Total Synthesis of Euphorbialoid A.

Euphorbialoid A () belongs to the rare diterpenoid family of premyrsinanes and exhibits potent anti-inflammatory effects. The 5/7/6/3-membered carbocycle (ABCD-ring) of contains 11 contiguous stereocenters and seven oxygen-containing functional groups. Moreover, four of the six hydroxy groups of are concentrated in the southern sector and flanked by four structurally different acyl groups.

Construction of the Akuammiline Alkaloid Core Structure via Stereoselective E-Ring Formation.

Construction of the core structure of akuammiline alkaloids with three-dimensional cage-like structures for their diversity-oriented synthesis was investigated. Extensive exploration centered around the introduction of nitrogen functional groups and construction of the E-ring in an intramolecular or intermolecular manner revealed that a Claisen rearrangement approach involving intramolecular amination provided a common precursor, potentially facilitating divergent access to various types of akuammiline alkaloids.

Comparison of blood and urine concentrations of equol by LC‒MS/MS method and factors associated with equol production in 466 Japanese men and women.

Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the producers. We aimed to examine the equol producer status in both men and women, and investigate the relationships among the serum and urinary isoflavones as well as to other biomedical parameters.

Comparison of the five different definitions of equol producers: The relationship between blood and urine equol concentrations and blood parameters in 466 healthy men and women.

Background And Aims: No studies have compared various definitions of "equol producers" until now. Therefore, we aimed to explore the accuracy of five different definitions of equol producers (EQP) and their associations with health benefits.

Methods: This is a cross-sectional study of 466 healthy Japanese men and women aged between 22 and 88 years.

Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody-drug conjugate (ADC), a bromodomain and extra-terminal (BET) protein degrader named EBET. We select CEACAM6/CD66c as an ADC target and developed an antibody, #84.

Gold(I)-Catalyzed Cascade Cyclization of Alkynyl Indoles for the Stereoselective Construction of the Quaternary Carbon Center of Akuammiline Alkaloids.

A gold-catalyzed cyclization reaction of alkynyl-indoles has been developed for the stereoselective construction of the quaternary carbon center of fused indolines. This reaction efficiently produces fused indolines via diastereoselective 6- cyclization controlled by a bulky TIPS group, followed by nucleophilic attack of the carboxy group on the resulting imine. The lactone moiety of the fused indoline can be reductively cleaved to produce a tricyclic indoline, which could be useful for the synthesis of akuammiline alkaloids.

Identification of circulating tumour DNA (ctDNA) from the liquid biopsy results: Findings from an observational cohort study.

Liquid biopsies can be a rapid, cost-effective and non-invasive alternative to tumour biopsies for detecting genetic mutations in somatic tumours. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their distribution in a small study cohort.

Brain atrophy in middle age using magnetic resonance imaging scans from Japan's health screening programme.

Although health screening plays a key role in the management of chronic diseases associated with lifestyle choices, brain health is not generally monitored, remaining a black box prior to the manifestation of clinical symptoms. Japan is unique in this regard, as brain MRI scans have been widely performed for more than two decades as part of Brain Dock, a comprehensive health screening programme. A vast number of stored images (well over a million) of longitudinal scans and extensive health data are available, offering a valuable resource for investigating the prevalence of various types of brain-related health conditions occurring throughout adulthood.

Prediction model of Graves' disease in general clinical practice based on complete blood count and biochemistry profile.

Although untreated Graves' disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease.

Pilot study of WT1 peptide-pulsed dendritic cell vaccination with docetaxel in esophageal cancer.

In the present study, the immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell (DC) vaccination combined with docetaxel (DCDOC) in advanced esophageal cancer patients who had already received first-line chemotherapy was investigated. Ten HLA-A*2402 patients were treated with docetaxel (50 mg/m) on day 1 and WT1 peptide-pulsed DC vaccination (1×10 cells) on days 15 and 22 (repeated every 4 weeks for 3 cycles). The delayed-type hypersensitivity skin test, HLA tetramer assay and interferon-γ enzyme-linked immunospot (ELISPOT) assay were used to evaluate the induction of a WT1-specific immune response.

Detection rates and sites of unruptured intracranial aneurysms according to sex and age: an analysis of MR angiography-based brain examinations of 4070 healthy Japanese adults.

Objectivie: The purpose of this study was to evaluate the detection rate and occurrence site according to patient sex and age of unruptured intracranial aneurysms detected through MRI and MR angiography (MRA).

Methods: A total of 4070 healthy adults 22 years or older (mean age [± SD] 50.6 ± 11.

Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma.

In this study, we aimed to evaluate the feasibility and efficacy of peptide-pulsed dendritic cell (DC) vaccine in combination with carboplatin and paclitaxel chemotherapy (DCCP) for patients with stage IV melanoma previously treated with dacarbazine-containing regimen. Six HLA-A24 and 3 HLA-A02 patients were treated with carboplatin (area under the curve 5) and paclitaxel (175 mg/m) on day 1 and DCs (2×10 cells) pulsed with Wilms tumor gene 1 (WT1), gp100, tyrosinase, and either MAGE-A3 (for HLA-A24) or MAGE-A2 (for HLA-A02) peptides on days 8 and 22 in 28-day cycle for up to three cycles. DCCP was well tolerated, and median progression-free survival and median overall survival were 2.

Development of system using beam's eye view images to measure respiratory motion tracking errors in image-guided robotic radiosurgery system.

The accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS) is considered to be patient-dependent because the SRTS relies on an individual correlation between the internal tumor position (ITP) and the external marker position (EMP), as well as a prediction method to compensate for the delay incurred to adjust the position of the linear accelerator (linac). We aimed to develop a system for obtaining pretreatment statistical measurements of the SRTS tracking error by using beam's eye view (BEV) images, to enable the prediction of the patient-specific accuracy. The respiratory motion data for the ITP and the EMP were derived from cine MR images obtained from 23 patients.

Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer.

This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) ) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors.

Effect of residual patient motion on dose distribution during image-guided robotic radiosurgery for skull tracking based on log file analysis.

Purpose: The present study aimed to assess the effect of residual patient motion on dose distribution during intracranial image-guided robotic radiosurgery by analyzing the system log files.

Materials And Methods: The dosimetric effect was analyzed according to the difference between the original and estimated dose distributions, including targeting error, caused by residual patient motion between two successive image acquisitions. One hundred twenty-eight treatments were analyzed.

Manganese superoxide dismutase polymorphism affects the oxidized low-density lipoprotein-induced apoptosis of macrophages and coronary artery disease.

Aims: Oxidative damage promotes atherosclerosis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme localized in mitochondria. We investigated the associations of the MnSOD polymorphism (valine-to-alanine in the mitochondrial-targeting domain) with its activity in leukocytes, with macrophage apoptosis by oxidized low-density lipoprotein (oxLDL), and with coronary artery disease (CAD).

Primary cardiac angiosarcoma: presenting with cardiac tamponade followed by cerebral hemorrhage with brain metastases.

A 49-year-old man presented with palpitation and shortness of breath. He was seen to have a massive pleural and pericardial effusion on radiography and echocardiography. Computed tomography (CT) scanning showed that cardiac tumors arose from the right atrium with epicardial and endocardial extension.

Compartment syndrome of bilateral lower extremities following laparoscopic surgery of rectal cancer in lithotomy position: report of a case.

A 67-year-old man underwent laparoscopic surgery for rectal cancer in the lithotomy position. After surgery he complained of bilateral lower limb pain, swollen legs, and sensory disturbance. The serum creatine kinase value was 46 662 U/l.