Search Results (45,771)

DOG1 is a transmembrane protein highly expressed in human GISTs. In dogs, DOG1 has been studied to a limited extent in GISTs, where its diagnostic value is considered comparable to KIT, while its expression in other canine tissues remains uncharacterized. The aim of this study is to assess the expression of DOG1 in canine normal and neoplastic tissues, with particular emphasis on a large cohort of GISTs to verify their diagnostic role in comparison with KIT. To achieve this, we analyzed a total of 143 FFPE samples of normal (n = 55) and neoplastic canine tissues (n = 88) by immunohistochemistry. DOG1 was strongly expressed in several cell types, with distribution and intensity patterns that partially overlap those reported in humans. In canine GISTs, DOG1 showed strong and widespread reactivity with a sensitivity slightly inferior to KIT (92% vs. 96%); however, one intestinal mesenchymal tumor KIT-negative/DOG1-positive highlights the importance of combining both markers to maximize the correct diagnosis. Moderate to strong immunohistochemistry for DOG1 has been found in several other tumors, sometimes comparable to that of GISTs. This suggests that DOG1 should not be associated exclusively with GISTs and may provide a basis for further investigation into the role of DOG1 in canine malignancy. Full article

Background/Objectives: Cardiac rehabilitation (CR) is known to improve clinical outcomes in cardiovascular disease, yet its benefits in patients with implantable cardioverter-defibrillators (ICD) are not well established. This meta-analysis evaluated the impact of CR on functional capacity and safety in ICD recipients. Methods: A systematic search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials (RCT) involving adults who underwent ICD implantation and were assigned to either CR or standard care. The primary outcome was the change in peak oxygen uptake (peak VO₂) from the baseline to the final follow-up. Random-effects models were applied, and subgroup analyses were conducted based on follow-up duration, supervision type, baseline peak VO₂, and ischemic vs. non-ischemic etiology. Results: Seven RCTs involving 1461 participants (784 CR; 677 control) met the inclusion criteria. CR was associated with a significant improvement peak VO₂ compared with usual care, expressed as the mean difference (MD) in change from the baseline to the last follow-up (MD 2 mL·kg⁻¹·min⁻¹; 95% CI 1.02–2.81; I² = 65.7%), with consistent effects across all subgroups. Quality of life improved in the CR group (MD 6.46; 95% CI 2.25–10.67; I² = 0%). A non-significant trend toward increased 6MWT distance was observed. CR did not increase adverse events, including ICD shocks, hospitalizations, or cardiac deaths. Conclusions: CR safely enhances exercise capacity and quality of life in ICD recipients without increasing arrhythmic events or mortality. Larger standardized trials are warranted to optimize CR delivery in this population. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with rising prevalence in the Middle East. Real-world comparative data on disease-modifying therapies from this region remain limited. This retrospective study compared the clinical outcomes and tolerability of fingolimod and interferon beta-1a (IFN-β1a) among patients with relapsing–remitting multiple sclerosis treated at a large public referral hospital in Jordan. Materials and Methods: All eligible RRMS patients received fingolimod or IFN-β1a at a single tertiary hospital. The annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and adverse effect frequencies were analyzed using descriptive and inferential statistics. A full-cohort inclusion approach was applied instead of sample-size calculation, as all available cases at Al-Basheer Hospital (Amman, Jordan) were included. Results: Fingolimod-treated patients showed a significantly higher ARR than those on IFN-β1a (0.51 vs. 0.26, p = 0.016), an association likely influenced by treatment sequencing and baseline disease activity. EDSS distributions were similar between treatment groups, with most patients demonstrating mild disability (EDSS ≤ 3.5). IFN-β1a was linked to injection site reactions, while fingolimod was better tolerated. Conclusions: The higher observed relapse rate among fingolimod-treated patients possibly reflects treatment sequencing and underlying disease severity rather than pharmacologic efficacy, as fingolimod was commonly prescribed as an escalation therapy. These findings highlight the importance of individualized treatment selection and underscore the need for prospective studies incorporating standardized baseline disease activity measures to better inform multiple sclerosis care in Jordan and the wider Middle Eastern region. Full article

