Distribution of Fibrosis-4 index and vibration-controlled transient elastography-derived liver stiffness measurement for patients with metabolic dysfunction-associated steatotic liver disease in health check-up.

AIMS: The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), alcohol-associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check-ups. Additionally, we analyzed the distribution of Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE)-derived liver stiffness measurement (LSM) for MASLD. METHODS: In this cross-sectional study, 6530 subjects undergoing a health check-up in Japan were included. Conventional B-mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE. RESULTS: The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE-derived LSM ≥8 kPa constituted 2.1% of MASLD. FIB-4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE-derived LSM ≥8 kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB-4 ≥1.30. "FIB-4 ≥1.3 in subjects <65 years and FIB-4 ≥2.0 in subjects ≥65 years" showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB-4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE-derived LSM ≥8 kPa. CONCLUSIONS: Acknowledging the selection bias in hepatology centers, we undertook this prospective health check-up study. Although the FIB-4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188).

The power of cultural habits: The role of effortless control in delaying gratification.

What factors lead children to delay gratification, holding out for larger rewards later instead of taking smaller rewards now? Traditionally, delay of gratification has been associated with effortful control and willpower. However, we propose that delay of gratification may be partially supported by effortless control employed through habits shaped within sociocultural contexts. Specifically, in sociocultural contexts where waiting is rewarding and socially valued, children are more likely to wait for larger, delayed rewards and to form associations between these contexts and waiting for rewards. These acquired habits enable waiting for rewards without requiring substantial cognitive effort. Based on this novel framework, we reconsider why childhood delay of gratification predicts life outcomes, and the role of cognitive, social, and cultural factors.

Positive correlation between working memory and face-to-face social interaction in everyday life.

Working memory (WM) plays a crucial role in various cognitive tasks from language comprehension to problem-solving. However, its influence on social activities has remained largely unexplored. The current two studies on individual differences, a pilot (N = 329) and a pre-registered direct replication (N = 338) study, investigated the relationship between WM and outside-the-lab social interaction by using a listening span task and three social network questionnaires (e.g., how many people a participant had contacted in the past month). The consistent patterns in the two studies were (a) WM recall was positively correlated with social network size, (b) WM recall remained positively correlated with social network size even when accounting for online interactions on WhatsApp and Facebook, and (c) WM recall was positively correlated with social network size by face-to-face interaction. These novel findings would suggest connections between WM and face-to-face social interaction. It was, however, acknowledged that the obtained effect sizes were small, and that further investigation is indeed necessary. In light of this, we also clarify future directions for understanding the relationship between WM and social interaction.

No evidence for cross-paradigm transfer of abstract task knowledge in adults and school-aged children.

Cognitive control is a hallmark of human cognition. A large number of studies have focused on the plasticity of cognitive control and examined how repeated task experience leads to the improvement of cognitive control in novel task environments. However, it has been demonstrated that training-induced changes are very selective and that transfer occurs within one task paradigm but not across different task paradigms. The current study tested the possibility that cross-paradigm transfer would occur if a common cognitive control strategy is employed across different task paradigms. Specifically, we examined whether prior experience of using reactive control in one task paradigm (i.e., either the cued task-switching paradigm or the AX-CPT) makes adults (N = 137) and 9- to 10-year-olds (N = 126) respond in a reactive way in a subsequent condition of another task paradigm in which proactive control could have been engaged. Bayesian generalized mixed-effects models revealed clear evidence of an absence of cross-paradigm transfer of reactive control in both adults and school-aged children. Based on these findings, we discuss to what extent learned control could be transferred across different task contexts and the task-specificity of proactive/reactive control strategies.

When stimulus variability accelerates the learning of task knowledge in adults and school-aged children.

Experience with instances that vary in their surface features helps individuals to form abstract task knowledge, leading to transfer of that knowledge to novel contexts. The current study sought to examine the role of this variability effect in how adults and school-aged children learn to engage cognitive control. We focused on the engagement of cognitive control in advance (proactive control) and in response to conflicts (reactive control) in a cued task-switching paradigm, and conducted four preregistered online experiments with adults (Experiment 1A: N = 100, Experiment 1B: N = 105) and 9- to 10-year-olds (Experiment 2A: N = 98, Experiment 2B: N = 97). It was shown that prior task experience of engaging reactive control makes both adults and 9- to 10-year-olds respond more slowly in a subsequent similar-structured condition with different stimuli in which proactive control could have been engaged. 9- to 10-year-olds (Experiment 2B) exhibited more negative transfer of a reactive control mode when uninformative cue and pre-target stimuli, which do not convey task-relevant information, were changed in each block, compared with when they were fixed. Furthermore, adults showed suggestive evidence of the variability effect both when cue and target stimuli were varied (Experiment 1A) and when uninformative cue and pre-target stimuli were varied (Experiment 1B). The collective findings of these experiments provide important insights into the contribution of stimulus variability to the engagement of cognitive control.

