Water-Compatible Staudinger-Diels-Alder Ligation.

The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Proline enhances the hepatic induction of lipogenic gene expression in male hepatic fasn reporter mice.

Hepatic de novo lipogenesis (DNL) is increased by both carbohydrate intake and protein consumption. In hepatic fat synthesis, a key role is played by the induction of the hepatic expression of lipogenic genes, including Fasn, Scd1, and Srebf1. Regarding carbohydrate intake, increased blood glucose and insulin levels promote the expression of hepatic lipogenic genes.

Incidence and Prognosis of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement for Bicuspid Aortic Stenosis.

Background: Evidence regarding the incidence of prosthesis-patient mismatch (PPM) and long-term mortality after transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS) is scarce.

Objectives: This study sought to assess the incidence and prognostic impact of PPM after TAVR for bicuspid AS compared with that for tricuspid AS.

Methods: In total, 7,393 patients who underwent TAVR were prospectively enrolled in the OCEAN-TAVI (Optimized Catheter Valvular Intervention Transcatheter Aortic Valve Implantation) registry, an ongoing Japanese, multicenter registry.

Petals Ameliorate Depressive-like Symptom and Cognitive Deficit in Unpredictable Chronic Mild Stress Mouse Model.

Chronic stress exposure has been widely recognized as a significant contributor to numerous central nervous system (CNS) disorders, leading to debilitating behavioral changes such as anxiety, depression, and cognitive impairments. The prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress disrupts the neuroendocrine balance and has detrimental effects on neuronal function and survival. () Gaertn.

Ligand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin.

Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since -KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among -KO, -R270L/H301Q, and wild-type (WT) rats.

Efficacy and safety of indocyanine green-fluorescence imaging guided liver resection: a single-arm prospective cohort study.

Purpose: This study aimed to evaluate the efficacy of indocyanine green (ICG)-fluorescence imaging for the identification of hepatic boundaries during liver resection and its advantages in surgical outcomes over conventional methods.

Methods: This prospective, exploratory, single-arm clinical trial included 47 patients with liver tumors who underwent liver resection using ICG-fluorescence imaging (ICG-LR) between 2019 and 2020. The primary outcome measure was the successful identification of hepatic boundaries during liver resection, from the perspective of both the hepatic surface and intrahepatic boundary, using ICG-fluorescence imaging.

Quadrant, necrosis, and infection criteria for the risk stratification of walled-off necrosis: external validation using multi-institutional data.

Background And Aims: Endoscopic ultrasound-guided peripancreatic fluid drainage (EUS-PFD) with on-demand endoscopic necrosectomy, increasingly utilized to manage walled-off necrosis (WON), is associated with substantial morbidity and mortality. This multicenter study aimed to externally validate recently developed quadrant (an abdominal quadrant distribution), necrosis, and infection (QNI) criteria for risk stratification in this setting.

Methods: Of 423 patients with pancreatic fluid collections treated in a large multi-institutional cohort between 2010 and 2020, 212 with available preprocedural computed tomography images were included.

Evaluation of gravity effect on liver and spleen volumes using multiposture MRI.

Liver and spleen volume measurements are important for early detection and monitoring of liver disease. However, alterations in liver and spleen volumes with postural changes, i.e.

The most important prognostic factors for predicting major adverse cardiovascular, cerebrovascular, and renal events during 5-year follow-up of patients with chronic kidney disease with or without haemodialysis.

Objective: Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. The purpose of this study is to evaluate the prognostic predictors over 5 years in patients with CKD including haemodialysis.

Methods: In this multicenter, prospective cohort study performed with the Gunma-CKD SPECT Study protocol, 311 patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml/1.

The Concept of Palliative Lymphaticovenular Anastomosis.

Lymphaticovenular anastomosis (LVA) is the first-line surgical treatment for lymphedema. The therapeutic effects of LVA, including edema reduction and cellulitis prevention, vary among patients. We examined cases of palliative LVA in patients with lymphedema who were in the terminal stage due to recurrence or distant metastasis of the primary disease, with a focus on the course and usefulness of palliative LVA.

Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA.

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations.

The importance of clinical experience in AI-assisted corneal diagnosis: verification using intentional AI misleading.

We developed an AI system capable of automatically classifying anterior eye images as either normal or indicative of corneal diseases. This study aims to investigate the influence of AI's misleading guidance on ophthalmologists' responses. This cross-sectional study included 30 cases each of infectious and immunological keratitis.

Do coping mechanisms moderate the effect of stressful life events on depression and anxiety in young people? A case-control study from Latin America.

Background: Stressful life events (SLEs) are associated with increased risk of depression or anxiety. Coping mechanisms may moderate this relationship but little is known on this topic in young people or in Latin America.

Aim: To investigate whether coping strategies predict odds of depression and/or anxiety and moderate the relationship between SLEs and depression and/or anxiety in young people in Peru, Lima and Bogotá.

Comparison of Patient Comfort and Acceleration Exposure During Lifting and Loading Operations Using Manual and Powered Stretchers.

Objectives: To compare the effects of powered and manual stretchers on participants' perceived comfort and measured acceleration during lifting and loading operations.

Methods: This non-randomized, laboratory-based crossover study involved forty-one participants (thirty-one firefighters and ten third-year paramedic students) who served as simulated patients experiencing lifting, lowering, loading, and unloading maneuvers using manual and powered stretchers. Four stretcher types were evaluated: one powered stretcher (Power-PRO XT) and three manual stretchers (Matsunaga GT, Exchange 4070, Scad Mate), with each group using the manual stretcher they routinely operated.

Enhanced Production of Rebaudioside D and Rebaudioside M through V155T Substitution in the Glycosyltransferase UGT91D2 from .

Steviol glycosides (SGs) are noncaloric natural sweeteners found in the leaves of stevia (). These diterpene glycosides are biosynthesized by attaching varying numbers of monosaccharides, primarily glucose, to steviol aglycone. Rebaudioside (Reb) D and Reb M are highly glucosylated SGs that are valued for their superior sweetness and organoleptic properties, yet they are present in limited quantities in stevia leaves.

Adenylate cyclase 9 expression level is associated with hormone receptor-positive breast cancer and predicts patient prognosis.

Adenylate cyclase family members have recently received attention as novel therapeutic targets. However, the significance of adenylate cyclase 9 (ADCY9) in breast cancer has not been elucidated. Here, we evaluated expression in breast cancer (BC) cell lines, and polymerase chain reaction array analysis was performed to determine the correlations between expression levels and 84 tumor-associated genes.

Genome Analysis of Japanese Yersinia pseudotuberculosis Strains Isolated From Kawasaki Disease Patients and Other Sources and Their Phylogenetic Positions in the Global Y. pseudotuberculosis Population.

Yersinia pseudotuberculosis (Ypt) is a gram-negative bacterium that infects both humans and animals primarily through fecal‒oral transmission. While Ypt causes acute gastroenteritis in humans, an association with Kawasaki disease (KD), a disease that primarily affects infants and young children and causes multisystemic vasculitis, has also been suspected. Although KD represents a significant health concern worldwide, the highest annual incidence rate is reported in Japan.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Efficacy of mapping biopsy using a novel sheath system for the histological diagnosis of superficial ductal spread in distal cholangiocarcinoma: A retrospective multicenter study.

Background: Mapping biopsy (MB) can evaluate superficial ductal spread (SDS) through the histopathological diagnosis of cholangiocarcinoma, enabling the selection of an appropriate surgical procedure. This retrospective study evaluated the efficacy of MB using a novel sheath system in distal cholangiocarcinoma (dCCA) cases.

Methods: A total of 199 cholangiocarcinoma cases underwent preoperative diagnosis.

Association Between Antibiotic Exposure During Pregnancy and Postpartum Depressive Symptoms: The Japan Environment and Children's Study.

Postpartum depressive symptoms (PDS) are a common mental health condition among women after delivery. Although various causative factors have been reported, PDS remains a challenging condition to predict and prevent. The disruption of the gut microbiota due to antibiotic exposure has been reported to affect psychiatric conditions.

Systematic searches for new inorganic materials assisted by materials informatics.

We introduce our proprietary Materials Informatics (MI) technologies and our chemistry-oriented methodology for exploring new inorganic functional materials. Using machine learning on crystal structure databases, we developed 'Element Reactivity Maps' that displays the presence or the predicted formation probability of compounds for combinations of 80 × 80 × 80 elements. By analysing atomic coordinates with Delaunay tetrahedral decomposition, we established the concept of Delaunay Chemistry.

Fast synthesis of Cu@zeolitic imidazolate framework-8 (ZIF-8) derived Cu/ZnO catalysts a facile mechanical grinding method for CO hydrogenation to methanol.

Direct conversion of CO with renewable H to produce methanol provides a promising way for CO utilization and H storage. Cu/ZnO catalysts are active, but their activities depend on the preparation methods. Here, we reported a facile mechanical grinding method for the fast synthesis of Cu@zeolitic imidazolate framework-8 (ZIF-8) derived Cu/ZnO catalysts applied in CO hydrogenation to methanol.