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Abstract Reinforcement Learning has emerged as a significant component of Machine Learning in the domain of highly automated driving, facilitating various tasks ranging from high-level navigation to control tasks such as trajectory tracking and lane keeping. However, the agent’s action choice during training is often constrained by a balance between exploitation and exploration, which can impede effective learning, especially in environments with sparse rewards. To address this challenge, researchers have explored combining RL with sampling-based exploration methods such as Rapidly-exploring Random Trees to aid in exploration. This paper investigates the effectiveness of classic exploration strategies in RL algorithms, particularly focusing on their ability to cover the state space and provide a quality experience pool for learning agents. The study centers on the lane-keeping problem of a dynamic vehicle model handled by RL, examining a scenario where reward shaping is omitted, leading to sparse rewards. The paper demonstrates how classic exploration techniques often cover only a small portion of the state space, hindering learning. By leveraging RRT to broaden the experience pool, the agent can learn a better policy, as exemplified by the dynamic vehicle model’s lane-following problem.

Abstract Background and aim The increasing frequency of heat waves is a major challenge for emergency care providers worldwide. The aim of this study was to analyze the clinical features, treatment options, and early outcomes of heat stroke patients presenting to a large academic emergency department (ED) in Hungary and to provide guidance in management for other emergency professionals. Methods Patients presenting to the ED between June 1, 2024, and July 31, 2024, with a body temperature above 40 °C were analyzed in a retrospective cohort study. Data collection included demographic, clinical and laboratory parameters. Predictors of mortality were analyzed with Mann-Whitney U test. Results Eight patients were included in our analysis. Three patients died in the ED (37.5%). Patients who died had significantly lower pH (7.07 vs. 7.4, p = 0.036), higher potassium (7.3 vs. 3.2 mmol/L, p = 0.036), higher calcium (1.19 vs. 0.97 mmol/L, p = 0.036), higher lactate (10.9 vs. 3.5 mmol/L, p = 0.036) and higher PaCO2 (57.2 vs. 28 mmHg, p = 0.036) at admission compared to those who did not die. Conclusions The risk of heat stroke due to climate change-induced heat stress and the consequent thermoregulatory disruption may now be significant in temperate climate zones where it was not previously present. Standardization of differential diagnostic and therapeutic procedures could reduce mortality. pH, potassium, lactate and calcium levels may play an important role in predicting the outcome of heat stroke.

Abstract Fast and accurate anomaly detection is critical in telemetry systems because it helps operators take appropriate actions in response to abnormal behaviours. However, recent techniques are accurate but not fast enough to deal with real-time data. There is a need to reduce the anomaly detection time, which motivates us to propose two new algorithms called AnDePeD (Anomaly Detector on Periodic Data) and AnDePed Pro. The novelty of the proposed algorithms lies in exploiting the periodic nature of data in anomaly detection. Our proposed algorithms apply a variational mode decomposition technique to find and extract periodic components from the original data before using Long Short-Term Memory neural networks to detect anomalies in the remainder time series. Furthermore, our methods include advanced techniques to eliminate prediction errors and automatically tune operational parameters. Extensive numerical results show that the proposed algorithms achieve comparable performance in terms of Precision, Recall, F-score, and MCC metrics while outperforming most of the state-of-the-art anomaly detection approaches in terms of initialisation delay and detection delay, which is favourable for practical applications.

Abstract In specific applications like ice-repellent coatings or membrane separation technology, wettability is a key parameter affecting the applicability of commodity polymers. This study presents a technique to fine-control the wetting properties of a hierarchically structured polypropylene surface, enabling the transition between superhydrophobic and superhydrophilic states. To demonstrate the tunability of the wetting properties of polypropylene (PP) substrate, we prepared in a consecutive way superhydrophobic (advancing contact angle (CAadv) of 152°) and superhydrophilic (CAadv of 0°) material by solvent-treatment and mild air plasma treatment. The optimal plasma treatment parameters to achieve superhydrophilic wetting behaviour, which is stable for at least one week of storage in air was also explored. Water contact angle measurement and X-ray photoelectron spectroscopy were used to monitor the time dependency of hydrophobic recovery on a hierarchically structured PP surface. With a simple model considering structural and wetting parameters, we characterized the droplet spreading behaviour of plasma-treated roughened surfaces, which exhibited superhydrophilic wetting behaviour with equilibrium CAadv of nearly 0°. The proposed model, which aligns well with experimental data, can be used to compare the droplet spreading behaviour of plasma-treated roughened surfaces.

Abstract In the present study, we aimed to establish and characterize a mature cortical spheroid model system for Kleefstra syndrome (KS) using patient-derived iPSC. We identified key differences in the growth behavior of KS spheroids determined by reduced proliferation marked by low Ki67 and high E-cadherin expression. Conversely, in the spheroid-based neurite outgrowth assay KS outperformed the control neurite outgrowth due to higher BDNF expression. KS spheroids were highly enriched in VGLUT1/2-expressing glutamatergic and ChAT-expressing cholinergic neurons, while TH-positive catecholamine neurons were significantly underrepresented. Furthermore, high NMDAR1 expression was also detected in the KS spheroid, similarly to other patients-derived neuronal cultures, denoting high NMDAR1 expression as a general, KS-specific marker. Control and KS neuronal progenitors and neurospheres were exposed to different toxicants (paraquat, rotenone, bardoxolone, and doxorubicin), and dose-response curves were assessed after acute exposure. Differentiation stage and compound-specific differences were detected with KS neurospheres being the most sensitive to paraquat. Altogether this study describes a robust 3D model system expressing the disease-specific markers and recapitulating the characteristic pathophysiological traits. This platform is suitable for testing developing brain-adverse environmental effects interactions, drug development, and screening towards individual therapeutic strategies.

Abstract The imperative need for sensitive and precise tools is underscored in cancer diagnostics, with biomarkers playing a pivotal role in facilitating early detection and tumor diagnosis. Despite their classical pathological classification, testicular tumors lack valuable markers, emphasizing the necessity to identify and apply serum tumor markers in clinical management. Unfortunately, existing biomarkers exhibit limited sensitivities and specificities. Recent years have witnessed the discovery of novel RNA molecules, presenting a potential breakthrough as diagnostic tools and promising biomarkers. This report presents compelling evidence supporting the detection of early testicular cancer by applying a set of nine microRNAs (miRNAs), establishing them as valuable serum biomarkers for diagnosis. We developed a standardized serum-based measurement protocol and conducted comprehensive statistical analyses on the dataset to underscore the diagnostic accuracy of the miRNA pool. Notably, with a sensitivity exceeding 93%, miR-21, miR-29a, and miR-106b surpass classical serum tumor markers in the context of testicular cancer. Specifically, these miRNAs are poised to enhance clinical decision-making in testicular cancer detection and hold the potential for assessing tumor growth in monitoring chemotherapy outcomes.

Abstract Background Sport enjoyment is one of the most important factors in physical activity (PA) and physical education (PE) domains. It is not only beneficial for regular participation but also has a positive effect on mental health. Due to these benefits, this study aims to understand the relationships between PA, two forms of enjoyment, and the dimension of self-concept. Methods The sample consisted of 315 students (Mage=12.63). The Self-Description Questionnaire-I was used to measure the domains of self-concept. Enjoyment was measured with two scales. The Physical Activity Enjoyment Scale reflects extracurricular PA enjoyment, and the Factors Influencing Enjoyment of Physical Education Questionnaire reflects school PE enjoyment. The International Physical Activity Questionnaire was used to assess vigorous, moderate, and walking types of extracurricular PA enjoyment. Results Hierarchical multivariate regression analysis revealed that vigorous PA predicted physical ability (β = 0.19) and physical appearance (β = 0.15). PA enjoyment was a significant predictor of general self-concept (β = 0.29), physical ability (β = 0.28), physical appearance (β = 0.16), peer relation (β = 0.16), and parental relations (β = 0.14). PE enjoyment significantly predicted general school (β = 0.17), physical ability (β = 0.27), peer relations (β = 0.21) and parental relations (β = 0.22). Furthermore, boys scored at a higher level on most of self-concept domains. Conclusions The present study suggested that enjoyment plays a more important role in self-concept than PA. PE enjoyment mainly strengthens boys’ self-concept, but PA enjoyment is an important predictor of general self-concept in both genders. It is concluded that extracurricular PA enjoyment is beneficial, but increasing enjoyment of physical education could increase girls’ self-concepts as well.

The aim of the article is to briefly describe our work together with Dr. Viktor Mutt. He discovered and purified many new gastrointestinal bioactive neuropeptides that have important applications as therapeutic agents in diabetes, epilepsy, migraine and weight control. Dr. Muttâs strategy was to search for C­-terminally amidated peptides. We determined neuropeptide Y equilibrium binding for its receptor. Our work also included the L­-Ala scan of pharmacophores of the neuropeptide galanin (1­28). Finally, the work led to the establishment of the coexistence of peptides with small molecule neurotransmitters, such as serotonin, acetylcholine, noradrenaline and dopamine in central and peripheral neurons.

Abstract Background End-stage and acquired cystic renal disease (ESRD/ACRD) kidneys are characterized by inflammatory remodelling and multiplex renal cell carcinomas (RCC). Eosinophilic vacuolated tumour (EVT) occurs exclusively in ACRD. The aim of this study was to identify the involvement of thioredoxin-interacting protein (TXNIP) and thioredoxin (TXN) in ESRD/ACRD pathology. Methods Expression of TXNIP and TXN was examined in histological slides of 6 ESRD and 6 ACRD kidneys, precursor lesions and associated tumours as well as of RCCs from the general population by immunohistochemistry. Results Strong TXNIP expression was seen in epithelial cells, myo-fibroblasts and endothelial cells and weak TXN expression in ESRD/ACRD kidneys and tumours. In ACRD specific EVT and its precursors TXN were translocated into nuclei. Conclusion The impaired TXNIP/TXN redox homeostasis might be associated with development of multiplex cancer especially of EVT in ESRD/ACRD kidney.

Abstract Background Mesenteric arterial thrombosis is an extremely rare thrombotic event, especially during pregnancy, that can cause rapid fatal consequences unless the patient receives early definitive treatment. Case presentation We report the case of a 34-year-old female presenting in her seventh week of gestation with severe abdominal pain who was promptly diagnosed with mesenteric artery occlusion amidst incipient miscarriage. The patient underwent a successful mesentery artery embolectomy, recovered and was later diagnosed with elevated factor VIII activity. Conclusion The diagnosis of mesenteric ischemia should be considered in pregnant women presenting with severe abdominal pain and any prior predisposing factors. Our case highlights the pivotal role of the emergency physician in maintaining a high index of suspicion coupled with timely and determined action. The prognosis of this high mortality condition depends on prompt diagnosis, early definite management and successful multidisciplinary cooperation.

Ice hockey is considered one of the most competitive sports, and it requires physical and mental preparation to perform appropriately under the pressure of a competitive environment. The present study aims to investigate the impact of competitive sports on executive functions such as emotion regulation, inhibitory control, working memory, and competitive attitudes among near-elite ice hockey players. Near-elite athletes have been gathered (N = 67) from the four Hungarian Ice-Hockey Academies. Our results indicated a small positive association between Canadian points and maladaptive emotion regulation and a slight positive correlation between maladaptive cognitive emotion regulation and false alarms of the N-back task. The result revealed a significant difference between National and Non-National Team members in maladaptive cognitive emotion regulation regarding hypercompetitive attitude. The result of linear regression revealed that maladaptive cognitive emotion regulation significantly predicts false alarms, indicating that the maladaptive cognitive emotion regulation explains 10% of the variance. In conclusion, we highlight the role of the environment, which affects executive functions and competitive attitudes alongside sports performance. Although the findings were mainly correlational, we can conclude that the nature of competitive ice hockey expects certain behavior for the players indifferent of the situation that could lead to emotion suppression, rumi-nation and other maladaptive emotion regulation strategies. We can also conclude that inadequate emotion regulation might be related to the overstimulation of players, characterized by a hypersensitive state to stimuli. We suggest that practitioners ensure the development of adequate competitive attitudes of players to enable long-term physical and psychological benefits.

Introduction: Natalizumab (NAT), a highly effective disease modifying therapy (DMT) in relapsing-remitting multiple sclerosis (RRMS), was approved for clinical use in Hungary on February 1, 2010. In this study we aimed to assess its effectiveness in view of the concept of “No Evidence of Disease Activity” (NEDA-3), furthermore evaluate its effect on limb function, pathopsychological symptoms (cognition, fatigue, depression) and quality of life (QoL). Patients and methods: From February 1, 2010, to December 1, 2022, 121 eligible patients were consecutively enrolled from the MS center of the University of Szeged, Hungary. Here, we report data on 6-years of follow-up. First, we evaluated the proportion of patients reaching the NEDA-3 state and any possible influencing factors. Then, we assessed the change of upper and lower limb functions via the 9-hole-peg test (9HPT) and the 25-feet walk test (TW25F). Finally, we assessed the change of pathopsychological symptoms (cognition, fatigue, depression) and QoL via the BICAMS, FIS, BDI-II and MSQoL-54 questionnaires, and the possible influencing factors behind it. Results: Cumulatively, 97 patients (80.2 %) achieved NEDA-3 throughout the follow-up period. On a year-by-year basis, the proportion changed from 95.9 % in the 1st year to 84.3 %, 81.3 %, 76.4 %, 74.5 % and 78.9 % in the 2nd, 3rd, 4th, 5th and 6th year respectively (p

Bimodal composite metal foams made from Al99.5 aluminium and quasi-eutectic Sr-modified AlSi12 matrix were investigated, where the bimodality was introduced by two alumina hollow sphere sets with nominal diameters of Ø7.0 and Ø2.4 mm in various volume concentrations. The research aimed to determine the effect of the cell structure (especially the unintended porosity) on the first compressive stress maximum, depending on the applied matrix material. The various features of the cell structure were quantitatively measured in composite metal foams by filtering raw computed tomography analysis data. The casting porosity, the wetting porosity, the porosity from the various-sized hollow spheres, and the partially matrix-filled hollow spheres have been successfully distinguished based on volumetric and geometrical conditions, such as sphericity and compactness. The unintended porosity (as the sum of the casting porosity and the wetting porosity) influences the first compressive stress maximum of the Al99.5 matrix composite metal foams. In contrast, for the AlSi12Sr bimodal foams, the results correlated with the total porosity values. The first compressive stress maximum could be estimated well from the compressive yield strength of the matrix and the total porosity of the foam.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for the minimally invasive management of biliary and pancreatic disorders. Under certain indications, performing ERCP without delay during the weekend can be important for improving outcomes. Objectives: To compare the outcomes of ERCP performed on weekends and holidays with those of regular weekday ERCPs. Design: Propensity score match analysis of the data from the Hungarian ERCP Registry. Methods: A total of 116 ERCPs were performed during weekends or holidays, and 3144 during weekday working hours. The analyses were performed on 1:2 propensity-matched groups (116 weekend and 232 weekday cases). Results: Weekend ERCPs were mostly performed for acute cholangitis and acute biliary pancreatitis (70% of cases), whereas in the weekday group, only 32% of cases were performed for these indications. No significant difference was found between weekday and weekend ERCPs in terms of the rates of successful (91.38% vs 93.1%, p = 0.565) and difficult (33.62% vs 36.64%, p = 0.511) biliary cannulations. We found no significant differences in the number of adverse events (bleeding, post-ERCP pancreatitis, and 30-day mortality) in ERCPs performed during weekends or weekdays. Moreover, no significant differences in the aforementioned outcomes were detected between the propensity-matched groups. Conclusion: In this propensity-matched study, no significant differences were found in the outcomes of weekend and weekday ERCPs.

A loss-of-coolant accident in a nuclear power plant was simulated in the CODEX-SLIM experiment. The electrically heated fuel rod bundle contained cladding material used at a VVER-440 power plant. The maximum temperature reached 900 °C and the experiment was terminated by water quenching. The condition of the bundle was investigated using non-destructive and destructive techniques. According to the experimental data, the fuel rods would maintain their integrity during a design basis loss-of-coolant accident.

Abstract Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Abstract Current density, the membrane current value divided by membrane capacitance (Cm), is widely used in cellular electrophysiology. Comparing current densities obtained in different cell populations assume that Cm and ion current magnitudes are linearly related, however data is scarce about this in cardiomyocytes. Therefore, we statistically analyzed the distributions, and the relationship between parameters of canine cardiac ion currents and Cm, and tested if dividing original parameters with Cm had any effect. Under conventional voltage clamp conditions, correlations were high for IK1, moderate for IKr and ICa,L, while negligible for IKs. Correlation between Ito1 peak amplitude and Cm was negligible when analyzing all cells together, however, the analysis showed high correlations when cells of subepicardial, subendocardial or midmyocardial origin were analyzed separately. In action potential voltage clamp experiments IK1, IKr and ICa,L parameters showed high correlations with Cm. For INCX, INa,late and IKs there were low-to-moderate correlations between Cm and these current parameters. Dividing the original current parameters with Cm reduced both the coefficient of variation, and the deviation from normal distribution. The level of correlation between ion currents and Cm varies depending on the ion current studied. This must be considered when evaluating ion current densities in cardiac cells.

Abstract Developing unique mechanisms of action are essential to combat the growing issue of antimicrobial resistance. Supramolecular assemblies combining the improved biostability of non-natural compounds with the complex membrane-attacking mechanisms of natural peptides are promising alternatives to conventional antibiotics. However, for such compounds the direct visual insight on antibacterial action is still lacking. Here we employ a design strategy focusing on an inducible assembly mechanism and utilized electron microscopy (EM) to follow the formation of supramolecular structures of lysine-rich heterochiral β3-peptides, termed lamellin-2K and lamellin-3K, triggered by bacterial cell surface lipopolysaccharides. Combined molecular dynamics simulations, EM and bacterial assays confirmed that the phosphate-induced conformational change on these lamellins led to the formation of striped lamellae capable of incising the cell envelope of Gram-negative bacteria thereby exerting antibacterial activity. Our findings also provide a mechanistic link for membrane-targeting agents depicting the antibiotic mechanism derived from the in-situ formation of active supramolecules.

Abstract Objective In the temporomandibular joint two separate movements of rotation and translation occur in two articular spaces during mouth opening. Over the years, the approach has changed considerably, but it is still subject to controversy as to which of these movement is involved in the initial stage of mouth opening. In the present study, the extent of rotation and translation was investigated in the first 5 mm of mouth opening. Materials and methods The study was carried out on 46 volunteers. Anamnesis was taken and patients were examined. For the investigation, an ultrasonic digital motion analyser (KaVo Arcus Digma 2) was applied. The measurements were made after calibration to an arbitrary axis. Each participant performed three open-close movements in succession, starting from maximum intercuspal position. Results Data were statistically processed using cubic spline interpolation. Linear regression was then used. The resulting line is significantly (p

Abstract Background The tumor-agnostic indication of immune checkpoint inhibitors to treat cancers with mismatch repair deficiency (dMMR)/microsatellite instability (MSI) increased the demand for such tests beyond Lynch syndrome. International guideline recommendations accept immunohistochemistry (IHC) for dMMR or molecular techniques (PCR or NGS) for MSI status determinations considering the two tests are equal, although there are scattered reports contradicting to this presumption. Materials and methods Here we have directly compared four protein MMR immunohistochemistry (IHC) to MSI Pentaplex PCR test in a large cancer patient cohort (n = 1306) of our diagnostic center where the two tests have been run parallel in 703 cases. Results In this study we have found a high discrepancy rate (19.3%) of the two tests which was independent of the tumor types. The MSI PCR sensitivity for MMR IHC status was found to be very low resulting in a relatively low positive and negative predicting values. As a consequence, the correlation of the two tests was low (kappa

With increasing realised traffic on transport networks, greenhouse gas emissions show a similar trend. Reducing them is a modern aspiration, creating a better place to live and moving towards sustainability. Expanding the infrastructure is often not an appropriate solution, as the system would only be fully utilised at peak times, while at less frequent times it would not even approach capacity and would require huge investment costs. An alternative to further construction work is the implementation of intelligent traffic systems, where smoother flows can achieve higher capacity by reducing the variability in the system. In a motorway environment, a common approach is Variable Speed Limit Control, where the road is divided into zones and individual speed limits are used to increase or decrease the load on the cells. This paper proposes a solution in which individual cells make decisions cooperatively, in contrast to classical state machine-based methods. Thanks to the jointly formulated goal of the agents, a predictive control method is created that leads to a reduction in emissions due to avoided shock waves and reduced waiting times. This paper presents a solution that provides a universal solution across multiple application lengths, illustrating the power of deep learning. https://github.com/istvan-knab/Variable-speed-limit-control.

Abstract Concerning the robustness of predicting the forced response of the El Niño—Southern Oscillation-Indian summer monsoon (ENSO-ISM) teleconnection based on 9 CMIP-class models, we come to distinguish three time periods. (1) In the late 20th century, the trend was insignificant in most models, which does not permit a statement on robustness in this period. Thus the weakening of the teleconnection reported from the observational data might not be truly forced. (2) Furthermore, we find it typical that under global warming in the first part of the 21st century, the teleconnection is strengthening or non-decreasing. This considerable inter-model robustness is owed to an increasing ENSO variability as well as coupling strength. (3) At the end of the 21st century, however, under strong forcing, the teleconnection change is not robustly modeled: the ENSO variability change is not projected robustly across models, either with respect to the start or the rate of the ENSO variance decline, competing this time with an increase of the coupling strength. The difference in the projected coupling coefficient between models is mainly attributed to the disagreement in the projected ENSO-induced changes in the regional Hadley cell and SST patterns over the ISM domain, despite the agreement on the projected eastward shift of the Walker cell over the Pacific Ocean.

Background: Milkrun-based material supply plays an important role in the automotive industry, as it is a material supply concept where high efficiency can be achieved. When implementing milkrun-based material supply, the milkrun supply of the production plant often has to be integrated with an existing warehouse material handling system, which frequently leads to a less efficient solution. Methods: In this paper, the author investigates the impact of a hub-based milkrun supply, where the collection processes in the component’s warehouse and the distribution processes in the assembly plant are connected to a hub, which is responsible for the sequencing of component demands. After a systematic literature review, the paper introduces a novel mathematical model, which makes it possible to describe the conventional milkrun-based solutions, the hub-based milkrun solutions, and to compare them in terms of the length of transportation routes, transportation time, total service time, and virtual emission points of view. Results: The scenario analysis demonstrates that the hub-based solution can lead to an efficiency improvement of about 13% in total service time, 23% savings in transportation time, and 45% savings in transportation time in the component’s warehouse. Conclusions: The article’s findings suggest that implementing a hub-based milkrun system in automotive material supply can significantly enhance efficiency. The described approach could lead to more streamlined operations in production plants by optimizing the integration of milkrun systems.

IntroductionLow socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants.MethodsOur study is a cross-sectional analysis using data from the “Ormánság Health Program”. The “Ormánság Health Program” was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age.ResultsOur study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34–9.18, p

The increased focus on green energy storage devices and the related rapid advancement in biomedical technologies makes the investigation of biocompatible integrated systems with medical relevance increasingly important. Peptides and their assembled morphologies with their innate biocompatibility and biodegradability are emerging as promising candidates in this respect due to their structural attributes which can be easily tuned to form supramolecular 3D architectures with extended pathways for ionic mobility. However, to comprehend their applicability in energy storage devices, it is crucial to explore their self‐assembling characteristics, charge‐storage mechanisms, and coating efficacies. Herein, all these aspects are compiled with specific emphasis on peptide‐based systems for supercapacitor applications. The electrochemical charge storage mechanisms that are used for categorizing conventional supercapacitors with the theories and mechanisms outlining biological electron transfer, such as tunneling, hopping, superexchange, and flickering resonance, are collated. Furthermore, the characterization techniques solely pertaining to the study of such systems and their role in predicting the morphology of self‐assembly patterns which could directly impact the overall electrochemical properties are also addressed. Finally, some of the critical challenges associated with these systems while realizing their future potential in the field of sustainable energy storage devices are highlighted.

Multi-RNA co-transfection is starting to be employed to stimulate immune responses to SARS-CoV-2 viral infection. While there are good reasons to utilize such an approach, there is little background on whether there are synergistic RNA-dependent cellular effects. To address this issue, we use transcriptome-induced phenotype remodeling (TIPeR) via phototransfection to assess whether mRNAs encoding the Spike and Nucleocapsid proteins of SARS-CoV-2 virus into single human astrocytes (an endogenous human cell host for the virus) and mouse 3T3 cells (often used in high-throughput therapeutic screens) synergistically impact host cell biologies. An RNA concentration-dependent expression was observed where an increase of RNA by less than 2-fold results in reduced expression of each individual RNAs. Further, a dominant inhibitory effect of Nucleocapsid RNA upon Spike RNA translation was detected that is distinct from codon-mediated epistasis. Knowledge of the cellular consequences of multi-RNA transfection will aid in selecting RNA concentrations that will maximize antigen presentation on host cell surface with the goal of eliciting a robust immune response. Further, application of this single cell stoichiometrically tunable RNA functional genomics approach to the study of SARS-CoV-2 biology promises to provide details of the cellular sequalae that arise upon infection in anticipation of providing novel targets for inhibition of viral replication and propagation for therapeutic intervention.

Abstract The aim of this study was to evaluate qualitative and quantitative differences in vascular density analysis of an established and a novel alternative for post-processing on optical coherence tomography angiography (OCTA) images in healthy individuals. OCTA examinations of 38 subjects were performed. After extracting the images, two semi-manual post-processing techniques, the already established Mexican hat filtering (MHF) and an alternative, the Shanbhag thresholding (ST) were applied. We assessed Vessel Density (VD), Skeleton Density (SkD) and Vessel Diameter Index (VDI). We analyzed the results in order to establish similarities or potentially relevant differences. Regarding SkD and VD, MHF generally gave higher values than ST. Simultaneously, mean values were also predominantly higher by MHF; however, standard deviations (SD) were higher by ST (range [mean ± SD]: 0.054 ± 0.038 to 0.134 ± 0.01 and 0.134 ± 0.095 to 0.362 ± 0.028 vs 0.012 ± 0.014 to 0.087 ± 0.03 and 0.039 ± 0.047 to 0.4 ± 0.095 for SkD and VD with MHF vs SkD and VD with ST, respectively). Values of VDI were considerably higher with ST than with MHF, while standard deviation was still significantly higher with ST (range [mean ± SD]: 2.459 ± 0.144 to 2.71 ± 0.084 and 2.983 ± 0.929 to 5.19 ± 1.064 for VDI with MHF and ST, respectively). The noise level reduction of the two methods were almost identical (noise levels: 65.8% with MHT and 65.24% with ST). Using MHF, the vascular network gets more fragmented by an average of 40% compared to ST. Both methods allow the segmentation of the vascular network and the examination of vascular density parameters, but they produce largely inconsistent results. To determine if these inconsistent results are clinically meaningful, and which method is more suitable for clinical use, our results provide further evidence that detailed understanding of the image analysis method is essential for reliable decision making for patients with retinal pathology. For longitudinal monitoring, use of the same image processing method is recommended.

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It is acknowledged that conventional renal cell carcinoma (cRCC), which makes up 85% of renal malignancies, is a highly vascular tumor. Humanized monoclonal antibodies were developed to inhibit tumor neo-angiogenesis, which is driven by VEGFA/KDR signaling. The results largely met our expectations, and in several cases, adverse events occurred. Our study aimed to analyze the expression of VEGFA and its receptor KDR by immunohistochemistry in tissue multi-array containing 811 cRCC and find a correlation between VEGFA/KDR signaling and new vessel formation. None of the 811 cRCC displayed VEGFA-positive immunostaining. However, each glomerulus in normal kidney showed VEGFA-positive endothelial cells. KDR expression in endothelial meshwork was found in only 9% of cRCC, whereas 2% of the cRCC displayed positive KDR reaction in the cytoplasm of tumor cells. Our results disclose the involvement of VEGFA/KDR signaling in the neo-vascularization of cRCC and explain the frequent resistance to drugs targeting the VEGFA/KDR signaling and the high frequency of adverse events.

First aid is a key factor in preventing further deterioration in an accident, saving lives, or improving treatment in emergencies. However, the reasons behind the willingness to provide first aid are still unclear. Therefore, this study aimed to investigate the role of social problem-solving and prosocial behavior in the dimension of first aid willingness. Self-administered questionnaires were used to evaluate the dimensions of first aid willingness (first aid willingness for peers, first aid willingness for strangers, knowledge, and negative emotions), social problem solving (positive problem orientation, negative problem orientation, rational problem solving, avoidance style, and impulsivity/carelessness) and prosocial behavior. A total of 497 school-aged students between the ages of 12 and 15 years (201 boys and 296 girls) participated in this study. Our results showed that positive problem orientation (p < 0.05) and rational problem solving (p < 0.001) are significant factors in determining first aid willingness for both peers and strangers. On the other hand, avoidance style orientation (p < 0.05) has a negative influence on the willingness to provide first aid to peers and strangers. Negative problem orientation (p < 0.001) only predicted negative emotions related to emergencies. Furthermore, prosocial behavior (p < 0.001) was more strongly associated with first aid willingness than social problem solving. Our study suggested that improving social competence could be a key factor in increasing first aid provision in real time, which could save lives in emergencies.

In recent years, convolutional neural networks (CNNs) have emerged as highly efficient architectures for image and audio classification tasks, gaining widespread adoption in state-of-the-art methodologies. While CNNs excel in machine learning scenarios where the data representation exhibits a grid structure, they face challenges in generalizing to other data types. For instance, they struggle with data structured on 3D meshes (e.g., measurements from a network of meteorological stations) or data represented by graph structures (e.g., molecular graphs). To address such challenges, the scientific literature proposes novel graph-based convolutional network architectures, extending the classical convolution concept to data structures defined by graphs. In this paper, we use such a deep learning architecture to examine graphs defined using the ICD-10 codes appearing in the medical data of patients who suffered hemorrhagic stroke in Hungary in the period 2006–2012. The purpose of the analysis is to predict the risk of stroke by examining a patient’s ICD graph. Finally, we also compare the effectiveness of this method with classical machine learning classification methods. The results demonstrate that the graph-based method can predict the risk of stroke with an accuracy of over 73%, which is more than 10% higher than the classical methods.

editorial

When planning the Institutional Artwork Protection of a temporary or permanent exhibition, it is not enough to adopt a template property protection plan or security protocol. In order to develop complex protection plans it is essential to consider professional specialities, since it is necessary to prepare for entirely different risk factors, hazards, and environmental conditions depending on the special characteristics of the protected work of art. In line with the smart city concept, research is also being carried out to examine the needs of smart public service infrastructure, the innovative implementation of which contributes to sustainable development and also provides security functions. In addition to describing the essential functions of Closed-circuit television, the authors also highlight the possibilities of further particular parts of Closed-circuit television systems installed in Smart City environments in the field of the structure of Institutional Artwork protection.

Abstract Cyclophosphamide, an oxazaphosphorine prodrug is frequently used in treatment of neuroblastoma, which is one of the most prevalent solid organ malignancies in infants and young children. Cytochrome P450 2B6 (CYP2B6) is the major catalyst and CYP2C19 is the minor enzyme in bioactivation and inactivation pathways of cyclophosphamide. CYP-mediated metabolism may contribute to the variable pharmacokinetics of cyclophosphamide and its toxic byproducts leading to insufficient response to the therapy and development of clinically significant side effects. The aim of the study was to reveal the contribution of pharmacogenetic variability in CYP2B6 and CYP2C19 to the treatment efficacy and cyclophosphamide-induced side effects in pediatric neuroblastoma patients under cyclophosphamide therapy (N = 50). Cyclophosphamide-induced hematologic toxicities were pivotal in all patients, whereas only moderate hepatorenal toxicity was developed. The patients’ CYP2B6 metabolizer phenotypes were associated with the occurrence of lymphopenia, thrombocytopenia, and monocytopenia as well as of liver injury, but not with kidney or urinary bladder (hemorrhagic cystitis) toxicities. Furthermore, the patients’ age (

Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective single-center analysis of patients (n = 317) who underwent surgical treatment for Klatskin tumors. Univariable and multivariable logistic regression and Cox proportional analysis were performed. The primary endpoint was to investigate the role of lymph node metastasis for patient survival after complete tumor resection. The secondary endpoint was the prediction of lymph node status and long-term survival from preoperatively available parameters. Results: In patients with negative resection margins, a negative lymph node status was the prognosis-determining factor with a 1-, 3-, and 5-year survival rate of 87.7%, 37%, and 26.4% compared with 69.5%, 13.9%, and 9.3% for lymph-node-positive patients, respectively. Multivariable logistic regression for complete resection and negative lymph node status demonstrated only Bismuth type 4 (p = 0.01) and tumor grading (p = 0.002) as independent predictors. In multivariate Cox regression analysis, independent predictors of survival after surgery were the preoperative bilirubin level (p = 0.03), intraoperative transfusion (p = 0.002), and tumor grading (G) (p = 0.001). Conclusion: Lymph node dissection is of utmost importance for adequate staging in patients undergoing surgery for perihilar cholangiocarcinoma. In spite of extensive surgery, long-term survival is clearly associated with the aggressiveness of the disease.

Color etching is a useful corrosive process, widely applied in metallography to study the microstructure of metals. To prove the existence of the previously hypothesized steady-state etching rate, in-situ investigations were performed with spectroscopic ellipsometry during the color etching of ferritic materials. Kinetic information regarding the refractive index, extinction coefficient, and layer thickness were used to calculate the steady-state layer buildup rate, which was 1.90 ± 0.15 nm/s for low-carbon steel and 0.99 ± 0.06 nm/s for cast iron owing to its better corrosion resistance. The presented methodology and findings could help understanding other processes that involve the development of layers on metallic surfaces.

The estimation and analysis of road traffic represent the preliminary steps towards satisfying the current needs for smooth, safe, and green transportation. Therefore, effective traffic monitoring is an essential topic alongside the planning of sustainable transportation systems and the development of new traffic management concepts. In contrast to classical traffic detection solutions, this study investigates the correlation between travelers' social activities and road traffic. The s's primary goal is to investigate the presence of the relationship between social activity and road traffic, which might allow an infrastructure-independent traffic monitoring technique as well. People's general activities at Point of Interest (POI) locations (measured as occupancy parameter) are correlated with traffic data so that, finally, proper proxys can be defined for link-level average traffic speed estimation. The method is tested and evaluated using real-world traffic and POI occupancy data from Budapest (District XI.). The results of the correlation investigation justify an indirect relationship between activity at POIs and road traffic, which holds promise for future practical applicability.

