Theoretical Study on the Internal Conversion Decay Pathways of Bithiophene-Fused Isoquinolines.

In this study, the radiative and nonradiative decay pathways from the first singlet excited states (denoted as S) of three bithiophene-fused isoquinolines were investigated by using the mixed-reference spin-flip time-dependent density functional theory approach. These isoquinolines, which are prepared via [2 + 2 + 2] cycloaddition reactions between three types of bithiophene-linked diynes and nitriles, exhibit different fluorescence quantum yields in response to the positions of their sulfur atoms. The decay processes, including the fluorescence emission and internal conversion, were considered.

Complete genome sequence of Flavobacteriaceae sp. strain GF1, isolated from the phycosphere of a coral endosymbiotic dinoflagellate.

A Flavobacteriaceae sp. strain GF1 was isolated from an endosymbiotic dinoflagellate of a coral, and the genome was sequenced using a PacBio Sequel IIe system. The genome consists of a circular 5,300,001 bp chromosome and is predicted to harbor 6 rRNA genes, 42 tRNA genes, and 4,465 coding sequences.

Efficacy of the Bridge Dry Swallowing Exercise for Refractory Gastroesophageal Reflux Disease.

Background Gastroesophageal reflux disease (GERD) is a condition characterized by reflux of gastric contents, leading to damage to the esophageal mucosa and/or unpleasant symptoms, with a global prevalence of 13%. Although acid-suppressive medications are currently the most effective treatments for GERD, they may be ineffective against its symptoms. We therefore investigated the efficacy of a physical exercise program for the treatment of intractable GERD symptoms.

Usefulness of Apple Watch Electrocardiograms for Identifying the Origin of Premature Ventricular Contractions.

Background: The Apple Watch (AW) can record single-lead electrocardiograms (ECGs) and has been investigated for arrhythmia detection. In this study we evaluated its accuracy in identifying the origin of premature ventricular contractions (PVCs) vs. standard 12-lead ECGs.

Compound 4f, a novel brain-penetrant reversible monoacylglycerol inhibitor, ameliorates neuroinflammation, neuronal cell loss, and cognitive impairment in mice with kainic acid-induced neurodegeneration.

Neuroinflammation, a hallmark of neurodegenerative diseases, is associated with neuronal cell loss and cognitive dysfunction. Monoacylglycerol lipase (MAGL) is involved in neuroinflammation in the brain via the degradation of endocannabinoid 2-arachidonoylglycerol to arachidonic acid, a precursor of some eicosanoids; therefore, MAGL inhibitors are expected to have anti-inflammatory effects. We recently developed a reversible, selective, central nervous system penetrant, and orally available MAGL inhibitor, compound 4f.

Effects of weight loss from oral semaglutide administration on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a retrospective analysis using propensity score matching.

Background: Obesity is increasingly being recognized as a chronic disease that exacerbates type 2 diabetes and its related complications. Oral semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in weight loss and diabetes control in Western populations. However, in real-world clinical practice, its effectiveness in Japanese patients, who typically exhibit a leaner phenotype and unique genetic susceptibilities affecting insulin secretion, remains unclear.

Respiratory hospitalizations and ICU admissions among children with and without medical complexity at the end of the COVID-19 pandemic.

Decreased severe respiratory illness was observed during the first 2 years of the COVID-19 pandemic, with a relatively smaller decrease among children with medical complexity (CMC) compared to non-CMC. We extended this analysis to the third pandemic year (April 1, 2022, to March 31, 2023) when pandemic public health measures were loosened. A population-based repeated cross-sectional study evaluated respiratory hospitalizations among CMC and non-CMC (<18 years) in Ontario, Canada.

Development of an online neutron beam monitoring system for accelerator-based boron neutron capture therapy in a hospital.

Background: Boron neutron capture therapy (BNCT) is a next-generation radiotherapy, utilizing both an external neutron beam and a -containing pharmaceutical. A compact accelerator for a high intensity neutron source was installed to conduct BNCT in a hospital. The dose administered to a patient was evaluated by measuring the proton beam current.

Involvement of Proton-Coupled Organic Cation Antiporter in Human Blood-Brain Barrier Transport of Mesoridazine and Metoclopramide.

Mesoridazine and metoclopramide are cationic drugs that are distributed in the human brain despite being substrates of multidrug resistance protein 1 (MDR1), an efflux transporter expressed at the blood-brain barrier (BBB). We investigated their transport mechanisms at the BBB using hCMEC/D3, a human cerebral microvascular endothelial cell line often used as an in vitro BBB model. The cells exhibited time- and concentration-dependent uptake of mesoridazine and metoclopramide, with K values of 34 and 277 µM, respectively.

Relationship between respiratory sarcopenia and respiratory muscle weakness in community-dwelling older adults: a preliminary cross-sectional study.

[Purpose] Using new diagnostic criteria, this study aimed to clarify the relationship between respiratory sarcopenia and respiratory muscle weakness in community-dwelling older adults. [Participants and Methods] Basic information, body composition, motor function, respiratory function, and respiratory muscle strength were analyzed for 43 elderly community residents who participated in a health promotion program between 2021 and 2023. Respiratory sarcopenia and respiratory muscle weakness were evaluated based on maximal intraoral pressure and skeletal muscle index.

Using multi-level regression to determine associations and estimate causes and effects in clinical anesthesia due to patient, practitioner and hospital or health system practice variability.

In this research methods tutorial of clinical anesthesia, we will explore techniques to estimate the influence of a myriad of factors on patient outcomes. Big data that contain information on patients, treated by individual anesthesiologists and surgical teams, at different hospitals, have an inherent multi-level data structure (Fig. 1).

Pseudo-walking Sensation by Anteroposterior or Lateral Galvanic Vestibular Stimulation and Synchronous Foot-sole Vibrations.

The walking sensation is a result of the synthesis of multisensory inputs from various systems. The vestibular system, typically used for detecting acceleration, is a crucial component of the walking sensation. This study investigated the use of galvanic vestibular stimulation(GVS) to enhance the sensation of walking in virtual reality (VR) environments, particularly when users are seated and not engaged in active movements.

Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.

DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation.

Effects of dexamethasone on opioid consumption in pediatric tonsillectomy: a systematic review with meta-analysis.

Purpose: Tonsillectomy is one of the most common ambulatory procedures performed in children worldwide, with around 40,000 procedures performed in Canada every year. Although a prior systematic review indicated a clear role for dexamethasone as an analgesic adjunct, the quantity effect on opioid consumption is unknown. In the current systematic review with meta-analysis, we hypothesized that the use of dexamethasone reduces perioperative opioid consumption in pediatric tonsillectomy but does not increase rates of postoperative hemorrhage.

Erythroid Differentiation Regulator 1 as a Regulator of Neuronal GSH Synthesis.

Erythroid differentiation regulator 1 (Erdr1) is a cytokine known to play important roles in cell survival under stressful conditions, maintenance of cellular growth homeostasis, and activation of the immune system. However, the impact of Erdr1 on neurons remains undefined. In this study, we present novel evidence that Erdr1 plays a role in regulating glutathione (GSH) synthesis via glutamate transporter-associated protein 3-18 (GTRAP3-18), an anchor protein in the endoplasmic reticulum that holds excitatory amino acid carrier 1 (EAAC1) in neurons.

Iridium-Catalyzed [2 + 2 + 2] Cycloaddition of Bithiophen-Linked Diynes with Nitriles: Scope and Mechanistic Study with Quantum Chemical Calculation.

We report a simple and atom-efficient method for the synthesis of bithiophene-fused isoquinolines by iridium-catalyzed [2 + 2 + 2] cycloaddition of bithiophene-linked diynes with nitriles. All three structural isomers of bithiophene-linked diynes underwent [2 + 2 + 2] cycloaddition, and the trend in the reactivity for cycloaddition was diyne = diyne > diyne . Dibenzothiophene-linked diyne also reacted with nitriles to form a variety of cycloadducts.

CRISPR/Cas9 gene editing clarifies the role of CD33 SNP rs12459419 in gemtuzumab ozogamicin-mediated cytotoxicity.

The single-nucleotide polymorphism (SNP) rs12459419 is located at the intron/exon junction of CD33 exon2. When exon2 is skipped by this CD33 SNP, the full-length CD33 (CD33FL) is converted to a short CD33 isoform (CD33D2). Since gemtuzumab ozogamicin (GO) only recognizes CD33FL, the CD33 SNP may affect the clinical efficacy of GO.

[Successful induction therapy for acute myeloid leukemia under management with extracorporeal membrane oxygenation].

A 53-year-old woman presented with shortness of breath and hyperleukocytosis and was admitted to our hospital. Shortly after, she went into cardiopulmonary arrest and was resuscitated. Her white blood cell count was 566,000/µl, with 94.