we read with interest the paper by Wellhöner et al. (1) about the effect of eradication of hepatitis C virus (HCV) infection on the gut microbiota. The Authors report that sustained virological response (SVR) at 24/48 weeks after hepatitis C virus (HCV) treatment does not lead to statistically significant changes in the gut microbiota of cirrhotic patients, but only in those with chronic hepatitis. Unfortunately, the Authors do not state the number of these two subgroups.Opioids are potent analgesics used to manage pain in both young and old, but the increased use in the pregnant population has significant individual and societal implications. Infants dependent on opioids, either through maternal or iatrogenic exposure, undergo neonatal opioid withdrawal syndrome (NOWS), where they may experience withdrawal symptoms ranging from mild to severe. We present a detailed and original review of NOWS caused by maternal opioid exposure (mNOWS) and iatrogenic opioid intake (iNOWS). While these two entities have been assessed entirely separately, recognition and treatment of the clinical manifestations of NOWS overlap. Neonatal risk factors such as age, genetic predisposition, drug type, and clinical factors like type of opioid, cumulative dose of opioid exposure, and disease status affect the incidence of both mNOWS and iNOWS, as well as their severity. Recognition of withdrawal is dependent on clinical assessment of symptoms, and the use of clinical assessment tools designed to determine the need for pharmacotherapy. Treatment of NOWS relies on a combination of non-pharmacological therapies and pharmacological options. Long-term consequences of opioids and NOWS continue to generate controversy, with some evidence of anatomic brain changes, but conflicting animal and human clinical evidence of significant cognitive or behavioral impacts on school-age children. We highlight the current knowledge on clinically relevant recognition, treatment, and consequences of NOWS, and identify new advances in clinical management of the neonate. This review brings a unique clinical perspective and critically analyzes gaps between the clinical problem and our preclinical understanding of NOWS.Knee effusion can be detected by physical examination, ultrasound and MRI, but the utility of each test is unclear. This study aimed to analyze the diagnostic value of physical examination and ultrasound for knee effusion. A systematic literature search of electronic databases was completed. Bivariate mixed-effects regression modelling was used to estimate sensitivity, specificity and diagnostic odds ratio of physical examination and ultrasound diagnosis of knee effusion. Sensitivity of ultrasound diagnosis of knee effusion was higher than the bulge sign and patellar tap, leading to improved positive and negative predictive values.KRAS is the most frequently mutated in ovarian endometriosis. However, it is unclear whether the KRAS mutant allele's mRNA is expressed and plays a biological role in ovarian endometriosis. Here, we performed mutation-specific RNA in situ hybridization to evaluate mutant allele expression of KRAS p.G12V, the most frequently detected mutation in ovarian endometriosis in our previous study, in formalin-fixed paraffin-embedded tissue (FFPE) samples of ovarian endometriosis, cancer cell lines, and ovarian cancers. First, we verified that mutant or wild-type allele of KRAS were expressed in all 5 cancer cell lines and 9 ovarian cancer cases corresponding to the mutation status. Next, we applied this assay to 26 ovarian endometriosis cases, and observed mutant allele expression of KRAS p.G12V in 10 cases. PLX4032 ic50 Mutant or wild-type allele of KRAS were expressed in line with mutation status in 12 available endometriosis cases for which KRAS gene sequence was determined. Comparison of clinical features between ovarian endometriosis with KRAS p.G12V mutant allele expression and with KRAS wild-type showed that KRAS p.G12V mutant allele expression was significantly associated with inflammation in ovarian endometriosis. Finally, we assessed the spatial distribution of KRAS mutant allele expression in 5 endometriosis cases by performing multiregional sampling. Intratumor heterogeneity of KRAS mutant allele expression was observed in two endometriosis cases, whereas the spatial distribution of KRAS p.G12V mutation signals were diffuse and homogenous in ovarian cancer. In conclusion, evaluation of oncogene mutant expression will be useful for clarifying the biological significance of oncogene mutations in benign tumors. The aim of this study is to evaluate the relationship between the aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ratio and local disease control in patients with head and neck squamous cell carcinomas (HNSCC) treated with radiotherapy/chemoradiotherapy. We calculated the pre-treatment AST/ALT ratio in 670 patients with HNSCC treated with radiotherapy (n= 309, 46.1%) or chemoradiotherapy (n= 361, 53.9%). Five-year local recurrence-free survival for patients with a low AST/ALT ratio value (n= 529, 79.0%) was 75.0% (95% CI 71.1-78.9), and for patients with a high value (n= 141, 21.0%) it was 53.4% (CI 95 44.4-62.4) (p= 0.0001). In a multivariable analysis, patients with a high ratio had nearly twice the risk of having a local tumor recurrence (HR 1.97, 95% CI 1.42-2.75, p= 0.0001). The AST/ALT ratio was independently associated with the risk of local recurrence in patients with HNSCC treated with radiotherapy or chemoradiotherapy.The AST/ALT ratio was independently associated with the risk of local recurrence in patients with HNSCC treated with radiotherapy or chemoradiotherapy. PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion-defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo. Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case-control follow-up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072-9.613; P=0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133-6.873; P=0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR).