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16 pages, 1087 KB  
Article
Age-Related Aesthetic Outcomes of Anterior Direct Composite Restorations: Color Match, Patient–Clinician Concordance, and Oral Health-Related Quality of Life
by Magda Mihaela Luca, Roxana Buzatu and Bogdan Andrei Bumbu
J. Clin. Med. 2026, 15(12), 4610; https://doi.org/10.3390/jcm15124610 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Anterior direct composite restorations are evaluated through instrumental color matching, clinician appraisal, and patient perception, but these endpoints may diverge by age. This cross-sectional study compared adolescents/young adults (AYA, 15–25 years) with adults/elderly (AE, 50–75 years) for spectrophotometric color difference (ΔE*ab), [...] Read more.
Background/Objectives: Anterior direct composite restorations are evaluated through instrumental color matching, clinician appraisal, and patient perception, but these endpoints may diverge by age. This cross-sectional study compared adolescents/young adults (AYA, 15–25 years) with adults/elderly (AE, 50–75 years) for spectrophotometric color difference (ΔE*ab), patient and clinician aesthetic ratings, patient–clinician agreement, and oral-health-related quality of life (OHRQoL). Methods: Consecutive recall patients with at least one anterior direct composite restoration placed ≥6 months earlier were screened; 128 were enrolled, and 126 completed all assessments (AYA n = 64; AE n = 62). Participants completed the OHIP-14 and aesthetic visual analogue scale (VAS) before receiving any USPHS, clinician VAS, or spectrophotometric feedback. A separate clinician, masked to patient scores and spectrophotometric outputs but not to patient age, recorded clinician VAS and modified USPHS criteria. Results: AE restorations showed higher ΔE*ab than AYA restorations (4.8 ± 1.6 vs. 3.2 ± 1.1; p < 0.001), whereas AYA reported lower patient VAS (72.4 ± 12.3 vs. 81.6 ± 10.8; p < 0.001) and higher OHIP-14 psychosocial burden (7.2 ± 2.8 vs. 4.0 ± 2.3; p < 0.001). Clinician VAS was higher in AYA (85.2 ± 7.3 vs. 79.4 ± 8.9; p < 0.001). Patient VAS correlated modestly with ΔE*ab (ρ = −0.38 in AYA; ρ = −0.31 in AE) and more strongly with psychosocial OHIP-14 scores (ρ = −0.54 and −0.47, respectively). Patient-clinician agreement was poor in AYA (ICC = 0.26) and moderate in AE (ICC = 0.58), with larger negative patient-minus-clinician discrepancies in AYA. Exploratory mediation statistically decomposed the age-related patient-satisfaction difference more through patient–clinician discrepancy than through ΔE*ab; causality cannot be inferred. Conclusions: Younger patients may experience dissatisfaction and psychosocial burden despite better instrumental color match. Assessment of anterior composites should combine objective shade measurement with patient-centered expectation clarification, and longitudinal studies should test temporal mechanisms and communication interventions. Full article
(This article belongs to the Special Issue Clinical Updates on Prosthodontics)
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36 pages, 4054 KB  
Article
Multifunctional Curcumin-Inspired 3,5-Diarylidene-4-Piperidones: Design, Synthesis, Biological Evaluation and Computational Mechanistic Studies
by Angel K. Nkosi, Adel S. Girgis, Ahmed Samir, Mohamed A. Morsy, Amira M. Shaban, Walid Fayad, Ahmed A. F. Soliman, Christine T. Williams, Shogo Mori, Leena Khanna, Guido F. Verbeck and Siva S. Panda
Pharmaceuticals 2026, 19(6), 935; https://doi.org/10.3390/ph19060935 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Antimicrobial resistance and bacterial persistence underscore the need to develop new chemotypes with multifunctional antibacterial mechanisms. This study aimed to design, synthesize, and evaluate curcumin-inspired 3,5-diarylidene-4-piperidones as versatile small molecules exhibiting antibacterial, antibiofilm, anti-efflux, DNA gyrase-inhibitory, and antiproliferative properties. Methods: A targeted [...] Read more.
Background/Objectives: Antimicrobial resistance and bacterial persistence underscore the need to develop new chemotypes with multifunctional antibacterial mechanisms. This study aimed to design, synthesize, and evaluate curcumin-inspired 3,5-diarylidene-4-piperidones as versatile small molecules exhibiting antibacterial, antibiofilm, anti-efflux, DNA gyrase-inhibitory, and antiproliferative properties. Methods: A targeted series of triazole-conjugated 3,5-diarylidene-4-piperidones was synthesized through copper-catalyzed azide-alkyne cycloaddition click chemistry and subsequently characterized using standard spectroscopic techniques. The compounds were assessed for antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. Selected active compounds underwent further evaluation for DNA gyrase inhibition, antibiofilm activity against multidrug-resistant S. aureus ATCC 33591, ethidium bromide accumulation, and antiproliferative effects on HCT116 and MCF7 cancer cells, with RPE1 cells serving as a control to evaluate cytotoxicity in normal cells. Additionally, computational studies, including QSAR analysis and molecular docking, were conducted to bolster structure–activity relationships and provide mechanistic insights. Results: Several derivatives demonstrated selective antibacterial activity against Gram-positive bacteria, particularly S. aureus, while exhibiting limited or no efficacy against E. coli. Compounds 7n and 7l emerged as the most potent against S. aureus, with minimum inhibitory concentrations (MICs) of 7.8 and 8.2 μM, respectively. Notably, compound 7l inhibited S. aureus DNA gyrase supercoiling, displaying an IC50 of 3.20 μM, comparable to ciprofloxacin. Compound 7e exhibited the strongest antibiofilm activity against multidrug-resistant S. aureus, whereas compound 7a resulted in the highest accumulation of ethidium bromide, indicating robust anti-efflux activity. Antiproliferative assays revealed that select halogenated derivatives were effective against HCT116 and MCF7 cells, while the most promising antibacterial compounds exhibited minimal cytotoxicity toward RPE1 cells. Quantitative structure–activity relationship (QSAR) and docking studies supported the observed structure–activity relationships and suggested potential interactions with the ATPase binding site of DNA gyrase B. Conclusions: Triazole-conjugated 3,5-diarylidene-4-piperidones are promising multifunctional scaffolds with selective anti-S. aureus activity, antibiofilm and anti-efflux properties, and, for compound 7l, potent DNA gyrase inhibition. These findings support further optimization of this chemotype as a platform for developing antibacterial agents with polymechanistic activity. Full article
(This article belongs to the Special Issue Antimicrobial and Anticancer Scaffolds in Medicinal Chemistry)
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31 pages, 13651 KB  
Article
Umbilical Cord Blood Gasometry and pH as Key Regulators of Growth Factor Expression Profile in Umbilical Cord-Derived Mesenchymal Stromal Cells (UC-MSCs)
by Dominika Przywara, Wiktor Babiuch, Alicja Petniak, Małgorzata Wasilewska, Jarosław Krzyżanowski, Monika Czuba, Arkadiusz Krzyżanowski, Adrianna Kondracka, Janusz Kocki and Paulina Gil-Kulik
Cells 2026, 15(12), 1076; https://doi.org/10.3390/cells15121076 (registering DOI) - 13 Jun 2026
Abstract
Umbilical cord mesenchymal stromal cells (UC-MSCs) are a key element of regenerative medicine due to their ability to secrete growth factors that stimulate proliferation and angiogenesis, and modulate the inflammatory response. Despite their widespread use, the influence of the perinatal microenvironment on their [...] Read more.
Umbilical cord mesenchymal stromal cells (UC-MSCs) are a key element of regenerative medicine due to their ability to secrete growth factors that stimulate proliferation and angiogenesis, and modulate the inflammatory response. Despite their widespread use, the influence of the perinatal microenvironment on their biological properties remains poorly understood. The aim of this study was to assess the influence of pH and blood gas parameters in umbilical cord blood on the global transcriptomic profile of UC-MSCs and to analyze the correlation between the metabolic status of the newborn and the expression of key trophic factors: EGF, FGF2, FGFR1, FGFR3, GDNF, HGF, IGF1, NES, NGF, and PGF. Methods: The study was conducted in two stages. In the first phase, transcriptomic screening was performed using Affymetrix HuGene 2.0 ST microarray on cells isolated from three environmental groups defined by cord blood pH: acidic (pH < 7.35), physiological (7.35–7.39), and alkaline (pH ≥ 7.4). In the second phase, the results were validated using qPCR on an expanded study group (N = 50). Gene expression levels (RQ) were related to blood gas parameters (pH, pCO2, pO2, cHCO3) and the presence of clinical features of threatened neonatal asphyxia. Results: Microarray analysis revealed that environmental pH acts as a molecular phenotypic switch. Under low pH conditions (<7.35), a shift in cell profile from proliferative to structural–migratory was observed. Significant overexpression of genes responsible for extracellular matrix (ECM) organization and adhesion (e.g., COMP, DCN, LUM, FMOD) was observed, while pathways related to cell cycle and cell division (↓CDK1, AURKA, TOP2A) were downregulated. qPCR validation confirmed these observations, demonstrating a strong positive correlation between blood pH and the expression of regenerative mediators: FGFR1 (r = 0.28), EGF (r = 0.30), NGF (r = 0.39), and IGF1 (r = 0.30). A negative correlation was also found between carbon dioxide pressure (pCO2) and the expression of NGF, FGFR1, and EGF. A significant clinical finding was that in newborns diagnosed with threatened asphyxia, EGF, FGFR1, and NGF gene expression was significantly reduced, indicating impaired trophic potential of the cells in response to metabolic stress. Conclusions: These results indicate that cord blood gas parameters are critical regulators of the genetic activity of UC-MSCs. Metabolic and respiratory acidosis not only inhibit the cells’ proliferative potential but also force them into a matrix remodeling mode, permanently modifying their transcriptomic profile. This suggests that the neonatal acid–base status may serve as an objective indicator of the “biological quality” of isolated stromal cells, which has significant implications for their future applications in cell therapies. Full article
(This article belongs to the Section Stem Cells)
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14 pages, 4057 KB  
Article
Prevalence, Clinical and Functional Determinants of Chronic Hypoxemia and Respiratory Failure in Patients with Stable COPD
by Giacobbe Marco Giuseppe Ricco, Dejan Radovanovic, Matteo Pecchiari, Marina Saad, Juan Camilo Signorello, Francesca Mandurino Mirizzi, Michele Mondoni, Massimo Guerriero and Pierachille Santus
J. Clin. Med. 2026, 15(12), 4605; https://doi.org/10.3390/jcm15124605 (registering DOI) - 13 Jun 2026
Abstract
Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining [...] Read more.
Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining predictive factors for chronic gas exchange abnormalities in COPD patients. Methods: A retrospective cohort study that enrolled clinically stable COPD patients referring to a pulmonary outpatient clinic. Anthropometrics, clinical characteristics, blood gas analysis and lung function were analyzed. Patients were grouped according to hypoxemia (PaO2 <80 and ≥60 mmHg), type 1 (PaO2 < 60 mmHg) or type II (PaO2 < 60 and PaCO2 > 45 mmHg) RF. A sensitivity analysis adopting an age-adjusted definition of hypoxemia was performed. Predictive factors for hypoxemia or RF were assessed with multifactorial analysis. Results: We analyzed data from 515 patients. Fixed-ratio hypoxemia, RF type 1 and type 2 were observed in 352 (68.3%), 27 (5.2%) and 43 (8.3%) patients, respectively. Risk of hypoxemia was associated with preserved alveolar volume, residual volume/total lung capacity, and lung diffusion capacity. Heart failure, ischemic heart disease, atrial fibrillation, and metabolic syndrome were predictive factors for RF. Patients with age-adjusted hypoxemia (n = 321 patients, 62.3%) showed no difference in terms of anthropometrics, lung function, and clinical characteristics as compared with fixed-threshold hypoxemia. Conclusions: Hypoxemia is frequent in stable COPD. Lung function parameters and comorbidities can support the identification of patients at risk of RF. Blood gas analysis should be always performed in patients with COPD to allow for personalized therapy and management. Full article
(This article belongs to the Section Respiratory Medicine)
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11 pages, 3558 KB  
Article
Quadriceps Corticospinal and Intracortical Excitability Assessment Using Transcranial Magnetic Stimulation: A Test–Retest Reliability Study
by Liam C. Tapsell, Molly E. Coventry, Colin Sylvester, Casey Whife and Myles C. Murphy
NeuroSci 2026, 7(3), 69; https://doi.org/10.3390/neurosci7030069 (registering DOI) - 13 Jun 2026
Abstract
Objective: Evaluate the test–retest reliability of quadriceps corticospinal excitability and intracortical excitability using transcranial magnetic stimulation (TMS). Design: A test–retest observational cohort study. Methods: Twelve healthy adults attended two laboratory sessions, seated with their knee at 90 degrees and fitted with electrodes on [...] Read more.
Objective: Evaluate the test–retest reliability of quadriceps corticospinal excitability and intracortical excitability using transcranial magnetic stimulation (TMS). Design: A test–retest observational cohort study. Methods: Twelve healthy adults attended two laboratory sessions, seated with their knee at 90 degrees and fitted with electrodes on the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM). TMS was used to assess the active motor threshold (AMT), motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Individual results were calculated as the mean and median of the 10 trials of each measure for MEP, SICI and ICF. Intraclass correlation coefficients were calculated. Results: All muscles showed good or excellent reliability for the mean and median measures of the MEP amplitude (ICC ≥ 0.820) as well as the AMT of the RF (ICC = 0.991). SICI showed good reliability in the mean and median measures of the RF and the mean measure of the VL (ICC ≥ 0.809), moderate reliability in both measures of the VM (ICC ≥ 0.655) and was not significant for the median measure of the VL (ICC = 0.513). ICF showed excellent reliability in the mean measure of each muscle and median measure of the RF (ICC ≥ 0.906), with good reliability in the median measure of the VL (ICC = 0.888) and moderate reliability in the median measure of the VM (ICC = 0.719). Conclusion: The mean of an individual’s quadriceps corticospinal excitability and intracortical excitability have good or excellent reliability for every TMS measure, in every muscle (except SICI of the VM). With the previous reliability of TMS measures mostly investigating the upper limbs, these results offer important context for neurophysiological research in the quadriceps. Full article
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62 pages, 4424 KB  
Review
The Mediterranean Diet as a Sustainable Dietary Pattern: A State-of-the-Art Narrative Review of Health, Environmental and Socioeconomic Dimensions
by Georgios K. Vasios, Maria Gialeli, Georgios Antasouras and Constantinos Giaginis
Nutrients 2026, 18(12), 1925; https://doi.org/10.3390/nu18121925 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: The increasing burden of non-communicable diseases, together with accelerating environmental degradation, highlights the urgent need for sustainable dietary patterns that promote both human and planetary health. The Mediterranean diet (MedDiet), traditionally followed in countries bordering the Mediterranean basin, has gained recognition as [...] Read more.
