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BackgroundThe nationwide HUN-CANCER EPI study examined cancer incidence and mortality rates in Hungary from 2011 to 2019.MethodsUsing data from the National Health Insurance Fund (NHIF) and Hungarian Central Statistical Office (HCSO), our retrospective study analyzed newly diagnosed malignancies between Jan 1, 2011, and Dec 31, 2019. Age-standardized incidence and mortality rates were calculated for all and for different tumor types using both the 1976 and 2013 European Standard Populations (ESP).FindingsThe number of newly diagnosed cancer cases decreased from 60,554 to 56,675 between 2011–2019. Age-standardized incidence rates were much lower in 2018, than previously estimated (475.5 vs. 580.5/100,000 person-years [PYs] in males and 383.6 vs. 438.5/100,000 PYs in females; ESP 1976). All-site cancer incidence showed a mean annual decrease of 1.9% (95% CI: 2.4%-1.4%) in men and 1.0% (95% CI:1.42%-0.66%) in women, parallel to mortality trends (-1.6% in males and -0.6% in females; ESP 2013). In 2018, the highest age-standardized incidence rates were found for lung (88.3), colorectal (82.2), and prostate cancer (62.3) in men, and breast (104.6), lung (47.7), and colorectal cancer (45.8) in women. The most significant decreases in incidence rates were observed for stomach (4.7%), laryngeal (4.4%), and gallbladder cancers (3.5%), with parallel decreases in mortality rates (3.9%, 2.7% and 3.2%, respectively).InterpretationWe found a lower incidence of newly diagnosed cancer cases for Hungary compared to previous estimates, and decreasing trends in cancer incidence and mortality, in line with global findings and the declining prevalence of smoking.

Neovascularization is implicated in the pathology of retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. In our work, we analyzed how heme released during hemorrhage affects hypoxic response and neovascularization. Our retrospective clinical analysis demonstrated, that hemorrhage was associated with more severe retinal neovascularization in ROP patients. Our heme-stimulated human retinal pigment epithelial (ARPE-19) cell studies demonstrated increased expression of positive regulators of angiogenesis, including vascular endothelial growth factor-A (VEGFA), a key player of ROP, DR and AMD, and highlighted the activation of the PI3K/AKT/mTOR/VEGFA pathway involved in angiogenesis in response to heme. Furthermore, heme decreased oxidative phosphorylation in the mitochondria, augmented glycolysis, facilitated HIF-1α nuclear translocation, and increased VEGFA/GLUT1/PDK1 expression suggesting HIF-1α-driven hypoxic response in ARPE-19 cells without effecting the metabolism of reactive oxygen species. Inhibitors of HIF-1α, PI3K and suppression of mTOR pathway by clinically promising drug, rapamycin, mitigated heme-provoked cellular response. Our data proved that oxidatively modified forms of hemoglobin can be sources of heme to induce VEGFA during retinal hemorrhage. We propose that hemorrhage is involved in the pathology of ROP, DR, and AMD.

PreambleRobotic magnetic navigation (RMN)-guided catheter ablation (CA) technology has been used for the treatment of cardiac arrhythmias for almost 20 years. Various studies reported that RMN allows for high catheter stability, improved lesion formation and a superior safety profile. So far, no guidelines or recommendations on RMN-guided CA have been published.PurposeThe aim of this consensus paper was to summarize knowledge and provide recommendations on management of arrhythmias using RMN-guided CA as treatment of atrial fibrillation (AF) and ventricular arrhythmias (VA).MethodologyAn expert writing group, performed a detailed review of available literature, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Recommendations on RMN-guided CA are presented in a guideline format with three levels of recommendations to serve as a reference for best practices in RMN procedures. Each recommendation is accompanied by supportive text and references. The various sections cover the practical spectrum from system and patient set-up, EP laboratory staffing, combination of RMN with fluoroscopy and mapping systems, use of automation features and ablation settings and targets, for different cardiac arrhythmias.ConclusionThis manuscript, presenting the combined experience of expert robotic users and knowledge from the available literature, offers a unique resource for providers interested in the use of RMN in the treatment of cardiac arrhythmias.

Surface modification, including the anchoring of functional groups is a popular method to increase the photocatalytic activity of semiconductor photocatalysts. These species can trap excited electrons, thus prolonging the life of the charge carriers. N-containing functional groups are suitable for this purpose due to their high electron density. Here, we report a facile synthesis method for preparing interfacial N-based functional groups-modified and nitrogen-doped SrTiO3 photocatalysts. Among the modified samples (with 0.42–11.14 at.% nominal nitrogen content), the one with 7.71 at.% nitrogen showed 6.4 times higher photooxidation efficiency for phenol and 2.2 times better photoreduction efficiency for CO2 conversion than the unmodified SrTiO3 reference. Characterization results showed that using a low amount of nitrogen source resulted in low but measurable nitrogen doping, which did not significantly affect the photocatalytic activity. The formation of surface amine groups was significant even at lower initial nitrogen concentrations, while higher amounts of nitrogen source gradually resulted in the incorporation of nitrogen in higher amounts. Surface amine groups decreased the recombination of charge carriers, resulting in increased photocatalytic activity.

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 Extracellular vesicles (EVs) constitute a vital component of intercellular communication, exerting significant influence on metastasis formation and drug resistance mechanisms. Malignant melanoma (MM) is one of the deadliest forms of skin cancers, because of its high metastatic potential and often acquired resistance to oncotherapies. The prevalence of BRAF mutations in MM underscores the importance of BRAF-targeted therapies, such as vemurafenib and dabrafenib, alone or in combination with the MEK inhibitor, trametinib. This study aimed to elucidate the involvement of EVs in MM progression and ascertain whether EV-mediated metastasis promotion persists during single agent BRAF (vemurafenib, dabrafenib), or MEK (trametinib) and combined BRAF/MEK (dabrafenib/trametinib) inhibition. Using five pairs of syngeneic melanoma cell lines, we assessed the impact of EVs – isolated from their respective supernatants – on melanoma cell proliferation and migration. Cell viability and spheroid growth assays were employed to evaluate proliferation, while migration was analyzed through mean squared displacement (MSD) and total traveled distance (TTD) measurements derived from video microscopy and single-cell tracking. Our results indicate that while EV treatments had remarkable promoting effect on cell migration, they exerted only a modest effect on cell proliferation and spheroid growth. Notably, EVs demonstrated the ability to mitigate the inhibitory effects of BRAF inhibitors, albeit they were ineffective against a MEK inhibitor and the combination of BRAF/MEK inhibitors. In summary, our findings contribute to the understanding of the intricate role played by EVs in tumor progression, metastasis, and drug resistance in MM.

Abstract We find closed formulas for the overlaps of Bethe eigenstates of gl $$ \mathfrak{gl} $$ (N) symmetric spin chains and integrable boundary states. We derive the general overlap formulas for gl $$ \mathfrak{gl} $$ (M) ⊕ gl $$ \mathfrak{gl} $$ (N − M) symmetric boundary states and give a well-established conjecture for the sp $$ \mathfrak{sp} $$ (N) symmetric case. Combining these results with the previously derived so $$ \mathfrak{so} $$ (N) symmetric formula, now we have the overlap functions for all integrable boundary states of the gl $$ \mathfrak{gl} $$ (N) spin chains which are built from two-site states. The calculations are independent from the representations of the quantum space therefore our formulas can be applied for the SO(6) and the alternating SU(4) spin chains which describe the scalar sectors of N $$ \mathcal{N} $$ = 4 super Yang-Mills and ABJM theories which are important application areas of our results.

Abstract Nanotechnology, especially in the field of photocatalysis, has witnessed rapid advancements, with titanium dioxide being one of the most widely used photocatalysts. As the use of products containing photoactive nanomaterials increases, concerns have arisen regarding their potential release into the environment over time. This release can impact soil, groundwater, and surrounding ecosystems, resulting in nanoparticles being dispersed in water and eventually depleted from the system. This study aimed to investigate how different soil solutions affect the structural, textural properties, and photocatalytic activity of titanium dioxide-based, commercial reference Evonik Aeroxide P25. The Regosol soil solution, characterized by acidic pH, low ionic content, and high organic matter content, induced nanoparticle aggregation and bandgap changes. In addition, the acidic pH hindered the adsorption process, potentially affecting the photocatalytic processes. In contrast, the Chernozem soil solution, with slightly alkaline pH, high ionic content, and low organic matter content, did not significantly alter the morphology or structure of the material. However, various organic compounds were absorbed on the surface, reducing the availability of active sites. The study highlights the importance of understanding the influence of soil solutions on nanomaterials, as it impacts their properties and environmental risks. Results show that the material is still activated, i.e., it can exert its photoactive effect on the environment. This sheds light on the challenges posed by nanoparticles in soil, particularly in terms of their toxicity and consequences for the surrounding ecosystems. The study underlines the need for further research in this area to assess potential risks and optimise the use of nanomaterials in environmental remediation.

Abstract Background Different mosquito control strategies have been implemented to mitigate or prevent mosquito-related public health situations. Modern mosquito control largely relies on multiple approaches, including targeted, specific treatments. Given this, it is becoming increasingly important to supplement these activities with rapid and mobile diagnostic capacities for mosquito-borne diseases. We aimed to create and test the applicability of a rapid diagnostic system for West Nile virus that can be used under field conditions. Methods In this pilot study, various types of adult mosquito traps were applied within the regular mosquito monitoring activity framework for mosquito control. Then, the captured specimens were used for the detection of West Nile virus RNA under field conditions with a portable qRT-PCR approach within 3–4 h. Then, positive samples were subjected to confirmatory RT-PCR or NGS sequencing in the laboratory to obtain genome information of the virus. We implemented phylogenetic analysis to characterize circulating strains. Results A total of 356 mosquito individuals representing 7 species were processed in 54 pools, each containing up to 20 individuals. These pools were tested for the presence of West Nile virus, and two pools tested positive, containing specimens from the Culex pipiens and Anopheles atroparvus mosquito species. As a result of subsequent sequencing, we present the complete genome of West Nile virus and Bagaza virus. Conclusions The rapid identification of infected mosquitoes is the most important component of quick response adulticide or larvicide treatments to prevent human cases. The conceptual framework of real-time surveillance can be optimized for other pathogens and situations not only in relation to West Nile virus. We present an early warning system for mosquito-borne diseases and demonstrate its application to aid rapid-response mosquito control actions. Graphical Abstract

Abstract Background Finding and registering the maxillary–mandibular jaw relation is crucial in dental practice. Several comparative studies have been conducted to investigate the reproducibility and accuracy of techniques for determining the centric relation (CR) position of the mandible. The aim of our study was to determine which of seven different CR determination methods had the smallest deviation from the theoretical zero with the help of a digital mandibular motion analyser. The chosen theoretical zero position, the maximal intercuspal position (MIP), is the most reproducible and widely used position. Methods Thirty-four volunteers (24 females and 10 males) with a mean (SD) age of 29.1 (± 7.3) years with a negative history of temporomandibular disorder (TMD) participated in the study. A digital mandibular motion analyser was used to register the condylar position after the use of each technique for the determination of CR. The calibration was performed to the maximal intercuspal position (MIP) for each volunteer. The investigated techniques were (A) the gothic arch tracer, (B) the adduction field method, (C) Dawson’s bimanual manipulation, (D) the patient placing the tongue tip on the palatal rugae, (E) the patient placing the tongue tip to the border of the hard and soft palate, (F) the patient actively pulling the chin backwards, and (G) the examiner pushing the patient’s chin back. Results The position of the mandibular condyle was illustrated in a three-dimensional coordinate system, where the origin represented the MIP. Among the seven methods examined, five showed significant deviations compared to the MIP. Among these, two methods resulted in posterior deviation of the condyles. Methods C and E coincided with the MIP in all directions. Conclusions Within the limitations of our study, we found that the smallest deviations from our theoretical zero (MIP) among the investigated centric relation determining methods were obtained with the bimanual mandibular manipulation technique derived from Dawson and the placement of the tongue tip on the border of the hard and soft palate (linguomandibular homotrophy theory).

Calcium titanate (CTO) photocatalysts were synthesized using a sol–gel method by adopting a cost-efficient, rapid calcination technique. The CTOs were characterized by X-ray diffractometry, X-ray photoelectron spectroscopy, infrared spectroscopy, nitrogen adsorption, porosimetry measurements, scanning/transmission electron microscopy, and diffuse reflectance spectroscopy. Their photocatalytic activity was assessed through the photocatalytic degradation of phenol, oxalic acid, and chlorophenol under UV light exposure, using a commercial CTO as a reference. The stability of the samples was evaluated using compounds with –OH, –COOH, and –Cl functional groups. Characterization results showed that CTO composites containing anatase, rutile, and brookite titania were obtained. Increasing the calcination temperature led to various crystalline compositions, higher crystallinity, larger primary crystallite sizes, and smaller specific surface areas. The photocatalytic activity of all CTO/TiO2 composites was superior compared to the commercial CTO we used as a reference. The high photocatalytic activity of the best-performing composites was attributed to their higher specific surface areas and the synergistic effect between the crystal phases. A cost comparison was also made between our unique calcination technique and conventional calcination, and it was found that our method is approximately 35% more cost-effective, while retaining the photocatalytic activity.

Pancreatic cystic lesions, frequently detected in abdominal imaging, pose diagnostic challenges due to their varying malignancy potential. This review article focuses on the crucial role of molecular diagnostics in differentiating these lesions, with an emphasis on the significance of KRAS and GNAS mutations identified through endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The use of next-generation sequencing (NGS) is highlighted for its precision in detecting genetic changes, crucial for accurate diagnosis and guiding management decisions.Integration of molecular studies into standardized reporting for pancreaticobiliary cytopathology is also discussed, enhancing diagnostic accuracy. The potential of precision oncology, informed by molecular insights, is explored for targeted treatments of pancreatic cystic lesions.Commercial platforms like PancreaSeq® Genomic Classifier and PancraGEN® are assessed for their effectiveness in analyzing pancreatic cystic fluid, proving beneficial in cases where traditional methods fall short.In summary, molecular studies are indispensable in evaluating pancreatic cystic lesions, offering a pathway to more personalized treatment and management strategies in patient-centered care.