Background Dilatation of the common bile duct (CBD) after cholecystectomy is frequently observed during follow-up imaging; however, its extent and clinical implications remain incompletely defined. Distinguishing physiological postoperative ductal enlargement from pathological dilatation is essential to avoid unnecessary diagnostic evaluation. This study aimed to compare CBD diameter in post-cholecystectomy patients with non-operated controls and to assess its association with time since surgery, age, and body mass index (BMI). Materials and methods This retrospective observational study included 165 adult patients who underwent abdominal ultrasound examination, comprising 91 post-cholecystectomy patients and 74 controls with an intact gallbladder. The CBD diameter was measured in the suprahilar segment. Group differences were evaluated using independent t-tests and chi-square tests. Logistic and linear regression analyses were used to assess predictors of CBD dilatation and continuous diameter change. All multivariable models were adjusted for age, sex, and BMI. Results CBD diameter was significantly greater in post-cholecystectomy patients compared with controls (6.61 mm vs. 4.56 mm; p < 0.001). Dilatation ≥7 mm occurred in 38.5% of post-cholecystectomy patients versus 5.4% of controls (p < 0.001), and prior cholecystectomy remained a strong independent predictor of dilatation after adjustment (aOR = 14.583; 95% CI: 4.449-47.807). Using a fixed ≥7 mm cutoff, increasing age was associated with lower odds of categorical CBD dilatation, whereas sex and BMI were not significant predictors. Linear regression analyses demonstrated a significant positive association between CBD diameter and both time elapsed since surgery and age, indicating gradual ductal enlargement over time. Marked dilatation (>10 mm) was uncommon and did not reach statistical significance in relation to cholecystectomy. Conclusion Cholecystectomy is associated with measurable and progressive enlargement of the CBD. While CBD diameter increases gradually with advancing age and postoperative duration, categorical dilation thresholds are more strongly influenced by surgical status than by age alone. Recognition of this expected postoperative anatomical pattern may help clinicians avoid unnecessary imaging and interventions in asymptomatic patients.

BACKGROUND One Class Modelling (CM) is popular among chemometricians, but not well known among omics scientists in general. One issue is that typical CM approaches, including SIMCA, often result in unsatisfactory results due to e.g. large variation, centring and scaling issues, sparsity, outliers, and non-linearities in typical omics data. These effects can cause an inflated decision boundary (of the target class), thereby returning many false positives (of non-target cases). Tree-based techniques are by nature resistant to these challenges. In this study we explore tree-Based SIMCA variants in omics scenarios and compare to existing strategies. RESULTS We present a non-linear form of SIMCA by making use of sample proximities obtained through Unsupervised Random Forest and Isolation Forest (termed URF-SIMCA and IF-SIMCA). We compare accuracy of the algorithms with (traditional) SIMCA, one-class support vector machines, and isolation forest. This comparison was based on five (previously published) clinical omics datasets and the wine-dataset. URF-SIMCA showed superior behaviour. Using the pseudo-sampling principles, an interpretation could be made on the important features for the separation between the target and non-target classes. Using the wine-dataset, we empirically show that these directly relate to information obtained through two-class algorithms. Moreover, feature trajectories in the score- and orthogonal distance spaces further enable interpretability of the model. SIGNIFICANCE URF-SIMCA offers an easy to use extension of SIMCA, which deflates the variance of the target class, allowing for better separation. The increased modelling performance comes at the cost of feature interpretation, but this can be tackled using the pseudo-sampling principle.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder that typically affects young adults and is primarily characterized by demyelinating lesions in the central nervous system (CNS). According to the Revised McDonald Criteria, the clinical diagnosis of MS can be established based on a combination of clinical observations, the presence of focal lesions in at least two distinct CNS areas on magnetic resonance imaging (MRI) and the detection of specific oligoclonal bands in the cerebrospinal fluid. Conventional MRI remains a cornerstone of MS diagnosis and disease monitoring, providing high-resolution assessments of lesion burden and brain atrophy. In addition, advanced MRI methods are increasingly applied in research settings to probe myelin integrity, iron deposition, and biochemical changes, with the potential to complement established diagnostic workflows in the future. Despite remarkable advances in the management of MS over the past two decades, complex differential diagnoses and the lack of effective imaging tools for therapy monitoring remain major obstacles, thus channeling the development of innovative molecular imaging probes that can be harnessed in clinical practice. Indeed, positron emission tomography (PET) has a significant potential to advance the contemporary diagnosis and management of MS. Given the solid body of evidence implicating myelin dysfunction in the pathophysiology of MS, myelin-targeted imaging probes have been developed, and are currently under clinical evaluation for MS diagnosis and therapy monitoring. In parallel, ligands for the 18 kDa translocator protein (TSPO) and the cannabinoid receptor type 2 (CB2R) have been employed to capture neuroinflammatory processes by visualizing microglial activation, while other tracers allow the assessment of synaptic integrity across various disease stages of MS. Further, PET probes have been employed to delineate the role of activated microglia and facilitate the assessment of synaptic dysfunction across all disease stages of MS. This review discusses the challenges and opportunities of translational molecular imaging by highlighting key molecular concepts that are currently leveraged for diagnostic imaging, patient stratification, therapy monitoring and drug development in MS. Moreover, we shed light on potential future developments that hold promise to advance our understanding of MS pathophysiology, with the ultimate goal to provide the best possible patient care for every individual MS patient.

Type 1 conventional dendritic cells (cDC1s) acquire and cross-present tumor antigens to prime CD8⁺ T cells. Whether this selects for specific neoantigens is unclear. DNGR-1 (CLEC9A), a cDC1 receptor for F-actin exposed on dead cells, promotes cross-presentation of cell-associated antigens. Here we show that DNGR-1-deficient mice develop chemically induced tumors more rapidly and at higher incidence, and these are more frequently rejected on transplantation into wild-type recipients. Whole-exome sequencing reveals enrichment of predicted neoantigens derived from mutated F-actin-binding proteins. Consistent with this observation, tethering model antigens to F-actin enhances DNGR-1-dependent cross-presentation. These results suggest that DNGR-1-mediated recognition of F-actin exposed by dead cancer cells favors priming of CD8⁺ T cells specific for cytoskeletal neoantigens, which can then drive immune escape of cancer cells lacking or reverting those mutations. Thus, neoantigen cross-presentation by cDC1 can determine the immune visibility of the tumor mutational landscape and sculpt cancer evolution by immunoediting. Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.

For patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) who are not considered to be at very high mortality risk at the time of admission, current clinical guidelines advocate for coronary angiography (CAG) to be performed during hospitalization. Therefore, in these patients, introduction of novel non-invasive methods for prediction of severity of coronary artery disease is needed in order to identify patients who could benefit from CAG earlier during their hospital stay. The aim of this study was to evaluate the association between severity of CAD and echocardiographically assessed global longitudinal strain (GLS) and post-systolic shortening (PSS) of left ventricular myocardium in patients with NSTE-ACS. This prospective cross-sectional study included patients admitted to the cardiology clinic with the diagnosis of NSTE-ACS. Inclusion criteria were: preserved left ventricular ejection fraction (>50%), absence of regional wall motion abnormalities and indication for CAG set by interventional cardiologist and performed during the hospital stay. Patients who were estimated to be at very high mortality risk were excluded from the study. In addition to conventional echocardiography parameters, post-systolic shortening index (PSI), LAD specific PSI (PSI-LAD) and GLS were measured. PSI was calculated as the average PSS across all 17 myocardial segments, generated from strain curves, while PSI-LAD was calculated as the average PSS across 10 myocardial segments vascularized by LAD. The severity of CAD was assessed using the SYNTAX score. Significant coronary artery stenosis was defined as ≥90% narrowing in one of the three main epicardial arteries. Among the 70 enrolled patients, 45.7% (n=32) were diagnosed with unstable angina, while 54.3% (n=38) were diagnosed with NSTEMI. There was a significant positive correlation between SYNTAX score and both GLS (rho=0.504; p<0.001) and PSI (rho=0.249; p=0.035). Patients with significant LAD stenosis had higher GLS values (-14.88±2.53% vs. -17.02±3.23%, p=0.001) and higher PSI-LAD values (10.65 [3.13–18.53] vs. 4.2 [2.53–8.3], p=0.015) compared to those without significant LAD stenosis. GLS emerged as an independent predictor of significant stenosis on one of three main epicardial arteries (p=0.001; OR 1.43; 95% CI: 1.16–1.76). Both PSI-LAD and GLS demonstrated significant predictive value for LAD stenosis, with AUCs of 0.672 (p=0.020) and 0.675 (p=0.019), respectively. In addition to other known clinical factors, GLS and PSI may serve as feasible non-invasive echocardiographic parameters for additional risk stratification in NSTE-ACS patients who are not at very high risk. These measures could help identify individuals who might benefit from earlier CAG during hospitalization. Further research is warranted to develop precise risk assessment models incorporating these parameters.

Human gustatory function is a complex trait combining taste, smell, and touch required for the safety and quality assessment of ingested food. Taste dysfunction is one of the most prominent symptoms of COVID‐19 that was reversible in most cases, but some patients reported permanent changes in their perception of different food sources. This symptom brought attention to the complexity of the regulation of smell and taste and their potential use in diagnostics and treatment of acute and chronic taste disorders. We investigated the genetic association of candidate genes with SARS‐CoV‐2 infection–related dysgeusia. A total of 96 individuals with confirmed virus infection were divided into groups according to the presence of self‐reported taste dysfunction and genotyped using a custom Illumina gene panel. Out of 18 functionally related taste genes, statistically significant differences were observed for HCN4 variants c∗2393C > G (p = 0.013) and c.2556G > A (p = 0.026), PLCB2 variants c.3037‐55T > C (p = 0.019) and c.582+958_582+959inv (p = 0.021), and TAS1R1 variant c.1594+41G > A (p = 0.03), which indicate possible association to taste dysfunction in response to virus infection.

Background/Objectives: Southeastern Europe and Croatia have served as a genetic crossroads between the Near East and Europe since prehistoric times, shaped by numerous and repeated migrations. By integrating 19 newly generated ancient genomes with 285 previously published ancient genomes from Croatia, we investigated patterns of maternal and paternal landscapes from the Neolithic, Bronze, and Iron Ages through to the Antiquity and medieval periods, as well as the modern Croatian population. Methods: Ancient DNA extraction from human remains and library preparation were conducted in dedicated clean-room facilities, followed by high-throughput sequencing on the Illumina platform. Sequencing data were analyzed with established pipelines to determine mitochondrial and Y-chromosomal haplogroups and the genetic sex of individuals. Results: New ancient data reveal a predominantly European maternal profile, dominated by haplogroups H, U, and HV0, whereas Y-chromosomal lineages are characterized by J subclades and R1a, with limited representation of R1b and the absence of I2a. When combined with published ancient Croatian genomes, the results reveal similar haplogroup diversity and patterns, as well as the expansion of mtDNA haplogroup H over time and a substantial increase in Y-chromosome R1a and I2a haplogroup frequency from the prehistoric to the modern period. Conclusions: Although the analyzed samples are heterogeneous and originate from different historical periods, their genetic signatures conform to the broader patterns expected for the region. In a wider context, the ancient Croatian mitochondrial data reveal stronger genetic persistence from prehistory to modern times, unlike paternal lineages, which show significantly higher divergence.

Exposure to volatile organic compounds (VOCs) such as benzene, styrene, toluene and formaldehyde is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of VOCs exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. The literature search led to 57 studies included in the review. Of these, 50 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to benzene (1.59, 95% CI: 0.94, 2.24), styrene (0.87, 95% CI: 0.23, 1.51), formaldehyde (0.39, 95% CI: -0.15, 0.92) and other organic solvents (2.14, 95% CI: 1.48, 2.81). Results originate mainly from studies on workers, with only a few studies on environmental benzene exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.81, 95% CI: 1.26, 2.36, n = 28) than studies from high-income countries (0.87, 95% CI: 0.49, 1.24, n = 22). This difference between middle- and high-income countries may be due to differences in exposure levels or exposure assessment. However, this might not be the only reason, as sensitivity analysis indicates that effect sizes are at risk of comet assay measurement bias, as 78% (39 out of 50 studies) and 60% (30 studies) have not reported the use of assay controls and blinded analysis of samples, respectively. Relatively few studies have a high risk of bias due to an inadequate comet assay procedure description (14%, 7 studies) and exposure misclassification (16%, 8 studies). Limitations of the study were the differences in protocols, comet descriptors, exposure assessment and control for confounding factors among the studies. In conclusion, this systematic review and meta-analysis shows that exposure to VOCs - benzene, styrene, formaldehyde and others - is associated with increased levels of DNA strand breaks in human leukocytes.

Anaesthetic gases are agents used to induce and maintain general anaesthesia during surgical procedures. Common examples include sevoflurane, isoflurane, and desflurane, which act by depressing the central nervous system to produce unconsciousness and analgesia. These gases are administered through a vaporiser and inhaled via a mask or endotracheal tube. While effective, they can contribute to environmental pollution and increase the risk of occupational exposure. Medical personnel working in operating or post-operating facilities are unavoidably exposed to anaesthetic gases. Several adverse health effects have been associated with anaesthetic gas exposure; therefore, this review aims to summarise findings on DNA strand breaks, assessed by the comet assay in leucocytes of exposed medical workers. Standardised mean differences (SMDs) have been calculated by random effects models. The meta-analysis included 16 studies. Of these, 11 showed statistically significant increased levels of DNA strand breaks, whereas another five studies showed no significant effect. Overall, there is an increased level of DNA strand breaks in exposed subjects in unadjusted analysis (SMD = 1.17, 95 % confidence interval: 0.71, 1.62) as well as analysis adjusted for missing studies by the trim-and-fill method (SMD = 0.53, 95 % confidence interval: -0.14, 1.21). In conclusion, this systematic review and meta-analysis demonstrate that exposure to anaesthetic gases in an occupational setting induces primary DNA damage in human leucocytes, warranting further research to minimise any adverse effects on exposed medical personnel. Besides, the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies is proven.

Humans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95% CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95% CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95% CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.

ABSTRACT Background Early childhood and education centres (ECECs) are key settings in the promotion of healthy levels of outdoor play and napping among young children. Aim This study aimed to examine the associations between environmental factors and preschoolers' outdoor play and napping in ECECs across an international sample. Methods Data from 187 ECECs in 27 countries (22 low‐ and middle–income countries) that participated in the third pilot phase (January 2021–April 2025) of the SUNRISE International Study were analysed. The director of each ECEC completed a questionnaire which asked if children participating in the SUNRISE Study were unable to participate in outdoor play and nap time due to a range of environmental barriers. Results Forty‐six percent (n = 86) of ECECs reported at least one environmental factor that prevented preschoolers' outdoor play, and 20% (n = 37) reported at least one factor that disrupted naptime. Hot and cold temperatures, rain and other factors were observed as barriers to outdoor play across regions and country income levels. Indoor noise, extreme temperatures, brightness and lack of space were reported as disrupting preschoolers' naptime across regions and country income levels. For rural ECECs, hot temperatures and lack of space were barriers for outdoor play and napping, respectively. Conclusions Context‐specific strategies are required to create climate‐resilient outdoor play spaces and more restful napping environments to optimise early childhood development within ECECs.

Abstract In this study, the possibility of using slag derived from hydrogen-plasma reduction of red mud (H2RMS) as a low-cost adsorbent for phosphate removal from aqueous solutions was investigated. Batch adsorption experiments were conducted to evaluate the effects of contact time, solution pH, sorbent dosage, and initial phosphate concentration under controlled laboratory conditions. Phosphate concentrations were determined spectrophotometrically using the ammonium molybdate method. These results demonstrated that phosphate adsorption onto H2RMS is strongly pH-dependent, with maximum removal efficiency achieved under acidic conditions (pH ≈ 2). Adsorption equilibrium was achieved after approximately 18 h of contact time. Increasing the sorbent dosage enhanced phosphate removal efficiency, although improvements became marginal beyond a dosage of 10 g/L. At optimal conditions, phosphate removal efficiency of approximately 90% was achieved. These findings indicate that H2RMS shows significant potential as an effective adsorbent for phosphate removal, offering a possible pathway for the valorization of metallurgical waste residues.