Search

Biodiversity loss and its potential threat on ecosystem functions call for a critical evaluation of human impacts on forest ecosystems. Management practices based on stand diversification offer a possible solution to biodiversity loss due to monoculture plantations, and these practices often involve planting introduced tree species. Although introduced non-native tree species may provide high economic returns, they may also form novel ecosystems and threaten local biodiversity, but this has been little studied. Here, we combined a taxonomic and trait-based approach and investigated communities of oribatid mites (Oribatida, Acari) across forest types of both native and introduced tree species in Northern Germany. Both trophic and life-history traits of oribatid mites were evaluated using native European beech (Fagus sylvatica) as reference, compared to native Norway spruce (Picea abies), introduced Douglas fir (Pseudotsuga menziesii) and beech-conifer mixtures. The abundance and diversity of oribatid mites were generally similar among monocultures of European beech, Norway spruce and Douglas fir. By contrast, species and trait compositions of oribatid mite communities were shifted to include more primary decomposers and more surface-living oribatid mites in Douglas fir, resulting in a trophic reorganization with less predators than in European beech forests. These results suggest that oribatid mites maintain a similar level of trait diversity regardless of forest type, but the changes in trophic guild composition and vertical distribution indicate greater availability of litter-based resources in Douglas fir than in European beech forests. The similar abundance and diversity of oribatid mite communities in Douglas fir mixed stands as in native European beech forests points to mixed forests as a promising management option for future forestry. Overall, our trait-based analyses provided insights into the changes of soil biota composition, revealing the impact of introduced tree species on the structure and functions of soil animal communities.

Abstract It is likely that individuals are turning to Large Language Models (LLMs) to seek health advice, much like searching for diagnoses on Google. We evaluate clinical accuracy of GPT-3·5 and GPT-4 for suggesting initial diagnosis, examination steps and treatment of 110 medical cases across diverse clinical disciplines. Moreover, two model configurations of the Llama 2 open source LLMs are assessed in a sub-study. For benchmarking the diagnostic task, we conduct a naïve Google search for comparison. Overall, GPT-4 performed best with superior performances over GPT-3·5 considering diagnosis and examination and superior performance over Google for diagnosis. Except for treatment, better performance on frequent vs rare diseases is evident for all three approaches. The sub-study indicates slightly lower performances for Llama models. In conclusion, the commercial LLMs show growing potential for medical question answering in two successive major releases. However, some weaknesses underscore the need for robust and regulated AI models in health care. Open source LLMs can be a viable option to address specific needs regarding data privacy and transparency of training.

Abstract Background Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models. Methods We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (e.g. test number, vaccine coverage). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios. Results At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12–50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts was more stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics. Discussion Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.

BackgroundGenetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain.MethodsWe engineered a novel App knock-in mouse model (AppSAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous AppSAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays.ResultsLeveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The AppSAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged.DiscussionOur findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.

Background: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results. Methods: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model’s quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data. Results: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models’ quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes. Conclusions: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort’s aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts.

The institutionalization of community engagement is a lengthy, complex process to which higher education change agents have turned their attention over the past few decades. This study examined the experiences of participants in leadership workshops designed specifically to develop the capacities of campus and community leaders to facilitate this work. Using Conner's (2006) curve of commitment, this research highlighted factors contributing to and deterring community engagement, and explored the role of leadership development in the institutionalization of community engagement. Findings revealed five critical issues related to this work: administrative support, faculty buy-in, positionality/power dynamics, resources, and embeddedness--with administrative support and leadership serving as a linchpin. In addition to the need for effective leadership development as a pathway to supporting this multifaceted organizational change, the results also underscored the need for a model of shared leadership to guide the purpose, planning, and persistence necessary for institutional change.

