferon-Gamma Receptor 1 showed high expression levels in the Alpha5 cell line, and the Interferon Regulatory Factor 6 was high in the Tumor2 cell line. Additionally, to further strengthen these data, publicly available datasets were analyzed. This analysis was conducted to assess the correlation between estrogen receptor alpha expression and the genes mentioned above in breast cancer patients, the differential gene expression between tumor and normal tissues, the immune infiltration level, the ER status, and the survival outcome adjusted by the clinical stage factor. It can be concluded that the genes of the interferon family and Tumor Necrosis factors can be potential therapeutic targets for breast cancer, since they are active before tumor formation as a defense of the body under radiation or estrogen effects.
Cannabis (THC) Aggravates the Deleterious Effects of Alcohol (EtOH) on Skeletal Muscles’ Mitochondrial Respiration: Modulation by Age and Metabolic Phenotypes
Authors: Charles Anne-Laure , Giannini Margherita , Meyer Alain , Charloux Anne , Talha Samy , Vogel Thomas , Raul Jean-Sébastien , Wolff Valérie , Geny Bernard
Published: December 2024

The anti-inflammatory and analgesic properties of cannabis might be useful to treat muscle diseases, including those linked or not to alcohol. Nevertheless, delta 9 tetrahydrocannabinol (THC) and ethanol (EtOH), often used concomitantly, can have deleterious effects on cardiac mitochondria. We therefore determined whether EtOH, alone and associated with THC, impairs skeletal muscle mitochondrial respiration. Further, we investigated potential modulation by metabolic phenotype and age by analyzing predominantly glycolytic gastrocnemius and oxidative soleus muscles in young and middle-aged rats (12 and 49 weeks). Considering the gastrocnemius, EtOH impaired mitochondrial respiration in a similar manner in young- and middle-aged muscles (−34.97 ± 2.97% vs. −37.50 ± 6.03% at 2.1 × 10−5 M; p < 0.05). Interestingly, concomitant THC aggravated EtOH-related mitochondrial impairment in young gastrocnemius (−49.92 ± 1.69%, vs. −34.97 ± 2.97 p < 0.05). Concerning the soleus, EtOH alone mainly decreased young muscle mitochondrial respiration (−42.39 ± 2.42% vs. −17.09 ± 7.61% at 2.1 × 10−5 M, p < 0.001, at 12 and 49 weeks). The soleus was less impaired at 12 weeks by THC and EtOH association than the gastrocnemius (−49.92 ±1.69 vs. −27.22 ± 8.96% in gastrocnemius and soleus, respectively, p < 0.05). In conclusion, EtOH, alone and associated with THC, significantly impairs skeletal muscle mitochondrial respiration and THC aggravates EtOH-induced effects on young glycolytic muscle. Age and metabolic phenotypes modulate these deleterious effects, with the glycolytic muscles of young rats being more prone to impairments than oxidative muscles.
OSI-027 as a Potential Drug Candidate Targeting Upregulated Hub Protein TAF1 in Potential Mechanism of Sinonasal Squamous Cell Carcinoma: Insights from Proteomics and Molecular Docking
Authors: Panthong Watcharapong , Pientong Chamsai , Nukpook Thawaree , Heawchaiyaphum Chukkris , Aromseree Sirinart , Ekalaksananan Tipaya
Published: December 2024

Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcinogenesis using proteomics and bioinformatic analysis. Dysregulated proteins were validated by RT-qPCR in SNSCC and nasal polyp (NP) tissues. Proteomic analysis revealed that differentially expressed proteins were clustered using MCODE scores ≥ 4 into three modules. The specific hub proteins in each module were analyzed in carcinogenesis pathways using STRING, highlighting potential mechanisms of histone modification and spliceosome dysregulation. Spliceosome components SNRNP200 and SF3A3 were significantly downregulated in SNSCC by RT-qPCR. Web-based applications L1000CDS2 and iLINCS were applied to identify 10 potential repurposable drugs that could reverse the gene expression pattern associated with SNSCC. Docking studies of TAF1, a protein in histone modification, with these 10 small molecule inhibitors indicated OSI-027 to be the most promising due to its strong binding interactions with key residues. These findings suggest that hub proteins involved in the underlying mechanism of SNSCC carcinogenesis may serve as valuable targets for drug development, with OSI-027 emerging as a novel candidate against TAF1 in SNSCC.
The Response Mechanism of the cbbM Carbon Sequestration Microbial Community in the Alpine Wetlands of Qinghai Lake to Changes in Precipitation
Authors: Li Lin , Wang Xia , Yang Yanli , Wang Siyu , Chen Kelong , Zhang Ni
Published: December 2024

