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18 pages, 3022 KB  
Article
Integrating Pretreatment Circulating Tumor HPV DNA and Tumor Volume for Risk Stratification in HPV-Positive Oropharyngeal Squamous Cell Carcinoma
by Lin Zhu, Chunying Shen, Wei Qian, Peiyao Liu, Tingting Xu, Huijuan Liu, Xin Zhou and Xueguan Lu
Cancers 2026, 18(14), 2194; https://doi.org/10.3390/cancers18142194 - 8 Jul 2026
Abstract
Background: Circulating tumor HPV DNA (ctHPV DNA) has shown clinical value in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), but its relationship with tumor burden and its role in prognosis, especially when combined with clinicoradiological factors, remain to be further defined. Methods: We analyzed [...] Read more.
Background: Circulating tumor HPV DNA (ctHPV DNA) has shown clinical value in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), but its relationship with tumor burden and its role in prognosis, especially when combined with clinicoradiological factors, remain to be further defined. Methods: We analyzed 103 patients with HPV-positive OPSCC enrolled in an observational biomarker study, most of whom received induction chemotherapy or chemoimmunotherapy followed by definitive radiotherapy. Blood samples were collected at pretreatment, post-radiotherapy, and follow-up time points, and ctHPV DNA levels were quantified using droplet digital PCR. Baseline clinicoradiological parameters from contrast-enhanced MR or CT and 18F-FDG PET/CT were analyzed for their association with ctHPV DNA levels and clinical outcomes. Results: Baseline ctHPV DNA correlated with primary tumor volume (VT), nodal volume (VN), total tumor volume (VT+N), and the number of involved primary tumor sites and lymph node regions, particularly LN-related features. VT and maximum LN diameter were independent predictors of baseline ctHPV DNA. Detectable follow-up ctHPV DNA was associated with inferior progression-free survival but showed low sensitivity and positive predictive value for relapse detection. Integrative stratification using baseline ctHPV DNA and VT+N identified a potential high-risk subgroup with high tumor volume but paradoxically low ctHPV DNA (VOLhighDNAlow). Exploratory RNA-seq analysis was performed to investigate potential biological features underlying this discordance, and a seven-gene signature associated with PFS was identified. Conclusions: These findings suggest that baseline ctHPV DNA reflects tumor burden and may provide additional information for upfront risk stratification in HPV-positive OPSCC, warranting further validation in larger prospective cohorts. Full article
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14 pages, 771 KB  
Article
Peripheral Blood Lymphocyte-Gated Flow Cytometry Parameters and 24-Month Mortality in COPD: An Exploratory Cohort Study
by Onur Çelik, Adil Furkan Kılıç, Konca Altınkaynak and Dursun Erol Afşin
J. Clin. Med. 2026, 15(14), 5333; https://doi.org/10.3390/jcm15145333 - 8 Jul 2026
Abstract
Background: Chronic obstructive pulmonary disease (COPD) is associated with substantial long-term morbidity and mortality. Peripheral blood flow cytometry may provide exploratory information regarding immune-cell distributions and activation-related markers. However, careful interpretation is required when flow cytometry outputs are derived from lymphocyte-gated percentages [...] Read more.
Background: Chronic obstructive pulmonary disease (COPD) is associated with substantial long-term morbidity and mortality. Peripheral blood flow cytometry may provide exploratory information regarding immune-cell distributions and activation-related markers. However, careful interpretation is required when flow cytometry outputs are derived from lymphocyte-gated percentages rather than marker-specific mean fluorescence intensity or sequential lineage-confirmed gating. We investigated whether specific lymphocyte-gated flow cytometry parameters are associated with mortality during follow-up in COPD patients. Methods: In this single-center observational cohort study, 51 consecutive clinically stable outpatients with COPD were enrolled in November 2023 and followed for 24 months. Baseline peripheral blood flow cytometry results were verified against archived original instrument reports. The principal exploratory flow cytometry-derived variables were CD45/SSC-defined lymphocyte-gate percentage and lymphocyte-gated CD138+ events; HLA-DR positivity was evaluated as a secondary exploratory variable. Group comparisons and descriptive receiver operating characteristic (ROC) analyses were performed. Multiplicity was assessed using a hierarchical Benjamini–Hochberg false discovery rate (FDR) framework that separated the two biologically prioritized principal variables from the remaining exploratory screening variables. For transparency, a more conservative pooled FDR correction across all ten flow cytometry-derived variables was also reported. A two-variable analysis was performed only as exploratory signal aggregation, with descriptive internal assessment using leave-one-out cross-validation (LOO-CV) and bootstrap optimism correction. Results: During the 24-month follow-up, 13 of 51 patients died (25.5%). In unadjusted analyses, non-survivors had lower arterial oxygen tension and nominally lower CD45/SSC-defined lymphocyte-gate percentages (median 13.08% vs. 22.63%, p = 0.008) and lymphocyte-gated CD138+ event percentages (median 0.07% vs. 0.39%, p = 0.026) than survivors. Within the hierarchical analytical-family framework, both CD45/SSC-defined lymphocyte-gate percentage and lymphocyte-gated CD138+ events retained significance in the principal-variable family (within-family q = 0.016 and 0.026), whereas no secondary-family parameter, including HLA-DR (within-family q = 0.50), did; significance was not retained under a single correction across all ten parameters (CD45 q = 0.081; CD138 q = 0.129). Descriptive AUCs were 0.749 for CD45/SSC-defined lymphocyte-gate percentage and 0.710 for CD138+ events. The two-variable signal-aggregation analysis yielded an apparent AUC of 0.858, an LOO-CV AUC of 0.796, and a bootstrap optimism-corrected AUC of 0.832. NLR was available for all 51 patients; NLR-adjusted analyses did not establish clinical incremental utility. Conclusions: Lower CD45/SSC-defined lymphocyte-gate percentage and lower lymphocyte-gated CD138+ event percentage showed within-cohort associations with 24-month mortality in this small COPD cohort. These observations should be regarded solely as hypothesis-generating signals. Neither principal finding was retained after pooled correction across all ten flow cytometry-derived parameters, and no incremental prognostic value beyond routine inflammatory indices or established clinical predictors was demonstrated. External validation was absent; prospective replication in larger, appropriately adjusted cohorts is required. Full article
(This article belongs to the Section Respiratory Medicine)
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16 pages, 258 KB  
Article
Association of Clinical, Radiological, and Procedural Characteristics with NIHSS at Discharge and 90-Day Modified Rankin Scale Outcomes in Individuals with Stroke Treated with Mechanical Thrombectomy
by Damljan Bogićević, Filip Vitošević, Marjana Vukićević, Anđela Gogić, Vojin Kovačević and Aleksandar Ćirović
Diagnostics 2026, 16(14), 2137; https://doi.org/10.3390/diagnostics16142137 - 8 Jul 2026
Abstract
Background: This study aimed to evaluate associations between baseline clinical status, radiological findings, prior medical history, procedural characteristics, and recanalization success with neurological outcome at discharge (NIHSS) and functional status at 90 days (mRS). Methods: This single-center retrospective study included 100 consecutive patients [...] Read more.
Background: This study aimed to evaluate associations between baseline clinical status, radiological findings, prior medical history, procedural characteristics, and recanalization success with neurological outcome at discharge (NIHSS) and functional status at 90 days (mRS). Methods: This single-center retrospective study included 100 consecutive patients with acute ischemic stroke treated with MT within 24 h of symptom onset. Clinical data, CT perfusion parameters, comorbidities, prior therapies, and detailed procedural characteristics (including anesthesia type, recanalization grade, blood pressure variability, hemorrhagic transformation, and procedure duration) were analyzed. Nonparametric tests (Mann–Whitney U, Kruskal–Wallis) and Spearman’s rank correlation were applied. Statistical significance was set at p < 0.05. Results: Early ischemic signs on baseline imaging were associated with higher NIHSS scores at discharge and worse 90-day mRS (p < 0.05). Patients undergoing CT perfusion imaging had higher discharge NIHSS. Admission NIHSS showed a moderate positive correlation with discharge NIHSS (rho = 0.367, p = 0.003). Strong correlations were observed between NIHSS at 24 h and discharge NIHSS (rho = 0.802, p < 0.001), as well as between 24 h NIHSS and 90-day mRS (rho = 0.842, p < 0.001). Successful recanalization was significantly associated with long-term outcomes, with mTICI 3 associated with the lowest 90-day mRS scores (p = 0.003). Intraprocedural blood pressure variability, hemorrhagic transformation, infections, and in-hospital complications were all linked to higher 90-day mRS values. Prolonged procedure duration showed a weak but significant correlation with worse 90-day outcome (rho = 0.232, p = 0.020). In contrast, prior comorbidities and pre-stroke therapy were not significantly associated with outcomes. A multivariable binary logistic regression analysis identified only the NIHSS score at 24 h remained as an independent predictor of favorable functional outcome at 90 days. Conclusions: Baseline stroke severity, early neurological evolution, successful reperfusion, procedural hemodynamic stability, and prevention of in-hospital complications are strongly associated with both early neurological recovery and long-term functional outcome after mechanical thrombectomy. Full article
19 pages, 5080 KB  
Article
Effects of Plant Invasion Along Environmental Gradients on Native Plant Communities in the Ertix River Basin Wetlands
by Xuan-Ming Chen, Ying-Fei Zhao, Michael Opoku Adomako, Hai-Chao Chang, Mu-Yao Li, Jun-Qin Gao, Bi-Cheng Dong, Mai-He Li and Fei-Hai Yu
Diversity 2026, 18(7), 411; https://doi.org/10.3390/d18070411 - 6 Jul 2026
Abstract
Biological invasions and environmental gradients are major drivers of biodiversity change in wetland ecosystems, but their associations on native plant diversity in Central Asian riverine wetlands remain poorly understood. We surveyed 158 wetland plant communities across 54 transects in the Ertix River Basin [...] Read more.
