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.

Background Takotsubo syndrome (TTS) is considered rare in premenopausal women and presents as a transient, nonischemic acute heart failure with relatively fast, spontaneous recovery of myocardial function. It is typically characterized by apical ballooning, or less commonly, akinesia of the midsegments of the left ventricle, commonly triggered by acute emotional stress and therefore also known as “broken‐heart syndrome” and “stress‐induced cardiomyopathy.” Case In this article, we present a case of a 26‐year‐old female patient pregnant with dichorionic–diamniotic twins, who developed TTS peripartum following emergency cesarean section due to premature membrane rupture at 33 weeks of gestation. On the first postoperative day, she suddenly developed dyspnea with desaturation to 80% oxygen on pulse oximetry. She became hypotensive and tachycardic. An electrocardiogram revealed T‐wave inversion in aVL and ST‐segment changes in leads V4–V6. An assay of cardiac enzymes was elevated. In order to exclude acute myocardial infarction and pulmonary thromboembolism, CT angiography of the lungs and coronary arteries was performed. Transthoracic echocardiography revealed akinesia of the midsegments of the left ventricle and a moderately reduced ejection fraction. After the introduction of cardioprotective therapy with bisoprolol 1.25 mg, her ECG normalized. She was normotensive, normocardic, and oxygen saturation on pulse oximetry was within the normal range. The echocardiogram on the 11th postpartum/postoperative day revealed partial spontaneous regression of segmental motion disorders and improvement of left ventricular ejection fraction. On the day of discharge, the patient was eupnoic with normal oxygen saturation without supplemental oxygen. She was normotensive and normocardic. The uterus was appropriately contracted, lochia normal, and the wound was healing normally. She was breastfeeding. She was prescribed with bisoprolol 1.25 mg once daily until follow‐up heart ultrasound 6 months after the discharge. Conclusions In a state that suggests cardiac emergency, TTS should be considered among other differential diagnoses, such as myocardial infarction, acute myocarditis, pulmonary embolism, and peripartal cardiomyopathy. It is very important to differentiate TTS from peripartal cardiomyopathy because of the differences in management and prognosis. The clinical awareness and holistic approach to differential diagnosis are crucial for management of acute heart failure after cesarean section.

In obstetrics, diazepam is commonly used to treat anxiety, insomnia and as a second‐line treatment for seizures in preeclampsia and eclampsia. However, the effects of diazepam on the oxidative balance and vascular function of the umbilical circulation are still insufficiently studied. In this study, we investigated the effects of suprapharmacological concentrations of diazepam in an in vitro model of human umbilical artery (HUA) injury, induced by incubation with 1 mM homocysteine, representing experimental conditions that mimic hyperhomocysteinemia. HUAs were divided into four groups: control (C), diazepam (D) alone (100 μmol/L), homocysteine (Hcy) alone (1 mM), and combined treatment (HcyD). For oxidative stress assays, data were obtained from 8–10 individual HUA samples per group, with lipid peroxidation, nitrite (NO2 −) levels, and SOD, CAT, and GSH activities determined spectrophotometrically. Histological and TUNEL analyses were performed in triplicate (n = 3 per group), whereas vascular reactivity experiments, using an organ bath system, included six individual vessel samples per group. Statistical analysis was performed using the paired Student′s t‐test (p < 0.05). Diazepam alone significantly reduced superoxide dismutase (SOD) activity, indicating an apparent impairment of antioxidant defenses. In contrast, concomitant treatment under hyperhomocysteinemia lowered the levels of thiobarbituric acid reactive substances (TBARSs) and NO2 −, suggesting partial protection against lipid peroxidation and nitrosative stress. Histologically, diazepam preserved arterial structure with minor subendothelial changes, whereas cotreatment reduced homocysteine‐induced endothelial disruption, smooth muscle disarray, and medial connective tissue loss. Apoptotic index was significantly reduced with cotreatment comparing to hyperhomocysteinemia, whereas diazepam alone showed values similar to control. Functionally, diazepam significantly reduced serotonin‐induced contraction of HUAs, but this vascular effect was attenuated under hyperhomocysteinemic conditions. Overall, concomitant treatment with diazepam partially attenuated oxidative and structural changes induced by hyperhomocysteinemia in our experimental setting, in a preclinical model mimicking selected pathophysiological aspects of preeclampsia.

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.