The dramatic changes in precipitation patterns on the Tibetan Plateau affected the carbon-sequestering microbial communities within wetland ecosystems, which were closely related to the responses and adaptation mechanisms of alpine wetland ecosystems to climate change. This study focused on wetland soils subjected to different precipitation gradient treatments and employed high-throughput sequencing technology to analyze the soil cbbM carbon-sequestering microbial communities. The results indicated that Proteobacteria were the dominant microbial community responsible for carbon sequestration in the Wayan Mountain wetland. A 50% increase in precipitation significantly raised the soil moisture content, while a 50% reduction and a 25% increase in precipitation notably enhanced the total soil carbon content. The 25% reduction in precipitation increased the differences in microbial community composition, whereas both the 50% increase and the 50% reduction in precipitation decreased these differences. The soil pH and temperature had the most significant impact on the carbon-sequestering microbial communities. In conclusion, changes in precipitation affect the cbbM carbon sequestration characteristics of soil microbial communities, and a moderate reduction in water input benefited carbon sequestration in wetlands.
The Development of Prenatal Muscle Satellite Cells (MuSCs) and Their Epigenetic Modifications During Skeletal Muscle Development in Yak Fetus
Authors: Nan Guoxiong , Peng Wei , Xu Shangrong , Wang Guowen , Zhang Jun
Published: December 2024

To investigate prenatal muscle satellite cell (MuSC) development and the associated epigenetic modifications in yak. Here, we conducted morphological and protein co-localization analyses of fetal longissimus dorsi muscle at various developmental stages using histology and immunofluorescence staining methods. Our study observed that primary muscle fibers began forming at 40 days of gestation, fully developed by 11 weeks, and secondary muscle fibers were predominantly formed by around 105 days. Throughout development, MuSCs were mainly located between the muscle fiber membrane and the basement membrane, acting as a reserve for the stem cell pool. MuSCs appeared within myotubes only during critical phases of primary and secondary muscle fiber formation. The proliferation of MuSCs gradually decreases until birth. MuSCs with 5mC modification show a trend of increasing first and then decreasing. MuSCs with 5hmC modification also present a dynamic change trend. The 41st day and 11th week are the critical periods for the changes of both. From the 11th week to around the 110th day of gestation, the modification effect of histone H3K4me3 is crucial for MuSCs during the development of the fetal longissimus dorsi muscle. Combined, our data identify key time points for yak fetal skeletal muscle growth and development and demonstrate that DNA methylation and histone modifications in MuSCs are closely related to this process, offering a valuable basis for future research into the molecular mechanisms underlying yak muscle development.
Identifying Hub Genes and miRNAs Associated with Alzheimer’s Disease: A Bioinformatics Pathway to Novel Therapeutic Strategies
Authors: Gascón Elisa , Calvo Ana Cristina , Molina Nora , Zaragoza Pilar , Osta Rosario
Published: December 2024

Alzheimer’s disease (AD) is a neurodegenerative disorder that mainly affects the elderly population. It is characterized by cognitive impairment and dementia due to abnormal levels of amyloid beta peptide (Aβ) and axonal Tau protein in the brain. However, the complex underlying mechanisms affecting this disease are not yet known, and there is a lack of standardized biomarkers and therapeutic targets. Therefore, in this study, by means of bioinformatics analysis, AD-affected brain tissue was analyzed using the GSE138260 dataset, identifying 612 differentially expressed genes (DEGs). Functional analysis revealed 388 upregulated DEGs associated with sensory perception and 224 downregulated DEGs linked to the regulation and modulation of synaptic processes. Protein–protein interaction network analysis identified 20 hub genes. Furthermore, miRNA target gene networks revealed 1767 miRNAs linked to hub genes, among which hsa-mir-106a-5p, hsa-mir-17-5p, hsa-mir-26a-5p, hsa-mir-27a-3p and hsa-mir-34a-5p were the most relevant. This study presents novel biomarkers and therapeutic targets for AD by analyzing the information obtained with a comprehensive literature review, providing new potential targets to study their role in AD.
Gramicidin A in Asymmetric Lipid Membranes
Authors: Kondrashov Oleg V. , Akimov Sergey A.
Published: December 2024

Gramicidin A is a natural antimicrobial peptide produced by Bacillus brevis. Its transmembrane dimer is a cation-selective ion channel. The channel is characterized by the average lifetime of the conducting state and the monomer–dimer equilibrium constant. Dimer formation is accompanied by deformations of the membrane. We theoretically studied how the asymmetry in lipid membrane monolayers influences the formation of the gramicidin A channel. We calculated how the asymmetry in the spontaneous curvature and/or lateral tension of lipid monolayers changes the channel lifetime and shifts the equilibrium constant of the dimerization/dissociation process. For the asymmetry expected to arise in plasma membranes of mammalian cells upon the addition of gramicidin A or its derivatives to the cell exterior, our model predicts a manifold increase in the average lifetime and equilibrium constant.
Binding Molecules in Tick Saliva for Targeting Host Cytokines, Chemokines, and Beyond
Authors: Desidério Chamberttan Souza , Flávio-Reis Victor Hugo Palhares , Pessoa-Gonçalves Yago Marcos , Tiveron Rafael Destro Rosa , Sales-Campos Helioswilton , Felice Andrei Giacchetto , Soares Siomar de Castro , Guillermo-Ferreira Rhainer , Rodrigues Wellington Francisco , Oliveira Carlo José Freire
Published: December 2024

Ticks have coevolved with their hosts over millions of years, developing the ability to evade hemostatic, inflammatory, and immunological responses. Salivary molecules from these vectors bind to cytokines, chemokines, antibodies, complement system proteins, vasodilators, and molecules involved in coagulation and platelet aggregation, among others, inhibiting or blocking their activities. Initially studied to understand the complexities of tick–host interactions, these molecules have been more recently recognized for their potential clinical applications. Their ability to bind to soluble molecules and modulate important physiological systems, such as immunity, hemostasis, and coagulation, positions them as promising candidates for future therapeutic development. This review aims to identify the binding molecules present in tick saliva, determine their primary targets, and explore the tick species involved in these processes. By associating the binding molecules, the molecules to which they bind, and the effect caused, the review provides a basis for understanding how these molecules can contribute to possible future advances in clinical applications.
MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction
Authors: Kawaguchi Satoshi , Sepúlveda Marisa N. , Teoh Jian-peng , Hayasaka Taiki , Moukette Bruno , Aonuma Tatsuya , Roh Hyun Cheol , Madhur Meena S. , Kim Il-man
Published: December 2024

MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration. Our mechanistic studies also showed that the protective roles of miR-150 in ischemic mouse hearts and human cardiac fibroblasts were, in part, attributed to the inhibition of fibroblast activation via the repression of multiple profibrotic genes. However, the extent to which miR-150 expression in adult myofibroblasts (MFs) modulates the response to myocardial infarction (MI) remains unknown. Here, we develop a novel 4-hydroxytamoxifen-inducible MF-specific miR-150 conditional knockout mouse model and demonstrate that the mouse line exhibits worse cardiac dysfunction after MI. Our studies further reveal that miR-150 ablation selectively in adult MFs exacerbates cardiac damage and apoptosis after chronic MI. Lastly, MF-specific miR-150 deletion in adult mice promotes the expression of proinflammatory and profibrotic genes as well as cardiac fibrosis following chronic MI. Our findings indicate a key protective role for MF-derived miR-150 in modulating post-MI responses.
Gut Microbiota Modulation: A Novel Strategy for Rheumatoid Arthritis Therapy
Authors: Chasov Vitaly , Gilyazova Elvina , Ganeeva Irina , Zmievskaya Ekaterina , Davletshin Damir , Valiullina Aygul , Bulatov Emil
Published: December 2024

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint inflammation, progressive tissue damage and significant disability, severely impacting patients’ quality of life. While the exact mechanisms underlying RA remain elusive, growing evidence suggests a strong link between intestinal microbiota dysbiosis and the disease’s development and progression. Differences in microbial composition between healthy individuals and RA patients point to the role of gut microbiota in modulating immune responses and promoting inflammation. Therapies targeting microbiota restoration have demonstrated promise in improving treatment efficacy, enhancing patient outcomes and slowing disease progression. However, the complex interplay between gut microbiota and autoimmune pathways in RA requires further investigation to establish causative relationships and mechanisms. Here, we review the current understanding of the gut microbiota’s role in RA pathogenesis and its potential as a therapeutic target.
Impact of Rhegmatogenous Retinal Detachment on Macular Vascular and Functional Integrity
Authors: Díaz-Barreda María Dolores , Boned-Murillo Ana , Bartolomé-Sesé Isabel , Sopeña-Pinilla María , Orduna-Hospital Elvira , Fernández-Espinosa Guisela , Pinilla Isabel
Published: December 2024

