Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination.

Background: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

Aims: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse.

Methods And Results: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation.

Fate and distribution of phosphorus in coking wastewater treatment: From sludge to its derived biochar.

Due to the phosphorus (P) deficiency in coking wastewater, sufficient P needs to be provided in the treatment process to maintain biotic activity. However, most of the dosed P sources are transferred to the sludge phase out of the chemical equilibrium. After an in-depth investigation of P morphology changes in coking wastewater treatment, it is found that above 71.

Nationwide survey of adult patients with pulmonary alveolar proteinosis using the National Database of designated intractable diseases of Japan.

Background: Autoimmune pulmonary alveolar proteinosis (APAP) and congenital/hereditary PAP were labeled intractable diseases in Japan in 2015. Since then, patients registered in the National Database of Designated Incurable Diseases (NDDID) who met certain requirements became eligible for medical subsidies. Epidemiological studies using recent data are needed for the development of management protocols for patients with PAP.

Pharmacological Profile of Difamilast, a Novel Selective Phosphodiesterase 4 Inhibitor, for Topical Treatment of Atopic Dermatitis.

PDE4 inhibitors are expected to be anti-inflammatory agents based on their mechanism of action, but the application of this drug class is limited by a narrow therapeutic window due to adverse effects associated with gastrointestinal function. Difamilast, a novel selective phosphodiesterase 4 (PDE4) inhibitor, demonstrated significant efficacy without adverse reactions such as nausea and diarrhea in patients with atopic dermatitis (AD) and was recently approved in Japan. In this study, we investigated the pharmacological and pharmacokinetic properties of difamilast to provide nonclinical data to help understand the clinical effects.

A multi-purpose Japanese phase I study in the global development of vupanorsen: Randomized, placebo-controlled, single-ascending dose study in adults.

Vupanorsen (PF-07285557) is a second-generation tri-N-acetyl galactosamine (GalNAc )-antisense oligonucleotide targeted to angiopoietin-like 3 (ANGPTL3) mRNA, shown to reduce lipids and apolipoproteins in subjects with dyslipidemia. To aid bringing innovative drugs to global patients efficiently, a multi-purpose Japanese phase I study was conducted, with integrated development approaches agreed by the Pharmaceuticals and Medical Devices Agency (PMDA). This randomized, double-blind, placebo-controlled, single-ascending dose (SAD) study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of vupanorsen administered subcutaneously to Japanese adults (20-65 years) with elevated triglycerides (TG).

Prognostic significance of the Naples prognostic score in colorectal cancer patients undergoing curative resection: a propensity score matching analysis.

Background: Systemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis.

Stem cell-based modeling and single-cell multiomics reveal gene-regulatory mechanisms underlying human skeletal development.

Although the skeleton is essential for locomotion, endocrine functions, and hematopoiesis, the molecular mechanisms of human skeletal development remain to be elucidated. Here, we introduce an integrative method to model human skeletal development by combining in vitro sclerotome induction from human pluripotent stem cells and in vivo endochondral bone formation by implanting the sclerotome beneath the renal capsules of immunodeficient mice. Histological and scRNA-seq analyses reveal that the induced bones recapitulate endochondral ossification and are composed of human skeletal cells and mouse circulatory cells.

Determinants of Subtype-Selectivity of the Anthelmintic Paraherquamide A on Nicotinic Acetylcholine Receptors.

The anthelmintic paraherquamide A acts selectively on the nematode L-type nicotinic acetylcholine receptors (nAChRs), but the mechanism of its selectivity is unknown. This study targeted the basis of paraherquamide A selectivity by determining an X-ray crystal structure of the acetylcholine binding protein (AChBP), a surrogate nAChR ligand-binding domain, complexed with the compound and by measuring its actions on wild-type and mutant nematodes and functionally expressed nAChRs. Paraherquamide A showed a higher efficacy for the levamisole-sensitive [L-type (UNC-38/UNC-29/UNC-63/LEV-1/LEV-8)] nAChR than the nicotine-sensitive [N-type (ACR-16)] nAChR, a result consistent with in vivo studies on wild-type worms and worms with mutations in subunits of these two classes of receptors.

Assessing Heterogeneity of Treatment Effect in Real-World Data.

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies.

Fragment imaging in the infrared photodissociation of the Ar-tagged protonated water clusters HO-Ar and H(HO)-Ar.

Infrared photodissociation of protonated water clusters with an Ar atom, namely HO-Ar and H(HO)-Ar, was investigated by an imaging technique for mass-selected ions, to reveal the intra- and intermolecular vibrational dynamics. The presented system has the advantage of achieving fragment ion images with the cluster size- and mode-selective photoexcitation of each OH stretching vibration. Translational energy distributions of photofragments were obtained from the images upon the excitation of the bound (ν) and free (ν) OH stretching vibrations.

Running Marathons in High School: A 5-Year Review of Injury in a Structured Training Program.

Objective: The aim in this study was to quantify the number, nature, and severity of injuries sustained by male and female high school students who took part in a running training program that culminated in the completion of a half or full marathon.

Design: This study is a retrospective clinical audit.

Methods: Injury reports from high school students (grades 9-12) who participated in a half or full marathon 30-week progressive training program comprising four training days per week (three running days and one cross-training day) were reviewed.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC ( = 44), V114-IM ( = 45), or 13-valent PCV (PCV13)-SC ( = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits.

Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Background: CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear.

Predictive value of the Naples prognostic score on postoperative outcomes in patients with rectal cancer.

Purpose: The Naples prognostic score (NPS) is a prognostic index based on the nutritional and inflammatory status. However, its utility in predicting postoperative complications (POCs) has not been examined in rectal cancer (RC). We evaluated the predictive value of the preoperative NPS for POCs in RC.

Potential Role of Lipase Activity on the Internal Exposure Assessment of Glycidol Released from Its Fatty Acid Esters.

Glycidyl fatty acid esters (GEs) can be found in food, and they can be converted into genotoxic animal carcinogen glycidol in vivo by the action of lipase. This study examined whether human ingestion of charbroiled pork containing high levels of GEs (300 µg/day) increased glycidol-hemoglobin adduct (diHOPrVal), a marker of internal exposure to glycidol using LC-MS/MS. Contrary to expectation, the diHOPrVal value before ingesting charbroiled pork was 3.

Changes of biomarkers for erythropoiesis, iron metabolism, and FGF23 by supplementation with roxadustat in patients on hemodialysis.

This study aimed to confirm changes in biomarkers of erythropoiesis and iron metabolism and serum fibroblast growth factor 23 (FGF-23) during darbepoetin-α treatment and then switching to the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat. A total of 28 patients on hemodialysis who received weekly doses of darbepoetin-α were switched to roxadustat. Biomarkers for erythropoiesis and iron metabolism and intact and C-terminal FGF-23 were measured in blood samples collected before the HD session on days - 7 (darbepoetin-α injection), - 4, and - 2, and days 0 (switch to roxadustat treatment, three times weekly), 3, 5, 7, 14, 21, and 28.

Consensus Statement on the definition and classification of metabolic hyperferritinaemia.

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage.

Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial.

The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10-90 μg) or placebo for 12 weeks.

XCR1 conventional dendritic cell-induced CD4 T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury.

Cardiac remodeling has no established therapies targeting inflammation. CD4 T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI/ApoeR61 mice.

Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

Background: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke.

Methods: CSPS.