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15 pages, 675 KB  
Systematic Review
Virtual Reality for Pain Management in Pediatric Phlebotomy: A Systematic Review
by André Caldas, Maria Rocha, Amadeu Gomes and Paulo Veloso Gomes
Future 2026, 4(3), 21; https://doi.org/10.3390/future4030021 (registering DOI) - 25 Jun 2026
Abstract
Pediatric phlebotomy is a common invasive procedure frequently associated with pain, anxiety, and fear, which may negatively affect children’s cooperation and overall healthcare experiences. Virtual reality (VR) has emerged as a promising non-pharmacological intervention capable of providing immersive distraction and emotional engagement during [...] Read more.
Pediatric phlebotomy is a common invasive procedure frequently associated with pain, anxiety, and fear, which may negatively affect children’s cooperation and overall healthcare experiences. Virtual reality (VR) has emerged as a promising non-pharmacological intervention capable of providing immersive distraction and emotional engagement during painful medical procedures. The aim of this systematic review was to evaluate the effectiveness of immersive VR in reducing pain perception and anxiety-related outcomes among pediatric patients undergoing phlebotomy procedures. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research question was developed using the PICO framework. Randomized controlled trials and comparative controlled studies published between January 2020 and September 2025 were identified through systematic searches of PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies involving children and adolescents aged 4–17 years undergoing phlebotomy or venipuncture procedures were eligible for inclusion. A total of six studies comprising 557 pediatric participants were included in the review. The VR interventions involved immersive and interactive environments, including educational simulations, animated scenarios, and game-based experiences delivered through head-mounted displays. Four studies reported statistically significant reductions in pain and/or anxiety among participants exposed to VR compared with control groups, whereas two studies found no significant differences. Across the included studies, VR interventions were generally well accepted by children, parents, and healthcare professionals, with only mild and transient adverse effects reported. However, substantial heterogeneity was observed regarding clinical settings, VR technologies, intervention protocols, and outcome assessment methods. The current evidence suggests that immersive VR is a promising adjunctive strategy for reducing pain and anxiety during pediatric phlebotomy procedures. Nevertheless, the available evidence remains limited by methodological heterogeneity and relatively small sample sizes. Future research should focus on larger, well-designed randomized controlled trials using standardized intervention protocols and outcome measures to support evidence-based implementation of VR in pediatric clinical practice. Full article
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25 pages, 1038 KB  
Systematic Review
The Latest Advances in Rosacea Treatment: A Systematic Review
by Anastazja Andrusiewicz, Sofiia Khimuk, Jakub Niżnik, Dmytro Sirko, Daniel Mijas and Danuta Nowicka
Pharmaceuticals 2026, 19(7), 982; https://doi.org/10.3390/ph19070982 (registering DOI) - 24 Jun 2026
Abstract
Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate [...] Read more.
Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate contemporary evidence regarding emerging and established treatment approaches for rosacea. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, and Web of Science were searched for studies published between 2016 and 2025. Original human studies evaluating therapeutic interventions for rosacea were included. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. Results: Fifteen studies involving 537 patients with rosacea and 77 controls (614 participants in total) met the eligibility criteria. Evaluated interventions included vascular-targeted therapies, topical anti-inflammatory agents, systemic and immunomodulatory treatments, and microbiome-oriented approaches. Oxymetazoline, pulsed-dye laser, platelet-rich plasma, ivermectin, azelaic acid, dapsone, sulfur preparations, and metronidazole demonstrated clinical benefits in reducing erythema, inflammatory lesions, or overall disease severity. Emerging therapies, including tofacitinib and oral ivermectin, showed promising results in refractory disease. Microbiome-related interventions, particularly Demodex-targeted therapies and Helicobacter pylori eradication, were also associated with clinical improvement. Risk-of-bias assessment identified two studies with low risk of bias, twelve with moderate risk of bias, and one study with high risk of bias. Conclusions: Current evidence supports a multimodal and mechanism-based approach to rosacea management, integrating vascular, inflammatory, immunological, and microbiological targets. However, the available evidence remains limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and a predominance of non-randomized study designs. Large, well-designed randomized controlled trials are needed to establish optimal evidence-based treatment strategies and define the long-term efficacy and safety of emerging therapies. Full article
(This article belongs to the Special Issue Drug Therapy for Autoimmune and Inflammatory Skin Conditions)
27 pages, 1090 KB  
Review
Management of Patients Diagnosed with Endometrial Hyperplasia: Comparison of Guidelines
by Stefano Restaino, Chiara Paglietti, Federico Paparcura, Bogani Giorgio, Capozzi Vito Andrea, Ursula Catena, Antonio Raffone, Maria Orsaria, Carlo Ronsini, Giuseppe Scibilia, Tommaso Simoncini, Diego Raimondo, Violante Di Donato, Muhammed Elhadi, Giampiero Capobianco, Ramon Rovira Negre, Anna Biasioli, Monica Della Martina, Mariuzzi Laura, Stefano Uccella, Andrea Ciavattini, Errico Zupi, Renato Seracchioli, Lorenza Driul, Paolo Scollo, Anna Miryam Perrone, Pierandrea De Iaco, Martina Arcieri, Francesco Fanfani, Giuseppe Vizzielli and on behalf of the Collaborative Groupadd Show full author list remove Hide full author list
Cancers 2026, 18(13), 2048; https://doi.org/10.3390/cancers18132048 (registering DOI) - 24 Jun 2026
Abstract
Endometrial hyperplasia (EH) is an estrogen-driven proliferative disorder with a measurable risk of progression to endometrial carcinoma. Although many guidelines have been issued over the years, clinical practice remains heterogeneous. In this paper, we aim to compare and summarize key recommendations and disagreements [...] Read more.
Endometrial hyperplasia (EH) is an estrogen-driven proliferative disorder with a measurable risk of progression to endometrial carcinoma. Although many guidelines have been issued over the years, clinical practice remains heterogeneous. In this paper, we aim to compare and summarize key recommendations and disagreements among major international guidelines for managing endometrial hyperplasia, focusing especially on conservative and fertility-sparing strategies. All guidelines align with some key principles: they all adopt the 2020 WHO classification, strongly prefer hysteroscopy-directed sampling, and recommend progestin therapy as the first-line treatment for non-atypical EH, favoring the levonorgestrel-releasing intrauterine system (LNG-IUS) over oral regimens. They designate total hysterectomy as definitive management for atypical hyperplasia/intraepithelial endometrial neoplasia (AEH/EIN) due to the substantial prevalence of concurrent carcinoma. Nevertheless, several key discrepancies appear, mainly concerning how long to continue progestin therapy and when to escalate treatment; and how intensively and for how long to conduct post-treatment surveillance. Variations in diagnostic and therapeutic protocols reflect evidence gaps and differences across healthcare settings. Future research should focus on harmonized outcomes, comparative studies of conservative strategies, and the integration of new pathology tools for personalized management. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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30 pages, 3324 KB  
Article
Ecological and Health Risk Assessment of Total Petroleum Hydrocarbons and Metals in Water Samples from Bille Mangrove, Niger Delta, Nigeria
by Onyinyechi G. Opara and Vsevolod V. Pavshintsev
Environments 2026, 13(7), 362; https://doi.org/10.3390/environments13070362 (registering DOI) - 24 Jun 2026
Abstract
Petroleum exploitation in the Niger Delta has caused widespread contamination of mangrove ecosystems, yet studies that integrate total petroleum hydrocarbons (TPH) and metals in mangrove water are still very limited. This study presents the first dual-pollutant baseline assessment of TPH and five priority [...] Read more.
