National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
9086 research outputs found
Sort by
Predictive Value for Increased Red Blood Cell Distribution Width in Unprovoked Acute Venous Thromboembolism at the Emergency Department
Get PDFObservational StudyAcute venous thromboembolism (VTE) is a common worldwide disease admitted to emergency departments (ED), usually presenting as pulmonary embolism or lower limb deep vein thrombosis (DVT). Due to the lack of typical clinical and biomarker diagnostic features of unprovoked VTE, early identification is challenging and has direct consequences on correct treatment delay. Longitudinal, prospective, observational study. Patients admitted to ED with a suspicion of unprovoked acute VTE between October 2020 and January 2021 were included. Clinical and laboratorial variables were compared between VTE positive and negative diagnoses. Red cell distribution width (RDW) cut point was determinate through a receiver operating characteristic analysis. RDW accuracy, sensitivity, and specificity were calculated. Fifty-eight patients were analyzed. And 82.8% of suspected patients with VTE were diagnosed with an acute thrombotic event confirmed by imaging examination. In patients with VTE, RDW at admission in ED was higher than with other diagnosis, respectively, 14.3% (13.2-15.1) and 13.5% (13.0-13.8). Platelet count was the only additional characteristic that revealed difference between the 2 groups (264×109/L for VTE and 209×109/L for non-VTE). Logistic regression models showed good discriminatory values for RDW≥14%, with an area under the curve (AUC) = 0.685 (95% confidence interval, 0.535-0.834). These findings were more pronounced in isolated DVT, with a sensitivity of 76.9%, specificity 100%, and accuracy 85.7%. Our study demonstrated a significant association between an early high RDW and the diagnosis of acute unprovoked DVT. RDW ≥ 14% has an independent predictor of unprovoked VTE in adult patientsFunding: The present study has been partially financed by Faculdade de Medicina da Universidade do Porto, in the context of the Doctoral Program of Medicine.info:eu-repo/semantics/publishedVersio
Exploring Cyanara cardunculus L. potential for the food industry: the antioxidant pattern
Get PDFCynara cardunculus L. (cardoon) is a versatile perennial crop indigenous to the Mediterranean region that has three botanical varieties including wild cardoon (var. sylvestris (Lamk) Fiori), cultivated cardoon (var. altilis DC.), and globe artichoke (var. scolymus (L.) Fiori). Cardoon is mostly renowned for its flower, which is used to coagulate milk in the production of soft cheeses, with the leaves serving as the primary by-product. The bioactive compound-rich leaves are employed in traditional medicine and have interesting antioxidant and antimicrobial properties1. Cardoon leaves may therefore be used in the food sector to prolong the shelf life of foods by preventing lipid oxidation and microbiological growth.
This study aims to evaluate the antioxidant capacity, through DPPH free radical scavenging and the β-carotene bleaching assays, and total phenolic compounds content (TPC) and total flavonoids content (TFC) of cultivated cardoon and globe artichoke leaves extracts, both methanolic and ethanolic.
Cardoon extracts, both ethanolic (2.1 mg/mL) and methanolic (0.8 mg/mL), presented lower EC50 than artichoke extracts (EC50EtOH= 3.9 mg/mL; EC50MeOH= 1.6 mg/mL), which means greater antioxidant capacity. For the β-carotene assay, cardoon extract (AACEtOH:448.06; AACMeOH:279.67) presented a higher antioxidant capacity coefficient (AAC) than the artichoke extract (AACEtOH:90.98; AACMeOH:114.97). Accordingly, cardoon extracts (EtOH: 81.98 mg GAE/g; MeOH: 112.84 mg GAE/g) also had a higher content of TPC than artichoke (EtOH: 49.14 mg GAE/g; MeOH: 29.79 mg GAE/g). The same can also be observed for TFC, where cardoon (EtOH: 145.47 mg ECE/g; MeOH: 129.27 mg ECE/g) presented greater total flavonoids content than artichoke (EtOH: 81.33 mg ECE/g; MeOH: 21.24 mg ECE/g).These results confirm that cardoon leaves are a natural source of antioxidant compounds that can be exploited by the food industry.This work was financially supported by the Mechanical Engineering and Resource Sustainability Center—MEtRICs, which is financed by national funds from the FCT/MCTES (UIDB/04077/2020 and UIDP/04077/2020). Cássia H. Barbosa thanks the Fundação para a Ciência e Tecnologia (FCT), Portugal for the Ph.D. Grant
2021.08154.BD.info:eu-repo/semantics/publishedVersio
DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway
Get PDFDIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3’end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that lack depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.This work was supported by Instituto Nacional de Saúde Doutor Ricardo Jorge and Fundação para a Ciência e a Tecnologia (FCT) [UID/MULTI/04046/2019 Research Unit Grant (to BioISI)]. Juan F. García-Moreno and Paulo J. da Costa were recipients of a fellowship from BioSys PhD programme (SFRH/BD/52495/2014, and PD/BD/142898/2018, respectively).info:eu-repo/semantics/publishedVersio
Portuguese wildland firefighters: assessing exposure and cytogenetic effects in non-fire settings during the pre-fire season
No full textIARC has recently listed occupational exposure as a firefighter carcinogenic to humans. However,
firefighter is among the least studied occupations. The goal of the present study was to assess
the level of cytogenetic damage in buccal mucosa (first-contact exposure tissue) of Portuguese
firefighters during the pre- wildland fire season, as well as, to evaluate firefighters ́ exposure to
particulate matter (PM) on fire stations as a baseline for occupational exposure characterization.
A group of 172 Portuguese wildland firefighters were enrolled in the study, relevant information
was obtained through a questionnaire. The frequency of micronucleus and other endpoints
were evaluated via buccal micronucleus cytome assay (BMCyt) along with the influence of
potential risk factors (e.g., smoking habits). Estimated inhalation doses of PM10 and PM2.5
(indoor/outdoor) were estimated for a group of 80 firefighters. No significant associations were
found between estimated inhaled doses and BMCyt endpoints. Some lifestyle/behavioural
variables were shown to significantly decrease the levels of cytogenetic endpoints, whereas
others were found to increase them. Firefighters of the Permanent Intervention Team also
shown to have significantly higher levels of BMCyt endpoints compared to other firefighters.
Fire seasons are getting longer and dangerous, and this trend will continue in a progressive
warming world. Implementing effective mitigation strategies for firefighters’ occupational
exposure is an urgent public health issue.This work received financial support from the project PCIF/SSO/0017/2018 by the Fundação para a Ciência e a Tecnologia (FCT), Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through national funds. Joana Pires is supported by the grant
PCIF/SSO/0017/2018. Filipa Esteves, the recipient of the PhD grant UI/BD/150783/2020, is supported by FCT and by the European Social Fund (ESF). Joana Madureira, under the grant SFRH/BPD/115112/2016, is supported by FCT and by ESF, through Programa
Operacional Capital Humano (POCH). This work is financed by national funds through the FCT within the scope of projects UIDB/04750/2020 and LA/P/0064/2020. Additional support was received from LA/P/0045/2020 (ALiCE) and UIDB/00511/2020 - UIDP/00511/2020 (LEPABE), UIDB/00690/2020 - UIDP/00690/2020 (CIMO) and SusTEC (LA/P/0007/2021).N/
Exposição ocupacional e infeção por SARS-CoV-2 nos profissionais de saúde no contexto hospitalar
Get PDFEste trabalho resulta de uma análise secundária de dados, no âmbito do projeto Cohort
study to measure COVID-19 vaccine effectiveness among hospital-based health
workers, realizado no Departamento de Epidemiologia do INSA, e colaboração com os
Centros Hospitalares Tondela-Viseu, Universitário de Coimbra e Lisboa OcidentalDissertação de Mestrado em Epidemiologia, Bioestatística e Investigação em Saúde, apresentada à Escola Nacional de Saúde Pública da Universidade NOVA de Lisboa, 2023Orientadores: Doutora Ausenda Machado (INSA) e da Professora Doutora Ema LeiteIntrodução: A doença do coronavírus descoberta em 2019 (COVID-19) é uma doença provocada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Devido a alta taxa de transmissibilidade do vírus e o contato próximo decorrente da prestação de cuidados, os profissionais de saúde representam uma população importante a ser estudada. O objetivo deste estudo consiste em avaliar se trabalhar num serviço dedicado ao acompanhamento de doentes com COVID-19 aumenta o risco de infeção por SARS-CoV-2 nos profissionais de saúde. Métodos: Realizou-se uma análise secundária de dados resultante do seguimento de uma coorte longitudinal com componente retrospetiva e prospetiva dos profissionais de saúde no contexto hospitalar. Fizeram parte da corte inicial, 3 034 profissionais de saúde seguidos durante um ano, porém o seguimento para este estudo foi de duas semanas. Foi considerado como exposto a dedicação exclusiva ao doente com COVID-19 e outcome a confirmação laboratorial de SARS-CoV-2 através do teste molecular RT-PCR, sendo o preenchimento destas consideradas como critério de inclusão. Foi utilizado o modelo de regressão de Poisson com a função de ligação logaritmo, com a utilização do estimador robusto do erro padrão de modo a estimar o risco de infeção por SARS-CoV-2 nos profissionais de saúde. Aceitou-se um nível de significância de 5%. Resultados: Foram analisados 747 profissionais de saúde, 126 com dedicação exclusiva e 621 sem dedicação exclusiva, a média de idade entre os grupos foi de 41,7 e 45,5 anos, respetivamente. A maior parte dos profissionais de saúde que fizeram parte da coorte foram profissionais de saúde com prestação direta de