Background and Objectives: Procalcitonin (PCT), presepsin (PSEP), interferon-λ3 (IFN-λ3), and bioactive adrenomedullin (bio-ADM) are promising sepsis biomarkers. We explored the clinical utility of a multi-marker approach using these four biomarkers in patients with suspected sepsis. Materials and Methods: In a total of 248 patients, the biomarkers were evaluated with the sequential organ failure assessment (SOFA) score. Receiver operating characteristic curves with area under the curve (AUC) were analyzed to diagnose sepsis and predict in-hospital mortality. Survival and reclassification analyses were also used to predict in-hospital mortality. Results: The four biomarkers showed comparable diagnostic performance (AUC = 0.61–0.95, p < 0.001–0.003), and sepsis proportion increased significantly as the number of biomarkers used in the multi-marker approach increased (7.7–91.7%, p < 0.001). The proportion of biomarker quartiles (Q1–Q4) differed significantly according to SOFA score (p < 0.001). The four biomarkers predicted in-hospital mortality (AUC = 0.63–0.84, p < 0.001–0.004). The multi-marker approach performed better than the SOFA score (mortality rate, 58.3% vs. 31.3%; adjusted hazard ratio [HR], 14.7 vs. 4.6), and the addition of biomarkers to the SOFA score increased the performance. The multi-marker approach resulted in a higher HR in patients aged ≥75 years than in the overall population (9.2 vs. 4.2). Conclusions: Each biomarker showed clinical utility in patients with suspected sepsis. The multi-marker approach showed complementary clinical utility in addition to the SOFA score and better prognostic performance in patients aged ≥75 years. The use of biomarkers, alone or in combination, would be a valuable tool in combination with the SOFA score. Full article

Objective: to clarify differences in the intermuscular coherence of core muscles during side kicks among male Sanda athletes at varying skill levels, particularly in critical frequency bands; to reveal the association between neuromuscular coordination mechanisms and technical proficiency; and to provide methodological references for quantitative analysis of combat sports techniques. Methods: Thirty-six male Sanda athletes were divided into professional (n = 18) and amateur (n = 18) groups based on athletic ranking and training duration. Surface electromyographic (EMG) signals from 15 core muscles and kinematic data were synchronously recorded using a wireless EMG system and a high-speed camera. Signal processing extracted root mean square amplitude (RMS) and integral EMG (iEMG). Muscle coordination was quantified via time-frequency coherence analysis across alpha (8–15 Hz), beta (15–30 Hz), and gamma (30–50 Hz) bands. Results: The professional group exhibited significantly higher RMS and iEMG values in most core muscles (e.g., rectus femoris RMS: 0.298 ± 0.072 vs. 0.214 ± 0.077 mV, p < 0.001). Regarding intermuscular coherence, the professional group demonstrated significantly superior coherence in the α, β, and γ bands for key muscle pairs, including upper limb–swing leg, support leg–swing leg, and upper limb–support leg. Notable differences were observed in pairs such as external oblique–rectus femoris (alpha band: 0.039 ± 0.012 vs. 0.032 ± 0.011, p < 0.01) and right rectus femoris–biceps femoris (beta band: 0.033 ± 0.010 vs. 0.023 ± 0.007, p < 0.01). Conclusions: The fundamental difference in side kick technique among Sanda athletes lies in neuromuscular control strategies and muscle coordination efficiency. Sensor-based intermuscular coherence analysis provides an objective quantitative indicator for distinguishing technical proficiency, offering a scientific basis for optimizing training and extending the methodological framework for technique assessment in combat sports. Full article

This study investigates the glycosylation patterns of serum IgG antibodies in relation to COVID-19 infection and vaccination, highlighting the potential of specific glycan profiles as biomarkers for immune responses. Using Spearman correlation analysis, distinct associations among glycan levels and various clinical laboratory parameters were identified, revealing complex, non-linear interactions that influence immune dynamics. Significant differences were observed in sialylated glycan profiles across patient groups, indicating that vaccination and natural infection elicit unique immune mechanisms and suggesting that vaccination induces favorable glycosylation changes. Notably, high-mannose glycans were found to correlate with other glycan types, underscoring their critical role in the immune response and suggesting their potential as biomarkers to differentiate between infection- and vaccination-induced immunity. The findings suggest that understanding these glycosylation dynamics may enhance diagnostic and therapeutic strategies, providing valuable tools for differentiating between immune responses elicited by infection and vaccination. Overall, this study contributes to the understanding of glycosylation’s impact on immune function in the context of COVID-19, emphasizing the importance of specific glycan markers, such as sialylated and high-mannose structures, in clinical applications. Full article

