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Abstract Turbulent market conditions, well-publicized advantages, and potential individual, social, and environmental risks make blockchain-based cryptocurrencies a popular focus of the public and scientific communities. This paper contributes to the literature on the future of crypto markets by analyzing a promising cryptocurrency innovation from a customer-centric point of view; it explores the factors influencing user acceptance of a hypothetical social network-backed cryptocurrency in Central Europe. The research model adapts an internationally comparative framework and extends the well-established unified theory of acceptance and use of the technology model with the concept of perceived risk and trust. We explore user attitudes with a survey on a large Hungarian sample and analyze the database with consistent partial least square structural equation modeling methodology. The results show that users would be primarily influenced by the expected usefulness of the new technology assuming it is easy to use. Furthermore, our analysis also highlights that while social influence does not seem to sway user opinions, consumers are susceptible to technological risks, and trust is an important determinant of their openness toward innovations in financial services. We contribute to the cryptocurrency literature with a future-centric technological focus and provide new evidence from an under-researched geographic region. The results also have practical implications for business decision-makers and policymakers.

To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive IKr tail current measured at −40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive IKs tail current was considerably larger in GM than in RM. In HM, the IKs tail was even smaller than in DM. At 30 mV, the IKr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the IKr component in HM, DM, and RM measured at −40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the IKr tail current was best fitted triexponentially. At 30 mV, the IKs component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, IKs component deactivation measured at −40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the IK in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization.

Grasping and object manipulation have been considered key domains of Cyber-Physical Systems (CPS) since the beginning of automation, as they are the most common interactions between systems, or a system and its environment. As the demand for automation is spreading to increasingly complex fields of industry, smart tools with sensors and internal decision-making become necessities. CPS, such as robots and smart autonomous machinery, have been introduced in the meat industry in recent decades; however, the natural diversity of animals, potential anatomical disorders and soft, slippery animal tissues require the use of a wide range of sensors, software and intelligent tools. This paper presents the development of a smart robotic gripper for deployment in the meat industry. A comprehensive review of the available robotic grippers employed in the sector is presented along with the relevant recent research projects. Based on the identified needs, a new mechatronic design and early development process of the smart gripper is described. The integrated force sensing method based on strain measurement and magnetic encoders is described, including the adjacent laboratory and on-site tests. Furthermore, a combined slip detection system is presented, which relies on an optical flow-based image processing algorithm using the video feed of a built-in endoscopic camera. Basic user tests and application assessments are presented.

Hungarian A műszaki és technológiai fejlődés legújabb vívmányai az elmúlt években a pénzügyi termékek, ezen belül a különböző biztosítási termékek piacán is megjelentek. A tanulmány célja a biztosítási szektorban megjelenő technológiai újdonságok elterjedési lehetőségeinek elemzése a fogyasztók általi elfogadás vizsgálatán keresztül. A szakértői fókuszcsoport vizsgálatból kiinduló kutatás 150 fő, felsőfokú képzettségű személy válaszai alapján vizsgálja a különböző innovációs nyitottságú fogyasztói csoportok közötti legfontosabb hasonlóságokat és eltéréseket. Az eredmények közül kiemelendő a digitális megoldásokra nyitott fogyasztók fokozott érzékenysége a bizalmat fokozó és költség-haszon szempontok, valamint a rugalmas, egyedi problémára szabott innovációkra vonatkozó várakozások megléte. Az eredmények alapján szükség van egy, a biztosítási iparág sajátosságait – köztük például hosszabb távú szemléletét – figyelembe vevő technológiaelfogadási modell bevezetésére a későbbi kutatások során. English In recent years, the latest technical and technological advances have also made their appearance in the market for financial products, including various insurance products. The aim of this study is to analyse the potential for the diffusion of technological innovations in the insurance sector by examining consumer acceptance. Based on the responses of 150 respondents with tertiary education, the research, which is based on a focus group survey of experts, examines the main similarities and differences between different groups of consumers with different levels of openness to innovation. The results highlight the increased sensitivity of consumers open to digital solutions, the increased confidence and cost-benefit aspects, and the expectations of flexible innovation tailored to specific problems. The results suggest the need to introduce a technology adoption model that takes into account the specificities of the insurance industry, including, for example, its longer-term perspective, in future research.

A kutatásunk célja az információtechnológia üzleti értékének nemzetközi szakirodalmi feldolgozása kvantitatív és kvalitatív szövegelemzési módszerekkel. A Scopus adatbázisból szűrt, 13 582 elemű szakirodalmi adatbázis objektív, szó- és szópár alapú elemzésével a tudományos kutatások központi fogalmait, témáit, technológiai és iparági fókuszát térké-peztük fel. Kiemelendő ezek között a kiadás-alapú értékfogalom túlsúlya, a folyamat- és projektszemlélet, illetve a felhasználói technológia-befogadásra és elégedettségre irányuló figyelem. Majd ezen korpuszból a leggyakrabban hivatkozott 26 cikket kiválasztva mé-lyebb képet kaphattunk az IT értékteremtés irodalmát az elmúlt tizenöt évben uraló el-méleti megközelítésekről (köztük elsősorban az erőforrás-alapú szemlélet, a dinamikus képességek elmélete és a tudásalapú megközelítés dominanciájáról), és az ezen elméletekbe ágyazott kutatások leg fontosabb eredményeiről. The aim of our research is to process and summarize the literature focusing on the business value of information technology using quantitative and qualitative text analysis methods. Word and word-pair analysis of a literature corpus of 13 582 elements filtered from the Scopus database, the central concepts, themes, technological and industrial focus of scien-tific research were explored. These key themes include the predominance of the expenditu-re-based value concept, the process and project approach and the attention to technology adoption and user satisfaction. Then, choosing and analysing the 26 most frequently cited articles of the corpus, we were able to get a deeper picture of the mainstream theoretical ap-proaches of IT value creation over the past 15 years (including, in particular, the dominan-ce of resource-based approach, dynamic ability theory and knowledge-based approach) and we summarize the most important results of the research embedded in these theories.

Definite descriptions with reference failure have been argued to give rise to different truth-value intuitions depending on the local linguistic context in which they appear. We conducted an experiment to investigate these alleged differences, thereby contributing new data to the debate. We have found that pragmatic strategies dependent on verification and topicalisation, suggested in the context of trivalent/partial theories, indeed play a role in people's subjective judgments. We discuss the consequences of these findings for all major approaches to definite descriptions (i.e. Russellian, Strawsonian, pragmatic). Finally, we offer a discussion of the relative contribution of verificational and topicality effects on truth values, reaching the conclusion that verification is primarily relevant and topicality is dependent on that. We thus support von Fintel's (2004) position on the primacy of verification, but not his dismissal of topicality as a factor. http://dx.doi.org/10.3765/sp.6.10 BibTeX info

It is proposed that wh-islands with degree questions are unacceptable because they cannot be given a most informative true answer. Wh-islands thus are shown to be similar to other cases of weak islands which have been argued to result from Maximization Failure, in particular negative islands (cf. Fox & Hackl 2007). Permanent DOI link: http://dx.doi.org/10.3765/sp.4.5 BibTeX info

The neuroprotective effect of l-kynurenine sulfate (KYN), a precursor of kynurenic acid (KYNA, a selective N-methyl-d-aspartate receptor antagonist), was studied. KYN (300 mg/kg i.p., applied daily for 5 days) appreciably decreased the number of injured pyramidal cells from 1850±100/mm2 to 1000±300/mm2 (p

Abstract Multiple stressor research in aquaria is a useful approach to better understand the ecophysiology of marine species under different environmental conditions, including global change scenarios. Long‐term experiments are helpful to detect the response of sustained exposure to selected environmental conditions. Here, we present an experimental set‐up suitable to run long‐term experiments, composed of a life support system, a cost‐effective aquaria set‐up and an open‐source controller based on the use of a Raspberry Pi. In this set‐up, temperature, pH and dissolved oxygen (DO) are individually manipulated and simultaneously controlled in eight different treatments. To prove the efficacy of the set‐up, we provide an assessment over a nine‐month experiment on a deep‐sea coral species, combining values from current in situ and IPCC AR5 RCP 8.5 scenarios for the aforementioned parameters. Recorded data from the controllers and independent measurements (e.g. cross‐checking with portable multiparameter devices and laboratory analyses) throughout the experimental time have been analysed and results have been discussed. Overall, the experimental set‐up performed well, proving the stability of the parameters over time, both individually and in combination. On average, low and high‐temperature treatments varied ~0.4 and 0.3°C, respectively. Low pH treatments were maintained within 0.05 pH units, whereas ambient pH treatments varied ~0.04 pH units. Low DO treatments had a variation of ~0.3 mg L−1, and ambient DO treatments varied ~0.2 mg L−1. No significant differences between scenarios for any parameter were detected (p

Abstract Background Cycling promotes health but carries significant injury risks, especially for older adults. In the U.S., cycling fatalities have increased since 1990, with adults over 50 now at the highest risk. As the population ages, the burden of cycling-related trauma is expected to grow, yet age-specific factors associated with mortality risk remain unclear. This study identifies age-specific mortality risk thresholds to inform targeted public health strategies. Methods We conducted a cross-sectional analysis of the National Trauma Data Bank (NTDB) data (2017–2023) on non-motorized cycling injuries. A total of 185,960 records were analyzed using logistic regression with splines to evaluate the relationship between age and mortality risk. The dataset was split into training (80%) and testing (20%) sets. Age thresholds where mortality risk changed were identified, and models were adjusted for injury severity, comorbidities, and helmet use. Results The median patient age was 43 years (IQR 20–58). Four key age thresholds (12, 17, 31, and 69) were identified, with the largest mortality increase after age 69. Our model achieved an AUC of 0.93, surpassing traditional age cutoff models, with 84.6% sensitivity and 88.0% specificity. Conclusions Age is a significant predictor of mortality in cycling trauma, with marked increases in risk during adolescence and for adults over 69. These findings underscore the need for age-targeted interventions, such as improved cycling infrastructure for teens and enhanced safety measures for older adults. Public health initiatives should prioritize these vulnerable age groups to reduce cycling-related mortality.

Abstract This study aims to assess the effect of combining virtual walking (VW) therapy with a physical exercise (PE) program compared to PE alone on lower limb strength and muscle activation in people with incomplete spinal cord injury (iSCI). 38 participants performed 3 sessions/week during 6 weeks of Experimental Intervention (EI): VW and PE; or Control intervention (CI): Placebo-VW and PE. Strength and muscle activation of main lower limb muscles were assessed. EI group exhibited a general strength increase after intervention (T2), (16.31–34.72 N), and maintained this improvement up to 1-month-follow-up (T3) for hip abduction and extension movements. The CI group only showed improvements in hip abduction and extension movements (18.34 (7.13) N and 19.98 (9.60) N, respectively). EI group also exhibited an increase of activation in all agonistic muscles in T2 (36.02–20.24 µV), except gastrocnemius. Gastrocnemius and rectus femoris activation as antagonistic decreased during dorsal flexion (− 14.28 (5.61) µV) and hip extension (− 14.78 [6.11] µV), respectively. CI group only showed an activation increase of agonistic muscles of hip abduction and extension (22.16 (9.80) µV and 28.82 (9.14) µV, respectively), without changes in antagonistic activation. VW could enhance the PE effects regarding muscle strength and activation in people with iSCI. Registration number: NCT04809987.

Abstract Aneurysm rupture is a life-threatening event, yet its underlying mechanisms remain largely unclear. This study investigated the fracture properties of the thoracic aneurysmatic aorta (TAA) using the symmetry-constraint Compact Tension (symconCT) test and compared results to native and enzymatic-treated porcine aortas’ tests. With age, the aortic stiffness increased, and tissues ruptured at lower fracture energy $$D$$ . Patients with bicuspid aortic valves were more sensitive to age, had stronger aortas and required more $$D$$ than tricuspid valves individuals (peak load: axial loading 4.42 $$\pm$$ 1.56 N vs 2.51 $$\pm$$ 1.60 N; circumferential loading 5.76 $$\pm$$ 2.43 N vs 4.82 $$\pm$$ 1.49 N. Fracture energy: axial loading 1.92 $$\pm$$ 0.60 kJ m-2 vs 0.74 $$\pm$$ 0.50 kJ m-2; circumferential loading 2.12 $$\pm$$ 2.39 kJ m-2 vs 1.47 $$\pm$$ 0.91 kJ m-2). Collagen content partly explained the variability in $$D$$ , especially in bicuspid cases. Besides the primary crack, TAAs and enzymatic-treated porcine aortas displayed diffuse and shear-dominated dissection and tearing. As human tissue tests resembled enzymatic-treated porcine aortas, microstructural degeneration, including elastin loss and collagen degeneration, seems to be the main cause of TAA wall weakening. Additionally, a tortuous crack developing during the symconCT test reflected intact fracture toughening mechanisms and might characterize a healthier aorta.

Abstract Background Interpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community. Results BiomiX tackles the bottleneck in high-throughput omics data analysis, enabling efficient and integrated analysis of multiomics data obtained from two cohorts. BiomiX incorporates diverse omics data, using DESeq2/Limma packages for transcriptomics, and quantifying metabolomics peak differences, evaluated via the Wilcoxon test with the False Discovery Rate correction. The metabolomics annotation for Liquid Chromatography-Mass Spectrometry untargeted metabolomics is additionally supported using the mass-to-charge ratio in the CEU Mass Mediator database and fragmentation spectra in the TidyMass package. Methylomics analysis is performed using the ChAMP R package. Finally, Multi-Omics Factor Analysis (MOFA) integration identifies shared sources of variation across omics data. BiomiX also generates statistics, report figures and integrates EnrichR and GSEA for biological process exploration and subgroup analysis based on user-defined gene panels enhancing condition subtyping. BiomiX fine-tunes MOFA models, to optimize factors number selection, distinguishing between cohorts and providing tools to interpret discriminative MOFA factors. The interpretation relies on innovative bibliography research on Pubmed, which provides the articles most related to the discriminant factor contributors. Furthermore, discriminant MOFA factors are correlated with clinical data, and the top contributing pathways are explored, all with the aim of guiding the user in factor interpretation. Conclusions The analysis of single-omics and multi-omics integration in a standalone tool, along with MOFA implementation and its interpretability via literature, represents significant progress in the multi-omics field in line with the “Findable, Accessible, Interoperable, and Reusable” data principles. BiomiX offers a wide range of parameters and interactive data visualization, allowing for personalized analysis tailored to user needs. This R-based, user-friendly tool is compatible with multiple operating systems and aims to make multi-omics analysis accessible to non-experts in bioinformatics.

