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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common liver disease. It has a rapidly growing patient population owing to the increasing prevalence of obesity and type 2 diabetes. Patients with MASLD are primarily treated by family physicians when fibrosis is absent or mild and by gastroenterologists/hepatologists when fibrosis is more advanced. It is imperative that a system for the appropriate treatment and surveillance of hepatocellular carcinoma be established in order to ensure that highly fibrotic cases are not overlooked among the large number of MASLD patients. Family physicians should check for viral hepatitis, autoimmune hepatitis, alcoholic liver disease, and drug-induced liver disease, and should evaluate fibrosis using NIT; gastroenterologists/hepatologists should perform liver biopsy, ultrasound elastography (260 units in Japan as of October 2023), and MR elastography (35 units in Japan as of October 2023). This review presents the latest findings in MASLD and the role, accuracy, and clinical use of NIT. It also describes the collaboration between Japanese primary care and gastroenterologists/hepatologists in Japan in the treatment of liver diseases, including MASLD. [ABSTRACT FROM AUTHOR]

Gathercole et al. (Journal of Memory and Language, 105, 19–42, 2019) presented a cognitive routine framework for explaining the underlying mechanisms of working memory (WM) training and transfer. This framework conceptualizes training-induced changes as the acquisition of novel cognitive routines similar to learning a new skill. We further infer that WM training might not always generate positive outcomes because previously acquired routines may affect subsequent task performance in various ways. Thus, the present study aimed to demonstrate the negative effects of WM training via two experiments. We conducted Experiment 1 online using a two-phase training paradigm with only three training sessions per phase and replicated the key findings of Gathercole and Norris (in prep.) that training on a backward circle span task (a spatial task) transferred negatively to subsequent training on a backward letter span task (a verbal task). We conducted Experiment 2 using a reversed task order design corresponding to Experiment 1. The results indicated that the transfer from backward letter training to backward circle training was not negative, but rather weakly positive, suggesting that the direction of the negative transfer effect is asymmetric. The present study therefore found that a negative transfer effect can indeed occur under certain WM training designs. The presence of this asymmetric effect indicates that backward circle and backward letter tasks require different optimal routines and that the locus of negative transfer might be the acquisition process of such optimal routines. Hence, the routines already established for backward circle might hinder the development of optimal routines for backward letter, but not vice versa. [ABSTRACT FROM AUTHOR]

Background and Aim: Ischemic colitis (IC) is a benign disease associated with acute lower gastrointestinal bleeding and frequent recurrence. While several studies have investigated risk factors for IC onset, few have assessed the risk factors for recurrent IC. This study aimed to identify risk factors for recurrent IC. Methods: Potential risk factors for recurrence were assessed by examining medical records and laboratory findings in this single‐center retrospective study. We extracted the following data from the patients' medical records: patient characteristics, clinical signs and symptoms, laboratory findings, method of treatment, length of hospital stay, disease course, and the frequency of IC morbidities. Patients with IC were selected from a total of 439 312 patients over an 11‐year period. Patients were divided into recurrent and nonrecurrent IC groups. Results: In total, 225 patients met the diagnostic criteria for IC during the specified study period; of these, 204 patients (90.7%) and 21 patients (9.3%) were included in the nonrecurrent and recurrent IC groups, respectively. Univariate and multivariate analyses showed a significant association between IC recurrence and both cerebral infarction (P = 0.008, odds ratio [OR] = 6.3) and history of appendectomy (P = 0.0005, OR = 6.2). The median (interquartile range [IQR]) follow‐up time for all patients was 1556 (353–2768) days; this was much longer than the median (IQR) time to recurrence of 291 (64–907) days in the recurrent IC group. Conclusion: The results of this study suggest that prior cerebral infarction and appendicectomy may be risk factors for IC recurrence. [ABSTRACT FROM AUTHOR]

The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, suggesting that periodontal disease is sometimes associated with systemic conditions. In this review, we summarize recent studies linking periodontal disease and NAFLD, the concept of the mouth–gut–liver axis, oral and intestinal microbiota, and liver disease. We suggest new research directions toward a detailed mechanistic understanding and novel targets for treatment and prevention. Forty years have passed since the concepts of NAFLD and NASH were first proposed. however, no effective prevention or treatment has been established. We also found that the pathogenesis of NAFLD/NASH is not limited to liver-related diseases but has been reported to be associated with various systemic diseases and an increasing number of causes of death. In addition, changes in the intestinal microbiota have been shown to be a risk factor for periodontal diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, and obesity. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate the diagnostic accuracy of the measurement of serum type IV collagen 7S (T4C7S) concentration for the staging of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Methods: A systematic search or published works was carried out using the PubMed, Cochrane Library, and Web of Science Core Collection databases for studies of the accuracy of serum T4C7S concentration for the staging of fibrosis using Fibrosis stage (F)0–4 in patients with NAFLD diagnosed by liver biopsy. Results: Nine articles describing 1475 participants with NAFLD were included. For fibrosis ≥F1, with n = 849, summary estimates of sensitivity of 0.79, specificity of 0.69, and area under the curve (AUC) of 0.80 were obtained using a median T7C4S cut‐off value of 4.6 ng/ml. For fibrosis ≥F2, with n = 1,090, summary estimates of sensitivity of 0.78, specificity of 0.78, and AUC of 0.84 were obtained using a median cut‐off value of 4.9 ng/ml. For fibrosis ≥F3, with n = 1311 participants and a median cut‐off value of 5.4 ng/ml, a pooled sensitivity of 0.82, specificity of 0.81, and AUC of 0.83 were obtained. For fibrosis ≥F4, with n = 753 and a median cut‐off value of 6.6 ng/ml, a pooled sensitivity of 0.85, specificity of 0.81, and AUC of 0.85 were obtained. Conclusions: Serum T4C7S concentration was found to be an accurate method of staging liver fibrosis in patients with NAFLD. [ABSTRACT FROM AUTHOR]

With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance and results from the atrophy of skeletal muscle, an insulin target organ. In addition, inflammatory cytokines that promote skeletal muscle protein breakdown, low adiponectin levels leading to decreased insulin sensitivity, and hyperleptinemia are also involved in NAFLD pathogenesis. The presence of sarcopenia is a prognostic factor and increases the risk of mortality in patients with cirrhosis and post-treatment liver cancer. Sarcopenia, the presence of which mainly occurs due to decreased muscle mass, combined with increased visceral fat, can lead to sarcopenia-associated obesity, which increases the risk of NASH, liver fibrosis, and cardiovascular disease. In order to treat sarcopenia, it is necessary to properly evaluate sarcopenia status. Patients with high BMI, as in sarcopenic obesity, may improve with caloric restriction. However, inadequate oral intake may lead to further loss of muscle mass. Aerobic and resistance exercise should also be used appropriately. [ABSTRACT FROM AUTHOR]

Background and Aim: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam‐equipped FibroScan for liver stiffness measurement (LSM). Methods: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam‐Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging‐based proton density fat fraction (MRI‐PDFF) measurements to assess its diagnostic performance. M or XL probes were selected based on the probe‐to‐liver capsule distance for all FibroScan examinations. Results: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam‐equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI‐PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam‐equipped FibroScan showed no significant difference. However, the SmartExam‐equipped FibroScan measurement (33.6 s) took 1.4 times longer than conventional FibroScan (23.2 s). Conclusions: SmartExam has a high diagnostic performance comparable with that of conventional FibroScan. Because the results of the conventional and SmartExam‐equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared with the conventional FibroScan. [ABSTRACT FROM AUTHOR]

Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014–2020) who were classified according to their body mass index (BMI) as normal (BMI < 25 kg/m2, n = 38), overweight (25 ≤ BMI < 30 kg/m2, n = 68), and obese (BMI ≥ 30 kg/m2, n = 57). VCTE and MRE detected fibrosis of stages ≥ 2, ≥ 3, and 4 with an area under the receiver operating curve (AUROC) of 0.83–0.94 (VCTE) and 0.85–0.95 (MRE) in all groups, without considerable differences. MRI-PDFF detected steatosis of grades ≥ 2 and 3 with high AUROC in all groups (0.81–1.00). CAP's diagnostic ability (0.63–0.95) was lower than that of MRI-PDFF and decreased with increasing BMI compared to MRI-PDFF. VCTE and MRE similarly accurately assess fibrosis, although MRI-PDFF is more accurate than CAP in detecting steatosis in overweight and obese patients with NAFLD. [ABSTRACT FROM AUTHOR]

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs. [ABSTRACT FROM AUTHOR]

Background and Aim: Non‐alcoholic fatty liver disease (NAFLD) can progress in non‐obese patients as in obese patients. Reports on long‐term prognosis in non‐obese NAFLD patients are controversial. Therefore, we aimed to examine the long‐term prognosis of non‐obese patients with NAFLD. Methods: This single‐center, retrospective cohort study enrolled biopsy‐proven non‐obese and obese NAFLD patients between January 2002 and December 2011 and followed them up until 31 March 2021, for death and clinical events (cardiovascular and liver‐related events and extrahepatic cancers). Results: Of the 223 NAFLD patients, 58 (26.0%) were non‐obese. Compared with obese patients, they had a lower fibrosis stage (0.8 ± 0.80 vs 1.2 ± 0.91; P = 0.004), milder lobular inflammation (0.9 ± 0.7 vs 1.1 ± 0.7; P = 0.02), and significantly lower serum creatinine, total bilirubin, ferritin, and type IV collagen 7S and higher high‐density lipoprotein levels. After a median follow‐up of 8.9 years, no significant difference was noted in mortality between the two groups (2 [3.4%] non‐obese vs 5 [3.0%] obese; log‐rank test, P = 0.63). Twelve patients (20.7%) in the non‐obese group and 32 (19.4%) in the obese group had clinical events. Although the obese group had a higher incidence of clinical events during the first 10 years of follow‐up, the non‐obese group had a higher incidence after that (log‐rank test, P = 0.67). The non‐obese group had a high incidence of malignancy (9 [15.5%] non‐obese vs 14 [8.3%] obese; P = 0.13). Conclusion: Non‐obese NAFLD does not necessarily have a good prognosis, and some cases have a poor prognosis such as extrahepatic cancers. Further validation is required in the future. [ABSTRACT FROM AUTHOR]

The incidence of nonalcoholic fatty liver disease (NAFLD) has recently increased and is related to obesity and the associated surge in type 2 diabetes mellitus (T2DM) and metabolic syndromes. This trial follows up on our previous work and forms part of the ToPiND study. We aimed to combine tofogliflozin and pioglitazone treatment for hepatic steatosis in patients with NAFLD and T2DM. In this open‐label, prospective, single‐center, randomized clinical trial, patients with NAFLD with T2DM and a hepatic fat fraction of ≥10% were assessed based on magnetic resonance imaging proton density fat fraction. Eligible patients received either 20 mg tofogliflozin or 15–30 mg pioglitazone orally, once daily for 24 weeks, followed by combination therapy with both medicines for an additional 24 weeks. The effects on diabetes mellitus and hepatic steatosis were examined at baseline and after the completion of monotherapy and combination therapy. Thirty‐two eligible patients received the combination therapy of tofogliflozin and pioglitazone. The combination therapy showed additional improvement in glycated hemoglobin compared with each monotherapy group and showed improvement in steatosis, hepatic stiffness, and alanine aminotransferase levels compared with the tofogliflozin monotherapy group. Pioglitazone monotherapy–mediated increase in body weight decreased following concomitant use of tofogliflozin. The combination therapy resulted in lower triglyceride, higher high‐density lipoprotein cholesterol, higher adiponectin, and higher ketone body levels. Conclusion: In addition to the additive effects of tofogliflozin and pioglitazone in patients with T2DM and NAFLD, combination therapy was suggested to reduce weight gain and induce cardioprotective effect. Further studies with more patients are needed to investigate the combination therapy of various drugs. [ABSTRACT FROM AUTHOR]

Children engage cognitive control reactively when they encounter conflicts; however, they can also resolve conflicts proactively. Recent studies have begun to clarify the mechanisms that support the use of proactive control in children; nonetheless, sufficient knowledge has not been accumulated regarding these mechanisms. Using behavioral and pupillometric measures, we tested the novel possibility that 5‐year‐old children (N = 58) learn to use proactive control via the acquisition of abstract task knowledge that captures regularities of the task. Participants were assigned to either a proactive training group or a control training group. In the proactive training group, participants engaged in a training phase where using proactive control was encouraged, followed by a test phase using different stimuli where both proactive and reactive control could be used. In the control training group, participants engaged in a training phase where both cognitive control strategies could be used, followed by a similarly‐structured test phase using different stimuli. We demonstrated children in the control training group responded more quickly and accurately and showed greater cue‐related pupil dilation in the test phase than in the training phase. However, there were no differences in response times, accuracies, and pupil dilation between the proactive and control training groups in the training and test phases. These findings suggest that prior task experience, that goes beyond specific knowledge about the timing of task goal activation, can lead children to engage more proactive control endogenously, even if they are not directly encouraged to do so. [ABSTRACT FROM AUTHOR]

We analyzed a Japanese lexical database to investigate the structure of the lexical environment based on the hypothesis that the lexical environment is optimized for the functioning of verbal working memory. Our prediction was that, as a consequence of the cultural transmission of language, low‐imageable meanings tend to be represented by frequent phonological patterns in the current vocabulary rather than infrequent phonological patterns. This prediction was based on two findings of previous laboratory studies on verbal working memory. (1) The quality of phonological (phonemic and accent) representations in verbal working memory depends on phonological regularity knowledge; therefore, short‐term phonological representations are less robust for words with infrequent phonological patterns. (2) Phonological representations are underpinned by contributions from semantic knowledge; therefore, phonological representations of highly imageable words are more robust than those for low‐imageable words. Our database analyses show that nouns with less imageable meanings tend to be associated with more frequent phonological patterns in Japanese vocabulary. This lexical structure can maintain the quality of phonological representations in verbal working memory through contributions of semantic and phonological regularity knowledge. Larger semantic contributions compensate for the less robust phonological representations of infrequent phonological forms. The quality of phonological representations is preserved by phonological regularity knowledge when larger semantic contributions are not expected. [ABSTRACT FROM AUTHOR]

Aversive memories have the potential to impair one's psychological well-being. It is desirable to reduce the anguish over such memories, as well as the chance that they will be retrieved. In two experiments, we investigated whether retrieval stopping reduces the distress elicited by negative memories retrieved from cues and how the effects of retrieval stopping are modulated by mental disorders, such as depression and anxiety. Participants engaged in retrieval stopping of aversive scene memories without any diversionary thoughts (direct suppression, Experiment 1) or with diversionary positive thoughts (thought substitution, Experiment 2). Direct suppression reduced arousal elicited by the retrieval of aversive memories, while thought substitution did not only reduce arousal but also increased positive valence. Self-reported anxious/depressive symptoms negatively modulated the effects of direct suppression. For no or mild anxious/depressed individuals, direct suppression alleviated negative valence and high arousal when retrieving aversive memories. The negative relationship was not observed between the severity of the symptoms and the effect of thought substitution. These findings suggest that both retrieval stopping strategies can reduce distress from aversive memories. [ABSTRACT FROM AUTHOR]

The Hebb repetition effect on serial-recall task refers to the improvement in the accuracy of recall of a repeated list (e.g., repeated in every 3 trials) over random non-repeated lists. Previous research has shown that both temporal position and neighboring items need to be the same on each repetition list for the Hebb repetition effect to occur, suggesting chunking as one of its underlying mechanisms. Accordingly, one can expect absence of the Hebb repetition effect in a complex span task, given that the sequence is interrupted by distractors. Nevertheless, one study by Oberauer, Jones, and Lewandowsky (2015, Memory & Cognition, 43[6], 852–865) showed evidence of the Hebb repetition effect in a complex span task. Throughout four experiments, we confirmed the Hebb repetition effect in complex span tasks, even when we included distractors in both encoding and recall phases to avoid any resemblance to a simple span task and minimized the possibility of chunking. Results showed that the Hebb repetition effect was not affected by the distractors during encoding and recall. A transfer cycle analysis showed that the long-term knowledge acquired in the complex span task can be transferred to a simple span task. These findings provide the first insights on the mechanism behind the Hebb repetition effect in complex span tasks; it is at least partially based on the same mechanism that improves recall performance by repetition in simple span tasks. [ABSTRACT FROM AUTHOR]

Background: We previously reported that two differentially methylated region (DMR) networks identified by DMR and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC). Methods: We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). The dataset GSE60753 was used for validation. Results: One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and cirrhosis, and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene may be correlated with reduced protection of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 may facilitate the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC may be associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD. Conclusions: Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. Furthermore, FABP1, SGK2, and HNF4A are potential candidate targets for the prevention and treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: We previously reported that two differentially methylated region (DMR) networks identified by DMR and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC).Methods: We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). The dataset GSE60753 was used for validation.Results: One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and cirrhosis, and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene may be correlated with reduced protection of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 may facilitate the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC may be associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD.Conclusions: Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. Furthermore, FABP1, SGK2, and HNF4A are potential candidate targets for the prevention and treatment of HCC. [ABSTRACT FROM AUTHOR]

An island formation method for fabrication of a miniaturized CAAC‐OS FET has been developed. With our etching process, the CAAC‐OS FET, which has a gate length as small as 6.5 nm, had a high on‐off drain current ratio. The high‐definition display had excellent characteristics of a low lateral leakage current. [ABSTRACT FROM AUTHOR]

We have investigated the total ionizing dose effect by X‐rays, which is a degradation mode of a single transistor, to find the radiation resistance of oxide semiconductor large scale integrated circuit. At 3000 Gy corresponding to the absorbed dose for 30 years in a space environment, or more specifically, on a geostationary orbit, an oxide semiconductor field‐effect transistor showed a negative drift in threshold voltage of less than 300m V and substantially no degradation in subthreshold slope and mobility. After 60 hours from the irradiation, approximately 40% of the threshold voltage variation was recovered. [ABSTRACT FROM AUTHOR]

