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Eva Pipan,1 Alexandros Apostolou,2 Maria Bograkou,2 Petra Brooks,2 Patrick Vigren,2 Helena Gauffin2 1University Medical Centre Ljubljana, Ljubljana, Slovenia; 2Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenCorrespondence: Eva PipanUniversity Medical Centre Ljubljana, University of Ljubljana, Ljubljana, SloveniaEmail eva.pipan@yahoo.comIntroduction: The purpose of this study was to examine patients’ experiences of vagal nerve stimulation (VNS) with a special interest in patients with cognitive deficit (CD).Materials and Methods: An open, retrospective study was conducted on 82 patients with pharmacoresistant epilepsy, who were treated with VNS for at least 10 months. Based on the inability to live independently, they were divided into two groups: patients with cognitive deficit (CD group) and patients without cognitive deficit (non-CD group). A specially designed questionnaire was used for semi-structured interviews about patients’ experiences of VNS treatment.Results: Approximately one-third described a continuous reduction of seizure frequency of 50% or more and were regarded as responders. Fewer subjects in the CD group were responders than in the non-CD group. Approximately one-third of all subjects had no positive effect of VNS treatment. More CD patients described additional improvements and the most common were milder seizures and improved alertness. The most commonly reported adverse effect was hoarseness.Discussion: VNS treatment in patients without CD had better effect on seizure frequency reduction than in patients with CD, but many patients with CD reported other benefits from the treatment.Conclusion: Non-CD patients had higher seizure frequency reduction than CD patients during VNS treatment, but many CD patients described other benefits.Keywords: epilepsy, vagus nerve stimulation, cognitive deficit, cognitive dysfunction

Abstract Identifying cell-type-specific 3D chromatin interactions between regulatory elements can help decipher gene regulation and interpret disease-associated non-coding variants. However, achieving this resolution with current 3D genomics technologies is often infeasible given limited input cell numbers. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps, including regulatory interactions, from single-cell ATAC sequencing (scATAC-seq) data alone. ChromaFold uses pseudobulk chromatin accessibility, co-accessibility across metacells, and a CTCF motif track as inputs and employs a lightweight architecture to train on standard GPUs. Trained on paired scATAC-seq and Hi-C data in human samples, ChromaFold accurately predicts the 3D contact map and peak-level interactions across diverse human and mouse test cell types. Compared to leading contact map prediction models that use ATAC-seq and CTCF ChIP-seq, ChromaFold achieves state-of-the-art performance using only scATAC-seq. Finally, fine-tuning ChromaFold on paired scATAC-seq and Hi-C in a complex tissue enables deconvolution of chromatin interactions across cell subpopulations.

Abstract Background As digital healthcare services handle increasingly more sensitive health data, robust access control methods are required. Especially in emergency conditions, where the patient’s health situation is in peril, different healthcare providers associated with critical cases may need to be granted permission to acquire access to Electronic Health Records (EHRs) of patients. The research objective of this work is to develop a proactive access control method that can grant emergency clinicians access to sensitive health data, guaranteeing the integrity and security of the data, and generating trust without the need for a trusted third party. Methods A contextual and blockchain-based mechanism is proposed that allows access to sensitive EHRs by applying prognostic procedures where information based on context, is utilized to identify critical situations and grant access to medical data. Specifically, to enable proactivity, Long Short Term Memory (LSTM) Neural Networks (NNs) are applied that utilize patient’s recent health history to prognose the next two-hour health metrics values. Fuzzy logic is used to evaluate the severity of the patient’s health state. These techniques are incorporated in a private and permissioned Hyperledger-Fabric blockchain network, capable of securing patient’s sensitive information in the blockchain network. Results The developed access control method provides secure access for emergency clinicians to sensitive information and simultaneously safeguards the patient’s well-being. Integrating this predictive mechanism within the blockchain network proved to be a robust tool to enhance the performance of the access control mechanism. Furthermore, the blockchain network of this work can record the history of who and when had access to a specific patient’s sensitive EHRs, guaranteeing the integrity and security of the data, as well as recording the latency of this mechanism, where three different access control cases are evaluated. This access control mechanism is to be enforced in a real-life scenario in hospitals. Conclusions The proposed mechanism informs proactively the emergency team of professional clinicians about patients’ critical situations by combining fuzzy and predictive machine learning techniques incorporated in the private and permissioned blockchain network, and it exploits the distributed data of the blockchain architecture, guaranteeing the integrity and security of the data, and thus, enhancing the users’ trust to the access control mechanism.