Biological invasions and environmental gradients are major drivers of biodiversity change in wetland ecosystems, but their associations on native plant diversity in Central Asian riverine wetlands remain poorly understood. We surveyed 158 wetland plant communities across 54 transects in the Ertix River Basin to examine how environmental gradients (elevation, mean annual temperature [MAT], and mean annual precipitation [MAP]) and non-native plant establishment jointly related to native plant importance values and alpha diversity indices. Non-native plants were classified according to invasion stage—non-naturalized, naturalized, and invasive—to elucidate how the associations between alien plants and native communities shift dynamically along the invasion continuum. Elevation emerged as the dominant predictor, explaining 82% (individual R2 = 0.15) of the variance in native species richness and 63.37% (individual R2 = 0.1) of the variance in the Shannon–Wiener diversity index, while MAT and MAP were not retained as significant predictors in the optimal models. Native plant importance values, richness, and diversity all increased with elevation. Unexpectedly, naturalized plant richness and abundance were positively associated with native diversity metrics, contrasting with the negative associations of all non-native categories (non-naturalized, naturalized, and invasive) on native importance values, partly reflecting the compositional nature of this metric. Our results reveal positive co-occurrence patterns between early-stage naturalized species and native species, but native dominance may eventually decline as invasion intensity increases. These findings highlight the importance of considering invasion stage when predicting wetland biodiversity responses to biological invasions under environmental heterogeneity. Full article
(This article belongs to the Section Plant Diversity)
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35 pages, 40681 KB  
Article
The Role of ULK3 in Cancer Progression: A Pan-Cancer Bioinformatics Analysis Integrated with Experimental Validation in Prostate Cancer
by Yangyang Han, Mengqi Zhang, Mannizire Rehemujiang, Xintong Li, Yimin Liu, Niuniu Zhang, Meng Sun, Yunbo Zhang, Ayshamgul Hasim and Mengjia Li
Int. J. Mol. Sci. 2026, 27(13), 6040; https://doi.org/10.3390/ijms27136040 - 5 Jul 2026
Viewed by 160
Abstract
Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely [...] Read more.
Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article
(This article belongs to the Special Issue Genetic and Molecular Markers in Prostate Cancer)
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11 pages, 522 KB  
Article
Predicting Oral Food Challenge Outcomes in Children with Suspected Cow’s Milk Allergy: Clinical Utility of Casein-Specific IgE and Skin Test Ratios
by Filiz Demir Şahin, Hilal Şahin Sindi, Ozan Kapçay and Mehmet Kılıç
Nutrients 2026, 18(13), 2187; https://doi.org/10.3390/nu18132187 - 5 Jul 2026
Viewed by 104
Abstract
Background: To investigate the diagnostic value of the SPT-to-histamine ratio, casein-specific immunoglobulin E (IgE), and cow’s milk-specific IgE in predicting oral food challenge (OFC) positivity in children with suspected cow’s milk allergy. Methods: In this single-center retrospective observational study, 126 children evaluated for [...] Read more.
Background: To investigate the diagnostic value of the SPT-to-histamine ratio, casein-specific immunoglobulin E (IgE), and cow’s milk-specific IgE in predicting oral food challenge (OFC) positivity in children with suspected cow’s milk allergy. Methods: In this single-center retrospective observational study, 126 children evaluated for suspected cow’s milk allergy who underwent OFC between January 2019 and July 2024 at a tertiary pediatric allergy and immunology center were included. Demographic and clinical characteristics, SPT parameters, and laboratory biomarkers were analyzed. Discriminatory performance was assessed using receiver operating characteristic (ROC) analysis, and independent predictors were identified using multivariable logistic regression. Results: OFC was positive in 66 patients (52.4%). Casein-specific IgE demonstrated strong discriminatory performance (AUC = 0.878), with 80.3% sensitivity and 85.0% specificity at a cutoff value of ≥2.55 kUA/L. The SPT-to-histamine ratio showed moderate discriminatory performance (AUC = 0.758). In multivariable analysis, only casein-specific IgE remained an independent predictor of OFC positivity (adjusted OR = 1.317, p < 0.001). Conclusions: Casein-specific IgE is a strong independent predictor of OFC positivity. Although SPT-derived ratios may provide complementary diagnostic information, their independent predictive contribution appears limited. These findings support the role of component-resolved diagnostics in pre-challenge risk stratification. Full article
(This article belongs to the Section Pediatric Nutrition)
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35 pages, 6978 KB  
Article
Assessment of the Forces Developed During Orthodontic Treatment Using the Finite Element Method
by Maria Manuela Nardin, Mihaela-Roxana Brătoiu, Cristina Teodora Preoteasa, Diana-Elena Vlăduțu, Dragoș Laurențiu Popa, Alexandra Elena Done, Anne Marie Rauten, Felicia Ileana Mărășescu, Luminița Dăguci and Veronica Mercuț
Dent. J. 2026, 14(7), 406; https://doi.org/10.3390/dj14070406 (registering DOI) - 4 Jul 2026
Viewed by 103
Abstract
Background/Objectives: This “in silico” study investigated the biomechanical behavior of fixed orthodontic systems by analyzing the forces generated by Ni–Ti archwires and their effects on the dento-maxillary system (DMS). The objectives were to estimate force levels for 0.012″, 0.014″, and 0.016″ archwires and [...] Read more.
Background/Objectives: This “in silico” study investigated the biomechanical behavior of fixed orthodontic systems by analyzing the forces generated by Ni–Ti archwires and their effects on the dento-maxillary system (DMS). The objectives were to estimate force levels for 0.012″, 0.014″, and 0.016″ archwires and to evaluate the resulting stress distribution, displacement and deformation, including the influence of dental malpositions such as infraposition and linguoposition on force transmission. Methods: A three-dimensional (3D) patient-specific model of the DMS was developed and finite element analysis (FEM) was performed. Orthodontic forces were determined analytically based on archwire deformation and applied as equivalent force systems at the bracket level. The analysis was performed under simplified assumptions, including linear elastic material behavior and the absence of bracket–archwire friction. Results: The results indicated a direct relationship between archwire diameter and force magnitude. Increased diameter was associated with higher stress, displacement and deformation values. Simulated infraposition and linguoposition produced localized variations in stress distribution, highlighting the influence of tooth position on biomechanical response. Conclusions: Within the limitations of the simplified analytical and numerical model, archwire diameter plays a significant role in determining force magnitude and stress distribution in orthodontic systems. The findings provide a comparative framework for understanding force transmission, although the results should be interpreted as theoretical estimates under idealized conditions rather than direct predictors of clinical behavior. Full article
11 pages, 509 KB  
Article
Positive-Pressure Extubation Improves Early Oxygenation but Not Desaturation After Cesarean Delivery Under General Anesthesia: A Randomized Controlled Trial
by Nurdan Yılmaz and Yaşar Gökhan Gül
Healthcare 2026, 14(13), 1991; https://doi.org/10.3390/healthcare14131991 - 4 Jul 2026
Viewed by 138
Abstract
Background/Objectives: Extubation technique, postoperative oxygenation, and hypoxemia are critical determinants of respiratory outcomes after general anesthesia. This study evaluated whether positive-pressure extubation improves early postoperative oxygenation and reduces desaturation in patients undergoing cesarean delivery. Methods: In this prospective randomized controlled trial, [...] Read more.
Background/Objectives: Extubation technique, postoperative oxygenation, and hypoxemia are critical determinants of respiratory outcomes after general anesthesia. This study evaluated whether positive-pressure extubation improves early postoperative oxygenation and reduces desaturation in patients undergoing cesarean delivery. Methods: In this prospective randomized controlled trial, 120 participants were randomly assigned to positive-pressure or suction extubation. The primary outcome was postoperative desaturation (SpO2 < 92%) within 60 min after extubation. Secondary outcomes included early post-extubation oxygenation and hemodynamic parameters. Multivariable logistic regression was used to identify independent predictors of desaturation. The trial was registered at ClinicalTrials.gov (NCT07251686. Results: Postoperative desaturation occurred in 13.3% of patients in the positive-pressure group and 20% in the suction group (p = 0.327). Mean SpO2 values were significantly higher in the positive-pressure group at 0, 5, and 10 min after extubation (p < 0.01), but were similar at later time points. Extubation technique was not independently associated with desaturation (OR 0.69, 95% CI 0.24–1.98; p = 0.491). Conclusions: Positive-pressure extubation improves early postoperative oxygenation but does not reduce clinically relevant desaturation compared with suction extubation. Overall postoperative respiratory outcomes were comparable between the two techniques in this low-risk obstetric population. Full article
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15 pages, 270 KB  
Article
Association Between Isometric Hip Muscle Strength and Y-Balance Test Performance in Healthy Adults
by Dragana Rasic, Kristijan Zulle, Bojan Miletic and Hrvoje Vlahovic
J. Clin. Med. 2026, 15(13), 5170; https://doi.org/10.3390/jcm15135170 - 2 Jul 2026
Viewed by 98
Abstract
Background/Objectives: Dynamic balance during the Y-Balance Test (YBT) relies on coordinated multi-joint control of the lower extremity. Although hip muscle strength is considered important for YBT performance, the relative contribution of individual hip muscle groups remains insufficiently understood. This study aimed to [...] Read more.
Background/Objectives: Dynamic balance during the Y-Balance Test (YBT) relies on coordinated multi-joint control of the lower extremity. Although hip muscle strength is considered important for YBT performance, the relative contribution of individual hip muscle groups remains insufficiently understood. This study aimed to examine the associations between isometric hip abduction, external rotation, and extension strength and YBT performance in healthy adults. Methods: In this cross-sectional study, 104 healthy adults underwent assessment of isometric hip abduction, external rotation, and extension strength using strap-stabilized handheld dynamometry. Hip extension strength was measured in the prone position with the knee flexed to 90°. Strength values were normalized and expressed as joint torque (Nm/kg). YBT performance was assessed in the anterior, posteromedial, and posterolateral directions and as a composite score. Associations were examined using Pearson correlation coefficients. To account for the dependency of bilateral measurements, a linear mixed model (LMM) was used to evaluate the collective and independent contribution of hip strength components to YBT performance, with sex, age, and BMI included as covariates. Results: All hip strength measures showed significant positive correlations with YBT performance (r = 0.19–0.49, p < 0.05). Hip extension strength demonstrated the strongest associations, particularly with posterolateral reach (r = 0.49). After adjustment for demographic covariates, sex was the strongest predictor of YBT performance across all directions (β = 7.8–8.9, p < 0.001), with males achieving higher scores than females. Hip extension and abduction strength were significant predictors of posterolateral reach (p < 0.05), whereas no hip strength variable independently predicted anterior reach or composite score after adjustment for demographic factors. No significant differences in YBT performance were observed between limbs. Conclusions: Sex was the strongest predictor of YBT performance in healthy adults. Hip extension and abduction strength were independently associated with posterolateral reach performance after controlling for demographic factors, suggesting that the association between hip muscle strength and dynamic balance may be direction-specific. These findings highlight the importance of accounting for sex when interpreting the relationship between hip strength and YBT performance. Full article
(This article belongs to the Section Sports Medicine)
14 pages, 445 KB  
Article
Willingness to Pay for Pharmacist-Led Weight Management Services in Community Pharmacies: A Cross-Sectional Study in an Academic Medical Center in Saudi Arabia
by Saja H. Almazrou, Danah Alwakail, Felwah Almanea and Shiekha S. AlAujan
Healthcare 2026, 14(13), 1953; https://doi.org/10.3390/healthcare14131953 - 2 Jul 2026
Viewed by 149
Abstract
Background: Obesity is a growing public health crisis in Saudi Arabia. Community pharmacists are well-positioned to deliver accessible weight management services, but data on public willingness to pay (WTP) for these interventions remains limited. Aim: To assess the willingness of the Saudi Arabian [...] Read more.
Background: Obesity is a growing public health crisis in Saudi Arabia. Community pharmacists are well-positioned to deliver accessible weight management services, but data on public willingness to pay (WTP) for these interventions remains limited. Aim: To assess the willingness of the Saudi Arabian public to pay for community pharmacist-led weight management services and identify factors associated with WTP. Methods: A cross-sectional, face-to-face survey was conducted among adults in a medical city in Riyadh between October 2025 and January 2026. WTP was elicited using the Payment Card method based on a hypothetical pharmacist-led service scenario. Payment values were validated by an expert panel. Univariable and multivariable regression models were used to identify independent predictors of WTP and payment amounts. Results: Of 746 participants, 66% expressed willingness to pay for the service. The most frequently selected maximum payment was 50 SAR per session. Multivariable logistic regression revealed that WTP was significantly associated with younger age, higher monthly income, perceived usefulness of pharmacy services (aOR: 3.10; 95% CI: 1.83–5.26), frequent pharmacy visits, and prior or desired access to a dietitian. Clinical burden, including BMI and chronic conditions, did not significantly influence WTP. Among those willing to pay, male gender was independently associated with a lower stated payment amount compared to females (β = −3.8 SAR; p = 0.006). Conclusions: Among adults attending a large academic medical city in Riyadh, there is substantial willingness to pay for pharmacist-led weight management services, with perceived value and healthcare engagement as the primary drivers. These preliminary findings warrant replication in broader, nationally representative samples. Full article
(This article belongs to the Topic Advances in Chronic Disease Management)
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20 pages, 849 KB  
Article
Clinically Inferred Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Association with Atrial Fibrillation Subtypes: A Prospective Clinical and Cardiometabolic Analysis
by Monika Różycka-Kosmalska, Boguslawa Luzak and Marcin Kosmalski
Life 2026, 16(7), 1101; https://doi.org/10.3390/life16071101 - 30 Jun 2026
Viewed by 144
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to atrial fibrillation (AF); however, its relationship with specific AF subtypes remains unclear. This prospective, single-center, observational case–control study investigated whether MASLD is independently associated with AF presence and its subtypes. Materials: A [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to atrial fibrillation (AF); however, its relationship with specific AF subtypes remains unclear. This prospective, single-center, observational case–control study investigated whether MASLD is independently associated with AF presence and its subtypes. Materials: A total of 327 participants were analyzed, including 119 controls and 208 patients with AF. Comprehensive clinical history, anthropometric measures, laboratory testing, 24 h Holter ECG, and echocardiography were performed. Clinically inferred MASLD was defined according to the current EASL–EASD–EASO guidelines using clinical and non-invasive indices (Hepatic Steatosis Index, Fatty Liver Index, Fibrosis-4 Index). No liver biopsy or imaging confirmation of steatosis or fibrosis was performed, and therefore, the diagnosis represents a clinically inferred (“probable”) MASLD. To minimize systematic bias and improve baseline comparability between groups, propensity score matching and complementary regression analyses were applied. Results: Overall probable MASLD prevalence did not differ between AF and controls (42% vs. 44%, p = 0.742). A clear phenotypic gradient emerged across subtypes: lowest in permanent AF (PermAF, 27.1%) versus paroxysmal (47.1%) and persistent AF (51.4%) (p = 0.021). PermAF exhibited the most advanced comorbidity—highest CHF (78.6%), CKD (71.4%), HFpEF (48.6%), FIB-4 (median 2.67), the lowest TG/HDL–cholesterol ratio (1.93 vs. 3.32; p < 0.001), and progressive renal impairment. Statin therapy reached 80% in clinically inferred MASLD-positive PermAF. The elevated FIB-4 observed in PermAF must be interpreted with explicit caution: this group was substantially older (median 79.5 years) and carried the highest burden of chronic heart failure and chronic kidney disease; therefore, in this subgroup, FIB-4 most plausibly reflects age and cardio-renal comorbidity rather than histologically confirmed hepatic fibrosis. After matching, MASLD was not an independent predictor of AF presence (OR = 0.96; 95% CI: 0.59–1.46) or its clinical severity. Conclusions: Probable MASLD, defined by clinical and non-invasive indices, was not independently associated with AF in this cohort, but AF subtypes exhibited a clear phenotypic gradient—from a metabolically driven profile in early AF to a cardio-renal and fibrotic pattern in advanced, elderly AF. Elevated FIB-4 values in PermAF most plausibly reflect age and cardio-renal comorbidity rather than true histologically confirmed hepatic fibrosis. These findings support a phenotype- and population-dependent MASLD–AF relationship and underscore the need for imaging- and histology-verified longitudinal studies. Full article
18 pages, 715 KB  
Article
Exploratory Assessment of Pasture Forage Nutritive Value and Beef Cattle Productivity Across Contrasting Grazing Environments in Kazakhstan
by Aibyn Torekhanov, Talgat Karymsakov, Kanysh Kushenov, Meruyert Tastybay, Ainur Seitbattalova, Kanat Shanbaev and Erlan Kambarbekov
Agriculture 2026, 16(13), 1430; https://doi.org/10.3390/agriculture16131430 - 30 Jun 2026
Viewed by 168
Abstract
Pasture ecosystems are a key component of livestock production in arid and semi-arid regions, where forage availability and nutritive value are often associated with animal performance under grazing conditions. This study aimed to provide an exploratory assessment of pasture productivity, forage nutritive value, [...] Read more.
Pasture ecosystems are a key component of livestock production in arid and semi-arid regions, where forage availability and nutritive value are often associated with animal performance under grazing conditions. This study aimed to provide an exploratory assessment of pasture productivity, forage nutritive value, and beef cattle productivity across contrasting natural–climatic settings in Kazakhstan. The study was conducted under commercial production conditions on five farms representing different grazing environments during the 2024–2025 grazing seasons. Because each zone was represented by a single farm, the study should be interpreted as an observational assessment of farm-level patterns rather than as a fully replicated experimental comparison. Pasture productivity and forage chemical composition, including crude protein, fiber, and dry matter content, varied among farms and seasons. Average daily gain ranged from 316.7 to 900 g day−1 depending on the study site and year of observation. Exploratory statistical analyses indicated variability among the studied systems; however, pairwise comparisons did not reveal statistically significant differences in animal productivity among farms (p > 0.05). Correlation analyses revealed moderate positive associations between average daily gain, crude protein content, and pasture yield, although these relationships were not statistically significant after adjustment for multiple comparisons. Similarly, linear models incorporating forage nutritive value indicators and study site did not identify statistically significant predictors of animal productivity within the current dataset. Overall, the results describe patterns of variation in pasture characteristics and animal productivity observed under extensive grazing conditions in continental environments. Given the observational design and limited replication at the farm level, the findings should be interpreted cautiously and regarded as preliminary. The study provides baseline information for future investigations of pasture–livestock interactions in arid and semi-arid grazing environments. Full article
(This article belongs to the Section Farm Animal Production)
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13 pages, 488 KB  
Article
Subclinical Structural and Functional Retinal Alterations in Clinically Normal Myopic Eyes
by Enes Ozturk and Kuddusi Erkilic
J. Clin. Med. 2026, 15(13), 5094; https://doi.org/10.3390/jcm15135094 - 30 Jun 2026
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Abstract
Background/Objectives: To evaluate subclinical structural and functional retinal alterations in clinically normal myopic eyes using optical coherence tomography (OCT) and automated visual field analysis. Methods: This retrospective observational study included 109 patients aged 18–42 years categorized according to spherical refractive component, [...] Read more.
Background/Objectives: To evaluate subclinical structural and functional retinal alterations in clinically normal myopic eyes using optical coherence tomography (OCT) and automated visual field analysis. Methods: This retrospective observational study included 109 patients aged 18–42 years categorized according to spherical refractive component, while spherical equivalent (SE) was calculated to quantify refractive severity. Only the right eye of each participant was analyzed. Patients were categorized into five refractive groups according to spherical refractive component. All participants underwent comprehensive ophthalmologic examination, axial length (AL) measurement, spectral-domain OCT imaging, and standard automated perimetry. Structural parameters included central retinal thickness (CRT) and OCT-derived nerve fiber layer central thickness (OCT-NFCT). Functional assessment included visual field central zone sensitivity (VF-CZ), peripheral zone defect value (VF-PZ), mean deviation/defect value (VF-MD), and square root of loss variance (VF-sLV). Correlation and regression analyses were performed to evaluate relationships among absolute myopia severity, AL, OCT parameters, and visual field indices. Results: Increasing myopia was associated with significant reductions in CRT (p < 0.001) and significant intergroup differences in OCT-NFCT (p = 0.012). A moderate negative correlation was observed between absolute spherical equivalent/myopia severity and CRT (r = −0.5398, p < 0.001), whereas the association with OCT-NFCT was not statistically significant (p = 0.149). Visual field parameters demonstrated significant deterioration with increasing myopia (all p < 0.001). VF-CZ showed a strong negative correlation with myopia severity (r = −0.8545, p < 0.001), whereas VF-PZ (r = 0.8196, p < 0.001), VF-MD (r = 0.8186, p < 0.001), and VF-sLV (r = 0.7606, p < 0.001) demonstrated strong positive correlations. In multivariable regression analysis, BCVA, AL, and absolute SE were independently associated with VF-CZ, whereas age and absolute SE were independently associated with VF-MD. CRT and OCT-NFCT were not independent predictors of visual field outcomes. Conclusions: Clinically normal myopic eyes demonstrate significant subclinical structural and functional retinal alterations. In this cross-sectional dataset, visual field alterations were detectable across refractive categories and appeared to be more strongly associated with axial elongation and myopia severity than isolated retinal thickness alterations. Combined OCT and visual field assessment may be valuable for early detection and monitoring of subclinical retinal involvement in myopic patients. Full article
(This article belongs to the Section Ophthalmology)
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19 pages, 404 KB  
Article
Predictors of Weekday and Weekend Screen Time in a Clinical Child and Adolescent Psychiatric Sample (Aged 12–18 Years)
by Helena Gampe, Lucas Rainer, Belinda Plattner and Kornelius Winds
Children 2026, 13(7), 875; https://doi.org/10.3390/children13070875 - 30 Jun 2026
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Abstract
Background/Objectives: Screen time in children and adolescents has become a prominent public health concern, yet most research has focused on community samples, leaving clinically referred youth underrepresented. This study examined predictors of weekday (WD-ST) and weekend screen time (WE-ST) in a clinical [...] Read more.
Background/Objectives: Screen time in children and adolescents has become a prominent public health concern, yet most research has focused on community samples, leaving clinically referred youth underrepresented. This study examined predictors of weekday (WD-ST) and weekend screen time (WE-ST) in a clinical child and adolescent psychiatric sample, with a particular focus on problematic use of the internet (PUI), externalizing symptoms, and fear of missing out (FoMO). Methods: A retrospective secondary analysis of pooled datasets from multiple clinical studies was conducted with 173 adolescents (66.5% female; age range 12–18 years) receiving child and adolescent psychiatric treatment at the University Hospital of Salzburg, Austria. Multivariate linear regression analyses examined self-esteem, adaptive and maladaptive emotion regulation strategies, internalizing and externalizing symptoms, FoMO, and PUI as predictors of WD-ST and WE-ST separately. p-values were adjusted for multiple comparisons using the Benjamini–Hochberg False Discovery Rate correction. Results: In the follow-up hierarchical regression models, PUI was the strongest and most consistent predictor across both models, independently explaining 15.0% of variance in WD-ST time and remaining the only significant predictor in the final WE-ST. Externalizing symptoms significantly predicted WD-ST (β = 0.219, p = 0.021) but not WE-ST. FoMO showed a consistent positive association with WD-ST across both regression models, though this did not reach statistical significance. Self-esteem, emotion regulation strategies, and internalizing symptoms were not significantly associated with screen time in either model. Conclusions: Screen time in clinical adolescent populations cannot be adequately captured by duration alone. PUI reflects a compulsive quality of digital engagement independent of broader psychopathological burden, and the observed difference in weekday versus weekend predictors is consistent with a potential role of daily structure, though this was not formally tested in the present study. Routine clinical assessment should prioritize PUI-focused evaluation over aggregate screen time as a more sensitive indicator of clinically relevant digital engagement. Full article
(This article belongs to the Special Issue Screen Time in Childhood: Risks, Benefits, and Outcomes)
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22 pages, 19695 KB  
Article
A VR–SEM Framework for Pre-Occupancy Evaluation of Classroom Spatial Experience
by Yuanzhao Liu, Sreenidhi Konduri and Changbae Park
Buildings 2026, 16(13), 2581; https://doi.org/10.3390/buildings16132581 - 28 Jun 2026
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Abstract
Architectural design decisions in educational buildings often rely on spatial parameters such as ceiling height and window layout, yet systematic methods for evaluating their influence on user experience during early design stages remain limited. This study investigates how spatial height, window position, and [...] Read more.
Architectural design decisions in educational buildings often rely on spatial parameters such as ceiling height and window layout, yet systematic methods for evaluating their influence on user experience during early design stages remain limited. This study investigates how spatial height, window position, and window-to-wall ratio affect students’ classroom usage intention (UI) through the mediating role of psychological experience. An evidence-based pre-occupancy evaluation approach was developed by integrating immersive virtual reality (VR) experiments with structural equation modeling (SEM). The study employed 61 university students for evaluating parametrically controlled virtual classrooms to examine perceived affective and cognitive experience (ACE), including emotional comfort, attentional focus, and spatial attractiveness, as well as classroom usage intention (UI). Using the data collected through VR experiment and followed by a questionnaire survey, using a stimulus–organism–response framework, the study modeled transmission pathways from spatial stimuli to behavioral outcomes. The results indicate that ACE is the strongest and most direct predictor of UI, highlighting psychological experience as the key pathway translating environmental exposure into behavioral preference. The relationship between perceived architectural attributes and psychological responses was context-dependent, suggesting a potential divergence between analytical spatial judgment and holistic emotional experience under explicit evaluation tasks. VR experience quality significantly influenced ACE but did not directly affect UI. The findings suggest the value of integrating VR and SEM as a pre-design evaluation tool and emphasize prioritizing experiential coherence as a measurable criterion for early-stage decision-making, rather than establishing direct causal links to long-term experiential responses. Full article
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