Societal Impact Statement Winegrape production is an essential cultural heritage and economic engine of many regions of the world. Regenerative management, which is gaining traction with industry and consumers alike, relies on soil biodiversity for agroecosystem function, reducing external inputs and increasing ecosystem resilience to climate change. We evaluated the effects of no‐till and sheep integration on vineyard soil biodiversity and soil ecosystem function. No‐till had stronger effects on microbial diversity, while sheep grazing stimulated microbial functioning. By providing a better understanding of the practices, we provide fundamental information for growers that want to embrace regenerative principles, ultimately contributing to the sustainability and resilience of the winegrape industry. Summary Regenerative management aims to optimize soil microbial function and diversity for enhanced agroecosystem functionality. Understanding the effects of management practices on soil microorganisms is crucial in the context of growing societal interest in this type of management. This study evaluated the short‐term effects of two soil conservation practices: sheep grazing and no‐till, on abundance, diversity, activity, and network complexity of prokaryotes and fungi in a vineyard soil. Four treatments were applied for 3 years: (1) grazed and tilled, (2) grazed and non‐tilled, (3) non‐grazed and tilled, and (4) non‐grazed and non‐tilled. We hypothesized that stacking of conservation practices (grazing and no‐till) would increase microbial diversity, function, and network complexity. Grazing had strong effects on microbial function, increasing the α‐glucosidase, β‐glucosidase, cellulase, phosphatase, and β‐xylosidase enzymatic activity by 82%, 48%, 61%, 39%, and 55%, respectively, compared to non‐grazed soils, while not causing significant changes in soil microbial diversity. Tillage had strong effects on soil prokaryotic and fungal diversity. For prokaryotes, significant interactions in alpha diversity were found between tillage and grazing, and between tillage and sampling location (tractor row and under vine). Fungal Shannon diversity index was higher in the subsoil (15–30 cm) while a significant interaction between depth, location, tillage, and grazing was found for the Chao‐1 index. Microbial network properties were only significantly affected by sampling depth. This study shows that the lack of disturbance in non‐tilled and non‐grazed soils resulted in a more diverse soil community, while grazing stimulated microbial function, thus showing a decoupling between diversity and function in vineyard soil ecosystems.

Language activity, and thus broadly understood linguistic communication, occurs on various levels and using diverse linguistic means. One of these tools is metaphor, the use of which helps in better visualization, and subsequently in the reception and understanding of abstract content. This statement also applies to issues within the realm of politics. This article analyzes the role of conceptual metaphor (cf. Lakoff/Johnson 1980), based on opposites (e.g., dark-light, cold-warm, strong-weak etc.), and points out its presence and significance in conceptualizing political struggle. The research material consists of articles from Polish and German online platforms, whose articles address the topic of parliamentary elections in Poland in 2023. The aim of the study is to answer the question of whether concepts expressed in the form of opposites can adequately capture the complexity of this problem. In the theoretical part of the article, we find a characteristic of conceptual metaphor and a description of its functions in press communications.

Abstract Grapes, renowned for their diverse phytochemical composition, have long been recognized for their health-promoting properties. This narrative review aims to synthesize the current research on grapes, with a particular emphasis on their role in disease prevention and health enhancement through bioactive compounds. A comprehensive review of peer-reviewed studies, including in vitro, in vivo, and clinical investigations, was conducted to elucidate the relationship between grape consumption and health outcomes. The review highlights the positive association of grape intake with a decreased risk of chronic diseases such as cardiovascular disease, type 2 diabetes, and certain cancers. Notable bioactive components like resveratrol are emphasized for their neuroprotective and antioxidative capabilities. Additionally, the review explores emerging research on the impact of grapes on gut microbiota and its implications for metabolic health and immune function. This updated review underscores the importance of future research to fully leverage and understand the therapeutic potential of grape-derived compounds, aiming to refine dietary guidelines and functional food formulations. Further translational studies are expected to clarify the specific bioactive interactions and their impacts on health. Graphical Abstract

Foundation: the impact measures the transformative effects of a training program on the institution, the faculty, the students, the community and the environment.Objective: to evaluate the impact of the doctoral program in Infectology and Tropical Medicine implemented at the Pedro Kourí Institute of Tropical Medicine.Methods: a quantitative-qualitative observational study was carried out during the years 2018-2023, with a population of 153 members and a sample of 137 participants. The Theory of Education was used. Interview, survey and observation, theoretical level methods and descriptive statistics were used.Results: the faculty is composed of 53 doctors in science, with 516 (9.92 average) awards, 522 (10.3 average) scientific articles, 550 events (10.57 per faculty member). The postdoctoral strategy projects the participation of academic and scientific networks. The enrollment is 62 doctoral students, predominantly female and over 60 years old, with 78 publications. They have received 97 awards (4.4 average), 14 awards from the Cuban Academy of Sciences and eight Annual Health Awards, the 2020 Public Health Excellence Award, recognition from the World Organization of Parasitology, two L`Oreal-Unesco Awards, and the Lifetime Achievement Award from the Veterinary Medicine Association.Conclusions: The Doctoral Program was evaluated as excellent and is inserted in the 2030 Agenda for Sustainable Development, with a well-strengthened postdoctoral academic training directed towards the search for sustainable and innovative solutions.

Introduction: In kidney transplant (KT) recipients diabetes mellitus (DM) are associated with an increased mortality and a poorer graft survival. Glucagon-like peptide 1 receptor agonists (GLP1-RA) have demonstrated cardiovascular and renal benefits in the general population. However, there is lacking evidence in KT recipients. Objective: To analyze the efficacy and safety of glucagon-like peptide 1 receptor GLP1-RA in a cohort of KT recipients. Methods: Multicenter retrospective cohort study of KT patients with DM who started subcutaneous GLP1-RA in 3 hospitals in the province of Cádiz between February 2016 and July 2022. Estimated glomerular filtration rate (eGFR), proteinuria, and weight at baseline and after 6 and 12 months were collected. We analyzed glycemic control, blood pressure, lipid profile, and doses and trough levels of tacrolimus. We document episodes of acute rejection (AR), de novo donor-specific antibodies (dnDSA), and adverse effects. Results: During this period, 96 KT with DM started treatment with GLP1-RA, of which 84 had a minimum follow-up of 6 months and 61 were followed for 12 months. A significant reduction was observed in proteinuria (−19.1 mg/g, p = 0.000; −46.6 mg/g, p = 0.000), weight (−3.6 kg, p = 0.000; −3.6 kg, p = 0.000), glycosylated hemoglobin (−0.7%, p = 0.000; −0.9%, p = 0.000), systolic blood pressure (−7.5 mmHg, p = 0.013; −7.3 mmHg, p = 0.004), total cholesterol (−11.5 mg/dL, p = 0.001; −15.6 mg/dl, p = 0.002) and LDL cholesterol (−9.2 mg/dl, p = 0.002; −16.8 mg/dl, p = 0.000) at 6 months and 1 year of follow-up. The eGFR remained stable and the dose and trough levels of tacrolimus did not change. No episodes of AR or development of dnDSA were observed during follow-up. Conclusions: GLP1-RA in KT patients can be a safe and effective option for the management of DM in KT. Resumen: Introducción: En los pacientes receptores de trasplante renal (TR) la diabetes mellitus (DM) se relaciona con una mayor mortalidad y menor supervivencia del injerto. Los agonistas del receptor del péptido 1 similar al glucagón (ar-GLP1) han demostrado beneficios cardiovasculares y renales en la población general. Sin embargo, su evidencia en pacientes TR es limitada. Objetivo: Analizar la eficacia y seguridad de los ar-GLP1 en una cohorte de pacientes TR. Métodos: Estudio de cohortes retrospectivo multicéntrico de los pacientes TR con DM que iniciaron ar-GLP1 de administración subcutánea en 3 hospitales de la provincia de Cádiz entre febrero de 2016 y julio de 2022. Se recogió filtrado glomerular estimado (FGe), proteinuria y peso al inicio del tratamiento y tras 6 y 12 meses. Analizamos control glucémico, tensión arterial, perfil lipídico y niveles valle y dosis de tacrolimus. Documentamos episodios de rechazo agudo (RA), anticuerpos donantes específicos de novo (DSAn) y efectos adversos. Resultados: En este periodo 96 TR con DM iniciaron tratamiento con ar-GLP1, de los cuales 84 cumplieron el seguimiento mínimo de 6 meses y 61 pacientes de 1 año. Se observó una reducción significativa de la proteinuria (−19.1 mg/g, p = 0.000; −46.6 mg/g, p = 0.000), peso (−3.6 kg, p = 0.000; −3.6 kg, p = 0.000), hemoglobina glicosilada (−0.7 %, p = 0.000; −0.9%, p = 0.000), tensión arterial sistólica (−7.5 mmHg, p = 0.013; −7.3 mmHg, p = 0.004), colesterol total (−11.5 mg/dL, p = 0.001; −15.6 mg/dl, p = 0.002) y LDL colesterol (− 9.2 mg/dl, p = 0.002; −16.8 mg/dl, p = 0.000) a los 6 meses y al año de seguimiento. El FGe se mantuvo estable y no se modificó ni la dosis ni los niveles valle de tacrolimus. No se objetivaron episodios de RA ni desarrollo de DSAn durante el seguimiento. Conclusiones: Los ar-GLP1 en pacientes TR demuestran que puede ser una opción segura y eficaz para el manejo de la DM en TR.

Hemodialysis (HD) is a treatment with a significant environmental impact. One dialysis cycle is equivalent to the daily consumption of 3.5–4 people, and the average annual electricity consumption of a center is equivalent to that of approximately 2.5–3 households (9 kWh/day per household). The carbon footprint (kg CO2 equivalent) measures direct and indirect greenhouse gas emissions and is influenced by the production of the various materials used, their transport, patients, and healthcare personnel. In this context, it is necessary to understand the real impact of each center on the environment and act sustainably. The aim of this review is to analyze the environmental footprint generated by dialysis, rethink processes, and propose management strategies to provide tools applicable to any unit to reduce the negative impact of this activity. Each center must measure and monitor indicators, set its own standards, design improvement plans, and carry out annual monitoring in a multidisciplinary manner. Resumen: La hemodiálisis (HD) es un tratamiento con gran impacto en el medio ambiente. Un ciclo de diálisis equivale al consumo diario 3,5−4 personas y el consumo anual medio de electricidad de un centro se equipara al de aproximadamente 2,5 a 3 hogares (9 kWh/día por hogar). La huella de carbono (kg CO2 equivalente) es la medida de las emisiones directas e indirectas de gases de efecto invernadero y está influida por la producción de los distintos materiales utilizados y el transporte de estos, de los pacientes y el personal sanitario. En este contexto se hace necesario conocer el impacto real de cada centro en el mediomabiente y actuar de una manera sostenible. El objetivo de esta revisión es analizar la huella medioambiental que genera la diálisis, repensar los procesos y plantear estrategias de gestión con el fin de aportar herramientas aplicables a cualquier unidad para reducir el impacto negativo de esta actividad. Cada centro debe medir y hacer seguimiento de indicadores, fijar su estándar, diseñar planes de mejora y realizar seguimiento anual de manera multidiciplinar.

Abstract Science diplomacy has been assuming a growing importance in the actions of states due to their need to respond to global challenges and to strengthen their power and influence through competitive advantage based on science and technology. Within the European Union (EU), science diplomacy can be seen as an instrument for the integration of the European project and for the projection of EU influence, standards, and values in the relationship with third countries. In this context, the present work aims at understanding and characterizing Portugal’s science diplomacy model and its relationship with the European project from 1986 (the moment of Portugal’s accession to the European Economic Community) to 2021. To this end, we mapped the science diplomacy designed and implemented by the Portuguese State by identifying its different instruments based on a methodology suggested by the European Commission, Directorate-General for Research and Innovation and Van Langenhove in 2017 and using a timeframe suggested by Heitor in 2015. The obtained dataset was subjected to a combination of analytical frameworks, including the general framing analysis proposed by Ruffini and Krasnyak in 2023, which allowed us to identify the objectives, strategic drivers and implementation approach of the Portuguese science diplomacy model. In the period under study Portugal has been developing a science diplomacy in parallel with the European project without ever losing a global vision of the relations in the field of science and technology.

Abstract Porcine transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) are swine coronaviruses belonging to the genus Alphacoronavirus in the family Coronaviridae. To date, there are no reports on the prevalence and genetic characterization of these viruses in domestic pigs from Poland. In this study, 828 serum samples were tested by TGEV/PRCV immunoassay to estimate TGEV and PRCV seroprevalence, while 277 nasal swabs and 221 stool samples were tested by real-time PCR to detect viral RNA. Our results revealed that 2.2% (95% CI 1.2, 3.2) of serum samples were positive for anti-TGEV antibodies, while 12.2% (95% CI 9.8, 14.4) of samples were positive for anti-PRCV antibodies. 2.5% (95% CI 1.5, 2.6) and 5.2% (95% CI 3.7, 6.7) of serum samples were inconclusive for TGEV and PRCV, respectively. RNA of TGEV was not detected in any of the tested samples, while PRCV RNA was detected in 6.22% of samples. Genetic and phylogenetic analysis revealed that all Polish PRCV strains were closely related to European and Korean PRCV strains than to American strains. Some of the Polish PRCV strains have a 672 nt deletion at the same position at the 5’ end of the S gene as other European and Korean PRCV strains, suggesting that they originated from the same precursor. Other Polish PRCV strains had a 690 nt deletion that differed in size and location from any of the known PRCV strains. This may suggest that these Polish PRCVs may have originated from different ancestor. Furthermore, the Polish PRCV strains showed some unique changes in their sequences, which may reflect their evolution. This study is the first report on the prevalence of TGEV/PRCV in pigs from Poland. In addition, this is the first report on the genetic characterization of Polish PRCV strains, which provide new information on PRCV heterogeneity.

Abstract Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.

Abstract Background Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients’ subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were “markedly or severely ill” showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration NCT06527885 retrospectively registered (01/08/2024).

Whiteflies (Hemiptera: Aleyrodidae) are significant agricultural pests worldwide, primarily because they act as vectors for various plant viruses, including geminiviruses. Additionally, whitefly activity fosters the development of fungal colonies, such as sooty mold (Capnodium spp.), which grows on the sugary secretions (honeydew) produced by these insects. The presence of sooty mold reduces the plant’s photosynthetic capacity, further worsening the negative impact on its growth and development. Together, these factors make whitefly control a challenge for farmers, who must implement integrated pest management strategies to mitigate both the direct damage and the associated diseases that whiteflies can spread. Although approximately 1,200 species of whiteflies have been described, fewer than 40 are considered primary pests, with Bemisia tabaci (Gennadius, 1889) and Trialeurodes vaporariorum (Westwood, 1889) responsible for the greatest agricultural losses worldwide. The emergence of B. tabaci biotypes has prompted significant research, as these biotypes have been linked to economic damage to crops in several nations of the Americas, including Argentina and Brazil. In Paraguay, there is a need to identify local biotypes of B. tabaci led to the collection of whitefly samples from soybean plots in Capitán Miranda and Natalio, Itapúa, Paraguay. DNA was extracted using the Wizard genomic purification kit, followed by PCR amplification of the mitochondrial cytochrome oxidase I (mtCOI) region using specific primers for B. tabaci and T. vaporariorum. Agarose gel electrophoresis confirmed the presence of B and Q biotypes of B. tabaci in both Paraguayan locations, with no detection of T. vaporariorum. Sequencing of the PCR products revealed a 100% match with known sequences for B. tabaci and its biotypes, as confirmed by GenBank BLAST analysis. This research highlights the critical importance of continuously monitoring the population dynamics and geographical distribution of different biotypes. While the expansion of a polyphagous and dynamic pest like the whitefly cannot always be prevented, constant monitoring enables early detection of its spread and allows for the adjustment of management strategies tailored to each region. These measures will not eliminate the pest but will help mitigate damage and manage the problem sustainably and efficiently. The study also emphasizes the need to evaluate the effectiveness of insecticides, as resistance has been reported in other countries—an issue not yet explored in Paraguay.

Interdisciplinary marine research is pivotal for addressing ocean sustainability challenges but may exclude diverse socio-economic, cultural, or identity groups. Drawing on perspectives of marine Early Career Researchers, we highlight the importance of Diversity, Equity, and Inclusion (DEI) in advancing interdisciplinary marine science and present ten recommendations to enhance DEI. As our ocean faces increasing threats, fostering DEI within this domain is not merely an aspirational goal but an ethical imperative.

Abstract Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between the HLA region and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4, HMGN2P18-KRTCAP2, NFKBIZ and APOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination.

Abstract Phonon polaritons – quasiparticles formed by strong coupling of infrared (IR) light with lattice vibrations in polar materials – can be utilized for surface-enhanced infrared absorption (SEIRA) spectroscopy and even for vibrational strong coupling with nanoscale amounts of molecules. Here, we introduce and demonstrate a compact on-chip phononic SEIRA spectroscopy platform, which is based on an h-BN/graphene/h-BN heterostructure on top of a metal split-gate creating a p-n junction in graphene. The metal split-gate concentrates the incident light and launches hyperbolic phonon polaritons (HPhPs) in the heterostructure, which serves simultaneously as SEIRA substrate and room-temperature infrared detector. When thin organic layers are deposited directly on top of the heterostructure, we observe a photocurrent encoding the layer’s molecular vibrational fingerprint, which is strongly enhanced compared to that observed in standard far-field absorption spectroscopy. A detailed theoretical analysis supports our results, further predicting an additional sensitivity enhancement as the molecular layers approach deep subwavelength scales. Future on-chip integration of infrared light sources such as quantum cascade lasers or even electrical generation of the HPhPs could lead to fully on-chip phononic SEIRA sensors for molecular and gas sensing.

Aim: To assess lung function in patients with persistent dyspnea 1 year after mild coronavirus disease 2019 (COVID-19) and compare with those hospitalized with moderate or critical COVID-19. Methods: Adults with confirmed severe acute respiratory syndrome coronavirus-2 infection with mild COVID-19 and persistent dyspnea (n = 18) or with moderate (n = 34) or critical COVID-19 (n = 19) were followed up 11–13 months after initial infection. Inclusion criteria were age < 65 years, no smoking history, and no preexisting respiratory diseases. Sociodemographic and clinical data were collected, and patients underwent spirometry and measurement of diffusing capacity for carbon monoxide (DLCO). Results: The non-hospitalized patients were significantly younger and more often female compared with those in the moderate and critical groups (P = 0.002 and P < 0.001, respectively). No significant differences in comorbidities or body mass index (BMI) were noted between severity groups. An obstructive spirometry pattern (ratio of forced expiratory volume during the first exhalation second to forced vital capacity under the lower limit of normal (LLN)) was found in 5.6, 5.9, and 5.3% of patients in the mild, moderate, and critical groups, respectively (P = 0.995). Abnormal DLCO (< LLN) rates were seen in 5.6, 16.7, and 47.4% in the mild, moderate, and critical groups, respectively (P = 0.018). DLCO, expressed as a z-score, was significantly lower in the critical group compared with the mild group after adjustment for age, sex, and BMI. Conclusion: Only a few subjects with mild COVID-19 and persistent dyspnea had abnormal lung function 1 year after initial infection, assessed based on spirometry and DLCO measurements. An obstructive spirometry pattern at 1-year follow-up was uncommon even in patients with moderate or critical COVID-19. Impaired DLCO was more common in patients with critical COVID-19.

Abstract Background and objectives There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. Methods EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. Results The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). Conclusion Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.

Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en 2 unidades de hemodiálisis (HD), de 2 hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo de 2021 hasta septiembre de 2022. Establecimos 3 definiciones de HTAID: - Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg. - Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg. - Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/h.Consideramos que había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre- y pos-HD. Se consideró función renal residual (FRR) una diuresis > 250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% varones), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5-67,5) meses. De ellos, 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def 1 (8,3%), Def 2 (27,2%) y Def 3 (29,6%). Se evidencia una asociación en la Def 2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def 3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD. Abstract: Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in two HD units, including all prevalent patients from March 2021 to September 2022. We established three definitions of IDH: Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD > 15 mmHg. Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD > 10 mmHg. Def 3: SBP difference >0 and ultrafiltration rate (UFR) > 5 ml/kg/h.IDH was considered present if the criterion was met in more than 50% of the six consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR: 17.5-67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units.

Abstract Background Atherosclerotic Cardiovascular Disease (ASCVD) is a global public health concern. This study aimed to estimate the healthcare resource utilization (HRU) and costs stratified by cardiovascular disease (CVD) risk categories using real-world evidence, in a regional population in Portugal. Methods This is a retrospective observational study, using data from Electronic Health Records between 2017 and 2021. Patients aged ≥ 40 years, and with at least one general practitioner (GP) appointment in the 3 years before 31st of December 2019, were included. CVD risk categories were determined based on 2021 ESC prevention guidelines. HRU encompassed hospital data (hospitalizations, outpatient and emergency room visits) and GP appointments. Total direct costs per patient were calculated based on the reference cost of the Portuguese legislation for payment methodology on Diagnosis-Related Groups (DRGs). Results Analysis of 3 122 695 episodes, revealed consistent HRU and costs across the five years. Very high-risk patients, showed higher HRU, particularly in hospital admissions. Costs tended to rise with higher CVD risk level. Very high-risk patients with ASCVD had higher costs for hospital admissions, while low-to-moderate risk patients had higher costs for GP visits. Despite a smaller proportion, very high-risk patients with prior ASCVD represent the highest costs per patient across healthcare settings (from 115€ in emergency visits to 2 673€ in hospitalizations), followed by very high-risk patients without prior ASCVD (ASCVD-risk equivalents). Conclusion This study revealed a substantial HRU and costs by patients with very high CVD risk, particularly those with prior ASCVD. Moreover, ASCVD-risk equivalents emerge as notable consumers, emphasizing the importance of risk assessment and preventive measures in cost-effective management of these patients.

Ana Marta,1,2 André Ferreira,1,3,4 Inês Couto,1 Miguel Mesquita Neves,1 Miguel Gomes,1 Luis Oliveira,1 Celia Azevedo Soares,5– 8 Maria João Menéres,1,2 Carolina Lemos,2,8 João Melo Beirão1,2 1Department of Ophthalmology, Centro Hospitalar Universitário de Santo António, Unidade Local de Saúde de Santo António, Porto, Portugal; 2Instituto Ciências Biomédicas Abel Salazar (ICBAS), Porto, Portugal; 3Department of Biomedicine - Unit of Anatomy, Faculty of Medicine of University of Porto, Porto, Portugal; 4Centre for Health Technology and Services Research, Health Research Network (CINTESIS@RISE), Faculty of Medicine of the University of Porto, Porto, Portugal; 5Medical Genetics Department, Centro Hospitalar Universitário de Santo António, Unidade Local de Saúde de Santo António, Porto, Portugal; 6Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; 7Medical Science Department, Universidade de Aveiro, Aveiro, Portugal; 8i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalCorrespondence: Ana Marta, Centro Hospitalar Universitário de Santo António, Unidade Saúde Local de Santo António, EPE (ULSSA), Largo do Prof. Abel Salazar, Porto, 4099-001, Portugal, Email analuisamarta2@gmail.comPurpose: Inherited retinal diseases (IRDs) are a group of degenerative disorders of the retina, that can be potentially associated with changes in the anterior segment, but their prevalence and impact are not known. Exploring these concomitant ophthalmologic changes with biomechanical assessment may help identify other non-retina causes of vision loss in these patients, such as corneal ectasia or susceptibility to glaucoma. This study aimed to measure and compare corneal biomechanics in patients with and without IRDs.Methods: A total of 77 patients (154 eyes) with IRD were recruited as the study group. The control group consisted of 77 healthy adults (154 eyes) with matched age and sphere equivalents. All participants underwent a comprehensive assessment including corneal tomography (Pentacam®) and biomechanical assessment (Corvis ST®). A total of 4 second-generation biomechanical parameters and 3 indexes were collected: Ambrosio Relational Thickness (ARTh), Deflection Amplitude Ratio Max (DARM), Integrated Radius (IR) and Stiffness Parameter at Applanation (SP-A1), the final deviation value D of the Belin/Ambrosio Enhanced Ectasia Display (BAD-D), Corvis Biomechanical Index (CBI) and Tomographic Biomechanical Index (TBI).Results: For IRD patients, there was a higher DARM (p < 0.001), lower ARTh (p < 0.001), higher CBI (p < 0.001), higher TBI (p< 0.001), and higher BAD-D (p < 0.001) compared to the control group. Regarding discrimination of healthy subjects and IRD patients, ARTh was the most sensitive parameter.Conclusion: The results showed that IRD patients tend to have softer corneal behaviour, compared to eyes without pathology, which may predispose patients to corneal ectasia or glaucoma development. ARTh could be used to screen IRD patients if a non-retina cause of vision loss is suspected.Keywords: IRD, corneal biomechanics, corneal tomography

Abstract Survival relies on an organism's intrinsic ability to instinctively react to stimuli such as food, water, and threats, ensuring the fundamental ability to feed, drink, and avoid danger even in the absence of prior experience. These natural, unconditioned stimuli can also facilitate associative learning, where pairing them consistently with neutral cues will elicit responses to these cues. Threat conditioning, a well-explored form of associative learning, commonly employs painful electric shocks, mimicking injury, as unconditioned stimuli. It remains elusive whether actual injury or pain is necessary for effective learning, or whether the threat of harm is sufficient. Approaching predators create looming shadows and sounds, triggering strong innate defensive responses like escape and freezing. This study investigates whether visual looming stimuli can induce learned freezing or learned escape responses to a conditioned stimulus in male rats. Surprisingly, pairing a neutral tone with a looming stimulus only weakly evokes learned defensive responses, in contrast to the strong responses observed when the looming stimulus is replaced by a shock. This dissociation sheds light on the boundaries for learned defensive responses thereby impacting our comprehension of learning processes and defensive strategies.

Abstract Background There has been a rise in endometrial cancer (EC) incidence leading to increased mortality. To counter this trend, improving the stratification of post-surgery recurrence risk and anticipating disease relapse and treatment resistance is essential. Liquid biopsy analyses offer a promising tool for these clinical challenges, though the best strategy for applying them in EC must be defined. This study was designed to determine the value of cfDNA/ctDNA monitoring in improving the clinical management of patients with localized and recurrent disease. Methods Plasma samples and uterine aspirates (UA) from 198 EC patients were collected at surgery and over time. The genetic landscape of UAs was characterized using targeted sequencing. Total cfDNA was analyzed for ctDNA presence based on the UA mutational profile. Results High cfDNA levels and detectable ctDNA at baseline correlated with poor prognosis for DFS (p-value

The manuscript provides an overview of the mid-term results of the citizen science campaign activities conducted within the Life CONCEPTU MARIS project (LIFE20 NAT/IT/001371) whose aim is to improve the conservation status of cetaceans and pelagic sea turtles by addressing information gaps, setting up an internationally agreed-upon approach for surveillance, and identifying appropriate conservation measures. It fosters a cooperative effort by engaging the scientific community, stakeholders, policy makers and citizens in a common effort to support biodiversity.

Immune thrombocytopaenia (ITP) is the most common cause of acquired thrombocytopaenia diagnosed in paediatric patients. It is described as an isolated thrombocytopaenia without other factors, which may cause a decrease in platelets. Therefore, the diagnosis is of exclusion. Over the last few years, its management has significantly developed, and a paradigm switch in second-line treatment is being observed. Currently, thrombopoietin receptor agonists (TPO-RA) are available in Poland, which reduce the need for splenectomy in affected patients. The use of thrombopoietin receptor agonists has also provoked a change in definitions, especially concerning refractory ITP. This review focuses on an overview of currently recommended diagnostics and treatment of ITP, ongoing research concerning genetic predisposition, the use of TPO-RA, other immunosuppressive agents, and the role of splenectomy. We summarise congenital thrombocytopaenic disorders, which are the most often mistaken as ITP and need to be considered in the differential diagnosis.

Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in 2 HD units, including all prevalent patients from March 2021 to September 2022. We established 3 definitions of IDH: • Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD >15 mmHg • Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD >10 mmHg • Def 3: SBP difference >0 and ultrafiltration rate (UFR) >5 ml/kg/hIDH was considered present if the criterion was met in more than 50% of the 6 consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR 17.5–67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units. Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en dos unidades de hemodiálisis (HD), de dos hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo 2021 hasta septiembre 2022. Establecimos 3 definiciones de HTAID: • Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg • Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg • Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/hConsideramos había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre y post HD. Se consideró función renal residual (FRR) una diuresis >250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% hombres), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5–67,5) meses. De ellos 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def1 (8,3%), Def 2 (27,2%) y Def3 (29,6%). Se evidencia una asociación en la Def2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD.

Actinobacteria and fungi are renowned for their metabolic diversity and adaptability to various environments, thus exhibiting significant potential for environmental decontamination and sustainable production. Both actinobacteria and fungi excel in producing diverse secondary metabolites and enzymes, offering valuable tools for industrial and environmental applications. Their ability to detoxify metals and degrade a wide range of organic pollutants, such as pesticides, hydrocarbons, and dyes, positions them as promising candidates for bioremediation.Recent shifts in microbiological sciences emphasize research on mixed microbial populations. Microbial interactions in mixed communities emulate natural processes and yield emergent properties such as stability, robustness, and enhanced metabolism. Co-cultures of actinobacteria and fungi harness a broader range of genes and metabolic capabilities through their distinctive interactions, opening new avenues for developing novel products and/or technologies. This review provides a critical analysis of the present status of knowledge regarding the potential of actinobacteria-fungi co-cultures with a particular focus on novel functionalities and heightened production efficiency. These consortia are promising in several fields, from environmental applications to the biosynthesis of industrially relevant metabolites and enzymes, and enhancements in agricultural production. Although challenges still exist, their potential to address complex problems has been demonstrated and deserves further investigation.

In the current study, we aimed (i) to evaluate sleep quality via wrist actigraphy monitoring of nonhospitalized and hospitalized post-COVID-19 condition (PCC) participants; (ii) to correlate actigraphy measures with subjective measures of sleep quality, such as the Pittsburgh Sleep Quality Index (PSQI); and (iii) to investigate whether total sleep time or sleep efficiency could affect PCC cognitive performance. We included 49 individuals with PCC from the NAUTILUS Project (NCT05307549 and NCT05307575) who were monitored for 1 week via actigraphy and who were also assessed with a comprehensive neuropsychological battery and the PSQI. We found that there were significant differences between nonhospitalized PCCs and hospitalized PCCs in the number of awakenings. We also found a correlation between the total sleep time of both measures (actigraphy and PSQI), but we did not observe correlations between objective and subjective parameters of latency and sleep efficiency. Regarding cognition and actigraphy measures, there was a trend of statistical significance in the performance of immediate visual memory, attention span and social cognition according to sleep efficiency. In conclusion, results indicate that although the PSQI provides clinically relevant indicators of sleep, there are divergent results between self-reported and objective sleep measures (actigraphy). Furthermore, we found a tendency toward statistical significance in cognitive performance in PCC participants according to their sleep efficiency which could indicate that is more important for cognitive function of post-COVID-19 patients than total sleep time.

Preexisting immunity may be associated with increased protection against non-related pathogens such as, SARS-CoV-2. There is little information regarding endemic human coronaviruses (HCOVs) from Pakistan, which experienced a relatively low COVID-19 morbidity and mortality. We investigated antibodies to SARS-CoV-2 and HCoVs NL63 and OC43, comparing sera from prepandemic controls (PPC) period with responses in healthy controls from the pandemic (HC 2021). Further, we investigated the effect of inactivated and mRNA COVID-19 vaccinations on antibody responses to the pandemic and endemic coronaviruses.We measured IgG antibodies to Spike of SARS-CoV-2, HCoV-NL63 and HCoV-OC43 by ELISA. Serum neutralizing capacity was determined using a SARS-CoV-2 psuedotyped virus assay. Vaccinees were sampled prior to vaccination as well after 6, 12 and 24 weeks after COVID-19 inactivated (Sinovac), or mRNA (BNT162b2) vaccine administration.PPC sera showed seropositivity of 15 % to SARS-CoV-2, whilst it was 45 % in the HC 2021 group. Five percent of sera showed virus neutralizing activity in PPC whilst it was 50 % in HC 2021. IgG antibodies to Spike of NL63 and OC43 were also present in PPC; anti-NL63 was 2.9-fold, and anti-OC43 was 10.1-fold higher than to anti-SARS-CoV-2 levels. IgG antibodies to Spike SARS-CoV-2 were positively correlated with HCoV-NL63 in HC 2021, indicating recognition of shared conserved epitopes. IgG antibody levels increased during the pandemic; 2.7-fold to HCoV-NL63 and 1.9-fold to HCoV-OC43.SinoVac and BNT162b2 vaccine induced an increase in IgG antibodies to Spike SARS-CoV-2 as well as HCoV-NL63 and HCoV-OC43.Our data show that antibodies to spike protein of endemic coronaviruses were present in the prepandemic population. Antibodies to SARS-CoV-2, NL63 and OC43 were all raised during the pandemic and further enhanced after COVID-19 vaccinations. The increase in antibodies to spike of coronaviruses would contribute to protection against SARS-CoV-2.

Background: The heterogeneous prognosis in neuroblastoma, shaped by telomere maintenance mechanisms (TMMs), notably the alternative lengthening of telomeres (ALT) pathway, necessitates a refined risk classification for high-risk patients. Current systems often lack precision, hindering tailored treatment approaches. This individual participant data (IPD) meta-analysis of survival among ALT-positive patients aims to improve risk classification systems, enhancing therapeutic strategies and patient outcomes. Methods: Following PRISMA-IPD guidelines, we conducted a comprehensive review of neuroblastoma patients retrieved from PubMed, Scopus, and Embase databases until March-2024. Patients were stratified into ALT-positive and TMM-negative subgroups. Overall and event-free survival probabilities were evaluated. Results: In our cohort of 293 patients (156 ALT-positive, 137 TMM-negative) obtained from eight different studies, ALT-positive individuals displayed lower survival rates than TMM-negative patients. Non-stage 4 ALT-positive patients had reduced overall and event-free survival probabilities compared to their TMM-negative counterparts, indicating potential misclassification. Stage 4 ALT-positive patients similarly showed poorer survival outcomes than non-stage 4 TMM-negative patients, underscoring the significance of ALT in patient prognosis. Conclusions: Our study highlights poorer outcomes in ALT-positive neuroblastoma patients, emphasizing the need to integrate TMM status into international risk classification guidelines. Standardizing TMM assessment is key for refining treatment strategies, considering the unique biology of ALT-positive patients.

Background: Congenital hypothyroidism (CH) is a preventable cause of neurodevelopmental delay in children, detectable by newborn screening (NBS) programs for CH. Since NBS for CH was started in Canada in 1974, numerous countries have successfully implemented this public health strategy. However, in 2014, only 29.3% of newborns worldwide were screened by NBS for CH. Objective: This study aimed to assess the implementation of new NBS programs for CH over the past decade, and screening methods and coverage rates of current programs. In addition, it sought to update the worldwide iodine status. Methods: We reviewed literature data on NBS programs for CH and their coverage rates for each country, using PubMed, Embase and Google searches. Results: Currently, 29.6% of children worldwide are screened for CH. Europe, North America, Oceania, China, Japan and Israel have efficient programs with optimal coverage. Recently, some countries of Central and Western Asia have implemented NBS programs for CH, and coverage has increased in several Asian countries. South America has also seen substantial improvements in coverage. In contrast, almost none of the African countries has widespread screening programs, but some attempts with pilot studies and local initiatives have been witnessed. Global iodine sufficiency has improved, with 149 of 193 countries achieving adequate iodine levels by 2023. Conclusions: Over the past decades, several countries have launched NBS programs for CH or conducted pilot studies, and the coverage of most existing NBS programs has increased. Nevertheless, approximately 70% of newborns worldwide still lack access to NBS for CH, predominantly in African and Asian countries, accounting for a significant part of annual births.

