Little is known about the mechanisms underlying the link between violence-related distress and asthma, particularly for asthma endotypes.

Cross-sectional analysis of violence-related distress in the previous 6 months (assessed using the Checklist of Children's Distress Symptoms [CCDS] scale) and nasal epithelial gene expression in 3 studies of youth with asthma aged 8-20 years: Stress and Treatment Response in Puerto Rican and African American Children with Asthma (STAR, n = 128), Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR, n = 228), and Vitamin D Kids Asthma (VDKA, n = 47). We then tested for the association between expression of CCDS-related genes and nasal epithelial transcriptomic profiles corresponding to T2-high and T17-high asthma endotypes.

In a meta-analysis of the CCDS score in the three cohorts, we identified 12 differentially expressed genes (DEGs) with false discovery rate-adjusted p value (FDR-P) < 0.05 and the same direction of association as in the discovery cohort (EVA-PR) in at least one replication cohort. Of these 12 DEGs, 9 (S100A7A, CCL2, CCL8, CXCL9-11, COL15A1, CD300E, and LILRB1) were upregulated and significantly associated with T17-high asthma in a meta-analysis of the three cohorts. Two genes belong to the CC Motif Chemokine Ligand family (CCL2, CCL8) and 3 belong to the CXC Motif Chemokine Ligand family (CXCL9, CXCL10, and CXCL11).

Nine novel genes were associated with violence-related distress and T17-high asthma in three cohorts of predominantly minoritized youth with asthma. Our findings may help uncover biologic processes underlying the violence-asthma link and could represent novel therapeutic targets for T17-high asthma.

ImportanceGlottal competence and cough effectiveness are associated with aspiration. In unilateral vocal fold paralysis (UVFP), injection laryngoplasty (IL) is the mainstay treatment for those with dysphonia and dysphagia. However, few data exist explaining how IL exerts its effects on aspiration prevention.ObjectiveTo evaluate the effect of IL on voluntary cough strength, glottal closure, and swallowing function. Furthermore, the effects were compared between patients with active treatment/disease and those without.Study DesignProspective cohort study.SettingLaryngology clinic of single tertiary hospital.ParticipantAdult patients underwent IL for UVFP between January 2021 and April 2023.Main Outcome MeasuresMaximum volitional cough pressure (MCoughP) was quantified before and after IL, as well as clinical voice outcomes and normalized glottal gap area. For those with a complaint of aspiration, the Eating Assessment Tool (EAT-10) questionnaire and Penetration-Aspiration Scale (PAS) were also evaluated.ResultsForty-one patients were included (26M:15F; age range 32 to 80 years old, mean age 58.7). Clinical voice outcomes and glottal closure were significantly improved in all patients, as well as EAT-10 score (16.22 ± 11.83 at pre-IL and 10.83 ± 11.17 at post-IL, P = .008) and PAS [2 (IQR 1.25, 2) at pre-IL and 1 (IQR 1, 2) at post-IL with 20 mL bolus, P = .02; 2 (IQR 2, 4) at pre-IL and 2 (IQR 1, 2) at post-IL with cup-sipping, P = .007]. Twelve patients had ongoing treatment/systemic diseases, who had significant improvement in voice and glottal closure but not in PAS. MCoughP was significantly increased in ongoing treatment/systemic diseases (-) group [42.90 ± 20.17 cmH₂O at pre-IL, 51.33 ± 21.15 at post-IL, 95% CI (-16.63, -0.23), P = .04] but decreased in ongoing treatment/systemic diseases (+) group [67.98 ± 40.06 cmH₂O at pre-IL, 55.32 ± 31.68 at post-IL, 95% CI (1.37, 23.97), P = .03].Conclusions and RelevanceIL significantly improved glottal competence and voice outcomes. However, increased volitional cough pressure and improved swallowing safety were only demonstrated in patients without ongoing treatment or systemic diseases. Patient's general condition may contribute to the observed effect of IL on dysphagia. Rehabilitation to optimize cough strength and prevent aspiration is beneficial for patients with deteriorating general conditions.

Missing information is common in real-world claims data, particularly on behavioral confounders, for example, smoking. Often one category of the variable, "yes" is partially observed while the other "no" remains completely missing-a pattern we call missing with truncation. A common way to handle these missing values is to naïvely treat missing values as absence of the risk factor, which may lead to substantial misclassification. Standard multiple imputation is impossible as only one level of the variable is observed.

A case study was conducted using data from the NOVELTY study, including 12 224 people with physician diagnosed asthma and/or COPD (NCT02760329). From this cohort, 9733 patients with complete information were included. This dataset was split into two where the first part was used to train an imputation model and the second part was used to evaluate the imputations based on the model (1) when used to impute a truncated and amputated smoking variable against the naïvely classifying missing as "no" (2) when varying the percent smokers retained, q.

