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18 pages, 6885 KB  
Article
Camera-Based Monocular Depth Estimation in Orthodontics: Vision Transformer vs. CNN Model Performance
by Arda Arısan and Gökhan Serhat Duran
Sensors 2025, 25(21), 6512; https://doi.org/10.3390/s25216512 (registering DOI) - 22 Oct 2025
Abstract
Background: Monocular Depth Estimation (MDE) is a computer vision approach that predicts spatial depth information from a single two-dimensional image. In orthodontics, where facial soft-tissue evaluation is integral to diagnosis and treatment planning, such methods offer new possibilities for obtaining sagittal profile information [...] Read more.
Background: Monocular Depth Estimation (MDE) is a computer vision approach that predicts spatial depth information from a single two-dimensional image. In orthodontics, where facial soft-tissue evaluation is integral to diagnosis and treatment planning, such methods offer new possibilities for obtaining sagittal profile information from standard frontal photographs. This study aimed to determine whether MDE can extract clinically meaningful information for facial profile assessment. Methods: Standardized frontal photographs and lateral cephalometric radiographs from 82 adult patients (48 Class I, 28 Class II, 6 Class III) were retrospectively analyzed. Three clinically relevant soft-tissue landmarks—Upper Lip Anterior (ULA), Lower Lip Anterior (LLA), and Soft Tissue Pogonion (Pog′)—were annotated on frontal photographs, while true vertical line (TVL) analysis from cephalograms served as the reference standard. For each case, anteroposterior (AP) relationships among the three landmarks were represented as ordinal rankings based on predicted depth values, and accuracy was defined as complete agreement between model-derived and reference rankings. Depth maps were generated using one vision transformer model (DPT-Large) and two CNN-based models (DepthAnything-v2 and ZoeDepth). Model performance was evaluated using accuracy, 95% confidence intervals, and effect size measures. Results: The transformer-based DPT-Large achieved clinically acceptable accuracy in 92.7% of cases (76/82; 95% CI: 84.8–97.3), significantly outperforming the CNN-based models DepthAnything-v2 (9.8%) and ZoeDepth (4.9%), both of which performed below the theoretical chance level (16.7%). Conclusions: Vision transformer-based Monocular Depth Estimation demonstrates the potential for clinically meaningful soft-tissue profiling from frontal photographs, suggesting that depth information derived from two-dimensional images may serve as a supportive tool for facial profile evaluation. These findings provide a foundation for future studies exploring the integration of depth-based analysis into digital orthodontic diagnostics. Full article
(This article belongs to the Section Intelligent Sensors)
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29 pages, 3978 KB  
Article
Synthesis of Novel Chloro-Benzo [d]imidazole Regioisomers as Selective CB2 Receptor Agonists: Indirect Functional Evaluation and Molecular Insights
by Valeria Zuñiga Salazar, Renato Burgos Ravanal, Jonathan Soto-Flores, Gianfranco Sabadini, José Vicente González, Jaime Mella and Javier Romero-Parra
Pharmaceuticals 2025, 18(11), 1599; https://doi.org/10.3390/ph18111599 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: The cannabinoid type 2 receptor (CB2 receptor) has been extensively studied in recent years due to the benefits associated with its modulation, including the regulation of the inflammatory response, neuroimmunomodulatory properties, and antitumor effects, all with the advantage of lacking significant [...] Read more.
