Search Results (66,872)

Background/Objectives: To evaluate the diagnostic performance of ultrasound-guided attenuation parameter (UGAP) for the assessment of hepatic steatosis in a population at risk for metabolic dysfunction-associated steatotic liver disease (MASLD), using MRI proton density fat fraction (PDFF) as the reference standard, and to also derive optimal population-specific diagnostic thresholds. Methods: In this single-center prospective study, 64 adults at risk for MASLD underwent UGAP measurement and MRI-PDFF. UGAP was performed according to standardized manufacturer-recommended protocols and standardized on the right hepatic lobe. Hepatic steatosis was staged using established MRI-PDFF thresholds. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Cohort-UGAP cut-offs were derived using the Youden index. Associations between UGAP and clinical parameters were assessed using correlation and regression analyses. Results: UGAP correlated strongly with MRI-PDFF (ρ = 0.82, p < 0.001). The areas under the ROC curve (AUCs) for detecting mild, moderate, and severe steatosis were 0.86, 0.96, and 0.96, respectively. Right-lobe acquisitions outperformed left-lobe measurements, while four-region averaging yielded the highest diagnostic performance. UGAP values were associated with BMI, waist circumference, and liver enzymes. Conclusions: UGAP provides an accurate noninvasive assessment of hepatic steatosis, demonstrating high overall diagnostic agreement with MRI-PDFF. Right-lobe acquisition and multi-regional averaging further improve its performance. While cohort-specific threshold optimization may enhance clinical applicability, larger studies are needed to fully confirm its accuracy in advanced stages. Full article

Background/Objectives: Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder. This retrospective study evaluated the demographic, genetic, and clinical characteristics of children diagnosed with DMD before age three to understand early clinical presentation profiles. Methods: The cohort included 198 boys diagnosed with DMD before three years of age between January 2020 and July 2025. Medical records, serum creatine kinase (CK) levels, language milestones via Denver II criteria, and multi-exon deletion maps were retrospectively evaluated. Results: Regarding the diagnostic entry pathways, the initial clinical trigger that led to medical investigation was incidental hyperCKemia in 91.4% of cases. Regardless of the presentation trigger, a definitive, confirmed diagnosis was established in all 198 cases: 196 patients (99.0%) were securely confirmed via genetic testing (MLPA or sequencing), while 2 patients (1.0%) with negative genetic panels were confirmed via muscle biopsy demonstrating a complete absence of dystrophin expression. Genetic analysis revealed deletions in 77.8% of patients, predominantly multi-exon deletions clustered in the distal hotspot region. Independent ambulation occurred at a median age of 16 months, and 14.6% achieved walking after 18 months. Delayed language development was observed in 29.8% of patients. Conclusions: Our findings indicate that early childhood DMD is characterized not only by early muscle involvement but also by prominent neurodevelopmental features. These findings underscore the value of early CK screening in young boys and support integrating standardized neurodevelopmental surveillance into early DMD care. Full article

Background/Objectives: Capsule endoscopy (CE) is a non-invasive tool for evaluating small bowel pathology, but prolonged reading times can lead to reader fatigue. Artificial intelligence-integrated reading software has shown promise to overcome this. This study assesses the diagnostic performance of TOP100 against standard human reading (SR) across different clinical indications. Methods: A retrospective single-centre cohort study was conducted at a tertiary referral centre, including patients who underwent PillCam™SB3 CE between January 2023 to August 2025. Initial reading was performed by expert CE readers (>1000 CE experience) considered as SR. Second blinded reading was performed with TOP100. CE findings from SR were compared with those from TOP100. Results: A total of 1382 CE were identified, of which 1374 had complete examinations and TOP100 data for analysis. The most common indications were inflammatory bowel disease (IBD) (51.5%) and iron-deficiency anaemia (IDA) (25.0%). Diagnostic yield was significantly higher with SR than TOP100 (36.0% vs. 27.5%, p < 0.001). TOP100 demonstrated moderate sensitivity but high specificity; 64.0% and 99.0% for active bleeding, 58.2% and 97.5% for angiodysplasia. In overt bleeding and IDA, sensitivity, and specificity for P2 lesions were 61.0% and 94.3%, respectively. Overall sensitivity and specificity were 55.3% and 95.9% for ulcers, 43.1% and 89.0% for erosions. In IBD, ulcer detection was similar, while TOP100 sensitivity for erosions improved by 9.4%. Conclusions: SR remains the reference standard for reading and reporting capsule endoscopies. However, TOP100 may be a useful adjunct to support interpretation and case prioritisation, especially in high-volume centres. Full article

