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Objectives: Adaptive platforms allow for the evaluation of multiple interventions at a lower cost and have been growing in popularity, especially during the COVID-19 pandemic. The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results., Methods: We performed a systematic review of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov from January 2015 to January 2022 for protocols or results of platform trials. Pairs of reviewers, working independently and in duplicate, collected data on trial characteristics of trial registrations, protocols, and publications of platform trials. We reported our results using total numbers and percentages, as well as medians with interquartile range (IQR) when appropriate., Results: We identified 15,277 unique search records and screened 14,403 titles and abstracts after duplicates were removed. We identified 98 unique randomized platform trials. Sixteen platform trials were sourced from a systematic review completed in 2019, which included platform trials reported prior to 2015. Most platform trials (n = 67, 68.3%) were registered between 2020 and 2022, coinciding with the COVID-19 pandemic. The included platform trials primarily recruited or plan to recruit patients from North America or Europe, with most subjects being recruited from the United States (n = 39, 39.7%) and the United Kingdom (n = 31, 31.6%). Bayesian methods were used in 28.6% (n = 28) of platform RCTs and frequentist methods in 66.3% (n = 65) of trials, including 1 (1%) that used methods from both paradigms. Out of the twenty-five trials with peer-reviewed publication of results, seven trials used Bayesian methods (28%), and of those, two (8%) used a predefined sample size calculation while the remainder used pre-specified probabilities of futility, harm, or benefit calculated at (pre-specified) intervals to inform decisions about stopping interventions or the entire trial. Seventeen (68%) peer-reviewed publications used frequentist methods. Out of the seven published Bayesian trials, seven (100%) reported thresholds for benefit. The threshold for benefit ranged from 80% to >99%., Conclusion: We identified and summarized key components of platform trials, including the basics of the methodological and statistical considerations. Ultimately, improving standardization and reporting in platform trials require an understanding of the current landscape. We provide the most updated and rigorous review of platform trials to date., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe., Methods: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available., Results: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases., Conclusions: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The European Bioinformatics Institute (EMBL-EBI) maintains a comprehensive range of freely available and up-to-date molecular data resources, which includes over 40 resources covering every major data type in the life sciences. This year's service update for EMBL-EBI includes new resources, PGS Catalog and AlphaFold DB, and updates on existing resources, including the COVID-19 Data Platform, trRosetta and RoseTTAfold models introduced in Pfam and InterPro, and the launch of Genome Integrations with Function and Sequence by UniProt and Ensembl. Furthermore, we highlight projects through which EMBL-EBI has contributed to the development of community-driven data standards and guidelines, including the Recommended Metadata for Biological Images (REMBI), and the BioModels Reproducibility Scorecard. Training is one of EMBL-EBI's core missions and a key component of the provision of bioinformatics services to users: this year's update includes many of the improvements that have been developed to EMBL-EBI's online training offering., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background and Aims: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease., Methods: We performed a GWAS of 35,839 participants in the UKB with high intake of alcohol against markers of hepatic fibrosis (FIB-4, APRI, and Forns index scores) and hepatocellular injury (levels of aminotransferases). Loci identified in the discovery analysis were tested for their association with alcohol-related cirrhosis in 3 separate European cohorts (phase 1 validation cohort; n=2545). Variants associated with alcohol-related cirrhosis in the validation at a false discovery rate of less than 20% were then directly genotyped in 2 additional European validation cohorts (phase 2 validation, n=2068)., Results: In the GWAS of the discovery cohort, we identified 50 independent risk loci with genome-wide significance (P < 5 × 10 -8 ). Nine of these loci were significantly associated with alcohol-related cirrhosis in the phase 1 validation cohort; 6 of these 9 loci were significantly associated with alcohol-related cirrhosis in phase 2 validation cohort, at a false discovery rate below 5%. The loci included variants in the mitochondrial amidoxime reducing component 1 gene (MARC1) and the heterogeneous nuclear ribonucleoprotein U like 1 gene (HNRNPUL1). After we adjusted for age, sex, body mass index, and type-2 diabetes in the phase 2 validation cohort, the minor A allele of MARC1:rs2642438 was associated with reduced risk of alcohol-related cirrhosis (adjusted odds ratio, 0.76; P=.0027); conversely, the minor C allele of HNRNPUL1:rs15052 was associated with an increased risk of alcohol-related cirrhosis (adjusted odds ratio, 1.30; P=.020)., Conclusions: In a GWAS of samples from the UKB, we identified and validated (in 5 European cohorts) single-nucleotide polymorphisms that affect risk of alcohol-related cirrhosis in opposite directions: the minor A allele in MARC1:rs2642438 decreases risk, whereas the minor C allele in HNRNPUL1:rs15052 increases risk., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Transmission of COVID-19 in developing countries is expected to surpass that in developed countries; however, information on community perceptions of this new disease is scarce. The aim of the study was to identify possible misconceptions among males and females toward COVID-19 in Uganda using a rapid online survey distributed via social media. Methods: A cross-sectional survey carried out in early April 2020 was conducted with 161 Ugandans, who purposively participated in the online questionnaire that assessed understandings of COVID-19 risk and infection. Sixty-four percent of respondents were male and 36% were female. Results: We found significant divergences of opinion on gendered susceptibility to COVID-19. Most female respondents considered infection risk, symptoms, severe signs, and death to be equally distributed between genders. In contrast, male respondents believed they were more at risk of infection, severe symptoms, severe signs, and death (52.7 vs. 30.6%, RR = 1.79, 95% CI: 1.14-2.8). Most women did not share this perception and disagreed that males were at higher risk of infection (by a factor of three), symptoms (79% disagree), severe signs (71%, disagree), and death (70.2% disagree). Overall, most respondents considered children less vulnerable (OR = 1.12, 95% CI: 0.55-2.2) to COVID-19 than adults, that children present with less symptoms (OR = 1.57, 95% CI: 0.77-3.19), and that there would be less mortality in children (OR = 0.92, 95% CI: 0.41-1.88). Of female respondents, 76.4% considered mortality from COVID-19 to be different between the young and the elderly (RR = 1.7, 95% CI: 1.01-2.92) and 92.7% believed young adults would show fewer signs than the elderly, and 71.4% agreed that elderly COVID-19 patients would show more severe signs than the young (OR = 2.2, 95% CI: 1.4, 4.8). While respondents considered that all races were susceptible to the signs and symptoms of infection as well as death from COVID-19, they considered mortality would be highest among white people from Europe and the USA. Some respondents (mostly male 33/102, 32.4%) considered COVID-19 to be a "disease of whites" (30.2%). Conclusion: The WHO has identified women and children in rural communities as vulnerable persons who should be given more attention in the COVID-19 national response programs across Africa; however, our study has found that men in Uganda perceive themselves to be at greater risk and that these contradictory perceptions (including the association of COVID-19 with "the white" race) suggest an important discrepancy in the communication of who is most vulnerable and why . Further research is urgently needed to validate and expand the results of this small exploratory study., (Copyright © 2020 Kasozi, MacLeod, Ssempijja, Mahero, Matama, Musoke, Bardosh, Ssebuufu, Wakoko-Studstil, Echoru, Ayikobua, Mujinya, Nambuya, Onohuean, Zirintunda, Ekou and Welburn.)

