Glycyrrhizic acid alleviates concanavalin A-induced acute liver injury by regulating monocyte-derived macrophages.

Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80loCD11bhiMHCIIhi MoMF-1 and decreased the abundance of pro-inflammatory F4/80loCD11bhiiNOShi MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.

Enhanced Cu2+ and Cd2+ removal by a novel co-pyrolysis biochar derived from sewage sludge and phosphorus tailings: adsorption performance and mechanisms.

The reutilization of municipal wastes has always been one of the hottest subjects of sustainable development study. In this study, a novel biochar co-pyrolyzed from municipal sewage sludge and phosphorus tailings was produced to enhance the adsorption performance of the composite on Cu2+ and Cd2+. The maximum Cu2+ and Cd2+ adsorption capacity of SSB-PT were 44.34 and 45.91 mg/g, respectively, which were much higher than that of sewage sludge biochar (5.21 and 4.58 mg/g). Chemisorption dominated the whole adsorption process while multilayer adsorption and indirect interaction were also involved. According to the result of X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectrum (XPS), the load of CO32-, Mg2+, and Ca2+ on the surface of SSB-PT enhanced the precipitation and ion exchange effect. Posnjakite and CdCO3 were formed after the adsorption of Cu2+ and Cd2+, respectively. Besides, complexation, and metal-π interaction were also involved during the adsorption process. Therefore, this study offered a promising method to reuse sewage sludge and phosphorus tailings as an effective adsorbent.

Enhanced object detection in pediatric bronchoscopy images using YOLO-based algorithms with CBAM attention mechanism.

Background and Objective: Bronchoscopy is a widely used diagnostic and therapeutic procedure for respiratory disorders such as infections and tumors. However, visualizing the bronchial tubes and lungs can be challenging due to the presence of various objects, such as mucus, blood, and foreign bodies. Accurately identifying the anatomical location of the bronchi can be quite challenging, especially for medical professionals who are new to the field. Deep learning-based object detection algorithms can assist doctors in analyzing images or videos of the bronchial tubes to identify key features such as the epiglottis, vocal cord, and right basal bronchus. This study aims to improve the accuracy of object detection in bronchoscopy images by integrating a YOLO-based algorithm with a CBAM attention mechanism. Methods: The CBAM attention module is implemented in the YOLO-V7 and YOLO-V8 object detection models to improve their object identification and classification capabilities in bronchoscopy images. Various YOLO-based object detection algorithms, such as YOLO-V5, YOLO-V7, and YOLO-V8 are compared on this dataset. Experiments are conducted to evaluate the performance of the proposed method and different algorithms. Results: The proposed method significantly improves the accuracy and reliability of object detection for bronchoscopy images. This approach demonstrates the potential benefits of incorporating an attention mechanism in medical imaging and the benefits of utilizing object detection algorithms in bronchoscopy. In the experiments, the YOLO-V8-based model achieved a mean Average Precision (mAP) of 87.09% on the given dataset with an Intersection over Union (IoU) threshold of 0.5. After incorporating the Convolutional Block Attention Module (CBAM) into the YOLO-V8 architecture, the proposed method achieved a significantly enhanced m A P 0.5 and m A P 0.5 : 0.95 of 88.27% and 55.39%, respectively. Conclusions: Our findings indicate that by incorporating a CBAM attention mechanism with a YOLO-based algorithm, there is a noticeable improvement in object detection performance in bronchoscopy images. This study provides valuable insights into enhancing the performance of attention mechanisms for object detection in medical imaging.

Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota.

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role and mechanism of HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover the beneficial effects of HT and its detailed mechanism in UC. Experimental colitis was induced by 2.5% dextran sodium sulfate (DSS) for seven days. HT ameliorated DSS-induced colitis in mice, showing marked improvement in weight loss, colon length, colonic pathological severity, and the levels of TNFα and IL6 in serum. A combination of informatics, network pharmacology, and molecular docking identified eight key targets and multi-pathways influenced by HT in UC. As a highlight, the experimental validation demonstrated that PTGS2, a marker of ferroptosis, along with other indicators of ferroptosis (such as ACSL4, Gpx4, and lipid peroxidation), were regulated by HT in vivo and in vitro. Additionally, the supplement of HT increased the diversity of gut microbiota, decreased the relative abundance of Proteobacteria and Gammaproteobacteria, and restored beneficial bacteria (Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001). In conclusion, HT is an effective nutritional supplement against experimental colitis by suppressing ferroptosis and modulating gut microbiota.

Risk of immune system and skin and subcutaneous tissue related adverse events associated with oxaliplatin combined with immune checkpoint inhibitors: a pharmacovigilance study.

Background: Few studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs). Methods: We evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients. Results: There were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex-mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678. Conclusion: Type II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.

Cost-effectiveness of different intervention strategies of HIV in Zhejiang, China.

OBJECTIVE: Mass screening for HIV and preexposure prophylaxis (PrEP) may be effective measures for reducing the probability of HIV transmission. Our study aimed to determine the cost-effectiveness of preliminary screening in the general population, PrEP for HIV-negative spouses in serodiscordant couples, or both approaches in Zhejiang Province. DESIGN: From a policy-maker's perspective, a Markov model was constructed to compare four strategies over a 30-year horizon. METHODS: In the Markov model, the implementation intensities of the strategies varied from 50 to 100%. Different strategies were evaluated by the reduction of unfavorable clinical outcomes, saved life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). RESULTS: The PrEP-screening strategy reduced the most unfavorable clinical outcomes and saved the most life-years and QALYs from 2023 to 2052. It always gained the maximum QALYs and NMB, while its ICER was always lower than the willingness-to-pay (WTP). The NMB of the PrEP-screening strategy gradually increased as the implementation intensity increased. CONCLUSION: With adequate manpower and policies, we suggest implementing the PrEP-screening strategy in Zhejiang Province, suggesting that the broader the population coverage of the strategy, the better. In addition, the PrEP strategy is an alternative.

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

Clinical Significance of a Novel Vasculogenic Mimicry-Based Prognostic Model in Hepatocellular Carcinoma.

BACKGROUND: Vasculogenic mimicry, a novel neovascularization pattern of aggressive tumors, is associated with poor clinical outcomes. OBJECTIVE: The aim of this research was to establish a new model, termed VC score, to predict the prognosis, Tumor Microenvironment (TME) components, and immunotherapeutic response in Hepatocellular Carcinoma (HCC). METHODS: The expression data of the public databases were used to develop the prognostic model. Consensus clustering was performed to confirm the molecular subtypes with ideal clustering efficacy. The high- and low-risk groups were stratified utilizing the VC score. Various methodologies, including survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Dysfunction and Exclusion scores (TIDE), Immunophenoscore (IPS), and nomogram, were utilized for verification of the model performance and to characterize the immune status of HCC tissues. GSEA was performed to mine functional pathway information. RESULTS: The survival and immune characteristics varied between the three molecular subtypes. A five-gene signature (TPX2, CDC20, CFHR4, SPP1, and NQO1) was verified to function as an independent predictive factor for the prognosis of patients with HCC. The high-risk group exhibited lower Overall Survival (OS) rates and higher mortality rates in comparison to the low-risk group. Patients in the low-risk group were predicted to benefit from immune checkpoint inhibitor therapy and exhibit increased sensitivity to immunotherapy. Enrichment analysis revealed that signaling pathways linked to the cell cycle and DNA replication processes exhibited enrichment in the high-risk group. CONCLUSIONS: The VC score holds the potential to establish individualized treatment plans and clinical management strategies for patients with HCC.

Clinical significance of RNA methylation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

Conjunctive encoding of exploratory intentions and spatial information in the hippocampus.

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

Emerging function of main RNA methylation modifications in the immune microenvironment of digestive system tumors.

Digestive system tumors have been reported in more than 25% of all cancer cases worldwide, bringing a huge burden on the healthcare system. RNA methylation modification-an important post-transcriptional modification-has become an active research area in gene regulation. It is a dynamic and reversible process involving several enzymes, such as methyltransferases, demethylases, and methylation reader proteins. This review provides insights into the role of three major methylation modifications, namely m6A, m5C, and m1A, in the development of digestive system tumors, specifically in the development of tumor immune microenvironment (TIME) of these malignancies. Abnormal methylation modification affects immunosuppression and antitumor immune response by regulating the recruitment of immune cells and the release of immune factors. Understanding the mechanisms by which RNA methylation regulates digestive system tumors will be helpful in exploring new therapeutic targets.

Development of a promising PPAR signaling pathway-related prognostic prediction model for hepatocellular carcinoma.

