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Abstract Iminophosphoranes with the general formula (R3P═NR′) have great potential in synthetic chemistry as valuable precursors/intermediates in organic synthesis or as building blocks for various organic compounds. However, the synthetic approaches and conditions to prepare iminophosphoranes are still poorly understood, limiting the utility of this chemistry for organic materials. In this article, a simple and efficient synthesis of previously unattainable poly(arylene iminophosphoranes) is reported. The azide-phosphine Staudinger polycondensation is used, and the reaction conditions are carefully studied, including consideration of light and air, the influence of solvent and temperature, and investigation of the electronic and steric effects of multiazides. The newly defined reaction conditions appear to be highly versatile, allowing the use of both electron-rich and electron-deficient arylazides for reaction with phosphines to synthesize a library of poly(arylene iminophosphorane) networks that exhibit exceptional thermal and oxidative stability. Interestingly, despite the ylidic-form of the iminophosphorane linkage as shown by theoretical calculations, these newly developed poly(arylene-iminophosphorane) networks exhibit semiconducting properties, such as absorption band edges up to 800 nm and optical band gaps in the range of 1.70 to 2.40 eV. Finally, we demonstrate the broad applicability of these polymers by processing them into glassy films, creating foam-like structures and synthesizing metallo-polymer hybrids.

AI is one of the fastest rising technologies today. Industry is tackling implementation in strategic areas, while education must respond by changing teaching methods The objective of this paper is to provide a comprehensive overview of AI implementation in industry and education, identify synergistic opportunities between these sectors, and explore future trends that foster innovation and competitiveness. The author focuses on the analysis and comparison of different approaches and methodologies, examining specific use cases of AI and their impact on transforming educational practices and industrial processes. This thesis is based on a literature search that summarizes current knowledge and practices of AI implementation. The author analyses existing studies and use cases to identify key trends and approaches in industry and education. The findings show that industry is actively integrating AI into strategic areas, leading to improvements in process automation, predictive maintenance and product innovation. Higher education is adapting to these changes and transforming its teaching methods and curricula to prepare students to work with AI. In conclusion, effective implementation of AI requires close collaboration between industry and education. Limitations include the rapidly changing technological environment and the need for continuous adaptation.

Objective. The best results in glioblastoma (GBM) are obtained through aggressive treatment comprising maximally radical but safe resection followed by chemoradiotherapy. However, certain patients will undergo only stereotactic biopsy. This paper aims to evaluate life expectancy in GBM patients who underwent only stereotactic biopsy, including the effect of subsequent oncological treatment. Patients and Methods. Patients with confirmed GBM histology who had undergone stereotactic biopsy between June 2006 and December 2016 were retrospectively selected. Each patient had received a CT scan, followed by an MRI scan with a contrast agent. None of the patients were amenable to microsurgical resection. Results. Of the 60 patients, 41 (69%) received no subsequent oncological treatment, while 14 (23%) underwent isolated radiotherapy. Mean survival time of all patients was 2.8 months. Those who received no additional treatment had an average survival time of 2.3 months; patients who received any type of oncological treatment was 3.7 months. Of these, those receiving radiotherapy alone had a mean survival of 3.1 months. Patients who received oncological treatment with the Stupp protocol had a survival time of 6.6 months. Conclusion. Diagnostic and surgical advances related to GBM treatment mean that radical resections can be performed even in eloquent brain areas. However, patients not indicated for resection will experience a major reduction in life expectancy. Patients who underwent stereotactic biopsy and received some form of oncological treatment experienced slightly increased overall survival relative to patients with a natural disease course. Patients with favorable clinical factors reacted better to treatment.

Abstract In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two. Singleton WES facilitated the diagnostic process in the Czech undiagnosed pediatric population. We believe it is an effective approach to enable appropriate counseling, surveillance, and personalized clinical management.

Abstract MICAL proteins play a crucial role in cellular dynamics by binding and disassembling actin filaments, impacting processes like axon guidance, cytokinesis, and cell morphology. Their cellular activity is tightly controlled, as dysregulation can lead to detrimental effects on cellular morphology. Although previous studies have suggested that MICALs are autoinhibited, and require Rab proteins to become active, the detailed molecular mechanisms remained unclear. Here, we report the cryo-EM structure of human MICAL1 at a nominal resolution of 3.1 Å. Structural analyses, alongside biochemical and functional studies, show that MICAL1 autoinhibition is mediated by an intramolecular interaction between its N-terminal catalytic and C-terminal coiled-coil domains, blocking F-actin interaction. Moreover, we demonstrate that allosteric changes in the coiled-coil domain and the binding of the tripartite assembly of CH-L2α1-LIM domains to the coiled-coil domain are crucial for MICAL activation and autoinhibition. These mechanisms appear to be evolutionarily conserved, suggesting a potential universality across the MICAL family.

This study explores the influence of metaverse experiences and social interaction on tourists’ engagement and satisfaction in virtual tourism environments. In the digital era, the metaverse provides an immersive, interactive platform for tourism, allowing users to experience destinations virtually. Drawing from theoretical frameworks on tourism experience, the metaverse experience in this study is categorized into three core dimensions: presence and telepresence, immersion, interactivity and vividness. Additionally, social interaction, which encompasses peer-to-peer engagement and community building within virtual settings, is examined as a mediating factor that may enhance the overall tourism experience. Data was collected from 400 tourists in Thailand and analyzed using structural equation modeling (SEM) to test two primary hypotheses: first, that the metaverse has a direct positive influence on tourism experience, and second, that social interaction mediates this relationship. Results support both hypotheses, demonstrating that the metaverse significantly enhances tourism experience through its immersive and interactive features, with social interaction further amplifying this effect as a partial mediator. These findings suggest valuable implications for tourism practitioners and developers of virtual tourism platforms, emphasizing the need to integrate high-quality, socially engaging digital experiences. The study contributes to understanding how metaverse technology, combined with social engagement, can enrich virtual tourism and align with Thailand’s broader digital tourism initiatives.

