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Space agencies have recognized the risks of astronauts’ exposure to space radiation and are developing complex model-based risk mitigation strategies. In the foundation of these models, there are still significant gaps of knowledge concerning nuclear fragmentation reactions which need to be addressed by ground-based experiments. There is a lack of data on neutron and light ion production by heavy ions, which are an important component of galactic cosmic radiation (GCR). A research collaboration has been set up to characterize the secondary radiation field produced by GCR-like radiation provided by a particle accelerator in thick shielding. The aim is to develop a novel method for producing high-quality experimental data on neutron and light ion production in shielding materials relevant for space radiation protection. Four complementary detector systems are used to determine the energy and angular distributions of high-energy secondary neutrons and light ions. In addition to the physical measurement approach, the biological effectiveness of the secondary radiation field is determined by measuring chromosome aberrations in human peripheral lymphocytes placed behind the shielding. The experiments are performed at the heavy ion

OBJECTIVES: To determine whether the tumor necrosis factor-[alpha] -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. DESIGN: Genetic association studies. SETTING: Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network). MEASUREMENTS AND MAIN RESULTS: In cohort I, 344 of 1944 (18.2%) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3% for G/G, 15.8% for G/A, 10.0% for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95% confidence interval, 1.03-1.71; G/G vs. A/A: odds ratio, 1.74; 95% confidence interval, 1.06-2.91; p = .03). There was a trend for association of tumor necrosis factor-[alpha] -308 A/G genotype with late-onset sepsis episodes (incidence: 17.2% for G/G, 12.5% for G/A, 10.0% for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95% confidence interval, 1.09-1.9; G/G vs. A/A: odds ratio, 2.05; 95% confidence interval, 1.19-3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk. CONCLUSIONS: No association was found between the tumor necrosis factor-[alpha] -308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-[alpha] -308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis. [ABSTRACT FROM AUTHOR]

Background: Erythropoietin (Epo) was originally defined as a hematopoietic growth factor, but also has potent tissue-protective properties. The cytokine-modulating actions of Epo have received scant attention. We hypothesized that Epo significantly influences the in vitro cytokine production in both neonates and adults. Methods: The effects of Epo were investigated using a standardized in vitro whole blood assay. Production of various cytokines was assessed by means of intracellular cytokine detection (IL-2, -6, -8, IFN-γ and TNF-α) in preterm infants, term neonates and adults. Furthermore, synthesis of IL-4, -5 and -10 in adults was investigated via cytometric bead array. Results: Epo significantly inhibits the production of various cytokines in preterm infants, term neonates and adults. In CD3+ lymphocytes, Epo predominantly decreases the number of IL-2-positive cells in all age groups. Similarly, in CD14+ cells, Epo significantly diminishes the number of IL-6- and TNF-α-producing cells. Furthermore, Epo significantly inhibits the synthesis of IL-4, IL-5 and IL-10 in adults. Conclusion: rhEpo has significant inhibitory potential on the production of various cytokines by leukocytes in preterm and term infants as well as in adults. The described effect likely contributes to the tissue protective properties of Epo. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-6 is a pleiotropic cytokine, produced by different cells. There is accumulating evidence that IL-6 promoter polymorphisms impact substantially on various diseases and we identified kidney transplant recipients carrying the IL-6 GGG/GGG −597/−572/−174genotype to have superior graft survival. To prove a functional impact on gene expression, we analysed systematically IL-6 production in healthy individuals with respect to the IL-6 −597/−572/−174genotype. IL-6 was determined in 100 healthy blood donors at protein and mRNA levels upon specific stimulation in monocytes and T lymphocytes under whole blood conditions. GGG/GGG individuals showed a lower IL-6 secretion upon lipopolysaccharide (LPS)-stimulation versus all others ( P = 0·039). This link was even stronger when −597 and −174GG genotypes were reanalysed separately ( P = 0·008, P = 0·017). However, we found neither a difference at the mRNA level or percentage of CD14+ cells nor after T cell stimulation. We found evidence for the IL-6 −597/−572/−174genotype to affect IL-6 synthesis, i.e. lower levels of IL-6 protein upon LPS-stimulation in GGG/GGG individuals. Further studies are needed in kidney transplant recipients to investigate the potential link between the GGG/GGG genotype and graft survival. In line with this, determination of the genetic risk profiles might be promising to improve the transplant outcome in the individual patient. [ABSTRACT FROM AUTHOR]