Data resources at the European Bioinformatics Institute (EMBL-EBI, https://www.ebi.ac.uk/) archive, organize and provide added-value analysis of research data produced around the world. This year's update for EMBL-EBI focuses on data exchanges among resources, both within the institute and with a wider global infrastructure. Within EMBL-EBI, data resources exchange data through a rich network of data flows mediated by automated systems. This network ensures that users are served with as much information as possible from any search and any starting point within EMBL-EBI's websites. EMBL-EBI data resources also exchange data with hundreds of other data resources worldwide and collectively are a key component of a global infrastructure of interconnected life sciences data resources. We also describe the BioImage Archive, a deposition database for raw images derived from primary research that will supply data for future knowledgebases that will add value through curation of primary image data. We also report a new release of the PRIDE database with an improved technical infrastructure, a new API, a new webpage, and improved data exchange with UniProt and Expression Atlas. Training is a core mission of EMBL-EBI and in 2018 our training team served more users, both in-person and through web-based programmes, than ever before., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.

The purpose of this study was to explore and compare different countries in what motivated research participants' decisions whether to share their de-identified data. We investigated European DIRECT (Diabetes Research on Patient Stratification) research project participants' desire for control over sharing different types of their de-identified data, and with who data could be shared in the future after the project ends. A cross-sectional survey was disseminated among DIRECT project participants. The results found that there was a significant association between country and attitudes towards advancing research, protecting privacy, and beliefs about risks and benefits to sharing data. When given the choice to have control, some participants (<50% overall) indicated that having control over what data is shared and with whom was important; and control over what data types are shared was less important than respondents deciding who data are shared with. Danish respondents indicated higher odds of desire to control data types shared, and Dutch respondents showed higher odds of desire to control who data will be shared with. Overall, what research participants expect in terms of control over data sharing needs to be considered and aligned with sharing for future research and re-use of data. Our findings show that even with de-identified data, respondents prioritise privacy above all else. This study argues to move research participants from passive participation in biomedical research to considering their opinions about data sharing and control of de-identified biomedical data.

