Artificial intelligence/neural network system that accurately diagnoses hepatocellular carcinoma in nonalcoholic steatohepatitis

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Artificial intelligence/neural network system that accurately diagnoses hepatocellular carcinoma in nonalcoholic steatohepatitis

Structure of HCC-Scope (with gray zone) for training and validation: artificial intelligence systems used for the identification of NASH-HCC.


Abstract

Background and Aim

The aim of this study was to develop a novel noninvasive test using an artificial intelligence/neural network system (called HCC-Scope) to diagnose early-stage hepatocellular carcinoma (HCC) on the background of nonalcoholic steatohepatitis (NASH).

Methods

In total, 175 patients with histologically proven nonalcoholic fatty liver disease and 55 patients with NASH-HCC were enrolled for training and validation studies. Of the 55 patients with NASH-HCC, 27 (49.1%) had very early-stage HCC, and six (10.9%) had early-stage HCC based on the Barcelona Clinic Liver Cancer staging system. Diagnosis with HCC-Scope was performed based on 12 items: age, sex, height, weight, AST level, ALT level, gamma-glutamyl transferase level, cholesterol level, triglyceride level, platelet count, diabetes status, and IgM-free apoptosis inhibitor of macrophage level. The FMVWG2U47 hardware (Fujitsu Co. Ltd, Tokyo, Japan) and the originally developed software were used.

Results

HCC-Scope had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% for the differential diagnosis between non-HCC and HCC in a training study with gray zone analysis. It was also excellent in the validation study (95.0% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV with gray zone analysis and 95.2% sensitivity, 100% specificity, 100% PPV, and 97.1% NPV without gray zone analysis). HCC-Scope had a significantly higher sensitivity (85.3%) and specificity (85.1%) than alpha-fetoprotein (AFP) level, AFP-L3 level, des-gamma-carboxy prothrombin (DCP) level, and the gender–age–AFP-L3–AFP–DCP (GALAD) score.

Conclusions

HCC-Scope can accurately differentially diagnose between non-HCC NASH and NASH-HCC, including very early-stage NASH-HCC.

Seroprevalence and incidence of hepatitis E virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study

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Abstract

Aim

Hepatitis E virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low.

Methods

Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2 years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction.

Results

Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20–89 years. A total of 90 participants were found to be positive for anti-HEV immunoglobulin G on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%–8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p < 0.001), and in those aged in their 50s–80s than in those aged in their 20s–40s (p = 0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%–1.0%), indicating the incidence of HEV infection to be 272 per 100 000 person-years (95% CI 109–561).

Conclusions

Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

You are who your friends are—nuclear pore proteins as components of chromatin‐binding complexes

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You are who your friends are—nuclear pore proteins as components of chromatin-binding complexes

Nuclear pore complexes are multicomponent assemblies that support nucleocytoplasmic transport and contribute to gene regulation. Some nuclear pore components are also known to bind chromatin and affect gene expression in the nuclear interior, away from sites of transport. In this review, we discuss chromatin-binding functions of intranuclear nuclear pore proteins and highlight their identity as components of chromatin regulatory complexes.


Nuclear pore complexes are large multicomponent protein complexes that are embedded in the nuclear envelope, where they mediate nucleocytoplasmic transport. In addition to supporting transport, nuclear pore components, termed nucleoporins (Nups), can interact with chromatin and influence genome function. A subset of Nups can also localize to the nuclear interior and bind chromatin intranuclearly, providing an opportunity to investigate chromatin-associated functions of Nups outside of the transport context. This review focuses on the gene regulatory functions of such intranuclear Nups, with a particular emphasis on their identity as components of several chromatin regulatory complexes. Recent proteomic screens have identified Nups as interacting partners of active and repressive epigenetic machinery, architectural proteins, and DNA replication complexes, providing insight into molecular mechanisms via which Nups regulate gene expression programs. This review summarizes these interactions and discusses their potential functions in the broader framework of nuclear genome organization.

Tert‐butylhydroquinone attenuates LPS‐induced pyroptosis of IPEC‐J2 cells via downregulating HMGB1/TLR4/NF‐κB axis

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Abstract

Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.

Impact of albumin–lymphocyte–platelet–C‐reactive protein index as a prognostic indicator of hepatocellular carcinoma after resection: Associated with nuclear factor erythroid 2–related factor 2

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Abstract

Aim

To investigate the prognostic value of the preoperative albumin–lymphocyte–platelet–C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels.

Methods

Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC.

Results

A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells.

Conclusions

We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

Usefulness of the Fibrosis‐4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients

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Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients

Nucleos(t)ide analog-treated chronic hepatitis B patients with a higher Fibrosis-4 index (≥1.58) at year 1 after the therapy showed a higher incidence of hepatocellular carcinoma. A fibrosis and alanine aminotransferase-1 (FAL-1) score that can be calculated simply with the Fibrosis-4 index and alanine aminotransferase at year 1 of nucleos(t)ide analog might be useful to predict hepatocellular carcinoma development in the clinical settings.


Abstract

Aim

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development.

Methods

Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC.

Results

The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001).

Conclusions

FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Benzoic acid promotes Fusarium wilt incidence by enhancing susceptibility and reducing photosynthesis of faba bean

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Benzoic acid promotes Fusarium wilt incidence by enhancing susceptibility and reducing photosynthesis of faba bean

The cell wall degrading enzymes showed a significant negative correlation with photosynthesis, while they positively related with disease incidence. Photosynthesis also presented a significant negative correlation with disease incidence rate. The incidence and disease index were positively correlated. Biomass positively correlated with leaf length and width, and photosynthesis positively correlated with transpiration rate and stomatal conductance.