In this study we explored the hassles and uplifts (i.e. negative and positive emotional events) experienced by registered nurses, nursing assistants and personal carers working with people with cognitive impairment in community and residential healthcare settings in Brisbane, Queensland, Australia. The primary aim of the research was to explore what aspects of caring for cognitively impaired clients hassles nurses, what helps to relieve these hassles, what aspects of this work nurses find rewarding and what detracts from those rewards, as well as the intensity with which each of these aspects were felt. A questionnaire developed to explore hassles and uplifts at work was administered and 57 responses obtained. Results indicated that caring for the cognitively impaired client provides many uplifts for nurses and few hassles. However, the hassles that occurred were of high importance. This paper will be of interest to managers, nurses and carers in settings where there are people with cognitive impairment as well as scholars, who may find that assessing emotional hassles and uplifts provides additional insights into other areas of nursing. [ABSTRACT FROM AUTHOR]

Interleukin 18 (IL-18) is an important cytokine and involved in the pathogenesis and genetics of many diseases. The authors studied two different populations of preterm infants to test whether polymorphisms within IL-18 are in association with prematurity itself or with typical pulmonary disease or measurements seen in preterm infants, such as bronchopulmonary dysplasia, pneumothoraces and application of surfactant, inhalation or mechanical ventilation. Whereas the fi rst population of 228 preterm infants showed strong association of IL-18 with preterm birth (p<0.001), this was not confirmed in the second population of 346 preterm infants. In addition, no association with any lung condition of prematurity was observed. The authors conclude that IL-18 does not play an important role in the genetics of preterm birth nor in the development of bronchopulmonary dysplasia and other lung complications in preterm infants. Caution must be taken in the interpretation of the results of genetic association studies performed in one population. [ABSTRACT FROM AUTHOR]

Studies the cerebral magnetic resonance imaging of a 14-year old boy with hypertensive encephalopathy and pharyngitis. Observance of acute onset of neurological symptoms including consciousness, seizures and hemiplegia; Causes of cerebral vascular vasodilatation.

BACKGROUND: Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late-onset sepsis, and gestational age is the most important risk factor for these infections. OBJECTIVE: To characterise innate immune responses to S epidermidis by assessment of whole blood in vitro cytokine production in a large group of preterm and term infants. RESULTS: The S epidermidis-induced in vitro production of proinflammatory cytokines such as intracytoplasmic interleukin (IL) 6 and tumour necrosis factor alpha in cord blood samples was found to be dependent on gestational age (R = 0.279, 95% CI 0.10 to 0.44, p = 0.002; R = 0.251, 95% CI 0.07 to 0.41, p = 0.005, respectively; n = 121). In contrast, the production of anti-inflammatory cytokines such as IL10 and transforming growth factor beta was not associated with gestational age. When different stimulation strategies were compared, a strong correlation was noted for cytokine responses after lipopolysaccharide and S epidermidis exposure--that is, IL6 (R = 0.431, 95% CI 0.29 to 0.55, p<0.001, n = 161) and IL10 (R = 0.332, 95% CI 0.18 to 0.47, p<0.001, n = 161). In addition, a lower IL6 production was found in supernatants of whole blood cultures infected with a clinically isolated IcaABD-positive (biofilm production) strain compared with a control IcaABD-negative ATCC strain (p = 0.009). CONCLUSIONS: These in vitro data suggest that proinflammatory responses to S epidermidis are dependent on gestational age in preterm infants, whereas the counteracting anti-inflammatory response to S epidermidis may not be directly related to gestational age. Individual host factors may have a role as well as bacterial determinants, such as biofilm production. Further studies are encouraged to investigate the different aspects of innate immune responses to CoNS in vivo. [ABSTRACT FROM AUTHOR]

Although it is clear that achievement goal orientations (how people define success) and attributional styles (how people explain success and failure) are related to achievement behaviour and motivation and that motivation is a critical factor in achieving success in work and sport, little sport or management research-based information is available regarding the identification of individuals likely to sustain high levels of motivation over time or in the development of sustained motivation levels. Data collected at two points in time from 224 employees and 272 athletes is presented. The findings contribute to resolving the debate over how specific attributional styles influence achievement goal orientation and help answer whether the optimal attributional style (how one explains success) depends on the adopted achievement goal orientation (how one defines success). Further, the preponderance of available research on these issues focuses on athletes and students. This knowledge largely has not been extended to the employment setting. In addition to addressing these issues in both a sporting and work context, this study represents the first empirical analysis of the popularly held view that the attributes necessary for excellence in motivation and performance at work are the same as those in sport. Thus, the research also contributes to the development of appropriate metaphors for the organisational context and expands understanding of motivational processes across contexts. [ABSTRACT FROM AUTHOR]

The ineffective management of diverse teams can result in exclusion of diverse team members, which impedes the utilisation of team member resources. Building on the Model of Focal Individual's Experience in a Diverse Workgroup (Elsass & Graves, 1997), we introduce the Model of the Diverse Intrateam Process in order to improve understanding of the process through which team members are attracted to and form subgroups with similar individuals and exclude dissimilar individuals. The level of exclusion behaviour present in the team is inversely related to the utilisation of dissimilar team members' potential and the dissimilar team members' satisfaction with the team. This information will assist practitioners in their ability to manage diverse teams to reach their full potential. In addition, this research aids organisations and diversity trainers in their ability to provide a work climate supporting positive social influences and avoiding negative social influences. Further, the research suggests that to facilitate improved work relations and interpersonal attraction, managers need to reduce the perception of similarity and dissimilarity based on observable attributes, reduce ingroup/out-group distinctions and encourage team performance over self performance. The paper contributes in two key ways. First, it takes a step towards explaining the reason for the inconsistent performance results observed across heterogeneous teams by identifying the individual intrateam behaviours that cause these outcomes and the factors that impact the process. Second, it is the first to examine the impact of social influence and perceiver characteristics on team behaviour. [ABSTRACT FROM AUTHOR]

Meningococcal disease is a leading infectious cause of death in children in industrialized countries. The induction of high levels of proinflammatory cytokines has been implicated in the pathogenesis of Neisseria meningitidis-related multi-organ failure. Here, we demonstrate that N. meningitidis serotypes A and B induce significantly higher levels of tumour necrosis factor (TNF)-α positive cells in vitro in infants and young children compared with adults (serotype A/B; infants: 64·9%/63·9%; children: 77·8%/64·3% versus adults: 27·7%/32%; P < 0·005). Serotype A induces also higher levels of interleukin (IL)-6 positive cells in neonates and infants compared with adults (serotype A; newborn 55·4%; infants 58·8% versus adults 49%; P < 0·05). Treatment with human recombinant erythropoietin in vitro resulted in significant attenuation of the N. meningitidis-induced proinflammatory response in all age groups (reduction rate of erythropoietin for IL-6 after stimulation with serotype B: newborn 28%, infants 15%, children 23% and adults 28% and for TNF-α after stimulation with serotype B: newborn 27%, infants 22%, children 20% and adults 28%; P < 0·05). We conclude that (i) Neisseria meningitidis induces a higher TNF-α response in infants and children compared with adults and (ii) erythropoietin was able to attenuate IL-6 and TNF-α production in all investigated age groups. These data may explain the high incidence of meningococcal infection in infants and makes erythropoietin a potentially attractive candidate for interventional strategies in an otherwise devastating course of the disease. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are two of the most common emergencies of the gastrointestinal tract in preterm infants with very low birth weight (VLBW, birth weight < 1500 g). Identification of risk factors among these children is crucial for earlier diagnosis and prompt intervention. In this study, we investigated a relationship between ABO blood groups and the risk for surgical NEC/FIP. We genotyped the ABO locus (rs8176746 and rs8176719) in VLBW infants enrolled in a prospective, population-based cohort study of the German Neonatal Network (GNN). Of the 10,257 VLBW infants, 441 (4.3%) had surgical NEC/FIP. In univariate analyses, the blood group AB was more prevalent in VLBW infants with surgical NEC/FIP compared to non-AB blood groups (OR 1.51, 95% CI 1.07–2.13, p = 0.017; absolute risk difference 2.01%, 95% CI 0.06–3.96%). The association between blood group AB and surgical NEC/FIP was observed in a multivariable logistic regression model (OR of 1.58, 95% CI 1.10–2.26, p = 0.013) as well. In summary, our study suggests that the risk of surgical NEC and FIP is higher in patients with blood group AB and lower in those having non-AB blood groups. [ABSTRACT FROM AUTHOR]

Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations. [ABSTRACT FROM AUTHOR]