The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status. Following, a prognostic prediction model of HCC was developed by using the random survival forest method and Cox regression analysis. Significant difference in survival outcome, immune landscape, drug sensitivity and pathological features were observed between patients with different prognosis. Additionally, decision tree and nomogram models were adopted to optimize the prognostic prediction model. Furthermore, the robustness of the model was verified through single-cell RNA-sequencing data. Collectively, this study systematically elucidated that the PPAR signaling pathway-related prognostic model has good predictive efficacy for patients with HCC. These findings provide valuable insights for further research on personalized treatment approaches for HCC.

Formation processes of groundwater in a non-ferrous metal mining city of China: Insights from hydrochemical and strontium isotope analyses.

Tongling is a significant non-ferrous metal mining city in China, which produces waste that negatively impacts the area's water environment. It is essential to comprehend the hydrochemical properties and formation processes of groundwater to safeguard and utilize it efficiently. We explored major ions, strontium, and its isotopes in water and river-bottom samples from the northern (i.e., A-A' section) and southern (i.e., B-B' section) areas. The hydrochemical facies show the mining activities have a greater impact on surface water than on groundwater. Groundwater hydrochemical formation results from several factors, with water-rock interaction and ion exchange being primary. Additionally, the dissolution of calcite, dolomite, and feldspar, oxidation of pyrite, and hydrolysis of carbonate minerals also impact the formation of groundwater chemistry. Our analysis of strontium and its isotopes indicates that carbonate dissolution primarily occurred in the recharge area; the runoff from the recharge to the discharge area results in the dissolution of certain silicate rocks; calcite dissolution sources account for > 70% contribution in both surface water and groundwater water-rock interactions, whereas silicate rock dissolution sources and dolomite dissolution sources account for < 30%. Due to changed order of dissolved carbonate and silicate minerals during groundwater flow, the distribution of strontium and its isotopes in the A-A' section is opposite to that in the B-B' section. The findings provide a basis for developing, utilizing, managing, and protecting groundwater resources, especially in similar mining areas.

Prognostic and immune predictive roles of a novel tricarboxylic acid cycle-based model in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Since the tricarboxylic acid cycle is widely involved in tumor metabolic reprogramming and cuproptosis, investigating related genes may help to identify prognostic signature of patients with HCC. Data on patients with HCC were sourced from public datasets, and were divided into train, test, and single-cell cohorts. A variety of machine learning algorithms were used to identify different molecular subtypes and determine the prognostic risk model. Our findings revealed that the risk score (TRscore), based on the genes OGDHL, CFHR4, and SPP1, showed excellent predictive performance in different datasets. Pathways related to cell cycle and immune inflammation were enriched in the high-risk group, whereas metabolism-related pathways were significantly enriched in the low-risk group. The high-risk group was associated with a greater number of mutations of detrimental biological behavior and higher levels of immune infiltration, immune checkpoint expression, and anti-cancer immunotherapy response. Low-risk patients demonstrated greater sensitivity to erlotinib and phenformin. SPP1 was mainly involved in the interaction among tumor-associated macrophages, T cells, and malignant cells via SPP1-CD44 and SPP1-(ITGA5 + ITGB1) ligand-receptor pairs. In summary, our study established a prognostic model, which may contribute to individualized treatment and clinical management of patients with HCC.

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications.

RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies. Video Abstract.

Global research status analysis of the association between aortic aneurysm and inflammation: a bibliometric analysis from 1999 to 2023.

Background: Aortic aneurysm is a chronic arterial disease that can lead to aortic rupture, causing severe complications and life-threatening risks for patients, and it is one of the common causes of death among the elderly. Increasing evidence suggests that inflammation plays an important role in the progression of aortic aneurysm. However, there is a lack of literature-based quantitative analysis in this field. Methods: Up to March 30, 2023, we collected 3,993 articles related to aortic aneurysm and inflammation from the Web of Science Core Collection (WoSCC) database for bibliometric analysis. The collected literature data were subjected to visual analysis of regional distribution, institutions, authors, keywords, and other information using tools such as CiteSpace, VOSviewer, the R package "bibliometric," and online platforms. Results: The number of publications in this research field has been steadily increasing each year, with the United States and China being the main contributing countries. Harvard University in the United States emerged as the most active and influential research institution in this field. Jonathan Golledge and Peter Libby were identified as the authors with the highest publication output and academic impact, respectively. Researchers in this field tend to publish their findings in influential journals such as the Journal of Vascular Surgery and Arteriosclerosis Thrombosis and Vascular Biology. "Abdominal aortic aneurysm," "giant cell arteritis," "arterial stiffness," and "smooth muscle cells" were identified as the hottest topics in the field of aortic aneurysm and inflammation. In terms of keyword co-occurrence analysis, "Clinical relevant studies of AA" (red), "Inflammatory activation" (green), "Inflammatory mechanisms related to pathogenesis" (dark blue), "Cytokines" (yellow), "Risk factors" (purple), and "Pathological changes in vascular wall" (cyan) formed the major research framework in this field. "Inflammation-related pathogenesis" and "inflammation activation" have emerged as recent hot research directions, with "monocytes," "progression," and "proliferation" being the prominent topics. Conclusion: This study provides a comprehensive analysis of the knowledge network framework and research hotspots in the field of aortic aneurysm and inflammation through a literature-based quantitative approach. It offers valuable insights to guide scholars in identifying meaningful research directions in this field.

