Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.

Introduction: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.

Case Presentation: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years.

Risk Factors for Frequent Infections in Patients With Extremely Severe Motor and Intellectual Disabilities.

Background: At our institution, patients of all ages with extremely severe motor and intellectual disabilities (ESMID) receive comprehensive management similar to intensive care for "extremely ill patients." Some patients with ESMID develop frequent infections that are difficult to manage. The purpose of this study was to identify risk factors for frequent infections in these patients.

Knowledge and Awareness of Human Papillomavirus Vaccination and Cervical Cancer among Men and Women in Japan: A Questionnaire Survey.

Background: In many advanced countries other than Japan, the incidence and mortality rates of cervical cancer, which is mainly caused by the human papillomavirus (HPV) infection, are decreasing probably due to the high rate of HPV vaccination and cervical cancer screening. In Japan, these rates are on the rise owing to the stagnation of vaccination and low screening rate. To improve these situations, active promotion of HPV vaccination and screening is required.

Recent topics and advanced therapies in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the inability of phagocytes to produce reactive oxygen species (ROS) owing to a defect in any of the five components (CYBB/gp91phox, CYBA/p22phox, NCF1/p47phox, NCF2/p67phox, and NCF4/p40phox) and a concomitant regulatory component of Rac1/2 and CYBC1/Eros of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Patients with CGD are at an increased risk of life-threatening infections caused by catalase-positive bacteria and fungi and of inflammatory complications such as CGD colitis. Antimicrobial and azole antifungal prophylaxes have considerably reduced the incidence and severity of bacterial and improved fungal infections and overall survival.

Volumetric computed tomography analysis for gastroduodenal and pancreaticoduodenal artery aneurysm formation: A retrospective single-center study.

Gastroduodenal artery aneurysms (GDAA) and pancreaticoduodenal artery aneurysms (PDAA) are rare, have high rupture risks, and are located in the arcade between the celiac artery and the superior mesenteric artery. Pancreaticoduodenal artery aneurysms are associated with celiac artery stenosis, and it is hypothesized that these celiac lesions might contribute to the formation of aneurysms. In contrast, a few studies have reported an association between a gastroduodenal artery aneurysm and celiac lesions.

Motion analysis of suturing technique with Leap Motion Controller. Proof-of-concept.

Purpose: Leap Motion Controller is a device that can capture hand gestures and reproduce these as data comprising several parametric elements. We analyzed surgical suture motion using this device and investigated the optical methodology for clinical applications.

Methods: We recruited medical students and residents (novice group) and vascular surgeons (specialist group).

Haemosuccus Pancreaticus Caused by Splenic Artery Aneurysm Derived from Isolated Spontaneous Coeliac Artery Dissection: Two Case Reports.

Objective: Two cases of haemosuccus pancreaticus (HP), a rare cause of gastrointestinal bleeding caused by splenic artery aneurysm derived from isolated spontaneous coeliac artery dissection (ISCAD), are reported.

Case Report: The first case was a 62-year-old man with a history of hypertension who presented with abdominal pain and melaena. Laboratory tests indicated slight anaemia and a high serum amylase level.

Sac enlargement due to perigraft seroma and back-bleeding from the remnant wall 11 years after open surgical repair of an infected abdominal aortic aneurysm.

We describe a case of sac enlargement that occurred 11 years after emergent open surgical repair of an infected abdominal aortic aneurysm. The diameter of the sac covering the Dacron graft had gradually expanded to 80 mm, and the flow of contrast medium into the sac was suspected. Elective surgery revealed a perigraft seroma and back-bleeding from the remnant wall.

Specific Features of Patients Under 40 Years Old With Small-to-Medium-Sized Arterial Deterioration.

Background: Arterial deterioration is mostly caused by atherosclerosis, which progresses with age. However, we have observed serious backgrounds or etiologies in younger patients with non-atherosclerotic diseases and deterioration of small-to-medium-sized arterial lesions. Therefore, we aimed to identify the specific features of patients aged <40 years with deterioration of small-to-medium-sized arteries.

Treatment with Polyethylene Glycol-Conjugated Fungal D-Amino Acid Oxidase Reduces Lung Inflammation in a Mouse Model of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency wherein phagocytes are unable to produce reactive oxygen species (ROS) owing to a defect in the nicotinamide adenine dinucleotide phosphate oxidase (NADPH) complex. Patients with CGD experience bacterial and fungal infections and excessive inflammatory disorders. Bone marrow transplantation and gene therapy are theoretically curative; however, residual pathogenic components cause inflammation and/or organic damage in patients.

Ten-Hour Simulation Training Improved the Suturing Performance of Medical Students.

Purpose: We evaluated the effectiveness of an original simulation training system in improving the suturing performance of medical students using a previously developed web application for scoring suturing performance.

Methods: Medical students were recruited for this study and trained on vascular graft anastomosis. Prosthetic grafts were anastomosed and evaluated after orientation, and after 1 hr and 10 hr after training.

Sick Sinus Syndrome Mimicking Autonomic Dysfunction of Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is recognized as the second most common form of dementia in aged people. It is well known that patients with DLB often develop various autonomic symptoms. Here, we present a case in which there was sick sinus syndrome mimicking the DLB-related autonomic dysfunctions.

Consistency between patients and families in recognizing cancer chemotherapy side effects: A questionnaire survey.

Background: Although the side effects of cancer chemotherapy impair a patient's quality of life, family members' awareness of side effects may relieve patient anxiety and distress.

Aim: We investigated whether patients and their families were consistent in recognizing the occurrence and severity of symptomatic side effects of chemotherapy treatment for cancer.

Methods And Results: This was a prospective observational study.

High aneurysm wall enhancement values are associated with late sac shrinkage after endovascular repair of abdominal aortic aneurysms.

To analyze the correlation between aneurysm wall enhancement (AWE) values and early and late sac shrinkage after endovascular aneurysm repair (EVAR).We retrospectively analyzed 28 patients who underwent EVAR for abdominal aortic aneurysms (AAA) using a bifurcated main body stent graft. The value of AWE in the slice of the maximum AAA diameter was measured using a volumetric analysis of computed tomography images.

E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling.

The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli ()-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of mice, in which mutation of activates the Wnt/β-catenin signaling pathway.

De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms.

The ubiquitin-proteasome system is the principal system for protein degradation mediated by ubiquitination and is involved in various cellular processes. Cullin-RING ligases (CRL) are one class of E3 ubiquitin ligases that mediate polyubiquitination of specific target proteins, leading to decomposition of the substrate. Cullin 3 (CUL3) is a member of the Cullin family proteins, which act as scaffolds of CRL.

West Syndrome in an Infant With Vitamin B12 Deficiency Born to Autoantibodies Positive Mother.

Infantile vitamin B12 deficiency, a rare nutritional disorder in developed countries, is characterized by megaloblastic anemia and non-specific symptoms, including failure to thrive, hypotonia, and seizure. Symptoms usually develop at 6 months of age. Exclusively breast-fed infants of vegan-diet mothers are particularly at risk.

Feature-based guidance of attention during post-saccadic selection.

Current models of trans-saccadic perception propose that, after a saccade, the saccade target object must be localized among objects near the landing position. However, the nature of the attentional mechanisms supporting this process is currently under debate. In the present study, we tested whether surface properties of the saccade target object automatically bias post-saccadic selection using a variant of the visual search task.

Instantaneous measurement of high-power millimeter-wave beam for 28 GHz gyrotron.

An instantaneous measurement system of high-power millimeter-wave was proposed and demonstrated with a 28 GHz gyrotron at the Plasma Research Center, University of Tsukuba. The high-power detector consists of an attenuator and a linear polarized microstrip antenna with an F-class load rectifier, which is a commonly used system for radio-frequency wireless power transmission. The detector obtained the power distribution of the gyrotron output beam which showed good agreement with the infrared camera image.

Genetic determinants and an epistasis of and HLA-B*52 in Takayasu arteritis.

Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK.

Concomitant carotid endarterectomy and aortic valve replacement in a patient with high risk of perioperative stroke.

Surgical strategy for significant carotid artery stenosis complicated with severe aortic valve stenosis is still controversial. Herein, we report a case of 80-year-old female in whom 78% stenosis by the NASCET criteria in left internal carotid artery was pointed out during preoperative checkup for symptomatic severe aortic stenosis. Carotid endarterectomy was done concomitantly with aortic valve replacement.