Summary In recent years galectin-3 has gained attention as a signalling molecule, mainly in inflammatory diseases. Data on galectin-3 expression in neonates, however, are limited, and expression of this lectin in cord blood has not yet been reported. The aim of this study was to determine galectin-3 levels in cord blood of term and preterm neonates as well as galectin-3 levels in cord blood of term neonates after stimulation with the prevalent pathogen Streptococcus agalactiae. Cord blood samples were incubated for 24 h and galectin-3 levels were assessed by enzyme-linked immunosorbent assay. There is a positive correlation between gestational age and galectin-3 levels in cord blood. Expression of galectin-3 is significantly higher in cord blood of small-for-gestational-age infants compared to appropriate-for-gestational-age infants. Stimulation with an invasive but not with a colonizing strain of S. agalactiae induced expression of galectin-3. Galectin-3 is expressed constitutively in cord blood of neonates and seems to play a role in the innate immunity of this population. [ABSTRACT FROM AUTHOR]

Aim: To further evaluate the underlying mechanism of a formerly demonstrated immature anti-inflammatory response in neonates ( 1 ). Methods: Interleukin (IL)-10 production was measured by enzyme-linked immunosorbent-assay (ELISA) after anti-CD3/anti-CD28 costimulation of neonatal and adult T cells. IL-10 receptor expression on T lymphocytes, B lymphocytes and monocytes were analysed by flow cytometry in neonates and adult controls. Results: After anti-CD3/anti-CD28 costimulation, IL-10 production of neonatal T lymphocytes was profoundly reduced (median 247 pg/mL vs. 1062 pg/mL, p < 0.0001). IL-10 receptor expression was diminished on neonatal T lymphocytes compared to adults (3% vs. 39.5% IL-10 receptor positive lymphocytes; p < 0.0001). On neonatal B lymphocytes and monocytes the IL-10 receptor expression was comparable to adult controls. Conclusion: The strongly reduced IL-10 receptor expression on the main immune regulative T lymphocytes in conjunction with a significantly impaired synthesis of IL-10 may play a crucial role in the formerly demonstrated deficient anti-inflammatory immune response in neonates. [ABSTRACT FROM AUTHOR]