Abstract The present study aimed to examine the associations between the desire for independence, perceived level of achievement, and relationship status. Specifically, we conducted the study with a sample of 667 Greek-speaking participants (389 women, 275 men, and three participants who did not indicate their sex) who were either single or in an intimate relationship. We employed close-ended questionnaires that included instruments developed using AI. We found that men and women who desired more independence were more likely to be voluntarily single than in an intimate relationship. Additionally, a higher desire for independence was associated with more years being single, but this effect was significant only for men. Furthermore, we found that the perceived level of achievement was not significantly associated with relationship status directly; however, higher scores in this dimension were associated with fewer years spent as single for men. Moreover, a higher perceived level of achievement was associated with a decreased probability of being involuntarily single rather than in an intimate relationship and fewer years spent as single indirectly, by being associated with higher self-esteem, which was associated with higher flirting capacity. These paths were significant for both men and women. Our findings suggest that the desire for independence and perceived achievement play an important role in explaining why some people are single and others in an intimate relationship.

Abstract Background Mining the vast pool of biomedical literature to extract accurate responses and relevant references is challenging due to the domain's interdisciplinary nature, specialized jargon, and continuous evolution. Early natural language processing (NLP) approaches often led to incorrect answers as they failed to comprehend the nuances of natural language. However, transformer models have significantly advanced the field by enabling the creation of large language models (LLMs), enhancing question-answering (QA) tasks. Despite these advances, current LLM-based solutions for specialized domains like biology and biomedicine still struggle to generate up-to-date responses while avoiding “hallucination” or generating plausible but factually incorrect responses. Results Our work focuses on enhancing prompts using a retrieval-augmented architecture to guide LLMs in generating meaningful responses for biomedical QA tasks. We evaluated two approaches: one relying on text embedding and vector similarity in a high-dimensional space, and our proposed method, which uses explicit signals in user queries to extract meaningful contexts. For robust evaluation, we tested these methods on 50 specific and challenging questions from diverse biomedical topics, comparing their performance against a baseline model, BM25. Retrieval performance of our method was significantly better than others, achieving a median Precision@10 of 0.95, which indicates the fraction of the top 10 retrieved chunks that are relevant. We used GPT-4, OpenAI's most advanced LLM to maximize the answer quality and manually accessed LLM-generated responses. Our method achieved a median answer quality score of 2.5, surpassing both the baseline model and the text embedding-based approach. We developed a QA bot, WeiseEule ( https://github.com/wasimaftab/WeiseEule-LocalHost ), which utilizes these methods for comparative analysis and also offers advanced features for review writing and identifying relevant articles for citation. Conclusions Our findings highlight the importance of prompt enhancement methods that utilize explicit signals in user queries over traditional text embedding-based approaches to improve LLM-generated responses for specialized queries in specialized domains such as biology and biomedicine. By providing users complete control over the information fed into the LLM, our approach addresses some of the major drawbacks of existing web-based chatbots and LLM-based QA systems, including hallucinations and the generation of irrelevant or outdated responses.

The concept of agency and the position of the speaking subject in interpreting are key for an understanding of the interpreter’s role and the importance of codes of ethics, especially in community interpreting settings. The attempt to address these issues in an effort to establish a higher level of professionalism has been ongoing for many decades, but there is still a lot of controversy both in academic circles and in the practice itself. Scholars are still split between those who propagate a code of ethics which ensures accuracy, confidentiality, and impartiality and those who believe that the practitioner, under a different name (inter/cultural inter/mediator), is a mediator between cultures and thus, as the only agent of knowledge for all cultures involved in the exchange, should play a more interventionist role. And in the midst of this argument, all parties of the interaction (practitioners, users and providers of public services) may be deprived of their agency as speaking subjects. This paper will highlight some of the main arguments in this very sensitive issue and attempt an understanding of the significance of codes of ethics in dis/empowering the speaking subject, by taking a detour through the significance of Shakespearean names and Aristotelean virtues.