Petroleum exploitation in the Niger Delta has caused widespread contamination of mangrove ecosystems, yet studies that integrate total petroleum hydrocarbons (TPH) and metals in mangrove water are still very limited. This study presents the first dual-pollutant baseline assessment of TPH and five priority metals (Cd, Cr, Pb, Ni, Zn) in Bille mangrove water, a severely oil-impacted system supporting about 50,000 residents. Water samples were collected from six sites along a contamination gradient (flow station, pipeline passage, old bunkering site) and analyzed for TPH (C8–C40) and metals. All concentrations are reported in mg/L for direct comparability with World Health Organization (WHO) drinking-water guidelines and United States Environmental Protection Agency (USEPA) thresholds. TPH concentrations ranged from 0.18 to 57.66 mg/L, with Site 3 (pipeline passage) showing levels about 320-fold higher than reference sites and exceeding the WHO drinking-water guideline (0.05 mg/L) by up to 1153-fold. Cadmium (0.040–0.350 mg/L) and nickel (0.055–0.561 mg/L) exceeded WHO drinking-water guidelines (Cd 0.003 mg/L; Ni 0.07 mg/L) by 13–117- and up to 8-fold, respectively. Health risk assessment, using USEPA Risk Assessment Guidance for Superfund (RAGS) protocols, revealed a total cancer risk of 4.15 × 10−3 at Site 3, 41-fold above the USEPA acceptable threshold of 1 × 10−4, and extreme non-carcinogenic risk (Hazard Index = 20.03–25.51) at petroleum-infrastructure sites; cadmium contributed 86–88% of both carcinogenic and non-carcinogenic effects. Ecological risk indices classified Site 3 as extreme (Potential Ecological Risk Index = 722, against the Håkanson PERI = 600 “very-high-risk” threshold), mainly driven by cadmium (Er = 310–350) and nickel (Er = 140–150). Source apportionment using the Carbon Preference Index, enrichment factors, and strong TPH–metal correlations (r > 0.88, p < 0.01) clearly identified petroleum operations as the dominant contamination source. This work demonstrates the critical importance of integrated multi-pollutant assessments in petroleum-degraded mangrove water for guiding environmental protection and public-health interventions. Full article
(This article belongs to the Special Issue Toxic and Potentially Toxic Metals and Their Health Risks)
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19 pages, 19132 KB  
Article
Chloroplast Genome Characterization, Comparative Analysis, and Phylogenetic Insights into Five Aegilops Species
by Shyryn Almerekova, Moldir Yermagambetova, Sayagul Turemuratova, Shynar Anuarbek, Minura Yessimbekova, Shun Sakuma and Yerlan Turuspekov
Int. J. Mol. Sci. 2026, 27(13), 5680; https://doi.org/10.3390/ijms27135680 (registering DOI) - 24 Jun 2026
Abstract
The genus Aegilops comprises important wild relatives of cultivated wheat and represents a valuable genetic resource for wheat improvement. In this study, the complete chloroplast genomes of five Aegilops species (Ae. crassa, Ae. cylindrica, Ae. juvenalis, Ae. tauschii, [...] Read more.