The inflammatory response plays a major role in the induction of several neonatal diseases. We hypothesize that an imbalance between the pro- and anti-inflammatory response is crucial for the previously shown enhanced production of proinflammatory cytokines in term and preterm infants during infection. To test this hypothesis, we compared the capacity to produce the main anti-inflammatory cytokines IL-10 and TGF- β in term infants, preterm infants and adults at different levels of synthesis by quantitative real time reverse-transcribed PCR, flow cytometry, as well as enzyme-linked immunoassay. Term and preterm infants showed a profoundly diminished IL-10 mRNA-expression and IL-10 production after stimulation. In addition, the amount of TGF- β-positive lymphocytes was significantly less in neonates than adults. Furthermore, there was a considerably lower inhibition of production of IL-1 α, IL-6, IL-8 and TNF- α by the use of recombinant IL-10 in term and preterm infants compared with adults. These results demonstrate not only a diminished anti-inflammatory capacity but also a reduced response to anti-inflammatory stimuli in term and preterm infants. From these data we conclude that neonates display an immature compensatory anti-inflammatory response syndrome (CARS) which may predispose preterm infants to harmful effects of proinflammatory cytokines resulting in severe organ sequelae during infection. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a major cause of mortality in preterm infants. Its pathophysiology remains poorly understood but intestinal epithelial barrier dysfunction contributes to the disease. We characterized junctional proteins in intestinal specimens from preterm infants. Samples from 27 patients with NEC and 20 patients with focal intestinal perforation (FIP) from the center of the specimens (affected) or the macroscopically healthy resection margins whenever available (non-affected) were collected. NEC patients displayed higher mortality and more commonly occurrence of impaired glucose homeostasis, patent ductus arteriosus, anemia and antibiotic treatment compared to FIP patients. Discrimination between NEC and FIP was not possible in affected areas based on H.E. staining using a newly developed scoring system. Immunofluorescence revealed reduced Claudin-3 in affected NEC samples and decreased Claudin-4 in affected FIP and all NEC samples. E-cadherin and Desmoglein-2 were reduced in a subgroup of the affected NEC samples. Plakophilin-2 was decreased in intestine affected by FIP and unaffected intestine in patients with NEC. In affected areas of NEC, Plakophilin-2 was completely lost. Plakoglobin reduction in affected NEC samples correlated with poor survival. This study provides novel insights into changes of junctional proteins in NEC, suggesting Claudin-3 and Plakophilin-2 as diagnostic markers to differentiate FIP from NEC and reduced Plakoglobin as a prognostic marker., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Objective: This study aims to understand the perspectives of young people towards their Covid-19 vaccination and their involvement in the decision-making process., Methods: Semi-structured interviews were conducted with 25 children and adolescents (aged 8-19 years), who attended a school in Germany during the pandemic. Interviews were explored with structured and evaluative content-analysis., Results: Five overarching themes were identified: 1) Motivators for vaccination: protection against Covid-19, secondary societal benefits and positive experience of peers 2) Barriers to vaccination: perceived lack of risk for severe disease 3) Participation in the decision-making process: mostly adult-initiated shared decisions 4) Role of vaccination status at school: issues of marginalization and stigmatization 5) Wishes to adults and politicians: need for better information CONCLUSION: Involving children at a high level of participation while taking into account their individual maturity could be a favourable strategy in a family`s decision-making process regarding vaccination. Expectations from peers or parents and societal benefits as primary incentive to get vaccinated should be minimized during the decision-process., Practice Implications: Our study highlights the need to include young people`s perspectives in vaccine research, -development and -education campaigns. Future research should develop instruments to structurally embed and promote children and youth participation in healthcare-related decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We hypothesized that previously healthy infants < 90 days of age with late-onset sepsis (LOS) have disturbances of the gut microbiome with yet undefined specific immunological patterns., Methods: We performed a prospective single-center convenience sample study between January 2019 and July 2021 in a case-control design. Routine diagnostics included conventional cultures (blood, cerebrospinal fluid, urine), PCRs and inflammatory markers in infants aged < 90 days with clinical LOS. We additionally analyzed blood lymphocyte subsets including CD4 + CD25 + forkhead box protein (FoxP3) + Tregs and performed 16 S rRNA sequencing of stool samples, both compared to age-matched healthy controls. Results were adjusted for potential confounders that may influence microbial composition., Results: 51 infants with fever and clinical LOS were enrolled. Bacterial sepsis was diagnosed in n = 24 (47.1%) and viral infection in n = 13 (25.5%) infants, whereas in 14 (27.3%) infants the cause of fever remained undetermined. When compared to healthy controls, the gut microbiome of LOS infants at disease onset was characterized by a shift in community composition, specifically, decreased abundance of B. longum and an increase of Bacteroidia spp. Intriguingly, the abundance of B. longum negatively correlated with the frequency of blood CD4-positive cells in healthy controls but not in infants with LOS. At one year of age, we observed microbiome differences in infants with history of LOS when compared to healthy controls, such as an increased gut microbial diversity., Conclusion: Our data suggest potential signatures of the microbiome-immunity interplay in infants with LOS, which should be investigated further as possible targets for prevention., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics alongside reverse transcription polymerase chain reaction (RT-qPCR) as reference., Methods: In a prospective performance assessment from 12 November 2020 to 30 June 2023 at a single centre tertiary care hospital, the sensitivity and specificity (primary endpoints) of RDTs from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to RT-qPCR as reference standard among patients, accompanying persons and staff aged ≥ six month in large-scale, clinical screening use. Regression models were used to assess influencing factors on RDT performance (secondary endpoints)., Findings: Among 78,798 paired RDT/RT-qPCR results analysed, overall RDT sensitivity was 34.5% (695/2016; 95% CI 32.4-36.6%), specificity 99.6% (76,503/76,782; 95% CI 99.6-99.7%). Over the pandemic course, sensitivity decreased in line with a lower rate of individuals showing typical COVID-19 symptoms. The lasso regression model showed that a higher viral load and typical COVID-19 symptoms were directly significantly correlated with the likelihood of a positive RDT result in SARS-CoV-2 infection, whereas age, sex, vaccination status, and the Omicron VOC were not., Interpretation: The decline in RDT sensitivity throughout the pandemic can primarily be attributed to the reduced prevalence of symptomatic infections among vaccinated individuals and individuals infected with Omicron VOC. RDTs remain valuable for detecting SARS-CoV-2 in symptomatic individuals and offer potential for detecting other respiratory pathogens in the post-pandemic era, underscoring their importance in infection control efforts., Funding: German Federal Ministry of Education and Research (BMBF), Free State of Bavaria, Bavarian State Ministry of Health and Care., Competing Interests: Declaration of interests Daniel Zeller receives honoraria from Angelini Pharma and Novartis outside of the submitted work. Manuel Krone receives honoraria from Abbott, GSK, Pfizer, and Sanofi outside of the submitted work. None of the other authors have any conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)