Background/Objectives: The increasing burden of non-communicable diseases, together with accelerating environmental degradation, highlights the urgent need for sustainable dietary patterns that promote both human and planetary health. The Mediterranean diet (MedDiet), traditionally followed in countries bordering the Mediterranean basin, has gained recognition as a model of sustainable nutrition due to its well-documented health benefits and relatively low environmental impact. However, its broader role within sustainable food systems requires comprehensive and interdisciplinary evaluation. The aim of this review is to provide a state-of-the-art synthesis of the evidence on the MedDiet as a sustainable dietary pattern, integrating its health, environmental, economic, and socio-cultural dimensions. Methods: This state-of-the-art narrative review synthesizes evidence from peer-reviewed literature on the MedDiet and sustainability. Relevant studies were identified through major scientific databases, focusing on publications addressing nutritional, environmental, economic, and socio-cultural dimensions. Both observational and interventional studies, as well as modeling and life cycle assessment analyses, were included. Additional sources from international organizations and policy reports were incorporated to contextualize global trends and challenges. Results: High adherence to the MedDiet is consistently associated with a reduced risk of cardiovascular disease, type 2 diabetes, cancer, and all-cause mortality. From an environmental perspective, the MedDiet is associated with lower greenhouse gas emissions, reduced land and water use, and enhanced biodiversity conservation compared with Western dietary patterns. Economically, it may represent a cost-effective dietary model and support local food systems when grounded in traditional practices, although affordability varies across contexts. Socio-culturally, the MedDiet promotes food heritage, culinary skills, and social cohesion. Nevertheless, globalization, urbanization, and the increasing consumption of ultra-processed foods have contributed to declining adherence, posing significant challenges to its sustainability and scalability. Moreover, the sustainability benefits of the MedDiet seem to be context-dependent rather than intrinsic, raising several challenges and limitations for its adoption. Conclusions: The MedDiet should be viewed not as a definitive solution to global food-system challenges but as a valuable reference model that illustrates how dietary practices can contribute simultaneously to human health, environmental sustainability, and cultural continuity. Modern sustainable dietary strategies should build upon the strengths of the MedDiet while recognizing its limitations, embracing contextual adaptation, and addressing the structural determinants that shape food choices. Full article
(This article belongs to the Section Nutritional Policies and Education for Health Promotion)
30 pages, 4874 KB  
Review
Beyond SINS: A Critical Review of Biomechanical, Microstructural, and Radiomic Biomarkers for Predicting Fracture Risk in Spinal Metastases
by An Sen Tan, Calvin Kai En Tjio, Jonathan Jiong Hao Tan, Naresh Kumar, Wilson Ong, Shuliang Ge, Yi Liang Tan, Eric Fang, Balamurugan A Vellayappan and James Thomas Patrick Decourcy Hallinan
Diagnostics 2026, 16(12), 1835; https://doi.org/10.3390/diagnostics16121835 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Although the Spinal Instability Neoplastic Score (SINS) is widely used to estimate spinal metastases fracture risk and guide decisions on stabilisation procedures, prior studies have demonstrated mixed results. Patients with the same score exhibit clinically heterogeneous outcomes, with some SINS criteria correlating [...] Read more.