The genus Aegilops comprises important wild relatives of cultivated wheat and represents a valuable genetic resource for wheat improvement. In this study, the complete chloroplast genomes of five Aegilops species (Ae. crassa, Ae. cylindrica, Ae. juvenalis, Ae. tauschii, and Ae. triuncialis) collected from Kazakhstan and Uzbekistan were sequenced, assembled, and comparatively analyzed. The chloroplast genomes exhibited a conserved quadripartite structure consisting of a large single-copy (LSC), a small single-copy (SSC), and two inverted repeat (IR) regions. Genome sizes ranged from 135,612 to 136,840 bp, with an identical GC content of 38% across all species. Comparative analyses revealed high structural conservation among chloroplast genomes, particularly within IR regions, whereas greater sequence divergence was observed in the non-coding regions of the LSC and SSC. Sliding-window analysis identified several highly polymorphic regions, including rpl32-trnL(UAG), ndhF-rpl32, trnC(GCA)-rpoA, psbA, and ndhD, which may serve as potential DNA barcodes and informative markers for phylogenetic studies. A total of 850 chloroplast simple sequence repeats (SSRs) were detected, predominantly A/T-rich mononucleotide repeats. Codon usage analysis demonstrated a conserved preference for A/U-ending codons across all species. Ka/Ks analysis indicated that most chloroplast protein-coding genes are under strong purifying selection, although relatively elevated evolutionary rates were detected in rpoA and ycf4. Phylogenetic analyses based on complete chloroplast genomes strongly supported sectional relationships within Aegilops and confirmed close maternal relationships among several species. Overall, this study provides chloroplast genome resources for Aegilops and contributes to understanding chloroplast genome evolution, phylogeny, and molecular marker development. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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16 pages, 3049 KB  
Article
Structure, Stability, and Initial Transformation of Clusters (NiO2)n: A DFT Study Targeting Oxygen-Rich Intermediates in Nit-Kel-Oxygen Systems
by Joaquín Hernández-Fernández, Rafael González-Cuello and Rodrigo Ortega-Toro
Chemistry 2026, 8(7), 87; https://doi.org/10.3390/chemistry8070087 (registering DOI) - 23 Jun 2026
Abstract
The structure, relative stability, spin-state preference, and preliminary oxygen-release behavior of small nickel–oxygen clusters, (NiO2)n (n = 1–4), were investigated using density functional theory at the M06-2X/def2-TZVP level of theory. Several initial topologies and spin multiplicities were explored to [...] Read more.
The structure, relative stability, spin-state preference, and preliminary oxygen-release behavior of small nickel–oxygen clusters, (NiO2)n (n = 1–4), were investigated using density functional theory at the M06-2X/def2-TZVP level of theory. Several initial topologies and spin multiplicities were explored to distinguish between dissociated Ni···O2 solutions, bonded dioxo-like arrangements, and side-on metal–dioxygen motifs. For the monomer, the lowest-energy solution of the fully explored set corresponds to a non-bonded Ni···O2 arrangement; however, when the analysis is restricted to chemically bonded NiO2 minima, the linear high-spin O–Ni–O structure is the most stable configuration. The side-on η2-O2 motif was found as a higher-energy bonded minimum, retaining an elongated O–O bond and therefore representing an activated dioxygen-like species. ELF and LOL analyses were used as complementary localization descriptors to distinguish between the electronically separated oxo-like domains of the linear structure and the more coupled localization pattern of the side-on dioxygen adduct. Aggregation from n = 2 to n = 4 suggests a transition from compact bridged motifs to more open Ni–O frameworks. However, the size-dependent trend is discussed only within the explicitly explored conformational space. Preliminary analysis of O2 release from the tetramer indicates that oxygen evolution is not a simple dissociation event but involves substantial structural reorganization. Overall, the results support the view that small (NiO2)n clusters may behave as metastable oxygen-rich intermediates, while also highlighting the strong sensitivity of their energetic ordering to spin state, topology, and structural relaxation. Full article
(This article belongs to the Section Theoretical and Computational Chemistry)
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20 pages, 1976 KB  
Article
Drivers and Barriers of Wine Consumption Among Predominantly Young, Highly Educated Chinese Consumers: A Sociodemographic and Network Analysis
by Lin Zhu, Xinshu Jiang, Yulin Fang and Xiangyu Sun
Foods 2026, 15(13), 2253; https://doi.org/10.3390/foods15132253 (registering DOI) - 23 Jun 2026
Abstract
Understanding the drivers and barriers of wine consumption is of substantial importance for both market development and sensory science research, and this is particularly salient in rapidly changing non-Western markets. Young, highly educated Chinese consumers represent one of the fastest-growing segments in the [...] Read more.
Understanding the drivers and barriers of wine consumption is of substantial importance for both market development and sensory science research, and this is particularly salient in rapidly changing non-Western markets. Young, highly educated Chinese consumers represent one of the fastest-growing segments in the global wine market, yet large-scale studies of their consumption preferences and rejection patterns remain limited. This study aimed to characterize the conditional dependence structure of wine-consumption behavior in this population and to examine the associations between common consumption barriers and sociodemographic variables. A nationwide cross-sectional online survey collected 4823 valid responses. Non-parametric tests were used to compare sociodemographic groups, and a regularized Gaussian graphical model (GGM) was estimated to characterize the conditional associations among 15 consumption-behavior variables. The sample was dominated by young respondents (18–24 years) and individuals with higher education. The three most frequently endorsed barriers were taste aversion (51.1%), price sensitivity (38.7%), and lack of knowledge (19.6%). Age and education were the most central sociodemographic variables in the network. The knowledge barrier showed a moderate negative conditional association with education (partial r ≈ −0.171), whereas taste aversion—although the most frequently endorsed barrier—did not show clear conditional associations with sociodemographic variables in the network. Gender was not conditionally associated with any other variable in the network. These observations suggest that the three consumption barriers may operate through different network pathways and may therefore have different implications for intervention design, a possibility that warrants further confirmatory and longitudinal research. Full article
(This article belongs to the Section Sensory and Consumer Sciences)
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28 pages, 1053 KB  
Systematic Review
Intelligent Orthotics Technology in the Management of Diabetic Foot Ulcers and Knee Osteoarthritis: A Comprehensive Systematic Review
by Wissam Osman Soubra, Dennis John Cordato, Kaneez Fatima Shad and Sara Lal
Appl. Sci. 2026, 16(13), 6301; https://doi.org/10.3390/app16136301 (registering DOI) - 23 Jun 2026
Abstract
Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables [...] Read more.
Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article
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21 pages, 2785 KB  
Article
Role of Organ-Specific Endothelial Cells in Melanoma Adhesion Patterns
by Marwa Hamdan, István Szász, Tünde Várvölgyi, Margit Balázs and Viktória Koroknai
Biomedicines 2026, 14(7), 1409; https://doi.org/10.3390/biomedicines14071409 (registering DOI) - 23 Jun 2026
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Abstract
Background: The metastatic dissemination of melanoma involves adhesion of circulating tumor cells within organ-specific vascular beds; however, the relative contribution of the endothelial environment versus that of the melanoma-intrinsic molecular state remains unclear. Materials and Methods: We quantified the in vitro [...] Read more.
Background: The metastatic dissemination of melanoma involves adhesion of circulating tumor cells within organ-specific vascular beds; however, the relative contribution of the endothelial environment versus that of the melanoma-intrinsic molecular state remains unclear. Materials and Methods: We quantified the in vitro adhesion of primary (n = 5) and metastatic (n = 3) melanoma cell lines to human hepatic, brain, and pulmonary endothelial cells under co-culture conditions, and we profiled the expression of 86 adhesion- and extracellular-matrix-related genes in melanoma and endothelial cells. Results: Adhesion was highest for the hepatic endothelium, intermediate for the pulmonary endothelium, and lowest for the brain endothelium. This endothelial preference was conserved in both primary and metastatic melanoma cells, though metastatic cells exhibited higher absolute adhesion. The linear mixed-effect models revealed that the effects of adhesion state on melanoma gene expression were modest and varied by endothelial type, whereas melanoma origin had more widespread and larger effects (mean absolute standardized coefficients of 0.32–0.47 versus 0.60–0.87, respectively). The expression of three genes (SPP1, ITGA11, and MMP2) was associated with melanoma origin in all endothelial types. Spearman’s co-expression analysis revealed endothelial-type-specific gene networks, and within-sample permutation confirmed the non-random coordination in all three endothelial types. Conclusions: Our findings support a model in which endothelial organ specificity contributes to melanoma cell adhesion behavior and associated transcriptional patterns, highlighting the importance of the vascular interface as a biologically active mediator of early metastatic cell–endothelium interactions. Full article
(This article belongs to the Special Issue Advanced Research in Melanoma Metastasis)
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2 pages, 129 KB  
Abstract
Multisubstance Screening Supports a High-Throughput Zebrafish Thigmotaxis Assay for One Health-Oriented Neurotoxicity Assessment
by Monica Torres-Ruiz, María Muñoz-Palencia, Laura Sánchez-Ramos, Ana I. Cañas-Portilla and Antonio de la Vieja
Proceedings 2026, 146(1), 107; https://doi.org/10.3390/proceedings2026146107 (registering DOI) - 22 Jun 2026
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Abstract
Introduction: Aquatic contaminants can alter fish behavior before overt toxicity becomes evident, making neurobehavioral endpoints relevant for ecosystem protection and for hazard prioritization within a One Health framework. We recently developed a high-throughput visual-acoustic zebrafish larval thigmotaxis assay in which edge preference is [...] Read more.
