Cystic fibrosis (CF) newborn screening in Türkiye uses a two-step immunoreactive trypsinogen (IRT/IRT) algorithm with fixed cutoffs. The infants missed by fixed-cutoff screening remain poorly characterized.

In this retrospective single-center cohort (2015-2025), 90 children with confirmed CF were classified as IRT-positive (n = 78; IRT-1 ≥ 90 ng/mL) or IRT-negative (n = 12; IRT-1 < 90 ng/mL). CFTR variants were re-evaluated (ACMG/AMP) and stratified by Welsh-Smith class and residual-function status. Clinical, perinatal, pre-analytical, microbiological and genotype data were compared with standardized effect sizes.

IRT-negative patients were diagnosed later (median 12 vs. 2 months; p < 0.001) and had higher early Pseudomonas aeruginosa colonization (33.3% vs. 9.0%; unadjusted p = 0.037). Height standard deviation score was higher in IRT-negative patients (p = 0.004; Cohen's d = -0.77; not retained after false-discovery-rate adjustment). Mean IRT-1 was four-fold lower (44.5 vs. 189.1 ng/mL; p < 0.001). Class IV-V variants accounted for 33.3% of classified IRT-negative versus 11.1% of IRT-positive alleles; IRT-negative patients were enriched for residual-function and splicing variants, including 2789 + 5 G > A (9.5% vs. 2.0%), R334W and Y1032C. Pre-analytical and perinatal factors did not differ.

In every missed case, the first-tier IRT value fell below the fixed national cutoff, without evidence of pre-analytical or perinatal contributions. Missed cases clustered among carriers of residual-function and splicing CFTR variants, whose attenuated pancreatic injury may keep neonatal IRT below the cutoff. Because the Turkish protocol forgoes second-tier testing in IRT-1-negative infants, this subgroup is invisible to the current algorithm; the fixed cutoff warrants optimization.

An extensive body of clinical and experimental evidence demonstrates that immune checkpoint blockade can invigorate recall immune responses. This phenomenon has previously been highlighted using ex vivo (healthy donor) and in vivo (immunotherapy patients) models of immune checkpoint inhibitor (ICI) administration that demonstrate an enhancement of the T-cell response to concomitant small-molecule drugs. However, the immunological and clinical impact of ICI therapy pre-ceding vaccination, where robust antigen-specific immunogenicity is essential, remains poorly defined. In this study, we utilized an ex vivo assay to evaluate lymphocyte recall responses within peripheral blood mononuclear cells (PBMC) derived from healthy donors and patients pre- and post-immunotherapy following exposure to SARS-CoV-2 derived peptides and ChAdOx1 nCoV-19. In line with the anticipated effects of the primary pharmacology of immune checkpoint inhibitors, we outline an acute increase in proliferation and cytokine and cytolytic molecule secretion following immune checkpoint blockade in response to CEF(T), wild-type SARS-CoV-2 spike pools 1 and 2, and ChAdOx1 nCoV-19. Future studies are needed to evaluate the clinical correlates of the veracity of such responses with protection and incidence of adverse events.

to describe the methodological framework of the 'Air and Health Atlas', an interactive web platform that integrates PM2.5 and NO2 concentrations, demographic and mortality data to estimate the burden-of-disease attributable to outdoor air-pollution in Italy.

methodological study with an illustrative application based on real-world data from the Air and Health Atlas.

annual PM2.5 and NO2 concentrations were modelled at 1×1 km spatial resolution for 2016-2024 using a random forest machine-learning approach combining airquality monitoring data, satellite observations, and spatiotemporal covariates. Population-weighted exposure (PWE) was estimated at municipality level by combining modelled concentrations with census-block population counts (Istat 2021). Mortality rates for natural (ICD-10 A00-R99), cardiovascular (ICD-10 I00-I99), respiratory causes (ICD-10 J00-J99), and for trachea, bronchus, and lung cancer (ICD-10 C33-C34) were obtained from death-certificate national database at provincial level, and for municipalities with >=500,000 residents, for 2016-2024.

attributable cases (AC) and attributable fractions (AF%) were estimated at municipality level using concentration-response functions based on epidemiological evidence (HRAPIE-2). The WHO counterfactual scenarios (5 μg/m³) were used. Atlas estimates are provided from 2017 onwards.

using 2019 as an illustrative application, the Atlas showed marked geographical differences in health impacts attributable to air pollution. National PWE were 16.0 μg/m³ for PM2.5 and 21.0 μg/m³ for NO2, with lower exposures in Southern Italy and higher levels in the Po Valley (Northern Italy). Under WHO counterfactual scenarios, estimated natural-cause AF% were 9.9% for PM2.5 and 5.2% for NO2. Northern regions experienced the highest burdens, reflecting the combination of elevated pollution and high population density. The platform supports both retrospective analysis and prospective scenario evaluation, allowing users to explore potential health benefits of alternative air-quality standards or emissionreduction policies.

the Atlas integrates advanced exposure modelling with an intuitive web interface to support evidence-based health policies and communication in Italy. Its design allows for annual updates and future expansions to morbidity outcomes and economic assessments.

Contemporary population-representative data on bronchiectasis epidemiology in the United States remain limited. Existing exacerbation estimates are derived primarily from referral registries that overrepresent severe disease under subspecialty care, while incidence and prevalence calculations are largely based on outdated single-payer data, limiting generalizability.

To estimate non-cystic fibrosis bronchiectasis prevalence and incidence among insured U.S. adults during 2016-2024, characterize exacerbation rates and their composition, and identify baseline factors associated with subsequent exacerbations.

We assembled a retrospective cohort of adults with bronchiectasis using MarketScan Commercial, Medicare Supplemental, and Medicaid databases. Cases required two or more bronchiectasis diagnostic claims separated by more than 30 days, excluding individuals with cystic fibrosis, human immunodeficiency virus infection, or organ transplantation. The observation time zero was the second qualifying claim. Quasi-Poisson models were used to estimate annual prevalence, incidence, and exacerbation rates during observable enrollment periods. Annual percent changes quantified temporal trends. A negative binomial model estimated associations between baseline characteristics and post-diagnosis exacerbation rates.

We identified 80,749 cases (64.6% female; mean age 65.9 years) and estimated prevalence and incidence of 105.3 and 32.1 per 100,000, respectively, in the combined Commercial-Medicare sample, and 66.1 and 19.0, respectively, in Medicaid. Prevalence increased steadily across payers, whereas incidence remained stable. The overall exacerbation rate was 0.88 events per person-year, declining by approximately 5% annually, with a reduction during the early pandemic period followed by a return to pre-pandemic trajectories by 2024. Outpatient events accounted for nearly 87% of exacerbations in the Commercial-Medicare sample and 65% in Medicaid. Calendar trends were attenuated by 12.3% after adjustment for follow-up. Frequent-exacerbator phenotype at cohort entry was the most strongly associated with higher subsequent exacerbation rates (adjusted rate ratio 1.96), followed by chronic airway infection and underlying respiratory conditions. Greater pulmonologist engagement at baseline was associated with lower exacerbation rates thereafter.

Observed prevalence-incidence widening gap suggests case accumulation over time and survival among continuously enrolled beneficiaries. Exacerbation burden was concentrated among individuals with prior exacerbations, chronic airway infection, and respiratory comorbidity, while exacerbation rates decreased over time across payers and subgroups, in part reflecting changes in cohort composition.

The reduction in human activities during the COVID-19 pandemic, known as the Anthropopause, offers a unique opportunity to evaluate its effects on groundwater, which remains poorly understood. The study aims to evaluate groundwater status during the COVID-19 period in the regional unit (RU) of Messenia, an agricultural area of high tourist interest. Qualitative and quantitative data from borehole investigations were analyzed using an integrated methodological framework. Descriptive statistical analyses, bivariate hydrogeochemical diagrams, geo-environmental indices, and hydrogeochemical evaluations characterized groundwater chemistry and variability, while thematic maps illustrated its spatial patterns. Furthermore, a combined DPSIR-SWOT approach was utilized to systematically assess the groundwater system responses and to evaluate the potential impacts of the Anthropopause on groundwater. The effects of Anthropopause were investigated over five years (2018-2022), allowing for comparison of groundwater characteristics across different phases of human activity (pre- and post-Anthropopause periods). The results showed that elevated EC values and increased concentrations of Cl^-, Na⁺, and NO₃^- in groundwater are consistent with seawater intrusion and nitrate pollution in Messenia. The data also indicated significant reductions in NO₃^-, Cl^-, and EC values during the Anthropopause, suggesting improved groundwater quality for various uses. In contrast, groundwater conditions deteriorated after tourism increased. The pause in human activities demonstrated significant effects on human-environment interactions, often benefiting natural processes and highlighting the need for effective groundwater resource management. This requires systematic spatiotemporal monitoring of groundwater data to provide insights into the impacts of human activities and climate change.

The SUPER-refractory status epilepticus (SE) after Cardiac Arrest Treatment (SUPER-CAT) study evaluated the efficacy and safety of dual antiglutamate therapy (combined AMPA and NMDA receptor blockade) in patients with super-refractory SE (SRSE) after cardiac arrest and without unfavorable prognostic indicators.

Multicenter cohort study including patients with postanoxic SRSE meeting the following criteria: bilaterally preserved N20 cortical responses, intact pupillary reflexes, and absence of generalized periodic discharges. Patients treated with dual antiglutamate therapy (DUAL; ketamine 1.5-7.5 mg/kg/h for 3 days plus perampanel 6-12 mg/d for 5 days with tapering) were compared with patients receiving other combinations of antiseizure and anesthetic agents (OTHERS). The primary outcome was resolution of SE. Secondary outcomes included awakening to follow commands and good neurologic outcome at 6 months (modified Rankin Scale 0-3) in patients with fewer than 2 unfavorable multimodal prognostic indicators and 6-month mortality for the entire cohort. Safety analysis included in-hospital mortality and potentially treatment-related adverse events. Patients treated with single antiglutamate agents were described separately.

Between May 2012 and May 2025, 95 of 1,352 consecutive post-cardiac arrest intensive care unit patients met inclusion criteria (mean age 66, interquartile range 55-73; 41% female; DUAL = 43; OTHERS = 41; single antiglutamate = 11). Compared with OTHERS, DUAL was associated with a higher rate of SE resolution (84% vs 49%; OR 5.4; 95% CI 1.9-14.9; p = 0.001), a greater likelihood of awakening before discharge (56% vs 32%; OR 2.7; 95% CI 1.0-7.3; p = 0.053) and lower 6-month mortality (52% vs 74%; OR 0.37; 95% CI 0.15-0.97; p = 0.043). A trend toward better 6-month neurologic outcome was observed in the DUAL group (39% vs 25%; OR 1.89; 95% CI 0.64-5.56; p = 0.245). Reversible cholestatic liver injury occurred more frequently in DUAL group, compared with OTHERS (77% vs 27%; OR 9.00; 95% CI 3.34-24.19; p < 0.001).

In patients with postanoxic SRSE without unfavorable prognostic indicators, dual antiglutamate therapy was highly effective in resolving SE and was associated with improved short-term clinical outcomes.

ClinicalTrials.gov NCT05756621.

Cardiometabolic diseases (CMDs) are a major health concern worldwide, with people living in socioeconomically disadvantaged areas being disproportionately affected. Knowing one's risk status for developing a CMD can help individuals in delaying or preventing the disease. Innovative tools and strategies such as the use of AI-based technology are needed to improve inclusivity, cost-effectiveness, and sustainability of screening processes.

This study aimed to assess users' perceptions of the usability and acceptance of the social robot "Furhat" for cardiometabolic risk assessment within a socioeconomically disadvantaged community in Uppsala, Sweden.

In this qualitative study, 13 semistructured interviews were conducted with participants living in socially disadvantaged areas within Uppsala, after they completed a CMD risk assessment delivered by the social robot. The study was conducted in one of the socioeconomically disadvantaged areas in Uppsala from October 19 to 26, 2023. Participants were purposefully sampled at different community events via phone or on the street to achieve the desired variation regarding personal characteristics such as age, gender, or area of living. The used interview guide for this study consisted of questions regarding the demographics, participants' experiences with the robot screening, and suggestions for improvements. A framework analysis approach was applied to the data.

Two themes were developed. The first theme Self-versus-others: a matter of perception, norms, and assumptions includes participants' perceptions of who would use the robot and why, if it was installed in the community. Participants perceived older individuals, immigrants, and, in some instances, women to be less interested in the robot screening or as having a harder time participating in it. However, there were between-group variations, especially among men and women, with participants often discounting opinions ascribed to their group by others. The second theme The robot is good, but humans are better captures participants' actual experiences of the interaction with the social robot once they have started the interaction. Although participants enjoyed the interaction with the robot, perceived it as nonjudgmental, and would recommend it to others, most would prefer conducting the screening with a human. Two major contributors for this preference were language barriers experienced during the robot-participant interaction, as well as their wish for more interactive, emotionally responsive, and communicative features of the robot.

This study provides insights into users' perceptions of the usability and acceptance of a social robot for risk assessment in a community context, which can help inform the further development of this technology for health screening in a community context. In the future, the robot could be further developed to conduct risk assessments in multiple languages and offer a broader service to users, such as providing appropriate information related to healthy and active living.

