Noncirrhotic portal hypertension has historically been described using heterogeneous and region-specific terminology-such as idiopathic portal hypertension (IPH), noncirrhotic portal fibrosis (NCPF), obliterative portal venopathy, and nodular regenerative hyperplasia-leading to substantial variability in diagnosis, reporting, and international research collaboration. Differences in guideline definitions from major societies (AASLD, EASL, and APASL), together with the presence of characteristic histologic lesions in patients without clinically overt portal hypertension, have further complicated disease classification. To address these challenges, a large, multisociety, international initiative was convened to harmonize nomenclature and diagnostic criteria. Representatives from liver, pathology, and pediatric hepatology societies across the Americas, Europe, and Asia participated in a structured consensus process that included specialized working groups and external Delphi validation. The initiative produced a globally harmonized and implementable diagnostic framework. Consensus was reached that the terms porto-sinusoidal vascular disorder (PSVD) and NCPF may be used interchangeably when identical diagnostic criteria are applied, and that they should be written as PSVD or NCPF. The diagnosis was defined as fundamentally clinicopathological, requiring integrated assessment. Core principles include the need for a high-quality liver biopsy (≥10 mm), mandatory exclusion of cirrhosis, and systematic exclusion of specific alternative conditions. Importantly, the consensus recognizes that PSVD or NCPF may be diagnosed even without clinical portal hypertension and may coexist with other liver diseases, provided cirrhosis is excluded. Standardized major and minor histologic criteria were developed collaboratively by expert pathologists and externally validated. Features of portal hypertension were harmonized into specific and nonspecific categories applicable to routine clinical practice. An integrated diagnostic scoring system incorporating histology, clinical features, associated conditions, and concommitant etiologies was developed and validated using the Delphi method. This consensus provides the first internationally endorsed, unified framework for the diagnosis of PSVD or NCPF. Its global implementation is expected to reduce diagnostic variability, improve comparability across regions, and facilitate the development of robust, internationally harmonized clinical and translational research cohorts.

Cell-free deoxyribonucleic acid (cfDNA) fragmentation patterns represent significant non-invasive diagnostic markers. In this study, A new paradigm for cfDNA diagnostics is established by Semantic Inductive Graph-based Diagnostics (SIGD) through the unification of semantic encoding and graph topology. A transformative perspective on cfDNA analysis is introduced by treating genomic fragmentation as a structured linguistic problem. In this research, SIGD was developed as a high-performance framework, leveraging a heterogeneous Graph Convolutional Network integrated with Bidirectional Long Short-Term Memory (BiLSTM) semantic encoders. The architecture is centered on a multi-relational graph topology where complex biological interactions are explicitly modeled. Specifically, Inverse Document Frequency (IDF) weights are utilized to quantify sequence-motif relevance, while Pointwise Mutual Information (PMI) is employed to capture co-occurrence dependencies between motifs. Within this framework, the Term Frequency and Category Relevancy Factor (TFCRF) weighting scheme is strategically implemented to formalize the direct relational mapping between motifs and diagnostic labels, enabling the extraction of category-aware features. Through this integrative approach, high-order patterns that often remain undetected by traditional models are effectively captured. Consequently, superior diagnostic sensitivity and enhanced interpretability in cancer detection are achieved. Finally, the framework was evaluated using 2451 plasma samples across multiple sequencing modalities. Superior performance was achieved by SIGD relative to established baselines. In the testing set, a diagnostic accuracy of 91.43% and an area under the receiver operating curve (AUROC) of 0.967 were attained for general cancer detection, with 64 end-motifs. For hepatocellular carcinoma (HCC)-specific classification, the model reached an accuracy of 99% and an AUROC of 0.998. Model reliability was confirmed via calibration analysis, facilitating real-time inductive inference without retraining. The framework is characterized by high accuracy, interpretability and computational efficiency.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in parallel with obesity and metabolic disorders. Recent evidence suggests that diet-induced low-grade metabolic acidosis, quantified by dietary acid load (DAL) indices such as potential renal acid load (PRAL) and net endogenous acid production (NEAP), may contribute to the pathogenesis of NAFLD. However, existing findings are inconsistent. This systematic review aimed to evaluate the association between dietary acid load and the risk of NAFLD in adult populations. We conducted a comprehensive search of PubMed, Web of Science, and Scopus databases from inception to January 2025. Observational studies examining the association between DAL and NAFLD in adults were included. Two reviewers independently screened and extracted data, and the methodological quality was assessed using the AXIS tool for cross-sectional studies and the Newcastle-Ottawa Scale for case-control studies. A narrative synthesis approach was adopted due to heterogeneity in outcome measurements. Of 809 records identified, five studies (four cross-sectional and one case-control), published between 2015 and 2023 and conducted in Iran, the United States, the Netherlands, and China, met the inclusion criteria. DAL was primarily assessed using PRAL and NEAP, while NAFLD was diagnosed using imaging techniques or validated non-invasive indices. Three studies reported positive associations between higher DAL and NAFLD, with adjusted odds ratios generally ranging from approximately 1.3 to 2.2 for higher versus lower DAL categories, particularly for PRAL or NEAP. One study reported no significant association after adjustment for confounders, and one case-control study identified a modest U-shaped relationship, with moderate PRAL levels inversely associated with NAFLD odds (adjusted OR ≈fsn371597-bib-00180.46; 95% CI, 0.24-0.89), while higher PRAL levels were not significantly associated. Current evidence suggests a possible association between higher dietary acid load and increased risk of NAFLD, although findings remain inconsistent. Further well-designed longitudinal studies are warranted to clarify this relationship and determine causality.