Background: Although the effects of individual-level factors on wellbeing change following work exit have been identified, the role of welfare-state variables at the country level has yet to be investigated., Methods: Data on 8037 respondents aged 50 years and over in 16 European countries were drawn from the Survey of Health, Ageing and Retirement in Europe (SHARE) and the English Longitudinal Study of Ageing (ELSA). We employed multilevel models to assess determinants of change in wellbeing following work exit, using CASP-12 change scores. After adjusting for institutionally defined route and timing of work exit, in addition to other individual-level variables, we tested country-level variables including welfare-state regime and measures of disaggregated welfare spending to determine their associations with wellbeing change and the proportion of between-country variance explained., Results: Individuals whose exit from paid work was involuntary or diverged from the typical retirement age experienced declines in wellbeing. Country effects accounted for 7% of overall variance in wellbeing change. Individuals residing in countries with a Mediterranean welfare regime experienced more negative changes in wellbeing, with a difference of -2.15 (-3.23, -1.06) CASP-12 points compared with those in Bismarckian welfare states. Welfare regime explained 62% of between-country variance. National per-capita expenditure on non-healthcare in-kind benefits (services) was associated with more positive wellbeing outcomes., Conclusions: National expenditure on in-kind benefits, particularly non-healthcare services, is associated with more favourable wellbeing change outcomes following work exit in early old age. Welfare-state effects explain the majority of between-country differences in change in wellbeing., (© The Author(s) 2018. Published by Oxford University Press on behalf of the International Epidemiological Association.)

The European Bioinformatics Institute (https://www.ebi.ac.uk/) archives, curates and analyses life sciences data produced by researchers throughout the world, and makes these data available for re-use globally (https://www.ebi.ac.uk/). Data volumes continue to grow exponentially: total raw storage capacity now exceeds 160 petabytes, and we manage these increasing data flows while maintaining the quality of our services. This year we have improved the efficiency of our computational infrastructure and doubled the bandwidth of our connection to the worldwide web. We report two new data resources, the Single Cell Expression Atlas (https://www.ebi.ac.uk/gxa/sc/), which is a component of the Expression Atlas; and the PDBe-Knowledgebase (https://www.ebi.ac.uk/pdbe/pdbe-kb), which collates functional annotations and predictions for structure data in the Protein Data Bank. Additionally, Europe PMC (http://europepmc.org/) has added preprint abstracts to its search results, supplementing results from peer-reviewed publications. EMBL-EBI maintains over 150 analytical bioinformatics tools that complement our data resources. We make these tools available for users through a web interface as well as programmatically using application programming interfaces, whilst ensuring the latest versions are available for our users. Our training team, with support from all of our staff, continued to provide on-site, off-site and web-based training opportunities for thousands of researchers worldwide this year.

Policy makers and governments are calling for coordination to address the crisis emerging from the ineffectiveness of current antibiotics and stagnated pipe-line of new ones - antimicrobial resistance (AMR). Wider contextual drivers and mechanisms are contributing to shifts in governance strategies in health care, but are national health system approaches aligned with strategies required to tackle antimicrobial resistance? This article provides an analysis of governance approaches within healthcare systems including: priority setting, performance monitoring and accountability for AMR prevention in three European countries: England, France and Germany. Advantages and unresolved issues from these different experiences are reported, concluding that mechanisms are needed to support partnerships between healthcare professionals and patients with democratized decision-making and accountability via collaboration. But along with this multi-stakeholder approach to governance, a balance between regulation and persuasion is needed., Competing Interests: Not applicableNot applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The European Bioinformatics Institute (EMBL-EBI) supports life-science research throughout the world by providing open data, open-source software and analytical tools, and technical infrastructure (https://www.ebi.ac.uk). We accommodate an increasingly diverse range of data types and integrate them, so that biologists in all disciplines can explore life in ever-increasing detail. We maintain over 40 data resources, many of which are run collaboratively with partners in 16 countries (https://www.ebi.ac.uk/services). Submissions continue to increase exponentially: our data storage has doubled in less than two years to 120 petabytes. Recent advances in cellular imaging and single-cell sequencing techniques are generating a vast amount of high-dimensional data, bringing to light new cell types and new perspectives on anatomy. Accordingly, one of our main focus areas is integrating high-quality information from bioimaging, biobanking and other types of molecular data. This is reflected in our deep involvement in Open Targets, stewarding of plant phenotyping standards (MIAPPE) and partnership in the Human Cell Atlas data coordination platform, as well as the 2017 launch of the Omics Discovery Index. This update gives a birds-eye view of EMBL-EBI's approach to data integration and service development as genomics begins to enter the clinic., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Therapeutic Patient Education (TPE) coordination function has been developed worldwide for several decades. In France, this function is an integral part of authorization of TPE programs. However, both in France and in other European countries, situations, activities and qualifications common to TPE coordinators are becoming progressively more structured, regardless of the disease and/or the type of practice concerned., Methods: The French National Institutefor Prevention and Health Education (INPES) conducted a project based on an innovative method comprising formalization of practices as perceived by professionals themselves (91 professionals in France and about thirty in five other European countries were interviewed) and consultation of a taskforce composed of national and international TPE experts, in a perspective of repeated construction with successive phases of consultation., Results: The analysis conducted in the course of this project demonstrated the pivotal role of TPE coordinators at the interface with the various TPE actors. The TPE coordinator function was defined by guidelines comprising six symbolic situations, 20 activities and 26 key skills in three domains., Discussion: This work constituted the basis for the elaboration of a new skill-based regulatory framework for TPE coordination. The TPE coordinator guidelines provide a relevant tool to organize training and validation of the experience acquired in thisfield and also open up new research perspectives.

Molecular Biology has been at the heart of the 'big data' revolution from its very beginning, and the need for access to biological data is a common thread running from the 1965 publication of Dayhoff's 'Atlas of Protein Sequence and Structure' through the Human Genome Project in the late 1990s and early 2000s to today's population-scale sequencing initiatives. The European Bioinformatics Institute (EMBL-EBI; http://www.ebi.ac.uk) is one of three organizations worldwide that provides free access to comprehensive, integrated molecular data sets. Here, we summarize the principles underpinning the development of these public resources and provide an overview of EMBL-EBI's database collection to complement the reviews of individual databases provided elsewhere in this issue.

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide-sequence repository. The ENA consists of three main databases: the Sequence Read Archive (SRA), the Trace Archive and EMBL-Bank. The objective of ENA is to support and promote the use of nucleotide sequencing as an experimental research platform by providing data submission, archive, search and download services. In this article, we outline these services and describe major changes and improvements introduced during 2010. These include extended EMBL-Bank and SRA-data submission services, extended ENA Browser functionality, support for submitting data to the European Genome-phenome Archive (EGA) through SRA, and the launch of a new sequence similarity search service.

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe's primary nucleotide sequence archival resource, safeguarding open nucleotide data access, engaging in worldwide collaborative data exchange and integrating with the scientific publication process. ENA has made significant contributions to the collaborative nucleotide archival arena as an active proponent of extending the traditional collaboration to cover capillary and next-generation sequencing information. We have continued to co-develop data and metadata representation formats with our collaborators for both data exchange and public data dissemination. In addition to the DDBJ/EMBL/GenBank feature table format, we share metadata formats for capillary and next-generation sequencing traces and are using and contributing to the NCBI SRA Toolkit for the long-term storage of the next-generation sequence traces. During the course of 2009, ENA has significantly improved sequence submission, search and access functionalities provided at EMBL-EBI. In this article, we briefly describe the content and scope of our archive and introduce major improvements to our services.

Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

Data from plaice, Pleuronectes platessa L., tagged with electronic data storage tags, were used to test whether these fishes exhibited migration route and spawning area fidelity in successive spawning seasons. Depth and temperature data were recorded for each fish over 365-512 days in the central North Sea and this information was used to reconstruct movements based on tidal locations. We discovered highly directed seasonal migrations from the winter spawning area south of a major topographical feature, Dogger Bank Tail End, to summer feeding grounds 250 km to the north in deep, cold, thermally stratified water. Our results show synchronous timing of migration, repeated pre- and post-spawning migration routes and 100% spawning area fidelity, including two individuals that returned to within 20 km of their previous season's spawning location. This is the first study to provide a complete reconstruction of annual migrations by individual fishes, showing strong homing behaviour along consistent migration routes.

As the amount of biological data grows, so does the need for biologists to store and access this information in central repositories in a free and unambiguous manner. The European Bioinformatics Institute (EBI) hosts six core databases, which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS-PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene expression (ArrayExpress). But just as a cell would be useless if it couldn't transcribe DNA or translate RNA, our resources would be compromised if each existed in isolation. We have therefore developed a range of tools that not only facilitate the deposition and retrieval of biological information, but also allow users to carry out searches that reflect the interconnectedness of biological information. The EBI's databases and tools are all available on our website at www.ebi.ac.uk.