Taylorella equigenitalis is the causative agent of sexually transmitted contagious equine metritis. Infections manifest as cervicitis, vaginitis and endometritis and cause temporary infertility and miscarriages of mares. While previous studies have analyzed this organism for various parameters, the evolutionary dynamics of this pathogen, including the emergence of antibiotic resistance, remains unresolved. The aim of this study was to isolate contemporary strains, determine their genome sequences, evaluate their antibiotic resistance and compare them with other strains. We determined nine complete whole genome sequences of T. equigenitalis strains, mainly from samples collected from Kladruber horses in the Czech Republic. While T. equigenitalis strains from Kladruby isolated between 1982 and 2018 were inhibited by streptomycin, contemporary strains were found to be resistant to streptomycin, suggesting the recent emergence of this mutation. In addition, we used the collection dates of Kladruber horse strains to estimate the genome substitution rate, which resulted in a scaled mean evolutionary rate of 6.9×10-7 substitutions per site per year. Analysis with other available T. equigenitalis genome sequences (n = 18) revealed similarity of the Czech T. equigenitalis genomes with the Austrian T. equigenitalis genome, and molecular dating suggested a common ancestor of all analyzed T. equigenitalis strains from 1.5-2.6 thousand years ago, dating to the first centuries A.D. Our study revealed a recently emerged streptomycin resistance in T. equigenitalis strains from Kladruber horses, emphasizing the need for antibiotic surveillance and alternative treatments. Additionally, our findings provided insights into the pathogen's evolution rate, which is important for understanding its evolution and preparing preventive strategies.

BackgroundThe research on possible cerebral involvement in Crohn’s disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI).ObjectiveThis cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset.Methods14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss.ResultsWhile no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy.ConclusionAlthough still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.

Development of novel therapeutic proteins and biosimilars requires a thorough understanding of the relationship between their structure and function. Particularly, how IgG glycosylation affects its effector functions is a point increasingly underscored in guidelines by the World Health Organization and regulatory agencies. Our results show that just a 1% decrease in Fc fucosylation can lead to a more than 25% increase in antibody-dependent cell-mediated cytotoxicity. The intercorrelated nature of glycan patterns, combined with the low variability and lack of well-defined glycan patterns in process development and manufacture samples, makes studying the effects of individual glycan structures challenging. The conventional approach to structure-function studies often relies on a suboptimal set of tools, such as the one-factor-at-a-time method for experimental planning and univariate data analysis. Here, we introduce a systematic approach to understanding and prediction of the impact of Fc glycans on effector functions, using a combination of the design of experiment, multivariate data analysis, and in-vitro glycoengineering. This approach adheres to quality-by-design principles and aligns with regulatory agency guidelines. A variety of analytical assays, including binding and cell-based assays, were applied to investigate the effect of individual glycans of the IgG1 molecule. The regression models developed here provide a quantitative explanation and prediction of the impact of individual glycan features on the binding to FcγRs and bioactivity of the therapeutic protein. To the best of our knowledge, this is the first report of a systematic approach to quantitatively understand the multivariate impact of glycosylation on the effector functionality of therapeutic monoclonal antibodies, providing valuable tools for advancing therapeutic protein development.

Background: Immunotherapy based on checkpoint inhibition is widely used in the treatment of metastatic renal cell carcinoma (RCC); however, predictive and prognostic biomarkers are yet to be explored. The objective of this study was to evaluate the prognostic value of the hemoglobin, albumin, lymphocyte, platelet (HALP) score in metastatic RCC patients receiving nivolumab. Methods: We enrolled 149 individuals (including 38 females) with a median age of 62 years, who were treated with nivolumab (at a dosage of 240 mg biweekly or 480 mg every 28 days) following progression on at least one tyrosine kinase inhibitor (TKI) between 2016 and 2024. The study population was dichotomized by the median HALP score (27.53), which was calculated as hemoglobin (g/L) × albumin (g/L) × absolute lymphocyte count/platelets (g/L) at immunotherapy initiation. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, with differences analyzed via a log-rank test. A multivariate Cox proportional hazards model was utilized for evaluation of the prognostic value of performance status, lactate dehydrogenase (LDH) levels, and HALP score. Results: At a median follow-up of 31.1 months, 122 patients had progressed on nivolumab and 87 had died. Poor performance status was associated with significantly worse PFS and OS (HR 0.20 and 0.14, respectively). Survival was worse in individuals with an LDH level higher than 1.5 times the normal range compared to those with lower LDH values (HR 0.45 for PFS and HR 0.41 for OS). Patients with low HALP scores had shorter PFS (HR 0.69) and OS (HR 0.58) versus patients with high HALP scores. In the multivariate analysis, the independent prognostic value of the HALP index for OS was revealed in a metastatic clear-cell RCC (ccRCC) population. Conclusions: The HALP score determined before nivolumab initiation as the second or third line of treatment is an independent prognostic factor of OS in metastatic ccRCC patients. Prospective validation could lead to the incorporation of this index into prognostic models for patients with RCC.

The Haber–Bosch process is a cornerstone in the field of ammonia production and represents a decisive advance in industrial chemistry. This method, developed in the early 20th century, revolutionizes agriculture and enables the mass production of fertilizers. As the world strives for sustainable energy and environmental protection, alternative methods such as the photo/photoelectrocatalytic nitrogen reduction reaction (NRR) are gaining momentum. By using sunlight, electricity, or a combination of both, these approaches promise sustainable ammonia production with renewable energy sources and innovative materials. Researchers are trying to understand the underlying principles, mechanisms, and advances of these methods to overcome the challenges and optimize their effectiveness. This research is a step toward sustainable energy and agriculture, and offers a greener and more efficient way forward. This review looks at advances in sustainable ammonia production, particularly through photo‐ and photoelectrocatalytic NRRs. It examines the hurdles in implementing these methods and provides an overview of the fundamentals of nitrogen fixation and a comparison of current mechanisms. In addition, thermodynamic, theoretical, and computational studies of these processes are summarized. Various photocatalysts and photoelectrocatalysts used for ammonia production are also presented.