Our daily lives are composed of several sequential actions that we perform routinely, such as making breakfast, taking a train, and changing clothes. Previous research has demonstrated that a routine system plays a role in performing and controlling repeated sequential actions in familiar situations, and a top‐down control system involves the control of the routine system in novel situations. Specifically, most developmental studies have focused on the top‐down control system (e.g., executive functions) as a factor enabling the control of goal‐directed actions in novel situations. Yet, it has not been thoroughly examined how young children learn, perform, and control repeated sequential actions in familiar contexts. In this review, based on recent computational accounts for adults, we highlight two critical aspects of the routine system from a developmental perspective: (1) automatic flexible changes of contextual representations, which enables humans to select context‐dependent actions appropriately; and (2) detection of deviant situations, which signals the need for control to avoid errors. In addition, we propose the developmental mechanism underlying the routine system and its potential driving factors such as statistical regularities and executive functions. Finally, we suggest that an investigation into the interplay between routine and executive functions can form foundations for understanding learning, performing, and controlling repeated sequential actions in young children and discuss future directions in this area. Yanaoka and Saito offer a review of developmental evidence about the routine system and its potential developmental mechanism and driving factors. They suggest that an investigation into the interplay between routine and executive functions can form foundations for understanding learning, performing, and controlling repeated sequential actions in young children. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM@50 Hz) using standard vibration‐controlled transient elastography (VCTE) have been studied as a noninvasive test for screening of gastroesophageal varices (GEV) in chronic liver disease (CLD). Recently, a novel spleen‐dedicated VCTE (SSM@100 Hz) has been developed. We evaluated the diagnostic performance of SSM@100 Hz, SSM@50 Hz, LSM, and other noninvasive tests using esophagogastroduodenoscopy (EGD) as the reference as well as the correlation with hepatic venous pressure gradient (HVPG). Methods: A total of 123 patients with CLD enrolled in this cross‐sectional study. SSM@100 Hz, SSM@50 Hz, and LSM were determined by VCTE. EGD and HVPG were performed within 12 weeks before or after VCTE. Results: GEV were present in 60 patients. Failure or suboptimal SSM were fewer at 100 Hz (4.0%) than at 50 Hz (17.7%). All SSM values obtained at 100 Hz were lower than the 100 kPa ceiling threshold, but 10 patients reached the 75 kPa ceiling threshold for SSM@50 Hz. SSM@100 Hz was most accurate (area under the receiver operating characteristic [AUROC] = 0.944) for the diagnosis of GEV compared to SSM@50 Hz, LSM, and scoring systems. AUROC of SSM@100 Hz for diagnosis of high‐bleeding risk varices (HRV) was 0.941, which was significantly higher than that of SSM@50 Hz (AUROC = 0.842, P = 0.002). SSM@100 Hz showed higher specificity (82.0%) for diagnosis of HRV than SSM@50 Hz (specificity = 67.1%). SSM@100 Hz was significantly correlated with HVPG (r = 0.71, P < 0.001). Conclusions: The novel spleen‐dedicated VCTE examination can be used for noninvasive assessment of GEV and HVPG in CLD. Japan Registry of Clinical Trials Registry No. jRCTs032200119. [ABSTRACT FROM AUTHOR]

Background: The role of hepatic iron overload (HIO) in nonalcoholic fatty liver disease (NAFLD) pathogenesis has not been fully elucidated. Purpose This study aimed to investigate the effect of HIO and examine the diagnostic usefulness of magnetic resonance imaging (MRI)‐based R2* quantification in evaluating hepatic iron content (HIC) and pathological findings in NAFLD. Study Type: Prospective and retrospective. Population A prospective study of 168 patients (age, 57.2 ± 15.0; male/female, 80/88) and a retrospective validation study of 202 patients (age, 57.0 ± 14.4; male/female, 113/89) with liver‐biopsy‐confirmed NAFLD were performed. Field Strength/Sequence: 3 T; chemical‐shift encoded multi‐echo gradient echo. Assessment Using liver tissues obtained by liver biopsy, HIC was prospectively evaluated in 168 patients by atomic absorption spectrometry. Diagnostic accuracies of HIC and R2* for grading hepatic inflammation plus ballooning (HIB) as an indicator of NAFLD activity were assessed. Statistical Tests: Student's t‐test and analysis of variance (ANOVA) with Scheffe's multiple testing correction for univariate comparisons; multivariate logistic analysis. P‐value less than 0.05 is statistically significant. Results: HIC was significantly correlated with HIB grades (r = 0.407). R2* was significantly correlated with HIC (r = 0.557) and HIB grades (r = 0.569). R2* mapped an area under the receiver operating characteristic (AUROC; 0.774) for HIC ≥808 ng/mL (median value) with cutoff value of 62.5 s−1. In addition, R2* mapped AUROC of HIB for grades ≥3 was 0.799 with cutoff value of 58.5 s−1. When R2* was <62.5 s−1, R2* correlated weakly with HIC (r = 0.372) as it was affected by fat deposition and did not correlate with HIB grades (P = 0.052). Conversely, when R2* was ≥62.5 s−1, a significant correlation of R2* with HIC (r = 0.556) and with HIB grades was observed (P < 0.0001) with being less affected by fat deposition. Data Conclusion: R2* ≥ 62.5 s−1 is a promising modality for non‐invasive diagnosis of clinically important high grades (≥3) of HIB associated with increased HIC. Level of Evidence: 1 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background & Aims: Tolvaptan, vasopressin V2‐receptor antagonist, has been used for patients with difficult‐to‐treat ascites in Japan. In this study, we conducted a genome‐wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. Methods: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non‐responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. Results: Genome‐wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome‐wide association (OR = 3.55, P = 2.01 × 10‐8). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P =.003; OR = 1.02, P =.02 and OR = 3.98, P =.000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*‐0.179) (1 + exp (score)) was determined for the detection of non‐responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. Conclusion: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non‐responders and help to avoid a lengthy period of futile treatment. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database. Methods: Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively. Results: The incidence rates of CVD were 0.97 (95% CI 0.94–1.01) and 2.82 (95% CI 2.64–3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98–1.03) and 2.69 (95% CI 2.55–2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM. Conclusions: Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD. [ABSTRACT FROM AUTHOR]

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are fatal adverse skin reactions characterized by high fever, epidermal detachment, and mucositis. It is well known that SJS/TEN occasionally affects various organs, leading to permanent damage and death in some patients. Although acute liver dysfunction is a relatively common complication of SJS/TEN, severe acute liver dysfunction requiring liver transplantation is rare. We present the case of a 14‐year‐old girl with SJS complicated by severe and rapidly progressive liver dysfunction, specifically, acute liver failure (ALF) requiring liver transplantation. A lymphocyte transformation test showed positive results for acetaminophen and cefdinir. Furthermore, human leukocyte antigen (HLA) genotyping revealed the presence of the HLA‐A*02:06 genotype, which is reported to be strongly associated with acetaminophen‐related SJS/TEN with severe ocular complications. These results suggested that our patient may have presented with acetaminophen‐induced SJS complicated by ALF, but no ocular complications. This is the first report of a pediatric patient with SJS who required liver transplantation. In rare instances, severe liver dysfunction requiring liver transplantation should be considered as a possible complication of SJS/TEN. [ABSTRACT FROM AUTHOR]

This study examined whether executive functions impact how flexibly children represent task context in performing repeated sequential actions. Japanese children in Experiments 1 (N = 52; 3–6 years) and 2 (N = 50, 4–6 years) performed sequential actions repeatedly; one group received reminders. Experiment 1 indicated that reminders promote flexible changes in contextual representations. Experiment 2 observed such effects in younger children and showed executive functions were associated with the flexible representation of task context. Reminders did not perfectly compensate for the role of executive functions but wiped out individual differences in executive functions that contribute to children's acquisition of routines. Therefore, setting goals before context‐dependent actions is necessary, but not sufficient, to modulate contextual representations in routines. [ABSTRACT FROM AUTHOR]

Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare intrahepatic tumor. There are usually no specific physical findings, and the tumors are often diagnosed incidentally and are frequently large-sized at diagnosis. The imaging findings of LELCC resemble those of hepatocellular carcinoma (HCC). Tumors are often found in large-sized and advanced at diagnosis, and the main treatment of the disease is surgical resection. Herein, we report treating a patient with early stage LELCC by radiofrequency ablation (RFA). We diagnosed this tumor in a 27-year-old Chinese female with a history of chronic hepatitis B (CHB). Based on the findings of blood examination, abdominal ultrasonography, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), this tumor was diagnosed as suspected HCC. Ultrasound-guided percutaneous tumor biopsy and RFA were performed at the same time. The histopathological findings finally revealed the diagnosis of LELCC. To the best of our knowledge, this is the first report, in the English-language literature, of the treatment of LELCC by RFA; we suggest that RFA might be a candidate treatment for small-sized early stage LELCC. [ABSTRACT FROM AUTHOR]

The literature suggests that semantic similarity has a weak or null effect for immediate serial reconstruction and a facilitative effect for immediate serial recall. These observed semantic similarity effects are inconsistent with the assumptions of short-term memory (STM) models on the detrimental effect of similarity (e.g., confusion) and with observations of a robust detrimental effect of phonological similarity. Our review indicates that the experimental results are likely dependent on the manipulation strength for semantic similarity and that manipulations used in previous studies might have affected semantic assvociation as well as semantic similarity. To address these possible issues, two indices are proposed: (a) strength of manipulation on semantic similarity, gained by quantifying semantic similarity based on Osgood and associates' dimensional view of semantics, and (b) inter-item associative strength, a possible confounding factor. Our review and the results of a meta-regression analysis using these two indices suggest that semantic similarity has a detrimental effect on both serial reconstruction and serial recall, while semantic association, which is correlated with semantic similarity, contributes to an apparent facilitative effect. An effect that is not attributable to similarity or association was also implied. Review on item and order memory further suggests the facilitative effect of semantic association on item memory and the detrimental effect of the semantic similarity on order memory. Based on our findings, we propose a unified explanation of observations of semantic similarity effects for both serial reconstruction and serial recall that is in good accord with STM models. [ABSTRACT FROM AUTHOR]

Introduction: Chronic constipation (CC) is a highly prevalent functional bowel disorder with low treatment satisfaction and impaired quality of life (QOL). However, physicians tend to emphasize only "stool frequency," and relationship between "stool form" and QOL remains unclear. In this study, we aimed to investigate the actual situation of CC treatment in Japan and elucidate the relationship between stool form and QOL in patients with CC. Methods: We conducted an online questionnaire survey in September 2018 targeting Japanese adult patients already diagnosed with CC and taking prescribed drugs. Assessments included the type of drug treatment, treatment duration, frequency of drug use, frequency of bowel movements (BMs), Bristol Stool Form Scale (BSFS), and Japanese version of the Patient Assessment of Constipation QOL (PAC-QOL) scores. Relationship between BSFS and Japanese PAC-QOL scores was analyzed, and most important factor that influences QOL was investigated. Results: A total of 614 subjects were enrolled. Of these, 398 (64.8%) regularly used magnesium oxide and 162 (26.4%) used stimulant laxative, especially 81 (50.0%) used stimulant laxative "everyday." Mean score of the PAC-QOL was 1.29 ± 0.74, and the lowest score (highest QOL) of 0.94 ± 0.61 was observed in BSFS type 4. Significant difference was seen between BSFS type 4 and all the other types except type 7. Multivariate analysis revealed that normal stool form (BSFS type 4) and BMs ≥3/week are strongly related to decreases of PAC-COL score. In BSFS types 6 and 7, 36% of individuals experienced self-discontinuation of prescribed drugs and 53% self-reduced drug intake because of excessive effects. Conclusions: Stool form and frequency of BMs are relevant to QOL, especially normal stool form (BSFS type 4) is important for improving the QOL in patients with constipation. Physicians should focus on "stool form" and reconsider the prescription especially in BSFS types 6–7 patients. [ABSTRACT FROM AUTHOR]

Background: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179). Methods: Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements. Results: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg. Conclusions: TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is expected to increase because of the current epidemics of obesity and diabetes, and NAFLD has become a major cause of chronic liver disease worldwide. Liver fibrosis is associated with poor long-term outcomes in patients with NAFLD. Additionally, increased mortality and liver-related complications are primarily seen in patients with nonalcoholic steatohepatitis (NASH); however, nonalcoholic fatty liver (NAFL) is believed to be benign and non-progressive. Therefore, distinguishing between NASH and NAFL is clinically important. Liver biopsy is the gold standard method for the staging of liver fibrosis and distinguishing between NASH and NAFL. Unfortunately, liver biopsy is an invasive and expensive procedure. Therefore, noninvasive methods, to replace biopsy, are urgently needed for the staging of liver fibrosis and diagnosing NASH. In this review, we discuss the recent studies on magnetic resonance imaging (MRI), including magnetic resonance elastography, proton density fat fraction measurement, and multiparametric MRI (mpMRI) that can be used in the assessment of NASH components such as liver fibrosis, steatosis, and liver injury including inflammation and ballooning. [ABSTRACT FROM AUTHOR]

Background: Patients taking opioids are known to develop opioid-induced constipation (OIC), which reduces their quality of life. The aim of this study is to compare magnesium oxide with naldemedine and determine which is more effective in preventing OIC.Methods: This proof-of-concept, prospective, randomized controlled trial commenced in Japan in March 2018. Initially, a questionnaire-based survey will be conducted targeting adult patients with cancer who concomitantly commenced opioid treatment and OIC prevention treatment. Patients will then be randomly allocated to a magnesium oxide group (500 mg thrice daily) or a naldemedine group (0.2 mg once daily). Each drug will be orally administered for 12 weeks. The primary endpoint is defined as any improvement in scores on the Japanese version of Patient Assessment of Constipation Quality of Life questionnaire (JPAC-QOL) from baseline to 2 weeks of treatment.Discussion: The primary endpoint is change in JPAC-QOL score from baseline to 2 weeks of intervention. The key secondary endpoint will be change in spontaneous bowel movements at 2 and 12 weeks of intervention. This study will determine whether magnesium oxide or naldemedine is more effective for the prevention of OIC.Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000031891. Registered March 25, 2018. [ABSTRACT FROM AUTHOR]

Although microwave ablation (MWA) exhibits a high thermal efficiency, the major limitation of conventional MWA systems is the lack of predictability of the ablation zone size and shape. Therefore, a specific newer generation MWA system, The Emprint™ Ablation System with Thermosphere™ Technology, was designed to create predictable large spherical zones of ablation that are not impacted by varying tissue environments. The time required for ablation with MWA systems is short, and the shape of the necrosis is elliptical with the older systems and spherical with the new system. In addition, because MWA has no heat-sink effect, it can be used to ablate tumors adjacent to major vessels. Although these factors yield a large ablation volume and result in good local control, excessive ablation of liver tissue and unexpected ablation of surrounding organs are possible. Therefore, MWA should be carefully performed. This review highlights the efficacy and complications of MWA performed with conventional systems and the newer generation system in patients with hepatocellular carcinoma (HCC). MWA with the newer generation system seems to be a promising treatment option for large HCCs and secondary hepatic malignancies, with several advantages over other available ablation techniques, including conventional MWA. However, further randomized controlled trials are necessary to fully clarify the benefits and pitfalls of this new system. [ABSTRACT FROM AUTHOR]

Aim: We investigated the characteristics of serum autotaxin (ATX) and its diagnostic performance for liver fibrosis in a large cohort of patients with non‐alcoholic fatty liver disease (NAFLD). Methods: We compared the usefulness of ATX and other fibrosis markers in 307 biopsy‐confirmed NAFLD patients. In addition, in 145 participants with NAFLD, we compared the diagnostic performance of ATX with that of non‐invasive imaging methods (vibration‐controlled transient elastography and magnetic resonance elastography [MRE]). Results: Serum ATX concentration was significantly correlated with fibrosis stage in male and female NAFLD patients. In male patients, the area under the receiver operating characteristic (AUROC) curve values of ATX for the diagnosis of ≥stage 1, ≥stage 2, ≥stage 3, and ≥stage 4 fibrosis were 0.65, 0.75, 0.81, and 0.95, respectively. In female NAFLD participants, the AUROC values were all >0.81. The sensitivity of ATX was highest for the diagnosis of ≥stage 2 and ≥stage 3 fibrosis in both men and women with NAFLD. In the comparison between ATX and non‐invasive imaging methods, the AUROC for MRE was the highest at every stage of fibrosis. Conclusions: Serum ATX concentration is significantly correlated with fibrosis stage in NAFLD patients. The diagnostic accuracy of ATX for liver fibrosis is lower than that of MRE, but the sensitivities of ATX for the diagnosis of ≥stage 2 and ≥stage 3 were highest. We conclude that ATX is useful for the selection of patients requiring further evaluation for liver fibrosis. [ABSTRACT FROM AUTHOR]

Background and Aim: In the condition of high prevalence of non‐alcoholic fatty liver disease (NAFLD), a new diagnostic algorithm to efficiently identify NAFLD patients with significant fibrosis is urgently required. We evaluated the predictive ability of the fibrosis‐4 index (FIB‐4 index) for significant liver fibrosis (F ≥ 2) in a cohort of Japanese patients with NAFLD. Methods: We prospectively calculated the FIB‐4 index in patients who were incidentally diagnosed as fatty liver in medical checkups and then conducted liver stiffness measurement by vibration‐controlled transient elastography (VCTE) only in patients in whom the FIB‐4 index was more than the low cut‐off index (> 1.45). Results: Of the 5929 people who underwent medical checkups, a total of 1374 people were identified as having fatty liver. Among these, we performed VCTE in 106 patients in whom the FIB‐4 index was higher than 1.45. The distribution of the fibrosis stage as estimated by VCTE in the patients was as follows: F0, 52.8%; F1, 10.3%; F2, 21.6%; F3, 11.3%; and F4, 3.7%. The positive predictive value of the FIB‐4 index for detecting NAFLD with significant fibrosis was 36.6%. The minimum value of the FIB‐4 index was constant for each estimated fibrosis stage. Conclusions: This is the first prospective study to evaluate the usefulness of the FIB‐4 index as the first step to screen NAFLD patients with significant fibrosis. In Japan, addition of one further step that combined with the FIB‐4 index is necessary to meaningfully reduce the number of patients needing liver stiffness measurement or liver biopsy. [ABSTRACT FROM AUTHOR]

Aim: Although liver biopsy is the gold standard for the diagnosis and staging of non‐alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10‐year changes in liver stiffness measurements (LSM) utilizing vibration‐controlled transient elastography in NAFLD patients. Methods: From January 2006 to September 2007, LSM was carried out for 97 biopsy‐proven NAFLD patients. Of these, 34 patients underwent 10‐year LSM reassessments (14 of them with paired biopsies). Results: We evaluated the changes in the fibrosis stage as estimated using LSM (FS‐LSM). Over a 10‐year period, 32.4% had FS‐LSM progression, 50% had static disease, and 17.6% had FS‐LSM improvement. From among the initially diagnosed non‐alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS‐LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). Conclusions: Vibration‐controlled transient elastography is likely to become a more clinically important tool for the long‐term monitoring of NAFLD patients. [ABSTRACT FROM AUTHOR]

Working memory (WM) helps maintain information during a variety of cognitive activities in scholastic and social situations. This study focused on a social aspect of WM, specifically, how it maintains information related to people. We investigated person-based organisation of information across four experiments using the reading span task (RST). Person information (i.e., an occupational title) was provided with sentences manipulated across conditions. In Experiment 1, consistent with the assumption that person-based organisation exists in WM, participants performed better when they could easily organise target items in a person-based manner (person-based organisation) than when they were prevented from using such information. Experiments 2 and 3 investigated the process of person-based organisation using alphabetical letters as targets (unlike words in Experiment 1), which prevented possible semantic associations between person information and target items. Experiment 2 replicated Experiment 1, suggesting that contextual retrieval is critical in person-based organisation. Experiment 3 showed the person-based organisation effect even after controlling for the difficulty of the process component in the RST. The results of Experiments 2 and 3 suggest that person information could serve as contextual retrieval cues in WM. Experiment 4, which did not show the organisation effect based on information about an object (i.e., a fruit name), suggests along with Experiments 1 to 3 that the observed organisation effect in Experiments 1 to 3 was specific to person information. In addition to showing the enhanced WM performance by person-based organisation, we have suggested contextual cue-dependent retrieval as the underlying cognitive process. [ABSTRACT FROM AUTHOR]

The Hebb repetition effect is a phenomenon in which a repeated presentation of the same list increases the performance in immediate serial recall. This provided the theoretical basis for a core assumption of the Atkinson and Shiffrin model regarding information transfer from short-term memory to long-term memory. The Hebb repetition effect was originally reported for the verbal domain, but subsequent studies found similar phenomena using visuospatial paradigms, for example, in serial-order memory for dot locations. The present study examined in two experiments the effects of presentation timing of nine spatial locations on Hebb repetition learning. In Experiment 1, the Hebb repetition effects were observed for spatial locations with constant timing presentation as well as temporal grouping presentation. In the latter condition, all lists were presented with the same temporal structure, that is, temporal pauses were inserted after the third and sixth serial positions. This manipulation led to a better recall performance in comparison with the constant presentation, but did not interact with the repetition. In Experiment 2, the Hebb list was presented with a different temporal structure in every repetition in the random-grouping condition. Although this manipulation is known to eliminate or weaken the Hebb effect in the verbal domain, we observed stable repetition effects in this experiment. This suggests that there might be some domain-specific mechanisms in Hebb repetition learning. These results may facilitate the development of theories of the relationship between short-term and long-term memory. [ABSTRACT FROM AUTHOR]

Joint cognition refers to the mental systems that support group performance when carrying out a shared, or jointly owned task. We focused here on understanding the social configurations that underpin key phenomena in joint cognition, in particular, whether individual cognition in task-sharing environments is mostly shaped by social factors or not. To this end, we investigated, first and mainly, whether human presence is necessary for the creation of joint performance; second and separately, whether prior experience of task sharing has an adaptive influence on subsequent individual choices; and third and additionally, whether individual differences in a social trait mediate joint performance. We describe an experiment in which participants combined with another human or a computer as they attempted to generate a paired sequence that was as random as possible. First, we found little difference in joint performance with regard to whether a human or a computer was the co-participant, except for immediate repetitive response. Second, we found evidence for choice adaptation, but only under the lower time pressure. Third, we replicated previous research in which no systematic link was established between social desirability and joint performance. We conclude that joint cognition phenomena may be rooted primarily in turn-taking configurations rather than in social dynamics per se. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the role and nature of phonology in silent reading of Japanese sentences. An experiment was conducted using a Japanese sentence acceptability judgment task. One important finding was that participants more rapidly rejected homophonic sentences in which one two-kanji compound word was replaced by its homophone word than non-homophonic sentences. In the latter, the word was replaced by a non-homophone spelling control; that is, we observed a homophone advantage. Participants were able to identify the correct word easily through foil's homophonic mate. This indicated that activated phonology played a role in the Japanese sentence acceptability judgment task and it contributed to the error detection/recovery process. Another important finding was that the homophone facilitation effect remained under articulatory suppression. It confirmed that phonology was activated at an early stage as abstract, non-articulatory phonology. [ABSTRACT FROM AUTHOR]

The current study investigated the ways long-term memory contributes to short-term serial order memory of novel verbal sequences, focusing on long-term knowledge of bi-element frequency, that is, co-occurrence frequency of two consecutive elements in a linguistic environment. Participants performed two types of immediate serial recall of nine-element (nine-mora) sequences: low bi-mora frequency sequences where all eight associations between the nine morae were low frequency, and mixed bi-mora frequency sequences, with high-frequency associations for six of the eight bi-morae. Experiment 1 confirmed the bi-directional bi-mora frequency effect, meaning better recall performance for morae having high-frequency association with either the preceding mora (forward association) or the following mora (backward association). In Experiment 2, two temporal pauses were inserted in each list to disrupt high-frequency associations with the preceding mora or the following mora. The results showed that the bi-element frequency effect diminished when the high-frequency backward association was disrupted but the effect remained when the high-frequency forward association was disrupted. We discuss possible mechanisms underlying the asymmetric influence of temporal pauses on interactions between short-term memory and linguistic long-term memory. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to assess the efficacy of a new microwave ablation (MWA) system, the Emprint Ablation System, for the ablation of unresectable large liver tumors (≥ 30 mm). Methods: Twenty‐one hepatic tumors (mean diameter, 34.7 mm) from 21 patients who underwent percutaneous MWA were included in this cross‐sectional study. A volume analyzer based on computed tomography imaging was used for all patients within the month before and month after the procedure to evaluate the shape and volume of ablation zones. In addition, computed tomography imaging was performed again 3 months after the procedure to evaluate the presence of residual tumors and local recurrence. Results: Mean ablation time was 11.3 min, and mean overall procedure time was 33.4 min. An ablated adrenal gland‐induced Takotsubo (stress) cardiomyopathy occurred immediately after MWA as a major complication in one patient. Roundness index A, B, and C presented a mean value of 0.94, 0.94, and 1.01, respectively (all values near 1 is a perfect sphere), indicating that a spherical ablation zone was achieved. The mean ablation volume was larger than the volume of tumors (24.5 vs 41.7 cm3). Residual tumors were confirmed in only 4.8% of tumors after a single ablation session. There was no local recurrence. Conclusions: In our experience, the new MWA system provides an effective treatment option for unresectable large liver tumors. However, to ablate the liver tumors safely, it is necessary to consider the surrounding organs, such as the adrenal glands. [ABSTRACT FROM AUTHOR]

Background and Aims: The Baveno VI criteria enable non‐invasive screening for esophageal varices. However, these criteria were established based on studies examining a large proportion of patients with viral hepatitis and relatively few patients with non‐alcoholic fatty liver disease (NAFLD). Furthermore, because vibration‐controlled transient elastography (VCTE) has a high incidence of measurement error, improved criteria are needed. We aimed to develop criteria based on magnetic resonance elastography (MRE) even among patients with NAFLD. Methods: We performed a cross‐sectional analysis of patients who had undergone MRE and/or VCTE as well as an esophagogastroduodenoscopy. The patients were classified as having either a low risk or a high risk of varices. The optimal cut‐offs for ruling out esophageal varices were calculated for the MRE and VCTE liver stiffness measurement (LSM), the platelet count in an estimation cohort, and the cut‐offs were then evaluated using validation cohorts composed of patients who had undergone only MRE or VCTE. Results: The study included 627 patients (39% with NAFLD). The optimal cut‐off values for the MRE‐LSM and the platelet count were 4.2 kPa and 18.0 × 104/μL, respectively. An MRE‐LSM of 4.2 kPa plus a platelet count of 18.0 × 104/μL had a negative predictive value of 1.00 for both low‐risk plus high‐risk varices as well as for high‐risk varices in a validation cohort, enabling the presence of varices to be ruled out. Conclusions: Magnetic resonance elastography might enable a safer avoidance of screening endoscopy, with a smaller measurement error, among patient populations with a high prevalence of NAFLD. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The fibrosis stage of liver is associated with the long‐term outcomes in patients with non‐alcoholic fatty liver disease (NAFLD). However, significant fibrosis, defined as fibrosis stages 2–4, is associated with an elevated risk of progression to severe liver disease; there have been scant reports about diagnosing significant fibrosis. We compare the noninvasive method and aim to identify appropriate liver fibrosis markers for detecting significant fibrosis in NAFLD patients. Methods: We compared the usefulness of liver fibrosis markers (Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein [WFA+‐M2BP], type 4 collagen 7S, etc.), clinical scoring systems, and liver stiffness measurement obtained using vibration‐controlled transient elastography and magnetic resonance imaging‐based magnetic resonance elastography in the same individuals and identified the most appropriate noninvasive method for detecting significant fibrosis in 165 patients with liver biopsy‐diagnosed NAFLD. Results: The area under the receiver operating characteristic curve based on the serum cutoff index values of WFA+‐M2BP/the serum levels of type IV collagen 7S for the diagnosis of significant fibrosis was 0.832 (95% confidence interval: 0.771–0.894)/0.837 (95% confidence interval: 0.778–0.898). “WFA+‐M2BP (cutoff index) ≥ 0.83 or type IV collagen 7S ≥ 5.2 ng/mL” showed a high sensitivity (91.4%) and negative predictive value (87.9%) for the diagnosis of significant fibrosis. Conclusions: We showed that serum WFA+‐M2BP or type IV collagen 7S levels serve as useful independent markers for detecting significant fibrosis and that use of both WFA+‐M2BP and type IV collagen 7S together increased the sensitivity and negative predictive value for the diagnosis of liver fibrosis. These results need to be validated in larger populations from multiple clinical centers. [ABSTRACT FROM AUTHOR]

Aim: The progression of non‐alcoholic fatty liver disease (NAFLD) is affected by epigenetics. We undertook co‐methylation and differentially methylated region (DMR) analyses to identify the genomic region that is under epigenetic regulation during NAFLD progression. Methods: We collected liver biopsy specimens from 60 Japanese patients with NAFLD and classified these into mild (fibrosis stages 0–2) or advanced (fibrosis stages 3–4) NAFLD. We carried out a genome‐wide DNA methylation analysis and identified the differentially methylated CpGs between mild and advanced NAFLD. Differentially methylated regions with multiple consecutive differentially methylated CpGs between mild and advanced NAFLD were extracted. Results: Co‐methylation analysis showed that individual differentially methylated CpG sites were clustered into three modules. The CpG sites clustered in one module were hypomethylated in advanced NAFLD and their annotated genes were enriched for “immune system” function. The CpG sites in another module were hypermethylated and their annotated genes were enriched for “mitochondria” or “lipid particle”, and “lipid metabolism” or “oxidoreductase activity”. Hypomethylated DMRs included tumorigenesis‐related genes (FGFR2, PTGFRN, and ZBTB38), the expressions of which are upregulated in advanced NAFLD. Tumor suppressor MGMT had two DMRs and was downregulated. Conversely, FBLIM1 and CYR61, encoding proteins that reduce cell proliferation, showed hypomethylated DMRs and were upregulated. Expression of the antioxidant gene NQO1 was upregulated, with a hypomethylated DMR. The DMR containing cancer‐related MIR21 was hypomethylated in advanced NAFLD. Conclusions: Co‐methylation and DMR analyses suggest that the NAFLD liver undergoes mitochondrial dysfunction, decreased lipid metabolism, and impaired oxidoreductase activity, and acquires tumorigenic potential at the epigenetic level. [ABSTRACT FROM AUTHOR]