Abstract Easy access to antimicrobial resistance data and meaningful visualization is essential to guide the empirical antimicrobial treatment and to promote the rational use of antimicrobial agents. Currently available solutions are commonly externally hosted, centralized systems. However, there is a need for close monitoring by local analysis tools. To fill this gap, we developed GEFAAR—a generic framework for the analysis of antimicrobial resistance data. Following the example of the German Robert Koch Institute (RKI), an interactive web-application is provided to determine basic pathogen and resistance statistics. In addition to the RKI’s externally maintained database, our application provides a generic framework to import tabular data and to analyze them safely in a local environment. Moreover, our application offers an intuitive web-based user interface to visualize resistance trend analysis as well as advanced cluster analyses on species- or clinic/unit level to generate alerts of potential transmission events.

Abstract Background Acute Kidney Injury (AKI) is a multifactorial condition which presents a substantial burden to healthcare systems. There is limited evidence on whether it is seasonal. We sought to investigate the seasonality of AKI hospitalisations in England and use unsupervised machine learning to explore clustering of underlying comorbidities, to gain insights for future intervention. Methods We used Hospital Episodes Statistics linked to the Clinical Practice Research Datalink to describe the overall incidence of AKI admissions between 2015 and 2019 weekly by demographic and admission characteristics. We carried out dimension reduction on 850 diagnosis codes using multiple correspondence analysis and applied k-means clustering to classify patients. We phenotype each group based on the dominant characteristics and describe the seasonality of AKI admissions by these different phenotypes. Results Between 2015 and 2019, weekly AKI admissions peaked in winter, with additional summer peaks related to periods of extreme heat. Winter seasonality was more evident in those diagnosed with AKI on admission. From the cluster classification we describe six phenotypes of people admitted to hospital with AKI. Among these, seasonality of AKI admissions was observed among people who we described as having a multimorbid phenotype, established risk factor phenotype, and general AKI phenotype. Conclusion We demonstrate winter seasonality of AKI admissions in England, particularly among those with AKI diagnosed on admission, suggestive of community triggers. Differences in seasonality between phenotypes suggests some groups may be more likely to develop AKI as a result of these factors. This may be driven by underlying comorbidity profiles or reflect differences in uptake of seasonal interventions such as vaccines.

The use of non-metallic reinforcement can significantly reduce the carbon footprint of the construction sector. Mixed structures made out of steel and non-metallic reinforcement should be avoided due to the risk of galvanic corrosion. So far, researchers have been focusing on the load-bearing behavior in the longitudinal direction of the fibers. In this study, the behavior of the fibers in the non-metallic reinforcements is analyzed perpendicular to the fiber orientation. Therefore, a uniaxial shear test on a single bar (uniaxial shear test), as well as a series of push-off tests with reinforcements embedded in the concrete, was carried out. For both experiments, bars made of carbon fiber-reinforced polymers (CFRPs) and glass fiber-reinforced polymers (GFRPs) were investigated. In order to analyze the influence of non-metallic reinforcement in the joint, specimens without reinforcement have been tested as well. Also, the joint roughness and reinforcement ratio of the concrete joint was varied in the tests. The determined transverse shear strengths for the single bar exceed the values of the producer. For the push-off test, high standard deviations occurred, making it difficult to draw firm conclusions. Nevertheless, it is shown that increasing the amount of reinforcement leads to higher ultimate forces. The presented study emphasizes the necessity of further studies of the shear transfer in concrete joints.

Abstract To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups—WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient’s mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations’ impact on carcinogenesis and cancer treatment.