Political parties have always utilized symbolism to get their messages across, or build, strengthen, and mobilise their base. It can be present in the public actions of political figures, or in the use of certain symbols either visually or in language. This study analyses the use of the Hungarian Parliament Building as a political symbol in the Socialist movement of the first half of the 20th century and during the period of the Hungarian Soviet Republic. The Parliament was used as a symbol to further society's understanding of the political goals and ideology of the Socialist movement, and later the Communist dictatorship, as well as to mobilise the regime's base. The first section of the article uses the articles of Népszava and the posters of Mihály Bíró to present how the Parliament was used in the political marketing and suffrage propaganda of the Social Democratic Party of Hungary. The second section examines the changes in the meaning of this symbol following the democratic revolution of October 1918. After the Social Democratic Party acquired leadership in Autumn 1918, and later when the Soviet Republic was established in March 1919, the symbol of the Parliament had to take on different meanings in propaganda. The final section of the article discusses the initial and long-term goals of this transformation process through the analysis of the works displayed at the Parliament Square during the regime's May Day celebration, and the decorations of the soviet congress and party congress in June 1919. [ABSTRACT FROM AUTHOR]

Abstract Background Colloid cysts are rare benign, slowly growing intracranial tumors of endodermal origin. Most colloid cysts are found incidentally and are asymptomatic, but rarely, they can lead to sudden death. Case presentation A 73-year-old female patient was admitted to our emergency department with complaints of dizziness, nausea, vomiting, fatigue, walking difficulties, and behavioral changes. CT imaging revealed acute obstructive hydrocephalus attributable to a third ventricular colloid cyst. The patient was immediately transferred to a tertiary center where she underwent successful neurosurgical resection of the mass. Pathology results of the lesion confirmed the diagnosis of colloid cyst. Conclusion The case we present emphasizes the critical importance of prompt identification of warning signs, complex thinking, and evaluation. Establishing the right diagnostic approach early on can facilitate accurate diagnosis.

Abstract Background In this study we evaluated the imaging capabilities of a novel Multi-pinhole collimator (MPH-Cardiac) specially designed for nuclear cardiology imaging on a Triple-NaI-detector based SPECT/CT system. Methods 99mTc point source measurements covering the field of view (FOV) were used to determine tomographic sensitivity (TSpointsource) and spatial resolution. Organ-size tomographic sensitivity (TSorgan) was measured with a left ventricle (LV) phantom filled with typical myocardial activity of a patient scan. Reconstructed image uniformity was measured with a 140 mm diameter uniform cylinder phantom. Using the LV phantom once filled with 99mTc and after with 123I, Contrast-to-noise ratio (CNR) was measured on the reconstructed images by ROI analysis on the myocardium activity and on the LV cavity. Furthermore, a polar map analysis was performed determining Spill-Over-Ratio in water (SORwater) and image noise. The results were compared with that of a dual-head parallel-hole low energy high resolution (LEHR) collimator system. A patient with suspected coronary artery disease (CAD) was scanned on the LEHR system using local protocol of 16 min total acquisition time, followed by a 4-min MPH-Cardiac scan. Results Peak TSpointsource was found to be 1013 cps/MBq in the axial center of the FOV while it was decreasing toward the radial edges. TSorgan in the CFOV was found to be 134 cps/MBq and 700 cps/MBq for the LEHR and MPH-Cardiac, respectively. Average spatial resolution throughout the FOV was 4.38 mm FWHM for the MPH-Cardiac collimator. Reconstructed image uniformity values were found to be 0.292% versus 0.214% for the LEHR and MPH-Cardiac measurements, respectively. CNR was found to be higher in case of MPH-Cardiac than for LEHR in case of 99mTc (15.5 vs. 11.7) as well as for 123I (13.5 vs. 8.3). SORwater values were found to be 28.83% and 21.1% for the 99mTc measurements, and 31.44% and 24.33% for the 123I measurements for LEHR and MPH-Cardiac, respectively. Pixel noise of the 99mTc polar maps resulted in values of 0.38% and 0.24% and of the 123I polar maps 0.62% and 0.21% for LEHR and MPH-Cardiac, respectively. Visually interpreting the patient scan images, MPH-Cardiac resulted in better image contrast compared to the LEHR technique with four times shorter scan duration. Conclusions The significant image quality improvement achieved with dedicated MPH-Cardiac collimator on triple head SPECT/CT system paves the way for short acquisition and low-dose cardiovascular SPECT applications.

Plain English summary The Rising Tide Foundation for Clinical Cancer Research (RTFCCR), a private philanthropy that funds academic research, has developed a novel approach for requiring and supporting partnerships among grantees (scientists) and patients in designing and conducting research projects. The decision to focus on patient involvement stems from an expressed focus area established by the RTFCCR board of directors. In conducting this work, RTFCCR partnered with Patvocates, a patient advocacy and engagement network. Patvocates conducted a landscape assessment, interviews with experts, and their collective experience as patient advocates. This work generated a set of guiding documents and resources. These resources are to help public and private health research funders to better understand current challenges and support scientists and patients through their funding mechanisms. Three guiding documents, one for funders, one for grant applicants, and one for patient advocates are now available for download at the RTFCCR website: https://www.risingtide-foundation.org/clinical-cancer-research/patient-engagement#start Delivering a paradigm change involves not only the introduction of additional requirements and rules, but also enhanced education of patients and investigators. By using its grantmaking function and developing standardized approaches for implementation of patient involvement, RTFCCR is seeking to advance patient-centric cancer clinical research. Development and implementation of consistent policies and procedures for the integration of the patients’ view in the design and review of research proposals is needed for funders as well as for research institutes, both public and private.

A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines’ induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents.