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Abstract Background and aim In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non‐cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non‐cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Deep learning is a powerful tool for neural decoding, broadly applied to systems neuroscience and clinical studies. Interpretable and transparent models that can explain neural decoding for intended behaviors are crucial to identifying essential features of deep learning decoders in brain activity. In this study, we examine the performance of deep learning to classify mouse behavioral states from mesoscopic cortex-wide calcium imaging data. Our convolutional neural network (CNN)-based end-to-end decoder combined with recurrent neural network (RNN) classifies the behavioral states with high accuracy and robustness to individual differences on temporal scales of sub-seconds. Using the CNN-RNN decoder, we identify that the forelimb and hindlimb areas in the somatosensory cortex significantly contribute to behavioral classification. Our findings imply that the end-to-end approach has the potential to be an interpretable deep learning method with unbiased visualization of critical brain regions.

Abstract Background and Aim Hepatocellular carcinoma (HCC) surveillance in low‐risk patients (annual incidence

Purpose The anatomical distribution of perianal warts is associated with patient characteristics such as sexual orientation. The purpose of this study is to confirm this experiential knowledge using a quantitative classification system and analysis and to obtain findings useful for future treatment. Methods From January 2014 to December 2020, 93 patients with perianal warts presented to our hospital. Patients were analyzed for age, sex, lesion site, and recurrence type, among other factors. The lesion site was divided into skin (S) and anal epithelium (anoderm, A), and the number and degree of each were classified into grades 0 to 3. The higher grade between S and A determines its dominant type, such as type S (e.g., S3A1) and type A (e.g., S0A2). Results The average age of the patients was 39.6 years, and the percentage of patients who were not married was 54.8%. In all, 95.8% of patients were positive for low-risk human papillomavirus (HPV). Type S accounted for 80.6%, whereas type A accounted for 9.7%. Type A cases were all male and were all presumed to be men who have sex with men (MSM). This indicates that the determination of type A may be highly specific for MSM. The type at the time of recurrence was the same type at the time of the first surgery in almost all cases. Conclusion In cases of perianal warts, it is useful to analyze the lesion by considering the range and grade separately for daily clinical practice on proctologist.

We conducted a secondary analysis of the data derived from a cross-sectional survey among parents of school-age children in Japan. The present study explored variables associated with parents’ satisfaction with the local parenting environment. Multivariable logistic regression was used by entering parental satisfaction as a dependent variable and basic and parenting-related items as independent variables. A total of 2218 respondents were stratified by self-determined financial circumstances. A higher proportion of respondents stated low satisfaction with the local parenting environment and support schemes among the financially struggling group (50.4%) than among the non-struggling group (33.8%). Among the financially struggling group, the variables significantly associated with low satisfaction were a lack of parenting support (adjusted odds ratio [aOR] = 1.612) and being unable to use after-school children’s clubs (aOR = 1.747). Our exploratory analysis suggests that after-school children’s clubs can be expected to play a role in widening social networks and community connectedness among parents struggling financially. This role should be reflected in municipal welfare policy.

Abstract Background and Aim To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virologic response (SVR). Methods This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α‐fetoprotein, was used as a composite predictive model. Results There were 645 (51.3%) patients in the low‐risk group, 228 (18.1%) in the intermediate‐risk group, and 385 (30.6%) in the high‐risk group based on GES categories. The 12‐, 36‐, and 60‐month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204–2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696–6.036), and albumin (HR, 0.489; 95% CI, 0.288–0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES‐based risk category (P

Abstract Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.

Abstract Background and Aim This study aimed to evaluate the long‐term clinical course of patients achieving a sustained virologic response (SVR) with daclatasvir plus asunaprevir (DCV/ASV) therapy. Methods A total of 911 patients who achieved SVR with DCV/ASV were assessed. To evaluate pretreatment factors contributing to hepatocellular carcinoma (HCC) after SVR, univariate and multivariate analyses were performed in all patients, in those with preexisting HCC, and in those without preexisting HCC. We selected a low‐risk group of HCC cases after SVR. Finally, we evaluated liver function after achieving SVR. Results In multivariable analyses, male sex, older age, patients with a history of HCC treatment, excess alcohol use, lower albumin, and low platelet count remained significant in the overall group; male sex and low albumin remained significant in patients with a history of HCC treatment; and male sex, older age, excess alcohol use, low platelet count, high alpha‐fetoprotein (AFP), and high des‐γ‐carboxy prothrombin (DCP) remained significant in those without a history of HCC treatment. Patients who had not received treatment for HCC, females, those under 70 years of age, and those with platelet count ≥13 (×104/μL), AFP

