A Modified Targetoid Feature Emphasizing Thin-Rim APHE to Improve the Diagnostic Performance of LI-RADS for Malignant Hepatic Tumors.

Objective: To identify imaging features that help distinguish between HCCs and non-HCC malignancies assigned to LI-RADS M (LR-M) and evaluate the diagnostic performance of a LI-RADS with targetoid criteria using thin-rim arterial phase hyperenhancement (APHE). Materials and Methods: This retrospective study included 381 patients (387 observations) at high-risk for HCC who underwent enhanced-MRI before surgery. Three radiologists reviewed images for LI-RADS categorization of hepatic observations. Univariate and multivariate analysis was conducted to determine reliable features to differentiate between HCC and non-HCC malignancies among the LR-M lesions. The thin-rim (<30%) APHE was defined based on the thickest thickness of rim APHE compared with the tumor radius, and a modified LI-RADS emphasizing thin-rim APHE as a specific feature of LR-M was established. We compared the diagnostic performance of modified LR-M and LI-RADS 5 (LR-5) with the conventional one. Results: Thin-rim APHE and targetoid diffusion-weighted imaging (DWI) were found as independent predictive factors of non-HCC malignancies, while enhancing capsule, thick-rim APHE and peripheral washout were noted as independent variables significantly associated with HCC of LR-M (P<0.05). The noticeable diagnostic performance of thin-rim APHE in distinguishing non-HCC malignancies from HCCs using the ROC curve. Emphasizing thin-rim APHE on targetoid features, the modified LR-M revealed significantly superior specificity and accuracy (89.4% vs 81.1%, P=0.004; and 87.9% vs 82.2%, P=0.027, respectively) while maintaining high sensitivity (82.2% vs 86.0%; P=0.529) compared with the LR-M. Meanwhile, the modified LR-5 achieved greater sensitivity and accuracy (88.6% vs 79.7%, P=0.004; and 85.8% vs 80.1%, P=0.036, respectively) for diagnosing HCC, without compromising specificity (78.3% vs.81.1%; P=0.608) compared with the LR-5. Conclusion: Thin-rim APHE may be the specific imaging feature for differentiating non-HCC malignancies from HCCs within LR-M. The modified targetoid criteria emphasizing thin-rim APHE can improve the diagnostic performance of LI-RADS for hepatic malignancies.

Altered Cortical Information Interaction During Respiratory Events in Children with Obstructive Sleep Apnea-Hypopnea Syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) significantly impairs children's growth and cognition. This study aims to elucidate the pathophysiological mechanisms underlying OSAHS in children, with a particular focus on the alterations in cortical information interaction during respiratory events. We analyzed sleep electroencephalography before, during, and after events, utilizing Symbolic Transfer Entropy (STE) for brain network construction and information flow assessment. The results showed a significant increase in STE after events in specific frequency bands during N2 and rapid eye movement (REM) stages, along with increased STE during N3 stage events. Moreover, a noteworthy rise in the information flow imbalance within and between hemispheres was found after events, displaying unique patterns in central sleep apnea and hypopnea. Importantly, some of these alterations were correlated with symptom severity. These findings highlight significant changes in brain region coordination and communication during respiratory events, offering novel insights into OSAHS pathophysiology in children.

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA. Here we investigated the clinical impact and underlying molecular characteristics of C. sinensis infection-related iCCA. METHODS: We performed single-cell RNA sequencing, whole-exome sequencing, RNA sequencing, metabolomics and spatial transcriptomics in 251 patients with iCCA from three medical centers. Alterations in metabolism and the immune microenvironment of C. sinensis-related iCCAs were validated through an in vitro co-culture system and in a mouse model of iCCA. RESULTS: We revealed that C. sinensis infection was significantly associated with iCCA patients' overall survival and response to immunotherapy. Fatty acid biosynthesis and the expression of fatty acid synthase (FASN), a key enzyme catalyzing long-chain fatty acid synthesis, were significantly enriched in C. sinensis-related iCCAs. iCCA cell lines treated with excretory/secretory products of C. sinensis displayed elevated FASN and free fatty acids. The metabolic alteration of tumor cells was closely correlated with the enrichment of tumor-associated macrophage (TAM)-like macrophages and the impaired function of T cells, which led to formation of an immunosuppressive microenvironment and tumor progression. Spatial transcriptomics analysis revealed that malignant cells were in closer juxtaposition with TAM-like macrophages in C. sinensis-related iCCAs than non-C. sinensis-related iCCAs. Importantly, treatment with a FASN inhibitor significantly reversed the immunosuppressive microenvironment and enhanced anti-PD-1 efficacy in iCCA mouse models treated with excretory/secretory products from C. sinensis. CONCLUSIONS: We provide novel insights into metabolic alterations and the immune microenvironment in C. sinensis infection-related iCCAs. We also demonstrate that the combination of a FASN inhibitor with immunotherapy could be a promising strategy for the treatment of C. sinensis-related iCCAs. IMPACT AND IMPLICATIONS: Clonorchis sinensis (C. sinensis)-infected patients with intrahepatic cholangiocarcinoma (iCCA) have a worse prognosis and response to immunotherapy than non-C. sinensis-infected patients with iCCA. The underlying molecular characteristics of C. sinensis infection-related iCCAs remain unclear. Herein, we demonstrate that upregulation of FASN (fatty acid synthase) and free fatty acids in C. sinensis-related iCCAs leads to formation of an immunosuppressive microenvironment and tumor progression. Thus, administration of FASN inhibitors could significantly reverse the immunosuppressive microenvironment and further enhance the efficacy of anti-PD-1 against C. sinensis-related iCCAs.

Predicting 5-year recurrence risk in colorectal cancer: development and validation of a histology-based deep learning approach.

BACKGROUND: Accurate estimation of the long-term risk of recurrence in patients with non-metastatic colorectal cancer (CRC) is crucial for clinical management. Histology-based deep learning is expected to provide more abundant information for risk stratification. METHODS: We developed and validated a weakly supervised deep-learning model for predicting 5-year relapse-free survival (RFS) to stratify patients with different risks based on histological images from three hospitals of 614 cases with non-metastatic CRC. A deep prognostic factor (DL-RRS) was established to stratify patients into high and low-risk group. The areas under the curve (AUCs) were calculated to evaluate the performances of models. RESULTS: Our proposed model achieves the AUCs of 0.833 (95% CI: 0.736-0.905) and 0.715 (95% CI: 0.647-0.776) on validation cohort and external test cohort, respectively. The 5-year RFS rate was 45.7% for high DL-RRS patients, and 82.5% for low DL-RRS patients respectively in the external test cohort (HR: 3.89, 95% CI: 2.51-6.03, P < 0.001). Adjuvant chemotherapy was associated with improved RFS in Stage II patients with high DL-RRS (HR: 0.15, 95% CI: 0.06-0.38, P < 0.001). CONCLUSIONS: DL-RRS has a good predictive performance of 5-year recurrence risk in CRC, and will better serve the clinical decision-making.

RFX6 facilitates aerobic glycolysis-mediated growth and metastasis of hepatocellular carcinoma through targeting PGAM1.

BACKGROUND: Hepatocellular carcinoma (HCC) cells undergo reprogramming of glucose metabolism to support uncontrolled proliferation, of which the intrinsic mechanism still merits further investigation. Although regulatory factor X6 (RFX6) is aberrantly expressed in different cancers, its precise role in cancer development remains ambiguous. METHODS: Microarrays of HCC tissues were employed to investigate the expression of RFX6 in tumour and adjacent non-neoplastic tissues. Functional assays were employed to explore the role of RFX6 in HCC development. Chromatin immunoprecipitation, untargeted metabolome profiling and sequencing were performed to identify potential downstream genes and pathways regulated by RFX6. Metabolic assays were employed to investigate the effect of RFX6 on glycolysis in HCC cells. Bioinformatics databases were used to validate the above findings. RESULTS: HCC tissues exhibited elevated expression of RFX6. High RFX6 expression represented as an independent hazard factor correlated to poor prognosis in patients with HCC. RFX6 deficiency inhibited HCC development in vitro and in vivo, while its overexpression exerted opposite functions. Mechanistically, RFX6 bound to the promoter area of phosphoglycerate mutase 1 (PGAM1) and upregulated its expression. The increased PGAM1 protein levels enhanced glycolysis and further promoted the development of HCC. CONCLUSIONS: RFX6 acted as a novel driver for HCC development by promoting aerobic glycolysis, disclosing the potential of the RFX6-PGAM1 axis for therapeutic targeting.

Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC).

PURPOSE: To investigate the efficacy, safety, and biomarkers of systemic chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) in combination with lenvatinib and toripalimab as the first-line treatment for advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis. PATIENTS AND METHODS: In this biomolecular exploratory, phase II trial, eligible patients underwent the triple combination therapy of lenvatinib, toripalimab, plus FOLFOX chemotherapy. Primary endpoint was progression-free survival (PFS) rate at 6 months by RECIST v1.1. Single-nucleus RNA sequencing (snRNA-seq) of tumor biopsy samples was performed for exploratory biomarker analyses. RESULTS: Between November 19, 2019, and July 4, 2021, 30 patients were enrolled. The primary endpoint was a 6-month PFS rate of 66.7%, with a median PFS of 9.73 months [95% confidence interval (CI), 2.89-16.58]. The median overall survival (OS) was 14.63 months (95% CI, 11.77-17.50), with an objective response rate of 43.3%. Twenty-four (80.0%) patients exhibited high-risk features, among whom the median OS and PFS were 13.7 months (95% CI, 9.24-18.16) and 8.3 months (95% CI, 3.02-13.58), respectively. The most common adverse events were neutropenia, and increased aspartate aminotransferase and alanine aminotransferase levels. Exploratory analyses of snRNA-seq profiles suggested that patients with higher abundance of tumor-infiltrating immune cells were more likely to benefit from this combination. In addition, two subtypes of hepatocytes (AKR1C2+ and CFHR4+ malignant hepatocytes) were associated with reduced clinical benefits. CONCLUSIONS: FOLFOX chemotherapy in combination with lenvatinib and toripalimab showed promising antitumor activity with manageable toxicities in advanced HCC with extrahepatic metastasis. AKR1C2+ and CFHR4+ hepatocyte subtypes may be predictive biomarkers of resistance to the combination therapy.

Improving Tumor Classification by Reusing Self-predicted Segmentation of Medical Images as Guiding Knowledge.

Differential diagnosis of tumors is important for computer-aided diagnosis. In computer-aided diagnosis systems, expert knowledge of lesion segmentation masks is limited as it is only used during preprocessing or as supervision to guide feature extraction. To improve the utilization of lesion segmentation masks, this study proposes a simple and effective multitask learning network that improves medical image classification using self-predicted segmentation as guiding knowledge; we call this network RS 2-net. In RS 2-net, the predicted segmentation probability map obtained from the initial segmentation inference is added to the original image to form a new input, which is then reinput to the network for the final classification inference. We validated the proposed RS 2-net using three datasets: the pNENs-Grade dataset, which tested the prediction of pancreatic neuroendocrine neoplasm grading, and the HCC-MVI dataset, which tested the prediction of microvascular invasion of hepatocellular carcinoma, and ISIC 2017 public skin lesion dataset. The experimental results indicate that the proposed strategy of reusing self-predicted segmentation is effective, and RS 2-net outperforms other popular networks and existing state-of-the-art studies. Interpretive analytics based on feature visualization demonstrates that the improved classification performance of our reuse strategy is due to the semantic information that can be acquired in advance in a shallow network.

Cognitive reserve disorder in age-related hearing loss: cognitive cortical compensatory to auditory perceptual processing.

The aim of this study is to ascertain the mechanisms of cognitive reserve disorder in age-related hearing loss (ARHL), to study the correlation between ARHL and cognitive decline via EEG, and to reverse the adverse remodeling of auditory-cognitive connectivity with hearing aids (HAs). In this study, 32 participants were enrolled, including 12 with ARHLs, 9 with HAs, and 11 healthy controls (HCs), to undergo EEG, Pure Tone Average (PTA), Montreal Cognitive Assessment (MoCA), and other general cognitive tests. There were the lowest MoCA in the ARHL group (P = 0.001), especially in language and abstraction. In the ARHL group, power spectral density of the gamma in right middle temporal gyrus was significantly higher than HC and HA groups, while functional connectivity between superior frontal gyrus and cingulate gyrus was weaker than HC group (P = 0.036) and HA group (P = 0.021). In the HA group, superior temporal gyrus and cuneus had higher connectivity than in the HC group (P = 0.036). In the ARHL group, DeltaTM_DTA (P = 0.042) and CTB (P = 0.011) were more frequent than in the HC group, while there was less DeltaTM_CTA (P = 0.029). PTA was found to be associated with MoCA (r = -0.580) and language (r = -0.572), DeltaTM_CTB had a likewise correlation with MoCA (r = 0.483) and language (r = 0.493), while DeltaTM_DTA was related to abstraction (r = -0.458). Cognitive cortexes compensate for worse auditory perceptual processing in ARHL, which relates to cognitive decline. The impaired functional connectivity between auditory and cognitive cortexes can be remodeled by HAs. DeltaTM may serve as a biomarker for early cognitive decline and decreased auditory speech perception in ARHL.

The influence of the extent of lymph node metastasis on the prognosis for patients with intrahepatic cholangiocarcinoma.

Purpose: Reports showed that some of intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM) may also gain survival benefit undergone resection. However, the effect of the extent of LNM on prognosis and surgical indication is barely discussed. Methods: From September 1994 to November 2018, primary ICC patients undergone initial curable surgery were enrolled. Based on the extent of LNM, we divided these patients into 4 groups, including patients with no LNM (group N0), LNM to hepatoduodenal ligament or common hepatic artery (region A, group A), LNM to gastrohepatic lymph nodes for left liver ICC and periduodenal and peripancreatic lymph node for right liver ICC (region B, group B), or LNM beyond these regions (region C, group C). Multivariable Cox regression analysis was performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in all groups. Results: A total of 133 patients were enrolled. There were 56, 21, 17, and 39 patients in groups N0, A, B, and C, respectively. There was significant difference between groups N0 and C in RFS (P < 0.001) and OS (P = 0.002). When we compared group N0 + A + B with group C, we also found that RFS (P < 0.001) and OS (P = 0.007) were significantly different. In multivariable analysis, the extent of LNM was an independent risk factor for RFS (P < 0.050). Conclusion: ICC patients with the LNM to regions A and B could still achieve good prognosis with resection. Surgery should be carefully considered when LNM to region C.

Development and external validation of a prognosis model to predict outcomes after curative resection of early-stage intrahepatic cholangiocarcinoma.

Background: Early-stage intrahepatic cholangiocarcinoma (ESICC) with curative resection and lymph node-negative still has the risk of poor prognosis, and there lacks prognosis-assessing tools for these patients. The objective of this study was to develop a prognosis model to predict outcomes and identify risk stratification for ESICC after resection. Methods: Totally 263 patients with ESICC after hepatectomy from January 2012 to January 2022 were analyzed. Clinicopathological factors were selected using multivariable Cox regression analysis and a prognosis model was developed. The performance of the model was evaluated by concordance index (C-index), calibration plots, decision curves analysis (DCA), and net reclassification index (NRI). Kaplan-Meier curves were analyzed for risk stratification of overall survival (OS) and recurrence-free survival (RFS) based on the prognosis model. Results: The clinicopathological features that were independently associated with OS of ESICC included carbohydrate antigen19-9, carcinoembryonic antigen, tumor size, tumor differentiation, and T stage. The prognosis model based on these prognostic factors demonstrated excellent discriminatory performance in both derivation cohort (C-index, 0.71) and external validation cohort (C-index, 0.78), which outperformed the TNM staging system (C-index, 0.59) and individual prognostic factors (all C-index < 0.7). Calibration plots, DCA and NRI also showed superior predictive performance. According to the risk for survival, the model stratified patients into low risk (median OS, 66.6 months; median RFS, 24.3 months) and high risk (median OS, 24.0 months; median RFS, 6.4 months) (P < 0.001). Conclusions: Our prognosis model can robustly predict the outcomes of ESICC after curative resection and provide precise evaluation on prognosis risk, facilitating clinicians to develop individualized postoperative treatment options.

Intraindividual Comparison of Contrast-Enhanced Ultrasound Using Perfluorobutane With Modified Criteria Versus CT/MRI LI-RADS Version 2018 for Diagnosing HCC in High-Risk Patients.

BACKGROUND. Previously proposed modifications to LI-RADS criteria for contrast-enhanced ultrasound (CEUS) performed using perfluorobutane contrast agent yielded increased sensitivity for hepatocellular carcinoma (HCC) without a significant decrease in specificity. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of CEUS with perfluorobutane using modified LI-RADS criteria versus contrast-enhanced CT or MRI using LI-RADS version 2018 (v2018) for characterizing lesions as HCC in high-risk patients. METHODS. This retrospective study included 171 patients (140 men, 31 women; mean age, 54 ± 12 [SD] years) at high-risk for HCC with a pathologically confirmed liver observation evaluated by both CEUS using perfluorobutane and contrast-enhanced CT or MRI between March 2020 and May 2021. A matching algorithm was used to select two patients with HCC for each patient with a non-HCC lesion. Two readers evaluated observations using previously proposed modifications to CEUS LI-RADS version 2017 that classify certain observations as LR-5 rather than as LR-4 or LR-M on the basis of the presence of Kupffer phase defect after perfluorobutane administration; two different readers evaluated observations using CT/MRI LI-RADS v2018. Each reader pair reached consensus. Diagnostic performance was evaluated. RESULTS. A total of 114 patients had HCC, 43 had a non-HCC malignancy, and 14 had a benign lesion. Modified CEUS criteria using perfluorobutane and CT/MRI LI-RADS v2018 showed no significant difference (p > .05) in sensitivity (92.1% vs 89.5%), specificity (87.7% vs 84.2%), or accuracy (90.6% vs 87.7%) of LR-5 for diagnosis of HCC. Of six observations assessed as LR-4 only by CT/MRI LI-RADS v2018, modified CEUS criteria using perfluorobutane assessed one as LR-3 (benign lesion) and five as LR-5 (all HCC). Of seven observations assessed as LR-M only by CT/MRI LI-RADS v2018, modified CEUS criteria using perfluorobutane assessed one as LR-3 (non-HCC malignancy) and six as LR-5 (all HCC). Eight of 12 observations assessed as LR-5 only by CT/MRI LI-RADS v2018 and 11 of 13 observations assessed as LR-5 only by modified CEUS criteria using perfluorobutane were HCC. CONCLUSION. The diagnostic performance of LR-5 for HCC diagnosis was not significantly different between modified CEUS criteria using perfluorobutane and CT/MRI LI-RADS v2018. CLINICAL IMPACT. The findings support the application of modified CEUS criteria using perfluorobutane for diagnosing HCC in high-risk patients.

Non-invasive diagnosis strategy of hepatocellular carcinoma in low-risk population.

AIMS: With prevalence of hepatocellular carcinoma (HCC) in low-risk population (LRP), establishing a non-invasive diagnostic strategy becomes increasingly urgent to spare unnecessary biopsies in this population. The purposes of this study were to find characterisics of HCC and to establish a proper non-invasive method to diagnose HCC in LRP. METHODS: A total of 681 patients in LRP (defined as the population without cirrhosis, chronic HBV infection or HCC history) were collected from 2 institutions. The images of computed tomography (CT) and magnetic resonance imaging (MRI) were manually analysed. We divided the patients into the training cohort (n = 324) and the internal validating cohort (n = 139) by admission time in the first institution. The cohort in the second institution was viewed as the external validation (n = 218). A multivariate logistic regression model incorporating both imaging and clinical independent risk predictors was developed. C-statistics was used to evaluate the diagnostic performance. RESULTS: Besides the major imaging features of HCC (non-rim enhancement, washout and enhancing capsule), tumor necrosis or severe ischemia (TNSI) on imaging and two clinical characteristics (gender and alpha fetoprotein) were also independently associated with HCC diagnosis (all P < 0.01). A clinical model (including 3 major features, TNSI, gender and AFP) was built to diagnose HCC and achieved good diagnostic performance (area under curve values were 0.954 in the training cohort, 0.931 in the internal validation cohort and 0.902 in the external cohort). CONCLUSIONS: The clinical model in this study developed a satisfied non-invasive diagnostic performance for HCC in LRP.

Prediction of microvascular invasion in hepatocellular carcinoma with expert-inspiration and skeleton sharing deep learning.

BACKGROUND AND AIMS: Radiological prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is essential but few models were clinically implemented because of limited interpretability and generalizability. METHODS: Based on 2096 patients in three independent HCC cohorts, we established and validated an MVI predicting model. First, we used data from the primary cohort to train a 3D-ResNet network for MVI prediction and then optimised the model with "expert-inspired training" for model construction. Second, we implemented the model to the other two cohorts using three implementation strategies, the original model implementation, data sharing model implementation and skeleton sharing model implementation, the latter two of which used part of the cohorts' data for fine-tuning. The areas under the receiver operating characteristic curve (AUCs) were calculated to compare the performances of different models. RESULTS: For the MVI predicting model, the AUC of the expert-inspired model was 0.83 (95% CI: 0.77-0.88) compared to 0.54 (95% CI: 0.46-0.62) of model before expert-inspiring. Taking this model as an original model, AUC on the second cohort was 0.76 (95% CI: 0.67-0.84). The AUC was improved to 0.83 (95% CI: 0.77-0.90) with the data-sharing model, and further improved to 0.85 (95% CI: 0.79-0.92) with the skeleton sharing model. The trend that the skeleton sharing model had an advantage in performance was similar in the third cohort. CONCLUSIONS: We established an expert-inspired model with better predictive performance and interpretability than the traditional constructed model. Skeleton sharing process is superior to data sharing and direct model implementation in model implementation.

Response of four evergreen savanna shrubs to an incidence of extreme drought: high embolism resistance, branch shedding and maintenance of nonstructural carbohydrates.

Extreme drought events are becoming frequent globally, resulting in widespread plant mortality and forest dieback. Although savanna vegetation cover ~20% of the earth's land area, their responses to extreme drought have been less studied than that of forests. Herein, we quantified branch dieback, individual mortality and the associated physiological responses of four evergreen shrubs (Tarenna depauperate Hutch., Maytenus esquirolii (H. Lév.) C.Y. Cheng, Murraya exotica L., Jasminum nudiflorum Lindl.) in a savanna ecosystem in Southwest China to an incidence of extreme drought during 2019 and 2020. We found that 80-100% of the individuals of these species exhibited branch dieback, whereas individual mortality was only found in T. depauperate (4.5%). All species showed high resistance to stem embolism (P50, water potential at 50% loss of hydraulic conductivity ranged from -5.62 to -8.6 MPa), whereas the stem minimum water potentials reached -7.6 to ca -10.0 MPa during the drought. The low water potential caused high native embolism levels (percentage loss of hydraulic conductivity (PLC) 23-65%) in terminal branches, and the remaining stems maintained 15-35% PLC at the end of the drought. Large within-individual variations in stem vulnerability to embolism were detected, and shedding of vulnerable branches could be a mechanism for shrubs to reduce water and carbon consumption. Overall, the content of total nonstructural carbohydrates (NSC) and their components in the stem were generally comparable to or higher than those in the rainy season in three of the four species. Because the leaves were turgor-less for most time during the drought, high NSC levels during the drought could be due to recycling of NSC from dead branches or translocation from roots. Our results suggest high tolerance of savanna shrub species to extreme drought, which could be facilitated by high embolism resistance in some stems and shedding of vulnerable branches to maintain individual water and carbon balance.

Comparison of Hepatic Resection with Percutaneous Ablation for Hepatocellular Carcinoma in the Caudate Lobe Within Milan Criteria.

PURPOSE: We aimed to compare the efficacy of hepatic resection and percutaneous ablation for resectable caudate HCC within Milan criteria and to investigate the prognostic factors. METHODS: Between August 2006 and August 2020, a total of 67 eligible patients with resectable caudate HCC within Milan criteria in three centers were retrospectively analyzed and divided into hepatic resection group (n = 46) and percutaneous ablation group (n = 21). Recurrence-free survival (RFS) and overall survival (OS) rates were compared between groups of hepatic resection and percutaneous ablation for these resectable caudate HCC patients with Kaplan-Meier curves and log-rank test. Univariable and multivariable Cox regression analyses were performed to identify the prognostic factors of RFS and OS. RESULTS: The 1-, 3-, and 5-year OS rates were 97.6%, 83.6%, and 71.5% for the hepatic resection group, and 89.4%, 58.5%, and 48.8% for the percutaneous ablation group (P = 0.032). The corresponding RFS rates were 77.6%, 47.9%, and 42.6% for the hepatic resection group, and 40.5%, 23.2%, and 15.4% for the percutaneous ablation group (P = 0.010). According to the univariable and multivariable analyses, tumor type (first recurrence) (HR = 3.54; 95%CI, 1.49-8.37; P = 0.004) was a significant independent prognostic factor of RFS for caudate HCC patients after resection or ablation, while total bilirubin (HR = 1.02; 95%CI, 1.01-1.04; P = 0.006) and treatment strategy (HR = 5.97; 95%CI, 1.48-24.12; P = 0.012) were significant independent prognostic factors of OS. CONCLUSIONS: Hepatic resection appears to outperform percutaneous ablation for caudate HCC patients within Milan criteria.

Hydraulic prediction of drought-induced plant dieback and top-kill depends on leaf habit and growth form.

Hydraulic failure caused by severe drought contributes to aboveground dieback and whole-plant death. The extent to which dieback or whole-plant death can be predicted by plant hydraulic traits has rarely been tested among species with different leaf habits and/or growth forms. We investigated 19 hydraulic traits in 40 woody species in a tropical savanna and their potential correlations with drought response during an extreme drought event during the El Niño-Southern Oscillation in 2015. Plant hydraulic trait variation was partitioned substantially by leaf habit but not growth form along a trade-off axis between traits that support drought tolerance versus avoidance. Semi-deciduous species and shrubs had the highest branch dieback and top-kill (complete aboveground death) among the leaf habits or growth forms. Dieback and top-kill were well explained by combining hydraulic traits with leaf habit and growth form, suggesting integrating life history traits with hydraulic traits will yield better predictions.

DeepHBV: a deep learning model to predict hepatitis B virus (HBV) integration sites.

BACKGROUND: The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation. RESULTS: An attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites. By learning local genomic features automatically, DeepHBV was trained and tested using HBV integration site data from the dsVIS database. Initially, DeepHBV showed an AUROC of 0.6363 and an AUPR of 0.5471 for the dataset. The integration of genomic features of repeat peaks and TCGA Pan-Cancer peaks significantly improved model performance, with AUROCs of 0.8378 and 0.9430 and AUPRs of 0.7535 and 0.9310, respectively. The transcription factor binding sites (TFBS) were significantly enriched near the genomic positions that were considered. The binding sites of the AR-halfsite, Arnt, Atf1, bHLHE40, bHLHE41, BMAL1, CLOCK, c-Myc, COUP-TFII, E2A, EBF1, Erra, and Foxo3 were highlighted by DeepHBV in both the dsVIS and VISDB datasets, revealing a novel integration preference for HBV. CONCLUSIONS: DeepHBV is a useful tool for predicting HBV integration sites, revealing novel insights into HBV integration-related carcinogenesis.

Induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: a randomized phase II trial.

This randomized phase II trial aims to compare the efficacy and safety of induction chemotherapy followed by definitive chemoradiotherapy (CRT) versus CRT alone in patients with esophageal squamous cell carcinoma (ESCC) unsuitable for surgery (N = 110). The primary outcome was overall response rate (ORR), whereas the secondary outcome was overall survival. This trial did not meet pre-specified endpoints. The ORR was 74.5% in the induction chemotherapy group versus 61.8% in the CRT alone group (P = 0.152). The 3-year overall survival rate was 41.8% in the induction chemotherapy group and 38.1% in the CRT alone group (P = 0.584; hazard ratio, 0.88; 95% CI, 0.54-1.41). Grade 3-5 adverse events were similar. Patients who responded to induction chemotherapy had improved survival in the post-hoc analysis. These results demonstrate no improvement in response rate or survival with the addition of induction chemotherapy to CRT in unselected patients with ESCC. Trial number: NCT02403531.

Predicting the recurrence risk of pancreatic neuroendocrine neoplasms after radical resection using deep learning radiomics with preoperative computed tomography images.

BACKGROUND: To establish and validate a prediction model for pancreatic neuroendocrine neoplasms (pNENs) recurrence after radical surgery with preoperative computed tomography (CT) images. METHODS: We retrospectively collected data from 74 patients with pathologically confirmed pNENs (internal group: 56 patients, Hospital I; external validation group: 18 patients, Hospital II). Using the internal group, models were trained with CT findings evaluated by radiologists, radiomics, and deep learning radiomics (DLR) to predict 5-year pNEN recurrence. Radiomics and DLR models were established for arterial (A), venous (V), and arterial and venous (A&V) contrast phases. The model with the optimal performance was further combined with clinical information, and all patients were divided into high- and low-risk groups to analyze survival with the Kaplan-Meier method. RESULTS: In the internal group, the areas under the curves (AUCs) of DLR-A, DLR-V, and DLR-A&V models were 0.80, 0.58, and 0.72, respectively. The corresponding radiomics AUCs were 0.74, 0.68, and 0.70. The AUC of the CT findings model was 0.53. The DLR-A model represented the optimum; added clinical information improved the AUC from 0.80 to 0.83. In the validation group, the AUCs of DLR-A, DLR-V, and DLR-A&V models were 0.77, 0.48, and 0.64, respectively, and those of radiomics-A, radiomics-V, and radiomics-A&V models were 0.56, 0.52, and 0.56, respectively. The AUC of the CT findings model was 0.52. In the validation group, the comparison between the DLR-A and the random models showed a trend of significant difference (P=0.058). Recurrence-free survival differed significantly between high- and low-risk groups (P=0.003). CONCLUSIONS: Using DLR, we successfully established a preoperative recurrence prediction model for pNEN patients after radical surgery. This allows a risk evaluation of pNEN recurrence, optimizing clinical decision-making.

Three-day postoperative antibiotics reduces post-hepatectomy infection rate in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIM: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients who underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in a hepatitis B virus (HBV)-related HCC population. METHODS: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection and remote site infection were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rates with different durations of POA was investigated. RESULTS: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of surgical site infection and 2.0% (19/934) of remote site infection. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (odds ratio = 0.50, 95% confidence interval = 0.30 to 0.83; P = 0.008). Albumin-bilirubin score, Barcelona Clinic Liver Cancer (BCLC) stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection. CONCLUSIONS: Postoperative antibiotic is necessary for HBV-related HCC patients to prevent postoperative infection, especially for those with higher albumin-bilirubin score, at BCLC stage B-C, or who underwent major hepatectomy. For HBV-related HCC patients, postoperative second-generation cephalosporins, or ceftriaxone for 3 days after surgery might be proper.