Background/Objectives: The cannabinoid type 2 receptor (CB2 receptor) has been extensively studied in recent years due to the benefits associated with its modulation, including the regulation of the inflammatory response, neuroimmunomodulatory properties, and antitumor effects, all with the advantage of lacking significant psychoactive effects. Herein, we report the design, synthesis, characterization, biological assays, and molecular modelling analyses of novel (5/6-chloro-2-aryl-1H-benzo [d]imidazol-1-yl)(4-methoxyphenyl)methanone and 5/6-chloro-1-(4-methoxybenzyl)-2-aryl-1H-benzo [d]imidazole regioisomers as potential cannabinoid type 2 receptor ligands. Methods: The compounds were evaluated for their presumed CB2 agonist activity using an indirect receptor-dependent apoptotic cell death assay exerted by cannabinoids, using the cell lines HEK293 (low CB1/CB2 expression), U-87 MG (high CB1 expression), and HL-60 (exclusive CB2 expression), and including the known cannabinoid ligands WIN-55,212-2 and AM630 as reference ligands. Flow cytometry was performed to assess apoptosis. Molecular docking and molecular dynamics simulations were used to explore ligand-receptor interactions at the CB2 active site. Results: Compounds 3a, 3b’, 3c, and 4b selectively reduced HL-60 cell viability, similar to WIN-55,212-2, while showing no toxicity toward HEK293 or U-87 MG cells. Flow cytometry indicated that compounds 3a and 3c induced apoptosis in HL-60 cells comparable to WIN-55,212-2. Computational studies suggested that both compounds bind within the CB2 receptor active site predominantly through π–π and hydrophobic interactions involving their benzo [d]imidazole cores, 2-aryl moieties, and 4-methoxybenzoyl scaffolds, resembling the binding patterns of established CB2 ligands. Conclusions: Compounds 3a and 3c exert selective cytotoxicity against HL-60 cells, likely via a CB2 agonist-mediated apoptotic mechanism. The applied combined experimental and computational approach provides a rapid, informative strategy for preliminary evaluation of CB2 ligands and guides subsequent detailed pharmacological studies. Full article
(This article belongs to the Section Medicinal Chemistry)
9 pages, 753 KB  
Article
Thoracic Motion Analysis Using a TrueDepth Camera in Patients with Relapsing Polychondritis: A Pilot Study
by Yoshihiro Nishi, Shohei Sato, Hiroshi Handa, Hiroki Nishine, Takemi Matsui and Masamichi Mineshita
Healthcare 2025, 13(21), 2664; https://doi.org/10.3390/healthcare13212664 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: Relapsing polychondritis (RP) is a rare autoimmune disorder marked by recurrent inflammation of cartilaginous tissues, including the airways. Airway involvement, such as subglottic stenosis and airway malacia, significantly impacts prognosis. Although spirometry is the standard for evaluating respiratory function, it may [...] Read more.
Background/Objectives: Relapsing polychondritis (RP) is a rare autoimmune disorder marked by recurrent inflammation of cartilaginous tissues, including the airways. Airway involvement, such as subglottic stenosis and airway malacia, significantly impacts prognosis. Although spirometry is the standard for evaluating respiratory function, it may be unfeasible in patients with severe airway narrowing or tracheostomy. This study evaluated the potential of a smartphone-based application, DepthRecorder, which uses the iPhone’s TrueDepth camera to analyze thoracic motion in real time. Methods: Twelve patients with RP were enrolled. All underwent simultaneous respiratory assessment using spirometry and the DepthRecorder application. Thoracic motion data were corrected for height using previously validated regression formulas. Correlation between DepthRecorder and spirometry values was analyzed using Spearman’s rank correlation for forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the FEV1/FVC ratio. Results: Mean age was 53.8 ± 13.3 years, with equal numbers of males and females. Before correction, DepthRecorder showed moderate correlations for FEV1 (ρ = 0.48, p = 0.003) and FEV1/FVC (%) (ρ = 0.57, p < 0.001). After correction, stronger correlations were observed for FVC (ρ = 0.76, p < 0.001), FEV1 (ρ = 0.72, p < 0.001), and FEV1/FVC (%) (ρ = 0.60, p < 0.001). Conclusions: The DepthRecorder application demonstrated strong correlations with spirometry following height-based correction. This method may offer a practical, non-invasive tool for respiratory assessment in RP patients who cannot undergo conventional lung function testing. Further studies are needed to validate these findings and establish clinical reference standards. Full article
18 pages, 793 KB  
Article
The Phosphate/Urea Nitrogen Ratio in Urine—A Method to Assess the Relative Intake of Inorganic Phosphate
by Carlos Novillo, Raquel M. García-Saez, Laura Sánchez-Molina, Cristian Rodelo-Haad, Andrés Carmona, Gonzalo Pinaglia-Tobaruela, Cristina Membrives-González, Daniel Jurado, Rafael Santamaría, Juan R. Muñoz-Castañeda, Alejandro Martín-Malo, Mariano Rodríguez, Sagrario Soriano and Victoria Pendón-RuizdeMier
Nutrients 2025, 17(21), 3323; https://doi.org/10.3390/nu17213323 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: It would be desirable to reduce the intake of inorganic phosphate (P), which is easily absorbed and is associated with cardiovascular disease. The phosphate-to-urea nitrogen ratio (P/UUN) in urine should reflect the proportion of inorganic P ingested relative to protein intake. In [...] Read more.