IntroductionMate-seekers employ several strategies to become more attractive as mates. In the present study, we examined the use of 10 strategies for becoming more desirable as a mate in the Lithuanian cultural context.MethodsUsing a sample of 295 Lithuanian-speaking participants, we explored the frequency and types of strategies employed to enhance mate appeal.ResultsThe most frequently used strategy was “Enhance looks,” followed by “Show off abilities and talents” and “Demonstrate similarity.” The least used strategies were “Show off and exaggerate wealth” and “Drastic appearance changes.” The 10 strategies could be classified into two domains or main strategies, with participants indicating a more frequent use of “Develop and demonstrate desirable traits” followed by “Deceive about undesirable traits.” Additionally, sex differences and age differences were identified for several strategies.DiscussionThe findings highlight the prominence of certain strategies over others in the Lithuanian context, with a notable emphasis on developing and demonstrating desirable traits. The study also reveals variations in strategy use based on sex and age, suggesting that these factors influence mate-seeking behaviors.

This paper addresses the interplay between Holocene landscape evolution and human settlement dynamics, drawing new evidence from the alluvial history of Xerolakkos, a continental stream in Grevena (Western Macedonia, Greece). We developed an integrated geoarchaeological survey combining remote sensing geomorphological mapping, litho-stratigraphic analysis and radiocarbon dating with the site evidence of a new archaeological survey. Results revealed four major alluviation phases, corresponding to 1) the beginning of the Holocene until the Early Neolithic (∼6300/6200 BCE), 2) the end of the Early and the Middle Neolithic (∼6000–5400 BCE), 3) from the Middle Bronze Age to the Late Roman period (∼1800 BCE – 500 CE), and 4) during the Byzantine and Ottoman eras (∼500–1800 CE), all separated by phases of floodplain incision. Furthermore, the effects of several Holocene Rapid Climatic Changes (RCC) are traced and discussed together with potential human responses; we also provide the first alluvial sequence recording the ∼6200 BCE (8.2 kyr BP) event in the Balkans. While the climate and the local geomorphological setting are considered the primary drivers behind instability and erosion during the Early and Middle Holocene, a landscape change starting in the Middle Bronze Age (after ∼1800 BCE) followed by a re-organisation of the rural economy in the Roman period suggests the increasing involvement of anthropogenic forcing which, by the Ottoman period, evolved into a dynamic situation between climatic variability and adaptive land management. Finally, we demonstrate how soil erosion in the upper catchment constitutes a serious taphonomic bias when studying the regional archaeological record.

Six wetlands along the Bulgarian Danube stretch were studied in 2009 and 2010. Totally 30 fish species were founded, 10 of them are of conservation significance. The highest species richness was recorded in the Srebarna Lake and the lowest one – in the Garvan marshes. Recently the commercial fishing in the wetlands has lost itseconomical significance because of the dramatic decline of fish stocks and degradation of fish communities. The volume of the permanent water bodies, the flooding regime and the regular connection with the river are the factors determining either the state or succession of the fish communities.

The present study focuses on high school students' acceptance of digital comics creation (DCC) in classroom learning and aims at identifying the factors that affect it. The DCC is a modern ICT activity, which combines the popular and familiar to students medium of comics with the computers. The research model used to explain the students' preference for DCC is based on the technology acceptance model. A partial least squares structural equation modeling was used to analyze the data and examine our research model and corresponding hypotheses. The results confirm the acceptance of the model and show that students' preference for DCC is directly influenced by perceived enjoyment, perceived usefulness and perceived ease of use. Among them, the perceived enjoyment is the stronger influencing factor. Digital comics creation self-efficacy was a significant indirect factor of students' preference for DCC through perceived ease of use. It is important that teachers take these into consideration and incorporate ICT activities that students enjoy, perceive them as useful and easy to use in order to capture their interest. Teachers should also enhance students' self-efficacy when providing them with ICT systems. Further relationships among the aforementioned factors and future research directions are also discussed.

Summary: Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased enhancer discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen in the human pluripotent stem cell (hPSC) pancreatic differentiation system. Among the enhancers identified, we focused on an enhancer we named ONECUT1e-664kb, ∼664 kb from the ONECUT1 promoter. Previous studies have linked ONECUT1 coding mutations to pancreatic hypoplasia and neonatal diabetes. We found that homozygous deletion of ONECUT1e-664kb in hPSCs leads to a near-complete loss of ONECUT1 expression and impaired pancreatic differentiation. ONECUT1e-664kb contains a type 2 diabetes-associated variant (rs528350911) disrupting a GATA motif. Introducing the risk variant into hPSCs reduced binding of key pancreatic transcription factors (GATA4, GATA6, and FOXA2), supporting its causal role in diabetes. This work highlights the utility of unbiased enhancer discovery in disease-relevant settings for understanding monogenic and complex disease.

Assessing the effectiveness of activated carbon is essential for the optimal operation of water treatment systems. Traditional evaluation methods, although precise, are typically labor-intensive and require complex equipment This study introduces a novel application of the B.EL.D™ device, utilizing redox potential measurements to gauge the activation level of carbon filters—an approach not previously employed. We hypothesized that redox potential is a reliable indicator of activated carbon's performance, a hypothesis that was rigorously validated through extensive testing against the standard iodine number test (ASTM D4607). Our analysis included both control and operational samples from ongoing water treatment processes over two years, confirming a definitive correlation between redox potential and carbon's adsorptive capacity. The findings demonstrate the potential of our method as a rapid, accurate, and cost-effective alternative to current testing practices. Currently under patent consideration, this study marks a significant advancement towards improving the assessment of activated carbon filters, providing an efficient pathway for water treatment facilities and establishing the foundation for a predictive maintenance model.

Objective: Enhanced recovery after surgery (ERAS) is a protocol of evidence based practices applied in major surgery. Open aortic aneurysm repair is major surgery in terms of complications and mortality. This study aimed to compare early outcomes of ERAS with a traditional post-operative protocol in patients undergoing elective open aortic surgery. Methods: This retrospective cohort study was conducted between 2018 – 2022 in two tertiary vascular surgery centres. The ERAS program was routinely implemented in one centre, while the other one used a standard peri-operative protocol. The primary outcome was post-operative length of stay (pLOS). Secondary outcomes were 30 day mortality rate, complications, re-interventions, and re-hospitalisations. Propensity score weighting was used to balance the two groups by comorbidities. Inverse probability of treatment weight (IPTW) was used to estimate the average treatment effect on the treated patients. Results: A total of 198 patients were enrolled: 128 in the ERAS group (EG) and 70 in the standard group (SG). Mean age was 70.8 ± 6.7 years in EG and 71.1 ± 6.7 in SG (p = 0.39). No significant differences were observed in pre-operative cardiovascular risk factors. The median pLOS was 5 days (IQR 3, 6) in the EG group and 8 days (IQR 6, 11) in the SG group (p < 0.001). No differences in terms of mortality, re-operations, and re-hospitalisations were observed. The IPTW analyses showed a 40% reduction in pLOS and a significant reduction in major complications in EG (OR 0.41, 95% CI 0.26–0.66; p < 0.001). A 45% increase in pLOS in patients with chronic obstructive pulmonary disease was found in both groups. Conclusion: Enhanced recovery after surgery is safe and feasible for elective open aortic surgery and is associated with earlier hospital discharge without differences in terms of mortality and lower complication rates compared with a standard protocol. Chronic obstructive pulmonary disease is a major risk factor for an increase in pLOS. The ERAS protocol is promising in terms of resource utilisation.