Background/Objectives: Although the Spinal Instability Neoplastic Score (SINS) is widely used to estimate spinal metastases fracture risk and guide decisions on stabilisation procedures, prior studies have demonstrated mixed results. Patients with the same score exhibit clinically heterogeneous outcomes, with some SINS criteria correlating less well with the estimated fracture risk than others. There are also barriers to implementation such as the time burden required for manual calculation and interobserver variability associated with qualitative morphological criteria. SINS also lacks sensitivity for detecting latent structural compromise in treatment-naive patients and those susceptible to the iatrogenic effects of stereotactic body radiation therapy. This review aims to evaluate emerging imaging, biomechanical, and microstructural markers with the potential to improve fracture risk stratification and prognostication for spinal oncology patients. Methods: We synthesise evidence across three innovative frontiers: (1) biomechanical modelling, including CT-derived finite element analysis and failure-load pattern models; (2) radiomics, utilizing radiomics features from radiological imaging to develop a predictive model; and (3) microstructural MRI biomarkers, exploring the translatability of the Vertebral Bone Quality score, fat fraction, and paraspinal muscle atrophy from osteoporosis to the metastatic spine. Results: Emerging biomechanical, radiomic and microstructural imaging markers show potential in addressing some limitations of traditional SINS criteria for fracture risk stratification across the spinal oncology treatment continuum, from initial diagnosis to post-radiation surveillance, thereby facilitating more precise risk assessment. However, current evidence remains largely retrospective and heterogeneous, and further validation is required before clinical adoption. Conclusions: We propose a framework that shifts the paradigm from conventional morphological scoring toward a multiparametric assessment of spinal stability. Full article
(This article belongs to the Special Issue Contemporary Spine Diagnostics and Management)
13 pages, 770 KB  
Article
Sex Differences in Clinical Profile, Revascularization and In-Hospital Outcomes in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
by Corina Cinezan, Camelia Bianca Rus and Timea Claudia Ghitea
J. Clin. Med. 2026, 15(12), 4604; https://doi.org/10.3390/jcm15124604 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Sex differences in ST-elevation myocardial infarction (STEMI) outcomes persist despite advances in primary percutaneous coronary intervention (PCI), but whether female sex independently influences early mortality remains unclear. study aimed to assess sex-based differences in clinical characteristics, management, in-hospital outcomes and to [...] Read more.
Background/Objectives: Sex differences in ST-elevation myocardial infarction (STEMI) outcomes persist despite advances in primary percutaneous coronary intervention (PCI), but whether female sex independently influences early mortality remains unclear. study aimed to assess sex-based differences in clinical characteristics, management, in-hospital outcomes and to determine whether female sex independently predicts in-hospital mortality. Methods: This retrospective observational study included 512 consecutive patients with STEMI presenting within 6 h of symptom onset and treated with primary PCI. Clinical, laboratory, echocardiographic and angiographic data were analyzed. The primary endpoint was in-hospital mortality. Multivariable logistic regression identified independent predictors of mortality. Results: Women comprised 32.0% of the cohort and were older than men (median 69 vs. 59 years, p < 0.001), with a higher prevalence of diabetes and hypertension, but lower rates of smoking (all p < 0.001). Women had lower hemoglobin levels and a higher prevalence of moderate-to-severe mitral regurgitation (17.1% vs. 8.0%, p = 0.004). Procedural characteristics, including door-to-balloon time and complete revascularization, were similar between sexes. Crude in-hospital mortality was higher in women (13.4% vs. 7.5%, p = 0.047); however, female sex was not independently associated with mortality after adjustment (adjusted OR 1.07, 95% CI 0.48–2.41; p = 0.864). Lower LVEF and reduced GFR were the strongest independent predictors of death. Conclusions: Higher mortality in women is primarily driven by a more adverse clinical profile rather than sex itself, emphasizing the importance of early risk stratification and management. Full article
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33 pages, 4510 KB  
Article
Antimitotic Naphthalene Sulfonamides Are Potent Antitumor Agents Acting Differently from Colchicine
by Miguel Marín, Raúl Fuentes-Martín, Baldomero Sánchez, Laura Gallego-Yerga and Rafael Peláez
Pharmaceutics 2026, 18(6), 733; https://doi.org/10.3390/pharmaceutics18060733 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Microtubule-targeting agents represent a pillar of cancer chemotherapy; however, their clinical utility is constrained by significant toxicity, pharmacokinetic instability, and susceptibility to multidrug resistance transporters. This study aimed to explore the impact of replacing substituted phenyl rings with a naphthalene moiety in [...] Read more.
