Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Background And Objectives: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

Lenvatinib-resistant hepatocellular carcinoma promotes malignant potential of tumor-associated macrophages via exosomal miR-301a-3p.

Background: The interactions between cancer cells and tumor-associated macrophages (TAMs) via microRNAs (miRNAs) play crucial roles in malignant potential and drug resistance. However, it remains unclear how lenvatinib-resistant hepatocellular carcinoma (LR HCC) promotes TAM tumor biology. Here we investigated the crosstalk between LR HCC cells and TAMs for cancer progression and lenvatinib resistance, focusing on an exosomal miRNA.

Assessment of fractal ratio of vessel diameters in coronary bifurcation lesions by angiography and intravascular ultrasound.

Physiological coronary branching at the bifurcation has a constant fractal ratio (FR) of the diameter of the mother vessel to the sum of daughter vessels on quantitative coronary angiography (QCA). We sought to investigate the FR of diseased coronary bifurcations using QCA and intravascular ultrasound (IVUS) and its impact on late lumen loss after percutaneous coronary intervention (PCI). In multicentre prospective studies of the J-REVERSE and 3D OCT Bifurcation Registry, 402 and 109 bifurcations treated with stenting that completed QCAs and IVUS examinations, respectively were analysed.

Effectiveness of directional coronary atherectomy in treating recurrent in-stent restenosis: a case report.

Background: In-stent restenosis (ISR) remains a significant clinical problem. It is estimated that 10-20% of patients who develop a first event of ISR will develop recurrent ISR (R-ISR). However, the pathology of R-ISR remains largely unknown, and recommendations for its optimal management are lacking.

Comparing preprocessing strategies for 3D-Gene microarray data of extracellular vesicle-derived miRNAs.

Background: Extracellular vesicle-derived (EV)-miRNAs have potential to serve as biomarkers for the diagnosis of various diseases. miRNA microarrays are widely used to quantify circulating EV-miRNA levels, and the preprocessing of miRNA microarray data is critical for analytical accuracy and reliability. Thus, although microarray data have been used in various studies, the effects of preprocessing have not been studied for Toray's 3D-Gene chip, a widely used measurement method.

Pancreatoduodenectomy combined with intestinal de-rotation as a complete artery-first approach for inexperienced surgeons.

Background: Recent technical advances have reduced the incidence of intraoperative complications associated with pancreatoduodenectomy (PD). We aimed to determine whether inexperienced surgeons (ISs) would be as successful as experienced surgeons (ESs) when performing the complete artery-first approach using the intestinal de-rotation method of PD.

Methods: Seventy patients who underwent PD using the intestinal de-rotation method in Tokushima University Hospital were enrolled in the present study.

Generation of Highly Functional Hepatocyte-like Organoids from Human Adipose-Derived Mesenchymal Stem Cells Cultured with Endothelial Cells.

Previously, we successfully established a highly functional, three-dimensional hepatocyte-like cell (3D-HLC) model from adipose-derived mesenchymal stem cells (ADSCs) via a three-step differentiation protocol. The aim of the present study was to investigate whether generating hepatocyte-like organoids (H-organoids) by adding endothelial cells further improved the liver-like functionality of 3D-HLCs and to assess H-organoids' immunogenicity properties. Genes representing liver maturation and function were detected by quantitative reverse transcription-PCR analysis.

Effects of green light-emitting diode irradiation on hepatic differentiation of hepatocyte-like cells generated from human adipose-derived mesenchymal cells.

Light-emitting diode (LED) irradiation has been used in the differentiation of mesenchymal stem cells into a variety of cell types. This study investigated the effect of green LED (GLED) irradiation on the differentiation of adipocyte-derived mesenchymal cells into hepatocyte-like cells (HLCs) and the mechanism of its action. HLCs in the hepatocyte maturation phase were irradiated with GLED (520 nm, 21 W/m, 5 min/day for 10 days).

Role of Nrf2 signaling in development of hepatocyte-like cells.

Generation of hepatocytes from human adipose-derived mesenchymal stem cells (hADSCs) could be a promising alternative source of human hepatocytes. However, mechanisms to differentiate hepatocytes from hADSCs are not fully elucidated. We have previously demonstrated that our three-step differentiation protocol with glycogen synthase kinase (GSK) 3 inhibitor was effective to improve hepatocyte functions.

Exercise attenuates polyglutamine-mediated neuromuscular degeneration in a mouse model of spinal and bulbar muscular atrophy.

Background: Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder caused by the expansion of trinucleotide cytosine-adenine-guanine (CAG) repeats, which encodes a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. Recent evidence suggests that, in addition to motor neuron degeneration, defective skeletal muscles are also the primary contributors to the pathogenesis in SBMA. While benefits of physical exercise have been suggested in SBMA, underlying mechanism remains elusive.

Preoperative Weight Loss Program for Hepatocellular Carcinoma Patients with High Body Mass Index in Hepatectomy.

Background: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC).

Methods: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014.

Clinical impact of myosteatosis measured by magnetic resonance imaging on long-term outcomes of hepatocellular carcinoma after radical hepatectomy.

Aims: A variety of factors have been reported to affect long-term outcomes after radical resection of hepatocellular carcinoma (HCC). However, the indicators remain controversial. The purpose of this study was to evaluate the relationship between myosteatosis of the multifidus muscle and long-term outcomes after radical surgery for HCC.

[Preimplantation Genetic Testing for Monogenic Disorders: The Role of Neurologists and Challenges].

Preimplantation genetic testing for monogenic disorders (PGT-M) has been implemented in Japan under a novel definition of severity to reduce the chances of giving birth to a child with an inherited genetic disorder. The redefinition of disease severity is not only about changing definitions and interpretations, but also a matter of potentially expanding the number of diseases covered by PGT-M and the range of clients, which could raise serious human rights-related issues. With the rapid development of therapies for neuromuscular diseases and the possibility of the clinical course of diseases previously considered to be serious becoming progressively becoming milder in the future, the "definition of severity" classification itself, as applied to PGT-M, may become debatable.

Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan.

Background: A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression.

Methods: We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study.

Hematogenous prosthetic knee joint infection with caused by asymptomatic gallbladder abscess: a case report and literature review.

has the ability to form biofilm; therefore, the treatment of prosthetic joint infection involving is often challenging. This report describes the first case of acute hematogenous prosthetic knee joint infection with that occurred as a result of an asymptomatic gallbladder abscess. The patient was a 78-year-old man who underwent bilateral total knee arthroplasty 6 years ago.

Effect of daikenchuto (TU-100) on carcinogenesis in non-alcoholic steatohepatitis.

Background: Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut?liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model.

Methods: Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used.

Impact of pancreatic resection in patients with liver cirrhosis.

Background: Several reports have shown a high mortality rate in patients with liver cirrhosis (LC) who undergo pancreaticoduodenectomy, however, there are few reports on its long-term prognosis.

Methods: Twelve patients with LC who had undergone pancreatic resection were enrolled. To compare clinicopathological variables, 159 non-LC patients who had undergone resection for pancreatic cancer were enrolled.

Impact of L-type amino acid transporter 1 on intrahepatic cholangiocarcinoma.

Background: Amino acid transporters, such as L-type amino acid transporter 1 (LAT1), have an effect on tumor growth, metastasis, and survival of various solid tumors. However, the role of LAT1 in patients with intrahepatic cholangiocarcinoma (IHCC) remains unknown.

Methods: Forty-six patients who had undergone initial hepatic resection for IHCC at Tokushima University Hospital were enrolled in this study.

Short- and long-term outcomes of pancreatectomy in patients with hemodialysis.

Background: Several reports have shown the high mortality rate of pancreatic resection in patients with hemodialysis (HD), however, its long-term outcome remains unclear. In this study, we examined cases of pancreatic resection in patients with HD and conducted a literature review.

Methods: Four patients with HD who underwent pancreatic resection from 2004 to 2019 were enrolled.

Phase II/III Study of Aceneuramic Acid Administration for GNE Myopathy in Japan.

Background: GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. No treatment has been established so far.

Objective: We evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy.

TU-100 Antagonizes the M2 Polarization Phenotype of Macrophages in the Tumor Microenvironment by Suppressing the TLR4/NF-B/STAT3 Axis.

Background/aim: Macrophages are the most abundant immune cells in the tumor stroma, and their polarization states within the tumor microenvironment (TME) exert critical roles in tumorigenesis. TU-100 (Daikenchuto) is a commonly prescribed Japanese herbal medicine that has shown anti-cancer effects by regulating cancer-associated fibroblasts (CAFs) in the TME. However, its effects on tumor-associated macrophages (TAMs) remain unclear.