Search Results (2,074)

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article

Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (²²⁹NGDDGEAGKPGRPGERGPpGp²⁴⁹). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article

Objectives: To investigate the reliability and validity of the Singer Reflux Symptom Score (sRSS), a new patient-reported outcome questionnaire documenting the severity of reflux symptoms in singing voice is proposed. Methods: Amateur and professional singers consulting the European Reflux Clinic for laryngopharyngeal reflux disease (LPRD) symptoms and findings were prospectively recruited from January 2022 to February 2023. The diagnosis was based on a Reflux Symptom Score (RSS) > 13 and Reflux Sign Assessment (RSA) > 14. A control group of asymptomatic singer subjects was recruited from the University of Mons. The sRSS was rated within a 7-day period to assess test–retest reliability. Internal consistency was measured using Cronbach’s α in patients and controls. A correlation analysis was performed between sRSS and Singing Voice Handicap Index (sVHI) to evaluate convergent validity. Responsiveness to change was evaluated through pre- to post-treatment sRSS changes. The sRSS threshold for suggesting a significant impact of LPRD on singing voice was determined by receiver operating characteristic (ROC) analysis. Results: Thirty-three singers with suspected LPRD (51.5% female; mean age: 51.8 ± 17.2 years) were consecutively recruited. Difficulty reaching high notes and vocal fatigue were the most prevalent LPRD-related singing complaints. The sRSS demonstrated high internal consistency (Cronbach-α = 0.832), test–retest reliability, and external validity (correlation with sVHI: r = 0.654; p = 0.015). Singers with suspected LPRD reported a significant higher sRSS compared to 68 controls. sRSS item and total scores significantly reduced from pre-treatment to 3 months post-treatment except for the abnormal voice breathiness item. ROC analysis revealed superior diagnostic accuracy for sRSS (AUC = 0.971) compared to sRSS-quality of life (AUC = 0.926), with an optimal cutoff at sRSS > 38.5 (sensitivity: 90.3%; specificity: 85.0%). Conclusions: The sRSS is a reliable and valid singer-reported outcome questionnaire for documenting singing symptoms associated with LPRD leading to personalized management of Singers. Future large-cohort studies are needed to evaluate its specificity for LPRD compared to other vocal fold disorders in singers. Full article

Background: Mobile health applications have emerged as a novel tool to support secondary prevention after myocardial infarction (MI) or percutaneous coronary intervention (PCI). However, the impact of app-based interventions on clinically meaningful outcomes such as hospital readmissions remains uncertain. Objective: To systematically evaluate the effectiveness of smartphone app-based interventions in reducing unplanned hospital readmissions among post-MI/PCI patients. Methods: A systematic search of PubMed was conducted for randomized controlled trials published between January 2020 and April 2025. Eligible studies evaluated smartphone apps designed for secondary cardiovascular prevention and reported on unplanned hospital readmissions. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were performed based on follow-up duration and user adherence. Results: Four trials encompassing 827 patients met inclusion criteria. App-based interventions were associated with a significant reduction in unplanned hospital readmissions compared to standard care (RR 0.45; 95% CI: 0.23–0.89; p = 0.0219). Greater benefits were observed in studies with longer follow-up durations and higher adherence rates. Improvements in patient-reported outcomes, including health-related quality of life, were also documented. Heterogeneity was moderate. Major adverse cardiovascular events (MACEs) were reported in only two studies and were not analyzed due to inconsistent definitions and low event rates. Conclusions: Smartphone applications for post-MI/PCI care are associated with reduced unplanned hospital readmissions and improved patient-reported outcomes. These tools may play a meaningful role in future cardiovascular care models, especially when sustained engagement and personalized features are prioritized. Full article

