Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems.

Despite its broad application in in vitro studies, the application of targeted protein degradation (TPD) to animal models faces considerable challenges. Here, we develop inducible and cell-type specific TPD systems in mice using two degron systems: Oryza sativa TIR1 (OsTIR1)-auxin-inducible degron 2 (AID2) and human cereblon (hCRBN)-SALL4 degron (S4D). Efficient degradation of Satb1 protein by these systems recapitulates phenotypes observed in the Satb1-deficient mice.

Association of endotheliopathy with coagulofibrinolytic reactions and disseminated intravascular coagulation after trauma: a retrospective observational study.

We carried out a retrospective observational investigation to explore the association of endotheliopathy with coagulofibrinolytic reactions and the progression of disseminated intravascular coagulation (DIC) in adult trauma patients. We measured syndecan-1 (SDC-1), an indicator of endotheliopathy, and biomarkers of coagulofibrinolysis in 100 trauma patients immediately transferred to Ehime University Hospital. We evaluated the correlations between the coagulofibrinolytic parameters and SDC-1.

Incidence and risk factors for venous thromboembolism in gynecological cancer: the GOTIC-VTE trial.

Real-world data on venous thromboembolism (VTE) in Japanese patients with gynecological cancer are lacking. The GOTIC-VTE trial aimed to evaluate the frequency of VTE-associated events and risk factors at the time of cancer diagnosis and during 1-year follow-up. From July 2017 to February 2019, patients with endometrial, cervical, ovarian, tubal, or peritoneal cancer who underwent VTE screening within 2 months before registration, were enrolled.

Relative age effect on the physical activity and sedentary behavior in children and adolescents aged 10 to 18 years old: a cross-sectional study in Japan.

Background: Few studies have shown that relatively younger children and adolescents (those born later in the same school year) were less likely to engage in physical activity in a phenomenon termed the relative age effect. Although these studies mainly targeted elementary and middle school students, no study has reported on the relative age effect on physical activity in ordinary high school students. Moreover, the relative age effect on sedentary behavior might show an opposite association with physical activity.

Synthesis and Properties of 5,15-Dioxaporphyrin Bearing Various meso-Aryl Substituents.

Herein, a scope of meso-substituents for the synthesis of 5,15-dioxaporphyrins (DOPs), a novel antiaromatic porphyrinoid, was investigated. DOPs with various types of aryl substituents were synthesized by nucleophilic aromatic substitution reaction of nickel bis(α,α'-dibromodipyrrin) complexes bearing corresponding meso-aryl substituents and subsequent intramolecular annulation reaction of β-hydroxy-substituted intermediates. Using a copper dipyrrin complex instead of nickel complexes, a copper complex of DOP was synthesized for the first time.

An estimation of the abundance of plastic litter generated by beach users nationwide in Japan.

Coastal regions, including beaches, constitute major tourism assets. Concurrently, beaches are hotspots for microplastic generation, and accumulated beached litter substantially influences future microplastic abundance in the marine environment. Although the stock of plastic litter on beaches has been estimated in previous studies, knowledge gaps exist with regard to the amount of annually generated litter by beach users and the absence of litter generation rate (LGR) in g/person/h or items/person/h.

AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection.

The accumulation of damaged mitochondria in the heart is associated with heart failure. Mitophagy is an autophagic degradation system that specifically targets damaged mitochondria. We have reported previously that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells.

Omission of lymph node dissection along the recurrent laryngeal nerve for lower thoracic esophageal squamous cell carcinoma with short esophageal invasion.

Background: Esophagectomy with lymphadenectomy is the primary treatment for esophageal squamous cell carcinoma (ESCC). However, intensive dissection of lymph nodes (LNs) along the recurrent laryngeal nerve (RLN) is associated with RLN palsy and pulmonary complications leading to poor survival. Therefore, this study aimed identify the risk factors for LNs metastasis along the RLN in patients with ESCC.

Remarkable Evolutionary Rate Variations Among Lineages and Among Genome Compartments in Malaria Parasites of Mammals.

Genes encoded within organelle genomes often evolve at rates different from those in the nuclear genome. Here, we analyzed the relative rates of nucleotide substitution in the mitochondrial, apicoplast, and nuclear genomes in four different lineages of Plasmodium species (malaria parasites) infecting mammals. The rates of substitution in the three genomes exhibit substantial variation among lineages, with the relative rates of nuclear and mitochondrial DNA being particularly divergent between the Laverania (including Plasmodium falciparum) and Vivax lineages (including Plasmodium vivax).

Image-based Re-evaluation of the JCOG0911 Study Focusing on Tumor Volume and Survival, Disease Progression Diagnosis, and Radiomic Prognostication for Newly Diagnosed Glioblastoma.

Purpose: To re-evaluate images recovered from JCOG0911, a randomized phase 2 trial for newly diagnosed glioblastoma (nGBM) conducted by the Japan Clinical Oncology Group (JCOG) Brain Tumor Study Group.

Methods: The correlation between tumor volumes and survival was evaluated, followed by progression-free survival (PFS) analysis by independent central review based on Response Assessment in Neuro-Oncology (RANO) criteria using MRI recovered from 118 nGBM patients enrolled in the JCOG0911 trial. A radiomic analysis was also performed to identify radiomic features predictive of nGBM prognosis.

Study on the chemical stability of β-lactam antibiotics in concomitant simple suspensions with magnesium oxide.

Background: A simple suspension method, where solid formulations are disintegrated and suspended by being soaked in warm water followed by tube administration, is widely used, especially for elderly patients with dysphagia in Japanese clinical settings. However, there is insufficient information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. The influence of occasional prolonged soakage on drug stability is also of concern.

Standardization of radiation therapy quality control system through mutual quality control based on failure mode and effects analysis.

The advancement of irradiation technology has increased the demand for quality control of radiation therapy equipment. Consequently, the number of quality control items and required personnel have also increased. However, differences in the proportion of qualified personnel to irradiation techniques have caused bias in quality control systems among institutions.

Prognostic Utility and Cutoff Differences in NT-proBNP Levels Across Subgroups in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry.

Objectives: N-terminal pro brain natriuretic peptide (NT-proBNP) is a biomarker for myocardial stress that is used in diagnosing and prognosticating heart failure (HF). However, its interpretation is complicated by clinical factors. This study aims to clarify the prognostic value of NT-proBNP in patients with heart failure with preserved ejection fraction (HFpEF), and risk-prediction cutoffs considering various clinical factors.

Preoperative tibiofemoral contact point on standing lateral radiograph predicts anteroposterior knee kinematics in total knee arthroplasty.

Purpose: This study investigated the tibiofemoral contact point (CP) on standing lateral radiographs in knee osteoarthritis and assessed the relationship between CP and pre- and postoperative knee kinematics in total knee arthroplasty (TKA).

Methods: The intraoperative knee status of 46 knees with varus deformity that underwent bicruciate stabilized TKA using a navigation system was investigated. The intraoperative anteroposterior (AP) position of the femur relative to the tibia at maximum extension, 15°, 30°, 45°, 60° and 90° was evaluated by the navigation system before and after TKA.

Mapping Drug Terms via Integration of a Retrieval-Augmented Generation Algorithm with a Large Language Model.

Objectives: This study evaluated the efficacy of integrating a retrieval-augmented generation (RAG) model and a large language model (LLM) to improve the accuracy of drug name mapping across international vocabularies.

Methods: Drug ingredient names were translated into English using the Japanese Accepted Names for Pharmaceuticals. Drug concepts were extracted from the standard vocabulary of OHDSI, and the accuracy of mappings between translated terms and RxNorm was assessed by vector similarity, using the BioBERT-generated embedded vectors as the baseline.

Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.

Background: The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated.

Methods: Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled.

Common protein-altering variant in GFAP is associated with white matter lesions in the older Japanese population.

The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).

Effect of ocean dynamic processes on the temporal-spatial pattern of persistent organic pollutants (PCB-153 and BDE-47) in the shelf seas.

Field observations of persistent organic pollutants (POPs) in shelf seas presented abnormal phenomena such as high-concentration patches in offshore areas and different vertical profiles of POPs at the same location. We assumed that these phenomena were associated with the presence of bottom cold water mass (BCWM) in shelf seas and used a hydrodynamic-ecosystem-POP coupled model to confirm this hypothesis. Based on model results, with the formation of BCWM during summer, POPs accumulated inside BCWM due to their transport across the thermocline by the sorption to sinking particles.