Introduction: Aquatic contaminants can alter fish behavior before overt toxicity becomes evident, making neurobehavioral endpoints relevant for ecosystem protection and for hazard prioritization within a One Health framework. We recently developed a high-throughput visual-acoustic zebrafish larval thigmotaxis assay in which edge preference is interpreted as an anxiety-like behavioral endpoint, thereby adding spatial phenotyping beyond conventional locomotion metrics. Objective: To evaluate assay performance in a multisubstance screening challenge and determine whether it can discriminate distinct behavioral fingerprints without prior knowledge of chemical identity. Methodology: Zebrafish larvae were exposed for 1 h at 120 hpf. For each substance, 24 larvae were tested per condition, with six concentrations per substance, plus positive and negative controls. Larvae were challenged using alternating light/dark and tapping/quiet paradigms. The primary endpoint was the percentage of time spent at the edge as a proxy for anxiety-like behavior, while total distance and mean total velocity when moving were used as contextual locomotor metrics; edge distance and edge velocity were used as supportive spatial metrics. Data from 37 substances were analyzed through a standardized automated workflow. Results: Controls performed as expected and supported assay stability across runs. The chemical screening revealed heterogeneous but reproducible behavioral fingerprints. Seven substances produced weak/minimal acute responses, ten showed predominantly suppressive profiles, three predominantly activating profiles, nine showed prominent thigmotaxis-specific anxiety-like signals not explained by locomotion alone, and eight displayed mixed or stimulus-dependent patterns, including non-monotonic responses. Several substances altered edge preference while distance and velocity changed less, differently, or in the opposite direction, indicating behavioral reorganization rather than simple hypo- or hyperactivity. The multi-stimulus design was critical because some effects were evident only under specific sensory contexts. Conclusions: The multisubstance challenge supports the discriminatory capacity, robustness, and added value of the assay for high-throughput neurobehavioral screening. By capturing anxiety-like behavior through thigmotaxis and complementing it with locomotor context, the method improves phenotypic resolution for aquatic pollution assessment and offers a sensitive fish-based NAM to prioritize chemicals of concern for both environmental and human health-oriented testing strategies. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
18 pages, 1148 KB  
Systematic Review
Torque Teno Virus (TTV) Plasma Load and Immune Reconstitution in People Living with HIV: A Systematic Review
by Federico Cesanelli, Ottavia Nozza, Martina Salvi, Maria Alberti, Irene Scarvaglieri, Giorgio Tiecco, Francesca Mosti, Maria Antonia De Francesco and Eugenia Quiros-Roldan
Microorganisms 2026, 14(6), 1386; https://doi.org/10.3390/microorganisms14061386 (registering DOI) - 22 Jun 2026
Viewed by 99
Abstract
Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load [...] Read more.
Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load in PLWH, focusing on its relationship with immunological markers. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus in January 2026 to identify studies assessing plasma TTV viral load before and/or during ART and reporting immunological outcomes. Eligible studies included prospective and retrospective longitudinal studies, cross-sectional studies, and mixed designs assessing plasma TTV viral load in relation to ART status and immune recovery markers. Results: Thirteen studies (n = 1700 PLWH) were included, predominantly observational and conducted in adult populations. Most studies (76.9%) reported a significant inverse association between TTV viral load and CD4 T-cell count, while all studies assessing HIV viral load found a direct correlation with TTV levels. An inverse relationship with the CD4/CD8 ratio was consistently observed where evaluated. Higher TTV loads were reported in ART-naïve individuals and in those with advanced immunosuppression, with longitudinal studies indicating a general decline during ART. Overall, methodological heterogeneity and moderate risk of bias were common. Conclusions: TTV viral load shows a consistent inverse association with CD4 cell count and may reflect global immune dysfunction in PLWH beyond conventional markers. However, its clinical utility remains investigational due to the heterogeneity in the study design, limited data on longitudinal dynamics, and lack of standardized assays and thresholds. Full article
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17 pages, 948 KB  
Review
Surgical and Transcatheter Approach of a Failed Mitral Valve Repair: A Comprehensive Review on Selecting the Most Suitable Approach
by Roberto Nerla, Martina Mandas, Gianluca Pillitteri, Elisa Mikus, Niki Bernardoni, Angelo Squeri, Davide Pacini, Carlo Savini and Fausto Castriota
J. Clin. Med. 2026, 15(12), 4847; https://doi.org/10.3390/jcm15124847 (registering DOI) - 22 Jun 2026
Viewed by 147
Abstract
Mitral valve regurgitation is the second most common valvular heart disease in Europe, and an estimated 10% of individuals older than 75 years have severe mitral regurgitation. Mitral valve repair is the preferred strategy to treat mitral regurgitation and is associated with better [...] Read more.
Mitral valve regurgitation is the second most common valvular heart disease in Europe, and an estimated 10% of individuals older than 75 years have severe mitral regurgitation. Mitral valve repair is the preferred strategy to treat mitral regurgitation and is associated with better outcomes than mitral valve replacement. Despite the proven efficacy of surgical repair, available data in functional aetiologies reported a non-negligible rate of echocardiographically detected severe mitral regurgitation within ten years of the index procedure, in some cases resulting in redo interventions. Data on the optimal management of patients with failed mitral repair remain limited. The aim of this review is to present the available approaches for treating failed mitral valve repair and to describe criteria for selecting the most appropriate strategy on the basis of the underlying mechanism of repair failure, with respect to possible surgical re-repair and novel transcatheter edge-to-edge repair techniques in the presence of favourable mitral valve anatomies. Full article
(This article belongs to the Special Issue Clinical Therapeutic Advances of Mitral Regurgitation)
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17 pages, 8255 KB  
Article
Global Postural Re-Education Versus Deep Neck Flexor Activation on Chronic Nonspecific Neck Pain with Forward Head Posture
by Huda B. Abd Elhamed, Esraa Ahmed Mohamed Ahmed, Enas Fawzy Youssif, Amr M. Yehia, Mohamed A. Abdel Ghafar, Safaa M. Elkholi and Shahesta Ahmed Osama
J. Clin. Med. 2026, 15(12), 4833; https://doi.org/10.3390/jcm15124833 (registering DOI) - 22 Jun 2026
Viewed by 157
Abstract
Background and Objectives: Chronic nonspecific neck pain (NSNP) is among the most common musculoskeletal disorders. Global postural re-education (GPR) might be effective in decreasing neck pain (NP) and dysfunction and improving forward head posture (FHP) by recovering muscle chains and reducing postural [...] Read more.