Abstract Background Modern genome sequencing leads to an ever-growing collection of genomic annotations. Combining these elements with a set of input regions (e.g. genes) would yield new insights in genomic associations, such as those involved in gene regulation. The required data are scattered across different databases making a manual approach tiresome, unpractical, and prone to error. Semi-automatic approaches require programming skills in data parsing, processing, overlap calculation, and visualization, which most biomedical researchers lack. Our aim was to develop an automated tool providing all necessary algorithms, benefiting both bioinformaticians and researchers without bioinformatic training. Results We developed overlapping annotated genomic regions (OGRE) as a comprehensive tool to associate and visualize input regions with genomic annotations. It does so by parsing regions of interest, mining publicly available annotations, and calculating possible overlaps between them. The user can thus identify location, type, and number of associated regulatory elements. Results are presented as easy to understand visualizations and result tables. We applied OGRE to recent studies and could show high reproducibility and potential new insights. To demonstrate OGRE’s performance in terms of running time and output, we have conducted a benchmark and compared its features with similar tools. Conclusions OGRE’s functions and built-in annotations can be applied as a downstream overlap association step, which is compatible with most genomic sequencing outputs, and can thus enrich pre-existing analyses pipelines. Compared to similar tools, OGRE shows competitive performance, offers additional features, and has been successfully applied to two recent studies. Overall, OGRE addresses the lack of tools for automatic analysis, local genomic overlap calculation, and visualization by providing an easy to use, end-to-end solution for both biologists and computational scientists.

Abstract Background The SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. Methods We used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021 and comprised of 29,292 participants providing a total of 111,103 completed surveys. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals. Results The results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables (p-value < 0.001). More specifically, participants who had low or neutral levels of perceived severity reported 1.25 (95% Confidence intervals (CI) 1.13 - 1.37) and 1.10 (95% CI 1.00 - 1.21) times more contacts compared to those who perceived COVID-19 to be a serious illness, respectively. Additionally, vaccination status was also a significant predictor of contacts (p-value < 0.001), with vaccinated individuals reporting 1.31 (95% CI 1.23 - 1.39) times higher number of contacts than the non-vaccinated. Furthermore, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors. Conclusion Our multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant.

Abstract Background Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes. Methods Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data. Results Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival. Conclusion Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options. Graphical Abstract

Abstract Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources’ opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource’s value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.

Abstract Background Chronic wounds are frequently colonized or infected with multiple bacterial or fungal species, which can both promote or inhibit each other. Network analyses are helpful to understand the interplay of these species in polymicrobial infections. Our aim was to analyse the network of bacterial and fungal species in chronic wounds. Methods Swabs (n = 163) from chronic wound infections (Masanga, Sierra Leone, 2019–2020) were screened for bacterial and fungal species using non-selective agars. Some of these wounds were suspected but not confirmed Buruli ulcer. Species identification was done with MALDI-TOF mass spectrometry. Network analysis was performed to investigate co-occurrence of different species within one patient. All species with n ≥ 10 isolates were taken into account. Results Of the 163 patients, 156 had a positive wound culture (median of three different species per patient; range 1–7). Pseudomonas aeruginosa (n = 75) was the dominating species with frequent co-detections of Klebsiella pneumoniae (21 cases; OR = 1.36, 95%CI: 0.63–2.96, p = 0.47), Staphylococcus aureus (14 cases; OR = 1.06, 95%CI: 0.44–2.55, p = 1) and Proteus mirabilis (13 cases; OR = 0.84, 95%CI: 0.35–1.99, p = 0.69). Conclusion The culturome of chronic wounds in Sierra Leonean patients is highly diverse and characterized by the co-occurrence of P. aeruginosa, K. pneumoniae and S. aureus.

The individual debates on housing poverty, energy poverty, and mobility poverty for the most part overlook the interwoven nature of all three cost burdens, especially for low-income households. This study examines how the three cost factors interact on a household level, the consequences for those affected by cost burdens, and how they cope and negotiate their expenses. Our research comprises two sets of semi-structured interviews, one before and one during the energy crisis, to gain insight into household experiences and constraints. We found that the freedom to choose where and how to live largely determines how households heat their homes and organize their mobility. The housing crisis together with housing market mechanisms appears to be the main driver of this cost trap; and from here, a complex interplay of causal factors unfolds. Location, often conceived of in terms of an urban–rural divide, seems to be of secondary importance. The intersection of cost burdens results in stress, anxiety, and social exclusion, further limiting the capacity for coping.

