The SLC6A14 gene on chromosome X modifies disease presentation in individuals with cystic fibrosis (CF). Population studies have revealed distinct proximal and distal SNP clusters associated with gastrointestinal and lung phenotypes, respectively. Given the co-localization of cis-eQTLs within the corresponding associated chromosomal regions, where less SLC6A14 expression aligns with improved phenotypic outcomes, we sought to understand the SNP contributions to SLC6A14 expression regulation. Using reporter gene assays, we show that the proximal cluster, aligning with pancreas eQTLs, provides variation in promoter activity that is allele-dependent. The more expansive distal cluster, aligning with primary nasal cell eQTLs, was surveyed and found to harbour an enhancer feature that augmented expression in conjunction with the promoter in cells of lung origin. The rs4446858 SNP present within the enhancer aligns with the binding motif of the IRF1 transcription factor, where the alternate C allele was found to respond to direct addition of IRF1 or its increase following IFN-γ stimulation, resulting in increased SLC6A14 expression. Our data support a conclusion that SLC6A14 expression in airway tissue is regulated, in part, by immune-responsive genetic features, likely involving goblet cells. While our findings support previous model system studies indicating beneficial acute effects of SLC6A14 expression, they also highlight a distinction between immune-related responses and cumulative effects of long term disease reflected as lung function in individuals with CF. Our studies emphasize the challenges of elucidating complex genetic loci where there are multiple levels of regulatory influence with competing contributions.

Handling clinical samples from patients suspected of SARS-CoV-2 infection puts healthcare workers at risk of exposure to infectious particles. To reduce this risk, samples are often heat-inactivated before nucleic acid isolation, but this procedure may affect the analytical sensitivity of the test. The aim of this study was therefore to evaluate the effects of heat inactivation (56 °C for 30 min) on RT-qPCR results of samples taken from nasopharyngeal and oropharyngeal (NP/OP) swabs collected from 200 symptomatic patients. Each sample was split into two aliquots - one subjected to heat inactivation and the other stored at 4 °C - followed by nucleic acid isolation and RT-qPCR analysis using the GeneFinder COVID-19 nucleic acid test. Heat inactivation did not significantly affect the overall SARS-CoV-2 detection rate (55.5 % vs. 55.0 % in untreated and heat-treated groups; χ²=0.01; p=0.91). However, discrepancies occurred in 15.3 % of samples, all with quantification cycle (Cq) values >31, including target loss, gain, or complete signal disappearance after heat treatment. Heat inactivation also slightly decreased Cq values for the RNA-dependent RNA polymerase (RdRp) and envelope (E) genes and increased those for the nucleocapsid (N) gene, with significant changes in strongly positive samples (Cq≤33). In positive samples (Cq≤40), the human ribonuclease (RNase) P gene also exhibited significantly higher Cq values after heat treatment. In the strongly positive subgroup, correlation analysis showed moderate correlation for RdRp and very strong correlation for the N and E genes, and a weaker correlation for weakly positive samples. In conclusion, heat inactivation at 56 °C for 30 min does not significantly affect viral gene detection but may diminish it in samples with low viral load.

Data collected by the Croatian Poison Control Centre (CPCC) in 2020 showed a significant increase in poisoning incidence with surface disinfectants and hand sanitisers compared to the same period in 2019. Considering that this rise in poisoning with biocidal products (BPs) coincided with the start of the COVID pandemic, we wanted to see if there was a trend by analysing six-years' worth of CPCC records of biocidal poisoning cases covering the COVID-19 pre-pandemic, pandemic, and post-pandemic period (2019-2024). During that period, we received 1320 BP-related calls (8.0 % of a total of 16.441 calls), and 99 % involved four types of BPs: surface disinfectants (542 cases), hand sanitisers (325 cases), insecticides (283 cases), and rodenticides (119 cases). Most poisonings were accidental and involved ingestion and inhalation as the exposure routes. Most patients were asymptomatic or had mild to moderate symptoms, while severe symptoms were mainly observed in suicide attempts, accounting for less than 3.0 % of the cases. Our analysis confirmed an increase in poisoning cases with hand sanitisers during the height of the pandemic (2020-2021) compared to the pre-pandemic 2019, with the numbers somewhat decreasing afterwards (2022-2024), although the number of cases remained higher than before the pandemic. The number of poisonings with surface disinfectants remained similar before and during the pandemic (2019-2021) but showed an increasing trend after the pandemic (2022-2024). Poisoning with rodenticides and insecticides remained stable across all periods. Our findings reinforce the need for greater public awareness of preventive measures, including appropriate labelling and packaging of biocidal products, and for the promotion of safe behaviour in households and workplaces.