The accuracy of approaches (1) and (2) was 0.79 and 0.43, respectively; for q = 90%, the accuracy of approaches (1) and (2) was 0.89 and 0.94, respectively. Transfer learning showed better accuracy than the naïve approach when the percentage of true smokers being recorded as smokers was < 80%.

The added value of transfer learning was greatest when low proportions of true ever-smokers were recorded, with its advantage depending on both the true prevalence of true smokers and the predictive model's performance.

Pulmonary histoplasmosis has traditionally been considered geographically restricted to disease-endemic regions. Taiwan, historically nonendemic, has recently witnessed rising infections. We conducted a retrospective study by reviewing adult patients in Taiwan who had pathologically confirmed pulmonary histoplasmosis during June 1997-December 2024. We analyzed 14 cases with lung involvement. Eight case-patients were male and 6 female; mean age was 56.6 years. Of note, 11 case-patients (78.6%) had no history of travel to histoplasmosis-endemic regions; 10 (71.4%) were immunocompetent. Left upper lobe involvement was most common (n = 4 [28.6%]), with nodular lesions predominating (n = 12 [85.7%]). Most (11 [78.6%]) patients received antifungal therapy, mostly with voriconazole. Outcomes were favorable; 1 (7.1%) patient died. Two additional case-patients without lung involvement exhibited similar demographics and clinical outcomes. Case identification rate has increased since 2015. This 27-year study documents the emergence of pulmonary histoplasmosis in Taiwan, emphasizing the need for heightened clinical suspicion in nonendemic regions.

Sexual and reproductive health (SRH) is essential for public health. COVID-19 led to major disruptions in the provision of essential services including SRH services. Within the context of a multi-country project, this study aimed to explore individual and service-level impacts on contraceptive and sexual health services during the COVID-19 pandemic and recovery phase in England.

A longitudinal, mixed-methods design was implemented, collecting data in two phases, approximately 9 months apart (November 2021 and July 2022). The study comprised in-depth interviews with staff (n = 4) and clients (n = 20) of a sexual health and contraceptive clinical service in the Southeast of England. Over the same timeframe, a quantitative service availability and readiness assessment (SARA) was completed, based on World Health Organization validated tools.

Sexual health and contraceptive services continued to operate throughout the pandemic, however measures taken to prevent COVID-19 transmission and staff capacity issues (due to staff redeployment, staff sickness) impacted on patient choice (e.g. how the service could be accessed, methods of contraception available) and patient experience (e.g. delays in accessing healthcare). Despite disruptions, staff described how in-person provision remained available almost continuously for urgent/vulnerable cases. SARA data confirmed service availability, and qualitative data indicate how this was managed. For example, postal home self-sampling for STIs/HIV was expanded and contraceptive counselling by telephone was introduced to reduce clinic visits, and was retained due to popularity. At Time 2, services were running close to normal.

COVID-19 disrupted sexual health and contraceptive services in England. Compared to pre-pandemic, more elements of these services were delivered remotely. Readiness to adapt was aided by the pre-pandemic direction-of-travel towards greater use of digital and telemedicine services. Innovations require robust evaluation to ensure optimisation for public health benefit both in the pandemic and post-pandemic context.

Obesity is a well-established risk factor for asthma, with genetic factors influencing both conditions. This study investigates the impact of genetic predisposition to increased body mass index (BMI) on adult asthma phenotypes. We recruited 1532 non-asthmatic healthy individuals and 779 adult asthma patients to assess the relationship between BMI-related genetic risk scores (BMI-GRS) and asthma. Among the 85 single nucleotide polymorphisms (SNPs) previously associated with BMI in Japanese populations, significant associations with BMI were confirmed for 6 SNPs in the healthy individuals. Using these, BMI-GRS was calculated for both groups. While asthma patients had higher BMI than healthy individuals (p = 0.004), no significant difference in BMI-GRS was observed between the groups (p = 0.56). A cluster analysis identified six distinct phenotypes of adult asthma patients: two overweight/obese clusters (one with elevated BMI-GRS, one without) and four non-obese clusters (with one showing significantly elevated BMI-GRS). This study demonstrates a genetic heterogeneity in the phenotype of adult asthma among a Japanese population, showing that genetic variants associated with BMI contribute to specific subtypes of asthma. Prospective longitudinal studies are essential to delineate the interactions between genetic predisposition, elevated BMI, subsequent changes in adiposity, and the evolution of asthma phenotypes, which would facilitate the development of mechanism-based therapeutic strategies tailored to genetically-defined patient subgroups.