Background/Objectives: The aim of our study was to evaluate clinical outcomes in patients with small pleomorphic adenoma (PA) after extracapsular dissection (ED) versus superficial parotidectomy (SP). Methods: Following the PRISMA guidelines, a systematic review covering the years from 1950 to 2025 was conducted using the Pubmed/MEDLINE, Cochrane Library, Scopus, Ovid MEDLINE and Embase databases. A single-arm meta-analysis was performed to evaluate intraoperative capsular rupture, recurrence, transient and permanent facial nerve palsy, Frey’s syndrome, salivary fistula, seroma and hematoma of patients who underwent ED vs. those who underwent SP, and funnel plots were constructed to evaluate the robustness of the findings. Results: Of the 1793 identified papers, 21 articles met the inclusion criteria. The meta-analysis (2507 patients) reported the following: (1) the risk of recurrence is similar in patients treated with ED and SP; (2) the transient facial nerve palsy rate is lower after ED (p < 0.05), while the permanent facial nerve palsy rate is similar with ED and SP; (3) post-operative complications, especially Frey’s syndrome (p < 0.05), are more common after SP. Conclusions: Given the similar recurrence rate and the lower morbidity compared to SP, ED could be considered the treatment of choice for pleomorphic adenomas of the parotid gland that are up to 3 cm in size, mobile and located in the superficial lobe of the parotid gland. Full article

Optimising the friction coefficient helps reduce friction losses and improve the efficiency of mechanical systems. The purpose of this study is to experimentally investigate the impact of roughness orientation on the friction coefficient in elastohydrodynamic (EHD) contact. Tests were carried out on a twin-disc machine. Three pairs of discs of identical material (nitrided steel) and geometry were tested: a smooth pair (the root mean square surface roughness Sq = 0.07 µm), a pair with transverse roughness and another with longitudinal roughness. The two rough pairs have similar roughness amplitudes (Sq = 0.5 µm). A comparison of the friction generated by these different pairs was carried out to highlight the effect of the roughness orientation under different operating conditions (oil injection temperature from 60 to 80 °C, Hertzian pressure from 1.2 to 1.5 GPa and mean rolling speed from 5 to 30 m/s). Throughout all the tests conducted in this study, longitudinal roughness resulted in higher friction than transverse, with an increase of up to 30%. Moreover, longitudinal roughness is more sensitive to variations in operating conditions. Finally, in all tests, the asperities of longitudinal roughness were found to influence the friction behaviour, unlike transverse roughness. Full article

Background and Objectives: this pilot study aimed to evaluate the diagnostic accuracy of ChatGPT-4o in analyzing oral mucosal lesions from clinical images. Materials and Methods: a total of 110 clinical images, including 100 pathological lesions and 10 healthy mucosal images, were retrieved from Google Images and analyzed by ChatGPT-4o using a standardized prompt. An expert panel of five clinicians established a reference diagnosis, categorizing lesions as benign or malignant. The AI-generated diagnoses were classified as correct or incorrect and further categorized as plausible or not plausible. The accuracy, sensitivity, specificity, and agreement with the expert panel were analyzed. The Artificial Intelligence Performance Instrument (AIPI) was used to assess the quality of AI-generated recommendations. Results: ChatGPT-4o correctly diagnosed 85% of cases. Among the 15 incorrect diagnoses, 10 were deemed plausible by the expert panel. The AI misclassified three malignant lesions as benign but did not categorize any benign lesions as malignant. Sensitivity and specificity were 91.7% and 100%, respectively. The AIPI score averaged 17.6 ± 1.73, indicating strong diagnostic reasoning. The McNemar test showed no significant differences between AI and expert diagnoses (p = 0.084). Conclusions: In this proof-of-concept pilot study, ChatGPT-4o demonstrated high diagnostic accuracy and strong descriptive capabilities in oral mucosal lesion analysis. A residual 8.3% false-negative rate for malignant lesions underscores the need for specialist oversight; however, the model shows promise as an AI-powered triage aid in settings with limited access to specialized care. Full article

AAA+ ATPases are ring-shaped hexameric protein complexes that operate as elaborate macromolecular motors, driving a variety of ATP-dependent cellular processes. AAA+ ATPases undergo large-scale conformational changes that lead to the conversion of chemical energy from ATP into mechanical work to perform a wide range of functions, such as unfolding and translocation of the protein substrate inside a proteolysis chamber of an AAA+-associated protease. Despite extensive biochemical studies on these macromolecular assemblies, the mechanism of substrate unfolding and degradation has long remained elusive. Indeed, until recently, structural characterization of AAA+ protease complexes remained hampered by the size and complexity of the machinery, harboring multiple protein subunits acting together to process proteins to be degraded. Additionally, the major structural rearrangements involved in the mechanism of this complex represent a crucial challenge for structural biology. Here, we report the main advances in deciphering molecular details of the proteolytic reaction performed by AAA+ proteases, based on the remarkable progress in structural biology techniques. Particular emphasis is placed on the latest findings from high-resolution structural analysis of the ClpXP proteolytic complex, using crystallographic and cryo-EM investigations. In addition, this review presents some additional dynamic information obtained using solution-state NMR. This information provides molecular details that help to explain the protein degradation process by such molecular machines. Full article

Background: Airway management in patients with obstructive sleep apnea (OSA) presents unique challenges for anesthesiologists and other airway practitioners. This comprehensive review examines current evidence and clinical practices for managing difficult airways in this high-risk population. OSA is characterized by specific anatomical and physiological alterations that increase both the likelihood of encountering difficult intubation and the risk of rapid desaturation during airway manipulation. Methods: Preoperative assessment of OSA patients requires integration of traditional difficult airway evaluation with OSA-specific considerations, including severity indices, oxygen desaturation patterns, and continuous positive airway pressure dependency. Conventional direct laryngoscopy often proves inadequate in these patients, prompting the development and refinement of alternative approaches. Videolaryngoscopy has emerged as a particularly valuable technique in OSA patients, offering improved glottic visualization while maintaining physiologic positioning. Flexible endoscopic techniques, particularly awake flexible bronchoscopic intubation, remain essential for high-risk scenarios, though they require considerable expertise. Results: Recent technological innovations have produced hybrid devices combining multiple modalities to address the specific challenges presented by OSA patients. Adjunctive tools and techniques, including specialized introducers, exchange catheters, and high-flow nasal oxygen, play critical roles in extending safe apnea time and facilitating successful intubation. Professional society guidelines now incorporate OSA-specific recommendations, emphasizing thorough preparation, appropriate device selection, and comprehensive monitoring. Conclusions: Effective management ultimately requires not only appropriate technology but also systematic preparation, strategic device selection, and meticulous execution. As OSA prevalence continues to rise globally, optimizing airway management approaches for this challenging population remains a critical priority for patient safety. Full article

Nokoué Lake is located in the south of Benin and is fed by the Ouémé and Sô Rivers. Its hydrosedimentary dynamics were modelled using Telemac2D, incorporating the main environmental factors of this complex ecosystem. The simulations accounted for flow rates and suspended solids concentrations during periods of high and low water. The main factors controlling sediment transport were identified. The model was validated using field measurements of water levels and suspended solids. The results show that the north–south current velocity ranges from 0.5 to 1 m/s during periods of high water and 0.1 to 0.5 m/s during low-water periods. Residual currents are influenced by rainfall, river discharge, and tides. Complex circulation patterns are caused by increased river flow during high water, while tides dominate during low water and transitional periods. The northern, western, and south-eastern parts of the lake have weak residual currents and are, therefore, deposition zones for fine sediments. The estimated average annual suspended solids load for 2022–2023 is 17 Mt. The model performance shows a strong agreement between the observed and simulated values: R² = 0.91 and NSE = 0.93 for water levels and R² = 0.86 and NSE = 0.78 for sediment transport. Full article

Incorporation of lanthanide (Ln) and actinide (An) ions into the human body poses significant chemotoxic and radiotoxic risks, necessitating effective decorporation strategies. This study investigates the displacement of biologically relevant ligands from trivalent ions of europium, Eu(III), and curium, Cm(III), in artificial biofluids by various complexing agents, i.e., ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), and spermine-based hydroxypyridonate chelator 3,4,3-LI(1,2-HOPO) (HOPO). Utilizing a modified unified bioaccessibility method (UBM) to simulate gastrointestinal conditions, we conducted concentration-dependent displacement experiments at both room and body temperatures. Time-resolved laser-induced fluorescence spectroscopy (TRLFS) supported by ²H nuclear magnetic resonance (NMR) spectroscopy and thermodynamic modelling revealed the complexation efficacy of the agents under physiological conditions. Results demonstrate that high affinity, governed by complex stability constants and ligand pK_a values, is critical to overcome cation and anion competition and leads to effective decorporation. Additionally, there is evidence that cyclic ligands are inferior to linear ligands for this application. HOPO and DTPA exhibited superior displacement efficacy, particularly in the complete gastrointestinal tract simulation. This study highlights the utility of in vitro workflows for evaluating decorporation agents and emphasizes the need for ligands with optimal binding characteristics for enhanced chelation therapies. Full article

Background/Objectives: Cancer research aims to understand the cellular and molecular mechanisms involved, in order to identify new therapeutic targets and provide patients with more effective therapies that generate fewer side undesirable and toxic effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we identified a new snoRNA (jouvence), first in Drosophila, and thereafter, by homology, in humans. Methods: Here, we characterize the effect of the knockdown of jouvence by a sh-lentivirus on human primary patient-derived glioblastoma cells. Results: The sh-lentivirus anti-jouvence induces a significant decrease in cell proliferation and leads to cell death. EdU staining confirmed this decrease, while TUNEL also showed the presence of apoptotic cells. An RNA-Seq analysis revealed a decrease, in particular, in the level of BAALC, a gene known to potentiate the oncogenic ERK pathway and deregulating p21, leading to cell cycle blockage. Conclusions: Altogether, these results allow the hypothesis that the knockdown of jouvence could potentially be used as a new anti-cancer treatment (sno-Therapy), especially against glioblastoma and also, potentially, against acute myeloid leukemia (AML) due to the BAALC deregulation. Full article

Two-dimensional (2D) materials have been proposed for use in a multitude of applications, with graphene being one of the most well-known 2D materials. Despite their potential to contribute to innovative solutions, the fabrication of such devices still faces significant challenges. One of the key challenges is the fabrication at a wafer-level scale, a fundamental step for allowing reliable and reproducible fabrication of a large volume of devices with predictable properties. Overcoming this barrier will allow further integration with sensors and actuators, as well as enabling the fabrication of complex circuits based on 2D materials. This work presents the fabrication steps for a process that allows the on-wafer fabrication of active and passive radiofrequency (RF) devices enabled by graphene. Two fabrication processes are presented. In the first one, graphene is transferred to a back gate surface using critical point drying to prevent cracks in the graphene. In the second process, graphene is transferred to a flat surface planarized by ion milling, with the gate being buried beneath the graphene. The fabrication employs a damascene-like process, ensuring a flat surface that preserves the graphene lattice. RF transistors, passive RF components, and antennas designed for backscatter applications are fabricated and measured, illustrating the versatility and potential of the proposed method for 2D material-based RF devices. The integration of graphene on devices is also demonstrated in an antenna. This aimed to demonstrate that graphene can also be used as a passive device. Through this device, it is possible to measure different backscatter responses according to the applied graphene gating voltage, demonstrating the possibility of wireless sensor development. With the proposed fabrication processes, a flat graphene with good quality is achieved, leading to the fabrication of RF active devices (graphene transistors) with intrinsic f_T and f_max of 14 GHz and 80 GHz, respectively. Excellent yield and reproducibility are achieved through these methods. Furthermore, since the graphene membranes are grown by Chemical Vapor Deposition (CVD), it is expected that this process can also be applied to other 2D materials. Full article

Intuitive eating is an adaptive eating style that could help explain part of the relation between affect and eating behaviors. However, research in this area remains limited. The objectives of this study are twofold. First, we examine the relation between affect, disordered eating attitudes and behaviors (DEABs), and orthorexia nervosa (ON). Second, we investigate the mediating role of intuitive eating regarding these relations. A sample of 197 French-speaking Canadian women, aged from 18 to 69, participated in the study. The results showed that negative affect was related to DEABs and ON, but not positive affect. Statistically significant associations were also found between affect (negative and positive) and the four dimensions of intuitive eating. Additionally, negative relations were found between intuitive eating dimensions and most types of eating behaviors (encompassing DEABs and ON), except for dieting. Finally, our results revealed that the relations between affect (positive and negative) and most types of eating behaviors were indirect (i.e., suggesting mediation) via intuitive eating. Based on these results, it seems that interventions addressing affect regulation and eating behaviors could benefit from including a focus on intuitive eating. Full article

The image of the vasa domus Dei, repeated on two occasions in the book of the prophet Daniel (Dan 1:2 and 5:4), enables Jerome to formulate an explicit judgement on pagan culture. Drawing extensively on a well-established repertoire, he highlights in one case its positive aspects and in the other its negative ones, and so in CDan 1,1,2b, he underlines the presence, at least in philosophy, of some truths drawn from the doctrine of God; in CDan 2,5,4, he discusses the wicked use the heretics make of the saeculares litterae. Full article