Background and Objectives: Chronic nonspecific neck pain (NSNP) is among the most common musculoskeletal disorders. Global postural re-education (GPR) might be effective in decreasing neck pain (NP) and dysfunction and improving forward head posture (FHP) by recovering muscle chains and reducing postural alteration. Deep neck flexor activation (DNF) might also decrease NP and improve FHP by improving DNF endurance. This study aimed to compare the effects of GPR versus DNF activation on pain, dysfunction, FHP, and DNF endurance. Materials and Methods: Forty-six physiotherapy students with chronic NSNP participated in this non-randomized comparative study and were allocated into two equal groups based on their availability and preference regarding session duration. Group A underwent GPR exercises combined with active neck exercises, whereas group B received DNF activation in addition to active neck exercises. All participants were assessed pre- and post-intervention for pain intensity using a visual analog scale (VAS), neck disability using the Arabic version of the neck disability index (NDI), FHP via a photometric method with Kinovea software, and DNF endurance using pressure biofeedback. Results: A significant effect of both treatments was reported on reducing pain intensity, improving the FHP and enhancing the neck functional status with no substantial differences between both groups. A significant improvement in DNF endurance was observed in both groups, with substantially higher values between groups in favor of the DNF group. Conclusions: Both GPR and DNF activation exercises were associated with reductions in pain and improvements in neck disability among physiotherapy students with chronic NSNP and FHP. Also, both CVA and DNF endurance improved, with more improvement observed in DNF endurance in the DNF group compared with the GPR group. Full article
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14 pages, 1491 KB  
Article
Epidemiological and Virological Characteristics of H9N2 Avian Influenza Virus in Jiangsu Province, China, 2024
by Xue Gao, Huiyan Yu, Na Zhang, Liqi Liu, Jing Tong, Xian Qi, Haodi Huang, Shenjiao Wang, Zi Li, Yangguang Du and Liguo Zhu
Viruses 2026, 18(6), 687; https://doi.org/10.3390/v18060687 (registering DOI) - 20 Jun 2026
Viewed by 287
Abstract
H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic [...] Read more.
H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended. Full article
(This article belongs to the Section Animal Viruses)
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24 pages, 9401 KB  
Article
Non-Contact Ultrasonic Assessment of Corrosion in Steel Specimens
by Lukas Peterson, Andrei Zagrai, ThankGod Nwokocha and T. David Burleigh
Sensors 2026, 26(12), 3923; https://doi.org/10.3390/s26123923 (registering DOI) - 20 Jun 2026
Viewed by 204
Abstract
Ultrasonic thickness resonance can be effectively used to detect and quantify the level of corrosion in steel nuclear storage containers as well as other corrosion-prone thin-walled structures, such as pipes and storage tanks. Electro-Magnetic Acoustic Transducers (EMATs) have several advantages over more traditional [...] Read more.
Ultrasonic thickness resonance can be effectively used to detect and quantify the level of corrosion in steel nuclear storage containers as well as other corrosion-prone thin-walled structures, such as pipes and storage tanks. Electro-Magnetic Acoustic Transducers (EMATs) have several advantages over more traditional piezoelectric-based transducers; namely, they can be used in a non-contact fashion on robotic platforms, allowing for measurements regardless of surface conditions or temperature. The major challenge of EMAT application is the power required to counteract the low actuation efficiency, which is achieved with a high-power ultrasonic pulse generator and a transformer circuit. Resonance techniques, in which most of the energy is concentrated near structural resonance frequencies, are preferable to improve efficiency of electro-magnetic acoustic measurements. This methodology was applied to 316L stainless steel thin plates subjected to uniform corrosion as well as pitting corrosion imitating different damage scenarios in a nuclear waste container. The resonant peak frequency shift was found to be proportional to the severity of corrosion for minimally corroded samples. However, the complete disappearance of the resonance peak was observed in the samples with severe corrosion damage. The EMAT liftoff distance was studied to quantify its effect on the amplitude, spread, and frequency of resonant peaks. Recommendations for use of EMATs for assessing corrosion damage are presented. The study demonstrates the success of frequency-based detection of corrosion damage in 316L stainless steel used in fabrication of nuclear waste storage containers. Full article
(This article belongs to the Special Issue Novel Sensors for Structural Health Monitoring: 2nd Edition)
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