An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation.

The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined.

Experimental and DFT Studies of Intermolecular Interaction-Assisted Oxindole Cyclization Reaction of Di-t-butyl 2-Aminophenyl-2-methyl Malonate.

Density functional theory calculations on the cyclization of di-t-butyl 2-(2-aminophenyl)-2-methyl malonate (1) to t-butyl 3-methyloxindole-3-carboxylate (2) reveal that acetic acid-assisted protonation of the carbonyl oxygen atom reduces the activation Gibbs free energy significantly lower than methanol-assisted pathways. Experimental data confirm that reaction concentration plays a pivotal role in oxindole formation. Experimental results also indicate distinct reaction mechanisms at low and high concentrations.

In-Situ Monitoring of Dissolution and Crystallization Processes of Carbamazepine Using Low-Frequency Raman Spectroscopy and Multivariate Analysis.

Optimization of the manufacturing process based on scientific evidence is essential for quality control of active pharmaceutical ingredients. Real-time monitoring can ensure the production of stable quality crystals in the crystallization process. Raman spectroscopy is an attractive tool for pharmaceutical quality evaluation and process analytical technology because of its ability to analyze samples non-destructively and rapidly.

Efficacy of asfotase alfa in a patient with adult-onset hypophosphatasia without obvious bone lesions: a case report with review of literature.

The use of asfotase alfa, a bone-targeted recombinant alkaline phosphatase (ALP) enzyme, for the treatment of adult-onset hypophosphatasia (HPP) remains controversial, particularly in patients without evident bone abnormalities. We report the case of a 41-year-old woman with a history of Graves' disease, who presented with progressive joint pain and severe fatigue. Despite the absence of bone lesions, the patient was diagnosed with HPP based on persistently low alkaline phosphatase levels, family history, and a novel heterozygous ALPL variant (p.

Lobectomy Increases Postoperative Pulmonary Artery Enlargement to a Greater Extent than Segmentectomy.

Purpose: The underlying mechanism why segmentectomy has demonstrated the non-inferiority to lobectomy in several randomized trials remains unclear. Computed tomography (CT)-measured pulmonary artery (PA) enlargement reflects PA pressure and predicts the prognosis of certain respiratory diseases. We compared the preoperative and postoperative PA diameter to the ascending aorta diameter (PA/A) ratio, investigating its impact on right ventricular function in lung resection.

Usefulness of Artificial Pneumothorax during Totally Endoscopic Off-Pump Left Atrial Appendage Closure and Surgical Ablation.

Purpose: In totally endoscopic off-pump left atrial appendage (LAA) closure and surgical ablation, securing the operative field is sometimes difficult in some patients because of a narrow working space caused by an elevated diaphragm or ventricles. In this study, we aimed to investigate the effectiveness of a method that facilitates securing the operative field using an artificial pneumothorax.

Methods: We analyzed 71 consecutive patients who underwent totally endoscopic off-pump LAA closure and bilateral pulmonary vein isolation.

Hans's algorithm and MYD88 mutation may affect prognosis of primary central nervous system B-cell lymphoma.

Primary central nervous system (CNS) lymphomas account for 1.9-3% of all brain tumors, with the majority being histologically classified as primary large B-cell lymphoma of the CNS (PCNS-LBCL). PCNS-LBCL is characterized by mature germinal center-exit B cells, and most cases of this phenotype are classified as activated B-cell-like phenotype according to gene expression profiling, or as non-germinal center B-cell-like phenotype (non-GCB type) according to Hans's algorithm.

Patient Journey to Transthyretin Cardiac Amyloidosis Diagnosis - A Japanese Claims Database Study.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) in older adults. Delayed ATTR-CM diagnosis may result in more advanced symptoms. This study describes the journey of Japanese patients with ATTR-CM.

Analytical and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non-Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02.

This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (HER2 [ERBB2])-mutated (HER2m) non-small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for HER2 mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02.

Analytical approaches to evaluate risk factors of multimorbidity: a systematic scoping review protocol.

Introduction: Understanding causal risk factors that contribute to the development of multimorbidity is essential for designing and targeting effective preventive strategies. Despite a large body of research in this field, there has been little critical discussion about the appropriateness of the various analytical approaches used. This proposed scoping review aims to summarise and appraise the analytical approaches used in the published literature that evaluated risk factors of multimorbidity and to provide guidance for researchers conducting analyses in this field.

Long-term retention of the pedicled thymic flap after bronchial stump coverage.

This study aimed to assess the feasibility and retention rates of pedicled thymic flaps to enhance understanding of bronchial stump coverage. A retrospective analysis of 22 consecutive patients who underwent anatomical lung resection followed by bronchial stump coverage with pedicled thymic flaps between January 2017 and December 2022 was conducted. The procedure was performed using a minimally invasive 3-port video-assisted thoracoscopic surgery technique for all patients with no complications related to graft harvest or fixation.

SSL-VQ: Vector-quantized variational autoencoders for semi-supervised prediction of therapeutic targets across diverse diseases.

Motivation: Identifying effective therapeutic targets poses a challenge in drug discovery, especially for uncharacterized diseases without known therapeutic targets (e.g. rare diseases, intractable diseases).

Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.

Sepsis is a life-threatening condition caused by severe infection and often complicates acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) due to the collapse of the oxidative and inflammatory balance induced by microbial pathogens, including lipopolysaccharides (LPS). In sepsis-related ARDS/ALI, NADPH oxidase (NOX) and toll-like receptors (TLR) in neutrophils and macrophages are key players in initiating oxidative and inflammatory imbalances. Although NOX and TLR activation has been linked to carbon monoxide (CO), the mechanism by which CO affects sepsis-related ARDS/ALI through NOX and TLR remains unknown.

Spinal ADAM17 contributes to the pathogenesis of painful diabetic neuropathy in leptin receptor-deficient mice.

The pathogenesis of painful diabetic neuropathy (PDN) is complicated and remains not fully understood. A disintegrin and metalloprotease 17 (ADAM17) is an enzyme that is responsible for the degradation of membrane proteins. ADAM17 is known to be activated under diabetes, but its involvement in PDN is ill defined.

Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report.

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization (WAO) published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Molecular characterization of feline caliciviruses isolated from several adult cats with atypical infection showing severe flu-like symptoms on a remote island in Ehime, Japan.

In November 2020, a volunteer group reported an outbreak of an infectious disease with a high fatality rate and flu-like symptoms among stray cats in Aoshima, a remote island in Ehime, Japan. Nine adult cats with severe symptoms were hospitalized. Feline calicivirus (FCV) was isolated from pharyngeal swabs of six hospitalized cats.

Age bias in changes in finger dexterity based on brain activation and spinal motor nerve excitability induced by motor imagery practice.

Elderly adults may have poorer recall ability than young adults and may not fully enjoy the effects of motor imagery. To understand the age bias of the effect of motor imagery on hand dexterity, we evaluated brain activation and spinal motor nerve excitability. Brain activation was evaluated from changes in oxygenated hemoglobin concentration, while spinal motor nerve excitability was evaluated from F-waves in eight young (mean age 21.

Prevalence, incidence, and clinical features of cardiac involvement in patients with pulmonary sarcoidosis.

Background: The epidemiology and characteristics of cardiac involvement in patients with pulmonary sarcoidosis remain unclear. We aimed to determine the prevalence, incidence, and clinical features of cardiac sarcoidosis in patients with pulmonary sarcoidosis.

Methods: The characteristics of patients with biopsy-proven pulmonary sarcoidosis were retrospectively evaluated.

Rare Disease Policy in High-Income Countries: An Overview of Achievements, Challenges, and Solutions.

Objectives: To provide an overview of policy initiatives in high-income countries aimed at supporting the development and accessibility of treatments for rare diseases.

Methods: We examine how legislative, research, and pricing policies in high-income countries address barriers that have historically hindered innovation and access to rare disease treatments. By analysing examples from the EU, UK, US, Canada, Japan, and Australia, the article identifies ongoing initiatives, outlines current challenges, and explores proposed solutions to foster a sustainable, innovative, and accessible rare disease treatment ecosystem.

Fetal fibroblast heterogeneity defines dermal architecture during human embryonic skin development.

To investigate heterogeneity of fibroblasts in human fetal skin, we analysed published single-cell RNA sequencing data (8 and 16 post conception weeks (PCW)) and performed single-molecule fluorescence in situ hybridisation to map their spatial distribution and predicted dynamic interactions. Clustering revealed 8 fibroblast populations with developmental stage-specific abundance changes. Proliferative cells (MKI67+) were present at all stages.

A 96-week real-world outcome of upadacitinib treatment for atopic dermatitis: systemic therapy-naive versus -experienced patients.

Background: Long-term (2-year) effectiveness of upadacitinib for atopic dermatitis (AD) is unknown in real-world practice.

Objective: To evaluate 96-week real-world effectiveness of upadacitinib in Japanese patients with moderate-to-severe AD, stratified by the presence or absence of prior systemic therapies.

Methods: This prospective study included 327 Japanese patients treated with upadacitinib 15 mg (n = 248) or 30 mg (n = 79).

Enhancing single-stage partial nitritation-anammox process with airlift inner-circulation and oxygen partition: a novel strategy for treating high-strength ammonium wastewater.

In the single-stage partial nitritation-anammox process for high-ammonium wastewater treatment, the presence of sufficient biomass with high activity is essential. This study developed an innovative airlift inner-circulation partition bioreactor (AIPBR) with a dual-cylinder structure. During the 362 days' operation, the AIPBR exhibited robust and stable nitrogen removal performance under diverse influent ammonium spanning from 300 to 1800 mg N/L.