Objectives: This study aimed to evaluate the correlations between optical coherence tomography angiography (OCTA), best corrected visual acuity (BCVA), and macular integrity assessment (MAIA) microperimetry (MP) in both a control group and patients with rhegmatogenous retinal detachment (RRD). Additionally, it assessed differences between the groups and examined whether the time from symptom onset to surgery influenced microvascular or functional changes in the RRD group. Methods: A cross-sectional study was conducted involving 47 patients who had undergone successful RRD surgery with pars plana vitrectomy (PPV) and sulfur-hexafluoride (SF6) gas injection, with or without scleral buckling (SB), and a control group of 136 healthy eyes. All participants underwent comprehensive ophthalmologic examinations, including BCVA, OCTA, and MAIA. In the RRD group, additional data on symptom duration, time from symptom onset to surgery, and time from surgery to testing were collected. Results: The RRD group exhibited significantly worse BCVA (p < 0.001) compared to the control group. Significant differences were found in all MAIA sectors, with controls showing superior macular integrity and average threshold values (p < 0.001). OCTA analysis revealed differences in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) across various sectors, particularly in the foveal avascular zone (FAZ). In the control group, the vertical diameter of the FAZ in the SCP was positively correlated with most MAIA sectors, while in the DCP, correlations were seen in nearly all sectors. The RRD group showed fewer correlations between OCTA and MAIA, and no significant correlations were found between OCTA parameters and BCVA. However, there were correlations between the time from surgery to testing and MAIA outcomes, indicating improved results with longer intervals. Earlier surgical intervention after symptom onset was associated with better microvascular outcomes. Conclusions: RRD group exhibited significant impairments in BCVA, retinal sensitivity, and microvascular parameters compared to healthy controls. Correlations between OCTA findings and microperimetry were stronger in the control group, whereas the RRD group showed fewer and weaker associations.
Therapeutic Potential of Nutritional Aryl Hydrocarbon Receptor Ligands in Gut-Related Inflammation and Diseases
Authors: Huang Fu-Chen
Published: December 2024

A solid scientific foundation is required to build the concept of personalized nutrition developed to promote health and a vision of disease prevention. Growing evidence indicates that nutrition can modulate the immune system through metabolites, which are either generated via microbiota metabolism or host digestion. The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating immune responses, particularly in the gut, and has emerged as a key modulator of gut-mediated inflammation and related diseases. AhR is a ligand-activated transcription factor that responds to environmental, dietary, and microbial-derived signals, influencing immune balance and maintaining intestinal homeostasis. Nutritional AhR ligands play a significant role in modulating intestinal immunity and the function of mucosal immune cells, thereby exerting clinical effects on colitis and innate immunity. Additionally, they have the capacity to orchestrate autophagy, phagocytic cell function, and intestinal epithelial tight junctions. Therapeutic strategies aimed at enhancing AhR activity, restoring gut integrity, and optimizing immune responses hold promise as avenues for future research and potential treatments for critically ill patients.
Cancer Therapy-Related Cardiac Dysfunction: A Review of Current Trends in Epidemiology, Diagnosis, and Treatment
Authors: Theofilis Panagiotis , Vlachakis Panayotis K. , Oikonomou Evangelos , Drakopoulou Maria , Karakasis Paschalis , Apostolos Anastasios , Pamporis Konstantinos , Tsioufis Konstantinos , Tousoulis Dimitris
Published: December 2024

Cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a significant concern with the rise of effective cancer treatments like anthracyclines and targeted therapies such as trastuzumab. While these therapies have improved cancer survival rates, their unintended cardiovascular side effects can lead to heart failure, cardiomyopathy, and arrhythmias. The pathophysiology of CTRCD involves oxidative stress, mitochondrial dysfunction, and calcium dysregulation, resulting in irreversible damage to cardiomyocytes. Inflammatory cytokines, disrupted growth factor signaling, and coronary atherosclerosis further contribute to this dysfunction. Advances in cardio-oncology have led to the early detection of CTRCD using cardiac biomarkers like troponins and imaging techniques such as echocardiography and cardiac magnetic resonance (CMR). These tools help identify asymptomatic patients at risk of cardiac events before the onset of clinical symptoms. Preventive strategies, including the use of cardioprotective agents like beta-blockers, angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors have shown promise in reducing the incidence of CTRCD. This review summarizes the mechanisms, detection methods, and emerging treatments for CTRCD, emphasizing the importance of interdisciplinary collaboration between oncologists and cardiologists to optimize care and improve both cancer and cardiovascular outcomes.
Acute Myeloid Leukemia with Normal Cytogenetics and NPM1-Mutation: Impact of Mutation Topography on Outcomes
Authors: Zhao Mingyue , Liao Mingyue , Gale Robert Peter , Zhang Meijie , Wu Lixin , Yan Nan , Liu Lixia , Qin Jiayue , Cao Shanbo , Chang Yingjun , Jiang Qian , Xu Lanping , Zhang Xiaohui , Huang Xiaojun , Jiang Hao , Ruan Guorui
Published: December 2024

Background: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have NPM1 mutations. There is controversy regarding their prognosis and best therapy. Methods: We studied 150 subjects with these features using targeted regional sequencing. Prognostic stratification was carried out based on risk factors, and we assessed the effects of two post-remission strategies with and without transplant across risk cohorts. Results: In multi-variable analyses, a positive MRD test after the second consolidation cycle (HR = 6.00; 95% CI [3.31, 10.85]; p < 0.001), DNMT3A mutations (HR = 3.01 [1.57, 5.78]; p < 0.001), FLT3-ITD mutation with high variant allele frequency (HR = 4.40 [1.89, 10.24]; p < 0.001) and DDX11 mutations (HR = 4.38 [2.38, 8.04]; p < 0.001) were independently correlated with higher cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) (HR = 5.49 [3.01, 10.04]; p < 0.001; HR = 2.99 [1.60, 5.62]; p < 0.001; HR = 4.20 [1.87, 9.40]; p < 0.001; and HR = 4.22, 95% CI [1.99, 8.95], p < 0.001). Subjects with ≥1 high-risk co-variate who received a transplant had a lower CIR and better LFS, whereas others did not. Conclusions: We identified co-variates associated with CIR and LFS in subjects of NPM1-mutated CN-AML.
Treatment Outcomes and Toxicities of Multiple Tyrosin Kinase Inhibitors for Metastatic Medullary Thyroid Cancer: A Case Series
Authors: Mormando Marilda , Lauretta Rosa , Puliani Giulia , Bianchini Marta , Spoltore Maria Elena , Appetecchia Marialuisa
Published: December 2024

Background: The current possible treatments of advanced medullary carcinoma (MTC) include different drugs belonging to the class of tyrosine kinase inhibitors (TKIs): vandetanib, cabozantinb, and selpercatinib. Although the effects of these TKIs have been well described in clinical trials, the real-practice evidence of the effectiveness and safety of these treatment is scant. This real-world case series aims to describe a niche of patients with advanced MTC treated with more than one TKI by focusing on treatment responses and any reported adverse events (AEs) and to provide additional insight on the individualized approach to the management of metastatic MTC. Methods: Five patients with a diagnosis of metastastic MTC, treated with at least two different molecules of TKIs, were retrospectively selected. Results: Three patients obtained a partial response (one with cabozantinb, one with selpercatinib, and one with vandetanib), and two patients obtained disease stability (both of them treated with all three TKIs, the first two lines discontinued for AEs). The AE profile agreed with the known clinical trials AEs except for non-neoplastic ascites related to selpercatinib and lung cavitations of non-neoplastic tissue related to cabozantinb. The latter was an AE never described so far in patients receiving TKIs. Conclusions: The best management of MTC relies on an individualized approach, keeping in mind and dealing with the potential toxicity in order to minimize the treatment withdrawal.
Nanotherapeutic and Nano–Bio Interface for Regeneration and Healing
Authors: Kumar Rajiv , Igwegbe Chinenye Adaobi , Khandel Shri Krishna
Published: December 2024

Wound and injury healing processes are intricate and multifaceted, involving a sequence of events from coagulation to scar tissue formation. Effective wound management is crucial for achieving favorable clinical outcomes. Understanding the cellular and molecular mechanisms underlying wound healing, inflammation, and regeneration is essential for developing innovative therapeutics. This review explored the interplay of cellular and molecular processes contributing to wound healing, focusing on inflammation, innervation, angiogenesis, and the role of cell surface adhesion molecules. Additionally, it delved into the significance of calcium signaling in skeletal muscle regeneration and its implications for regenerative medicine. Furthermore, the therapeutic targeting of cellular senescence for long-term wound healing was discussed. The integration of cutting-edge technologies, such as quantitative imaging and computational modeling, has revolutionized the current approach of wound healing dynamics. The review also highlighted the role of nanotechnology in tissue engineering and regenerative medicine, particularly in the development of nanomaterials and nano–bio tools for promoting wound regeneration. Moreover, emerging nano–bio interfaces facilitate the efficient transport of biomolecules crucial for regeneration. Overall, this review provided insights into the cellular and molecular mechanisms of wound healing and regeneration, emphasizing the significance of interdisciplinary approaches and innovative technologies in advancing regenerative therapies. Through harnessing the potential of nanoparticles, bio-mimetic matrices, and scaffolds, regenerative medicine offers promising avenues for restoring damaged tissues with unparalleled precision and efficacy. This pursuit marks a significant departure from traditional approaches, offering promising avenues for addressing longstanding challenges in cellular and tissue repair, thereby significantly contributing to the advancement of regenerative medicine.
Adaptive Disturbance Rejection Motion Control of Direct-Drive Systems with Adjustable Damping Ratio Based on Zeta-Backstepping
Authors: Zhang Zhongjin , Liu Zhitai , Lin Weiyang , Cheng Wei
Published: December 2024

Direct-drive servo systems are extensively applied in biomimetic robotics and other bionic applications, but their performance is susceptible to uncertainties and disturbances. This paper proposes an adaptive disturbance rejection Zeta-backstepping control scheme with adjustable damping ratios to enhance system robustness and precision. An iron-core permanent magnet linear synchronous motor (PMLSM) was employed as the experimental platform for the development of a dynamic model that incorporates compensation for friction and cogging forces. To address model parameter uncertainties, an indirect parameter adaptation strategy based on a recursive least squares algorithm was introduced. It updates parameters based on the system state instead of output error, ensuring robust parameter convergence. An integral sliding mode observer (ISMO) was constructed to estimate and compensate for residual uncertainties, achieving finite-time state estimation. The proposed Zeta-backstepping controller enables adjustable damping ratios through parameterized control laws, offering flexibility in achieving desired dynamic performance. System stability and bounded tracking performance were validated via a second-order Lyapunov function analysis. Experimental results on a real PMLSM platform demonstrated that, while achieving adjustable damping ratio dynamic characteristics, there is a significant improvement in tracking accuracy and disturbance suppression. This underscores the scheme’s potential for advancing precision control in biomimetic robotics and other direct-drive system applications.
Competitive Electrochemical Apta-Assay Based on cDNA–Ferrocene and MXenes for Staphylococcus aureus Surface Protein A Detection
Authors: Tătaru Ana-Maria , Canciu Alexandra , Chiorean Alin-Dan , Runcan Ioana , Radu Alexandru , Bordea Mădălina Adriana , Suciu Maria , Tertiș Mihaela , Cernat Andreea , Cristea Cecilia
Published: December 2024

Staphylococcus aureus (S. aureus) represents one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. It is a part of the infamous ESKAPE group, which is highly connected with increased rates of healthcare-associated infections and antimicrobial resistance. S. aureus can cause a large variety of diseases. Protein A (PrA) is a cell-wall-anchored protein of S. aureus with multiple key roles in colonization and pathogenesis and can be considered as a marker of S. aureus. The development of aptasensors, having an aptamer as a specific biorecognition element, increases selectivity, especially when working with complex matrices. The association with state-of-the-art materials, such as MXenes, can further improve the analytical performance. A competitive aptasensor configuration based on a ferrocene (Fc)-labeled cDNA hybridized (cDNA-Fc S13) on a specific aptamer (APT) for PrA in the presence of MXene nanosheets was designed for the indirect detection of S. aureus. The aptasensor displayed a linear range of 10–125 nM, an LOD of 3.33 nM, and a response time under 40 min. This configuration has been tested in real samples from volunteers diagnosed with S. aureus infections with satisfactory results, enabling the perspective to develop decentralized devices for the rapid detection of bacterial strains.