Precise visualization of vascular structures is crucial for planning and performing stent-assisted interventions in cerebral aneurysms. Traditional 2D imaging frequently lacks sufficient spatial information, which restricts clinicians' ability to evaluate vessel morphology, branching patterns, and how stents would interact with the vessel wall. This paper introduces an integrated visual support platform that unites workflow-driven medical image processing, numerical simulation of stent deployment, and augmented reality (AR) visualization via Microsoft HoloLens. The platform features a configurable workflow engine to handle medical data processing covering: vessel segmentation, medial-axis computation, mesh creation, and region-of-interest definition, followed by interactive simulation of stent expansion using computationally efficient approximation techniques. The resulting 3D models of the vasculature and stent are displayed in a dedicated AR environment that supports gesture-based interaction, real-time stent adjustment, and immersive navigation inside the vessels. This system provides intraoperative decision support by enabling clinicians to analyze stent placement, aneurysm coverage, and possible geometric limitations, and it also supports replay of simulations for training and educational purposes. The work shows that integrating 3D imaging, numerical modeling of stent-vessel interactions, and augmented reality can markedly improve precision, safety, and situational awareness in neurointerventional procedures.

Testosterone replacement therapy (TRT) is a standard treatment for men with hypogonadism, offering potential benefits including improvements in sexual function, body composition, bone mineral density, mood, and metabolic health. However, its cardiovascular safety remains uncertain due to conflicting evidence.

To assess the cardiovascular safety of testosterone replacement therapy in middle-aged and older men.

PubMed, Web of Science, EMBASE and the Cochrane Library databases were searched for randomized-controlled trials (RCTs) published up to July 25, 2024. The Cochrane Handbook for Systematic Reviews of Interventions, version 6.0, guided our meta-analysis. PROSPERO registration number 42,023,421,479.

This meta-analysis included 31 RCTs with a total of 9,437 participants, and treatment durations ranged from 40 days to 36 months. TRT was associated with significant reductions in total cholesterol (WMD: -10.20; 95% CI: -14.52, -5.88 mg/dL; P = 0.005), triglyceride (WMD: -7.03; 95% CI: -12.25, -1.81 mg/dL; P = 0.008), and low-density lipoprotein (WMD: -6.64; 95% CI: -8.65, -4.63 mg/dL; P < 0.00001), whereas no significant change was observed in high-density lipoprotein cholesterol (WMD: -1.39; 95% CI: -3.12, 0.35 mg/dL; P = 0.12), compared with placebo. Additionally, TRT significantly prolonged the exercise time to the onset of 1-mm ST-segment depression during treadmill exercise testing (single-dose to 14 weeks; WMD: 67.37; 95% CI: 55.05, 79.69 s; P < 0.00001), and reduced carotid intima-media thickness (12-36 months; WMD: -0.03; 95% CI: -0.05, -0.02 mm; P = 0.0003). Among nonfatal cardiovascular events, a potential arrhythmia safety signal was observed (6598 participants, OR: 1.58; 95% CI: 1.21, 2.05; P = 0.0007).

TRT appears to reduce overall cardiovascular risk factors in middle-aged and older men with low or low-normal testosterone levels, but the clinical significance of the observed arrhythmia signal remains uncertain.

Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interrelated progression of metabolic dysfunction, chronic kidney disease, and vascular risk. The hemoglobin glycation index (HGI), a marker of inter-individual glycation heterogeneity beyond fasting glycemia, has been associated with adverse cardiovascular outcomes; however, its role in early-stage CKM syndrome remains unclear. We investigated the associations of baseline HGI and cumulative HGI (CumHGI) with incident cardiovascular and cerebrovascular events in adults with CKM stages 0-3.

We analyzed 3,783 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (2011-2018) without baseline cardiovascular or cerebrovascular disease. Baseline HGI was assessed using a residual-based approach and analyzed as quartiles and a median-based dichotomous variable. CumHGI was calculated as the arithmetic mean of HGI measured in 2011 and 2015, reflecting average long-term glycation discordance. Incident cardiovascular and cerebrovascular events were evaluated using Kaplan-Meier curves, multivariable Cox proportional hazards models, and restricted cubic spline analyses.

During follow-up, 904 participants (23.9%) developed incident cardiovascular or cerebrovascular events. Compared with the lowest quartile of baseline HGI, adjusted hazard ratios were 1.24 (95% CI 1.02-1.49) for Q2, 1.30 (1.08-1.57) for Q3, and 1.24 (1.02-1.50) for Q4. High CumHGI was also associated with increased risk (HR 1.26, 95% CI 1.10-1.44). Associations were approximately linear across exposure levels. In models including conventional risk factors, addition of HGI or CumHGI did not materially improve discrimination (AUC 0.658 vs. 0.659 and 0.660, respectively).

Higher baseline HGI and higher cumulative HGI were associated with increased risk of incident cardiovascular and cerebrovascular events in adults with early-stage CKM syndrome. These findings suggest that glycation discordance is associated with cardiovascular risk in this preclinical population; however, HGI-derived metrics provide limited incremental discrimination beyond established risk factors and may be more informative as risk-associated biomarkers than as standalone prediction tools.