Myocardial infarction with non-obstructive coronary arteries (MINOCA) accounts for approximately 5–15% of all myocardial infarctions and disproportionately affects women. Once treated as a diagnosis of exclusion, MINOCA is now recognised as a heterogeneous, mechanism-based syndrome encompassing atherosclerotic plaque disruption, epicardial and microvascular vasospasm, microvascular dysfunction, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD). Despite the absence of obstructive disease, it carries substantial morbidity and mortality, underscoring the need for accurate aetiological characterisation and tailored therapy. Our aim is to review the contemporary evidence of the role of advanced imaging modalities—cardiac magnetic resonance imaging (CMR), optical coherence tomography (OCT), intravascular ultrasound (IVUS) and invasive functional testing—in the diagnosis, prognostic stratification, and therapeutic guidance of patients with MINOCA. CMR is the non-invasive reference standard for differentiating true ischaemic MINOCA from non-ischaemic mimics such as myocarditis and Takotsubo syndrome, reclassifying the working diagnosis in up to two-thirds of cases. OCT and IVUS provide intracoronary characterisation of culprit substrates that are invisible via angiography, particularly plaque rupture, erosion, intramural haematoma and SCAD, while acetylcholine and adenosine testing identify endothelium-dependent vasospasm and endothelium-independent microvascular dysfunction respectively. Coronary Computed Tomography Angiography (CCTA) could also play an additional role in the diagnosis of epicardial CAD. Each modality additionally carries independent prognostic value, with abnormal findings consistently linked to higher rates of major adverse cardiovascular events. The recently completed PROMISE trial provided the first randomised evidence that stratified, imaging-guided treatment might have some positive impact on angina status and quality of life compared with empirical standard care. In conclusion, advanced imaging has transformed MINOCA from a diagnosis of exclusion into a mechanism-based syndrome amenable to personalised therapy. Broader integration of these modalities into routine practice, supported by further randomised trials, is needed to optimise outcomes. Full article

Background and Objectives: Laryngostroboscopy is considered the gold standard for the functional assessment of vocal fold vibration and enables the detection of subtle structural and vibratory abnormalities that may not be apparent during routine examination. In interdisciplinary research involving speech analysis and prosthetic rehabilitation, exclusion of underlying laryngeal pathology is methodologically important. The aim of the present study was to evaluate the diagnostic findings obtained through laryngostroboscopic screening in asymptomatic Bulgarian adults examined within a broader research project on speech function and prosthetic rehabilitation. Materials and Methods: A prospective observational study was conducted between April 2022 and July 2023 at the Medical University–Varna, Bulgaria. Eighty adults without self-reported voice-related symptoms underwent laryngostroboscopic examination using an ATMOS Strobo 21 LED system (Advanced Technology Medical Systems GmbH, Lenzkirch, Germany). Participants were assessed for structural and functional laryngeal abnormalities, including alterations in movement frequency, oscillation amplitude, phase symmetry, and visible pathological changes. Descriptive statistics and chi-square tests and Fisher’s exact test analyses were used to evaluate possible associations between laryngeal pathology and demographic variables. Results: Normal laryngeal status was observed in 64 participants (80.0%), whereas 16 (20.0%) showed laryngostroboscopic findings. Isolated vibratory deviations were recorded separately and were not automatically classified as laryngeal pathology. Minor structural or functional variations were found in 5 participants (6.3%), functional laryngeal disorders in 6 (7.5%), benign lesions in 1 (1.3%), and diffuse inflammatory changes consistent with laryngitis in 4 (5.0%). Deviations in vibratory parameters were identified in 25 participants (31.3%) for movement frequency, 16 (20.0%) for oscillation amplitude, and 22 (27.5%) for phase synchronization. No statistically significant associations were found between laryngeal pathology and gender or age group (p > 0.05). Conclusions: Laryngostroboscopic examination identified structural and functional laryngeal findings in a proportion of asymptomatic adults recruited within a speech-function research framework. Functional vibratory deviations were observed more frequently than overt structural pathology. These findings demonstrate that previously unrecognized laryngeal abnormalities may be present even in individuals without apparent voice-related complaints. Further studies incorporating speech-function outcomes and larger cohorts are required to clarify the clinical significance of these observations. Full article

Alcohol-associated liver cirrhosis (ALC) lacks aetiology-specific molecular diagnostic biomarkers. This study aims to quantify the association between alcohol and cirrhosis risk, and to identify transcriptomic diagnostic biomarkers and candidate therapeutics. Methods: Survey-weighted logistic regression was applied to 17,007 adults from NHANES (2017–2023) to quantify alcohol-cirrhosis associations. ALC transcriptomic data from four GEO datasets were analysed using weighted gene co-expression network analysis (WGCNA) and three parallel machine learning algorithms (LASSO, Random Forest, SVM-RFE). External validation was performed in an independent cohort of 93 samples. Candidate therapeutics were identified via drug signature database querying and validated by molecular docking. Heavy drinking conferred a 5.14-fold increased cirrhosis risk (95% CI: 2.60–10.20, p < 0.001). Transcriptomic analysis revealed global downregulation of long non-coding RNAs (with 91.7% of dysregulated lncRNAs being suppressed). A five-gene diagnostic signature (IL1B, CCL3, LUM, SPP1, ITGA6), specifically developed to distinguish ALC from histologically normal liver tissue, achieved an area under the receiver operating characteristic curve (AUC) of 0.824 in an external validation cohort. Immune infiltration analysis uncovered global contraction of macrophage-associated transcriptomic signatures across M0, M1, and M2 subtypes, inversely correlated with fibrotic hub gene upregulation. Fluvastatin and honokiol were identified as candidate therapeutic agents, with strong binding affinities to IL1B and CCL3, respectively. This study confirms a dose-dependent alcohol-cirrhosis association and establishes a five-gene diagnostic signature (distinguishing ALC from normal liver tissue) alongside candidate therapeutics, warranting prospective clinical validation. The identified tissue-derived signature and therapeutic candidates provide a foundation for future ALC-specific diagnostic and therapeutic strategies; their translation into a non-invasive (e.g., blood-based) assay will require dedicated validation in circulating samples. Full article

This article introduces explanatory entitlement as an epistemic category: the inferential right to deploy a construct as a basis for causal inference in a given domain. Drawing on Woodward’s interventionist account and Cartwright’s analysis of causal portability the article argues that this entitlement is conferred by demonstrated invariance and does not transfer automatically across levels or domains. When constructs are projected beyond their invariance conditions without bridging support, they undergo conceptual inflation: retention of explanatory authority without the evidential conditions that license it. The article formalizes this failure, distinguishes it from seven neighboring frameworks, and proposes a diagnostic structure. Full article

Gastrointestinal (GI) cancers account for a quarter of all cancer cases worldwide and are responsible for a third of cancer deaths. One of the characteristic features of GI tissue is its multilayered structure, which, in addition to multiple scattering, complicates optical spectral analysis. The use of spectroscopic diagnostics and photodynamic therapy for the detection and treatment of GI cancer is a rapidly developing field. The method proposed in this paper for layer-by-layer optical properties assessment, suitable for real-time clinical application to the walls of hollow organs, allows us to calculate the absorbed dose layer by layer. This paper proposes a method for recording spectral data in two geometries, diffuse reflectance and transmission, using light delivery from both the external and internal surfaces of the gastrointestinal tract wall. Layer-by-layer assessment of optical properties was performed using a developed algorithm based on the inverse adding–doubling method with initial optical properties values determined using the modified two-stream Kubelka–Munk model with the accuracy equal to 86 ± 13%. The method was approved in clinical conditions. Based on the results of the work, the developed method for assessing the optical properties of multilayered biological tissues exhibited sufficient speed and accuracy for in vivo application to personalize laser-induced therapy by correction of the laser dose. Full article

Background/Objectives: Novel vision-language models (VLMs) can integrate patient textual data with image data to support medical diagnosis. Recent studies reported conflicting results regarding the performance of multimodal VLMs compared to other models and physician performance. This systematic review aims to assess the diagnostic performance of multimodal VLMs integrating both patient textual and image data across diverse real-world hospital settings. Methods: We performed comprehensive searches of eight resources, including Embase, MEDLINE, and SCOPUS, on 17 December 2025. Eligible studies reporting diagnostic performance of VLMs integrating both image and patient history textual data from real-world adult patients compared to that of other models and physicians were included. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Prediction model study Risk Of Bias Assessment Tool + AI (PROBAST + AI) was used to assess the quality and risk of bias. The study protocol was registered in the PROSPERO database (CRD420251244054). This review received no external funding. Results: We screened 11,026 records, of which 18 studies met the inclusion criteria. Six studies comparing multimodal and unimodal models demonstrated the consistent superiority of the multimodal models. Four studies evaluating VLM accuracy as standalone agents compared with physician performance reported conflicting evidence. One study assessing VLMs as a clinical copilot demonstrated higher accuracy from the group of physicians using VLM assistance. A meta-analysis could not be performed due to the heterogeneity across study populations and outcomes. The majority of the studies were assessed as having a high risk of bias due to dataset quality. Primary limitations identified across studies include small sample size, a lack of external validation, and the need for prospective clinical deployment studies. No study provided documented considerations regarding model safety or data security. Conclusions: This systematic review suggests that multimodal VLMs consistently outperform unimodal models with access to only image or text. While model performance as standalone agents compared to humans remains inconclusive, a copilot model has demonstrated high diagnostic accuracy. Given substantial methodological concerns across studies, cautious interpretation is required, No firm clinical recommendation can be made regarding the use of standalone VLMs. Further research employing high-quality datasets is needed to ensure the reliability and clinical applicability of future VLMs. Full article

Background/Objectives: Cardiovascular involvement is among the most consequential sequelae of SARS-CoV-2 infection. Myocardial injury, arrhythmia, and thromboembolic disease have been characterized in depth, yet the relationship between COVID-19 and valvular heart disease (VHD), and its interplay with heart failure (HF), has received comparatively limited synthesis. This narrative review consolidates current evidence on the mechanisms, diagnosis, differential assessment, and clinical outcomes linking acute and post-acute COVID-19 to valvular dysfunction and to incident or worsening heart failure, with emphasis on practical implications for cardiologists and internists. Methods: We searched PubMed, Scopus, and Web of Science (January 2020–January 2026) for studies on valvular dysfunction, heart failure, myocardial injury, and endothelial pathology in SARS-CoV-2 infection, and synthesized findings narratively. Results: Convergent pathways—endothelial injury, systemic hyperinflammation, micro- and macrovascular thrombosis, and pressure–volume overload—contribute to functional and, less frequently, structural valvular changes. Available evidence suggests that clinically relevant post-COVID valvular abnormalities are more often secondary/functional (mitral and tricuspid regurgitation) than primary structural lesions, although dedicated prospective valvular studies remain scarce. Pre-existing severe VHD markedly worsens acute COVID-19 prognosis. Elevated NT-proBNP, troponin, and interleukin-6 consistently predict decompensation and mortality, and a substantial minority of survivors show persistent fibrotic pulmonary changes and restrictive ventilatory defects on follow-up (pulmonary rather than cardiac findings). Conclusions: Post-COVID valvular dysfunction appears, on currently available but largely indirect evidence, predominantly functional and inflammation-related, and may overlap with HFpEF phenotypes in selected patients when objective diagnostic criteria are fulfilled. Biomarker-guided, multimodality follow-up is reasonable in high-risk survivors, and prospective longitudinal studies with standardized valvular endpoints remain a priority. Dedicated longitudinal evidence on valvular outcomes specifically remains very limited. Full article

Background/Objectives: The common quail (Coturnix coturnix) is a game species facing conservation challenges, particularly hybridization with the Japanese quail (Coturnix japonica). To address this issue, one proposed measure is the urgent prohibition of releasing farmed quails into the wild. If authorized, mechanisms should be established to guarantee their genetic origin and prevent contamination of native populations. This work focuses on the development of a genetic tool based on Single-Nucleotide Polymorphism (SNP) markers that can differentiate between the two species and their hybrids. Our goal was to incorporate the selected markers into an OpenArray^® platform, to allow efficient, rapid, and cost-effective analysis. Methods: We tested two mitochondrial DNA SNPs (previously described in the literature) as diagnostic markers for species differentiation. We also assessed 24 nuclear DNA SNPs for compatibility with the OpenArray^® platform. Results: Of the 26 total SNPs, eight were excluded due to their limited utility. The remaining 18 SNPs achieved an overall genotyping success rate of 96.21%. Using the OpenArray^® platform with these 18 SNPs in a trial with samples from diverse Spanish field populations, we found 1.00% of C. japonica alleles (affecting 15.63% of individuals), suggesting introgression in the field. Population genetic analyses revealed strong differentiation between species and confirmed the presence of admixed individuals in field populations. Conclusions: This paper presents a new tool to differentiate between quail species and to identify foreign alleles in stocks and populations, by using an open platform system that optimizes the practical application of the diagnostic procedure based on the to-date most-reliable SNP markers for this goal. Full article

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by a highly heterogeneous clinical course, with some patients remaining stable for years while others require early treatment. Identifying reliable and easily accessible predictors of treatment requirement at diagnosis remains an important clinical challenge. Methods: This retrospective cohort study included 226 patients diagnosed with CLL between 2015 and 2024 at a tertiary care center. Baseline demographic, clinical, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of treatment requirement. A hierarchical mixed-effects model was constructed to account for temporal clustering across diagnostic periods. A clinical risk score was derived from independent predictors, using regression coefficient-based weighting, and its discriminative performance was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 226 patients were included (mean age: 62.4 ± 13.8 years; 56.6% male). During follow-up, 104 patients (46.0%) required treatment. Lower hemoglobin and platelet levels, higher lymphocyte counts and LDH levels, and the presence of B symptoms, splenomegaly, and advanced disease stage were independently associated with treatment requirement. These associations remained significant in hierarchical modeling. The derived risk score demonstrated acceptable discriminative ability (AUC: 0.84; 95% CI: 0.79–0.89), with a cut-off value of ≥4 yielding a sensitivity of 81.7% and specificity of 73.8%. Conclusions: Baseline clinical and laboratory parameters are associated with treatment requirement in CLL. A combination of readily available variables may support risk stratification at diagnosis. The proposed risk score may provide a practical adjunct to routine clinical assessment, particularly in settings where advanced molecular testing is not readily available; however, external validation in independent cohorts is required before clinical implementation. Full article

Multiple endocrine neoplasia (MEN) syndromes are rare hereditary disorders characterized by the development of multiple endocrine and non-endocrine tumours with variable penetrance and age-dependent expression. Although uncommon, these syndromes are highly relevant from both biological and clinical perspectives, as they exemplify the direct link between germline genetic alterations and tumorigenesis. Early tumour detection is critical in MEN syndromes because many associated neoplasms—such as medullary thyroid carcinoma (MTC), pancreatic neuroendocrine tumours (NETs), pheochromocytomas, and parathyroid disease—may remain clinically silent for prolonged periods while retaining malignant potential. Delayed diagnosis is associated with advanced disease and worse outcomes, whereas early identification enables curative or organ-preserving interventions. This clinical challenge has driven the development of integrated diagnostic strategies combining genetic testing, biochemical markers, and imaging. Among these, genetic testing plays a pivotal role, providing definitive diagnosis, enabling family screening, and guiding risk-adapted surveillance. The aim of this review is to provide a comprehensive synthesis of genetically driven diagnostics in MEN syndromes, outlining the current state of the art and future directions in precision medicine. Full article

Aspartame is a widely used artificial sweetener, but its possible relationship with rheumatoid arthritis (RA) remains insufficiently understood. This study aimed to explore, rather than prove, potential molecular links between aspartame-related targets and RA-associated gene networks. Three public RA transcriptomic datasets (GSE55235, GSE55457, and GSE77298) from the Gene Expression Omnibus (GEO) database were integrated as discovery/training data. Because these datasets included different tissue origins, batch correction was used to reduce dataset-level technical variation, whereas tissue-origin-related biological variation was not assumed to be fully removable. After differential expression analysis, RA-associated differentially expressed genes (DEGs) were identified. The single-cell dataset GSE200815 was used for cell annotation and cellular expression visualization; because its comparator group consists of psoriatic arthritis (PsA) samples rather than healthy controls, single-cell results were interpreted as RA-vs-PsA observations and were not treated as disease-versus-healthy-control evidence. Potential targets of aspartame were retrieved from ChEMBL, SwissTargetPrediction, and the Similarity Ensemble Approach (SEA), and were intersected with RA-related DEGs to construct an aspartame-gene-RA regulatory network. Diagnostic models were developed using 113 machine-learning algorithm combinations to determine an optimal multigene model and its core genes. HLA-DRB1 was selected for exploratory scTenifoldKnk-based virtual knockout mainly because it was included in the optimal model and has a well-established role in RA immunogenetics; the single-cell analysis was used only to describe cellular distribution in the RA/PsA dataset. Molecular docking was then used to evaluate the possible interaction between aspartame and HLA-DRB1. Forty-four intersected genes linked the predicted aspartame targets with RA DEGs. The random forest plus partial least-squares generalized linear model (RF + plsRglm) identified 16 core genes. Network-level interpretation indicated that these genes were distributed across immune/antigen-processing, inflammatory-signaling, protease/extracellular-matrix-remodeling, adhesion, metabolic, and proliferation-related modules; therefore, HLA-DRB1 was treated as a prioritized immune-module candidate rather than as the sole driver of the network. Following virtual knockout of HLA-DRB1, affected genes were enriched in extracellular matrix organization, extracellular structure organization, extracellular matrix, collagen trimer, extracellular matrix structural constituent, and collagen binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included integrin signaling, focal adhesion, proteoglycans in cancer, cytoskeleton in muscle, and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling. Molecular docking showed a minimum binding energy of −6.7 kcal/mol, which was more negative than the preset stability criterion of −5.0 kcal/mol, and the docking pose suggested contacts around ARG-146. This integrative analysis suggests a hypothesis-generating association between aspartame-related predicted targets and RA-relevant molecular networks involving HLA-DRB1 and other core genes. The findings do not establish causality and require experimental, epidemiological, biophysical, and tissue-stratified validation before any causal or clinical inference can be made. Full article

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. While established molecular biomarkers such as microsatellite instability (MSI), KRAS, and BRAF are routinely used in clinical practice, the prognostic relevance of tumor suppressor proteins p53 and PTEN remains incompletely defined, particularly when assessed using immunohistochemistry. Objective: The primary aim of this study was to evaluate the prognostic significance of p53 expression and PTEN deficiency in colorectal adenocarcinoma. Secondary aims included assessment of their association with clinicopathological characteristics. Methods: This retrospective cohort study included 103 consecutive patients who underwent surgical resection for colorectal adenocarcinoma. Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples was performed to assess aberrant p53 expression and PTEN deficiency. Associations with clinicopathological variables were evaluated, and overall survival was analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. Results: Aberrant p53 expression and PTEN deficiency were both associated with shorter overall survival in univariate analyses. Patients with concurrent aberrant p53 expression and PTEN deficiency demonstrated the poorest survival outcomes. However, in multivariate Cox regression analysis, only nodal status and age remained independent predictors of overall survival, while p53 and PTEN did not retain independent prognostic significance after adjustment for clinicopathological variables. Conclusions: Aberrant p53 expression and PTEN deficiency are associated with reduced overall survival in colorectal cancer; however, their prognostic impact appears secondary to established clinicopathological factors. The combined presence of these alterations may identify a biologically aggressive subgroup of patients with particularly unfavorable outcomes, although this observation should be considered exploratory. Further validation in larger, independent cohorts is required. Full article