Background: The hepatitis B core-related antigen (HBcrAg) correlates with HBV DNA in patients with chronic HBV infection without antiviral treatment. Its utility in monitoring patients during and after the cessation of nucleos(t)ide analog (NA) treatment is unknown. Methods: The levels of HBcrAg were longitudinally determined in two cohorts of chronic HBV-infected patients with (A) newly started NA treatment or (B) after NA cessation during a median follow up (FU) of 60 months or 48 weeks, respectively. The correlation of HBcrAg and HBV DNA and the predictive value for HBeAg seroconversion and HBsAg loss were evaluated. Results: Fifty-six patients with newly-started NA treatment and 22 patients with NA cessation were identified. HBcrAg and HBV DNA strongly correlated before NA treatment (r = 0.77, p < 0.0001) and at virological relapse (0.66, p = 0.0063). At the individual level, the discrepant kinetics of HBcrAg and HBV DNA became evident. During NA treatment, 33% (6/18) and 9% (5/56) of patients showed HBeAg seroconversion or HBsAg loss/HBsAg < 100 IU/mL, respectively. Low levels of HBcrAg were associated with these endpoints. Conclusion: HBcrAg levels before antiviral treatment help to identify patients with chances of HBsAg loss or HBeAg seroconversion. However, its utility in replacing quantitative HBV DNA to evaluate treatment efficacy or virological relapse off-treatment is limited.

Objectives The economic burden of COVID-19 pandemic is substantial, with both direct and indirect costs playing a significant role.Design A systematic literature review was conducted to estimate the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions. All cost data were adjusted to the 2021 Euro, and interventions compared with null.Data sources Ovid MEDLINE and EMBASE were searched from January 2020 through 22 April 2021.Eligibility criteria Studies regarding COVID-19 outbreak or public health preparedness measures or interventions with outcome measures related to the direct and indirect costs for disease and preparedness and/or response in countries of the European Union (EU), the European Economic Area (EEA), the UK and the Organisation for Economic Co-operation and Development (OECD) of all relevant epidemiological designs which estimate cost within the selected time frame were considered eligible.Data extraction and synthesis Studies were searched, screened and coded independently by two reviewers with high measure of inter-rater agreement. Data were extracted to a predefined data extraction sheet. The risk of bias was assessed using the Consensus on Health Economic Criteria checklist.Results We included data from 41 economic studies. Ten studies evaluated the cost of the COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness and response measures. Overall, the economic burden of the COVID-19 pandemic was found to be substantial. Community screening, bed provision policies, investing in personal-protective-equipment and vaccination strategies were cost-effective. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented.Conclusions COVID-19 pandemic is associated with substantial short-term and long-term economic costs to healthcare systems, payers and societies, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.

Summary: Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded. However, little is still known about the natural history of the disease, host-viral interactions, and the role of the immune system in HDV persistence. Diagnosis of HDV is still challenging due to a lack of standardised assays, while accurate viral load quantification is needed to assess response and endpoints of antiviral treatment. Until recently, interferon has represented the only treatment option in patients with chronic hepatitis delta; however, it is associated with low efficacy and a high burden of side effects. The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease. In the meantime, other compounds (i.e. lonafarnib, new anti-hepatitis B virus drugs) are under development to provide alternative or combined strategies for HDV cure. The first international Delta Cure meeting was organised in Milan in October 2022 with the aim of sharing and disseminating the latest data; this review summarises key takeaway messages from state-of-the-art lectures and research data on HDV.

ABSTRACT Wildlife can be a reservoir and source of zoonotic pathogens for humans. For instance, pangolins were considered one of the potential animal reservoirs of SARS-CoV-2. The aim of this study was to assess the prevalence of antimicrobial-resistant species (e.g., extended-spectrum β-lactamase [ESBL]-producing Enterobacterales) and Staphylococcus aureus-related complex and to describe the bacterial community in wild Gabonese pangolins. The pharyngeal colonization of pangolins sold in Gabon (n = 89, 2021 to 2022) was analyzed using culture media selective for ESBL-producing Enterobacterales, S. aureus-related complex, Gram-positive bacteria and nonfermenters. Phylogenetic analyses of ESBL-producing Enterobacterales was done using core-genome multilocus sequence typing (cgMLST) and compared with publicly available genomes. Patterns of cooccurring species were detected by network analysis. Of the 439 bacterial isolates, the majority of species belonged to the genus Pseudomonas (n = 170), followed by Stenotrophomonas (n = 113) and Achromobacter (n = 37). Three Klebsiella pneumoniae isolates and one Escherichia coli isolate were ESBL-producers, which clustered with human isolates from Nigeria (MLST sequence type 1788 [ST1788]) and Gabon (ST38), respectively. Network analysis revealed a frequent cooccurrence of Stenotrophomonas maltophilia with Pseudomonas putida and Pseudomonas aeruginosa. In conclusion, pangolins can be colonized with human-related ESBL-producing K. pneumoniae and E. coli. Unlike in other African wildlife, S. aureus-related complex was not detected in pangolins. IMPORTANCE There is an ongoing debate if pangolins are a relevant reservoir for viruses such as SARS-CoV-2. Here, we wanted to know if African pangolins are colonized with bacteria that are relevant for human health. A wildlife reservoir of antimicrobial resistance would be of medical relevance in regions were consumption of so-called bushmeat is common. In 89 pangolins, we found three ESBL-producing Klebsiella pneumoniae strains and one ESBL-producing Escherichia coli strains, which were closely related to isolates from humans in Africa. This points toward either a transmission between pangolins and humans or a common source from which both humans and pangolins became colonized.

Die Covid-19-Pandemie war und ist ein in der (medialen) Öffentlichkeit überaus präsentes und vieldiskutiertes Thema. Nach Habermas stellt ein normativer Anspruch an öffentliche Diskurse dar, dass sich prinzipiell alle gesellschaftlichen Gruppen an ihnen beteiligen können. Dies gilt insbesondere dann, wenn politische Handlungsentscheidungen bezüglich gesellschaftlich relevanter Fragen und Probleme getroffen werden müssen. Wir fragen, welche gesellschaftlichen Akteur:innengruppen zu welchen Anteilen in den medialen, öffentlichen Corona-Diskurs eingebunden wurden und mit welcher Art von Aussagen sie in den Artikeln zu Wort kamen. Diese Fragen beantworten wir jeweils im Vergleich zu sechs anderen medial-öffentlichen Gesundheitsdebatten mittels quantitativer Inhaltsanalysen der Medienberichterstattung. Ein besonderer Fokus der Analyse liegt auf wissenschaftlichen Akteur:innen, die gemäß des Weberschen Prinzips der Werturteilsfreiheit der Wissenschaft idealerweise in der Rolle sachlicher ‚Aufklärer:innen‘ in den Diskurs eingebunden werden sollten, jedoch keine politischen Handlungsempfehlungen aussprechen sollten. Unsere Analyse zeigt einige Spezifika das Corona-Diskurses im Vergleich zu den anderen Gesundheitsdebatten. Er präsentierte sich im Jahr 2020 als relativ stark vermachteter Diskurs, in dem insbesondere Akteur:innen der politischen Exekutive sowie Par tialinteressenvertreter:innen stark präsent waren. Vertreter:innen von Kollektivgüterinteressen spielten hingegen so gut wie keine Rolle, wissenschaftliche Akteur:innen zumindest keine dominierende. Verhältnismäßig stark gekoppelt ist das Vorkommen wissenschaftlicher Akteur:innen innerhalb der Corona-Artikel mit Akteur:innen aus der Politik. Dies deutet darauf, dass die politische Exekutive in der Corona-Krise stark auf wissenschaftliche Expertise angewiesen war. Substantiierende Aussagen dominieren die Aussagenstruktur in der Covid-19-Berichterstattung deutlich. Wissenschaftliche Expert:innen äußerten in der Corona-Debatte moderat häufiger politische Handlungsempfehlungen als in den Vergleichsdebatten.