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Preterm birth, affecting about 10% of pregnancies, significantly contributes to perinatal morbidity and mortality. Recent research indicates that metabolomics could enhance pregnancy outcomes and reduce costs by identifying biomarkers related to common pregnancy complications. Our team focused on analyzing amniotic fluid collected during the second trimester to identify potential biomarkers for preterm birth using 1H-NMR metabolomic analysis. We compared amniotic fluid samples from women who delivered prematurely with those who delivered at term. Multivariate principal component analysis revealed dimethylglycine, glucose, myo-inositol, and succinic acid as potential biomarkers for preterm birth prognosis and early diagnosis. Further analysis demonstrated distinct regulation patterns of these metabolites in relation to fetal growth centiles. For instance, dimethylglycine and glucose were upregulated in fetuses above the 20th centile, while citrate and succinate were upregulated in those below it. With Area Under the Curve (AUROC) values over 0.75 and p-values less than 0.05, these metabolites show promise as reliable biomarkers for predicting fetal growth restriction. This approach could significantly impact maternal-fetal medicine by facilitating early diagnosis and personalized interventions. Future research should focus on validating these findings in larger populations and exploring the underlying mechanisms of metabolite regulation.

Abstract Medication can affect the gut microbiota composition and function. The aim of this study was to investigate connections between use of common non-antibiotic medicines and the gut microbiota composition and function in a large Swedish cohort (N = 2223). Use of 67 medications and polypharmacy (≥ 5 medications), based on self-reported and prescription registry data, were associated with the relative abundance of 881 gut metagenomic species (> 5% prevalence) and 103 gut metabolic modules (GMMs). Altogether, 97 associations of 26 medications with 40 species and of four medications with five GMMs were observed (false discovery rate

Pyrus communis (P. communis) is the most cultivated and consumed species of pear within the European continent. This fruit has been a staple in Greece since ancient times, hence the name “Gift of the Gods”. Given the extensive utilization of this fruit in the industrial sector and the focus on the exploitation of by-products to create new food and beverage products, the present research aimed to enhance the antioxidant activity of the P. communis peel through the implementation of a multifactor extraction system. Increased total polyphenols and ascorbic acid concentration, and enhanced antioxidant activity through radical scavenging and Fe3⁺ to Fe2⁺ reduction, all assist in boosting the health benefits of the extracts. The results indicated that the best conditions for compound yields were a 75% v/v hydroethanolic concentration, an extraction temperature of 80 °C, and 30 min of extraction time. Under the optimal conditions, the total polyphenol content was up to 4.98 mg of gallic acid equivalents (GAE)/g dried weight (dw). The radical scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) method was expressed as 18.36 μmol ascorbic acid equivalents (AAE)/g dw, while by the ferric-reducing antioxidant power (FRAP) method, it was 35.09 μmol AAE/g dw. Finally, the amount of ascorbic acid was measured at 20.16 mg/100 g dw. In this regard, this study has been conducted to assess and enhance the level of these bioactive compounds in the extract of the P. communis peel, leading to an extract with several applications in different food and beverage industries.

Purpose: This paper aims to investigate the relationship between prospective teachers' cultural profiles and service quality expectations in a pedagogical training program in Greece. Design/methodology/approach: Using the EppekQual scale and an alternative Hofstede's cultural scale, 113 prospective teachers in a Greek training program were surveyed. The study uses descriptive statistics, correlation analysis and multiple regression, validating measurements through confirmatory factor analysis. Findings: Prospective teachers exhibit a low-power orientation and a preference for feminine values. Rejecting hierarchy correlates with quality expectations, especially in the curriculum dimension, emphasizing student-centric education. A positive correlation with acceptance/avoidance of uncertainty is observed, notably in learning outcomes and administrative services. The cultural aversion to ambiguity shapes individuals' prioritization of all quality dimensions. A realistic long-term perspective correlates positively with expectations in learning outcomes, aligning with Greek culture's emphasis on security. Contrary to expectations, a predilection for feminine values positively impacts service quality expectations, particularly in curriculum, learning outcomes and academic staff dimensions. The hypothesis related to individualism/collectivism is not substantiated, indicating a negative association with the curriculum dimension. Practical implications: Tailoring program designs to embrace student-centric and collaborative learning environments is recommended. Acknowledging cultural aversions to uncertainty, program flexibility and clarity are essential. Integrating career planning and mentorship aligns with realistic long-term perspectives. The need for a balanced approach to personal and intellectual development is also suggested. Originality/value: This study uncovers specific cultural dimensions that shape quality expectations within a Greek teacher training context.

This study explored the use of mandarin peels as an important source of health-promoting compounds by utilizing green methods (i.e., pulsed electric field and ultrasound-assisted extraction), along with conventional stirring. The impact of several extraction parameters, such as extraction duration, temperature, and solvent composition, on the recovery of bioactive compounds was evaluated through a response surface methodology. To identify the most effective conditions for all assays, a partial least-squares analysis was implemented. It was revealed that a combination of the above techniques was optimal at 80 °C for 30 min, with 75% v/v of ethanol in water as the extraction solvent. The concentration of bioactive compounds in the optimum extract had a total polyphenol content of 18.69 mg of gallic acid equivalents (GAE) per gram of dry weight (dw), and an ascorbic acid concentration of 18.25 mg/g dw. However, correlation analyses revealed a rather negative relationship between these bioactive compounds. The chromatographic analysis of optimum extracts supported this result by quantifying 20.53 mg/g dw of total individual polyphenols, with hesperidin being the dominant compound (13.98 mg/g dw). The antioxidant assays, including ferric-reducing antioxidant power and DPPH• inhibition activity, were measured at 123.21 and 65.12 μmol of ascorbic acid equivalents (AAE) per gram of dw, respectively. This research enhances the valorization of mandarin peels as a renewable source of bioactive compounds, providing the opportunity to generate high-added-value products from food waste in the food and pharmaceutical sectors.

Abstract Background There is an emerging need to systematically investigate the causes for the increased cesarean section rates in Greece and undertake interventions so as to substantially reduce its rates. To this end, the ability of the participating Greek obstetricians to follow evidence-based guidelines and respond to other educational and behavioral interventions while managing labor will be explored, along with barriers and enablers. Herein discussed is the protocol of a stepped-wedge designed intervention trial in Greek maternity units with the aforementioned goals in mind, named ENGAGE (ENhancinG vAGinal dElivery in Greece). Methods Twenty-two selected maternity units in Greece will participate in a multicenter stepped-wedge randomized prospective trial involving 20,000 to 25,000 births, with two of them entering the intervention period of the study each month (stepped randomization). The maternity care units entering the study will apply the suggested interventions for a period of 8–18 months depending on the time they enter the intervention stage of the study. There will also be an initial phase of the study lasting from 8 to 18 months including observation and recording of the routine practice (cesarean section, vaginal birth, and maternal and perinatal morbidity and mortality) in the participating units. The second phase, the intervention period, will include such interventions as the application of the HSOG (the Hellenic Society of Obstetrics and Gynecology) Guidelines on labor management, training on the correct interpretation of cardiotocography, and dealing with emergencies in vaginal deliveries, while the steering committee members will be available to discuss and implement organizational and behavioral changes, answer questions, clarify relevant issues, and provide practical instructions to the participating healthcare professionals during regular visits or video conferences. Furthermore, during the study, the results will be available for the participating units in order for them to monitor their own performance while also receiving feedback regarding their rates. Τhe final 2-month phase of the study will be devoted to completing follow-up questionnaires with data concerning maternal and neonatal morbidities that occurred after the completion of the intervention period. The total duration of the study is estimated at 28 months. The primary outcome assessed will be the cesarean section rate change and the secondary outcomes will be maternal and neonatal morbidity and mortality. Discussion The study is expected to yield new information on the effects, advantages, possibilities, and challenges of consistent clinical engagement and implementation of behavioral, educational, and organizational interventions described in detail in the protocol on cesarean section practice in Greece. The results may lead to new insights into means of improving the quality of maternal and neonatal care, particularly since this represents a shared effort to reduce the high cesarean section rates in Greece and, moreover, points the way to their reduction in other countries. Trial registration NCT 04504500 (ClinicalTrials.gov). The trial was prospectively registered. Ethics Reference No: 320/23.6.2020, Bioethics and Conduct Committee, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Background: Endometrial scratching (ES) remains controversial regarding its potential effectiveness in improvingpregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) duringhysteroscopy on reproductive outcomes in a population of oocyte recipients.Materials and Methods: A randomized controlled trial was conducted between 2020 and 2023 at the Third Departmentof Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessalonikiand “Assisting Nature Centre of Reproduction and Genetics”. The study population consisted of women whounderwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransferwith donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates werethe primary outcomes.Results: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 womenunderwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the twogroups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470).Conclusion: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterinepathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution beforethe implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).

Abstract Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Hemp, commonly known as Cannabis sativa L., is a medicinal plant species of the Cannabaceae family. For the efficient extraction of C. sativa leaves using the conventional stirring process with water as the solvent, three crucial extraction parameters (i.e., extraction duration, liquid–solid ratio, and temperature) were investigated through the response surface methodology (RSM). The concentrations of the extracted bioactive compounds (polyphenols, ascorbic acid, and carotenoids) showed significant variations in the RSM design points, suggesting the importance of finding the optimal extraction conditions in which liquid–solid ratio and extraction temperature were found to have the highest impact. Further analysis was conducted on the optimal extract employing several assays to determine their polyphenol content, total carotenoid content, color evaluation, anti-inflammatory activity, and antioxidant capacity through FRAP, DPPH, and H2O2 assays. A low extraction time (30 min) at 50 °C and a high liquid–solid ratio (50:1) were required for the highest possible yield of polyphenols. The total polyphenol content was determined to be 9.76 mg gallic acid equivalents/g under optimum conditions, with pelargonin being the most abundant polyphenol (1.51 mg/g) in C. sativa extracts. Ascorbic acid was measured at 282.23 μg/g and total carotenoids at 356.98 μg/g. Correlation analyses revealed that anti-inflammatory activity was negatively correlated with specific polyphenols. As determined by DPPH (27.43 μmol ascorbic acid equivalents (AAE)/g), FRAP (49.79 μmol AAE/g), and H2O2 (230.95 μmol AAE/g) assays, the optimized aqueous extract showed a high antioxidant capacity. Furthermore, it demonstrated considerable anti-inflammatory activity at 17.89%, with the potential to increase to 75.12% under particular extraction conditions. Given the high added-value of the aqueous extracts, the results of this study highlight the potential utility of C. sativa leaves as a source of health-improving antioxidant compounds in the pharmaceutical and food industries.

Abstract Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional “reprogramming” of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

In recent decades, three major volcanic eruptions of different intensity have occurred (Mount Agung in 1963, El Chichón in 1982 and Mount Pinatubo in 1991), with reported climate impacts on seasonal to decadal timescales that could have been potentially predicted with accurate and timely estimates of the associated stratospheric aerosol loads. The Decadal Climate Prediction Project component C (DCPP-C) includes a protocol to investigate the impact of volcanic aerosols on the climate experienced during the years that followed those eruptions through the use of decadal predictions. The interest of conducting this exercise with climate predictions is that, thanks to the initialisation, they start from the observed climate conditions at the time of the eruptions, which helps to disentangle the climatic changes due to the initial conditions and internal variability from the volcanic forcing. The protocol consists of repeating the retrospective predictions that are initialised just before the last three major volcanic eruptions but without the inclusion of their volcanic forcing, which are then compared with the baseline predictions to disentangle the simulated volcanic effects upon climate. We present the results from six Coupled Model Intercomparison Project Phase 6 (CMIP6) decadal prediction systems. These systems show strong agreement in predicting the well-known post-volcanic radiative effects following the three eruptions, which induce a long-lasting cooling in the ocean. Furthermore, the multi-model multi-eruption composite is consistent with previous work reporting an acceleration of the Northern Hemisphere polar vortex and the development of El Niño conditions the first year after the eruption, followed by a strengthening of the Atlantic Meridional Overturning Circulation the subsequent years. Our analysis reveals that all these dynamical responses are both model- and eruption-dependent. A novel aspect of this study is that we also assess whether the volcanic forcing improves the realism of the predictions. Comparing the predicted surface temperature anomalies in the two sets of hindcasts (with and without volcanic forcing) with observations we show that, overall, including the volcanic forcing results in better predictions. The volcanic forcing is found to be particularly relevant for reproducing the observed sea surface temperature (SST) variability in the North Atlantic Ocean following the 1991 eruption of Pinatubo.

Each year, a substantial amount of food is discarded around the globe. A significant portion of this waste consists of by-products derived from Citrus fruits such as lemons. The purpose of this research is to examine the polyphenol extraction and the antioxidant ability of lemon peel using cloud point extraction (CPE), a sustainable approach. CPE was conducted using three steps with a 20% w/v concentration of Span 20 as the surfactant, which has a critical micellar concentration of 6.13 × 10−5 mol/L. The pH was set at 7 and a salt concentration of 20% was maintained at 45 °C for 20 min. The subsequent outcomes of the analysis were obtained: total polyphenol content (TPC): 526.32 mg gallic acid equivalents per liter; total flavonoid content (TFC): 90.22 mg rutin equivalents per liter; FRAP, DPPH, and hydrogen peroxide assays: 2.40, 2.68 and 1.03 mmol ascorbic acid equivalents per liter, respectively, and 168.63 mg/L ascorbic acid content. The quantification of the polyphenolic compounds through High-Performance Liquid Chromatography showed that the most abundant compounds in the lemon peels are eriocitrin (159.43 mg/L) and hesperidin (135.21 mg/L). The results indicate that the proposed CPE technique is successful in extracting antioxidant compounds from lemon peels. The generated extracts have the potential to be exploited as dietary additives to enhance human health and can also be utilized for nutraceuticals or pharmaceutical purposes.

Background Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity.Methods We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs. We also used the entire set of summary statistics to compute polygenic risk scores (PRSs) and carried out comparisons at the population and continental level.Results We observed the strongest differences among continental regions for the five top SNPs in chromosome 3. European, American, and South Asian populations showed similar LD patterns. Average PRSs in South Asian and American populations were consistently higher than those observed in Europeans. While PRS distributions were similar among South Asians, the American populations showed striking differences among them.Conclusions Considering the caveats of PRS transferability across ethnicities, our analysis showed that American populations present the highest genetic risk score, hence potentially higher propensity, for COVID-19 severity. Independent validation is warranted with additional summary statistics and phenotype data.

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

The coefficients of the chain polynomial of a finite poset enumerate chains in the poset by their number of elements. The chain polynomials of the partition lattices and their standard type \(B\) analogues are shown to have only real roots. The real-rootedness of the chain polynomial is conjectured for all geometric lattices and is shown to be preserved by the pyramid and the prism operations on Cohen-Macaulay posets. As a result, new families of convex polytopes whose barycentric subdivisions have real-rooted \(f\)-polynomials are presented. An application to the face enumeration of the second barycentric subdivision of the boundary complex of the simplex is also included.Mathematics Subject Classifications: 05A05, 05A18, 05E45, 06A07, 26C10Keywords: Chain polynomial, geometric lattice, partition lattice, real-rooted polynomial, flag \(h\)-vector, convex polytope, barycentric subdivision

Automated Driving Systems (ADS) are aimed to improve traffic efficiency and safety, however these systems are not yet capable of handling all driving tasks in all types of road conditions. The role of a human driver remains crucial in taking over control, if an ADS fails or reaches its operational limits. Takeover performance of human drivers in authority transitions is typically assessed by means of the takeover time (TOT) taken within an available time budget (TB). This approach assumes a uniform perception and reaction time of human drivers in ADS disengagements, and does not include the time needed to execute the actual driving maneuver required to ensure safety. This paper aims to develop and test a set of new indicators to reflect takeover performance and its safety attributes, namely the ‘time to control’ (TC) and the ‘safe time budget’ (STB), in which the actual task execution (i.e. braking) time is taken into account, in addition to the perception and reaction time. It also proposes new thresholds for identifying critical conflicts in takeover situations and assessing the safety of authority transitions. A traffic simulation experimental setup is used with mixed traffic of conventional vehicles and ACC/CACC platoons in order to test these indicators and thresholds. The results suggest that the time difference between TC and STB is a more sensitive and potentially more realistic safety indicator, as it may capture the variability of driver behavior in takeovers and identify critical conflicts, as well as virtual crashes, that would not have been identified by the previously used indicators (TOT and TB). Takeover performance worsens when the speed difference of the vehicles involved is higher, and the initial speed of the rear vehicle is higher. These findings can be useful towards a more dynamic design of takeover request strategies.