Dynamic network conditions in precision agriculture motivate a scalable, privacy preserving federated learning architecture that tightly integrates ground-based edge intelligence with a space-assisted hierarchical aggregation layer. In Phase 1, heterogeneous tractors act as intelligent farm nodes that train local models, form capability- and task-aware clusters, and employ Network Quality Index (NQI)-driven scheduling, similarity-based check pointing, and compressed transmissions to cope with highly variable 3G/4G/5G connectivity. In Phase 2, cluster drivers synchronize with Low Earth Orbit (LEO) and Geostationary Earth Orbit (GEO) satellites that perform regional and global aggregation using staleness- and fairness-aware weighting, while end-to-end Salsa20 + MAC encryption preserves the confidentiality and integrity of all model updates. Across two representative tasks—nutrient prediction and crop health assessment—our full hierarchical system matches or exceeds centralized performance (e.g., AUC 0.92 vs. 0.91 for crop health) while reducing uplink traffic by ∼90% relative to vanilla FedAvg and cutting the communication energy proxy by more than 4×. The proposed fairness-aware GEO aggregation substantially narrows regional performance gaps (standard deviation of AUC across regions reduced from 0.058 to 0.017) and delivers the largest gains in low-connectivity areas (AUC 0.74 → 0.88). These results demonstrate that coupling on-farm intelligence with multi-orbit federated aggregation enables near-centralized model quality, strong privacy guarantees, and communication efficiency suitable for large-scale, connectivity-challenged agricultural deployments. Full article

Background: No machine learning (ML) models for sepsis prediction have been specifically developed for patients with prolonged or chronic critical illness (PCI/CCI). Objective: This study aimed to develop and validate an ML-based sepsis prediction model for this cohort. Methods: We analyzed ICU admissions from the Russian Intensive Care Dataset (RICD, 575 patients with PCI/CCI) and two public ICU datasets from the PhysioNet (>40,000 patients with acute critical illness). Models were trained within a right-aligned prediction framework using a case–crossover–control sampling approach and a 6 h prediction window. Two strategies were evaluated: (1) a PCI/CCI-focused model trained on RICD with external testing on PhysioNet data and (2) a universal model trained on combined RICD and PhysioNet cohorts. Models were developed with tree-based algorithms (XGBoost, LightGBM, Random Forest, AdaBoost), with internal and external validation. Primary outcome was model discrimination (AUROC). Subgroup analyses were performed for sepsis phenotypes. Results: The PCI/CCI-focused XGBoost model achieved an AUROC of 0.82 in the RICD cohort but failed to generalize to external ICU populations (AUROC 0.47). A universal model trained on mixed data demonstrated reduced discrimination in PCI/CCI patients (AUROC mean difference 0.02, p = 0.0012). Respiratory rate, heart rate, body temperature, and age were among the most important features. Predictive performance was higher in hypoinflammatory sepsis phenotype (AUROC 0.84 vs. 0.81 for hyperinflammatory, p < 0.001). Despite worthless positive predictive value (up to 21%) for PCI/CCI-focused model, negative predictive value exceeded 97%. Conclusions: A right-aligned ML model tailored to PCI/CCI demonstrated strong internal performance for sepsis exclusion but limited cross-population generalizability, underscoring the need for population-specific prediction models and prospective validation before clinical application. Full article

Background: Accurate microbiological diagnosis of bone and joint infections (BJIs) is frequently hampered by low bacterial load, biofilm formation, and suboptimal tissue processing. This study evaluated the diagnostic performance of mechanical bead-milling using the Ultra-Turrax^® Tube Drive system compared with standard vortex homogenization. Methods: In a prospective cohort of 116 patients undergoing surgery for suspected BJIs, 540 intraoperative samples were processed using both methods. Culture and 16S rRNA PCR results were analyzed using classical and Bayesian statistical approaches. Diagnostic performance was assessed globally and across specimen types and anatomical sites. Results: Ultra-Turrax^® significantly improved sensitivity across all sample types (87.1% vs. 75.2%, p < 0.0001), while maintaining comparable specificity (>99%). Culture positivity increased by 17%, with the greatest gains observed in bone samples and hip prosthesis infections. Quantitative cultures demonstrated a 1.5–2 log₁₀ CFU/mL increase in bacterial yield. In culture-negative specimens, 16S rRNA PCR detection doubled with Ultra-Turrax^® processing (26% vs. 13%, p = 0.04). No increase in contamination was observed. Time to positivity was similar between methods, although Ultra-Turrax^® provided earlier results in 17% of cases. Bayesian modeling confirmed superior sensitivity (posterior probability > 0.995). Conclusions: Ultra-Turrax^® bead-milling markedly enhances microbiological detection in BJIs, particularly in low-biomass and bone-derived specimens. Its simplicity, reproducibility, and compatibility with routine workflows support its integration into diagnostic pathways. This pre-analytical optimization may improve etiological identification and guide more targeted antimicrobial therapy. Full article

Characterizing tight reservoirs is challenging due to the complex pore structure and strong heterogeneity at various scales. Current digital rock physics often struggles to reconcile high-resolution imaging with representative sample sizes, and 3D digital cores are frequently used primarily as visualization tools rather than predictive, computable platforms. Thus, a clear methodological gap persists: high-resolution models typically lack macroscopic geological features, while existing 3D digital models are seldom leveraged for quantitative, predictive analysis. This study, based on a full-diameter core sample of a single lithology (gray-black shale), aims to bridge this gap by developing an integrated workflow to construct a high-fidelity, computable 3D model that connects the micro–nano to the macroscopic scale. The core was scanned using high-resolution X-ray computed tomography (CT) at 0.4 μm resolution. The raw CT images were processed through a dedicated pipeline to mitigate artifacts and noise, followed by segmentation using Otsu’s algorithm and region-growing techniques in Avizo 9.0 to isolate minerals, pores, and the matrix. The segmented model was converted into an unstructured tetrahedral finite element mesh within ANSYS 2024 Workbench, with quality control (aspect ratio ≤ 3; skewness ≤ 0.4), enabling mechanical property assignment and simulation. The digital core model was rigorously validated against physical laboratory measurements, showing excellent agreement with relative errors below 5% for key properties, including porosity (4.52% vs. 4.615%), permeability (0.0186 mD vs. 0.0192 mD), and elastic modulus (38.2 GPa vs. 39.5 GPa). Pore network analysis quantified the poor connectivity of the tight reservoir, revealing an average coordination number of 2.8 and a pore throat radius distribution of 0.05–0.32 μm. The presented workflow successfully creates a quantitatively validated “digital twin” of a full-diameter core. It provides a tangible solution to the scale-representativeness trade-off and transitions digital core analysis from a visualization tool to a computable platform for predicting key reservoir properties, such as permeability and elastic modulus, through numerical simulation, offering a robust technical means for the accurate evaluation of tight reservoirs. Full article

Background and Objectives: This study aimed to identify clinicopathological factors associated with axillary pathological complete response (ApCR) in patients with HER2-positive breast cancer presenting with clinically node-positive disease (cN+) confirmed by biopsy who received neoadjuvant therapy (NAT), and to assess the prognostic significance of ApCR on survival outcomes. Materials and Methods: A total of 221 patients with clinically node-positive (cN+) HER2-positive invasive breast cancer, with nodal involvement confirmed by fine-needle aspiration or core needle biopsy, who received neoadjuvant therapy (NAT) and subsequently underwent surgery at three centers between January 2015 and January 2025 were retrospectively reviewed. The association between clinicopathological factors and axillary pathological complete response (ApCR) was analyzed using logistic regression. Survival analyses were performed using the Kaplan–Meier method. Results: The median follow-up duration was 34.3 months. Axillary pathological complete response (ApCR) was achieved in 67.9% of patients. The ApCR rate was higher in stage II disease compared with stage III (76.9% vs. 62.9%). Patients with HER2 3+ tumors demonstrated a higher ApCR rate (70.8%) than those with HER2 2+/FISH+ tumors (46.2%). In multivariable logistic regression, HER2 3+ status (OR = 2.745; 95% CI: 1.138–6.619; p = 0.025) and lower clinical stage (OR = 2.251; 95% CI: 1.182–4.287; p = 0.014) were independently associated with a higher likelihood of achieving ApCR. In survival analyses, the 3-year event-free survival rate was 92% (95% CI: 86–98%) in the ApCR group, compared with 75% (95% CI: 63–87%) in the non-ApCR group. Kaplan–Meier analysis demonstrated that ApCR was a significant prognostic factor for EFS (p = 0.001). Median overall survival (OS) was not reached in either group due to the limited number of death events. Conclusions: ApCR was frequent in node-positive HER2-positive breast cancer after neoadjuvant therapy. HER2 3+ status and lower clinical stage independently predicted ApCR, which in turn was associated with improved event-free survival. These findings underscore the prognostic relevance of ApCR in this setting. Full article

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and many patients cannot undergo curative surgery due to frailty. Multimodal prehabilitation: combining exercise, nutrition, and psychological support improves functional readiness, but its biological impact on the PDAC tumor microenvironment (TME) is unclear. In this exploratory pilot study, we profiled resected PDAC tissues from prehabilitation-treated patients and matched controls using NanoString GeoMx Digital Spatial Profiling across immune, tumor, and stromal compartments (n = 4). Transcriptomic signatures were analyzed via differential expression, pathway enrichment, and MCP-counter deconvolution; protein-level validation used multiplex immunofluorescence (n = 8). Ligand–receptor modeling assessed cell–cell communication, and prognostic relevance was evaluated in TCGA-PDAC (n = 178). Prehabilitation was associated with increased NK-cell cytotoxicity, interferon response, and chemokine recruitment, as well as higher neutrophil signatures (p < 0.01) and reduced fibroblast signatures (p < 0.05). Tumor regions showed lower MAPK and PI3K/AKT activity, while stroma exhibited decreased TGF-β and Wnt signaling. Immunofluorescence confirmed neutrophil infiltration and reduced fibroblast density. TCGA analysis linked neutrophil-high/fibroblast-low profiles to longer survival (1044.6 vs. 458.7 days, p = 0.0052). These findings suggest prehabilitation may promote a more immune-active, less fibrotic TME in PDAC, resembling transcriptional states associated with improved survival. Prospective studies integrating biological and clinical endpoints are warranted. Full article

Introduction: Radiotherapy plays a critical role in the management of head and neck squamous-cell carcinoma (HNSCC); however, the influence of overall treatment time on patient outcomes remains an area of ongoing investigation. The use of radiation, either in conjunction with concurrent chemotherapy or on its own, is crucial when treating HNSCC. Despite the longstanding hypothesis that treatment gaps may adversely affect tumor response and overall survival, there is a paucity of literature on this particular area. This study aims to bridge the knowledge gap and assess the correlation of treatment gaps on recurrences in HNSCC patients. Materials and Methodology: This retrospective study is based on an analysis of data obtained from a single institution between 2017 and 2021. Patients were selected on the basis of the presence of treatment gaps. Data were extracted from medical records and analyzed to evaluate the association between overall treatment time and various patient and treatment-related factors. Various factors thought to contribute to treatment gaps, such as age, TNM Stage, radiation dose, and use of concurrent chemotherapy, were also examined. Results: A total of 212 patients with treatment gaps were evaluated. Of these, 80 individuals experienced recurrences. It was observed that compared to distant metastases, locoregional failure was more frequent (n = 2, 4.2% vs. n = 45, 95.74%). The patients underwent both adjuvant and definitive therapy and were treated with a dose range of 60–70 Gy and concurrent cisplatin chemotherapy. It was noticed that this cohort had a range of 4–43 days of treatment gaps. Notably, 19 out of 47 patients had treatment gaps ≤ 5 days, while 28 out of 47 had gaps exceeding 5 days. It was also observed that patients with treatment gaps of >5 days had poorer quality of life and overall survival. Conclusions: This study identified that the Overall Treatment Time (OTT) had a strong statistical correlation with the development of recurrences. Further, the age of the patient, presence of neutropenia and the duration of the treatment gap were also identified to significantly correlate with the chance of developing recurrences. Full article

