Rhinoviruses are the most prevalent respiratory viruses across age groups, responsible for a wide spectrum of illnesses ranging from mild upper respiratory symptoms to lower airway involvement. Moreover, rhinovirus infection is also a major driver of asthma exacerbation and development, imposing a substantial disease burden. Rhinoviruses are classified into three species: Rhinovirus A, Rhinovirus B, and Rhinovirus C, each utilizing distinct host cell receptors and exhibiting different clinical patterns. Rhinovirus A and Rhinovirus C are more frequently associated with clinically significant disease outcomes compared to Rhinovirus B. Rhinovirus C binds to cadherin-related family member 3 (CDHR3), and a missense variant in CDHR3 (rs6967330) increases epithelial expression of the receptor, enhancing susceptibility to infection and severe illness, particularly in early life. Rhinovirus infection induces complex immune responses, characterized by impaired interferon signaling, type 2 inflammation, and epithelial barrier disruption. In individuals with asthma, altered interferon responses and T2-high immune profiles are closely linked to rhinovirus-induced exacerbations.In infants with atopic traits, such as eosinophilia, allergen sensitization, or a family history of allergic diseases, rhinovirus infection is strongly associated with subsequent development of asthma. Rhinovirus vaccine is needed to prevent severe respiratory infections and asthma exacerbations, particularly in vulnerable populations. Rhinovirus vaccine development has been challenging due to extensive antigenic diversity and limited cross-protective immunity. Recent progress in high-valency inactivated vaccines has demonstrated the feasibility of eliciting broad neutralizing responses. Prioritizing rhinovirus types linked to greater clinical severity may enable targeted vaccine strategies for high-risk populations, offering a promising approach to reducing the global burden of rhinovirus-associated illnesses.

Purpose: Asthma is characterized by chronic type 2/eosinophilic inflammation in the airway mucosa. This study aimed to explore the clinical value of 2 cutoffs of blood eosinophil counts (≥ 300/μL and ≥ 150/μL) in eosinophilic asthma, with relation to eosinophilderived neurotoxin (EDN), a surrogate marker of eosinophilic activity. Methods: To compare clinical features and eosinophil-related mediators according to 2 cutoffs of peripheral blood eosinophil counts (≥ 300/μL and ≥ 150/μL), 137 adult asthmatics who had maintained antiasthmatic medications, including inhaled corticosteroid and long-acting beta 2 agonist, without biologics, were enrolled. EDN levels in serum, urine and sputum were measured by enzymelinked immunosorbent assay. Results: Patients with asthma and higher blood eosinophil counts ( ≥ 300/μL) had a higher prevalence of severe asthma, chronic rhinosinusitis, partly controlled/uncontrolled status, and higher levels of sputum eosinophils and EDN in serum/sputum than those with lower blood eosinophil counts (< 300/μL). When compared between patients with asthma having higher blood eosinophils ( ≥ 150/μL) and those with lower eosinophils ( < 150/μL), there were no differences in symptom severity, control status or lung function parameters. Conclusion These findings suggest that blood eosinophil count ≥ 300/μL may identify asthma patients at higher risk for severity and heightened eosinophil activity, supporting its utility as a biomarker in a real clinical setting.

Purpose: Treatment responses to Mycoplasma pneumoniae (MP) pneumonia in children exhibit considerable variability. It is essential to identify predictive indicators and elucidate mechanisms associated with treatment responses. This study aimed to characterize the clinical, radiological, laboratory, and cytokine profiles associated with treatment responses in pediatric MP pneumonia. Methods: A retrospective analysis was performed in 85 children hospitalized with MP pneumonia between May 2019 and March 2020.Patients were categorized into the good response group (n=74) or the poor response group (n=11) based on clinical responses to step-wise treatment. Clinical characteristics, radiological findings, laboratory parameters, and serum levels of 27 cytokines obtained at admission were compared between the groups. Results: Compared to the good response group, the poor response group exhibited significantly longer fever duration (11.36 ± 5.33 days vs. 5.77 ± 3.95 days, P = 0.006), more frequent lobar consolidation (63.6% vs. 20.3%, P = 0.043), and higher lactate dehydrogenase levels (1,146±505 IU/L vs. 731±231 IU/L, P=0.008) and MP-specific immunoglobulin M index (6.49±3.01 vs. 3.85±3.28, P=0.014).Among the cytokines assessed, IL-21, IL-22, and IL-31 levels were significantly elevated in the good response group. IL-17A levels were also higher in this group, albeit not statistically significant. Conclusion Early identification of clinical, laboratory, and radiologic markers may facilitate early prediction of treatment response in pediatric MP pneumonia. Elevated IL-21, IL-22, and IL-31 levels in the good response group suggest a potential role for Th17-related cytokine activity in favorable treatment outcomes, warranting further investigation in larger cohorts.

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

Background: Infantile hemangioma (IH) is a common benign vascular tumor that occurs during infancy. Oral propranolol is used as a first-line treatment. However, standardized guidelines for evaluating treatment efficacy, particularly the appropriate timing and parameters for Doppler ultrasound (US), have not been established. This study reports on the evaluation of therapeutic efficacy of oral propranolol solution in IH patients using Doppler US, and aims to propose the appropriate timing and parameters for using Doppler US based on this experience. Methods: A retrospective analysis was conducted on 120 patients with IH who were treated with oral propranolol solution and maintained for over 6 months from May 2017 to April 2023. Doppler US evaluation of IH was performed at diagnosis, 1-2 and 6-12 months after treatment initiation, and 6 months post-therapy cessation. A complete response (CR) was identified as a reduction in vascularity along with a decrease in longest diameter (LD) or thickness of 50% or more. Recurrence was evaluated based on increased vascularity or size 6 months after treatment discontinuation. Results: Of 120 patients with IH, 82 females and 38 males were analyzed. IH was first detected at a median age of 12 days (range, 1-240 days), and treatment began at 76 days (range, 27-570 days), continuing for an average of 10.4 months (range, 5-24 months). Initial Doppler US measurements showed an LD of 2.65±1.52 cm and a thickness of 0.79±0.55 cm, with prominent vascularity. After 1-2 months of treatment, LD and thickness decreased by 12.9% and 25.9%, respectively. By 6-12 months, reductions reached 37.2% and 53.6%. CR occurred in 77 patients (64.2%) after 6-12 months of treatment. Eleven patients (9.2%) experienced a recurrence. Conclusion Doppler US is a valuable modality for evaluating the characteristics, treatment response, and recurrence of IH treated with oral propranolol.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants. Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index. Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p ＜ 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p ＜ 0.001).WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use. Conclusion Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Background: Long-term use of bisphosphonate is a risk factor for atypical femoral fractures (AFFs). Femoral bowing is known to be associated with AFFs. However, whether femoral bowing quickens the occurrence of AFF is unknown. The purpose of this study was to determine whether AFF occurs earlier in patients with severe femoral bowing than in those without severe bowing. Methods: One hundred and sixty-four patients (186 AFFs) from January 2006 to December 2022 were included in this study.According to severity of femoral bowing, patients were divided into 2 groups: severe bowing group (26 femurs) and minimal to moderate bowing group (160 femurs). Age, sex, and completeness and location of AFF were compared between the 2 groups. We compared the time of AFF occurrence after bisphosphonate therapy using cumulative percentage between the 2 groups. Results: Age and sex were similar between the 2 groups, while body mass index (BMI) was lower (22.5 ± 3.0 kg/m 2 vs. 24.5 ± 3.5 kg/m 2 , p = 0.003) in the severe bowing group. The duration of bisphosphonate use was shorter in the severe bowing group than in the minimal to moderate bowing group (3.3 ± 3.8 years vs. 5.0 ± 4.0 years, p = 0.048). In the severe bowing group, 85% of AFFs were diaphyseal in contrast to the 46% in the minimal to moderate bowing group (p < 0.001). Cumulative percentage plot of AFFs in the severe bowing group was left-shifted compared to the minimal to moderate bowing group. Conclusions At the time of AFF diagnosis, the severe bowing group exhibited shorter duration of bisphosphonate use, lower BMI, and a higher incidence of diaphyseal location. Shortening the duration of bisphosphonate therapy may be advisable in patients with severe femoral bowing.

Background: and Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer’s disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging. Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories:the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability. Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability. Conclusions Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multicenter studies and underscore their potential for standardized applications in AD research and clinical practice.