cuidados aos doentes, o que corresponde a 75,9% (n = 567). Não houve diferença estatisticamente significativa (p = 0,705) entre os grupos de dedicação exclusiva e não exclusiva no que diz respeito ao resultado positivo no teste de COVID-19. No que concerne ao risco relativo de infeção por SARS-CoV-2 nos profissionais com dedicação exclusiva em comparação com profissionais sem dedicação exclusiva, não houve aumento do risco bruto e ajustado para confundimento, uma vez que o risco relativo bruto foi 0,90 (IC95%: 0,523-1,551) e o ajustado foi 1,011 (IC95%: 0,974-1,049). Não seguir as recomendações de prevenção e controlo da infeção aumentaram o risco de infeção em 1,452 vezes no grupo de DE (IC95%: 1,354-2,026) e 1,998 (IC95%: 1,354-2,026) nos profissionais de saúde que exerceram atividades geradoras de aerossóis. Conclusão: Trabalhar exclusivamente com doentes com COVID-19 não aumentou o risco de infeção por SARS-CoV-2, porém, o risco é aumentado para os profissionais de saúde que não seguiram as medidas de prevenção e controlo da infeção.Introduction: Coronavirus disease discovered in 2019 (COVID-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the high transmissibility rate of the virus and the close contact arising from care provision, healthcare professionals represent an important population to be studied. The aim of this study is to evaluate whether working in a service dedicated to monitoring patients with COVID-19 increases the risk of SARS-CoV-2 infection in healthcare workers. Methods: A secondary data analysis resulting from the follow-up of a longitudinal cohort with a retrospective and prospective component of health professionals in hospital settings was conducted. The initial cohort included 3,034 healthcare professionals who were followed for one year, but the follow-up for this study was two weeks. Exclusive dedication to the patient with COVID-19 and outcome the laboratory confirmation of SARS-CoV-2 through RT-PCR molecular test were considered as exposed, being the fulfilment of these considered as inclusion criteria. We used the Poisson regression model with logarithm link function, using the robust standard error estimator to estimate the risk of SARS-CoV-2 infection in healthcare professionals. A 5% significance level was accepted. Results: A total of 747 health professionals were analysed, 126 with exclusive dedication and 621 without exclusive dedication, the mean age between the groups was 41.7 and 45.5 years, respectively. Most of the healthcare professionals in the cohort were healthcare professionals providing direct patient care, corresponding to 75.9% (n = 567). There was no statistically significant difference (p = 0.705) between the exclusive and non-exclusive dedication groups regarding the positive result in the COVID-19 test. Regarding the relative risk of SARS-CoV-2 infection in professionals with exclusive dedication compared to professionals without exclusive dedication, there was no increase in the crude and adjusted risk for confounding, as the crude relative risk was 0.90 (95%CI: 0.523-1.551) and the adjusted one was 1.011 (95%CI: 0.974-1.049). Not following the recommendations for infection prevention and control increased the risk of infection by 1.452 in the ED group (95%CI: 1.354-2.026) and 1.998 (95%CI: 1.354-2.026) in healthcare professionals who performed aerosol-generating activities. Conclusion: Working exclusively with patients with COVID-19 did not increase the risk of SARS-CoV-2 infection, but the risk is increased for healthcare workers who have not followed infection prevention and control measures.N/
Caracterização dos hábitos de pequeno-almoço de crianças portuguesas em idade escolar – Programa Escola Missão Continente 2021/2022
Get PDFIntrodução: O pequeno-almoço (PA) desempenha um papel importante nos hábitos alimentares das crianças, constituindo parte de uma dieta saudável e equilibrada fundamental para o seu crescimento e desenvolvimento.
Objetivos: Caracterizar os hábitos de PA de crianças em idade escolar participantes no Programa Escola Missão Continente (EMC), quanto à sua composição, frequência e local, associando estes fatores ao estado nutricional infantil.
Metodologia: No âmbito do Programa EMC, decorrido no ano letivo 2021/2022, foi desenvolvida uma análise transversal, contando com uma amostra de 573 crianças (51.5% sexo masculino, idades 6-8 anos) de 35 escolas de todos os distritos de Portugal Continental e Regiões Autónomas dos Açores e da Madeira. Foram recolhidos dados antropométricos (peso e estatura) para avaliar o estado nutricional, utilizando a classificação no Índice de Massa Corporal e o referencial de curvas de crescimento da Organização Mundial de Saúde para crianças dos 5 aos 19 anos. A caracterização dos hábitos alimentares foi realizada através de um questionário aplicado aos Encarregados de Educação com questões relativas ao PA. Para o teste de hipóteses, aplicou-se o teste estatístico Qui-quadrado.
Resultados: Verificou-se que a maioria das crianças consumia PA diariamente (94,5%) em casa (95,9%), sendo esta composto por produtos lácteos (24,6%), pão e equivalentes (20,7%) e cereais de pequeno-almoço (17,7%). O grupo de crianças que não consumia PA todos os dias da semana apresentava índices de pré-obesidade (25,8%) e obesidade (22,6%), significativamente superiores (p=0,01) comparativamente ao grupo de crianças que consumia pequeno-almoço diariamente (pré-obesidade = 17,0% e obesidade = 10.4%). Os resultados obtidos para os fatores local e composição não foram estatisticamente significativos.
Conclusão: A frequência de PA parece estar associada com o estado nutricional infantil. Deste modo, torna-se fundamental implementar bons hábitos alimentares ao PA, desde a infância, em prol da promoção em saúde como parte de todo o desenvolvimento da criança.info:eu-repo/semantics/publishedVersio
Genomic and epidemiological insight of an outbreak of carbapenemase-producing Enterobacterales in a Portuguese hospital with the emergence of the new KPC-124
No full textBackground: Carbapenemase-producing Enterobacterales (CPE) is an increasing problem in healthcare settings. This study aimed to identify the source of a CPE outbreak that occurred in 2022, in a tertiary hospital in the North of Portugal, to identify exposed patients, and to assess the risk of becoming CPE-positive following hospital admission.
Methods: A multi-disciplinary investigation was conducted including descriptive, analytical, and molecular epidemiology, environmental screening, and assessment of infection control measures. Clinical and environmental isolates were analyzed using whole-genome sequencing and phylogenetic analysis. Additionally, a prospective observational cohort study was conducted to further investigate the risk factors associated with the emergence of new cases in cohorts of CPE-negative admitted patients.
Results: We observed the presence of multispecies KPC-, IMP-, and/or NDM-producing isolates. Genetically indistinguishable clinical and environmental isolates were found on the same room/ward. The ST45 KPC-3-producing Klebsiella pneumoniae clone was the responsible for the outbreak. During patients' treatment, we detected the emergence of resistance to ceftazidime-avibactam, associated with mutations in the blaKPC-3 gene (blaKPC-46, blaKPC-66 and blaKPC-124, the last variant never previously reported), suggesting a vertical evolutionary trajectory. Patients aged ≥ 75 years, hygiene/feeding-care dependent, and/or subjected to secretion aspiration were risk factors for CPE colonization after hospital admission. Additionally, cases with previous admission to the emergency department suggest that CPE dissemination may occur not only during hospitalization but also in the emergency department.
Conclusion: Overall, the study highlights that selection pressure with antibiotics, like ceftazidime-avibactam, is a contributing factor to the emergence of new β-lactamase variants and antibiotic resistance. It also shows that the hospital environment can be a significant source of CPE transmission, and that routine use of infection control measures and real-time molecular epidemiology investigations are essential to ensure the long-term termination of CPE outbreaks and prevent future resurgences.This work was financial supported with funding from FCT/MCTES (UIDB/00211/2020) through national funds.info:eu-repo/semantics/publishedVersio
Intersectoral collaboration in a One Health approach: Lessons learned from a country-level simulation exercise
Get PDFSimEx Portuguese Team (alphabetical order):
Ângela Pista (National Reference Laboratory for Gastrointestinal Infections, Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal); João Vieira Martins (Directorate of Information and Analysis, Directorate-General of Health, Lisbon, Portugal); Lurdes Clemente (National Reference Laboratory for Animal Health, Laboratory of Bacteriology and Mycology, National Institute of Agrarian and Veterinary Research, Oeiras, Portugal); Nuno Santos Rodrigues (Public Health Unit of ACES South West, Regional Health Administration of Lisbon and Tagus Valley, Portugal); Paula Vasconcelos (Support Unit of National Health Authority and the Emergency Management in Public Health, Public Health Emergencies Operations Centre, Directorate-General of Health, Lisbon, Portugal); Pedro Nabais (Food Risks Unit, Economic and Food Safety Authority, Lisbon, Portugal); Renata Carvalho (Animal Health and Epidemiology Division, Directorate-General for Food and Veterinary).Intersectoral collaboration is an essential component of the One Health (OH) approach, which recognises the interconnectedness of the health of humans, animals, and the environment. The OH European Joint Programme (OHEJP) developed a national foodborne outbreak table-top simulation exercise (SimEx) to practice OH capacity and interoperability across the public health, animal health, and food safety sectors, improving OH preparedness for future disease outbreaks. The Portuguese OHEJP SimEx highlighted strengths and weaknesses regarding the roles and functions of available systems, the constraints of existing legislation, the importance of harmonisation and data sharing, and the creation of common main messages adapted to each target sector. However, there is still a long way to go to ensure cooperation among the Public Health, Animal Health, and Food Safety sectors, as a OH approach relies not only on the awareness of "field experts" but also on political and organisational willingness and commitment.Highlights: - Intersectoral collaboration is an essential component of the One Health approach. - Skilled entities engaged in the system, but lack intersectoral communication. - Need of One Health join national multisectoral guidelines and common databases. - One Health approach needs political and organisational willingness and commitment.This work was supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No 773830: One Health European Joint Programme.info:eu-repo/semantics/publishedVersio
Effect of individual's characteristics on volatile organic compoounds profile analysed by an electronic nose
No full textBreath analysis using an electronic nose (eNose) is a technology for exhaled volatile organic compounds (VOCs) that has shown potential in the diagnosis of respiratory diseases. However, the effect of an individual’s characteristics in the exhaled VOCs profile is far from fully understood. This pilot study aimed to identify the relevant characteristics of participants that may influence the VOCs profiles by the eNose. The study population consisted of 91 volunteers (57.1% males) with an average age of 38 years, randomly recruited among nonexposed individuals to VOCs in Porto, Portugal. Exhaled breath air samples were analysed using the Cyranose® 320. Physiological (e.g. height, weight) and sociodemographic characteristics, behavioural patterns, and occupational/environmental exposures were collected through a self-administered questionnaire. Other data (e.g. type of consumed food, liquids and oral hygiene) was recorded via face-to-face interviews. Results showed that exhaled VOCs profiles are influenced by water intake prior to breath sample air collection. It is suggested that individuals should abstain from drinking water for 2.5 h before VOC analysis. This work will support other ongoing research in occupational exposure scenarios, such as forest firefighters’, to further the understanding of this under-explored scientific area, since we hypothesise that VOCs patterns will differ between persons occupationally exposed to VOCs and those unexposed.This work was financially supported by LA/P/0045/2020 (ALiCE); UIDB/00511/2020 -
UIDP/00511/2020 (LEPABE); PTDC/CTAAMB/3040/2021, PCIF/SSO/0017/2018 financed by Fundação para a
Ciência e a Tecnologia (FCT) through Ministério da Ciência, Tecnologia e Ensino Superior and national funds. J.
Madureira and F. Esteves are supported by FCT and European Social Fund through Programa Operacional
Capital Humano (POCH) via the respective fellowships: SFRH/BPD/115112/2016 and UI/BD/150783/2020info:eu-repo/semantics/publishedVersio
Hazard characterisation of the mycotoxins enniatins and Alternaria toxins to close data gaps and improve risk assessment for human health
No full textMycotoxins are secondary metabolites of fungi that may contaminate food and feed, e.g., cereals, (dried) fruits and spices. As they are natural substances, there are no manufacturers or suppliers responsible for providing hazard data, in contrast to e.g. industrial chemicals or pesticides. Humans are widely exposed to mycotoxins mainly through diet and, due to climate changes, the human exposure to these toxins will likely increase. Accordingly, regulatory agencies need more hazard data, particularly regarding emerging (non-regulated) toxins to improve risk assessment and consumer protection. Thus, this project was designed in order to fill data gaps with regulatory relevance regarding the main representatives of two groups of emerging mycotoxins - enniatins and Alternaria toxins.
Within the project, in vitro assays on genotoxic, carcinogenic, immunotoxic and endocrine effects of enniatins and Alternaria toxins as well as in silico analyses and further studies on adverse outcome pathway will be performed by a total of 16 partners from the European Union and Norway. Standardized OECD test guidelines as well as so-called New Approach Methodologies will be used to generate in vitro data.
The results of the study are expected to identify critical toxicological effects of the toxins for subsequent in vivo studies required to establish health based guidance values and thus to perform an appropriate risk assessment in order to provide an efficient health consumer protection.This work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) and has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.N/