Growing pressure on water resources and mineral fertilizer use calls for innovative and resource-efficient agri-food systems. Aquaponics, integrating aquaculture and hydroponics, represents a promising approach for sustainable greenhouse production. This study, aiming to explore alternative water and nutrient sources for greenhouse tomato production without compromising plant adaptability or yield, evaluated the co-cultivation of grape tomato and rainbow trout in a vertical decoupled aquaponic system under controlled greenhouse conditions. Two aquaponic nutrient strategies were tested: unmodified aquaponic water (AP) and complemented aquaponic water (CAP), with conventional hydroponics (HP) as a control, in a Deep Water Culture hydroponic system. Plant performance was assessed through marketable yield and physiological parameters, while system performance was evaluated using combined-biomass Energy Use Efficiency (EUE), Freshwater Use Efficiency (fWUE) and Nitrogen Use Efficiency (NUE), accounting for both plant and fish production. CAP significantly improved tomato yield (9.86 kg m⁻²) compared to AP (2.40 kg m⁻²), although it remained lower than HP (12.14 kg m⁻²). Fresh WUE was comparable between CAP and HP (9.22 vs. 9.24 g L⁻¹), demonstrating effective water reuse. In contrast, EUE and NUE were lower in CAP, reflecting the additional energy demand of the recirculating aquaculture system and nutrient limitations of fish wastewater. These results highlight aquaponics as a water-efficient production system while emphasizing that optimized nutrient management and energy strategies are critical for improving its overall sustainability and performance. Full article

Background/Objectives: Insulin resistance (IR) is a relevant metabolic concern in patients with rheumatic diseases; however, data regarding its clinical influence on the systemic sclerosis (SSc) phenotype is lacking. This study aimed to evaluate the characteristics of patients exhibiting IR in a monocentric SSc cohort. Methods: We conducted a cross-sectional study on 178 SSc patients, stratified according to the presence of IR, defined as a HOMA-IR value >1.85 for men and >2.07 for women, based on thresholds previously validated in the Estudio Epidemiológico de la Insuficiencia Renal en España (EPIRCE) cross-sectional study. The rationale for applying the current cut-offs is based on its discriminative potential when using sex- and age-specific thresholds in a nondiabetic population. This approach is particularly applicable to SSc, where the prevalence of diabetes is very low and the median ages of the two cohorts are comparable. Data collected included demographic-, clinical-, laboratory-, pulmonary function-, capillaroscopic-, and treatment-related parameters. A multivariable logistic regression model was used to identify independent predictors of IR. Results: Patients with IR (n = 76) had a significantly higher prevalence of diffuse cutaneous subset (26.3% vs. 11.8%, p = 0.012) and interstitial lung disease (39.5% vs. 17.6%, p = 0.001), along with the positivity for anti-Scl70 antibodies and the current presence of musculoskeletal symptoms (p = 0.021) and digital ulcers (p = 0.037). As expected, body mass index (BMI) was significantly higher in the IR population (24.6 ± 5.2 vs. 22.9 ± 4.1, p = 0.012), along with fasting glucose, insulin, HOMA-IR, and HbA1c levels. IR patients exhibited higher percentages of dyslipidemia and liver steatosis. Medications such as hydroxychloroquine, statins, and Iloprost were more frequently used in the IR group; as for corticosteroids usage (21.1% vs. 5.9%, p = 0.002), however, cumulative glucocorticoid dosage did not differ between the groups. In multivariable analysis, BMI (OR 1.09; p = 0.038) and interstitial lung disease (ILD) (OR 3.03; p = 0.034) were independent predictors of IR. Conclusions: In SSc, IR is associated with ILD, digital ulcers, musculoskeletal involvement, and anti-Scl70 autoantibodies. Full article