Background/Objectives: Microtubule-targeting agents represent a pillar of cancer chemotherapy; however, their clinical utility is constrained by significant toxicity, pharmacokinetic instability, and susceptibility to multidrug resistance transporters. This study aimed to explore the impact of replacing substituted phenyl rings with a naphthalene moiety in sulfonamide-based colchicine-site ligands, with the goal of identifying new antiproliferative candidates with improved profiles. Methods: We designed, synthesized, and evaluated a library of 35 naphthalene sulfonamides bearing varied aryl groups and sulfonamide nitrogen substituents. We assessed the antiproliferative activity against multiple cancer cell lines. Mechanistic studies, including fluorescence microscopy, cell cycle analysis, and cell death assays, were performed to evaluate the effect of these compounds on microtubule polymerization dynamics and cell fate. Molecular docking and in silico pharmacokinetic profiling were carried out to support the proposed binding mode at the colchicine site and to assess drug-likeness. Results: Exclusively, compounds bearing a trimethoxyphenyl group showed antiproliferative activity in the submicromolar range, thus identifying it as a structural requirement. The most potent compound (2) reached double-digit nanomolar IC50 values (67–104 nM) across multiple cancer cell lines. Microscopy confirmed intracellular disruption of microtubule polymerization. Unlike colchicine, these compounds did not induce canonical mitotic arrest but instead triggered apoptotic cell death. In silico analyses supported binding at the colchicine site and revealed favorable predicted pharmacokinetic properties. Conclusions: The naphthalene sulfonamides described herein demonstrate potent antiproliferative activity through a distinct mechanism compared to colchicine, and their favorable in silico profiles position them as promising candidates for further development as antitumor agents. Full article
(This article belongs to the Section Drug Targeting and Design)
18 pages, 934 KB  
Article
Functional Differences Across Playing Roles in Volleyball: A Sensor-Based Assessment
by Juri Taborri, Mauro Strippoli, Luca Molinaro and Stefano Rossi
J. Funct. Morphol. Kinesiol. 2026, 11(2), 238; https://doi.org/10.3390/jfmk11020238 (registering DOI) - 13 Jun 2026
Abstract
Objectives: Volleyball playing positions are associated with different functional demands. This study compared postural control, jump performance, and upper-limb mobility across playing roles in competitive male volleyball players. Methods: Fifty male volleyball players competing in the Italian Serie C championship were equally [...] Read more.
Objectives: Volleyball playing positions are associated with different functional demands. This study compared postural control, jump performance, and upper-limb mobility across playing roles in competitive male volleyball players. Methods: Fifty male volleyball players competing in the Italian Serie C championship were equally distributed across five roles: middle blockers (MB), liberos (LIB), opposite hitters (OH), setters (SET), and outside hitters (HIT). Using a wearable inertial sensor, athletes performed bipodalic balance tasks with eyes open and closed, dominant- and non-dominant-leg single-leg balance, squat jump (SJ), countermovement jump (CMJ), and bilateral upper-limb flexion and extension tests. Results: Significant role-related differences emerged in balance and jump performance. In bipodalic balance, the eyes-open condition showed a mixed pattern, with HIT displaying the largest ellipse area and SET showing the highest path-related values, whereas in the eyes-closed condition, HIT showed the highest values across all stabilometric parameters. In the single-leg stance, OH showed the largest postural excursions on the dominant side, while LIB stood out on the non-dominant side. In jump tests, MB showed the best vertical performance in both SJ and CMJ, whereas LIB and SET generally showed the lowest outputs. Temporal differences also emerged across roles. Upper-limb mobility was similar across roles in flexion, while extension showed a role-specific pattern, with SET displaying greater ROM than LIB, HIT, and OH. Conclusions: Volleyball roles are associated with distinct functional profiles in balance, jump mechanics, and upper-limb mobility. This integrated assessment may support more specific training, monitoring, and injury-prevention strategies. Full article
23 pages, 1272 KB  
Article
Dynamic Optimization of Incoming Quality Control Policies for Cost, Carbon, and Energy Reduction Using Bayesian Reinforcement Learning
by David Massetti, Mehdi Raoofi, Tiziano Miroglio, Marco Mosca and Flavio Tonelli
Sustainability 2026, 18(12), 6094; https://doi.org/10.3390/su18126094 (registering DOI) - 13 Jun 2026
Abstract
The transition towards sustainable manufacturing necessitates complex optimization that integrates economic goals with environmental factors, such as energy consumption and greenhouse gas emissions. This research addresses the critical challenge of optimizing the Incoming Quality Control (IQC) policy for raw material batches. The primary [...] Read more.
The transition towards sustainable manufacturing necessitates complex optimization that integrates economic goals with environmental factors, such as energy consumption and greenhouse gas emissions. This research addresses the critical challenge of optimizing the Incoming Quality Control (IQC) policy for raw material batches. The primary objective is formulated as a multi-criteria control problem that jointly minimizes the weekly final product cost, carbon footprint, and energy consumption. To handle sequential decision making under uncertainty, we adopt a scalarized reinforcement learning (RL) reward that combines these objectives into a single value function and explores different trade-offs through alternative weight configurations. To effectively handle the uncertainty in incoming quality and the sequential decision making required for dynamic control, the optimization problem is modeled as a Bayesian Adaptive Markov Decision Process (BAMDP). To maintain computational tractability despite the continuous belief space inherent in the BAMDP formulation, we employ a Deep Q-Network (DQN) architecture acting as an approximate dynamic programming solver. The Bayesian framework represents model uncertainty explicitly, updates beliefs as new inspection evidence becomes available, and allows prior domain knowledge on supplier quality to be incorporated into the learning process. The BAMDP formulation is used to learn a set of adaptive inspection policies that adjust the IQC strategy over time to achieve conflicting goals: reducing inspection costs while maintaining standard quality, minimizing energy consumption, and lowering CO2-equivalent emissions. The goal is to find robust policies that balance these trade-offs under different quality and demand conditions. This methodology aligns with the principles of Industry 5.0 by leveraging advanced artificial intelligence (AI) methods, such as reinforcement learning (RL), coupled with a stochastic simulation of the production system, based on a geometric/physical model of the component’s tolerance chains, to support decision-makers in designing and assessing sustainable IQC strategies. Comparative simulations on the case study, including a benchmark against ISO 2859-1 sampling plans, confirm that this dynamic and risk-aware optimization paradigm can reduce overall cost, energy use, and environmental impact across various quality conditions, while preserving outgoing quality. Full article
13 pages, 233 KB  
Article
Functional Status of Patients with Long-Term Mechanical Left Ventricular Assist Device Support in Relation to Physical Activity
by Julia Zuzanna Bura, Zuzanna Strząska-Kliś, Radosław Wilimski, Mariusz Kuśmierczyk and Daniel Karaszewski
J. Clin. Med. 2026, 15(12), 4602; https://doi.org/10.3390/jcm15124602 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Advanced heart failure is associated with reduced functional capacity and impaired quality of life. Left ventricular assist devices (LVADs) are increasingly used as a long-term treatment option in patients with end-stage heart failure. Despite improvements in hemodynamic function after LVAD implantation, [...] Read more.
Background/Objectives: Advanced heart failure is associated with reduced functional capacity and impaired quality of life. Left ventricular assist devices (LVADs) are increasingly used as a long-term treatment option in patients with end-stage heart failure. Despite improvements in hemodynamic function after LVAD implantation, many patients continue to experience limitations in daily functioning. The aim of this study was to evaluate the relationship between physical activity and functional status in patients with LVAD support. Methods: This study included 262 adult participants divided into four groups according to LVAD support and declared physical activity. Functional status and quality of life were assessed using the Short Form-36 Health Survey (SF-36) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Results: Significant differences were observed between the analyzed groups in both SF-36 and MLHFQ scores. Physically active patients with LVAD achieved the most favorable results, indicating a better functional status and lower symptom burden, whereas inactive individuals demonstrated poorer outcomes. Significant correlations were found between physical activity and selected aspects of daily functioning, including walking, climbing stairs, performing household activities, and carrying groceries. Higher levels of physical activity were associated with better quality of life and fewer functional limitations. Conclusions: Physical activity may positively influence functional status and quality of life in patients with LVAD support. The findings suggest that regular physical activity should be considered an important component of rehabilitation and long-term management in patients with advanced heart failure treated with LVAD therapy. Full article
17 pages, 582 KB  
Systematic Review
Accuracy and Outcomes of Computer-Aided Surgical Planning in Deep Circumflex Iliac Artery (DCIA) Free Flap Reconstruction of Maxillofacial Defects: A Systematic Review
by Hyo-Joon Kim, Ji-Su Oh, Kun-Woo Kim, Jun-Seong Kim and Seong-Yong Moon
J. Clin. Med. 2026, 15(12), 4600; https://doi.org/10.3390/jcm15124600 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Computer-aided surgical planning (CASP) technologies, including virtual surgical planning (VSP), 3D printed cutting guides, and patient-specific implants, have been increasingly applied to deep circumflex iliac artery (DCIA) free flap reconstruction of maxillofacial defects. Despite growing adoption, no systematic review has specifically [...] Read more.
Background/Objectives: Computer-aided surgical planning (CASP) technologies, including virtual surgical planning (VSP), 3D printed cutting guides, and patient-specific implants, have been increasingly applied to deep circumflex iliac artery (DCIA) free flap reconstruction of maxillofacial defects. Despite growing adoption, no systematic review has specifically evaluated their accuracy and clinical outcomes. This study aimed to comprehensively assess the impact of CASP on reconstruction accuracy, operative efficiency, flap survival, and implant rehabilitation in DCIA flap surgery. Methods: A systematic search of PubMed, Web of Science, and Google Scholar was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Studies reporting CASP-assisted DCIA free flap reconstruction with three or more patients were included. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist and the Cochrane Risk of Bias 2.0 tool for the randomized controlled trial (RCT). Results: Thirty studies (1 RCT, 13 comparative, and 16 non-comparative) involving 844 patients were included. VSP with 3D-printed cutting guides was the most frequently used technology (n = 22). Mean linear deviations between planned and actual outcomes ranged from 0.40 to 4.4 mm, with most studies reporting 0.7–2.7 mm. The sole RCT demonstrated significantly better accuracy (1.3 vs. 5.5 mm, p < 0.001) and shorter reconstruction time (16 vs. 39 min, p < 0.001) with CASP. Flap survival ranged from 90% to 100%. Conclusions: CASP technologies, particularly VSP with 3D-printed cutting guides, appear to improve the accuracy and predictability of DCIA flap reconstruction. However, the evidence base is predominantly retrospective and heterogeneous; prospective multicenter studies with standardized outcome measures are needed before definitive clinical guidelines can be established. Full article
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17 pages, 382 KB  
Review
Review of 2D Spectral Image Processing Techniques
by Bo Qiu, Tao Lu, Siqi Liu and Ali Luo
Universe 2026, 12(6), 177; https://doi.org/10.3390/universe12060177 (registering DOI) - 13 Jun 2026
Abstract
The processing of two-dimensional (2D) spectral images constitutes a critical and multifaceted discipline in contemporary astronomical data analysis. As spectroscopic instruments evolve towards higher multiplexing, resolution, and sensitivity, the raw 2D data captured by detectors present increasingly complex challenges that transcend simple one-dimensional [...] Read more.