Abstract Pyrolysis is one method for treating sewage sludge, particularly in remote areas or decentralised systems. The end product of pyrolysis, sludge-char, can serve as a soil improver. However, there is a lack of comprehensive data on the organic pollutants’ behaviour in sludge-char. In our work, we focused on the behaviour of per- and polyfluoroalkyl substances (PFASs). Sludge was pyrolyzed at 200–700 °C to determine the minimum safe temperature for effective PFASs removal. It is important to note that PFASs may not only be mineralized but also cleaved to unanalyzed PFASs and other organofluorinated substances. To address this issue, we incorporated additional measurements of organic fluorine in the experiment using combustion ion chromatography (CIC). Due to the inherent heterogeneity of sludge, containing a variety of pollutants and their precursors, we conducted pyrolysis on artificially contaminated sand. This allowed us to assess and compare the behaviour of PFASs in a homogeneous matrix. Based on our analyses, we determined that a temperature greater than 400 °C is imperative for effective PFASs and organic fluorine removal. The results were verified by analyzing samples from a commercial sludge pyrolysis unit at the Bohuslavice-Trutnov WWTP, which confirmed our measurements. In light of these results, it becomes evident that sludge pyrolysis below 400 °C is unsuitable for PFAS removal from sewage sludge. Graphical Abstract

Individual indicators linked to labour market developments during the COVID-19 pandemic provide a view of a particular area but fail to capture the issue of the impact of the crisis comprehensively. This problem can be addressed by integrating them using multicriteria methods, resulting in a synthetic indicator of a specific labour market. Thus, the issue of the impact of the pandemic on important macroeconomic and labour market indicators can be evaluated by calculating a single indicator. The main objective of this study is to identify the labour market with the highest positive flexibility in relation to the impacts of the pandemic and thus reveal the critical factor that fundamentally reduces the resistance of the labour market to negative pandemic externalities. During the first wave of the COVID-19 pandemic (2020-Q2), Slovakia reached the highest value of the integral indicator, but in the last recorded wave (2022-Q1), it moved to the last place. Its average integral indicator for all three waves reached the highest average value. However, the highest value of the integral indicator and thus the highest positive flexibility of the labour market during the third wave was recorded by Germany, which evokes the assumption that the approach of the local government and authorities in the mentioned period most effectively protected the labour market from negative fluctuations. The results of the countries during the third wave of the pandemic consider the impact of the most current measures that were implemented at the time of the pandemic.

Extracellular nanoparticles (EPs) are a subject of increasing interest for their biological role as mediators in cell–cell communication; however, their harvesting and assessment from bodily fluids are challenging, as processing can significantly affect samples. With the aim of minimizing processing artifacts, we assessed the number density (n) and hydrodynamic diameter (Dh) of EPs directly in diluted plasma and blood using the following recently developed technique: interferometric light microscopy (ILM). We analyzed 613 blood and plasma samples from human patients with inflammatory bowel disease (IBD), collected in trisodium citrate and ethylenediaminetetraacetic acid (EDTA) anticoagulants, and 163 blood and plasma samples from canine patients with brachycephalic obstructive airway syndrome (BOAS). We found a highly statistically significant correlation between n in the plasma and n in the blood only in the human (i.e., but not canine) blood samples, between the samples with trisodium citrate and EDTA, and between the respective Dh for both species (all p < 10−3). In the human plasma, the average was 139 ± 31 nm; in the human blood, was 158 ± 11 nm; in the canine plasma, was 155 ± 32 nm; and in the canine blood, was 171 ± 33 nm. The differences within species were statistically significant (p < 10−2), with sufficient statistical power (P > 0.8). For , we found no statistically significant differences between the human plasma and blood samples or between the samples with trisodium citrate and EDTA. Our results prove that measuring n and Dh of EPs in minimally processed fresh blood and in diluted fresh plasma by means of ILM is feasible for large populations of samples.

In this study, advanced techniques such as atom probe tomography, atomic force microscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy were used to determine the corrosion mechanism of the as-ECAPed Zn-0.8Mg-0.2Sr alloy. The influence of microstructural and surface features on the corrosion mechanism was investigated. Despite its significance, the surface composition before exposure is often neglected by the scientific community. The analyses revealed the formation of thin ZnO, MgO, and MgCO3 layers on the surface of the material before exposure. These layers participated in the formation of corrosion products, leading to the predominant occurrence of hydrozincite. In addition, the layers possessed different resistance to the environment, resulting in localized corrosion attacks. The segregation of Mg on the Zn grain boundaries with lower potential compared with the Zn-matrix was revealed by atom probe tomography and atomic force microscopy. The degradation process was initiated by the activity of micro-galvanic cells, specifically Zn – Mg2Zn11/SrZn13. This process led to the activity of the crevice corrosion mechanism and subsequent attack to a depth of 250 μm. The corrosion rate of the alloy determined by the weight loss method was 0.36 mm·a−1. Based on this detailed study, the degradation mechanism of the Zn-0.8Mg-0.2Sr alloy is proposed.

Nano- and micro-sized vesicular and colloidal structures mediate cell–cell communication. They are important players in the physiology of plants, animals, and humans, and are a subject of increasing interest. We investigated the effect of three surfactants, N-cetylpyridinium chloride (CPC), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), and two anionic polyelectrolytes, sodium polystyrene sulfonate (NaPSS) and sodium polymethacrylate (NaPMA), on nanoliposomes. In addition, the effect of SDS and TX100 on selected biological membranes (erythrocytes and microalgae) was investigated. The liposomes were produced by extrusion and evaluated by microcalorimetry and light scattering, based on the total intensity of the scattered light (Itot), hydrodynamic radius (Rh), radius of gyration (Rg), shape parameter p (=Rh/Rg,0), and polydispersity index. The EPs shed from erythrocytes and microalgae Dunaliella tertiolecta and Phaeodactylum tricornutum were visualized by scanning electron microscopy (SEM) and analyzed by flow cytometry (FCM). The Rh and Itot values in POPC liposome suspensions with added CPC, SDS, and TX100 were roughly constant up to the respective critical micelle concentrations (CMCs) of the surfactants. At higher compound concentrations, Itot dropped towards zero, whereas Rh increased to values higher than in pure POPC suspensions (Rh ≈ 60–70 nm), indicating the disintegration of liposomes and formation of larger particles, i.e., various POPC–S aggregates. Nanoliposomes were stable upon the addition of NaPSS and NaPMA, as indicated by the constant Rh and Itot values. The interaction of CPC, SDS, or TX100 with liposomes was exothermic, while there were no measurable heat effects with NaPSS or NaPMA. The SDS and TX100 increased the number density of EPs several-fold in erythrocyte suspensions and up to 30-fold in the conditioned media of Dunaliella tertiolecta at the expense of the number density of cells, which decreased to less than 5% in erythrocytes and several-fold in Dunaliella tertiolecta. The SDS and TX100 did not affect the number density of the microalgae Phaeodactylum tricornutum, while the number density of EPs was lower in the conditioned media than in the control, but increased several-fold in a concentration-dependent manner. Our results indicate that amphiphilic molecules need to be organized in nanosized particles to match the local curvature of the membrane for facilitated uptake. To pursue this hypothesis, other surfactants and biological membranes should be studied in the future for more general conclusions.

Abstract Antiferromagnetic CuMnAs thin films have attracted attention since the discovery of the manipulation of their magnetic structure via electrical, optical, and terahertz pulses, enabling convenient approaches for switching between magnetoresistive states of the film for information storage. However, the magnetic structure and, thus, the efficiency of the manipulation can be affected by the film morphology and growth defects. In this study, the properties of CuMnAs thin films are investigated by probing the asymmetrical growth‐related uniaxial anisotropy of electric conductivity by contact‐free terahertz transmission spectroscopy. It is shown that the terahertz measurements conveniently detect the conductivity anisotropy that is consistent with conventional DC Hall‐bar measurements. Moreover, the terahertz technique allows for considerably finer determination of anisotropy axes, and it is less sensitive to the local film degradation. Thanks to the averaging over a large detection area, the THz probing also allows an analysis of strongly non‐uniform thin films. Using scanning electron and near‐field terahertz microscopies, the observed anisotropic conductivity of CuMnAs is related to the elongation and orientation of growth defects, which both originate in the anisotropic growth of the films. In addition, control over the morphology of defects is demonstrated by using vicinal substrates.

Abstract The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.

Measurement(s) COVID-19 Protocols, Restrictions • Health Behaviors • Personality and Behavioral Change, CTCAE • Emotion • Message Framing • Self-Determination Technology Type(s) Survey • Experiment Design Type Factor Type(s) COVID-19 Protocols, Restrictions • Health Behaviors • Loss-Gain Framing • Cognitive Reappraisal • Self-Determination Messaging Sample Characteristic - Organism Homo Sample Characteristic - Environment Daily Life Sample Characteristic - Location North America • South America • Africa • Australia • Europe • United Kingdom • Asia

ABSTRACTThis paper summarises the results of an inventory of abandoned underground mines within the Nízký Jeseník Upland (Czechia, Central Europe). The area has a long and complex history of mining. During the period between the 11th and 13th centuries, the upland was the centre of ore mining, and later, during the 18th and 19th centuries, it transitioned into slate mining for roofing. From 2016 through 2018, we collected detailed data from 137 mines to better understand their parameters and functioning within the contemporary landscape. The data were mainly focused on the geomorphic character of underground mines, as the existing inventories focus on various other aspects. The results were processed into an interactive web map using ArcGIS Online's online mapping software. Relations between parameters were assessed using three methods: the χ2 test for a contingency table, ANOVA and linear regression.

The article discusses the production of platform chemicals from various biological sources, including glycerol, lignin, cellulose, bio-oils, and sea products. It presents the results of catalytic and downstream processes involved in the conversion of these biomass-derived feedstocks. The experimental approaches are complemented by numerical descriptions, ranging from density functional theory (DFT) calculations to kinetic modellingof the experimental data. This multi-scale modelling approach helps to understand the underlying mechanisms and optimize the production of platform chemicals from renewable resources.

Nicotine activates nicotinic acetylcholine receptors (nAChRs), which are overexpressed in numerous cancer types, leading to signaling pathways that increase lung cancer invasiveness and resistance to chemotherapeutic agents. In this study, the effects of APS12-2, a synthetic analog of marine sponge toxin that acts as an antagonist of nAChRs, was investigated in vitro on A549 human lung adenocarcinoma cells and non-tumorigenic human lung epithelial BEAS-2B cells. In addition, gelatin nanoparticles (GNPs) loaded with APS12-2 (APS12-2-GNPs) were prepared and their effects were compared with those of free APS12-2. Nicotine reduced cytotoxicity, the formation of reactive oxygen species, and the formation of lipid droplets caused by cisplatin on A549 cells. The effects of nicotine on the decreased efficacy of cisplatin were reduced by APS12-2 and APS12-2-GNPs. APS12-2-GNPs showed a substantial advantage compared with free APS12-2; the cytotoxicity of APS12-2 on BEAS-2B cells was greatly reduced when APS12-2 was loaded in GNPs, whereas the cytotoxicity on A549 cells was only slightly reduced. Our results suggest that both APS12-2 and APS12-2-GNPs hold promise as supportive agents in the cisplatin-based chemotherapy of lung cancer.

Abstract It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (N total = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions—warmth and competence—plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.

Abstract Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in the treatment of patients experiencing cardiogenic shock (CS). However, increased VA-ECMO blood flow (EBF) may significantly impair left ventricular (LV) performance. The objective of the present study was to assess the effect of VA-ECMO on LV function in acute CS with concomitant severe aortic stenosis (AS) or mitral regurgitation (MR) in a porcine model. Eight female swine (45 kg) underwent VA-ECMO implantation under general anaesthesia and mechanical ventilation. Acute CS was induced by global myocardial hypoxia. Subsequently, severe AS was simulated by obstruction of the aortic valve, while severe MR was induced by mechanical destruction of the mitral valve. Haemodynamic and LV performance variables were measured at different rates of EBF rates (ranging from 1 to 4 L/min), using arterial and venous catheters, a pulmonary artery catheter, and LV pressure–volume catheter. Data are expressed as median (interquartile range). Myocardial hypoxia resulted in declines in cardiac output to 2.7 (1.9–3.1) L/min and LV ejection fraction to 15.2% (10.5–19.3%). In severe AS, increasing EBF from 1 to 4 L/min was associated with a significant elevation in mean arterial pressure (MAP), from 33.5 (24.2–34.9) to 56.0 (51.9–73.3) mmHg (P ˂ 0.01). However, LV volumes (end-diastolic, end-systolic, stroke) remained unchanged, and LV end-diastolic pressure (LVEDP) significantly decreased from 24.9 (21.2–40.0) to 19.1 (15.2–29.0) mmHg (P ˂ 0.01). In severe MR, increasing EBF resulted in a significant elevation in MAP from 49.0 (28.0–53.4) to 72.5 (51.4–77.1) mmHg (P ˂ 0.01); LV volumes remained stable and LVEDP increased from 17.1 (13.7–19.1) to 20.8 (16.3–25.6) mmHg (P ˂ 0.01). Results of this study indicate that the presence of valvular heart disease may alleviate negative effect of VA-ECMO on LV performance in CS. Severe AS fully protected against LV overload, and partial protection was also detected with severe MR, although at the cost of increased LVEDP and, thus, higher risk for pulmonary oedema.

The importance and value of real-world data in healthcare cannot be overstated because it offers a valuable source of insights into patient experiences. Traditional patient-reported experience and outcomes measures (PREMs/PROMs) often fall short in addressing the complexities of these experiences due to subjectivity and their inability to precisely target the questions asked. In contrast, diary recordings offer a promising solution. They can provide a comprehensive picture of psychological well-being, encompassing both psychological and physiological symptoms. This study explores how using advanced digital technologies, i.e., automatic speech recognition and natural language processing, can efficiently capture patient insights in oncology settings. We introduce the MRAST framework, a simplified way to collect, structure, and understand patient data using questionnaires and diary recordings. The framework was validated in a prospective study with 81 colorectal and 85 breast cancer survivors, of whom 37 were male and 129 were female. Overall, the patients evaluated the solution as well made; they found it easy to use and integrate into their daily routine. The majority (75.3%) of the cancer survivors participating in the study were willing to engage in health monitoring activities using digital wearable devices daily for an extended period. Throughout the study, there was a noticeable increase in the number of participants who perceived the system as having excellent usability. Despite some negative feedback, 44.44% of patients still rated the app’s usability as above satisfactory (i.e., 7.9 on 1–10 scale) and the experience with diary recording as above satisfactory (i.e., 7.0 on 1–10 scale). Overall, these findings also underscore the significance of user testing and continuous improvement in enhancing the usability and user acceptance of solutions like the MRAST framework. Overall, the automated extraction of information from diaries represents a pivotal step toward a more patient-centered approach, where healthcare decisions are based on real-world experiences and tailored to individual needs. The potential usefulness of such data is enormous, as it enables better measurement of everyday experiences and opens new avenues for patient-centered care.

We report a multi-modal spiking neuron that allows optical and electronic input and control, and wavelength-multiplexing operation, for use in novel high-speed neuromorphic sensing and computing functionalities. The photonic-electronic neuron is built with a micro-scale, nanostructure resonant tunnelling diode (RTD) with photodetection (PD) capability. Leveraging the advantageous intrinsic properties of this RTD-PD system, namely highly nonlinear characteristics, photo-sensitivity, light-induced I – V curve shift, and the ability to deliver excitable responses under electrical and optical inputs, we successfully achieve flexible neuromorphic spike activation and inhibition regimes through photonic-electrical control. We also demonstrate the ability of this RTD-PD spiking sensing-processing neuron to operate under the simultaneous arrival of multiple wavelength-multiplexed optical signals, due to its large PD spectral window (covering the 1310 and 1550 nm telecom wavelength bands). Our results highlight the potential of RTD photonic-electronic neurons to reproduce multiple key excitatory and inhibitory spiking regimes, at high speed (10 s of ns-rate spiking responses, with faster sub-ns regimes theoretically predicted) and low energy (requiring only ∼10 mV and ∼150 µ W, electrical and optical input amplitudes, respectively), similar in nature to those commonly found in the biological neurons of the visual system and the brain. This work offers a highly promising approach for the realisation of high-speed, energy-efficient photonic-electronic spiking neurons and spiking neural networks, enabling multi-modal and multi-wavelength operation for sensing and information processing tasks, whilst also yielding enhanced system capacity, performance and parallelism. This work therefore paves the way for innovative high-speed, photonic-electronic, and spike-based neuromorphic sensing and computing systems and artificial intelligence hardware.

The surgical treatment of paediatric thalamic gliomas has been burdened with high morbidity, and these lesions were often considered inoperable. With new approaches and intraoperative technologies, we can remove tumours once deemed inoperable. In our single centre, we have operated on 11 paediatric patients over the course of 8 years. We have performed eight GTR resections and three intended subtotal resections. The postoperative neurological deficit ranged from mild to very severe for motor weakness and none to severe for aphasia after surgery, with all of the patients improving at 3-month follow-up. Radicality in the surgical approach to thalamic gliomas in children has shown significant benefits when compared to more conservative approaches. For children with LGGs, extensive surgical resection is associated with improved prognosis and longer progression-free survival. However, it does not yield the same proportional benefit for HGGs due to its aggressive nature and worse outlook.

Histological staining is the primary method for confirming cancer diagnoses, but certain types, such as p63 staining, can be expensive and potentially damaging to tissues. In our research, we innovate by generating p63-stained images from H&E-stained slides for metaplastic breast cancer. This is a crucial development, considering the high costs and tissue risks associated with direct p63 staining. Our approach employs an advanced CycleGAN architecture, xAI-CycleGAN, enhanced with context-based loss to maintain structural integrity. The inclusion of convolutional attention in our model distinguishes between structural and color details more effectively, thus significantly enhancing the visual quality of the results. This approach shows a marked improvement over the base xAI-CycleGAN and standard CycleGAN models, offering the benefits of a more compact network and faster training even with the inclusion of attention.

Spiking neurons and neural networks constitute a fundamental building block for brain-inspired computing, which is poised to benefit significantly from photonic hardware implementations. In this work, we experimentally investigate an interconnected optical neuromorphic system based on an ultrafast spiking vertical cavity surface emitting laser (VCSEL) neuron and a silicon photonics (SiPh) integrated micro-ring resonator (MRR). We experimentally demonstrate two different functional arrangements of these devices: first, we show that MRR weight banks can be used in conjunction with the spiking VCSEL-neurons to perform amplitude weighting of sub-ns optical spiking signals. Second, we show that a continuously firing VCSEL-neuron can be directly modulated using a locking signal propagated through a single weighting MRR, and we utilise this functionality to perform optical spike firing rate-coding via thermal tuning of the MRR. Given the significant track record of both integrated weight banks and photonic VCSEL-neurons, we believe these results demonstrate the viability of combining these two classes of devices for use in functional neuromorphic photonic systems.

Economic growth and GDP growth have been dramatically affected by the COVID-19 pandemic. Both indicators are the factors that decisively affect the situation in the labour market, which is currently facing major challenges. One of the challenges is aging population. The number of the working- age population is declining, which may also have a significant impact on GDP growth in the future. The main purpose of the study is to analyse past and predicted GDP growth rates and the past and predicted shares of the working age population in the selected economies. Based on the analyses, the study attempts to identify the factors that are able to stimulate GDP growth while the size of working age population is predicted to shrink in the future. In the opening section of the empirical part, a comparison of the GDP evolution in China, Russia, USA, India, Slovakia and the EU is presented. Subsequently, long-term GDP and demographic forecasts are presented. It follows from the analyses that it is necessary to introduce new technologies to replace the shrinking workforce if sustainable economic growth is to achieve.

Background. Stroke-like syndrome is defined as a rare, delayed complication of brain oncotherapy. Cases with more favorable brain cancer diagnoses and longer life expectancy have been previously reported, but here we present, for the first time, three long-term survivors of glioblastoma with stroke-like syndromes. Methods and Results. Three young or middle-aged patients underwent tumor resection and chemoradiotherapy. They received regular clinical and imaging follow-up with stable neurological status and no signs of tumor recurrence. They exhibited varied signs and symptoms (motor and sensory deficits, aphasia, memory and cognitive disorders, seizures, and headache) accompanied by imaging abnormalities. Stroke-like syndromes developed within 2-5 days and resolved in 2-6 weeks. Diffusion-weighted MRI and T2 brain perfusion abnormalities were demonstrated in all patients. In addition, there was focal T1 MRI contrast enhancement due to blood-brain barrier disruption. In addition to tumor recurrence, classic stroke, encephalitis, metabolic and mitochondrial disorders, and post-seizure swelling should be excluded. The imaging indicated intensive MRI scanning and symptomatic medication (steroids supplemented by antiepileptics, vasoactive agents, etc.) for judicious management. With respect to the course, an invasive procedure was still considered an option. Conclusion. All stroke-like syndromes are diagnoses of exclusion. To avoid misinterpretation of imaging findings as glioblastoma recurrence and avert recall oncotherapy or redundant interventions, better understanding of delayed complications of brain tumor therapy is crucial.

In order to prepare optimal platelet and extracellular vesicle (EV)-rich plasma for the treatment of chronic temporal bone inflammation, we studied effects of centrifugation parameters on redistribution of blood constituents in blood samples of 23 patients and 20 volunteers with no record of disease. Concentrations of blood cells and EVs were measured by flow cytometry. Sample content was inspected by scanning electron microscopy. A mathematical model was constructed to interpret the experimental results. The observed enrichment of plasma in platelets and EVs after a single spin of blood depended on the erythrocyte sedimentation rate, thereby indicating the presence of a flow of plasma that carried platelets and EVs in the direction opposite to settling of erythrocytes. Prolonged handling time correlated with the decrease of concentration of platelets and larger EVs in platelet and EV-rich plasma (PVRP), R = −0.538, p = 0.003, indicating cell fragmentation during the processing of samples. In further centrifugation of the obtained plasma, platelet and EV enrichment depended on the average distance of the sample from the centrifuge rotor axis. Based on the agreement of the model predictions with observations, we propose the centrifugation protocol optimal for platelet and EV enrichment and recovery in an individual sample, adjusted to the dimensions of the centrifuge rotor, volume of blood and erythrocyte sedimentation rate.

IntroductionColorectal cancer (CRC) is one of the most common types of cancer worldwide. The carcinogenesis of CRC is indeed complex, and there are many different mechanisms and pathways that contribute to the development of malignancy and the progression from primary to metastatic tumors. The OCT4A, encoded by the POU5F1 gene, is a transcription factor responsible for the phenotype of stem cells, maintaining pluripotency and regulation of differentiation. The POU5F1 gene is made up of five exons that can create numerous isoforms through alternative promoter or alternative splicing. In addition to OCT4A, other isoforms called OCT4B are also translated into protein; however, their role in cells has been unclear. The aim of our work was to investigate the expression patterns of OCT4 isoforms in primary and metastatic CRC, providing us with useful information about their role in the development and progression of CRC.MethodsSurgical specimens from a total of 78 patients were collected and isolated from primary tumors (n = 47) and metastases (n = 31). The relative gene expression of OCT4 isoforms was investigated using the RT-qPCR method together with the TaqMan probes for particular OCT4 isoforms.ResultsOur results suggest significantly downregulated expression of the OCT4A and OCT4Bs isoforms in both primary (p = 0.0002 and p < 0.0001, respectively) and metastatic tumors (p = 0.0006 and p = 0.00051, respectively) when compared with the control samples. We also observed a correlation between reduced expression of all OCT4 isoforms and both primary and left-sided tumors (p = 0.001 and p = 0.030, respectively). On the other hand, the expression of all OCT4 isoforms was significantly upregulated in metastases compared with primary tumors (p < 0.0001).DiscussionUnlike previous reports, we found out that the expression of OCT4A, OCT4Bs, and all OCT4 isoforms was significantly reduced in primary tumors and metastases compared with control samples. On the other hand, we supposed that the expression rate of all OCT4 isoforms may be related to the cancer type and side, as well as to liver metastases. However, further studies are required to investigate the detailed expression patterns and significance of individual OCT4 isoforms in carcinogenesis.

IntroductionPathogenic strains of Escherichia coli have been clearly identified as the causative agents of extraintestinal and diarrheal infections; however, the etiopathogenic role of E. coli in other conditions, including colorectal cancer, remains unclear.MethodsThis study aimed to characterize mucosal E. coli isolates (n = 246) from 61 neoplasia patients and 20 healthy controls for the presence of 35 genetic determinants encoding known virulence factors.ResultsVirulence determinants encoding invasin (ibeA), siderophore receptor (iroN), S-fimbriae (sfa), and genotoxin (usp) were more prevalent among E. coli isolated from patients with neoplasia compared to the control group (p < 0.05). In addition, the prevalence of these virulence determinants was increased in more advanced neoplasia stages (padj < 0.0125). Compared to patients with advanced colorectal adenoma and carcinoma, the ibeA gene was rarely found in the control group and among patients with non-advanced adenoma (p < 0.05), indicating its potential as the advanced-neoplasia biomarker. Patients with neoplasia frequently had E. coli strains with at least one of the abovementioned virulence factors, whereby specific combinations of these virulence factors were found.DiscussionThese findings suggest that E. coli strains isolated from patients with colorectal neoplasia possess several virulence factors, which could contribute to the development of neoplastic processes in the large intestine.

Abstract The ever-increasing demand for artificial intelligence (AI) systems is underlining a significant requirement for new, AI-optimised hardware. Neuromorphic (brain-like) processors are one highly-promising solution, with photonic-enabled realizations receiving increasing attention. Among these, approaches based upon vertical cavity surface emitting lasers (VCSELs) are attracting interest given their favourable attributes and mature technology. Here, we demonstrate a hardware-friendly neuromorphic photonic spike processor, using a single VCSEL, for all-optical image edge-feature detection. This exploits the ability of a VCSEL-based photonic neuron to integrate temporally-encoded pixel data at high speed; and fire fast (100 ps-long) optical spikes upon detecting desired image features. Furthermore, the photonic system is combined with a software-implemented spiking neural network yielding a full platform for complex image classification tasks. This work therefore highlights the potential of VCSEL-based platforms for novel, ultrafast, all-optical neuromorphic processors interfacing with current computation and communication systems for use in future light-enabled AI and computer vision functionalities.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies approved for the treatment of numerous cancer types. Toxicities induced by ICIs may affect any organ system and manifest as endocrinopathy. The main side effects related to treatment are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Rare endocrine irAEs are diabetes insipidus, hypoparathyroidism, thyrotoxic crisis and hypogonadism. We report a case of hypoparathyroidism induced by ICI treatment with durvalumab, which has not previously been described.

Photonic technologies offer great prospects for novel, ultrafast, energy-efficient, and hardware-friendly neuromorphic (brain-like) computing platforms. Moreover, neuromorphic photonic approaches based on ubiquitous, technology-mature, and low-cost vertical-cavity surface-emitting lasers (VCSELs) (devices found in fiber-optic transmitters, mobile phones, and automotive sensors) are of particular interest. Given that VCSELs have shown the ability to realize neuronal optical spiking responses (at ultrafast GHz rates), their use in spike-based information-processing systems has been proposed. In this study, spiking neural network (SNN) operation, based on a hardware-friendly photonic system of just one VCSEL, is reported alongside a novel binary weight “significance” training scheme that fully capitalizes on the discrete nature of the optical spikes used by the SNN to process input information. The VCSEL-based photonic SNN was tested with a highly complex multivariate classification task (MADELON) before its performance was compared using a traditional least-squares training method and an alternative novel binary weighting scheme. Excellent classification accuracies of >94% were achieved by both training methods, exceeding the benchmark performance of the dataset in a fraction of the processing time. The newly reported training scheme also dramatically reduces the training set size requirements and the number of trained nodes (≤1% of the total network node count). This VCSEL-based photonic SNN, in combination with the reported “significance” weighting scheme, therefore grants ultrafast spike-based optical processing highly reduced training requirements and hardware complexity for potential application in future neuromorphic systems and artificial intelligence applications.

Stochastic population models are widely used to model phenomena in different areas such as cyber-physical systems, chemical kinetics, collective animal behaviour, and beyond. Quantitative analysis of stochastic population models easily becomes challenging due to the combinatorial number of possible states of the population. Moreover, while the modeller easily hypothesises the mechanistic aspects of the model, the quantitative parameters associated to these mechanistic transitions are difficult or impossible to measure directly. In this paper, we investigate how formal verification methods can aid parameter inference for population discrete-time Markov chains in a scenario where only a limited sample of population-level data measurements-sample distributions among terminal states-are available. We first discuss the parameter identifiability and uncertainty quantification in this setup, as well as how the existing techniques of formal parameter synthesis and Bayesian inference apply. Then, we propose and implement four different methods, three of which incorporate formal parameter synthesis as a pre-computation step. We empirically evaluate the performance of the proposed methods over four representative case studies. We find that our proposed methods incorporating formal parameter synthesis as a pre-computation step allow us to significantly enhance the accuracy, precision, and scalability of inference. Specifically, in the case of unidentifiable parameters, we accurately capture the subspace of parameters which is data-compliant at a desired confidence level.

The aims of this study were to evaluate and compare the radical scavenging activities (DPPH), phenolic concentrations and concentrations of selected phenolic acids (PAs) of spelt cultivars and breeding lines with common wheat in a three-year controlled field experiment under conditions of organic farming. No significant variations were observed in the total and free DPPH of Altgold, Ebners Rotkorn, Ostro and PN-1-36 with common wheat. The total DPPH ranged from 52.13% to the lowest value of 44.01% in Franckenkorn. Total, free and bound phenolic concentrations were the highest for common wheat (1902.55 µg FAE g−1 DM of total), while all spelt cultivars achieved significantly lower values (from 1434.94 µg FAE g−1 DM in Franckenkorn to 1650.22 µg FAE g−1 DM in Ebners Rotkorn). Bound phenolic compounds represented 86.3% of the total ones. An extremely dry and warm ripening period had a negative impact on the synthesis of phenolic compounds. The highest concentration of total PAs was observed in spelt Ebners Rotkorn (681.75 µg g−1 DM) and the lowest in common wheat (396.05 µg g−1 DM). The total share of free and bound PAs was 5.7% and 74.8%, respectively. The extremely dry and very warm grain filling period had a more evident negative impact on the concentration of free PAs compared to bound forms. The dominant free PA was ferulic (70.48%), followed by syringic (9.30%), p-HBA (5.59%), sinapic acid (5.40%), salicylic (4.18%), p-coumaric acid (3.22%) and caffeic acid (1.93%). Spelt cultivar Ebners Rotkorn was distinguished by the highest concentration of free and bound forms of PAs.

Background and Aims. COVID-19 pandemic has impacted on all endoscopy centers in the Czech Republic, that belongs to the most affected countries in the world. The aim of our study was to analyze all procedures following routine RT-PCR testing in our tertiary center during the peak of the pandemic. Methods. We retrospectively analyzed all procedures performed from October 2020 to January 2021 after a new RT-PCR center had been set up. Main outcomes were type of scheduled procedure, indication, rate of therapeutic interventions and rate of new relevant and malignant findings. Comparison to the same period before the pandemic and SARS-CoV-2 infection in endoscopy staff are also reported. Results. A total of 1,953 procedures were performed. 624 patients were referred with a negative RT-PCR test and the remaining 1,346 patients were tested in the new center. 1,293 negative tests led to 1,329 procedures. A new relevant finding was reported in 589 (44.3%), including new malignancy in 56 (4.2%). 53 patients tested positive (3.9%). There was a reduction by 9% in the number of all procedures compared to the same period before the pandemic and an increase in the number of screening colonoscopies and ERCP procedures. In the study period, 9 of 54 staff members contracted SARS-CoV-2 infection. Conclusions. Routine RT-PCR testing of patients scheduled for elective endoscopy during the peak of COVID-19 pandemic enabled us to essentially maintain our unit productivity, including activities such as screening colonoscopy, endoscopic resection and pancreatobiliary endoscopy.

This contribution discusses the optical properties of different structures of some herbaceous understorey plant species from temperate deciduous and mixed forests. These forests are marked by annual dynamics of radiation level that is related to the vegetation cycle of forest trees. During winter and early spring, the understorey is exposed to full solar radiation, whilelater in the growing season radiation is limited due to the closing of the tree storey. The plasticity of optical properties ofphotosynthetic structures of understorey plants is directly related to their structural and biochemical phenotypic plasticity that optimises harvesting and use of energy. The optimisation of energy harvesting is also achieved by specific adaptations of green leaves, such as variegation (Pulmonaria officinalis, Cyclamen sp.), anthocyanic lower epidermis (Cyclamen sp.), and by using structures other than green leaves for photosynthesis, such as bracts (Hacquetia epipactis) and sepals (Helleborus sp.). The optical properties of these structures are similar to those of green leaves. The understanding of optical responses of different structures contributes to the understanding of the forest understorey functioning.

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Horvath et al. structurally and biochemically characterize the full-length human DAPK2-14-3-3 complex to investigate the effects of binding to DAPK2 on its dimerization, activation by dephosphorylation of Ser318, and Ca2+/calmodulin binding. Their results provide mechanistic insights into 14- 3-3-mediated DAPK2 inhibition and highlight the potential of the DAPK2:14-3-3 complex as a target for anti-inflammatory therapies.

Abstract Background It is encouraging to see a substantial increase in individuals surviving cancer. Even more so since most of them will have a positive effect on society by returning to work. However, many cancer survivors have unmet needs, especially when it comes to improving their quality of life (QoL). Only few survivors are able to meet all of the recommendations regarding well-being and there is a body of evidence that cancer survivors’ needs often remain neglected from health policy and national cancer control plans. This increases the impact of inequalities in cancer care and adds a dangerous component to it. The inequalities affect the individual survivor, their career, along with their relatives and society as a whole. The current study will evaluate the impact of the use of big data analytics and artificial intelligence on the self-efficacy of participants following intervention supported by digital tools. The secondary endpoints include evaluation of the impact of patient trajectories (from retrospective data) and patient gathered health data on prediction and improved intervention against possible secondary disease or negative outcomes (e.g. late toxicities, fatal events). Methods/design The study is designed as a single-case experimental prospective study where each individual serves as its own control group with basal measurements obtained at the recruitment and subsequent measurements performed every 6 months during follow ups. The measurement will involve CASE-cancer, Patient Activation Measure and System Usability Scale. The study will involve 160 survivors (80 survivors of Breast Cancer and 80 survivors of Colorectal Cancer) from four countries, Belgium, Latvia, Slovenia, and Spain. The intervention will be implemented via a digital tool (mHealthApplication), collecting objective biomarkers (vital signs) and subjective biomarkers (PROs) with the support of a (embodied) conversational agent. Additionally, the Clinical Decision Support system (CDSS), including visualization of cohorts and trajectories will enable oncologists to personalize treatment for an efficient care plan and follow-up management. Discussion We expect that cancer survivors will significantly increase their self-efficacy following the personalized intervention supported by the m-HealthApplication compared to control measurements at recruitment. We expect to observe improvement in healthy habits, disease self-management and self-perceived QoL. Trial registration ISRCTN97617326. https://doi.org/10.1186/ISRCTN97617326 . Original Registration Date: 26/03/2021.