Background: The Mediterranean diet (MD) has been related with a decreased probability of overweight/obesity as well as central obesity at all stages of the human life, decreasing the risk of diverse disease states and improving quality of life. Over the last few years, the prevalence of childhood overweight/obesity and especially abdominal obesity has highly increased worldwide, being associated with a higher likelihood of overweight/obesity as well as central obesity at the next stages of the life during adulthood. The purpose of the present study was to explore the relationship of MD compliance with sociodemographic, anthropometry and lifestyle features in pre-school children aged 2–5 years old. Methods: This is a cross-sectional study, which includes 5188 pre-school children from diverse regions of Greece. Relevant questionnaires were applied to evaluate the sociodemographic features of the enrolled children. Anthropometric parameters were measured by relevant techniques. Qualified questionnaires were utilized for assessing several lifestyle factors such as physical activity, quality of life, breastfeeding practices, MD adherence, as well as the prevalence of childhood asthma and diabetes mellitus type I. Results: Of the enrolled children, 41.7% showed low MD compliance and 36.4% of them indicated moderated compliance, while only 21.9% of them showed a high MD adherence. Overweight/obesity was noted in 24.2% of the assigned children, while abdominal obesity was noticed in 18.2% of them. Higher MD compliance was related with an elevated prevalence of sex (boys, p = 0.0005), Greek nationality (p = 0.0088), rural type of residence (p = 0.0099), childhood overweight/obesity (p < 0.0001) and abdominal obesity (p < 0.0001), lower childbirth weight (p < 0.0001), increased physical activity (p = 0.0041), improved quality of life (p = 0.0008), exclusive breastfeeding (p < 0.0001), childhood asthma (p = 0.0001) and diabetes mellitus type 1 (p = 0.0002). Conclusions: A higher MD adherence is associated with specific sociodemographic, better anthropometric, and beneficial lifestyle factors in pre-school children. However, MD compliance remains low or moderate in the vast majority of children aged 2–5 years old. Thus, future public strategies and policies should be performed to inform parents of the potential beneficial effects of MD against obesity and related chronic diseases at the next stage of their children’s lives.

This paper discusses the evolution of human settlement in ancient Macedonia from the Neolithic to the Late Roman periods, based on the results of a new multi-disciplinary and multi-scale archaeological survey in northern Grevena (NW Greece). Building upon an unpublished (legacy) survey, we developed a GIS-structured workflow that integrates site-revisiting and surveying strategies (material collection and test pits) with multi-temporal remote-sensing analyses, offering analytical information about site distribution, characterisation, dating, and taphonomy. Notably, the new study led to a 64% increase in the number of known sites. The combined results indicate that prehistory is less represented in the surface record than historical periods, likely due to the impact of soil erosion episodes. The Late Bronze Age and Early Iron Age saw increased site numbers and the emergence of a settlement structure that characterised the area until the Hellenistic period. During the Roman period, the pattern shifted from a seemingly limited use of the landscape towards a model of more extensive habitation. This was driven by the appearance of new rural sites that introduced a land-use regime designed to support agricultural intensification by implementing anti-erosion measures, such as field terraces.

Background and Objectives: Adolescent Idiopathic Scoliosis (AIS) affects individuals aged 10–18 years and is characterized by spinal deformity, three-dimensional axis deformation, and vertebral rotation. Schroth method exercises and braces have been shown to reduce the Cobb angle and halt spinal deformity progression. The aim of this study was to investigate the impact of a 12-month, supervised Schroth exercise program on scoliosis severity and quality of life in adolescents with AIS. Materials and Methods: Eighty adolescents with AIS (aged 10–17 years) were prescribed a brace and were divided into two groups. The intervention group followed a supervised Schroth exercise program three times a week for 12 months in addition to wearing a brace. The control group used only the brace. Outcomes included the Cobb angle of the main curvature and the sum of curves using radiography, the maximum angle of trunk rotation (ATR maximum, using a scoliometer), and quality of life with the Scoliosis Research Society-22 (SRS-22) questionnaire. Evaluations were conducted at baseline, after 12 months, and 6 months post-intervention. A multivariate analysis of covariance (MANCOVA) was used for statistical analysis (p-Value < 0.05). Results: The intervention group showed statistically significant improvement compared to the control group in the 12th month in Cobb angle (mean differences, 95% CI: −3.65 (−5.81, −1.53), p-Value < 0.001, Cohen’s d = 0.30), ATR maximum (mean differences, 95% CI: −3.05 (−3.86, −2.23), p-Value < 0.001, Cohen’s d = 0.74), and SRS-22 score (mean differences, 95% CI: 0.87 (0.60, 1.13), p-Value < 0.001, Cohen’s d = 0.58). Differences in ATR maximum and SRS-22 score remained significant at the 18-month measurement. No significant differences were found between groups in the sum of curves (p-Value > 0.05). Conclusions: A 12-month supervised Schroth exercise program in AIS patients undergoing brace treatment significantly improves scoliosis severity (Cobb angle and ATR maximum) and quality of life. Improvements were greater than those in shorter-duration studies, suggesting a linear dose–response relationship. Further clinical studies are needed to clarify the impact of long-term Schroth programs.

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer.