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12 pages, 608 KB  
Article
Natural History of Treated and Untreated Bland Portal Vein Thrombosis in Patients with Hepatocellular Carcinoma
by Tim Weber, Antonina Antonenko, Jonas Schropp, Pompilia Radu and Annalisa Berzigotti
Cancers 2026, 18(13), 2148; https://doi.org/10.3390/cancers18132148 - 3 Jul 2026
Viewed by 295
Abstract
Background/Objectives: The prevalence and management options of bland (non-neoplastic) portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) are poorly characterized and data remain limited. Methods: We performed a retrospective analysis of a prospectively collected single-center cohort of 638 patients [...] Read more.
Background/Objectives: The prevalence and management options of bland (non-neoplastic) portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) are poorly characterized and data remain limited. Methods: We performed a retrospective analysis of a prospectively collected single-center cohort of 638 patients with HCC. Bland PVT was identified at baseline or during follow-up. Treatment exposure was modeled as time-varying to account for differences in timing of anticoagulation initiation. Results: Bland PVT was identified in 39 patients (25 at baseline and 14 during follow-up). Patients with PVT showed features of more advanced portal hypertension (lower platelet count and higher prevalence of ascites) and had a higher tumor burden (more often outside the Milan criteria; higher AFP). A total of 30 patients received anticoagulation. Anticoagulation was associated with partial or complete recanalization in 30% of cases at three months and with decrease in bilirubin, but was not associated with improved 1 year survival. Bleeding events occurred in four anticoagulated patients (13.3%). Conclusions: Bland PVT in HCC is associated with more severe liver disease. Our data indicate that anticoagulation in patients with HCC and concomitant bland PVT was generally well-tolerated and was associated with thrombus regression in one-third of cases. However, we did not observe an improved survival in patients on anticoagulation. Full article
(This article belongs to the Section Cancer Therapy)
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19 pages, 3856 KB  
Article
CRAFITY and PALBI Define a Machine Learning-Supported Prognostic Framework in Hepatocellular Carcinoma—Data from an Eastern European Cohort with Low Macrotrabecular-Massive Prevalence
by Cristiana Grapa, Tudor Mocan, Daniel Leucuta, Rares Craciun, Lavinia-Patricia Mocan, Miroslaw T. Kornek, Emil Mois, Nadim Al Hajjar, Florin Graur, Teodora Mocan and Zeno Sparchez
Diseases 2026, 14(7), 234; https://doi.org/10.3390/diseases14070234 - 29 Jun 2026
Viewed by 293
Abstract
Background and Aims: To develop an inclusive, predictive framework for hepatocellular carcinoma patients, beyond what the Barcelona Clinic Liver Cancer (BCLC) staging system captures alone, non-invasive scores have emerged as potential contributors. Among them, the CRAFITY score (CRP and AFP in ImmunoTherapY), [...] Read more.
Background and Aims: To develop an inclusive, predictive framework for hepatocellular carcinoma patients, beyond what the Barcelona Clinic Liver Cancer (BCLC) staging system captures alone, non-invasive scores have emerged as potential contributors. Among them, the CRAFITY score (CRP and AFP in ImmunoTherapY), originally developed for immunotherapy-treated HCC populations, and the Platelet-Albumin-Bilirubin (PALBI) score have shown promising prognostic performance in selected cohorts. Likewise, the macrotrabecular-massive (MTM) histological subtype has been identified as a strong independent predictor of tumor recurrence, particularly in surgical series; whether it retains the prognostic significance in a mixed-treatment cohort remains unexplored. We aimed to evaluate the independent prognostic performance of CRAFITY and PALBI across all HCC treatment modalities, determine MTM prevalence and assess whether histological subtyping adds prognostic value beyond these readily available clinical scores. Methods: The study included 500 consecutive, pathologically confirmed HCC patients at a tertiary gastroenterology center in Cluj-Napoca, Romania. MTM subtype was defined as >50% macrotrabecular architectural pattern on histological review by two senior pathologists. Overall survival (OS) and recurrence-free survival (RFS) were assessed by Kaplan–Meier analysis and multivariable Cox regression. A random survival forest (RSF) model was constructed to identify dominant prognostic predictors. Results: MTM was identified in 14 patients (2.8%) and did not independently predict OS (HR 0.94, 95% CI 0.49–1.81, p = 0.85) or recurrence (OR 3.78, p = 0.116). In this heterogeneous cohort spanning multiple treatment modalities, CRAFITY (HR 1.68, 95% CI 1.42–1.98, p < 0.001) and PALBI (HR 1.51, 95% CI 1.22–1.87, p < 0.001) were strong independent predictors of OS after BCLC stage. RSF analysis confirmed this hierarchy with a C-index of 0.734. Conclusions: CRAFITY and PALBI demonstrated strong, independent predictive performance for a large, underrepresented, heterogenous Eastern European HCC cohort. In contrast, MTM subtype showed limited prognostic value in this cohort. The results support the broader applicability of CRAFITY beyond its original immunotherapy context and underline the low prevalence of MTM subtype. Full article
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16 pages, 1041 KB  
Article
Gd-EOB-DTPA-Enhanced MRI Combined with ALBI Score and AFP for Predicting Histologic Grade in Hepatocellular Carcinoma: A Multicentre Study from Vietnam
by Van Hung Nguyen, Dang Luu Vu, The Anh Pham, Cong Long Nguyen, Van Khang Le, Ngoc Trung Nguyen, Le Minh Vu and Ham Hoi Nguyen
Diagnostics 2026, 16(13), 2018; https://doi.org/10.3390/diagnostics16132018 - 28 Jun 2026
Viewed by 257
Abstract
Objectives: The histologic grade is an important prognostic factor in hepatocellular carcinoma (HCC). A Gd-EOB-DTPA-enhanced MRI may provide noninvasive imaging markers related to tumour differentiation. This study aimed to evaluate the association of Gd-EOB-DTPA-enhanced MRI features, together with the albumin–bilirubin (ALBI) score and [...] Read more.
Objectives: The histologic grade is an important prognostic factor in hepatocellular carcinoma (HCC). A Gd-EOB-DTPA-enhanced MRI may provide noninvasive imaging markers related to tumour differentiation. This study aimed to evaluate the association of Gd-EOB-DTPA-enhanced MRI features, together with the albumin–bilirubin (ALBI) score and alpha-fetoprotein (AFP), with the HCC histologic grade and to assess the performance of combined predictive models. Methods: In this prospective cross-sectional study, 75 patients (mean age, 56.4 years; 66 men) with 88 histopathologically confirmed HCC lesions were enrolled. Patients were classified into well-differentiated (grades I–II, n = 24) and poorly differentiated (grades III–IV, n = 51) groups according to the Edmondson–Steiner system. The MRIs were performed on a 1.5-T scanner and included T1-weighted in-phase/opposed-phase imaging; T2-weighted imaging; diffusion-weighted imaging; and dynamic Gd-EOB-DTPA-enhanced sequences, including arterial, portal venous, transitional, and 20 min hepatobiliary phases. Two radiologists, blinded to the pathology, assessed predefined imaging features, and the lesion-to-liver ratio (LLR) was measured. Group comparisons were performed using Student’s t-test, a Mann–Whitney U test, and a chi-square or Fisher’s exact test, followed by a multivariable logistic regression and ROC analysis with bootstrap resampling. Results: Compared with well-differentiated HCC, poorly differentiated HCC showed a higher frequency of peritumoral hepatobiliary phase (HBP) hypointensity (62.7% vs. 4.2%, p < 0.001) and peritumoral arterial hyperintensity (39.2% vs. 0%, p < 0.001). In the multivariable analysis, peritumoral HBP hypointensity remained independently associated with poorly differentiated HCC (OR = 30.89, p = 0.002). The two-parameter MRI model, including peritumoral HBP hypointensity and HBP tumour signal, yielded an AUC of 0.84. The combined MRI + ALBI + AFP model yielded an AUC of 0.87 and an accuracy of 78.7%, representing only a small exploratory improvement over the two-parameter MRI model (AUC = 0.84) in this cohort. Conclusions: Gd-EOB-DTPA-enhanced MRI features, particularly peritumoral HBP hypointensity, were associated with a high histologic grade in HCC. In this surgically treated, predominantly HBV-related cohort with mostly preserved liver function, these findings provide a preliminary basis for preoperative histologic risk stratification; however, they remain exploratory and require external validation in larger, more diverse cohorts before broader clinical application. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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14 pages, 756 KB  
Article
Exploring the Predictive Value of Circulating Cell-Free DNA Within a Multiparameter Panel for Hepatocellular Carcinoma Detection
by Ioana Manea, Speranta Maria Iacob, Razvan Iacob, Alina-Veronica Ghionescu, Andrei Sorop, Roxana Elena Saizu, Daria-Ana-Arina Gheorghe, Delia Prisecariu, Simona Olimpia Dima and Liliana Simona Gheorghe
Life 2026, 16(7), 1079; https://doi.org/10.3390/life16071079 - 27 Jun 2026
Viewed by 225
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. Alpha-fetoprotein (AFP), a widely used and accessible tumoral marker, has limited performance in the early detection of HCC among high-risk populations. This study aims to evaluate the potential added [...] Read more.
Background: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. Alpha-fetoprotein (AFP), a widely used and accessible tumoral marker, has limited performance in the early detection of HCC among high-risk populations. This study aims to evaluate the potential added value of ccfDNA (circulating cell-free DNA) fragment size, alone or in a multiparameter panel, using accessible, feasible ccfDNA analysis. Methods: A prospective cohort of 125 patients with chronic liver disease was analyzed. Patients with incomplete clinical or laboratory data and patients without cirrhosis were excluded from the final analysis. Nonparametric tests, logistic regression and ROC curve analysis were performed. ccfDNA fragment size was measured using on-chip electrophoresis. Results: ccfDNA fragment size was significantly lower in the cirrhosis-HCC subgroup compared to the cirrhosis-only subgroup (p < 0.001). While AFP remains an independent predictor of HCC among cirrhosis patients, ccfDNA fragment size did not prove to be an independent predictor in this cohort. AUROC (area under the receiver operating characteristic curve) analysis revealed that a combined model of AFP, age, liver reserve, and ccfDNA fragment size did not perform better than the corresponding panel without ccfDNA. Moreover, after DeLong comparison, the difference between the two AUROCs proved statistically insignificant. Age and platelet count remain the strongest independent predictors in our exploratory cohort. Conclusions: Although ccfDNA fragment size proved to be lower in the HCC subgroup, its statistical significance fades when included into a multimarker panel. However, all panels should undergo further validation in a larger cohort, in order to better assess the individual contribution of each parameter and to discriminate between added diagnostic value and confounding effect of age and liver reserve parameters. Full article
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14 pages, 2169 KB  
Article
Baseline Tumor-Specific Prognosis in Early-Stage Hepatocellular Carcinoma: Time-Dependent Role of Biomarker Profile and Modified ALBI Grade
by Kelley Núñez, Juan Gimenez, Ari J. Cohen, Jeffrey Burton, Tyler Sandow and Paul Thevenot
Cancers 2026, 18(13), 2073; https://doi.org/10.3390/cancers18132073 - 26 Jun 2026
Viewed by 342
Abstract
Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage [...] Read more.
Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage disease is unclear. In this single-center, prospective study, biomarker profiling with AFP, AFP-L3, and DCP, along with modified albumin–bilirubin (mALBI), and neutrophil–lymphocyte ratio (NLR)/platelet–lymphocyte ratios (PLRs) were evaluated to determine their prognostic role in assessing clinical manifestations of aggressive biology by stratifying HCC progression risk. Methods: Indices and biomarkers were assessed at BCLC-A-stage HCC diagnosis and prior to liver-directed therapy (LDT). The primary prospective study endpoint was time-to-advanced-stage tumor progression (TTP). Results: The cohort included 232 patients diagnosed with early-stage HCC who underwent treatment with LDT. A multivariate model revealed that mALBI grade (p = 0.021), cumulative lesion size (p = 0.005), and elevations in HCC biomarkers (p < 0.001) were associated with TTP. Biomarker profile stratified TTP (p < 0.001) in which patients with complex profiles (3+) had 1-year progression risks of 69%. The biomarker system retained the ability to stratify TTP within small (≤3 cm) and large (>3 cm) cumulative tumor burden (p < 0.001, p = 0.005). While PLR was not prognostic for TTP, NLR disappeared from the multivariate model and mALBI stratified long-term progression risk (p = 0.003). In low-complex biomarker patients (0–1+), mALBI stratified progression risk (p = 0.001). Conclusions: Multi-positive biomarker profiling in early-stage HCC identifies a population with clinical manifestations of aggressive tumor biology at high risk of rapid post-treatment disease progression that may benefit from more aggressive treatment approaches. In patients with low-risk biomarker profiles (0–1+), mALBI can assess longer-term (>1-year) post-treatment disease progression risk, while scores based on systemic inflammation were not associated with tumor-restricted outcomes. Full article
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23 pages, 4877 KB  
Article
Metabolomics Approach Identifies Predictive Serum Markers for Hepatocellular Carcinogenesis Following Hepatitis C Virus Elimination
by Takeshi Chida, Satoshi Sakai, Masahiko Ito, Kazumasa Sekihara, Kazuyoshi Ohta, Masahiro Matsushita, Gou Murohisa, Fujito Kageyama, Yuzo Sasada, Tatsuki Oyaizu, Minoru Tsugiki, Katsutoshi Tamakoshi, Tomomi Okubo, Sachiyo Yoshio, Masanori Atsukawa, Akihito Tsubota, Yasuhito Tanaka, Tatsuya Kanto, Toshiyuki Ojima, Kazuhito Kawata, Takafumi Suda and Tetsuro Suzukiadd Show full author list remove Hide full author list
Cancers 2026, 18(12), 2003; https://doi.org/10.3390/cancers18122003 - 20 Jun 2026
Viewed by 379
Abstract
Background: Abnormalities in energy and amino acid metabolism are potentially involved in hepatocellular carcinoma (HCC) development. This study aimed to identify serum metabolites predictive of HCC following sustained virological response (SVR) with hepatitis C virus (HCV) treatment. Methods: Comparative metabolomics was [...] Read more.
Background: Abnormalities in energy and amino acid metabolism are potentially involved in hepatocellular carcinoma (HCC) development. This study aimed to identify serum metabolites predictive of HCC following sustained virological response (SVR) with hepatitis C virus (HCV) treatment. Methods: Comparative metabolomics was conducted using time-course serum samples from patients who failed interferon-based therapy but subsequently achieved SVR with direct-acting antivirals (DAAs), minimizing inter-individual variability. Predictive biomarkers for post-SVR HCC were extracted from the results and validated by comparing 29 patients who developed post-SVR HCC with 58 age-matched patients who remained HCC-free during follow-up. Results: Metabolite concentrations changed more markedly after treatment in SVR cases than in non-SVR cases. Significant changes in methionine (Met), methionine sulfoxide (MetO), and ornithine (Orn) levels before and after treatment (Pre- and Post-Tx) were found only in the non-HCC group. Regression and survival analyses identified high levels of Pre- and Post-Tx Orn, Pre-Tx Met, and Post-Tx MetO as predictors of post-SVR HCC and enabled risk stratification. The integration of these metabolites with the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) facilitated risk stratification and discriminated between high- and low-risk patients. The Pre-Tx FIB-4/Met model and the Post-Tx AFP/MetO/Orn model identified low- and high-risk groups with 3-year HCC incidence rates of 6.4% and 81.8%, respectively. Conclusions: Serum Met, MetO, and Orn were identified as candidate biomarkers associated with post-SVR HCC development, which remains a concern in the fight against hepatitis C. Combining these metabolites with established clinical markers may improve post-SVR HCC risk stratification. Full article
(This article belongs to the Section Cancer Biomarkers)
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15 pages, 1313 KB  
Article
Circulating Cell-Free DNA Analysis for Diagnostic and Prognostic Assessment of Hepatocellular Carcinoma in Cirrhosis
by Inés Aznar-Peralta, Amparo Roa-Colomo, Javier López Hidalgo, Cristobal Fresno, Valeria Denninghoff and María José Serrano
Int. J. Mol. Sci. 2026, 27(12), 5590; https://doi.org/10.3390/ijms27125590 - 20 Jun 2026
Viewed by 371
Abstract
Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples [...] Read more.
Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples from 39 HCC and 46 LC patients were analyzed for cfDNA concentration and fragment patterns. A multivariate logistic regression model (CMAC), integrating cfDNA concentration, mononucleosome proportion (%MN), alpha-fetoprotein (AFP), and c-reactive protein (CRP), was developed and validated using Leave-One-Out Cross-Validation and bootstrapping. HCC patients exhibited significantly higher cfDNA concentrations (p < 0.0001) and longer fragment lengths (p < 0.05) compared to LC patients. The CMAC model demonstrated superior diagnostic performance (AUROC = 0.946) compared to AFP alone (AUROC = 0.777, p < 0.001). Notably, in early-stage HCC, the CMAC model remained highly accurate (AUROC = 0.941), whereas AFP failed to reach statistical significance. Higher CMAC scores were significantly associated with advanced BCLC stages (p = 0.009), lymphovascular invasion (p = 0.0063) and reduced overall survival (p = 0.0037). Integration of cfDNA analysis with established clinical markers in the CMAC model shows promise as a complementary tool for the early detection of HCC in LC patients. Validation in larger, multicenter cohorts will be necessary to confirm these findings and their clinical applicability. Full article
(This article belongs to the Special Issue Biomarkers in Oncology)
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20 pages, 3089 KB  
Article
Chitosan–PLGA Hybrid Nanocarriers Enhance Therapeutic Delivery of Doxorubicin for Hepatocellular Carcinoma
by Shajahan Azeez, Anbazhagan Sathiyaseelan, Mohana Thiruchenduran, Kaviyarasan Venkatesan and Latha Ragunathan
Macromol 2026, 6(2), 42; https://doi.org/10.3390/macromol6020042 - 10 Jun 2026
Viewed by 520
Abstract
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal malignancies worldwide, with limited therapeutic outcomes due to systemic toxicity and suboptimal efficacy of conventional chemotherapeutics such as doxorubicin (DOX). In this study, we formulated and standardized DOX-loaded chitosan/poly (lactic-co-glycolic acid) nanoparticles (DLCNs) [...] Read more.
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal malignancies worldwide, with limited therapeutic outcomes due to systemic toxicity and suboptimal efficacy of conventional chemotherapeutics such as doxorubicin (DOX). In this study, we formulated and standardized DOX-loaded chitosan/poly (lactic-co-glycolic acid) nanoparticles (DLCNs) via a nanoprecipitation method and evaluated their therapeutic potential in a diethylnitrosamine (DEN)-induced Wistar rat model of HCC. Physicochemical analyses confirmed nanoscale size, favorable zeta potential, and high encapsulation efficiency, while Fourier-transform infrared spectroscopy (FTIR) verified polymer–drug interactions. Biochemical analysis revealed that DLCNs significantly normalized elevated liver function markers (Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), restored serum α-fetoprotein (AFP) to near-control levels, and reduced lipid peroxidation compared with free DOX and DEN controls. Antioxidant profiling demonstrated marked recovery of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), indicating restoration of hepatic redox balance. Histopathological evaluation further corroborated these findings, showing recovery of hepatic lobular architecture and reduction in necrosis and inflammatory infiltrates in DLCN-treated Wistar Albino rats, while free DOX groups exhibited hepatocellular damage. Overall, the results demonstrate that encapsulating DOX in a chitosan/PLGA nanocarrier improves therapeutic efficacy, mitigates hepatotoxicity, and enhances antioxidant defense, establishing DLCNs as a favorable candidate for HCC. Full article
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37 pages, 3405 KB  
Article
Hypoxia Associated Integration of Epigenetic, Metabolic, and Immune Biomarkers in Blood and Urine for Early Colorectal Cancer Detection: A Multimarker Panel
by Christopher Birigwa, Bing Qu, Yongqing Tong, Teng Zuo, Wenzheng Yuan, Qingbo Wang, Wei Song, Weiwei Wan, Jing Xiong, Jianfei Luo and Qiang Tong
Diagnostics 2026, 16(12), 1753; https://doi.org/10.3390/diagnostics16121753 - 6 Jun 2026
Viewed by 493
Abstract
Background: Detection of colorectal cancer (CRC) currently relies mainly on invasive procedures such as colonoscopy. In experimental models, tumor hypoxia induces epigenetic, metabolic, and immune changes via hypoxia-inducible factor (HIF) signaling. Building on these published insights, this study evaluated whether a panel of [...] Read more.
Background: Detection of colorectal cancer (CRC) currently relies mainly on invasive procedures such as colonoscopy. In experimental models, tumor hypoxia induces epigenetic, metabolic, and immune changes via hypoxia-inducible factor (HIF) signaling. Building on these published insights, this study evaluated whether a panel of biomarkers previously associated with hypoxia-related processes, plasma methylated SEPT9 (mSEPT9), urinary N1, N12-diacetylspermine (DiAcSpm), and systemic inflammatory indices (NLR, PLR, and LMR)—could be combined into a non-invasive diagnostic panel and compared with standard serum tumor markers. This study focused solely on diagnostic performance; it did not directly assess tumor hypoxia or HIF expression in patients. This study was conducted in a clinical diagnostic setting (patients with confirmed CRC, polyps, or benign surgical conditions) and does not represent a population-based screening cohort. Limitations include the lack of an external validation cohort; all analyses were performed on a single dataset, and the reported performance metrics may be optimistic. Independent validation is required before clinical implementation. Methods: This prospective single-center study enrolled 382 participants: 142 with CRC, 62 with colorectal polyps, and 178 non-malignant controls. Plasma mSEPT9 was quantified by real-time PCR, urinary DiAcSpm by ELISA, and inflammatory indices from blood counts. Serum tumor markers (CEA, CA19-9, CA125, and AFP) were measured by immunoassay. Diagnostic accuracy was assessed using ROC analysis and multivariable logistic regression. Results: mSEPT9 (AUC 0.843) and DiAcSpm (AUC 0.831) demonstrated significantly higher diagnostic accuracy than CEA (AUC 0.660) and CA19-9 (AUC 0.649). A combined panel including mSEPT9, DiAcSpm, NLR, PLR, and LMR achieved an AUC of 0.947, with 85.9% sensitivity and 92.9% specificity. This panel also showed strong performance for early-stage CRC (AUC 0.905). Conclusions: A multimarker panel of biomarkers (mSEPT9, DiAcSpm, NLR, PLR, and LMR) provides a non-invasive diagnostic approach for CRC detection in a clinical case–control setting. Validation in asymptomatic screening populations is required before any screening claim can be made. These findings are associative; direct evidence that tumor hypoxia drives these biomarker changes was not obtained and requires future investigation. Full article
(This article belongs to the Special Issue Advancements in Diagnosis of Colorectal Cancer)
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17 pages, 16423 KB  
Article
Experimental Study on Permeability and Infusion Simulation of Automatically Placed Dry Fiber Preforms
by Wei Du, Jun Liu, Hao Song, Minqiang Jiang, Bo Ning, Yang Yang, Weiping Liu, Keqing Han, Hui Zhang and Jianyong Yu
J. Compos. Sci. 2026, 10(5), 279; https://doi.org/10.3390/jcs10050279 - 21 May 2026
Viewed by 683
Abstract
To investigate the resin infusion molding process for novel dry fiber-reinforced epoxy composite wing skin, dry fiber preforms were fabricated via an automated fiber placement (AFP) system, and the out-of-plane permeability of the preforms at different lay-up speeds was measured using the ultrasonic [...] Read more.
To investigate the resin infusion molding process for novel dry fiber-reinforced epoxy composite wing skin, dry fiber preforms were fabricated via an automated fiber placement (AFP) system, and the out-of-plane permeability of the preforms at different lay-up speeds was measured using the ultrasonic transmission method to determine the optimal lay-up parameters. A scaled-down composite wing skin structure was modeled and meshed via numerical simulation, and different resin infusion schemes were simulated and analyzed using PAM-RTM software. The optimal infusion scheme was determined by comparing the infusion time, infusion pressure and defect formation during resin flow for different schemes, and the wing skin component was fabricated through the vacuum-assisted resin infusion (VARI) process. Results indicate that the infusion time predicted by PAM-RTM simulation is 3883 s, while the actual measured value in the VARI process is 3611 s with an error of approximately 7% within a reasonable range. Both simulation and actual wing skin fabrication exhibited no significant defects, validating the accuracy of the three-dimensional permeability measurement of dry fiber preforms as well as the reliability of the simulation results. Full article
(This article belongs to the Special Issue Carbon Fiber Composites, 4th Edition)
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22 pages, 8262 KB  
Article
Antifreeze Protein for Freeze–Thaw Durability Enhancement of Cement Mortar: Effects and Action Analysis
by Qiyu Zhang, Jingwei Gong and Miaomiao Gong
Materials 2026, 19(10), 1997; https://doi.org/10.3390/ma19101997 - 12 May 2026
Viewed by 424
Abstract
Enhancing the freeze–thaw resistance of cement-based materials in a green and efficient manner is crucial for hydraulic structures in cold regions. This study investigated the effects of soybean antifreeze protein (AFP) on the freeze–thaw durability of cement mortar through mechanical testing, low-temperature microscopy, [...] Read more.
Enhancing the freeze–thaw resistance of cement-based materials in a green and efficient manner is crucial for hydraulic structures in cold regions. This study investigated the effects of soybean antifreeze protein (AFP) on the freeze–thaw durability of cement mortar through mechanical testing, low-temperature microscopy, NMR analysis, and frost-heaving stress monitoring. The results show that AFP improves freeze–thaw durability, with 0.5% dosage outperforming 1.0%. Relative to the control, the relative ice content at −20 °C decreased from 62.81% to 40.01%, and frost-heaving stress declined from 321.15 kPa to 123.04 kPa. Microscopy and pore structure analyses revealed that AFP transforms ice crystals from needle-like to fine granular forms, inhibiting ordered growth and retarding pore coarsening. A frost-heaving stress model based on the Gibbs–Thomson effect and ice-crystal fractal characteristics indicated that AFP suppresses stress development by reducing effective ice formation, weakening stress transfer, and increasing ice-crystal boundary complexity. This study offers insights for developing green antifreeze admixtures for cement-based materials in cold regions. Full article
(This article belongs to the Section Construction and Building Materials)
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12 pages, 1866 KB  
Article
Prognostic Value of 18F-FDG and 18F-FEC Uptake in Hepatocellular Carcinoma Using Contrast-Enhanced Integrated PET/MRI: Correlation with Histology and Survival
by Marzieh Nejabat, Lucian Beer, Theresa Servus, Ahmed Ba-Ssalamah, Peter Mazal, Lukas Nics, Marcus Hacker, Georgios Karanikas and Sazan Rasul
Cancers 2026, 18(10), 1526; https://doi.org/10.3390/cancers18101526 - 9 May 2026
Viewed by 661
Abstract
Background: Dual-tracer positron emission tomography/magnetic resonance imaging (PET/MRI) using [18F]-fluorodeoxyglucose (18F-FDG) and [18F]-fluoroethylcholine (18F-FEC) may reveal complementary aspects of hepatocellular carcinoma (HCC) biology. This retrospective study evaluates whether PET parameters obtained from 18F-FDG and [...] Read more.
Background: Dual-tracer positron emission tomography/magnetic resonance imaging (PET/MRI) using [18F]-fluorodeoxyglucose (18F-FDG) and [18F]-fluoroethylcholine (18F-FEC) may reveal complementary aspects of hepatocellular carcinoma (HCC) biology. This retrospective study evaluates whether PET parameters obtained from 18F-FDG and 18F-FEC correlate with MRI enhancement parameters, tumor histological grade, and survival in patients with HCC. Methods: We retrospectively evaluated 25 patients who underwent integrated PET/MRI. Lesions were analyzed on pre-contrast MRI and at early (3–5 min) and late (20–30 min) post-contrast phases. For 18F-FDG and 18F-FEC, standardized uptake values (SUV maximum, mean, and peak) and metabolic tumor volume were measured, along with lesion size, MRI enhancement ratios, AFP levels, and survival. For patient-level imaging analyses, the largest lesion per patient was defined as the index lesion. Correlation analysis using Spearman’s rank correlation coefficient, Kaplan–Meier analysis, log-rank testing, and exploratory Cox proportional hazards models were performed. Results:18F-FDG SUVmean (index lesion) showed the strongest inverse association with survival (r = −0.61, p = 0.003), followed by SUVpeak (r = −0.50, p = 0.012). 18F-FDG SUVmean differed across tumor grades (G1–G3; p = 0.040), without a consistent trend. In Cox regression, 18F-FDG SUVpeak was significantly associated with shorter overall survival (HR 1.22, 95% CI 1.05–1.42, p = 0.01), whereas SUVmean showed only a borderline association (p = 0.07). When split at the median, SUVmean was also significantly associated with shorter survival (p < 0.001; HR 10.39, 95% CI 2.75–39.3). 18F-FEC parameters were not associated with survival but showed a moderate correlation with AFP levels (r = 0.41, p = 0.01). Dynamic MRI early and delayed enhancement of the index lesion were strongly correlated (r = 0.70, p < 0.001) but not associated with survival. Conclusions: In HCC, 18F-FDG uptake provides prognostic information beyond MRI enhancement and histology, reflecting tumor aggressiveness and independently predicting survival. While 18F-FEC-PET complements lesion characterization and correlates with AFP, it does not show meaningful prognostic value. MRI enhancement parameters were not associated with survival in this cohort. 18F-FDG-based metabolic imaging may improve pre-treatment risk stratification, whereas dual-tracer PET/MRI should be considered a selective, exploratory approach rather than routine imaging. Full article
(This article belongs to the Section Methods and Technologies Development)
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22 pages, 3091 KB  
Article
Functional Characterization of BbroAFP Reveals Its Pleiotropic Antifungal Activity in Botrytis cinerea
by Arda Örçen, Yunus Doğan, Amjad Tulimat, Beyza Goncu, Batu Erman and Günseli Bayram Akçapınar
J. Fungi 2026, 12(5), 305; https://doi.org/10.3390/jof12050305 - 23 Apr 2026
Viewed by 1347
Abstract
Fungal pathogens pose a major threat to global agriculture and human health, necessitating alternative antifungal strategies with high efficacy and low resistance potential. Antifungal proteins (AFPs) from filamentous fungi are promising candidates due to their stability, selectivity, and diverse mechanisms of action. Here, [...] Read more.
Fungal pathogens pose a major threat to global agriculture and human health, necessitating alternative antifungal strategies with high efficacy and low resistance potential. Antifungal proteins (AFPs) from filamentous fungi are promising candidates due to their stability, selectivity, and diverse mechanisms of action. Here, we characterize Beauveria brongniartii antifungal protein (BbroAFP), a novel cysteine-rich protein from the entomopathogenic fungus B. brongniartii, and investigate its antifungal activity against Botrytis cinerea. Recombinant BbroAFP was expressed in Pichia pastoris, purified, and verified by liquid chromatography–tandem mass spectroscopy (LC–MS/MS) and in silico modeling. BbroAFP showed potent antifungal activity with minimum inhibitory concentrations (MICs) as low as 1 µM against several phytopathogenic fungi, while exhibiting no significant antibacterial activity. Activity was maintained across a wide range of pH and temperature conditions. Confocal microscopy revealed rapid surface binding followed by cytosolic internalization without major cell wall disruption. BbroAFP induced a rapid, transient burst of reactive oxygen species (ROS), accompanied by nuclear DNA fragmentation. Gene expression analysis revealed a transient increase in aif1, whereas mca1 expression decreased at later time points and mca2 remained largely unchanged, suggesting a metacaspase-independent response. Detached tomato leaf assays showed effective protection against B. cinerea without detectable phytotoxicity. Cytotoxicity assays confirmed a favorable safety profile, supporting further evaluation of BbroAFP for plant protection. Full article
(This article belongs to the Special Issue Advances in the Control of Plant Fungal Pathogens)
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30 pages, 7534 KB  
Article
Multi-Gait In-Pipe Locomotion via Programmable Friction Reorientation
by Jaehyun Lee and Jongwoo Kim
Biomimetics 2026, 11(4), 285; https://doi.org/10.3390/biomimetics11040285 - 20 Apr 2026
Viewed by 1170
Abstract
In-pipe robots must navigate narrow, curved passages where rigid mechanisms often require bulky steering units. Soft crawlers offer better compliance but typically rely on multiple actuators or reconfigurable contacts to achieve multi-directional motion. Drawing inspiration from biological soft crawlers that exploit directional friction [...] Read more.
In-pipe robots must navigate narrow, curved passages where rigid mechanisms often require bulky steering units. Soft crawlers offer better compliance but typically rely on multiple actuators or reconfigurable contacts to achieve multi-directional motion. Drawing inspiration from biological soft crawlers that exploit directional friction and coordinated anchor–slip patterns, this study focuses on locomotion principles observed in caterpillars, water boatmen, and whirligig beetles. Based on these bioinspired concepts, we present a tendon-driven soft in-pipe robot that combines continuum bending–twisting deformation with modular anisotropic friction pads (AFPs), enabling three locomotion modes using only two motors. AFP inclination, curvature, and ridge geometry were optimized through friction tests, constant-curvature modeling, and finite element analysis to enhance directional adhesion on flat and curved surfaces. A deformation-based locomotion framework was developed to couple tendon actuation with friction orientation, achieving longitudinal crawling, transverse translation, in-place rotation, and smooth transitions via programmed twisting. Driving experiments demonstrated repeatable anchor–slip locomotion with average speeds of 28.6 mm/s, 15.7 mm/s, and 11.5°/s for the three modes. Pipe tests in straight, curved, and T-junction sections further validated stable contact and reliable gait transitions. These findings highlight the potential of friction-programmed continuum robots as compact, bioinspired platforms for advanced in-pipe inspection and diagnostic tasks. Full article
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18 pages, 2311 KB  
Article
A Non-Invasive Integrated Model for Accurate Preoperative Identification of the Aggressive Macrotrabecular-Massive Subtype of Hepatocellular Carcinoma: A Single-Center Retrospective Study
by Yuanqing Zhang, Yang He, Yifei Chen, Xiaorong Lv, Rong Yang, Guo Chen and Fang Nie
Diagnostics 2026, 16(6), 877; https://doi.org/10.3390/diagnostics16060877 - 16 Mar 2026
Viewed by 685
Abstract
Objective: The objective of this study was to develop and validate a predictive model for MTM-HCC by integrating preoperative ultrasound (US) and contrast-enhanced ultrasound (CEUS) features with relevant clinical characteristics. Methods: This retrospective study analyzed data from patients with histopathologically confirmed hepatocellular carcinoma [...] Read more.
Objective: The objective of this study was to develop and validate a predictive model for MTM-HCC by integrating preoperative ultrasound (US) and contrast-enhanced ultrasound (CEUS) features with relevant clinical characteristics. Methods: This retrospective study analyzed data from patients with histopathologically confirmed hepatocellular carcinoma who underwent preoperative CEUS examination at the Ultrasound Department of the Lanzhou University Second Hospital between December 2021 and March 2025. The study cohort comprised 45 patients diagnosed with MTM-HCC and 194 patients with non-MTM-HCC. Ultrasound and CEUS images were independently reviewed by two senior abdominal radiologists with extensive experience in hepatic imaging, ensuring objective feature assessment. Clinical variables and imaging characteristics were systematically compared between the two groups to identify distinguishing patterns. To evaluate the associations among clinical data, ultrasound-derived features, and MTM-HCC, univariate analyses were first performed, followed by multivariate logistic regression to construct and assess predictive models. Results: A total of 239 patients (mean age: 57.28 ± 9.60 years; 187 males and 52 females) were included in the analysis. Among them, 45 HCC patients (18.8%) were classified as MTM-HCC. Multivariate analysis identified four independent predictors: elevated alpha-fetoprotein (AFP ≥ 467 ng/mL) (OR = 8.5, 95% CI: 4.2–17.30; p < 0.001), presence of non-enhancing necrotic areas (OR = 5.92, 95% CI: 1.82–19.30, p = 0.003), intratumoral arteries (OR = 6.61, 95% CI: 2.28–19.22, p < 0.001), and peritumoral feeding arteries (OR = 3.13, 95% CI: 1.15–8.50, p = 0.025). Conclusions: An integrated prediction model that combines ultrasound imaging and clinical parameters offers a feasible, non-invasive approach for accurate preoperative identification of MTM-HCC. Full article
(This article belongs to the Special Issue Abdominal Ultrasound: A Left Behind Area—2nd Edition)
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