As the COVID-19 pandemic waned, Mycoplasma pneumoniae reemerged in the pediatric population in Ohio, USA. The rate of macrolide-resistant M. pneumoniae fluctuated by month, ranging from 0 to 8.7%, and mirrored the azithromycin prescribing rate. Real-time surveillance for macrolide-resistant M. pneumoniae provides accurate information for management of children with these infections.

Public health and social measures are essential tools for countries to control epidemic transmission but may also disrupt normal socioeconomic activities. This study aims to analyze differences in public health and social measures policy stringency, temporal trends, and their association with corona virus disease 2019 (COVID-19) control outcomes in 118 countries from January 2020 to September 2022, providing evidence to support the formulation of scientifically grounded public health and social measures policies.

Boxplots were used to describe the distribution of overall and individual public health and social measures policy stringency scores across 118 countries during the pandemic. Linear and nonlinear models were fitted to examine temporal trends in public health and social measures policy stringency. A two-way fixed-effects model was applied to analyze the association between public health and social measures policy stringency and the effective reproduction number of COVID-19.

The overall public health and social measures stringency scores across the 188 countries ranged from 7.78 to 69.75. Among these countries, temporal trend models for public health and social measures stringency were statistically significant in 108 countries (all third-order polynomial models), with coefficients of determination exceeding 0.25. Overall public health and social measures stringency increased over time in 59 countries but decreased in 49 countries. After adjusting for covariates, country-level fixed effects, and time fixed effects, the overall public health and social measures policy stringency score was negatively associated with effective reproduction number (β'=-0.076, P<0.05). Five individual public health and social measures components, school closures, workplace closures, gathering restrictions, domestic movement restrictions, and mask-wearing policies, were each negatively associated with the effective reproduction number (β'=-0.020, β'=-0.046, β'=-0.032, β'=-0.011, and β'=-0.030, respectively; all P<0.05). In contrast, international travel restrictions were positively associated with the effective reproduction number (β'=0.053, P<0.05).

During the COVID-19 pandemic, the average intensity of public health and social measures implementation varied widely across 118 countries. School closures, workplace closures, gathering restrictions, domestic movement restrictions, and mask-wearing measures effectively curbed COVID-19 transmission, whereas the effectiveness of international travel restrictions diminished over time.

Chronic obstructive pulmonary disease (COPD) incurs significant mortality worldwide. Less is known about the burden in the last decade across Europe. We report trends and variations in mortality for patients with COPD across 27 European countries from 2011 to 2021.

COPD mortality was extracted from the EUROSTAT database, using the International Classification of Diseases 10 codes J43 and J44 for each country. Age-standardised and sex-standardised mortality rates (SMR) were calculated and joinpoint regression identified average annual percentage change (AAPC) in deaths from 2011 to 2021. Global Burden of Disease tobacco prevalence data were used to try and best contextualise the mortality.

The overall SMR in Europe for this period was 32.1 (95% CI 32.0 to 32.1) per 100 000 person-years, with substantial geographical heterogeneity. There was a fivefold difference in mortality rates between the countries with the greatest versus the least deaths. Although there was an apparent 3% (95% CI -4.4% to -1.6%) decrease in average annual deaths from 2011 to 2021 across Europe, there was no significant change in deaths from 2011 to 2018, prior to the UK leaving the dataset (a noticeably high outlier in SMR) and the COVID-19 pandemic. A 2% reduction (95% CI -2.6% to -1.2%) in annual mortality rate was noted in males from 2011 to 2018, while females increased (AAPC 1.3% (95% CI 0.1% to 2.6)%) in the same time frame.

The plateau in COPD-related deaths across Europe from 2011 to 2018 demands focus. Geographical variation in mortality suggests under-reporting in some countries, which may underestimate the true burden.

Housing insecurity, an important determinant of mental health, worsened during the COVID-19 pandemic in the US. The federal Emergency Rental Assistance (ERA) program sought to reduce housing insecurity among low-income renters. Using 2021-23 Household Pulse Survey data, we employed a quasi-experimental design to assess the effects of ERA on anxiety and depression symptoms and on mental health care use. We conducted causal mediation analyses to determine whether and how ERA affected these outcomes through indirect effects-by alleviating housing insecurity-or through direct effects, which freed up resources to seek care. ERA significantly reduced anxiety and depression symptoms through both indirect and direct effects. Among renters with anxiety or depression symptoms, it increased psychotherapy use through direct effects. Future rental assistance programs could strengthen these dual impacts by including features to improve both housing and health status-for example, by streamlining applications and expediting benefit delivery to provide resources that recipients can use to address urgent mental health needs even before full housing stability is achieved.

To investigate the value of serum chitinase-3-like protein 1 (CHI3L1) in predicting intravenous immunoglobulin (IVIG) nonresponse in children with Kawasaki disease (KD) and to develop a prediction model incorporating CHI3L1.This study enrolled 152 KD children (23 IVIG nonresponders, 129 IVIG-responders). Serum CHI3L1 levels were measured before IVIG infusion using an enzyme-linked immunosorbent assay (ELISA). Independent predictors were identified by univariate and multivariate logistic regression analyses, and a nomogram was constructed. The model performance was evaluated by the area under the receiver operating characteristic curve (AUC), calibration plot, decision curve analysis (DCA), clinical impact curve (CIC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Serum CHI3L1 levels were significantly higher in the IVIG-nonresponsive group. Multivariate analysis identified CHI3L1 and C-reactive protein (CRP) as independent risk factors for IVIG nonresponse. The nomogram incorporating these two factors achieved an AUC of 0.83, with a sensitivity of 0.91 and a specificity of 0.67. Compared to CHI3L1 or CRP alone, the nomogram provided significant NRI and IDI. Both the calibration curve and DCA demonstrated favorable accuracy and clinical utility of the model.

 Serum CHI3L1 is an independent predictor of IVIG nonresponse in KD. The nomogram combining CHI3L1 and CRP shows favorable predictive performance and may serve as a practical tool for early identification of IVIG-nonresponsive patients.

• Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease, and IVIG nonresponse increases the risk of coronary artery lesions. • Several biomarkers and scoring systems have been proposed to predict IVIG resistance, but their generalizability and performance remain limited.

• Serum CHI3L1, a chitinase family protein, is identified for the first time as an independent predictor of IVIG nonresponse in KD. • A novel nomogram integrating CHI3L1 and CRP demonstrates excellent predictive performance, with high sensitivity and improved net reclassification.

This study evaluated the efficacy and safety of N-butyl-2-cyanoacrylate (NBCA)-based middle meningeal artery embolization (MMAE) in preventing recurrence of chronic subdural hematoma (CSDH) in elderly patients. We retrospectively analyzed 221 patients aged ≥ 65 years who underwent burr hole surgery (BHS) with or without adjunctive MMAE between April 2023 and March 2025. Clinical, radiological, and perioperative variables were assessed, with the primary outcome being 90-day recurrence requiring retreatment. Among the cohort, 92 patients received BHS with MMAE and 129 underwent BHS alone. The median age was 82.0 years (IQR 77.0-86.0), and 64.3% were male. The overall recurrence rate was 12.7% (n = 28). Multivariate analysis identified male sex as an independent risk factor for recurrence (OR 4.95, 95% CI 1.61-21.7, P = 0.004), while acute hemorrhage within the hematoma (OR 0.19, 95% CI 0.01-0.99, P = 0.048) and BHS combined with MMAE (OR 0.37, 95% CI 0.13-0.94, P = 0.04) were associated with reduced recurrence risk. Subgroup analyses suggested that MMAE was particularly effective in male patients and in those with septated hematomas. Additionally, the BHS with MMAE group experienced fewer symptomatic complications (0% vs. 4.6%, P = 0.044) and required postoperative Goreisan far less frequently (16.5% vs. 92.3%, P < 0.001). These findings support that NBCA-based MMAE is associated with lower odds of recurrence and fewer symptomatic complications in elderly patients with CSDH, especially in anatomically and clinically favorable subgroups.

Williams-Beuren syndrome (WBS; OMIM #194050), caused by 7q11.23 deletions, is well-characterized postnatally, but prenatal manifestations remain poorly defined. This study aims to delineate the prenatal phenotypes, inheritance patterns, and outcomes of 7q11.23 copy number variations (CNVs).

A retrospective study of 20 prenatal cases with 7q11.23 CNVs diagnosed by SNP array or CNV sequencing (CNV-seq) was conducted. Clinical data, including ultrasound findings, genetic results, and pregnancy outcomes, were analyzed.

Classic 7q11.23 deletions (1.42 Mb median size) were associated with ultrasound anomalies in 100% of cases (11/11), predominantly cardiovascular defects (36.4%, 4/11) and growth restriction (18.2%, 2/11). While 7q11.23 duplications (1.42-3.03 Mb) were associated with anomalies in 50% of cases (3/6), including cleft palate and ventriculomegaly. Inheritance pattern analysis revealed 50% of deletions (6/12) and 42.9% of duplications (3/7) were inherited, either from phenotypically normal or abnormal parents. Termination of pregnancy (TOP) occurred in 76.5% (13/17) of ongoing pregnancies, primarily for de novo CNVs. Four live births involved inherited CNVs.

7q11.23 CNVs exhibit significant prenatal phenotypic variability and inheritance heterogeneity. Advanced genomic testing and inheritance pattern analysis are critical for accurate diagnosis and counseling.