Background/Objectives: It would be desirable to reduce the intake of inorganic phosphate (P), which is easily absorbed and is associated with cardiovascular disease. The phosphate-to-urea nitrogen ratio (P/UUN) in urine should reflect the proportion of inorganic P ingested relative to protein intake. In this manuscript, we will refer to this parameter as P/UUN, which is conceptually equivalent to the phosphate-to-urea ratio (P/U). These studies aim to evaluate whether an increased intake of inorganic P translates into an increase in the P/UUN. Methods: A total of 18 healthy volunteers (Study-1) and 18 chronic kidney disease patients (Study-2) were included. At baseline, all participants completed a 3-day dietary survey, and on the third day collected a 24 h urine sample. In Study-2, blood samples were also obtained. Participants were then stratified into three groups (6 per group) for a 3-day dietary intervention: control group: maintained their usual diet; soda group: consumed soda zero, a source of added inorganic P; and processed cheese group: consumed fresh processed cheese, which includes both organic and inorganic P additives. At last visit, all participants again completed a 3-day dietary survey and collected a 24 h urine sample (and blood samples in Study-2). Dietary P intake was estimated using two tools: the diet calibrator and the Spanish Food Composition Database (BEDCA). Results: After the intervention, neither BEDCA nor the diet calibrator was able to provide an accurate measurement of inorganic P ingested. However, only in the soda group, P/UUN increased in both studies (p = 0.046 and 0.047). In Study-2, the levels of FGF23 and klotho remained unchanged (p = 0.9 and p = 0.7, respectively). Conclusions: These findings suggest that urinary P/UUN ratio may be a useful biomarker to monitor changes in inorganic P intake and could help to individualize dietary recommendations to reduce inorganic P exposure without restricting protein intake. Full article
(This article belongs to the Special Issue Nutritional Epidemiology of Chronic Kidney Disease and Complications)
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16 pages, 1589 KB  
Article
Diagnostic Predictive Scores of Amyloid Cardiomyopathy in Patients with Heart Failure with Preserved Ejection Fraction and Left Ventricular Hypertrophy
by Denise Cristiana Faro, Fabrizia Romeo, Valentina Losi, Dario Simonetti, Davide Capodanno and Ines Paola Monte
J. Cardiovasc. Dev. Dis. 2025, 12(11), 417; https://doi.org/10.3390/jcdd12110417 (registering DOI) - 22 Oct 2025
Abstract
Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is a frequent but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early identification is essential given the availability of disease-modifying therapies. The T-Amylo and Davies scores are non-invasive tools [...] Read more.
Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is a frequent but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early identification is essential given the availability of disease-modifying therapies. The T-Amylo and Davies scores are non-invasive tools for estimating ATTR CM probability, but their comparative performance in the same real-world population is not well defined. Objectives: To compare the diagnostic accuracy of T-Amylo and Davies scores in consecutive patients referred for suspected cardiac amyloidosis. Methods: We retrospectively analyzed 81 patients (mean age 76.8 ± 8.3 years, 74% male) who underwent a standardized work-up: ECG, echocardiography with strain, NT-proBNP and troponin, bone scintigraphy, and immunofixation. ATTR CM was diagnosed according to established non-biopsy criteria. Both scores were calculated retrospectively, and sensitivity, specificity, predictive values, accuracy, and agreement were assessed. Results: ATTR CM was confirmed in 28 patients (34.5%). T-Amylo showed higher sensitivity (91.2% vs. 73.5%) and NPV (89.7% vs. 79.1%), while Davies had greater specificity (85.0% vs. 65.0%) and PPV (80.5% vs. 70.8%). Overall accuracy was comparable (T-Amylo 77.0% vs. Davies 79.7%). Agreement between scores was moderate (κ = 0.59). Conclusions: T-Amylo is best suited as a screening tool for suspected ATTR CM, while Davies offers confirmatory value in high-probability cases. Combining these tools in a sequential strategy may optimize diagnostic efficiency, reduce unnecessary testing, and expedite initiation of disease-modifying therapy. Full article
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22 pages, 1639 KB  
Article
Digital Mapping of Central Asian Foods: Towards a Standardized Visual Atlas for Nutritional Research
by Zhuldyz Omarova, Bibinur Nurmanova, Aibota Sanatbyek, Huseyin Atakan Varol and Mei-Yen Chan
Nutrients 2025, 17(21), 3315; https://doi.org/10.3390/nu17213315 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: Portion size estimation is important for dietary assessment and nutrition research, but has remained understudied in Central Asia, a region characterized by red meat-rich diets and high rates of diet-related noncommunicable diseases (NCDs). Therefore, this study aimed to develop a digital visual [...] Read more.
