Search Results (15,001)

Background: Periapical lesions are common consequences of pulp necrosis but may remain undetectable on conventional intraoral radiographs, becoming evident only on cone-beam computed tomography (CBCT). Improving lesion recognition on plain radiographs is therefore of high clinical relevance. Methods: This retrospective, single-center study analyzed 56 matched pairs of intraoral periapical radiographs (RVG) and CBCT scans. A total of 109 regions of interest (ROIs) were included, which were classified as CBCT-positive/RVG-negative (onlyCBCT, n = 64) or true negative (noLesion, n = 45). Radiomic texture features were extracted from circular ROIs on RVG images using PyRadiomics. Feature distributions were compared using Mann–Whitney U tests with false discovery rate correction, and classification was performed using a logistic regression model with nested cross-validation. Results: Forty-four radiomic texture features showed statistically significant differences between onlyCBCT and noLesion ROIs, predominantly with small to medium effect sizes. For a 40-pixel ROI radius, the classifier achieved a mean area under the ROC curve of 0.71, mean accuracy of 68%, and mean sensitivity of 73%. Smaller ROIs (20–40 pixels) yielded higher AUCs and substantially better accuracy than larger sampling regions (≥60 pixels). Conclusions: Quantifiable radiomic signatures of periapical pathology are present on conventional radiographs even when lesions are visually occult. Radiomics may serve as a complementary decision support tool for identifying CBCT-only periapical lesions in routine clinical imaging. Full article

Objective: the aim of this systematic review and meta-analysis was to evaluate the effectiveness of photobiomodulation therapy (PBM) on perineal pain and wound healing following episiotomy. Methods: Electronic databases were searched for randomized controlled trials (RCTs) and non-RCTs investigating PBM after episiotomy. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for non-RCTs. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analyses were performed using random-effects models. Results: Eight studies were included in the systematic review, and six studies were included in the meta-analysis. According to RoB 2, one trial was judged at low risk of bias, two trials raised some concerns, and three trials were at high risk of bias. ROBINS-I showed the serious risk of bias of two non-RCTs. GRADE for both pain and wound-healing outcomes was rated as very low. Meta-analysis of pain showed no significant difference between PBM and control groups (SMD = 0.04; 95% CI −0.60 to 0.68; p = 0.89), with considerable heterogeneity (I² = 91%). For wound-healing outcomes, meta-analysis showed no significant difference (MD = 0.94; 95% CI −0.69 to 2.56; p = 0.26), with substantial heterogeneity (I² = 94%). Conclusions: PBM therapy did not demonstrate a significant benefit for reducing perineal pain or improving wound healing after episiotomy compared with control interventions. Interpretation of these findings should be made cautiously due to small study numbers, substantial heterogeneity, and the inability to perform sensitivity or subgroup analyses, highlighting the need for high-quality RCT with standardized PBM protocols before clinical recommendations can be made. Full article

Background/Objective: This systematic review aims to evaluate ex vivo brain slice models in glioblastoma (GBM) research, with a specific focus on tumour invasion, tumour–microenvironment interactions, and therapeutic response. Methods: A systematic search looking for studies employing ex vivo organotypic brain slice models in GBM research was conducted across multiple databases (January 2010–July 2025) in accordance with PRISMA guidelines. The study was registered in PROSPERO database (CRD420251138341). Inclusion criteria encompassed patient-derived brain slices, hybrid rodent–human slice co-cultures, and microfluidic-integrated ex vivo platforms designed to assess tumour invasion, microenvironmental interactions and therapeutic responses. Exclusion criteria included reviews, abstracts, conference proceedings, in vivo-only studies, purely in vitro models without organotypic integration, and studies not focused on GBM. Results: Twenty-six studies met the inclusion criteria. Among these, 18/26 (69%) investigated GBM invasion, 18/26 (69%) evaluated therapeutic responses, and 5/26 (19%) examined tumour–microenvironment interactions, with several studies spanning multiple domains. Across platforms, organotypic slices consistently recapitulated key features of GBM biology—including perivascular and white-matter-aligned invasion, stromal–immune interactions, and patient-specific drug sensitivity—while engineered systems enhanced perfusion and exposure control. Methodological variability, particularly regarding slice preparation, oxygenation and viability assessment, limits direct comparability between studies. Conclusions: Organotypic brain slice models represent an extremely relevant tool for translational investigations of GBM biology and treatment response. However, substantial methodological heterogeneity together with limited standardisation hamper reproducibility and cross-study validation. Future work should focus on enhancing reproducibility and harmonising protocols to support the development of clinically meaningful precision oncology strategies. Full article

Background: Hip joint disorders exhibit diverse and overlapping radiological features, complicating early diagnosis and limiting the diagnostic value of single-modality imaging. Isolated imaging or clinical data may therefore inadequately represent disease-specific pathological characteristics. Methods: This retrospective study included 605 hip joints from Center A (2018–2024), comprising normal hips, osteoarthritis, osteonecrosis of the femoral head (ONFH), and femoroacetabular impingement (FAI). An independent cohort of 24 hips from Center B (2024–2025) was used for external validation. A multimodal deep learning framework was developed to jointly analyze radiographs, CT volumes, and clinical texts. Features were extracted using ResNet50, 3D-ResNet50, and a pretrained BERT model, followed by attention-based fusion for four-class classification. Results: The combined Clinical+X-ray+CT model achieved an AUC of 0.949 on the internal test set, outperforming all single-modality models. Improvements were consistently observed in accuracy, sensitivity, specificity, and decision curve analysis. Grad-CAM visualizations confirmed that the model attended to clinically relevant anatomical regions. Conclusions: Attention-based multimodal feature fusion substantially improves diagnostic performance for hip joint diseases, providing an interpretable and clinically applicable framework for early detection and precise classification in orthopedic imaging. Full article

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. Full article

Background/Objectives: Differential diagnosis between Crohn’s disease (CD) and ulcerative colitis (UC) can be sometimes difficult resulting in the diagnosis of unspecified inflammatory bowel diseases (IBD-U). Data suggest that IgG antibodies against integrin αvβ6 (V6 Ab) help to identify UC patients. Recent studies suggest that measuring V6 Ab serum levels may be valuable for differential diagnostic purposes. The primary objective of the study was to assess the sensitivity and specificity of V6 Ab serum-level measurement in our IBD population to differentiate between colonic/ileocolonic CD and UC with an established diagnosis. Furthermore, we assessed the correlation between disease characteristics, activity and V6 Ab serum levels in UC patients. Methods: Consecutive IBD patients with an established diagnosis undergoing control colonoscopy in a tertiary IBD center were included. Baseline demographic data, current treatment, disease extent, clinical, biomarker, endoscopic and histologic disease activity were collected. V6 Ab serum levels were measured with the Anti-Integrin αvβ6 ELISA Kit (RUO). Patients’ written informed consent was obtained. Results: A total of 40 IBD patients, including 10 CD and 30 UC patients (15 with clinical activity and 15 in clinical remission) were enrolled. V6 Ab serum levels were significantly higher in UC patients compared to CD (p = 0.039). ROC analysis found 1.33 U/mL to be the best cut-off level (p = 0.04; AUC: 0.71) with 100% sensitivity and 50% specificity and a positive predictive value of 85.7% and a negative predictive value of 100% to differentiate between UC and CD. No significant correlation was found between V6 Ab serum levels and CRP (p = 0.057), fecal calprotectin (p = 0.77), endoscopic activity (p = 0.624) or disease extent (p = 0.624) in UC patients. Conclusions: Our study supports the value of V6 Ab serum level measurement as a differential diagnostic tool in IBD patients; however, the optimal cut-off value is yet to be determined. Our data do not support its role in disease activity monitoring. Full article

Background: Malnutrition is frequently under-investigated during remission in patients with Inflammatory Bowel Disease (IBD), despite its significant impact on clinical outcomes and quality of life. This study aimed to evaluate the increase in diagnostic performance of five nutritional screening tools (NSTs) when serially administered to IBD outpatients in sustained clinical remission. Methods: In this prospective, single-center cohort study, NSTs were administered, and body composition analysis was performed in IBD patients at baseline and after six months. At both time points, the sensitivity, specificity, predictive values, and accuracy of NSTs in detecting malnutrition and persistent malnutrition per ESPEN and GLIM criteria were evaluated, comparing repeated to single-point assessments. A sensitivity analysis using low FFMI as a reference was also performed. Results: Sixty-six IBD patients (32 Crohn’s disease; 34 ulcerative colitis) were enrolled. At baseline, 25.7% and 9% of patients were malnourished according to ESPEN and GLIM criteria, respectively, with 7.5% exhibiting low FFMI. Malnutrition prevalence increased over time to 53%, 16.6%, and 16.6%, respectively. Among NSTs, MUST and SaskIBD-NR consistently exhibited the highest specificity for malnutrition detection at baseline, at 6 months, and for persistent malnutrition for ESPEN, GLIM and low FFMI. Serial (repeated) NST administration markedly improved the specificity of all tools, compared to single-point assessments. Conclusions: Serial nutritional screening with MUST or SaskIBD-NR significantly enhances the specificity of malnutrition risk detection in IBD patients in remission, supporting the incorporation of repeated nutritional assessments into clinical practice to offer a practical strategy to enhance screening effectiveness in IBD outpatient care. Full article

Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article

Background/Objectives: The aim of this study was to evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) in allergic adults and children treated with a polymerized-glutaraldehyde undiluted mixture of house dust mites (HDMs) under routine clinical practice. Methods: This was an observational, ambispective, controlled, real-world, multicenter study including patients ≥ 5 years with allergic rhinitis (AR), due to Dermatophagoides sensitization. Patients who started AIT with a D. pteronyssinus/D. farinae extract and those who continued symptomatic treatment were included in the treatment (DP&DF) and untreated (UT) groups, respectively. We evaluated adverse reactions (ARs) and changes in effectiveness variables through changes in symptoms, disease control, medication use, and patient- and investigator-reported outcomes. Results: We included 130 patients in the DP&DF group, and 90 (69.2%) adults, 23 adolescents (17.7%), 17 (13.1%) children, and 94 patients in the UT group. Patients received treatment for a mean (SD) of 9.01 (3.1) months at the time of evaluation. Seven (5.4%) patients, all adults, reported eight ARs, five local and three systemic (mean rate of 0.62 ARs per 100 injections); all recovered, and epinephrine was not required. The proportion of patients reporting no rhinitis symptoms at follow-up significantly increased (+13.6%; p < 0.001). Rhinitis frequency, intensity, and control significantly improved overall and in specific age groups. Similarly, the proportion of patients reporting no asthma symptoms at follow-up significantly increased (+29.0%; p < 0.001). The use of all symptomatic medications significantly decreased, while the UT group showed no significant changes, except for worsened asthma classification and control in specific age groups. Both investigators and patients perceived a marked improvement in symptoms and medication use, with high satisfaction scores reported on the visual analogue scale. Conclusions: A subcutaneous allergen extract with a mixture of HDMs is safe and effective for allergic rhinitis and asthma in adults and children in the real-world setting. Full article

Background: The profound heterogeneity of glioblastoma and the often-limited efficacy of conventional treatments, including arsenic trioxide (ATO), underscore the urgent and critical demand for innovative combination strategies specifically designed to overcome treatment resistance. Methods: We evaluated the therapeutic effects of ATO as a single agent and in combination with the MNK1 inhibitor AUM001 across patient-derived xenograft (PDX) models and investigated molecular determinants of sensitivity and synergy. Our results demonstrated that GBM models resistant to ATO, particularly those of the mesenchymal subtype, are more likely to show synergistic cytotoxicity when AUM001 is added. The combination significantly reduces the frequency of glioblastoma stem cells (GSCs) compared to either drug alone, especially in ATO-resistant models. Results: These observations suggest that targeting the MNK1 pathway in conjunction with ATO is a promising strategy to specifically eradicate GSCs, which are major drivers of GBM recurrence and therapeutic failure. Transcriptomic analyses revealed that ATO sensitivity correlated with activated translation-related pathways and cell cycle processes, while synergistic responses to the combination were driven by distinct molecular signatures in different GBM subtypes. Overall, synergistic response to the combination therapy is more associated with cellular organization, amino acid transmembrane transporter activity, ion channels, extracellular matrix organization and collagen formation. Conclusions: Our findings highlight that specific molecular pathways and their activities, including those involving translation, cell cycle and ion transport, appear to modulate the synergistic efficacy of the ATO and AUM001 combination, thereby offering potential biomarkers for improved patient stratification in future GBM clinical trials of such ATO-based treatments. Full article

Background/Objectives: With the rising incidence of obesity-related endometrial cancer, there is renewed interest in physiologic, low-cost approaches to identify women with hormonally active endometrium who may benefit from early preventive interventions. The progesterone challenge test (PCT), an established clinical tool for evaluating amenorrhea, has been previously proposed as a method to detect endometrial pathology. This study systematically evaluated the diagnostic accuracy of the PCT for detecting endometrial hyperplasia, intraepithelial neoplasia, and carcinoma in asymptomatic postmenopausal women to determine its potential role as a physiologic marker of endometrial cancer risk. Methods: A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. MEDLINE, EMBASE, EBM Reviews, and CINAHL were searched from inception to 20 January 2025, along with ClinicalTrials.gov and grey literature. Eligible studies prospectively evaluated the PCT with endometrial biopsy as the reference standard. Data extraction and risk-of-bias assessment were performed in duplicate. Risk of bias was assessed using QUADAS-2. Pooled sensitivity, specificity, and predictive values were estimated using hierarchical summary receiver operating characteristic models. Results: Nineteen studies (n = 3902) met the inclusion criteria. The pooled sensitivity and specificity of the PCT for detecting endometrial pathology were 95% (95% CI 86–100%) and 87% (76–96%), respectively. The positive predictive value was 32% (95% CI, 16–50%) and the negative predictive value was 100% (100–100%). When endometrial proliferation was included in the target condition, sensitivity decreased to 82%, but positive predictive value increased to 70%. Conclusions: The PCT shows high diagnostic accuracy for identifying estrogen-driven endometrial pathology in asymptomatic postmenopausal women. Re-evaluating this simple, physiologic test as a functional risk-stratification tool could inform precision prevention strategies for endometrial cancer. Full article

Background/Objectives: Children undergoing cancer treatment experience multiple distressing symptoms that often go undetected in routine care. This study evaluated the potential impact of integrating the Symptom Screening in Pediatrics Tool (SSPedi) into clinical workflows, focusing on symptom detection and implications for service delivery. Methods: Seventy children (aged 4–18 years) receiving active treatment, and/or their caregivers completed SSPedi weekly for eight weeks (n = 479 completions). Medical records were audited for documentation of symptom assessments and symptom prevalence. SSPedi completions were categorized using a clinical algorithm (low, moderate, immediate concerns) and compared with score-only threshold. Results: The most bothersome symptoms were appetite changes (12%), fatigue (11%), nausea/vomiting (9%) and pain (9%). Severe bother detected by SSPedi was more frequent while hospitalized than at home (e.g., appetite changes 17% versus 9%). Documentation rates of severe symptoms in medical records were substantially lower than SSPedi reports—12% when SSPedi was completed at home and 49% when completed in hospital. Applying the clinical algorithm flagged 58% of SSPedi completions as an immediate concern in home and 63% in hospital, compared with score-only thresholds (31% at home and 17% in hospital). Algorithm-based alerts for immediate concerns would have triggered almost twice as many phone calls as score-based thresholds (168 vs. 91). Conclusions: Routine PROM integration could improve symptom detection and timely intervention. Clinical algorithms enhance sensitivity but increase alert burden, highlighting the need to review thresholds and redesign workflows. Full article

Evaluating artificial intelligence (AI) models in clinical medicine requires more than conventional metrics such as accuracy, Area Under the Receiver Operating Characteristic (AUROC), or F1-score, which often overlook key considerations such as fairness, reliability, and real-world utility. We introduce CUES as a multiplicative composite score for clinical prediction models; it is defined as $\mathrm{CUES}=(C\cdot U\cdot E\cdot S{)}^{1/4}$, where C represents calibration, U integrated clinical utility, E equity across patient subpopulations, and S sampling stability. We formally establish boundedness, monotonicity, and differentiability on the domain ${\left(\mathrm{0,1}\right]}^4$, derive first-order sensitivity relations, and provide asymptotic approximations for its sampling distribution via the delta method. To facilitate inference, we propose bootstrap procedures for constructing confidence intervals and for comparative model evaluation. Analytic examples illustrate how CUES can diverge from traditional metrics, capturing dimensions of predictive performance that are essential for clinical reliability but often missed by AUROC or F1-score alone. By integrating multiple facets of clinical utility and robustness, CUES provides a comprehensive tool for model evaluation, comparison, and selection in real-world medical applications. Full article

Background/Objectives: Parkinsonian gait is characterized by impaired motor adaptability, altered temporal organization, and reduced movement variability. While data augmentation is commonly used to mitigate class imbalance in gait-based machine learning models, conventional strategies often ignore physiological differences between healthy and pathological movements, potentially distorting meaningful motor dynamics. This study explores whether preserving healthy motor variability while selectively augmenting pathological gait signals can improve the robustness and physiological coherence of gait pattern classification models. Methods: Eight patients with Parkinsonian gait patterns and forty-eight healthy participants performed walking tasks on the Motigravity platform under hypogravity conditions. Full-body kinematic data were acquired using wearable inertial sensors. A selective augmentation strategy based on smooth time-warping was applied exclusively to pathological gait segments (×5, σ = 0.2), while healthy gait signals were left unaltered to preserve natural motor variability. Model performance was evaluated using a hybrid convolutional neural network–long short-term memory (CNN–LSTM) architecture across multiple augmentation configurations. Results: Selective augmentation of pathological gait signals achieved the highest classification performance (94.1% accuracy, AUC = 0.97), with balanced sensitivity (93.8%) and specificity (94.3%). Performance decreased when augmentation exceeded an optimal range of variability, suggesting that beneficial augmentation is constrained by physiologically plausible temporal dynamics. Conclusions: These findings demonstrate that physiology-informed, selective data augmentation can improve gait pattern classification under constrained data conditions. Rather than supporting disease-specific diagnosis, this proof-of-concept study highlights the importance of respecting intrinsic differences in motor variability when designing augmentation strategies for clinical gait analysis. Future studies incorporating disease-control cohorts and subject-independent validation are required to assess specificity and clinical generalizability. Full article