Abstract Background Solid pseudopapillary neoplasms of the pancreas are rare. Moreover, pancreatoduodenectomy (PD) and postoperative care are not common in pediatric surgery. Herein, we report a case of PD and nonalcoholic fatty liver disease (NAFLD) after PD and present a literature review. Case presentation A 10-year-old girl with a suspected liver tumor was referred to our hospital. Echography, enhanced computed tomography and magnetic resonance imaging showed that the tumor coexisted with the solid and cystic parts of the pancreatic head. Since the patient was a young woman and the imaging findings were consistent with that of pancreatic solid pseudopapillary neoplasms (SPNs), we diagnosed her with pancreatic SPN. Thereafter, PD was performed, and she was discharged 10 days after the operation. Although her postoperative course was mostly uneventful, she experienced few episodes of abdominal pain and diarrhea before hospital discharge. These symptoms subsequently became more frequent and severe. The patient was urgently readmitted to the hospital for watery steatorrhea and lower abdominal colic pain. Her serum aspartate aminotransferase and alanine aminotransferase levels were elevated, and a fatty liver was detected on echography. The patient was diagnosed with steatorrhea, peristaltic pain, and NAFLD after PD. Pancrelipase (containing pancreatic digestive enzymes), antidiarrheal agents, and probiotics were started. Dosage increase of these drugs reduced the defecation frequency and abdominal pain and switched diarrhea to loose stools. However, more lipids in meals or more meals caused diarrhea and abdominal pain. Therefore, the doses of these drugs were further increased, and another antidiarrheal agent, loperamide hydrochloride, was added. Exocrine pancreatic enzymes supplementation and careful follow-up should prevent NAFLD progression after PD. At present, the patient has occasional abdominal pain, but has tangible soft stools once or twice a day. Although echography still shows a mottled fatty liver, her hepatic enzymes are only mildly elevated. Conclusions Pediatric PD is rare, and residual pancreatic function is usually sufficient, unlike in adult cases. However, we experienced a case of NAFLD after PD for a pediatric pancreatic SPN, in which pancreatic enzyme supplementation effectively improved this condition. Further attention must be paid to worsening of NAFLD that can develop nonalcoholic steatohepatitis.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum‐based risk model that could identify patients with low‐risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma‐glutamyl transferase

Abstract Background and Aim The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients. Methods This study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB‐4 index, and α‐fetoprotein, was used as a composite predictive model for HCC development. Results The 1‐, 3‐, and 5‐year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790–3.911), FIB‐4 index >3.25 (HR, 2.891; 95% CI, 1.947–4.293), and α‐fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914–4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P

Abstract Background Inappropriate parental behaviors of mothers toward young children require further study; few epidemiological studies have utilized longitudinal analysis of region-based cohorts. This study examined the frequency of incidence of and improvements in inappropriate parental behaviors of mothers with young children and related factors. Methods Among the mothers who underwent a checkup in Fukushima City in 2017, 586 mothers with data from 4-, 18-, and 42-month-old checkups were included in analysis. In this retrospective cohort study, an anonymous database was created by transcribing and matching health checkup records with questionnaires stored at the city health center. Data were analyzed using chi-square tests and logistic regression analysis, using the SPSS Ver.20.0. Results In 28.5% of mothers, inappropriate parental behaviors were not reported in the 18-month-old data but were reported in the 42-month-old data. In 3.8%, inappropriate parental behaviors were reported in the 18-month-old data but were not reported in the 42-month-old data. The most common inappropriate parental behavior reported was “yelling at the child using emotional words” (18-month-old data, 16.2%; 42-month-old data, 39.5%). Mothers with financial difficulties were 2.19 times (95%CI: 1.13–4.26) more likely to begin inappropriate parental behaviors between 18 and 42 months. Improvements in parental behaviors were significantly higher in mothers under 30 years old (p = 0.03). Conclusions It is necessary to identify mothers with financial difficulties early and to examine how to provide childcare and financial support from a local government at the time of child health checkup.

Abstract Introduction Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. Methods A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. Results The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child–Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5–13). The albumin–bilirubin (ALBI) score ranged from − 3.01 to − 0.45 (median − 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child–Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child–Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10−4 and 2.42 × 10−4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. Conclusion Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. Trial Registration UMIN registration no, 000038587.

Abstract The IKKT matrix model is a promising candidate for a nonperturbative formulation of superstring theory. In this model, spacetime is conjectured to emerge dynamically from the microscopic matrix degrees of freedom in the large-N limit. Indeed in the Lorentzian version, Monte Carlo studies suggested the emergence of (3+1)-dimensional expanding spacetime. Here we study the Euclidean version instead, and investigate an alternative scenario for dynamical compactification of extra dimensions via the spontaneous symmetry breaking (SSB) of 10D rotational symmetry. We perform numerical simulations based on the complex Langevin method (CLM) in order to avoid a severe sign problem. Furthermore, in order to avoid the singular-drift problem in the CLM, we deform the model and determine the SSB pattern as we vary the deformation parameter. From these results, we conclude that the original model has an SO(3) symmetric vacuum, which is consistent with previous results obtained by the Gaussian expansion method (GEM). We also apply the GEM to the deformed matrix model and find consistency with the results obtained by the CLM.

Abstract Background Biliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC). Case presentation A man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm. Conclusions We encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.

Pancreatic arteriovenous malformation (PAVM) is defined as a vascular anomaly with an abnormal anastomosis of the arterial and portal networks within the pancreas. Treatment modalities of PAVM include transarterial embolisation (TAE), irradiation and operation. Most patients treated with TAE alone will experience recurrence, so surgery is the best radical treatment. A female patient was admitted to our institution for the treatment of haematemesis. Examination revealed varices in the oesophagus and stomach, collateral circulation development caused by portal hypertension and PAVM of the pancreas. Surgical treatment was intended to reduce left portal hypertension. In this case, collateral circulation were considered dangerous points for unexpected bleeding. TAE was performed on the splenic artery before surgery to reduce blood flow in the areas with collateral circulation. En bloc resection of retroperitoneal tissue using the surgical procedure of radical antegrade modular pancreatosplenectomy was effective to minimise blood loss.

Background & Aims: We aimed to clarify the features of resistance-associated substitutions (RASs) after failure of multiple interferon (IFN)-free regimens in HCV genotype 1b infections. Methods: A total of 1,193 patients with HCV for whom direct-acting antiviral (DAA) treatment had failed were enrolled from 67 institutions in Japan. The RASs in non-structural protein (NS)3, NS5A, and NS5B were determined by population sequencing. Results: Failure of 1, 2, and 3 regimens was observed in 1,101; 80; and 12 patients, respectively. Among patients with failure of 1 regimen, Y56H and D168V in NS3 were more frequently detected after failure of paritaprevir, whereas D168E was more frequently detected after failure of regimens including asunaprevir. R30H and L31-RAS in NS5A were frequently detected after failure of regimens including daclatasvir. The prevalence of Y93-RAS was high irrespective of the regimen. S282T RAS in NS5B was detected in 3.9% of ledipasvir/sofosbuvir failures. The prevalence of D168-RAS increased significantly according to the number of failed regimens (p

Abstract In recent years the complex Langevin method (CLM) has proven a powerful method in studying statistical systems which suffer from the sign problem. Here we show that it can also be applied to an important problem concerning why we live in four-dimensional spacetime. Our target system is the type IIB matrix model, which is conjectured to be a nonperturbative definition of type IIB superstring theory in ten dimensions. The fermion determinant of the model becomes complex upon Euclideanization, which causes a severe sign problem in its Monte Carlo studies. It is speculated that the phase of the fermion determinant actually induces the spontaneous breaking of the SO(10) rotational symmetry, which has direct consequences on the aforementioned question. In this paper, we apply the CLM to the 6D version of the type IIB matrix model and show clear evidence that the SO(6) symmetry is broken down to SO(3). Our results are consistent with those obtained previously by the Gaussian expansion method.

Abstract In this paper, we study the finite-temperature matrix quantum mechanics with chemical potential term linear in the single trace of U(N) matrices, via Monte Carlo simulation. In the bosonic case, we exhibit the existence of the Gross-Witten-Wadia (GWW) type third-order phase transition. We also extend our studies to the model with the fermionic degrees of freedom employing the non-lattice simulation via Fourier expansion, and explore the possibilities that there is a phase transition between the gapped and ungapped phase both in the absence and presence of the chemical potential term. We make a comparison of the phase diagram between the bosonic and fermionic cases.