The processing of two-dimensional (2D) spectral images constitutes a critical and multifaceted discipline in contemporary astronomical data analysis. As spectroscopic instruments evolve towards higher multiplexing, resolution, and sensitivity, the raw 2D data captured by detectors present increasingly complex challenges that transcend simple one-dimensional extraction. This review provides a systematic and comprehensive examination of the methodological evolution in this field over the past two decades. It gathered relevant studies by searching mainstream academic repositories and general search engines with the core keyword ‘2D Spectral Image’, and selected qualified references according to accessibility and research relevance. We categorize the landscape into three major paradigms: (1) physics-based modeling and algorithmic correction techniques for geometric distortion, scattered light, and sky background; (2) data-driven machine learning and deep learning approaches for image correction, spectral classification, and faint signal detection; and (3) the development of open-source software pipelines that democratize advanced processing. A central contribution of this review is a detailed comparative analysis of the performance metrics, underlying assumptions, and practical limitations of prominent algorithms. We highlight the transformative impact of convolutional neural networks (CNNs) and vision transformers (ViTs) on tasks such as celestial object classification and exoplanet detection, while also acknowledging the enduring importance of robust physical models for calibration and uncertainty quantification. The discussion culminates in an assessment of persistent challenges—including computational scalability, model generalizability, and interpretability—and outlines promising future directions at the intersection of AI, statistical inference, and large-scale survey science. Full article
(This article belongs to the Special Issue Applications of Artificial Intelligence in Modern Astronomy)
10 pages, 523 KB  
Article
The Prevalence and Diagnostic of Silent Ischemic Heart Disease in Polish Kidney Transplant Candidates
by Piotr B. Kuczera, Aleksandra Grzmil, Szymon Domagała, Jakub Milczarek, Anna Walukiewicz, Andrzej Więcek and Aureliusz Kolonko
J. Clin. Med. 2026, 15(12), 4596; https://doi.org/10.3390/jcm15124596 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of ischemic heart disease (IHD). Some discrepancies exist between cardiological and nephrological guidelines regarding the extent of diagnostic procedures in CKD patients who are candidates for kidney transplantation. The aim of [...] Read more.
Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of ischemic heart disease (IHD). Some discrepancies exist between cardiological and nephrological guidelines regarding the extent of diagnostic procedures in CKD patients who are candidates for kidney transplantation. The aim of this study was to assess the cardiac status of these patients after cardiological checkup. Methods: The present study included all kidney transplant candidates referred to the Regional Qualification Center between January 2021 and February 2024. We characterized the group of patients in whom IHD was diagnosed during the cardiological checkup. Results: Among 346 patients, IHD was newly identified in 44 (12.7%) subjects. These patients were significantly older [median 62.9 (51.9–65.4) vs. 47.2 (36.8–57.9) years; p < 0.001], had longer dialysis vintage [median 20 (12.5–42) vs. 14 (6–31) months; p < 0.05] and were more frequently diabetic (29.6 vs. 16.9%, p < 0.05) than the rest of the study cohort. Of note, they were also characterized by significantly more frequent manifestation of atherosclerosis lesions visualized using routine imaging methods (i.e., chest X-ray and abdominal aorta and iliac artery visualization). The stepwise logistic regression analysis revealed that age [OR 1.05 (1.02–1.09); p <0.01] and the ad hoc atherosclerotic score [OR 1.88 (1.27–2.77); p < 0.001] independently predicted the diagnosis of IHD during the cardiological qualification of potential kidney transplant candidates. Conclusions: During the cardiological examination, IHD was diagnosed in a substantial number of kidney transplant candidates. The presence of atherosclerotic lesions detected by routine noninvasive vascular system imaging methods may suggest the need for extending IHD diagnostics even in relatively young patients without clinical symptoms. Full article
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