Abstract Objectives To assess the contemporary malignancy rate in isolated de novo red patches in the bladder and associated risk factors for better selection of red patch biopsy. Patients Patients from the IDENTIFY dataset; Patients referred to secondary care with suspected urinary tract cancer and found to have isolated de novo red patches on cystoscopy. Methods We reported the unadjusted cancer prevalence in isolated de novo red patches that were biopsied; multivariable logistic regression was used to explore cancer‐associated risk factors including age, sex, smoking, type of haematuria, LUTS, UTIs and a suspicious‐looking red patch (as reported by the cystoscopist). Sub‐analysis of these by clinical role and experience was performed. Results A total of 1110 patients with isolated de novo red patches were included. 41.5% (n = 461) were biopsied, with a malignancy rate of 12.8% (59/461), which was significantly higher in suspicious versus non‐suspicious red patches (19.1% vs. 2.81%, p

Abstract BackgroundChronic pain is among the most common conditions worldwide and requires a multidisciplinary treatment approach. Spinal cord stimulation is a possible treatment option for pain management; however, patients undergoing this intervention require close follow-up, which is not always feasible. eHealth apps offer opportunities for improved patient follow-up, although adherence to these apps tends to decrease over time, with rates dropping to approximately 60%. To improve adherence to remote follow-up, we developed a remote follow-up system consisting of a mobile app for patients, a website for health care professionals, and a remote support center. ObjectiveOur objective was to evaluate patient adherence to remote follow-up using a system that includes a mobile app and a remote support center. MethodsAfter review of the literature and approval of the design of the follow-up system by a multidisciplinary committee, a team of experts developed a system based on a mobile app, a website for health care professionals, and a remote support center. The system was developed in collaboration with health care professionals and uses validated scales to capture patients’ clinical data at each stage of treatment (ie, pretreatment phase, trial phase, and implantation phase). Data were collected prospectively between January 2020 to August 2023, including the number of total surveys sent, surveys completed, SMS text message reminders sent, and reminder calls made. ResultsA total of 64 patients were included (n=40 women, 62.5%) in the study. By the end of the study, 19 (29.7%) patients remained in the pretreatment phase, 8 (12.5%) patients had completed the trial phase, and 37 (57.8%) reached the implantation phase. The mean follow-up period was 15.30 (SD 9.43) months. A total of 1574 surveys were sent, along with 488 SMS text message reminders and 53 reminder calls. The mean adherence rate decreased from 94.53% (SD 20.63%) during the pretreatment phase to 65.68% (SD 23.49%) in the implantation phase, with an overall mean adherence rate of 87.37% (SD 15.37%) for the app. ANOVA showed that adherence was significantly higher in the earlier phases of treatment (P ConclusionsOur remote follow-up system, supported by a remote support center improves adherence to follow-up in later phases of treatment, although adherence decreased over time. Further studies are needed to investigate the relationship between adherence to the app and pain management.

Background Advancing evidence-based, tailored interventions for substance use disorders (SUDs) requires understanding temporal directionality while upholding ecological validity. Previous studies identified loneliness and craving as pivotal factors associated with alcohol consumption, yet the precise directionality of these relationships remains ambiguous. Objective This study aims to establish a smartphone-based real-life intervention platform that integrates momentary assessment and intervention into everyday life. The platform will explore the temporal directionality of contextual influences on alcohol use among individuals experiencing loneliness and craving. Methods We will target 180 individuals aged 18 to 70 in Germany who report loneliness, alcohol cravings, and meet risk or binge drinking criteria (over 14 standard drinks per week or five drinks in a single day for males, and over seven drinks per week or four drinks in a single day for females). Using a Within-Person-Encouragement-Design and Just-In-Time-Adaptive-Interventions, we will manipulate the contexts of loneliness and alcohol craving with cognitive reappraisal and physical activity interventions against a control condition (working memory task). Results Recruitment started in June 2024, with data collection and processing expected by June 2027. Conclusion Our real-life intervention platform endeavors to serve as a robust tool for discerning the directionality of the effects from time series data in everyday life influences on alcohol use for the future study. Ultimately, it will pave the way for low-threshold prevention, clinical treatment, and therapy to target diverse contexts of everyday life in SUD. Trial registration German Clinical Trials Register DRKS00033133.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain. Methods: Data from adult IPD cases (≥18 years) were collected from six Spanish hospitals in 2019–2021. Strains were serotyped, tested for antibiotic susceptibility and subjected to whole genome sequencing (WGS). Findings were compared with data from previous periods (2008–2016). Results: A total of 655 IPD episodes were examined. Pneumonia was the main focus (515/655), and 366 episodes occurred in adults over 64 years. Although IPD incidence decreased during COVID-19 pandemic, the burden of disease caused by PCV13 serotypes was significant. Notably, serotype 3 persisted (GPSC12-ST180 and GPSC83-ST260), and a new serotype 4 lineage emerged (GPSC162-ST13022). Among non-PCV13 serotypes, serotype 8 expanded (GPSC3-ST53) and a new serotype 12F lineage emerged (GPSC55-ST8060). Most serotypes presented a dominant Global Pneumococcal Sequencing Cluster (GPSC) like GPSC16-ST67 of 9N or GPSC19-ST433 of 22F. Nevertheless, some GPSCs were associated with several serotypes, the most numerous were GPSC3 (serotypes 8, 11A, and 33F) and GPSC6 (serotypes 11A and 14). The overall penicillin non-susceptibility rate was 17.0 %, 14.6 % resistance for meningitis and 1.6 % for pneumonia (15.1 % susceptible at increased exposure [SIE]). Serotypes 11A and 14 (GPSC6-ST156/6521) and 19A (GPSC1-ST320) had penicillin MICs above 1 mg/L. Acquired resistance genes associated with macrolide and/or tetracycline resistance were present in 19.4 % of isolates, particularly among serotypes 6C (GPSC47-ST386/4310) and 19A (GPSC1-ST320). Conclusions: The burden of PCV13 serotypes in adult IPD remains significant, and serotype 3 is the primary contributor. However, the rise of stable lineages associated with non-PCV13 serotypes, particularly 8, 9N, and 22F highlights a shifting epidemiology. The persistence of multidrug-resistant lineages, such as GPSC6-ST156 and GPSC1-ST320, emphasizes the need for continued surveillance. Vaccination of high-risk adults with current and broader coverage PCVs would help to control the burden of pneumonia and IPD among adults.

A escola tem procurado implementar novas dinâmicas de trabalho, impulsionada não só por normativos legais, mas também para encontrar respostas para os inúmeros desafios com que se depara. Assim, tem procurado reorganizar as suas dinâmicas de trabalho, tentando substituir um modelo tradicionalmente individualista por um modelo que assente em práticas de trabalho colaborativo (TC), como são disso exemplo as Equipas Educativas (EE) (Formosinho & Machado, 2009). Após um inquérito por questionário, aplicado aos professores que integraram as EE e um inquérito por entrevista, aplicado aos coordenadores das EE, bem como pela análise de documentos estruturantes da escola, verificou-se que estas práticas resultam da realização de reuniões, que decorrem de acordo com o definido pela escola, onde são abordados essencialmente casos individuais de alunos e situações de indisciplina. São apontadas, como barreiras ao TC, a constituição da própria equipa ou as atitudes dos professores e, como facilitadores, a existência de um tempo previsto para as reuniões, a estabilidade do corpo docente e a relação entre professores. Na perceção dos professores, a colaboração docente nas EE é benéfica para alunos, professores e para a escola em geral. Contudo, há alterações que é necessário introduzir para melhorar a eficácia do TC, como uma maior flexibilidade nas reuniões e a promoção de um ambiente que incentive a participação ativa de todos os membros. Acresce a autonomia das EE, que deve ser ampliada para que possam adaptar as suas práticas às necessidades específicas de cada contexto escolar.