Pulmonary sarcoidosis and asthma can present identical symptoms, making clinical evaluation difficult if the two diseases overlap. Diagnostic challenges often lead to either overdiagnosis of asthma in patients with confirmed sarcoidosis or withholding appropriate asthma treatment. The true prevalence of patients with bronchial hyperresponsiveness, the hallmark of asthma, among sarcoidosis patients remains unknown, although it is suspected to be significantly higher compared to the general population. Therefore, a positive bronchial challenge test, often considered crucial for confirming asthma in symptomatic individuals with normal spirometry, should not be regarded as decisive in patients with pulmonary sarcoidosis. However, the coexistence of both diseases is possible and should always be considered. Caution is advised as patients prematurely and incorrectly diagnosed with asthma are exposed to unnecessary medical costs and lifelong treatment. Nevertheless, inhaled glucocorticosteroids and bronchodilators may be temporarily used in sarcoidosis patients because of their beneficial effect on symptom control, regardless of a concurrent asthma diagnosis. Despite the existing evidence that patients with sarcoidosis can develop asthma and atopy, the complex cellular pathways and genetic predispositions involved in the pathogenesis of both diseases remain largely unknown. To address these issues in clinical practice, the article aims to discuss the mechanisms involved in the etiopathogenesis of asthma and sarcoidosis and to analyze the available diagnostic and therapeutic methods relevant to both conditions.

To investigate whether iron metabolism exerts a causal influence on chronic rhinosinusitis (CRS) and to identify iron-related biomarkers and regulatory genes with diagnostic and therapeutic potential.

A two-sample Mendelian randomization (MR) analysis was conducted using large-scale GWAS summary statistics for four iron-related traits and three nasal inflammatory diseases. Significant SNPs were mapped to proximal genes and analyzed via Gene Ontology (GO), KEGG pathway enrichment, and protein-protein interaction (PPI) network construction. Candidate gene expression was validated using the GSE69093 transcriptomic dataset and qRT-PCR in nasal mucosal tissues from CRS patients and healthy controls. Molecular docking simulations were performed to assess ligand interactions, and clinical association and machine learning models were applied to evaluate diagnostic relevance and predictive performance.

MR analysis identified transferrin saturation (TSAT) as a causal protective factor for CRS (OR = 0.9988, P = 0.014). Thirty-one genes were mapped from MR-associated SNPs, with SLC17A4 highlighted as a key candidate gene. Enrichment analysis indicated involvement in iron metabolism and inflammatory regulation. SLC17A4 expression was significantly downregulated in both GSE69093 and clinical qRT-PCR samples. TSAT and SLC17A4 levels showed strong inverse correlations with Lund-Mackay and SNOT-22 scores. Molecular docking identified Troglitazone as a strong-binding ligand to SLC17A4 (-10.0 kcal/mol). Machine learning models integrating iron biomarkers and SLC17A4 expression achieved high discriminative performance (AUC = 0.828-0.849) and demonstrated good calibration and net clinical benefit according to calibration and decision curve analyses, supporting their potential clinical applicability.

TSAT confers protective effects in CRS, and SLC17A4 represents a promising biomarker and therapeutic target. The integrative strategy combining causal inference, transcriptomic validation, molecular docking, and machine learning modeling links iron homeostasis to CRS pathophysiology and demonstrates translational potential through clinically applicable predictive models.

Despite decades of research, HIV-1 continues to infect millions annually, underscoring the urgent need for a safe and effective vaccine to curb the ongoing global pandemic. Among the many strategies explored, viral vectors have been the most intensively studied, with adenoviral and poxviral platforms serving as the leading approaches. These vectors have advanced through extensive preclinical evaluation and multiple large-scale clinical trials, demonstrating safety and the ability to induce cellular and humoral responses. Yet, they have also revealed key challenges, including pre-existing vector immunity, limited durability of responses, and in some cases, increased susceptibility to infection. Importantly, these trials clarified the limitations of Env-focused immunity, highlighted the value of heterologous prime-boost regimens, and reinforced the dual need for broadly neutralizing antibodies and functional T cell responses. While vector-based COVID vaccines achieved protective efficacy, lessons learned from adenoviral and poxviral efforts continue to shape the field, directly informing the design of next-generation platforms such as mRNA and engineered viral vectors.

Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration. However, evidence of ChP structural and perfusion alterations in long coronavirus disease (COVID) and their clinical relevance remains limited.

This study included 86 long COVID, 67 recovered COVID, and 26 COVID-negative healthy controls (HCs). ChP volume and cerebral blood flow (CBF) were quantified, and their associations with Alzheimer's disease (AD) symptoms and plasma biomarkers were examined.

Both patient groups showed higher ChP volume and lower CBF than HC. Relative to recovered COVID, long COVID patients had a larger ChP volume, but no significant difference in CBF. ChP volume correlated positively with glial fibrillary acidic protein (r = 0.35) and phosphorylated tau217 (p-tau217; r = 0.54), while CBF correlated negatively with p-tau217 (r = -0.56). Both ChP volume and CBF were associated with cognitive decline measured with Mini-Mental State Examination and Clinical Dementia Rating.

These findings suggest that ChP differences in long COVID are associated with AD-related cognitive decline and increased plasma biomarkers.

Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.