Abstract

Continuous faba bean (Vicia faba L.) cropping causes adverse effects, including increased secretion of autotoxic substances (benzoic acid) and incidence of diseases (Fusarium wilt). Fusarium commune infects faba bean seedlings and is treated with different benzoic acid concentrations. Therefore, this investigation analysed the association of benzoic acid with faba bean wilt incidence and the mechanisms involved. Furthermore, seedling growth, tissue structure, Fusarium wilt incidence, cell wall degrading enzymes (CWDEs) activity, lignin levels, and leaf photosynthetic parameters were assessed. The results indicated that fungal infection markedly reduced biomass and photosynthesis in the faba bean. Microscopic analysis showed slightly thickened stems' xylem vessels. Benzoic acid treatment with F. commune infection substantially increased F. commune-mediated CWDEs activity in the faba bean stem and lignin level but reduced photosynthesis and biomass, elevating Fusarium wilt incidence. Furthermore, broken tissues, xylem thickening, and stem cavities were observed. The investigation indicated that benzoic acid treatment and F. commune infection-induced stem lignin might be a resistance response; however, increased pathogenicity and reduced photosynthesis enhanced susceptibility and aggravated Fusarium wilt.

Serum inducible protein 10 kDa/C‐X‐C motif chemokine 10 levels predict regression of M2BPGi‐based liver fibrosis after hepatitis C virus eradication by direct‐acting antiviral agents

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Abstract

Aim

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy.

Methods

The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively.

Results

Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline.

Conclusions

Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate

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Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate

The authors demonstrate that white-tailed deer calving is a substantial zoogeochemical input in northeastern forests, which can ultimately contribute to fine-scale ecosystem heterogeneity. The impact of the subsidy, however, was strongly dependent on and modulated by the plant–fungal community, demonstrating the need for animal subsidies to be contextualized in plant–fungal frameworks.


Abstract

Animals interact with and impact ecosystem biogeochemical cycling—processes known as zoogeochemistry. While the deposition of various animal materials (e.g. carcasses and faeces) has been shown to create nutrient hotspots and alter nutrient cycling and storage, the inputs from parturition (i.e. calving) have yet to be explored. We examine the effects of ungulate parturition, which often occurs synchronously during spring green-up and therefore aligns with increased plant nitrogen demand in temperate biomes. Impacts of zoogeochemical inputs are likely context-dependent, where differences in material quality, quantity and the system of deposition modulate their impacts. Plant mycorrhizal associations, especially, create different nutrient-availability contexts, which can modify the effects of nutrient inputs. We, therefore, hypothesize that mycorrhizal associations modulate the consequences of parturition on soil nutrient dynamics and nitrogen pools. We established experimental plots that explore the potential of two kinds of zoogeochemical inputs deposited at ungulate parturition (placenta and natal fluid) in forest microsites dominated by either ericoid mycorrhizal (ErM) or ectomycorrhizal (EcM) plants. We assess how these inputs affect rates of nutrient cycling and nitrogen content in various ecosystem pools, using isotope tracers to track the fate of nitrogen inputs into plant and soil pools. Parturition treatments accelerate nutrient cycling processes and increase nitrogen contents in the plant leaf, stem and fine root pools. The ecosystem context strongly modulates these effects. Microsites dominated by ErM plants mute parturition treatment impacts on most nutrient cycling processes and plant pools. Both plant–fungal associations are, however, equally efficient at retaining nitrogen, although retention of nitrogen in the parturition treatment plots was more than two times lower than in control plots. Our results highlight the potential importance of previously unexamined nitrogen inputs from animal inputs, such as those from parturition, in contributing to fine-scale heterogeneity in nutrient cycling and availability. Animal inputs should therefore be considered, along with their interactions with plant mycorrhizal associations, in terms of how zoogeochemical dynamics collectively affect nutrient heterogeneity in ecosystems.

Association between age at menarche and cardiometabolic risk among Samoan adults

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Abstract

Objectives

Recent studies suggest that early menarche may increase cardiometabolic morbidity and mortality. Yet few studies have examined this association in the Pacific Islands, where obesity prevalence is among the highest globally. We sought to examine associations between age at menarche and cardiometabolic risk in Samoa.

Methods

Participants were from the Soifua Manuia study (n = 285, age 32–72 years) conducted in Samoa from 2017 to 2019. Logistic regressions were conducted to estimate odds of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome per one-year increase in age at menarche. Linear regressions were conducted to examine associations between age at menarche and continuous measures of adiposity, blood pressure, insulin resistance, and serum lipids.

Results

Median age at menarche was 14 years (IQR = 2). After controlling for relevant covariates, each one-year increase in age at menarche was associated with a 15% decrease (OR = 0.85, 95% CI: 0.72–1.01, p = .067) in odds of hypertension, but a 21% increase (OR = 1.21, 95% CI: 1.01–1.45, p = .044) in odds of diabetes and 18% increase (OR = 1.18, 95% CI: 0.98–1.42, p = .081) in odds of high total cholesterol. Each additional year in age at menarche was associated with a 1.60 ± 0.52 kg (p = .002) decrease in lean mass and 1.56 ± 0.51 kg (p = .003) decrease in fat-free mass.

Conclusions

Associations between age at menarche and cardiometabolic risk may be population-specific and are likely influenced by both current and historical nutritional and epidemiological contexts. Prospective studies are needed to clarify the role of childhood adiposity and other early life exposures on age at menarche and subsequent cardiometabolic risk.