Background/Objectives: Portion size estimation is important for dietary assessment and nutrition research, but has remained understudied in Central Asia, a region characterized by red meat-rich diets and high rates of diet-related noncommunicable diseases (NCDs). Therefore, this study aimed to develop a digital visual food atlas for Central Asian cuisine that would provide high-quality images of commonly consumed foods and beverages, while special focus was given to meat dishes that were not present in previous atlases. Methods: Foods were selected based on the Central Asian Food Dataset (CAFD) and Central Asian Food Scenes Dataset (CAFSD) and photographed in three portion sizes: small, average, and large. There were nine broad categories: main dishes, soups, meat dishes, salads, snacks, side dishes, bakery and bread, desserts, and beverages. Similar settings were preserved for each photograph: the 60° angle, sufficient lighting, and food setup (including reference objects like utensils, a ruler, and a neatly folded napkin). Results: The final digital visual food atlas comprised 115 items (95 food series, 20 beverage guides), with 12 meat-based dishes, reflecting the central role of meat in regional diets. Each entry included portion weights and names in both English and local languages, improving cultural and linguistic relevance. The digital format with clear labeling ensured accessibility on web and mobile platforms. Conclusions: This was the first digital visual food atlas developed for Central Asia, providing standardized portion-size references. The atlas offered a practical tool for dietary assessment, with applications in nutrition research, mobile health technologies, artificial intelligence (AI)-driven portion estimation, and policy development. Full article
(This article belongs to the Special Issue Advances in Technology for Dietary Assessment)
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10 pages, 614 KB  
Article
Hand Size Measurements in Children Aged 1–15 Years to Help the Development of Pediatric Electromyography Sensors for Neuromuscular Monitoring
by Réka Nemes, Erzsébet Németh, Katalin A. Szatmári, Adrienn Timkó, Péter Luterán, Sorin J. Brull, Béla Fülesdi and Adrienn Pongrácz
J. Clin. Med. 2025, 14(21), 7462; https://doi.org/10.3390/jcm14217462 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: The aim of this observational study was to collect hand measurements and anthropometric data in children aged 1–15 years of age to help the design of a pediatric skin electrode for electromyography-based neuromuscular monitoring. Methods: Data collection was performed at the Pediatric [...] Read more.
Background/Objectives: The aim of this observational study was to collect hand measurements and anthropometric data in children aged 1–15 years of age to help the design of a pediatric skin electrode for electromyography-based neuromuscular monitoring. Methods: Data collection was performed at the Pediatric Department of the University of Debrecen Medical Centre between 1 December 2019 and 31 January 2021. After gaining written informed consent from the parents or legal representatives and verbal acceptance from age-appropriate (12–35 months) patients, a total of 153 children were enrolled. The following parameters were recorded: demographics (age, sex, weight, height, and hand dominance) and hand size parameters, defined as the distance between the following reference points: the ulnar groove and the midpoint of the hypothenar eminence (A); the midpoint of the hypothenar eminence and the first interphalangeal joint of the 5th finger (B); the ulnar groove and the midpoint of the thenar eminence (C); the midpoint of the thenar eminence and the interphalangeal joint of the thumb (D); the midpoint of the wrist crease and the tip of the third finger; wrist circumference (E); and forearm length. All measurements were made in centimeters (cm). Results: The children were divided into 4 groups (12–23 months, 2–5 years, 6–11 years and 12+ years). The number of children in the groups ranged between 6 and 16. The hand size parameters increased according to the children’s age (A: 4.3 ± 0.4, 5.0 ± 0.7, 6.3 ± 0.6, and 6.9 ± 1.0 cm; B: 3.2 ± 0.4, 4.1 ± 0.7, 5.0 ± 0.6, and 5.9 ± 0.6 cm; C: 3.0 ± 0.3, 3.6 ± 0.7, 4.1 ± 0.6, and 4.9 ± 0.6 cm; D: 4.1 ± 0.4, 4.8 ± 0.8, 6.2 ± 0.8, and 7.2 ± 0.9 cm; E: 10.1 ± 0.6, 12.0 ± 1.1, 15.3 ± 1.3, and 17.7 ± 1.7 cm, respectively, in the four groups, [mean ± SD]). The height of the children showed a closer correlation with hand size parameters (Pearson’s correlation coefficients: 0.702–0.961) than with age (0.665–0.904) or weight (0.675–0.863). The correlation was weaker when data were examined in prespecified age groups. Conclusions: The current pediatric hand size database provides previously unavailable information that was used in one manufacturer’s design, which may help with the future design of pediatric electrodes of electromyography-based neuromuscular monitors; this information may facilitate adoption of quantitative neuromuscular monitoring in routine pediatric anesthesia practice. Full article
(This article belongs to the Special Issue Paediatric Anaesthesia: Clinical Updates and Perspectives)
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13 pages, 481 KB  
Article
Serum Iodine Levels and 8-Year Survival in Patients After Kidney Cancer Diagnosis
by Elżbieta Złowocka-Perłowska, Piotr Baszuk, Adam Kiljańczyk, Wojciech Marciniak, Róża Derkacz, Aleksandra Tołoczko-Grabarek, Andrzej Sikorski, Marcin Słojewski, Adam Gołąb, Artur Lemiński, Michał Soczawa, Magdalena Marciniak, Rodney J. Scott, Jacek Gronwald and Jan Lubiński
Cancers 2025, 17(21), 3400; https://doi.org/10.3390/cancers17213400 (registering DOI) - 22 Oct 2025
Abstract
Background/Objectives: The aim of this study was to evaluate the association between serum iodine (I) levels and kidney cancer mortality. The role of serum iodine levels in relation to 8-year survival rates in survivors of kidney cancer has not previously been established. In [...] Read more.
Background/Objectives: The aim of this study was to evaluate the association between serum iodine (I) levels and kidney cancer mortality. The role of serum iodine levels in relation to 8-year survival rates in survivors of kidney cancer has not previously been established. In this prospective study, we analyzed 284 consecutive, unselected survivors of kidney cancer and determined their 8-year survival in relation to iodine levels. Methods: Micronutrient levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). Each survivors of kidney cancer was assigned to one of four groups based on the quartile distribution of iodine levels, ranked in ascending order. The multivariable models included covariates such as age at diagnosis, sex, smoking status, type of surgery, histopathological classification and serum levels of selenium, zinc, copper and the zinc-to-copper ratio. Results: We observed that survivors of kidney cancer with serum iodine levels in quartiles III and IV had significantly higher all-cause mortality compared to those in quartile II (reference quartile) (HR = 2.83; p = 0.012; HR = 2.64; p = 0.017). Furthermore, multivariable analysis revealed a significant association between serum iodine levels (quartiles III and IV vs. quartile II) and mortality due to kidney cancer progression (HR = 4.17; p = 0.031; HR = 3.94; p = 0.038, respectively). This association was significant only among men in quartile IV (HR = 16.5; p = 0.027). Additionally a positive association was observed between iodine levels in quartile IV and all-cause mortality from non–kidney cancer–related deaths (HR = 5.41; p = 0.05). Conclusions: To our knowledge, this study is the first investigation of relationship between serum iodine levels and survival of survivors of kidney cancer. Full article
(This article belongs to the Special Issue Advancements in “Cancer Biomarkers” for 2025–2026)
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25 pages, 2302 KB  
Review
Reference Tolerance Ellipses in Bioelectrical Impedance Vector Analysis Across General, Pediatric, Pathological, and Athletic Populations: A Scoping Review
by Sofia Serafini, Gabriele Mascherini, Raquel Vaquero-Cristóbal, Francisco Esparza-Ros, Francesco Campa and Pascal Izzicupo
J. Funct. Morphol. Kinesiol. 2025, 10(4), 415; https://doi.org/10.3390/jfmk10040415 (registering DOI) - 22 Oct 2025
Abstract
Background: Bioelectrical Impedance Vector Analysis (BIVA) is a qualitative method that standardizes resistance and reactance relative to stature (R/H and Xc/H) and plots them as vectors on an R-Xc graph. This equation-free approach assesses body composition, allowing for the evaluation of hydration [...] Read more.
Background: Bioelectrical Impedance Vector Analysis (BIVA) is a qualitative method that standardizes resistance and reactance relative to stature (R/H and Xc/H) and plots them as vectors on an R-Xc graph. This equation-free approach assesses body composition, allowing for the evaluation of hydration status and cellular integrity through tolerance ellipses. This study aimed to systematically map BIVA reference ellipses across general, pediatric, pathological, and athletic populations. Methods: A scoping review was conducted according to PRISMA-ScR guidelines. Five databases were searched. Extracted data included (a) sample characteristics (sample size, age, sex, BMI, country, ethnicity), (b) population type, (c) analyzer specifications, and (d) R/H and Xc/H means, standard deviations, and correlation values. Results: A total of 53 studies published between 1994 and July 2025 were included. From these, 508 tolerance ellipses were identified: 281 for the general population (18–92 years), 133 for children/adolescents (0–18 years), 49 for athletes, and 45 for pathological groups. Studies were primarily conducted in Europe and the Americas, using 11 analyzers with variations in measurement protocols, including body side, posture, and electrode placement. Conclusions: This scoping review categorizes the existing BIVA tolerance ellipses by population type, sex, age, BMI, device used, and measurement protocol. The structured presentation is intended to guide researchers, clinicians, nutritionists, and sports professionals in selecting appropriate reference ellipses tailored to specific populations and contexts. Full article
(This article belongs to the Special Issue Body Composition Assessment: Methods, Validity, and Applications)
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19 pages, 4823 KB  
Article
From Bench to Bioactivity: An Integrated Medicinal Development Based on Kinetic and Simulation Assessment of Pyrazolone-Oxadiazole Coupled Benzamide as Promising Inhibitors of Diabetes Mellitus
by Manal M. Khowdiary and Shifa Felemban
Pharmaceuticals 2025, 18(11), 1595; https://doi.org/10.3390/ph18111595 (registering DOI) - 22 Oct 2025
Abstract
Background: In this research work, novel pyrazolone-derived oxadiazole-based benzamide derivatives (1–10) were synthesized through unique and facile synthetic routes. Introduction: These scaffolds were designed to be therapeutically more effective and have fewer side effects. Methods: To confirm the structure of analogs [...] Read more.
Background: In this research work, novel pyrazolone-derived oxadiazole-based benzamide derivatives (1–10) were synthesized through unique and facile synthetic routes. Introduction: These scaffolds were designed to be therapeutically more effective and have fewer side effects. Methods: To confirm the structure of analogs in detail, we employed 1HNMR, 13CNMR, and HREI-MS spectroscopy. The potential of all derivatives was tested by screening them against alpha-amylase and alpha-glucosidase in comparison with reference anti-diabetic drug acarbose (4.50 ± 0.20 µM and 4.90 ± 0.30 µM). Results & Discussion: Among all tested analogs and standard drugs, derivative 3 proved to be the most promising candidate. It exhibited the most powerful inhibitory effect (IC50 = 3.20 ± 0.20 µM and 3.60 ± 0.10 µM). To further investigate its activity, the experimental results were supported by in silico investigations. Molecular docking demonstrated strong and viable interactions between enzymes and the most potent compound. DFT calculations validated the electronic configuration, stability, and reactivity of lead molecules. Furthermore, the ADMET profile predicted the favorable drug likeness properties and low toxicity. The results of docking were further confirmed via molecular dynamics analysis, whereas the pharmacophore model of analog 3 supports the formation of a stable hydrogen bond network of derivatives with the receptor site of the enzyme. Conclusions: Collectively in silico and in vitro results underscore the therapeutic potential of these derivatives for the effective treatment of diabetes in the future. Full article
(This article belongs to the Section Medicinal Chemistry)
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14 pages, 3262 KB  
Article
Advancing Duodenoscope Reprocessing with Alginate-Coated Calcium Peroxide Nanoparticles
by Adrian Fifere, Cristian-Dragos Varganici, Elena-Laura Ursu, Tudor Pinteala, Vasile Sandru, Ioana-Andreea Turin-Moleavin, Irina Rosca and Gheorghe G. Balan
Life 2025, 15(11), 1643; https://doi.org/10.3390/life15111643 - 22 Oct 2025
Abstract
Background/Objectives: Although significant advances in duodenoscope reprocessing have been introduced since mid-2010s—including enhanced cleaning protocols, disposable distal endcaps, and the introduction of fully single-use duodenoscopes—residual contamination and infection risks remain unresolved. Moreover, repeated reprocessing may cause cumulative damage to the polymer surfaces, elevator [...] Read more.
Background/Objectives: Although significant advances in duodenoscope reprocessing have been introduced since mid-2010s—including enhanced cleaning protocols, disposable distal endcaps, and the introduction of fully single-use duodenoscopes—residual contamination and infection risks remain unresolved. Moreover, repeated reprocessing may cause cumulative damage to the polymer surfaces, elevator mechanisms, and internal channels of the duodenoscopes, making them more susceptible to residual contamination. To minimize the duodenoscope polymer degradation caused by intensive use and reprocessing, new alternatives are urgently needed. In this context, calcium peroxide nanoparticles coated with sodium alginate (CaO2–Alg NPs), synthesized by our group, were tested for the first time as a disinfectant capable of combating nosocomial pathogens while reducing device deterioration associated with repeated investigations and reprocessing. Methods: The disinfectant properties of the CaO2–Alg NPs were evaluated under biomimetic conditions using reference bacterial strains commonly associated with nosocomial infections. In addition, the compatibility of the nanoparticles with the polymeric duodenoscope coatings was assessed after simulated intensive use. The external polymer coating was structurally and morphologically characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Atomic Force Microscopy (AFM), and Scanning Electron Microscopy (SEM). Results: The nanoparticles exhibited important antimicrobial activity against the reference bacterial strains Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae after only 20 min of incubation. Intensive exposure to the CaO2–Alg NPs did not cause additional structural or morphological damage to the duodenoscope’s external polymers and did not alter their anti-adhesive properties. Conclusions: The CaO2–Alg NPs appear to be a safe and effective disinfectant for the duodenoscope reprocessing, offering both antimicrobial efficacy and material compatibility. Full article
(This article belongs to the Special Issue Emerging Applications of Nanobiotechnology in Medicine and Health)
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22 pages, 3139 KB  
Article
A Phylogenetic Perspective on the Evolutionary Patterns of the Animal Interleukin-10 Signaling System
by Liu Tang, Zeyu Zhou, Weibin Wang, Dawei Li, Tingting Hao and Yue Chen
Genes 2025, 16(11), 1243; https://doi.org/10.3390/genes16111243 - 22 Oct 2025
Abstract
Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to [...] Read more.
Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to different Protein families in evolution, but achieve functional synergy through the conserved JAK-STAT pathway. Understanding their evolutionary and functional dynamics is essential for elucidating immune mechanisms and therapeutic targeting. Methods: Through phylogenetic reconstruction, homology analysis, and sequence alignment across >400 animal species, we traced the evolutionary trajectory and structural–functional diversification of IL-10s and IL-10Rs. Results and Conclusions: IL-10 signaling components emerged in early vertebrates, with IL-10Rs originating in cartilaginous fishes (~450 Mya) and IL-10s diversifying in bony fishes (~400 Mya). Functional divergence yielded immunosuppressive (IL-10), barrier-protective (IL-20 subfamily), and antiviral (type III IFN) subgroups. Structurally, conserved motifs (e.g., IL-10R1 GYXXQ, IL-22 N54-glycosylation) underpin receptor–ligand binding and JAK/STAT signaling. Evolutionarily invariant residues suggest candidate therapeutic epitopes. This study provides an evolutionary framework highlighting functional conservation and species-specific adaptation within IL-10 signaling, with implications for immunotherapy and animal breeding. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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15 pages, 544 KB  
Systematic Review
Breastfeeding During and After Breast Cancer Diagnosis—A Systematic Review of the Literature
by Anna Ampatzi, Nikoleta Aikaterini Xixi, Rozeta Sokou, Eleni Karapati, Zoi Iliodromiti, Paraskevi Volaki, Styliani Paliatsiou, Nicoletta Iacovidou and Theodora Boutsikou
J. Clin. Med. 2025, 14(20), 7450; https://doi.org/10.3390/jcm14207450 - 21 Oct 2025
Abstract
Background/Objectives: Breast cancer diagnosis in lactating women is relatively uncommon. The term Pregnancy-Associated Breast Cancer (PABC) refers to breast cancer diagnosed during pregnancy or within the first year postpartum. There are several factors that limit the ability to breastfeed. Despite emerging evidence suggesting [...] Read more.
Background/Objectives: Breast cancer diagnosis in lactating women is relatively uncommon. The term Pregnancy-Associated Breast Cancer (PABC) refers to breast cancer diagnosed during pregnancy or within the first year postpartum. There are several factors that limit the ability to breastfeed. Despite emerging evidence suggesting that breastfeeding may be feasible and should be supported in women with PABC, there is still limited evidence regarding the percentage of them who attempt breastfeeding, and the challenges they may encounter. This study aims to systematically reviewing the literature on the available evidence regarding breastfeeding in women diagnosed with PABC. Methods: PubMed and Scopus were systematically searched for studies on breastfeeding in PABC until 26 June 2025. Data on breastfeeding outcomes and diagnostic challenges in relation to PABC were extracted. The systematic review is registered in PROSPERO (CRD420251043141). Results: A total of 15 studies met the inclusion criteria and were included in this review. The results showed a scarcity of literature regarding the percentage of women with PABC who breastfeed. Existing data revealed that a small percentage successfully breastfeed. A common occurrence throughout the studies was the concern of breastfeeding during cancer treatment. In almost all cases, reduced milk production was reported, along with the co-administration of formula as a substitute for breast milk. Conclusions: Management of women with PABC should not be limited to oncologic treatment but should also encompass structured breastfeeding counseling and multidisciplinary support, ideally within specialized breast cancer centers. Such integrated care has the potential to optimize maternal health outcomes, improve quality of life, and promote a more favorable pregnancy and postpartum experience. Full article
(This article belongs to the Section Clinical Pediatrics)
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18 pages, 1905 KB  
Article
Trends and Hot Spots in Research Related to Rivaroxaban: Bibliometric Analysis
by Kornel Pawlak, Łukasz Kruszyna, Anna Wesołowska and Marta Karaźniewicz-Łada
Clin. Pract. 2025, 15(10), 190; https://doi.org/10.3390/clinpract15100190 - 21 Oct 2025
Abstract
Background: The number of publications related to rivaroxaban is growing, making it difficult for scientists to review relevant materials. Objectives: This bibliometric analysis is focused on highlighting hot spots and new trends associated with rivaroxaban studies and provides references and guidance for further [...] Read more.
Background: The number of publications related to rivaroxaban is growing, making it difficult for scientists to review relevant materials. Objectives: This bibliometric analysis is focused on highlighting hot spots and new trends associated with rivaroxaban studies and provides references and guidance for further research. Methods: A comparison between countries, journals, authors, and organizations was performed. Microsoft Excel 2021 and VOSviewer were used to process and visualize data extracted from Web of Science. The time range was set from 1991 to late 2024. A total of 6979 articles were analyzed and bibliometric maps of co-citations of references and co-occurrences of the keywords were built. Results: Relative research interest increased until 2021, when it started to drop. The new trends in publications related to rivaroxaban are associated with a comparison of NOAC therapy outcomes with previously used vitamin K antagonists (warfarin). The research was focused also on new NOAC representatives, medical conditions treated with NOAC, and safety of the therapy. New trending topics are related to ABCB1, peripheral artery disease, direct-acting oral anticoagulants, PCI, and SARS-CoV-2. Conclusions: This bibliometric analysis showed that increasing attention is being paid to the medical conditions treated with NOACs and issues related to the safety of this therapy. Full article
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16 pages, 3329 KB  
Article
Comparison of Phenotypic and Whole-Genome Sequencing-Derived Antimicrobial Resistance Profiles of Legionella pneumophila Isolated in England and Wales from 2020 to 2023
by Rediat Tewolde, Rebecca Thombre, Caitlin Farley, Sendurann Nadarajah, Ishrath Khan, Max Sewell, Owen B. Spiller and Baharak Afshar
Antibiotics 2025, 14(10), 1053; https://doi.org/10.3390/antibiotics14101053 - 21 Oct 2025
Abstract
Background: Antimicrobial resistance (AMR) in Legionella pneumophila is emerging as a concern, particularly with resistance to macrolides and fluoroquinolones. Although clinically significant resistance in Legionella pneumophila remains uncommon, systematic genomic surveillance using whole-genome sequencing (WGS) is needed to anticipate treatment failure as metagenomic [...] Read more.
Background: Antimicrobial resistance (AMR) in Legionella pneumophila is emerging as a concern, particularly with resistance to macrolides and fluoroquinolones. Although clinically significant resistance in Legionella pneumophila remains uncommon, systematic genomic surveillance using whole-genome sequencing (WGS) is needed to anticipate treatment failure as metagenomic diagnostics move toward routine use. Objectives: We assessed the UK Health Security Agency AMR pipeline for predicting resistance in L. pneumophila by analysing 522 L. pneumophila isolates from England and Wales (2020–2023) together with nine database sequences that carry confirmed 23S rRNA mutations conferring high-level azithromycin resistance. The objective of the present study was to examine the presence of antimicrobial resistance genes (ARGs) in L. pneumophila isolates and to determine whether they exhibited phenotypic resistance through minimum inhibitory concentration (MIC) testing. Methods: Serogroups (sgs) were determined using an in-house qPCR assay, and L. pneumophila non-sg1 isolates were serogrouped using the Dresden monoclonal antibody (mAb) typing method. Sequence types were determined using the standard sequence-based typing method by Sanger sequencing. WGS reads were screened against standard AMR databases to identify resistance genes and resistance-mediating mutations. Agar dilution measured MICs for azithromycin, erythromycin, ampicillin, levofloxacin, tetracycline and spectinomycin in isolates possessing the blaOXA-29, lpeAB or aph(9)-Ia gene. Results: AMR screening detected lpeAB, two allelic β-lactamase variants (blaOXA-29 and blaLoxA) and aph(9)-Ia in 165 of the 522 L. pneumophila isolates, while all high-azithromycin MIC reference sequences contained the expected 23S mutation. Only lpeAB was associated with a significant twofold elevation in macrolide MICs. Neither β-lactamase variant increased ampicillin MICs, and aph(9)-Ia carriage did not correlate with higher spectinomycin MICs. Conclusions: Advanced genomic analytics can now deliver timely therapeutic guidance, yet database-flagged genes may not translate into phenotypic resistance. Continuous pairing of curated mutation catalogues with confirmatory testing remains essential for distinguishing clinically actionable determinants such as 23S mutations and lpeAB from silent markers like blaOXA-29 and aph (9)-Ia. Full article
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