PDM-SHD NFDM transmission with envelope-detection feedback polarization tracking and optical injection locking.

Nonlinear frequency division multiplexing (NFDM) systems, especially the eigenvalue communications have the potential to overcome the nonlinear Shannon capacity limit. However, the baud rate of eigenvalue communications is typically restricted to a few GBaud, making it challenging to mitigate laser frequency impairments such as the phase noise and frequency offset (FO) using digital signal processing (DSP) algorithms in intradyne detections (IDs). Therefore, we introduce the polarization division multiplexing-self-homodyne detection (PDM-SHD) into the NFDM link, which could overcome the impact of phase noise and FO by transmitting a pilot carrier originating from the transmitter laser to the receiver through the orthogonal polarization state of signal. To separate the signal from the carrier at the receiver, a carrier to signal power ratio (CSPR) unrestricted adaptive polarization controlling strategy is proposed and implemented by exploiting the optical intensity fluctuation of the light in a particular polarization rather than its direct optical power as the feedback. Optical injection locking (OIL) is used subsequently to amplify optical power of pilot carrier and mitigate the impact of signal-signal beat interference (SSBI). Additionally, the effects of cross-polarization modulation (XPolM) and modulation instability (MI) in long haul transmission are explored and inhibited. The results show that the tolerable FO range is about 3.5 GHz, which is 17 times larger than the ID one. When 16-amplitude phase shift keying (APSK) or 64-APSK constellations are used, identical Q-factor performance can be obtained by using distributed feedback (DFB, ∼10 MHz) laser, external cavity laser (ECL, ∼100kHz), or fiber laser (FL, ∼100 Hz), respectively, which demonstrates that our proposed PDM-SHD eigenvalue communication structure is insensitive to the laser linewidth. Under the impact of cycle slip, the Q-factor difference of 16-APSK signal between the ECL-ID system and ECL-SHD system can be up to 8.73 dB after 1500 km transmission.

Cardioprotective effect of epigallocatechin gallate in myocardial ischemia/reperfusion injury and myocardial infarction: a meta-analysis in preclinical animal studies.

This meta-analysis aims to determine the efficacy of Epigallocatechin gallate (EGCG) in the treatment of myocardial ischemia-reperfusion injury (MIRI) and summarize the mechanisms involved. Literature from six databases including Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP) were systematically searched. All the analysis were conducted by R. Twenty-five eligible studies involving 443 animals were included in this meta-analysis. The results indicated that compared to controls, EGCG exerts a cardioprotective effect by reducing myocardial infarct size (SMD = -4.06; 95% CI: -5.17, -2.94; P < 0.01; I2 = 77%). The funnel plot revealed publication bias. Moreover, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models. This meta-analysis demonstrates that EGCG exhibits therapeutic promise in animal models of MIRI. However, further validation is still needed in large animal models and large clinical studies.

HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis.

BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.

TMS-induced inhibition of the left premotor cortex modulates illusory social perception.

Communicative actions from one person are used to predict another person's response. However, in some cases, these predictions can outweigh the processing of sensory information and lead to illusory social perception such as seeing two people interact, although only one is present (i.e., seeing a Bayesian ghost). We applied either inhibitory brain stimulation over the left premotor cortex (i.e., real TMS) or sham TMS. Then, participants indicated the presence or absence of a masked agent that followed a communicative or individual gesture of another agent. As expected, participants had more false alarms in the communicative (i.e., Bayesian ghosts) than individual condition in the sham TMS session and this difference between conditions vanished after real TMS. In contrast to our hypothesis, the number of false alarms increased (rather than decreased) after real TMS. These pre-registered findings confirm the significance of the premotor cortex for social action predictions and illusory social perception.