Chronological Course and Clinical Features after Denver Peritoneovenous Shunt Placement in Decompensated Liver Cirrhosis.

BACKGROUND: Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. OBJECTIVES: To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. MATERIALS AND METHODS: This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. RESULTS: No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. CONCLUSIONS: PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Emerging drugs for the treatment of hepatic fibrosis on nonalcoholic steatohepatitis.

INTRODUCTION: Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important. AREAS COVERED: This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis. EXPERT OPINION: Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways. The method of assessing fibrosis is important when considering treatment for liver fibrosis in NASH. The Food and Drug Administration considers an important fibrosis endpoint to be histological improvement in at least one fibrosis stage while preventing worsening of fatty hepatitis. To obtain approval as a drug for NASH, efficacy needs to be demonstrated on endpoints such as liver-related events and myocardial infarction. Among the current therapeutic agents for NASH, thiazolidinedione, sodium-glucose co-transporter 2, and selective peroxisome proliferator-activated receptors α modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.

The Semantic Similarity Effect on Short-Term Memory: Null Effects of Affectively Defined Semantic Similarity.

Studies on short-term memory have repeatedly demonstrated the beneficial effect of semantic similarity. Although the effect seems robust, the aspects of semantics targeted by these studies (e.g., categorical structure, associative relationship, or dimension of meaning) should be clarified. A recent meta-regression study inspired by Osgood's view, which highlights affective dimensions in semantics, introduced a novel index for quantifying semantic similarity using affective values. Building on the results of the meta-regression of past studies' data with that index, this study predicts that semantic similarity is deleterious to short-term memory if it is manipulated by affective dimensions, after controlling for other confounding factors. This prediction was directly tested. The experimental results of the immediate serial recall task (Study 1) and immediate serial reconstruction of order task (Study 2) indicated null effects of semantic similarity by affective dimensions and thus falsified the prediction. These results suggest that semantic similarity based on affective dimensions is negligible.

Identification of differentially methylated regions associated with both liver fibrosis and hepatocellular carcinoma.

BACKGROUND: Liver fibrosis is a major risk factor for hepatocellular carcinoma (HCC). We have previously reported that differentially methylated regions (DMRs) are correlated with the fibrosis stages of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the methylation levels of those DMRs in liver fibrosis and subsequent HCC were examined. METHODS: The methylation levels of DMRs were investigated using alcoholic cirrhosis and HCC (GSE60753). The data of hepatitis C virus-infected cirrhosis and HCC (GSE60753), and two datasets (GSE56588 and GSE89852) were used for replication analyses. The transcriptional analyses were performed using GSE114564, GSE94660, and GSE142530. RESULTS: Hypomethylated DMR and increased transcriptional level of zinc finger and BTB domain containing 38 (ZBTB38) were observed in HCC. Hypermethylated DMRs, and increased transcriptional levels of forkhead box K1 (FOXK1) and zinc finger CCCH-type containing 3 (ZC3H3) were observed in HCC. The methylation levels of DMR of kazrin, periplakin interacting protein (KAZN) and its expression levels were gradually decreased as cirrhosis progressed to HCC. CONCLUSIONS: Changes in the methylation and transcriptional levels of ZBTB38, ZC3H3, FOXK1, and KAZN are important for the development of fibrosis and HCC; and are therefore potential therapeutic targets and diagnostic tools for cirrhosis and HCC.

Prediction of outcomes in patients with metabolic dysfunction-associated steatotic liver disease based on initial measurements and subsequent changes in magnetic resonance elastography.

BACKGROUND: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with liver fibrosis. We aimed to investigate whether liver stiffness measurement (LSM) and changes in LSM (ΔLSM) on magnetic resonance elastography (MRE) can predict clinical events in patients with MASLD. METHODS: We included 405 patients with MASLD who underwent at least two MREs. The patients were divided into five groups corresponding to fibrosis stages (0-4) based on initial LSM and classified as progressors (ΔLSM ≥ 19%) or non-progressors (ΔLSM < 19%) based on the difference between the first and last LSM. RESULTS: The mean follow-up period was 72.6 months, and the mean interval between MREs was 23.5 months. There were 52 (12.8%) progressors and 353 (87.2%) non-progressors. The initial LSM was significantly associated with the cumulative probabilities of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver-related events, extrahepatic malignancies, and overall mortality but not with cardiovascular disease. Progressors had significantly higher hazard ratios (HRs) for decompensated cirrhosis, HCC, and liver-related events but not for extrahepatic malignancies, cardiovascular disease, or overall mortality. Among patients without cirrhosis, the HR for developing cirrhosis among progressors was 60.15. Progressors had a significantly higher risk of liver-related events, even in the low initial LSM (fibrosis stage 0-2) subgroups. CONCLUSIONS: Both initial LSM and ΔLSM can predict liver-related events in patients with MASLD, even for low initial LSM. This integrated assessment can allow more detailed risk stratification compared with single LSM assessments and identify high-risk patients with MASLD among those previously considered as low risk.